Mar 2006

PNN Quarterly File—First Quarter 2006

PNN Pharmacotherapy Line
Jan. 3, 2006 Vol. 13, No. 1
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 3 issue of the Annals of Internal Medicine (www.annals.org; 2006; 144).

Effects of Childhood Pneumococcal Immunization on Disease in HIV-Infected Adults:
The introduction of the pediatric conjugate vaccine has lowered the rate of invasive pneumococcal disease among HIV-infected adults, report investigators who analyzed laboratory-based surveillance data on 10.8 million adults (pp. 1-9). Focusing on 38,314 individuals living with AIDS, the authors observe: “Of 8582 cases of invasive pneumococcal disease in adults, 2013 (24%) occurred among persons infected with HIV. Between baseline (1998 to 1999) and 2003, the ratio of invasive pneumococcal disease in HIV-infected adults to the number of adults living with AIDS in the surveillance areas decreased from 1127 to 919 cases per 100,000 AIDS population, a reduction of 19% (P = 0.002). Among HIV-infected adults, the ratio for disease caused by pneumococcal serotypes included in the conjugate vaccine decreased 62% (P < 0.001), although the ratio for disease caused by nonvaccine serotypes increased 44% (P < 0.001).” (B. Flannery, bflannery@cdc.gov)

Walking for PAD: Among 417 men and women with peripheral arterial disease, self-directed walking at least three times weekly was linked to significantly less functional decline over the ensuing year (pp. 10-20). “Patients who walked for exercise at least 3 times per week experienced a smaller average annual decline in the usual-paced 4-meter walking velocity (–0.014 m/s per year compared with –0.022 m/s per year for those who walked 1 to 2 times per week and –0.045 m/s per year for nonexercisers; P = 0.005),” report the writers. “Similar findings were observed for the fast-paced 4-meter walk. The subset of asymptomatic patients who walked for exercise 3 or more times per week had annual declines in 6-minute walking performance (P = 0.107), normal-paced walking velocity (P = 0.065), and the summary performance score (P = 0.115); however, these declines were smaller than those observed in asymptomatic participants who walked fewer than 3 times per week.” (M. M. McDermott, mdm608@northwestern.edu)

Protein/Energy Supplements in Older People: Hospitalized, undernourished elderly people have lower mortality and complications when they receive oral nutritional supplements, but routine use of such products in at-home and well-nourished patients is not supported by current evidence, according to a meta-analysis of 55 trials involving 9,187 participants (pp. 37-48). The researchers report: “For patients in short-term care hospitals who were given oral supplements, evidence suggested fewer complications (Peto odds ratio, 0.72 [95% CI, 0.53 to 0.97]) and reduced mortality (Peto odds ratio, 0.66 [CI, 0.49 to 0.90]) for those undernourished at baseline. Few studies reported evidence that suggested any change in mortality, morbidity, or function for those given supplements at home. Ten trials reported gastrointestinal disturbances, such as nausea, vomiting, and diarrhea, with oral supplements.” (A. C. Milne, U. Aberdeen, Aberdeen, Scotland, U.K.; a.c.milne@abdn.ac.uk)

>>>PNN NewsWatch
* A new study, released over the weekend and being published in the Jan. issue of the American Journal of Psychiatry, paints a better safety profile for antidepressants than recent epidemiologic studies indicate. Funded by the National Institute of Mental Health, the evidence shows more favorable outcomes with higher-than-usual drug doses, close monitoring, and frequent dose adjustments.

>>>PNN JournalWatch
* Update in Infectious Diseases, in Annals of Internal Medicine, 2006; 144: 49–56. Reprints: www.annals.org; J. G. Bartlett, Johns Hopkins U., Baltimore, jb@jhmi.edu

* Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss. An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism, in
Circulation, 2005; doi: 10.1161/CIRCULATIONAHA.106.171016. Reprints: circ.ahajournals.org; P. Poirier.

* Thiazolidinediones: The Case for Early Use, in
Diabetes Care, 2006; 29: 154 –7. Reprints: care.diabetesjournals.org; D. M. Kendall, International Diabetes Ctr., Minneapolis; david.kendall@parknicollet.com

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 © 2006, 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
Jan. 4, 2006 Vol. 13, No. 2
Providing news and information about medications and their proper use

>>>FDA Approves Conivaptan For Hyponatremia
An arginine vasopressin antagonist, conivaptan hydrochloride, has been approved by FDA for treatment of euvolemic hyponatremia in hospitalized patients. It will be marketed as Vaprisol by Astellas Pharma US (formerly Fujisawa). FDA also issued an approvable letter for use of the drug in treating hypervolemic hyponatremia.

Conivaptan will be used in hospitalized patients with conditions such as syndrome of inappropriate secretion of antidiuretic hormone, hypothyroidism, adrenal insufficiency, or pulmonary disorders. Conivaptan is contraindicated in patients who have hypovolemic hyponatremia and in those who have hypersensitivity to any of the product’s components. The coadministration of conivaptan with potent CYP 3A4 inhibitors—such as ketoconazole, itraconazole, clarithromycin, ritonavir, and indinavir—is also contraindicated.

Common adverse reactions reported with conivaptan administration include infusion site reactions, hypokalemia, headache, thirst, and vomiting. The majority of the reactions were mild and did not lead to discontinuation of the drug. The use of conivaptan in patients with hepatic impairment (including ascites, cirrhosis, or portal hypertension) has not been systematically evaluated. Conivaptan is not indicated for treatment of patients with congestive heart failure.

In a randomized, double-blind, placebo-controlled study, intravenous administration of conivaptan 40 mg/day for 4 days corrected the balance of sodium and water in hospitalized patients with mild to moderate euvolemic hyponatremia. Significant improvements in serum sodium levels were observed within the first day of treatment with conivaptan. The most common adverse events associated with conivaptan were generally mild and self-limiting infusion site reactions.

Conivaptan therapy begins with a loading dose of 20 mg intravenously followed by 20 mg administered as a continuous infusion over 24 hours. Following the initial day of treatment, conivaptan is administered for an additional 1 to 3 days as a continuous infusion of 20 mg/day. If serum sodium does not rise at the desired rate, conivaptan may be titrated upward to a daily dose of 40 mg.

>>>JAMA Highlights
Source:
Jan. 4 issue of JAMA (www.jama.com; 2006; 295).

Post-MI Arginine: l-Arginine should not be recommended after acute myocardial infarction as it provides no benefits and possibly increases mortality, according to results of the Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) trial (pp. 58-64). In the trial, which was terminated early because of safety concerns, 153 patients with a first ST-segment–elevation MI had these outcomes: “Baseline characteristics, vascular stiffness measurements, and left ventricular function were similar between participants randomized to receive placebo or l-arginine. The mean (SD) age was 60 (13.6) years; of the participants, 104 (68%) were men. There was no significant change from baseline to 6 months in the vascular stiffness measurements or left ventricular ejection fraction in either of the 2 groups, including those 60 years or older and the entire study group. However, 6 participants (8.6%) in the l-arginine group died during the 6-month study period vs none in the placebo group (P = .01). Because of the safety concerns, the data and safety monitoring committee closed enrollment.” (S. P. Schulman, Johns Hopkins Hosp., Baltimore; sschulma@jhmi.edu)

Statins & Cancer Risk: Statins have no effect on cancer risk or cancer death risk, conclude authors who conducted a meta-analysis of 26 randomized controlled trials (pp. 74-80). Finding no type of cancer affected by statin use and no specific agent in this class affecting the risk of cancer, the authors report: “In meta-analyses including 6662 incident cancers and 2407 cancer deaths, statins did not reduce the incidence of cancer (OR, 1.02; 95% CI, 0.97–1.07) or cancer deaths (OR, 1.01; 95% CI, 0.93–1.09). No reductions were noted for any individual cancer type. This null effect on cancer incidence persisted when only hydrophilic, lipophilic, naturally derived, or synthetically derived statins were evaluated.” (C. M. White, Hartford Hosp., Hartford, Conn.; cmwhite@harthosp.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 © 2006, 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
Jan. 5, 2006 Vol. 13, No. 3
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 5 issue of the New England Journal of Medicine (content.nejm.org; 2005; 354).

Rotavirus Vaccines: Two articles and an editorial provide information on new rotavirus vaccines.

A live attenuated G1P[8] human rotavirus vaccine was protective in a Phase III trial without any instances of intussusception, the adverse effect that resulted in the 1999 market withdrawal of a tetravalent rhesus–human reassortant vaccine (RotaShield, Wyeth Laboratories; pp. 11-22). Use of the vaccine or placebo among 63,225 healthy infants in 11 Latin American countries and Finland provided these results: “The efficacy of the vaccine against severe rotavirus gastroenteritis and against rotavirus-associated hospitalization was 85 percent (P < 0.001 for the comparison with placebo) and reached 100 percent against more severe rotavirus gastroenteritis. Hospitalization for diarrhea of any cause was reduced by 42 percent (95 percent confidence interval, 29 to 53 percent; P < 0.001). During the 31-day window after each dose, six vaccine recipients and seven placebo recipients had definite intussusception (difference in risk, –0.32 per 10,000 infants; 95 percent confidence interval, –2.91 to 2.18; P = 0.78).” (M. O'Ryan, U. Chile, Santiago;
moryan@med.uchile.cl)

Similar results followed use of a pentavalent human–bovine (WC3) reassortant rotavirus vaccine in infants aged 6–12 weeks (pp. 23-33): “The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1–G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1–G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1–G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent).” (P. M. Heaton,
penny_heaton@merck.com)

Noting the need for effective and safe rotavirus vaccines around the world, editorialists write (pp. 75-7): “The two reports in the
Journal document these very large trials, conducted before licensure, to demonstrate both the safety and efficacy of these new vaccines against diarrhea, the second most common disease in children. As vaccines become licensed and used in the United States and Europe, we should expect to see a substantial reduction in winter hospitalizations, visits to doctors and clinics, and parents' workdays lost due to childhood diarrhea. With the successful introduction of rotavirus vaccines in industrialized countries, the global health community will be charged with expediting the availability of these lifesaving vaccines at an affordable price in the developing world. After a long period of waiting, the time for a rotavirus vaccine may have finally arrived.” (R. I. Glass, CDC, Atlanta)

Intraperitoneal Treatment of Ovarian Cancer: Intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel proved superior to intravenous administration of the drugs in 415 women with stage III ovarian carcinoma or primary peritoneal carcinoma (pp. 34-43). While completion of six cycles of therapy was poor (42%) among those in the intraperitoneal group, median duration of progression-free survival (18.3 versus 23.8 months) and overall survival (49.7 versus 65.6 months) were significantly improved with that route of administration. (D. Mackey, Gynecologic Oncology Group, Philadelphia; dmackey@gog.org)

DEA & End-of-Life Care: A Perspective article describes the “chilling” effects of Drug Enforcement Administration involvement in clinical decisions involving end-of-life care (pp. 1-3). The article focuses on implications for the upcoming U.S. Supreme Court decision in the Gonzales v. Oregon case. (T. E. Quill, U. Rochester, Rochester, 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 © 2006, 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
Jan. 6, 2006 Vol. 13, No. 4
Providing news and information about medications and their proper use

>>> Psychiatry Highlights
Source:
Jan. issue of the American Journal of Psychiatry (ajp.psychiatryonline.com; 2005; 163).

Real-World SSRI Evaluation: The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study reports real-world, highly generalizable results that closely match those of 8-week clinical efficacy trials of selective serotonin reuptake inhibitors (pp. 28-40). Participants were patients in 23 psychiatric and 18 primary-care settings whose major depressive disorder was treated with flexible doses of citalopram, and responses were measured with the 17-item Hamilton Depression Rating Scale and the 16-item Quick Inventory of Depressive Symptomatology, Self-Report. The investigators report: “Nearly 80% of the 2,876 outpatients in the analyzed sample had chronic or recurrent major depression; most also had a number of comorbid general medical and psychiatric conditions. The mean exit citalopram dose was 41.8 mg/day. Remission rates were 28% (HAM-D) and 33% (QIDS-SR). The response rate was 47% (QIDS-SR). Patients in primary and psychiatric care settings did not differ in remission or response rates. A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment. Participants who were Caucasian, female, employed, or had higher levels of education or income had higher HAM-D remission rates; longer index episodes, more concurrent psychiatric disorders (especially anxiety disorders or drug abuse), more general medical disorders, and lower baseline function and quality of life were associated with lower HAM-D remission rates.” (M. H. Trivdei)

An editorialist writes that this “landmark study” supports the National Institute of Mental Health “vision of developing personalized care” (pp. 5-7): “Personalized care, whether in cancer or depression, will be based on a thorough understanding of risk and resilience of each individual as well as a deep understanding of the pathophysiology of the disorder. By beginning to identify which particular treatment benefits which patient, the STAR*D trial takes us a little closer to realizing this vision for nonpsychotic depression. From Phase 1 it appears that the SSRI citalopram is only sufficient for a minority of patients, particularly high functioning, well-educated women with few comorbid psychiatric or medical problems. Since there was no placebo control group, we do not know how many of these patients would remit without active drug treatment, so even for this 30%, can we be certain of the value of the drug? This trial was not designed to test efficacy of citalopram treatment, for which comparable remission rates with SSRIs in placebo-controlled, 8-week, randomized, controlled trials had already been reported. But the bigger question is how to choose the treatment for the other 70% of patients. With the forthcoming Phase 2 results, we should soon know even more about how to choose treatments for those who do not respond to the first trial of an SSRI.” (T. R. Insel)

Suicidality with Antidepressants: An analysis of 65,103 patients treated with 82,285 courses of antidepressants in 1992–2003 counters concerns about suicidality with newer agents in this class (pp. 41-7). “In the 6 months after the index prescription of antidepressant treatment, 31 suicide deaths (40 per 100,000 treatment episodes) and 76 serious suicide attempts (93 per 100,000) were identified in the study group,” the authors note. “The risk of suicide attempt was 314 per 100,000 in children and adolescents, compared to 78 per 100,000 in adults. The risk of death by suicide was not significantly higher in the month after starting medication than in subsequent months. The risk of suicide attempt was highest in the month before starting antidepressant treatment and declined progressively after starting medication. When the 10 newer antidepressants included in the FDA advisory were compared to older drugs, an increase in risk after starting treatment was seen only for the older drugs.” (G. E. Simon)

>>>PNN NewsWatch
* New-onset or worsened diabetic macular edema, usually accompanied by peripheral edema, is being reported rarely among patients taking rosiglitazone, FDA and GlaxoSmithKline note in alerts to health professionals.

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 © 2006, 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
Jan. 9, 2006 Vol. 13, No. 5
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Jan. 7 issue of BMJ (www.bmj.org; 2006; 332).

PPIs for GERD-Associated Cough: While proton pump inhibitors are effective for cough associated with gastroesophageal reflux disease in some patients, the effect “is less universal than suggested in consensus guidelines on chronic cough and its magnitude of effect is uncertain,” according to a systematic review and meta-analysis of 11 studies (pp. 11-7). “Meta-analysis was limited to five studies in adults that compared proton pump inhibitors with placebo,” write the authors. “All outcomes favoured proton pump inhibitors: the odds ratio for clinical failure (primary outcome) was 0.24 (95% confidence interval 0.04 to 1.27); number needed to treat (NNT) was 5 (harm 50 to infinity to benefit 2.5). For secondary outcomes, the standardised mean difference between proton pump inhibitors and placebo was -0.51 (-1.02 to 0.01) for mean cough score at the end of the trial and -0.29 (-0.62 to 0.04) for change in cough score at the end of the trial. Subgroup analysis with generic inverse variance analysis showed a significant mean change in cough (-0.41 SD units, -0.75 to -0.07).” (A. Chang, Royal Children's Hosp., Herston, Brisbane, Australia; annechang@ausdoctors.net)

Migraine Treatments: New drugs that prevent migraine, acute treatments for these headaches without vascular effects, and new strategies for managing intractable migraine are three unmet needs, advises an author of a review article (pp. 25-9). Focusing on preventive drugs, the writer notes: “On average, two thirds of patients will have a 50% reduction in headache frequency with most preventive drugs. They can then choose between the potential for sleepiness, exercise intolerance, erectile impotence, nightmares, dry mouth, weight gain, tremor, hair loss, or fetal deformities as possible side effects. The fact that migraineurs are prepared to accept such side effects indicates the level of disability they experience. The recent positive results from clinical trials of topiramate show its utility in migraine. [The list of possible medications] shows the range of options for prevention, none of which is ideal.” (P. J. Goadsby, Inst. of Neurology, National Hosp. for Neurology and Neurosurgery, London; peterg@ion.ucl.ac.uk)

>>>Lancet Highlights
Source:
Jan. 7 issue of Lancet (www.thelancet.com; 2006; 367).

Maternal Vitamin D Status and Offspring Bone Calcium: Vitamin D supplementation for pregnant women, especially during winter months, is needed to counteract insufficiency that can lead to poor bone-mineral accrual among offspring during childhood (pp. 36-43). That conclusion is reached in a longitudinal study of 198 children born in 1991-92 who were followed to age 9. The investigators found: “49 (31%) mothers had insufficient and 28 (18%) had deficient circulating concentrations of 25(OH)-vitamin D during late pregnancy. Reduced concentration of 25(OH)-vitamin D in mothers during late pregnancy was associated with reduced whole-body (r = 0.21, p = 0.0088) and lumbar-spine (r = 0.17, p = 0.03) bone-mineral content in children at age 9 years. Both the estimated exposure to ultraviolet B radiation during late pregnancy and the maternal use of vitamin D supplements predicted maternal 25(OH)-vitamin D concentration (p < 0.0001 and p = 0.0110, respectively) and childhood bone mass (p = 0.0267). Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass (p = 0.0286).” (C. Cooper, Southampton General Hosp., Southampton, U.K.; cc@mrc.soton.ac.uk)

>>>PNN JournalWatch
* Clinical Features, Complications, and Outcome in Adults with Pneumococcal Meningitis: A Prospective Case Series, in Lancet Neurology, 2006; DOI:10.1016/S1474-4422(05)70288-X. Reprints: www.thelancet.com; M. S. Penn, Cleveland Clinic Foundation, Cleveland; pennm@ccf.org

* Preconditioning: A New Concept About the Benefit of Exercise, in
Circulation, 2006; 113: e1–e3. Reprints: circ.ahajournals.org; R. J. Domenech, Facultad de Medicina Universidad de Chile, Santiago, Chile; rdomenec@med.uchile.cl

* Pharmacotherapy for Idiopathic Pulmonary Arterial Hypertension During the Past 25 Years, in
Pharmacotherapy, 2006; 26: 68–94. Reprints: www.pharmacotherapy.org; A. M. Hackman, hack0076@umn.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 © 2006, 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
Jan. 10, 2006 Vol. 13, No. 6
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 9 issue of the Archives of Internal Medicine (www.archinternmed.com; 2006; 166).

Emtricitabine for Chronic Hepatitis B: Significant histologic, virologic, and biochemical improvement was observed among 248 patients with chronic HBV, both positive and negative for HBe antigen, during 48 weeks of emtricitabine treatment (pp. 49-56). Comparing the drug with placebo in a 2:1 ratio trial, the investigators noted: “At the end of treatment, 103 (62%) of 167 patients receiving active treatment had improved liver histologic findings vs 20 (25%) of 81 receiving placebo (P < .001), with significance demonstrated in subgroups positive (P < .001) and negative (P = .002) for hepatitis Be (HBe) antigen. Serum HBV DNA readings showed less than 400 copies/mL in 91 (54%) of 167 patients in the emtricitabine group vs 2 (2%) of 81 in the placebo group (P < .001); alanine aminotransferase levels were normal in 65% (109/167) vs 25% (20/81), respectively (P < .001). At week 48, 20 (13%) of 159 patients in the emtricitabine group with HBV DNA measured at the end of treatment had detectable virus with resistance mutations (95% confidence interval, 8%-18%). The rate of seroconversion to anti-HBe (12%) and HBe antigen loss were not different between arms. The safety profile of emtricitabine during treatment was similar to that of placebo. Posttreatment exacerbation of HBV infection developed in 23% of emtricitabine-treated patients.” (F. Rousseau, frank.rousseau@gilead.com)

Editorialists critique this trial, pointing out inadequate sample size and mixing of HBe antigen subtypes, and provide this perspective on emtricitabine (pp. 9-12): “With the advent of newer antiviral agents with significantly lower risk of resistance, emtricitabine on its own will not have a role in the treatment of hepatitis B. Whether the combination of emtricitabine and tenofovir is superior to other approved treatments for hepatitis B remains to be determined. Tenofovir is an antiviral agent that has been approved to treat HIV infection and has antiviral efficacy against wild-type and lamivudine-resistant as well as emtricitabine-resistant HBV. Combination therapies have proven superior to monotherapy in the treatment of HIV and hepatitis C infection. To date, none of the combination therapies evaluated for the treatment of hepatitis B (lamivudine plus standard or peginterferon, lamivudine plus adefovir, and lamivudine plus telbivudine) confer demonstrable advantage over monotherapy.” (A.S.F. Lok,
aslok@umich.edu)

Insurance & TNF-Alpha Inhibitor Therapy: When it comes to choosing between etanercept and infliximab therapy, the type of health coverage a patient has is a significant predictor, with Medicare beneficiaries significantly more likely to receive infliximab, according to an observational cohort study of 1,663 patients with rheumatoid arthritis (pp. 57-63). Using patient records from the National Databank for Rheumatic Diseases, researchers found that the preferential Medicare reimbursement for infusion drugs produced these differences: “Treatment groups who received etanercept and infliximab differed in 6 of 8 demographic variables and in 8 of 10 disease variables. However, stratification by type of insurance reduced many of these differences. In multivariable analyses, type of insurance plan and demographic factors were strong predictors of differential prescribing of etanercept compared with prescribing of infliximab, whereas disease characteristics generally were not. Patients with public insurance were 30% more likely to receive infliximab than those who were privately insured (P < .001).” (E. M. DeWitt, morga073@mc.duke.edu)

>>>PNN NewsWatch
* Published as a supplement to the Jan. issue of Chest, Diagnosis and Management of Cough: Evidence-Based Practice Guidelines provides the American College of Chest Physicians’ best advice. The guidelines strongly recommend that adults up to 65 years old receive a new adult vaccine for pertussis. They also stress that most over-the-counter cough expectorants or suppressants, including cough syrups and cough drops, fail to treat the underlying cause of the cough, instead recommending older antihistamines plus decongestant for acute cough or upper airway cough syndrome (previously named postnasal drip syndrome).

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 © 2006, 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
Jan. 11, 2006 Vol. 13, No. 7
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 11 issue of JAMA (www.jama.com; 2006; 295).

Preventing Shocks from Implanted Defibrillators: Amiodarone is a useful addition to beta-blocker prophylaxis during the first year after patients receive implantable cardioverter defibrillators, reports the OPTIC study (pp. 165-71). Administered to prevent some of the common shocks that occur with ICD implants, these drugs reduced the occurrence of these unpleasant events among 412 patients over a 3-year period, but they did so at the cost of increased drug-related adverse events, the authors report: “Shocks occurred in 41 patients (38.5%) assigned to beta-blocker alone, 26 (24.3%) assigned to sotalol, and 12 (10.3%) assigned to amiodarone plus beta-blocker. A reduction in the risk of shock was observed with use of either amiodarone plus beta-blocker or sotalol vs beta-blocker alone (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.28-0.68; P < .001). Amiodarone plus beta-blocker significantly reduced the risk of shock compared with beta-blocker alone (HR, 0.27; 95% CI, 0.14-0.52; P < .001) and sotalol (HR, 0.43; 95% CI, 0.22-0.85; P = .02). There was a trend for sotalol to reduce shocks compared with beta-blocker alone (HR, 0.61; 95% CI, 0.37-1.01; P = .055). The rates of study drug discontinuation at 1 year were 18.2% for amiodarone, 23.5% for sotalol, and 5.3% for beta-blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients randomized to amiodarone.” (S. J. Connolly, McMaster U., Hamilton, Ont., Canada; connostu@hhsc.ca)

Asking whether all patients ICDs should receive antiarrhythmic drugs, an editorialist writes (pp. 211-3): “Importantly, the OPTIC study applies primarily to ICDs placed as secondary prevention, in which sustained ventricular arrhythmias have been observed clinically. There are less data to support the use of antiarrhythmic agents in patients with prophylactic or primary prevention ICD therapy and this group appears to have less frequent need for such therapy; thus, empirical antiarrhythmic therapy cannot be recommended for this setting. For patients who receive an ICD for secondary prevention, one could argue for empirical initiation of amiodarone or sotalol. As per the OPTIC study, such therapy would reduce the absolute risk of shock by 28% or 14%, respectively, and as such would provide a substantial benefit in comfort and possibly quality of life.” (R. L. Page,
rpage@u.washington.edu)

Diagnosing PE: A simple clinical decision rule combined with D-dimer testing and computed tomography studies provides an effective strategy for evaluating and managing clinically suspected pulmonary embolism, conclude the Christopher Study investigators (pp. 172-9). Based on results from this prospective cohort study of 3,305 consecutive patients with suspected PE, the authors found, “Pulmonary embolism was classified as unlikely in 2206 patients (66.7%). The combination of pulmonary embolism unlikely and a normal D-dimer test result occurred in 1057 patients (32.0%), of whom 1028 were not treated with anticoagulants; subsequent nonfatal VTE occurred in 5 patients (0.5% [95% confidence interval {CI}, 0.2%-1.1%]). Computed tomography showed pulmonary embolism in 674 patients (20.4%). Computed tomography excluded pulmonary embolism in 1505 patients, of whom 1436 patients were not treated with anticoagulants; in these patients the 3-month incidence of VTE was 1.3% (95% CI, 0.7%-2.0%). Pulmonary embolism was considered a possible cause of death in 7 patients after a negative CT scan (0.5% [95% CI, 0.2%-1.0%]). The algorithm was completed and allowed a management decision in 97.9% of patients.” (M. V. Huisman, Leiden U. Med. Ctr., Leiden, the Netherlands; m.v.huisman@lumc.nl)

>>>PNN NewsWatch
* FDA has slated for Feb. 8-9 a public workshop and vendor display on the use of radiofrequency identification to combat counterfeit drugs. The Bethesda, Md., conference will feature technology that can provide reliable electronic records (“e-pedigrees&rdquoWinking that track prescription drugs from the manufacturer to the pharmacist. RFID also could provide for rapid location and distribution of drugs in case of national emergencies.

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 © 2006, 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
Jan. 12, 2006 Vol. 13, No. 8
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 12 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).

Benazepril for Advanced Chronic Renal Insufficiency: In patients without diabetes who have advanced renal insufficiency, the ACE inhibitor benazepril provides “substantial renal benefits,” according to a study of 422 patients (pp. 131-40). During a mean follow-up period of 3.4 years, the researchers observed the following among patients with serum creatinine levels of 1.5-3 mg/dL (group 1) or 3.1-5 mg/dL (group 2): “Of 102 patients in group 1, 22 (22 percent) reached the primary end point, as compared with 44 of 108 patients given benazepril in group 2 (41 percent) and 65 of 107 patients given placebo in group 2 (60 percent). As compared with placebo, benazepril was associated with a 43 percent reduction in the risk of the primary end point in group 2 (P = 0.005). This benefit did not appear to be attributable to blood-pressure control. Benazepril therapy was associated with a 52 percent reduction in the level of proteinuria and a reduction of 23 percent in the rate of decline in renal function. The overall incidence of major adverse events in the benazepril and placebo subgroups of group 2 was similar.” (F. F. Hou, Nanfang Hosp., Guangzhou, China; ffhou@public.guangzhou.gd.cn)

An editorialist focuses on when ACE inhibitor therapy should be stopped or temporarily discontinued once it is begun in those with renal insufficiency (pp. 189-91): “Common sense mandates that an ACE inhibitor (or an angiotensin-receptor blocker) should certainly be discontinued in the presence of uncontrollable hyperkalemia. Such agents should also be halted to see whether an increase in GFR will ensue, possibly averting the need for dialysis until vascular access is adequate or preemptive kidney transplantation can be performed. By demonstrating that ACE inhibitors can be used successfully in patients with advanced chronic kidney disease, Hou et al. suggest that abandoning treatment with an ACE inhibitor (or angiotensin-receptor blocker) when chronic kidney disease progresses to stage 3 or 4 is not necessary and hastens the onset of end-stage renal disease.” (L. A. Hebert, Ohio State U., Columbus)

Inhaled Cyclosporine: Administration of cyclosporine by inhalation improved survival and extended periods of chronic rejection-free survival among 58 patients with lung transplants, but rates of acute rejection were not significantly different than with placebo (pp. 141-50). Beginning within 6 weeks after transplantation, aerosol cyclosporine 300 mg or placebo was administered 3 days per week for 2 years, with these results: “The rates of acute rejection of grade 2 or higher were similar in the cyclosporine and placebo groups: 0.44 episode (95 percent confidence interval, 0.31 to 0.62) vs. 0.46 episode (95 percent confidence interval, 0.33 to 0.64) per patient per year, respectively (P=0.87 by Poisson regression). Survival was improved with aerosolized cyclosporine, with 3 deaths among patients receiving cyclosporine and 14 deaths among patients receiving placebo (relative risk of death, 0.20; 95 percent confidence interval, 0.06 to 0.70; P = 0.01). Chronic rejection-free survival also improved with cyclosporine, as determined by spirometric analysis (10 events in the cyclosporine group and 20 events in the placebo group; relative risk of chronic rejection, 0.38; 95 percent confidence interval, 0.18 to 0.82; P = 0.01) and histologic analysis (6 vs. 19 events, respectively; relative risk, 0.27; 95 percent confidence interval, 0.11 to 0.67; P = 0.005). The risks of nephrotoxic effects and opportunistic infection were similar for patients in the cyclosporine group and the placebo group.” (A. T. Iacono, aiacono@medicine.umaryland.edu)

>>>PNN NewsWatch
* FDA has scheduled a media teleconference for this morning “to discuss an important new initiative to advance the earliest phases of clinical research,” and the Wall Street Journal is reporting that the agency will announce new manufacturing standards for making small batches of experimental drugs. Revised requirements could enable academic researchers to manufacture agents without meeting standards that are more applicable to industrial laboratories.

