Sep 2005

PNN Quarterly File—Third Quarter 2005

PNN Pharmacotherapy Line
July 1, 2005 Vol. 12, No. 127
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
July issue of Diabetes Care (care.diabetesjournals.org; 2005; 28).

Glitazones & Lipids: Pioglitazone has noticeably better effects on patients’ lipid profiles than does rosiglitazone, including improved triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size, according to a study of 802 patients with type 2 diabetes (pp. 1547-54). Study participants had been treated with diet alone or monotherapy for diabetes and were untreated for dyslipidemias; they received pioglitazone 30 mg once daily for 12 weeks followed by 45 mg once daily for 12 weeks or rosiglitazone 4 mg once daily for 12 weeks followed by 4 mg twice daily for 12 weeks. “Triglyceride levels were reduced by 51.9 ± 7.8 mg/dl with pioglitazone, but were increased by 13.1 ± 7.8 mg/dl with rosiglitazone (P < 0.001 between treatments),” the authors report. “Additionally, the increase in HDL cholesterol was greater (5.2 ± 0.5 vs. 2.4 ± 0.5 mg/dl; P < 0.001) and the increase in LDL cholesterol was less (12.3 ± 1.6 vs. 21.3 ± 1.6 mg/dl; P < 0.001) for pioglitazone compared with rosiglitazone, respectively. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone (P < 0.001). LDL particle size increased more with pioglitazone (P = 0.005).” (S. J. Jacober, sjacober@lilly.com)

Need for Fibrates After Raloxifene Therapy Is Begun: Women with a history of triglyceridemia while on oral estrogen therapy should be monitored closely following institution of raloxifene treatment, as increases in serum triglyceride levels that may require addition of fibrates for control sometime result (pp. 1555-61). This finding comes from an 8-week trial conducted in 12 postmenopausal women whose serum triglyceride levels were 300 mg/dL or more during estrogen treatment. The authors write: “At week 2 of the study, three (25%) of the subjects withdrew from the trial because they developed marked hypertriglyceridemia (≥11.3 mmol/l [≥1,000 mg/dl]) during raloxifene therapy. These three women had higher baseline triglyceride and glucose levels, were not being treated with lipid-lowering agents, and were more likely to have diabetes than the other study subjects. The remaining nine patients (75%) completed the 8-week trial and experienced a nonsignificant increase in mean triglyceride levels from baseline to end point. Raloxifene treatment also resulted in a significant 16% decrease in hepatic lipase activity and a 26% increase in HDL2 levels (P = 0.013 and 0.03, respectively).” (M. C. Carr, carr@northwestern.edu)

Diabetes as CHD Equivalent Risk: Women with diabetes are at particularly increased risk of vascular death, even without having frank cardiovascular heart disease, concludes a prospective cohort study of men (n = 7,052) and women (n =8,354) aged 45–64 years from Renfrew and Paisley, Scotland, who were first screened in 1972–1976 and followed for 25 years (pp. 1588-93). “The highest mortality was in the group with both diabetes and CHD (100.2 deaths/1,000 person-years in men, 93.6 in women) and the lowest in the group with neither (29.2 deaths/1,000 person-years in men, 19.4 in women),” note the researchers. “The adjusted hazard ratio (HR) for CHD mortality in men with diabetes only compared with men with CHD only was 1.17 (95% CI 0.78–1.74; P = 0.56). Corresponding HR for women was 1.97 (1.27–3.08; P = 0.003).” (C. Isles, Dumfries and Galloway Royal Infirmary, Dumfries, Scotland, U.K.; c.isles@dgri.scot.nhs.uk)

>>>PNN NewsWatch
* Marketing of an influenza vaccine in the U.S. as early as this fall is one of the elements in GlaxoSmithKline’s vaccine plans for the next few years, the company noted yesterday in an update for investors. In addition to an application filing with FDA for flu vaccine earlier this year, the company is working on five new vaccines that it hopes will reach the market within 5 years: Cervarix, for prevention of the human papilloma virus that causes cervical cancer; Rotarix for rotavirus gastroenteritis; Streptorix for pneumococcal disease; an improved vaccine for influenza; and vaccine combinations against meningitis (www.gsk.com/media/pressreleases.htm).

*
PNN will not be published on Mon., July 4, Independence Day.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail
PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 5, 2005 Vol. 12, No. 128
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Online articles and the July 2 issue of BMJ (www.bmj.org; 2005; 331).

Perioperative Beta Blockers in Noncardiac Surgery: Major cardiovascular events may be reduced by perioperative administration of beta-blockers, according to a systematic review and meta-analysis, but the data are too unreliable to allow definitive conclusions to be drawn (doi:10.1136/bmj.38503.623646.8F). “Twenty two trials that randomised a total of 2437 patients met the eligibility criteria,” the authors write. “Perioperative beta blockers did not show any statistically significant beneficial effects on any of the individual outcomes and the only nominally statistically significant beneficial relative risk was 0.44 (95% confidence interval 0.20 to 0.97, 99% confidence interval 0.16 to 1.24) for the composite outcome of cardiovascular mortality, non-fatal myocardial infarction, and non-fatal cardiac arrest. Methods adapted from formal interim monitoring boundaries applied to cumulative meta-analysis showed that the evidence failed, by a considerable degree, to meet standards for forgoing additional studies. The individual safety outcomes in patients treated with perioperative beta blockers showed a relative risk for bradycardia needing treatment of 2.27 (95% CI 1.53 to 3.36, 99% CI 1.36 to 3.80) and a nominally statistically significant relative risk for hypotension needing treatment of 1.27 (95% CI 1.04 to 1.56, 99% CI 0.97 to 1.66).”(P. J. Devereaux, philipj@mcmaster.ca)

Treatment of Ocular Hypertension, Open Angle Glaucoma: Treatments that lower ocular pressure in patients with ocular hypertension or open-angle glaucoma reduce long-term risks of visual loss, conclude investigators who conducted a systematic review and meta-analysis of the sometimes-conflicting literature (doi:10.1136/bmj.38506.594977.E0). The group notes, “Meta-analysis of trials in ocular hypertension showed a significant preventive effect of reducing intraocular pressure on progression to glaucoma (hazard ratio 0.56, 95% confidence interval 0.39 to 0.81, P = 0.01; number needed to treat 12). Pooled data of studies in manifest glaucoma showed a significant delay of visual field deterioration (0.65, 0.49 to 0.87, P = 0.003; NNT = 7), with subgroup analysis showing a larger effect in patients with raised pressure and a reduced effect in normal tension glaucoma (subgroup comparison: not significant).” (P. C. Maier, U. Hosp., Freiburg, Germany; maierphi@aug.ukl.uni-freiburg.de)

>>>PNN NewsWatch
* Adults taking antidepressants have an increased risk of suicidal behavior similar to that noted earlier in children and adolescents, FDA has warned in a public health advisory. These patients should be watched closely for worsening of depression and for increased suicidal thinking or behavior, the agency cautioned, especially when antidepressant medications are started for the first time or when doses for the specific drugs prescribed have been changed (www.fda.gov/cder/drug/advisory/SSRI200507.htm).

* FDA approval of reformulated cough and cold products would be facilitated under bills currently being considered by Congress. With an increasing number of states now requiring placement of
pseudoephedrine products behind pharmacy counters because of use of the drug in illicit manufacture of methamphetamine, nonprescription medication manufacturers are increasingly looking at replacing this ingredient with phenylephrine in reformulated products.

>>>PNN JournalWatch
* Screening for Human Immunodeficiency Virus Infection, in Annals of Internal Medicine, 2005; 143: 32 ff. Reprints: www.annals.org; http://www.ahrq.gov/clinic/uspstf/uspshivi.htm; U.S. Preventive Services Task Force.

* Elimination of
Haemophilus influenzae Type b (Hib) Disease from The Gambia After the Introduction of Routine Immunisation with a Hib Conjugate Vaccine: A Prospective Study, in Lancet, 2005; early online publication. Reprints: www.thelancet.com; R. A. Adegbola, Medical Research Council Laboratories, The Gambia; radegbola@mrc.gm

* Sex Work, Drug Use, HIV Infection, and Spread of Sexually Transmitted Infections in Moscow, Russian Federation, in
Lancet, 2005; 366:57–60. Reprints: www.thelancet.com; A. Shakarishvili, afs9@cdc.gov

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail
PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 6, 2005 Vol. 12, No. 129
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
July 6 issue of JAMA (www.jama.com; 2005; 294).

Women’s Health Study: Results from the Women’s Health Study are analyzed in two articles and two editorials.

Aspirin 100 mg every other day, administered for a mean of 10.1 years, failed to prevent cancer among 39,876 U.S. women in the WHS (pp. 47-55). A statistical trend (P = .08) was observed in reduction of risk of lung cancer, but total, breast, colorectal, and other site-specific cancers were just as common with aspirin as among those on placebo. (N. R. Cook,
ncook@rics.bwh.harvard.edu)

Major cardiovascular events, cancer frequency and deaths, and total mortality were similarly unaffected by supplementation with natural-source vitamin E 600 IU every other day, but the intervention did provide a significant 24% reduction in cardiovascular mortality (pp. 56-65). “These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women,” study investigators conclude. (I-M Lee,
ilee@rics.bwh.harvard.edu)

Focusing on the cancer-prevention aspect of the trial, editorialists note that the search for pharmacologic means of preventing cancer is unlikely to produce substantial changes in overall cancer rates in the near future but that other interventions are available today (pp. 105-6): “Effective methods for reducing cancer incidence and mortality have already been discovered, but are underapplied. For instance, colorectal cancer screening is greatly underused, providing an important cancer prevention opportunity for physicians and other health care professionals. Reducing tobacco use is essential for cancer prevention, and strong evidence indicates that policy measures, such as increases in tobacco excise taxes and clean indoor air regulations, are effective in reducing tobacco use. In addition, clinicians can play an invaluable role in cancer prevention by asking patients about tobacco use and ensuring that patients who use tobacco receive appropriate counseling and treatment.” (E. J. Jacobs,
eric.jacobs@cancer.org)

“Although vitamin E is not a successful primary prevention strategy for women, one should not make the mistake of concluding that it will not turn out to be beneficial for men,” notes a second editorial. “The WHS highlights the importance of recognizing biological differences between the sexes in cardiovascular research by providing valuable sex-specific data on primary prevention.” (R. F. Redberg,
redberg@medicine.ucsf.edu)

>>>Internal Medicine Report
Source:
July 5 issue of the Annals of Internal Medicine (www.annals.org; 2005; 143).

Cardiovascular Effects of Soybean Protein: Soybean bean protein supplements lowered blood pressure in some patients, according to a study of 302 adults with initial untreated systolic blood pressures of 130–159 mm Hg and/or diastolic blood pressures of 80–99 mm Hg (pp. 1-9). The study, conducted in China, randomly assigned to participants to receive isolated soybean protein supplements 40 g/day or complex carbohydrate control for 12 weeks, with the results: “At baseline, the mean systolic and diastolic blood pressures were 135.0 mm Hg (SD 10.9) and 84.7 mm Hg (SD 6.9), respectively. Compared with the control group, the net changes in systolic blood pressure and diastolic blood pressure were –4.31 mm Hg (95% CI, –2.11 to –6.51 mm Hg; P < 0.001) and –2.76 mm Hg (CI, –1.35 to –4.16 mm Hg; P < 0.001), respectively, after the 12-week intervention. The net changes in systolic and diastolic blood pressure reductions were –7.88 mm Hg (CI, –4.66 to –11.1 mm Hg) and –5.27 mm Hg (CI, –3.05 to –7.49 mm Hg), respectively, in persons with hypertension and –2.34 mm Hg (CI, 0.48 to –5.17 mm Hg) and –1.28 mm Hg (CI, 0.52 to –3.07 mm Hg), respectively, in those without hypertension.” (J. He, jhe@tulane.edu)

Editorialists comment (pp. 74-5): “Given the incomplete evidence about feasibility, safety, and specificity, recommending soybean protein supplements to prehypertensive patients is premature. However, higher protein intake may prove to be healthful, and we agree with current blood pressure control guidelines that recommend diets higher in total protein, such as the DASH diet.” (J. A. Cutler, NIH, Bethesda, Md.)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail
PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 7, 2005 Vol. 12, No. 130
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
July 7 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Nitric Oxide Use in Premies: Two articles present conflicting data on use of inhaled nitric oxide in critically ill premature infants, and editorialists provide clinical guidance to clinicians.

Among 420 neonates born at less than 34 weeks’ gestation with birth weights of 401–1,500 g, overall mortality and morbidity rates were unaffected by inhaled nitric oxide therapy (pp. 13-22). An important weight-based distinction was identified after the study, the authors report: “Post hoc analyses suggest that rates of death and bronchopulmonary dysplasia are reduced for infants with a birth weight greater than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled nitric oxide have higher mortality and increased rates of severe intracranial hemorrhage.” (K. P. Van Meurs,
vanmeurs@stanford.edu)

A prospective longitudinal study of 138 premature infants shows significantly improved neurodevelopmental outcomes at 2 years of age in those given nitric oxide (pp. 23-32). Compared with 46% of children in the placebo group who had disabilities such as cerebral palsy, bilateral blindness, bilateral hearing loss, or neurodevelopmental delays, only 24% of those treated with nitric oxide had such outcomes. Further analysis showed that the significant difference resulted from fewer treated patients with cognitive impairment. (M. D. Schreiber,
mschreiber@peds.bsd.uchicago.edu)

Editorialists offer clinicians this advice based on these study results (pp. 82-4): “The sobering finding of increased mortality and increased hemorrhagic or ischemic brain injury with inhaled nitric oxide therapy in the subgroup of severely ill infants with birth weights of 1000 g or less, although a post hoc finding, must not be ignored. It may reflect the production of biologically toxic byproducts, such as peroxynitrite, from the combination of nitric oxide with the high oxygen concentration to which these very sick infants are exposed. Therefore, short-term use of inhaled nitric oxide cannot be considered an effective rescue therapy for very preterm infants with profound respiratory failure. In contrast, less ill preterm infants may benefit from this therapy, both in the short term and over the long term.” (R. J. Martin, Rainbow Babies and Children's Hosp., Cleveland)

Treatment of Thrombocythemia: For treatment of high-risk essential thrombocythemia, hydroxyurea plus low-dose aspirin proved superior to anagrelide plus low-dose aspirin in an 809-patient study (pp. 33-45). Considering a primary end point that included arterial and venous thrombosis, serious hemorrhage, or death from thrombotic or hemorrhagic causes, the investigators found, “After a median follow-up of 39 months, patients in the anagrelide group were significantly more likely than those in the hydroxyurea group to have reached the primary end point (odds ratio, 1.57; 95 percent confidence interval, 1.04 to 2.37; P = 0.03). As compared with hydroxyurea plus aspirin, anagrelide plus aspirin was associated with increased rates of arterial thrombosis (P = 0.004), serious hemorrhage (P = 0.008), and transformation to myelofibrosis (P = 0.01) but with a decreased rate of venous thromboembolism (P = 0.006). Patients receiving anagrelide were more likely to withdraw from their assigned treatment (P < 0.001). Equivalent long-term control of the platelet count was achieved in both groups.” (A. R. Green, Cambridge Inst. of Med. Research, Cambridge, U.K.; arg1000@cam.ac.uk)

>>>PNN NewsWatch
* A large, 6-year NIH study, Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH), will evaluate Kos Pharmaceuticals’ extended-release niacin plus a statin versus a statin alone in patients established vascular disease plus atherogenic dyslipidemia (low HDL and high triglycerides).

*
Rite Aid has announced plans to open 10 Take Care Health Centers staffed by nurse practitioners in the Portland area, a development that is picked up in this morning’s Wall Street Journal. Four pharmacist-staffed medication therapy management clinics—dubbed Rite Care—operated in conjunction with U. Pittsburgh School of Pharmacy opened late last month in the Pittsburgh area.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail
PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 8, 2005 Vol. 12, No. 131
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
July issue of Pharmacotherapy (www.pharmacotherapy.org; 2005; 25).

Stimulant Adherence in Pediatrics: Adherence with stimulants was poor among 9,549 children and adolescents being treated for attention-deficit/hyperactivity disorder (pp. 909-17). Based on a retrospective analysis of 28,344 prescriptions paid by the Texas Medicaid system in 2001–02, the investigators report: “Adherence was evaluated based on the drug therapy prescribed (i.e., mixed amphetamine salts, immediate-release methylphenidate, and extended-release methylphenidate–OROS [oral-osmotic formulation]) and the age and sex of the patient. Adherence measures were persistence and medication possession ratio (MPR). Persistence was higher for extended-release methylphenidate–OROS (0.50 ± 0.33) than for mixed amphetamine salts (0.42 ± 0.29) or immediate-release methylphenidate (0.37 ± 0.26; p<0.001). The MPR was also higher for extended-release methylphenidate–OROS (0.76 ± 0.37) than for mixed amphetamine salts (0.73 ± 0.37) or immediate-release methylphenidate (0.69 ± 0.37; p<0.001). Patients aged 5–9 years had equal or better persistence and MPR than those aged 10–14 and 15–18 years (p<0.001). No sex-related differences in adherence were observed.” (M. L. Crismon, CRISMONL@mail.utexas.edu)

Hyperlipidemia Management Among Transplant Patients: LDL monitoring and management of identified hyperlipidemia was poor among 3,414 patients who had received liver, kidney, or pancreas transplants, a retrospective analysis of medical records indicates (pp. 918-23). The investigators note: “...1638 (48%) [patients] had hyperlipidemia. Of these, 711 (43%) were receiving antihyperlipidemic drugs; 227 (32%) of the 711 patients had achieved the total cholesterol goal of 200 mg/dl or below. Low-density lipoprotein cholesterol (LDL) levels were available for 1953 (57%) patients. Of these, 537 patients were receiving cholesterol-lowering drugs, and 384 (72%) of the 537 patients achieved the LDL goal of less than 130 mg/dl.” The group concludes, “Clinicians must be aggressive in diagnosing, monitoring, and treating hyperlipidemia to decrease the rate of cardiovascular disease and to prolong patient survival after transplantation.” (K. S. Schonder, schonderks@msx.upmc.edu)

GI Expenses After COX-2 Denials: Among 737 patients who were using COX-2 inhibitors before institution of a prior authorization program, no evidence of gastrointestinal problems were evident after coverage of the agents ended (pp. 924-34). In an analysis performed from the payer’s perspective, researchers show, “In the 3 months after PA program implementation, 620 (84.1%) of 737 members had no claims for a COX-2 inhibitor, and during this period their pharmacy and medical costs initially declined 40.0% (p<0.001) and 18.7% (p<0.001), respectively, and remained significantly lower. Among a subgroup of 156 members who tried to fill a COX-2 inhibitor prescription but were denied coverage, pharmacy and medical costs initially declined, 48.1% (p<0.001) and 10.3% (p<0.001), respectively, with pharmacy costs remaining significantly lower; however, overall medical expenditures increased, then returned to baseline. No change was noted in physician outpatient encounters, and two members had an emergency department visit for abdominal pain with no gastrointestinal ulcerations or bleeds during the 12-month follow-up.”
(P. P. Gleason, Prime Therapeutics, Eagan, Minn.;
pgleason@primetherapeutics.com)

>>>PNN NewsWatch
* Dapsone gel 5% (Aczone, QLT USA) was approved yesterday by FDA for topical treatment of acne vulgaris. Glucose 6-phosphate dehydrogenase levels should be measured before initiating therapy, and closer follow-up for blood hemoglobin levels and reticulocyte counts should be implemented in patients with a history of anemia and G6PD deficiency or other predispositions to increased hemolytic effect with dapsone.

* Inadequate staffing levels and lack of trained technicians are at issue in a strike of 1,200
Walgreens pharmacists in the Chicago area. Today’s Chicago Sun-Times reports that between 120 and 200 of the pharmacists have resigned from the union to return to work.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail
PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 11, 2005 Vol. 12, No. 132
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2005; 331).

OTC Emergency Contraceptives in the U.K.: The availability of over-the-counter emergency hormonal contraception in the U.K. has not increased its use, led to a decrease in unprotected sex, or caused people to reduce their use of more reliable methods of contraception, according to survey results, but one difference emerged: nearly one third of women began obtaining the therapy from pharmacies rather than physicians or clinics (doi:10.1136/bmj.38519.440266.8F). The products were switched to nonprescription status in Jan. 2001 for those aged 16 years and older, and the researchers analyzed survey results from 7,600 British households from 2000 and 2002. “After emergency hormonal contraception was made available over the counter, levels of use of different types of contraception by women aged 16-49 remained similar,” the authors write. “No significant change occurred in the proportion of women using emergency hormonal contraception (8.4% in 2000, 7.9% in 2001, 7.2% in 2002) or having unprotected sex. A change did, however, occur in where women obtained emergency hormonal contraception; a smaller proportion of women obtained emergency hormonal contraception from physicians and a greater proportion bought it over the counter. No significant change occurred in the proportion of women using more reliable methods of contraception, such as the oral contraceptive pill, or in the proportion of women using emergency hormonal contraception more than once during a year.” (C. Marston, Imperial College Faculty of Medicine, London; c.marston@imperial.ac.uk)

Bus Explosion Outside BMA House: The bus explosion during last Thursday’s terrorist attacks in London occurred outside BMA House, the headquarters of the British Medical Association and the BMJ Publishing Group, and the resulting chaos is described briefly in an online only article on the BMJ Web site. Physicians on staff at BMA House triaged injured bus riders and assisted first responders in managing the scene, according to an NPR news report (www.npr.org/templates/story/story.php?storyId=4735858). Expressions of sympathy can be posted on the journal’s Web site.

>>>Lancet Report
Source:
Early-release articles from Lancet (www.thelancet.com; 2005; 366).

Ceftriaxone for Meningococcal Meningitis: Single-dose ceftriaxone provides an alternative to chloramphenicol for epidemic meningococcal meningitis, according to a study from Niger (DOI:10.1016/S0140-6736(05)66792-X). “Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up,” note authors of the open-label noninferiority trial. “The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI –3.8 to 4..5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported.” (P. J. Guerin, Epicentre, Paris; philippe.guerin@epicentre.msf.org)

>>>PNN NewsWatch
* FDA on Friday mandated addition of sudden vision loss to the adverse effects listed in product labeling of the three marketed phosphodiesterase 5 inhibitors (sildenafil, tadalafil, and vardenafil). The problem is believed to result from nonarteritic ischemic optic neuropathy, a condition that is also common in men with clinical profiles similar to those of many men with erectile dysfunction.

>>>PNN JournalWatch
* Acupuncture in Patients with Osteoarthritis of the Knee: A Randomised Trial, in Lancet, 2005; 366: 136–43. Reprints: www.thelancet.com; C. Witt, Charité U. Med. Ctr., Berlin; claudia.witt@charite.de

* Aspirin Resistance: An Evaluation of Current Evidence and Measurement Methods, in
Pharmacotherapy, 2005; 25: 942–53. Reprints: www.pharmacotherapy.org; R. L. Talbert, U. Texas Health Sci. Ctr., San Antonio

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail
PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 12, 2005 Vol. 12, No. 133
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
July 11 issue of Archives of Internal Medicine (www.archinternmed.com; 2005; 165).

Adherence to Therapy Guidelines in U.S. Hospitals: Two articles and an editorial explore clinicians’ adherence with guidelines for antithrombotic therapy and heart failure treatment in hospitalized patients in the U.S.

Inadequate antithrombotic therapy is provided to “a significant percentage of hospitalized patients,” concludes an analysis of medical records at 38 hospitals of inpatients treated for atrial fibrillation, acute myocardial infarction, deep vein thrombosis, or pulmonary embolism or given prophylaxis for total knee replacement, total hip replacement, or hip fracture surgery between July 1, 2000, and June 30, 2003 (pp. 1458-64). “The medical records of 3778 patients (53.3% men) were included. The mean patient age was 66.1 years. Of patients with atrial fibrillation at high risk for stroke, only 54.7% received warfarin sodium, and 20.6% received neither aspirin nor warfarin. Of patients with acute myocardial infarction, only 75.5% received aspirin on hospital arrival. After orthopedic surgery procedures, only 85.6% of patients received prophylaxis with a parenteral anticoagulant agent or warfarin. In 49.4% of patients with deep vein thrombosis, pulmonary embolism, or both, unfractionated or low-molecular-weight heparin use was discontinued before an international normalized ratio of 2.0 or greater was achieved for 2 consecutive days. Patients with deep vein thrombosis or pulmonary embolism were rarely discharged from the hospital with bridge therapy (an injectable anticoagulant agent plus warfarin), although the length of hospitalization was significantly shorter than if discharged taking warfarin alone (4.0 vs 8.1 days; P < .001).” (V. F. Tapson, tapso001@mc.duke.edu)

Educational initiatives and quality improvement systems are needed to reduce clinician variability in conformity to quality-of-care guidelines and address a gap in overall performance, according to a report of data on 81,142 admissions in 2002–03 as recorded in the Acute Decompensated Heart Failure National Registry (ADHERE; pp. 1469-77). Four Joint Commission on Accreditation of Healthcare Organizations core performance measures were used: discharge instructions (HF-1), assessment of left ventricular function (HF-2), use of ACE inhibitors in patients with left ventricular systolic dysfunction (HF-3), and smoking cessation counseling (HF-4), with these results: “Across all hospitals, the median rates of conformity with HF-1, HF-2, HF-3, and HF-4 were 24.0%, 86.2%, 72.0%, and 43.2%, respectively. Rates of conformity at individual hospitals varied from 0% to 100%, with statistically significant differences between academic and nonacademic hospitals. Statistically significant positive independent predictors of overall conformity included the prevalence of comorbidities and the use of more intense pharmacologic management.” (G. C. Fonarow, gfonarow@mednet.ucla.edu)

The health care system needs “intelligent efforts,” writes an editorialist, such as those in the Cardiac Goal Program now being tested in an NIH trial (pp. 1455-6): “This stand-alone program does not require the implementation of an entire electronic medical record or computerized physician order entry (present in less than 10% of institutions), has the ability to communicate with available software programs already in place at most institutions (eg, laboratory information system), and extends across the cardiovascular disease spectrum (heart failure, lipids, atrial fibrillation, coronary artery disease, MI). The program’s embedded algorithms use information from one disease state to influence others. For example, if a patient has heart failure along with chronic atrial fibrillation, the physician is automatically alerted to the fact that the patient is at a high risk for an embolic event and should receive warfarin (reminder). Patient and physician summaries are generated with a single mouse click, which can serve as documentation to physicians and an educational tool for both physicians and patients. In addition to the features already mentioned, the Cardiac Goal Program contains a detailed preprogrammed data analysis package, which can provide ‘report cards’ for physicians (feedback), patients, and payors.” (L. Baruch, VA Med. Ctr., Bronx, N.Y.; baruchlarry@att.net)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 13, 2005 Vol. 12, No. 134
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
July 13 issue of JAMA (www.jama.com; 2005; 294).

Symptoms After Hormonal Therapy Discontinuance: When therapy was stopped at the interruption of the conjugated equine estrogen plus medroxyprogesterone arm of the Women’s Health Initiative, symptoms recurred in more than one half of women who had vasomotor symptoms at baseline, according to a survey of 8,405 participants (pp. 183-93). Considering hot flushes and night sweats along with nonvasomotor symptoms such as pain and stiffness, the investigators report, “Moderate or severe vasomotor symptoms after discontinuing study pill use were reported by 21.2% of former CEE + MPA and 4.8% of placebo group respondents overall and by 55.5% and 21.3%, respectively, with these symptoms at baseline (randomization). Compared with respondents in the former placebo group, moderate or severe vasomotor symptoms (adjusted odds ratio [AOR] 5.82; 95% confidence interval [CI], 4.92-6.89) and pain or stiffness symptoms (AOR, 2.16; 95% CI, 1.95-2.40) were more likely in respondents in the former CEE + MPA group. Both vasomotor symptoms (AOR, 5.36; 95% CI, 4.51-6.38) and pain or stiffness symptoms (AOR, 3.21; 95% CI, 2.90-3.56) also were more likely in women with these symptoms at baseline. Women reported a wide range of strategies to manage symptoms.” (J. K. Ockene, Judith.Ockene@umassmed.edu)

An editorialist concludes that gradual tapering may be needed when menopausal hormone therapy is discontinued (pp. 245-6): “Most clinicians would agree with the American College of Obstetricians and Gynecologists that when symptoms of menopause necessitate hormone therapy, treatment should be prescribed at the lowest effective dose for the shortest possible time. The high frequency of symptoms reported by the WHI participants may be a result of the abrupt withdrawal from hormone (or placebo) therapy. Thus, when it is time to consider discontinuing hormone therapy, gradual tapering of the dose would be a logical clinical strategy arising from these new observations from the WHI.” (D. Petitti, Kaiser Permanente Southern California, Pasadena)

Hepatitis A Vaccination: Routine administration of hepatitis A vaccine to U.S. children has dropped frequency of the disease to historic lows, report authors who analyzed cases reported to the National Notifiable Diseases Surveillance System since 1990 (pp. 194-201). “Between the baseline period (1990–1997) and 2003, overall hepatitis A rates declined 76% to 2.6 per 100,000, significantly lower than previous nadirs in 1983 (9.2/100,000) and 1992 (9.1/100,000). The rate in vaccinating states declined 88% to 2.5 per 100,000 compared with 53% elsewhere (to 2.7/100,000). In 2003, cases from vaccinating states accounted for 33% of the national total vs 65% during the baseline period. Declines were greater among children aged 2 to 18 years (87%) than among persons older than age 18 years (69%); the proportion of cases in children dropped from 35% to 19%. Since 2001, rates in adults have been higher than among children, with the highest rates now among men aged 25 through 39 years.” (A. Wasley, awasley@cdc.gov)

Similar efforts in Israel have produced evidence of herd immunity, add authors of a second study (pp. 202-10): “The annual incidence of 2.2 to 2.5 per 100 000 during 2002–2004 represents a 95% or greater reduction for each year with respect to the mean incidence during 1993–1998 (P < .001). For children aged 1 through 4 years, a 98.2% reduction in disease was observed in 2002–2004, compared with the prevaccination period (P < .001). However, a sharp decline was also observed in all other age groups (84.3% [<1 year], 96.5% [5–9 years], 95.2% [10–14 years], 91.3% [15–44 years], 90.6% [45–64 years], and 77.3% [65 years]). Among the Jewish population in the Jerusalem district, in whom the active surveillance program was successfully conducted, a more than 90% reduction of disease was demonstrated. Of the 433 cases reported nationwide in 2002–2004 in whom vaccination status could be ascertained, 424 (97.9%) received no vaccine and none received 2 doses.” (R. Dagan, Soroka U. Med. Ctr., Beer-Sheva, Israel;
rdagan@bgu.ac.il)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 14, 2005 Vol. 12, No. 135
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
July 14 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Erlotinib for Previously Treated NSCLC: Two articles and an editorial present new information on management of patients with non–small-cell lung cancer after the failure of first- or second-line chemotherapy.

