Dec 2008

PNN Quarterly File—Fourth Quarter 2008

PNN Pharmacotherapy Line
Oct. 1, 2008 * Vol. 15, No. 191
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 1 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Schedule, Route for Anthrax Vaccine: Intramuscular administration of anthrax vaccine on a 3- or 4-dose schedule was noninferior to the first 4 subcutaneous doses in the licensed schedule and produced fewer injection site reactions, researchers report (pp. 1532-43). Among the first 1,005 enrollees in a multisite, randomized, double-blind, noninferiority, Phase IV human clinical trial that has been ongoing since May 2002, healthy adults received anthrax vaccine adsorbed (AVA) by the SQ (reference group) or IM route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM) or at a reduced 3-dose schedule (3-IM). Compared with saline administered to a control group, the vaccine produced these changes in anti–protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4xR): ìAt week 8, the 4-IM group (GMC, 90.8 µg/mL; GMT, 1,114.8; %4xR, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 µg/mL; GMT, 1,315.4; %4xR, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4xR (GMC, 52.2 µg/mL; GMT, 650.6; %4xR, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs.î (C. P. Quinn, cquinn@cdc.gov)
News Media Coverage of Medication Research: Despite newspaper editors’ claims to the contrary, articles in the lay media frequently fail to disclose industry sponsorship of research and refer to medications by brand rather than generic names when summarizing journal articles, a study shows (pp. 1544-50). Researchers reviewed newspaper and online articles on industry-sponsored research published in five general medical journals between 2004 and 2008 and surveyed editors at the 100 most widely circulated newspapers in the U.S., with these results: ìOf the 306 news articles about medication research identified,130 (42%; 95% confidence interval [CI], 37%–48%) did not report that the research had received company funding. Of the 277 of these articles reporting on medications with both generic and brand names, 186 (67%; 95% CI, 61%–73%) referred to the study medications by their brand names in at least half of the medication references. Eighty-two of the 93 (88%) newspaper editors who responded to our survey reported that articles from their publications always or often indicated when studies had received company funding (95% CI, 80%–94%), and 71 of 92 (77%) responding editors also reported that articles from their publications always or often referred to medications by the generic names (95% CI, 67%–85%). However, only 3 of 92 newspapers (3%) had written policies stating that company funding sources of medical studies be reported (95% CI 1%–9%), and 2 of 93 (2%) newspapers had written policies stating that medications should be referred to by their generic names (95% CI 1%–8%).î (M. Hochman, miehochman@challiance.org)
Long-term Psychodynamic Psychotherapy: For treating complex mental disorders—patients with personality disorders, chronic mental disorders, multiple mental disorders, and complex depressive and anxiety disorders—long-term psychodynamic psychotherapy is effective, concludes a meta-analysis of 23 studies with 1,053 participants (pp. 1551-65). Adding that outcomes and cost-effectiveness of LTPP should be included in future trials, the writers note: ìAccording to comparative analyses of controlled trials, LTPP showed significantly higher outcomes in overall effectiveness, target problems, and personality functioning than shorter forms of psychotherapy. With regard to overall effectiveness, a between-group effect size of 1.8 (95% confidence interval [CI], 0.7–3.4) indicated that after treatment with LTPP patients with complex mental disorders on average were better off than 96% of the patients in the comparison groups (P = .002). According to subgroup analyses, LTPP yielded significant, large, and stable within-group effect sizes across various and particularly complex mental disorders (range, 0.78–1.98).î (F. Leichsenring, falk.leichsenring@psycho.med.uni-giessen.de)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 2, 2008 * Vol. 15, No. 192
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 2 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Maraviroc for Previously Treated R5 HIV-1 Infection: Two research studies and an editorial present data on use of maraviroc in patients with R5 HIV-1 infection, which predominates during early phases of infection.
Compared with placebo, maraviroc provided significantly greater suppression of HIV-1 and greater increases in CD4 cell counts at 48 weeks in previously treated patients with R5 HIV-1 who were also receiving optimized background therapy (OBT), according to Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) studies 1 and 2 (pp. 1429-41). Using once- or twice-daily doses of maraviroc, the researchers determined: ìA total of 1,049 patients received the randomly assigned study drug; the mean baseline HIV-1 RNA level was 72,400 copies per milliliter, and the median CD4 cell count was 169 per cubic millimeter. At 48 weeks, in both studies, the mean change in HIV-1 RNA from baseline was greater with maraviroc than with placebo: –1.66 and –1.82 log
10 copies per milliliter with the once-daily and twice-daily regimens, respectively, versus –0.80 with placebo in MOTIVATE 1, and –1.72 and –1.87 log10 copies per milliliter, respectively, versus –0.76 with placebo in MOTIVATE 2. More patients receiving maraviroc once or twice daily had HIV-1 RNA levels of less than 50 copies per milliliter (42% and 47%, respectively, vs. 16% in the placebo group in MOTIVATE 1; 45% in both maraviroc groups vs. 18% in MOTIVATE 2; P < 0.001 for both comparisons in each study). The change from baseline in CD4 counts was also greater with maraviroc once or twice daily than with placebo (increases of 113 and 122 per cubic millimeter, respectively, vs. 54 in MOTIVATE 1; increases of 122 and 128 per cubic millimeter, respectively, vs. 69 in MOTIVATE 2; P < 0.001 for both comparisons in each study). Frequencies of adverse events were similar among the groups.î (R. M. Gulick, rgulick@med.cornell.edu)
A subgroup analysis of MOTIVATE 1 and 2 showed that the drug was valuable in a broad spectrum of patient types (pp. 1442-55): ìA treatment benefit of maraviroc plus OBT over placebo plus OBT was shown in all subgroups, including patients with a low CD4 cell count at baseline, those with a high viral load at screening, and those who had not received active agents in OBT. Analyses of the virologic response according to the first use of selected background drugs showed the additional benefit of adding a potent new drug to maraviroc at the initiation of maraviroc therapy. More patients in whom maraviroc failed had a virus binding to the CXC chemokine receptor 4 (CXCR4) at failure, but there was no evidence of a decrease in the CD4 cell count at failure in such patients as compared with those in whom placebo failed. Subanalyses involving patients coinfected with HBV or HCV revealed no evidence of excess hepatotoxic effects as compared with baseline.î (G. F‰tkenheuer,
g.faetkenheuer@uni-koeln.de)
Writing that maraviroc and other inhibitors of the human chemokine receptor 5 (CCR5) are a welcome addition to the available agents but ones for which ìoptimal use is a challenge that will require continued study and vigilance by investigators, clinicians, and patients themselves,î an editorialist writes (pp. 1509-11): ìThe current studies indicate that maraviroc is useful in patients with a substantial history of antiretroviral treatment—that is, in the later stages of disease. However, arguments can be made for the potential advantage of the use of CCR5 inhibitors early in disease. R5 viruses are more prevalent early on, whereas the insensitive X4 viruses predominate late in disease. R5 viruses encountered later in disease may be somewhat more resistant to CCR5 inhibitors than R5 viruses found earlier in disease. The fact that CCR5 inhibitors can prevent entry of HIV-1 may make them particularly attractive for early use—either orally or perhaps by topical administration, as a microbicide—as a means of interrupting viral transmission. Effective therapy early in infection might also interfere with the rapid loss of CCR5+CD4+ T cells from gut-associated lymphoid tissue, which is a devastating early result of HIV-1 infection.î (R. Dolin)

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 3, 2008 * Vol. 15, No. 193
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Oct. issue of Pharmacotherapy (www.atypon-link.com/PPI/toc/phco/28/10; 2008; 28).
Propacetamol & Blood Pressure: Intravenous propacetamol, used in antipyretic doses among 14 febrile critically ill patients, caused a significant decrease in blood pressure, researchers report, requiring interventions to control blood pressure (pp. 1205-10). Administered on 72 occasions, the acetaminophen precursor produced these effects in the 14 patients: ìMean ± SE systolic, diastolic, and mean arterial pressures recorded 15 minutes after propacetamol administration were significantly lower than baseline measurements: 123 ± 29 versus 148 ± 33, 62 ± 12 versus 70 ± 15, and 83 ± 16 versus 97 ± 19 mm Hg, respectively (p < 0.05). In 24 (33%) of the72 infusions, systolic blood pressure decreased to below 90 mm Hg and required intervention with fluid bolus administration on six occasions; a fluid bolus was accompanied by a dosage increase or initiation of a norepinephrine infusion on 18 occasions. No correlation, however, was noted between the degree of decrease in mean arterial pressure and decrease in temperature (r2 = 0.01), or the degree of decrease in mean arterial pressure and decrease in heart rate (r2 = 0.23), at each data collection time point, as measured by linear regression.î (M. Hersch, hersch@szmc.org.il)
Pediatric Carbamazepine to Oxcarbazepine Switches: Among 26 children and adolescents, overnight switching from carbamazepine to oxcarbazepine was well tolerated, according to results gathered in a retrospective chart review at a children’s hospital (pp. 1211-4). ìDose conversion ratios for switching from carbamazepine to oxcarbazepine ranged from 1:1–1.5,î report the authors. ìThe transition was well tolerated, with only three patients experiencing an adverse event (rash). Among the other 23 patients, seizure frequency decreased in 12 (52%), increased in two (9%), and remained unchanged in nine (39%).î (I. I. Vaisleib, Inna.Vaisleib@chp.edu)
Etravirine Bioavailability: Because of decreased absorption when administered in the fasting state, etravirine should be administered following a meal to improve bioavailability, a Phase I trial shows (pp. 1215-22). Pharmacokinetic profiles determined for up to 96 hours following drug doses showed the following: ìThe least-squares mean ratio for the area under the plasma concentration–time curve from time of administration to the last time point with a measurable concentration after dosing (AUClast) was 0.49 (90% confidence interval [CI] 0.39–0.61) for the fasted state compared with dosing after a standard breakfast. When dosing occurred after a light or enhanced-fiber breakfast, the corresponding values were 0.80 (90% CI 0.69–0.94) and 0.75 (90% CI 0.63–0.90), respectively. When administered after a high-fat breakfast the least-squares mean ratio of AUClast was 1.09 (0.84–1.41), compared with dosing after a standard breakfast. Adverse events were also assessed. Under all conditions, single doses of etravirine 100 mg were generally safe and well tolerated.î (M. Schˆller-Gy¸re, mscholle@tibbe.jnj.com)
Combination Antiplatelet Agents for Secondary Prevention of Ischemic Stroke: The antiplatelet combination of aspirin and clopidogrel should be reserved for special populations such as those who have had coronary artery stenting, concludes a review article (pp. 1233-42): ìAHA-ASA guidelines suggest that either extended-release dipyridamole plus aspirin or clopidogrel monotherapy should be used over aspirin monotherapy. Both guidelines recommend avoiding the combination of clopidogrel and aspirin for most patients with previous stroke or [transient ischemic attack].... The [European-Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT)] compared aspirin monotherapy with the combination of aspirin plus extended-release dipyridamole for prevention of secondary ischemic events in patients with a history of TIA or minor stroke. The [Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA)] trial compared aspirin plus clopidogrel with aspirin alone in a population at high risk for atherothrombotic events using the composite outcome of myocardial infarction, stroke, and death from cardiovascular causes. Data from ESPRIT add to evidence that the combination of aspirin plus extended-release dipyridamole is superior to aspirin alone.î (J. P. Vande Griend, joseph.vandegriend@ucdenver.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 6, 2008 * Vol. 15, No. 194
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 4 issue of Lancet (www.thelancet.com; 2008; 372).
Omega-3 Fatty Acids in Patients with HF: Mortality and hospital admissions were reduced among patients with symptomatic heart failure who received n-3 polyunsaturated fatty acids (PUFA) 1 gram daily, compared with placebo, according to results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico (GISSI)–Heart Failure (HF) trial (pp. 1223-30). Nearly 7,000 patients were followed for a median of 3.9 years, with these results noted for primary endpoints of time to death and time to death or admission to hospital for cardiovascular reasons: ìWe analysed all randomised patients. 955 (27%) patients died from any cause in the n-3 PUFA group and 1014 (29%) in the placebo group (adjusted hazard ratio [HR] 0.91 [95.5% CI 0.833–0.998], p = 0.041). 1981 (57%) patients in the n-3 PUFA group and 2053 (59%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 0.92 [99% CI 0.849–0.999], p = 0.009). In absolute terms, 56 patients needed to be treated for a median duration of 3.9 years to avoid one death or 44 to avoid one event like death or admission to hospital for cardiovascular reasons. In both groups, gastrointestinal disorders were the most frequent adverse reaction (96 [3%] n-3 PUFA group vs 92 [3%] placebo group).î (GISSI-HF Coordinating Ctr., gissihf@anmco.it)
Rosuvastatin in Heart Failure: A second report from the GISSI–HF trial concludes that rosuvastatin 10 mg daily had no effect on clinical outcomes in patients with chronic heart failure of any cause (pp. 1231-9). Among 4,574 patients for whom rosuvastatin was safe, these results were noted: ìWe analysed all randomised patients. 657 (29%) patients died from any cause in the rosuvastatin group and 644 (28%) in the placebo group (adjusted hazard ratio [HR] 1.00 [95.5% CI 0.898–1.122], p = 0.943). 1,305 (57%) patients in the rosuvastatin group and 1,283 (56%) in the placebo group died or were admitted to hospital for cardiovascular reasons (adjusted HR 1.01 [99% CI 0.908–1.112], p = 0.903). In both groups, gastrointestinal disorders were the most frequent adverse reaction (34 [1%] rosuvastatin group vs 44 [2%] placebo group).î (GISSI-HF Coordinating Ctr., gissihf@anmco.it)
Once-Weekly Exenatide: Among 295 patients with type 2 diabetes, a long-acting formulation of exenatide administered once weekly in doses of 2 mg resulted in significantly greater improvements in glycemic control than exenatide 10 mcg given twice a day, researchers report (pp. 1240-50). Risk of hypoglycemia was similar with the two treatments and reductions in body weight were similar, the investigators note, adding these details about the mean of 6.7 years of study results: ìAt 30 weeks, the patients given exenatide once a week had significantly greater changes in HbA1c than those given exenatide twice a day (−1.9 [SE 0.1%] vs −1.5 [0.1%], 95% CI −0.54% to −0.12%; p = 0.0023). A significantly greater proportion of patients receiving treatment once a week versus twice a day achieved target HbA1c levels of 7.0% or less (77% vs 61% of evaluable patients, p = 0.0039).î (D. J. Drucker, d.drucker@utoronto.ca)

>>>PNN JournalWatch
* Early Identification and Management of Chronic Kidney Disease: Summary of NICE Guidance, in BMJ, 2008; a1530. Reprints: P. Stevens, paul.stevens@ekht.nhs.uk
* Drug Interactions and Pharmacogenomics in the Treatment of Breast Cancer and Depression, in
American Journal of Psychiatry, 2008; 165: 1251–5. Reprints: N. L. Henry.
* Preventing the Onset of Depressive Disorders: A Meta-Analytic Review of Psychological Interventions, in
American Journal of Psychiatry, 2008; 165: 1272–80. Reprints: P. Cuijpers.
* Management of Atopic Dermatitis in the Pediatric Population, in
Pediatrics, 2008; 122: 812–24. Reprints: A. C. Krakowski.
* Large Outbreak of Measles in a Community with High Vaccination Coverage: Implications for the Vaccination Schedule, in
Clinical Infectious Diseases, 2008; 47: 1143–9. Reprints: A. Dominguez, angela.dominguez@ub.edu
* Gastrointestinal Flu: Norovirus in Health Care and Long-Term Care Facilities, in
Clinical Infectious Diseases, 2008; 47: 1202–8. Reprints: C. L. Sears, csears@jhmi.edu
* Treatment of Extensively Drug-Resistant Tuberculosis and Role of the Pharmacist, in
Pharmacotherapy, 2008; 28: 1243–54. Reprints: B. M. Mitrzyk, bmitrzyk@umich.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 7, 2008 * Vol. 15, No. 195
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 7 issue of the Annals of Internal Medicine (www.annals.org/current.shtml; 2008; 149).
Improving Antimicrobial Prescribing: A quality improvement collaborative focused on improving preoperative antimicrobial prophylaxis had no significant effect, researchers report (pp. 472-80). The group notes that the trial was conducted during a time of ìheightened national attention toward measures of antimicrobial prophylaxis performance,î and this might have affected the 44-hospital study. Among approximately 100 surgical patients at each site, investigators monitored for the change in the proportion of patients receiving at least 1 antibiotic dose within 60 minutes of surgery (primary outcome) and change in the proportions of patients given any antibiotics, given antibiotics for 24 hours or less, given an appropriate drug, and given a single preoperative dose and receipt of any of the 5 measures (secondary outcome). Comparing 22 hospitals where a quality improvement collaborative (two in-person meetings led by experts, monthly teleconferences, and receipt of supplemental materials) occurred over 9 months with control hospitals, the investigators found: ìThe groups did not differ in the change in proportion of patients who received a properly timed antimicrobial prophylaxis dose (–3.8 percentage points [95% CI, –13.9 to 6.2 percentage points]) after adjustment for region, hospital size, and surgery type. Similarly, the groups did not differ in individual measures of antibiotic duration; use of appropriate drug; receipt of a single preoperative dose; or an all-or-none measure combining timing, duration, and selection.î (B. I. Braun, bbraun@jointcommission.org)
Monitoring d-Dimers After Anticoagulant Cessation: d-dimer tests can be used to discriminate between patients with higher and lower risks for recurrent venous thrombus embolism at the time of anticoagulation cessation, concludes a systematic review (pp. 481-90). All selected studies included patients who had been on at least 3 months of anticoagulation for prevention of VTE recurrence. They showed: ìSeven studies, totaling 1,888 patients with a first unprovoked VTE, were eligible for analysis. During 4,500 person-years of follow up, annual rates of recurrent VTE differed statistically significantly: 8.9% (95% CI, 5.8% to 11.9%) in patients with positive d-dimer results and 3.5% (CI, 2.7% to 4.3%) in patients with negative d-dimer results.î (J. D. Douketis, jdouket@mcmaster.ca)
Insulin-like Growth Factors & Prostate Cancer Risk: Men with high levels of insulin-like growth factor I concentrations have a moderately increased risk for prostate cancer, according to an analysis of 12 prospective studies of 3,700 men with prostate cancer and 5,200 control participants (pp. 461-71). ìOn average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection,î write the authors. ìThe greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGF [binding protein II (IGFBP-II] concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake.î (A. W. Roddam, andrew.roddam@ceu.ox.ac.uk)
Behavioral Counseling to Prevent Sexually Transmitted Infections: All sexually active adolescents should receive high-intensity behavioral counseling about the risks of acquiring sexually transmitted diseases, as should adults at increased risk for STIs, concludes a recommendation statement of the U.S. Preventive Services Task Force (pp. 491-6; www.preventiveservices.ahrq.gov) A separate article provides a systematic review of the subject (pp. 497-508; www.preventiveservices.ahrq.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 8, 2008 * Vol. 15, No. 196
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 8 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
5-Alpha Reductase Inhibition & Hip Fracture: No increase in risk of hip fracture was observed among men using 5-alpha reductase inhibitors for treatment of benign prostatic hyperplasia, but investigators found an association between exposure to alpha-blockers and incident hip fractures (pp. 1660-4). Concluding that this association should be investigated further, the researchers reported these results from their case–control analysis of Kaiser Permanente records of 14,152 men: ìOverall, 2,547 (36%) and 2,488 (35%) case and control patients, respectively, had a diagnosis of BPH (P = .30), and 109 (1.5%) and 141 (2.0%) of case and control patients, respectively, had been exposed to finasteride prior to the index date (matched odds ratio, 0.77; 95% confidence interval, 0.59–1.00; P = .04). There was no suggestion of a dose-response relationship between exposure to 5-alpha reductase inhibitors when the exposure was stratified into tertiles of total exposure (P = .12). By contrast, there was a slightly higher prevalence of alpha-blocker use in case vs control patients (32% vs 30%, respectively; P = .04).î (S. J. Jacobsen, steven.j.jacobsen@kp.org)

>>>Allergy/Immunology Report
Source:
Oct. issue of the Journal of Allergy and Clinical Immunology (www.jacionline.org/current; 2008; 122).
Controller Medications & Asthma Exacerbations: Inhaled corticosteroids were significantly better than montelukast for prevention of repeat exacerbations of asthma in a trial of children aged 6–14 years with persistent asthma (pp. 741-7.e4). The 48-week Pediatric Asthma Controller Trial study randomized participants to receive either fluticasone propionate 100 mcg twice daily (FP monotherapy), combination fluticasone 100 mcg AM and salmeterol twice daily, or montelukast 5 mg once daily, with these results: ìOf the 285 participants randomized, 48% had 231 exacerbations. Using a multivariate analysis, which included numerous demographic, pulmonary, and inflammatory parameters, only a history of an asthma exacerbation requiring a systemic corticosteroid in the past year (odds ratio [OR], 2.10; P < .001) was associated with a subsequent exacerbation during the trial. During the trial, treatment with montelukast versus FP monotherapy (OR, 2.00; P = .005), season (spring, fall, or winter vs summer; P .001), and average seasonal 5% reduction in AM peak expiratory flow (OR, 1.21; P = .01) were each associated with exacerbations. Changes in worsening of symptoms, beta-agonist use, and low peak expiratory flow track together before an exacerbation, but have poor positive predictive value of exacerbation.î (R. A. Covar, covarr@njc.org)
Probiotics & Atopic Disease: Supplementation with Lactobacillus rhamnosus HN001 but not Bifidobacterium animalis subsp lactis strain HN019 substantially reduced the cumulative prevalence of eczema but not atopy by 2 years among 474 infants (pp. 788-94). Mothers received the randomized treatment in late pregnancy and during any breastfeeding. Results showed a significant 49% reduction in risk of eczema with L. rhamnosus but no other significant associations. (K. Wickens, kristin.wickens@otago.ac.nz)

>>>PNN NewsWatch
* No increased risk of stroke is associated with use of tiotropium bromide (Spiriva HandiHaler, Boehringer Ingelheim), according to preliminary results from the UPLIFT (Understanding the Potential Long-Term Impacts on Function with Tiotropium) study, FDA said yesterday. Complete results from the large, 4-year, placebo-controlled clinical trial of 6,000 patients with chronic obstructive pulmonary disease (COPD) are expected in Nov., the agency added. The data will be analyzed in the coming months in conjunction with results of two recently published trials showing increased mortality with use of tiotropium and inhaled cholinergics among patients with COPD (see PNN, Sept. 16 and 24).
*
You and Your Pharmacist: A Winning Team is a new video produced by APhA as part of the profession’s annual Oct. celebration of American Pharmacists Month. Information and materials supporting the theme of ìKnow Your MEDICINE, Know Your PHARMACISTî are available on APhA’s pharmacist.com website.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 9, 2008 * Vol. 15, No. 197
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 9 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Tiotropium in COPD: Symptoms improved but long-term declines in lung function continued during 4 years of tiotropium treatment of chronic obstructive pulmonary disease, according to results from the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) trial (pp. 1543-54). Patients in the study could use all respiratory medications for managing their COPD except for inhaled anticholinergic drugs. Looking at changes in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), St. George’s Respiratory Questionnaire (SGRQ), and other measures, the investigators found: ìOf a total of 5,993 patients (mean age, 65 ± 8 years) with a mean FEV1 of 1.32 ± 0.44 liters after bronchodilation (48% of predicted value), we randomly assigned 2,987 to the tiotropium group and 3,006 to the placebo group. Mean absolute improvements in FEV1 in the tiotropium group were maintained throughout the trial (ranging from 87 to 103 ml before bronchodilation and from 47 to 65 ml after bronchodilation), as compared with the placebo group (P < 0.001). After day 30, the differences between the two groups in the rate of decline in the mean FEV1 before and after bronchodilation were not significant. The mean absolute total score on the SGRQ was improved (lower) in the tiotropium group, as compared with the placebo group, at each time point throughout the 4-year period (ranging from 2.3 to 3.3 units, P < 0.001). At 4 years and 30 days, tiotropium was associated with a reduction in the risks of exacerbations, related hospitalizations, and respiratory failure.î (D. P. Tashkin, dtashkin@mednet.ucla.edu)
Arguing that patients with COPD need to be analyzed in subgroups that may show efficacy of drugs among specific patient types, an editorialist writes (pp. 1616-8): ìCOPD in the singular is probably a misnomer. It is more appropriate to view COPD as a syndrome that encompasses a variety of obstructive diseases that share a common exposure but differ in terms of mechanism of disease and response to therapy.Ö As a reflection of this recognized heterogeneity, investigators have developed new classification systems, such as the BODE index, which evaluates the body-mass index, the degree of airflow obstruction and dyspnea, and exercise capacity to create a 10-point scale in which higher scores indicate a higher risk of death. In addition, investigators have attempted to define other homogeneous subgroups of patients with COPD.î (J. J. Reilly, U. Pittsburgh, Pittsburgh)
Benefits of Maternal Influenza Immunization: Maternal immunization using inactivated influenza vaccine provides ìsubstantial benefits for both mothers and infants,î researchers report, pointing to a 63% reduction in proven influenza illness in infants during their first 6 months of life and averting one-third of febrile respiratory illness among both mothers and infants (pp. 1555-64). A total of 340 mothers received either inactivated influenza vaccine or 23-valent pneumococcal polysaccharide vaccine as a control. Interviews, clinical assessments of those with febrile illness, and tests of infants for influenza antigen showed the following: ìMothers and infants were observed from August 2004 through December 2005. Among infants of mothers who received influenza vaccine, there were fewer cases of laboratory-confirmed influenza than among infants in the control group (6 cases and 16 cases, respectively), with a vaccine effectiveness of 63% (95% confidence interval [CI], 5 to 85). Respiratory illness with fever occurred in 110 infants in the influenza-vaccine group and 153 infants in the control group, with a vaccine effectiveness of 29% (95% CI, 7 to 46). Among the mothers, there was a reduction in the rate of respiratory illness with fever of 36% (95% CI, 4 to 57).î (M. C. Steinhoff, m.steinhoff@gmail.com)
Long-Term Effects in Tight Blood Pressure, Glycemic Control in Diabetes: Two reports of posttrial monitoring of patients in the United Kingdom Prospective Diabetes Study (UKPDS) show that blood pressure control must be continued to maintain benefits (pp. 1565-76), but glycemic control produces long-term reductions in risks of microvascular disease, myocardial infarction, and death (pp. 1577-89). (R. R. Holman, rury.holman@dtu.ox.ac.uk)

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 10, 2008 * Vol. 15, No. 198
Providing news and information about medications and their proper use

>>>Circulation Highlights
Source:
Oct. 7 issue of Circulation (http://circ.ahajournals.org/current.dtl; 2008; 118).
Passive Smoking & Cardiovascular Disease: Exposure of Chinese women to secondhand smoke (SHS) was associated with coronary heart disease as well as ischemic stroke and peripheral arterial disease (PAD), researchers report (pp. 1535-40). In a population-based cross-sectional study in Beijing, these relationships were identified between SHS and disease: ìAmong 1,209 women who never smoked, 39.5% were exposed to SHS at home or in workplaces. Those individuals who were exposed to SHS had a significantly higher risk of coronary heart disease (adjusted odds ratio [OR], 1.69; 95% CI, 1.31 to 2.18) and ischemic stroke (OR, 1.56; 95% CI, 1.03 to 2.35) than those never exposed to SHS after adjustment for 13 potential risk factors. The adjusted ORs of PAD defined by intermittent claudication, by ankle-brachial index <0.90, and by either intermittent claudication or ankle-brachial index <0.90 were 1.87 (95% CI, 1.30 to 2.68), 1.47 (95% CI, 1.07 to 2.03), and 1.67 (95% CI, 1.23 to 2.16), respectively. Dose-response relationships were found between SHS exposure amount (cigarettes per day) and duration (minutes per day) and increasing prevalence of coronary heart disease, ischemic stroke, and PAD.î (F. B. Hu, frankhu@channing.harvard.edu)
Terming education on the dangers of passive smoking ìa cessation strategy past due,î editorialists write (pp. 1521-3): ìAlthough clinician and patient education is needed to encourage complete cessation, public health policies that support smokefree homes (including nursing homes and assisted-living facilities) and workplaces are important, not only to minimize the burden of disease, including cardiovascular mortality, but to create an environment that motivates and helps smokers quit. The combination of patient and physician education coupled with public health activism can reduce active and passive smoking, resulting in immediate health benefits, particularly with regard to cardiovascular disease.î (S. A. Glantz,
glantz@medicine.ucsf.edu)
Risk Factors for Stroke Among American Indians: Blood pressure and glucose control, along with smoking avoidance, are important factors in reducing the risk for stroke among American Indians, according to an analysis from the Strong Heart Study (pp. 1577-84). Baseline data were obtained in 1989–92, with these outcomes recorded during the study: ìThrough December 2004, 306 (6.8%) of 4,507 participants without prior stroke suffered a first stroke at a mean age of 66.5 years. The age- and sex-adjusted incidence was 679/100,000 person-years. Nonhemorrhagic cerebral infarction occurred in 86% of participants with incident strokes; 14% had hemorrhagic stroke. The overall age-adjusted 30-day case-fatality rate from first stroke was 18%, with a 1-year case-fatality rate of 32%. Age, diastolic blood pressure, fasting glucose, hemoglobin A1c, smoking, albuminuria, hypertension, prehypertension, and diabetes mellitus were risk factors for incident stroke.î (Y. Zhang, Ying-zhang4@ouhsc.edu)