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 © 2006, 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
Jan. 13, 2006 Vol. 13, No. 9
Providing news and information about medications and their proper use

>>>Pharmacotherapy Update
Source:
Jan. issue of Pharmacotherapy (www.pharmacotherapy.org; 2006; 26).

Antibiotics & Bioterrorism: Based on effectiveness considerations, susceptibility patterns, and relative costs, doxycycline should be the agent of first choice in managing bioterrorism pathogens such as anthrax, plague, tularemia, Q fever, and brucellosis, conclude authors of a special article (pp. 3-14). Using an evidence-based approach to gather information about this agent and the fluoroquinolones, the investigators found: “Little published data are available on these pathogens, and much of the data are from studies that used older strains obtained from patient or animal sources in outbreaks decades ago. Doxycycline appears to show comparable minimum inhibitory concentrations to those of the fluoroquinolone class in most clinical and in vitro studies, perhaps with the exception of inhalation plague. Studies also suggest that development of antibiotic resistance is less likely to occur with doxycycline. Doxycycline is several-fold less expensive than most fluoroquinolones and appears to have similar efficacy in most scenarios based on clinical case studies and established Clinical and Laboratory Standards Institute (formerly known as the National Committee for Clinical Laboratory Standards) breakpoints for staphylococci. Therefore, doxycycline should be considered as a first-line antibiotic in the management of bioterrorism agents.” (C. M. Terriff, Deaconess Med. Ctr., Spokane, Wash.; terrifc@empirehealth.org)

Urokinase v. rt-PA for Peripheral Arterial Occlusion: Recombinant tissue plasminogen activator is a reasonable substitute for urokinase, which has been withdrawn from the U.S. market, for treating patients with peripheral arterial occlusion, according to a systematic review and meta-analysis (pp. 34-43). The authors report: “The primary outcome measure was successful complete lysis of the occlusion. Other outcome measures were hemorrhage (major, minor, or combined), intracranial hemorrhage, limb loss, and mortality. Six trials were identified, five of which were randomized. On meta-analysis, the rate of clot lysis was higher with rt-PA than with urokinase (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.12-2.10, p = 0.007). However, urokinase was associated with lower rates of minor (OR 0.52, 95% CI 0.28-0.97, p = 0.04) and total (OR 0.51, 95% CI 0.29-0.91, p = 0.02) bleeding. Rates of major hemorrhage, intracranial hemorrhage, limb loss, and mortality were similar between agents.” (C. I. Coleman, Hartford Hosp., Hartford, Conn.; ccolema@harthosp.org)

Pediatric Influenza: While antiviral agents are safe and effective for treatment and prophylaxis of influenza in pediatric patients, they are no substitute for an annual influenza vaccination, conclude authors of a review article (pp. 95-103). Transmission among children is common, the authors note, and annual infection rates in preschool and school-aged children are 15% to 42%. (L. S. Eiland, eilanls@auburn.edu)

>>>PNN NewsWatch
* FDA is warning professionals and patients that many foreign medications, although marketed under the same or similar-sounding brand names as those in the United States, contain different active ingredients. From a long list of potential problems posted on the Web as a public health advisory, the agency highlighted two examples in a news release: "Flomax" is a U.S. brand name for the prostate drug tamsulosin, while in Italy, the active ingredient in the product called "Flomax" is morniflumate, an anti-inflammatory drug. "Norpramin" in the U.S. contains the antidepressant desipramine, but in Spain, "Norpramin" contains the PPI omeprazole.

* At
FDA’s request, U.S. Marshals yesterday seized five unlabeled boxes allegedly containing various quantities of a dietary supplement product containing ephedrine alkaloids, Lipodrene, from ATF Fitness Products, Inc., in Oakmont, Penn., the agency reported in a news release. Each bottle of Lipodrene contained 100 tablets and was labeled with the recommended daily serving of 50 mg of ephedrine alkaloids. The agency said the seized products are valued at approximately $16,000.

*
PNN will not be published on Mon., Jan 16, M. L. King 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 © 2006, 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
Jan. 17, 2006 Vol. 13, No. 10
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2006; 332).

Impact of Warfarin Bleeds on Physicians: While not affected by adverse events possibly associated with warfarin underuse, physicians are significantly more likely to reduce their prescribing of the drug following bleeding events in patients with atrial fibrillation taking oral anticoagulants, according to a population-based, matched-pair, before and after analysis from Ontario (doi: 10.1136/bmj.38698.709572.55). Using prescribing patterns for ACE inhibitors as a control, the investigators found: “For the 530 physicians who had a patient with an adverse bleeding event (exposure) and who treated other patients with atrial fibrillation during the 90 days before and the 90 days after the exposure, the odds of prescribing warfarin was 21% lower for patients after the exposure (adjusted odds ratio 0.79, 95% confidence interval 0.62 to 1.00). Greater reductions in warfarin prescribing were found in analyses with patients for whom more time had elapsed between the physician's exposure and the patient's treatment. There were no significant changes in warfarin prescribing after a physician had a patient who had a stroke while not on warfarin or in the prescribing of ACE inhibitors by physicians who had patients with either bleeding events or strokes.” (N. K. Choudhry, nchoudhry@partners.org)

Acetylcysteine & Contrast-Associated Nephropathy: The consistency of systematic reviews on a single topic—role of acetylcysteine in prevention of contrast-associated nephropathy—is assessed in a study that focuses on predictors and correlates of quality of reporting of meta-analysis (QUORUM) scores (doi: 10.1136/bmj.38693.516782.7C). “10 systematic reviews, published August 2003 to March 2005, were included,” the authors explain. “Nine pooled events despite heterogeneity and five recommended routine use of acetylcysteine, whereas the remaining studies called for further research. Compliance with the 18 items on the QUOROM checklist was relatively high (median 16, range 11 to 17), although shorter manuscripts had significantly lower scores (R = 0.73; P = 0.016). Reviewers who reported previous not for profit funding were more likely to score higher on the Oxman and Guyatt quality index. No association was found between QUOROM and Oxman and Guyatt scores (R = -0.06; P = 0.86), mainly because of greater emphasis of the Oxman and Guyatt scores on the appraisal of bias in selection and validity assessment (inadequate in five reviews).” (G. G. L. Biondi-Zoccai, Policlinico San Donato, San Donato Milanese, Italy; gbiondizoccai@gmail.com)

>>>Lancet Highlights
Source:
Jan. 14 issue of Lancet (www.thelancet.com; 2006; 367).

Controversies in Depression Treatment: “Moral panic” is contributing undue concerns among patients and professionals, conclude authors who review the past 5 years’ developments in depression research (pp. 153-67). They write: “Increasingly detailed knowledge about impairment of information processing in depression is being supplemented by quantitative studies of the brain processes underlying these impairments. Most patients improve with present treatments. The mechanisms of action of antidepressants are not fully understood; the hypothesis that reversing hippocampal cell loss in depression may be their active principle is a fascinating new development. Moral panic about the claim that antidepressant serotonin reuptake inhibitors cause patients to commit suicide and become addicted to their medication may have disconcerted the public and members of the medical profession.” (K. P. Ebmeier, U. Edinburgh, Edinburgh, U. K.; k.ebmeier@ed.ac.uk)

>>>PNN JournalWatch
* Gastro-oesophageal Reflux Disease, in BMJ, 2006; 332: 88-93. Reprints: www.bmj.org; I. Forgacs, King’s Coll. Hosp., London; ian.forgacs@kcl.ac.uk

* Chronic Daily Headache, in
New England Journal of Medicine, 2006; 354: 158-65. Reprints: content.nejm.org; D. W. Dodick, dodick.david@mayo.edu

* Treatment of Acute Lymphoblastic Leukemia,
New England Journal of Medicine, 2006; 354: 166-78. Reprints: content.nejm.org; C-H Pui, ching-hon.pui@stjude.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 © 2006, 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
Jan. 18, 2006 Vol. 13, No. 11
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 17 issue of the Annals of Internal Medicine (www.annals.org; 2006; 144).

Genotyping H. pylori for Clarithromycin Resistance: A point mutation, A2143G, is associated with a reduced eradication rate when clarithromycin is used in Helicobacter pylori infections, report authors who assessed 156 patients at two Italian hospitals (pp. 94-100). Seven-day triple therapy eradicated the organism in 14 of 15 (93%) of patients harboring A2142G or A2142C strains but only 11 of 23 patients (48%) whose H. pylori carried the A2143G mutation. In these patients, a sequential regimen of rabeprazole plus amoxicillin followed by triple therapy with clarithromycin achieved a higher cure rate. (E. Ierardi, U. Foggia, Foggia, Italy; e.ierardi@virgilio.it)

Tamoxifen for Nonmalignant Retroperitoneal Fibrosis: A small observational study of 19 patients with nonmalignant retroperitoneal fibrosis reports positive results with tamoxifen (pp. 101-6). “Fifteen patients reported substantial resolution of symptoms after a median treatment duration of 2.5 weeks,” the authors write. “Erythrocyte sedimentation rate and C-reactive protein also improved. Gallium scanning at follow-up showed incomplete disappearance of pathologic gallium-67 activity. Repeated CT scanning showed slow but steady mass regression in 14 of 15 clinical responders. Five patients failed treatment, including 1 patient who improved clinically. Disease recurred in 1 patient who responded to reintroduction of tamoxifen. One patient developed reversible hepatitis.” (E. F. H. van Bommel, Albert Schweitzer Hosp., Dordrecht, the Netherlands; e.f.h.vanbommel@asz.nl)

Systems Approach to ‘Problem Doctors’: While acknowledging that “monitoring and ensuring acceptable physician performance must occur at the local level,” two leaders in the patient safety movement call on national organizations to develop a systems approach that can be implemented by hospitals (pp. 107-15). The effort would have three goals, the authors note: “Develop standards and measures for annual data-based assessment of physician performance and require that they be implemented by all hospitals, launch a major effort to develop better measures of competence and behavior, and develop more state and regional centers for assessment and remediation of physicians with performance deficiencies.” (L. L. Leape, leape@hsph.harvard.edu)

>>>JAMA Highlights
Source:
Jan. 18 issue of JAMA (www.jama.com; 2006; 295).

100,000 Lives: Preventing adverse drug events and central-line infections are two of five interventions that form the heart of the 100,000 Lives Campaign, a national initiative with a goal of saving 100,000 lives among hospitalized patients by June 14 of this year (pp. 324-7). An effort launched by the Institute of Healthcare Improvement in Dec. 2004, the campaign also calls for deployment of rapid response teams before patients code, provision of evidence-based care for acute myocardial infarction, and prevention of surgical site infections. (D. M. Berwick, Inst. for Healthcare Improvement, Cambridge, Mass., dberwick@ihi.org)

Off-Label Factor VIIa Use: Most of the thromboembolic events reported with recombinant human coagulation factor VIIa involved patients being treated for off-label uses, according to data from FDA’s Adverse Event Reporting System database (pp. 293-8): “Unlabeled indications accounted for 151 of [168] reports [describing 185 events], most with active bleeding (n = 115). Reported AEs were thromboembolic cerebrovascular accident (n = 39), acute myocardial infarction (n = 34), other arterial thromboses (n = 26), pulmonary embolism (n = 32), other venous thromboses (including deep vein thrombosis) (n = 42), and clotted devices (n = 10). In 36 (72%) of 50 reported deaths, the probable cause of death was the thromboembolic event. In 144 patients with timing information, 73 events (52%) occurred in the first 24 hours after the last dose (30 events within 2 hours). Sixty-four reports (38%) noted concomitant use of hemostatic agents. Most reports lacked sufficient information to evaluate potential dosage associations.” (K. A. O’Connell, connellk@cber.fda.gov">oconnellk@cber.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 © 2006, 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
Jan. 19, 2006 Vol. 13, No. 12
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 19 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).

Hypertonic Saline in Cystic Fibrosis: Hypertonic saline inhalation after a bronchodilator is an “inexpensive, safe, and effective additional therapy for patients with cystic fibrosis,” according to results of a 164-patient trial (pp. 229-40). Study participants, all of whom were at least 6 years old, inhaled their usual bronchodilator followed by 4 mL of either hypertonic (7%) or normal (0.9%) saline twice daily for 48 weeks. The authors report: “The primary outcome measure, the rate of change (slope) in lung function (reflected by the forced vital capacity [FVC], forced expiratory volume in one second [FEV1], and forced expiratory flow at 25 to 75 percent of FVC [FEF25–75]) during the 48 weeks of treatment, did not differ significantly between groups (P = 0.79). However, the absolute difference in lung function between groups was significant (P = 0.03) when averaged across all post-randomization visits in the 48-week treatment period. As compared with the control group, the hypertonic-saline group had significantly higher FVC (by 82 ml; 95 percent confidence interval, 12 to 153) and FEV1 (by 68 ml; 95 percent confidence interval, 3 to 132) values, but similar FEF25–75 values. The hypertonic-saline group also had significantly fewer pulmonary exacerbations (relative reduction, 56 percent; P = 0.02) and a significantly higher percentage of patients without exacerbations (76 percent, as compared with 62 percent in the control group; P = 0.03). Hypertonic saline was not associated with worsening bacterial infection or inflammation.” (P. T. P. Bye, Royal Prince Alfred Hosp., Camperdown, Australia; peterb@med.usyd.edu.au)

An editorialist explores the possible mechanisms by which hypertonic saline produces benefits in cystic fibrosis (pp. 291-3): “Previous studies in a small number of patients with cystic fibrosis showed that inhalation of hypertonic saline increased mucociliary transport. Even though hypertonic saline could potentially increase the amount of airway surface liquid, it was thought that this effect should be rather short-lived, since sodium applied to the epithelial surface would rapidly be taken up through active transport mechanisms. In this issue of the Journal, [a study of mucus clearance and lung function] demonstrate[s] that this assumption is probably incorrect, since the administration of hypertonic saline not only had a prolonged effect on the amount of airway surface liquid in epithelial cells from patients with cystic fibrosis in vitro but also resulted in a sustained improvement of mucociliary transport. Although the exact mechanism of the prolonged action remains to be elucidated, these observations suggest that inhaled hypertonic saline may indeed be a therapeutic option for increasing the volume of airway surface liquid in patients with cystic fibrosis.” (F. Ratjen, U. Toronto, Toronto)

HIV Treatments: In a 48-week, open-label trial, tenofovir disoproxil fumarate, emtricitabine, and efavirenz once daily fulfilled noninferiority criteria as compared with a regimen of fixed-dose zidovudine and lamivudine twice daily plus efavirenz once daily (pp. 251-60). “Significantly more patients in the tenofovir–emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine–lamivudine group (84 percent vs. 73 percent, respectively; 95 percent confidence interval for the difference, 4 to 19 percent; P = 0.002),” the investigators write. “This difference excludes the inferiority of the tenofovir DF, emtricitabine, and efavirenz regimen, indicating a significantly greater response with this regimen.” (J. E. Gallant, Johns Hopkins U., Baltimore; jgallant@jhmi.edu)

>>>PNN NewsWatch
* FDA yesterday issued a final rule that includes the first major revision to the content and format of product labeling (package inserts) in a quarter century. Clearer and more concise language will convey information using a more easily read format, the agency said. The new label will start with a half-page Highlights section with boxed warnings, indications and usage, and dosage and administration. Drug interactions and patient counseling sections will also be added.

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 © 2006, 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
Jan. 20, 2006 Vol. 13, No. 13
Providing news and information about medications and their proper use

>>>Chest Highlights
Source:
Jan. issue of Chest (www.chestjournal.org; 2006; 129).

Salmeterol for Asthma: Clinical results from SMART, the Salmeterol Multicenter Asthma Research Trial, confirm previous reports of small but statistically significant increases in respiratory-related and asthma-related deaths in patients using the drug, with problems especially evident among blacks (pp. 15-26). The 28-week trial, terminated after interim analysis of 26,355 participants, showed the following: “The occurrence of the primary outcome, respiratory-related deaths, or life-threatening experiences was low and not significantly different for salmeterol vs placebo (50 vs 36; relative risk [RR] = 1.40; 95% confidence interval [CI], 0.91 to 2.14). There was a small, significant increase in respiratory-related deaths (24 vs 11; RR, 2.16; 95% CI, 1.06 to 4.41) and asthma-related deaths (13 vs 3; RR, 4.37; 95% CI, 1.25 to 15.34), and in combined asthma-related deaths or life-threatening experiences (37 vs 22; RR, 1.71; 95% CI, 1.01 to 2.89) in subjects receiving salmeterol vs placebo. The imbalance occurred largely in the African-American subpopulation: respiratory-related deaths or life-threatening experiences (20 vs 5; RR, 4.10; 95% CI, 1.54 to 10.90) and combined asthma-related deaths or life-threatening experiences (19 vs 4; RR, 4.92; 95% CI, 1.68 to 14.45) in subjects receiving salmeterol vs placebo.” (P. M. Dorinsky, paul.m.dorinsky@gsk.com)

High-Dose Formoterol: Asthma exacerbations occurred no more frequently with formoterol doses of 24 mcg twice daily than with lower doses of the drug taken with or without extra, as-needed doses (pp. 27-38). About 2,085 study participants aged 12 years or older with stable persistent asthma, the authors wrote, “Nine patients had respiratory-related serious adverse events (SAEs) requiring hospitalization: two patients (0.4%) in the 24-mcg-bid group; one patient (0.2%) in the 12-mcg-bid plus on-demand group; five patients (0.9%) in the 12-mcg-bid group; and one patient (0.2%) in the placebo group. All of these events were asthma related, except for two SAEs in the 12-mcg-bid group that were later considered not to be asthma related by independent reviewers who were not associated with the conduct of the study.” (J. Wolfe, Allergy and Asthma Associates of Santa Clara Valley Res. Ctr., San Jose, Calif.; aaascv@asthmaresearch.com)

Fish Oil Supplements for Exercise-Induced Asthma: In 16 asthmatic patients with exercise-induced bronchospasm, fish oil supplementation improved pulmonary function significantly, compared with placebo (pp. 39-49). For 3 weeks, participants daily took either placebo capsules or fish oil capsules containing eicosapentaenoic acid 3.2 g and docosahexaenoic acid 2.0 g, with these results: “On the normal and placebo diet, subjects exhibited EIB. However, the fish oil diet improved pulmonary function to below the diagnostic EIB threshold, with a concurrent reduction in bronchodilator use. Induced sputum differential cell count percentage and concentrations of [leukotriene (LT) C4-LTE4], [prostaglandin D2], [interleukin 1-beta], and TNF-alpha were significantly reduced before and following exercise on the fish oil diet compared to the normal and placebo diets. There was a significant reduction in LTB4 and a significant increase in LTB5 generation from activated [polymorphonuclear leukocytes] on the fish oil diet compared to the normal and placebo diets.” (T. D. Mickleborough, tmickleb@indiana.edu)

Cilomilast for COPD: Among patients with chronic obstructive pulmonary disorder, the phosphodiesterase 4 inhibitor cilomilast maintained pulmonary function, improved health status, and reduced the rate of COPD exacerbations during a 24-week trial (pp. 56-66; S. I. Rennard, srennard@unmc.edu)

>>>PNN NewsWatch
* FDA yesterday updated the product labeling for topical pimecrolimus (Elidel Cream) and tacrolimus (Protopic Ointment) to include a boxed warning about a possible risk of cancer, a Medication Guide, and a clarification that these eczema drugs are second-line treatments.

* Some
Accu-Chek Aviva Meters (Roche Diagnostics) are being recalled worldwide because of electronic malfunctions.

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 © 2006, 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
Jan. 23, 2006 Vol. 13, No. 14
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release article from the Lancet (www.thelancet.com; 2006; 367).

Antivirals for Influenza: In addition to calling for a moratorium on use of amantadine and rimantadine, authors of a review article recommend that the neuraminidase inhibitors be reserved for “a serious epidemic or pandemic” of influenza (DOI: 10.1016/
S0140-6736(06)67970-1). The authors write: “In prophylaxis, compared with placebo, neuraminidase inhibitors have no effect against influenza-like illness (1.28, 0.45-3.66 for oral oseltamivir 75 mg daily, 1.51, 0.77-2.95 for inhaled zanamivir 10 mg daily). Higher doses appear to make no difference. The efficacy of oral oseltamivir 75 mg daily against symptomatic influenza is 61% (15-82), or 73% (33-89) at 150 mg daily. Inhaled zanamivir 10 mg daily is 62% efficacious (15-83). Neither neuraminidase inhibitor appeared effective against asymptomatic influenza. Oseltamivir induces nausea (OR 1.79, 1.10-2.93), especially at higher prophylactic doses (2.29, 1.34-3.92). Oseltamivir in a post-exposure prophylaxis role has a protective efficacy of 58.5% (15.6-79.6) for households and from 68% (34.9-84.2) to 89% (67-97) in contacts of index cases. In influenza cases, compared with placebo the hazard ratios for time to alleviation of symptoms were 1.33, 1.29-1.37 for zanamivir; 1.30, 1.13-1.50 for oseltamivir provided medication was started within 48 h of symptom onset. Viral nasal titres were significantly diminished by both drugs (weighted mean difference -0.62, -0.82 to -0.41). Oseltamivir at 150 mg daily was effective in preventing lower respiratory tract complications in influenza cases (OR 0.32, 0.18-0.57). We could find no credible data on the effects of oseltamivir on avian influenza.” (T. Jefferson, Cochrane Vaccines Field, Alessandria, Italy;
Toj1@aol.com)

>>>BMJ Highlights
Source:
Early-release article from BMJ (www.bmj.org; 2006; 332).

H. pylori Eradication: Community screening and eradication of Helicobacter pylori is a feasible strategy but one whose costs must be balanced against benefits, conclude authors who tested screening programs in seven general practices in southwest England (doi: 10.1136/bmj.38702.662546.55). In all, 10,537 unselected people were tested using the carbon-13 urea breath test; 1,558 of 1,636 participants who tested positive were randomized to treatment with ranitidine bismuth citrate 400 mg plus clarithromycin 500 mg twice daily for 2 weeks or placebo. “In the eradication group, 35% fewer participants consulted for dyspepsia over two years compared with the placebo group (55/787 v 78/771; odds ratio 0.65, 95% confidence interval 0.46 to 0.94; P = 0.021; number needed to treat 30) and 29% fewer participants had regular symptoms (odds ratio 0.71, 0.56 to 0.90; P = 0.05),” the authors found. “[National Health Service] costs were £84.70 (£74.90 to £93.91) greater per participant in the eradication group over two years, of which £83.40 ($146; 121 euros) was the cost of eradication treatment. No difference in quality of life existed between the two groups.” (J. A. Lane, U. Bristol, Bristol, U.K.; Athene.lane@bristol.ac.uk)

>>>PNN NewsWatch
* The Annals of Internal Medicine on Friday released early an article detailing cases of serious hepatotoxicity in three patients taking telithromycin. FDA responded by advising that patients on the antibiotic be monitored for changes in liver function and drug treatment be stopped in those with signs of problems.

>>>PNN JournalWatch
* Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men: A Sex-Specific Meta-analysis of Randomized Controlled Trials, in JAMA, 2006; 295: 306-13. Reprints: www.jama.com; D. L. Brown, david.brown@stonybrook.edu

* Estrogen Carcinogenesis in Breast Cancer, in
New England Journal of Medicine, 2006; 354: 270-82. Reprints: content.nejm.org; J. D. Yager, Johns Hopkins Bloomberg School of Public Health, Baltimore; jyager@jhsph.edu

* Immunotherapy for Fungal Infections, in
Clinical Infectious Diseases, 2006; 42: 507-15. Reprints: www.journals.uchicago.edu/CID; B. H. Segal, Roswell Park Cancer Ins., Buffalo, N.Y.; brahm.segal@roswellpark.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 © 2006, 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
Jan. 24, 2006 Vol. 13, No. 15
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Jan. 23 issue of Archives of Internal Medicine (www.archinternmed.com; 2006; 166).

Adverse Effects in Placebo Groups: The high frequency of and wide divergence in reports of adverse effects reported by patients taking placebo during clinical trials is an area of concern for clinicians and researchers, conclude authors of a review article (pp. 155-60). Focusing on randomized, placebo-controlled trials of statins published since 1992 and with sample sizes greater than 100, the investigators found, “Overall, 4% to 26% of patients in the control groups of large trials of statin drugs discontinued placebo use because of perceived adverse effects. The symptom rate in placebo groups varied substantially across trials (up to a ratio of 13:1 for possibly drug-related symptoms, eg, headache, 0.2%-2.7%, or abdominal pain, 0.9%-3.9%) and were often markedly lower than those found in the general population (eg, fatigue, 1.9%-3.4%) in trials of statin drugs vs 17.7% in the general population.”

The authors conclude by calling for greater attention and effort to sort out perceived from real adverse effects: “Adverse effects have a major role for drug use discontinuation in research and in clinical practice. Improved assessment of adverse effects should help to better estimate risk-benefit ratios of drugs and to advise patients more properly. Adverse effect assessment should be done with the same accuracy as efficacy assessment.” (W. Rief, Philipps U., Marburg, Germany;
rief@staff.uni-marburg.de)

Osteoporotic Fractures & Warfarin Therapy: Especially among men with atrial fibrillation, long-term warfarin therapy was linked to occurrence of osteoporotic fractures in a retrospective cohort study of Medicare beneficiaries in 1998-99 (pp. 241-6-). Adding that beta-blockers may be protective against fractures, the investigators report: “Compared with 7587 patients who were not prescribed warfarin, the adjusted odds ratio (OR) of fracture was 1.25 (95% confidence interval [CI], 1.06-1.48) in 4461 patients prescribed long-term warfarin therapy (1 year). The association between osteoporotic fracture and long-term warfarin use was significant in men (OR, 1.63; 95% CI, 1.26-2.10) but nonsignificant in women (OR, 1.05; 95% CI, 0.88-1.26). In 1833 patients prescribed warfarin for less than a year, the risk of osteoporotic fracture was not increased significantly (OR, 1.03). Odds ratios (95% CIs) of independent predictors of osteoporotic fractures were as follows: increasing age, 1.63 (1.47-1.80) per decade; high fall risk, 1.78 (1.42-2.21); hyperthyroidism, 1.77 (1.16-2.70); neuropsychiatric disease, 1.51 (1.28-1.78); and alcoholism, 1.50 (1.01-2.24). Factors with a reduced OR (95% CI) included African American race, 0.30 (0.18-0.51); male sex, 0.54 (0.46-0.62); and use of beta-adrenergic antagonists, 0.84 (0.70-1.00).” (B. F. Gage, Washington U., St. Louis; bgage@im.wustl.edu)

PDE-5 Inhibition in Raynaud Disease: Phosphodiesterase type 5 inhibition improved peripheral blood flow and clinical symptoms in a large subset of patients with Raynaud disease in an open-label pilot study of 40 patients (pp. 231-30). Based on treatment with vardenafil, investigators report, “Laser-Doppler flowmetry revealed that vardenafil improved digital blood flow in 28 (70%) patients, whereas 12 (30%) did not respond. In individuals responding, digital blood flow significantly increased by a mean ± SEM of 21.0% ± 4.9% and 30.0% ± 5.7% at 1 hour and 2 weeks of treatment at room temperature, respectively, and by 18.8% ± 4.4% and 35.1% ± 7.5% at 1 hour and 2 weeks during the cold-exposure test, respectively (P < .01 for all). Consistently, clinical symptoms improved in 27 (68%) of the 40 patients, and the Raynaud condition score declined from a mean ± SEM of 5.05 ± 0.38 to 3.54 ± 0.31 (P < .001).” (S. Rosenkranz, Universität zu Köln, Köln, Germany; stephan.rosenkranz@uk-koeln.de)

Acetylcysteine & Contrast-Induced Nephropathy: The process by which research evidence accumulates and the possibility that alternative approaches could result in more clinically useful and definitive conclusions are explored in a case study of the use of acetylcysteine in prevention of contrast-induced nephropathy (pp. 161-6; W. A. Ghali, wghali@ucalgary.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 © 2006, 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
Jan. 25, 2006 Vol. 13, No. 16
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 25 issue of JAMA (www.jama.com; 2006; 295).