In a Canadian study, oral erlotinib 150 mg daily prolonged survival among a small but significant fraction of such patients (pp. 123-32): “The median age of the 731 patients who underwent randomization was 61.4 years; 49 percent had received two prior chemotherapy regimens, and 93 percent had received platinum-based chemotherapy. The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group (P < 0.001); the median duration of the response was 7.9 months and 3.7 months, respectively. Progression-free survival was 2.2 months and 1.8 months, respectively (hazard ratio, 0.61, adjusted for stratification categories; P < 0.001). Overall survival was 6.7 months and 4.7 months, respectively (hazard ratio, 0.70; P < 0.001), in favor of erlotinib. Five percent of patients discontinued erlotinib because of toxic effects.” (F. A. Shepherd)

An analysis of tumor biopsy samples from the above clinical trial shows that expression of epidermal growth factor receptor (EGFR) improves but not does not assure response to erlotinib therapy (pp. 133-44): “In univariate analyses, survival was longer in the erlotinib group than in the placebo group when EGFR was expressed (hazard ratio for death, 0.68; P = 0.02) or there was a high number of copies of
EGFR (hazard ratio, 0.44; P = 0.008). In multivariate analyses, adenocarcinoma (P = 0.01), never having smoked (P < 0.001), and expression of EGFR (P = 0.03) were associated with an objective response. In multivariate analysis, survival after treatment with erlotinib was not influenced by the status of EGFR expression, the number of EGFR copies, or EGFR mutation.” (M-S Tsao)

Given the “initial overly enthusiastic interest, subsequent critical disappointment, and eventual renewed appreciation” that marked the development of the EGFR inhibitors, caution and prudence are indicated as new agents are introduced into cancer care, writes an editorialist (pp. 200-2): “With the development of trastuzumab therapy for breast cancer as a model, it is now clear that predictive molecular assays must be devised before the initiation of clinical trials for new targeted anticancer agents if the specificity and usefulness of these drugs are to be meaningfully evaluated in the population of patients most likely to benefit from the treatment. Furthermore, the designs of modern phase 2 and phase 3 clinical trials must incorporate specific molecular assays to maximize the likelihood of definitive clinical results. This work will require substantially more effort to develop standardized assay procedures for assessing and predicting the effects of whole classes of molecularly targeted agents and highly standardized methods for the prospective collection of human tumor tissue.” (J. H. Doroshow, Natl. Cancer Inst., Bethesda, Md.)

Nesiritide: Lack of clinical evidence, FDA policies, and an aggressive Scios marketing campaign are at issue in a Perspectives article on nesiritide (pp. 113-6): “The nesiritide story reflects some recurring themes: in other recent cases, too, major safety problems have been uncovered after a drug has been approved. Nesiritide was approved on the basis of a single trial in which surrogate end points were assessed three hours after administration. In cardiovascular medicine, we learned long ago that therapies directed at surrogate end points — such as the suppression of premature ventricular contractions or, for inotropic agents, an improved ejection fraction — can be associated with excess deaths. With the low threshold set for regulatory approval, the FDA did not demand appropriate warnings on the label regarding an increased risk of death or worsened renal function and did not require the performance of trials that would have provided definitive verification of the safety and efficacy of nesiritide.” (E. J. Topol, Cleveland Clinic, Cleveland; an audio interview with Topol is available at on the journal’s Web site)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.


PNN Pharmacotherapy Line
July 15, 2005 Vol. 12, No. 136
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
July issue of Pediatrics (www.pediatrics.org; 2005; 116).

Reducing Medication Infusion Errors: Use of standard drug concentrations, “smart” syringe pumps, and user-friendly medication labels reduced reported errors associated with continuous medication infusions, according to a study conducted in a 242-bed pediatric hospital (e21-e25). “The number of reported errors dropped by 73% for an absolute risk reduction of 3.1 to 0.8 per 1000 doses” following implementation of the changes, the authors report. “Preparation errors that occurred in the pharmacy decreased from 0.66 to 0.16 per 1000 doses; the number of 10-fold errors in dosage decreased from 0.41 to 0.08 per 1000 doses.” (G. Y. Larsen, U. Utah, Salt Lake City)

Atomoxetine Effect on Height: Use of atomoxetine for treating attention-deficit/hyperactivity disorder had minimal effect on children’s rate of growth and had no effect on those in the lowest quartile of height in a 2-year study of 412 patients aged 6 to 16 years (e74-e80). “Weight increased an average of 10.8 kg, a decrease relative to baseline normative weight of 2.7 percentiles, corresponding to 0.87 kg,” the investigators note in reporting the effects of the atomoxetine doses, which were 1.8 mg/kg/day or lower. “Height increased an average of 13.3 cm, a decrease relative to baseline normative heights of 2.2 percentiles, corresponding to 0.44 cm. For both weight and height, the quartile of patients who were smallest at baseline had an increase in end-point percentile, whereas patients in the highest quartile had a decrease.” (T. J. Spencer, Mass. Genl. Hosp., Boston)

>>>PNN NewsWatch
* A potentially fatal interaction between an extended-release formulation of hydromorphone hydrochloride (Palladone, Purdue Pharma) and ethanol has led to suspension of the product’s marketing. Palladone, intended to replace OxyContin in Purdue’s offerings as the latter agent becomes available generically, was formulated in small pellets that slowly release drug as they travel through the gastrointestinal tract. The pellets were specially designed to avoid the crush-and-abuse problems that have plagued OxyContin. But a bioavailability study conducted after in vitro tests indicated a possible degradation of the pellets by ethanol showed potentially fatal serum hydromorphone levels among 24 healthy volunteers who took the product with 240 mL of a 40% ethanol solution. Peak concentrations were 5.5 times higher with ethanol than when the product was taken with water, and the study showed similar problems with lower concentrations of alcohol (4% and 20%) simulating the levels in other alcoholic beverages. Thus, deliberate or naive consumption of alcohol with Palladone could lead to dose dumping, and the danger of overdose swayed FDA to request suspension of marketing. The product may return in a limited distribution scheme that focuses on hospital and inpatient hospice settings where access to alcohol is controllable, or the company may seek to reformulate Palladone using pellets that are not affected by ethanol. Patients who currently have Palladone can continue to use it, FDA advised, but they should be strongly cautioned about this possible drug interaction and should see their physician for prescribing of an appropriate substitute analgesic.

*
“Physician-pitchmen” are increasingly used by the pharmaceutical industry for marketing of its products, explains a front-page article in today’s Wall Street Journal. The number of meetings and talks sponsored by drug companies and featuring physicians as speakers nearly doubled between 2003 and 2004, the article notes, going from 134,000 to 237,000 such events. “Companies formerly curried favor with doctors by taking them on free golf outings or filling up their cars with a tank of gas in exchange for listening to a sales pitch,” the reporters write. “But a voluntary marketing code adopted by the largest drug companies three years ago barred such inducements. Hiring a doctor as a speaker and providing a free meal for the attendees is still acceptable—and, data suggest, highly effective. An internal study done by Merck & Co. several years ago calculated the ‘return on investment’ from doctor-led discussion groups was almost double the return on meetings led by the company's own sales force.”

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 18, 2005 Vol. 12, No. 137
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
July 16 issue of Lancet (www.thelancet.com; 2005; 366).

Buccal Midazolam for Seizures: For emergency treatment of acute febrile or afebrile seizures in children, buccal doses of midazolam were superior to the current drug of choice, rectal diazepam, in a study of 177 infants and children (pp. 205-10). The children, whose median age was 3 years, were admitted to the study if they were at least 6 months old and had active seizures but no intravenous access. Based on a primary endpoint of cessation of seizures within 10 minutes and for at least 1 hour without respiratory depression requiring intervention, the investigators found, “Therapeutic success was 56% (61 of 109) for buccal midazolam and 27% (30 of 110) for rectal diazepam (percentage difference 29%, 95% CI 16–41). Analysing only initial episodes revealed a similar result. The rate of respiratory depression did not differ between groups. When centre, age, known diagnosis of epilepsy, use of antiepileptic drugs, prior treatment, and length of seizure before treatment were adjusted for with logistic regression, buccal midazolam was more effective than rectal diazepam.” (J. McIntyre, U. Nottingham, Derby, U.K.; john.mcintyre@nhs.net)

>>>BMJ Highlights
Source
: July 16 issue of BMJ (www.bmj.org; 2005; 331).

Antidepressant Debate: A point-counterpoint exchange reviews the evidence supporting use of newer antidepressants.

Taking the con position, authors point to recent meta-analyses showing that SSRIs “have no clinically meaningful advantage over placebo” (pp. 155-7): “Evidence that antidepressants are more effective in more severe conditions is not strong, and data on long term outcome of depression and suicide do not provide convincing evidence of benefit. In children, the balance of benefits to risks is now recognised as unfavourable. We suggest this may also be the case for adults, given the continuing uncertainty about the possible risk of increased suicidality as well as other known adverse effects. This conclusion implies the need for a thorough re-evaluation of current approaches to depression and further development of alternatives to drug treatment. Since antidepressants have become society's main response to distress, expectations raised by decades of their use will also need to be addressed.” (J. Moncrieff, U. Coll., London;
j.moncrieff@ucl.ac.uk)

Noting that the above writers limit their remarks to the effects of antidepressants, a writer implies that even less evidence support psychotherapy: “Patients, clinicians, and funders still have to make decisions about treatment. These decisions are based on the evidence but also are influenced by values and resources. Moncrieff and Kirsch make clear where their values lie—antidepressants bad, psychological therapies good. But when criticising the evidence, why stop at antidepressants?” (S. Hatcher, U. Auckland, Auckland, New Zealand;
s.hatcher@auckland.ac.nz)

>>>PNN NewsWatch
* FDA has issued a public health advisory regarding deaths in patients using transdermal fentanyl patches.

* Sept. 1 is FDA’s new self-imposed deadline for making a decision regarding nonprescription sales of
Plan B, the emergency contraceptive product marketed by Barr Laboratories.

>>>PNN JournalWatch
* Selective Cyclooxygenase 2 Inhibitors and Cardiovascular Events, in Arthritis & Rheumatism, 2005; 52: 1968–78. Reprints: http://www3.interscience.wiley.com/cgi-bin/abstract/110548971/ABSTRACT; D. H. Solomon; dhsolomon@partners.org

* Tyrosine Kinases as Targets for Cancer Therapy, in
New England Journal of Medicine, 2005; 353: 172–87. Reprints: content.nejm.org; R. A. Van Etten, rvanetten@tufts-nemc.org

* Androgen Deprivation Therapy for Prostate Cancer, in
JAMA, 2005; 294: 238–44. Reprints: www.jama.com; J. L. Gulley, gulleyj@mail.nih.gov

* Allergen Avoidance in Asthma: What Do We Do Now?, in
Journal of Allergy and Clinical Immunology, 2005; 116: 26–30. Reprints: www2.us.elsevierhealth.com; G. T. O'Connor, Boston U., Boston; goconnor@bu.edu

* Effect of Pravastatin on Rate of Kidney Function Loss in People With or at Risk for Coronary Disease, in
Circulation, 2005; 112: 171–8. Reprints: circ.ahajournals.org/cgi/content/abstract/112/2/171; M. Tonelli, mtonelli@ualberta.ca

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 19, 2005 Vol. 12, No. 138
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
July 19 issue of the Annals of Internal Medicine (www.annals.org; 2005; 143).

Cost-Effectiveness of ACE Inhibitors: Lives would be extended and overall costs reduced through first-dollar Medicare coverage of ACE inhibitors for patients with diabetes, according to a cost-effectiveness analysis conducted from both the program and societal perspectives (pp. 89-99). Using a Markov model and discounting costs and benefits at 3% in 2003 US dollars, the researchers found, “Compared with current practice, first-dollar coverage of ACE inhibitors saved both lives and money (0.23 [quality-adjusted life-years] gained and $1606 saved per Medicare beneficiary). Compared with the new Medicare drug benefit, first-dollar coverage remained a dominant strategy (0.15 QALYs gained, $922 saved).” Sensitivity analysis showed that the results held with increases in costs of ACE inhibitors of up to 7.2%. (A. B. Rosen, abrosen@umich.edu)

High-Dose Vitamin E Intake: Eleven letters to the editor, a research note, and an editorial explore the use of vitamin E in doses of 400 IU/day or higher.

Responding to the 11 letters to the editor chosen for publication from among more than 40 letters submitted in response to a
meta-analysis published in the Jan. 4 issue of Annals that showed increased all-cause mortality among users of high-dose vitamin E, researchers write (pp. 156-8): “... 19 randomized trials that together enrolled more than 135,000 participants have failed to document a survival benefit with vitamin E supplementation. In contrast, we have provided evidence that high-dosage vitamin E supplementation may increase total mortality. While future trials will refine the estimates of the effect of vitamin E supplementation and the dose at which the relative risk for death exceeds 1, we stand by our conclusions that use of high-dosage vitamin E supplementation should be avoided.” (E. R. Miller, Johns Hopkins Medical Institutions, Baltimore)

Especially among American whites, the intake of vitamin E in daily doses of 400 IU was fairly common as recently as 1999–2000, concludes an assessment of data from the National Health and Nutrition Examination Survey (pp. 116-20). “Among 4609 adults, 11.3% (95% CI, 9.7% to 13.1%) consumed at least 400 IU of vitamin E per day from supplements,” report the researchers. “Such intake increased with age, was about equal for men and women, and was more common among white persons (14.1%; CI, 11.9% to 16.7%) than African-American (3.7% [CI, 2.6% to 5.2%]) or Mexican-American persons (3.9% [CI, 2.8% to 5.4%]). The median dietary intake of vitamin E was 8.8 IU per day.” (E. Ford, CDC, Atlanta)

Given what we now know or strongly suspect about the lack of benefits and possible detrimental effects of high-dose vitamin E, the data from this and other recently published studies should be a call for action for health professionals, write editorialists (pp. 143-5): “Vitamin E has enjoyed superstar status among dietary supplements. Because of perceived health benefits, vitamin E supplements are consumed by many people.... Recent trials have further weakened the evidence for benefit, while the evidence for harm has accumulated. We did not fully appreciate just how many people may be putting themselves at risk by using high-dosage vitamin E supplementation until this issue of Annals, in which Ford and colleagues use data from the 1999–2000 National Health and Nutrition Examination Survey to estimate that about 12% of U.S. adults (24 million people) consumed 400 IU or more of vitamin E daily from supplements. Furthermore, older adults were more likely to use high-dosage vitamin E supplementation. We are disturbed that a presumption of benefit by so many may increase risk for mortality. We call on health professionals to warn the public against the use of ineffective or even harmful interventions, such as vitamin E, that may compete with well-established preventive measures. High-dosage vitamin E is a prime example of misplaced priorities.” (E. Guallar, Johns Hopkins U., Baltimore;
eguallar@jhsph.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 20, 2005 Vol. 12, No. 139
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
July 20 issue of JAMA (www.jama.com; 2005; 294).

Refining Measures of CVD Risk: Of the many ways to slice and dice cholesterol fractions and other measures of the risk of cardiovascular disease, non–HDL cholesterol and the ratio of total cholesterol to HDL-C proved as good as or better than apolipoprotein fractions in a prospective cohort study of 15,632 initially healthy U.S. women aged 45 years or older (pp. 326-33). But data on C-reactive protein “added prognostic information beyond that conveyed by all lipid measures,” the investigators report. During 10 years of follow-up after enrollment of patients in 1992–95, the researchers observed these relationships among hazard ratios for first-ever cardiovascular events, “After adjustment for age, smoking status, blood pressure, diabetes, and body mass index, the HRs for future cardiovascular events for those in the extreme quintiles were 1.62 (95% CI, 1.17–2.25) for LDL-C, 1.75 (95% CI, 1.30–2.38) for apolipoprotein A-I, 2.08 (95% CI, 1.45–2.97) for total cholesterol, 2.32 (95% CI, 1.64–3.33) for HDL-C, 2.50 (95% CI, 1.68–3.72) for apolipoprotein B100, 2.51 (95% CI, 1.69–3.72) for non–HDL-C, and 2.98 (95% CI, 1.90–4.67) for high-sensitivity CRP (P < .001 for trend across all quintiles). The HRs for the lipid ratios were 3.01 (95% CI, 2.01–4.50) for apolipoprotein B100 to apolipoprotein A-I, 3.18 (95% CI, 2.12–4.75) for LDL-C to HDL-C, 3.56 (95% CI, 2.31–5.47) for apolipoprotein B100 to HDL-C, and 3.81 (95% CI, 2.47–5.86) for the total cholesterol to HDL-C (P < .001 for trend across all quintiles). The correlation coefficients between high-sensitivity CRP and the lipid parameters ranged from –0.33 to 0.15, and the clinical cut points for CRP of less than 1, 1 to 3, and higher than 3 mg/L provided prognostic information on risk across increasing levels of each lipid measure and lipid ratio.” (P. M. Ridker, pridker@partners.org)

Insulin Resistance & HF: In a large community-based sample of men in Sweden, presence of insulin resistance was a significant predictor of first hospitalizations for congestive heart failure, even after data were adjusted for diabetes and other established risk factors (pp. 334-41). Among 104 men who developed CHF during a median of 8.9 years of follow-up, increased risk of CHF was significantly “associated with a 1-SD increase in the 2-hour glucose value of an oral glucose tolerance test (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.08–1.93), fasting serum proinsulin level (HR, 1.29; 95% CI, 1.02–1.64), body mass index (HR, 1.35; 95% CI, 1.11–1.65), and waist circumference (HR, 1.36; 95% CI, 1.10–1.69),” the authors report. These “observations indicate that the previously described association between obesity and subsequent CHF may be mediated partly by insulin resistance,” add the researchers. (E. Ingelsson, Uppsala U., Uppsala, Sweden; erik.ingelsson@pubcare.uu.se)

Foods v. Supplements: Based on evidence to date, public health policy should emphasize dietary intake of essential nutrients, as studies that have provided vitamins and micronutrients as dietary supplements have produced either equivocal results or outright detrimental effects (pp. 351-8). That conclusion is reached in a special communication in which authors note, “Recent attempts using [nutrient supplementation] for cardiovascular disease and lung cancer have been disappointing, as demonstrated with vitamin E and beta carotene. Moreover, previously unrecognized risks caused by nutrient toxicity and nutrient interactions have surfaced during intervention studies. The most promising data in the area of nutrition and positive health outcomes relate to dietary patterns, not nutrient supplements. These data suggest that other factors in food or the relative presence of some foods and the absence of other foods are more important than the level of individual nutrients consumed. Finally, unknown are the implications on public health behavior of shifting the emphasis away from food toward nutrient supplements.” (A. H. Lichtenstein, alice.lichtenstein@tufts.edu)

>>>PNN NewsWatch
* FDA and CDC are investigating four septic deaths among women undergoing off-label medical abortions using oral mifepristone and intravaginal misoprostol. Two of the cases involve the rarely encountered pathogen Clostridium sordellii.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 21, 2005 Vol. 12, No. 140
Providing news and information about medications and their proper use

Notice to PNN readers: Beginning Aug. 1, PNN will be sent each morning from a different e-mail address, PNNInfo@mac.com. Please add this address to your system or discuss the change with your information technology staff so that receipt will not be blocked by spam filters and firewalls.

>>>NEJM Highlights
Source:
July 21 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Atorvastatin in Late-Stage Diabetic Renal Failure: Among 1,255 patients with type 2 diabetes with renal failure that had progressed to the hemodialysis stage, addition of atorvastatin had no significant effects on a composite end point of cardiovascular death, nonfatal myocardial infarction, and stroke (pp. 238-48). Comparing atorvastatin 20 mg daily with placebo, the German Diabetes and Dialysis Study Investigators found that the intervention comes too late and might be associated with strokes: “After four weeks of treatment, the median level of low-density lipoprotein cholesterol was reduced by 42 percent among patients receiving atorvastatin, and among those receiving placebo it was reduced by 1.3 percent. During a median follow-up period of four years, 469 patients (37 percent) reached the primary end point, of whom 226 were assigned to atorvastatin and 243 to placebo (relative risk, 0.92; 95 percent confidence interval, 0.77 to 1.10; P = 0.37). Atorvastatin had no significant effect on the individual components of the primary end point, except that the relative risk of fatal stroke among those receiving the drug was 2.03 (95 percent confidence interval, 1.05 to 3.93; P = 0.04). Atorvastatin reduced the rate of all cardiac events combined (relative risk, 0.82; 95 percent confidence interval, 0.68 to 0.99; P = 0.03, nominally significant) but not all cerebrovascular events combined (relative risk, 1.12; 95 percent confidence interval, 0.81 to 1.55; P = 0.49) or total mortality (relative risk, 0.93; 95 percent confidence interval, 0.79 to 1.08; P = 0.33).” (C. Wanner, U. Hosp., Würzburg, Germany; wanner_c@medizin.uni-wuerzburg.de)

Quality of Care in U.S. Hospitals: Following implementation of standardized performance measures by JCAHO in July 2002, care for acute myocardial infarction, heart failure, and pneumonia improved consistently in U.S. hospitals over a 2-year period (pp. 255-64). Improvement ranged from 3% to 33%, with facilities with low levels of performance at baseline showing the most improvement. (S. C. Williams, swilliams@jcaho.org)

>>>PNN NewsWatch
* In what is beginning to feel like a repeat of last year’s influenza vaccine debacle, Chiron announced yesterday that its German plant will not be able to supply Begrivac product, which is distributed outside the U.S. Just 5 days earlier, the company had reduced the amount of vaccine the plant would supply from 12 million to 4 million doses. An FDA inspection of Chiron’s plant in Liverpool, England, is underway, and it will determine whether compliance with Good Manufacturing Practices will permit release of 18 million to 26 million doses of Fluvirin for use in the U.S.

* An Associated Press article published earlier this week in
USA Today reports that the incidence of strokes and other clot-related problems is 3 times higher among women using the transdermal contraceptive patch Ortho Evra (Ortho McNeil) than with oral contraceptives. Using data obtained from FDA records and clinical trials, the article claims a rate of nonfatal clots of 12 in 10,000 users of the transdermal patch and 3 clot-related deaths per 200,000 users.

* In one of several warnings posted to the
MedWatch Web site in the past 2 days, Genentech and FDA announced addition of warnings about immune-mediate hemolytic anemia in patients receiving efalizumab (Raptiva) for treatment of severe plaque psoriasis. The adverse effect seems to occur about 4–6 months after treatment initiation. Also added to product labeling were warnings regarding thrombocytopenia and serious infections including necrotizing fasciitis, tuberculous pneumonia, bacterial sepsis with seeding of distant sites, severe pneumonia with neutropenia, and worsening of infection (e.g., cellulitis, pneumonia) despite antimicrobial treatment.

* Product labeling for
nesiritide (Natrecor, Scios) has been updated to reflect the advice of an expert panel reviewing use of the heart failure drug (see PNN, June 15). The panel provided a consensus statement, provided advice about clinical development programs, made recommendations about the appropriate use of the drug, and recommended an educational campaign to ensure that clinicians understand when the use of nesiritide is and is not appropriate.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 21, 2005 Special Alert
Providing news and information about medications and their proper use

>>>PNN Special Alert
FDA announced this Class I worldwide recall of all models of Baxter’s Colleague Volumetric Infusion Pumps because they can shut down while delivering critical medication and fluids to patients. Baxter has received six reports of serious injury and three reports of death associated with this problem. The affected models are 2M8151, 2M8151R, 2M8161, 2M8161R, 2M8153, 2M8153R, 2M8163, and 2M8163R.

More details about this recall will be in tomorrow’s PNN.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail
PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 22, 2005 Vol. 12, No. 141
Providing news and information about medications and their proper use

Notice to PNN readers: Beginning Aug. 1, PNN will be sent each morning from a different e-mail address, PNNInfo@mac.com. Please add this address to your system or discuss the change with your information technology staff so that receipt will not be blocked by spam filters and firewalls.

>>>JAPhA Highlights
Source:
Jul/Aug issue of the Journal of the American Pharmacists Assoc. (www.japha.org; 2005; 45).

Business Case for Quality Improvement: In a speech delivered at the APhA Foundation Pinnacle Awards in June, Andrew Webber, president and CEO of the National Business Coalition on Health, challenged pharmacy to find a “suite of value-added health care services that consumers want and demand” (pp. 437-42). He put his recommendation in this context, “Realizing any new vision … is about change and leadership and represents a real struggle. But this new vision for pharmacy connects you in a meaningful way to your roots as a healing profession and to the total value you can provide in the health care delivery system. It also allows you to begin rewriting the current competitive rules of the game from ‘who can dispense medications more efficiently?’—a competition that will be hard for you to win in the long run—to ‘who can provide a suite of value-added health care services that consumers want and demand’—a competitive fight that you are uniquely equipped to win. So I leave you with this challenge: in this new world of value-based purchasing, can pharmacy envision a mix of products and services that can contribute in significant ways to improving health and health care delivery for all Americans?

Patient Medication Leaflets: Pharmacies will need to make additional efforts to meet federally mandated information and quality goals by next year, according to data from a 2001 study of randomly selected pharmacies in 44 states (pp. 443-51). Professional shoppers (acting as patients) presented four new prescriptions to 384 pharmacies, and expert and consumer raters judged the written information provided with the medications. Noting that federal law requires that useful leaflets must be provided to 95% of individuals receiving new prescriptions by 2006, the authors report: “Leaflets were provided by pharmacies with 89% of 1,536 prescriptions presented by professional shoppers posing as patients. Leaflet quality varied: 95% of leaflets received high ratings on accuracy, but only 19% received high ratings on the specificity of directions. Fewer than 10% of all leaflets met quality criteria regarding contraindications, precautions, and how to avoid harm. One fourth of all leaflets had poor print size, according to the shoppers.” (B. L. Svarstad, blsvarstad@pharmacy.wisc.edu)

>>>PNN NewsWatch
* Some 255,000 Colleague Volumetric Infusion Pumps have been recalled by Baxter Healthcare Corp. following shut-down problems that have produced six serious injuries and three deaths. The Class I recall was ordered by FDA following an agency inspection of Baxter, independent analysis of pump failures by FDA's Office of Science and Engineering Laboratories, and comprehensive review of adverse event reports in FDA’s database. Baxter had issued a voluntary “urgent device correction” notice on March 15, alerting users to several user interface and error code issues with pump models 2M8151, 2M8151R, 2M8161, 2M8161R, 2M8153, 2M8153R, 2M8163, and 2M8163R. Users were inadvertently pressing the on/off key instead of the start key when attempting to start an infusion, the company noted. Baxter also cautioned of external communications port failures when users failed to power off the pump when connecting and disconnecting a cable to this port. In addition, Baxter advised customers to stop using any pumps that exhibited a failure code beginning with 402, 403, 533, 535, or 599, related to these electronic problems. Finally, Baxter advised customers to take out of service any pumps that exhibited failure codes 810:04 and 810:11 related to air-in-line sensor problems until they were inspected by authorized service personnel. While hospitals, physicians, and pharmacies should take the recalled pumps out of service, Baxter at this time requests that the units not be returned, as it is developing a number of corrections to address these issues. More information is available by contacting the company at 1-800-THE-PUMP (800-843-7867).

*
Adolor announced this morning that alvimopan (Entereg), an agent for management of postoperative ileus that it is developing with GlaxoSmithKline, is approvable at FDA. The drug accelerates the time to recovery of g.i. function following bowel surgery.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 25, 2005 Vol. 12, No. 142
Providing news and information about medications and their proper use

Notice to PNN readers: Beginning Aug. 1, PNN will be sent each morning from a different e-mail address, PNNInfo@mac.com. Please add this address to your system or discuss the change with your information technology staff so that receipt will not be blocked by spam filters and firewalls.

>>>Melatonin Receptor Agonist Approved for Sleep
Ramelteon (Rozerem, Takeda) has been approved by FDA for treatment of insomnia characterized by difficulty with sleep onset. The agent, a melatonin receptor agonist with affinity for MT1 and MT2 but not MT3, is the first prescription hypnotic agent with a new mechanism of action approved in 35 years, and since it has no potential for abuse and dependence, it is not a controlled substance and is suitable for long-term use.

MT
1 and MT2 receptors are located in the brain’s suprachiasmatic nucleus, considered the body’s “master clock” because it regulates circadian rhythms, Takeda explained in a news release. In clinical trials, ramelteon was safe and effective in 4,200 patients ranging in age from 18 to 93. Daily doses were administered for up to 1 year in a study of 472 patients, and other trials showed that the drug was safe for use in older adults, including those with mild or moderate chronic obstructive pulmonary disease and mild or moderate sleep apnea.

The product is contraindicated only in those hypersensitive to ramelteon or product constituents, but it should not be used in patients with severe hepatic impairment or in combination with fluvoxamine, a drug with which it interacts. Ramelteon is metabolized primarily by the cytochrome P450 1A2 isoenzyme and to some degree by the 2C subfamily and 3A4 isoenzymes.

In clinical trials, adverse effects were rare and similar in frequency among patients on ramelteon and placebo. Somnolence (5% of those taking ramelteon and 3% of patients on placebo), fatigue (4% and 2%), and dizziness (5% and 3%) were the only adverse effects with at least 2% differences between study groups. After taking ramelteon, patients should confine their activities to those necessary for preparing for bed, and they should exercise caution if using alcoholic beverages concomitantly with the drug.

Takeda expects Rozerem to be available to pharmacies in late Sept.

>>>Lancet Report
Source:
July 23 issue of Lancet (http://www.thelancet.com; 2005; 366).