>>>PNN NewsWatch
* Silodosin, a selective alpha-1A blocker, has been approved by FDA for treatment of benign prostatic hyperplasia, Watson Pharmaceuticals announced this week. The agent, which will be marketed as Rapaflo, demonstrated strong efficacy against BPH symptoms with minimal cardiovascular effects, the company said in a news release, including no meaningful prolongation of the QT interval. The most common drug-related adverse effect was retrograde ejaculation, followed by dizziness.
*
FDA is supporting a voluntary action by the Consumer Healthcare Products Association (CHPA). Its members are voluntarily modifying the product labels for consumers of OTC cough and cold medicines to state ìdo not useî in children under 4 years of age, and are introducing new child-resistant packaging and new measuring devices for use with the products. ìFDA will continue to work with the Centers for Disease Control and Prevention to monitor the ongoing use of these products and to develop educational materials for parents and consumers,î a news release stated. ìThe agency will also continue to reach out to the scientific community to obtain more up-to-date information and scientific data about the effects of these products in children.î
*
PNN will not be published on Mon., Oct. 13, Columbus 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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 14, 2008 * Vol. 15, No. 199
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 13 issue of the Archives of Internal Medicine (http://archinte.ama-assn.org/current.dtl; 2008; 168).
Smoking & Quality of Life: In addition to shortening life expectancy by 7 to 10 years, smoking also decreases health-related quality of life, a study of 1,658 white Finnish men shows (pp. 1968-74). Participants in the Helsinki Businessmen Study were all healthy at baseline in 1974. Combining data from mailed questionnaires in 2000, HRQoL as measured using the RAND 36-Item Health Survey, and death reports in Finnish national registers, the researchers determined: ìParticipants who had never smoked (n = 614) lived a mean of 10 years longer than heavy smokers (>20 cigarettes daily; n = 188). Among survivors in 2000 (n = 1,131), the never-smokers had the highest (ie, best) scores on all RAND 36-Item Health Survey scales. The differences were greatest between never-smokers and heavy smokers, ranging from 4 points on the scale of social functioning to 14 points on the physical functioning scale. The physical component summary score showed a graded deterioration of HRQoL with an increasing number of cigarettes smoked daily (P = .01).î (A. Y. Strandberg, arto.strandberg@kolumbus.fi)
Using a title that recalls the saying ìlive fast, die young, leave a good-looking corpse,î an editorialist writes (pp. 1946-7): ìMost individuals who counsel smokers on smoking cessation using information on the disease risks of smoking have encountered the response encapsulated in the title of this article, namely, that everyone dies of something, and losing a few years of life at the ‘old and gray’ stage is not much of a loss. However, the article by Strandberg and colleagues provides powerful new information to counter this belief. It is not just that the heavy smoker loses 10 years of life expectancy but rather that at any given age, the functional capacities of the heavy smoker are equivalent to those of nonsmokers who are 10 years older. The clear message is that smoking makes you old before your time, and this reality may be far less attractive to younger smokers than the macho image of dying young while still strong and active. Perhaps this reframing of the value of smoking cessation can increase its saliency for the ‘live fast’ group of smokers, who may become a larger fraction of the patients seen in the health care system as their more rational peers successfully achieve abstinence.î (D. M. Burns,
dburns@ucsd.edu)

>>>Lancet Highlights
Source:
Oct. 11 issue of Lancet (www.thelancet.com; 2008; 372).
Alteplase After Ischemic Stroke: For patients with ischemic stroke who do not receive alteplase within the standard 3-hour timeframe, the agent can be safely administered by 4.5 hours, a prospective audit of the International Stroke Thrombolysis Registry (ISTR) shows (pp. 1303-9). Compared with 11,865 patients who received alteplase within the first 3 hours, 664 patients who were given the drug between 3 and 4.5 hours had these outcomes: ìIn the 3–4.5-h cohort, treatment was started at a median of 55 min later after symptom onset (195 min [IQR 187–210] vs 140 min [115–165], p < 0.0001), median age was 3 years younger (65 years [55–73] vs 68 years [58–74], p < 0.0001), and stroke severity was lower ([stroke scale] score 11 [7–16] vs 12 [8–17], p < 0.0001) than in the 3-h cohort. We recorded no significant differences between the 3–4.5-h cohort and the within 3-h cohort for any outcome measure—rate of symptomatic intracerebral haemorrhage: 2.2% (14 of 649) versus 1.6% (183 of 11,681) (odds ratio [OR] 1.18 [95% CI 0.89–1.55], p = 0.24; adjusted OR 1.32 [1.00–1.75], p = 0.052); mortality: 12.7% (70 of 551) versus 12.2% (1263 of 10,368) (OR 1.02 [0.90–1.17]; p = 0.72; adjusted OR 1.15 [1.00–1.33]; p = 0.053); and independence: 58.0% (314 of 541) versus 56.3% (5756 of 10,231) (OR 1.04 [0.95–1.13], p = 0.42; adjusted OR 0.93 [0.84–1.03], p = 0.18).î (N. Wahlgren, nils.wahlgren@karolinska.se)

>>>PNN JournalWatch
* Predictors of Smoking Cessation After a Myocardial Infarction: The Role of Institutional Smoking Cessation Programs in Improving Success, in Archives of Internal Medicine, 2008; 168: 1961–7. Reprints: S. Parashar, susmita.parashar@emory.edu
* 2008 Focused Update Incorporated into the ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease, in
Circulation, 2008; 118: e523–661. Reprints: American College of Cardiology/American Heart Association Task Force on Practice Guidelines.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 15, 2008 * Vol. 15, No. 200
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 15 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
High-Dose B Vitamins & Cognitive Decline in Alzheimer Disease: Among patients with mild or moderate symptoms of Alzheimer’s disease, a regimen of high-dose B vitamins failed to slow rates of cognitive decline over an 18-month period, researchers report (pp. 1774-83). At clinical research sites of the Alzheimer Disease Cooperative Study, patients with normal serum levels of folic acid, vitamin B12, and homocysteine received either placebo or supplements containing high-dose folate, vitamin B6, and vitamin B12, with these results: ìA total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], –2.42 [3.35] in active treatment group vs –0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, –0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements.î (P. S. Aisen, paisen@ucsd.edu)
Editorialists conclude that the evidence on use of B vitamins for slowing cognitive decline in Alzheimer’s disease is ìinsufficient ... to justify treatmentî (pp. 1819-21): ìMandatory folic acid fortification was introduced in the United States and Canada in 1998 for the prevention of neural tube defects. Folic acid fortification has resulted in more than a doubling in the mean serum folate concentrations but serum vitamin B
12 concentrations did not change appreciably.Ö Some countries, such as England, delayed fortification because of concerns about ‘masking’ of vitamin B12 deficiency in older adults or acceleration of neurological disease associated with vitamin B12 deficiency by exposing older adults with vitamin B12 deficiency to very high levels of folic acid. Unequivocal demonstration of any beneficial or hazardous effects of B vitamins on cognitive function, vascular disease and nonvascular disease from the large-scale homocysteine-lowering trials would have important implications for public health policy.
ìAny theoretical concerns about hazards of folate supplementation can be alleviated by ensuring an adequate dose of vitamin B
12 (>500 µg) in multivitamin supplements containing high-dose folic acid (>400 µg). However, until and unless new data suggest otherwise, there is insufficient evidence to justify routine use of homocysteine-lowering vitamin supplements for the prevention of Alzheimer disease and cognitive decline among individuals with normal vitamin status.î (R. J. Clarke, robert.clarke@ctsu.ox.ac.uk)
Amiodarone Dosing in AF: Continuous and episodic administration of amiodarone yielded mixed results in 209 patients with prior atrial fibrillation, with greater recurrence, more hospitalizations, and higher all-cause mortality observed with episodic use (pp. 1784-92). Looking at a primary end point of a composite of amiodarone and underlying heart disease–related major events, CONVERT researchers found: ìAfter a median follow-up of 2.1 years (range, 0.4–2.5 years), 51 (48%) of those receiving episodic treatment vs 64 (62%) receiving continuous treatment had sinus rhythm (P = .05). There were 85 atrial fibrillation recurrences (80%) among the episodic treatment group vs 56 (54%) in the continuous treatment group (P < .001). No significant difference existed in the incidence of the primary composite end point between each group (37 [35%] episodic vs 34 [33%] continuous; incidence rate difference, 0.2; 95% confidence interval [CI], –10.2 to 10.6). However, there were nonstatistically significant differences in the incidence of amiodarone-related major events (20 [19%] episodic vs 25 [24%] continuous; incidence rate difference, –2.0; 95% CI, –8.7 to 4.6) and underlying heart disease–related major events (17 [16%] episodic vs 9 [9%] continuous; incidence rate difference, 3.6; 95% CI, –1.6 to 8.7). All-cause mortality and cardiovascular hospitalizations were higher among those receiving episodic treatment (56 [53%] vs 35 [34%], P = .02).î (I. C. Van Gelder, I.C.van.Gelder@thorax.umcg.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 16, 2008 * Vol. 15, No. 201
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 16 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Polio Vaccine in Newborns: Monovalent type 1 oral poliovirus vaccine, administered to newborns in Egypt at birth, proved superior to trivalent oral poliovirus vaccine for inducing humoral antibodies against type 1 poliovirus, overcoming high preexisting levels of maternally derived antibodies, and increasing the resistance to excretion of type 1 poliovirus after administration of a challenge dose 30 days after birth (pp. 1655-65). Newborns in the study received either the monovalent or trivalent poliovirus vaccine at birth, and a single challenge dose of monovalent type 1 oral poliovirus vaccine was administered 30 days later. Viral shedding data were collected through day 60, and results showed: ìA total of 530 subjects were enrolled, and 421 fulfilled the study requirements. Thirty days after the study vaccines were administered, the rate of seroconversion to type 1 poliovirus was 55.4% in the monovalent-vaccine group, as compared with 32.1% in the trivalent-vaccine group (P < 0.001). Among those with a high reciprocal titer of maternally derived antibodies against type 1 poliovirus (>64), 46.0% of the subjects in the monovalent-vaccine group underwent seroconversion, as compared with 21.3% in the trivalent-vaccine group (P < 0.001). Seven days after administration of the challenge dose of monovalent type 1 vaccine, a significantly lower proportion of subjects in the monovalent-vaccine group than in the trivalent-vaccine group excreted type 1 poliovirus (25.9% vs. 41.5%, P = 0.001). None of the serious adverse events reported were attributed to the trial interventions.î (R. W. Sutter, sutterr@who.int)
Reflecting on the progress toward achieving the 1988 WHO goal of polio eradication, editorialists note that monovalent vaccines are ìa good tool but not a total solutionî (pp. 1726-7): ìThe damper on the fire of enthusiasm, however, is the growing realization that complete eradication of poliomyelitis must include eventual eradication of the live oral poliovirus vaccine itself, whether trivalent or monovalent. Documentation of the genetic instability of the oral poliovirus vaccine, emergence of circulating neurovirulent vaccine–derived polioviruses, long-term excretion of virus by immunodeficient vaccinees, and promiscuous recombination between vaccine polioviruses and nonpoliovirus enteroviruses have all been presented and discussed in the recent literature. Use of oral poliovirus vaccine must eventually stop; this step has been part of the eradication plan from the beginning. Unfortunately, poliovirus will not go away after circulation of wild-type virus is halted, and a high level of immunity in the global population must be maintained—and not just in high-income countries that have already switched to the safer but more expensive inactivated poliovirus vaccine.î (E. Ehrenfeld, FDA)
McCain, Obama on Health Care: Two Perspectives articles take a dim view of the health care reform proposals offered by the two major-party presidential candidates.
Violating the principle of first doing no harm, the McCain plan would lead to ìhealth insecurity,î writes a physician who serves an unpaid advisor to the Obama campaign (pp. 1645-7): ìJohn McCain emerges not as a maverick or centrist but as a radical social conservative firmly in the grip of the ideology that animates the domestic policies of President George W. Bush. The central purpose of President Bush’s health policy, and John McCain’s, is to reduce the role of insurance and make Americans pay a larger part of their health care bills out of pocket. Their embrace of market forces, fierce antagonism toward government, and determination to force individuals to have more ‘skin in the game’ are overriding—all other goals are subsidiary.î (D. Blumenthal)
The Obama plan would offer ìsymptomatic relief but no cure,î a second writer parries (pp. 1648-50). The author, a scholar at the American Enterprise Inst., notes: ì[Obama’s] plan would reorganize the health-insurance market—but not change the basic financial incentives in the system that drive up spending. Although the plan would significantly increase the number of Americans with health insurance, it remains to be seen whether that would come at a price Americans would be willing to pay.î (J. R. Antos)

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 17, 2008 * Vol. 15, No. 202
Providing news and information about medications and their proper use

>>>Infectious Disease Report
Source:
Nov. 15 issue of Clinical Infectious Diseases (http://www.journals.uchicago.edu/toc/cid/current; 2008; 47).
Nevirapine Monitoring in Resource-Limited Settings: A thin-layer chromatography method proved ìsensitive, specific, and robustî when used for therapeutic drug monitoring in Tanzania (pp. 1339-44). Compared with high-performance liquid chromatography, the TLC method yielded these results: ìTwenty-five (9%) of 286 African adults had a subtherapeutic plasma nevirapine concentration. The median ratio of nevirapine concentrations in saliva to those in plasma was 0.51:1. The rate of false-positive results for TLC was 0% (0 of 23 specimens) when TLC results were compared with HPLC results for saliva specimens and 8% (2 of 25 specimens) when TLC results were compared with HPLC results for plasma specimens. The rate of false-negative results for TLC was 1% (3 of 263 specimens) when TLC results were compared with HPLC results for saliva specimens and 1% (3 of 261 specimens) when TLC results were compared with HPLC results for plasma specimens. The extent of agreement of TLC results was substantial for the 5 technicians (Fleiss’s kappa = 0.77) and for the 2 batches of sheets (Cohen’s kappa = 0.80).î (D. M. Burger, .Burger@akf.umcn.nl">D.Burger@akf.umcn.nl)
Pneumococcal Vaccination in the Elderly: In an invited article, authors review the impact of pneumococcal vaccination on disease in the elderly (pp. 1328-38): ìObservational studies have demonstrated that pneumococcal polysaccharide vaccine reduces the risk of invasive pneumococcal disease in immunocompetent elderly individuals, but neither observational studies nor clinical trials have demonstrated consistent evidence for a reduction in the incidence of pneumonia in vaccinated older adults. The introduction of pneumococcal protein conjugate vaccine among children has led to a herd immunity effect that has resulted in a 38% decrease in the rate of invasive pneumococcal disease among elderly adults. The high efficacy of pneumococcal protein conjugate vaccine in children has renewed interest in evaluating pneumococcal protein conjugate vaccines in adults for prevention of invasive pneumococcal disease and pneumonia. Moreover, the recognition of the presence and function of noncapsular pneumococcal protein antigens and the increasing availability of adjuvants highlight the promise of new vaccination strategies to decrease the burden of pneumococcal infection in this high-risk population.î (L. Jackson, Jackson.L@ghc.org)

>>>PNN NewsWatch
* FDA last week licensed C1 inhibitor (human), which will be marketed as Cinryze by Lev Pharmaceuticals, for routine prophylaxis against angioedema attacks in adolescent and adult patients with hereditary angioedema (HAE), or C1 inhibitor deficiency. This rare and potentially life-threatening genetic disease affects 6,000–10,000 individuals in the U.S. HAE is characterized by painful, debilitating, and sometimes fatal swelling of the extremities, face, genitals, abdomen, and laryngeal tract. In clinical trials, the agent was effective in preventing or decreasing the frequency of attacks in most but not all HAE patients. Common adverse reactions— upper respiratory infection, sinusitis, rash, and headache—have been mild or moderate in severity. Severe hypersensitivity reactions may occur, as can thrombotic events with high dose off-label C1 inhibitor therapy.
* A
drug-safety page on the FDA website provides patients and professionals with a single portal through which to obtain a wide variety of safety information about prescription medications, the agency noted in a news release this week. The page, accessible at www.fda.gov/cder/drugSafety.htm, contains information on drug labeling, lists of drugs with a Risk Evaluation and Mitigation Strategy (REMS), drug-specific safety information, warnings and recalls, and information on how to report problems.
*
Dextroamphetamine Sulfate 5 mg tablets from Ethex Corp. have been recalled because of possible presence of oversized tablets containing up to twice the labeled amount of the active ingredient.
*
FDA has added a Boxed Warning to the labeling of efalizumab (Raptiva, Genentech) that warns of life-threatening infections, including progressive multifocal leukoencephalopathy (PML), in those using the agent.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 20, 2008 * Vol. 15, No. 203
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 18 issue of Lancet (www.thelancet.com; 2008; 372).
Candesartan & Retinopathy Diabetes: Results of two DIabetic REtinopathy Candesartan Trials [DIRECT] are published in this issue.
Among patients with type 2 diabetes with mild or moderate retinopathy, candesartan treatment possibly improved the disease-related changes in the eye, reports the first article (pp. 1385-93). Testing daily candesartan doses of 16 mg for the first month and 32 mg thereafter, the investigators found: ì1,905 participants (aged 37–75 years) were randomised to candesartan (n = 951) or placebo (n = 954). 161 (17%) patients in the candesartan group and 182 (19%) in the placebo group had progression of retinopathy by three steps or more on the Early Treatment Diabetic Retinopathy Study scale. The risk of progression of retinopathy was non-significantly reduced by 13% in patients on candesartan compared with those on placebo (hazard ratio [HR] 0.87, 95% CI 0.70–1.08, p = 0.20). Regression on active treatment was increased by 34% (1.34, 1.08–1.68, p = 0.009). HRs were not attenuated by adjustment for baseline risk factors or changes in blood pressure during the trial. An overall change towards less severe retinopathy by the end of the trial was observed in the candesartan group (odds 1.17, 95% CI 1.05–1.30, p = 0.003). Adverse events did not differ between the treatment groups.î (A. K. Sj¯lie,
A.K.Sjoelie@ouh.regionsyddanmark.dk)
The same candesartan doses were tested among patients with type 1 diabetes and no retinopathy in the DIRECT–Protect 1 trials, with these results (pp. 1394-402): ì1,421 participants (aged 18–50 years) were randomly assigned to candesartan (n = 711) or to placebo (n = 710) in DIRECT-Prevent 1, and 1905 (aged 18–55 years) to candesartan (n = 951) or to placebo (n = 954) in DIRECT-Protect 1. Incidence of retinopathy was seen in 178 (25%) participants in the candesartan group versus 217 (31%) in the placebo group. Progression of retinopathy occurred in 127 (13%) participants in the candesartan group versus 124 (13%) in the placebo group. Hazard ratio (HR for candesartan vs placebo) was 0.82 (95% CI 0.67–1.00, p=0.0508) for incidence of retinopathy and 1.02 (0.80–1.31, p = 0.85) for progression of retinopathy. The post-hoc outcome of at least a three-step increase for incidence yielded an HR of 0.65 (0.48–0.87, p = 0.0034), which was attenuated but still significant after adjustment for baseline characteristics (0.71, 0.53–0.95, p = 0.046). Final [Early Treatment Diabetic Retinopathy Study (ETDRS) scale] level was more likely to have improved with candesartan treatment in both DIRECT-Prevent 1 (odds 1.16, 95% CI 1.05–1.30, p = 0.0048) and DIRECT-Protect 1 (1.12, 95% CI 1.01–1.25, p = 0.0264). Adverse events did not differ between the treatment groups.î (N. Chaturvedi,
n.chaturvedi@imperial.ac.uk)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2008; 337).
Aspirin, Antioxidants in Primary Prevention of Arterial Disease: Among 1,276 patients with diabetes, aspirin or antioxidants failed to prevent cardiovascular events or mortality, researchers report (a1840). The study used 100-mg daily doses of aspirin, with these results: ìOverall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% v 18.3%): hazard ratio 0.98 (95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89).î (J. Belch, J.J.F.Belch@dundee.ac.uk)

>>>PNN JournalWatch
* Statins and Interstitial Lung Disease: A Systematic Review of the Literature and of Food and Drug Administration Adverse Event Reports, in Chest, 2008; 134: 824–30. Reprints: P. D. Thompson, pthomps@harthosp.org
* How Antirheumatic Drugs Protect Joints from Damage in Rheumatoid Arthritis, in
Arthritis & Rheumatism, 2008; 58: 2936–48. Reprints: G. Schett, georg.schett@uk-erlangen.de

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 21, 2008 * Vol. 15, No. 204
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 21 issue of the Annals of Internal Medicine (www.annals.org/current.shtml; 2008; 149).
Sildenafil for PAH: Addition of sildenafil to long-term intravenous epoprostenol therapy is beneficial for some patients, according to results of a 16-week trial of 267 patients in 11 countries (pp. 521-30). Patients received either placebo or sildenafil in doses of 20 mg three times daily, with dose escalations to 40 mg and 80 mg at 4-week intervals as tolerated. Results showed: ìA placebo-adjusted increase of 28.8 meters (95% CI, 13.9 to 43.8 meters) in the 6-minute walk distance occurred in patients in the sildenafil group; these improvements were most prominent among patients with baseline distances of 325 meters or more. Relative to epoprostenol monotherapy, addition of sildenafil resulted in a greater change in mean pulmonary arterial pressure by –3.8 mm Hg (CI, –5.6 to –2.1 mm Hg); cardiac output by 0.9 L/min (CI, 0.5 to 1.2 L/min); and longer time to clinical worsening, with a smaller proportion of patients experiencing a worsening event in the sildenafil group (0.062) than in the placebo group (0.195) by week 16 (P = 0.002). Health-related quality of life also improved in patients who received combined therapy compared with those who received epoprostenol monotherapy. There was no effect on the Borg dyspnea score. Of the side effects generally associated with sildenafil treatment, the most commonly reported in the placebo and sildenafil groups, respectively, were headache (34% and 57%; difference, 23 percentage points [CI, 12 to 35 percentage points]), dyspepsia (2% and 16%; difference, 13 percentage points [CI, 7 to 20 percentage points]), pain in extremity (18% and 25%; difference, 8 percentage points [CI, –2 to 18 percentage points]), and nausea (18% and 25%; difference, 8 percentage points [CI, –2 to 18 percentage points]).î (G. Simonneau, gerald.simonneau@abc.ap-hop-paris.fr)
Bedtime Insulins in Poorly Controlled Type 2 Diabetes: In 116 patients with type 2 diabetes poorly controlled with metformin plus a sulfonylurea, similar outcomes were observed following addition of bedtime doses of intermediate-acting neutral protamine lispro (NPL) or the basal agent insulin glargine (pp. 531-9). Titrated insulin regimens produced these changes in outcomes during the 36-week trial: ìImprovement in HbA1c levels was similar in both groups (1.83% and 1.89% for NPL and glargine, respectively). The difference between the groups was 0.06 percentage point (95% CI, –0.1 to 0.15 percentage points). Secondary outcomes did not differ between groups. Hemoglobin A1c levels less than 7% occurred in 62% of patients receiving NPL and 64% of patients receiving glargine (difference, 2.0 percentage points [CI, –1.1 to 5.0 percentage points]). Fasting plasma glucose levels less than 5.6 mmol/L (<100 mg/dL) occurred in 40% of patients receiving NPL and 41% of patients receiving glargine (difference, 1.0 percentage point [CI, –0.9 to 3.0 percentage points]). Any hypoglycemic event occurred in 74% of patients receiving NPL and 67% of patients receiving glargine (difference, 7 percentage points [CI, –5 to 13 percentage points]). Continuous glucose level monitoring in the patients who had this measurement did not differ statistically.î (D. Giugliano, dario.giugliano@unina2.it)
Costs of Nurse-Led Heart Failure Management: At ambulatory clinics in Harlem, NY, a nurse-led disease management program for patients with systolic heart failure proved ìreasonably cost-effective,î researchers conclude (pp. 540-8). During the 12-month study patients met once face-to-face with a nurse, after which regular telephone follow-up was maintained. Taking the societal and payer perspectives and looking at quality of life using the Health Utilities Index Mark 3 and EuroQol-5D and cost-effectiveness with the incremental cost-effectiveness ratio (ICER), the researchers found these base-case and sensitivity-analysis results: ìCosts and quality of life were higher in the nurse-managed group than the usual care group. The ICERs over 12 months were $17,543 per EuroQol-5D–based quality-adjusted life-year (QALY) and $15,169 per Health Utilities Index Mark 3–based QALY (in 2001 U.S. dollars).Ö From a payer perspective, the ICER ranged from $3,673 to $4,495 per QALY. Applying national prices in place of New York City prices yielded a societal ICER of $13,460 to $15,556 per QALY. Cost-effectiveness acceptability curves suggest that the intervention was most likely cost-effective for patients with less severe Ö heart failure.î (P. L. Hebert, Paul.Hebert2@va.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 22, 2008 * Vol. 15, No. 205
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 22 issue of JAMA, a theme issue on Health of the Nation (http://jama.ama-assn.org/current.dtl; 2008; 300).
Safety-Related Regulatory Actions for Biologicals: Infections and other immunomodulatory adverse effects are the most common problems that lead to safety-related regulatory actions for biologicals in the U.S. and the European Union, report researchers who analyzed actions taken between Jan. 1995 and June 2008 (pp. 1887-96). ìA total of 174 biologicals were approved (136 in the United States and 105 in the European Union, of which 67 were approved in both regions). Eighty-two safety-related regulatory actions (46 dear healthcare professional letters, 17 direct healthcare professional communications, 19 black box warnings, and no withdrawals) were issued for 41 of the 174 different biologicals (23.6%). The probability of a first safety-related regulatory action, derived from Kaplan–Meier analyses, was 14% (95% confidence interval [CI], 9%–19%) 3 years after approval and 29% (95% CI, 20%–37%) 10 years after approval. Biologicals first in class to obtain approval had a higher risk for a first safety-related regulatory action compared with later approved products in that class (12.0/1,000 vs 2.9/1,000 months, respectively; hazard ratio, 3.7 [95% CI, 1.5–9.5]). Warnings mostly concerned the classes general disorders and administration site conditions, infections and infestations, immune system disorders and neoplasms benign, malignant, and unspecified.î (A. K. Mantel-Teeuwisse, A.K.Mantel@uu.nl)
JAMA editors, commenting on this study and the possibility of tort reform in the U.S., write (pp. 1939-41): ìEven though the current postmarketing surveillance system might not yet be effective, vigilant, and trustworthy enough to completely protect the public, how much worse would it be to eliminate the system completely? Patients (consumers) would be left at the mercy of a system that cannot possibly determine the safety of drugs if left as it is. If the court rules for preemption in Wyeth v Levine, congressional action will be necessary to remove preemption of state tort litigation involving claims of products liability for prescription drugs. Otherwise, the current system of FDA approval of drugs would have to be changed to preserve the health of the public. Under this alternative approach, no drug could be fully approved until long-term studies with large numbers of participants had been completed and marketing would have to be greatly limited until full FDA approval is achieved. Surely, the drug manufacturers would not be pleased with such a system; however, without such safeguards, patient safety would be jeopardized. Either way, Congress, not the Supreme Court, seems better suited to decide public policy on patient safety, and it is telling that many members of Congress have joined amici briefs to remind the court that Congress already has decided not to grant preemption to drug manufacturers.î (P. B. Fontanarosa, phil.fontanarosa@jama-archives.org)
Health of the Nation 2008: In a second editorial by JAMA editors, recommendations are made for the next U.S. president about suboptimal health care in this country (pp. 1941-2): ìFirst, the next presidential administration should consider appointing a physician to the position of secretary of the Department of Health and Human Services.Ö In addition, the office of the Surgeon General, whose authority and independence have been reduced, should be revitalized and strengthened, so that the physician in this office can effectively advocate for the health of the public.
ìSecond, an independent commission should be appointed immediately to assess the nation’s health care system and provide recommendations and priorities for short-term and long-range changes to improve the nation’s health. The commission should be chaired by a physician and should include representation from other health care professionals, such as nurses, dentists, pharmacists, and others, as well as representation from health care organizations, such as hospitals, public health centers, health insurance companies, and managed care organizations.î (P. B. Fontanarosa,
phil.fontanarosa@jama-archives.org)