Omega-3 Fatty Acids & Cancer Risk: No significant association of omega-3 fatty acid intake and cancer incidence was identifiable in a systematic review of 38 articles (pp. 403-15). Concluding that “dietary supplementation with omega-3 fatty acids is unlikely to prevent cancer,” the authors write: “Across 20 cohorts from 7 countries for 11 different types of cancer and using up to 6 different ways to categorize omega-3 fatty acid consumption, 65 estimates of the association between omega-3 fatty acid consumption were reported. Among these, only 8 were statistically significant. The high degree of heterogeneity across these studies precluded pooling of data. For breast cancer 1 significant estimate was for increased risk (incidence risk ratio [IRR], 1.47; 95% confidence interval [CI], 1.10-1.98) and 3 were for decreased risk (RR, 0.68-0.72); 7 other estimates did not show a significant association. For colorectal cancer, there was 1 estimate of decreased risk (RR, 0.49; 95% CI, 0.27-0.89) and 17 estimates without association. For lung cancer one of the significant associations was for increased cancer risk (IRR, 3.0; 95% CI, 1.2-7.3), the other was for decreased risk (RR, 0.32; 95% CI, 0.13-0.76), and 4 other estimates were not significant. For prostate cancer, there was 1 estimate of decreased risk (RR, 0.43; 95% CI, 0.22-0.83) and 1 of increased risk (RR, 1.98; 95% CI, 1.34-2.93) for advanced prostate cancer; 15 other estimates did not show a significant association. The study that assessed skin cancer found an increased risk (RR, 1.13; 95% CI, 1.01-1.27). No significant associations between omega-3 fatty acid consumption and cancer incidence were found for aerodigestive cancer, bladder cancer, lymphoma, ovarian cancer, pancreatic cancer, or stomach cancer.” (C. H. MacLean, maclean@rand.org)

Biomedical Patents: “The thorny balance between protecting the intellectual property rights of companies and the sometimes competing needs of patients” is illustrated by recent controversies with regard to AIDS drugs, oseltamivir, and torcetrapib, note authors of a commentary (pp. 434-7). Asking whether the principles of eminent domain can be applied to biomedical patents, the authors conclude, “For better or worse, most of current therapeutics is based on private ownership of pharmaceutical discoveries, even if the origin of those therapies is based on publicly funded university-based research. Advocates of such ownership argue that it is necessary for the public good of new drug development. In some circumstances, however, this ownership may jeopardize another widely regarded public good, namely the right of those who are ill to have access to lifesaving medicine or other health care services. A stark choice arises if these two public goods are irreconcilable: ‘When free enterprise and the freedom to live clash, which freedom will we limit?’ While the role of eminent domain in this context is a legal question, application of this authority is an inherently political decision, as Kelo v New London [the 2005 U.S. Supreme Court decision permitting government to take over private property for redevelopment] (and its contentious aftermath) make clear.” (A. S. Kesselheim, akesselheim@partners.org)

Post-Katrina Health Policy: Concluding that “the notion that the world's most powerful nation would continue to lurch from disaster to disaster, jury-rigging inadequate and temporary solutions, is simply untenable,” a commentary author provides this premise for action (pp. 437-40): “Hurricane Katrina exposed a health care system incapable of withstanding the long-term impact of a major disaster. Through destruction and permanent displacement, Katrina illuminated the fundamental weaknesses inherent in the national approach to health care financing, as well as the extent to which these weaknesses can threaten recovery. Yet almost from the moment that health care emerged as a major issue, a battle rapidly ensued over the appropriate scope of the response. Now, several months after this disaster, prospects are increasingly dim that this catastrophic event will yield at least modest improvements in the national policy arsenal for effectively responding to disasters, manmade or national.” (S. Rosenbaum, George Washington U, Washington, D.C.; sarar@gwu.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 © 2006, 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
Jan. 26, 2006 Vol. 13, No. 17
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 26 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).

Adverse Events with Aprotinin: The antifibrinolytic agent aprotinin, commonly used during coronary-artery surgery following ST-elevation myocardial infarction, is associated with serious end-organ damage, according to results of an observational study of 4,374 patients (pp. 353-65). The investigators conclude that the less expensive aminocaproic acid and tranexamic acid are safer alternatives, citing this evidence: “Use of aprotinin was associated with a doubling in the risk of renal failure requiring dialysis among patients undergoing complex coronary-artery surgery (odds ratio, 2.59; 95 percent confidence interval, 1.36 to 4.95) or primary surgery (odds ratio, 2.34; 95 percent confidence interval, 1.27 to 4.31). Similarly, use of aprotinin in the latter group was associated with a 55 percent increase in the risk of myocardial infarction or heart failure (P < 0.001) and a 181 percent increase in the risk of stroke or encephalopathy (P = 0.001). Neither aminocaproic acid nor tranexamic acid was associated with an increased risk of renal, cardiac, or cerebral events. Adjustment according to propensity score for the use of any one of the three agents as compared with no agent yielded nearly identical findings. All the agents reduced blood loss.” (D. T. Mangano, Ischemia Res. and Ed. Foundation, San Bruno, Calif.; dtb@iref.org)

Noting “the value of phase 4 clinical testing,” an editorialist points out the importance of real-world research following FDA approval of medications (pp. 413-5): “Although the FDA can mandate the post-approval gathering of data, vendors are given the task of designing the subsequent clinical trials. Thus, the design of clinical trials may still be subject to business considerations. This conflict of interest creates a disincentive to fully explore the safety of a drug in various patient populations. Clinical-investigation groups such as the Multicenter Study of Perioperative Ischemia Research Group, which is able to recruit a large number of patients from excellent clinical centers, may offer the pharmaceutical industry a faster and more economical means of gathering phase 4 data. From the standpoint of patient safety, such research entities can explore new indications and dosing regimens in various patient populations and in a setting relatively free of conflicts of interest. In addition, input from academic medical centers may increase the likelihood of broader applications not originally considered by drug companies in the design of clinical trials.” (G. J. Vlahakes, Harvard Med. Sch., Boston)

Ethnicity & Lung Cancer Risk: Ethnic and racial differences in smokers’ risk of lung cancer are uncovered in a study 183,813 participants in the Multiethnic Cohort Study (pp. 333-42). “The risk of lung cancer among ethnic and racial groups was modified by the number of cigarettes smoked per day,” write the investigators. “Among participants who smoked no more than 30 cigarettes per day, African Americans and Native Hawaiians had significantly greater risks of lung cancer than did the other groups. Among those who smoked no more than 10 and those who smoked 11 to 20 cigarettes per day, relative risks ranged from 0.21 to 0.39 (P < 0.001) among Japanese Americans and Latinos and from 0.45 to 0.57 (P < 0.001) among whites, as compared with African Americans. However, at levels exceeding 30 cigarettes per day, these differences were not significant. Differences in risk associated with smoking were observed among both men and women and for all histologic types of lung cancer.” (C. A. Haiman, haiman@usc.edu)

>>>PNN NewsWatch
* FDA advisory panels, meeting earlier this week, backed the nonprescription availability of the weight-loss drug orlistat and voted that Primatene Mist is a nonessential product. If the Rx-to-OTC switch is approved by FDA, orlistat would be marketed as Alli by GlaxoSmithKline in a 60-mg dose. The Primatene Mist vote relates to its ozone-depleting chlorofluorocarbons, which the U.S. is supposed to eliminate in nonessential products by the end of 2008. While Wyeth intends to reformulate the asthma inhaler, the process could take longer than that, leading to a period of unavailability.

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 © 2006, 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
Jan. 27, 2006 Vol. 13, No. 18
Providing news and information about medications and their proper use

>>>Sunitinib Approved for GIST, Advanced RCC
FDA has approved sunitinib malate (Sutent, Pfizer), an oral multikinase inhibitor targeting several receptor tyrosine kinases, for treatment of patients with gastrointestinal stromal tumors (GIST) or advanced renal cell carcinoma. The action marks the first time FDA has approved a new oncology drug for two indications simultaneously.
Sunitinib was approved for the treatment of patients with GIST whose disease has progressed or who are unable to tolerate treatment with imatinib, the current treatment for GIST patients. An interim analysis of data showed a median time-to-tumor progression for patients treated with sunitinib of 27 weeks, compared with 6 weeks for patients on placebo.
Accelerated approval for sunitinib was issued for treatment of advanced RCC. This approval was based only on sunitinib’s ability to reduce the size of the tumors in patients. An overall response rate of 26% to 37% was found in patients with metastatic kidney cancer whose tumors had progressed following cytokine-based therapy.
For both uses, the recommended dose of sunitinib is 50 mg orally once daily for 4 weeks followed by 2 weeks off treatment. The medication can be taken without regard to food.
The most commonly reported adverse effects noted in clinical trials of sunitinib were nausea, vomiting, diarrhea, several dermatologic problems (skin rash, discoloration, dry skin, hair color changes, hand-foot syndrome, and alopecia), mucositis/stomatitis, weakness, and altered taste. Patients treated with the drug also experienced fatigue, hypertension, peripheral edema, bleeding, and hypothyroidism.
>>>JAPhA Highlights
Source:
Jan/Feb issue of the Journal of the American Pharmacists Assoc. (www.japha.org; 2006; 46).
Emergency Contraception: A window into knowledge of and attitudes about emergency contraception is offered by a survey of 523 New Mexico pharmacists (pp. 33-43). “Pharmacists who had participated in a state-approved EC prescribing training program and had time in their practice setting to prescribe EC had significantly higher knowledge scores,” the authors write. “Mean scores indicated that pharmacists have positive attitudes and beliefs toward prescribing EC. Overall, 40% of respondents indicated that they would like to become certified to prescribe EC. Pharmacists who agreed that they would like to be certified to prescribe EC were significantly more likely to be male, non-Hispanic, non-Christian, to have liberal or moderate political views, and to indicate that they had employer/manager approval, time, and privacy in their practice setting to prescribe EC.” (M. E. Borrego, mborrego@salud.unm.edu)
A related commentary exhorts pharmacists to provide leadership so that access to EC is improved (pp. 84-8): “Increased visibility and access to EC in the several states that allow pharmacists to provide EC directly to women have resulted from the active participation and leadership of pharmacists. In these states, women are showing interest in and receptivity to reproductive health services provided by pharmacists. In California, some 3,000 pharmacists statewide have completed training, and in 2004 they provided EC directly to approximately 175,000 women. Pharmacists who provide EC overwhelmingly (91%) report that they do so because they see it as an important community service, and many (57%) recognize the opportunity for professional development.” (N. Monastersky, Public Health Inst., Oakland, Calif.;
nmonastersky@phi.org)

>>>PNN NewsWatch
* Interferon-experienced patients taking hydroxyurea for myeloproliferative disorders are experiencing serious cutaneous vasculitic toxicities, Bristol-Myers Squibb is warning health professionals. Product labeling for Hydrea and Droxia is being updated to include vasculitic ulcerations and gangrene and to advise that treatment be stopped if these problems occur. The new labeling also recommends monitoring of kidney function in elderly patients taking the renally excreted medication and advises that disposable gloves be worn by nonpatients—including pharmacists and other health professionals—who are handling hydroxyurea bottles or capsules to avoid dermal exposure.

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 © 2006, 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
Jan. 30, 2006 Vol. 13, No. 19
Providing news and information about medications and their proper use

>>>Inhaled Insulin Approved
An inhaled powder form of recombinant human insulin (rDNA)—Pfizer’s Exubera—has been approved by FDA for treatment of adult patients with type 1 and type 2 diabetes, providing 5 million American patients with the first new insulin delivery option introduced since the discovery of insulin in the 1920s.
The safety and efficacy of this inhaled insulin product were studied in approximately 2,500 adult patients with type 1 and type 2 diabetes. In clinical studies, Exubera produced peak insulin concentrations more quickly than regular insulin administered subcutaneously. Peak insulin levels were achieved at 49 minutes (range, 30-90 minutes) with Exubera inhaled insulin, compared with 105 minutes (range, 60-240 minutes) with regular insulin.
In patients with type 1 diabetes, inhaled insulin may be added to longer-acting insulins as a replacement for short-acting insulin taken with meals. In those with type 2 diabetes, inhaled insulin may be used alone, in combination with oral hypoglycemic medications, or with longer-acting insulins.
Pharmacists must provide an FDA-approved Medication Guide to patients when dispensing Exubera. FDA advises patients to read the entire Medication Guide and talk with their health care professionals if they have further questions.
As with all insulin products, hypoglycemia is an adverse effect of Exubera and patients should carefully monitor their blood glucose levels regularly. Other adverse effects associated with Exubera therapy seen in clinical trials included cough, shortness of breath, sore throat, and dry mouth.
In addition to these local pulmonary effects of inhaled insulin, another concern has been the induction of antibodies to the polypeptide chain when it comes in direct contact with the lungs. However, according to a 47-patient study reported last year in
Diabetes Care, development of high- or low-affinity insulin antibodies during inhaled-insulin therapy has no clinical relevance. Insulin antibody 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 insulin antibodies.
Exubera is not to be used in patients who smoke or who quit smoking within the last 6 months. It is not recommended for use in patients with asthma, bronchitis, or emphysema. Baseline tests for lung function are recommended before beginning treatment and every 6 to 12 months thereafter.
While inhaled insulin has been extensively studied for safety, FDA noted in a news release that the sponsor has committed to performing long-term studies to confirm the continued safety of Exubera after it is marketed and to examine more thoroughly the issue of the efficacy and safety of Exubera in patients with underlying lung disease.
Patients and health care providers can call 1-800-EXUBERA and register to receive more information about Exubera when it is available.

>>>PNN JournalWatch
* Efficacy and Safety of Fondaparinux for the Prevention of Venous Thromboembolism in Older Acute Medical Patients: Randomised Placebo Controlled Trial, in BMJ, 2006; doi: 10.1136/bmj.38733.466748.7C. Reprints: www.bmj.org; A. T. Cohen, Guy's, King's, and St. Thomas's Sch. of Med., London; alexander.cohen@kcl.ac.uk
* Chronic Fatigue Syndrome, in
Lancet, 2006; 367: 346-55. Reprints: www.thelancet.com; J. B. Prins, Radboud U. Nijmegen Med. Ctr., Nijmegen, the Netherlands; j.prins@mps.umcn.nl
* Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like Peptide 1, in
Diabetes Care, 2006; 29: 435-49. Reprints: care.diabetesjournals.org; D. J. Drucker, d.drucker@utoronto.ca
* Exenatide: From the Gila Monster to the Pharmacy, in
Journal of the American Pharmacists Assoc., 2006; 46: 44-55. Reprints: www.japha.org; C. Triplitt, U. Texas Health Sci. Ctr., San Antonio, Tex.; curtis.triplitt@uhs-sa.com
* Achieving Patient Centeredness in Pharmacy Practice: Openness and the Pharmacist's Natural Attitude, in
Journal of the American Pharmacists Assoc., 2006; 46: 56-66. Reprints: www.japha.org; S. J. Shoemaker, shoe0019@umn.edu
* Soy Protein, Isoflavones, and Cardiovascular Health. An American Heart Association Science Advisory for Professionals from the Nutrition Committee, in
Circulation, 2006; 10.1161/CIRCULATIONAHA.106.171052. Reprints: circ.ahajournals.org; F. M. Sacks, et al., for the American Heart Association Nutrition Committee

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 © 2006, 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
Jan. 31, 2006 Vol. 13, No. 20
Providing news and information about medications and their proper use

>>>Ranolazine Approved as Back-up Antianginal Agent
Ranolazine (Ranexa, CV Therapeutics), an orally active drug with an unknown mechanism of action, has been approved for treatment of chronic angina. Because the medication prolongs the QT interval, it should be reserved for patients who have not achieved an adequate response with other antianginal drugs. Ranolazine should be used only as part of combination regimens that also contain amlodipine, beta-blockers, or nitrates.
In clinical trials, ranolazine lowered the frequency of anginal attacks (3.3 per week, compared with 4.3 per week with placebo) and nitroglycerin use (2.7 times per week, compared with 3.6 times per week with placebo). However, the drug’s effect on angina rate or exercise tolerance appeared to be smaller in women than men.
Ranolazine is contraindicated in patients with pre-existing QT prolongation or hepatic impairment and in those who are taking other QT-prolonging drugs or potent or moderately potent cytochrome P450 3A inhibitors, including diltiazem. Adverse effects of the drug include dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%). During clinical trials, 6% of patients taking ranolazine discontinued treatment because of perceived adverse effects, compared with 3% of those taking placebo. Treatment-emergent adverse effects that led to drug discontinuation included dizziness, nausea, asthenia, constipation, and headache.

>>>Diabetes Highlights
Source:
Feb. Diabetes Care (care.diabetesjournals.org; 206; 29).
Smoking & Inhaled Insulin: The pharmacokinetics of inhaled insulin are greatly affected by cessation and resumption of smoking, concludes a study of 30 participants (pp. 277-82). Among 20 male smokers and 10 matched nonsmoking study participants, the authors wrote, “Before smoking cessation, maximum insulin concentration (Cmax) and area under the curve (AUC) for insulin concentration time (AUC-Insulin0–360) with inhaled insulin were higher, and time to Cmax(tmax) shorter, in smokers than nonsmokers (Cmax26.8 vs. 9.7 µU/ml; AUC-Insulin0–360 2,583 vs. 1,645 µU • ml–1 • min–1; tmax 20 vs. 53 min, respectively; all P < 0.05), whereas with subcutaneous insulin, systemic exposure was unchanged (AUC-Insulin0–360 2,324 vs. 2,269 µU • ml–1 • min–1; P = NS). After smoking cessation, AUC-Insulin0–360 decreased with inhaled insulin by up to 50% within 1 week and approached nonsmoker levels. Cmax decreased and tmax increased relative to baseline but were still not comparable with nonsmoker values. Smoking resumption completely reversed the effect of smoking cessation. Glucodynamics corroborated the observed findings in insulin pharmacokinetics.” These findings support recommendations made in the Exubera product labeling (see PNN, Jan. 30) and the general advice that people with diabetes should not smoke. (R. H. A. Becker, reinhard.becker@sanofi-aventis.com)
Fiber Intake & Systemic Inflammation: Eating whole grains and consuming a low glycemic index diet appears to reduce systemic inflammation among women with type 2 diabetes, report Nurses’ Health Study investigators (pp. 207-11). Assessing intakes of whole grains and dietary fiber among 902 study participants with type 2 diabetes, the investigators report, “After adjustment for age, BMI, lifestyle, and dietary covariates, intakes of whole grains and bran were both associated with significantly decreasing trends of C-reactive protein (CRP) (P for trend = 0.03 and 0.007, respectively) and tumor necrosis factor-alpha receptor 2 (TNF-R2) (P for trend = 0.017 and 0.06). High intake of cereal fiber was also inversely associated with the lower levels of CRP (P for trend = 0.03) and TNF-R2 (P for trend = 0.01). The concentrations of CRP and TNF-R2 were 18 and 8% lower in the highest quintile of cereal fiber as compared with the lowest quintile. Dietary glycemic index was positively associated with CRP (P for trend = 0.04) and TNF-R2 (P for trend = 0.0008) levels. The concentrations of CRP and TNF-R2 were 32 and 11% higher, respectively, in the highest quintile of dietary glycemic index as compared with the lowest quintile.” (L. Qi, nhlqi@channing.harvard.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 © 2006, 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
Feb. 1, 2006 Vol. 13, No. 21
Providing news and information about medications and their proper use

>>>Lubiprostone Approved for Chronic Constipation
FDA yesterday added another drug to its rapidly growing list of 2006 new chemical entity approvals. Lubiprostone (Amitiza—Sucampo Pharmaceuticals; Takeda Pharmaceuticals America), the first drug of its chemical type, becomes the first agent approved for treatment of chronic idiopathic constipation in adults.
Chronic idiopathic constipation, one of the most common disorders suffered by Americans, is generally defined as infrequent and difficult passage of stool. This condition affects women more often than men and more frequently affects patients older than 65 years of age. Symptoms of chronic idiopathic constipation are abdominal pain and discomfort, bloating, straining, and hard stools.
Lubiprostone, a chloride channel activator, works by increasing intestinal fluid secretion, which helps ease the passage of stool and thereby alleviate symptoms associated with chronic idiopathic constipation. FDA based its decision to approve the drug on the results from two clinical trials, which were conducted in patients with, on average, fewer than three spontaneous bowel movements per week with symptoms of constipation for at least 6 months before entry into the studies. The studies demonstrated that subjects treated with lubiprostone had a higher frequency of bowel movements in the first week than did placebo subjects. In both studies, results similar to those in week 1 were also observed in weeks 2, 3, and 4 of therapy. Three long-term studies showed that lubiprostone decreased constipation severity, abdominal bloating, and discomfort over 6-12 months of use.
The most common adverse events reported in the clinical trials of lubiprostone included headache, nausea, diarrhea, abdominal pain, and distension. The drug should be taken twice a day with food. Physicians and patients should periodically assess the need for continued treatment.

>>>JAMA Highlights
Source:
Feb. 1 issue of JAMA (www.jama.com; 2006; 295).
Depression During Pregnancy: Continuation of antidepressants is needed during pregnancy to prevent relapses of major depressive disorder, according to a prospective, naturalistic, longitudinal investigation (pp. 499-507). Concluding that pregnancy is not the “protective” state of emotional well-being that some assume it to be, the investigators report, “Among the 201 women in the sample, 86 (43%) experienced a relapse of major depression during pregnancy. Among the 82 women who maintained their medication throughout their pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who discontinued medication. Women who discontinued medication relapsed significantly more frequently over the course of their pregnancy compared with women who maintained their medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P < .001).” (Lee S. Cohen, lcohen2@partners.org)
Stem-Cell Transplant for SLE: A preliminary study of 50 patients with severe refractory systemic lupus erythematosus provides the “foundation and justification for a definitive randomized trial” of intense immunosuppression and autologous hematopoietic stem cell support (pp. 527-35). Study participants, who all had either organ- or life-threatening visceral involvement of the disease, underwent nonmyeloablative HSCT with cyclophosphamide and granulocyte colony-stimulating factor mobilization. “Fifty patients were enrolled and underwent stem cell mobilization. Two patients died after mobilization, one from disseminated mucormycosis and another from active lupus after postponing the transplantation for 4 months. Forty-eight patients underwent nonmyeloablative HSCT. Treatment-related mortality was 2% (1/50). By intention to treat, treatment-related mortality was 4% (2/50). With a mean follow-up of 29 months (range, 6 months to 7.5 years) for patients undergoing HSCT, overall 5-year survival was 84%, and probability of disease-free survival at 5 years following HSCT was 50%. Secondary analysis demonstrated stabilization of renal function and significant improvement in SLEDAI score, ANA, anti-ds DNA, complement, and carbon monoxide diffusion lung capacity adjusted for hemoglobin.” (R. K. Burt, rburt@northwestern.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 © 2006, 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
Feb. 2, 2006 Vol. 13, No. 22
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 2 issue of the New England Journal of Medicine (content.nejm.org; 2006; 254).
Intensive Insulin Therapy in MICUs: Among 1,200 adult patients admitted to a medical intensive care unit, strict normalization of blood glucose levels was associated with reduced morbidity but not mortality (pp. 449-61). Study participants, 16.9% of whom had histories of diabetes, received either insulin infusions targeted to achieve strict glucose normalization (80-100 mg/dL) or conventional insulin therapy (administered when blood glucose levels of higher than 215 mg/dL and tapered at 180 mg/dL). Results showed the following: “Intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality (40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group, P = 0.33). However, morbidity was significantly reduced by the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. Although length of stay in the ICU could not be predicted on admission, among 433 patients who stayed in the ICU for less than three days, mortality was greater among those receiving intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU for three or more days, in-hospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent (P = 0.009) and morbidity was also reduced.” (G. Van den Berghe, Catholic U., Leuven, Belgium; greta.vandenberghe@med.kuleuven.be)
This study is preliminary, making its immediate implications for practice unclear, but an editorialist provides this perspective (pp. 516-8): “As clinicians struggle to understand the best way to manage blood glucose levels in the ICU, one thing is clear: the days of ignoring blood sugar levels or tolerating marked hyperglycemia in the ICU (which was commonplace even five years ago) are over. As we await the outcome of ongoing large-scale, multicenter, randomized trials examining the issue of glycemic control in the ICU (the Glucontrol study and the Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation [NICE-SUGAR] study), physicians will need to interpret the available data in the context of their clinical practices.” (A. Malhotra, Harvard Med. Sch., Boston)
Schizophrenia Treatment: Use of multiple antipsychotic agents in treatment of patients with schizophrenia provided no better results than monotherapy, according to a short-term study of 68 patients (pp. 472-82). Participants had poor responses to clozapine, and they were randomly assigned to augmentation with risperidone 3 mg or placebo for 8 weeks, followed by an optional 18 weeks of risperidone augmentation. The investigators report, “The mean total score for the severity of symptoms decreased from baseline to eight weeks in both the risperidone and the placebo groups. There was no statistically significant difference in symptomatic benefit between augmentation with risperidone and placebo: 9 of 34 patients receiving placebo and 6 of 34 receiving risperidone responded to treatment (P = 0.38). The mean difference in the change in [Positive and Negative Syndrome Scale] scores from baseline to eight weeks between those receiving risperidone and those receiving placebo was 0.1 (95 percent confidence interval, –7.3 to 7.0). The verbal working-memory index showed a small decline in the risperidone group and a small improvement in the placebo group (P = 0.02 for the comparison between the two groups in the change from baseline). The increase in fasting blood glucose levels was mildly greater in the risperidone group than in the placebo group (16.2 vs. 1.8 mg per deciliter [0.90 vs. 0.10 mmol per liter], P = 0.04). The incidence and severity of other side effects did not differ between the two groups.” (W. G. Honer, honer@interchange.ubc.ca)
“Several second-generation atypical agents must be tried before it is clear that no further improvement is possible,” notes an editorialist, adding that the adverse effects patients have with these drugs are not “always have the [ones] that worry clinicians” (pp. 518-20). “Clinicians must balance efficacy, the prevention of disease progression, and the side effects of medication as they tailor treatment to the individual patient.” (J. M. Davis, U. Ill., Chicago)

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 © 2006, 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
Feb. 3, 2006 Vol. 13, No. 23
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Feb. issue of Pharmacotherapy (www.pharmacotherapy.org; 2006; 26).
HIV Drugs & Lipoatrophy: Fat distribution is significantly improved in patients with HIV following long-term withdrawal of stavudine but not protease inhibitors, according to an observational, retrospective study of 80 men with HIV infection and 151 healthy matched control men (pp. 154-61). Comparing results from a cross-sectional (part 1) and longitudinal (part 2) study, the investigators report, “In part 1, body composition and fat distribution of the HIV-infected men were compared by dual energy x-ray absorptiometry (DEXA) with those of the controls to determine whether body fat distribution is altered in HIV-infected men. In part 2, we analyzed modifications of body composition and fat distribution in 45 of the 80 patients. These 45 had been exposed to antiretroviral drugs, including stavudine and a protease inhibitor, for at least 5 months before the first of two DEXA assessments. They received three different treatment strategies for several months. In group 1, stavudine was withdrawn; in group 2, protease inhibitor was discontinued, and in group 3, stavudine plus protease inhibitor were continued. Group 1 showed a significant fat gain in the lower extremities 31.7 ± 5.9 months after stavudine discontinuation (p < 0.0001). Group 2 did not show any significant modification of total body, lower limb, or trunk fat despite protease inhibitor discontinuation for 35.2 ± 6.6 months. Findings were similar for group 3, who continued receiving stavudine–protease inhibitor therapy for 21.2 ± 12.8 months.” (N. Tavassoli, Centre Midi-Pyrénées de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, Toulouse, France; neda67@yahoo.com)
RCTs v. Case Reports: An analysis of the literature on a possible link between beta-blockers and depression illustrates the importance of considering case reports when randomized controlled trials are inadequately designed to detect adverse effects (pp. 162-7): “We reviewed 24 published case reports showing an association between beta-blockers and depression and eight randomized controlled trials included in a meta-analysis of the adverse effects of these drugs. We abstracted the beta-blocker taken, patients’ age and sex, diagnoses, history of depression, type of depressive symptoms reported, and method and timing of the assessment of depression. Naranjo criteria were used to evaluate the strength of evidence from each case report for a possible association between beta-blockers and depression. Twelve case reports had a Naranjo score of 5 or more (suggesting a likely causal relationship), nine of which involved propranolol. In all nine, depression began soon after treatment, and in four, the patient had a history of depression. Three randomized controlled trials assessed propranolol. Depression rates in the control groups of these studies differed substantially from each other (0–40%, p < 0.0001). In only one randomized controlled trial did investigators assess depression systematically; they evaluated depression after 1 year of treatment and eliminated patients who had previously been prescribed an antidepressant.” (A. J. Hartz, arthur-hartz@uiowa.edu)
Pharmacist-Managed Diabetes Service: Patients had significant improvements in clinical parameters after they were referred to a pharmacist-managed diabetes mellitus drug therapy management service, notes an author of a retrospective chart review of 316 adults (pp. 248-53): “Mean ± SD A1C reduction was 1.4% ± 1.94% (p < 0.001); the percentage of patients whose A1C was at goal level at baseline (< 7%) increased from 14.8% to 43.2% (p < 0.001). Mean ± SD LDL level reduction was 14 ± 41.1 mg/dl (p = 0.002), mean ± SD triglyceride level reduction 42 ± 97.6 mg/dl (p < 0.001). The percentage of patients who reached goal for LDL level (< 100 mg /dl), HDL level (> 40 mg/dl), and blood pressure (< 130/80 mm Hg) did not increase significantly from baseline, whereas those who reached the triglyceride level goal (< 150 mg/dl) increased from 36% to 55% (p < 0.005). Frequency of annual dilated retinal examinations and monofilament foot examinations increased by 29% (p < 0.05) and 12.5% (p < 0.05), respectively. Daily aspirin use increased from 35% to 59% (p < 0.05).” (A. D. McCord, amccor@midwestern.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 © 2006, 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
Feb. 6, 2006 Vol. 13, No. 24
Providing news and information about medications and their proper use

>>>New Rotavirus Vaccine Licensed by FDA
RotaTeq (Merck), a live oral vaccine for use in preventing rotavirus gastroenteritis in infants, has been licensed by FDA. It is the only vaccine approved in the United States that can help protect against rotavirus, a viral infection that may cause diarrhea, vomiting, fever, and dehydration.
In 1998, FDA approved a different live vaccine against rotavirus that was later withdrawn from the market because of its association with an increased risk of intussusception, a rare, life-threatening type of blockage or twisting of the intestine. Intussusception occurs spontaneously in approximately 1 in 2,000 healthy young infants and children per year, but occurred at an increased rate during the first week or two following vaccination with the previous rotavirus vaccine.
The risk of intussusception for RotaTeq was evaluated in a large-scale trial of more than 70,000 children. RotaTeq was not associated with an increased risk of intussusception when compared with placebo. In addition, RotaTeq was not associated with an increased risk of other serious adverse events when compared with placebo.
RotaTeq is a liquid vaccine given by mouth in three doses, between the ages of 6 and 32 weeks. The following adverse events were reported more often in infants who received RotaTeq when compared with infants who received placebo: diarrhea (24.1% in vaccine recipients versus 21.3% in those receiving placebo), vomiting (15.2% versus 13.6%), ear infection (14.5% versus 13.0%), runny nose and sore throat (6.9% versus 5.8%), and wheezing and coughing (1.1% versus 0.7%).