Carboplatin for Testicular Cancer: While findings need to be confirmed beyond 4 years, a single dose of carboplatin was superior to radiotherapy in a trial of men with stage I seminoma (pp. 293-300). Based on a median of 4 years of follow-up, the authors reported these results for 885 and 560 patients who received radiotherapy or carboplatin, respectively: Relapse-free survival rates were similar (96.7% and 97.7%); patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy; new, second primary testicular germ-cell tumors were reported in 10 and 2 patients; and seminoma-related deaths occurred in 1 and 0 patients. (R. T. D. Oliver, St. Bart's and London Hospital, London; r.t.oliver@qmul.ac.uk)

Radioisotopes & Airport Security: Patients can set off radiation detectors at airports, banks, and other locations for up to 1 month after thallium-201 scans, note authors who present the case of a 55-year-old commercial pilot who had undergone myocardial imaging (p. 342). While the sensitivity of radiation scanners is classified information, the half-lives of some radioisotopes in clinical use could cause exposed patients to set off alarms for substantial time periods. Problematic isotopes include iodine-131 (90 days), thallium-201 (30 days), gallium-67 (30 days), and indium-111 (20 days). Isotopes with shorter half-lives, including fluorine-18, technitium-99m, and iodine-123, might cause patients to set off detectors for only a few days. (S. R. Underwood, Royal Brompton Hosp., London; r.underwood@imperial.ac.uk)

>>>PNN JournalWatch
* Statin Therapy May Be Associated with Lower Mortality in Patients with Diastolic Heart Failure, in Circulation, 2005; 112: 357–63. Reprints: circ.ahajournals.org; W. C. Little, Wake Forest U., Winston-Salem, N.C.; wlittle@wfubmc.edu

* Global Antimicrobial Resistance Alerts and Implications, in
Clinical Infectious Diseases, 2005; 41(suppl 4). Reprints: www.journals.uchicago.edu/CID

* Therapeutic Lifestyle Changes and Pharmaceutical Care in the Treatment of Dyslipidemias in Adults, in
Journal of the American Pharmacists Assoc., 2005; 45: 492–501. Reprints: www.japha.org; T. L. Lenz, tlenz@creighton.edu

* Rosuvastatin: A High-Potency HMG-CoA Reductase Inhibitor, in
Journal of the American Pharmacists Assoc., 2005; 45: 503–13. Reprints: www.japha.org; L. M. Lopez, lopez@cop.ufl.edu

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 26, 2005 Vol. 12, No. 143
Providing news and information about medications and their proper use

Notice to PNN readers: Beginning Aug. 1, PNN will be sent each morning from a different e-mail address, PNNInfo@mac.com. Please add this address to your system or discuss the change with your information technology staff so that receipt will not be blocked by spam filters and firewalls.

>>>Internal Medicine Report
Source:
Jul. 25 issue of Archives of Internal Medicine (www.archinternmed.com; 2005; 165).

Pain-Management Recommendations: New recommendations from the American Pain Society call on clinicians to implement and evaluate “improvements in pain treatment that are timely, safe, evidence based, and multimodal” (pp. 1574-80). Updating a 1995 document, 11 members of an APS task force made this comment about their new guidelines: “The recommendations specify that all care settings formulate structured, multilevel systems approaches (sensitive to the type of pain, population served, and setting of care) that ensure prompt recognition and treatment of pain, involvement of patients and families in the pain management plan, improved treatment patterns, regular reassessment and adjustment of the pain management plan as needed, and measurement of processes and outcomes of pain management.” (D. B. Gordon, db.gordon@hosp.wisc.edu)

Transdermal Testosterone in Menopausal Women: Hypoactive sexual desire in surgically menopausal women was effectively treated with a 300 mcg/day testosterone patch, according to findings from a 24-week study (pp. 1582-9). “Of the 447 women randomized, 318 (71%) completed the trial,” the investigators write. “Compared with placebo, women receiving the 300-mcg/d testosterone patch had significantly greater increases from baseline in sexual desire (67% vs 48%; P = .05) and in frequency of satisfying sexual activity (79% vs 43%; P = .049). The 150-mcg/d group showed no evidence of a treatment effect. The 450-mcg/d group also was not statistically different from the 300-mcg/d or placebo groups. Marginally significant linear dose-response trends were observed for total satisfying sexual activity and sexual desire at 24 weeks (P = .06 and .06, respectively). Adverse events occurred with similar frequency in both groups; no serious safety concerns were observed.” (G. D. Braunstein, Cedars-Sinai Med. Ctr., Los Angeles; Glenn.Braunstein@cshs.org)

Pointing out the limitations of the above study, an editorialist cautions, “It may be easier to say who should not be treated with ‘physiologic’ doses of testosterone rather than who should be if transdermal testosterone receives FDA approval. Because patients with dyslipidemia, depression, gynecologic and breast cancer, and moderate or severe hirsutism were excluded from participating in the study by Braunstein et al, it would seem prudent to avoid its use in patients with those conditions until further safety data are available. Caution also applies to its use in patients with the ‘metabolic syndrome,’ who have insulin resistance and/or dyslipidemia that may be exacerbated by androgen treatment. Finally, because sexual dysfunction in naturally menopausal women may not be androgen related, the use of ‘physiologic’ testosterone doses should not be used in them until efficacy and safety data are available specifically in this group.” (R. A. Vigersky, Walter Reed Army Med. Ctr., Washington, D.C.;
robert.vigersky@na.amedd.army.mil)

Topiramate for Smoking Cessation: In a proof-of-concept study that supports similar research on alcohol dependence, topiramate in doses up to 300 mg/day enabled patients to abstain from tobacco use for up to 12 weeks (pp. 1600-5). “Topiramate recipients were significantly more likely than placebo recipients to abstain from smoking (odds ratio, 4.46; 95% confidence interval, 1.08–18.39; P = .04),” researchers wrote. “Using a serum cotinine level of 28 ng/mL or lower to segregate nonsmokers from smokers, we found that the topiramate group had 4.97 times the odds of being nonsmokers (95% confidence interval, 1.1–23.4;P = .04). Smoking cessation rates for topiramate recipients were 19.4% and 16.7% at weeks 9 and 12, respectively, compared with 6.9% at both time points for placebo recipients.” (B. A. Johnson, bankolejohnson@virginia.edu)

Vitamin D Supplements in Black Women: Markers of bone loss and turnover were unaffected by vitamin D3 supplementation in 280 black postmenopausal women (pp. 1618-23). Use of calcium/vitamin D3 supplements among women of other ethnicities should be re-examined, the authors conclude. (J. F. Aloia, Winthrop U. Hosp., Mineola, N.Y.; jaloia@winthrop.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 27, 2005 Vol. 12, No. 144
Providing news and information about medications and their proper use

Notice to PNN readers: Beginning Aug. 1, PNN will be sent each morning from a different e-mail address, PNNInfo@mac.com. Please add this address to your system or discuss the change with your information technology staff so that receipt will not be blocked by spam filters and firewalls.

>>>JAMA Highlights
Source:
July 27 issue of JAMA (www.jama.com; 2005; 294).

Treatment of MI: While the use of percutaneous coronary interventions for patients with ST-elevation myocardial infarction improved between 1995 and 2004 at 775 U.S. hospitals with revascularization capability, clinicians need to more closely follow guidelines established by the American College of Cardiology and the American Heart Association (pp. 448-54). That conclusion is reached in an article that analyzed the care provided to nearly 294,000 patients with STEMI during a time when national guidelines were changing with regard to acute interventions. “There was an increase in primary PCI rates from 27.4% to 54.4% (P < .001) in hospitals with revascularization capability that paralleled the change in PCI for ST-elevation myocardial infarction,” the authors note. “There was no significant change in rates of immediate coronary artery bypass graft surgery (from 2.1% to 3.2%). Propensity-adjusted multivariable analyses demonstrated that primary PCI was associated with a decreased odds of death during hospitalization (odds ratio, 0.46; 95% confidence interval, 0.40–0.53). There were no differences in the rates of change in revascularization rates based on the date when the guidelines were released regardless of patient age. Overall in-hospital cardiogenic shock mortality decreased from 60.3% in 1995 to 47.9% in 2004 (P < .001).” (J. S. Hochman, judith.hochman@med.nyu.edu)

Management of Hypertension: “Rates of blood pressure control in the community are low, especially among older women with hypertension,” concludes an article describing a community-based cohort study that included all Framingham Heart Study examinations of the 1990s (pp. 466-72). Among 5,295 participants, the investigators found, “Prevalence of hypertension and drug treatment increased with advancing age, whereas control rates were markedly lower in older women (systolic <140 and diastolic <90 mm Hg). For ages younger than 60 years, 60 to 79, and 80 years and older, respectively, control rates were 38%, 36%, and 38% in men (P = .30) and 38%, 28%, and 23% in women (P < .001). Relative risks for cardiovascular disease associated with increasing blood pressure stage did not decline with advancing age, and absolute risks increased markedly. Among participants 80 years of age or older, major cardiovascular events occurred in 9.5% of the normal blood pressure (referent) group, 19.8% of the prehypertension group (HR, 1.9; 95% CI, 0.9–3.9), 20.3% of the stage 1 hypertension group (HR, 1.8; 95% CI, 0.8–3.7), and 24.7% of the stage 2 or treated hypertension group (HR, 2.4; 95% CI, 1.2–4.6).”

The authors comment, “JNC 7 recommends that for the elderly, physicians should start with low doses, add additional medications that can work synergistically at low doses, and gradually continue to increase doses and add medications to attempt to reach goal blood pressure levels. In the recently completed Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) of antihypertensive therapies among hypertensive patients aged 55 years and older (mean [SD] age, 66.9 [7.7] years), two thirds of those who achieved goal blood pressure required 2 or more medications to do so, consistent with the findings of other studies. Among older hypertensive patients, achieving goal levels would be expected to require even more. Polypharmacy and medication expenses for the elderly are of great concern, but there are a number of inexpensive, highly effective, once-daily medications (including thiazide diuretics) that have proven efficacy at lowering blood pressure and reducing [cardiovascular disease] events. There are also increasing numbers of combination pills available with variable doses of standard agents.” (D. M. Lloyd-Jones,
dlj@northwestern.edu)

Preventive Care: Delivery of routine preventive services, including pneumococcal and influenza vaccination, is suboptimal by primary care physicians, according to an analysis of Medicare data and physician surveys from 2000 and 2001 (pp. 473-81). Diabetic monitoring or eye examinations and screening for colon and breast cancer also need improvement, the study notes. (H. H. Pham, Ctr. for Studying Health System Change, Washington, D.C.; mpham@hschange.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 28, 2005 Vol. 12, No. 145
Providing news and information about medications and their proper use

Notice to PNN readers: Beginning Aug. 1, PNN will be sent each morning from a different e-mail address, PNNInfo@mac.com. Please add this address to your system or discuss the change with your information technology staff so that receipt will not be blocked by spam filters and firewalls.

>>>NEJM Highlights
Source:
July 28 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Echinacea for Rhinovirus: Extracts of Echinacea angustifolia root had no significant effects on rhinovirus infection or the associated symptoms, according to a study of 437 volunteers who underwent a viral challenge (pp. 341-8). Three different extracts from E. angustifolia roots were prepared using supercritical carbon dioxide, 60% ethanol, and 20% ethanol. Prophylaxis with the extracts began 7 days before the virus challenge, and participants were kept sequestered for 5 days thereafter. Of the 399 participants who completed the study, the authors report, “There were no statistically significant effects of the three echinacea extracts on rates of infection or severity of symptoms. Similarly, there were no significant effects of treatment on the volume of nasal secretions, on polymorphonuclear leukocyte or interleukin-8 concentrations in nasal-lavage specimens, or on quantitative-virus titer.” (R. B. Turner, rbt2n@virginia.edu)

In a Perspectives article, a writer asks “why are we doing randomized clinical trials of folkway uses of herbs and sectarian remedies?” and writes (pp. 337-9): “What is needed is knowledge-based medicine, with randomized clinical trials of treatments with histories that indicate some reasonable chance of efficacy. This approach mandates a medicine based on evidence that has passed through the sieve of plausibility and that is consistent with basic sciences, other applied sciences, and history—all molded by wisdom and common sense. [The National Center for Complementary and Alternative Medicine], if it is to justify its existence, must consider halting its search for active remedies through clinical trials of treatments of low plausibility. A wealth of information also awaits discovery in the psychology of personal beliefs in irrational proposals, in the study of erroneous thinking, and in the study of the mechanisms behind errant social–medical trends such as the alternative-medicine movement.” (W. Sampson, Stanford U., Stanford, Calif.)

Perioperative Beta-Blocker Therapy: A large retrospective cohort analysis shows that beta-blocker therapy during major noncardiac surgery reduces in-hospital mortality only among high-risk patients (pp. 349-61). “The relationship between perioperative beta-blocker treatment and the risk of death varied directly with cardiac risk; among the 580,665 patients with [a Revised Cardiac Risk Index] score of 0 or 1, treatment was associated with no benefit and possible harm, whereas among the patients with an RCRI score of 2, 3, or 4 or more, the adjusted odds ratios for death in the hospital were 0.88 (95 percent confidence interval, 0.80 to 0.98), 0.71 (95 percent confidence interval, 0.63 to 0.80), and 0.58 (95 percent confidence interval, 0.50 to 0.67), respectively.” (P. K. Lindenauer, Baystate Med. Ctr., Springfield, Mass.; Peter.Lindenauer@bhs.org)

Editorialists explain that ongoing trials should aid in clarifying the best ways to prevent perioperative myocardial infarction among lower-risk patients (pp. 412-4): “The POISE (Perioperative Ischemic Evaluation) study is designed to evaluate the ability of metoprolol to prevent death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal cardiac arrest in 10,000 patients undergoing all types of noncardiac surgery. DECREASE-IV is designed to evaluate the efficacy of combination therapy with fluvastatin and bisoprolol in 6000 patients scheduled to undergo noncardiac, nonvascular surgery, excluding minor surgery. Pending the availability of data from these trials (expected within four years), we believe it is appropriate to continue beta-blocker therapy in patients at low or intermediate risk, given the potential cardiac risks associated with the sudden interruption of beta-blocker therapy.” (D. Poldermans, Erasmus Med. Ctr., Rotterdam, the Netherlands)

>>>PNN NewsWatch
* At FDA’s request, a federal judge yesterday issued a permanent injunction that shuts down operation of Pharmakon Labs. The company has a history of continued violations since 2001, FDA says, and the injunction “was based on the defendants' demonstrated unwillingness to comply with the law.”

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
July 29, 2005 Vol. 12, No. 146
Providing news and information about medications and their proper use

Notice to PNN readers: Beginning Aug. 1, PNN will be sent each morning from a different e-mail address, PNNInfo@mac.com. Please add this address to your system or discuss the change with your information technology staff so that receipt will not be blocked by spam filters and firewalls.

>>>Diabetes Highlights
Source:
Aug. issue of Diabetes Care (care.diabetesjournals.org; 2005; 28).

Glyburide, Glipizide, & Breastfeeding: Use of glyburide and glipizide by breastfeeding mothers appears to be safe, based on a study of 13 women and 3 nursing infants (pp. 1851-5). A single-dose of glyburide 5 or 10 mg was administered to eight women, and maternal blood and milk concentrations of the drug were measured for 8 hours after the dose. Separately, five women began glyburide or glipizide 5 mg daily on the first postpartum day, and blood and milk concentrations of the respective drug were measured for 5 to 16 days after delivery. Blood glucose was measured in three nursing infants. The results showed: “In the single-dose glyburide study, the mean maximum theoretical infant dose (MTID) as a percent of the weight-adjusted maternal dose (WAMD) was <1.5 and <0.7% for the 5- and 10-mg doses, respectively. For the five women taking daily dosages, the mean MTID as a percent of the WAMD was <28% for glyburide and <27% for glipizide. The high estimates were due to the insensitivity of the assay. Neither glyburide nor glipizide were detected in breast milk in either study and blood glucose was normal in the three infants (one glyburide and two glipizide) who were wholly breast-fed when the drug concentrations were at steady state.” (D. S. Feig, Mount Sinai Hosp., Toronto; dfeig@mtsinai.on.ca)

Fast-Acting Insulin for DKA: In pediatric patients, treatment of diabetic ketoacidosis with subcutaneous insulin lispro is a “cost-effective and technically simplified procedure that precludes intensive care unit admission,” concludes a study from Brazil (pp. 1856-61). Over a 2-year period, 60 episodes of DKA were randomly managed with subcutaneous insulin lispro every 2 hours or continuous intravenous regular insulin. “Capillary glucose levels decreased by 2.9 and 2.6 mmol/L/h in the lispro and CIRI groups, respectively, but blood glucose fluctuated at different time intervals,” the investigators report. “In the CIRI group, metabolic acidosis and ketosis resolved in the first 6-h period after capillary glucose reached 13.8 mmol/L, whereas in the lispro group, they resolved in the next 6-h interval; however, both groups met DKA recovery criteria without complications.” (D. Damiani, São Paulo U. Med. Sch., São Paulo, SP, Brazil; durvald@terra.com.br)

Inhaled Insulin in Early Type 2 Diabetes: Inhaled insulin could be an effective therapy for patients during the early stages of type 2 diabetes, according to a study that compared the Exubera product with oral rosiglitazone treatment (pp. 1922-8). “The INH and rosiglitazone groups had comparable baseline A1C values (9.5 vs. 9.4%, respectively),” the authors note of the 145 patients in the study. “Significantly more patients achieved A1C <8.0% (83 vs. 58%, adjusted odds ratio 7.14 [95% CI 2.48–20.58], P = 0.0003), A1C <7.0% (44 vs. 18%, 4.43 [1.94–10.12]), and A1C ≤ 6.5% (28 vs. 7.5% 5.34 [1.83–15.57]) with INH. A1C decrease was greater with INH (–2.3% vs. –1.4%, adjusted treatment group difference: –0.89% [95% CI –1.23 to –0.55]) with final mean A1C values of 7.2 and 8.0% for INH and rosiglitazone, respectively. Hypoglycemia (episodes per subject-month) was higher with INH (0.7 vs. 0.05, risk ratio 14.72 [95% CI 7.51–28.83]), with no severe hypoglycemic episodes. Pulmonary function changes were small and comparable between groups.” (R. A. DeFronzo, albarado@uthscsa.edu)

>>>PNN NewsWatch
* Acting on a concern about emergence of antibiotic resistance in the human pathogen Campylobacter, FDA yesterday banned use of enrofloxacin for treating bacterial infections in poultry. Other uses of the veterinary drug are unaffected.

* Concerns over editorial oversight and pharma influence have led to a severance of the relationship between the
American Society of Hypertension and the American Journal of Hypertension, effective Oct. 1. The Wall Street Journal reports this morning that the journal editor announced the split in a July editorial, citing improper influence of association leaders by the pharmaceutical industry. ASH noted it had been unable to achieve an agreement with the journal concerning editorial oversight and journal direction and philosophy.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 1, 2005 Vol. 12, No. 147
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
July 30 issue of Lancet (www.thelancet.com; 2005; 366).

Long-Term Effectiveness of HAART: Data from the Swiss HIV Cohort Study indicate that reduced morbidity and mortality are associated with use of highly active antiretroviral therapy in HIV-infected patients but that those infected through injection drug use do not respond as readily as other individuals (pp. 378-84). “Low CD4 counts and increasing HIV-1 viral load were associated with increased probability of starting HAART,” write the authors. “Overall hazard ratios were 0.14 (95% CI 0.07–0.29) for HAART compared with no treatment, and 0.49 (0.31–0.79) compared with dual therapy. Compared with no treatment, HAART became more beneficial with increasing time since initiation but was less beneficial for patients whose presumed mode of transmission was via intravenous drug use (hazard ratio 0.27, 0.12–0.61) than for other patients (0.08, 0.03–0.19).” (J. A. C. Sterne, U. Bristol, Bristol, U.K.; jonathan.sterne@bristol.ac.uk)

BMJ Highlights
Source:
July 30 issue of BMJ (www.bmj.org; 2005; 331).

Compendial Renal Dosing Information: Information on dosing of medications in renally compromised is insufficient in four commonly used compendial drug information sources, according to a systematic comparison article (pp. 263 ff). The investigators compared terms used and recommendations made for the 100 most commonly used drugs in their hospital using the British National Formulary, Martindale: the Complete Drug Reference, American Hospital Formulary System Drug Information, and Drug Prescribing in Renal Failure, with these results: “The four sources differed in their recommendations for adjustments of dosage and dosing interval. They vary in their definitions of renal impairment; some are qualitative and remain unclear. All sources provide only a general description; the methods on which the advice is based and references for original data are rarely presented.”

These authors conclude, “The remarkable variation in definitions and recommendations, along with scarce details of the methods used to reach this advice, makes the available sources of drug information ill suited for clinical use. The methods used to retrieve information and use data should be described and made available to the reader. Advice on drug prescription, dose and dosing interval, contraindications, and adverse effects should be evidence based.” (L. Leibovici, Rabin Med. Ctr., Petah-Tiqva, Israel;
leibovic@post.tau.ac.il)

>>>PNN NewsWatch
* A British recall of counterfeit Lipitor tablets resulted in an FDA alert to American consumers who have obtained atorvastatin tablets through Internet sources, storefront operations, or state-run drug-importation programs that do not supply FDA-approved products. The affected product is "Lipitor" 20 mg and is sold in packages of 28 tablets. The drug packages are marked with batch number 004405K1 and an expiration date of "11 2007." Legitimate U.K. Lipitor has this same batch number.

>>>PNN JournalWatch
* Persistence of Oral Polio Vaccine Virus After Its Removal from the Immunisation Schedule in New Zealand, in Lancet, 2005; 366: 394–6. Reprints: Q. S. Huang, Institute of Environmental Science and Research, Porirua, New Zealand; Sue.Huang@esr.cri.nz

* Treatment of Menopausal Symptoms: What Shall We Do Now?, in
Lancet, 2005; 366: 409–21. Reprints: M. Hickey, U. Western Australia, Subiaco, Western Australia, Australia; mhickey@obsgyn.uwa.edu.au

* Best Practices for Safe Handling of Products Containing Concentrated Potassium, in
BMJ, 2005; 331: 274–7. Reprints: T. P, Klassen, Alberta Research Centre for Child Health Evidence, Edmonton; terry.klassen@ualberta.ca

* Update on the Drug Treatment of Hypertension in Patients with Cardiovascular Disease, in
American Journal of Medicine, 2005; 118: 695–705. Reprints: W. B. White.

* Numerous reviews on addiction, anticraving medications, pharmacogenetics of nicotine dependence, and drug abuse, in
American Journal of Psychiatry, 2005; 162.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 2, 2005 Vol. 12, No. 148
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Aug. 2 issue of the Annals of Internal Medicine (www.annals.org; 2005; 143).

Obesity & GERD: Patients’ risk for symptoms of gastroesophageal reflux disease, erosive esophagitis, and esophageal adenocarcinoma increases progressively as weight climbs, with patients with obesity showing a significantly increased risk, concludes a meta-analysis (pp. 199-211). Based on a Medline search of articles from 1966 through Oct. 2004, the authors note the following results in full studies that provided risk estimates: “Nine studies examined the association of body mass index (BMI) with GERD symptoms. Six of these studies found statistically significant associations. Six of 7 studies found significant associations of BMI with erosive esophagitis, 6 of 7 found significant associations with esophageal adenocarcinoma, and 4 of 6 found significant associations with gastric cardia adenocarcinoma. In data from 8 studies, there was a trend toward a dose–response relationship with an increase in the pooled adjusted odds ratios for GERD symptoms of 1.43 (95% CI, 1.158 to 1.774) for BMI of 25 kg/m2 to 30 kg/m2 and 1.94 (CI, 1.468 to 2.566) for BMI greater than 30 kg/m2. Similarly, the pooled adjusted odds ratios for esophageal adenocarcinoma for BMI of 25 kg/m2 to 30 kg/m2 and BMI greater than 30 kg/m2 were 1.52 (CI, 1.147 to 2.009) and 2.78 (CI, 1.850 to 4.164), respectively.” (H. B. El-Serag, VA Med. Ctr., Houston; hasheme@bcm.tmc.edu)

Internal Medicine Update: The past year’s “clinically important research papers” in a variety of primary care settings are reviewed (pp. 212-21). Topics include cardiovascular disease and statin use; coronary artery disease; hypertension; weight-loss programs; COX-2 inhibitors; hormone-replacement therapy; dementia; pulmonary medicine; prostate cancer; and preventive medicine. (E. B. Larson, Group Health Cooperative, Seattle)

National Health Information Network: Information technology needed to develop a national health information network in the U.S. could be developed for $156 billion over the next 5 years—about 2% of annual health care spending—and maintained for $48 billion annually thereafter, according to a model developed by an expert panel (pp. 165-73). “Approximately two thirds of the capital costs would be required for acquiring functionalities and one third for interoperability,” write the authors. “Ongoing costs would be more evenly divided between functionality and interoperability. If the current trajectory continues, the health care system will spend $24 billion on functionalities over the next 5 years or about one quarter of the cost for functionalities of a model NHIN.” (R. Kaushal, MD, rkaushal@partners.org)
Two related articles are published in this issue. A perspectives article shares the experiences of developing a full-featured electronic health record in an independent, 4-internist practice (pp. 222-6; R. J. Baron, Greenhouse Internists, P.C., Philadelphia; rbaron@greenhouseinternists.com), and an editorialist discusses the interface between the electronic health record and an NHIN (pp. 227-8; P. Basch, MedStar Health, Washington, D.C.).

>>>PNN NewsWatch
* A wide variety of infants’ oral drops are being recalled because of problems with dosing syringes provided with the medications, FDA has announced. Perrigo Company produced the acetaminophen, dextromethorphan, and pseudoephedrine products, Infant Pain Reliever 160 mg Acetaminophen (0.5 oz. and 1.0 oz) in cherry and grape flavors; Cherry Flavor Cough and Cold Infant Drops (0.5 oz); and Cherry Flavor Decongestant and Cough Infant Drops (0.5 oz). These were sold nationally at retail chains under store-brand labels, including those for CVS, Eckerd, Good Neighbor, Kroger, Longs, Medicine Shoppe, Meijer, Publix, Rite Aid, Safeway, Target, Walgreen, and Winn Dixie. The oral syringe packaged with the products has only a single mark, 1.6 mL, making it impossible to measure smaller volumes of liquids for those younger than 2 years and/or weighing less than 24 pounds. Until recently, the products had a syringe with 0.4 mL and 0.8 mL markings.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 3, 2005 Vol. 12, No. 149
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
Aug. issue of Pediatrics (www.pediatrics.org; 2005; 116).

Pertussis Vaccines for Infants and Children: While all pertussis vaccines are highly protective against the disease among infants and children receiving three or more of the five recommended doses, the products vary in their vaccine effectiveness (VE), according to a case–control study conducted in Cincinnati, Colorado, Idaho, and Minnesota (e285-94). Researchers report: “Among children who received 4 pertussis vaccine doses, a combination of 3 [diphtheria-tetanus toxoids-pertussis] doses followed by 1 [diphtheria-tetanus toxoids-acellular pertussis] dose had a slightly higher VE than other combinations; among children who received 3 or 4 DTaP vaccine doses, 1 DTaP vaccine performed less well. The finding that pertussis dose 4 was more effective when given to children at ≥14 months of age might be confounded if health care providers were more likely to vaccinate children at 12 months of age because of a perceived risk of undervaccination and if these same children were also at higher risk for pertussis. Household members of any age group and relationship could have been the source of pertussis, and household structure was associated with risk for pertussis for children 6 to 23 months of age. In contrast to control children in the study, 26% of case children had never been vaccinated against pertussis. Unvaccinated children are at risk for pertussis and, in a community with other unvaccinated children, can lead to community-wide pertussis outbreaks. Parents need to be educated about the morbidity and mortality risks associated with Bordetella pertussis infection, and they need to be encouraged to vaccinate their children against pertussis on time and with the recommended number of vaccine doses for optimal protection.” (K. M. Bisgard, CDC, Atlanta)

Meningococcal Vaccine in Adolescents: The rationale for use of meningococcal A, C, Y, W-135 conjugate vaccine in adolescents is provided in an official statement from the American Academy of Pediatrics (pp. 496-505). Recommendations for use of meningococcal polysaccharide vaccine in pediatric patients are updated, including routine administration to young adolescents (11 and 12 year olds), those entering high school (15 year olds), and college freshmen living in dormitories. (AAP Committee on Infectious Diseases)

>>>PNN NewsWatch
* Studies in today’s JAMA show that prenatal exposure to famine doubles the risk of schizophrenia in later life and that cognitive therapy is an effective intervention for suicidality. The prenatal study analyzes data on those born in China during the 1959–61 famine and confirms findings of a previous Dutch study of those conceived during a brief World War II famine in the Netherlands (pp. 557-62; L. He, Inst. for Nutritional Sciences, Shanghai Institute of Biological Sciences, Shanghai, China; helin@nhgg.org). Compared with “enhanced usual care,” cognitive therapy among adults who had attempted suicide significantly reduced subsequent attempts (24.1% versus 41.6% of patients). While statistically equivalent members of the two groups were taking psychotropic medications, self-reported depression was significantly lower in the cognitive therapy group (pp. 563-70; G. K. Brown, gregbrow@mail.med.upenn.edu).