>>>PNN NewsWatch
* Patients under financial pressure are cutting back on prescription drugs, the New York Times reports this morning. The number of prescriptions dispensed in the third quarter fell slightly, the first downturn in more than a decade.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 23, 2008 * Vol. 15, No. 206
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 23 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Pharmacogenetics of Cetuximab in Colorectal Cancer: Presence of a wild-type K-ras gene is associated with response to cetuximab, researchers report, adding that mutations in exon 2 of this gene make tumors resistant to the drug’s actions (pp. 1757-65). Tumor samples from 394 of 572 patients with advanced colorectal cancer were analyzed genetically, with these results regarding the K-ras gene, whose product is a guanosine triphosphate–binding protein that turns off and on cellular growth and survival pathways: ìOf the tumors evaluated for K-ras mutations, 42.3% had at least one mutation in exon 2 of the gene. The effectiveness of cetuximab was significantly associated with K-ras mutation status (P = 0.01 and P < 0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival, respectively). In patients with wild-type K-ras tumors, treatment with cetuximab as compared with supportive care alone significantly improved overall survival (median, 9.5 vs. 4.8 months; hazard ratio for death, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P < 0.001) and progression-free survival (median, 3.7 months vs. 1.9 months; hazard ratio for progression or death, 0.40; 95% CI, 0.30 to 0.54; P < 0.001). Among patients with mutated K-ras tumors, there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival (hazard ratio, 0.98; P = 0.89) or progression-free survival (hazard ratio, 0.99; P = 0.96). In the group of patients receiving best supportive care alone, the mutation status of the K-ras gene was not significantly associated with overall survival (hazard ratio for death, 1.01; P = 0.97).î (C. S. Karapetis, c.karapetis@flinders.edu.au)
Noting that cetuximab is an antibody to the epidermal growth factor receptor (EGFR), an editorialist sounds this cautionary note (pp. 1834-6): ìLest the field of EGFR biology become carried away with the success of
K-ras as a molecular marker, it should be noted that the difference in survival between the groups of patients identified by K-ras testing is small. The response rate with cetuximab treatment among patients with wild-type K-ras tumors remains less than 15%, with only a modest overall survival benefit over those given best supportive care alone (median survival, 9.5 months with cetuximab vs. 4.8 months with best supportive care alone). There was no effect of cetuximab on median survival among patients with mutated K-ras tumors (4.5 months with cetuximab vs. 4.6 months with best supportive care alone). Although the 5-month improvement in median survival among the patients with wild type K-ras tumors who were treated with cetuximab generates excitement among oncologists, who are accustomed to such marginal improvements, the reaction among patients with colorectal cancer and other persons in the general population may be more muted. In fact, in countries that include an analysis of cost-effectiveness as part of the approval process, EGFR-targeting antibodies are frequently not approved, owing to a marginal benefit at high cost. Perhaps further molecular analysis will yield other markers that will identify patients who benefit from EGFR-targeting antibodies and will point to other targets and combination strategies needed to overcome drug resistance.î (W. A. Messersmith, U. Colorado Cancer Ctr., Aurora)
Alemtuzumab in Early MS: In 334 patients with early, relapsing–remitting multiple sclerosis, alemtuzumab proved more effective than interferon beta-1a in a Phase II trial (pp. 1786-807). Benefits of the monoclonal antibody included significantly improved rates of sustained accumulation of disability (9.0% vs. 26.2%; hazard ratio, 0.29; 95% confidence interval [CI], 0.16 to 0.54; P < 0.001), annualized rate of relapse (0.10 vs. 0.36; hazard ratio, 0.26; 95% CI, 0.16 to 0.41; P < 0.001); mean disability score (on a 10-point scale, improvements of 0.39 point in the alemtuzumab group and worsening by 0.38 point in the interferon beta-1a group [P < 0.001]); lesion burden (P = 0.005); and brain volume (P = 0.02). However, autoimmunity adverse reactions were more common with the new agent, including immune thrombocytopenic purpura. (CAMMS223 Trial Investigators, ajc1020@medschl.cam.ac.uk)

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 24, 2008 * Vol. 15, No. 207
Providing news and information about medications and their proper use

>>>Nephrology Highlights
Source:
Oct. issue of the American Journal of Kidney Diseases (www.ajkd.org/current; 2008; 52).
Mycophenolate Mofetil in Membranous Nephropathy: Among 36 patients with biopsy-proven idiopathic membranous glomerulonephritis and nephrotic syndrome, a 12-month course of mycophenolate mofetil monotherapy failed to decrease mean proteinuria over creatinuria ratio or increase partial and complete remissions, researchers report (pp. 699-705). Testing 2 g/d doses of the drug as monotherapy, the study showed these intention-to-treat results: ìMean proteinuria over creatinuria ratio was stable in both groups throughout the study (P = 0.1). Mean proteinuria over creatinuria ratio was 4,690 ± 2,212 mg/g in the MMF group and 6,548 ± 4,601 mg/g in the control group (95% confidence interval of the difference, −619 to +4,247; P = 0.1). Remission was complete in 3 patients (1 in the MMF group, 2 in the control group; P = 0.5) and partial in 11 patients (6 in the MMF group, 5 in the control group; P = 0.9). The probability of complete or partial remission did not differ between the 2 groups after 12 months (relative risk, 0.92; 95% confidence interval, 0.48 to 1.75; P = 0.7). Kidney function was stable in the 2 groups according to estimated glomerular filtration rate and serum creatinine level.î (B. Dussol, bdussol@ap-hm.fr)
Mycophenolate Mofetil in Children: An open-label trial of 12 children and adolescents with congenital uropathies establishes the need for a controlled study of the use of mycophenolate mofetil for preventing decrease in kidney function (pp. 706-15). Patients received MMF 600 mg/sq m/dose twice daily for 24 months, with these results: ì12 patients aged 8.9 ± 4.8 years (10 boys, 2 girls) were treated with MMF for 18.6 ± 8.0 months; 7 patients completed the entire treatment period. MMF dosage at the final study visit was 381 ± 241 mg/sq m twice daily. Gastrointestinal symptoms were the most common adverse effect. There was only 1 serious adverse event, an episode of fever and neutropenia requiring parenteral antibiotic therapy after 21 months of MMF therapy. [Glomerular filtration rate] remained stable throughout the treatment period. Nutritional status, blood pressure, and serum calcium, phosphorus, and cholesterol levels were unchanged during this period.î (H. Trachtman, trachtma@lij.edu)
Glycemic Control in Diabetes & Chronic Kidney Disease: A narrative review provides an overview of agents in development for treatment of diabetic kidney disease (pp. 766-77): ìDiabetes mellitus (DM) is a leading cause of chronic kidney disease (CKD) and a major source of morbidity and mortality in patients with established CKD. Loss of kidney function and dialytic therapies conspire to change glycemic regulation in ways that can both worsen and improve blood glucose control. Despite the unique nature of DM in patients with CKD, there currently are no specific guidelines to direct glycemic therapy in these patients. There is benefit of glycemic therapy in preventing such complications as diabetic kidney disease and mortality in patients with no kidney disease, but such benefits are largely unproven in patients with advanced CKD. By reviewing the relevant literature, we argue that glycemic control can still be beneficial in preventing complications, even in dialysis-dependent patients, but there is need for a much better understanding of the CKD-related characteristics of DM. More research is needed to determine whether uremia-related improvement in glycemic control can have a beneficial impact. Finally, we are at an important crossroads in the development of several novel therapeutic agents against diabetic kidney disease.î (C. P. Kovesdy, csaba.kovesdy@va.gov)

>>>PNN NewsWatch
* The ìPharmacogenomics Education Program: Bridging the Gap between Science and Practiceî (PharmGenEd) is a project of the U. Calif., San Diego, Skaggs School of Pharmacy and Pharmaceutical Sciences in collaboration with APhA, ASHP, and AACP. Principal investigator Grace M. Kuo, PharmD, MPH, will work with others to develop an educational curriculum that focuses on basic pharmacogenomics concepts as well as their clinical applications, incorporating live and online methods. Target audiences include pharmacy practitioners and students as well as other health care professionals. A $1 million CDC grant funds the effort.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 27, 2008 * Vol. 15, No. 208
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 25 issue of Lancet (www.thelancet.com; 2008; 372).
Oral Fumarate for MS: Clinical trial efficacy and safety results for BG00012, an oral formulation of dimethyl fumarate, show that the compound should be studied in long-term Phase III trials of patients with relapsing–remitting multiple sclerosis, investigators conclude (pp. 1463-72). Among 257 adult patients with the disease who were included in a dose-ranging, placebo-controlled trial, these results were recorded during efficacy and safety periods of the study: ìTreatment with BG00012 240 mg three times daily reduced by 69% the mean total number of new [gadolinium enhancing] lesions from week 12 to 24 compared with placebo (1.4 vs 4.5, p < 0.0001). It also reduced number of new or enlarging T2-hyperintense (p = 0.0006) and new T1-hypointense (p = 0.014) lesions compared with placebo. BG00012 reduced annualised relapse rate by 32% (0.44 vs 0.65 for placebo; p = 0.272). Adverse events more common in patients given BG00012 than in those given placebo included abdominal pain, flushing, and hot flush. Dose-related adverse events in patients on BG00012 were headache, fatigue, and feeling hot.î (L. Kappos, lkappos@uhbs.ch)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2008; 337).
Placebo Prescribing Patterns: Internists and rheumatologists in the U.S. often prescribe placebo treatments, usually without disclosure to patients and with mixed motivations for doing so, authors of a 1,200-physician survey report (a1938). Based on responses from 679 physicians, 57% of the surveyed sample, the investigators found: ìAbout half of the surveyed internists and rheumatologists reported prescribing placebo treatments on a regular basis (46–58%, depending on how the question was phrased). Most physicians (399, 62%) believed the practice to be ethically permissible. Few reported using saline (18, 3%) or sugar pills (12, 2%) as placebo treatments, while large proportions reported using over the counter analgesics (267, 41%) and vitamins (243, 38%) as placebo treatments within the past year. A small but notable proportion of physicians reported using antibiotics (86, 13%) and sedatives (86, 13%) as placebo treatments during the same period. Furthermore, physicians who use placebo treatments most commonly describe them to patients as a potentially beneficial medicine or treatment not typically used for their condition (241, 68%); only rarely do they explicitly describe them as placebos (18, 5%).î (J. Tilburt, tilburt.jon@mayo.edu)
Prophylactic Steroids After Extubation: Episodes of laryngeal edema and the need for reintubation were reduced among adult patients who received injectable corticosteroids before planned extubation, authors of a meta-analysis conclude (a1841). Six trials of 1,923 patients showed these trends in pooled data: ìCompared with placebo, steroids given before planned extubation decreased the odds ratio for laryngeal oedema (0.38, 95% confidence interval 0.17 to 0.85) and subsequent reintubation (0.29, 0.15 to 0.58), corresponding with a risk difference of –0.10 (–0.12 to –0.07; number needed to treat 10) and –0.02 (–0.04 to –0.01; 50), respectively. Subgroup analyses indicated that a multidose regimen of steroids had marked positive effects on the occurrence of laryngeal oedema (0.14; 0.08 to 0.23) and on the rate of subsequent reintubation (0.19; 0.07 to 0.50), with a risk difference of –0.19 (–0.24 to –0.15; 5) and –0.04 (–0.07 to –0.02; 25). In single doses there was only a trend towards benefit, with the confidence interval including 1. Side effects related to steroids were not found.î (G. Wang, wcums-respiration@hotmail.com)

>>>PNN JournalWatch
* US Senator John McCain and Risk of Melanoma-Associated Mortality [letter], in Lancet, 2008; 372: 1462. Reprints: J. Alam, jalam@comcast.net
* Retail Clinics, Primary Care Physicians, and Emergency Departments: A Comparison Of Patients’ Visits, in
Health Affairs, 2008; 27: 1272–82. Reprints: A. Mehrotra.
* An Empirical Basis for Standardizing Adherence Measures Derived from Administrative Claims Data Among Diabetic Patients, in
Medical Care, 2008; 46: 1125–33. Reprints: S. Karve.
* Migraine-Preventive Medications: Ensuring Their Appropriate Use, in
Journal of the American Pharmacists Association, 2008; 48: e107–24. Reprints: R. G. Wenzel, rwenz@hotmail.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 28, 2008 * Vol. 15, No. 209
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 27 issue of the Archives of Internal Medicine (http://archinte.ama-assn.org/current.dtl; 2008; 168).
Increasing Cost of Diabetes Care: As increasingly complex and costly diabetes treatments are provided to the growing population of patients with type 2 diabetes, costs of treating the disease are spiraling, report investigators who analyzed office visits between 1994 and 2007 for patients 35 years and older (pp. 2088-94). Linking office-visit data with 2001–07 costs from the National Prescription Audit, the researchers found: ìThe estimated number of patient visits for treated diabetes increased from 25 million (95% confidence interval [CI], 23 million to 27 million) in 1994 to 36 million (95% CI, 34 million to 38 million) by 2007. The mean number of diabetes medications per treated patient increased from 1.14 (95% CI, 1.06–1.22) in 1994 to 1.63 (1.54–1.72) in 2007. Monotherapy declined from 82% (95% CI, 75%–89%) of visits during which a treatment was used in 1994 to 47% (43%–51%) in 2007. Insulin use decreased from 38% of treatment visits in 1994 to a nadir of 25% in 2000 and then increased to 28% in 2007. Sulfonylurea use decreased from 67% of treatment visits in 1994 to 34% in 2007. By 2007, biguanides (54% of treatment visits) and glitazones (thiazolidinediones) (28%) were leading therapeutic classes. Increasing use of glitazones, newer insulins, sitagliptin phosphate, and exenatide largely accounted for recent increases in the mean cost per prescription ($56 in 2001 to $76 in 2007) and aggregate drug expenditures ($6.7 billion in 2001 to $12.5 billion in 2007).î (G. C. Alexander, galexand@uchicago.edu)
Oral Antidiabetic Medications & Cardiovascular Outcomes: A systematic review and meta-analysis of oral antidiabetic medications shows that cardiovascular outcomes are moderately improved by metformin therapy and possibly worsened with rosiglitazone treatment (pp. 2070-80). These results were recorded for 40 controlled trials that met inclusion criteria: ìTreatment with metformin hydrochloride was associated with a decreased risk of cardiovascular mortality (pooled OR, 0.74; 95% CI, 0.62–0.89) compared with any other oral diabetes agent or placebo; the results for cardiovascular morbidity and all-cause mortality were similar but not statistically significant. No other significant associations of oral diabetes agents with fatal or nonfatal cardiovascular disease or all-cause mortality were observed. When compared with any other agent or placebo, rosiglitazone was the only diabetes agent associated with an increased risk of cardiovascular morbidity or mortality, but this result was not statistically significant (OR, 1.68; 95% CI, 0.92–3.06).î (E. Selvin, lselvin@jhsph.edu)
Commenting on this review article, an editorialist argues for a 21st century approach to pharmacovigilance (pp. 2064-6): ìSelvin et al noted that, when it comes to choosing the safest oral agents, the quality of the data are problematic. We do not know whether the effects of diabetes management on CVD, beneficial or adverse, are related to glycemia per se or to the methods used to achieve glycemic control. The current approach to assessing the relatively rare but clinically important adverse effects of diabetes management is unsatisfactory. The vagaries of meta-analyses make them unreliable. On the other hand, increasing the size and duration of controlled clinical trials to provide adequate statistical power to detect relatively infrequent events would potentially bankrupt the pharmaceutical industry that supports most of the trials and delay the development of new drugs. Innovative approaches are necessary to ensure the safety of drugs, without slowing their development. For example, the phased introduction of new medications with uniform, standardized collection of adverse outcome data might identify relatively rare complications before the drugs are used by millions. Similarly, the use of clinical databases may provide an early alert regarding adverse outcomes. None of these solutions is perfect, but they could provide affordable surveillance for safety concerns. In the meantime, there are well-established and safe treatments that, if used aggressively, can improve the long-term health of patients with type 2 diabetes.î (D. M. Nathan,
dnathan@partners.org)

>>>PNN NewsWatch
* Divine Mercy Care Pharmacy, recently opened in Chantilly, VA, is one of at least seven pharmacies in the U.S. that carry no contraceptive products of any type.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 29, 2008 * Vol. 15, No. 210
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Oct. issue of the Journal of the American Geriatrics Society (http://www3.interscience.wiley.com/journal/117995531/home; 2008; 56).
Drug Coverage & Recommended Use of Medications: In a study conducted before implementation of Medicare Part D, researchers find that patients with prescription drug benefits are more likely to be using medications recommended in guidelines (pp. 1879-86). Patients, all participants in the 2003 Medicare Current Beneficiary Survey, were 65 years or older with type 2 diabetes. Their prescription drug claims were analyzed with regard to statin, ACE inhibitor, and angiotensin II receptor blocker use. Results showed: ìThe final study sample was 1,181 (weighted N = 4.0 million). Overall, 23% had no drug coverage, 16% Medicaid coverage, 43% employer coverage, 9% Medigap coverage, and 9% Department of Veterans Affairs (VA) or state-sponsored low-income coverage. Overall, 33% received a statin and an ACEI/ARB, 44% only an ACEI/ARB or a statin, and 23% neither. After adjustment, VA and state-sponsored drug benefits were most strongly associated with combined ACEI/ARB and statin use (relative risk ratio (RRR) = 4.83, 95% confidence interval (CI) = 2.24–10.4)), followed by employer-sponsored coverage (RRR = 2.60, 95% CI = 1.67–4.03)).î (J. Tjia, jennifer.tjia@umassmed.edu)
Revising Prescribing: Authors argue that a new prescribing system is needed, one that can be used to discontinue medications when that is the rational thing to do (pp. 1946-52). ìThousands of Americans are injured or die each year from adverse drug reactions, many of which are preventable,î the authors write. ìThe burden of harm conveyed by the use of medications is a significant public health problem, and therefore, improving the medication-use process is a priority. Recent and ongoing efforts to improve the medication-use process have focused primarily on improving medication prescribing, and not much emphasis has been put on improving medication discontinuation. A formalized approach for rationally discontinuing medications is a necessary antecedent to improving medication safety and improving the nation’s quality of care. This article proposes a conceptual framework for revising the prescribing stage of the medication-use process to include discontinuing medications. This framework has substantial practice and research implications, especially for the clinical care of older persons, who are particularly susceptible to the adverse effects of medications.î (K. T. Bain, kbain@excellerx.com)
Low Systolic Blood Pressure & Mortality in the Old–Old: People older than 85 who have lower systolic blood pressures have greater mortality rates, authors report, regardless of their health status (pp. 1853-9). Assessing patients in a Swedish county, the investigators found: ìBaseline systolic blood pressure (SBP), diastolic blood pressure, and pulse pressure were all inversely associated with mortality within 4 years according to univariate analysis. SBP was the strongest predictor. In Cox regression analyses, low SBP (120 mm Hg) correlated with greater 4-year all-cause mortality alone and when controlling for health status. This connection persisted after exclusion of deaths within the first year. There was a tendency toward a U-shaped mortality curve for the adjusted model, with SBP of 164.2 mmHg (95% confidence interval = 154.1–183.8 mm Hg) being associated with the lowest mortality.î (L. Molander, lena.molander@germed.umu.se)

>>>PNN NewsWatch
* Nine barriers are preventing pharmacists from providing medication therapy management services to chronically ill patients, reports the third and final installment of a series of articles in the International Journal of Pharmaceutical Compounding. Melanie Morgan, PhD, and colleagues from Purdue U. cite lack of management support as the most prevalent problem. Lack of time, education, and privacy are also listed, along with insufficient reimbursement, problems in communicating with prescribers, lack of standardization and unclear definition of MTM, and lack of training for counseling patients on medication management. The study was based on a survey of more than 80 Indiana pharmacists and six in-depth interviews.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 30, 2008 * Vol. 15, No. 211
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 30 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Early Neonatal Insulin Therapy: In 389 very low birth weight infants, early insulin therapy offered little benefit, as it reduced hyperglycemia but also may have increased hypoglycemia, researchers report (pp. 1873-84). In the intervention group, neonates received insulin 0.05 units/kg/hr with 20% dextrose support. Compared with standard neonatal care on days 1–7, the early insulin therapy produced these results: ìAs compared with infants in the control group, infants in the early-insulin group had lower mean (± SD) glucose levels (6.2 ± 1.4 vs. 6.7 ± 2.2 mmol per liter [112 ± 25 vs. 121 ± 40 mg per deciliter], P = 0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P = 0.008). The early-insulin group had significantly more carbohydrate infused (51 ± 13 vs. 43 ± 10 kcal per kilogram per day, P < 0.001) and less weight loss in the first week (standard-deviation score for change in weight, –0.55 ± 0.52 vs. –0.70 ± 0.47; P = 0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P = 0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P = 0.04).î (D. B. Dunger, dbd25@cam.ac.uk)
Editorialists provide this guidance for clinicians (pp. 1951-3): ìOn the basis of the results of higher mortality at 28 days of age and the increased incidence of hypoglycemia in the early-insulin group, the routine early use of insulin to achieve tighter control of glucose levels cannot be recommended. Recommendations have been made to consider the use of continuous insulin therapy only in infants with severe hyperglycemia (plasma glucose concentrations >14 mmol per liter [>250 mg per deciliter]). Maintaining higher target levels of plasma glucose concentrations (5.5 to 8.3 mmol per liter [100 to 150 mg per deciliter]) in infants receiving insulin to avoid the risk of hypoglycemia has also been recommended. Until large, controlled trials provide the much-needed evidence of the short-term and long-term benefit and safety of continuous insulin therapy in very-low-birth-weight or extremely-low-birth-weight infants (especially those weighing <1,000 g), it is advisable to use this therapy with caution.î (S. Kashyap, Columbia U., New York)
GAD Treatment in Recent-Onset Type 1 Diabetes: Alum-formulated glutamic acid decarboxylase (GAD-alum) preserves residual insulin secretion in recent-onset type 1 diabetes in adolescents, a study concludes (pp. 1909-20). Using the 65-kD isoform of GAD, a major autoantigen in type 1 diabetes, researchers found these results among patients aged 10–18 years who had been diagnosed with the disease within the prior 18 months: ìInsulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (–0.21 vs. –0.27 nmol per liter [–0.62 vs. –0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (–0.72 vs. –1.02 nmol per liter per 2 hours [–2.20 vs. –3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response.î (J. Ludvigsson, johnny.ludvigsson@lio.se)
An editorialist points out numerous concerns with use of GAD-alum immunization in children with type 1 diabetes (pp. 1956-8). Noting that numerous self proteins are present in patients with type 1 diabetes, she asks whether ìcocktails designed to generate immune toleranceî will be the future of immune therapy for new-onset disease. (D. L. Faustman, Harvard Med. Sch., 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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Oct. 31, 2008 * Vol. 15, No. 212
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Nov. issue of Diabetes Care (http://care.diabetesjournals.org/current.shtml; 2008; 31).
Antidiabetic Drugs & Lactic Acidosis, Hypoglycemia: Lactic acidosis is a rare event among patients taking metformin or sulfonylureas, researchers report, and when it occurs, the patient often has comorbidities (pp. 2086-91). In a study that also confirms that hypoglycemia is more of a problem with sulfonylureas than metformin, investigators found these trends in a nested case–control analysis of the U.K. General Practice Research Database: ìAmong the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person–years among metformin users and 4.8 cases per 100,000 person–years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects. A total of 2,025 case subjects with hypoglycemia and 7,278 matched control subjects were identified. Use of sulfonylureas was associated with a materially elevated risk of hypoglycemia. The adjusted odds ratio for current use of sulfonylureas was 2.79 (95% CI 2.23–3.50) compared with current metformin use.î (C. R. Meier, meierch@uhbs.ch)
Vitamin K & Insulin Resistance: Phylloquinone supplements administered in doses of 500 mcg/day reduced the progression of insulin resistance among older men, concludes a 36-month study conducted in 355 older patients (pp. 2092-6). Noting that this vitamin K dosage is achievable from dietary sources, the researchers report the following trends in body mass index, weight, and insulin resistance as measured by the homeostasis model assessment: ìThe effect of 36-month vitamin K supplementation on HOMA-IR differed by sex (sex X treatment interaction P = 0.02). HOMA-IR was statistically significantly lower at the 36-month visit among men in the supplement group versus the men in the control group (P = 0.01) after adjustment for baseline HOMA-IR, BMI, and body weight change. There were no statistically significant differences in outcome measures between intervention groups in women.î (S. L. Booth, sarah.booth@tufts.edu)
Cardiovascular Care in Diabetes: An analysis of the administrative databases of Saskatchewan Health shows that adherence to evidenced-based drug therapies improved between 1993 and 2001, but all-cause mortality was static (pp. 2136-42). ìFrom 1993 to 2001, diabetes prevalence increased 34% (4.7–6.5%, P < 0.001) with the highest rates in men and those aged 65 years,î write the authors. ìThe rate of increase in diabetes prevalence appeared to slow in those aged <65 years (P < 0.01 for trend). Significant increased use of evidence-based drug therapies was observed (41% increase in antihypertensive agents, 97% increase in ACE inhibitors, 223% increase in statin therapies; all P < 0.05 for trend). During this period, both cerebrovascular and cardiac-related hospitalizations declined by 36% (9.5 vs. 6.1 per 1,000) and 19% (38.0 vs. 30.6 per 1,000) (P < 0.05 for trends), respectively, with similar reductions regardless of sex. No change in all-cause mortality was observed (17.7 vs. 17.8 deaths per 1,000; P > 0.05).î (D. Eurich, deurich@ualberta.ca)
Technosphere Inhaled Insulin Formulation: Among 126 insulin-naive patients with type 2 diabetes, Technosphere insulin delivered by inhalation improved glycemic control and was well tolerated (pp. 2177-82). The 12-week study produced these results: ìA1C reduction from a mean baseline of 7.9% was greater with Technosphere insulin than with Technosphere powder (–0.72 vs. –0.30%; P = 0.003). Postprandial glucose excursions were reduced by 56% with Technosphere insulin compared with baseline, and maximal postprandial glucose levels were reduced by 43% compared with Technosphere powder. Incidences of hypoglycemia, hyperglycemia, cough, and other adverse events were low in both groups. Body weight was unchanged in both groups.î (J. Rosenstock, juliorosenstock@dallasdiabetes.com)

>>>PNN NewsWatch
* Bayer Women’s Low Dose Aspirin + Calcium and Bayer Aspirin with Heart Advantage are unlawful OTC products and lack adequate directions for use, FDA this week warned in a warning letter to the company, citing lack of compliance with OTC monographs.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 3, 2008 * Vol. 15, No. 213
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release articles from Lancet (www.thelancet.com; 2008; 372).
Weight Loss with Tesofensine: In a Phase II trial, tesofensine produced greater weight loss than that generally achieved with currently available agents (doi: 10.1016/S0140-6736(08)61525-1). The drug—an inhibitor of presynaptic uptake of norepinephrine, dopamine, and serotonin—produced these results in 203 obese patients when give at various doses in a 24-week trial: ì161 (79%) participants completed the study. After 24 weeks, the mean weight loss produced by diet and placebo was 2.0% (SE 0.60). Tesofensine 0.25 mg, 0.5 mg, and 1.0 mg and diet induced a mean weight loss of 4.5% (0.87), 9.2% (0.91), and 10.6% (0.84), respectively, greater than diet and placebo (p < 0.0001). The most common adverse events caused by tesofensine were dry mouth, nausea, constipation, hard stools, diarrhoea, and insomnia. After 24 weeks, tesofensine 0.25 mg and 0.5 mg showed no significant increases in systolic or diastolic blood pressure compared with placebo, whereas heart rate was increased by 7.4 beats per min in the tesofensine 0.5 mg group (p = 0.0001).î (A. Astrup, ast@life.ku.dk)

Primary Care Crisis in U.S.: Commenting on ìthe solution to the U.S. health-care crisis,î authors argue that that more medical students in this country must be drawn into primary-care practice (doi: 10.1016/S0140-6736(08)61600-1): ìDefinitive steps must now be taken to support and promote careers in primary care to meet the health-care needs of the USA. Those steps need action in three domains. First, increase the attractiveness of careers in primary-care medicine, including appropriate payment for primary-care services and more control over one’s lifestyle. Second, prioritisation of medical students’ interests in primary-care careers that practise the generalist approach to health care, by contrast with practising only a narrow scope of care. Third, support for training programmes for primary-care physicians.î (P. A. Pugno, ppugno@aafp.org)

>>>PNN NewsWatch
* The U.S. Supreme Court today hears arguments in a case that could clarify the extent of pharmaceutical manufacturers’ liability when FDA-approved products are involved. While the Court last year supported a legal shield for manufacturers of medical devices when these have been approved for marketing by FDA, that case turned on immunity written into law by Congress. Laws governing medications do not include such language, the Washington Post writes in an editorial published this morning, concluding, ìCongress’s silence speaks volumes, and the justices should respect that determination. If Wyeth and other pharmaceuticals [sic] want change, they should take their case to Congress.î
* A new algorithm for
medical management of diabetes specifically cautions against use of rosiglitazone. In an article slated for publication in the January issue of Diabetes Care (2009; 32: 1–11), the American Diabetes Association and the European Association for the Study of Diabetes write this about a second-tier algorithm: ìSpecifically, when hypoglycemia is particularly undesirable (e.g., in patients who have hazardous jobs), the addition of exenatide or pioglitazone may be considered. Rosiglitazone is not recommended. If promotion of weight loss is a major consideration and the A1C level is close to target (8.0%), exenatide is an option. If these interventions are not effective in achieving target A1C, or are not tolerated, addition of a sulfonylurea could be considered. Alternatively, the tier two interventions should be stopped and basal insulin started.î