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2006; 332).
LMWHs in Palliative Care: In patients with advanced cancer and receiving palliative care, addition of low molecular weight heparins for thromboprophylaxis is acceptable and produces a better overall quality of life, according to a 28-patient study (doi: 10.1136/bmj.38733.616065.802). Noting that patients found antiembolic stockings unacceptable, the authors report: “Patients knew about the risks of venous thromboembolism and the purpose of treatment with low molecular weight heparin. Media coverage had raised awareness about venous thromboembolism, and many had previous experience of thromboprophylaxis. All found low molecular weight heparin an acceptable intervention, and many said that it improved their quality of life by giving them a feeling of safety and reassurance. Antiembolic stockings were considered uncomfortable and had a negative impact on quality of life. Patients were concerned that because they had advanced disease they might not be eligible for thromboprophylaxis.” (S. I. R. Noble, Cardiff U., Cardiff, U.K.; simon.noble@gwent.wales.nhs.uk)

>>>PNN JournalWatch
* Self-Monitoring of Oral Anticoagulation: A Systematic Review and Meta-analysis, in Lancet, 2006; 367: 404–11. Reprints: www.thelancet.com; C. Heneghan, U. Oxford, Oxford, U.K.; carl.heneghan@dphpc.ox.ac.uk
* Statins and Sepsis in Patients with Cardiovascular Disease: A Population-Based Cohort Analysis, in
Lancet, 2006; 367: 404–11. Reprints: www.thelancet.com; D. Redelmeier, Sunnybrook & Women's College Health Sci. Ctr., Toronto; dar@ices.on.ca
* Oral Misoprostol for Induction of Labour at Term: Randomised Controlled Trial, in
BMJ, 2006; doi:10.1136/bmj.38729.513819.63. Reprints: www.bmj.org; J. M. Dodd, U. Adelaide, North Adelaide, Australia; jodie.dodd@adelaide.edu.au
* Non-degenerative Mild Cognitive Impairment in Elderly People and Use of Anticholinergic Drugs: Longitudinal Cohort Study, in
BMJ, 2006; doi:10.1136/bmj.38740.439664.DE. Reprints: www.bmj.org; K. Ritchie, Inserm, Pathologies of the Nervous System, Montpellier, France; ritchie@montp.inserm.fr
* Reducing the Risk of HIV Infection Associated with Illicit Drug Use, in
Pediatrics, 2006; 117: 566–71. Reprints: www.pediatrics.org; American Academy of Pediatrics Committee on Pediatric AIDS.
* Dietary Recommendations for Children and Adolescents: A Guide for Practitioners, in
Pediatrics, 2006; 117: 544–59. Reprints: www.pediatrics.org; American Heart Association.
* C-Reactive Protein: A Family of Proteins to Regulate Cardiovascular Function, in
American Journal of Kidney Diseases, 2006; 47: 212–22. Reprints: www.ajkd.org; S. B. Schwedler, U. Hosp., Würzburg, Germany.

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 © 2006, 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
Feb. 7, 2006 Vol. 13, No. 25
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 7 issue of the Annals of Internal Medicine (www.annals.org; 2006; 144).
Antihypertensives in Older High-Risk Patients: Coronary heart disease should be a bigger concern than end-stage renal disease among older patients with moderate to severe reductions in glomerular filtration rate, according to a large, multicenter trial in which patients were followed for 6 years (pp. 172-80). Because chlorthalidone is superior to amlodipine and lisinopril for preventing heart failure and equivalent to those drugs in preventing coronary heart disease, it may be the preferred agent in this population, the investigators conclude, based on this evidence: “In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure.” (B. R. Davis, U. Texas Health Sci. Ctr., Houston; barry.r.davis@uth.tmc.edu)
Editorialists provide this guidance for clinicians about selecting among the available antihypertensive agents (pp. 213-5): “Current guidelines recommend a target blood pressure less than 130/80 mm Hg for all patients with chronic kidney disease and selection of antihypertensive agents based on the cause of kidney disease and level of proteinuria. These recommendations are consistent with the results from the previous studies of chronic kidney disease and the ALLHAT chronic kidney disease subgroup. Although some uncertainty remains, patients with diabetic kidney disease or nondiabetic kidney disease with a total protein-to-creatinine ratio of 200 mg/g or greater are probably similar to those enrolled in the chronic kidney disease studies and should be treated with an ACE inhibitor or ARB; a diuretic and other agents should be added as necessary to reach the target blood pressure. Patients with nondiabetic kidney disease and spot urine total protein-to-creatinine ratio less than 200 mg/g may be more similar to those enrolled in ALLHAT and should be treated with a diuretic and additional agents as necessary to reach the target blood pressure.” (K. Uhlig,
kuhlig@tufts-nemc.org)
Daclizumab for Pure Red-Cell Aplasia: Results of a 15-patient pilot study support further research into the use of daclizumab, a humanized monoclonal antibody to the interleukin-2 receptor, in patients with pure red-cell aplasia (pp. 181-5). Of the 15 patients with the rare combination of anemia, reticulocytopenia, and absence of bone marrow erythroid precursors, six patients responded to daclizumab 1 mg/kg every 2 weeks for a total of five infusions. “All responders became transfusion-independent and achieved normal or near-normal hemoglobin values and normal reticulocyte counts,” the authors add. (E. M. Sloand, sloande@nih.gov)
Clinical Prediction Rules: Considerations that “should inform the future development and evaluation of” clinical prediction (or decision) rules are outlined in a review article (pp. 201-9): “The potential impact of a prediction rule can be estimated by assessing its predictive validity and clinical sensibility and by measuring its potential to improve current decision making. However, the actual impact of a prediction rule also will depend on how its predictions are translated into decisions and how clinician input is effectively incorporated before, during, and after testing in actual practice. Measures of safety and efficiency are clinically relevant outcomes of its use, but the impact of clinicians’ disagreements with, or misuse of, the rule when making actual decisions must be assessed.” (B. M. Reilly, MD, Cook County [Stroger] Hosp., Chicago; breilly@cchil.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 © 2006, 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
Feb. 8, 2006 Vol. 13, No. 26
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Feb. issue of the Journal of the American Geriatrics Society (www.blackwell-synergy.com/toc/jgs; 2006; 54).
Vaccination of Veterans: Older veterans cared for at Veterans Affairs facilities have higher rates of influenza and pneumococcal vaccination, but proportions of immunized patients still fall short of Healthy People 2010 goals (pp. 217 ff). That conclusion is reached in an analysis of responses from those older than 65 years of age who participated in the 2003 Behavioral Risk Factor Surveillance System: “Thirty percent of adults aged 65 and older were veterans, and 21% of veterans reported receiving care at VA health facilities. Veterans, especially VA users, were older and described poorer self-perceived health than nonveterans. Influenza and pneumococcal vaccination rates were higher for veterans than for nonveterans (74% vs 68% and 68% vs 63%, respectively, P < .001 for both) and for VA users than non-VA users (80% vs 72% and 81% vs 64%, respectively, P < .001 for both). For veterans, VA care was independently associated with influenza (odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.5-2.2) and pneumococcal (OR = 2.4, 95% CI = 2.0-2.9) vaccine use after adjusting for sociodemographics factors, perceived health status, diabetes mellitus, asthma, and smoking. Current smoking and black race were independent predictors of low influenza vaccine uptake.” (R-C Chi, rchi@u.washington.edu)
Benzodiazepine Use & Physical Disability: Use of both short- and long-acting benzodiazepines is associated with mobility disability (inability to walk half a mile or climb one flight of stairs) and activities of daily living disability (inability to perform one or more basic ADLs [bathing, eating, dressing, transferring from a bed to a chair, using the toilet, or walking across a small room]), according to a prospective cohort study conducted in 9,093 subjects aged 65 years or older (pp. 224 ff). “At baseline, 5.5% of subjects reported benzodiazepine use,” the authors explained. “In multivariable models, benzodiazepine users were 1.23 times as likely as nonusers (95% confidence interval (CI)=1.09-1.39) to develop mobility disability and 1.28 times as likely (95% CI=1.09-1.52) to develop ADL disability. Risk for incident mobility was increased with short- (hazard ratio (HR) = 1.27, 95% CI = 1.08-1.50) and long-acting benzodiazepines (HR = 1.20, 95% CI = 1.03-1.39) and no use. Risk for ADL disability was greater with short- (HR = 1.58, 95% CI = 1.25-2.01) but not long-acting (HR = 1.11, 95% CI = 0.89-1.39) agents than for no use.” (S. L. Gray, slgray@u.washington.edu)
Pain Medications in Nursing Homes: A Pain Medication Appropriateness Scale scored well during an assessment of the tool in six treatment and six control nursing homes in Colorado (pp. 231 ff). The investigators, based on PMAS scores obtained for residents in pain versus those without pain and before and after an intervention, found these results: “The mean total PMAS was 64% of optimal. Fewer than half of residents with predictably recurrent pain were prescribed scheduled pain medication; 23% received at least one high-risk medication. PMAS scores were better for residents not in pain (68% vs 60%, P = .004) and in homes where nurses' knowledge of pain assessment and management improved or stayed the same during the intervention (69% vs 61%, P = .03).” (E. Hutt, VA Med. Ctr., Denver; Evelyn.Hutt@uchsc.edu)

>>>PNN NewsWatch
* Three reports published in today’s JAMA fail to show significant benefits from low-fat diets in reduction of risks of breast cancer, colorectal cancer, and cardiovascular disease. While some P values from the Women’s Health Initiative showed a statistical trend (being below .1 but not reaching .05) among 48,835 postmenopausal women who were followed an average of 8.1 years, the results appear to support the position of experts such as Walter Willett, MD, of Harvard U., who has maintained that not all fats are bad, advocating instead healthy diets that are low in saturated and trans fats, regular exercise, and maintenance of appropriate weight.
*
FDA has extended beyond 24 months postimplantation the at-risk period for streptococcal meningitis among children with Advanced Bionics Corp. cochlear implants with positioners.
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 © 2006, 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
Feb. 9, 2006 Vol. 13, No. 27
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 9 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).
Saw Palmetto for BPH: In a study of 225 men with moderate or severe symptoms of benign prostatic hyperplasia, saw palmetto failed to improve symptoms or objective measures of the disease (pp. 557-66). Observing changes in the scores on the American Urological Association Symptom Index and the maximal urinary flow rate, the authors noted: “There was no significant difference between the saw palmetto and placebo groups in the change in AUASI scores (mean difference, 0.04 point; 95 percent confidence interval, -0.93 to 1.01), maximal urinary flow rate (mean difference, 0.43 ml per minute; 95 percent confidence interval, -0.52 to 1.38), prostate size, residual volume after voiding, quality of life, or serum prostate-specific antigen levels during the one-year study. The incidence of side effects was similar in the two groups.” (S. Bent, bent@itsa.ucsf.edu)
Editorialists write of the uncertainty surrounding research into safety and effectiveness of dietary supplements (pp. 632-4): “Rigorous phase 3 studies, such as the one by Bent et al., provide important and helpful data, but they leave questions about the efficacy of other products and preparations and the means to ensure the long-term quality and safety of these products. Perhaps the larger question is how patients can be better guided with respect to the issues surrounding the use of herbal therapies. We believe that these products should be studied as pharmaceutical agents have been that were approved by the FDA. Even with the best regulatory provisions for herbal products, reasonable assurance of their long-term efficacy and safety will require clinical trials of the same quality required for the approval of standard drugs and, possibly, the development of pure compounds. Until there is adequate research on an herbal or other botanical product, it is the responsibility of physicians to inform their patients and protect them from the inherent risks of unproven therapies.” (R. S. DiPaola, U. Med. and Dentistry of New Jersey, New Brunswick)
Cetuximab for Head-and-Neck Cancer: “High-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck,” conclude authors who studied 424 patients with locoregionally advanced head and neck cancer (pp. 567-78). They report: “The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups.” (E. K. Rowinsky, eric.rowinsky@imclone.com)
SSRIs & PPHN: Use of SSRIs late in pregnancy is associated with persistent pulmonary hypertension of the newborn, according to a case-control study (pp. 579-87). Interviews of 377 women whose infants had PPHN and 836 matched controls showed: “Fourteen infants with PPHN had been exposed to an SSRI after the completion of the 20th week of gestation, as compared with six control infants (adjusted odds ratio, 6.1; 95 percent CI, 2.2 to 16.8). In contrast, neither the use of SSRIs before the 20th week of gestation nor the use of non-SSRI antidepressant drugs at any time during pregnancy was associated with an increased risk of PPHN.” (C. D. Chambers, achchambers@ucsd.edu)
An editorialist adds (pp. 636-8): “Some evidence suggests that the children of women with untreated depression may have adverse effects ranging from low birth weight to developmental delay. Thus, although it is preferable to manage depression in pregnant women without the use of antidepressants when possible, often it is not possible.” (J. L. Mills, 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 © 2006, 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
Feb. 10, 2006 Vol. 13, No. 28
Providing news and information about medications and their proper use

>>>Psychiatry Highlights
Source:
Feb. issue of the American Journal of Psychiatry (ajp.psychiatryonline.org; 2006; 163).
Treatment-Resistant Bipolar Depression: Several articles (as well as editorials not covered here) in this issue focus on the challenges of treating treatment-resistant bipolar affective disorders.
Data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) show that recurrence is frequent, especially when residual mood symptoms are present at initial recovery (pp. 217-24). “Of 1,469 participants symptomatic at study entry, 858 (58.4%) subsequently achieved recovery,” the authors report. “During up to 2 years of follow-up, 416 (48.5%) of these individuals experienced recurrences, with more than twice as many developing depressive episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes (118, 13.8%). The time until 25% of the individuals experienced a depressive episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence. Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic, hypomanic, or mixed episode recurrence.” (R. H. Perlis)
Lamotrigine showed some superiority over inositol and risperidone in post-hoc secondary analyses of data from the STEP-BD trial of 66 patients with current major depressive episode that was nonresponsive to a combination of adequate doses of established mood stabilizers plus at least one antidepressant (pp. 210-6). The investigators write: “No significant between-group differences were seen when any pair of treatments were compared on the primary outcome measure. However, the recovery rate with lamotrigine was 23.8%, whereas the recovery rates with inositol and risperidone were 17.4% and 4.6%, respectively. Patients receiving lamotrigine had lower depression ratings and Clinical Global Impression severity scores as well as greater Global Assessment of Functioning scores compared with those receiving inositol and risperidone.” (A. A. Nierenberg)
Continuation treatment with adjunctive antidepressants is associated with “substantial risks of threshold switches to full-duration hypomania or mania in both acute and long-term continuation treatment,” concludes a third article (pp. 232-9). Noting that venlafaxine has the highest risk of such switching and bupropion the lowest risk, the researchers provide these results from 228 acute (10-week) trials of involving 159 patients: “Threshold switches into full-duration hypomania and mania occurred in 11.4% and 7.9%, respectively, of the acute treatment trials and in 21.8% and 14.9%, respectively, of the continuation trials. The rate of threshold switches was higher in the 169 trials in patients with bipolar I disorder (30.8%) than the 59 trials in patients with bipolar II disorder (18.6%). The ratio of threshold switches to subthreshold brief hypomanias was higher in both the acute (ratio = 3.60) and continuation trials (ratio = 3.75) of venlafaxine than in the acute and continuation trials of bupropion (ratios = 0.85 and 1.17, respectively) and sertraline (ratios = 1.67 and 1.66, respectively). In only 37 (16.2%) of the original 228 acute antidepressant trials, or in only 23.3% of the patients, was there a sustained antidepressant response in the continuation phase in the absence of a threshold switch.” (G. S. Leverich)
Nalmefene for Pathological Gambling: The opioid antagonist nalmefene significantly reduced the severity of pathological gambling among 207 participants in a 16-week clinical trial (pp. 303-12). “Estimated regression coefficients showed that the 25 mg/day and 50 mg/day nalmefene groups had significantly different scores on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling, compared to the placebo group,” report the authors. “A total of 59.2% of the subjects who received 25 mg/day of nalmefene were rated as ‘much improved’ or ‘very much improved’ at the last evaluation, compared to 34.0% of those who received placebo. Adverse experiences included nausea, dizziness, and insomnia.” (J. E. Grant)

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 © 2006, 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
Feb. 13, 2006 Vol. 13, No. 29
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release articles and the Feb. 11 issue of Lancet (www.thelancet.com; 2006; 367).
Developing Avian Influenza Vaccine: An egg-independent strategy for producing human adenoviral-vector-based, hemagglutinin subtype 5 influenza vaccine (HAd-H5HA) was developed and tested in mice (pp. 475-81). Scientists report this progress in making an avian influenza vaccine that can be stockpiled for use in pandemics: “Immunisation of mice with HAd-H5HA provided effective protection from H5N1 disease, death, and primary viral replication (p < 0.0001) against antigenically distinct strains of H5N1 influenza viruses. Unlike the recombinant H5HA vaccine, which is based on a traditional subunit vaccine approach, HAd-H5HA vaccine induced a three-fold to eight-fold increase in HA-518-epitope-specific interferon-gamma-secreting CD8 T cells (p = 0.01).” (S. Sambhara, ssambhara@cdc.gov)
Cigarette Testing: Tobacco companies manipulated limitations of cigarette-testing protocols to design products that produced low yields of tar and nicotine on machines but then delivered more of these harmful substances during actual smoking, according to an article that analyzes internal tobacco industry documents (DOI: 10.1016/S0140-6736(06)68077-X). “[British-American Tobacco] developed elastic cigarettes that produced low yields under standard testing protocols, whereas in consumers' hands they elicited more intensive smoking and provided higher concentrations of tar and nicotine to smokers,” the authors write. “Documents also show that BAT pursued this product strategy despite the health risks to consumers and ethical concerns raised by senior scientists, and paired it with an equally successful marketing campaign that promoted these cigarettes as low-tar alternatives for health-concerned smokers. Overall, the documents seem to reveal a product strategy intended to exploit the limitations of the testing protocols and to intentionally conceal from consumers and regulators the potential toxicity of BAT products revealed by BAT's own research. Tobacco industry research underscores the serious limitations of the current cigarette testing protocols and the documents describe deceptive business practices that remain in place.” (D. Hammond, U. Waterloo, Waterloo, Ont., Canada; dhammond@uwaterloo.ca)

>>>BMJ Highlights
Source:
Early-release articles of BMJ (http://www.bmj.org; 2006; 332).
Exogenous Melatonin: While evidence supports the safety of short-term use, exogenous melatonin is not effective for treating either secondary sleep disorders or sleep-restriction conditions such as jet lag or shiftwork disorder, conclude authors of a meta-analysis (DOI: 10.1136/bmj.38731.532766.F6). The authors note: “Six randomised controlled trials with 97 participants showed no evidence that melatonin had an effect on sleep onset latency in people with secondary sleep disorders (weighted mean difference -13.2 (95% confidence interval -27.3 to 0.9) min). Nine randomised controlled trials with 427 participants showed no evidence that melatonin had an effect on sleep onset latency in people who had sleep disorders accompanying sleep restriction (-1.0 (-2.3 to 0.3) min). 17 randomised controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short term use (three months or less).” (N. Buscemi, nina.buscemi@ualberta.ca)

>>>PNN JournalWatch
* Oral Protein Energy Supplements for Children with Cystic Fibrosis: CALICO Multicentre Randomised Controlled Trial, in BMJ, 2006; doi:10.1136/bmj.38737.600880.AE. Reprints: www.bmj.org; R. L. Smyth, U. Liverpool, U.K.; r.l.smyth@liv.ac.uk
* Statins as Antiinflammatory and Immunomodulatory Agents: A Future in Rheumatologic Therapy?, in
American Journal of Rheumatology, 2006; 54: 393–407. Reprints: www.rheumatology.org; M. H. Pillinger, Manhattan VA Hosp., New York; michael.pillinger@med.nyu.edu
* Why Olanzapine Beats Risperidone, Risperidone Beats Quetiapine, and Quetiapine Beats Olanzapine: An Exploratory Analysis of Head-to-Head Comparison Studies of Second-Generation Antipsychotics, in
American Journal of Psychiatry, 2006; 163: 185–94. Reprints: ajp.psychiatryonline.org; S. Heres.
* Models for Integrating Buprenorphine Therapy into the Primary HIV Care Setting, in
Clinical Infectious Diseases, 2006; 42: 716–21. Reprints: www.journals.uchicago.edu; F. L. Altice, frederick.altice@yale.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 © 2006, 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
Feb. 14, 2006 Vol. 13, No. 30
Providing news and information about medications and their proper use

>>>Internal Medicine Update
Source:
Feb. 13 issue of Archives of Internal Medicine (www.archinternmed.com; 2006; 166).
Adherence & Managed Care Plans: Patients who receive prescriptions for generic or preferred agents within three-tier pharmacy benefit plans are significantly more likely to adhere to treatment than those who must pay more out of pocket (pp. 332-7). This message comes from an analysis of claims filed over a 2-year period for six classes of long-term medications: statins, calcium-channel blockers, oral contraceptives, orally inhaled corticosteroids, angiotensin receptor blockers, and ACE inhibitors. Comparing the proportion of days covered in each class for the first year of therapy, the researchers found, “A total of 7532 new prescriptions were filled in 1 of the classes evaluated: 1747 (23.2%) for nonpreferred medications, 4376 (58.1%) for preferred drugs, and 1409 (18.7%) for generic drugs. After controlling for patient sociodemographic characteristics and drug class, PDC was 12.6% greater for patients initiated on generic medications vs nonpreferred medications (58.8% vs 52.2%; P < .001). The PDC was 8.8% greater for patients initiated on preferred vs nonpreferred medications (56.8% vs 52.2%; P < .001). Patients initiated on generic and preferred medications had 62% and 30% greater odds, respectively, of achieving adequate adherence compared with those who received nonpreferred medications.” (W. H. Shrank, wshrank@partners.org)
Effectiveness of Black-Box Warnings: In an analysis of prescriptions in 51 outpatient practices, only 7 in 1,000 patients received prescriptions that violated black-box warnings in product labeling, and few incidents resulted in detectable harm (pp. 338-44): “Of 324,548 outpatients who received a medication in 2002, 2354 (0.7%) received a prescription in violation of a black box warning. After adjustment, receipt of medication in violation of a black box warning was more likely when patients were 75 years or older or female. The number of medications taken, the number of medical problems, and the site of care were also associated with violations. Less than 1% of patients who received a drug in violation of a black box warning had an adverse drug event as a result.” But even this low level of violations places large numbers of patients at risk, investigators conclude: “Our results suggest that although a few outpatients seem to receive prescriptions in violation of black box warnings for drug-drug, drug-laboratory, and/or drug-disease interactions, the absolute number of outpatients at risk is substantial. To increase adherence to black box warnings, such warnings need to be clarified, simplified, and made consistent with commonly used practice guidelines. Future studies should explore the effectiveness of [electronic health record]-based alerts for the most commonly violated medication warnings and for warnings that, when violated, have a high potential to cause patient harm.” (K. E. Lasser, Cambridge Health Alliance, Cambridge, Mass.; klasser@challiance.org)
Estrogens After Menopause: In healthy postmenopausal women, addition of conjugated equine estrogens provided no overall protection against myocardial infarction or coronary death, according to an update from the Women’s Health Initiative (pp. 357-65). One subgroup did benefit from an associated reduction in cardiovascular risk: women aged 50 to 59 years at baseline, in whom coronary revascularization was less frequent with CEE (hazard ratio, 0.55; 95% CI, 0.35-0.86), and several composite outcomes showed improvements.” (J. Hsia, George Washington U., Washington, D.C.; jhsia@mfa.gwu.edu)

>>>PNN NewsWatch
* A decision by the Veterans Health Administration to stop using benzocaine sprays for numbing mouths and throats during minor surgical procedures has led FDA to update its advice regarding these products. Cases of methemoglobinemia have resulted from routine use of benzocaine sprays as well as medication errors due to incorrect use of the products (e.g., longer duration or more frequent sprays than recommended), FDA noted in a public health advisory posted on its Web site. The VA is ending use of benzocaine sprays because it believes other topical anesthetics are less likely to cause methemoglobinemia and because the procedures themselves might cause similar signs.