*
Direct-to-consumer advertising will remain in the news for the foreseeable future, with the industry and FDA making moves. PhRMA yesterday announced voluntary “guiding principles” that go into effect in Jan. The principles call for pharmaceutical companies to submit DTC ads to FDA before releasing them for broadcast, provide a “balanced presentation of benefits and risks” of medications in TV and print advertising, and “spend an appropriate amount of time to educate health professionals about new medicines or new therapeutic indications before beginning the first” DTC ad campaign launching a new products or uses. The industry trade group will establish an Office of Accountability that will be responsible for receiving comments from the general public and health professionals about DTC advertising. FDA appears set to respond by announcing plans for a major review of DTC advertising, its first since 1995. According to this morning’s Wall Street Journal, the agency will begin the process with public hearings on the matter.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 4, 2005 Vol. 12, No. 150
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Aug. 4 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Modafinil for Shift-Work Sleepiness: While treatment with modafinil 200 mg reduced extreme sleepiness among patients with shift-work sleep disorder, a “residual sleepiness ... underscores the need for the development of interventions that are even more effective,” conclude authors of a 3-month, 209-patient study (pp. 476-86). Monthly assessments of study participants showed the following, “Treatment with modafinil, as compared with placebo, resulted in a modest improvement from baseline in mean (±SEM) nighttime sleep latency (the interval between the time a person attempts to fall asleep and the onset of sleep) (1.7 ± 0.4 vs. 0.3 ± 0.3 minutes, respectively; P = 0.002), and more patients had improvement in their clinical symptoms (74 percent vs. 36 percent, respectively; P < 0.001). Patients who were receiving modafinil also had a reduction in the frequency and duration of lapses of attention during nighttime testing of their performance on the Psychomotor Vigilance Test (change from baseline, a reduction in lapse frequency of 2.6 vs. an increase of 3.8, respectively; P < 0.001), and proportionally fewer patients reported having had accidents or near accidents while commuting home (29 percent vs. 54 percent, respectively; P < 0.001). Despite these benefits, patients treated with modafinil continued to have excessive sleepiness and impaired performance at night. Modafinil did not adversely affect daytime sleep as compared with placebo. Headache was the most common adverse event.” (C. A. Czeisler, caczeisler@hms.harvard.edu)

For the 20% of workers in industrialized nations who work at night or on rotating shifts, “the glass is more than half empty,” adds an editorialist (pp. 519-21): “Reduction of sleepiness and improvement of vigilance are clearly a major therapeutic imperative for shift workers, but the investigators' own most robust conclusion from this study appears to be that ‘modafinil is of some value in the clinical management of sleepiness associated with shift-work sleep disorder.’ Modafinil has a reasonable safety profile to date, and it may well be that it will be shown to be an effective and safe adjunct to comprehensive treatment strategies for shift-work sleep disorder. But the current study does not adequately assess the clinical value of this particular drug in shift-work sleep disorder, nor does it justify writing more prescriptions for modafinil. Rather, it serves as a wake-up call for the design and implementation of further scientific studies to address in a cohesive manner the serious health and safety issues that surround us by virtue of our having become, to a large extent, a shift-working society.” (R. C. Basner, Columbia U., New York)

Medication Adherence: Quoting former Surgeon General C. Everett Koop’s admonition that “drugs don’t work in patients who don’t take them,” authors review the literature on adherence to medication (pp. 487-97). After summarizing knowledge on measures of adherence, epidemiology of medication-taking behavior, ways of identifying poor adherence, barriers to adherence, and interventions, the authors provide examples of challenges to adherence. The writers conclude: “Poor adherence to medication regimens is common, contributing to substantial worsening of disease, death, and increased health care costs. Practitioners should always look for poor adherence and can enhance adherence by emphasizing the value of a patient's regimen, making the regimen simple, and customizing the regimen to the patient's lifestyle. Asking patients nonjudgmentally about medication-taking behavior is a practical strategy for identifying poor adherence. A collaborative approach to care augments adherence. Patients who have difficulty maintaining adequate adherence need more intensive strategies than do patients who have less difficulty with adherence, a more forgiving medication regimen, or both. Innovative methods of managing chronic diseases have had some success in improving adherence when a regimen has been difficult to follow. New technologies such as reminders through cell phones and personal digital assistants and pillboxes with paging systems may be needed to help patients who have the most difficulty meeting the goals of a regimen.” (L. Osterberg, larso@stanford.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 5, 2005 Vol. 12, No. 151
Providing news and information about medications and their proper use

>>>Pharmacotherapy Update
Source:
Aug. issue of Pharmacotherapy (www.pharmacotherapy.org; 2005; 25).

Cardiovascular Morbidity & Statin Nonadherence: Many heart attacks could be prevented if patients would improve their adherence to statin pharmacotherapy, conclude authors who found “a detectable excess of cardiovascular morbidity” among 1,221 patients taking the drugs for secondary prevention (pp. 1035-43). Retrospectively analyzing health databases for the Canadian province of Saskatchewan, the investigators compared prescription-fill frequencies of patients who began statin therapy within 1 year of their first cardiovascular event; those who had prescriptions filled for 80% of months of observation were classified as adherent. The authors write: “Patients in the adherent group were half as likely to experience a subsequent myocardial infarction as the patients in the nonadherent group (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.20–0.99, p = 0.047). In patients younger than 65 years (both adherent and not), the associated reduction in myocardial infarction was even more profound (HR 0.14, 95% CI 0.04–0.46, p = 0.001) and was accompanied by a trend for a lower frequency of unstable angina (HR 0.37, 95% CI 0.13–1.03, p = 0.06). In patients 65 years or older (301 patients), adherence was not associated with significant changes in cardiovascular end points.”(D. F. Blackburn, d.blackburn@usask.ca)

Monitoring for Antibiotic–Warfarin Interaction Effects: Among older patients prescribed antimicrobial therapy during warfarin treatment, international normalized ratios were appropriately monitored within 7 days in a health-maintenance organization, according to a retrospective cohort study (pp. 1055-61). “Patients who received dispensings of both warfarin and an antimicrobial agent were identified,” the authors note. “We found 2959 coprescribing instances in 1816 patients. The INR values were obtained for 2267 (77%) coprescribing situations within 14 days. Monitoring occurred more frequently (p < 0.001) when warfarin was coprescribed with fluoroquinolones (641 [85%] of 755 situations), metronidazole (59 [81%] of 73), tetracyclines (274 [80%] of 341), or macrolides (201 [83%] of 243) than when warfarin was coprescribed with sulfonamides (35 [66%] of 53), penicillins (604 [71%] of 856), or cephalosporins (419 [71%] of 591). Among monitored patients, a higher proportion of monitoring (p < 0.001) occurred within 7 days for patients prescribed antifungals (87%), fluoroquinolones (88%), tetracyclines (82%), metronidazole (86%), sulfonamides (86%), or macrolides (85%) than for patients prescribed cephalosporins (68%) or penicillins (75%).” (M. A. Raebel, Kaiser Permanente, Denver; Marsha.A.Raebel@kp.org)

Warfarin Use & Pharmacist Access: Use of warfarin prophylaxis among patients with atrial fibrillation is higher when prescribers have access to pharmacist-managed anticoagulation services, according to retrospective data from two ambulatory care clinics in a managed-care system (pp. 1062-7). Over a 1-year period in 2000–01, 178 patients were seen in the two clinics, one of which had ACS and one did not. “The overall rate of warfarin use in atrial fibrillation was higher in the clinic with access to AMS than in the clinic without access (77.9% vs 61.7%, p = 0.03),” the author reports. “In patients with no known contraindications, warfarin use increased by 20.2% with access to AMS versus no access (80.2% vs 60.0%, p = 0.023). Patients aged 65 years or older with one or more risk factors for stroke and no contraindications were more likely to receive warfarin in the clinic with access to AMS than in the clinic without access (85.1% vs 53.8%, p = 0.001). Access to AMS was an independent predictor of warfarin use (odds ratio 2.19, 95% confidence interval [CI] 1.05–4.56). Female sex was an independent negative predictor of warfarin use (odds ratio 0.48, 95% CI 0.24–0.96).” (J. S. Burkiewicz, jburki@midwestern.edu)

Reviews: Among the topics reviewed this month are ziconotide (pp. 1084-94; D. P. Wermeling, dwermel@uky.edu); i.v. N-acetylcysteine for contrast-media nephropathy (pp. 1095-103; S. J. Shalansky, sshalansky@providencehealth.bc.ca); and ketamine for pediatric conscious sedation (pp. 1104-11; M. C. Nahata, Nahata.1@osu.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 8, 2005 Vol. 12, No. 152
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
Aug. 6 issue of Lancet (www.thelancet.com; 2005; 366).

Adjunctive Anastrozole After Breast Cancer: Postmenopausal women with hormone-responsive early breast cancer benefit when switched to anastrozole after 2 years of tamoxifen therapy, according to data from the Austrian Breast and Colorectal Cancer Study Group (ABCSG; pp. 455-62). In two prospective, randomized, open-label trials, women were assigned after 2 years of adjuvant oral tamoxifen 20 or 30 mg to continue on that agent or switch to oral anastrazole 1 mg for the remainder of their adjuvant therapy. “3224 patients were included in analyses,” investigators report. “At a median follow-up of 28 months, we noted a 40% decrease in the risk for an event in the anastrozole group as compared with the tamoxifen group (67 events with anastrozole vs 110 with tamoxifen, hazard ratio 0.60, 95% CI 0.44–0.1, p = 0.0009). Both study treatments were well tolerated. There were significantly more fractures (p = 0.015) and significantly fewer thromboses (p = 0.034) in patients treated with anastrozole than in those on tamoxifen.” (R. Jakesz, Vienna Med. U., Vienna; raimund.jakesz@meduniwien.ac.at)

>>>BMJ Highlights
Source:
Aug. 6 issue of BMJ (www.bmj.org; 2005; 331).

Cholinesterase Inhibitors for AD: The evidence supporting efficacy and safety of the cholinesterase inhibitors for Alzheimer’s disease is “questionable” because of flawed methods and small clinical benefits, according to authors who conducted a systematic review of trials of donepezil, rivastigmine, and galantamine (pp. 321-7). Of the 22 studies included in the analysis, the authors write, “Follow-up ranged from six weeks to three years. 12 of 14 studies measuring the cognitive outcome by means of the 70 point Alzheimer's disease assessment scale–cognitive subscale showed differences ranging from 1.5 points to 3.9 points in favour of the respective cholinesterase inhibitors. Benefits were also reported from all 12 trials that used the clinician's interview based impression of change scale with input from caregivers. Methodological assessment of all studies found considerable flaws—for example, multiple testing without correction for multiplicity or exclusion of patients after randomisation.” (H. Kaduszkiewicz, U. Med. Ctr., Hamburg, Germany; kaduszki@uke.uni-hamburg.de)

Multivitamins in Older People: Self-reported infection-related morbidity is unaffected by routine use of vitamin and mineral supplements, conclude investigators who studied 910 men and women aged 65 or older who were not taking supplements before study admission (pp. 324-9). Comparing daily multivitamin and multimineral supplements with placebo, the researchers found, “Supplementation did not significantly affect contacts with primary care and days of infection per person (incidence rate ratio 0.96, 95% confidence interval 0.78 to 1.19 and 1.07, 0.90 to 1.27). Quality of life was not affected by supplementation. No statistically significant findings were found for secondary outcomes or subgroups.” (A. Avenell, U. Aberdeen, Aberdeen, U.K.; a.avenell@abdn.ac.uk)

>>>PNN JournalWatch
* Combination Antibiotic Susceptibility Testing To Treat Exacerbations of Cystic Fibrosis Associated with Multiresistant Bacteria: A Randomised, Double-Blind, Controlled Clinical Trial, in Lancet, 2005; 366: 463–71. Reprints: S. D. Aaron, Ottawa Hosp., Ottawa, Ont., Canada; saaron@ottawahospital.on.ca

* Chemotherapy Versus Allogeneic Transplantation for Very-High-Risk Childhood Acute Lymphoblastic Leukaemia in First Complete Remission: Comparison by Genetic Randomisation in an International Prospective Study, in
Lancet, 2005; early online publication (DOI:10.1016/S0140-6736(05)66998-X). Reprints: A. Balduzzi, Clinica Pediatrica dell'Università degli Studi di Milano Bicocca, Milan, Italy; adriana.balduzzi@pediatriamonza.it

* Relationship of Serum Digoxin Concentration to Mortality and Morbidity in Women in the Digitalis Investigation Group Trial: A Retrospective Analysis, in Journal of the American College of Cardiology, 2005; 46: 497–504. Reprints: K. F. Adams, Jr., kfa@med.unc.edu

* Symptomatic Treatment of Migraine in Children: A Systematic Review of Medication Trials, in
Pediatrics, 2005; 116: e295–e302. Reprints: A. P. Verhagen, Erasmus Med. Ctr., Rotterdam, the Netherlands. a.verhagen@erasmusmc.nl

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 9, 2005 Vol. 12, No. 153
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Aug. 8/22 issue of Archives of Internal Medicine (www.archinternmed.com; 2005; 165).

CV Effects of Pseudoephedrine: Use of shorter durations of pseudoephedrine produces relatively greater increases in systolic and diastolic blood pressure, according to a meta-analysis that also looked at the nonprescription ingredient’s effects on heart rate (pp. 1686-94). “Twenty-four trials had extractable vital sign information (45 treatment arms; 1285 patients),” write the authors. “Pseudoephedrine caused a small but significant increase in SBP (0.99, mm Hg; 95% CI, 0.08 to 1.90) and HR (2.83 beats/min; 95% CI, 2.0 to 3.6), with no effect on DBP (0.63 mm Hg, 95% CI, –0.10 to 1.35). The effect in patients with controlled hypertension demonstrated an SBP increase of similar magnitude (1.20 mm Hg; 95% CI, 0.56 to 1.84 mm Hg). Higher doses and immediate-release preparations were associated with greater BP increases. Studies with more women had less effect on BP or HR.” (S. M. Salerno, Tripler Army Med. Ctr., Honolulu; smsalerno@mindspring.com)

Starting Levothyroxine Doses: In cardiac-asymptomatic patients with primary hypothyroidism, a full starting dose of levothyroxine was safe, according to a 50-patient study conducted over 24 weeks (pp. 1714-20). The investigators surmise that using such doses may be more convenient and cost-effective than a low starting dose regimen, based on these findings: “At baseline, the severity of hypothyroidism and age were comparable in the full-dose (n = 25) vs the low-dose group (n = 25): thyrotropin, 61 vs 48 mIU/L; free thyroxine, 0.56 vs 0.64 ng/dL (7.2 vs 8.2 pmol/L); and age, 47 vs 47 years. No cardiac complaints or events were documented during treatment or at bicycle ergometry at baseline, 12 weeks, or 24 weeks. Euthyroidism was reached in the full-dose vs the low-dose group in 13 vs 1 (4 weeks), 19 vs 3 (8 weeks), 19 vs 9 (12 weeks), 20 vs 14 (16 weeks), 20 vs 18 (20 weeks), and 21 vs 20 (24 weeks) patients (P = .005). However, signs and symptoms of hypothyroidism and quality of life improved at a comparable rate.” (A. Berghout, Medical Centre Rijnmond-Zuid, Rotterdam, the Netherlands; berghouta@mcrz.nl)

Based on decades of more cautious initiation of levothyroxine therapy, an editorialist advises clinicians not to put too much stock in this small-scale study (pp. 1683-4): “With recommendations for gradual levothyroxine replacement appearing in virtually all major textbooks, professional society guidelines, and numerous publications, how will the practicing physician defend against malpractice allegations in the event that a patient develops a fatal myocardial infarction or arrhythmia after starting a full-replacement dosage? Thus, although I find their study results interesting, given that there are no compelling reasons to ‘go fast’ with levothyroxine replacement therapy with the exception of myxedema coma, this clinician would rather remain safe than sorry.” (L. Wartofsky, Washington Hosp. Ctr., Washington, D.C.;
leonard.wartofsky@medstar.net)

>>>PNN NewsWatch
* The first evidence-based clinical guidelines for prevention and management of postoperative atrial fibrillation were released yesterday by the American College of Chest Physicians. Published in the Aug. issue of Chest, the guidelines offer specific recommendations on cardiac pacing, anticoagulation therapy, pharmaceutical prophylaxis, intraoperative interventions, and pharmacologic control of ventricular rate and rhythm. The guidelines recommend the use of beta-blockers over calcium-channel blockers and against the routine use of magnesium and digitalis for the prevention of postoperative AF. Amiodarone may be considered for patients in whom beta-blockers are contraindicated and as therapy for postoperative sinus rhythm control. Use of a pacemaker for atrial pacing reduced the incidence of AF after cardiac surgery; however, biatrial pacing is recommended over single atrial pacing. Additionally, mild hypothermia and heparin-coated circuits are recommended to reduce the occurrence of AF during intraoperative procedures. For prevention of thromboembolism, the guidelines recommend cautious anticoagulation therapy for patients in whom AF has persisted for more than 48 hours.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 10, 2005 Vol. 12, No. 154
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Aug. 10 issue of JAMA (www.jama.com; 2005; 294).

Safety of Childhood Vaccinations: A longitudinal study of all children born in Denmark in 1990 through 2001 provides no evidence supporting a controversial “overload” theory of harm caused by simultaneous administration of multiple childhood vaccines (pp. 699-705). Researchers gathered information on type and number of vaccine doses received and hospitalizations for infectious diseases, specifically acute upper respiratory tract infection, viral and bacterial pneumonia, septicemia, viral central nervous system infection, bacterial meningitis, and diarrhea, with these results: “During 2,900,463 person–years of follow-up, 84,317 cases of infectious disease hospitalization were identified. Out of 42 possible associations (6 vaccines and 7 infectious disease categories), the only adverse association was for Haemophilus influenzae type b vaccine and acute upper respiratory tract infection (rate ratio, 1.05; 95% confidence interval, 1.01–1.08 comparing vaccinated participants with unvaccinated participants). This one adverse association of 42 possible outcomes was within the limits of what would be expected by chance alone and the effect was not temporal or dose-response. When considering aggregated vaccine exposure, we found no adverse associations between an increasing number of vaccinations and infectious diseases.” (A. Hviid, Statens Serum Institut, Copenhagen; aii@ssi.dk)

Duration of VTE Anticoagulation: Continued anticoagulation reduces risk of subsequent venous thromboembolism among patients with VTE, according to a meta-analysis of 15 randomized controlled trials (pp. 706-15). “If patients in the long-term therapy group remained receiving anticoagulation, the risk of recurrent VTE with long- vs short-term therapy was reduced (weighted incidence rate, 0.020 vs 0.126 events/person-year; rate difference, –0.106 [95% confidence interval {CI}, –0.145 to –0.067]; P < .001; pooled incidence rate ratio [IRR], 0.21 [95% CI, 0.14 to 0.31]; P < .001). If anticoagulation in the long-term therapy group was discontinued, the risk reduction was less pronounced (weighted incidence rate, 0.052 vs 0.072 events/person-year; rate difference, –0.020 [95% CI, –0.039 to –0.001]; P = .04; pooled IRR, 0.69 [95% CI, 0.53 to 0.91]; P = .009). The risk of major bleeding with long- vs short-term therapy was similar (weighted incidence rate, 0.011 vs 0.006 events/person-year; rate difference, 0.005 [95% CI, –0.002 to 0.011]; P = .14; pooled IRR, 1.80 [95% CI, 0.72 to 4.51]; P = .21).” (D. Ost, North Shore U. Hosp., Manhasset, N.Y.; dost@nshs.edu)

Adverse Effects of Clinical Practice Guidelines: Current clinical practice guidelines for some of the most common chronic diseases can have undesirable effects when applied to care of older patients with multiple comorbid diseases, according to an article that also discusses implications of the findings on “pay for performance” for physicians (pp. 716-24). A hypothetical 79-year-old woman with chronic obstructive pulmonary disease, type 2 diabetes, osteoporosis, hypertension, and osteoarthritis would be prescribed 12 medications if the recommendations in the guidelines for each disease were aggregated, leading in some cases to adverse interactions among drugs and diseases. A complicated nonpharmacologic regimen was also noted. (C. M. Boyd, Johns Hopkins U., Baltimore; cyboyd@jhmi.edu)

>>>PNN NewsWatch
* Transparency is the issue in employer dealings with pharmacy benefits managers, according to an article in this morning’s Wall Street Journal. Some 52 large employers will today endorse “a new purchasing model that would require ... PBMs to disclose and pass on to their clients their acquisition costs for retail and mail-order prescriptions,” the article reports.

* The number of
Medicare beneficiaries expected to sign up for Part D coverage has been lowered to 28–30 million by CMS, down from Jan. estimates of 39 million. The premium has also come in lower than expected, at $32.20 per month, and the first-year, per-person cost to the federal government is now projected to be $1,129, a decrease of 14% from earlier estimates, according to today’s New York Times.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 11, 2005 Vol. 12, No. 155
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Aug. 11 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Therapy Options with PTH, Alendronate: For improvements in bone mineral density to be maintained after parathyroid hormone (1–84) is discontinued, treatment with an antiresorptive agent such as alendronate should follow PTH therapy, according to a study of 119 women with osteoporosis (pp. 555-65). Study participants received 1 year of PTH(1–84) 100 mcg daily and were then randomly assigned to receive placebo or alendronate for an additional year. The authors report: “Over two years, alendronate therapy after parathyroid hormone therapy led to significant increases in bone mineral density in comparison with the results for placebo after parathyroid hormone therapy, a difference particularly evident for bone mineral density in trabecular bone at the spine on quantitative CT (an increase of 31 percent in the parathyroid hormone–alendronate group as compared with 14 percent in the parathyroid hormone–placebo group). During year 2, subjects receiving placebo lost substantial bone mineral density.” (D. M. Black, dblack@psg.ucsf.edu)

A second study finds that use of cyclic PTH(1–34), alternating in 3-month cycles with alendronate is an effective way of dissociating the early phase of PTH action (pure stimulation of bone formation) from later activation of bone remodeling (pp. 566-75). Following 1 year or more of alendronate, 126 women were randomly assigned to one of three groups: alendronate plus PTH(1–34) subcutaneously daily, continued alendronate plus PTH(1–34) daily for three 3-month cycles alternating with 3-month periods without PTH, or alendronate alone for 15 months. The results showed: “In both parathyroid hormone groups, bone formation indexes rose swiftly. Among the women who were receiving cyclic parathyroid hormone, bone formation declined during cycles without parathyroid hormone and increased again during cycles with parathyroid hormone. Bone resorption increased in both parathyroid hormone groups but increased progressively more in the daily-treatment group than in the cyclic-therapy group. Spinal bone mineral density rose 6.1 percent in the daily-treatment group and 5.4 percent in the cyclic-therapy group (P < 0.001 for each parathyroid hormone group as compared with the alendronate group and no significant difference between para-thyroid hormone groups). One woman in the daily-treatment group, two in the cyclic-therapy group, and four in the alendronate group had new or worsening vertebral deformities.” (F. Cosman, Helen Hayes Hosp., West Haverstraw, N.Y.;
cosmanf@helenhayeshosp.org)

Editorialists wonder whether PTH(1–84) should be advanced to first-line therapy for some patients with osteoporosis (pp. 624-5): “Given the heterogeneity of osteoporosis, it is unlikely that all patients will have an equally good response to all drugs in either class. ‘What is the treatment of choice for my patient?’ remains an important question, particularly since treatment with parathyroid hormone (1–34) is limited by approved indications to a two-year period. Established efficacy data apply to groups of patients, not necessarily to individual patients, some of whom may appear to have no response to treatment with a particular regimen. Indeed, the delineation of such so-called treatment failure is a complicated and still unresolved issue. However, in the world of clinical practice, apparent failure often leads to a change in medication and is a major driver of the sequences discussed here. Although some of the issues involved in the sequential use of these drugs have been addressed by Black et al. and Cosman et al., other therapeutically important questions remain. For example, should patients with low initial rates of bone remodeling receive a suppressor of bone remodeling, or would they be better served by treatment with parathyroid hormone from the outset?” (R. P. Heaney, Creighton U., Omaha, Nebr.)

Dog Ticks as Vector for Rocky Mountain Spotted Fever: The common brown dog tick was the unexpected vector in a rash of Arizona cases of Rocky Mountain spotted fever (pp. 587-94). Widespread distribution of the tick raises concerns about its potential role as a vector for Rickettsia rickettsii (L. J. Demma, ldemma@cdc.gov)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 12, 2005 Vol. 12, No. 156
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Aug. issue of the Journal of Allergy and Clinical Immunology (journals.elsevierhealth.com/periodicals/ymai; 2005; 116).

Roflumilast for Asthmatic Reactions: Early and late asthmatic reactions were attenuated by once-daily oral therapy with roflumilast, a phosphodiesterase type 4 inhibitor, in 23 patients with mild allergic asthma (pp. 292-8). In a crossover study with treatment periods of 7 to 10 days, roflumilast produced these results: “Late asthmatic reactions (LARs) were reduced by 27% (P = .0110) and 43% (P = .0009) in patients treated with 250 and 500 mcg of roflumilast, respectively, versus placebo. Roflumilast, 250 and 500 mcg, also attenuated early asthmatic reactions by 25% (P = .0038) and 28% (P = .0046), although not to the same extent as LAR attenuation. Roflumilast was well tolerated. No serious adverse events or discontinuations caused by adverse events were reported.” (P. G. Bardin, Monash U. and Med. Ctr., Melbourne, Australia; p.bardin@southernhealth.org.au)

Infection v. Immunity: Writing about the journal’s theme issue of infection versus immunity, an author notes (pp. 263-6): “These interrelated concepts can be considered the 2 sides of a coin. Perhaps a better analogy is that of a teeter-totter: when the sitting board is horizontal, there is a balance between immunity and infection. When immunity is down, infections rise and immunity must be strengthened to gain balance, with the result that the inflammation of immunity often overshoots and infection drops. However, evidence is being gathered to strongly suggest that when this balance is upset, as is the case with immunodeficiency diseases, certain viruses are able to escape strong immune response and hide in a latent condition. When individuals who harbor latent viruses, such as patients receiving immunosuppressive drugs or therapeutic radiation, encounter an additional force, the latent virus is forced into its life cycle that yields outgrowths of clones of virus-containing transformed cells. More understanding of these balancing forces of immunity and infection is necessary so that we, as clinician-investigators, can intervene with the sometimes threatening consequences of imbalances in the forces of the immune system and infection.” (W. T. Shearer, Baylor Coll. of Med., Houston; wtsheare@TexasChildrensHospital.org)

>>>PNN NewsWatch
* Contingency plans for a possible H5N1 avian influenza pandemic include stockpiling of antiviral drugs, especially oseltamivir and zanamivir, write authors in tomorrow’s Lancet (pp. 533-4). Reports in the lay media this week have detailed how governments around the world are purchasing large quantities of Tamiflu (Roche), the oseltamivir product that is easier to administer since it is an oral agent. However, the Lancet authors note that Relenza (GlaxoSmithKline), an inhaled product, is less likely to produce antiviral resistance and has fewer adverse effects. The Lancet authors add these observations about health care workers, “Epidemiological modelling suggests that influenza is more infectious than severe acute respiratory syndrome, and that severe acute respiratory syndrome infection control measures might not be adequate for a pandemic of influenza. There will, therefore, be an overwhelming strain on health-care workers and hospitals in an H5N1 pandemic, and staff could be rapidly demoralised and degenerate into deserters, if colleagues develop hospital-acquired H5N1 infection, especially if not given adequate intensive-care unit treatment. Protection of core personnel should also be planned to underpin recovery in the aftermath, when many key players in health care and governmental institutions would have perished.” (K. W. T. Tsang, U. Hong Kong, Pokfulam, Hong Kong SAR, China; kwttsang@hku.hk)

*
Pfizer yesterday announced changes to its direct-to-consumer advertising of prescription medicines, including more physician education about new medications before DTC ads begin, helping consumers better understand the risks and benefits of products, and motivating people to overcome potential barriers to better health through a “Pfizer Helpful Answers” campaign.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 15, 2005 Vol. 12, No. 157
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
Aug. 13 issue of Lancet (www.thelancet.com; 2005; 366).

Curing HIV by Targeting Latent Virus: Cure of HIV is theoretically possible, based on an in vivo proof-of-concept study that added valproic acid to highly active antiretroviral therapy in an effort to target latent virus in four volunteers (pp. 549-55). “After intensifying the effect of HAART with subcutaneous enfuvirtide 90 mcg twice daily for 4–6 weeks to prevent the spread of HIV, we added oral valproic acid 500–750 mg twice daily to their treatment regimen for 3 months,” write the researchers. “The frequency of resting cell infection was stable before addition of enfuvirtide and valproic acid, but declined thereafter. This decline was significant in three of four patients (mean reduction 75%, range 68% to >84%). Patients had slight reactions to enfuvirtide at the injection site, but otherwise tolerated treatment well.”
The investigators conclude, “Our findings suggest that eradication of established HIV infection might be achieved in a staged approach. Patients should perhaps first be treated with standard antiretroviral regimens at an early stage of infection. For those in whom viral replication is suppressed, latent viral infection should then be tackled with [histone deacetylase 1] inhibitors [such as valproic acid], intensified therapy, or both. Alternatively, or additionally, therapeutic vaccination might augment the antiviral immune response.” (D. M. Margolis,
dmargo@med.unc.edu)

Roflumilast for COPD: The phosphodiesterase 4 inhibitor roflumilast—subject of an item in Friday’s PNN in which use of the agent in asthmatic reactions was reported—is also a “promising candidate” for treating patients with anti-inflammatory chronic obstructive pulmonary disorder, according to a Phase III trial of 1,411 participants (pp. 53-71). Comparing 250- and 500-mcg doses of the drug with placebo in a 24-week study, the authors report, “Postbronchodilator FEV1 at the end of treatment significantly improved with roflumilast 250 mcg (by 74 mL [SD 18]) and roflumilast 500 mcg (by 97 mL [18]) compared with placebo (p < 0.0001). Improvement in health-related quality of life was greater with roflumilast 250 mcg (–3.4 units [0.6]) and roflumilast 500 mcg (–3.5 units [0.6]) than with placebo (–1.8 units [0.8]), although the differences between treatment groups were not significant. The mean numbers of exacerbations per patient were 1.13 (2.37), 1.03 (2.33), and 0.75 (1.89) with placebo, roflumilast 250 mcg, and roflumilast 500 mcg, respectively. Most adverse events were mild to moderate in intensity and resolved during the study.” (K. F. Rabe, Leiden U. Med. Ctr., Leiden, the Netherlands; k.f.rabe@lumc.nl)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2005; 331).

Medication Appropriateness in the Elderly: Better physician–patient and physician–physician relationships and improved systems for transferring information between acute-care and ambulatory settings are two of the needs identified in a study from Belgium of prescribing patterns among older patients (doi: 10.1136/bmj.38551.410012.06). Based on interviews of physicians, nurses, and pharmacists and focus groups of inpatients on five acute wards, the researchers made these observations: “Review of treatment was driven by acute considerations, the transfer of information on medicines from primary to secondary care was limited, and prescribing was often not tailored to elderly patients. Secondly, some doctors had a passive attitude towards learning: they thought it would take too long to find the information they needed about medicines and lacked self directed learning. Finally, a paternalistic doctor-patient relationship and difficulties in sharing decisions about treatment between prescribers led to inappropriate use of medicines. Several factors, such as the input of geriatricians and good communication between members of the multidisciplinary geriatric team, led to better use of medicines.” (A. Spinewine, School of Pharmacy, Université catholique de Louvain, Brussels, Belgium; anne.spinewine@facm.ucl.ac.be)

>>>PNN JournalWatch
* Chemotherapy for Elderly Patients With Non-Small Cell Lung Cancer, in Chest, 2005; 128: 947–57. Reprints: http://www.chestjournal.org; 2005; 128: 947-57. C. Gridelli, S. G. Moscati Hosp., Avellino, Italy; cgridelli@libero.it

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 16, 2005 Vol. 12, No. 158
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Aug. 16 issue of the Annals of Internal Medicine (www.annals.org; 2005; 143).