>>>PNN JournalWatch
* Patients’ Preferences Within Randomised Trials: Systematic Review and Patient Level Meta-analysis, in BMJ, 2008; 32: a1864. Reprints: H. Tilbrook, het2@york.ac.uk
* Influence of Race, Ethnicity, and Culture on Childhood Obesity: Implications for Prevention and Treatment: A Consensus Statement of Shaping America’s Health and the Obesity Society, in
Diabetes Care, 2008; 31: 2211–21. Reprints: M. S. Kirkman, skirkman@diabetes.org
* Prevention of Influenza: Recommendations for Influenza Immunization of Children, 2008–2009, in
Pediatrics, 2008; 122: 1135–41. Reprints: Committee on Infectious Diseases.
* Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents, in
Pediatrics, 2008; 122: 1142–52. Reprints: C. L. Wagner.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 4, 2008 * Vol. 15, No. 214
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 4 issue of the Annals of Internal Medicine (www.annals.org/current.shtml; 2008; 149).
Ghrelin Mimetic in Healthy Older Adults: An orally active ghrelin mimetic, MK-677, produced beneficial changes in 65 healthy adults aged 60 to 81 years, researchers report (pp. 601-11). Pulsatile growth hormone secretion was enhanced, fat-free mass increased significantly, and the drug was well tolerated, the authors note, adding these details about the 2-year study: ìDaily administration of MK-677 significantly increased growth hormone and insulin-like growth factor I levels to those of healthy young adults without serious adverse effects. Mean fat-free mass decreased in the placebo group but increased in the MK-677 group (change, –0.5 kg [95% CI, –1.1 to 0.2 kg] vs. 1.1 kg [CI, 0.7 to 1.5 kg], respectively; P < 0.001), as did body cell mass, as reflected by intracellular water (change, –1.0 kg [CI, –2.1 to 0.2 kg] vs. 0.8 kg [CI, –0.1 to 1.6 kg], respectively; P = 0.021). No significant differences were observed in abdominal visceral fat or total fat mass; however, the average increase in limb fat was greater in the MK-677 group than the placebo group (1.1 kg vs. 0.24 kg; P = 0.001). Body weight increased 0.8 kg (CI, –0.3 to 1.8 kg) in the placebo group and 2.7 kg (CI, 2.0 to 3.5 kg) in the MK-677 group (P = 0.003). Fasting blood glucose level increased an average of 0.3 mmol/L (5 mg/dL) in the MK-677 group (P = 0.015), and insulin sensitivity decreased. The most frequent side effects were an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain. Low-density lipoprotein cholesterol levels decreased in the MK-677 group relative to baseline values (change, –0.14 mmol/L [CI, –0.27 to –0.01 mmol/L]; –5.4 mg/dL [CI, –10.4 to –0.4 mg/dL]; P = 0.026); no differences between groups were observed in total or high-density lipoprotein cholesterol levels. Cortisol levels increased 47 nmol/L (CI, 28 to 71 nmol/L (1.7 µg/dL [CI, 1.0 to 2.6 µg/dL]) in MK-677 recipients (P = 0.020). Changes in bone mineral density consistent with increased bone remodeling occurred in MK-677 recipients. Increased fat-free mass did not result in changes in strength or function. Two-year exploratory analyses confirmed the 1-year results.î (M. O. Thorner, mot@virginia.edu)
An editorialist concludes that growth hormone secretagogues (GHS) need much more study before being used widely for preventing or treating the effects of aging (pp. 677-9): ìClearly, many questions about the potential utility and safety of an oral GHS in older persons remain unanswered. What might be the optimal intervention paradigm, for what clinical outcomes, and in what populations? Would long-term administration of MK-677 or other secretagogues improve physical and psychological functions and quality of life; have different effects according to age or racial or genetic predisposition; overstimulate the pituitary gland or central nervous system, with increased risk for pituitary neoplasms or neurobehavioral dysfunction; increase cancer frequency in older individuals, who are already at greater risk for malignant diseases; or supplant the less physiologic and more costly use of recombinant growth hormone or injectable GHRH or its analogues? At present, the clinical use of growth hormone axis manipulation in aged persons should be restricted to carefully controlled clinical studies and is not ready for prime time. However, [this study’s] findings raise many questions that we need to address.î (M. R. Blackman,
Marc.Blackman@va.gov)

>>>PNN NewsWatch
* U.S. Supreme Court justices yesterday seemed divided in their opinions as they questioned lawyers representing the parties in Wyeth v. Diana Levine. A dose of promethazine, ordered IV push, was inadvertently administered into an artery, which caused extensive tissue damage, gangrene, and loss of the right arm of the patient, a professional guitarist. Justice Scalia appeared skeptical of a plaintiff attorney’s arguments that a Vermont product liability law could create a standard different from that extant in FDA statutes and regulations. Justices Alito, Kennedy, and Souter seemed more aligned with the plaintiff’s position as they questioned attorneys on both sides. In the balance is a $6.7 million award the plaintiff received in Vermont courts and a huge potential product liability problem for the pharmaceutical industry.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 5, 2008 * Vol. 15, No. 215
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 5 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Continuing Buprenorphine–Naloxone After Detoxification: Among 152 adolescents and young adults requiring detoxification for opioid addiction, outcomes were better when buprenorphine–naloxone was continued for up to 12 weeks, according to a randomized trial (pp. 2003-11). Compared with a 14-day taper of the agents after short-term detoxification, extended treatment showed these benefits: ìThe number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 (22 = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%–75%) vs 58 12-week buprenorphine–naloxone patients (26%; 95% CI = 14%–38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%–70%) vs 52 12-week buprenorphine–naloxone patients (23%; 95% CI = 11%–35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%–67%) vs 49 12-week buprenorphine–naloxone patients (43%; 95% CI = 29%–57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine–naloxone patients (70%; chi-square[1] = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine–naloxone group reported less opioid use (chi-square[1] = 18.45, P < .001), less injecting (chi-square[1] = 6.00, P = .01), and less nonstudy addiction treatment (chi-square[1] = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12.î (G. E. Woody, woody@tresearch.org)
Quick fixes do not exist but the need is great for better treatment of detoxification in this age group, an editorialist writes (pp. 2057-9): ìThe high rate of relapse seen with both medication taper protocols in the current trial involving opioid-dependent adolescents, combined with the adverse social, legal, and infectious consequences of opioid dependence—and the risk for overdose with relapse—makes the need for rigorous evidence in this area urgent. These findings are another important reminder that there are no quick fixes for opioid dependence.î (D. A. Fiellin,
david.fiellin@yale.edu)
B Vitamins & Cancer Risk in Women: The overall risk of total invasive cancer or breast cancer was unaffected by daily folate 2.5 mg, vitamin B6 50 mg, and vitamin B12 1 mg supplementation among 5,442 health professionals in the Women’s Antioxidant and Folic Acid Cardiovascular Study, researchers report (pp. 2012-21): ìA total of 379 women developed invasive cancer (187 in the active treatment group and 192 in the placebo group). Compared with placebo, women receiving the active treatment had similar risk of developing total invasive cancer (101.1/10,000 person–years for the active treatment group vs 104.3/10,000 person–years for placebo group; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.79–1.18; P = .75), breast cancer (37.8/10,000 person–years vs 45.6/10,000 person–years, respectively; HR, 0.83; 95% CI, 0.60–1.14; P = .24), or any cancer death (24.6/10,000 person–years vs 30.1/10,000 person–years, respectively; HR, 0.82; 95% CI, 0.56–1.21; P = .32).î (S. M. Zhang, szhang@rics.bwh.harvard.edu)

>>>PNN NewsWatch
* In CNN exit polls on Election Day in the United States, 9% of presidential voters named health care as the issue that most influenced their vote for U.S. president, trailing the economy at 62% and Iraq at 10%. President-elect Barack Obama’s plan for the nation’s health care financing system addresses the problem of the uninsured by requiring coverage for all children but leaves adults at risk. The devil will be in the details as health care reform is debated in a Democratically controlled Congress, but the Obama plan as pitched during the campaign relied on a mixture of continuation of private insurance, lower premiums achieved partly through importation of medications from other developed countries and greater use of generics, subsidies for low-income workers whose employers do not provide insurance, and public insurance for those not otherwise covered.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 6, 2008 * Vol. 15, No. 216
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Nov. 6 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Testosterone in Postmenopausal Women: Transdermal testosterone 300 µg/day yielded a modest but meaningful improvement in libido among 814 women with hypoactive sexual desire who were not taking estrogen (pp. 2005-17). The 52-week trial compared daily testosterone doses of 150 and 300 µg and placebo, with these results: ìAt 24 weeks, the increase in the 4-week frequency of satisfying sexual episodes was significantly greater in the group receiving 300 µg of testosterone per day than in the placebo group (an increase of 2.1 episodes vs. 0.7, P < 0.001) but not in the group receiving 150 µg per day (1.2 episodes, P = 0.11). As compared with placebo, both doses of testosterone were associated with significant increases in desire (300 µg per day, P < 0.001; 150 µg per day, P = 0.04) and decreases in distress (300 µg per day, P < 0.001; 150 µg per day, P = 0.04). The rate of androgenic adverse events—primarily unwanted hair growth—was higher in the group receiving 300 µg of testosterone per day than in the placebo group (30.0% vs. 23.1%). Breast cancer was diagnosed in four women who received testosterone (as compared with none who received placebo); one of the four received the diagnosis in the first 4 months of the study period, and one, in retrospect, had symptoms before undergoing randomization.î (S. R. Davis, susan.davis@med.monash.edu.au)
After reviewing the high levels of testosterone found in women in this study at weeks 24 and 52, an editorialist sounds a cautionary note (pp. 2047-9): ìAlthough different testosterone compounds and delivery systems require separate evaluations, the results of the present report support previous findings that testosterone has positive effects on sexuality and that higher doses show greater effects. At the same time, the findings suggest the need for caution in using testosterone until we understand more about its possible link with breast cancer and are better able to predict which patients are more likely to be subject to negative effects.î (J. R. Heiman, Indiana U., Bloomington)
Varenicline in Smoking Cessation: In a clinical vignette, the case of 57-year-old with a 60 pack–year history of smoking is presented and discussed before the authors reach this conclusion (pp. 2018-24): ìThe patient in the clinical vignette has many of the chronic conditions classically associated with tobacco use, and his history reflects the ‘hardening’ of smokers (i.e., increasing resistance to cessation) that has been hypothesized. Although retreatment with one or more of the drugs that he has previously used is an option, his motivation to quit now may be enhanced by the fact that varenicline is a treatment option that he has not tried. We would recommend varenicline along with behavioral counseling to give him the best opportunity for abstinence from smoking. He has no contraindications for varenicline treatment with the typical 1-week period of dose adjustment up to the target dose of 1 mg twice daily. Similar to all patients receiving varenicline, he will need to be apprised of the potential for adverse neuropsychiatric effects, and he should be advised to report these symptoms immediately if they occur. If he continues to smoke after reaching his target quitting date, we would advise continuing treatment as long as he remains engaged in a plan that will lead to abstinence in the first 8 to 10 weeks of treatment. Given his history of repeated episodes of relapse and heavy cigarette use, he may remain at an increased risk for relapse for many weeks after quitting. We would plan to continue his treatment with varenicline for 6 months, with periodic follow-up for counseling and assessment for adverse effects and to ensure ongoing support for abstinence.î (J. T. Hays, hays.taylor@mayo.edu)

>>>PNN NewsWatch
* One lot of ReliOn sterile, single-use, disposable, hypodermic syringes with permanently affixed hypodermic needles is being recalled because of possible mislabeling, FDA and Tyco announced yesterday. The products are distributed by Can-Am Care Corp and sold only by Wal-Mart at Wal-Mart stores and Sam’s Clubs. The recall applies to lot no. 813900 of ReliOn 1cc, 31-gauge, 100 unit syringes for use with U-100 insulin. Patients can receive replacement products at Wal-Mart or Sam’s Club pharmacies.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 7, 2008 * Vol. 15, No. 217
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Nov. issue of Pharmacotherapy (www.pharmacotherapy.org; 2008; 28).
GI Effects of Inhaled Steroids: A slight risk of gastrointestinal adverse effects with inhaled corticosteroids can be eliminated through use of spacer devices, report investigators of a retrospective cohort study (pp. 1325-34). Looking at 19,443 adults with a mean age of 31.8 years, the researchers found these patterns among those using inhaled corticosteroids plus albuterol or albuterol alone in 1977–2002: ìThe frequency of adverse gastrointestinal events in the patients who used inhaled corticosteroids and albuterol was compared with that in the patients who used albuterol alone. Adverse gastrointestinal outcomes included events such as gastritis, ulcers, and bleeding. Cox proportional hazards models were used to determine the risk of adverse events, controlling for possible confounders such as alcohol use or nonsteroidal antiinflammatory drug use. Adverse gastrointestinal events were observed in 461 (6.4%) patients using inhaled corticosteroids and albuterol and in 302 (2.5%) patients using only albuterol. After controlling for potential confounders, patients who used inhaled corticosteroids and albuterol had an increased risk for adverse gastrointestinal events compared with patients who used only inhaled albuterol (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.02–1.56). A prescription for a spacer device reduced this risk among patients using an inhaled corticosteroid (HR 0.26, 95% CI 0.20–0.34).î (M. D. Murray, Chapel Hill)
Erythropoietin in Premature Infants: Extremely low-birth-weight infants who received recombinant human erythropoietin (rHuEPO) had no increase in frequency of severe retinopathy of prematurity and they required fewer transfusions, according to a retrospective cohort analysis of 276 neonates (pp. 1335-40). Comparing 138 infants who received no rHuEPO with an equal number given the agent, the researchers found: ìThe rHuEPO was started before the 8th day of life in 115 (83%) of the 138 infants. Stages III–V retinopathy of prematurity occurred with similar frequency in both groups of infants (rHuEPO group 19% [26 infants] vs control group 20% [27 infants], p > 0.05). Infants in the rHuEPO group received fewer transfusions on average during their hospitalization compared with those in the control group (4.2 vs 6.1 transfusions, p < 0.01).î (J. K. Schneider, Jacqueline.Schneider@nationwidechildrens.org)
Allergies & the Medical Record: Allergies reported and recorded in the medical record are frequently questionable, authors report, and because allergies frequently alter antibiotic therapy, increased efforts to verify them are needed (pp. 1348-53). Information was obtained from medical records about patient-reported allergies and interviews were conducted with a subset of the involved patients, with these results: ìA total of 416 allergies to antibiotics were reported. Penicillins were the agents most commonly reported (198 reports), followed by sulfonamides, cephalosporins, macrolides, and fluoroquinolones. The reported allergies altered antibiotic therapy in 91 (30.3%) patients. Report of a penicillin or cephalosporin allergy and use of antibiotics for prophylaxis were strong predictors of altered therapy. The subgroup consisted of 100 patients who were interviewed to determine the specific details of their reported allergic reactions. For 22 of the 100 patients, major discrepancies were found between their verbal reports and medical record documentation. The Naranjo adverse drug reaction probability scale was used to determine the validity of their reactions. Among these 100 patients, 109 (78.4%) of 139 reported reactions to antibiotics were deemed to be allergic in nature. For 55 (50.5%) of the 109 allergic reactions, the Naranjo score was 5 or greater, which correlates with probable to definite validity.î (D. M. Lutomski, University Hosp., Cincinnati, OH)

>>>PNN NewsWatch
* Fesoterodine fumarate (Toviaz, Pfizer) has been approved by FDA for treatment of overactive bladder. The muscarinic receptor antagonist works similarly to the related agent tolterodine to relax smooth muscle tissue of the bladder, thereby reducing the urinary frequency, urge to urinate, and sudden urinary incontinence.
*
FDA yesterday seized 11 lots of oversulfated chondroitin–contaminated heparin at Celsus Laboratories in Cincinnati.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 10, 2008 * Vol. 15, No. 218
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2008; 337).
Alcohol Consumption v. Counseling: Excessive and binge drinking is relatively common among U.S. medical students, and those who drink excessively are less likely to counsel patients about alcohol consumption, a study shows (a2155). Concluding that medical schools should routinely train students to screen and counsel patients and should consider discouraging excessive drinking, the researchers report these results from questionnaires administered to students in their first, third, and fourth years of medical school: ì78% (3,777/4,847) of medical students reported drinking in the past month, and a third (1,668/ 4,847) drank excessively; these proportions changed little over time. The proportion of those who believed alcohol counselling was highly relevant to care of patients was higher at entrance to wards (61%; 919/1,516) than in final year students (46%; 606/1,329). Although students intending to enter primary care were more likely to believe alcohol counselling was highly relevant, only 28% of final year students (391/1,393) reported usually or always talking to their general medical patients about their alcohol consumption. Excessive drinkers were somewhat less likely than others to counsel patients or to think it relevant to do so. In multivariate models, extensive training in alcohol counselling doubled the frequency of reporting that alcohol counselling would be clinically relevant (odds ratio 2.3, 95% confidence interval 1.6 to 3.3) and of reporting doing counselling (2.2, 1.5 to 3.3).î (E. Frank, efrank@emory.edu)
Physicians Treated for Substance Use: Five years after treatment for substance use disorders, three-quarters of physicians had favorable outcomes (a2038). Treatment, support, and sanctions provided an effective combination intervention, the article notes, with these results among 904 physicians who were admitted to a treatment program in 1995–2001: ì155 of 802 physicians (19.3%) with known outcomes failed the programme, usually early during treatment. Of the 647 (80.7%) who completed treatment and resumed practice under supervision and monitoring, alcohol or drug misuse was detected by urine testing in 126 (19%) over five years; 33 (26%) of these had a repeat positive test result. At five year follow-up, 631 (78.7%) physicians were licensed and working, 87 (10.8%) had their licences revoked, 28 (3.5%) had retired, 30 (3.7%) had died, and 26 (3.2%) had unknown status.î (A. T. McLellan, mtmclellan@tresearch.org)

>>>PNN NewsWatch
* Influenza vaccinations reduce patients’ risk of venous thromboembolism by 26%, according to research presented yesterday at the American Heart Association’s Scientific Sessions 2008 in New Orleans. Researchers conducted a case–control study among 1,454 age- and sex-matched patients (average age, 52 years) from 11 centers in France (the FARIVE study). The vaccination’s protective effect was more pronounced before rather than after age 52, with a 48% lower likelihood of VTE in those younger than 52. Women in the younger age group had a 50% reduction, and those taking oral contraceptives had a 59% reduction in VTE risk.
* In patients without high cholesterol levels but with elevated high-sensitivity C-reactive protein levels,
rosuvastatin significantly lowered the risk of major cardiovascular events, AHA researchers reported. Results of the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, published simultaneously on the New England Journal of Medicine website, showed a 44% decrease in CVD events (hazard ratio, 0.56; 95% CI, 0.46–0.69; P < 0.00001) during a median of 1.9 years of follow-up.

>>>PNN JournalWatch
* Adjunctive Psychotherapy for Bipolar Disorder: State of the Evidence, in American Journal of Psychiatry, 2008; 165: 1408–19. Reprints: D. J. Miklowitz.
* Naltrexone for the Treatment of Amphetamine Dependence: A Randomized, Placebo-Controlled Trial, in
American Journal of Psychiatry, 2008; 165: 1442–8. Reprints: N. Jayaram-Lindstrˆm.
* Sexual Risk Factors and Bacterial Vaginosis: A Systematic Review and Meta-Analysis, in
Clinical Infectious Diseases, 2008; 47: 1426–35. Reprints: K. Fethers, kfethers@mshc.org.au
* New Generation of Inactivated Poliovirus Vaccines for Universal Immunization after Eradication of Poliomyelitis, in
Clinical Infectious Diseases, 2008; 47 (early release). Reprints: K. Chumakov, konstantin.chumakov@fda.hhs.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 11, 2008 * Vol. 15, No. 219
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 10 issue of the Archives of Internal Medicine (http://archinte.ama-assn.org/current.dtl; 2008; 168).
Thrombolytic Therapy in Pulmonary Embolism: Thrombolytic therapy is used infrequently in patients with pulmonary embolism, and when it is used in suboptimal candidates, their in-hospital and 30-day mortality is increased, researcher report (pp. 2183-90). A logistic regression analysis of care provided in 186 acute care Pennsylvania hospitals to 15,116 patients discharged after pulmonary embolism shows the following: ìOf the 15,116 patient discharges, only 356 (2.4%) received thrombolytic therapy. The overall 30-day mortality rate for patients who received thrombolytic therapy was 17.4% compared with 8.6% for those who did not. The corresponding in-hospital mortality rates were 19.6 and 8.3, respectively, per 1,000 person–days. However, mortality risk associated with thrombolysis varied with the propensity to receive thrombolysis: the odds ratios of 30-day mortality were 2.8 (P = .007), 3.9 (P < .001), 1.8 (P = .09), 1.0 (P = .98), and 0.7 (P = .30) for patients in the lowest to the highest quintiles of the propensity score distribution who received thrombolysis. A similar pattern was observed in the risk ratios for in-hospital death. (S. A. Ibrahim, said.ibrahim2@va.gov)
Authors of an invited commentary welcome these real-world data but conclude that much remains unknown about this use of thrombolytics (pp. 2191-2): ìDo the data in the present study guide us in choosing the appropriate clinical threshold for thrombolysis in patients with PE? Probably not. But these findings do provide, in our view, a reasonable benchmark for the rates of use of thrombolysis in patients with PE (<5% of patients with PE) and also suggest that the rate of excess fatal bleeding associated with the judicious use of thrombolysis in clinical practice (about 2% excess in this study) is not inconsistent with those observed in the clinical trial setting. Given that the overall mortality rate in this large cohort approached 10%, we believe that the potential for fatal bleeding is a risk worth taking in selected patients with PE. However, exactly how those patients should be selected remains an unanswered question.î (D. J. Brotman,
brotman@jhmi.edu)
Sustained Post-MI Interventions: Continuing multiple interventions with patients after myocardial infarctions produce significant but small decreases in the risk of nonfatal MI and other cardiovascular outcomes, according to the Global Secondary Prevention Strategies to Limit Event Recurrence After Myocardial Infarction (GOSPEL) study (pp. 2194-204). The 3,241 participants were randomized to usual care or a 3-year multifactorial continued educational and behavioral program during post-MI cardiac rehabilitation, with these results: ìEnd point events occurred in 556 patients (17.2%). Compared with usual care, the intensive intervention did not decrease the primary end point significantly (16.1% vs 18.2%; hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.74–1.04). However, the intensive intervention decreased several secondary end points: CV mortality plus nonfatal MI and stroke (3.2% vs 4.8%; HR, 0.67; 95% CI, 0.47–0.95), cardiac death plus nonfatal myocardial infarction (2.5% vs 4.0%; HR, 0.64; 95% CI, 0.43–0.94), and nonfatal MI (1.4% vs 2.7%; HR, 0.52; 95% CI, 0.31–0.86). A marked improvement in lifestyle habits (ie, exercise, diet, psychosocial stress, less deterioration of body weight control) and in prescription of drugs for secondary prevention was seen in the intervention group.î (P. Giannuzzi, pantaleo.giannuzzi@fsm.it)
Antibacterial Use in Teaching Hospitals: At 22 U.S. university teaching hospitals in 2002–06, these trends were noted in use of antibacterial agents (pp. 2254-60): ìThe mean (SD) total antibacterial use increased from 798 (113) days of therapy per 1000 patient days in 2002 to 855 (153) in 2006 (P < .001). Fluoroquinolones were the most commonly used antibacterial class from 2002 through 2006, and use remained stable. Piperacillin sodium–tazobactam sodium and carbapenem use increased significantly, and aminoglycoside use declined. Cefazolin sodium was the most commonly used antibacterial drug in 2002 and 2003 but was eclipsed by vancomycin hydrochloride in 2004. The strongest predictor of broad-spectrum antibacterial use was explained by differences across hospitals in the mean durations of therapy.î (R. E. Polk, rpolk@vcu.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 12, 2008 * Vol. 15, No. 220
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 12 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Vitamins E/C & Cardiovascular Disease in Men: In the Physicians’ Health Study II, a randomized controlled trial of 14,461 U.S. men, neither vitamin E 400 IU nor vitamin C 500 mg supplementation reduced the risk of major cardiovascular events (pp. 2123-33). All participants were 50 years or older at randomization, and 5.1% initially had cardiovascular disease. Results showed: ìDuring a mean follow-up of 8 years, there were 1245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events (both active and placebo vitamin E groups, 10.9 events per 1000 person–years; hazard ratio [HR], 1.01 [95% confidence interval {CI}, 0.90–1.13]; P = .86), as well as total myocardial infarction (HR, 0.90 [95% CI, 0.75–1.07]; P = .22), total stroke (HR, 1.07 [95% CI, 0.89–1.29]; P = .45), and cardiovascular mortality (HR, 1.07 [95% CI, 0.90–1.28]; P = .43). There also was no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1000 person–years, respectively; HR, 0.99 [95% CI, 0.89–1.11]; P = .91), as well as total myocardial infarction (HR, 1.04 [95% CI, 0.87–1.24]; P = .65), total stroke (HR, 0.89 [95% CI, 0.74–1.07]; P = .21), and cardiovascular mortality (HR, 1.02 [95% CI, 0.85–1.21]; P = .86). Neither vitamin E (HR, 1.07 [95% CI, 0.97–1.18]; P = .15) nor vitamin C (HR, 1.07 [95% CI, 0.97–1.18]; P = .16) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke (HR, 1.74 [95% CI, 1.04–2.91]; P = .04).î (H. D. Sesso, hsesso@hsph.harvard.edu)
Low-Dose Aspirin in Type 2 Diabetes: For primary prevention of atherosclerotic events in patients with type 2 diabetes, low-dose aspirin had no significant effect on risk of fatal or nonfatal ischemic heart disease, fatal or nonfatal stroke, and peripheral arterial disease (pp. 2134-41). The Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial included 2,539 patients with type 2 diabetes without a history of atherosclerotic disease who had these responses to aspirin 81 or 100 mg daily over a median follow-up of 4.37 years: ìA total of 154 atherosclerotic events occurred: 68 in the aspirin group (13.6 per 1,000 person–years) and 86 in the nonaspirin group (17.0 per 1000 person–years) (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58–1.10; log-rank test, P = .16). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in 1 patient (stroke) in the aspirin group and 10 patients (5 fatal myocardial infarctions and 5 fatal strokes) in the nonaspirin group (HR, 0.10; 95% CI, 0.01–0.79; P = .0037). A total of 34 patients in the aspirin group and 38 patients in the nonaspirin group died from any cause (HR, 0.90; 95% CI, 0.57–1.14; log-rank test, P = .67). The composite of hemorrhagic stroke and significant gastrointestinal bleeding was not significantly different between the aspirin and nonaspirin groups.î (H. Ogawa, gawah@kumamoto-u.ac.jp">ogawah@kumamoto-u.ac.jp)
Use of aspirin for primary prevention of cardiovascular events in patients with diabetes is ìstill an open question,î writes an editorialist (pp. 2180-1): ì[While awaiting results of ongoing trials] the decision to prescribe aspirin should be made on an individual patient basis after careful evaluation of the balance between the expected benefits and the risk of major bleeding. The issue of aspirin therapy for patients with diabetes is an example of how, in the presence of a long-lasting uncertainty, scientific organizations or governmental bodies should provide the foundation for answering this question by promoting pragmatic, large-scale clinical trials. Considering all diabetic patients with no history of cardiovascular disease (except those with documented contraindications or perceived indications) as candidates for randomized clinical trials would represent a major contribution to the credibility of scientific methods in guiding practice.î (A. Nicolucci,
nicolucci@negrisud.it)
Extensively Drug-Resistant Tuberculosis: Between 1993 and 2007, the number of reported cases of extensively drug-resistant tuberculosis declined in the U.S., a trend that coincided with better TB and HIV/AIDS control, researchers report (pp. 2153-60). Cases continue to be reported, however, the article concludes, providing data on this condition. (J. P. Cegielski, gzc2@cdc.gov)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 13, 2008 * Vol. 15, No. 221
Providing news and information about medications and their proper use