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 © 2006, 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
Feb. 15, 2006 Vol. 13, No. 31
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 15 issue of JAMA (www.jama.com; 2006; 295).
Rimonabant for Weight Loss: Modest improvements in weight, HDL cholesterol, and triglycerides were recorded among 3,045 patients with obesity who participated in a randomized controlled trial of the investigational agent rimonabant (pp. 761-75). The drug, a selective endocannabinoid CB1 receptor blocker, was used in the 1-year trial in conjunction with caloric-reduction diets and exercise, with these results: “At year 1, the completion rate was 309 (51%) patients in the placebo group, 620 (51%) patients in the 5 mg of rimonabant group, and 673 (55%) patients in the 20 mg of rimonabant group. Compared with the placebo group, the 20 mg of rimonabant group produced greater mean (SEM) reductions in weight (-6.3 [0.2] kg vs -1.6 [0.2] kg; P < .001), waist circumference (-6.1 [0.2] cm vs -2.5 [0.3] cm; P < .001), and level of triglycerides (percentage change, -5.3 [1.2] vs 7.9 [2.0]; P < .001) and a greater increase in level of high-density lipoprotein cholesterol (percentage change, 12.6 [0.5] vs 5.4 [0.7]; P < .001). Patients who were switched from the 20 mg of rimonabant group to the placebo group during year 2 experienced weight regain while those who continued to receive 20 mg of rimonabant maintained their weight loss and favorable changes in cardiometabolic risk factors. Use of different imputation methods to account for the high rate of dropouts in all 3 groups yielded similar results. Rimonabant was generally well tolerated; the most common drug-related adverse event was nausea (11.2% for the 20 mg of rimonabant group vs 5.8% for the placebo group).” (F. X. Pi-Sunyer, fxp1@columbia.edu)
While the reasons to reduce weight in individuals with obesity are many, editorialists provide this analysis of the gaps in research and practice (pp. 826-8): “Medications, diets, and lifestyle interventions all may have a role for high-risk patients in clinical practice but more research is needed on the effectiveness of diet and lifestyle interventions actually delivered in practice, as well as on the long-term efficacy and safety of medications. In addition to interventions aimed at individual patients, there is a need for a much broader spectrum of approaches to address the widespread obesity problem. Overweight or obesity seems almost inevitable in adulthood, the proportion of overweight children has tripled from 5% to 15% over the past 30 years and there is increasing evidence that environmental factors may influence the development of obesity. Because obesity seems to be a societal problem, a public health approach should complement a clinical high-risk approach. Interventions for obesity prevention and reduction are needed in settings where people live, work, and play (including communities, work sites, and schools) as well as in clinical practice. Drug treatments for obesity should be considered within this broader context and their current role should be limited pending further evidence.” (D. G. Simons-Morton,
simonsd@nhlbi.nih.gov)
Morphine/Tetracaine in Preterm Neonates: While causing some respiratory depression, morphine proved a useful addition to tetracaine in management of analgesia during central line placement in a group of 132 ventilated neonates with mean gestational age of 30.6 weeks (pp. 793-800): “Compared with no treatment, pain scores were lower in the morphine and tetracaine-morphine groups during skin preparation (mean difference, -0.22; 95% confidence interval [CI], -0.4 to -0.04; P = .02 and -0.29; 95% CI, -0.49 to -0.09; P = .01, respectively), and needle puncture (mean difference, -0.35; 95% CI, -0.57 to -0.13; P = .003 and -0.47; 95% CI, -.71 to -0.24; P < .001, respectively), but pain scores did not differ statistically for tetracaine alone vs no treatment. Pain scores were lower for morphine and tetracaine-morphine vs tetracaine during the skin preparation phase and for tetracaine-morphine vs tetracaine during needle puncture. Compared with neonates without morphine, morphine-treated neonates required larger increases in ventilation rate in the first 12 hours (mean difference, 3.9/min; 95% CI, 1.3-6.5/min; P = .003). Local skin reactions occurred in 30% of neonates given tetracaine vs 0% for morphine (risk difference, 0.30; 95% CI, 0.19-0.41; P < .001).” (A. Taddio, Hospital for Sick Children, Toronto; anna.taddio@sickkids.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 © 2006, 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
Feb. 16, 2006 Vol. 13, No. 32
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 16 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).
Calcium/Vitamin D & Fractures: While hip bone density improved among postmenopausal women assigned to calcium/vitamin D supplements, the frequency of hip fracture was not significantly reduced and the risk of kidney stones was increased significantly, according to a report from the Women’s Health Initiative (pp. 669-83). Using placebo or daily doses of elemental calcium 1,000 mg (as the carbonate salt) and vitamin D3 400 IU in the 36,282 study participants, the investigators found: “Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P < 0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels.” (R. D. Jackson, jackson.20@osu.edu)
An editorialist suggests this course of action for clinicians when making recommendations for postmenopausal women (pp. 750-2): “Although there was an increased risk of kidney stones, the possible benefits of calcium with vitamin D supplementation for the risk of fracture cannot be totally ignored. It seems reasonable to recommend that women consume the recommended daily levels of calcium and vitamin D through diet, supplements, or both. But one message is clear: calcium with vitamin D supplementation by itself is not enough to ensure optimal bone health. Clinicians and patients should be aware that even if a woman is receiving adequate calcium with vitamin D supplementation, she may still be at risk for fracture, particularly if she has low bone mineral density or other clinical risk factors. Additional therapy with agents that have been proved to reduce the risk of fracture in women with osteoporosis, such as antiresorptive medications or teriparatide, may be indicated. Calcium with vitamin D supplementation is akin to the ante for a poker game: it is where everyone starts. If the clinical data suggest that the risk of fracture is significant, however, a woman probably needs something more.” (J. S. Finkelstein, Mass. Genl. Hosp., Boston)
Calcium/Vitamin D & Colorectal Cancer: In a second report from the Women’s Health Initiative, calcium/vitamin D supplements had no significant effect on the incidence of colorectal cancer over an average of 7 years of treatment (pp. 684-96). Compared with placebo, the same doses of calcium/vitamin D as in the above report produced these results: “The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P = 0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.” (J. Wactawski-Wende, jww@buffalo.edu)
Noting that the vitamin and mineral doses used in WHI might be too low to achieve colorectal cancer prevention, editorialists suggest these future research efforts (pp. 752-4): “A controlled feeding study could be designed to provide and keep track of all foods eaten by participants and to monitor their weight, physical activity, and exposure to ultraviolet light. Another study might examine the effects of various doses of calcium with vitamin D supplements in healthy postmenopausal women who follow a low-fat diet high in fruits and vegetables as compared with women who follow their usual diet.” (M. Forman, U. Texas M.D. Anderson Cancer Ctr., Houston)

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 © 2006, 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
Feb. 17, 2006 Vol. 13, No. 33
Providing news and information about medications and their proper use

>>>Circulation Highlights
Source:
Early-release articles from Circulation (circ.ahajournals.org; 2006; 113).
Metoprolol in HF: Beta-blockade may produce rises in cardiac natriuretic peptides that are not related to a degradation in clinical status, according to a study of 16 men with mild, stable heart failure (doi: 10.1161/CIRCULATIONAHA.105.567727). Clinicians need to be aware of the possibility of rises in plasma brain natriuretic peptide (BNP)/N-terminal pro brain natriuretic peptide (NTproBNP), atrial natriuretic peptide (ANP), and other cardiac peptides, the authors explain, adding this evidence: “Plasma natriuretic peptides (BNP, NTproBNP, ANP, and NTproANP) were increased by metoprolol (P < 0.01 for all). The natriuretic responses to ANP and BNP infusions were sustained with the introduction of metoprolol despite reduced renal perfusion pressure. The levels of the noninfused natriuretic peptide were increased by both ANP and BNP infusions, and this effect was enhanced by metoprolol. The early plasma half-life of BNP was prolonged by metoprolol (5.6 ± 0.45 to 11 ± 1.3 versus 5.7 ± 0.8 to 6.6 ± 1.3 minutes in control subjects; P = 0.019).” (M. E. Davis, Christchurch Sch. of Med. and Health Sci., Christchurch, New Zealand; mark.davis@chmeds.ac.nz)

>>>Allergy/Immunology Update
Source:
Feb. issue of Journal of Allergy and Clinical Immunology (www.jacionline.org; 2006; 117).
CEA of Inhaled Steroids in Asthma: Inhaled corticosteroids compare favorably with other mild/moderate asthma interventions based on a cost-effectiveness analysis and an assessment of the drugs’ impact on bone mineral density (pp. 359-66). “Assuming a dose of 200 mcg twice per day of ICS, a literature-based average effect of ICS on BMD and a 10-year time horizon, we observed a minimal increase in the costs attributed to hip fracture and incremental cost effectiveness ratio of $26,000 per quality-adjusted life-year and $14.00 per symptom-free day gained,” the authors report. “Over an extended the time horizon (lifetime), the incremental cost effectiveness ratio increased to $42,000/quality-adjusted life-year. Only under a scenario of high-dose ICS, a lifetime horizon, and a large effect of ICS on BMD did the potential impact of ICS on BMD dramatically affect the economic attractiveness of therapy.” (A. L. Fuhlbrigge, Channing Laboratory, Boston; anne.fuhlbrigge@channing.harvard.edu)

>>>PNN NewsWatch
* Bristol-Myers Squibb yesterday announced labeling changes for gatifloxacin (Tequin). Detailed in a letter to health care professionals, the warnings update the prescription information as a result of continued reports of serious cases of hypoglycemia and hyperglycemia in patients receiving gatifloxacin. Since the approval of gatifloxacin in 1999, life-threatening events have been reported rarely around the world in patients treated with this antibiotic. Most of these events were reversible when properly managed, but a few had fatal outcomes. The labeling changes strengthen the existing warning on hypoglycemia and hyperglycemia, add a contraindication against use in patients with diabetes, and include information identifying other risk factors for developing low and high blood glucose, including advanced age, renal insufficiency, and concomitant use of glucose-altering medications while taking gatifloxacin.
* The
CDC has enhanced recommendations for influenza vaccine in an effort to increase the proportion of health care workers who received the annual immunization. About 40% of these workers are currently immunized in the typical flu season. In a guidance from the Healthcare Infection Control Practices Advisory Committee and the Advisory Committee on Immunization Practices, CDC advises that facilities offer influenza vaccine annually to all eligible personnel, including students, through onsite immunization efforts that are offered during all shifts and at no cost to workers; use proven strategies such as education, reminders, and leadership to motivate workers to get vaccinated; and obtain a signed form from staff who decline to participate to aid in identifying employee concerns and barriers and developing strategies for overcoming them.
*
PNN will not be published on Mon., Feb. 20, Presidents 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 © 2006, 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
Feb. 21, 2006 Vol. 13, No. 34
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 21 issue of Annals of Internal Medicine (www.annals.org; 2006; 144).
Statins, Beta-Blockers, & CHD: While requiring confirmation in randomized controlled trials, statins and beta-blockers were protective against unstable, higher-risk presentations of coronary heart disease in a case–control study of adults whose first presentation of coronary disease was acute myocardial infarction (n = 916) or stable exertional angina (n = 468; pp. 229-38). “Compared with patients with incident stable exertional angina, patients with incident acute myocardial infarction were more likely to be men, smokers, physically inactive, and hypertensive but were less likely to have a parental history of coronary disease,” the authors write. “Patients presenting with myocardial infarction were much less likely to have received statins (19.3% vs. 40.4%; P < 0.001) and beta-blockers (19.0% vs. 47.7%; P < 0.001) than patients presenting with exertional angina. After adjustment for potential confounders, recent use of statins (adjusted odds ratio, 0.45 [95% CI, 0.32 to 0.62]) and beta-blockers (adjusted odds ratio, 0.26 [CI, 0.19 to 0.35]) was associated with lower likelihoods of presenting with an acute myocardial infarction than with stable angina.” (A. S. Go, Kaiser Permanente, Oakland, Calif.; Alan.S.Go@kp.org)
An editorialist, after detailing prior research on statin therapy, points out that beta-blockers have a less extensive body of evidence supporting their use in this clinical situation (pp. 296-7): “One randomized clinical trial evaluated low-dose (25 mg/d) metoprolol (controlled release/extended release) in 793 patients. Of these patients, only 4% had a history of cardiovascular disease and none had a history of angina or myocardial infarction in the preceding 3 months. The progression of intima–media thickness in the carotid bulb at 18 months and 36 months was slower with metoprolol. The effect did not seem to be related to reduction in blood pressure. Metoprolol was associated with a trend toward reduction in nonfatal and fatal myocardial infarction and nonfatal stroke (P = 0.055). In addition to better control of blood pressure, a stabilizing vascular effect resulting from beta-blocker therapy could contribute to the lower incidence of myocardial infarction in Go and colleagues' study.” (S. C. Smith Jr., U. North Carolina, Chapel Hill, N.C.)
Zoledronate After Liver Transplant: During the first year after liver transplantation, zoledronic acid therapy is an effective preventive against bone loss, according to a 62-patient study conducted at two large Australian transplant centers (pp. 239-48). Zoledronic acid 4 mg or saline was infused within 7 days of transplantation and at 1, 3, 6, and 9 months after transplantation, with these results: “There were statistically significant interactions between treatment effects and time for BMD measurements at the lumbar spine (P = 0.002), femoral neck (P = 0.001), and total hip (P < 0.001). Differences in acute bone loss 3 months after transplantation favored zoledronic acid over placebo. Differences between groups in percentage change from baseline adjusted for baseline weight and serum parathyroid hormone (PTH) level were 4.0% (95% CI, 1.1% to 7.0%) for the lumbar spine, 4.7% (CI, 1.9% to 7.6%) for the femoral neck, and 3.8% (CI, 1.7% to 6.0%) for the total hip. At 12 months after transplantation, the difference in percentage change from baseline between the 2 groups adjusted for baseline weight and serum PTH level was 1.1% (CI, –2.1% to 4.4%) for the lumbar spine, 2.7% (CI, 0.0% to 5.4%) for the femoral neck, and 2.4% (CI, 0.1% to 4.7%) for the total hip. Treatment with zoledronic acid induced temporary secondary hyperparathyroidism and postinfusion hypocalcemia statistically significantly more often than did placebo.” (G. W. McCaughan, Royal Prince Alfred Hosp., Camperdown, New South Wales, Australia)

>>>PNN JournalWatch
* Procedural Sedation and Analgesia in Children, in Lancet, 2006; DOI:10.1016/S0140-6736(06)68230-5. Reprints: www.lancet.com; B. Krauss; baruch.krauss@childrens.harvard.edu
* Treatment of Low Back Pain by Acupressure and Physical Therapy: Randomised Controlled Trial, in
BMJ, 2006; doi:10.1136/bmj.38744.672616.AE. Reprints: www.bmj.org; T. H-H Chen, National Taiwan U., Taipei, Taiwan; stony@episerv.cph.ntu.edu.tw

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 © 2006, 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
Feb. 22, 2006 Vol. 13, No. 35
Providing news and information about medications and their proper use

>>>Anidulafungin Approved
Pfizer yesterday announced FDA approval of anidulafungin (Eraxis) for treatment of candidemia, a potentially fatal complication in hospitalized patients that affects an estimated 60,000 Americans each year. The new antifungal agent, a member of the echinocandin class, was also approved for treating candidal peritonitis and intra-abdominal abscesses as well as esophageal candidiasis.
Patients at high risk for candidemia and systemic candidiasis include those with compromised immune systems, stem-cell and organ-transplant recipients, patients on chemotherapy, patients with catheters, critically ill patients in intensive care units, surgical patients, and patients on prolonged antibiotic therapy. In the U.S., patients with candidemia on average spend an additional 10 days in the hospital at an average increase in hospital charges of about $39,000 per patient.
In clinical studies, anidulafungin was as well tolerated as fluconazole, with similar numbers of drug-related adverse events with the two medications. The most common treatment-related adverse events for anidulafungin in the candidemia study were hypokalemia (3.1%), diarrhea (3.1%), and elevated ALT levels (2.3%). In the esophageal candidiasis study, the most common treatment-related adverse events for anidulafungin were headache (1.3%) and an increase in the liver enzyme GGT (1.3%).
Anidulafungin has not been associated with renal toxicity and has no clinically relevant drug–drug interactions. Anidulafungin also does not require dose adjustments based on gender, race, age, HIV status, hepatic insufficiency, or renal insufficiency. Safety and effectiveness of anidulafungin in pediatric patients has not been established.
Anidulafungin is contraindicated in patients with hypersensitivity to anidulafungin, any other component of Eraxis, or other echinocandin agents. In some patients with serious underlying medical conditions receiving multiple concomitant medications along with anidulafungin, clinically significant hepatic abnormalities have occurred. Possible histamine-mediated symptoms have been reported infrequently with anidulafungin, including rash, urticaria, flushing, pruritus, dyspnea, and hypotension.

>>>JAMA Highlights
Source:
Feb. 22 issue of JAMA (www.jama.com; 2006; 295).
Adamantane Resistance: An article reporting the rapid emergence of amantadine resistance among influenza A isolated during the current influenza season in the U.S. concludes that “these drugs should not be used for the treatment or prophylaxis of influenza in the United States until susceptibility to adamantanes has been reestablished among circulating influenza A isolates” (pp. 891-4). Considering resistance to amantadine and rimantadine in viral strains isolated between Oct. 1 and Dec. 31, 2005, the investigators found these mutations in the M2 gene that confers adamantane resistance: “A total of 209 influenza A(H3N2) viruses isolated from patients in 26 states were screened, of which 193 (92.3%) contained a change at amino acid 31 (serine to asparagine [S31N]) in the M2 gene known to be correlated with adamantane resistance. Two of 8 influenza A(H1N1) viruses contained the same mutation. Drug-resistant viruses were distributed across the United States.” (R. A. Bright, CDC, Atlanta)
Editorialists, calling this report a “clarion call for action,” advocate these steps (pp. 934-6): “Physicians and other health care professionals must (1) educate patients and communities; (2) organize an international response through governmental and nongovernmental organizations; (3) advocate against the release of over-the-counter antiviral drugs, either directly by major drug companies or through licensing agreements with generic manufacturers; and (4) recognize the powerful influences that affect prescribing practices before assigning culpability to those who have inappropriately used adamantanes. To the latter point, fear of an avian influenza pandemic in the summer of 2005 resulted in so many prescriptions for oseltamivir being written that the drug's manufacturer temporarily stopped shipping it to the United States.” (D. M. Weinstock, Memorial Sloan-Kettering Cancer Ctr., New York;
weinstod@mskcc.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 © 2006, 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
Feb. 23, 2006 Vol. 13, No. 36
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 23 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354)
Glucosamine, Chondroitin for Knee Osteoarthritis: Patients with moderate to severe knee pain caused by osteoarthritis may benefit from treatment with the dietary supplements glucosamine and chondroitin, but the agents provide no panacea for patients with this condition (pp. 795-808). That conclusion comes from the multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT), which included 1,583 patients with symptomatic knee osteoarthritis who received glucosamine 1,500 mg daily, chondroitin sulfate 1,200 mg daily, both glucosamine and chondroitin sulfate, celecoxib 200 mg daily, or placebo for 24 weeks.
GAIT investigators report these results: “The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P = 0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P = 0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P = 0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P = 0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P = 0.002). Adverse events were mild, infrequent, and evenly distributed among the groups.” (D. O. Clegg,
gait.study@hsc.utah.edu)
Because GAIT used the hydrochloride salt of glucosamine and studies of the sulfate salt have produced more positive findings, an editorialist provides this advice to share with patients (pp. 858-60): “On the basis of the results from GAIT, it seems prudent to tell our patients with symptomatic osteoarthritis of the knee that neither glucosamine hydrochloride nor chondroitin sulfate alone has been shown to be more efficacious than placebo for the treatment of knee pain. If patients choose to take dietary supplements to control their symptoms, they should be advised to take glucosamine sulfate rather than glucosamine hydrochloride and, for those with severe pain, that taking chondroitin sulfate with glucosamine sulfate may have an additive effect. Three months of treatment is a sufficient period for the evaluation of efficacy; if there is no clinically significant decrease in symptoms by this time, the supplements should be discontinued. Furthermore, there is no evidence that these agents prevent osteoarthritis in healthy persons or in persons with knee pain but normal radiographs.” (M. C. Hochberg, U. Maryland, Baltimore)
Denosumab in Low BMD: Data from a preliminary study of the human monoclonal antibody denosumab show that that agent may be an effective treatment for osteoporosis (pp. 821-31). Among 412 postmenopausal women with low bone mineral density, 12 months of treatment with denosumab 6, 14, or 30 mg every 3 months, open-label alendronate 70 mg once weekly, or placebo produced these results: “Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent.” (M. R. McClung, Oregon Osteoporosis Ctr., Portland; mmcclung@orost.com)

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 © 2006, 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
Feb. 24, 2006 Vol. 13, No. 37
Providing news and information about medications and their proper use

>>>Infectious Disease Update
Source:
Mar. 15 issue of Clinical Infectious Diseases (www.journals.uchicago.edu/CID; 2006; 42).
Preventing Transmission of Multidrug-Resistant Bacteria in Health Care Settings: “Aggressive and widespread adoption of control measures for multidrug-resistant organisms is urgently needed,” conclude authors of an invited article who review two guidelines for accomplishing this goal that have been published within the past 3 years (pp. 828-35). Referring to documents put forth by the Society for Healthcare Epidemiology of America and the Healthcare Infection Control Practices Advisory Committee of the CDC, the authors write: “These guidelines reflect universal concern in the infection-control community about today's unprecedented levels of activity of multidrug-resistant organisms and about inadequate or inconsistent application of potentially effective control measures. The 2 guidelines provide detailed reviews of pertinent issues and evidence-based, rated recommendations, which overlap considerably. Recommendations regarding indications for active surveillance cultures and the extent of their use constitute the major divergence. (L. J. Strausbaugh, VA Med. Ctr., Portland, Oreg.; strausba@ohsu.edu)
Controlling VRE Outbreak: Faced with a large outbreak of vancomycin-resistant Enterococcus faecium at a Dutch university hospital, officials successfully contained the 2000 situation through use of genotyping-targeted infection control, isolation of VRE carriers, enhancement of hand-hygiene compliance, and preemptive isolation successfully controlled nosocomial spread of epidemic VRE infection (pp. 739-46). Infection-control procedures changed during the outbreak as the situation emerged. Period I included active surveillance, isolation of carriers, and cohorting, and lasted for 4 months; during the 7 months of period II, preemptive isolation of high-risk patients for VRE colonization was added; and in period III, which lasted for 18 months, cohorting and preemptive isolation were abandoned. The investigators report these results: “When the outbreak was identified, 27 patients in 6 wards were colonized; 93% were colonized with an epidemic VRE strain. Detection rates of nonepidemic VRE were 3.5%, 3.0%, and 2.9% among 683, 810, and 977 screened patients in periods I, II, and III, respectively, comparable to a prevalence of 2% (95% confidence interval [CI], 1%–3.5%) among 600 nonhospitalized persons. The relative risks of detecting epidemic VRE in periods II and III, compared with period I, were 0.67 (95% CI, 0.41-1.10) for period II and 0.02 (95% CI, 0.002–0.6) for period III. Infection-control measures were withheld for patients colonized with nonepidemic VRE (76 [54%] of 140 patients with a test result positive for VRE). Use of alcohol-based hand rubs increased by 31%-275% in outbreak wards. ” (M. J. M. Bonten, U. Med. Ctr., Utrecht, the Netherlands; mbonten@umcutrecht.nl)
Antibiotic Control & Education: At a tertiary-care center in Thailand, researchers found education and an antibiotic-control program to be an effective and cost-saving strategy for optimizing antibiotic use (pp. 768-75). Assessing the impact of this two-pronged approach, the authors report these results: “After the intervention, there was a 24% reduction in the rate of antibiotic prescription (640 vs. 400 prescriptions/1000 admissions; P < .001). The incidence of inappropriate antibiotic use was significantly reduced (42% vs. 20%; P < .001). A sustained reduction in antibiotic use was observed (R2 = 0.692; P < .001). Rates of use of third-generation cephalosporins (31 vs. 18 defined daily doses [DDDs]/1000 patient-days; P < .001) and glycopeptides (3.2 vs. 2.4 DDDs/1000 patient-days; P = .002) were significantly reduced. Rates of use of cefazolin (3.5 vs. 8.2 DDDs/1000 patient-days; P < .001) and fluoroquinolones (0.68 vs. 1.15 DDDs/1000 patient-days; P < .001) increased. There were no significant changes for other antibiotic classes.... Total costs saving were US$32,231 during the study period.” (A. Apisarnthanarak, Thammasart U. Hosp., Pratumthani, Thailand; anapisarn@yahoo.com)

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 © 2006, 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
Feb. 27, 2006 Vol. 13, No. 38
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from and Feb. 25 issue of BMJ (www.bmj.org; 2006; 332).
Bias in CEA Studies: Published cost-effectiveness analyses sponsored by the pharmaceutical industry are more likely to report incremental CEA ratios below each of three key thresholds, while studies with better methodologies or conducted in Europe or the U.S. were significantly less likely to report ratios below $20,000 per quality-adjusted life-year (doi: 10.1136/bmj.38737.607558.80). That conclusion comes from a systematic review of 494 studies published in English and measuring health effects in QALYs. With dollar values set to the year of study publication, the authors report, “Approximately half the reported incremental cost effectiveness ratios (712 of 1433) were below $20,000/QALY. Studies funded by industry were more likely to report cost effectiveness ratios below $20,000/QALY (adjusted odds ratio 2.1, 95% confidence interval 1.3 to 3.3), $50,000/QALY (3.2, 1.8 to 5.7), and $100,000/QALY (3.3, 1.6 to 6.8). Studies of higher methodological quality (adjusted odds ratio 0.58, 0.37 to 0.91) and those conducted in Europe (0.59, 0.33 to 1.1) and the United States (0.44, 0.26 to 0.76) rather than elsewhere were less likely to report ratios below $20,000/QALY.” (C. M. Bell, St Michael's Hosp., Toronto; bellc@smh.toronto.on.ca)
Anticholinergic Drug Use & Cognitive Function: Among 372 people aged 60 years or older in southern France, those “taking anticholinergic drugs had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired, although not at increased risk for dementia” (pp. 455-9). In a longitudinal cohort study, investigators observed these trends: “9.2% of subjects continuously used anticholinergic drugs during the year before cognitive assessment. Compared with non-users, they had poorer performance on reaction time, attention, delayed non-verbal memory, narrative recall, visuospatial construction, and language tasks but not on tasks of reasoning, immediate and delayed recall of wordlists, and implicit memory. Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35% of non-users, and anticholinergic drug use was a strong predictor of mild cognitive impairment (odds ratio 5.12, P = 0.001). No difference was found between users and non-users in risk of developing dementia at follow-up after eight years.” (K. Ritchie, Hôpital La Colombière, Montpellier, France; ritchie@montp.inserm.fr)
Meningococcal Risk Factors Among Adolescents: For adolescents considering the meningococcal vaccine, a study from England identifies and quantifies various risk factors and shows that immunization lowers disease risk by 88% (pp. 445-50). In this prospective matched cohort study of 144 case–control pairs, researchers found: “114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4 to 5.9), intimate kissing with multiple partners (3.7, 1.7 to 8.1), being a university student (3.4, 1.2 to 10) and preterm birth (3.7, 1.0 to 13.5). Religious observance (0.09, 0.02 to 0.6) and meningococcal vaccination (0.12, 0.04 to 0.4) were associated with protection.” (R. Booy, U. London, London; robertb2@chw.edu.au)

>>>PNN JournalWatch
* Seasonal Intermittent Preventive Treatment with Artesunate and Sulfadoxine-Pyrimethamine for Prevention of Malaria in Senegalese Children: A Randomised, Placebo-Controlled, Double-Blind Trial, in Lancet, 2006; 367: 659–67. Reprints: www.thelancet.com; B. Cissé, London School of Hygiene & Tropical Medicine, London; badara.cisse@lshtm.ac.uk
* Soy Protein, Isoflavones, and Cardiovascular Health: An American Heart Association Science Advisory for Professionals From the Nutrition Committee, in
Circulation, 2006; 113: 1034–44. Reprints: circ.ahajournals.org
* Secondary-Prevention Drug Prescription in the Very Elderly After Ischemic Stroke or TIA, in
Neurology, 2006; 66: 313–8. Reprints: www.neurology.org; B. Ovbiagele, Ovibes@mednet.ucla.edu
* Nutrition and HIV Infection: Review of Weight Loss and Wasting in the Era of Highly Active Antiretroviral Therapy from the Nutrition for Healthy Living Cohort, in
Clinical Infectious Diseases, 2006; 42: 836–42. Reprints: www.journals.uchicago.edu/CID; A. Mangili, amangili@tufts-NEMC.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 © 2006, 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
Feb. 28, 2006 Vol. 13, No. 39
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 27 issue of the Archives of Internal Medicine (www.archinternmed.com; 2006; 166).
Vitamin K & Excessive Anticoagulation: A meta-analysis calls into question the relative efficacy of phytonadione when administered by the oral, intravenous, and subcutaneous routes in the management of excessive anticoagulation with warfarin (pp. 391-7). Investigators conclude that oral and i.v. vitamin K “are equivalent and more effective for excessive anticoagulation than simply withholding warfarin sodium,” adding, “Subcutaneous vitamin K, however, is inferior to oral and intravenous vitamin K for this indication and is similar to placebo. Whether treatment with vitamin K decreases hemorrhagic events cannot be determined from the published literature.”
The authors provide this evidence from the meta-analysis in support of this conclusion: “Twenty-one studies (10 randomized and 11 prospective trials) were included. Among oral vitamin K treatment arms (4, n = 75), the proportion with a target INR at 24 hours was 82% (95% confidence interval [CI], 70%-93%), which was similar to intravenous vitamin K treatment arms (6, n = 69; target INR, 77%; 95% CI, 60%-95%). Treatment arms of subcutaneous vitamin K (3, n = 58; 31%; 95% CI, 7%-55%) and placebo/observation (2, n = 27; 20%; 95% CI, 0%-47%) were less likely to achieve target INR at 24 hours. Only 1 of 21 trials appropriately assessed for adverse events, so a summary estimate for bleeding risk could not be generated.” (K. J. DeZee, William Beaumont Army Med. Ctr., El Paso, Tex.,
kent.dezee@us.army.mil)
Estrogens, MI, & Stroke: Esterified estrogens appear to differ from conjugated equine estrogens in terms of effects on risk for myocardial infarction and stroke, report researchers who conducted a population-based case-control study within a health-maintenance organization (pp. 399-404). Comparing postmenopausal women with an incident MI (n = 1,644) or stroke (n = 1,080) and controls (n = 4,205), the investigators observe: “There was no difference in risk of MI or stroke associated with current use of CEE or EE compared with nonuse or for current use of CEE compared with EE. In analyses restricted to hormone users, there was a suggestion of higher ischemic stroke risk associated with CEE alone (without progestin) compared with EE alone (odds ratio, 1.57; 95% confidence interval, 0.98-2.53). There was also a suggestion that when initiated in the previous 6 months, CEE was associated with a higher risk of MI than EE (odds ratio, 2.33; 95% confidence interval, 0.93-5.82).” (R. N. Lemaitre, rozenl@u.washington.edu)
Cocoa, Blood Pressure, & Mortality: Among 470 elderly men free of chronic disease in 1985, use of cocoa was associated with lower blood pressures and decreased 15-year cardiovascular and all-cause mortality (pp. 411-7). Cocoa contains flavan-3-ols, which have been linked to lower blood pressure and improved endothelial function. In this study, mean systolic blood pressure among those in the highest tertile of cocoa intake was a mean of 3.7 mm Hg lower (95% CI, -7.1 to -0.3), and diastolic blood pressures averaged 2.1 mm Hg lower (-4.0 to -0.2). “During follow-up, 314 men died, 152 of cardiovascular diseases,” the authors note. “Compared with the lowest tertile of cocoa intake, the adjusted relative risk for men in the highest tertile was 0.50 (95% CI, 0.32-0.78; P = .004 for trend) for cardiovascular mortality and 0.53 (95% CI, 0.39-0.72; P < .001) for all-cause mortality.” (B. Buijsse, National Inst. for Public Health and the Environment, Bilthoven, the Netherlands; brian.buijsse@rivm.nl)

>>>PNN NewsWatch
* A page 1 article in today’s Wall Street Journal questions conclusions reached about dietary fat, calcium, and hormones in the Women’s Health Initiative and claims data have been overblown by the media. “Design problems in all of the trials mean the results don't really answer the questions they were supposed to address,” writes Tara Parker-Pope. “And a flawed communications effort led to widespread misinterpretation of results by the news media and public.”