Warfarin/Aspirin After Cardiac Events: Cardiovascular benefits of warfarin plus aspirin outweigh the drugs’ bleeding risks in patients with acute coronary syndrome who are at low or intermediate risk of bleeding, according to a meta-analysis of studies from 1990 through Oct. 2004 (pp. 241-50). “Ten trials involving a total of 5,938 patients (11,334 patient-years) met the study criteria,” the authors note. “Compared with aspirin alone, warfarin plus aspirin was associated with a decrease in the annual rate of myocardial infarction (0.022 vs. 0.041; rate ratio, 0.56 [95% CI, 0.46 to 0.69]), ischemic stroke (0.004 vs. 0.008; rate ratio, 0.46 [CI, 0.27 to 0.77]), and revascularization (0.115 vs. 0.135; rate ratio, 0.80 [CI, 0.67 to 0.95]). Warfarin was associated with an increase in major bleeding (0.015 vs. 0.006; rate ratio, 2.5 [CI, 1.7 to 3.7]). Mortality did not differ.” (M. B. Rothberg, Baystate Med. Ctr., Springfield, Mass.; Michael.Rothberg@bhs.org)

Intervention Costs in Preventing Diabetes: For patients at high risk for developing diabetes, interventions aimed at improving lifestyle are not cost-effective unless reduced to about $100 per patient per year, according to a long-term study conducted from patient, health plan, and societal perspectives (pp. 251-64). Considering time horizons of 5 to 30 years, the researchers used an Archimedes model to find, “Compared with no prevention program, the DPP lifestyle program would reduce a high-risk person's 30-year chances of getting diabetes from about 72% to 61%, the chances of a serious complication from about 38% to 30%, and the chances of dying of a complication of diabetes from about 13.5% to 11.2%. Metformin would deliver about one third the long-term health benefits achievable by immediate lifestyle modification. Compared with not implementing any prevention program, the expected 30-year cost/quality-adjusted life-year (QALY) of the DPP lifestyle intervention from the health plan's perspective would be about $143,000. From a societal perspective, the cost/QALY of the lifestyle intervention compared with doing nothing would be about $62,600. Either using metformin or delaying the lifestyle intervention until after a person develops diabetes would be more cost-effective, costing about $35,400 or $24,500 per QALY gained, respectively, compared with no program. Compared with delaying the lifestyle program until after diabetes is diagnosed, the marginal cost-effectiveness of beginning the DPP lifestyle program immediately would be about $201,800.... Compared with no program, lifestyle modification for high-risk people can be made cost-saving over 30 years if the annual cost of the intervention can be reduced to about $100.” (D. M. Eddy, Kaiser Permanente, Aspen, Colo.; eddyaspen@yahoo.com)

Quality of Care & Survival in Older Patients: Community-dwelling patients aged 65 or older lived longer when they received higher quality of care in managed-care organizations, conclude authors who studied experiences of enrollees in the late 1990s (pp. 274-81). “The 372 vulnerable older patients were eligible for a mean of 21 quality indicators (range, 8 to 54) and received, on average, 53% of the care processes prescribed in quality indicators (range, 27% to 88%),” report the authors. “Eighty-six (23%) persons died during the 3-year follow-up. There was a graded positive relationship between quality score and 3-year survival. After adjustment for sex, health status, and health service use, quality score was not associated with mortality for the first 500 days, but a higher quality score was associated with lower mortality after 500 days (hazard ratio, 0.64 [95% CI, 0.49 to 0.84] for a 10% higher quality score).” (N. S. Wenger, Rand Health, Santa Monica, Calif.)

An editorialist provides a physician’s perspective on this study (pp. 305-6): “Part of the problem is the way clinicians use, or don't use, existing medical knowledge to care for patients. None of us knows everything. Even when we know enough, we may be rushed or tired or distracted or we may not have the right resources to do the best job possible. We can always do better, but we need more help than that. Many thoughtful people have concluded that we need more and better systems to support us.” (S. V. Williams, U. Penn., Philadelphia)


PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 17, 2005 Vol. 12, No. 159
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Aug. 17 issue of JAMA (www.jama.com; 2005; 294).

Impact of Varicella Vaccination: Varicella hospitalizations, ambulatory visits, and associated expenditures have declined among all age groups in the United States since institution of routine immunizations for the disease in 1995, report authors of a retrospective population-based study (pp. 797-802). Based on data from more than 100 insurance plans of about 40 large U.S. employers, the researchers report: “From the prevaccination period to 2002, hospitalizations due to varicella declined by 88% (from 2.3 to 0.3 per 100 000 population) and ambulatory visits declined by 59% (from 215 to 89 per 100,000 population). Hospitalizations and ambulatory visits declined in all age groups, with the greatest declines among infants younger than 1 year. Total estimated direct medical expenditures for varicella hospitalizations and ambulatory visits declined by 74%, from an average of $84.9 million in 1994 and 1995 to $22.1 million in 2002.” (F. Zhou, faz1@cdc.gov)

Assessing whether cost-effectiveness of varicella vaccine has lived up to expectations, an editorialist writes (pp. 845-6): “These findings do not conclusively confirm that childhood varicella vaccination is as cost-effective as originally anticipated, for several reasons. First, the cost of the vaccine has increased more than $10 per dose in inflation-adjusted terms since 1995 (the current public sector price per dose is $52.25), although an increase of this magnitude was not anticipated to change the cost-effectiveness dramatically. Second, the national varicella vaccine recommendation prompted states to measure and react to varicella as a reportable vaccine-preventable illness. The costs of such monitoring and of responding to outbreaks of varicella (eg, in day care or school settings) may be substantial and were not included in the original analysis by Lieu et al.

“Third, and perhaps most important, there is great uncertainty about the extent to which parents and other adults experienced reductions in lost work time attributable to varicella. As with other childhood and adolescent vaccines that have recently been recommended (eg, pneumococcal and meningococcal conjugate vaccines), indirect cost savings with varicella vaccine were expected to be larger than savings in direct medical costs. With varicella vaccine, the ratio of indirect cost savings to direct cost savings was expected to be nearly 5:1. Despite the importance of indirect cost quantification to the evaluation of vaccination programs, there are no established mechanisms to measure such effects.” (M. M. Davis,
mattdav@med.umich.edu)

>>>PNN NewsWatch
* A bill signed in Oregon yesterday shifted all products containing pseudoephedrine to prescription status. The new law could be implemented by the Board of Pharmacy within 3 months, according to this morning’s Wall Street Journal. The newspaper also quotes Oregon pharmacy exec Tom Holt as saying “he thinks the law will drive the pseudoephedrine-containing cold and allergy pills out of the market with a year or two.” Legislation is being considered in Congress that would move pseudoephedrine into a nonprescription Schedule V category, making it a behind-the-counter product nationally. This Oregon law, being more restrictive than federal regulations, would presumably take precedent in that state.

*
Prices of medications continue to outpace the general rate of inflation, AARP noted in a report released this week. Prepared in conjunction with the U. Minnesota’s PRIME Institute, the Rx Watchdog Report notes that more than one-half of the drugs in the sample, 110 of 195, had increases in manufacturer price during the period from December 31, 2004, through March 31, 2005. As a result of this and increases in recent years, AARP said that a typical older American (taking three prescription drugs) is likely to have experienced an increase, on average, in the cost of therapy from 2000 through March 31, 2005, of $866.16 if the drugs are brandname products used to treat chronic conditions and the full price increases were passed along to the consumer.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 18, 2005 Vol. 12, No. 160
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Aug. 18 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Sirolimus vs. Paclitaxel in Stents: Two research studies and an editorial explore the relative efficacy and safety of stents that elute sirolimus or paclitaxel.

Sirolimus-eluting stents produced fewer major cardiac events, compared with paclitaxel-eluting stents, among 1,012 patients who were undergoing percutaneous coronary interventions (pp. 653-62). Analyzing a composite of major adverse cardiac events (death from cardiac causes, myocardial infarction, and ischemia-driven revascularization of the target lesion) over 9 months after stent placement, the authors found, “The two groups had similar baseline clinical and angiographic characteristics. The rate of major adverse cardiac events at nine months was 6.2 percent in the sirolimus-stent group and 10.8 percent in the paclitaxel-stent group (hazard ratio, 0.56; 95 percent confidence interval, 0.36 to 0.86; P = 0.009). The difference was driven by a lower rate of target-lesion revascularization in the sirolimus-stent group than in the paclitaxel-stent group (4.8 percent vs. 8.3 percent; hazard ratio, 0.56; 95 percent confidence interval, 0.34 to 0.93; P = 0.03). Rates of death from cardiac causes were 0.6 percent in the sirolimus-stent group and 1.6 percent in the paclitaxel-stent group (P = 0.15); the rates of myocardial infarction were 2.8 percent and 3.5 percent, respectively (P = 0.49); and the rates of angiographic restenosis were 6.6 percent and 11.7 percent, respectively (P = 0.02).” (S. Windecker, U. Hosp., Bern, Switzerland;
stephan.windecker@insel.ch)

Sirolimus-eluting stents also performed better among a group of 250 patients with diabetes and coronary artery disease, reducing the extent of late luminal loss (pp. 663-70). “The extent of in-segment late luminal loss was 0.24 mm (95 percent confidence interval, 0.09 to 0.39) greater in the paclitaxel-stent group than in the sirolimus-stent group (P = 0.002),” write the investigators. “In-segment restenosis was identified on follow-up angiography in 16.5 percent of the patients in the paclitaxel-stent group and 6.9 percent of the patients in the sirolimus-stent group (P = 0.03). Target-lesion revascularization was performed in 12.0 percent of the patients in the paclitaxel-stent group and 6.4 percent of the patients in the sirolimus-stent group (P = 0.13).” (Adnan Kastrati, Deutsches Herzzentrum, Munich, Germany;
kastrati@dhm.mhn.de)

An editorialist uses the myth of Achilles to provide a current perspective on drug-eluting stents (pp. 724-7): “Terrific strides have been made in the battle against restenosis with the development of drug-eluting stents. The analogy of Achilles and restenosis may be more fitting today than it was when PCI was first developed. Thetis, in an attempt to give her newborn son immortality, grasped his heel and immersed him upside down in the river Styx. Unfortunately, the area under her hand was not exposed to the magical waters, and Achilles was left vulnerable in a small but distinct area. So too, drug-eluting stents have conquered restenosis except in a small percentage of patients. The data overall, from randomized clinical trials and from registries, suggest that the currently available sirolimus-eluting stents provide an angiographic and clinical edge over the currently available paclitaxel-eluting stents. In contrast, the currently available paclitaxel-eluting stent holds an edge on availability, deliverability, and cost. Whereas a large-scale, randomized trial may help settle this score more definitively, the testing of second-generation drug-eluting stent platforms, with various stent struts, polymers, and drugs is already well under way.” (D. J. Moliterno, U. Kentucky, Lexington)

>>>PNN NewsWatch
* FDA yesterday denied a Public Citizen petition asking for withdrawal of sibutramine (Meridia, Abbott) from the U.S. market. Despite cardiovascular risks of the serotonin/norepinephrine reuptake inhibitor, FDA concluded that physicians can generally determine appropriate candidates for therapy and monitor them appropriately.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 19, 2005 Vol. 12, No. 161
Providing news and information about medications and their proper use

>>>Oncology Highlights
Source:
Aug. 20 issue of the Journal of Clinical Oncology (www.jco.org; 2005; 23).

Docetaxel v. Paclitaxel for Advanced Breast Cancer: Docetaxel provided significant advantages over paclitaxel in a Phase III trial of 449 women with advanced breast that had progressed following an anthracycline-containing chemotherapy regimen (pp. 5542-51). While adverse effects were more common with docetaxel, patients’ quality of life was unaffected by these problems, the authors report: “In the intent-to-treat population, both the median overall survival (OS, 15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI, 1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher for docetaxel. These results were confirmed by multivariate analyses. The incidence of treatment-related hematologic and nonhematologic toxicities was greater for docetaxel than for paclitaxel; however, quality-of-life scores were not statistically different between treatment groups over time.” (S. E. Jones, Texas Oncology, Dallas; steve.jones@usoncology.com)

Genotypes & Chemotherapy Failure: The chances of failure of high-dose adjuvant chemotherapy for node-positive breast cancer are influenced by drug-metabolizing enzyme polymorphisms (pp. 5552-9). Addressing functional polymorphisms in cytochrome P450 (CYP) and glutathione S-transferases (GST) in 90 patients, the authors found, “Patients who carried homozygous CYP3A4*1B and CYP3A5*3 variants and did not carry homozygous deletions in both GSTM1 and GSTT1 (denoted low-drug genotype group) had a 4.9-fold poorer [disease-free survival] (P = .021) and a four-fold poorer [overall survival] (P = .031) compared with individuals who did not carry any CYP3A4*1B or CYP3A5*3 variants but had deletions in both GSTT1 and GSTM1 (denoted high-drug genotype group). After adjustment for other significant prognostic factors, the low-drug genotype group retained a significantly poorer DFS (hazard ratio [HR] = 4.9; 95% CI, 1.7 to 14.6; P = .004) and OS (HR = 4.8; 95% CI, 1.8 to 12.9; P = .002) compared with the high- and intermediate-drug combined genotype group. In the multivariate model, having low-drug genotype group status had a greater impact on clinical outcome than estrogen receptor status.” (A. DeMichele, dma@mail.med.upenn.edu)

Genotypes & Bladder Cancer: Polymorphisms in inflammation genes affect the risk, treatment response, and survival of bladder cancer, report authors who looked at single nucleotide polymorphisms in interleukin (IL) -6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and peroxisome proliferator-activated receptor gamma (PPARG; pp. 5746-56). “We found that the IL-6 variant genotype (C/C) was associated with an increased BC risk (OR, 1.77; 95% CI, 1.25 to 2.51),” note the authors. “There were joint effects between the variant IL-6 genotypes and smoking status, and between the variant genotypes of IL-6 and other genes. To assess effect on recurrence, we grouped non-muscle-invasive BC patients according to intravesical Bacillus Calmette-Guerin (BCG) treatment status: no BCG, induction BCG (iBCG), and maintenance BCG (mBCG). In the Cox proportional hazards model, the variant IL-6 genotype was associated with an increased recurrence risk (hazard ratio [HR], 4.60; 95% CI, 1.24 to 17.09) in patients receiving mBCG. The variant PPARG genotype was associated with a reduced recurrence risk (HR, 0.41; 95% CI, 0.20 to 0.86) among untreated patients. In patients with non-muscle-invasive BC, the variant IL-6 genotype was associated with an increased progression risk (HR, 1.88; 95% CI, 0.80 to 4.11). In patients with invasive BC, variant IL-6 was associated with improved 5-year overall and disease-specific survival (HR, 0.43; 95% CI, 0.19 to 0.94 and HR, 0.39; 95% CI, 0.15 to 1.00, respectively).” (X. Wu, xwu@mdanderson.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 22, 2005 Vol. 12, No. 162
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
Aug. 20 issue of Lancet (www.thelancet.com; 2005; 366).

Treatment of Lymphoblastic Leukemia: The “dismal prognosis” for very-high-risk childhood acute lymphoblastic leukemia could be improved through use of related-donor hematopoietic stem-cell transplantation rather than chemotherapy, according to a study conducted in seven countries. (pp. 635-42). The gap between the two therapies increased as patient’s risk profile worsened: “Between April, 1995, and December, 2000, 357 children entered the study, of whom 280 were assigned chemotherapy and 77 related-donor haemopoietic-cell transplantation. 5-year disease-free survival was 40.6% (SE 3.1) in children allocated chemotherapy and 56.7% (5.7) in those assigned transplantation (hazard ratio 0.67 [95% CI 0.46–0.99]; p=0.02); 5-year survival was 50.1% (3.1) and 56.4% (5.9), respectively (0.73 [0.49–1.09]; p=0.12).” (A. Balduzzi, Clinica Pediatrica dell'Università degli Studi di Milano Bicocca, Milan; adriana.balduzzi@pediatriamonza.it)

>>>BMJ Highlights
Source:
Aug. 20 issue of BMJ (www.bmj.org; 2005; 331).

CBT for IBS: In a study of 149 patients with moderate or severe irritable bowel syndrome, cognitive behavior therapy delivered by primary care nurses offered additional benefit over the antispasmodic drug mebeverine for up to 6 months, but the effect waned by 12 months (pp. 435 ff). Comparing the effects of CBT with those of 270-mg doses of mebeverine on the irritable bowel syndrome symptom severity scale, the investigators found, “Cognitive behaviour therapy had considerable initial benefit on symptom severity compared with mebeverine alone, with a mean reduction in score of 68 points (95% confidence interval 103 to 33), with the benefit persisting at three months and six months after therapy (mean reductions 71 points [109 to 32] and 11 points [20 to 3]) but not later. Cognitive behaviour therapy also showed significant benefit on the work and social adjustment scale that was still present 12 months after therapy (mean reduction 2.8 points [5.2 to 0.4]), but had an inconsistent effect on the hospital anxiety and depression scale.” (R. Jones, King's College, London; roger.jones@kcl.ac.uk)

Telephone Intervention for HF: A simple, centralized telephone intervention by nurses significantly reduced hospital admissions for heart failure, according to a 51-center study from Argentina (pp. 425 ff). “The 758 patients in the usual care group were more likely to be admitted for worsening heart failure or to die (235 events, 31%) than the 760 patients who received the telephone intervention (200 events, 26.3%) (relative risk reduction = 20%, 95% confidence interval 3 to 34, P = 0.026),” the authors report. “This benefit was mostly due to a significant reduction in admissions for heart failure (relative risk reduction = 29%, P = 0.005). Mortality was similar in both groups. At the end of the study the intervention group had a better quality of life than the usual care group (mean total score on Minnesota living with heart failure questionnaire 30.6 v 35, P = 0.001).” (H. Grancelli, Fundación GESICA, Buenos Aires, Argentina; gesica@advancedsl.com.ar)

>>>PNN NewsWatch
* Sumatriptan and zolmitriptan are being considered by the U.K. Medicines and Healthcare products Regulatory Agency for pharmacist-only availability without prescription for the acute relief of migraine attacks. An 8-week comment period for the proposal opened on August 11. The U.K. has a third class of drugs, ones available only in pharmacies, that supplements the Rx and OTC categories currently available in the U.S.

>>>PNN JournalWatch
* Should Aspirin Be Discontinued Before Coronary Artery Bypass Surgery?, in Circulation, 2005; 112: 1073–9. Reprints: circ.ahajournals.org; D. Praticò.

* Overview of Nosocomial Infections Caused by Gram-Negative Bacilli, in
Clinical Infectious Diseases, 2005; 41: 848–54. Reprints: www.journals.uchicago.edu/CID; R. Gaynes, CDC, Atlanta.

* Perspective on HIV Infection and Aging: Emerging Research on the Horizon, in
Clinical Infectious Diseases, 2005; 41: 855–63. Reprints: www.journals.uchicago.edu/CID; N. C. Casau, Albert Einstein Coll. of Med., Bronx, N.Y.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 23, 2005 Vol. 12, No. 163
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Aug. issue of the Journal of the American Geriatrics Society (www.blackwell-synergy.com/toc/jgs/53/8; 2005; 53).

Antiresorptive Therapy: Based on an analysis of pharmacy claims from the Kansas Medicaid program in 2000 and 2001, antiresorptive therapies are underused among older women both in nursing facilities and the community (pp. 1275-81). NF residents in particular were significantly less likely to receive bisphosphonates and more likely to be prescribed calcitonin despite its more questionable efficacy, compared with community dwellers. The authors added: “The final study sample (N = 2,289) included 898 NF (mean age 85.2) residents and 1,391 CDs (mean age 76.6). CDs were more likely to receive any ART (24.5%) than NF residents (19.6%). After adjustment for potential confounders, NF residents aged 65 to 84 were less likely (odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.440.85) to receive ART than CDs of the same age. Conversely, of those aged 85 and older, NF residents were more likely than CDs to receive ART (OR = 1.96, 95% CI = 1.183.25). Calcitonin was the most common non-ERT ART prescribed for NF residents, whereas bisphosphonates were more often prescribed for CDs.” (C. M. Jachna, U. Kansas, Kansas City; cmjachna@hotmail.com)

Inappropriate Prescribing: “Are we using the wrong drug, wrong dose, or wrong duration” for elderly veterans, asks the title of a retrospective national VA database analysis (pp. 1282-9). Using a combination of Beers criteria and recommendations of an expert panel convened by the Agency for Healthcare Research and Quality (Zhan criteria), the authors found these potential problems among the drugs prescribed for 1.3 million veterans who had at least one outpatient visit during 2000: “After adjusting for diagnoses, dose, and duration, inappropriate prescribing decreased from 33% to 23%. Exposure to inappropriate drugs was prolonged. Pain relievers, benzodiazepines, antidepressants, and musculoskeletal agents constituted 61% of inappropriate prescribing. Whites, patients with psychiatric comorbidities, and patients receiving more medications were most likely to receive inappropriate drugs. Women were more likely to receive Zhan criteria drugs; men were more likely to receive dose-limited drugs.” (M. J. V. Pugh, South Texas Veterans Health Care System, San Antonio; pughm@uthscsa.edu)

Influenza Vaccine Myths: Myths surrounding inactivated influenza vaccine and alleged adverse events associated with the product need to be dispelled among older Americans, conclude authors of a longitudinal study conducted at two Pittsburgh-area community health centers (pp. 1354-9). Looking at vaccination status for the 2000–01, 2001–02, and 2002–03 influenza seasons for 253 patients aged 50 years and older, the investigators found that those vaccinated across all 3 years were significantly more likely to be older, believe that social forces influence vaccination behavior, and disagree with the view that the vaccine is detrimental. “National educational efforts should be intensified to dispel the myths about alleged adverse events, including contracting influenza from inactivated influenza vaccine,” the study concludes. “Physicians should continue to share their personal experiences of treating patients with influenza, including the incidence of hospitalization and death.” (M. P. Nowalk, tnowalk@pitt.edu)

>>>PNN NewsWatch
* Has FDA raised the bar for new-drug approvals in the wake of the Vioxx debacle? The answer to that question should become apparent in the coming weeks as FDA advisory committees take up three “potential blockbuster drugs,” reports today’s Wall Street Journal. Inhaled insulin (Exubera, Pfizer) and two Bristol-Myers Squibb products, the antidiabetic agent muraglitazar (Pargluva) and abatacept (Orencia), for rheumatoid arthritis, will be considered during the first 2 weeks of September.

*
FDA yesterday approved the Invader UGT1A1 Molecular Assay (Third Wave Technologies) for detection of gene differences that affect patient expression of the enzyme UDP-glucuronosyltransferase, which metabolizes irinotecan (Camptosar, Pfizer).

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 24, 2005 Vol. 12, No. 164
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Aug. 24/31 issue of JAMA (www.jama.com; 2005; 294).

Anesthesia-Assisted Heroin Detoxification: Buprenorphine proved just as effective and safer than general anesthesia for rapid antagonist induction among 106 heroin-dependent adult patients (pp. 903-13). The study randomly assigned patients to receive either anesthesia-assisted rapid opioid detoxification with naltrexone induction, buprenorphine-assisted rapid opioid detoxification with naltrexone induction, or clonidine-assisted opioid detoxification with delayed naltrexone induction, with these results: “Mean withdrawal severities were comparable across the 3 treatments. Compared with clonidine-assisted detoxification, the anesthesia- and buprenorphine-assisted detoxification interventions had significantly greater rates of naltrexone induction (94% anesthesia, 97% buprenorphine, and 21% clonidine), but the groups did not differ in rates of completion of inpatient detoxification. Treatment retention over 12 weeks was not significantly different among groups with 7 of 35 (20%) retained in the anesthesia-assisted group, 9 of 37 (24%) in the buprenorphine-assisted group, and 3 of 34 (9%) in the clonidine-assisted group. Induction with 50 mg of naltrexone significantly reduced the risk of dropping out (odds ratio, 0.28; 95% confidence interval, 0.15–0.51). There were no significant group differences in proportions of opioid-positive urine specimens. The anesthesia procedure was associated with 3 potentially life-threatening adverse events.” (E. D. Collins, edc3@columbia.edu)

An editorialist advises clinicians to turn first to maintenance therapy rather than detox in patients with relapsing opioid dependence (pp. 961-3): “Anesthesia-assisted detoxification should have no significant role in the treatment of opioid dependence. When detoxification is provided to patients, other approaches using clonidine, methadone, or buprenorphine are likely to be at least as effective as anesthesia-assisted detoxification and also are safer and far less costly. In the larger context of treating opioid dependence, the major implication of the overall results of this study and other studies is that regardless of the protocol used, detoxification-based treatment of opioid dependence has a low likelihood of long-term success for most opioid-dependent patients. Further research on detoxification-based treatment should focus on how to provide effective relapse prevention treatment. In the meantime, for the majority of individuals with chronic relapsing opioid dependence, opioid maintenance using methadone or buprenorphine is much more effective than detoxification in terms of decreasing drug use, supporting treatment retention, improving health outcomes, and improving social functioning. Thus, maintenance therapy should be considered first-line treatment for such patients.” (P. G. O’Connor,
patrick.oconnor@yale.edu)

NSAIDs & Colorectal Cancer: Long-term use of aspirin and other NSAIDs for 10 years or more can reduce a woman’s risk of developing colorectal cancer, but the doses needed appear to be substantially higher than those used for cardioprotection, making the risk of GI bleeding a concern (pp. 914-23). That conclusion comes from the Nurses’ Health Study and the data on 82,911 women who were followed from 1980 through mid-2000. “Among women who regularly used aspirin (2 standard [325-mg] tablets per week), the multivariate relative risk (RR) for colorectal cancer was 0.77 (95% confidence interval [CI], 0.67–0.88) compared with nonregular users,” the authors report. “However, significant risk reduction was not observed until more than 10 years of use (P < .001 for trend). The benefit appeared related to dose.... Notably, women who used more than 14 aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47 (95% CI, 0.31–0.71). A similar dose-response relationship was found for nonaspirin NSAIDs (P = .007 for trend). The incidence of reported major gastrointestinal bleeding events per 1000 person-years also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin tablets per week; 1.07 for 2 to 5 aspirin per week; 1.40 for 6 to 14 aspirin per week; and 1.57 for more than 14 aspirin per week.” (A. T. Chan, achan@partners.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 25, 2005 Vol. 12, No. 165
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Aug. 25 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Management of Early Pregnancy Failure: Intravaginal administration of misoprostol 800 mcg is an effective treatment strategy for early pregnancy failure, with an 84% success rate, according to a study that compared pharmacologic and surgical strategies (pp. 761-9). Among 652 women with a first-trimester pregnancy failure (anembryonic gestation, embryonic or fetal death, or incomplete or inevitable spontaneous abortion), misoprostol and the standard of care, vacuum aspiration, produced these results: “Of the 491 women assigned to receive misoprostol, 71 percent had complete expulsion by day 3 and 84 percent by day 8 (95 percent confidence interval, 81 to 87 percent). Treatment failed in 16 percent of the misoprostol group and 3 percent of the surgical group (absolute difference, 12 percent; 95 percent confidence interval, 9 to 16 percent) by day 30. Hemorrhage or endometritis requiring hospitalization was rare (1 percent or less in each group), with no significant differences between the groups. In the misoprostol group, 78 percent of the women stated that they would use misoprostol again if the need arose and 83 percent stated that they would recommend it to others.” (J. Zhang, zhangj@mail.nih.gov)

Commenting on this study, an editorialist writes that it is “time for a change” (pp. 834-6): “For the future, both public and private sectors can work toward increasing the availability of dedicated misoprostol products for women's health indications. For now, clinicians have the opportunity to improve care for women by substituting a nonsurgical treatment for curettage or aspiration procedures, but they must be willing to make this transition in the context of the off-label use of a medication. That said, the report by Zhang et al., along with earlier peer-reviewed literature and wide community backing, provides support for such a transition.” (B. Winikoff, Gynuity Health Projects, New York)

Belatacept for Renal Transplantation: In a noninferiority study, an investigational selective costimulation blocker, belatacept, “did not appear to be inferior to cyclosporine as a means of preventing acute rejection after renal transplantation” and showed signs that it preserves glomerular function and reduces the rate of chronic allograft nephropathy (pp. 770-81). Intensive belatacept, less-intensive belatacept, and cyclosporine were compared in this Phase II trial, with these results: “At six months, the incidence of acute rejection was similar among the groups: 7 percent for intensive belatacept, 6 percent for less-intensive belatacept, and 8 percent for cyclosporine. At 12 months, the glomerular filtration rate was significantly higher with both intensive and less-intensive belatacept than it was with cyclosporine (66.3, 62.1, and 53.5 ml per minute per 1.73 m2, respectively), and chronic allograft nephropathy was less common with both regimens of belatacept than with cyclosporine (29 percent, 20 percent, and 44 percent, respectively). Lipid levels and blood-pressure values were similar or slightly lower in the belatacept groups, despite the greater use of lipid-lowering and antihypertensive medications in the cyclosporine group.” (C. Larsen, clarsen@emory.org)

Erythropoietin in Retinopathy: While erythropoietin administration is beneficial in many clinical situations, the hormone may play a detrimental role in development of proliferative diabetic retinopathy, according to vascular endothelial growth factor data from 144 patients (pp. 782-92): “Median vitreous erythropoietin level in 73 patients with proliferative diabetic retinopathy was significantly higher than that in 71 patients without diabetes (464.0 vs. 36.5 mIU per milliliter, P < 0.001). The median VEGF level in patients with retinopathy was also significantly higher than that in patients without diabetes (345.0 vs. 3.9 pg per milliliter, P < 0.001).... Erythropoietin and VEGF gene-expression levels are up-regulated in the murine ischemic retina, and the blockade of erythropoietin inhibits retinal neovascularization in vivo and endothelial-cell proliferation in the vitreous of patients with diabetic retinopathy in vitro.” (H. Takagi, Hyogo Prefectural Amagasaki Hosp., Amagasaki, Japan; hitoshi@kuhp.kyoto-u.ac.jp)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 26, 2005 Vol. 12, No. 166
Providing news and information about medications and their proper use

>>>Rheumatology Highlights
Source:
Aug. issue of Arthritis & Rheumatism (www3.interscience.wiley.com/cgi-bin/jhome/76509746; 2005; 52).