>>>Circulation Highlights
Source:
Nov. 11 issue of the Circulation (http://circ.ahajournals.org/current.dtl; 2008; 118).
Anticoagulant v. Antiplatelet Therapy in AF: Differences are wide among medical centers and countries in the time that patients on oral anticoagulants (OACs) are in the therapeutic international normalized ratio range, and if patients are not in the therapeutic INR range at least 58% to 65% of the time, they might be better off on an antiplatelet drug, an article concludes (pp. 2029-37). The posthoc analysis used data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE W) to calculate the mean time in therapeutic range (TTR) for 526 centers in 15 countries, with these results: ìA wide variation in TTRs was found between centers, with mean TTRs for centers in the 4 quartiles of 44%, 60%, 69%, and 78%. For patients at centers below the median TTR (65%), no treatment benefit was demonstrated as measured by relative risk for vascular events of clopidogrel plus aspirin versus OAC (relative risk, 0.93; 95% confidence interval, 0.70 to 1.24; P = 0.61). However, for patients at centers with a TTR above the study median, OAC had a marked benefit, reducing vascular events by >2-fold (relative risk, 2.14; 95% confidence interval, 1.61 to 2.85; P < 0.0001). Mean TTR also varied between countries from 46% to 78%; relative risk (clopidogrel plus aspirin versus OAC) varied from 0.6 to 3.6 (a 5-fold difference). A population-average model predicted that a TTR of 58% would be needed to be confident that patients would benefit from being on OAC.î (S. Connolly, connostu@phri.ca)
Fondaparinux in ACS: The clinical superiority of fondaparinux over heparin in treatment of acute coronary syndromes is evident in an analysis of combined data from the Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) trials (pp. 2038-46). Among 26,512 patients who received fondaparinux 2.5 mg daily or dose-adjusted unfractionated heparin or enoxaparin, these trends were present: ìFondaparinux was superior to heparin in reducing the composite of death, myocardial infarction, or stroke (8.0% versus 7.2%; hazard ratio [HR], 0.91; P = 0.03) and death alone (4.3% versus 3.8%; HR, 0.89; P = 0.05). Fondaparinux reduced major bleeding by 41% (3.4% versus 2.1%; HR, 0.59; P < 0.00001) and had a more favorable net clinical outcome than heparin (11.1% versus 9.3%; HR, 0.83; P < 0.0001). In 19,085 patients treated with an invasive strategy, fondaparinux suppressed ischemic events to an extent similar to heparin and reduced major bleeding by more than one-half, resulting in a superior net clinical outcome (10.8% versus 9.4%; HR, 0.87; P = 0.008). A similar benefit also was observed in those treated with a conservative strategy (HR, 0.74; 95% confidence interval, 0.64 to 0.85; P < 0.001).î (S. R. Mehta, smehta@mcmaster.ca)

>>>Cardiology Highlights
Source:
Nov. 18 issue of the Journal of the American College of Cardiology (http://content.onlinejacc.org/current.dtl; 2008; 52).
Clopidogrel in ACS/CABG: Use of clopidogrel may be detrimental in patients with acute coronary syndromes who receive the drug before coronary artery bypass graft surgery, according to data from a cross section of U.S. hospitals (pp. 1693-701). These data were obtained from 14 hospitals in this retrospective cohort analysis: ìOf the 596 patients enrolled in the study, 298 had been exposed to clopidogrel within 5 days (Group A). Patients in Group A were more than 3-fold more likely to require reoperation for assessment of bleeding than patients not exposed to clopidogrel (6.4% vs. 1.7% Group B, p = 0.004). Major bleeding occurred in 35% of Group A patients versus 26% of Group B patients (p = 0.049). Length of stay was greater in Group A compared with Group B (9.7 ± 6.0 days vs. 8.6 ± 4.7 days, unadjusted p = 0.016). After logistic regression analysis, clopidogrel exposure within 5 days of CABG was the strongest predictor of reoperation (odds ratio [OR]: 4.60, 95% confidence interval [CI]: 1.45 to 14.55) and major bleeding (OR: 1.824, 95% CI: 1.106 to 3.008).î (R. C. Becker, richard.becker@duke.edu)

>>>PNN NewsWatch
* A Web-based New England Journal of Medicine video Perspective roundtable on the future of primary care is supplemented by several short print articles in today’s issue of that journal.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 14, 2008 * Vol. 15, No. 222
Providing news and information about medications and their proper use

>>>Psychiatry Highlights
Source:
Nov. issue of the American Journal of Psychiatry (http://ajp.psychiatryonline.org/current.dtl; 2008; 165).
First- v. Second-Generation Antipsychotic Pediatric Therapy: In pediatric patients with early-onset schizophrenia and schizoaffective disorder, a comparison of first- and second-generation antipsychotic agents questions the ìnear exclusive useî of the latter (pp. 1420-31). Patients were randomized to olanzapine 2.5–20 mg/day, risperidone 0.5–6 mg/day, or molindone 10–140 mg/day, plus 1 mg/day of benztropine, for 8 weeks, with these results: ìIn total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia.î (L. Sikich, Lsikich@med.unc.edu)
Aripiprazole for Adolescents with Schizophrenia: Aripiprazole 10 or 30 mg/day was superior to placebo in treatment of schizophrenia among adolescent patients, a study shows (pp. 1432-41). With a primary endpoint of mean change from baseline to endpoint (last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS), the investigators found: ìOf 302 patients, 85% completed the 6-week study. The mean baseline PANSS score was 94.1. At the end of the study, both aripiprazole doses showed statistically significant differences from placebo in reduction in PANSS total score. Adverse events occurring in more than 5% of either aripiprazole group and with a combined incidence at least twice the rate for placebo were extrapyramidal disorder, somnolence, and tremor. Mean changes in prolactin were –8.45, –11.93, and –15.14 ng/ml for placebo and 10 mg and 30 mg of aripiprazole, respectively. Mean body weight changes were –0.8, 0.0, and 0.2 kg for placebo and 10 mg and 30 mg of aripiprazole, respectively.î (R. L. Findling, robert.findling@UHhospitals.org)
Commenting on the above two studies, an editorialist writes (pp. 1369-72): ìChild- and adolescent-onset schizophrenia are continuous with the adult-onset versions of the disorder, yet there are psychological, physiological, and metabolic issues unique to this group. Early disconcerting side effects, such as akathisia or other extrapyramidal symptoms, may bias children against long-term use of effective medications. Risk of weight gain may be greater in younger populations, and early weight gain has strong lifelong negative metabolic implications. The effects of elevated prolactin levels in prepubertal children are unknown but worrisome, particularly in boys. Given the prevalence of symptom onset in childhood and adolescence, and the factors unique to this age group, treatment studies specifically focused on children and adolescents are critical. These two studies are an excellent addition to the literature, but additional work is required, including longer-term follow-up studies, before formalized treatment strategies or policy decisions such as hierarchical formularies should be inferred.î (R. G. Ross,
randy.ross@ucdenver.edu)

>>>Chest Report
Source:
Nov. issue of Chest (www.chestjournal.org/current.shtml; 2008; 134).
ìObesity Paradoxî in PAD: Chronic obstructive pulmonary disease may be the cause of increased mortality among lower-weight patients with peripheral arterial disease, according to a study (pp. 925-30; D. Poldermans, d.poldermans@erasmusmc.nl) and accompanying editorial (pp. 896-8; C. J. Lavie, clavie@ochsner.org). The editorialists debate whether purposeful weight loss might exacerbate the problem but conclude that the cardiovascular benefits of weight loss should prevail: ìAs we continue to investigate the mechanisms for this puzzling obesity paradox, the ‘weight’ of evidence clearly supports purposeful weight loss, particularly with therapies that do not reduce lean body mass, such as exercise training in addition to caloric restriction, for the primary and secondary prevention of CV diseases.î

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 17, 2008 * Vol. 15, No. 223
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 15 issue of Lancet (www.thelancet.com; 2008; 372).
HIV & Injecting Drug Use: Injecting drug use is on the rise, and a high prevalence of HIV infections among those who do so represents a substantial worldwide health problem, according to an epidemiologic analysis and systematic review (pp. 1733-45). ìInjecting drug use was identified in 148 countries; data for the extent of injecting drug use was absent for many countries in Africa, the Middle East, and Latin America,î the authors noted based on their review of 11,022 documents. ìThe presence of HIV infection among injectors had been reported in 120 of these countries. Prevalence estimates of injecting drug use could be ascertained for 61 countries, containing 77% of the world’s total population aged 15–64 years. Extrapolated estimates suggest that 15.9 million (range 11.0–21.2 million) people might inject drugs worldwide; the largest numbers of injectors were found in China, the USA, and Russia, where mid-estimates of HIV prevalence among injectors were 12%, 16%, and 37%, respectively. HIV prevalence among injecting drug users was 20–40% in five countries and over 40% in nine. We estimate that, worldwide, about 3.0 million (range 0.8–6.6 million) people who inject drugs might be HIV positive.î (B. M. Mathers, b.mathers@med.unsw.edu.au)
Intranasal Insulin & Diabetes Prevention: Development of type 1 diabetes was not prevented by intranasal insulin in children at the point of onset of autoantibody production, researchers report (pp. 1746-55). At three Finnish university hospitals, the cord blood of 116,720 consecutively born infants was analyzed for presence of HLA-DQB1 susceptibility alleles. The researchers then monitored 17,397 children and 1,613 of their siblings for diabetes-associated autoantibodies every 3 to 12 months, and for 224 infants and 40 siblings with two or more autoantibodies, randomization to short-acting human insulin 1 unit/kg or placebo once daily produced these results: ìMedian duration of the intervention was 1.8 years (range 0–9.7). Diabetes was diagnosed in 49 index children randomised to receive insulin, and in 47 randomised to placebo (hazard ratio [HR] 1.14; 95% CI 0.73–1.77). 42 and 38 of these children, respectively, continued treatment until diagnosis, with yearly rates of diabetes onset of 16.8% (95% CI 11.7–21.9) and 15.3% (10.5–20.2). Seven siblings were diagnosed with diabetes in the insulin group, versus six in the placebo group (HR 1.93; 0.56–6.77). In all randomised children, diabetes was diagnosed in 56 in the insulin group, and 53 in the placebo group (HR 0.98; 0.67–1.43, p = 0.91).î (K. N‰ntˆ-Salonen, kirsti.nanto-salonen@tyks.fi)
Final APPROVe Results on Rofecoxib: Use of rofecoxib is associated with increased risk of the Antiplatelet Trialists’ Collaboration [APTC] combined endpoint of non-fatal myocardial infarction, nonfatal stroke, and death from cardiovascular, hemorrhagic, and unknown causes, according to final results of this study (pp. 1756-64). The final data reflect an early increase in risk that persists for 1 year after drug discontinuation, the researchers report: ìWe obtained extended post-treatment cardiovascular follow-up data from 84% of participants, and extended mortality follow-up from 95%. In total, 59 individuals had an APTC endpoint in the rofecoxib group and 34 in the placebo group (hazard ratio 1.79, 95% CI 1.17–2.73; p = 0.006). In the first year after cessation of treatment, there was a non-significant increase in the risks of APTC endpoints. The APTC hazard ratio did not substantially change over time.î (J. A. Baron, John.A.Baron@Dartmouth.edu)

>>>PNN JournalWatch
* Cognitive Dysfunction in Systemic Lupus Erythematosus: Past, Present, and Future, in Arthritis & Rheumatism, 2008; 58: 3286–98. Reprints: E. Kozora, kozorae@njc.org
* Neurologic Manifestations of Localized Scleroderma: A Case Report and Literature Review, in
Neurology, 2008; 71: 1538–45. Reprints: I. Kister, ilya.kister@gmail.com
* Anti–Cytotoxic T-Lymphocyte Antigen-4 Antibody: The First in an Emerging Class of Immunomodulatory Antibodies for Cancer Treatment, in
Journal of Clinical Oncology, 2008; 26: 5275–83. Reprints: L. Fong, lfong@medicine.ucsf.edu
* A Systematic Review of the Preventive Effect of Oral Hygiene on Pneumonia and Respiratory Tract Infection in Elderly People in Hospitals and Nursing Homes: Effect Estimates and Methodological Quality of Randomized Controlled Trials, in
Journal of the American Geriatrics Society, 2008; 56: 2124–30. Reprints: P. Sjˆgren, petteri.sjogren@oralcare.se

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 18, 2008 * Vol. 15, No. 224
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 18 issue of the Annals of Internal Medicine (www.annals.org/current.shtml; 2008; 149).
Adverse Events with Antitubercular Medications: Four months of treatment with rifampin produced significantly fewer adverse events and better rates of adherence than did 9 months of antitubercular therapy with isoniazid, according to a study of 847 patients (pp. 689-97). At clinics in Canada, Brazil, and Saudi Arabia, researchers recorded these results in a randomized open-label trial: ìSeventeen of 422 participants who started isoniazid therapy developed grade 3 to 4 adverse events compared with 7 of 418 who started rifampin therapy (risk difference [rifampin minus isoniazid], –2.3% [95% CI, –5% to –0.1%]; P = 0.040). Grade 3 or 4 hepatitis occurred in 16 of 422 isoniazid recipients compared with 3 of 418 rifampin recipients (risk difference, –3.1% [CI, –5% to –1%]; P = 0.003). Grade 1 or 2 adverse events attributed to study drugs occurred with similar frequency. Asymptomatic reduction in platelet and leukocyte counts were more frequent in rifampin recipients. More patients completed rifampin treatment (78%) than isoniazid treatment (60%) (difference, 18% [CI, 12% to 24%]; P < 0.001]).î (D. Menzies, dick.menzies@mcgill.ca)
Clinical Practice Guideline for Second-Generation Antidepressants: Based on a review of the available literature (pp. 734-50; G. Gartlehner, gerald.gartlehner@donau-uni.ac.at), the American College of Physicians made the following recommendations about use of second-generation antidepressants for treatment of depressive disorders (pp. 725-33; A. Qaseem, aqaseem@acponline.org):
n When clinicians choose pharmacologic therapy to treat patients with acute major depression, they [should] select second-generation antidepressants on the basis of adverse effect profiles, cost, and patient preferences (Grade: strong recommendation; moderate-quality evidence).
n Clinicians should assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy (Grade: strong recommendation; moderate-quality evidence).
n Clinicians [should] modify treatment if the patient does not have an adequate response to pharmacotherapy within 6 to 8 weeks of the initiation of therapy for major depressive disorder (Grade: strong recommendation; moderate-quality evidence).
n Clinicians [should] continue treatment for 4 to 9 months after a satisfactory response in patients with a first episode of major depressive disorder. For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial (Grade: strong recommendation; moderate-quality evidence).
Enhancing Motivation Among Patients with Diabetes: Among patients with poorly controlled type 1 diabetes, nurse-delivered motivational enhancement therapy was effective for improving clinical results when combined with cognitive–behavioral therapy but not when delivered alone, a study shows (pp. 708-19). Conducted at 8 diabetes centers in London and Manchester, U.K., the trial included 344 adult patients who had been diagnosed 2 or more years earlier and who had hemoglobin A1c levels of 8.2% to 15%. Nurses provided either 4 motivational enhancement therapy delivered over 2 months, 12 such sessions plus cognitive–behavioral therapy over 6 months, or usual care, with these results: ìIn an analysis including all randomly assigned patients, the 12-month change in hemoglobin A1c levels compared with usual care was –0.46% (95% CI, –0.81% to –0.11%) in the motivational enhancement therapy plus cognitive behavior therapy group and –0.19% (CI, –0.53% to 0.16%) in the motivational enhancement therapy group alone. There was no evidence of treatment effects on secondary outcomes.î (K. Ismail, khalida.ismail@iop.kcl.ac.uk)

>>>PNN NewsWatch
* The medication therapy management practice of Jeffrey Brewer was described in yesterday’s Baltimore Sun. A pharmacist who practices collaboratively in the internal medicine division of Johns Hopkins Community Physicians at Wyman Park, Brewer described his efforts as ìpart prescription manager, educator and coachî for patients with diabetes and other chronic diseases.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 19, 2008 * Vol. 15, No. 225
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 19 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Ginkgo biloba Falters in Alzheimer’s Trial: Ginkgo biloba, administered as an extract in doses of 120 mg twice daily, did not lower the overall incidence of dementia or Alzheimer’s disease among older patients with normal or mild impaired cognition, according to results of the Ginkgo Evaluation of Memory (GEM) Study (pp. 2253-62). Described by the authors as ìthe largest and first adequately powered randomized clinical trial conducted to evaluate the effect of G. biloba on dementia incidence,î the study produced the following results among 2,587 patients older than 75 years with normal cognition and 482 such patients with MCI during a median of 6.1 years of follow-up: ìFive hundred twenty-three individuals developed dementia (246 receiving placebo and 277 receiving G biloba) with 92% of the dementia cases classified as possible or probable AD, or AD with evidence of vascular disease of the brain. Rates of dropout and loss to follow-up were low (6.3%), and the adverse effect profiles were similar for both groups. The overall dementia rate was 3.3 per 100 person–years in participants assigned to G biloba and 2.9 per 100 person–years in the placebo group. The hazard ratio (HR) for G biloba compared with placebo for all-cause dementia was 1.12 (95% confidence interval [CI], 0.94–1.33; P = .21) and for AD, 1.16 (95% CI, 0.97–1.39; P = .11). G biloba also had no effect on the rate of progression to dementia in participants with MCI (HR, 1.13; 95% CI, 0.85–1.50; P = .39).î (S. T. DeKosky, dekosky@virginia.edu)
Patients should not expect benefits from use of this agent, writes an editorialist, adding these remarks about other
G. biloba claims (pp. 2306-8): ìThe GEM study adds to the substantial body of evidence that G biloba extract as it is generally used does not prevent dementia in individuals with or without cognitive impairment and is not effective for Alzheimer disease. With respect to preventing stroke or minimizing the damaging sequelae from stroke, the slight evidence is vague and contradictory. Users of this extract should not expect it to be helpful. Moreover, the potential adverse effects of G biloba extract illustrate why it is untenable to recommend a drug or nutraceutical in the absence of efficacy evidence simply because it could possibly help and initially appears harmless.î (L. S. Schneider, lschneid@usc.edu)
VTE After Bevacizumab Use: Patients with cancer who are treated with bevacizumab are at significantly higher risk of venous thromboembolism, according to a meta-analysis (pp. 2277-85). Studies of the angiogenesis inhibitor showed these trends: ìA total of 7,956 patients with a variety of advanced solid tumors from 15 randomized controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidences of all-grade and high-grade venous thromboembolism were 11.9% (95% CI, 6.8%–19.9%) and 6.3% (95% CI, 4.8%–8.3%), respectively. Patients treated with bevacizumab had a significantly increased risk of venous thromboembolism with an RR of 1.33 (95% CI, 1.13–1.56; P < .001) compared with controls. The risk was significantly increased for both all-grade and high-grade venous thromboembolism. In addition, the risk was similarly increased for bevacizumab at 2.5 mg/kg per week (low dose; RR, 1.31 [95% CI, 1.08–1.60]; P = .007) and 5 mg/kg per week (high dose; RR, 1.31 [95% CI, 1.02–1.68]; P = .04).î (S. Wu, shenhong.wu@stonybrook.edu)

>>>PNN NewsWatch
* CSI USA Inc. and FDA yesterday informed consumers and professionals of a nationwide recall of all lots of 1 ounce tubes of 10% Benzoyl Peroxide Acne Cream because of contamination with Burkholderia cepacia. Risk of infections may be increased for those with cuts, scrapes, rashes, or other compromised skin conditions, or weakened or suppressed immune systems. Consumers should discontinue using the product and should return it to the place of purchase.
*
Extortion: Patients’ personal prescription information would be exposed if Express Scripts failed to pay an undisclosed amount, the FBI said. FDA is warning consumers of a scheme to get them to wire money to the Dominican Republic in payment for prescription drugs and subsequent threats by people posing as FDA inspectors.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 20, 2008 * Vol. 15, No. 226
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Nov. 20 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Rosuvastatin for Elevated C-Reactive Protein: In a study released last week in conjunction with the American Heart Association convention (see PNN, Nov. 10), rosuvastatin proved effective for lowering the risk of major cardiovascular events among patients with normal lipids but elevated C-reactive protein levels (pp. 2195-207). Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) included 17,802 apparently healthy men and women with LDL cholesterol levels of less than 130 mg/dL and high-sensitivity C-reactive protein levels of 2.0 mg/L or higher. They were randomized to rosuvastatin 20 mg daily or placebo and followed for a combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes, as follows: ìThe trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person–years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P < 0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P = 0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P = 0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P < 0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P < 0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P = 0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes.î (P. M. Ridker, pridker@partners.org)
While agreeing that JUPITER expands ìthe orbit of primary prevention,î an editorialist calls for more attention to costs and relative benefits and safety before practices are changed (pp. 2280-2): ìJUPITER provides yet more evidence about the effectiveness of statin therapy in reducing cardiovascular risk, even among persons who would not currently be considered for pharmacotherapy. Guidelines for primary prevention will surely be reassessed on the basis of the JUPITER results, but the appropriate size of the orbit of statin therapy depends on the balance between the benefits of treatment and its long-term safety and cost.î (M. A. Hlatky, Stanford U., Stanford, CA)
NEJM editors invite readers to vote online by Nov. 26 as to whether JUPITER will change their practices.
Early Antiretroviral Therapy in Infants: Among 377 infants with HIV infection, early diagnosis and antiretroviral treatment significantly reduced early infant mortality and HIV progression, according to a study conducted in South Africa (pp. 2233-44): ìAt a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P < 0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P < 0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy.î (A. Violari, violari@mweb.co.za)

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 21, 2008 * Vol. 15, No. 227
Providing news and information about medications and their proper use

>>>Gastroenterology Report
Source:
Nov. issue of Gastroenterology (www.gastrojournal.org/current; 2008; 135).
Adalimumab in Crohn’s Disease: Risks of hospitalization and surgery were reduced by 1 year of adalimumab therapy in 778 patients with moderate to severe Crohn’s disease, researchers report (pp. 1493-9). After an induction regimen, participants received either placebo or adalimumab 40 mg once weekly or every other week, with these results: ìBoth 3- and 12-month hospitalization risks were significantly lower for patients who received adalimumab. Hazard ratios for all-cause hospitalization were 0.45, 0.36, and 0.40 for the adalimumab every other week, weekly, and combined groups, respectively (all P < .01 vs placebo). Hazard ratios for CD-related hospitalization were 0.50, 0.34, and 0.42, respectively (all P < .05). Cox model estimates demonstrated adalimumab every other week and weekly maintenance therapies were associated with 52% and 60% relative reductions in 12-month, all-cause hospitalization risk, and 48% and 64% reductions in 12-month risk of CD-related hospitalization. The combined adalimumab group was associated with 56% reductions in both all-cause and CD-related hospitalization risks. Fewer CD-related surgeries occurred in the adalimumab every other week, weekly, and combined groups compared with placebo (0.4, 0.8, and 0.6 vs 3.8 per 100 patients; all P < .05).î (B. G. Feagan, bfeagan@robarts.ca)
Oral Budesonide for Collagenous Colitis: Long-term maintenance of remission was achieved with oral budesonide in patients with collagenous colitis, according to a 6-month study (pp. 1510-6). All 48 participants received 6 weeks of open-label oral budesonide 9 mg/d, after which double-blind randomization of the 46 patients in remission to placebo or oral budesonide 6 mg/d produced these results: ìThere were 21 relapses during maintenance therapy, and almost all occurred during the first 2 months. Budesonide therapy was associated with a significantly lower cumulative rate of relapse compared with placebo (6/23 [26%] and 15/23 [65%], respectively; P = .022), and high correlation between clinical remission and histologic improvement was observed. Budesonide was well tolerated with no serious adverse events.î (S. Miehlke, Stephan.Miehlke@uniklinikum-dresden.de)
Lower GI Effects with Etoricoxib: Similar rates of lower gastrointestinal clinical events were observed among patients older than 50 who were taking the traditional NSAID diclofenac or the COX-2–selective agent etoricoxib for osteoarthritis or rheumatoid arthritis (pp. 1517-25). ìWe enrolled 34,701 patients with mean duration of therapy of 18 months,î the authors report. ìRates were 0.32 and 0.38 lower GI clinical events per 100 patient–years for etoricoxib and diclofenac (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.63–1.13). Bleeding was the most common event (rates of 0.19 and 0.23 per 100 patient–years, respectively). Multivariable analysis revealed significant risk factors to be prior lower GI event (HR = 4.06; 95% CI, 2.93–5.62) and age 65 years (HR = 1.98; 95% CI, 1.45–2.71).î (L. Laine, llaine@usc.edu)
Long-Term Ursodeoxycholic Acid for Portal Hypertension, Biliary Cirrhosis: Among 132 patients being seen in a primary biliary cirrhosis clinic, portal hypertension was a common complication, and changes in the portohepatic gradient (PHG) and normalized AST level after 2 years of ursodeoxycholic acid treatment effectively identified a subgroup of responders with survival comparable with that of a control population, a study shows (pp. 1552-60; P–M Huet, pierre-michel.huet@orange.fr)

>>>PNN NewsWatch
* APhA reports that these pharmacists were elected or re-elected to state office in the elections held earlier this month: Chuck Hopson, Texas State Representative; Oren ìBuddyî Harden, Jr., Georgia State Representative; Utah, Evan Vickers, State House; and Jim Thompson, Oregon Representative.
*
John A. Gans, PharmD, will receive the 2009 Remington Honor Medal, pharmacy’s highest honor, during the APhA Annual Meeting and Exposition in San Antonio, TX, April 3–6, 2009. Gans has been APhA’s Executive Vice President and Chief Executive Officer since 1989. He is stepping down on June 30, 2009, at which time Thomas E. Menighan will become the APhA Executive Vice President/CEO.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 24, 2008 * Vol. 15, No. 228
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 22 issue of Lancet (www.thelancet.com; 2008; 372).
Gefitinib for Non-Small-Cell Lung Cancer: In the Iressa NSCLC Trial Evaluating REsponse and Survival versus Taxotere (INTEREST), gefitinib compared favorably with docetaxel among pretreated patients with non-small-cell lung cancer (pp. 1809-18). The open-label Phase III trial included patients who had previously received one or more platinum-based regimens. They were randomized to gefitinib 250 mg/d or docetaxel 75 mg/m2 intravenously as a 1-h infusion every 3 weeks, with these results: ì1,433 patients were analysed per protocol (723 in gefitinib group and 710 in docetaxel group). Non-inferiority of gefitinib compared with docetaxel was confirmed for overall survival (593 vs 576 events; hazard ratio [HR] 1.020, 96% CI 0.905—1.150, meeting the predefined non-inferiority criterion; median survival 7.6 vs 8.0 months). Superiority of gefitinib in patients with high EGFR-gene-copy number (85 vs 89 patients) was not proven (72 vs 71 events; HR 1.09, 95% CI 0.78—1.51; p = 0.62; median survival 8.4 vs 7.5 months). In the gefitinib group, the most common adverse events were rash or acne (360 [49%] vs 73 [10%]) and diarrhoea (255 [35%] vs 177 [25%]); whereas in the docetaxel group, neutropenia (35 [5%] vs 514 [74%]), asthenic disorders (182 [25%] vs 334 [47%]), and alopecia (23 [3%] vs 254 [36%]) were most common.î (E. S. Kim, edkim@mdanderson.org)

>>>PNN NewsWatch
* FDA has approved rufinamide (Banzel, Eisai) for the adjunctive treatment of seizures associated with Lennox–Gastaut syndrome (LGS) in children 4 years and older and adults. A triazole derivative that is structurally unrelated to currently marketed antiepileptic drugs, rufinamide is believed to exert its effect by regulating the activity of sodium channels in the brain. A double-blind, placebo-controlled pivotal study of LGS patients treated with rufinamide as adjunctive therapy showed a 42.5% median reduction in frequency of seizures that cause a person to lose consciousness and fall to the ground (drop attacks), compared with a 1.4% median increase for placebo-treated patients. Drop attacks are a primary cause of injury in LGS patients. The drug is contraindicated in patients with Familial Short QT syndrome and should be used with caution with other drugs that shorten the QT interval.
*
Eltrombopag (Promacta, GlaxoSmithKline) has also been approved by FDA. It is indicated for treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The orally active thrombopoietin-receptor agonist carries a black-box warning for hepatotoxicity, and a restricted distribution system, Promacta Cares, is in place. Efficacy data were reported last year in the New England Journal of Medicine (see PNN, Nov. 29, 2007).