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 © 2006, 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
Mar. 1, 2006 Vol. 13, No. 40
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 1 issue of JAMA (www.jama.com; 2006; 295).
G-CSF Stem-Cell Mobilization in AMI: A randomized controlled trial of stem-cell mobilization with granulocyte colony-stimulating factor in patients with ST-segment–elevation acute myocardial infarction failed to support positive results observed in previous pilot and early-phase clinical trials (pp. 1003-10). Researchers had believed that G-CSF stem-cell mobilization might improve cardiac regeneration and neovascularization, but they made these observations after administering placebo or G-CSF 5 mcg daily for 5 days: “Of the 114 patients, 56 were assigned to receive treatment with G-CSF and 58 were assigned to receive placebo. Treatment with G-CSF produced a significant mobilization of stem cells. Between baseline and follow-up, left ventricular infarct size according to scintigraphy was reduced by a mean (SD) of 6.2% (9.1%) in the G-CSF group and 4.9% (8.9%) in the placebo group (P = .56) and left ventricular ejection fraction was improved by 0.5% (3.8%) in the G-CSF group and 2.0% (4.9%) in the placebo group (P = .14). Angiographic restenosis occurred in 19 (35.2%) of 54 patients in the G-CSF group and in 17 (30.9%) of 55 patients in the placebo group (P = .79). The most common adverse event among patients assigned to G-CSF was mild to moderate bone pain and muscle discomfort.” (A. Schömig, Deutsches Herzzentrum, Munich, Germany; aschoemig@dhm.mhn.de)
An editorialist provides this perspective on the state of research into post-AMI interventions (pp. 1058-60): “Even 3 to 6 hours after AMI, certain therapies still may benefit the heart. However, therapies aimed at recruiting stem cells and regenerating new myocardium remain experimental and have yet to be proven effective in large, long-term multicenter trials in which therapies are administered in a randomized, placebo-controlled, double-blind fashion and the size of the initial MI and baseline cardiac function are taken into account. The [above] study ... yielded negative results and some investigators may be disappointed with these results or may try to find fault with the study. However, this investigation is one of the first, controlled, larger, and more carefully designed studies to assess the effect of an attempt to recruit stem cells to an AMI. Additional large, carefully designed trials are needed to assess the true potential (or possibly lack of potential) of stem cell therapy to treat AMI, chronic ischemic heart disease (such as ‘hibernating’ myocardium), and nonischemic dilated cardiomyopathy. Only with such trials will it be possible to differentiate between the hype often generated by smaller, less well-controlled trials and reality.” (R. A. Kloner, Good Samaritan Hosp., Los Angeles;
rkloner@goodsam.org)
Subclinical Hypothyroidism & CVD: Among 3,233 community-dwelling Americans aged 65 years or older, subclinical hypothyroidism was associated with development of atrial fibrillation but not other cardiovascular disorders or mortality (pp. 1033-41). “Eighty-two percent of participants (n = 2639) had normal thyroid function, 15% (n = 496) had subclinical hypothyroidism, 1.6% (n = 51) had overt hypothyroidism, and 1.5% (n = 47) had subclinical hyperthyroidism,” the authors report. “After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function (67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07 (95% confidence interval, 0.90-1.28) for incident coronary heart disease.” (A. R. Cappola, acappola@cceb.med.upenn.edu)

>>>PNN NewsWatch
* FDA has approved a transdermal selegiline patch (Emsam; Bristol-Myers Squibb, Somerset) for treatment of depression. The 6 mg/24 hr patch can be used without the MAO inhibitor food restrictions.

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 © 2006, 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
Mar. 2, 2006 Vol. 13, No. 41
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release articles from and the Mar. 2 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).
Gatifloxacin & Dysglycemia: Use of gatifloxacin among outpatients is associated with an increased risk of in-hospital treatment for both hypoglycemia and hyperglycemia, according to an article released in advance of publication (doi: 10.1056/NEJMoa-055191). In two population-based, nested case-control studies, investigators found: “Between April 2002 and March 2004, we identified 788 patients treated for hypoglycemia within 30 days after antibiotic therapy. As compared with macrolide antibiotics, gatifloxacin was associated with an increased risk of hypoglycemia (adjusted odds ratio, 4.3; 95 percent confidence interval, 2.9 to 6.3). Levofloxacin was also associated with a slightly increased risk (adjusted odds ratio, 1.5; 95 percent confidence interval, 1.2 to 2.0), but no such risk was seen with moxifloxacin, ciprofloxacin, or cephalosporins. We then identified 470 patients treated for hyperglycemia within 30 days after antibiotic therapy. As compared with macrolides, gatifloxacin was associated with a considerably increased risk of hyperglycemia (adjusted odds ratio, 16.7; 95 percent confidence interval, 10.4 to 26.8), but no risk was noted with the other antibiotics. Risks were similar in the two studies regardless of the presence or absence of diabetes.” (D. N. Juurlink, Sunnybrook and Women’s College Health Sci. Ctr., Toronto; dnj@ices.on.ca)
An editorialist writes that these problems should result in far less use of gatifloxacin (doi: 10.1056/NEJMe068051):“Gatifloxacin now takes its place among an ever-growing list of medications that have been associated with very serious adverse effects. The most immediate question is what should be done with gatifloxacin. It seems clear that the drug’s place among broad-spectrum antibiotics available for outpatient use is tenuous at best. For every approved indication for gatifloxacin, there are safer, equally effective, and less costly alternatives. In comparison with other recent experiences regarding adverse drug effects, this choice should not be a difficult one for physicians, patients, regulators, and manufacturers. ” (J. H. Gurwitz, Meyers Primary Care Inst., Worcester, Mass.)
Natalizumab in Relapsing MS: Three articles and an editorial (pp. 965-7; A. H. Ropper, Caritas St. Elizabeth's Medical Center, Boston) address use of natalizumab for relapsing multiple sclerosis and assess risk of progressive multifocal leukoencephalopathy during use of the alpha-4 integrin antagonist.
In the AFFIRM study, natalizumab reduced the risk of sustained disability by 42% among 942 patients with relapsing MS, compared with placebo (pp. 899-910). The rate of clinical relapse was also significantly lower, by 68%, with drug treatment. (C. H. Polman, Vrije Universiteit Med. Ctr., Amsterdam, the Netherlands,
ch.polman@vumc.nl)
The second article, detailing results of the SENTINEL investigation, assessed combination therapy with natalizumab plus interferon beta-1a among 1,171 patients who had at least one relapse during the 12 months before randomization and while continuing interferon beta-1a (pp. 911-23). “Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P < 0.001) and with fewer new or enlarging lesions on T2-weighted magnetic resonance imaging (0.9 vs. 5.4, P<0.001),” the authors report. (R. A. Rudick, Cleveland Clinic Foundation, Cleveland, Ohio;
rudickr@ccf.org)
The risk of PML during use of natalizumab is about 1 in 1,000 patients, concludes the third article (pp. 934-41). “Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML,” the investigators noted. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, but only the condition was ruled out in all but one patient. (E. O. Major,
majorg@ninds.nih.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 © 2006, 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
Mar. 3, 2006 Vol. 13, No. 42
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Mar. Diabetes Care (care.diabetesjournal.org; 2006; 29).
Triple Therapy: The addition of either insulin glargine or rosiglitazone to sulfonylurea plus metformin therapy in 217 insulin-naive patients with type 2 diabetes is explored in an emerging-treatments article (pp. 554-9). The study, using a randomized but open-label design, included patients whose A1c levels and body mass indices were elevated despite dual therapy. After adding insulin glargine 10 units/day or rosiglitazone 4 mg/day (both titrated as needed) for 24 weeks, the investigators noted: “A1C improvements from baseline were similar in both groups (-1.7 vs. -1.5% for insulin glargine vs. rosiglitazone, respectively); however, when baseline A1C was >9.5%, the reduction of A1C with insulin glargine was greater than with rosiglitazone (P < 0.05). Insulin glargine yielded better [fasting plasma glucose] values than rosiglitazone (-3.6 ± 0.23 vs. -2.6 ± 0.22 mmol/l; P = 0.001). Insulin glargine final dose per day was 38 ± 26 IU vs. 7.1 ± 2 mg for rosiglitazone. Confirmed hypoglycemic events at plasma glucose <3.9 mmol/l (<70 mg/dl) were slightly greater for the insulin glargine group (n = 57) than for the rosiglitazone group (n = 47) (P = 0.0528).” The group concludes, “Low-dose insulin glargine combined with a sulfonylurea and metformin resulted in similar A1C improvements except for greater reductions in A1C when baseline was 9.5% compared with add-on maximum-dose rosiglitazone. Further, insulin glargine was associated with more hypoglycemia but less weight gain, no edema, and salutary lipid changes at a lower cost of therapy.” (J. Rosenstock, Dallas Diabetes and Endocrine Ctr. at Medical City, Dallas; juliorosenstock@dallasdiabetes.com)

>>>PNN NewsWatch
* FDA has updated the prescribing information for bosentan (Tracleer—Actelion) to reflect reported cases of hepatotoxicity in those taking the drug. Monthly liver function monitoring should be continued for the duration of bosentan treatment, and recommended dosage adjustment and monitoring guidelines as described in the product labeling should be adhered to.
* Hospitals, clinics, and users should immediately stop using four lots (379,975 vials) of
Cefazolin for Injection, USP, 1 g/10 mL vials, distributed by Sandoz (lots C4650, C4537) and Watson Pharmaceuticals (lots C4689, C4665), FDA says in a recall notice. Certain lots of the active ingredient used to manufacture the product have been shown to contain microbial contamination that poses a serious or life-threatening risk for some patients.
*
Cetuximab (Erbitux; ImClone Systems, Bristol-Myers Squibb) has been approved for use in combination with radiation therapy to treat patients with squamous cell cancer of the head and neck that cannot be removed by surgery (unresectable SCCHN). This is the first drug approved for head and neck cancer that has shown a survival benefit in this population. Cetuximab was also approved as monotherapy to treat patients whose head and neck cancer has metastasized despite the use of standard chemotherapy.
* In two guidance documents released yesterday—one for seasonal and one for pandemic
influenza vaccinesFDA provides manufacturers with guidance on developing and submitting clinical data to show safety and effectiveness for new vaccines. For licensed vaccines, the guidelines describe the process for changing rapidly from the currently licensed seasonal vaccine to a new pandemic vaccine by supplementing the existing license. For new vaccines, they describe defined pathways for both traditional and accelerated approval approaches. Accelerated approval allows for evaluation based on biological indicators, such as immune response to the vaccine, likely to demonstrate effectiveness.
*
Rituximab (Rituxan; Genentech, Biogen Idec), approved in mid-February for first-line treatment of diffuse large B-cell, CD20+, non-Hodgkin's lymphoma, in combination with CHOP or other anthracycline-based chemotherapy regimens, gained its first nononcologic indication on February 28. FDA approved the monoclonal antibody for use in combination with methotrexate to reduce signs and symptoms in adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

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 © 2006, 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
Mar. 6, 2006 Vol. 13, No. 43
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release articles from and the Mar. 4 issue of Lancet (www.thelancet.com; 2006; 367).
Cytotoxic Drugs for Severe Avian Flu: Based on similarities among avian influenza A (H5N1), an overactivity of macrophages, and Epstein-Barr virus infection, researchers propose use of cytotoxic agents such as etoposide in treating severe cases of bird flu (doi: 10.1016/S0140-6736(06)68232-9). “The mortality rate in documented avian influenza A virus subtype H5N1 infection is still high, which is currently reported by WHO at about 50%,” the authors write. “Post-mortem analyses in affected patients have revealed haemophagocytosis similar to that found in patients with haemophagocytic lymphohistiocytosis (HLH); such haemophagocytosis could be a very prominent post-mortem feature in H5N1 infection. There are also clinical similarities between H5N1 infection and HLH, such as massive hypercytokinaemia, cytopenia, and acute encephalitis. Importantly, patients with another severe viral infection that may be complicated by secondary HLH, severe Epstein-Barr-virus-associated HLH, have significantly better survival if specific HLH therapy (including the cytotoxic and pro-apoptotic drug etoposide) is initiated early, with survival reported to rise from about 50% to 90%. With this notable improvement in survival, specific HLH treatment, including cytotoxic therapy, could be considered in patients with severe avian influenza A infection complicated by secondary HLH.” (J-I Henter, Karolinska U. Hosp., Stockholm, Sweden; Jan-Inge.Henter@ki.se)
Global Tobacco Use: Efforts to reduce tobacco consumption worldwide are needed to address a “large proportion of young people who currently use tobacco” and to address a high exposure to second-hand smoke both at home and in public places, according to researchers who conducted the Global Youth Tobacco Survey at 395 sites in 131 countries, the Gaza Strip, and the West Bank (pp. 749-53). The group reports: “The difference in current cigarette smoking between boys and girls is narrower than expected in many regions of the world. Use of tobacco products other than cigarettes by students is as high as cigarette smoking in many regions. Almost one in five never-smokers reported they were susceptible to smoking in the next year. Student exposure to secondhand smoke was high both at home (more than four in ten) and in public places (more than five in ten). Never-smokers were significantly less likely than current smokers to be exposed to secondhand smoke at home (prevalence 39.1% [95% CI 36.6-41.6] vs 72.8% [64.0-81.6]) and in public places (49.5% [46.7-52.3] vs 81.2% [74.2-88.2]).” (C. W. Warren, wcw1@cdc.gov)

>>>BMJ Highlights
Source:
Mar. 4 issue of BMJ (www.bmj.org; 2006; 332).
Chronic Job Stress & Metabolic Syndrome: A study of 10,308 middle-aged men and women employed in London civil service departments provides “evidence for the biological plausibility of the link between psychosocial stressors from everyday life and heart disease” (pp. 521-5). The researchers note: “A dose-response relation was found between exposure to work stressors over 14 years and risk of the metabolic syndrome, independent of other relevant risk factors. Employees with chronic work stress (three or more exposures) were more than twice as likely to have the syndrome than those without work stress (odds ratio adjusted for age and employment grade 2.25, 95% confidence interval 1.31 to 3.85).” (T. Chandola, U. Coll., London; t.chandola@ucl.ac.uk)

>>>PNN JournalWatch
* Clinical Value of the Metabolic Syndrome for Long Term Prediction of Total and Cardiovascular Mortality: Prospective, Population Based Cohort Study, in BMJ, doi:10.1136/bmj.38766.624097.1F. Reprints: www.bmj.org; J. Sundström, Uppsala U. Hosp.; Uppsala, Sweden; johan.sundstrom@medcsci.uu.se

* Update on Prostate Cancer Chemoprevention, in
Pharmacotherapy, 2006; 26: 353–9. Reprints: www.pharmacotherapy.org; J. F. Lowe, Akron General Med. Ctr., Akron, Ohio; jfisher1@agmc.org

* Incretin Mimetics and Dipeptidyl Peptidase-IV Inhibitors: Potential New Therapies for Type 2 Diabetes Mellitus, in
Pharmacotherapy, 2006; 26: 360–74. Reprints: www.pharmacotherapy.org; C. Triplitt, curtis.triplitt@uhs-sa.com

* Cognitive Behavior Therapy for Schizophrenia, in
American Journal of Psychiatry, 2006; 163: 365–73. Reprints: ajp.psychiatryonline.org; D. Turkington.

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 © 2006, 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
Mar. 7, 2006 Vol. 13, No. 44
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 7 issue of the Annals of Internal Medicine (www.annals.org; 2006; 144).
MRSA & Skin Infections: A study from Atlanta shows that methicillin-resistant Staphylococcus aureus was the predominant cause of community-onset skin and soft-tissue infections (pp. 309-17). Focusing on 384 individuals with microbiologically confirmed infections, the investigators report: “Community-onset skin and soft-tissue infection due to S. aureus was identified in 389 episodes, with MRSA accounting for 72% (279 of 389 episodes). Among all S. aureus isolates, 63% (244 of 389 isolates) were community-acquired MRSA. Among MRSA isolates, 87% (244 of 279 isolates) were community-acquired MRSA. When analysis was restricted only to MRSA isolates that were available for pulsed-field gel electrophoresis, 91% (159 of 175 isolates) had a pulsed-field type consistent with community-acquired MRSA; of these, 99% (157 of 159 isolates) were the MRSA USA 300 clone. Factors independently associated with community-acquired MRSA infection were black race (prevalence ratio, 1.53 [95% CI, 1.16 to 2.02]), female sex (prevalence ratio, 1.16 [CI, 1.02 to 1.32]), and hospitalization within the previous 12 months (prevalence ratio, 0.80 [CI, 0.66 to 0.97]). Inadequate initial antibiotic therapy was statistically significantly more common among those with community-acquired MRSA (65%) than among those with methicillin-susceptible S. aureus skin and soft-tissue infection (1%).” (H. M. Blumberg, henry.m.blumberg@emory.edu)
Commenting on this and a second study of MRSA patterns in the U.S. (pp. 318-25; P. L. Graham III, pg143@columbia.edu), an editorialist provides this advice about MRSA (pp. 368-70): “First, and most important, the clinician must be aware that the prevalence of community-acquired MRSA is rapidly increasing in the United States. The clinician should have a correspondingly low threshold for obtaining material for culture and susceptibility testing from community-acquired abscesses and other skin infections, especially those that initially resemble ‘spider bites’ with areas of necrosis. Second, the clinician should know when to use drugs with activity against community-acquired MRSA (minocycline, doxycycline, trimethoprim–sulfamethoxazole, clindamycin [if the organism is susceptible to erythromycin], or vancomycin). These drugs are indicated if the patient does not respond rapidly to appropriate drainage (when indicated) and standard antimicrobial agent therapy or in settings with a high incidence of community-acquired MRSA infections. In choosing an antibiotic, the physician should remember that trimethoprim–sulfamethoxazole is often ineffective for infections due to group A streptococci (which is the other common cause of skin infections and abscesses). Finally, in the setting of more invasive infections (necrotizing fasciitis, septic thrombophlebitis, ‘pelvic syndrome,’ or pneumonia), the clinician should immediately start therapy with vancomycin or linezolid (or daptomycin if there is no pulmonary involvement) and obtain an infectious disease consultation.” (Robert C. Moellering, Jr., Beth Israel Deaconess Med. Ctr., Boston)
CUA of ASA, Statins: For middle-aged men seeking to prevent onset of coronary heart disease, aspirin monotherapy provides the best option when 10-year risk of an event reaches 7.5%, according to a cost-utility analysis conducted from the perspective of a third-party payer (pp. 326-36). Using a Markov model and a lifetime horizon, the researchers found these results: “For 45-year-old men who do not smoke, are not hypertensive, and have a 10-year risk for CHD of 7.5%, aspirin was more effective and less costly than no treatment. The addition of a statin to aspirin therapy produced an incremental cost-utility ratio of $56 200 per quality-adjusted life-year gained compared with aspirin alone.” The group concluded, “Compared with no treatment, aspirin is less costly and more effective for preventing CHD events in middle-aged men whose 10-year risk for CHD is 7.5% or higher. The addition of a statin to aspirin therapy becomes more cost-effective when the patient's 10-year CHD risk before treatment is higher than 10%” (M. Pignone, pignone@med.unc.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 © 2006, 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
Mar. 8, 2006 Vol. 13, No. 45
Providing news and information about medications and their proper use

>>>Pharmacotherapy Update
Source:
Mar. issue of Pharmacotherapy (www.pharmacotherapy.org; 2006; 26).
Pharmacists’ Strategy for Pandemics: “Pharmacists are uniquely positioned to initiate near-term practice changes that may positively impact both seasonal and potential pandemic morbidity and mortality,” write authors who review the possibility of widespread avian (H5N1) influenza A infections (pp. 312-22). “Pharmacists must be immunization advocates and provide pharmaceutical care that includes evaluation of immunization status,” the authors note. “Increasing immunization to prevent invasive pneumococcal disease, as well as seasonal influenza immunization, is encouraged. A pandemic vaccine represents the most effective strategy to mitigate the effects of a pandemic. Antiviral agents represent a treatment bridge until a pandemic-specific vaccine is available. The neuraminidase inhibitors oseltamivir and zanamivir are active against H5N1, although oseltamivir resistance has been reported. Advances in vaccine research, development, and production through the use of reverse-genetics systems represent the most effective technology to rapidly produce a pandemic influenza vaccine.” (S. M. Ford, Stephen.Ford1@amedd.army.mil)
Daptomycin for Bacteremia, Endocarditis: In patients with drug-resistant, gram-positive bacteremia and/or infective endocarditis, daptomycin provides a safe and well tolerated option, according to a retrospective case series of 31 patients (pp. 347-52). The investigators report: “Patients were given daptomycin 4–6 mg/kg intravenously every 24–48 hours based on the practitioner’s discretion and depending on the patient’s clinical condition and presence of comorbidities. Primary end points were resolution of signs and symptoms of infection and discharge from the hospital. Methicillin-resistant Staphylococcus aureus ([MRSA] 11 patients) and vancomycin-resistant enterococci ([VRE] 11 patients) were the most common pathogens, whereas 7 patients had methicillin-sensitive S. aureus infection and 1 patient had coagulase-negative Staphylococcus infection. One patient with endocarditis had a negative culture result. Overall, 24 (77%) of the 31 patients achieved clinical resolution and were discharged, including all patients infected with MRSA; 7 patients died, 6 of whom had VRE infection. Duration of treatment for infective endocarditis lasted longer (typically 22-43 days) than that for bacteremia only (≤ 14 days), and no patients discontinued daptomycin because of adverse events.” (J. A. Segreti, John_Segreti@rush.edu)

>>>PNN NewsWatch
* Individuals who have a genetic variation associated with slower caffeine metabolism have an increased risk of nonfatal myocardial infarction associated with higher amounts of coffee intake, according to an article in today’s JAMA (pp. 1135-41; A. El-Sohemy, a.el.sohemy@utoronto.ca). Overall, 55% of cases (n = 1,114) and 54% of controls (n = 1,082) were carriers of the slow CYP 1A2 *1F allele. For carriers of the *1F allele, those who drank 2 to 3 cups of coffee a day had a 36% increased odds of MI; those who drank 4 or more cups per day had a 64% increased odds of MI. Corresponding consumption for individuals with the rapid *1A/*1A genotype resulted in the reduced odds of heart attack by 22% and 1%, respectively. Younger individuals showed an increased risk. Among the slow metabolizers, the risk associated with drinking 4 cups/day or more compared with less than 1 cup/day increased from 2-fold for individuals younger than 59 years to more than 4-fold for those younger than 50 years.
* Managing the risks associated with use of an effective drug for multiple sclerosis is the challenge facing an FDA advisory panel that today will make recommendations regarding return of
natalizumab (Tysabri; Biogen Idec, Elan) to the U.S. market. The advisors yesterday heard testimony from medical researchers about cases of progressive multifocal leukoencephalopathy in patients taking the drug but also from consumers about how much the drug has improved their conditions. FDA last month allowed a resumption of clinical testing of natalizumab in patients with multiple sclerosis, but the medication remains unavailable for general distribution.

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 © 2006, 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
Mar. 9, 2006 Vol. 13, No. 46
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 9 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).
Entecavir for Hepatitis B: In patients with chronic hepatitis B infection, entecavir provided superior rates of histologic, virologic, and biochemical improvement, compared with lamivudine, and it did so without evidence of viral resistance (pp. 1001-10). In the 52-week trial, the 715 participants had hepatitis B e antigen–positive chronic hepatitis B and had not previously received a nucleoside analogue. Doses of entecavir 0.5 mg or lamivudine 100 mg once daily produced these results: “Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group (72 percent) and 195 of 314 patients in the lamivudine group (62 percent, P = 0.009). More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay (67 percent vs. 36 percent, P < 0.001) and normalization of alanine aminotransferase levels (68 percent vs. 60 percent, P = 0.02). The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine (6.9 vs. 5.4 log [on a base-10 scale] copies per milliliter, P < 0.001). HBeAg seroconversion occurred in 21 percent of entecavir-treated patients and 18 percent of those treated with lamivudine (P = 0.33). No viral resistance to entecavir was detected. Safety was similar in the two groups.” (T-T Chang, National Cheng Kung U. Hosp., Tainan, Taiwan; ttchang@mail.ncku.edu.tw)
In a second study of entecavir in HBeAg-positive patients, entecavir again outperformed lamivudine (pp. 1011-20). This Phase III trial of 648 patients used the same doses and timeframe as in the first study, with these results: “Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated (70 percent), as compared with 174 of 287 such patients in the lamivudine group (61 percent, P = 0.01). More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus (HBV) DNA levels according to a polymerase-chain-reaction assay (90 percent vs. 72 percent, P < 0.001) and normalization of alanine aminotransferase levels (78 percent vs. 71 percent, P = 0.045). The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine (5.0 vs. 4.5 log [on a base-10 scale] copies per milliliter, P < 0.001). There was no evidence of resistance to entecavir. Safety and adverse-event profiles were similar in the two groups.” (C-L Lai, Queen Mary Hosp., Hong Kong, China;
hrmelcl@hkucc.hku.hk)
Thalidomide for Multiple Myeloma: As part of high-dose therapy for multiple myeloma, thalidomide increased the number of complete responders and extended event-free survival, but it also increased the number of adverse effects and failed to improve overall survival (pp. 1021-30). A total of 688 patients with newly diagnosed multiple myeloma received two cycles of intensive melphalan-based chemotherapy supported by autologous hematopoietic stem-cell transplantation. The investigators report these results: “After a median follow-up of 42 months among survivors, the thalidomide and control groups had rates of complete response of 62 percent and 43 percent, respectively (P < 0.001), and five-year event-free survival rates of 56 percent and 44 percent (P = 0.01). The five-year rate of overall survival was approximately 65 percent in both groups (P = 0.90). Median survival after relapse was 1.1 years in the thalidomide group and 2.7 years in the control group (P = 0.001). Severe peripheral neuropathy and deep-vein thrombosis occurred more frequently in the thalidomide group than in the control group.” (B. Barlogie, barlogiebart@uams.edu)

>>>PNN NewsWatch
* An advisory panel yesterday recommended unanimously that FDA allow the multiple sclerosis (MS) agent natalizumab (Tysabri; Biogen Idec, Elan) to return to the U.S. market., but it split on the specifics of the new indications. An FDA decision is expected by Mar. 29, according to media reports.