Abatacept for RA: The investigational costimulation modulator abatacept, under development by Bristol-Myers Squibb as Orencia (see PNN, Aug. 23), improved clinical symptoms among 339 patients with rheumatoid arthritis that had been refractory to methotrexate alone (pp. 2263-71). The authors compared placebo with abatacept in doses of 2 mg/kg or 10 mg/kg in the 12-month study, with these results: “A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted.” (J. M. Kremer, Ctr. for Rheumatology, Albany, N.Y.;
jkremer@joint-docs.com)

Knee Pain in the Presence of Other Pain: Most patients with knee pain have multiple joint site pain, conclude authors who surveyed 8,995 individuals older than 50 years of age (pp. 2350-4). Based on responses from 70% of those surveyed, the authors found, “Fifty-seven percent of responders with knee pain had pain in at least 2 other joint areas. Pain elsewhere was associated with lower physical function and with anxiety and depression both in the knee-pain group and in the other-pain group (associations were stronger in the knee-pain group). Knee pain and disability were less severe in those with knee pain alone than in those with knee pain and pain elsewhere, even after adjusting for age, sex, obesity, laterality of pain, and depression.” The researchers conclude, “The importance of [these findings] to clinicians and researchers is that the severity of knee pain and related disability is worse in the presence of pain elsewhere. This finding has implications for the management and treatment of older people with knee pain.” (C. Jinks, Keele U., Keele, Staffordshire, U.K.; c.jinks@cphc.keele.ac.uk)

Efficacy v. Adverse Effects in OA: Adverse effects of NSAIDs are more important than efficacy of the drugs among patients with milder osteoarthritis states, while those with severe cases are more likely to discount drug-induced problems in favor of greater effectiveness (pp. 2366-75). Those findings come from an analysis of health state preferences of 4,386 adults with OA conducted on the Internet. “Ratings were lower among men (P < 0.001) and among respondents with OA pain in the previous 24 hours (P < 0.001),” the group reports. “Disease severity had a greater effect on ratings than did side effect severity.” (K. A. Schulman, kevin.schulman@duke.edu)

>>>PNN NewsWatch
* Health Canada yesterday reversed its Feb. suspension (see PNN, Feb. 10) of sales of Adderall XR (extended-release amphetamine salts, Shire), requiring only modifications in labeling and patient information as conditions for the product’s return to the market. Health Canada, when it suspended sales, had cited 20 cases of sudden unexplained deaths, heart problems, and stroke associated with the use of that product or the immediate-release formulation, Adderall, which is marketed in the U.S. but not Canada. An independent, external committee had reviewed the suspension of the attention-deficit/hyperactivity disorder medication and supported the Health Canada action, but it also recommended that use of the product resume. Health Canada accepted all the committee’s recommendations.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 29, 2005 Vol. 12, No. 167
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
Aug. 27 issue of Lancet (www.thelancet.com; 2005; 366).

Artesunate Treatment of Severe Malaria: The artemisinin (qinghaosu) derivative artesunate should become the treatment of choice for severe falciparum malaria in adults, according to results presented by the South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) group (pp. 717-25). A comparison of intravenous artesunate 2.4 mg/kg at hours 0, 12, and 24 and then daily versus i.v. quinine 20 mg/kg loading dose followed by 10 mg/kg three times daily produced these results: “Mortality in artesunate recipients was 15% (107 of 730) compared with 22% (164 of 731) in quinine recipients; an absolute reduction of 34.7% (95% CI 18.5–47.6%; p = 0.0002). Treatment with artesunate was well tolerated, whereas quinine was associated with hypoglycaemia (relative risk 3.2, 1.3–7.8; p = 0.009).” (N. J White, Mahidol U., Bangkok, Thailand; nickw@tropmedres.ac)

Effects of Homeopathy: The effects of homeopathic preparations are about the same of those of placebo, conclude investigators who analyzed data from 110 homeopathy trials and 110 matched conventional-medicine studies (pp. 726-32). “The median study size was 65 participants (range ten to 1573),” report the authors. “21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65–1.19) for homoeopathy (eight trials) and 0.58 (0.39–0.85) for conventional medicine (six trials).” (M. Egger, U. Berne, Berne, Switzerland; egger@ispm.unibe.ch)

Lancet editors comment that these results ought to spell “the end of homeopathy” (p. 690): “Surely the time has passed for selective analyses, biased reports, or further investment in research to perpetuate the homoeopathy versus allopathy debate. Now doctors need to be bold and honest with their patients about homoeopathy’s lack of benefit, and with themselves about the failings of modern medicine to address patients’ needs for personalised care.”

>>>PNN NewsWatch
* FDA released its long-awaited decision on OTC status for the emergency contraceptive Plan B on Friday, but it turned out to be a nondecision. Taking another 60 days to weigh various options, FDA said that it was ready to approve nonprescription status for the product for women aged 17 years and older but that it had not determined a legally permissible means of restricting access to those younger than 17. The situation seems to open the door to a third class of drugs in the U.S., one available only from pharmacists, but that category has long been opposed by the politically powerful nonprescription drug industry. The lack of a final FDA ruling on Plan B angered Senate Democrats who in July had allowed the nomination of Lester M. Crawford as FDA commissioner to proceed on the promise of a decision by Sept. 1.

>>>PNN JournalWatch
* Gene Analysis for Exploring the Effects of Drugs in Rheumatoid Arthritis, in Arthritis & Rheumatism, 2005; 52: 2248–56. Reprints: www.rheumatology.org/publications/index.asp; C. Ospelt, U. Hosp., Zurich, Switzerland.

* The Impact of ACE Inhibitors or Angiotensin II Type 1 Receptor Blockers on the Development of New-Onset Type 2 Diabetes, in
Diabetes Care, 2005; 28: 2261–6. Reprints: care.diabetesjournals.org/cgi/content/abstract/28/9/2261; C. I. Coleman, Hartford Hosp., Hartford, Conn.; ccolema@harthosp.org

* Enteral Nutritional Support and Use of Diabetes-Specific Formulas for Patients with Diabetes, in
Diabetes Care, 2005; 28: 2267–79. Reprints: care.diabetesjournals.org/cgi/content/abstract/28/9/2267; M. Elia, U. Southampton, Southampton, U.K.; m.elia@soton.ac.uk

* The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement from the American Diabetes Association and the European Association for the Study of Diabetes, in
Diabetes Care, 2005; 28: 2289–304. Reprints: care.diabetesjournals.org/cgi/content/abstract/28/9/2289; R. Kahn, rkahn@diabetes.org

* Why Atrial Fibrillation Ablation Should Be Considered First-Line Therapy for Some Patients, in
Circulation, 2005; 112: 1214–22. Reprints: circ.ahajournals.org; A. Verma.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 30, 2005 Vol. 12, No. 168
Providing news and information about medications and their proper use

>>>Infectious Diseases Update
Source:
Sept. 15 issue of Clinical Infectious Diseases (www.journals.uchicago.edu/CID; 2005; 41).

HAART Adherence & Memory-Prompting Device: For memory-impaired patients with HIV infection, use of a memory-prompting device improved medication adherence, but the device had no impact for memory-intact study participants (pp. 875-82). Monthly adherence counseling was provided to all of 58 patients, and the Disease Management Assistance System was provided to those assigned to the intervention group. Assessing adherence with electronic drug exposure monitor caps over a 24-week period, the investigators found, “Mean adherence scores did not differ significantly between DMAS users (80%) and control subjects (65%). Post hoc analysis of 31 memory-impaired subjects (14 DMAS users and 17 control subjects) revealed significantly higher adherence rates among DMAS users (77%), compared with control subjects (57%) (P = .001). However, analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users (83%), compared with control subjects (77%) (P = .25). At week twelve, 38% of the DMAS users and 14% of the control subjects had an undetectable plasma HIV RNA load (P = .014), and at week 24, the plasma HIV RNA load was undetectable for 34% of the DMAS users and 38% of the control subjects (P = .49). CD4+ cell counts did not differ between the study arms. Virological and immunological responses were not related to DMAS use in memory-impaired subjects.” (A. S. A. Andrade, Johns Hopkins U., Baltimore)

Mortality Among Drug Users: Improvements in use of HAART in HIV-infected drug users, better preventive care, and timely management of bacterial infections and other treatable conditions are areas that need emphasis in the care of patients who abuse drugs, according to a study of 398 HIV-infected and 656 at-risk drug users in 1996–2001 (pp. 864-72). “The mean age at the time of death was 43.6 years for HIV-infected subjects and 47.7 years in HIV-uninfected subjects (P < .001),” the researchers note. “For 398 HIV-infected participants who were observed for 1443 person-years, death rates decreased from 11.4 to 5.4 deaths per 100 person-years over the 6-year period (P = .04). Among all participants, causes of death were as follows: HIV/AIDS, 27% of subjects; substance abuse, 31%; bacterial infection, 25%; other medical illness, 14%; and violence, 3%.... In a multivariate Cox model of HIV-infected subjects, factors independently associated with mortality included receipt of HAART (adjusted hazard ratio [HRadj], 0.44; 95% confidence interval [CI], 0.28–0.68) and CD4+ lymphocyte count of 200 cells/mm3 (HRadj, 4.23; 95% CI, 2.24–7.60). Use of methadone or illicit drugs did not predict mortality.” (R. Kohli, Albert Einstein College of Medicine, Bronx, N.Y.)

>>>PNN NewsWatch
* FDA yesterday announced two major recalls. The Medline brand of alcohol-free mouthwash and hygiene kits containing the mouthwash were recalled because of possible contamination with Burkholderia cepacia. The mouthwash, manufactured by Carrington Laboratories in Irving, Texas, was distributed nationally by Medline as 2- and 4-ounce bottles or in Medline Personal Hygiene Hospital Admission Kits. Products being recalled have lot numbers beginning 0503 through 0508 stamped on the bottoms of bottles. Additionally, affected product can be identified by checking for the identification code RA05CRR on the lower portion of back display panel of the product label. The second recall involved Trypan Blue 0.06% Ophthalmic Solution from Custom RX Compounding Pharmacy. Recalled because of possible Pseudomonas aeruginosa contamination, the cataract-surgery product was distributed to hospitals and clinics in Maryland, Minnesota, Illinois, Nebraska, North Dakota, Michigan, the District of Columbia, and Pennsylvania. The recall includes but may not be limited to these lot numbers:
—05042005:86@17
—05252005:36@13
—06282005:91@27
—08012005:63@24
—08182005:43@17


PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Aug. 31, 2005 Vol. 12, No. 169
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Sept. issue of Diabetes Care (care.diabetesjournals.org; 2005; 28).

Nateglinide/Metformin for Type 2 DM: In a 2-year study, nateglinide plus metformin was a safer regimen among 428 drug-naive patients with type 2 diabetes than was glyburide/metformin (pp. 2093-9). Doses of glyburide and metformin were titrated to maximum daily doses of 10 mg and 2,000 mg, respectively, while nateglinide was administered in standard doses of 120 mg before meals. “In nateglinide/metformin-treated patients, mean A1C was 8.4% at baseline and 6.9% at week 104,” the authors write. “In glyburide/metformin-treated patients, mean A1C was 8.3% at baseline and 6.8% at week 104 (P < 0.0001 vs. baseline for both treatments, NS between treatments). The [change in postprandial glucose excursions] averaged –96 ± 19 (P < 0.0001) and –57 ± 22 mmol/L/min (P < 0.05) in patients receiving nateglinide/metformin and glyburide/metformin, respectively, whereas [change in fasting plasma glucose] was –1.6 ± 0.2 (P < 0.0001) and –2.4 ± 0.2 mmol/l (P < 0.0001) in patients receiving nateglinide/metformin and glyburide/metformin, respectively (P < 0.01 between groups). Thus, the two treatments achieved similar efficacy with differential effects on FPG versus PPGE. Hypoglycemia occurred in 8.2 and 17.7% of patients receiving nateglinide/metformin and glyburide/metformin, respectively.” (M. A. Baron, michelle.baron@novartis.com)

Spironolactone in Diabetic Nephropathy: In patients with type 2 diabetes and nephropathy who are already on maximally recommended of ACE inhibitors and/or angiotensin 2 receptor blockers, spironolactone safely adds to the renoprotective and cardiovascular protective effects of the regimen (pp. 2106-12). The agent acts by reducing albuminuria and blood pressure, the authors explain. Of the 21 patients included in a crossover study, the investigators noted, “During the addition of spironolactone, albuminuria was reduced by 33% (95% CI 25–41) (P < 0.001), fractional clearance of albumin by 40% (24–53) (P < 0.001), and 24-h [ambulatory blood pressure] by 6 mmHg (2–10) for systolic and 4 mmHg (2–6) for diastolic (P < 0.001 for both). The change in albuminuria did not correlate with the change in systolic 24-h ABP (r = 0.19, P = 0.42) or diastolic 24-h ABP (r = 0.01, P = 0.96). Spironolactone treatment induced an insignificant reversible reduction in GFR of 3 ml/min per 1.73 m2 (–0.3 to 6) (P = 0.08). One patient was excluded from the study due to hyperkalemia. Otherwise treatment was well tolerated.” (K. Rossing, Steno Diabetes Ctr., Gentofte, Denmark; karo@steno.dk)

Beta-Blockers After MI: While safe, beta-blockers failed to reduce mortality or lower the number of recurrent events following myocardial infarction in patients with type 2 diabetes (pp. 2113-7). Focusing on 625 patients whose records were obtained through the Saskatchewan Health Databases, the authors found, “Patients were aged 69 ± 11 years old, 66% were male, and mean follow-up was 2.7 ± 2.1 years. Overall, beta-blockers were prescribed for 48% of patients. There were fewer deaths in the beta-blocker group versus control subjects (55 of 298 [18.5%] vs. 126 of 327 [38.5%], respectively, P < 0.001). However, beta-blockers were not associated with improved survival in multivariate analyses (hazard ratio [HR] 0.89 [95% CI 0.63–1.25]). There were no differences in rates of recurrent MI (adjusted HR 1.35 [0.93–1.95]) or rehospitalizations (adjusted odds ratio 1.40 [0.83–2.37]) between the groups.” (C. McDonald, U. Western Ontario, London, Ont., Canada; charlotte.mcdonald@sjhc.london.on.ca)

Insulin Antibodies & Inhaled Insulin: Development of high- or low-affinity insulin antibodies during inhaled-insulin therapy has no clinical relevance, according to authors who studied 47 patients with type 1 diabetes (pp. 2161-9). IAB levels rose by 28-fold during treatment, but changes in maximal plasma glucose levels, area under the plasma glucose concentration time cure, and duration of insulin action were similar between inhaled and subcutaneous insulin groups at week 24. In addition, no adverse effects were attributable to IABs. (T. Heise, Profil Institut für Stoffwechselforschung, Neuss, Germany; tim.heise@profil-research.de)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 1, 2005 Vol. 12, No. 170
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Sept. 1 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Fluid Therapy in Dengue Shock Syndrome: Adverse reactions to dextran make starch a preferable fluid for resuscitation in patients with dengue shock syndrome, note investigators who conducted a fluid comparison among 383 children with moderately severe conditions and 129 children with severe shock (pp. 877-89). Comparing Ringer's lactate, 6% dextran 70, or 6% hydroxyethyl starch, the researchers found, “Only one patient died (<0.2 percent mortality). The primary outcome measure—requirement for rescue colloid—was similar for the different fluids in the two severity groups. The relative risk of requirement for rescue colloid was 1.08 (95 percent confidence interval, 0.78 to 1.47; P = 0.65) among children with moderate shock who received Ringer's lactate as compared with either of the colloid solutions, 1.13 (95 percent confidence interval, 0.74 to 1.74; P = 0.59) among children who received dextran as compared with starch in the group with severe shock, and 0.88 (95 percent confidence interval, 0.66 to 1.17; P = 0.38) among children who received dextran as compared with starch in the combined analysis. Although treatment with Ringer's lactate resulted in less rapid improvement in the hematocrit and a marginally longer time to initial recovery than did treatment with either of the colloid solutions, there were no differences in all other measures of treatment response. Only minor differences in efficacy were detected between the two colloids, but significantly more recipients of dextran than of starch had adverse reactions. Bleeding manifestations, coagulation derangements, and severity of fluid overload were similar for all fluid-treatment groups.” (B. A. Wills, Oxford U., Ho Chi Minh City, Vietnam; bridgetw@hcm.vnn.vn)

Zoledronic Acid for Paget’s Disease: Compared with 2 months of daily risedronate 30 mg, a single infusion of zoledronic acid 5 mg provided better bone outcomes at 6 months among patients with Paget’s disease (pp. 898-908). “96.0 percent of patients receiving zoledronic acid had a therapeutic response (169 of 176), as compared with 74.3 percent of patients receiving risedronate (127 of 171, P < 0.001),” report the researchers. “Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group (P < 0.001). Zoledronic acid was associated with a shorter median time to a first therapeutic response (64 vs. 89 days, P < 0.001). Higher response rates in the zoledronic acid group were consistent across all demographic, disease-severity, and treatment-history subgroups and with changes in other bone-turnover markers.... During post-trial follow-up (median, 190 days), 21 of 82 patients in the risedronate group had a loss of therapeutic response, as compared with 1 of 113 patients in the zoledronic acid group (P < 0.001).” (I. R. Reid, U. Auckland, Auckland, New Zealand; i.reid@auckland.ac.nz)

>>>PNN NewsWatch
* FDA yesterday licensed Fluarix, a GlaxoSmithKline influenza vaccine that can be used to immunize adults, and gave the go-ahead to Chiron to produce Fluvirin for the 2005–2006 season. While Chiron has more work to do and the amount of vaccine it can produce is uncertain, the dual actions should assure an adequate supply of flu vaccine as the nation enters the immunization season.
 
* Pharmacists are helping in
Hurricane Katrina relief efforts. University of Louisiana at Monroe pharmacy professor Edwin H. Adams (eadams@ulm.edu) has called on pharmacists to help through donation of time and money, and he is participating in an effort to gather foods and money at a ULM football game scheduled for tonight in Monroe. In Mississippi, the state Medicaid program has advised pharmacists that beneficiaries south of Interstate 20 can obtain early prescription refills if needed because of storm-related problems. The Georgia Pharmacy Association this morning has activated its Disaster Relief Volunteer System to meet the medication needs for a large influx of refugees from New Orleans expected at shelters being opened in nine Georgia cities by the state Department of Human Resources.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail
PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 2, 2005 Vol. 12, No. 171
Providing news and information about medications and their proper use

>>>FDA Approves Pair of New Drug Products
FDA in recent days has approved two new chemical entities: nepafenac ophthalmic suspension (Nevanac, Alcon), indicated for treatment of pain and inflammation following cataract surgery, and mecasermin [rDNA origin] injection (Increlex, Tercica), an agent for long-term treatment of growth failure in children with severe primary insulin-like growth factor-1 deficiency (primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

Nepafenac, approved after a 6-month priority review, is a prodrug that rapidly penetrates ocular tissues, Alcon explained in a news release. The NSAID was tested in two clinical trials involving some 680 patients. The suspension was dosed three times daily beginning on the day before cataract surgery and continuing for 14 days after the removal of clouded lenses and replacement with artificial lenses. Based on evaluations on postoperative days 1, 3, 7, and 14, the investigators found significantly less ocular pain and inflammation among those on active drug at all time points, compared with those using placebo drops.

Adverse effects reported in clinical trials were those common in all patients following cataract surgery: capsular opacity, decreased visual acuity, foreign body sensation, increased intraocular pressure, and sticky sensation. These events occurred in similar numbers of patients in the treatment and placebo groups (5%–10%).

Designated an orphan drug by FDA for treatment of severe primary IGFD, mecasermin is identical to natural IGF-1, produced by the body in response to GH. While secretion of GH in the body is necessary for growth in children, IGF-1 is actually the primary mediator of growth.

FDA's approval of mecasermin is based on clinical trial data from 71 patients. Data reported at the 2004 annual meeting of the Endocrine Society demonstrated a significant increase in growth rate over an 8-year period in response to therapy. Compared with pretreatment growth patterns, on average, children gained an additional inch per year for each year of therapy over the course of 8 years.

Long-term treatment with mecasermin was well tolerated and had an acceptable safety profile. The most common adverse events in clinical trials were hypoglycemia, lipohypertrophy, and tonsillar hypertrophy. Adverse effects were generally mild to moderate in nature, and no patient withdrew from the study as a result of them.

>>>PNN NewsWatch
* To help pharmacists coordinate their efforts to assist victims of Hurricane Katrina and the subsequent flooding of New Orleans, APhA has placed an information resource center on its APhANet.org Web site. The center contains news and information provided by state pharmacy organizations as well as individual pharmacists making specific requests. In a message calling for pharmacists in Baton Rouge to help set up relief centers on the campus of Louisiana State University, April Reed wrote, “The situation is quite desperate. There are so many people without their maintenance medications along with many people that are now ill from consuming spoiled food. This is truly unbelievable. Continue to pray and please do not hesitate to call. These people really need help.”

*
Health care professionals remaining at New Orleans hospitals are especially hard pressed as they try to evacuate ill patients amid the anarchy and chaos of city streets. According to media reports and an article in this morning’s Wall Street Journal, helicopters evacuated 400–600 patients on Thursday, but up to 1,500 others remain in area hospitals. At Charity Hospital, the city’s trauma center, sniper fire disrupted evacuations on Thursday afternoon, and physicians report having to move patients to higher floors to avoid looters. The hospital has power only in intensive-care units, is out of food, and has little remaining water. Within the hospital, staff must climb stairs to reach patients, and to get to nearby facilities, canoes are the mode of transportation.

*
PNN will not be published on Mon., Sept. 5, Labor Day.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 6, 2005 Vol. 12, No. 172
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
Early online publication in Lancet (www.thelancet.com; 2005; 366).

Amlodipine for Hypertension: Two articles and an editorial posted early to the Lancet Web site explore treatment of hypertension with amlodipine versus atenolol.

The premature stoppage of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) is described in a second article. Study participants were aged 40–79 years and randomly received either amlodipine plus perindopril as needed or atenolol plus bendroflumethiazide and potassium as needed. The authors report these results: “The study was stopped prematurely after 5.5 years' median follow-up and accumulated in total 106,153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0.90, 95% CI 0.79–1.02, p = 0.1052), fatal and non-fatal stroke (327 vs 422; 0.77, 0.·66–0.89, p = 0.·0003), total cardiovascular events and procedures (1362 vs 1602; 0.84, 0.78–0.90, p < 0.0001), and all-cause mortality (738 vs 820; 0.89, 0.81–0.99, p=0.025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0.70, 0.63–0.78, p < 0.0001).” (B. Dahlöf, Sahlgrenska U. Hosp./Östra, Göteborg, Sweden;
bjorn.dahlof@scri.se)

Using data from the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), researchers show that benefits of amlodipine treatment may have been overstated in some aspects but that stroke benefits of the drug remain after multivariate analysis. An updated Cox-regression model was used to analyze the differences observed among the 19,257 study participants: “Serial mean matching for differences in systolic blood-pressure attenuated [hazard ratios] for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0.86 (0.77–0.96) to 0.88 (0.79–0.98) and from 0.77 (0.66–0.89) to 0.83 (0.72–0.96), respectively. Multivariate adjustment gave HRs of 0.94 (0.81–1.08) for coronary events (HDL cholesterol being the largest contributor) and 0.87 (0.73–1.05) for stroke events.” (N. R. Poulter, Imperial College, London;
n.poulter@imperial.ac.uk)

Editorialists comment that this trial provides “evidence that new antihypertensives are superior to older drugs”: “ASCOT ... supports the use of newer drugs, especially in patients with complicated hypertension, associated risk factors, or metabolic disturbances. The mean number of antihypertensive drugs used by ASCOT patients was around 2.2. At the end of the ASCOT trial, as in most other trials, including one which implemented a systolic blood pressure initiative,14 only 32.2% of the diabetic and 60.0% of the non-diabetic population were properly controlled. These dismal statistics underscore the need for use of multiple drug combinations spanning newer and older drug classes in a large group of hypertensive patients, and a need to up-titrate treatment more rapidly than is commonly done to capitalise on the massive benefits of early versus delayed blood pressure control.” (J. A. Staessen, U. Leuven, Leuven, Belgium;
jan.staessen@med.kuleuven.be)

>>>PNN JournalWatch
* Incremental Cost-Effectiveness of Drug-Eluting Stents Compared with a Third-Generation Bare-Metal Stent in a Real-World Setting: Randomised Basel Stent Kosten Effektivitäts Trial (BASKET), in Lancet, DOI:10.1016/S0140-6736(05)67221-2. Reprints: www.thelancet.com; M. Pfisterer, U. Basel, Basel, Switzerland; pfisterer@email.ch

* A Randomised Multicentre Trial of Integrated Versus Standard Treatment for Patients with a First Episode of Psychotic Illness, in
BMJ, doi:10.1136/bmj.38565.415000.E01. Reprints: www.bmj.org; M. Nordentoft, Bispebjerg Hosp., Copenhagen, Denmark; merete.nordentoft@dadlnet.dk

* Prevention of Exacerbations of Chronic Obstructive Pulmonary Disease with Tiotropium, a Once-Daily Inhaled Anticholinergic Bronchodilator, in
Annals of Internal Medicine, 2005; 143: 317–26. Reprints: www.annals.org; D. E. Niewoehner, niewo001@umn.edu

* Anoretics on Trial: A Half Century of Federal Regulation of Prescription Appetite Suppressants, in
Annals of Internal Medicine, 2005; 143: 380–5. Reprints: www.annals.org; E. Colman, colmane@cder.fda.gov

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 7, 2005 Vol. 12, No. 173
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Sept. 7. issue of JAMA (www.jama.com; 2005; 294).

Residents’ Performance After Heavy Night Call: As part of a special theme issue on medical education, a research study reports that heavy night call is just as detrimental as social alcohol ingestion on the neurobehavioral performance of medical residents (pp. 1025-33). Using tests of attention, vigilance, and driving performance along 34 participants’ self-reports, the researchers reported these effects of night-call patterns and blood alcohol concentrations of 0.04–0.05 g/dL: “Compared with light call, heavy call reaction times were 7% slower (242.5 vs 225.9 milliseconds, P < .001); commission errors were 40% higher (38.2% vs 27.2%, P < .001); and lane variability (7.0 vs 5.5 ft, P < .001) and speed variability (4.1 vs 2.4 mph, P < .001) on the driving simulator were 27% and 71% greater, respectively. Speed variability was 29% greater in heavy call with placebo than light call with alcohol (4.2 vs 3.2 mph, P = .01), and reaction time, lapses, omission errors, and off-roads were not different. Correlation between self-assessed and actual performance under heavy call was significant for commission errors (r = –0.45, P = .01), lane variability (r = –0.76, P<.001), and speed variability (r = –0.71, P < .001), but not for reaction time.” (J. T. Arnedt, tarnedt@med.umich.edu)

Medical Students & Drug Companies: Medical students are subject to unrecognized marketing efforts of the pharmaceutical industry, conclude authors who surveyed 826 third-year students at eight U.S. medical schools in 2003 (pp. 1034-42). “762/818 (93.2%) were asked or required by a physician to attend at least 1 sponsored lunch,” the authors note. “Regarding attitudes, 556/808 (68.8%) believed gifts would not influence their practices and 464/804 (57.7%) believed gifts would not affect colleagues’ practices. Of the students, 553/604 (80.3%) believed that they were entitled to gifts. Of 183 students who thought a gift valued at less than $50 was inappropriate, 158 (86.3%) had accepted one. The number of students who simultaneously believed that sponsored grand rounds are educationally helpful and are likely to be biased was 452/758 (59.6%).” (F. S. Sierles, Rosalind Franklin U. Med. and Sci./The Chicago Medical School, North Chicago, Ill.; frederick.sierles@rosalindfranklin.edu)

>>>Internal Medicine Report
Source:
Sept. 6 issue of the Annals of Internal Medicine (www.annals.org; 2005; 143).

Tiotropium for COPD:
The long-acting anticholinergic bronchodilator tiotropium reduced exacerbations and possibly reduced health care utilization among 1,829 patients with moderate or severe chronic obstructive pulmonary disease (pp. 317-26). Comparing once-daily doses of 18 mcg of the drug with placebo for 6 months, the investigators found, “Tiotropium significantly reduced the percentage of patients experiencing 1 or more exacerbations compared with placebo (27.9% vs. 32.3%, respectively; difference, –5.7 percentage points [95% CI, –10.4 to –1.0 percentage points]; P = 0.037). Fewer tiotropium patients were hospitalized because of COPD exacerbation (7.0% vs. 9.5%, respectively; difference, –3.0 percentage points [CI, –5.9 to –0.1 percentage points]; P = 0.056), although this difference was of borderline statistical significance. Analysis of secondary outcomes indicates that tiotropium may lengthen the time to first COPD exacerbation (P = 0.028) and reduce health care utilization for exacerbations, including the frequency of hospitalizations (P = 0.047), unscheduled clinic visits (P = 0.019), and days of antibiotic treatment (P = 0.015). Tiotropium did not statistically significantly reduce all-cause hospitalization rates.” (D. E. Niewoehner, niewo001@umn.edu)

An editorialist points out the therapeutic gains afforded through prolonged bronchial dilatation (pp. 386-7): “The clinical and economic benefits of effective bronchodilator therapy are meaningful. Tiotropium should rightfully be considered a first-line medication in therapy for COPD, and long-term studies longer than 1 year ... may indicate that prolonged reduction of bronchial obstruction may lessen the annual decrease in lung function in patients with COPD over the long term.” (G. M. Turino, St. Luke's-Roosevelt Hosp., New York)


PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 8, 2005 Vol. 12, No. 174
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source: Sept. 8 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Antibiotic Prophylaxis & Cancer Chemotherapy: Two articles and an editorial discuss approaches for preventing chemotherapy-related neutropenic fevers and infections.

Prophylaxis with levofloxacin proved an effective and well tolerated means of preventing neutropenic fevers and infections among 760 adult patients receiving cancer chemotherapy (pp. 977-87). Compared with placebo, oral levofloxacin 500 mg daily provided these benefits in patients with protracted neutropenia: “An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, –20 percent; 95 percent confidence interval, –26 to –14 percent; P = 0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, –17 percent; 95 percent confidence interval, –24 to –10 percent; P < 0.001), bacteremias (difference in risk, –16 percent; 95 percent confidence interval, –22 to –9 percent; P < 0.001), and single-agent gram-negative bacteremias (difference in risk, –7 percent; 95 percent confidence interval, –10 to –2 percent; P < 0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma.” (A. Del Favero, Università di Perugia, Perugia, Italy;
delfa@unipg.it)

Prophylactic levofloxacin reduced the incidence of fever, probable infection, and hospitalization among 1,565 patients being treated with chemotherapy for solid tumors or lymphoma (pp. 988-98): “During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P < 0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P = 0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P = 0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P = 0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P = 0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections.” (M. Cullen, U. Hosp., Birmingham, U.K.;
michael.cullen@uhb.nhs.uk)

An editorialist cautions that prophylactic levofloxacin should be reserved for high-risk patients (pp. 1052-4): “The prophylactic use of fluoroquinolones has already been associated with the synchronous emergence of resistant gram-negative rods in patients undergoing cancer chemotherapy, thus implying that the resistance threshold is not high. There is little diminution of fitness in fluoroquinolone-resistant gram-negative rods such as
E. coli, and once a resistant clone becomes established, it is difficult to control. Since the emergence and dissemination of antimicrobial resistance take time, it is very difficult to assess all the implications in an exhaustive manner. As resistant organisms emerge at a given center, the use of broad-spectrum antimicrobial agents will increase, further accelerating this evolutionary process. One way to maintain the benefits described in the two current studies but minimize the risk is to restrict its use to those at highest risk.” (L. R. Baden)

>>>PNN NewsWatch
* Proquad, a combination MMR/chickenpox vaccine from Merck, has been approved by FDA for simultaneous vaccination against measles, mumps, rubella, and varicella and for booster doses in children 12 months to 12 years of age.