>>>PNN JournalWatch
* Association Between the SERPING1 Gene and Age-Related Macular Degeneration: A Two-Stage Case—Control Study, in Lancet, 2008; 372: 1828–34. Reprints: A. Lotery, a.j.lotery@southampton.ac.uk
* Influenza Vaccine in the Over 65s [editorial], in
BMJ, 2008; 337: a2545. Reprints: R. E. Jordan, r.e.jordan@bham.ac.uk
* Safety of Ferumoxytol in Patients with Anemia and CKD, in
American Journal of Kidney Diseases, 2008; 52: 907–15. Reprints: L. Brenner, lbrenner@amagpharma.com(with related editorial)
* Vascular Access–Related Infections: Definitions, Incidence Rates, and Risk Factors, in
American Journal of Kidney Diseases, 2008; 52: 982–93. Reprints: J-P Lafrance, jean-philippe.lafrance@mail.mcgill.ca
* The American Heart Association’s 2008 Statement of Principles for Healthcare Reform, in
Circulation, 2008; 118: 2209–18. Reprints: R. J. Gibbons.
* Antiplatelet Therapy Use After Discharge Among Acute Myocardial Infarction Patients with In-Hospital Bleeding, in
Circulation, 2008; 118: 2139–45. Reprints: T. Y. Wang, wang0085@mc.duke.edu
* Price Transparency for Medical Devices, in
Health Affairs, 2008; 27: 1544–53. Reprints: M. V. Paulty.
* Innate Microbial Sensors and their Relevance to Allergy, in
Journal of Allergy and Clinical Immunology, 2008; 122: 846–58. Reprints: A. H. Liu, liua@njc.org
* Promoting Health Communication Between the Community-Dwelling Well-Elderly and Pharmacists: The Ask Me 3 Program, in
Journal of the American Pharmacists Assoc., 2008; 48: 784–92. Reprints: M. J. Miller, michael-miller@ouhsc.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 25, 2008 * Vol. 15, No. 229
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 24 issue of the Archives of Internal Medicine (http://archinte.ama-assn.org/current.dtl; 2008; 168).
Pharmacist/Nurse Management of Hypertension: In a randomized controlled trial conducted in 14 community pharmacies in Edmonton, a pharmacist- and nurse-based intervention helped patients with diabetes lower their blood pressures even when their hypertension was relatively well controlled at baseline (pp. 2355-61). The pharmacist–nurse team provided these interventions to patients/physicians at two consecutive visits conducted 2 weeks apart: a wallet card with recorded BP measures, cardiovascular risk reduction education and counseling, a hypertension education pamphlet, referral to the patient’s primary care physician for further assessment or management, and a 1-page local opinion leader–endorsed evidence summary sent to the physician reinforcing the guideline recommendations for the treatment of hypertension and diabetes. Four follow-up visits were then conducted over 6 months. Compared with a control group that received the wallet card, diabetes pamphlet, general diabetes advice, and usual care by their physicians, the intervention produced these results: ìA total of 227 eligible patients were randomized to intervention and control arms between May 5, 2005, and September 1, 2006. The mean (SD) patient age was 64.9 (12.1) years, 59.9% were male, and the mean (SD) baseline systolic/diastolic BP was 141.2 (13.9)/77.3 (8.9) mm Hg at baseline. The intervention group had an adjusted mean (SE) greater reduction in systolic BP at 6 months of 5.6 (2.1) mm Hg compared with controls (P = .008). In the subgroup of patients with a systolic BP greater than 160 mm Hg at baseline, BP was reduced by an adjusted mean (SE) of 24.1 (1.9) mm Hg more in intervention patients than in controls (P < .001).î (R. T. Tsuyuki, ross.tsuyuki@ualberta.ca)
Electronic Health Records & Malpractice Claims: Physicians who use electronic health records may have fewer claims against them for malpractice, according to a survey of 1,345 physicians in Mass. (pp. 2362-7). Overall, researchers report, 6.1% of physicians using EHRs had a history of a paid malpractice claim, compared with 10.8% of physicians without EHRs (unadjusted odds ratio, 0.54; 95% confidence interval, 0.33–0.86; P = 0.01). Further, among EHR adopters, the investigators found that 5.7% of physicians identified as high users of EHR had paid malpractice claims compared with 12.1% of low users of the technology (P = 0.14). (S. R. Simon, steven_simon@hphc.org)

>>>PNN NewsWatch
* An FDA advisory committee yesterday recommended that the agency approve febuxostat for treatment of hyperuricemia in patients with gout. The Takeda drug is a potent nonpurine, selective inhibitor of xanthine oxidase.
*
FDA is investigating new preliminary data regarding a potential increased risk of serious skin reactions including Stevens–Johnson syndrome and toxic epidermal necrolysis from phenytoin therapy in Asian patients positive for human leukocyte antigen allele, HLA-B*1502. Until the FDA evaluation is completed, health care providers should consider avoiding phenytoin and fosphenytoin as alternatives for carbamazepine in patients who test positive for HLA-B*1502, almost all of whom have Han Chinese, Filipino, Malaysian, South Asian Indian, or Thai ancestry.
*
FDA has approved tapentadol hydrochloride (Johnson & Johnson), an immediate-release oral tablet for the relief of moderate to severe acute pain. Tapentadol is a centrally acting synthetic analgesic that will be available in doses of 50, 75, or 100 mg. The drug is also a norepinephrine reuptake inhibitor, which FDA noted in a news release possibly provides an analgesic effect. The most common adverse effects from tapentadol are nausea, dizziness, vomiting, sleepiness, and headaches. The labeling for tapentadol includes warnings about the risk of respiratory depression; addictive depressive effects on the central nervous system when taken with alcohol, other opioids, or illicit drugs; and abuse potential.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Nov. 26, 2008 * Vol. 15, No. 230
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 26 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Inhaled Corticosteroids in COPD: All-cause mortality at 1 year was unaffected by treatment of chronic obstructive pulmonary disease with inhaled corticosteroids, according to a systematic review and meta-analysis of 11 randomized controlled trials that included 14,426 participants (pp. 2407-16). ìIn trials with mortality data, no difference was observed in 1-year all-cause mortality (128 deaths among 4,636 patients in the treatment group and 148 deaths among 4,597 patients in the control group; relative risk [RR], 0.86; 95% confidence interval [CI], 0.68–1.09; P = .20; I2 = 0%). In the trials with data on pneumonia, ICS therapy was associated with a significantly higher incidence of pneumonia (777 cases among 5,405 patients in the treatment group and 561 cases among 5,371 patients in the control group; RR, 1.34; 95% CI, 1.03–1.75; P = .03; I2 = 72%). Subgroup analyses indicated an increased risk of pneumonia in the following subgroups: highest ICS dose (RR, 1.46; 95% CI, 1.10–1.92; P = .008; I2 = 78%), shorter duration of ICS use (RR, 2.12; 95% CI, 1.47–3.05; P < .001; I2 = 0%), lowest baseline forced expiratory volume in the first second of expiration (RR, 1.90; 95% CI, 1.26–2.85; P = .002; I2 = 0%), and combined ICS and bronchodilator therapy (RR, 1.57; 95% CI, 1.35–1.82; P < .001; I2 = 24%).î (E. Fan, eddy.fan@jhmi.edu)
Including Observational Data in Meta-analyses: Adverse drug data from observational studies should be included in systematic reviews and meta-analyses, authors of a Commentary article argue (pp. 2417-9). After discussing the lack of real-world perspective in randomized controlled trials and acknowledging the lack of reliability of observational studies with respect to drug efficacy, the authors make these claims for observational studies: ìAdverse effects of new drugs are often unknown and unanticipated when those drugs enter the market. The adverse event is usually unrelated to the condition under treatment. At prescribing, physicians are unable to pay attention to risk factors of an as-yet-unknown adverse effect. Even when an adverse effect, such as hepatic failure, is already established, it may be completely unpredictable or idiosyncratic, or its risk factors may not be known. When risk factors for the adverse effects are known, the potential confounding caused by risk-adverse prescribing can often be countered by suitable restriction and careful choice of a comparison group.î
The authors conclude, ìFor a future that combines benefit and harms assessment, systematic reviews will need to incorporate and integrate the best information from both randomized trials and observational studies.î (B. M. Psaty,
psaty@u.washington.edu)

>>>PNN NewsWatch
* Antidepressants, antipsychotics, and anxiolytic–sedatives are among 14 medications that are frequently prescribed off-label, researchers report in the Dec. issue of Pharmacotherapy. In an article getting a lot of attention this week in the lay media, investigators analyzed drug-prescribing patterns among office-based physicians as recorded in commercial databases, observing: ìOur findings identified a high volume of off-label prescribing in the absence of good evidence for a substantial number of drugs, particularly antidepressants, antipsychotics, and anxiolytic–sedatives. Drugs that consistently ranked high in both our base model and sensitivity analyses were quetiapine, warfarin, escitalopram, risperidone, montelukast, bupropion, sertraline, venlafaxine, celecoxib, lisinopril, duloxetine, trazodone, olanzapine, and epoetin alfa.î The researchers conclude: ìFuture research into off-label drug use should focus on drugs used frequently with inadequate supporting evidence, particularly if further concerns are raised by known safety issues, high drug cost, recent market entry, and extensive marketing. Our quantitative analysis identified particular concerns with the off-label use of antipsychotic and antidepressant drugs. Targeted research and policy activities on our list of prioritized drugs have high potential value.î (S. M. Walton, walton@uic.edu)
* During the upcoming holiday season,
PNN will not be published on Nov. 27–28, Thanksgiving; Dec. 25–26, Christmas; and Jan. 1–2, New Year’s.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 1, 2008 * Vol. 15, No. 231
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 29 issue of Lancet (www.thelancet.com; 2008; 372).
HIV-1 Vaccine Assessment: A cell-mediated immunity vaccine failed to prevent HIV-1 infections or reduce early viral levels in a 34-site, Phase II study, leading researchers to search for reasons for the lack of efficacy and increased infection rates in some vaccinated subgroups (pp. 1881-93). Among 3,000 HIV-1-seronegative participants who received three injections of either MRKAd5 HIV-1 gag/pol/nef vaccine or placebo in the Step Study, these results were noted: “In a prespecified interim analysis in participants with baseline Ad5 antibody titre 200 or less, 24 (3%) of 741 vaccine recipients became HIV-1 infected versus 21 (3%) of 762 placebo recipients (hazard ratio [HR] 1.2 [95% CI 0.6—2.2]). All but one infection occurred in men. The corresponding geometric mean plasma HIV-1 RNA was comparable in infected male vaccine and placebo recipients (4.61 vs 4.41 log10 copies per mL, one tailed p value for potential benefit 0.66). The vaccine elicited interferon-gamma ELISPOT responses in 75% (267) of the 25% random sample of all vaccine recipients (including both low and high Ad5 antibody titres) on whose specimens this testing was done (n = 354). In exploratory analyses of all study volunteers, irrespective of baseline Ad5 antibody titre, the HR of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men (HR 2.3 [95% CI 1.2—4.3]) and uncircumcised men (3.8 [1.5—9.3]), but was not increased in Ad5 seronegative (1.0 [0.5—1.9]) or circumcised (1.0 [0.6—1.7]) men.” (S. P. Buchbinder, susan.buchbinder@sfdph.org)
Also released in a conjunction with today’s observance of
World AIDS Day, a second article analyzes Step Study data using a case–cohort approach to identify possible future approaches to HIV-1 vaccine development (pp. 1894-905). The investigators conclude, “Our findings suggest that future candidate vaccines have to elicit responses that either exceed in magnitude or differ in breadth or function from those recorded in this trial,” adding: “Strategies hold promise that improve T-cell breadth of relevant epitopes with use of HIV-1 inserts that provide enhanced coverage of circulating strains, such as more centralised or even mosaic HIV inserts. Further, optimisation of the functional antiviral responses of the T cells elicited, on the basis of findings from more sophisticated genomics and proteomics approaches, might improve the chances for success in achieving long-term antiviral CD8+ T-cell memory against HIV-1 infection. Faced with an epidemic that will be best halted by an effective vaccine, there is no better time to channel knowledge from data, not hindsight or opinion, into careful planning for the next steps in the search for a preventive HIV vaccine.” (M. J. McElrath, jmcelrat@fhcrc.org)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2008; 337).
Drug Use in Children: Analysis of data from the Netherlands, United Kingdom, and Italy shows this pattern of prescription drug use in European pediatric patients (a2245): “For all age categories, anti-infective, dermatological, and respiratory drugs were in the high use group, whereas cardiovascular and antineoplastic drugs were always in the low use group. Emollients, topical steroids, and asthma drugs had the highest prevalence of recurrent use, but relative use of low prevalence drugs was more often recurrent than acute. In the top five highest prevalence drugs topical inhaled and systemic steroids, oral contraceptives, and topical or systemic antifungal drugs were most commonly used off label.” (M. C. J. M. Sturkenboom, m.sturkenboom@erasmusmc.nl)

>>>PNN NewsWatch
* Balanced Health Products is recalling one lot of its Starcaps product because of presence of an undeclared drug ingredient, the sulfonamide diuretic bumetanide, FDA announced last week. Consumers who have product with lot number 12/2011—84810 should immediately discontinue taking it and return the product to the manufacturer.

>>>PNN JournalWatch
* Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease, in New England Journal of Medicine, 2008; 359: 2355–65. Reprints: S. Sethi, ssethi@buffalo.edu
* Depression and Diabetes Treatment Nonadherence: A Meta-Analysis, in
Diabetes Care, 2008; 31: 2398–403. Reprints: J. S. Gonzalez, jsgonzalez@partners.org

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 2, 2008 * Vol. 15, No. 232
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and the Dec. 2 issue of the Annals of Internal Medicine (http://www.annals.org/current.shtml; 2008; 149).
QTc Interval Screening in Methadone Treatment: A consensus guideline on the need for QTc interval screening during methadone treatment is presented (early release). Based on available literature, the Center for Substance Abuse Treatment expert panel makes these recommendation (M. J. Krantz, Colorado Prevention Ctr., Denver):
* Recommendation 1 (Disclosure): The panel recommends that clinicians inform patients of arrhythmia risk when they prescribe methadone.
* Recommendation 2 (Clinical History): The panel recommends that clinicians ask patients about any history of structural heart disease, arrhythmia, and syncope.
* Recommendation 3 (Screening): The panel recommends obtaining a pretreatment electrocardiogram for all patients to measure the QTc interval and a follow-up electrocardiogram within 30 days and annually. The panel recommends additional electrocardiography if the methadone dosage exceeds 100 mg/d or if patients have unexplained syncope or seizures.
* Recommendation 4 (Risk Stratification): If the QTc interval is greater than 450 ms but less than 500 ms, discuss the potential risks and benefits with patients and monitor them more frequently. If the QTc interval exceeds 500 ms, the panel recommends considering discontinuation or reduction of the methadone dose; elimination of contributing factors, such as drugs that promote hypokalemia; or use of an alternative therapy.
* Recommendation 5 (Drug Interactions): The panel recommends that clinicians be aware of interactions between methadone and other drugs that possess QT interval–prolonging properties or slow the elimination of methadone.
Alcohol Misuse & Medication Nonadherence: An increased risk of medication nonadherence was associated with alcohol misuse in an observational study conducted at 7 VA primary care clinics (pp. 795-803). Study participants—including 5,473 patients taking a statin, 3,468 patients taking oral hypoglycemic agents, and 13,729 patients taking antihypertensive medications—completed the Alcohol Use Disorder Identification Test–Consumption (AUDIT-C) questionnaire, a validated 3-question alcohol misuse screening test. Results showed: ìThe proportion of patients treated for hypertension and hyperlipidemia who were nonadherent increased with higher AUDIT-C scores. For 1-year adherence to statins, the percentage of adherent patients was lower in the 2 highest alcohol misuse groups (adjusted percentage of adherent patients, 58% [95% CI, 52% to 65%] and 55% [CI, 47% to 63%]) than in the nondrinker group (66% [CI, 64% to 68%]). For 1-year adherence to antihypertensive regimens, the percentage of adherent patients was lower in the 3 highest alcohol misuse groups (adjusted percentage of adherent patients, 61% [CI, 58% to 64%]; 60% [CI, 56% to 63%]; and 56% [CI, 52% to 60%]) than in the nondrinker group (64% [CI, 63% to 65%]). No statistically significant differences were observed for oral hypoglycemics in adjusted analyses.î (C. L. Bryson, christopher.bryson@va.gov)
State ìApologyî Laws: Laws recently enacted to encourage physicians to disclose medical errors are reviewed (pp. 811-5). Based on analysis of the statutes in the 50 states and the District of Columbia, the authors find substantial variability in apology laws and assess their potential impact as currently written. (W. M. McDonnell, william.mcdonnell@hsc.utah.edu)
Routine HIV Screening: The American College of Physicians joins other expert groups in calling for routine screening of patients for HIV infection (early release). Using the National Guideline Clearinghouse to identify guidelines on screening for HIV in the United States and the AGREE (Appraisal of Guidelines Research and Evaluation) instrument to evaluate guidelines from the U.S. Preventive Services Task Force and the Centers for Disease Control and Prevention, the College make two recommendations (A. Qaseem, aqaseem@acponline.org):
* ACP recommends that clinicians adopt routine screening for HIV and encourage patients to be tested.
* ACP recommends that clinicians determine the need for repeat screening on an individual basis.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 3, 2008 * Vol. 15, No. 233
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 3 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Brand-Name v. Generic Drugs for Cardiovascular Disease: While studies do not demonstrate any bioequivalent differences between generic and brand-name drug products, editorialists frequently warn of problems when the less expensive generic products are substituted for brand-name counterparts used in cardiovascular disease, researchers report (pp. 2514-26). In a systematic review and meta-analysis of literature published since 1984, investigators found: ìWe identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of beta-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of alpha-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was –0.03 (95% confidence interval, –0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution.î (A. S. Kesselheim, akesselheim@partners.org)
Alcohol Consumption & Atrial Fibrillation in Women: Risk of incident atrial fibrillation in 34,715 initially healthy women was unchanged by consumption of up to 2 alcoholic beverages per day, a study shows (pp. 2489-96). Risks were increased among those consuming 2 or more drinks each day, the authors conclude, adding these details: ìOver a median follow-up of 12.4 years, 653 cases of incident atrial fibrillation were confirmed. Age-adjusted incidences among women consuming 0 (n = 15,370), more than 0 and less than 1 (n = 15,758), 1 or more and less than 2 (n = 2,228), and 2 or more (n = 1,359) drinks per day were 1.59, 1.55, 1.27, and 2.25 events/1,000 person-years of follow-up. Thus, compared with nondrinking women, women consuming 2 or more drinks per day had an absolute risk increase of 0.66 events/1,000 person–years. The corresponding multivariate-adjusted hazard ratios (HRs) for incident atrial fibrillation were 1, 1.05 (95% CI, 0.88–1.25), 0.84 (95% CI, 0.58–1.22), and 1.60 (95% CI, 1.13–2.25), respectively. The increased hazard in the small group of women consuming 2 or more drinks per day persisted when alcohol intake was updated at 48 months (HR, 1.49; 95% CI, 1.05–2.11) or when women were censored at their first cardiovascular event (HR, 1.68; 95% CI, 1.18–2.39).î (D. Conen, conend@uhbs.ch)
Surgery for Pharmacoresistant Temporal Lobe Epilepsy: Anterior temporal lobe resection should be considered when medical management of temporal lobe epilepsy fails, according to investigators who conducted a decision analysis (pp. 2497-505). ìCompared with medical management, anterior temporal lobe resection for a 35-year-old patient with an epileptogenic zone identified in the anterior temporal lobe would increase survival by 5.0 years (95% CI, 2.1–9.2) with surgery preferred in 100% of the simulations,î the authors wrote of their Monte Carlo method. ìAnterior temporal lobe resection would increase quality-adjusted life expectancy by 7.5 quality-adjusted life–years (95%, CI, –0.8 to 17.4) with surgery preferred in 96.5% of the simulations, primarily due to increased years spent without disabling seizures, thereby reducing seizure-related excess mortality and improving quality of life. The results were robust to sensitivity analyses.î (H. Choi, hc323@columbia.edu)

>>>PNN NewsWatch
* FDA continues to recommend alternatives to tinzaparin (Innohep, Celgene) in patients older than 70 with renal insufficiency and deep-vein thrombosis, pulmonary embolism, or both. The Innohep in Renal Insufficiency Study (IRIS) was stopped in Feb. 2008 because of an interim finding of an increase in all-cause mortality in patients who received this drug, and FDA noted that it is expecting the final study report in Jan. 2009. The agency will issue its conclusions and recommendations after the complete data are reviewed.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 4, 2008 * Vol. 15, No. 234
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 4 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Treatment of High-Risk Hypertension: Among 11,506 patients with hypertension who were at high risk for cardiovascular events, benazepril–amlodipine proved a better combination treatment than did benazepril–hydrochlorothiazide, according to results of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial (pp. 2417-28). Assessing for a primary end point of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization, the investigators found: ìThe baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril–amlodipine group and 132.5/74.4 mm Hg in the benazepril–hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril–amlodipine group (9.6%) and 679 in the benazepril–hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril–amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P < 0.001). For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P = 0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs.î (K. Jamerson, emarshal@umich.edu)
An editorialist points to individual patient results as more important than study findings (pp. 2485-8): ìMost patients with hypertension will require two or more drugs to control their hypertension, and combination drug formulations may also be useful. Although specific benefits may be provided by a given drug or drug combination, the evidence is overwhelming that the most important aspect of treatment is to reduce blood pressure to goal levels. How this is achieved is less important. Unfortunately, despite the remarkable progress in therapy, blood pressure remains inadequately controlled in almost two thirds of patients with hypertension in the United States. We must do better.î (A. V. Chobanian, Boston U., Boston)
Irbesartan in HF with Preserved Ejection Fraction: In a study of 4,128 patients with heart failure and a preserved left ventricular ejection fraction of at least 45%, irbesartan did not improve primary or secondary outcomes, investigators from the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE) report (pp. 2456-7). The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause (heart failure, myocardial infarction, unstable angina, arrhythmia, or stroke), and results showed: ìDuring a mean follow-up of 49.5 months, the primary outcome occurred in 742 patients in the irbesartan group and 763 in the placebo group. Primary event rates in the irbesartan and placebo groups were 100.4 and 105.4 per 1,000 patient–years, respectively (hazard ratio, 0.95; 95% confidence interval [CI], 0.86 to 1.05; P = 0.35). Overall rates of death were 52.6 and 52.3 per 1,000 patient–years, respectively (hazard ratio, 1.00; 95% CI, 0.88 to 1.14; P = 0.98). Rates of hospitalization for cardiovascular causes that contributed to the primary outcome were 70.6 and 74.3 per 1,000 patient–years, respectively (hazard ratio, 0.95; 95% CI, 0.85 to 1.08; P = 0.44). There were no significant differences in the other prespecified outcomes.î (B. M. Massie, barry.massie@va.gov)
Treatment of Hepatitis B, C: Two studies present evidence regarding treatment of patients with either hepatitis B or C. Among patients with chronic hepatitis C and advanced fibrosis who did not initially respond to peginterferon and ribavirin, long-term peginterferon therapy failed to reduce the rate of disease progression (pp. 2429-41; A. M. Di Bisceglie, dibiscam@slu.edu). During weeks 10–48 of two Phase III trials, tenofovir disoproxil fumarate 300 mg daily decreased viral markers better than did adefovir dipivoxil 10 mg (pp. 2442-55; F. Rousseau; frank.rousseau@gilead.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 5, 2008 * Vol. 15, No. 235
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Dec. issue of Diabetes Care (http://care.diabetesjournals.org/current.shtml; 2008; 31).
Efficacy, Safety of Alogliptin: The dipeptidyl peptidase-4 (DPP-4) inhibitor alogliptin safely provided efficacious lowering of glycemic markers among 329 drug-naive patients with poorly controlled type 2 diabetes, researchers report (pp. 2315-7). Comparing 12.5- and 25-mg daily doses of the drug with placebo over a 26-week period, the investigators found: ìAt week 26, mean change in A1C was significantly greater (P < 0.001) for 12.5 mg (–0.56%) and 25 mg (–0.59%) alogliptin than placebo (–0.02%). Reductions in fasting plasma glucose were also greater (P < 0.001) in alogliptin-treated patients than in those receiving placebo. Overall, incidences of adverse events (67.4–70.3%) and hypoglycemia (1.5–3.0%) were similar across treatment groups.î (R. A. DeFronzo, albarado@uthscsa.edu)

>>>Pharmacotherapy Report
Source:
Dec. issue of Pharmacotherapy (http://www.atypon-link.com/PPI/toc/phco/28/12; 2008; 28).
Lethal Injection for Capital Punishment: The legal basis and possibility of future changes in lethal injection as a means of capital punishment are reviewed (pp. 1429-36). ìLethal injection as a method of state-sanctioned capital punishment was initially proposed in the United States in 1977 and used for the first time in 1982,î the authors explain. ìMost lethal injection protocols use a sequential drug combination of sodium thiopental, pancuronium bromide, and potassium chloride. Lethal injection was originally introduced as a more humane form of execution compared with existing mechanical methods such as electrocution, toxic gassing, hanging, or firing squad. Lethal injection has not, however, been without controversy. Several states are considering whether lethal injection meets constitutional scrutiny forbidding cruel and unusual punishment. Recently in the case of Ralph Baze and Thomas C. Bowling, Petitioners, v John D. Rees, Commissioner, Kentucky Department of Corrections et al, the United States Supreme Court upheld the constitutionality of the lethal injection protocol as carried out in the Commonwealth of Kentucky. Most of the debate has surrounded the dosing and procedures used in lethal injection and whether the drug combinations and measures for administering the drugs truly produce a timely, pain-free, and fail-safe death. Many have also raised issues regarding the ‘medicalization’ of execution and the ethics of health care professionals’ participation in any part of the lethal injection process. As a result of all these issues, the future of lethal injection as a means of execution in the United States is under significant scrutiny. Outcomes of ongoing legislative and judicial reviews might result in cessation of lethal injection in totality or in alterations involving specific drug combinations or administration procedures.î (F. Romanelli, Froma2@uky.edu)
Patient’s Postsurgical Opioid Requirements: Opioid-tolerant patients undergoing total knee arthroplasty had significantly greater need for analgesics postoperatively yet experienced more pain, according to a 29-patient study (pp. 1453-60). Based on use of at least 30 mg of oral morphine equivalent in the week before surgery, 9 patients were classified as opioid tolerant. Comparing them with remaining 20 opioid-naive patients, the investigators found: ìPostoperative opioid consumption (in intravenous morphine equivalents) was significantly greater in the opioid-tolerant group than in the opioid-naive group in the [postanesthesia care unit] (median 56 vs 8.2 mg, p = 0.0013), during the first 24 hours after discharge from the PACU (108 vs 20.5 mg, p = 0.0004), and 24–48 hours after discharge from the PACU (152.3 vs 25 mg, p = 0.0001). Pain scores, assessed by using a verbal numeric scale from 0–10, were significantly greater in the opioid-tolerant group than in the opioid-naive group during the first 24 hours after discharge from the PACU (5.9 vs 4.1, p = 0.03). We observed no significant difference in pain scores during the other time periods studied. Sedation scores and adverse effects were similar between groups.î (B. L. Erstad, Erstad@pharmacy.arizona.edu)
ACCP Documents: ACCP publishes in this issue a white paper (p. 1547) and position statement (pp. 1548-51) on quality experiential education and a guideline on pharmacoeconomic and outcomes research fellowship training (p. 1552).