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 © 2006, 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
Mar. 10, 2006 Vol. 13, No. 47
Providing news and information about medications and their proper use

>>>Health Affairs Update
Source:
Online article in Health Affairs (www.healthaffairs.org).
Altering Medicine Through Science: Increases in the intensity of care, and consequent increases in costs, have rendered the current method of medical practice unsustainable, according to Elias Zerhouni, MD, NIH director (doi: 10.1377/hlthaff.25.w94). In the first of a series of Health Affairs interviews with leading biomedical innovators, Zerhouni said, “If you looked at the medical team caring for one patient in 1960, you probably had the doctor and nurse and part-time work from a laboratory person—two and a half people,” says Zerhouni. Nowadays, “you’re talking about seventeen, eighteen, nineteen people per patient per encounter.”
The situation calls for “major changes, not changes at the margin,” the former Johns Hopkins professor declares. Electronic medical records—the current darling of many commentators—would be nice, “but they are at the margins.” The same is true for national health insurance: “Because you have no billing and no administration, you will gain another 5%. That’s not enough to make a dent.”
The solution advanced by Zerhouni is to intervene earlier in the disease process. He says that medicine should take aim at the “preclinical phase”—when “something is happening biologically that you’re not aware of”—rather than at later, symptomatic phases of disease, when intervention is likely to require costly treatments. Zerhouni refers to this as moving from a “curative” model to a “preemptive” model, and he takes care to differentiate prevention from preemption: “Prevention is stopping something you know is there.… Preemption is removing the initial molecular event—precluding the possibility of that thing even happening.”
Transforming medicine in this way requires an equally profound transformation in the biomedical scientific enterprise, Zerhouni says. “We need to get away from the reductionist approach” in which “one gene or one event causes disease,” and move toward an “integrated understanding of systems biology,” of entire “groups of molecules interacting with each other.” Zerhouni suggests that new technologies such as genomics, proteomics, and nanotechnology have laid the groundwork for the revolutionary progress needed.

>>>Pediatrics Highlights
Source:
Mar. issue of Pediatrics (www.pediatrics.org; 2006; 117).
Pneumococcal Vaccination & Otitis Media: Among children aged 2 to 8 years with persistent otitis media with effusions, administration of combined pneumococcal conjugate and polysaccharide vaccine did not prevent OME recurrence (pp. 603-8). The study included 161 children with persistent bilateral OME, and all were treated with tympanostomy tubes. Among those given the 7-valent pneumococcal vaccine 3-4 weeks before and the 23-valent pneumococcal vaccine 3 months after tube insertion, rates of OME recurrence were no different than among control patients despite significant increases in serotype antibodies to Streptococcus pneumoniae. “Pneumococcal vaccines are not indicated for the treatment of children suffering from recurrent OME,” the authors conclude. (N. van Heerbeek, Radboud U. Nijmegen Med. Ctr., Nijmegen, the Netherlands)
Preventing DTaP Reactions: Prophylaxis with acetaminophen or ibuprofen had no effect on rates of local reactions to the fifth dose of diphtheria-tetanus toxoids-acellular pertussis vaccine (pp. 620-5). Since local reactions increase in frequency during the DTaP series and most children have such reactions to the fifth dose, investigators randomly administered three doses of acetaminophen, ibuprofen, or placebo, beginning 2 hours before the fifth DTaP injection and continuing every 6 hours, with these results: “Local reactions with a ≥5-cm area of redness or discoloration were reported for 35% of children in the placebo group, compared with 33% of children in the acetaminophen group and 37% of children in the ibuprofen group. There was also no significant difference between the placebo and treatment groups in the proportions of children with a ≥2-cm increase in mid-limb circumference or with a persistent local reaction.” (L. A. Jackson, Ctr. for Health Studies)

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 © 2006, 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
Mar. 13, 2006 Vol. 13, No. 48
Providing news and information about medications and their proper use

>>>ACC.06 Highlights
Thirty thousand cardiologists, researchers, and others in cardiovascular medicine have convened in Atlanta for the 55th annual scientific session of the American College of Cardiology. Here are the highlights of the meeting so far:
* Addition of clopidogrel to standard, low-dose aspirin failed to significantly reduce the combined rate of death, myocardial infarction, or stroke in an international study of more than 15,603 high-risk patients. However, in an unexpected finding, patients with established cardiovascular disease did benefit from dual antiplatelet therapy, whereas patients whose risk consisted only of multiple risk factors may have suffered some harm, reported Deepak L. Bhatt, MD, and colleagues in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study. Full research results and a related editorial were released simultaneously with the presentation on the Web site of the
New England Journal of Medicine (content.nejm.org).
* Dietary supplements containing folic acid and vitamins B6 and B12 failed to reduce the risk of death and MI in patients with vascular disease, according to results of the Heart Outcomes Prevention Evaluation (HOPE) 2 trial. Also released early in full-text form on the
NEJM Web site, this study identified significant improvements in plasma homocysteine levels among patients on the supplements, compared with placebo, but this did not translate into significant improvements in primary outcomes (death from cardiovascular causes, MI) of any of several secondary outcomes. Patients on active therapy had significantly fewer strokes but significantly increased hospitalizations for unstable angina.
* A second study of B vitamins, also presented at ACC.06 and released simultaneously on the
NEJM Web site, supports the findings of the above study, concluding that these supplements are not beneficial and may in fact be harmful. Study participants received either placebo, vitamin B6 alone, folic acid plus vitamin B12, or folic acid plus vitamins B6 and B12. As in the HOPE 2 trial, plasma homocysteine levels were lowered significantly, but this provided no significant effect on a composite primary end point of recurrent MI, stroke, and sudden death attributed to coronary artery disease. Furthermore, the investigators added, the group receiving folic acid plus vitamins B6 and B12 had a trend toward increased risk of this end point.

>>>BMJ Highlights
Source:
Mar. 11 issue of BMJ (www.bmj.org; 2006; 332).
LMWHs During Palliative Care: Patients with advanced metastatic cancer who are receiving palliative care find antiembolic stockings unacceptable and would prefer to receive treatment with thromboprophylaxis with low molecular weight heparins, according to results of a 28-patient study (pp. 577-80). In this qualitative study, authors report, “Major emerging themes showed that patients knew about the risks of venous thromboembolism and the purpose of treatment with heparin. Media coverage had raised awareness about venous thromboembolism, and many had previous experience of thromboprophylaxis. All found low molecular weight heparin an acceptable intervention, and many said that it improved their quality of life by giving them a feeling of safety and reassurance. Antiembolic stockings were considered uncomfortable and had a negative impact on quality of life. Patients were concerned that because they had advanced disease they might not be eligible for thromboprophylaxis.” (S. I. R. Noble, Royal Gwent Hosp., Newport, U.K.; simon.noble@gwent.wales.nhs.uk)

>>>PNN JournalWatch
* Mortality of HIV-1-Infected Patients in the First Year of Antiretroviral Therapy: Comparison Between Low-Income and High-Income Countries, in Lancet, 2006; 367: 817–24. Reprints: www.thelancet.com; M. Egger, U. Bern, Bern, Switzerland; egger@ispm.unibe.ch
* Hydroxymethylglutaryl-CoA Reductase Inhibitors in Older Persons with Acute Myocardial Infarction: Evidence for an Age-Statin Interaction, in
Journal of the American Geriatrics Society, 2006; 54: 421 ff. Reprints: www.blackwell-synergy.com; J. M. Foody, joanne.foody@yale.edu
* Longitudinal Analysis of Clinical Markers Following Antiretroviral Therapy Initiated During Acute or Early HIV Type 1 Infection, in
Clinical Infectious Diseases, 2006; 42: 1024–31. Reprints: www.journals.uchicago.edu; S. Kassutto.

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 © 2006, 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
Mar. 14, 2006 Vol. 13, No. 49
Providing news and information about medications and their proper use

>>>ACC.06 Highlights
The 55th annual scientific session of the American College of Cardiology closes today in Atlanta. Monday’s highlights included the following:
* For the first time, researchers demonstrated regression of plaque build-up in coronary arteries through use of intensive statin therapy. In the ASTEROID (A Study To Evaluate the Effect of Rosuvastatin On Intravascular Ultrasound-Derived Coronary Atheroma Burden) trial, Steven Nissen, MD, FACC, of the Cleveland Clinic and ACC president-elect, and colleagues tested rosuvastatin 40 mg daily, comparing results after 24 months of treatment with patients’ baseline measures. Mean LDL cholesterol values fell from 130.4 to 60.8 mg/dL. This reduction of 53.2% is largest ever observed in a major statin outcome trial. Mean HDL cholesterol increased from 42.1 to 49.0 mg/dL, and arterial plaque was reduced by 6.8% to 9.1% for three measures of intraluminal status.
* Care of patients with myocardial infarction will be changed by results of three papers presented on Monday. One study, presented by Mahmoud Suleiman, MD, of Rambam Health Campus in Israel, linked elevations in blood glucose concentrations with increased rates of post-MI mortality over the subsequent 23 months. Mortality rates were 36.6% for those with hyperglycemia, 17% among patients with impaired fasting blood glucose, and 6.2% for those with normal blood glucose levels. A second study of the association between heart disease and glucose homeostasis showed that administration of insulin may have an effect on atrial fibrillation. Among more than 28,000 patients with heart failure who were assessed retrospectively by Somjot S. Brar, MD, of Kaiser Permanente, and colleagues, patients with diabetes who used insulin had a 19% lower risk of AF, compared with a control group of heart failure patients without diabetes. The third study, reported by Kapil Parakh, MPH, of Johns Hopkins Bayview Medical Center, refutes the commonly held belief that post-MI depression is associated with increased mortality. Among 280 patients with MI, depressed patients did not have an increased risk of mortality at 3, 5, or 8 years, compared with nondepressed patients.

>>>Internal Medicine Report
Source:
Mar. 13 issue of Archives of Internal Medicine (www.archinternmed.com; 2006; 166).
Pharmacist Discharge Counseling: By reducing medication discrepancies, pharmacist counseling of and follow-up with hospitalized patients at discharge were associated with lower rates of preventable adverse drug events, according to a randomized study of 178 general medicine patients (pp. 565-71). Interventions included a pharmacist counseling session at discharge and a follow-up telephone call 3 to 5 days later, with attention on “clarifying medication regimens; reviewing indications, directions, and potential side effects of medications; screening for barriers to adherence and early side effects; and providing patient counseling and/or physician feedback when appropriate.” The authors report these results: “Pharmacists observed the following drug-related problems in the intervention group: unexplained discrepancies between patients’ preadmission medication regimens and discharge medication orders in 49% of patients, unexplained discrepancies between discharge medication lists and postdischarge regimens in 29% of patients, and medication nonadherence in 23%. Comparing trial outcomes 30 days after discharge, preventable ADEs were detected in 11% of patients in the control group and 1% of patients in the intervention group (P = .01). No differences were found between groups in total ADEs or total health care utilization.” (J. L. Schnipper, jschnipper@partners.org)
Adherence Alerts: Alerts to physicians about antidepressant nonadherence using real-time pharmacy information failed to increase adherence rates among 13,128 members of a managed care plan (pp. 498-504). Gaps of more than 10 days in obtaining medication refills during the first 180 days of antidepressant therapy caused alerts to be faxed to prescribing physicians, but rates of nonadherence among patients with delayed refills during the 2-year study were constant at about 75%. Nonadherence rates increased over time, reaching 40% of days without dispensed drug. (K. Z. Bambauer, kzbambauer@post.harvard.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 © 2006, 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
Mar. 15, 2006 Vol. 13, No. 50
Providing news and information about medications and their proper use

>>>ACC.06 Highlights
As the 55th annual scientific session of the American College of Cardiology wrapped up in Atlanta yesterday, researchers presented these important studies:
* Fondaparinux significantly reduced mortality and reinfarction among 12,092 patients with ST-segment elevation myocardial infarction, especially those who were not undergoing percutaneous coronary interventions. This conclusion comes from the OASIS-6 (Organization for the Assessment of Strategies for Ischemic Syndromes) trial, which was simultaneously released in full manuscript form on the
JAMA Web site along with an accompanying editorial. Salim Yusuf, DPhil, FRCPC, FRSC, of McMaster University in Hamilton, Ont., reported that patients received add-on therapy with fondaparinux or placebo. Investigators adjusted the dose and treatment plan to take into account other blood-thinning medications used, such as glycoprotein IIb/IIIa inhibitors or unfractionated heparin. Death or reinfarction at 30 days was reduced significantly in the fondaparinux group (9.7%, compared with 11.2% among those receiving placebo; hazard ratio, 0.86; 95% CI, 0.77-0.96). In an analysis of patients undergoing PCI, no difference between the groups was evident. Another subgroup analysis, this one of patients for whom unfractionated heparin was indicated, showed lower death or reinfarction rates with fondaparinux at 30 days (HR, 0.82; 95% CI, 0.66-1.02) and at 3-6 months (HR, 0.77; 95% CI, 0.64-0.93).
* Enoxaparin reduced the combined risk of death and MI within 30 days by 17%, compared with unfractionated heparin, in the Enoxaparin and Thrombosis Reperfusion for Acute Myocardial Infarction Treatment: Thrombosis in Myocardial Infraction (ExTRACT-TIMI 25) study. Similarly, enoxaparin reduced the 30-day risk of nonfatal repeat MI by 33%, and the 30-day combined risk of death, nonfatal MI, and need for emergent reperfusion by 19% among 20,506 patients at 674 medical centers in 48 countries. Principal investigator Elliott Antman, MD, of Harvard Medical School, Boston, reported that the “study provides compelling evidence that the enoxaparin strategy is superior to the standard unfractionated heparin strategy as antithrombin therapy to support fibrinolytic therapy,"
* Failure to treat hypercholesterolemia in high-risk patients is evident in results of an analysis of the PharMetrics’ Patient-Centric database, which contains anonymous medical and pharmaceutical claims for members of more than 75 health plans. Looking at 142,389 patients aged 25 years or older who began treatment for hypertension between Sept. 2001 and Feb. 2004, Richard H. Chapman, PhD, of ValueMedics Research, and colleagues found that 30% had been diagnosed with high cholesterol, but only 17.3% were already on statin therapy when they started treatment for high blood pressure and only 29.4% began taking statins in the subsequent year. In the group of patients who had high blood pressure and established heart disease (14,647 patients), just 11.5% were already on statin therapy, with an additional 30.9% starting during the first year. More than one half (57.6%) of this group did not receive a statin. Similarly, for the study populations with diabetes (17,567 patients) or with three or more cardiovascular disease risk factors (15,701 patients), the majority did not receive a statin in the first year (61% and 53.7%, respectively).

>>>JAMA Highlights
Source:
Mar. 15 issue of JAMA (www.jama.com; 2006; 295).
Drug-Eluting Stents: In 396 patients with in-stent restenosis of a previously implanted bare-metal stent, treatment with paclitaxel-eluting stents proved a superior strategy, compared with angioplasty followed by vascular brachytherapy (pp. 1253-63). At 9 months, angiographic restenosis was 31.2% with VBT and 14.5% with paclitaxel-eluting stents (relative risk, 0.47; 95% CI, 0.30-0.71). Also significantly improved with the drug-eluting stents were the number of events and 9-month rates for ischemic target lesion revascularization and overall major adverse cardiac events. Rates of cardiac death or MI and target vessel thrombosis were similar between the groups. (G. W. Stone, gs2184@columbia.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 © 2006, 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
Mar. 16, 2006 Vol. 13, No. 51
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 16 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).

Maintenance Treatment of Major Depression in Old Age: Two years of maintenance therapy with paroxetine significantly reduced older patients’ risk of recurrent depression, according to a study of 116 patients (pp. 1130-8). Participants were 70 years of age or older and had depression; 55% of patients were having a first episode. Comparing paroxetine with monthly psychotherapy sessions, the investigators report, “Major depression recurred within two years in 35 percent of the patients receiving paroxetine and psychotherapy, 37 percent of those receiving paroxetine and clinical-management sessions, 68 percent of those receiving placebo and psychotherapy, and 58 percent of those receiving placebo and clinical-management sessions (P = 0.02). After adjustment for the effect of psychotherapy, the relative risk of recurrence among those receiving placebo was 2.4 times (95 percent confidence interval, 1.4 to 4.2) that among those receiving paroxetine. The number of patients needed to be treated with paroxetine to prevent one recurrence was 4 (95 percent confidence interval, 2.3 to 10.9). Patients with fewer and less severe coexisting medical conditions (such as hypertension or cardiac disease) received greater benefit from paroxetine (P = 0.03 for the interaction between treatment with paroxetine and baseline severity of medical illness).” (C. F. Reynolds III, Western Psychiatric Inst. and Clinic, Pittsburgh, reynoldscf@upmc.edu)

Noting that “it is difficult to overstate the effect depression has on health,” an editorialist calls on clinicians to manage this disease as a chronic one requiring at a minimum follow-up and often lifelong treatment (pp. 1189-90): “On the basis of the findings of Reynolds et al., it is premature to recommend lifelong antidepressant therapy after a single episode of depression late in life. However, except in patients with irreversible cognitive impairment so severe that the diagnosis of depression is moot, it is not premature to recommend lifelong follow-up. In my judgment, it is better to view an older person who has fully recovered from depression as a patient who is in remission, rather than as a patient who has been cured. Periodic reevaluation is just as important for an elderly patient who has recovered from depression as it is for a patient who has recovered from cancer.” (B. V. Reifler, Wake Forest U., Winston-Salem, N.C.)

>>>PNN NewsWatch
* FDA has approved for marketing a new blood glucose monitoring system that requires the smallest blood sample of any meter. In a news release, Abbott claims that its FreeStyle Freedom blood glucose monitoring system offers virtually pain-free testing because it measures glucose levels using a very small blood sample size (0.3 microliter). FreeStyle Freedom provides results in 5 seconds and features a large, high contrast display, making it easy to read and hold. The new meter also allows people with diabetes to test on less sensitive parts of the body such as the forearm, thigh, and palm. FreeStyle blood glucose meters offer the most approved alternative testing sites of any glucose monitoring system available, Abbott noted.

* Preparing for next week’s meeting of the psychopharmacologic advisory panel,
FDA staff posted on the agency Web site its analysis of serious adverse effects associated with use of ADHD medications, according to reports in the media. FDA is recommending stronger warnings for psychosis and mania that have been observed in children, including some younger than 10 years of age, during drug treatment of ADHD. Another advisory panel last month called for addition of black-box warnings about cardiovascular adverse effects of these drugs.

* An FDA advisory panel this week recommended that the agency reject an supplemental indication for use of
gemcitabine (Gemzar, Lilly) in patients with advanced ovarian cancer. If the agency concurs, the chemotherapy drug would remain approved for treatment of nonsmall-cell lung cancer, pancreatic cancer, and metastatic breast cancer.

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 © 2006, 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
Mar. 17, 2006 Vol. 13, No. 52
Providing news and information about medications and their proper use

>>>JAPhA Highlights
Source:
Mar/Apr issue of the Journal of the American Pharmacists Association (www.japha.org; 2006; 46).

Asheville Project Adds Asthma: Significantly improved clinical and humanistic outcomes and decreased overall health care costs were observed in an extension of the Asheville Project, this one involving 207 patients with asthma (pp. 133-47). Using the same model that was successful in the earlier diabetes portion of the project (education by a certified educator plus regular long-term follow-up by pharmacists using scheduled consultations, monitoring, and recommendations to physicians), the investigators found: “All objective and subjective measures of asthma control improved and were sustained for as long as 5 years. [Force expiratory volume in 1 second] and severity classification improved significantly. The proportion of patients with asthma action plans increased from 63% to 99%. Patients with emergency department visits decreased from 9.9% to 1.3%, and hospitalizations from 4.0% to 1.9%. Spending on asthma medications increased; however, asthma-related medical claims decreased and total asthma-related costs were significantly lower than the projections based on the study population’s historical trends. Indirect costs due to missed/nonproductive workdays decreased from 10.8 days/year to 2.6 days/year. Patients were six times less likely to have an emergency department/hospitalization event after program interventions.” (B. A. Bunting, Mission Hosp., Asheville, N.C.; barry.bunting@msj.org)

Immunization Effort Marks 10th Anniversary: “Pharmacists have made significant strides in immunizations over the past decade,” conclude authors of a review article that tracks the profession’s progress in establishing a niche in the adult immunizations arena (pp. 168-82). “While pharmacists have been involved with vaccines dating back to the mid-1800s and the distribution of smallpox vaccine, only 10 years have passed since pharmacists began routinely immunizing patients in their communities as a standard practice activity,” the group notes. “The Washington State Pharmacists Association initiated the first ongoing formalized training of pharmacists in vaccine administration in 1994. On November 1, 1996, the American Pharmaceutical (now Pharmacists) Association (APhA) began its nationally recognized training program for pharmacists, Pharmacy-Based Immunization Delivery: A National Certificate Program for Pharmacists. By 2004, an estimated 15,000 pharmacists and student pharmacists had been formally trained through recognized programs as vaccine experts, and the practice of pharmacist-administered immunizations, particularly for adult patients, has become routinely accepted as an important role of the pharmacist. Arguably, few initiatives have done more to move the pharmacy profession forward in direct patient care than the pharmacist-administered immunization movement.” (M. D. Hogue, mdhogue@samford.edu)

Continuity in Medication-Use Standards: The standards under which medications are used ought to be the same from clinical testing through to practice, argue authors of a commentary (pp. 205-12). “Pharmaceutical care practice standards can create a continuum of high quality care for patients from research through practice and are presented as a rational solution to managing the benefits and risks of medication use. By implementing these practice standards, patients are empowered to become active participants in the treatment process, knowledge of drug effectiveness and safety is increased, and the pharmaceutical care practitioner’s responsibilities are delineated. More than a quarter century ago, the research community adopted the ethical principles of respect for persons, beneficence, and justice, as outlined in the Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research.... However, these guidelines only apply to the life cycle of a drug before approval by the Food and Drug Administration. Once the product is released for general use, fewer standards are applied. Pharmacy has the opportunity to establish parallel standards for the clinical use of medications in patients by establishing patient care practices in consonance with pharmaceutical care practice.” (C. L. Cipolle, cipo0006@umn.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 © 2006, 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
Mar. 20, 2006 Vol. 13, No. 53
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release articles and Mar. 18 issue of Lancet (www.thelancet.com; 2006; 367).
Nutrition in Adults with Functioning GI Tracts: Enteral feedings should be preferred over parenteral nutrition in malnourished hospitalized patients with functioning gastrointestinal tracts, according to a review article (DOI: 10.1016/S0140-6736(06)68307-4): “Almost all outcome studies from clinical trials comparing parenteral with enteral nutrition or intravenous fluids in acutely ill adults with functioning gastrointestinal tracts fail to document improved outcomes from parenteral nutrition. In many patient groups, enteral nutrition resulted in significantly reduced rates of infection, sepsis, length of stay in hospital, and costs. The exact reasons for the effectiveness of enteral over parenteral nutrition in patients with functional gastrointestinal tracts are not wholly clear. Potential reasons include the nature of the substrates, support of the gastrointestinal tract, adverse effects from the technique of nutrient administration (ie, overfeeding, hyperglycaemia), use in subgroups that do not benefit, methodological constraints of the clinical trials (ie, patient selection, size of the studies, heterogeneity of the study populations), and pre-injury nutritional and organ status of the patients.” (G. P. Zaloga, Indiana U., Indianapolis; gzaloga@clarian.org)
Family-Member Directly Observed Therapy: In 10 hill and mountain districts of Nepal where health care workers are not available to directly observe therapy for tuberculosis, family and community members successfully filled this role (pp. 903-9). During 1 year of DOTS in 907 patients with TB, the investigators found this support for both options: “Community DOTS and family-member DOTS achieved success rates of 85% and 89%, respectively (odds ratio of success for community DOTS relative to family-member DOTS, 0.67 [95% CI 0.41-1.10]; p = 0.09). Estimated case-finding rates were 63% with the community strategy and 44% with family-member DOTS.” (J. N. Newell, U. Leeds, Leeds, U.K.; j.n.newell@leeds.ac.uk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (www.bmj.org; 2006; 332).
Tinzaparin & Hysterectomy: The risk of serious postoperative bleeding in women undergoing hysterectomy is increased twofold when tinzaparin is used for thromboprophylaxis, compared with heparin calcium (DOI: 10.1136/bmj.38783.624444.55). Over a 6-year period, the outcomes were identified among 2,108 women: “54 cases of serious postoperative bleeding were identified, 46 of which were readmissions. These 54 cases were compared with 179 controls. Regression analysis indicated a positive relation between prophylaxis with tinzaparin and serious postoperative bleeding. There was a significant twofold increase in odds (odds ratio 2.02, 95% confidence interval 1.02 to 4.05) after adjustment for type of operation, age, and type of pain relief.” (G. Cook, Stepping Hill Hosp., Stockport, U.K.; Gary.cook@stockport.nhs.uk)

>>>PNN NewsWatch
* Two additional deaths of women following medical abortion led FDA to issue another public health advisory about use of mifepristone. The agency emphasizes that clinicians should use the approved regimen and avoid alternative dosing strategies such as vaginal rather than oral administration of misoprostol tablets.

>>>PNN JournalWatch
* Osteoarthritis, in BMJ, 2006; 332: 637-8. Reprints: www.bmj.org; D. J. Hunter, Boston U., Boston; djhunter@bu.edu
* Pharmacist Participation in the Workforce: 1990, 2000, and 2004 (one of four articles released by the Pharmacy Manpower Project in advance of publication), in
Journal of the American Pharmacists Association, 2006; 46: e14-e22. Reprints: www.pharmacist.com; D. A. Mott, damott@pharmacy.wisc.edu
* Severe Asthma: An Overview, in
Journal of Allergy and Clinical Immunology, 2006; 117: 487-94. Reprints: www.jacionline.org; W. C. Moore, Wake Forest U., Winston-Salem, N.C.; wmoore@wfubmc.edu
* Effects of Tiotropium With and Without Formoterol on Airflow Obstruction and Resting Hyperinflation in Patients With COPD, in
Chest, 2006; 129: 509-17. Reprints: www.chestjournal.org; J. A. van Noord, Atrium medisch centrum, Heerlen, the Netherlands; j.a.vannoord@atriummc.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 © 2006, 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
Mar. 21, 2006 Vol. 13, No. 54
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 21 issue of the Annals of Internal Medicine (www.annals.org; 2006; 144).
Smoking Continuance & Mortality Rates: A study from Norway shows that mortality rates among middle-aged people were increased by continuing to smoke and decreased by smoking cessation, with significantly greater numbers of cardiovascular events among men than women (pp. 381-9). Focusing on 24,505 women and 25,034 men born in 1925-41, the investigators report, “During follow-up, 2,333 women and 4,680 men died in middle age. Among women and men, 9% and 14% of never smokers, respectively, and 26% and 41% of continuing heavy smokers (≥20 cigarettes per day), respectively, died in middle age. Years of life lost among heavy smokers between 40 and 70 years of age were 1.4 years in women and 2.7 years in men, compared with never smokers. Rates of smoking-associated lung cancer were similar in women and men, while lower cardiovascular mortality rates in women explained most of the difference in smoking-associated all-cause mortality between men and women.” (S. E. Vollset, U. Bergen, Bergen, Norway)
Telithromycin & Hepatotoxicity: An article describing three cases of hepatotoxicity that had been released early by Annals (see PNN, Jan. 23) is published in this issue (pp. 415-20). “Within a few days of receiving telithromycin, the patients presented with acute hepatitis,” the authors report. “All had jaundice and markedly abnormal results on liver function tests. Results of viral serologic tests were negative. One patient spontaneously recovered, 1 required orthotopic liver transplantation, and 1 died. Histologic examination in the latter 2 patients showed massive hepatic necrosis.” (K. D. Clay, Carolinas Med. Ctr., Charlotte; kimberly.clay@carolinashealthcare.org)

>>>PNN NewsWatch
* With more than 7,000 pharmacists, student pharmacists, and others in attendance, APhA2006 has been underway in San Francisco since Friday. At Sunday evening’s Remington Honor Medal presentation, 2006 recipient Robert D. Gibson painted a broad perspective on how changes in society have affected the profession of pharmacy and him personally. Speaking on “The Pursuit of Dignity,” this former U. Calif., San Francisco, pharmacy professor and past APhA president said, “I know that the people in this room have already reported for duty in the battle to seek paths of racial amity, to understand that conscience has no color, that justice anywhere threatens justice everywhere. Not everyone has joined this battle, but I would hope that you will assist me in recruiting them, because there are among us children who sleep in hunger, rise in cold, live in ignorance, and they are of every color and every tribe. Their suffering is unacceptable.... I have intended to convey to you my belief that the dignity and rights of any one of us is the concern of all. In this I am ever vigilant.”
* The
APhA Foundation has announced plans to launch Project ImPACT: Depression in conjunction with the City of Asheville, Mission Hospitals, and the Western North Carolina Health Care Coalition, all located in Asheville, N.C., and Ohio State University Wellness Plan. Each of the participating employer pilot sites is enrolling 100 patients being treated for depression who are not currently being monitored in a pharmacy setting. Similar to the Asheville Project (see PNN, Mar. 17), employers will waive copayments for medications used to treated depression, and pharmacists will be compensated for patient care services related to improving adherence and persistence with treatment regimens.
* Also released during APhA2006 is information showing that pharmacists continue to overestimate the number of interactions between drugs and
grapefruit juice. Compared with data from 2002, 50% more pharmacists were well informed about such interactions, but 70% of pharmacists still indicated that they never ask patients about use of grapefruit juice. One fourth of respondents incorrectly believed that all statins are affected by grapefruit juice, noted the KRC Research/Florida Department of Citrus survey. A comprehensive listing of interacting drugs is available at www.DrugInteractionCenter.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 © 2006, 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
Mar. 22, 2006 Vol. 13, No. 55
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 22/29 issue of JAMA (special theme issue on women’s health; www.jama.com; 2006; 295).
Treatment of Maternal Depression: Remission of a mother's depression within the first 3 months of pharmacotherapy decreases the likelihood of her children having psychiatric disorders within the same time period, concludes a study of 151 mother-child pairs in 8 primary care and 11 psychiatric outpatient clinics who were part of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial (pp. 1389-98). Children in the study were aged 7–17 years, and the authors made these observations about them: “Remission of maternal depression after 3 months of medication treatment was significantly associated with reductions in the children's diagnoses and symptoms. There was an overall 11% decrease in rates of diagnoses in children of mothers whose depression remitted compared with an approximate 8% increase in rates of diagnoses in children of mothers whose depression did not. This rate difference remained statistically significant after controlling for the child's age and sex, and possible confounding factors (P = .01). Of the children with a diagnosis at baseline, remission was reported in 33% of those whose mothers' depression remitted compared with only a 12% remission rate among children of mothers whose depression did not remit. All children of mothers whose depression remitted after treatment and who themselves had no baseline diagnosis for depression remained free of psychiatric diagnoses at 3 months, whereas 17% of the children whose mothers remained depressed acquired a diagnosis. Findings were similar using child symptoms as an outcome. Greater level of maternal response was associated with fewer current diagnoses and symptoms in the children, and a maternal response of at least 50% was required to detect an improvement in the child.” (M. M. Weissman, mmw3@columbia.edu)
Gender Differences in Platelet Reactivity: Platelets of women react to aspirin differently than do those of men, according to a study of 571 men and 711 women (pp. 1420-7). “After aspirin therapy, the percent aggregation to arachidonic acid (the direct COX-1 pathway) decreased more in women than in men (P < .001) and demonstrated near total suppression of residual platelet reactivity in both men and women,” the investigators note. “In COX-1 indirect pathways, women experienced the same or more platelet inhibition than men in 8 of the 9 assays yet retained modestly greater platelet reactivity after aspirin therapy.” (D. M. Becker, Johns Hopkins Med. Inst., Baltimore; dbecker@jhmi.edu)

>>>APhA House of Delegates Adopts Policies
As APhA2006 closed yesterday in San Francisco, professionwide policy was set by the APhA House of Delegates, and Bruce Canaday of North Carolina was installed as president for 2006-07.
New policies adopted by the APhA House support activities in these areas: Restructuring the current prescription/nonprescription drug classification system and drug approval process in the United States; addressing the problem of conversion of nonprescription products into illicit drugs through a variety of legal and private-sector means; addressing problems associated with cultural health beliefs and medication use; and assuring better means to assure continuity of care when patients move among various care settings where pharmacists practice, including development of an electronic health record with clinical data elements needed for medication reconciliation
The APhA policy committee also looked into the issue of medication use by athletes, but no new policy was recommended to the House of Delegates. Existing policy, adopted in 1986, opposes the use of performance-enhancing drugs by athletes and calls for educational activities and enforcement actions.
Adele H. Pietrantoni served as Speaker of the House. Elected as Speaker-elect was Michael Ira Smith; he will begin a 2-year term as Speaker at the close of the 2007 House of Delegates in Atlanta.
In his installation address, Canaday called on the profession to “stand with him” as a new model for professional practice is created for pharmacy.