* Efforts by
Abbott, Lilly, Wyeth, and GlaxoSmithKline to get medications to victims of Hurricane Katrina are featured in an article in today’s Wall Street Journal. Pharmacies can provide emergency-dispensing services to enrolled patients by signing up for Wyeth’s Patient Assistance Program at 800/666-7248.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 9, 2005 Vol. 12, No. 175
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Sept. issue of Pharmacotherapy (www.pharmacotherapy.org; 2005; 25).

Pneumococcal Antibiotic Effectiveness: In a Monte Carlo simulation, ceftriaxone remained effective against recent Streptococcus pneumoniae isolates as resistance increased, while the “rate of decline of the pharmacodynamic curve was most pronounced for ... two levofloxacin regimens” (pp. 1161-7). Using 7,866 clinical isolates, the investigators simulated the experiences expected for 10,000 patients based on pharmacokinetic parameters, variability, and minimum inhibitory concentrations, with results expressed as the percentage of time above the MIC (%T>MIC) for ceftriaxone and area under the concentration-time curve:MIC ratio from 0–150 for the fluoroquinolones. Results showed: “For ceftriaxone, probability of target attainment remained 90% or greater against the three isolate groups until a %T>MIC of 70% or greater, and it remained 90% or greater against susceptible and intermediate isolates over the entire interval (%T>MIC 0–100%). For levofloxacin 500 mg, probability of target attainment was 90% at an AUC:MIC ≥30, but the curve declined sharply with further increases in pharmacodynamic target. Levofloxacin 750 mg achieved a probability of target attainment of 99% at an AUC:MIC ratio ≥30; the probability remained approximately 90% until a target of 70 or greater, when it declined steeply. Gatifloxacin demonstrated a high probability (99%) of target attainment at an AUC:MIC ratio ≥30, and it remained above 90% until a target of 70.” (D. S. Burgess, BurgessD@uthscsa.edu)

Postsurgical PCA: Individualized treatment is needed to provide successful postoperative patient-controlled analgesia, according to evaluations of 60 patients who rated their pain intensity at rest and after activity (pp. 1168-73). “During the first 12 hours of intravenous PCA use, 75% of the patients reported moderate-to-severe pain (≥5 on a verbal numeric rating scale) at rest, 80% after activity,” report the authors. “Corresponding values, respectively, were 33% and 72% for the 12–24-hour period, 43% and 76% for the 24–36-hour period, and 36% and 64% for the 36–48-hour period of intravenous PCA use. Within 4 hours of stopping PCA, 30% and 58% of the patients had moderate-to-severe pain at rest and after activity, respectively. In approximately 50% of patients, presence of pain was described with words signifying sensory and affective dimensions of pain. Pain control was rated as good or very good by 54% of patients during the first 12 hours of intravenous PCA. Ratings of pain control tended to improve with time.” (G. E. Larijani, Cooper U. Hosp., Camden, N.J.; larijanig@aol.com)

Review Articles: Major reviews in this issue of Pharmacotherapy include the following:

* Infections Associated with Tumor Necrosis Factor-Alpha Antagonists (pp. 1181-92; J. T. DiPiro, Med. U. South Carolina, Charleston)

*
Streptococcus pneumoniae (pp. 1993-212; A. Bridy-Pappas, Wyeth)

* Protective Effects of Angiotensin II Interruption: Evidence for Antiinflammatory Actions (pp. 1213-29; F. Jamali,
fjamali@pharmacy.ualberta.ca)

* Patient Education and Treatment Strategies Implemented at a Pharmacist-Managed Hepatitis C Virus Clinic (pp. 1230-41; B. Kolor, VA, Long Beach, Calif.;
bonkolor@yahoo.com)

>>>PNN NewsWatch
* Positive votes this week by FDA advisory panels portend good news for developers of the rheumatoid arthritis agent abatacept (Orencia, Bristol-Myers Squibb) and inhaled insulin (Exubera, Pfizer). Because of a higher rate of serious infections with abatacept (3% of patients, compared with 2% of those on placebo) that were more common with concomitant TNF-alpha antagonists, FDA is likely to recommend that these agents not be used together. Panelists supported use of inhaled insulin for both type 1 and type 2 diabetes despite concerns over pulmonary adverse effects. One role for pharmacists with the agent is patient education about correct administration technique that ensures delivery to the lungs.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 12, 2005 Vol. 12, No. 176
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles in BMJ (www.bmj.org; 2005; 331).

Immunosuppression After Kidney Transplant: Tacrolimus provides better protection against acute rejection than does cyclosporine, according to a meta-analysis and meta-regression of 123 reports from 30 trials involving 4,102 patients, but it also produces a higher rate of insulin-dependent diabetes (doi:10.1136/bmj.38569.471007.AE). “At six months, graft loss was significantly reduced in tacrolimus treated recipients (RR = 0.56, 95% confidence interval 0.36 to 0.86), and this effect persisted up to three years,” the authors report. “The relative reduction in graft loss with tacrolimus diminished with higher concentrations of tacrolimus (P = 0.04) but did not vary with ciclosporin formulation (P=0.97) or ciclosporin concentration (P = 0.38). At one year, tacrolimus treated patients had less acute rejection (RR = 0.69, 0.60 to 0.79) and less steroid resistant rejection (RR = 0.49, 0.37 to 0.64) but more diabetes mellitus requiring insulin (RR = 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia, and vomiting. The relative excess of diabetes increased with higher concentrations of tacrolimus (P = 0.003). Ciclosporin treated recipients had significantly more constipation and cosmetic side effects. No differences were seen in infection or malignancy.” (A. C. Webster, Children's Hosp., Westmead, NSW, Australia; angelaw2@chw.edu.au)

MRSA & Antibiotic Policies: For hospital readmissions, policies and diagnostic algorithms need to recognize that about one fourth of cases of methicillin-resistant Staphylococcus aureus occur in previously admitted patients who are returning to the hospital, conclude authors who analyzed records from a teaching hospital and a general hospital in Oxford(doi:10.1136/bmj.38558.453310.8F): “In the teaching hospital, there were 479 patients with MSSA and 116 with MRSA bacteraemia admitted from the community. Among this group, which comprised 24% of all hospital MRSA cases, 31% (36 cases) of patients had been admitted to renal, oncology, or haematology services for intensive day case therapy. The 69% remaining were most commonly patients admitted as medical or surgical emergencies. At least 91% had been in hospital previously; the median time since discharge was 46 days. About half of cases were in patients in whom MRSA had not been isolated before. Similar epidemiology was observed in the district general hospital.” (D. H. Wyllie, U. Oxford, Oxford, U.K.; david.wyllie@ndcls.ox.ac.uk)

Treating UTIs in Nursing Homes: Use of algorithms and other interventions can improve prescribing for urinary-tract infections among nursing home residents, concludes a study of 24 facilities in the U.S. and Canada (doi:10.1136/bmj.38602.586343.55). Comparing a multifaceted intervention with usual care, the investigators found, “Fewer courses of antimicrobials for suspected urinary tract infections per 1000 resident days were prescribed in the intervention nursing homes than in the usual care homes (1.17 v 1.59 courses; weighted mean difference –0.49, 95% confidence intervals –0.93 to –0.06). Antimicrobials for suspected urinary tract infection represented 28.4% of all courses of drugs prescribed in the intervention nursing homes compared with 38.6% prescribed in the usual care homes (weighted mean difference –9.6%, –16.9% to –2.4%). The difference in total antimicrobial use per 1000 resident days between intervention and usual care groups was not significantly different (3.52 v 3.93; weighted mean difference –0.37, –1.17 to 0.44). No significant difference was found in admissions to hospital or mortality between the study arms.” (M. Loeb; loebm@mcmaster.ca)

>>>PNN JournalWatch
* Effect on Survival and Hospitalization of Initiating Treatment for Chronic Heart Failure with Bisoprolol Followed by Enalapril, as Compared With the Opposite Sequence. Results of the Randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III, in Circulation, 2005; published early. Reprints: circ.ahajournals.org; R. Willenheimer, U. Hosp., Malmö, Sweden; ronnie.willenheimer@med.lu.se

* New Targeted Approaches in Chronic Myeloid Leukemia, in
Journal of Clinical Oncology, 2005; 23: 6316–24. Reprints: www.jco.org; J. Cortes, jcortes@mdanderson.org

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 13, 2005 Vol. 12, No. 177
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Sept. 12 issue of Archives of Internal Medicine (www.archinternmed.com; 2005; 165).

Posthospital Medication Discrepancies: One in seven older patients is discharged from the hospital with discrepancies in medications, and those with such apparent errors have a significantly higher rate of rehospitalization within 30 days, according to a study of 375 community-dwelling adults aged 65 years or older (pp. 1842-7). Based on a geriatric nurse practitioner’s in-home medication evaluation using a Medication Discrepancy Tool conducted 24–72 hours postdischarge, the investigators found, “A total of 14.1% of patients experienced 1 or more medication discrepancies. Using the Medication Discrepancy Tool, 50.8% of identified contributing factors for discrepancies were categorized as patient-associated, and 49.2% were categorized as system-associated. Five medication classes [anticoagulants, 13%; diuretics, 10%; ACE inhibitors, 10%; lipid-lowering agents, 10%; and proton pump inhibitors, 7%] accounted for half of all medication discrepancies. Medication discrepancies were associated with the total number of medications taken and the presence of congestive heart failure. A total of 14.3% of the patients who experienced medication discrepancies were rehospitalized at 30 days compared with 6.1% of the patients who did not experience a discrepancy (P = .04).” (E. A. Coleman, U. Colorado Health Sci. Ctr., Aurora, Colo.; Eric.Coleman@uchsc.edu)

Disclosing Medical Errors: The dilemma over whether to disclose medical errors to patients is explored in a commentary (pp. 1819-24). Considering how “improving the disclosure process could enhance patients’ satisfaction and their trust in physicians’ integrity,” the author reaches this conclusion, “The risk that disclosing an error to a patient could prompt a lawsuit cannot be disregarded. However, the medical profession cannot continue to ignore its failure to communicate effectively with patients who have been harmed by medical errors. Our patients unequivocally want and certainly deserve full disclosure of harmful medical errors. Rather than remaining paralyzed by the litigious health care environment, we must start taking the necessary steps to achieve this goal.” (T. Gallagher, thomasg@u.washington.edu)

Influenza Vaccination Trends: Vaccination of target populations against influenza seems to be leveling off, with elderly black and Hispanic populations still not meeting the Healthy People 2000 goal of 60%, notes a study based on data from the 1989–2002 National Health Interview Surveys (pp. 1849-56). To meet the Healthy People 2010 goal of 90% vaccination coverage, “innovative initiatives are needed,” the authors note. “Among the elderly, influenza vaccination coverage increased from 30.5% in 1989 to 65.6% in 2002, with only a 2.4% increase from 1997 to 2002,” the group explains. “In 2002, coverage remained lower for the non-Hispanic black (49.6%) and Hispanic (48.5%) populations compared with non-Hispanic whites (68.6%). Characteristics associated with a lower likelihood of influenza vaccination included fewer than 4 physician contacts in the past year and whether a person (1) was divorced or separated, (2) was non-Hispanic black or Hispanic, (3) had no regular physician, and (4) had less than a high school education. Individuals with chronic medical conditions and those 75 years or older were more likely to be vaccinated.” (P-J Lu, plu@cdc.gov)

Atypical Antipsychotics & Parkinsonism: High-dose second-generation antipsychotic agents produce parkinsonism about as frequently as do first-generation agents, making caution necessary (pp. 1882-8). A retrospective cohort study of 25,769 older adults in Ontario shows a 30% greater adjusted hazard ratio for those on typical antipsychotics than on atypical agents. Patients receiving higher-potency typical agents had a 44% increase in risk of parkinsonism, and those on high-dose atypical antipsychotic agents were at similar risk for the adverse event as were those on typical agents. (P. A. Rochon, paula.rochon@utoronto.ca)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 14, 2005 Vol. 12, No. 178
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Sept. 14 issue of JAMA (www.jama.com; 2005; 294).

Treatment Mismatch in HF: Patients at highest risk of mortality from heart failure are least likely to be treated with ACE inhibitors, angiotensin II receptor blockers, and/or beta-blockers, according to data from the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study (pp. 1240-7). A population-based cohort of 9,942 patients younger than 80 years in Ontario, EFFECT showed these results, “At hospital discharge, prescription rates for patients in the low-, average-, and high-risk groups were 81%, 73%, 60%, respectively, for ACE inhibitors; 86%, 80%, 65%, respectively, for ACE inhibitors or ARBs; and 40%, 33%, 24%, respectively, for beta-adrenoreceptor antagonists (all P < .001 for trend). Within 90 days following hospital discharge, the rates were 83%, 76%, and 61% for ACE inhibitors; 89%, 83%, and 67% for ACE inhibitors or ARBs; and 43%, 36%, and 28% for -adrenoreceptor antagonists for the 3 risk groups, respectively (all P < .001 for trend). The pattern of lower rates of drug administration in those patients at increasing risk was maintained up to 1 year postdischarge (P < .001). After accounting for varying survival time and potential contraindications to therapy, low-risk patients were more likely to receive ACE inhibitors or ARBs (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.49–1.74) and beta-adrenoreceptor antagonists (HR, 1.80; 95% CI, 1.60-2.01) compared with high-risk patients (both P<.001).” (A. Laupacis, Inst. for Clinical Evaluative Sci., Toronto; alaupacis@ices.on.ca)

Clopidogrel Pretreatment Before PCI: Among 1,863 patients with recent ST-segment elevation myocardial infarction, clopidogrel pretreatment “significantly reduces the incidence of cardiovascular death or ischemic complications both before and after [percutaneous coronary intervention] without a significant increase in major or minor bleeding” (pp. 1224-32). In the PCI-Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) trial, patients received aspirin and were then randomized to clopidogrel or placebo initiated with fibrinolysis until coronary angiography 2–8 days later. “Pretreatment with clopidogrel significantly reduced the incidence of cardiovascular death, MI, or stroke following PCI (34 [3.6%] vs 58 [6.2%]; adjusted odds ratio [OR], 0.54 [95% CI, 0.35–0.85]; P = .008). Pretreatment with clopidogrel also reduced the incidence of MI or stroke prior to PCI (37 [4.0%] vs 58 [6.2%]; OR, 0.62 [95% CI, 0.40–0.95]; P = .03). Overall, pretreatment with clopidogrel resulted in a highly significant reduction in cardiovascular death, MI, or stroke from randomization through 30 days (70 [7.5%] vs 112 [12.0%]; adjusted OR, 0.59 [95% CI, 0.43–0.81]; P = .001; number needed to treat = 23). There was no significant excess in the rates of TIMI major or minor bleeding (18 [2.0%] vs 17 [1.9%]; P > .99).” (M. S. Sabatine, msabatine@partners.org)

>>>PNN NewsWatch
* FDA has rejected an NDA for lasofoxifene (Oporia), a selective estrogen receptor modulator (SERM) under development by Pfizer for prevention of osteoporosis. FDA does not publicly state why NDAs are rejected, and Pfizer disclosed little in a news release announcing the development, stating only that it would consider “various possible courses of action.”

* FDA’s Oncology Drug Advisory Committee encouraged
Abbott Laboratories to continue clinical studies of atrasentan (Xinlay), an oral drug being considered for treatment of men with hormone-refractory prostate cancer that has metastasized to the bone, but recommended that FDA reject the current NDA. The agent, a selective endothelin-A receptor antagonist (SERA), has shown some promise in patient subgroups. In addition, utility of the oral agent is being studied in Phase III trials of those without prostate-cancer metastases.

* Seniors will face a broad and bewildering array of
Medicare Part D choices when marketing of drug plans begins on Oct. 1, cautions an article in this morning’s Wall Street Journal. Medicare Advantage plans as well as Medigap policies will be among the items seniors must consider in deciding whether to participate and which of 11–23 plans to pick.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 15, 2005 Vol. 12, No. 179
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Sept. 15 issue of the New England Journal of Medicine (content.nejm.org; 2005;353).

Management of ACS: For patients with acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level, an early invasive strategy provided no benefit over a selectively invasive strategy (pp. 1095-104). All patients were receiving aspirin daily, enoxaparin for 48 hours, and abciximab at the time of percutaneous coronary intervention, and the use of clopidogrel and intensive lipid-lowering therapy was recommended. Looking at a composite end point of death, nonfatal myocardial infarction, or rehospitalization for anginal symptoms within 1 year after randomization, the investigators found, “The estimated cumulative rate of the primary end point was 22.7 percent in the group assigned to early invasive management and 21.2 percent in the group assigned to selectively invasive management (relative risk, 1.07; 95 percent confidence interval, 0.87 to 1.33; P = 0.33). The mortality rate was the same in the two groups (2.5 percent). Myocardial infarction was significantly more frequent in the group assigned to early invasive management (15.0 percent vs. 10.0 percent, P = 0.005), but rehospitalization was less frequent in that group (7.4 percent vs. 10.9 percent, P = 0.04).” (R. J. de Winter, Academic Med. Ctr., Amsterdam; r.j.dewinter@amc.uva.nl)

Abatacept for RA: The selective costimulation modulator abatacept—under review at FDA (see PNN, Aug. 26, Sept. 9)—was effective and safe for treating patients with refractory rheumatoid arthritis in a Phase III study of 391 patients whose symptoms were unresolved during at least 3 months of anti-TNF-alpha therapy (pp. 1114-23). Investigators compared abatacept with placebo during treatment with at least one disease-modifying antirheumatic drug. Based on response rates to the American College of Rheumatology criteria and scores on the Health Assessment Questionnaire, the researchers showed, “After six months, the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P < 0.001); the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 percent vs. 3.8 percent, P < 0.001; and 10.2 percent vs. 1.5 percent, P = 0.003). At six months, significantly more patients in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 percent vs. 23.3 percent, P < 0.001). The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence of serious infections was 2.3 percent in each group.” (M. C. Genovese, genovese@stanford.edu)

Use of Stimulants and Antidepressants by College Students: Seeking to “get an edge” in today’s competitive college environment, students are seeking prescriptions for antidepressants and stimulants, according to a Perspective article (pp. 1089-91). “The current rates of depression, stress-related symptoms, insomnia, and eating disorders in U.S. colleges and universities are staggering; not surprisingly, so are the rates of substance abuse,” the author writes. “In a recent national survey of 13,500 college students, nearly 45 percent reported being so depressed that they had difficulty functioning, and 94 percent reported feeling overwhelmed by everything they had to do. Various studies have shown that about 45 percent of college students intermittently engage in binge drinking.

“Some of these students no doubt meet the criteria for therapy with effective, new psychotropic medications. The trouble is that many more of them, affected by the increased stress of college life—overextended by extracurricular activities taken on in order to build their résumés, sleeping even less than their predecessors, and worrying more than ever about financial, social, and academic pressures—are at risk for misusing or abusing these drugs, which can have serious adverse effects.” (R. Kadison, Harvard U., Cambridge, Mass.)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 16, 2005 Vol. 12, No. 180
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
Sept. issue of Pediatrics (www.pediatrics.org; 2005; 116).

Lovastatin in Adolescent Girls: Among 54 adolescent girls with familial hypercholesterolemia, lovastatin 40 mg/day proved an effective and well-tolerated therapy (pp. 682-8). The 24-week, placebo-controlled trial showed: “Baseline values of lipids, lipoproteins, and apolipoproteins (apo) were comparable between treatment groups. Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23% to 27%, total cholesterol by 17% to 22%, and apo B by 20% to 23% at weeks 4 and 24, respectively. Between-treatment group differences were not statistically significant for triglycerides, very-low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or apo A-I. Lovastatin was generally safe and well tolerated. There were no clinically significant alterations in vital signs (blood pressure and pulse rate), anthropomorphic measurements (height, weight, and BMI), hormone levels (luteinizing hormone, follicle-stimulating hormone, dehydroepiandrosterone sulfate, estradiol, and cortisol), menstrual cycle length, or tests of liver and muscle function.” (S. B. Clauss, Johns Hopkins Med. Inst., Baltimore)

Exercise & Insulin Pumps: Late hypoglycemia is a risk when patients exercise with insulin pumps on, according to a study of 10 subjects with type 1 diabetes mellitus and aged 10 to 19 years (e348-55). Seeking to better define guidelines for pump use during exercise, the investigators provided a standard breakfast and a bolus insulin lispro dose. About 2 hours later, exercise performed with the pump on (PO) or off (PF) had these effects: “During exercise, blood glucose concentrations decreased by 59 ± 58 mg/dL (mean ± SD: 29 ± 24%) with PF and by 74 ± 51 mg/dL (35.5 ± 18%) with PO (not significant). No significant differences were found in cortisol, growth hormone, or noradrenaline levels between PO and PF. There were no differences in cardiorespiratory parameters, blood lactate concentrations, or free fatty acids concentrations between pump modes. Hypoglycemic events during exercise were asymptomatic and occurred for 2 subjects with PO and 2 with PF. Nine subjects had late hypoglycemia after PO, compared with 6 after PF (not significant).” (G. Admon, Schneider Children's Med. Ctr., Petach Tikva, Israel)

Acute Vitamin D Intoxication: Persistent hypercalcemia and hypertension resulted from an inadvertent overdose with vitamin D in a previously healthy 2-year-old boy (e453-6). The boy’s mother had been administering an ampule of an imported vitamin D supplement, with 600,000 IU per ampule, for 4 days rather than the intended two drops of the solution. “The patient's hypercalcemia persisted for 14 days and was complicated by persistent hypertension,” write the authors. “No renal, cardiac, or neurologic complications were noted. At discharge, the vitamin D concentration was still elevated at 389 ng/mL and the total calcium level had decreased to 11 mg/dL [from a peak of 15.0 mg/dL on hospital day 2]. The boy made a complete clinical recovery. This case highlights the need for caution when using imported and/or unregulated medicines, as well as the dangers of parental dosing errors.” (F. Barrueto, Jr., U. Maryland, Baltimore)

>>>PNN NewsWatch
* Adding its voice to calls this week by CDC and CMS officials for influenza vaccination for Americans, APhA asked pharmacists to “lead by example and get vaccinated against influenza.” Pharmacists interact with patients everyday who are at risk of complications if they get influenza and pneumococcal disease, notes an APhA news story. Pharmacists and other health care professionals can contribute to prevention of these diseases by providing consistent messages and delivery of vaccine.

* Widespread adoption and effective use of electronic medical records and other health
information technology could save the U.S. health system as much as $162 billion annually by improving the way medical care is managed, reducing preventable medical errors, lowering mortality from chronic disease, and reducing employee sick days, according to two Rand Corp. studies released this week by Health Affairs.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 19, 2005 Vol. 12, No. 181
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
Sept. 17 issue of Lancet (www.thelancet.com; 2005; 366).

Weekly Zinc Supplements for Young Children in Bangladesh: While adherence outside a research setting might be “problematic,” weekly supplements of zinc 70 mg reduced pneumonia and mortality among 1,665 poor, urban children aged 60 days to 12 months in Bangladesh (pp. 999-1004). The 1-year study showed these benefits of zinc in comparison with placebo: “There were significantly fewer incidents of pneumonia in the zinc group than the control group (199 vs 286; relative risk 0.83, 95% CI 0.73–0.95), and a small but significant effect on incidence of diarrhoea (1881 cases vs 2407; 0.94, 0.88–0.99). There were two deaths in the zinc group and 14 in the placebo group (p = 0.013). There were no pneumonia-related deaths in the zinc group, but ten in the placebo group (p = 0.013). The zinc group had a small gain in height, but not weight at 10 months compared with the placebo group. Serum copper and haemoglobin concentrations were not adversely affected after 10 months of zinc supplementation.” (W. A. Brooks, Intl. Ctr. for Diarrhoea Disease Res., Mohakhali Dhaka, Bangladesh; abrooks@icddrb.org)

>>>BMJ Highlights
Source:
Sept. 17 issue of BMJ (www.bmj.org; 2005; 331).

Tetraparesis with Colchicine–Verapamil Interaction: A case of flaccid tetraparesis associated with colchicine therapy in an 83-year-old man is attributed to verapamil inhibition of the P-glycoprotein efflux pump in the blood-brain barrier (p. 613). The man had treated himself with colchicine during an acute attack of gout and had also received diclofenac. He developed muscle weakness in his limbs, and this progressed over 4 days to immobility. While the initial clinical impression was an atypical Guillain-Barré syndrome, the diagnosis was revised to neuromyopathy based on serum and cerebrospinal fluid colchicine levels. “Typical features of colchicine induced myoneuropathy such as high cumulative doses, long term treatment, or renal insufficiency were not found in our case,” the authors report. “Verapamil is an inhibitor of CYP3A and a potent inhibitor (with norverapamil threefold stronger) of the P-glycoprotein transporter acting as a blood-brain barrier drug efflux pump. An increase of colchicine uptake was seen in a rat's brain as well as in a rat's plasma by verapamil up to 4.5-fold and 1.65-fold, respectively. These results indicate a dominant responsibility of the P-glycoprotein inhibition for the colchicine accumulation in cerebrospinal fluid. Colchicine is a substrate for CYP3A4 in the liver. Its inhibition might be responsible for increased colchicine serum concentrations.” (U Tröger, Otto-von-Guericke-U., Magdeburg, Germany; uwe.troeger@medizin.uni-magdeburg.de)

>>>PNN JournalWatch
* Single-Dose Ciprofloxacin Versus 12-Dose Erythromycin for Childhood Cholera: A Randomised Controlled Trial, in Lancet, DOI:10.1016/S0140-6736(05)67290-X. Reprints: www.thelancet.com/journals/lancet/article/PIIS014067360567290X; D. Saha, dsaha@icddrb.org

* Twenty Five years of HIV Infection in Haemophilic Men in Britain: An Observational Study, in
BMJ, DOI:10.1136/bmj.38604.468785.DE. Reprints: www.bmj.org; C. A. Sabin, Royal Free and UC Med. Sch., London; c.sabin@pcps.ucl.ac.uk

* Protease Inhibitor Use in 233 Pregnancies, in
Journal of Acquired Immune Deficiency Syndromes, 2005; 40: 30–3. Reprints: www.jaids.com/pt/re/jaids/abstract.00126334-200509010-00005.htm; A. B. Morris.

* Psychosocial Implications of Disaster or Terrorism on Children: A Guide for the Pediatrician, in
Pediatrics, 2005; 116: 787–95. Reprints: pediatrics.aappublications.org/cgi/content/abstract/116/3/787; J. F. Hagan, Jr., and the American Academy of Pediatrics Committee on Psychosocial Aspects of Child and Family Health and the Task Force on Terrorism.

* Retrospective Detection of Potential Medication Errors Involving Drugs with Similar Names, in
Journal of the American Pharmacists Association, 2005; 45: 616–24. Reprints: www.japha.org; H. M. Phatak, hemant_phatak@merck.com

* Definition of Medication Therapy Management: Development of Professionwide Consensus, in
Journal of the American Pharmacists Association, 2005; 45: 566–72. Reprints: www.japha.org; B. M. Bluml, bbluml@aphanet.org

* Medication Therapy Management in Community Pharmacy Practice: Core Elements of an MTM Service (Version 1.0), in
Journal of the American Pharmacists Association, 2005; 45: 573–9. Reprints: www.japha.org; A. Burns, aburns@aphanet.org

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 20, 2005 Vol. 12, No. 182
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Sept. 20 issue of the Annals of Internal Medicine (www.annals.org; 2005; 143).

Cost Savings with Canadian Pharmaceuticals: Americans can achieve substantial savings by purchasing medications from Canadian Internet pharmacies, according to a cross-sectional study that compared 12 such sources with three major online U.S. chain drug pharmacies (pp. 397-403). For purchases of 44 brand-name medications, the investigators calculated these cost reductions: “Americans can save a mean of approximately 24% per unit of drug if they purchase their medications from Canadian Internet pharmacies instead of from major online U.S. drug chain pharmacies. Forty-one of the 44 brand-name medications examined were less expensive in Canada. The medications offering the largest mean yearly savings were Zyprexa (olanzapine) (Eli Lilly, Indianapolis, Indiana) ($1159), Actos (pioglitazone) (Eli Lilly, Indianapolis, Indiana) ($852), and Nexium (esomeprazole) (AstraZeneca, Wilmington, Delaware) ($772). Only 3 medications, all in the erectile dysfunction category, were more expensive in Canada.” (M. J. Eisenberg, meisenberg@epid.jgh.mcgill.ca)

Treatment of Depression: Second-generation antidepressants differ little in their effectiveness, and evidence about adverse events is quite variable and therefore difficult to assess (pp. 415-26). This conclusion comes from a systematic review of 46 head-to-head randomized, controlled trials comparing second-generation antidepressants and 24 observational studies and placebo-controlled trials. “According to fair to good evidence, the second-generation antidepressants that were compared had only minimal differences in efficacy, and 88% of comparative efficacy studies reported no statistically significant difference in any outcome measure at the end of the study,” the authors note. “One effectiveness trial rated good and 2 effectiveness trials rated fair reported no statistically significant differences in primary outcome measures for compared drugs. Meta-analyses showed a modest but statistically significant additional treatment effect for sertraline and venlafaxine compared with fluoxetine. About 96% of comparative trials were sponsored by or had at least 1 author affiliated with a pharmaceutical company; the remaining trials did not report funding sources. Adverse event profiles differed among drugs; however, the degree and quality of adverse event assessment varied and only 13% of trials used a standardized scale to assess adverse events.” (R. A. Hansen, rahansen@unc.edu)

Self-Management of Chronic Disease in Older Adults: Diabetes mellitus and hypertension are good target diseases for self-management programs in older adults, according to a meta-analysis of 53 randomized trials (pp. 427-38). “Self-management interventions led to a statistically and clinically significant pooled effect size of –0.36 (95% CI, –0.52 to –0.21) for hemoglobin A1c, equivalent to a reduction in hemoglobin A1c level of about 0.81%. Self-management interventions decreased systolic blood pressure by 5 mm Hg (effect size, –0.39 [CI, –0.51 to –0.28]) and decreased diastolic blood pressure by 4.3 mm Hg (effect size, –0.51 [CI, –0.73 to –0.30]). Pooled effects of self-management interventions were statistically significant but clinically trivial for pain and function outcomes for osteoarthritis. No consistent results supported any of the 5 characteristics examined as essential for program success.” (J. Chodosh, VA Healthcare System, Los Angeles)

Commenting on this evaluation and another one in this issue that focused on chronic disease management initiatives in the Medicare program, an editorialist compares chronic disease care with “rearranging the [Titanic’s] deck chairs” (pp. 458-9): “The impact of a specific tool or intervention, therefore, is not the central issue. Instead, we must accelerate and expand our search for the underlying chassis: the combination of organizational models, care delivery production systems, and payment systems that can reverse the shortcomings in today's chronic care, meet the demand that lies ahead, and incorporate the new diagnostic, treatment, and monitoring tools that are on the horizon. Our seriously constrained physician and nurse supply adds further urgency and complexity to the task.” (D. M. Lawrence,
david.lawrence@kp.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 21, 2005 Vol. 12, No. 183
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release articles from the New England Journal of Medicine (content.nejm.org; 2005; 353).