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 8, 2008 * Vol. 15, No. 236
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release articles from and Dec. 6 issue of Lancet (www.thelancet.com; 2008; 372).
Perioperative Beta-Blockers During Noncardiac Surgery: Contrary to the guidelines of the American College of Cardiology and American Heart Association, perioperative beta-blockers during noncardiac surgery provide little benefit, according to a meta-analysis of 33 trials of 12,306 patients (pp. 1962-76). The authors report: ìBeta blockers were not associated with any significant reduction in the risk of all-cause mortality, cardiovascular mortality, or heart failure, but were associated with a decrease (odds ratio [OR] 0.65, 95% CI 0.54—0.79) in non-fatal myocardial infarction (number needed to treat [NNT] 63) and decrease (OR 0.36, 0.26—0.50) in myocardial ischaemia (NNT 16) at the expense of an increase (OR 2.01, 1.27—3.68) in non-fatal strokes (number needed to harm [NNH] 293). The beneficial effects were driven mainly by trials with high risk of bias. For the safety outcomes, beta blockers were associated with a high risk of perioperative bradycardia requiring treatment (NNH 22), and perioperative hypotension requiring treatment (NNH 17). We recorded no increased risk of bronchospasm.î (F. H. Messerli, fmesserl@chpnet.org)
Carrageenan-Based Compound for HIV Prevention: Carraguard, a female-initiated carrageenan-based product, failed to prevent transmission of HIV in a randomized controlled study of 6,202 sexually active women aged 16 or older in South Africa (pp. 1977-87). In addition to condom use, participants were instructed to insert vaginally one applicatorful of Carraguard or a placebo methylcellulose preparation. After 2 years, these results were noted: ìHIV incidence was 3.3 per 100 woman–years (95% CI 2.8—3.9) in the Carraguard group (134 events) and 3.8 per 100 woman–years (95% CI 3.2—4.4) in the placebo group (151 events), with no significant difference in the distribution of time to seroconversion (p = 0.30). The covariate-adjusted hazard ratio was 0.87 (95% CI 0.69—1.09). Rates of self-reported gel use (96.2% Carraguard, 95.9% placebo) and condom use (64.1% in both groups) at last sex acts were similar in both groups. On the basis of applicator testing, however, gel was estimated to have been used in only 42.1% of sex acts, on average (41.1% Carraguard, 43.1% placebo). 1,420 (23%) women in the intention-to-treat population had adverse events (713 Carraguard, 707 placebo), and 95 (2%) women had adverse events that were related to gel use (48 Carraguard, 47 placebo). Serious adverse events occurred in 72 (2%) women in the Carraguard group and 78 (3%) in the placebo group, only one of which was considered possibly related to gel use (placebo group).î (B. Friedland, bfriedland@popcouncil.org)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2008; 337).
Hypersensitivity Reactions to Papillomavirus Vaccine: Analysis of the cases of 35 Australian schoolgirls who had suspected hypersensitivity reactions to human papillomavirus vaccine shows how infrequent such reactions are and that most patients were able to tolerate subsequent doses of the product (a2642). In a retrospective cohort study, researchers found these results at a point when 380,000 doses of the vaccine had been administered in Australian schools: ìOf these 35 schoolgirls, 25 agreed to further evaluation. Twenty three (92%) experienced reactions after the first dose. Thirteen (52%) experienced urticaria or angio-oedema, and of these, two experienced anaphylaxis. Thirteen had generalised rash, one with angio-oedema. The median time to reaction was 90 minutes. Nineteen (76%) underwent skin testing with the quadrivalent vaccine: all were skin prick test negative and one was intradermal test positive. Eighteen (72%) were subsequently challenged with the quadrivalent vaccine and three (12%) elected to receive the bivalent vaccine. Seventeen tolerated the challenge and one reported limited urticaria four hours after the vaccine had been administered. Only three of the 25 schoolgirls were found to have probable hypersensitivity to the quadrivalent vaccine.î (S. Choo, sharon.choo@rch.org.au)

>>>PNN JournalWatch
* Dynamic Spread of Happiness in a Large Social Network: Longitudinal Analysis over 20 years in the Framingham Heart Study, in BMJ, 2008; a2338. Reprints: N. A. Christakis, christak@hcp.med.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 9, 2008 * Vol. 15, No. 237
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Dec. 8/22 issue of the Archives of Internal Medicine (http://archinte.ama-assn.org/current.dtl; 2008; 168).
Full- Versus Half-Doses of Influenza Vaccine: Among adults aged 18–49 years, administration of half-doses of influenza vaccine proved effective, leading researchers to conclude that this approach could be used during vaccine shortages (pp. 2405-14). The study’s primary outcome of noninferiority was a difference of less than 20% in the upper 95% confidence interval of the proportion of subjects with strain-specific hemagglutination inhibition antibody titers of 1:40 or higher after vaccination. Administration of full- or half-dose intramuscular trivalent inactivated vaccine (TIV) showed: ìAmong previously immunized subjects (N = 1114) receiving half- vs full-dose TIV (age, 18–49 years, n = 284 [half] and n = 274 [full]; and age 50-64 years, n = 276 [half] and n = 280 [full]), CIs for proportions of subjects with hemagglutination inhibition antibody titers of 1:40 or higher excluded substantial reduction for all antigens in the 18- to 49-year age group and for B/Shanghai/361/2002 (B) and A/Fujian/411/2002 (A/H3N2) in the 50- to 64-year age group. Geometric mean titer in the female 18- to 49-year age group exceeded male responses for all strains: responses to half-dose TIV that were comparable with male full-dose responses for A/New Caledonia/20/99 (A/H1N1) antigen, 25.4 (95% CI, 20.9–30.9) vs 25.6 (95% CI, 21.3–30.9); A/H3N2 antigen, 60.8 (95% CI, 50.8–72.7) vs 44.1 (95% CI, 37.6–51.8); and B antigen, 64.4 (95% CI, 53.9–76.9) vs 60.7 (95% CI, 51.4–71.7) (findings were similar for the 50- to 64-year age group). Some injection site and systemic reactions (myalgias and/or arthralgias [P < .05], headache [P < .001], and impact of fatigue [P < .05]) were significantly lower in men. The relative risk of medical visits and hospitalizations for influenza-like illnesses were similar in the half- and full-dose groups regardless of age.î (R. J. M. Engler, renata.engler@amedd.army.mil)
Commenting on this study, an editorialist questions whether administration of half-doses would be stretching the influenza vaccine supply or wasting it (pp. 2402-3): ìIn trying to stretch vaccine supplies to protect the largest number of persons, we must use care to not waste vaccine by using low doses, which will ultimately not be protective. This study clearly shows that half-dose TIV in young healthy women is a rational way to extend vaccine supply in times of critical shortage. Since a substantial number of health care workers fall into this category, the implications of these data are noteworthy. Caution should be used when considering a half-dose vaccine in older age groups, particularly in men because the titers of antibody achieved with a half-dose vaccine are diminished compared with standard-dose vaccine. Although the results of this study are useful and can provide a guide to extending the vaccine supply during periods of shortage, perhaps the real message of this study is that better methods of influenza vaccine production that are less prone to problems are clearly needed. Cell culture and recombinant vaccine–based production are needed, and the time has come to relegate the use of eggs back to the kitchen where they belong.î (A. R. Falsey,
ann.falsey@viahealth.org)
Electronic Formulary Decision Support & Medication Costs: Physicians using e-prescribing systems with formulary decision support (FDS) software were significantly more likely to prescribe tier 1 medications, resulting in substantial cost savings, researchers report (pp. 2433-9). Over an 18-month period ending on Mar. 31, 2005, a pre–post study with concurrent controls showed these results: ìMore than 1.5 million patients filled 17.4 million prescriptions during the study period. Multivariate models controlling for baseline differences between prescribers and for changes over time estimated that e-prescribing corresponded to a 3.3% increase (95% confidence interval, 2.7%–4.0%) in tier 1 prescribing. The proportion of prescriptions for tiers 2 and 3 (brand-name medications) decreased correspondingly. e-Prescriptions accounted for 20% of filled prescriptions in the intervention group. Based on average costs for private insurers, we estimated that e-prescribing with FDS at this rate could result in savings of $845,000 per 100,000 patients. Higher levels of e-prescribing use would increase these savings.î (M. A. Fischer, mfischer@partners.org)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 10, 2008 * Vol. 15, No. 238
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release articles and the Dec. 10 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Antioxidant Supplements: Two studies provide further evidence of the lack of efficacy of antioxidant supplements for cancer prevention, and an editorialist comments on the new evidence. The first trial, Physicians’ Health Study II, concludes that ìneither vitamin E nor C supplementation reduced the risk of prostate or total cancerî over a mean follow-up of 8.0 years (doi: 10.1001/jama.2008.862; J. M. Gaziano, jmgaziano@partners.org). Selenium and vitamin E failed to prevent prostate cancer in a population of 35,533 relatively healthy men, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) shows (doi: 10.1001/jama.2008.864; S. M. Lippman, slippman@mdanderson.org)
The editorialist discusses the various possible explanations for the variance in antioxidant studies over the years (doi: 10.1001/jama.2008.863): ìEpidemiology teaches that every statistical association has only 3 possible explanations: bias, chance, and cause. Regarding nutritional prevention of prostate cancer, first-generation phase 3 trials were too reliant on biased interpretation of prior research; second-generation trials may have been too reliant on chance; yet there is every reason to believe that the next generation will have a firmer basis for causal hypotheses. Until then, physicians should not recommend selenium or vitamin E—or any other antioxidant supplements—to their patients for preventing prostate cancer.î (P. H. Gann,
pgann@uic.edu)
Unintentional Pharmaceutical Overdose Fatalities: In West Virginia during 2006, most overdose deaths resulted from nonmedical use and diversion of pharmaceuticals—most of them opioid analgesics—according to a population-based, observational study (pp. 2613-20). ìOf 295 decedents, 198 (67.1%) were men and 271 (91.9%) were aged 18 through 54 years,î the researchers report. ìPharmaceutical diversion was associated with 186 (63.1%) deaths, while 63 (21.4%) were accompanied by evidence of doctor shopping. Prevalence of diversion was greatest among decedents aged 18 through 24 years and decreased across each successive age group. Having prescriptions for a controlled substance from 5 or more clinicians in the year prior to death was more common among women (30 [30.9%]) and decedents aged 35 through 44 years (23 [30.7%]) compared with men (33 [16.7%]) and other age groups (40 [18.2%]). Substance abuse indicators were identified in 279 decedents (94.6%), with nonmedical routes of exposure and illicit contributory drugs particularly prevalent among drug diverters. Multiple contributory substances were implicated in 234 deaths (79.3%). Opioid analgesics were taken by 275 decedents (93.2%), of whom only 122 (44.4%) had ever been prescribed these drugs.î (A. J. Hall, ajhall@cdc.gov)
Editorialists provide advice for clinicians to stem the tide of such unintentional deaths, including several suggestions relevant to pharmacists (pp. 2672-3): ìWhen deciding whether to prescribe an opioid, physicians should ask patients about their prior and current histories of alcohol and other drug use. Patients with histories of substance use, mental health problems, or both should receive special attention and comanagement from pain management specialists when possible. Treatment of mental health disorders should be considered part of successful pain management.
ìPhysicians also should consider an opioid treatment agreement (contract) with the patient stipulating the frequency of obtaining medications, timely refills but no early replacements for lost prescriptions, safe storage, no sharing, single-source prescribing, monitoring through urine screens, and adherence to monitoring visits. The agreement should be presented as a way of simultaneously protecting the patient from adverse events and promoting a collaborative, responsible relationship.î (A. T. McLellan,
tmclellan@tresearch.org)

>>>PNN NewsWatch
* One lot of Hospira’s 20 meq Potassium Chloride in 5% Dextrose and 0.45% Sodium Chloride Injection, USP, in 1,000 mL flexible plastic containers is being recalled (lot 65-620-FW, exp. date May 1, 2010, NDC 0409-7902-09). A small number of the containers may be incorrectly labeled with a bar code for 5% Dextrose Injection, USP.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 11, 2008 * Vol. 15, No. 239
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 11 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Malaria Vaccine: Two research articles and an editorial describe progress in development of a vaccine against malaria.
The malaria vaccine RTS,S, which targets the organism’s circumsporozoite protein, showed promise in a trial of children aged 5–17 months of ag (pp. 2521-32). A previous study had combined the vaccine with the AS02A adjuvant system, and this combination showed a 30% rate of protection, the authors note. In the current study, use of a more immunogenic adjuvant system, AS01E, yielded these results: ìA total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P < 0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P < 0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P < 0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria.î (P. Bejon,
pbejon@kilifi.kemri-wellcome.org)
In a Phase 2B study of 340 infants, RTS,S/AS02D ìhad a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection,î researchers report. (pp. 2533-44). These events were noted during a 9-month surveillance period: ìAt least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P = 0.01).î (S. Abdulla,
sabdulla@ihi.or.tz)
Describing these studies as ìa hopeful beginning for malaria vaccines,î editorialists write (pp. 2599-601): ìAs the RTS,S vaccine heads into phase 3 trials in 2009, large areas across Africa still have moderate-to-intense malaria transmission. Malaria transmission of yet higher intensity, with greater and more continuous assault by mosquito-injected sporozoites, could affect the efficacy of this vaccine. This is the first malaria vaccine to reach this stage of development, and it will be essential to learn how it performs in areas of more intense transmission. Only then will we have a clear idea of what effect it will have on the well-being of children in Africa and elsewhere and its role in malaria control. It is, indeed, a hopeful beginning.î (W. E. Collins, CDC, Atlanta)
Combination Antimalarial Therapies: In a study of 2,802 febrile children in Papua New Guinea, artemether–lumefantrine was identified as the most effective regimen against Plasmodium falciparum and dihydroartemisinin–piperaquine as best against P. vivax (pp. 2545-57). A high rate of treatment failure with dihydroartemisinin–piperaquine against P. falciparum ìmay reflect cross-resistance between chloroquine and piperaquine,î report the investigators. ìThe highest rate of adequate clinical and parasitologic response for P. falciparum was in the artemether–lumefantrine group (95.2%), as compared with 81.5% in the chloroquine–sulfadoxine–pyrimethamine group (P = 0.003), 85.4% in the artesunate–sulfadoxine–pyrimethamine group (P = 0.02), and 88.0% in the dihydroartemisinin–piperaquine group (P = 0.06).î (T. M. E. Davis, tdavis@cyllene.uwa.edu.au)

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 12, 2008 * Vol. 15, No. 240
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Dec. 9 issue of the Journal of the American College of Cardiology (http://content.nejm.org/current.shtml; 2008; 359).
Vitamin D Deficiency as Cardiovascular Risk Factor: A highly prevalent condition found in 30–50% of the population, vitamin D deficiency is an important and treatable cardiovascular risk factor, authors of a review article write (pp. 1949-56): ìA growing body of data suggests that low 25-hydroxyvitamin D levels may adversely affect cardiovascular health. Vitamin D deficiency activates the renin–angiotensin–aldosterone system and can predispose to hypertension and left ventricular hypertrophy. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. Epidemiologic studies have associated low 25-hydroxyvitamin D levels with coronary risk factors and adverse cardiovascular outcomes. Vitamin D supplementation is simple, safe, and inexpensive. Large randomized controlled trials are needed to firmly establish the relevance of vitamin D status to cardiovascular health. In the meanwhile, monitoring serum 25-hydroxyvitamin D levels and correction of vitamin D deficiency is indicated for optimization of musculoskeletal and general health.î (J. H. O’Keefe, jhokeefe@cc-pc.com)
Poor Thienopyridine Responders & Drug Metabolism:
Provision of an active metabolite (AM) improves poor responders’ pharmacodynamic response to thienopyridines, a research study reports (pp. 1968-77). Among 100 aspirin-treated patients with coronary artery disease (some of whom also had diabetes), clopidogrel 600 mg loading dose and 75 mg maintenance dose or prasugrel 60 mg LD/10 mg MD were administered, with these results: ìThe proportion of patients with poor responsiveness was greater in the clopidogrel group for all definitions at all time points from 1 h to 29 days. Poor responders had significantly lower plasma AM levels compared with responders. Patients with diabetes were over-represented in the poor-responder groups and had significantly lower levels of AM. Platelets of both poor responders and diabetic patients responded fully to AM added ex vivo.î (D. Erlinge, david.erlinge@med.lu.se)
High-Dose Adenosine & Myocardial Perfusion Reserve:
A study explores the antagonism of adenosine receptors by caffeine from coffee and addresses ways of overcoming this effect in myocardial perfusion scintigraphy using high-dose adenosine (pp. 2008-16). Researchers identified these effects on adenosine-induced hyperemia among 30 patients before and after coffee ingestion: ìCaffeine reduced the magnitude of perfusion abnormality induced by standard adenosine as measured by the summed difference score (SDS) (12.0 ± 4.4 at baseline vs. 4.1 ± 2.1 after caffeine, p < 0.001) as well as defect size (18% [3% to 38%] vs. 8% [0% to 22%], p < 0.01), whereas it had no effect on the abnormalities caused by high-dose adenosine (SDS, 7.7 ± 4.0 at baseline vs. 7.8 ± 4.2 after caffeine, p = 0.7). There was good agreement between baseline and caffeine studies for segmental defect category (kappa = 0.72, 95% confidence interval: 0.65 to 0.79) in the high-dose group. An increase in adenosine after caffeine intake was well tolerated.î (E. Reyes, e.reyes@rbht.nhs.uk)

>>>PNN NewsWatch
* FDA yesterday issued a warning about acute phosphate nephropathy associated with the use of oral sodium phosphate products (OSP) for bowel cleansing before colonoscopy or other procedures. Prescription products such as Visicol and OsmoPrep and nonprescription products such as Fleet Phospho-soda have produced serious adverse events, sometimes in patients without identifiable renal risk factors, FDA cautioned. The agency is requiring manufacturers of the two prescription products to add boxed warnings to their labeling.
* Use of combination products that include
long-acting beta-agonists for asthma was supported by an FDA advisory panel in voting yesterday, but the group concluded that the risk–benefit relationships for single-ingredient products with LABAs was unfavorable and that labeling for such products should be revised. FDA staff must make the final call on what actions to take regarding these agents; they generally follow recommendations of advisory panels.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 15, 2008 * Vol. 15, No. 241
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 13 issue of Lancet (www.thelancet.com; 2008; 372).
Universal Childhood Immunization: Progress is being made toward universal immunization for diphtheria, tetanus, and pertussis vaccine (DTP3) throughout the world, but the ultimate goal remains elusive, according to an analysis of surveys and administrative data in 193 countries for the 1986–2006 timeframe (pp. 2031-46). ìCrude coverage of DTP3 based on surveys increased from 59% (95% uncertainty interval 51—65) in 1986 to 65% (60—68) in 1990, 70% (65—74) in 2000, and 74% (70—77) in 2006,î the investigators write. ìThere were substantial differences between officially reported and survey-based coverage during [Universal Childhood Immunisation]. [Global Alliance on Vaccines and Immunisations (GAVI)] [immunisation services support (ISS)] significantly increased the difference between officially reported coverage and survey coverage. Up to 2006, in 51 countries receiving GAVI ISS payments, 7.4 million (5.7 million to 9.2 million) additional children were immunised with DTP3 based on surveys compared with officially reported estimates of 13.9 million. On the basis of the number of additional children immunised from surveys at a rate of US$20 each, GAVI ISS payments are estimated at $150 million (115 million to 184 million) compared with actual disbursements of $290 million.î (C. J. L. Murray, cjlm@u.washington.edu)
Right to Health Care: Marking the 60th anniversary of the Universal Declaration of Human Rights, authors describe how this document ìlaid the foundations for the right to the highest attainable standard of healthî (pp. 2047-85): ìThis right is central to the creation of equitable health systems. We identify some of the right-to-health features of health systems, such as a comprehensive national health plan, and propose 72 indicators that reflect some of these features. We collect globally processed data on these indicators for 194 countries and national data for Ecuador, Mozambique, Peru, Romania, and Sweden. Globally processed data were not available for 18 indicators for any country, suggesting that organisations that obtain such data give insufficient attention to the right-to-health features of health systems. Where they are available, the indicators show where health systems need to be improved to better realise the right to health. We provide recommendations for governments, international bodies, civil-society organisations, and other institutions and suggest that these indicators and data, although not perfect, provide a basis for the monitoring of health systems and the progressive realisation of the right to health. Right-to-health features are not just good management, justice, or humanitarianism, they are obligations under human-rights law.î (G. Backman, gunillabackman@yahoo.com)

>>>BMJ Highlights
Source:
Early-release article from BMJ (www.bmj.org; 2008; 337).
Prescribing Exercise: Prescribing exercise programs for 1,089 women at 17 primary care practices in New Zealand increased physical activity but also upped the number of falls and injuries, researchers report (a2509). Concluding that the data support this intervention, the investigators provide these details about the 24-month study: ìAt baseline, 10% of intervention participants and 11% of control participants were achieving 150 minutes of at least moderate intensity physical activity a week. At 12 months rates increased to 43% and 30% and at 24 months to 39.3% and 32.8% (P < 0.001), respectively. SF-36 physical functioning (P = 0.03) and mental health (P < 0.05) scores improved more in intervention compared with control participants, but role physical scores were significantly lower (P < 0.01). There were no significant differences in clinical outcomes. More falls (P<0.001) and injuries (P = 0.03) were recorded in the intervention group.î (B. Lawton, Bev.Lawton@otago.ac.nz)

>>>PNN JournalWatch
* Intravenous Immunoglobulin: Adverse Reactions and Management, in Journal of Allergy and Clinical Immunology, 2008; 122: 1238–9. Reprints: F. A. Bonilla.
* Emerging Pharmacotherapies for COPD, in
Chest, 2008; 134: 1278–86. Reprints: P. J. Barnes, p.j.barnes@imperial.ac.uk
* Technical Review of Polysomnography, in
Chest, 2008; 134: 1310–9. Reprints: B. V. Vaughn, vaughnb@glial.med.unc.edu
* Challenges to the Therapeutic Pipeline for Irritable Bowel Syndrome: End Points and Regulatory Hurdles, in
Gastroenterology, 2008; 135: 1877–91. Reprints: M. Camilleri, camilleri.michael@mayo.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 16, 2008 * Vol. 15, No. 242
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Dec. 16 issue of the Annals of Internal Medicine (www.annals.org/current.shtml; 2008; 149).
Hospitalizations During Medicaid Coverage Interruptions: Hospitalizations for conditions normally handled on an ambulatory basis were common among 4.7 million Californians when their Medicaid coverage was interrupted, researchers report (pp. 854-60). In a retrospective cohort study, analysis of patients’ health care needs in 1998–2002 showed these trends: ìSixty-two percent of Medicaid beneficiaries experienced at least 1 interruption in coverage during the study period. The 3 most common ambulatory care–sensitive conditions resulting in a hospitalization were heart failure, diabetes, and chronic obstructive pulmonary disease. Interruptions in coverage were associated with a higher risk for hospitalization for an ambulatory care–sensitive condition (adjusted hazard ratio, 3.66 [95% CI, 3.59 to 3.72]; P < 0.001). In subgroup analyses, the association between interrupted coverage and hospitalization was stronger for beneficiaries eligible through the Temporary Aid to Needy Families program (adjusted hazard ratio, 8.56 [CI, 8.06 to 9.08]) than for beneficiaries eligible through the Supplemental Security Income program (adjusted hazard ratio, 1.72 [CI, 1.67 to 1.76]), who typically retain Medicare coverage even when their Medicaid coverage is interrupted.î (A. B. Bindman, abindman@medsfgh.ucsf.edu)
Home Rehab for COPD: Provision of rehabilitative services in the homes of patients with chronic obstructive pulmonary disease provides outcomes equivalent to those of outpatient care, a study shows (pp. 869-78). At 10 Canadian medical centers, 252 with moderate or severe COPD completed a 4-week educational program, after which they were randomly assigned to home or outpatient rehabilitation for 8 weeks. Results showed: ìBoth interventions produced similar improvements in the Chronic Respiratory Questionnaire dyspnea subscale at 1 year: improvement in dyspnea of 0.62 (95% CI, 0.43 to 0.80) units in the home intervention (n = 107) and 0.46 (CI, 0.28 to 0.64) units in the outpatient intervention (n = 109). The difference between the 2 treatments at 1 year was small and clinically unimportant. The 95% CI of the difference did not exceed the prespecified noninferiority margin of 0.5: difference in dyspnea score of 0.16 (CI, –0.08 to 0.40). Most adverse events were related to COPD exacerbations. No serious adverse event was considered to be related to the study intervention.î (F. Maltais, francois.maltais@med.ulaval.ca)
Detecting Unhealthy Alcohol Use: Three questions may not be enough to detect unhealthy alcohol use in patients, according to a review of 14 studies (pp. 879-88). Combining data on trials that compared the 10-item Alcohol Use Disorders Identification Test (AUDIT) with the 3-item AUDIT-C, the researchers found better results with the longer form in detecting risky drinking, alcohol use disorders, or unhealthy alcohol use (L. Kriston, levente.kriston@uniklinik-freiburg.de)

>>>PNN NewsWatch
* FDA has approved fenofibric acid delayed-release capsules (Trilipix, Abbott) for use along with diet or a statin to help lower triglycerides and LDL cholesterol, and to raise HDL cholesterol in patients with lipid problems. In a news release, Abbott notes that fenofibric acid is the first and only fibrate to be approved for use in combination with a statin. Fenofibric acid was studied in 2,698 patients with mixed dyslipidemia. These 12-week studies demonstrated that fenofibric acid used in combination with statins helped patients manage all three key lipids better than the corresponding therapies alone. The most common adverse effects with fenofibric acid include headache, heartburn, nausea, muscle aches, and increases in muscle or liver enzymes. Fenofibric acid should not be taken by people with liver, gallbladder, or severe kidney disease, nursing mothers, or those allergic to any product ingredient. Unexplained muscle pain, tenderness, or weakness may be a sign of a serious side effect and should be reported to a health care provider right away. Rarely, muscle-related problems can cause kidney damage. These side effects may be increased when fenofibric acid is used with a statin. Patients should contact their health care provider if they experience abdominal pain, nausea, or vomiting while taking fenofibric acid.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 17, 2008 * Vol. 15, No. 243
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 17 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Evidence-Based Feeding Guidelines: Implementation of an evidence-based nutritional support guideline promoted earlier feeding and greater nutritional adequacy, but clinical outcomes were not altered significantly at 27 community and tertiary hospitals in Australia and New Zealand (pp. 2731-41). Among 1,118 critically ill patients who were expected to remain in intensive care for at least 2 more days at baseline, these trends were observed for those management under the guideline or usual care: ìGuideline and control ICUs enrolled 561 and 557 patients, respectively. Guideline ICUs fed patients earlier (0.75 vs 1.37 mean days to enteral nutrition start; difference, –0.62 [95% confidence interval {CI}, –0.82 to –0.36]; P < .001 and 1.04 vs 1.40 mean days to parenteral nutrition start; difference, –0.35 [95% CI, –0.61 to –0.01]; P = .04) and achieved caloric goals more often (6.10 vs 5.02 mean days per 10 fed patient–days; difference, 1.07 [95% CI, 0.12 to 2.22]; P = .03). Guideline and control ICUs did not differ with regard to hospital discharge mortality (28.9% vs 27.4%; difference, 1.4% [95% CI, –6.3% to 12.0%]; P = .75) or to hospital length of stay (24.2 vs 24.3 days; difference, –0.08 [95% CI, –3.8 to 4.4]; P = .97) or ICU length of stay (9.1 vs 9.9 days; difference, –0.86 [95% CI, –2.6 to 1.3]; P = .42).î (G. S. Doig, gdoig@med.usyd.edu.au)
Smoking and Colorectal Cancer: A significant association between smoking and colorectal cancer incidence and mortality is established based on a meta-analysis of 106 observational studies (pp. 2765-78): ìTwenty-six studies provided adjusted risk estimates for ever smokers vs never smokers, leading to a pooled relative risk of 1.18 (95% confidence interval [CI], 1.11-1.25). Smoking was associated with an absolute risk increase of 10.8 cases per 100,000 person–years (95% CI, 7.9-13.6). We found a statistically significant dose-relationship with an increasing number of pack–years and cigarettes per day. However, the association was statistically significant only after 30 years of smoking. Seventeen cohort studies were included in the analysis of mortality. The pooled risk estimate for ever vs never smokers was 1.25 (95% CI, 1.14–1.37). Smoking was associated with an absolute risk increase of 6.0 deaths per 100,000 person–years (95% CI, 4.2–7.6).î (E. Botteri, edoardo.botteri@ieo.it)

>>>PNN NewsWatch
* Fospropofol disodium injection (Lusedra, Eisai) has been approved by FDA for use during monitored anesthesia care sedation in adult patients undergoing diagnostic or therapeutic procedures. A scheduling decision for the controlled substance is pending at DEA. The water-soluble prodrug is converted in the body by alkaline phosphatase to propofol.
* Recommendations from an
I.V. Safety Summit convened in summer 2008 by ASHP are published in the December 15 issue of the American Journal of Health-System Pharmacy. Actions recommended to be taken within the next 1–3 years include: universally standardizing concentrations of ìhigh-alertî i.v. medications (those most likely to cause harm if an error occurs) for all patients, including highly vulnerable patients, such as elderly, newborns, and those with chronic medical conditions; streamlining the process to bring ready-to-administer standardized infusion concentrations to market; using ìintelligentî i.v. pumps (e.g., those with safety features that help prevent unsafe rates and doses); making the business case for i.v. safety to hospital leadership; and establishing multidisciplinary medication safety committees in hospitals to address the prevention of i.v. medication errors.
* An NABP/U. Florida study, commissioned by
FDA, shows that nearly all consumers receive written drug information with their new prescription medications, but the quality of the information falls short of the level called for in a 1996 law. The failure opens the door for FDA to replace the current voluntary system with a federally defined effort. In the legislation, Congress had called for 95% of consumers to receive useful medication information by 2006. The study showed that 94% of consumers received information with new prescriptions but that only 75% of the pamphlets met minimum criteria for usefulness as defined by a panel of stakeholders. FDA is calling for comments and will host a public meeting on the issue in early 2009.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 18, 2008 * Vol. 15, No. 244
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 18 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
Alfuzosin Effectiveness: In a study of men who had not previously received treatment with an alpha-adrenergic antagonist, alfuzosin failed to reduce the symptoms of chronic prostatitis–chronic pelvic pain syndrome, researchers report (pp. 2663-73). During 12 weeks of treatment with alfuzosin 10 mg daily or placebo, these results were recorded: ìA total of 272 eligible participants underwent randomization, and in both study groups, 49.3% of participants had a decrease of at least 4 points in their total [National Institutes of Health Chronic Prostatitis Symptom Index] score (rate difference associated with alfuzosin, 0.1%; 95% confidence interval, –11.2 to 11.0; P = 0.99). In addition, a global response assessment showed similar response rates at 12 weeks: 33.6% in the placebo group and 34.8% in the alfuzosin group (P = 0.90). The rates of adverse events in the two groups were also similar.î (J. C. Nickel, jcn@queensu.ca)
Contaminated Heparin Reactions: An epidemiologic study links 152 adverse reactions in 113 patients to administration of heparin contaminated with oversulfated chondroitin sulfate (pp. 2674-84). ìThe use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P < 0.001),î the researchers write of the late 2007–early 2008 outbreak. ìVials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin.î (P. R. Patel, ppatel@cdc.gov)