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 © 2006, 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
Mar. 23, 2006 Vol. 13, No. 56
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 23 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).
Treatment of Refractory Depression: Two articles and an editorial assess strategies for treating depression that has not responded to first-line SSRIs.
About one fourth of patients responded to a second agent following unsuccessful treatment with an SSRI, making bupropion-SR, sertraline, or venlafaxine-XR all reasonable alternatives, according to a study of 727 adult outpatients with nonpsychotic major depressive disorder (pp. 1231-42). All patients had not responded to or been unable to tolerate citalopram. During 14 weeks of therapy with second agents, the patients had these responses: “Remission rates as assessed by the [17-item Hamilton Rating Scale for Depression] and the [Quick Inventory of Depressive Symptomatology — Self Report], respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events.” (A. J. Rush,
john.rush@utsouthwestern.edu)
Sustained-release bupropion and buspirone were useful for augmentation of citalopram treatment when the latter was ineffective as monotherapy, note authors of a second study (pp. 1243-52). After a mean of 11.9 weeks of citalopram therapy at a mean final dose of 55 mg/day, therapy was augmented for 565 adult outpatients with nonpsychotic major depressive disorder, with these results: “The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P < 0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P < 0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P < 0.009).” (M. H. Trivedi,
madhukar.trivedi@utsouthwestern.edu)
An editorialist, after reviewing the positive aspects of “practical trials” or “effectiveness trials” such as the above studies, provides this assessment of the discouraging tidings they bear (pp. 1305-7): “First, the results suggest that at least half of patients with depression do not have a remission. Second, if medications with various mechanisms of action are all roughly equivalent, as these trials suggest, what can we possibly infer about the pathophysiology of depression, particularly since there was neither a placebo group nor a group that continued to receive citalopram? This problem might be approached by considering advances in behavioral neuroscience that convincingly reveal behavioral disorders and their components as products of interactions between susceptibility and a precipitant, between gene products and environment. Stated differently, environmental events will have very different long-term and short-term effects in the context of various genetic backgrounds. Although the susceptibility to depression is heritable, it is likely to be encoded at multiple sites in specific gene networks in the brain. The same disorder, then, may involve effectors and response characteristics that vary among patients. This hypothesis suggests that much of the promise of the [Sequenced Treatment Alternatives to Relieve Depression (STAR*D)] trials may be found in the identification of predictors of response to antidepressant therapies — the differences among patients that should permit the design of more specific, individualized treatment. Third, the ongoing "nature–nurture" dialogue increasingly provides an explanation for what we already know: depression is bad for your health.” (D. R. Rubinow, U. North Carolina, Chapel Hill)

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 © 2006, 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
Mar. 24, 2006 Vol. 13, No. 57
Providing news and information about medications and their proper use

>>>Infectious Disease Update
Source:
Apr. 15 issue of Clinical Infectious Diseases (www.journals.uchicago.edu/CID; 2006; 42).
Benefits of Pneumococcal Vaccine: Among patients hospitalized for community-acquired pneumonia, prior pneumococcal vaccination is associated with improved survival, decreased chance of respiratory failure or other complications, and decreased length of stay, according to a study at 109 community and teaching hospitals (pp. 1093-101). Concluding that the findings “reinforce current efforts to improve compliance with existing pneumococcal vaccination recommendations for adults,” the authors report these results based on analysis of a database: “Of 62,918 adults hospitalized with community-acquired pneumonia between 1999 and 2003, 7,390 (12%) had a record of prior pneumococcal vaccination. Vaccine recipients were less likely to die of any cause during hospitalization than were individuals with no record of vaccination (adjusted odds ratio [OR], 0.50; 95% confidence interval [CI], 0.43-0.59), even after adjustment for the presence of comorbid illnesses, age, smoking, and influenza vaccination and under varying assumptions about missing vaccination data. Vaccination also lowered the risk of respiratory failure (adjusted OR, 0.67; 95% CI, 0.59-0.76) and other complications and reduced median length of stay by 2 days, compared with nonvaccination (P < .001).” (D. N. Fisman, dfisman@princeton.edu)
Influenza Immunization of Health Care Workers: Point-counterpoint articles debate the wisdom of mandating influenza vaccination of health care workers.
Taking the opposing view, an author provides seven reasons not to make the vaccine mandatory (pp. 1141-3): Coercion would create resistance among staff and degrade employee relationships; legal challenges are almost certain; liability issues would come into play; many other vaccines would similarly reduce the risk of transmitting disease yet are not mandated; attention would be diverted from other means of controlling infectious diseases; a better approach is educating the general public; and strong voluntary programs can be highly effective. (M. Finch, San Francisco)
Noting that HCWs’ high risk of becoming ill during nosocomial influenza outbreaks, a second author argues for mandatory vaccination (pp. 1144-7): “The Joint Commission on Accreditation of Healthcare Organizations [has] released for review a new proposed infection control standard that would require accredited organizations to offer influenza vaccinations to staff, volunteers, and licensed independent practitioners with close patient contact. Although this will increase vaccination rates, there is currently no evidence that these rates will routinely achieve levels beyond 60%-70%. Leaving one-third to one-fourth of HCWs susceptible to influenza is still unacceptable. Sometimes, coercive action is needed, and the failure to apply it is an abrogation of our responsibility of leadership. This active approach is appropriate in public health practice and other settings when used judiciously and applied fairly. HCWs should not have the right to harm patients by introducing disease to the most vulnerable populations that constitute the majority of our acute care hospital and long-term care patients.” (H. Backer,
hbacker@dhs.ca.gov)
TDM for HIV: Noting that “intraindividual variability in concentrations of antiretrovirals was surprisingly high in virologically suppressed patients” with HIV infection, a research team concludes that such “high intraindividual pharmacokinetic variability may limit the utility of single measurements in therapeutic drug monitoring for some antiretroviral agents” (pp. 1189-96). The study focused on 10 patients who had undetectable plasma HIV RNA levels for 11 months or longer. Based on plasma samples collected at the same time of day three times per week for up to 4 months, the investigators found several factors that could have contributed to their observed high intraindividual variation in drug levels: food intake, concomitant use of prescription and herbal medications, assay variability, and medication timing. (C. Flexner, Johns Hopkins U., Baltimore; flex@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 © 2006, 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
Mar. 27, 2006 Vol. 13, No. 58
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release article from Lancet (www.thelancet.com; 2006; 367).
Donepezil for Severe AD: Among 248 nursing home residents with severe Alzheimer’s disease, donepezil treatment for 6 months improved cognition and preserved function, compared with placebo (DOI: 10.1016/S0140-6736(06)68350-5). Donepezil was dosed at 5 mg/day for 30 days and up to 10 mg/day thereafter, with these results: “95 patients assigned donepezil and 99 patients assigned placebo completed the study. Patients treated with donepezil improved more in [severe impairment battery] scores and declined less in [Alzheimer's Disease Cooperative Study activities of daily living inventory for severe Alzheimer's disease] scores at 6 months after initiation of treatment compared with baseline than did controls (least squares [LS] mean difference, 5.7, 95% CI 1.5-9.8; p = 0.008, and 1.7, 0.2-3.2; p = 0.03, respectively). The incidence of adverse events was comparable between groups (donepezil 82% [n = 105] vs placebo 76% [n = 91]), with most being transient and mild or moderate in severity. More patients discontinued treatment because of adverse events in the donepezil group (n = 20) than in the placebo group (n = 8).” (B. Winblad, Karolinska U. Hosp., Stockholm, Sweden; bengt.winblad@ki.se)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2006; 332).
Omega-3 Fatty Acids & CVD: No consistent benefits of long-chain or short-chain omega-3 fats were evident in research identified in systematic review through Feb. 2002, and the possibility of adverse effects could not be ruled out (doi: 10.1136/bmj.38755.366331.2F). “Of 15,159 titles and abstracts assessed, 48 RCTs (36,913 participants) and 41 cohort studies were analysed,” the authors write. “The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded.” (L. Hooper, U. East Anglia, Norwich, U.K.; l.hooper@uea.ac.uk)
Injectable Penicillin for Meningococcal Disease: Outcomes among 158 children admitted for suspected meningococcal disease were worse when general practitioners had given the patients injectable penicillin beforehand, but the differences might have been the result of more severely ill children being treated in advance (doi: 10.1136/bmj.38789.723611.55). The investigators report, “Administration of parenteral penicillin by general practitioners was associated with increased odds ratios for death (7.4, 95% confidence interval 1.5 to 37.7) and complications in survivors (5.0, 1.7 to 15.0). Children who received penicillin had more severe disease on admission (median Glasgow meningococcal septicaemia prognostic score (GMSPS) 6.5 v 4.0, P = 0.002). Severity on admission did not differ significantly with time taken to reach hospital.” (A. Harnden, U. Oxford, Oxford; anthony.harnden@dphpc.ox.ac.uk)

>>>PNN JournalWatch
* ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic), in Circulation, 2006; 113: 1474–547. Reprints: circ.ahajournals.org
* Update in Neurology, in
Annals of Internal Medicine, 2006; 144: 421–6. Reprints: www.annals.org; R. F. Józefowicz, Ralph_Jozefowicz@urmc.rochester.edu
* Cancer Symptom Assessment Instruments: A Systematic Review, in
Journal of Clinical Oncology, 2006; 24: 1459–73. Reprints: www.jco.org; D. Walsh, Cleveland Clinic Foundation, Cleveland; walsht@ccf.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 © 2006, 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
Mar. 28, 2006 Vol. 13, No. 59
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 27 issue of Archives of Internal Medicine (www.archinternmed.com; 2006; 166)
Pharmacotherapy in the Elderly: After reviewing the problem of polypharmacy in older patients with multiple chronic diseases and reviewing past literature such as the Beers’ criteria, authors develop a framework for clinicians to use in reconsidering their prescribing decisions for this age group (pp. 605-9): “We propose a framework that may help guide the discontinuation or withholding of treatments otherwise indicated, appropriate, and recommended according to current guidelines. However, discontinuing or withholding medications proved safe and effective in well-designed studies can be challenging. Stopping the use of medications runs contrary to the directions that patients have received from their physicians to adhere to treatment. With more access to computerized medical information and more direct-to-consumer pharmaceutical advertising, patient requests for medications may affect decision making and promote medication overuse. Despite these pressures, physicians still may overestimate patients' discomfort with stopping the use of medicines.” (H. M. Holmes, hholmes@medicine.bsd.uchicago.edu)
Risks for Early Colorectal Cancer: Based on data in the IMPAC Medical Registry Services Cancer Information Resource File, alcohol use, tobacco use, and male gender are all risk factors for an earlier onset of colorectal cancer but also for the more easily detected distal occurrence for these tumors (pp. 629-34). Using data from 1993 to 2003 in their analysis, the investigators identified several groups for whom early colonoscopy or sigmoidoscopy might be indicated based on an individual’s risk factors: “Our data set consisted of 161,172 patients with CRC. Current drinking, smoking, and smoking plus drinking were associated with younger ages at onset of CRC (adjusted age difference, 5.2, 5.2, and 7.8 years, respectively; P < .001 for all). A distal location of CRC was more likely to occur in current drinkers (odds ratio, 1.192; 95% confidence interval, 1.15-1.23) and smokers (odds ratio, 1.164; 95% confidence interval, 1.12-1.21). Colorectal cancer in men tended to occur earlier (adjusted age difference, 1.9 years; P < .001) and have a distal predominance (odds ratio, 1.42; P < .001) compared with women. The smoking but not the drinking effect size was greater in women than in men (adjusted age difference, 2.6 years; P < .001).” (H. K. Roy, h-roy@northwestern.edu)
Antibiotic Therapy for UTIs: In women, quinolones are now the most frequently prescribed antibiotics for urinary tract infections, surpassing sulfa drugs, according to an analysis of data from the 2000-02 National Ambulatory Medical Care Survey (pp. 635-9). Looking at 2,638 isolated outpatient UTIs following visits to physicians’ offices, hospital clinics, and emergency departments, the researchers found: “Quinolones were more commonly prescribed than sulfa antibiotics in each year evaluated. In the most recent year of data, quinolones were prescribed in 48% and sulfas in 33% of UTI visits (P < .04). Quinolones were significantly more likely to be prescribed to older patients and in visits occurring in the Northeast; however, no difference in quinolone prescribing was seen when evaluating insurance status, setting, race, ethnicity, health care provider type, and year. Approximately one third of the quinolones used were broader-spectrum agents.” (A. J. Kallen, alexander.j.kallen@dartmouth.edu)
Diagnosing Acute Pharyngitis: Inappropriate antibiotic prescribing for acute pharyngitis can be reduced through use of the rapid streptococcal antigen test and clinical findings in symptomatic adults, notes a Swiss study (pp. 640-4). Compared with the gold standard throat culture, “RSAT had high sensitivity (91%) and specificity (95%) for the diagnosis of streptococcal pharyngitis,” the authors write. “Systematic throat culture resulted in the highest antibiotic use, in 38% of patients with streptococcal pharyngitis. Systematic RSAT led to nearly optimal treatment (94%) and antibiotic prescription (37%), with minimal antibiotic overuse (3%) and underuse (3%).” (J-P Humair, U. Hosp., Geneva; Jean-Paul.Humair@hcuge.ch)

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 © 2006, 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
Mar. 29, 2006 Vol. 13, No. 60
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Apr. issue of Diabetes Care (care.diabetesjournals.org; 2006; 29).
Extended-Release Metformin: In a 24-week study, a 2,000-mg, extended-release formulation of metformin that is under development provided glycemic control at least equivalent to and possibly better than other available extended- and immediate-release products (pp. 759-64). Adults with type 2 diabetes were randomly assigned to immediate-release metformin 750 mg twice daily or one of three extended-release metformin regimens: 1,500 mg once daily, 750 mg twice daily, or 2,000 mg once daily. Results were as follows: “Significant decreases (P < 0.001) in mean HbA1c (A1C) levels were observed by week 12 in all treatment groups. The mean changes from baseline to end point in the two groups given 1,500 mg extended-release metformin (–0.73 and –0.74%) were not significantly different from the change in the immediate-release metformin group (–0.70%), whereas the 2,000-mg extended-release metformin group showed a greater decrease in A1C levels (–1.06%; mean difference [2,000 mg extended-release metformin – immediate-release metformin]: –0.36 [98.4% CI –0.65 to –0.06]). Rapid decreases in fasting plasma glucose levels were observed by week 1, which continued until week 8, and were maintained for the duration of the study. The overall incidence of adverse events was similar for all treatment groups, but fewer patients in the extended-release metformin groups discontinued treatment due to nausea during the initial dosing period than in the immediate-release metformin group.” (B. Berner, Depomed, Menlo Park, Calif.; bberner@depomedinc.com)
Intensive Insulin in MI: Tight glycemic control may carry some benefits in patients with myocardial infarction, but no mortality advantage was evident in a trial of 240 patients (pp. 765-70). Infusions of insulin and dextrose were titrated to keep patients blood glucose levels below 10 mmol/L (180 mg/dL), with these results generated in comparison with conventional therapy: “Insulin/dextrose infusion did not reduce mortality at the inpatient stage (4.8 vs. conventional 3.5%, P = 0.75), 3 months (7.1 vs 4.4%, P = 0.42), or 6 months (7.9 vs. 6.1%, P = 0.62). There was, however, a lower incidence of cardiac failure (12.7 vs. 22.8%, P = 0.04) and reinfarction within 3 months (2.4 vs. 6.1%, P = 0.05). When analyzed by mean BGL achieved during the first 24 h, mortality was lower among subjects with a mean BGL 8 mmol/l, compared with subjects with a mean BGL >8 mmol/l (2 vs. 11% at 6 months, P = 0.02).” (N. W. Cheung, Westmead Hosp., Westmead, Australia; wah@westgate.wh.usyd.edu.au)
Diabetes & Acute Stroke: The majority of patients with acute stroke have disorders of glucose metabolism, and most of these are unrecognized, according to a study of 286 consecutively admitted patients (pp. 792-7). Among 238 patients for whom fasting blood glucose levels were available during the first 10 days of hospitalization after acute stroke, 20.2% had previously known diabetes, 16.4% had newly diagnosed diabetes, 23.1% had impaired glucose tolerance, 0.8% had impaired fasting glucose, and only 19.7% had normal glucose levels. (K. Matz, Donau-Universität, Maria Gugging, Austria; karl.matz@donauklinikum.at)
Glucose Monitoring in Schizophrenia: All patients with schizophrenia or schizoaffective disorders should be monitored for glucose metabolic abnormalities regardless of the specific medications they are prescribed, according a study of 200 mostly Western European men conducted in the Netherlands (pp. 786-91). “Hyperglycemia was present in 7% of the population: 1.5% with impaired fasting glucose and 5.5% with impaired glucose tolerance,” the researchers report. “The prevalence of diabetes was 14.5%, of which 8% was previously known and 6.5% was newly diagnosed..... Insulin resistance was increased in the study population as a whole..., irrespective of the use of antipsychotic medication and, if used, irrespective of its type (typical or atypical). No indication of beta-cell defect was found, whereas a nonsignificant increased insulin resistance was found with antipsychotic medication.” (D. Cohen, Ctr. for Mental Health Care Rijngeestgroep, Noordwijkerhout, the Netherlands; d.cohen@ggz-nhn.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 © 2006, 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
Mar. 30, 2006 Vol. 13, No. 61
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 30 issue of the New England Journal of Medicine (content.nejm.org; 2006; 354).
Avian Influenza Vaccine: Two doses of an avian influenza vaccine produced neutralizing antibody responses among 451 healthy adults without any severe adverse effects, according to a dose-ranging effectiveness study (pp. 1343-51). Administered intramuscularly were doses of an egg-grown, subvirion influenza A (H5N1) vaccine with 90, 45, 15, or 7.5 mcg of hemagglutinin antigen or placebo. During 56 days of monitoring, the researchers noted: “Mild pain at the injection site was the most common adverse event for all doses of vaccine. The frequency of a serum antibody response was highest among subjects receiving doses of 45 mcg or 90 mcg. Among those who received two doses of 90 mcg, neutralization antibody titers reached 1:40 or greater in 54 percent, and hemagglutination-inhibition titers reached 1:40 or greater in 58 percent. Neutralization titers of 1:40 or greater were seen in 43 percent, 22 percent, and 9 percent of the subjects receiving two doses of 45, 15, and 7.5 mcg, respectively. No responses were seen in placebo recipients.” (J. J. Treanor, john_treanor@urmc.rochester.edu)
Describing development of an avian influenza vaccine as “a race against time,” an editorialist writes (pp. 1411-3): “We need efficient, rapid, high-yield, low-cost manufacturing innovations; the rapid generation of candidate vaccines for other, potentially pandemic influenza viruses (including emerging clade-2 influenza A [H5N1] viruses); and the rapid movement of those vaccines into clinical trials. In turn, this effort will require creativity along the entire pipeline: in the development and manufacture of candidate vaccines; the synchronization among countries of regulatory approaches; the resolution of issues concerning liability and intellectual property; ensuring the efficiency of clinical trials; and the use of methods to stockpile and rapidly deploy these vaccines. To do otherwise, with the pandemic clock ticking, could prove to be too little, too late.” (G. A. Poland, Mayo Clinic, Rochester, Minn.)
Gatifloxacin & Dysglycemia: As reported in PNN on Mar. 2, use of gatifloxacin among outpatients is associated with an increased risk of in-hospital treatment for both hypoglycemia and hyperglycemia (pp. 1352-61). In two population-based, nested case-control studies, investigators found: “Between April 2002 and March 2004, we identified 788 patients treated for hypoglycemia within 30 days after antibiotic therapy. As compared with macrolide antibiotics, gatifloxacin was associated with an increased risk of hypoglycemia (adjusted odds ratio, 4.3; 95 percent confidence interval, 2.9 to 6.3). Levofloxacin was also associated with a slightly increased risk (adjusted odds ratio, 1.5; 95 percent confidence interval, 1.2 to 2.0), but no such risk was seen with moxifloxacin, ciprofloxacin, or cephalosporins. We then identified 470 patients treated for hyperglycemia within 30 days after antibiotic therapy. As compared with macrolides, gatifloxacin was associated with a considerably increased risk of hyperglycemia (adjusted odds ratio, 16.7; 95 percent confidence interval, 10.4 to 26.8), but no risk was noted with the other antibiotics. Risks were similar in the two studies regardless of the presence or absence of diabetes.” (D. N. Juurlink, Sunnybrook and Women’s College Health Sci. Ctr., Toronto; dnj@ices.on.ca)
An editorialist writes that these problems should result in far less use of gatifloxacin (pp. 1413-5):“Gatifloxacin now takes its place among an ever-growing list of medications that have been associated with very serious adverse effects. The most immediate question is what should be done with gatifloxacin. It seems clear that the drug’s place among broad-spectrum antibiotics available for outpatient use is tenuous at best. For every approved indication for gatifloxacin, there are safer, equally effective, and less costly alternatives. In comparison with other recent experiences regarding adverse drug effects, this choice should not be a difficult one for physicians, patients, regulators, and manufacturers.” (J. H. Gurwitz, Meyers Primary Care Inst., Worcester, Mass.)
D Is for Defective: The Medicare Part D benefit is defective and needs reform, as does prescribing in general, writes an author of a Perspectives article (pp. 1339-41; J. Avorn, Brigham and Women’s Hosp., Boston).

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 © 2006, 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
Mar. 31, 2006      Vol. 13, No. 62
Providing news and information about medications and their proper use
 
>>>Neurology Highlights
Source: Mar. 28 issue of Neurology (www.neurology.org; 2006; 66).
HIV-Associated Neuropathies: Patients with HIV infection who are taking stavudine or didanosine have a significantly greater risk for symptomatic sensory neuropathy, according to a study of 147 adults (pp. 867-73). The prospective cohort analysis showed these results at two study sites: “There were significant differences between subjects at Johns Hopkins University (JHU) and Monash University (MU) [in Melbourne, Australia] in gender, race, HIV transmission route, and HCV seroprevalence. Symptomatic SN was present in 49% at JHU and 55% at MU (chi square = 4.02, p = 0.134) and was significantly more common in those at least age 40 than younger patients (odds ratio [OR] = 2.87, 95% CI = 1.27, 6.49). After adjusting for site, age, and CD4 cell count, exposure to didanosine (ddI) or stavudine (d4T) was associated with an significantly increased likelihood of symptomatic SN (ddI: OR = 3.21, 95% CI: 1.56, 6.60; d4T: OR = 7.66, 95% CI: 2.89, 20.33). Plasma HIV RNA, lactate, and [hepatitis C virus] were not associated with SN. Quantitative vibratory testing identified neuropathy with a positive predictive value of 76% and epidermal nerve fiber densities 59%.” (J. C. McArthur, Johns Hopkins Hosp., Baltimore; jm@jhmi.edu)
Teriflunomide for MS: An investigational immunomodulator, teriflunomide, reduced the number of lesions seen on MRI scans, according to a dose-ranging study conducted in patients with relapsing-remitting multiple sclerosis (n = 157) or secondary progressive MS with relapses (n = 22; pp. 894-900). “The median number of combined unique active lesions per scan was 0.5, 0.2, and 0.3 in the placebo, teriflunomide 7 mg/day (p < 0.03 vs placebo), and teriflunomide 14 mg/day (p < 0.01 vs placebo) groups during the 36-week double-blind treatment phase,” the researchers write. “Teriflunomide-treated patients also had significantly fewer T1 enhancing lesions per scan, new or enlarging T2 lesions per scan, and new T2 lesions. Patients receiving teriflunomide 14 mg/day had significantly reduced T2 disease burden. Teriflunomide treatment resulted in trends toward a lower annualized relapse rate and fewer relapsing patients (14 mg/day only) vs placebo. Significantly fewer patients receiving teriflunomide 14 mg/day vs placebo demonstrated disability increase. Treatment was well tolerated; numbers of adverse events and serious adverse events were similar in all treatment groups.” (P.W. O’Connor, St. Michael’s Hospital, Toronto; connorp@smh.toronto.on.ca">oconnorp@smh.toronto.on.ca)
 
>>>PNNNewsWatch
*
FDA yesterday approved tacrolimus for prevention of graft rejection in the recipients of heart transplants. Prograf capsules and Prograf for injection (Astellas Pharma), the first products approved in the United States for heart transplantation in 8 years, had been previously approved for the prevention of graft rejection in the recipients of liver and kidney transplants. The safety and effectiveness of tacrolimus- and cyclosporine-based immunosuppression in heart transplantation were compared in two trials. In a European trial, the survival of patients and grafts 18 months after the transplantation in the tacrolimus group (91.7%) was similar to the cyclosporine group (89.8%). Similar results were recorded in a U.S. study, with patient and graft survival at 12 months after transplantation similar in the tacrolimus (93.5%) and cyclosporine (86.1%) groups. Increased risk or neurotoxicity, renal function impairment, infection, and posttransplant diabetes mellitus were associated with tacrolimus use, along with an increased risk of malignancies, particularly nonmelanoma skin cancers.
* Patients with epilepsy and their family members or caregivers should inspect carefully their
Diastat AcuDial prefilled syringes (diazepam rectal gel) for cracks immediately and every month, FDA explains in a public health advisory. These cracks can result in leakage of the drug product when it is given, so that the patient may not get enough of the medicine to control seizures. Detailed instructions on how the syringes should be inspected without removing the product’s cap are available at www.diastat.com.
 
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 © 2006, 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.