Antipsychotic Drugs for Chronic Schizophrenia: Intolerable adverse effects of neuroleptics leading to drug discontinuation limit interpretation of results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE; 10.1056/NEJMoa051688). The first-generation agent perphenazine was compared with four second-generation (atypical) agents: olanzapine 7.5–30 mg/day, perphenazine 8–32 mg/day, quetiapine 200–800 mg/day, risperidone 1.5–6.0 mg/day, and after it was marketed, ziprasidone 40–160 mg/day. The authors report these findings: “Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P < 0.001) or risperidone (P = 0.002) group, but not in the perphenazine (P = 0.021) or ziprasidone (P = 0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P = 0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects.” (J. A. Lieberman, jlieberman@columbia.edu)

An editorialist adds (10.1056/NEJMe058200): “New drugs that do not have metabolic side effects but that do confer the antipsychotic effects of clozapine and olanzapine would be desirable. Just as the second generation of drugs moved beyond D2 antagonism, aripiprazole—a partial agonist at dopamine D2 receptors that facilitates low levels of receptor activation while blocking higher levels—as well as other new drugs in development have mechanisms that move beyond the dopamine D2–5-hydroxytryptamine-2A hypothesis. How these drugs perform in comparison with olanzapine is still unknown. The value of CATIE is that it provides solid evidence to help clinicians and their patients make the difficult decisions needed to optimize the treatment of schizophrenia with the compounds currently available.” (R. Freedman, U. Colorado, Denver)

>>>JAMA Highlights
Source:
Sept. 21 issue of JAMA, a theme issue on medical research (www.jama.com; 2005; 294).

Stem Cell Research: The political, religious, and ethical issues surrounding stem cell research are explored (pp. 1359-66): “Governments have intervened previously on the type of biomedical research that can be done, such as famously occurred when Stalin took the advice of Trofim Lysenko and banned Darwinian genetics in favor of Lamarckian views. Russia suffered greatly for this ideological ban, and until recently could not participate in the biomedical revolution of modern genetics. In the United States, recombinant DNA research was opposed for safety, ideological, and religious reasons, but in the end it was regulated, not banned, ushering in the era of biotechnology that now cures and treats hundreds of thousands of Americans each year.” (I. Weissman, irv@stanford.edu)

Academic Medical Centers: The challenges of facilitating medical research within economically pressed academic medical centers lead authors to write (pp. 1367-72): “Although the present era offers more promise for medical research progress than ever before, academic medical centers also face more daunting challenges for the conduct of medical research.... The interconnectedness of these challenges magnifies their difficulties and importance. Maintaining academic medicine’s integrity and effectiveness in pursuing its vital research mission will be a crucial challenge for medical schools and teaching hospitals in the years ahead.” (E. K. Siegel, Association of American Medical Colleges, Washington, D.C.; esiegel@aamc.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 22, 2005 Vol. 12, No. 184
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Sept. 22 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Single-Dose Azithromycin for Early Syphilis: Particularly in developing countries, single-dose azithromycin, administered as 2 grams orally, may be a useful alternative to intramuscular penicillin G benzathine 2.4 million units in the treatment of early syphilis, according to a study of 328 individuals in Tanzania (pp. 1236-44). While development of resistance to azithromycin by Treponema pallidum isolates in the United States reflects the need for vigilant monitoring of resistance patterns, the authors note these positive results in this study: “The average age of participants was 27.0 years, 235 (71.6 percent) were female, and 171 (52.1 percent) were seropositive for human immunodeficiency virus. Cure rates were 97.7 percent (95 percent confidence interval, 94.0 to 99.4) in the azithromycin group and 95.0 percent (95 percent confidence interval, 90.6 to 97.8) in the penicillin G benzathine group (95 percent confidence interval for the difference, –1.7 to 7.1 percent), achieving prespecified criteria for equivalence. Cure rates were also similar three and six months after treatment in the two groups and in all subgroups. Cure rates at three months were 59.4 percent (95 percent confidence interval, 51.8 to 67.1) in the azithromycin group and 59.5 percent (95 percent confidence interval, 51.8 to 67.3) in the penicillin G benzathine group and at six months were 85.5 percent (95 percent confidence interval, 79.4 to 90.6) and 81.5 percent (95 percent confidence interval, 74.8 to 87.4), respectively.” (G. Riedner; riednerg@emro.who.int)

An editorialist adds to concerns about development of resistance with wider use of azithromycin for early syphilis (pp. 1291-3): “Macrolide resistance in
T. pallidum has been found everywhere it has been sought among men who have sex with men with early syphilis in North America and Dublin. Although we can hope that macrolide-resistant T. pallidum has not and will not spread rapidly from sexual networks of men having sex with men in North America and Ireland to sexual networks elsewhere, it will be wise to ensure close follow-up of any patients treated with azithromycin for early syphilis throughout the world. It is also essential to gather more data on the global prevalence of macrolide resistance in T. pallidum and its effect on treatment.” (K. K. Holmes, U. Washington, Seattle)

Science & FDA: Expressing dismay over alleged “political meddling in the drug-approval process” in FDA’s “nondecision” over the Plan B emergency contraceptive, three prominent authors write that it is “a sad day for science at the FDA” (pp. 1197-9): “Imagine the scene at the checkout counter: with a line of impatient customers waiting behind you, you must show an identification card to a sales clerk in order to purchase a product that clearly reveals your exposure to unprotected intercourse during the past few hours. If chain pharmacies followed the rules they have used for beer and cigarettes (whose sales are currently subject to similar age restrictions), only clerks over a certain age would be allowed to authorize sales—which would delay the purchase even longer and expose the purchaser to further embarrassment. Moreover, many potential users of all ages—particularly poor women and those from inner-city neighborhoods—have no driver's licenses. Such women would not be able to obtain emergency contraception even if they were older than the arbitrary age limit set by the FDA.”

The authors conclude: “The FDA has, on occasion, been criticized for being too bureaucratic and slow to approve important new drugs, too quick to approve new drugs to please the corporate patrons who provide much of its budget, and too slow to withdraw drugs that seem to pose a danger to public health. But the agency has previously resisted political pressure to reflect a particular social policy or ideology. The recent actions of the FDA leadership have made a mockery of the process of evaluating scientific evidence, disillusioned many of the participating scientists both inside and outside the agency, squandered the public trust, and tarnished the agency's image. American women and the dedicated professionals at the FDA deserve better. Will we ever again be able to believe in the FDA's independence?” (A. J. J. Wood, Vanderbilt U., Nashville)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 23, 2005 Vol. 12, No. 185
Providing news and information about medications and their proper use

>>>JAPhA Highlights
Source:
Sept/Oct issue of the Journal of the American Pharmacists Association (www.japha.org; 2005; 45).

MTM Under Medicare Part D: Three articles provide community and other pharmacists with a consensus definition of medication therapy management (pp. 566-72; B. M. Bluml, bbluml@aphanet.org), a set of core elements for MTM in community pharmacy practice (pp. 573-9; A. Burns, aburns@aphanet.org), and a critical review of how MTM services are being provided and compensated in public and private sector programs (pp. 580-7; A. Burns, aburns@aphanet.org). “Development of a viable payment strategy for MTM programs and services is essential if the Medicare Part D benefit is to succeed in its mission of improving the lives of the nation’s elderly and disabled citizens,” notes the last article. “Past research clearly shows that the cost of medication-related morbidity and mortality at least equals the cost of the medications themselves, and for frail elderly patients, this cost reaches $3 for morbidity and mortality for every $1 spent on drugs. Without a drug therapy expert on the health care team to avert medication-related problems when possible and minimize their impact when they occur, not only will money be wasted on medications, the Medicare system will be strained by the costs of unnecessary hospitalizations, physician visits, and other interventions, and patients and their families will suffer needlessly.”

Financial Analysis of Pharmaceutical Care Program: Revenues generated by Heart Smart, a pharmaceutical care program provided by Osterhaus Pharmacy in Maquoketa, Iowa, exceeded developmental and operational costs during the first year of operation (pp. 588-92). Using data generated for provision of care to 36 employees of a self-insured employer and varying costs based on whether community pharmacy residents were available, the authors projected, “For pharmacies without a resident pharmacist, the net benefit was $106; for Heart Smart in a second employer, the net benefit was $6,024; for the second year, the projected net benefit was $6,844; factoring in a lower pharmacist salary, the net benefit was $2,905; and for a higher pharmacist salary, the net benefit was $1,265.” (J. B. Wilson, Valu-Med Pharmacy, Midwest City, Okla.; justin.wilson@cox.net)

OTC Pregnancy Tests: Claims of 99% accuracy on the first day of a missed menstrual period are not justified based on laboratory performance of OTC pregnancy tests, according to a results of study that tested six concentrations of a mixture of human chorionic gonadotropin–related molecules in urine (pp. 608-15). First Response Early Result performed best and would detect 95% of such pregnancies, and Clearblue Easy Earliest Results would detect 80%. But five other products would detect 16% or fewer pregnancies, the authors report. (L. A. Cole, U. New Mexico Health Sci. Ctr., Albuquerque;: larry@hcglab.com)

>>>PNN NewsWatch
* “Fierce bidding” among companies seeking to provide Medicare beneficiaries with Part D prescription drugs is resulting in premiums 14% lower than expected, reports this morning’s Wall Street Journal. But “that’s raising questions about the new market's prospects—as well as the specter of a disruptive shakeout among participating companies down the road,” the article adds.

*
Pfizer this week announced its second FDA nonapproval in 2 weeks (see PNN, Sept. 14), this one for an injectable COX-2–selective NSAID, parecoxib. With the agent marketed as Dynastat in much of the world, Pfizer expressed surprise in a news release and indicated it would meet with FDA officials in an effort to change minds. Parecoxib is used postoperatively for short periods of time, and the company believes this avoids the problems associated with longer-term use of the no-longer-marketed rofecoxib and valdecoxib.

*
KatrinaHealth.org is a Web site launched yesterday to provide authorized health professionals with prescription medication records of evacuees affected by Hurricane Katrina. Using data provided by national organizations and pharmacy benefits management companies, the Markle Foundation spearheaded development of the site.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 26, 2005 Vol. 12, No. 186
Providing news and information about medications and their proper use

>>>Lancet Report
Source:
Early-release articles from Lancet (www.thelancet.com; 2005; 366).

Effectiveness of Influenza Vaccines in the Elderly: A Cochrane review paints a gray picture of the effectiveness of influenza immunization campaigns that target the elderly, concluding that such efforts meet their goals “at least in part” in long-term care facilities but have “modest” effects among community-dwelling older patients [DOI:10.1016/S0140-6736(05)67339-4]. Using data from 5 randomized, 49 cohort, and 10 case–control studies, the investigators report, “In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against influenza-like illness was 23% (95% CI 6–36) and non-significant against influenza (RR 1.04, 0.43–2.51). Well matched vaccines prevented pneumonia (VE 46%, 30–58) and hospital admission (VE 45%, 16–64) for and deaths from influenza or pneumonia (VE 42%, 17–59), and reduced all-cause mortality (VE 60%, 23–79). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19, 0.02–2.01), influenza-like illness (RR 1.05, 0.58–1.89), or pneumonia (RR 0.88, 0.64–1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%, 12–38) and all-cause mortality (VE 42%, 24–55). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%, 21–33), respiratory diseases (VE* 22%, 15–28), and cardiac disease (VE* 24%, 18–30), and for all-cause mortality (VE* 47%, 39–54).” (T. Jefferson, Cochrane Vaccines Field, Alessandria, Italy; Toj1@aol.com)

Resistance to Anti-influenza Agents: A research study and a commentary assess the state of resistance to antiviral agents that target influenza.

Influenza A viruses are increasingly resistant to amantadine, according to data from the WHO Collaborating Center for Influenza at the CDC [DOI:10.1016/S0140-6736(05)67340-0]. “More than 7000 influenza A field isolates were screened for specific aminoacid substitutions in the M2 gene known to confer drug resistance,” the researchers write. “During the decade of surveillance a significant increase in drug resistance was noted, from 0.4% in 1994–1995 to 12.3% in 2003–2004. This increase in the proportion of resistant viruses was weighted heavily by those obtained from Asia with 61% of resistant viruses isolated since 2003 being from people in Asia.” (R. A. Bright,
rbright@cdc.gov)

Commenting on both this study and the above one on influenza vaccines, writers note: “The studies published today reinforce the shortcomings of our efforts to control influenza. For too long, the development and manufacture of influenza vaccines and antiviral drugs has been of limited interest to drug companies. Since the existing defences are limited, it is critical that the most is made of them. Thus, although increasing resistance to adamantine is a cause for concern, it is still too early to call for market withdrawal or exclusion from stockpiling. What is needed is to improve control over the distribution and availability of the adamantine drugs, particularly in developing and southeast Asian countries, and to increase surveillance for resistance, so that these cheap and easily administered drugs can continue to play a part in our influenza control strategies.” (Y. Guan, Shantou U. Med. Coll., Shantou, Guangdong, China;
yguan@hkucc.hku.hk)

>>>PNN NewsWatch
* Andrew von Eschenbach is the new acting FDA commissioner, named by President Bush following the abrupt resignation of Lester M. Crawford, DVM, PhD, late Friday afternoon. von Eschenbach will continue as director of the Natl. Cancer Inst. in addition to his new FDA duties in reaching closure on the Plan B controversy (see PNN, Aug. 29) and addressing the challenges of an agency in turmoil over drug approvals and drug safety and without a permanent head for much of the Bush Administration. A urologic surgeon and survivor of melanoma, prostate cancer, and basal cell carcinoma, von Eschenbach had established a controversial goal at NCI of transforming cancer from a fatal disease to a chronic one by 2015.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 27, 2005 Vol. 12, No. 187
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Sept. 26 issue of Archives of Internal Medicine (www.archinternmed.com; 2005; 165).

Colchicine for Recurrent Pericarditis: Recurrence of pericarditis was less frequent following treatment of first episodes with colchicine rather than aspirin or prednisone, conclude authors of an open-label, randomized study (pp. 1987-91). Comparing conventional treatment with aspirin (or prednisone 1–1.5 mg/kg/day in those for whom aspirin was contraindicated) with colchicine 1–2 mg on day 1 followed by 0.5–1 mg/day for 6 months, the investigators found, “During 1682 patient-months (mean follow-up, 20 months), treatment with colchicine significantly decreased the recurrence rate (actuarial rates at 18 months were 24.0% vs 50.6%; P = .02; number needed to treat = 4.0; 95% confidence interval 2.5–7.1) and symptom persistence at 72 hours (10% vs 31%; P = .03). In multivariate analysis, previous corticosteroid use was an independent risk factor for further recurrences (odds ratio, 2.89; 95% confidence interval, 1.10–8.26; P = .04). No serious adverse effects were observed.” (M. Imazio, Maria Vittoria Hosp., Torino, Italy; massimo_imazio@yahoo.it)

Empirical Coverage for Atypical Pathogens in CAP Inpatients: No survival benefit or indicator of clinical efficacy was apparent in a meta-analysis of studies of empirical coverage for atypical pathogens in those hospitalized for community-acquired pneumonia (pp. 1992-2000). “We included 24 trials encompassing 5015 patients,” the authors note. “We found no studies of a drug without atypical coverage that compared it with the same drug supplemented with a drug with atypical coverage; nearly all compared a beta-lactam with a single quinolone or macrolide. There was no difference in mortality between the 2 arms (RR, 1.13 [95% CI, 0.82–1.54]). Regimens with coverage of atypical pathogens showed a trend toward clinical success and a significant advantage to bacteriological eradication. Both disappeared when evaluating methodologically high-quality studies alone. These regimens further showed a significant advantage in clinical success for Legionella pneumophila, whereas no advantage for pneumococcal pneumonia was seen. There was no difference between study arms in the frequency of total adverse events.” (D. Shefet, Rabin Med. Ctr., Petah-Tiqva, Israel; dshefet@yahoo.com)

Fractures & Statin Use: In a population of mostly male veterans, use of statins was associated with a significantly lower risk of fractures (pp. 2007-12). The study included 91,052 VA patients in the New England region, 28,063 of whom were prescribed statins and 2,195 who were prescribed nonstatin lipid-lowering agents. Compared with no lipid-lowering therapy, those on statins had a 36% reduction in fracture risk. A 32% reduction was observed when patients on statins were compared with those taking other lipid-lowering drugs. Findings were similar for new users of statins in the study. Since evidence on statins’ impact on fracture risk has been mixed, the authors conclude, “It is evident that more studies need to be performed to address this controversy. The potential public health impact is too great to leave this question unanswered” (R. E. Scranton, richard.scranton@med.va.gov)

Physicians & Bioterrorism: Diagnosis and clinical management of cases of smallpox, anthrax, botulism, and plague need to be improved to help deal with the eventualities of a bioterrorism attack, according to a study of an educational intervention provided to 631 physicians at 30 internal medicine residency programs (pp. 2002-6). Pretests and posttests conducted with a didactic module on these diseases showed: “[Pretet] correct diagnoses of diseases due to bioterrorism agents were as follows: smallpox, 50.7%; anthrax, 70.5%; botulism, 49.6%; and plague, 16.3% (average, 46.8%). Correct diagnosis averaged 79.0% after completing the didactic module (P < .001). Correct management of smallpox was 14.6%; anthrax, 17.0%; botulism, 60.2%; and plague, 9.7% (average, 25.4%). Correct management averaged 79.1% after completing the didactic module (P < .001). Performance did not differ based on year of training (P = .54) or geographic location (P = .64). Attending physicians performed better than residents (P < .001).” (S. D. Sisson, Johns Hopkins U., Baltimore; ssisson@jhmi.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 28, 2005 Vol. 12, No. 188
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Sept. 28 issue of JAMA (www.jama.com; 2005; 294).

Dietary Phytoestrogens and Lung Cancer Risk: A case–control study adds support to the epidemiologic evidence that a diet high in phytoestrogens is associated with reduced risk of lung cancer (pp. 1493-504). Combining data from patient interviews and food frequency questionnaires over an 8-year period, the investigators found dietary and gender effects among 1,674 patients with lung cancer and 1,735 matched controls, “Reductions in risk of lung cancer tended to increase with each increasing quartile of phytoestrogen intake. The highest quartiles of total phytosterols, isoflavones, lignans, and phytoestrogens were each associated with reductions in risk of lung cancer ranging from 21% for phytosterols (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.64–0.97; P = .03 for trend) to 46% for total phytoestrogens from food sources only (OR, 0.54; 95% CI, 0.42–0.70; P < .001 for trend). Sex-specific effects were also apparent. For men, statistically significant trends for decreasing risk with increasing intake were noted for each phytoestrogen group, with protective effects for the highest quartile of intake ranging from 24% for phytosterols (OR, 0.76; 95% CI, 0.56–1.02; P = .04 for trend) to 44% for isoflavones (OR, 0.56; 95% CI, 0.41–0.76; P < .001 for trend), while in women, significant trends were only present for intake of total phytoestrogens from food sources only, with a 34% (OR, 0.66; 95% CI, 0.46–0.96; P = .01 for trend) protective effect for the highest quartile of intake. The apparent benefits of high phytoestrogen intake were evident in both never and current smokers but less apparent in former smokers. In women, statistically significant joint effects were evident between hormone therapy use and phytoestrogen intake. Specifically, high intake of the lignans enterolactone and enterodiol and use of hormone therapy were associated with a 50% (OR, 0.50; 95% CI, 0.31–0.68; P = .04 for interaction) reduction in risk of lung cancer.” (M. R. Spitz, mspitz@mdanderson.org)

Smoking Reduction & Lung Cancer Risk: In those unable to stop smoking, a 50% reduction in cigarettes smoked per day produces a significantly reduced risk of lung cancer, according to a population-based cohort study with up to 31 years of follow-up (pp. 1505-10). Dividing the 19,714 participants into six groups based on their smoking histories, the investigators calculated adjusted hazard ratios for lung cancer of 0.73 among those who were smoking at least 15 cigarettes per day and who reduced consumption by 50% or more, compared with those who continued smoking 15 or more cigarettes. Hazard ratios were 0.44 for light smokers (1–14 cigarettes/day), 0.50 for those who quit, 0.17 for stable ex-smokers, and 0.09 for never smokers. (N. S. Godtfredsen, H:S Hvidovre Hosp., Hvidovre, Denmark; duegodt@dadlnet.dk)

Based on this and the above study, an editorialist comments, “Physicians and other health care professionals should do all they can to help their patients who smoke reduce their risk of getting lung cancer. Total discontinuation of smoking, no matter the age of the patient, will provide the greatest benefit. The most effective interventions to achieve permanent smoking cessation combine pharmacological therapy and referral for intensive behavioral support from a trained counselor. Those patients who cannot quit smoking despite all efforts should be strongly encouraged to cut down on their cigarette consumption as much as possible, since doing so will significantly decrease their risk of lung cancer. Finally, patients should be informed that they may further reduce their risk of developing cancer by adopting a diet rich in fruits and vegetables. Clinicians who actively and aggressively educate their patients and follow up on their efforts to modify their cancer risks will help lessen the great personal suffering and societal burden inflicted by lung cancer.” (L. J. Dacey,
lawrence.j.dacey@dartmouth.edu)

>>>PNN NewsWatch
* Major congenital malformations are 2.2 times as likely with paroxetine as with other antidepressants when taken during the first trimester, FDA and Paxil manufacturer GlaxoSmithKline warned yesterday, adding that alternative treatments should be discussed with women for pregnancy.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 29, 2005 Vol. 12, No. 189
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Sept. 29 issue of the New England Journal of Medicine (content.nejm.org; 2005; 353).

Drotrecogin Alfa in Low-Risk Sepsis: Drotrecogin alfa (activated) should not be used in patients with severe sepsis who have a low mortality risk, based on findings from a study that included patients with single-organ failure or an APACHE II score less than 25 (pp. 1332-41). “Enrollment in the trial was terminated early because of a low likelihood of meeting the prospectively defined objective of demonstrating a significant reduction in the 28-day mortality rate with the use of DrotAA,” the authors report. “The study enrolled 2640 patients and collected data on 2613 (1297 in the placebo group and 1316 in the DrotAA group) at the 28-day follow-up. There were no statistically significant differences between the placebo group and the DrotAA group in 28-day mortality (17.0 percent in the placebo group vs. 18.5 percent in the DrotAA group; P = 0.34; relative risk, 1.08; 95 percent confidence interval, 0.92 to 1.28) or in in-hospital mortality (20.5 percent vs. 20.6 percent; P = 0.98; relative risk, 1.00; 95 percent confidence interval, 0.86 to 1.16). The rate of serious bleeding was greater in the DrotAA group than in the placebo group during both the infusion (2.4 percent vs. 1.2 percent, P = 0.02) and the 28-day study period (3.9 percent vs. 2.2 percent, P = 0.01).” (E. Abraham, U. Colorado Health Sci. Ctr., Denver; edward.abraham@UCHSC.edu)

Referring to DrotAA as activated protein C, an editorialist writes that clinicians continue to refine the optimal use of this expensive agent (pp. 1398-400): “Where do all these clinical trials leave the clinician faced with patients who have severe sepsis—patients in shock requiring vasopressor support and those with acute lung injury and respiratory failure requiring mechanical ventilation who are likely to benefit from activated protein C? In my judgment, the FDA decision in 2001 was correct.... With approval of activated protein C in 2001, the FDA's Jay Siegel wrote that the agency hoped to save lives with this therapy and to ‘gather the information necessary to refine its use further.’ This refinement is under way.” (J. E. Parrillo, U. Med. and Dentistry of N.J., Camden)

Vasodilator Therapy for Severe Aortic Regurgitation: Long-term treatment with nifedipine or enalapril failed to reduce or delay the need for aortic-valve replacement in patients with asymptomatic severe aortic regurgitation and normal left ventricular systolic function, according to authors who analyzed open-label drug therapy in 95 patients (pp. 1342-9). The investigators report, “After a mean of seven years of follow-up, the rate of aortic-valve replacement was similar among the groups: 39 percent in the control group, 50 percent in the enalapril group, and 41 percent in the nifedipine group (P = 0.62). In addition, there were no significant differences among the groups in aortic regurgitant volume, left ventricular size, left ventricular mass, mean wall stress, or ejection fraction. One year after valve replacement, the left ventricular end-diastolic diameter and end-systolic diameter had decreased to a similar degree among the patients who underwent surgery in each of the three groups, and all the patients had a normal ejection fraction.” (A. Evangelista, Hospital Universitari Vall d'Hebron, Barcelona, Spain; aevangel@vhebron.net)

Neuraminidase Inhibitors: In a review, an author assesses the utility of neuraminidase inhibitors for preventing and treating influenza (pp. 1363-73): “Current supplies of neuraminidase inhibitors are inadequate for any proposed strategy for pandemic response, even for the least satisfactory option of treating only the ill. There is little capacity to increase production in the time of need, and therefore anticipatory stockpiling of drugs and the development of efficient distribution methods in case of need are high priorities. In 2005, we have in hand greatly improved tools for surveillance and diagnosis, as well as highly effective drugs, which is a better state of affairs than that during previous influenza pandemics. Identifying feasible strategies for mass production and distribution of these antiviral agents, combined with research into the incidence and mechanisms of drug resistance, may hold the key to our ability to lessen considerably the impact of the next pandemic.” (A. Moscona, anm2047@med.cornell.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.

PNN Pharmacotherapy Line
Sept. 30, 2005 Vol. 12, No. 190
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Oct. issue of Diabetes Care (care.diabetesjournals.org; 2005; 28).

Metformin in Patients with Concomitant HF: In a retrospective analysis of Saskatchewan Health databases from 1991–96, use of metformin was associated with lower morbidity and mortality among patients with type 2 diabetes plus heart failure, compared with sulfonylurea monotherapy (pp. 2345-51). Focusing on 1,833 patients with incident heart failure—selected from 12,272 new users of oral antidiabetic agents—the investigators found, “Average age of subjects was 72 years, 57% were male, and average follow-up was 2.5 ± 2.0 (SD) years. Compared with sulfonylurea therapy, fewer deaths occurred in subjects receiving metformin: 404 (52%) for sulfonylurea monotherapy versus 69 (33%) for metformin monotherapy (hazard ratio [HR] 0.70 [95% CI 0.54–0.91]) and 263 (31%) for combination therapy (0.61 [0.52–0.72]). A reduction in deaths or hospitalizations was also observed: 658 (85%) for sulfonylurea monotherapy versus 160 (77%) for metformin monotherapy (0.83 [0.70–0.99]) and 681 (80%) for combination therapy (0.86 [0.77–0.96]). There was no difference in time to first hospitalization between study groups.” (J. A. Johnson, jeff.johnson@ualberta.ca)

Endocrinologist Support of Primary Care Physicians: Glycemic control among 4,138 patients with type 2 diabetes was improved by a system of endocrinologist feedback provided to internal medicine resident primary care physicians in an academic medical center (pp. 2352-60). Interventions included hard copy computerized reminders with patient-specific recommendations for management at the time of each patient’s visit, individual face-to-face feedback on performance for 5 minutes every 2 weeks, or both. “Over an average patient follow-up of 15 months within the intervention site, improvements in and final HbA1c (A1C) with feedback + reminders (A1C 0.6%, final A1C 7.46%) were significantly better than control (A1C 0.2%, final A1C 7.84%, P < 0.02); changes were smaller with feedback only and reminders only (P = NS vs. control),” the authors report.“ Trends were similar but not significant with systolic blood pressure (sBP) and LDL cholesterol. Multivariable analysis showed that the feedback intervention independently facilitated attainment of American Diabetes Association goals for both A1C and sBP. Over a 2-year period, overall glycemic control improved in the intervention site but did not change in other primary care sites (final A1C 7.5 vs. 8.2%, P < 0.001).” (L. S. Phillips, medlsp@emory.edu)

Hyperglycemia During TPN: During total parenteral nutrition, occurrence of hyperglycemia is a predictor of poor outcomes, regardless of patients’ prior diabetes status, according to a study of 111 individuals receiving 122 treatment courses of TPN (pp. 2367-71). The study notes, “Increased blood glucose levels were associated with an increased risk of cardiac complications (odds ratio 1.61, 95% CI 1.09–2.37, P = 0.02), infection (1.4, 1.08–1.82, P = 0.01), systemic sepsis (1.36, 1.00–1.86, P = 0.05), acute renal failure (1.47, 1.00–2.17, P = 0.05), and death (1.77, 1.23–2.52, P < 0.01).” (N. W. Cheung, Westmead Hosp., Westmead, Australia; wah@westgate.wh.usyd.edu.au)

>>>PNN NewsWatch
* A boxed warning and Medication Guide are on the way for atomoxetine (Strattera), warning of suicidality in children and adolescents taking the ADHD drug, FDA and Lilly announced yesterday. The cautionary notes will be similar to those used with other norepinephrine reuptake inhibitors, which are generally indicated for depression rather than ADHD.

* Consumers are mislead by FDA-sanctioned
health claims that are allowed on food labels, according to a government study. The Center for Science in the Public Interest forced release of the study, access to which it said had previously been denied to the group and several members of Congress. FDA has scheduled a Nov. 17 hearing to review this study along with other relevant research, according to this morning’s Wall Street Journal.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2005, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 800/211-4223 to request missing copies of PNN.