>>>PNN NewsWatch
* Plerixafor injection (Mozobil, Genzyme) has been approved by FDA for use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). In pivotal studies of the orphan drug, 59% of patients with NHL who received plerixafor and G-CSF collected the target number of at least 5 million stems cells/kg of body weight in four or fewer apheresis sessions compared with 20% of placebo patients. Prescribing physicians and patients should be aware of the potential for tumor cell mobilization in leukemia patients, increased circulating leukocytes and decreased platelet counts, splenic enlargement, and fetal harm when administered to pregnant women. The most common adverse reactions, reported in 10% or more of patients and exceeding the reported rate in patients on placebo, were diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness, and vomiting.
* The first
face transplant performed in the U.S., which took place this week at the Cleveland Clinic, involved replacement of 80% of the patient’s face. Maria Siemionow, MD, PhD, led a multidisciplinary team, which included a pharmacist who was on the dais with the team at a news conference on Wednesday, during the 22-hour procedure.
* Manufacturers developing
new drugs and biologics for type 2 diabetes should provide evidence that the therapy will not increase the risk of such cardiovascular events as myocardial infarction, especially when the drugs are used by patients of advanced age or by those with advanced diabetes or renal impairment, FDA maintains in a new guidance released yesterday. The recommendation is part of a new guidance for industry that applies to all antidiabetic medications currently under development; it will be published in tomorrow’s Federal Register. The guidance, which FDA said benefited from suggestions provided in a July 2008 meeting of the endocrine advisory panel, is effective immediately.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 19, 2008 * Vol. 15, No. 245
Providing news and information about medications and their proper use

>>>Psychiatry Highlights
Source:
Dec. issue of the American Journal of Psychiatry (http://ajp.psychiatryonline.org/; 2008; 165).
Sleep Disturbance & Depression: Among community-dwelling elderly patients, sleep disturbance is an independent risk factor for recurrence of depression, a study shows (pp. 1543-50). The investigators recommend a two-step strategy for identifying at-risk patients, with assessment for prior depressive episodes along with inquiries about difficulties in sleeping. The study included 145 persons with a history of major or nonmajor depression in full remission and 206 without a prior history of depression or any mental illness. Results showed: ìTwenty-three subjects (16.9%) with prior depression developed depressive episodes during follow-up, compared to only one person in the group without prior mental illness (0.5%). Within the group with prior depression, depression recurrence was predicted by sleep disturbance, and this association was independent of other depressive symptoms, chronic medical disease, and antidepressant medication use.î (M. R. Irwin, mirwin1@ucla.edu)
Melatonin & Depression During and After Pregnancy: Disturbances in melatonin may be connected to pregnancy and postpartum depression, according to a study 25 pregnant and 24 postpartum women (pp. 1551-8). Researchers demonstrated lower plasma nocturnal melatonin concentrations among pregnant women with depression but higher levels among postpartum women with the condition, as noted in the results: ìMorning melatonin levels from 2:00 a.m. to 11:00 a.m. were significantly lower in pregnant women with major depression relative to healthy pregnant women. However, these levels were significantly higher in postpartum women with major depression across time intervals relative to postpartum healthy women. Pregnant but not postpartum women with a personal or family history of depression, regardless of their current diagnosis, had significantly earlier melatonin synthesis and baseline offset times relative to women without a family history of depression. In pregnant healthy women but not pregnant women with major depression, melatonin levels increased during the course of pregnancy. This association was not found among postpartum women with major depression or postpartum healthy women.î (B. L. Parry, bparry@ucsd.edu)

>>>Pediatrics Highlights
Source:
Dec. issue of Pediatrics (http://pediatrics.aappublications.org/current.shtml; 2008; 122).
Children Taking Asthma Meds on Own: Self-administration of controller medications for asthma by children is assessed in a telephone survey of 351 parents, and the investigators conclude that ìclinicians may need to screen for child daily controller-medication management and include even young children when educating families on the use of asthma medications and other key asthma-management tasksî (e1186-92). ìChild daily controller-medication responsibility increased with age,î the authors write. ìBy age 7, children had assumed, on average, almost 20% of daily controller-medication responsibility; by age 11, 50%; by age 15, 75%; and by age 19, 100%. In multivariate models, child age and male gender remained significantly associated with child daily controller-medication responsibility, and child’s age and parents’ race/ethnicity remained significantly associated with daily controller-medication adherence.î (J. K. Orrell–Valente, joan.valente@ucsf.edu)
Childhood Poisoning Cases: Even when toxic substances are in child-resistant packaging, the products should be kept out of the reach of children, according to researchers who analyze data on 86,194 unintentional product-related poisonings among young children presenting to U.S. emergency departments in 2004 (pp. 1244-51): ìApproximately 70% of the poisonings involved children 1 or 2 years of age, slightly more than one half involved boys, and 13.3% resulted in hospital admission. Approximately 59.5% of the poisonings involved oral prescription drugs, oral nonprescription drugs, or supplements. Other major product categories resulting in poisonings included cleaning products (13.2%), drugs and ointment preparations intended for external use (4.9%), and personal care products (4.7%). Approximately 54.7% of the poisonings involved products already subject to child-resistant packaging requirements under the Poison Prevention Packaging Act.î (G. B. Rodgers, grodgers@cpsc.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 22, 2008 * Vol. 15, No. 246
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 20 issue of Lancet (www.thelancet.com; 2008; 372).
Telcagepant for Acute Migraine: Compared with zolmitriptan 5 mg, telcagepant 300 mg was effective for acute treatment of migraine and produced fewer adverse effects, according to results of an 81-center study conducted in Europe and the U.S. (pp. 2115-23). Moderate or severe migraine attacks in 1,380 patients were treated randomly with one of two doses of telcagepant or zolmitriptan, with these results: ìTelcagepant 300 mg was more effective than placebo for pain freedom (95 [27%] of 353 patients vs 33 [10%] of 343 [p < 0.0001]), pain relief (194 [55%] of 353 vs 95 [28%] of 343 [p < 0.0001]), and absences of phonophobia (204 [58%] of 353 vs 126 [37%] of 342 [p < 0.0001]), photophobia (180 [51%] of 353 vs 99 [29%] of 342 [p < 0.0001]), and nausea (229 [65%] of 352 vs 189 [55%] of 342 [p = 0.0061]). Efficacy of telcagepant 300 mg and zolmitriptan 5 mg were much the same, and both were more effective than telcagepant 150 mg. Adverse events were recorded for 31% taking telcagepant 150 mg, 37% taking telcagepant 300 mg, 51% taking zolmitriptan 5 mg, and 32% taking placebo.î (T. W. Ho, tony_ho@merck.com)
While the lower rate of adverse events of telcagepant ìmarks a new era in migraine therapy,î an editorialist writes that the site of action remains uncertain with calcitonin-gene-related peptide (CGRP) receptor antagonists (pp. 2089-90): ìThere are three potential targets: the intracranial blood vessels, parts of the trigeminal nerve, either at the peripheral or central ends, or the CNS, in several areas that include the trigeminal nucleus caudalis, periaqueductal grey matter, nucleus solitarius, amygdala, and the colliculiÖ. Ho’s data are intriguing because the clinical dose is high in view of the potency of telcagepant, which suggests a central antimigraine action within the CNS. While this new drug will be of value to clinicians, scientists will battle with these questions. Despite the use of triptans for two decades, their site of antimigraine effect remains debated. As for CGRP-receptor antagonists, the question will be whether inhibition of CGRP released peripherally from sensory nerves is sufficient for their antimigraine action, or is inhibition of CGRP acting centrally in brainstem trigeminal pain-relay nuclei of the brainstem or other nuclei also a key contributor to their clinical effectiveness?î (L. Edvinsson,
lars.edvinsson@med.lu.se)
Corticosteroids for Preterm Birth: Multiple courses of antenatal corticosteroids provide no advantage over single courses and are linked to decreased weight, length, and head circumference at birth, researchers report (pp. 2143-51). The study included 1,858 women at 25–32 weeks’ gestation who had not delivered 14–21 days after an initial course of corticosteroids. They were randomized to corticosteroid courses or placebo administered every 14 days until week 33 or deliver, with these results: ìInfants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2,216 g vs 2,330 g, p = 0.0026), were shorter (44.5 cm vs 45.4 cm, p < 0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p < 0.001).î (K. E. Murphy, kmurphy@mtsinai.on.ca)

>>>PNN JournalWatch
* Management of Low Back Pain, in BMJ, 2008; a2718. Reprints: S. P. Cohen, scohen40@jhmi.edu
* Coca-Cola Douches and Contraception, in
BMJ, 2008;a2873. Reprints: D. Anderson, eborah.Anderson@BMC.org">Deborah.Anderson@BMC.org
* Emerging Roles of Serine Proteinases in Tissue Turnover in Arthritis, in
Arthritis & Rheumatism, 2008; 58: 3644–56. Reprints: J. M. Milner, j.m.milner@ncl.ac.uk
* Cardiac Mechanics Revisited: The Relationship of Cardiac Architecture to Ventricular Function, in
Circulation, 2008; 118: 2571–87. Reprints: G. D. Buckberg, gbuckberg@mednet.ucla.edu
* Tuberculosis and Illicit Drug Use: Review and Update, in
Clinical Infectious Diseases, 2009; 48: 72–82. Reprints: R. S. Garfein, rgarfein@ucsd.edu
* Immune Reconstitution Inflammatory Syndrome: A Reappraisal, in
Clinical Infectious Diseases, 2009; 48: 101–7. Reprints: M. French, martyn.french@health.wa.gov.au
* The Effect of Transitioning to Medicare Part D Drug Coverage in Seniors Dually Eligible for Medicare and Medicaid, in
Journal of the American Geriatrics Society, 2008; 56: 2304–10. Reprints: W. Shrank, wshrank@partners.org

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 23, 2008 * Vol. 15, No. 247
Providing news and information about medications and their proper use

>>>Neurology Highlights
Source:
Dec. 9 issue of Neurology (www.neurology.org/current.shtml; 2008; 71).
Interferon-Beta Nonresponders: Interferon-alpha/beta receptor (IFNAR)-2 isoforms are important regulators of the responsiveness to endogenous and systemically administered interferon beta (IFN-beta), researchers conclude, showing a dual agonistic and antagonistic action that influences both the magnitude and the nature of the biologic response to IFN-beta (pp. 1940-7). In 141 patients on short- or long-term treatment with IFN-beta, data were gathered on IFNAR-1 and -2 isoforms and on anti-IFN-beta neutralizing antibodies (NAbs), as follows: ìPretreatment levels of IFNAR-2 in patients were lower overall than in controls (p = 0.038), and high levels correlated with greater bioactivity. Upon prolonged treatment, NAb-negative patients displayed a state of decreased transmembrane IFNAR-2 expression (p 0.025), whereas levels of soluble IFNAR-2 were slightly increased (p < 0.0001). The presence of NAbs reversed these effects (p 0.0056). In NAb-positive patients, pretreatment expression levels of both transmembrane IFNAR-2 isoforms were significantly lower than in NAb-negative patients (p 0.0089).î (F. Gilli, neurobiologia@sanluigi.piemonte.it)
An editorialist describes these findings as important in the search for a way of identifying IFN-beta nonresponders early in therapy for multiple sclerosis (pp. 1936-7): ìCurrently, alternative therapies to IFN-beta exist and, therefore, it would be of great importance to identify potential IFN-beta nonresponders before or soon after start of therapy in order to facilitate rational evidence-based therapeutic decisions. While development of NAbs remains the best validated factor for IFN-beta nonresponsiveness, the observations of Gilli et al. are yet another piece of evidence that fits into the pattern that depicts the responsiveness to IFN-beta. The ultimate goal would be, before initiation of immunomodulatory therapy, to be able to outline all biomarkers of treatment efficacy necessary to tailor the optimal therapy for the single patient with MS.î (P. S. Sorensen,
pss@rh.dk)

>>>Nephrology Highlights
Source:
Jan. issue of the American Journal of Kidney Diseases (www.ajkd.org/current; 2009; 53).
Adding Steroids to ACE Inhibitor Treatment of IgA Nephropathy: A small study provides evidence of benefit with combination treatment of IgA nephropathy using steroids plus cilazapril, compared with the ACE inhibitor alone (pp. 26-32). Describing outcomes based on a primary end point of kidney survival (50% increase in baseline serum creatinine level) among 63 patients who were randomized to one of two treatment groups, the investigators write: ìAfter follow-up for up to 48 months, 7 patients in the ACE-inhibitor group (24.1%) reached the primary end point compared with 1 patient (3%) in the combination group. Kaplan–Meier kidney survival was significantly better in the combination group than the ACE-inhibitor group after 24 and 36 months (96.6% versus 75.7%, 96.6% versus 66.2%; P = 0.001). Urine protein excretion significantly decreased in patients in the combination group compared with the ACE-inhibitor group (time-average proteinuria, 1.04 ± 0.54 versus 1.57 ± 0.86 g/d of protein; P = 0.01). Multivariate analysis showed that combination treatment (hazard ratio, 0.1; 95% confidence interval, 0.014 to 0.946) and time-average proteinuria (hazard ratio, 14.3; 95% confidence interval, 2.86 to 71.92) were independent predictors of kidney survival.î (H. Zhang, hongzh@bjmu.edu.cn)
N-Acetylcysteine After Major Surgery: Evidence is lacking on use of N-acetylcysteine perioperatively to improve mortality or renal outcomes when radiocontrast is not used, a meta-analysis of 10 studies concludes (pp. 33-40): ìN-Acetylcysteine use was not associated with a decrease in mortality (OR, 1.05; 95% CI, 0.58 to 1.92), acute renal failure requiring dialysis (OR, 1.04; 95% CI, 0.45 to 2.37), incremental increase in serum creatinine concentration greater than 25% above baseline (OR, 0.84; 95% CI, 0.64 to 1.11), or length of intensive care unit stay (WMD in days, 0.46; 95% CI, −0.43 to 1.36). N-Acetylcysteine did not appear to increase the risk of surgical reexploration for bleeding (OR, 1.16; 95% CI, 0.57 to 2.38) or amount of allogeneic blood transfusion required (WMD in units, 0.31; 95% CI, −0.21 to 0.84).î (K. M. Ho, kwok.ho@health.wa.gov.au)

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 24, 2008 * Vol. 15, No. 248
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 24/31 issue of JAMA (http://jama.ama-assn.org/current.dtl; 2008; 300).
Americans’ Medication/Dietary Supplement Use: One in 25 Americans is at risk for a major drug–drug interaction, according to medication and dietary supplement usage data compiled for 3,500 community-dwelling Americans aged 57–85 years (pp. 2867-78). Based on in-home interviews, including medication logs for those agents used regularly (ìlike every day or every weekîWinking, administered between June 2005 and March 2006, the researchers note: ìThe unweighted survey response rate was 74.8% (weighted response rate, 75.5%). Eighty-one percent (95% confidence interval [CI], 79.4%–83.5%) used at least 1 prescription medication, 42% (95% CI, 39.7%–44.8%) used at least 1 over-the-counter medication, and 49% (95% CI, 46.2%–52.7%) used a dietary supplement. Twenty-nine percent (95% CI, 26.6%–30.6%) used at least 5 prescription medications concurrently; this was highest among men (37.1%; 95% CI, 31.7%–42.4%) and women (36.0%; 95% CI, 30.2%–41.9%) aged 75 to 85 years. Among prescription medication users, concurrent use of over-the-counter medications was 46% (95% CI, 43.4%–49.1%) and concurrent use of dietary supplements was 52% (95% CI, 48.8%–55.5%). Overall, 4% of individuals were potentially at risk of having a major drug–drug interaction; half of these involved the use of nonprescription medications. These regimens were most prevalent among men in the oldest age group (10%; 95% CI, 6.4%–13.7%) and nearly half involved anticoagulants. No contraindicated concurrent drug use was identified.î (D. M. Qato, dqato@babies.bsd.uchicago.edu)
The Power of Hope: In a holiday message to readers, JAMA Editor Catherine D. DeAngelis writes with her physician–husband about the need for physicians to care for patients in a way that generates hope (pp. 2919-20): ìPersonal care begins with establishing a sense of hope for the patient and seeking to maintain that sense throughout the course of treatment. For patients, that means a hopeful prognosis; a promise that something can be done for their illness; that they will be actively involved in their treatment; or knowledge that hospice care may provide solace for their last days if their illness is terminal.
ìHope begins with sincere emotional engagement with a physician who addresses the patient’s fears. The human nervous system has evolved to allow for hope. With hope, sleep is restorative, easing daytime fears as emotion is modulated while dreaming, allowing for waking more refreshed and alert to the challenges of a new day.î

>>>PNN NewsWatch
* FDA has approved once-yearly zoledronic acid injection (Reclast, Novartis) for treatment to increase bone mass in men with osteoporosis. The approval was based on data from a 2-year, double-blind, head-to-head trial comparing zoledronic acid injection with oral weekly bisphosphonate therapy in more than 300 men with osteoporosis. Zoledronic acid increased lumbar spine bone mineral density by 6.1% over 2 years and was noninferior to the active control.
*
FDA is alerting consumers nationwide not to purchase or consume more than 25 different products (listed on the agency’s website) marketed for weight loss because they contain undeclared active pharmaceutical ingredients such as sibutramine, rimonabant, phenytoin, and phenolphthalein. FDA advises consumers who have used any of these products to stop taking them and consult their health care professional immediately.
*
Imatinib mesylate (Gleevec, Novartis) has been approved by FDA for the postsurgery treatment of adult patients following complete surgical removal of Kit (CD117)-positive gastrointestinal stromal tumors (GIST). The efficacy of imatinib was established in a clinical trial in which patients received either imatinib or a placebo for 1 year after surgical removal of the tumor. The optimal treatment duration is not known. There were significantly fewer recurrences of GIST in patients receiving imatinib than in patients who did not. The most frequently reported adverse reactions were diarrhea, fatigue, nausea, swelling of the feet, decreased red blood cell counts, rash, vomiting, and abdominal pain.
*
PNN will not be published on Dec. 25–26, Christmas, and Jan. 1–2, New Year’s.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 29, 2008 * Vol. 15, No. 249
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (www.bmj.org; 2008; 337).
OTC Oral Contraceptives: Authors debate the wisdom of a pilot project in London that is making oral contraceptives available to women without a prescription.
Arguing that this is a good idea, the first writer notes that prescription-related barriers are a common cause of women running out of pills and having unplanned pregnancies as a result (a3044). He concludes: ìThe prescription requirement is an out of date, paternalistic barrier to contraceptive use that is not evidence based. If governments are committed to addressing the challenge of unintended pregnancy—and the related problem of maternal mortality in the developing world, health systems must create mechanisms to allow freer access to hormonal contraception for all women at low or no cost.î (D. Grossman,
Grossman@ibisreproductivehealth.org">DGrossman@ibisreproductivehealth.org)
Long-acting contraceptives and a strong physician–patient relationship would provide a better answer, counters an opponent, who maintains (a3056): ìThe availability of emergency contraception without prescription has done little to change the rate of teenage pregnancies. This is hardly surprising, when among under 25s, only 37% use emergency contraception on every occasion that they have unprotected intercourse. Increased uptake of reliable, non user-dependent methods has to be the key. Rather than making a potentially unreliable method of contraception more easily available, our best avenue for reducing unplanned pregnancies is to encourage general practitioners to help their patients to make the best choices.î (S. Jarvis,
Sarah.jarvis@gp-e85016.nhs.uk)

>>>NEJM Highlights
Source:
Dec. 25 issue of the New England Journal of Medicine (http://content.nejm.org/current.shtml; 2008; 359).
CBT, Sertraline for Childhood Anxiety: The combination of cognitive behavioral therapy plus sertraline provided the best responses among 488 children and adolescents with separation anxiety disorder, generalized anxiety disorder, or social phobia (pp. 2753-66). In a 12-week trial, 14 sessions of CBT, sertraline in doses of up to 200 mg/day, both, or neither yielded these outcomes: ìThe percentages of children who were rated as very much or much improved on the Clinician Global Impression–Improvement scale were 80.7% for combination therapy (P < 0.001), 59.7% for cognitive behavioral therapy (P < 0.001), and 54.9% for sertraline (P < 0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P < 0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline.î (J. T. Walkup, Johns Hopkins Med. Inst., Baltimore)

>>>PNN NewsWatch
* A single lot of Ethex’s hydromorphone hydrochloride 2 mg tablets (lot 90219, expires 03/2010) has been recalled because of potential for oversized tablets. Parent company KV Pharmaceutical has advised FDA that it is voluntarily suspending shipments of all of its FDA-approved drug products in tablet form as a precaution until manufacturing issues are addressed.

>>>PNN JournalWatch
* Oh, What a Year It Was: A Look Back at Medicine in 2008, in Lancet, 2008; 372: 2087. Reprints: Lancet Editors.
* Cytochrome P-450 Polymorphisms and Response to Clopidogrel, in
New England Journal of Medicine, 2009; early release. Reprints: J. L. Mega, jmega@partners.org
* Genetic Determinants of Response to Clopidogrel and Cardiovascular Events, in
New England Journal of Medicine, 2009; early release. Reprints: T. Simon, tabassome.simon@sat.aphp.fr
* Azathioprine or Methotrexate Maintenance for ANCA-Associated Vasculitis, in
New England Journal of Medicine, 2008; 359: 2790–803. Reprints: C. Pagnoux, christian.pagnoux@cch.aphp.fr
* Surprised by Hope, in
Journal of Clinical Oncology, 2008; 26: 6001–2. Reprints: P. A. Francis, prue.francis@petermac.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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 30, 2008 * Vol. 15, No. 250
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Jan. issue of Diabetes Care (http://care.diabetesjournals.org/content/vol32/issue1/; 2009; 32).
Patient Beliefs & Medication Use: In a study of patients on antihyperglycemic and antihypertensive medications living in an economically distressed area, those who were younger, African American, or of low health literacy were concerned about medication harmfulness, and this was associated with medication underuse and higher blood pressure (pp. 19-24). The researchers found these trends among 803 patients on antihyperglycemic medications and 573 individuals on antihypertensive drugs: ìAfter correction for multiple analyses, multivariate models indicated that perceived need for antihyperglycemic medication was associated with being younger, being prescribed insulin, and being prescribed multiple medications. Concern about antihyperglycemic medications was associated with being younger, African American, dissatisfied with information received about medication, and of low health literacy. For antihypertensives, perceived necessity was associated with having numerous medical comorbidities and being dissatisfied with medication information; concern was associated with being younger, dissatisfied with information received about medication, and of low health literacy. Up to one-half of patients underused at least one of the types of medication; many of these patients attributed this underuse to cost. For both types of medications, concern was significantly associated with both cost-related and non–cost-related underuse, and antihypertensive concern was associated with higher SBP and DBP.î (J. E. Aikens, aikensj@umich.edu)

>>>Medical Care Highlights
Source:
Jan. issue of Medical Care (http://www.lww-medicalcare.com/pt/re/medcare/currenttoc.htm; 2009; 47).
Pharmacy Interventions for Refill Persistence: Neither of two pharmacist interventions improved refill persistence among 3,048 patients with chronic diseases, researchers report (pp. 32-40). At nine pharmacies located in a South Carolina grocery chain, pharmacists either telephoned the patient, contacted the prescriber by facsimile, or provided usual care. The investigators made these observations in discussing their study results: ìThe study demonstrated that neither of the pharmacist-initiated interventions had a significant positive impact on encouraging overdue patients to refill prescriptions for chronic diseases. There was no significant impact on patients’ time-to-refill for prescriptions for their index chronic disease; nor was there any significant impact on patients filling a prescription for their index chronic disease within 30 or 60 days of their index date, or filling any prescription within 30 days of their index date. Overall, the directionality of the parameter estimates suggested that Usual Care may actually be superior to the Phone Patient and fax Physician interventions. In fact, one post hoc analysis indicated that patients in the Usual Care arm had significantly shorter time-to-refills than patients in the Fax Physician arm. Although this finding was not consistent across all analyses, it does raise concern that the Fax Physician arm may be inferior to Usual Care.î (P. J. Nietert, nieterpj@musc.edu)

>>>PNN NewsWatch
* FDA has approved degarelix for injection 80 and 120 mg (Ferring Pharmaceuticals) for treatment of prostate cancer. The gonadotropin releasing hormone (GnRH) receptor inhibitor is intended to treat men with advanced prostate cancer. The efficacy of degarelix was established in a clinical trial in which patients with prostate cancer received either degarelix or leuprolide. Degarelix treatment did not cause the temporary increase in testosterone that is seen with some other drugs that affect GnRH receptors. In fact, FDA noted in a news release that nearly all of the patients on either drug had suppression of testosterone to levels seen with surgical removal of the testes. The most frequently reported adverse reactions in the clinical study included injection site reactions (pain, redness, and swelling), hot flushes, increased weight, fatigue, and increases in hepatic enzymes.
*
Gadofosveset trisodium last week became the first agent approved by FDA for use in patients undergoing magnetic resonance angiography (MRA). The agent is indicated for use during MRA to evaluate aortoiliac occlusive disease in adults with known or suspected peripheral vascular disease.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.

PNN Pharmacotherapy Line
Dec. 31, 2008 * Vol. 15, No. 251
Providing news and information about medications and their proper use

>>>PNN’s Top 10 for 2008
From the election of the first American president of African descent to a deepening economic crisis, 2008 certainly has the markings of a historic year. For those concerned with the use of medications in people, the year was also noteworthy, with signs of change—both positive and troublesome—on many fronts.
1. Health Care Reform as the Population Ages: Both Barack Obama and John McCain promised to do something about America’s fractured health care system (Sept. 25, Oct. 16, 22), and this challenge looms for the 111th Congress and the incoming Democratic administration. Current discussion centers on building a new system based on a medical home for patients (Aug. 20, Sept. 18), but people wonder whether any primary care physicians (Nov. 13) and enough health professionals of all types will be available to address the needs of an aging baby-boom generation (Apr. 17).
2. New Drugs, Old Drugs: FDA approved a large number of new chemical/biologic entities this year, but other than progress in the antiretroviral arena (Jan. 22), most were for orphan diseases or were prodrugs and me-too versions of existing agents. Instead, clinical medicine was more focused this year on fine-tuning the use of older agents, including ezetimibe, erythropoiesis-stimulating agents, and varenicline (Jan 3, 16; Feb. 4, 27; Mar. 13, Aug. 1, Sept. 3).
3. Pharmacogenetics Demanding Attention: For such fine-tuning of the use of currently marketed drugs, pharmacogenetics is clearly the next great tool. With reports in the media that medications are ineffective or dangerous about half the time for the patients who take them, the demand will grow louder for better use of available and emerging knowledge about genes and drugs such as warfarin, abacavir, antidyslipidemic agents, clopidogrel, and cetuximab (Jan. 23, Feb. 1, 5, 7, 11 Mar. 6, 10; May 20; June 4; July 25; Aug. 21; Sept. 5; Oct. 23, 24; Dec. 23, 30).
4. Safety of Drug Supply: The story of contaminated heparin finding its way from family farms in China to patients’ veins in the U.S. (Feb. 12, 14, 29; Mar. 6, 7, 20, 25; Apr. 22, 24; Jun. 5; Nov. 7) certainly proved that business as usual is over in the pharmaceutical industry. Combined with an unprecedented number of warnings issued by FDA for everything from adverse drug reactions to claims that some aspirin products were illegally marketed, the integrity of the drug-supply chain was in question.
5. FDA Facing Reality: The federal agency designated to protect Americans from unsafe drug products reacted to the contaminated heparin and other such stories by admitting that it is in dire need of reform (Mar. 4). Critics criticized, bureaucrats reacted, and professionals and patients wondered just how FDA can be recreated in 21st century mode (Feb. 21, 27; Mar. 27, 30; Apr. 4, 24; June 5; July 8, 10, 11; Sept. 24; Dec. 17).
6. Dietary Supplements Gain, Falter: The news for herbals was largely negative this year (June 11, for example), but vitamin therapy had a more mixed record. Antioxidants and B vitamins did not always prove beneficial, but studies on vitamin D showed a wide variety of benefits (Aug. 19, Dec. 12).
7. Pharmacists’ MTM Services: Medication therapy management continued to be pharmacy’s buzzword in 2008, and studies in both pharmacy and medical journals showed pharmacists could help with hypertension (June 25, Nov. 25,) diabetes (Apr. 1), statin conversion (May 2), and adverse drug reactions in nursing homes (May 23). But barriers remain, writers warned (Oct. 29).
8. Vaccines Still Key: Many pharmacists have built MTM practices on immunization services, and that looked like a great idea this year, as evidence emerged for everything from transdermal patches for travelers diarrhea (June 16) to hypertension (Mar. 10).
9. Improving Adherence, Persistence: Another area for pharmacists’ focus has been in helping patients get on and stay on their prescribed medications (Apr. 23, May 19, June 9, Aug. 29, Dec. 2).
10. E-prescribing: Increasing and improving the electronic interface between prescribers and pharmacies completes the Top 10 list. Technology can be used to decrease some types of errors (July 10) and keep formulary choices in front of physicians within networks (Dec. 9).

>>>PNN NewsWatch
* PNN will not be published on Jan. 1–2, New Year’s holidays.

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 © 2008, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN.