Dec 2009

PNN Quarterly File—Fourth Quarter 2009

PNN Pharmacotherapy Line
Oct. 1, 2009 * Vol. 16, No. 189
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 1 issue of the New England Journal of Medicine (2009; 361).
Cardiac-Resynchronization Therapy for Preventing Heart-Failure Events: Use of cardiac-resynchronization therapy (CRT), combined with biventricular pacing using an implantable cardioverter–defibrillator (ICD), decreases the risk of heart-failure events in relatively asymptomatic patients, compared with the ICD alone, a study shows (pp. 1329–38). Researchers assigned 1,820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms, to CRT plus ICD or ICD alone. These results were noted: “During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT–ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT–ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P = 0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups.” (A. J. Moss, heartajm@heart.rochester.edu)
Treatment for Mild Gestational Diabetes: Dietary intervention, self-monitoring of blood glucose, and as-needed insulin therapy failed to reduce some complications in a group of women with mild gestational diabetes, but the intervention did produce fewer cases of fetal overgrowth, shoulder dystocia, cesarean delivery, and hypertensive disorders, researchers report (pp. 1339–48). Comparing usual prenatal care with the intervention, the study found these changes in a composite primary outcome of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma: “A total of 958 women were randomly assigned to a study group—485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; P = 0.14). There were no perinatal deaths. However, there were significant reductions with treatment as compared with usual care in several prespecified secondary outcomes, including mean birth weight (3,302 vs. 3,408 g), neonatal fat mass (427 vs. 464 g), the frequency of large-for-gestational-age infants (7.1% vs. 14.5%), birth weight greater than 4000 g (5.9% vs. 14.3%), shoulder dystocia (1.5% vs. 4.0%), and cesarean delivery (26.9% vs. 33.8%). Treatment of gestational diabetes mellitus, as compared with usual care, was also associated with reduced rates of preeclampsia and gestational hypertension (combined rates for the two conditions, 8.6% vs. 13.6%; P = 0.01).” (Landon at mark.landon@osumc.edu)

>>>PNN NewsWatch
* Tackling the challenge of getting prescribers and patients to pay more attention to a growing number of warnings and precautions about medications, FDA yesterday issued its Strategic Plan for Risk Communication. The plan outlines the agency’s efforts to disseminate more meaningful public health information and lays out a framework for providing information to professionals and consumers in the “form they need it and when they need it, and for how the agency oversees industry communications,” FDA said. The plan also defines three key areas—FDA’s science base, its operational capacity, and its policy and processes—in which strategic actions can help improve the FDA’s communication about the risks and benefits of regulated products. More than 70 specific actions were listed for FDA to take over the next 5 years, including 14 for the coming year. In a related move, FDA also yesterday issued its first draft guidance for Risk Evaluation and Mitigation Strategies, or REMS, which are required for certain drugs or biologics.

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 © 2009, 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, 2009 * Vol. 16, No. 190
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Oct. issue of Diabetes Care (2009; 32).
Insulin for Weight Loss in Cystic Fibrosis: Chronic weight loss associated with cystic fibrosis–related diabetes without fasting hyperglycemia (CFRD FH&minusWinking can be reversed using insulin therapy, researchers report (pp. 1783–8). A 1-year trial compared premeal insulin aspart, repaglinide, and oral placebo, with these results: “One hundred adult patients were enrolled. Eighty-one completed the study, including 61 with CFRD FH− and 20 with severely impaired glucose tolerance (IGT). During the year before therapy, BMI declined in all groups. Among the group with CFRD FH−, insulin-treated patients lost 0.30 ± 0.21 BMI units the year before therapy. After 1 year of insulin therapy, this pattern reversed, and they gained 0.39 ± 21 BMI units (P = 0.02). No significant change in the rate of BMI decline was seen in placebo-treated patients (P = 0.45). Repaglinide-treated patients had an initial significant BMI gain (0.53 ± 0.19 BMI units, P = 0.01), but this effect was not sustained. After 6 months of therapy they lost weight so that by 12 months there was no difference in the rate of BMI change during the study year compared with the year before (P = 0.33). Among patients with IGT, neither insulin nor repaglinide affected the rate of BMI decline. No significant differences were seen in the rate of lung function decline or the number of hospitalizations in any group.” (A. Moran, moran001@umn.edu)

>>>PNN NewsWatch
* Manufacturers of heparin for the U.S. market have begun using a new USP standard, FDA said yesterday, one that is expected to decrease the potency of the drug by about 10% and thereby result in a need for generally greater dosages of the drug. USP manufacturing controls took effect Oct. 1 for production, but FDA has asked that companies not ship this new product until Oct. 8, 2009, or later. The delay will give health care providers and facilities time to learn about the changes and to make adjustments to their pharmacy procedures and dosing practices. The changes adopted by USP for the heparin unit dose match the World Health Organization’s International Standard (IS) unit dose definition that has been in use in Europe for many years. The revised USP reference standard and unit definition for heparin is about 10% less potent than the former USP unit. FDA has asked all manufacturers to label their new products in a manner that will help health care providers differentiate them from the old products. Labels of heparin products from APP, Baxter, and B. Braun made according to the new standard will have an “N” in the lot number or following the expiration date. Products manufactured by Hospira can be identified by the number “82” or higher (e.g., 83, 84) at the start of their lot numbers.
* Many people who have died from
2009 H1N1 influenza in the U.S. had co-infections with Streptococcus pneumoniae that likely contributed to their deaths, according to a report published in today’s Morbidity and Mortality Weekly Report. Based on clinical characteristics of patients during initial phases of the pandemic in the spring, investigators did not find many cases of co-infections contributing to patient demise, but this report is reversing the assumption that co-infections are rare. “These findings confirm that bacterial lung infections are occurring among patients with fatal cases of 2009 pandemic influenza A (H1N1) and underscore both the importance of pneumococcal vaccination for persons at increased risk for pneumococcal pneumonia and the need for early recognition of bacterial pneumonia in persons with influenza,” the authors write. Clinical characteristics of 22 patients who died from H1N1 and who had histopathologic evidence of bacterial lung function are presented in the report, and 16 of 21 patients with information on past medical history showed that they had underlying medical conditions known to increase influenza-related complications or that were indications for the 23-valent pneumococcal vaccine. In other H1N1 news, CDC said yesterday that deliveries of the vaccine will begin on Tuesday. Only the intranasal formulation will be available initially, and most health care workers up to age 49 with no chronic conditions can use that product.

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 © 2009, 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. 5, 2009 * Vol. 16, No. 191
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 3 issue of Lancet (2009; 374).
Bivalirudin in Primary Angioplasty for STEMI: Bivalirudin reduced adverse clinical events and major bleeding at 1 year, compared with heparin plus a glycoprotein IIb/IIIa inhibitor (GPI), in patients with acute ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary interventions (pp. 1149–59). In the HORIZONS-AMI trial, these results were found for net and major adverse clinical events (NACE and MACE, respectively): “1-year data were available for 1,696 patients in the bivalirudin group and 1,702 patients in the control group. Reasons for participant dropout were loss to follow-up and withdrawal of consent. The rate of NACE was lower in the bivalirudin group than in the control group (15.6% vs 18.3%, hazard ratio [HR] 0.83, 95% CI 0.71—0.97, p = 0.022), as a result of a lower rate of major bleeding in the bivalirudin group (5.8% vs 9.2%, HR 0.61, 0.48—0.78, p < 0.0001). The rate of MACE was similar between groups (11.9% vs 11.9%, HR 1.00, 0.82—1.21, p = 0.98). The 1-year rates of cardiac mortality (2.1% vs 3.8%, HR 0.57, 0.38—0.84, p = 0.005) and all-cause mortality (3.5% vs 4.8%, HR 0.71, 0.51—0.98, p = 0.037) were lower in the bivalirudin group than in the control group.” (R. Mehran, rm2266@columbia.edu)
Tiotropium in COPD: In the Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) study, early treatment of chronic obstructive pulmonary disease was supported, as tiotropium appeared to improve lung function in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II disease (pp. 1171–8). In 2,739 participants with a mean age of 64 years, these results were noted in a comparison of once-daily tiotropium and placebo: “The rate of decline of mean postbronchodilator FEV1 was lower in the tiotropium group than in the control group (43 mL per year [SE 2] vs 49 mL per year [SE 2], p = 0.024). For prebronchodilator pulmonary function, 1221 patients in the tiotropium group and 1158 in the control group had three or more measurements and were included in the analysis. The rate of decline of mean prebronchodilator FEV1 did not differ between groups (35 mL per year [SE 2] vs 37 mL per year [SE 2]; p = 0.38). Health status, measured with the St George’s Respiratory Questionnaire, was better at all timepoints in the tiotropium group than in the control group (p ≤ 0.006 for all timepoints). Time to first exacerbation and time to exacerbation resulting in hospital admission were also longer in the tiotropium group than in the control group (hazard ratio 0.82, 95% CI 0.75—0.90, and 0.74, 0.62—0.88, respectively).” (M. Decramer, Marc.Decramer@uzleuven.be)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 339).
Varenicline & Suicidal Behavior: No significant association between varenicline use and self-harm behaviors was found in a cohort study of 80,660 adults who received smoking-cessation therapies in the U.K. between 2006 and 2008 (b3805). While acknowledging that the upper limit of the hazard ratio indicated a possible twofold increase in risk, the investigators noted these overall results of an analysis of the General Practice Research Database: “There was no clear evidence that varenicline was associated with an increased risk of fatal (n = 2) or non-fatal (n = 166) self harm, although a twofold increased risk cannot be ruled out on the basis of the upper limit of the 95% confidence interval. Compared with nicotine replacement products, the hazard ratio for self harm among people prescribed varenicline was 1.12 (95% CI 0.67 to 1.88), and it was 1.17 (0.59 to 2.32) for people prescribed bupropion. There was no evidence that varenicline was associated with an increased risk of depression (n = 2244) (hazard ratio 0.88 (0.77 to 1.00)) or suicidal thoughts (n = 37) (1.43 (0.53 to 3.85)).” (D. Gunnell, d.j.gunnell@bristol.ac.uk)

>>>PNN JournalWatch
* Is Combining or Alternating Antipyretic Therapy More Beneficial than Monotherapy for Febrile Children?, in BMJ, 2009; b3540. (M. Nabulsi, mn04@aub.edu.lb)
* Statin Therapy and Risk of Developing Type 2 Diabetes: A Meta-Analysis, in
Diabetes Care, 2009; 32: 1924–9. (S. Rajpathak, srajpath@aecom.yu.edu)
* Clinical Messages from the Treatment for Adolescents with Depression Study (TADS), in
American Journal of Psychiatry, 2009; 166: 1118–23. (J. S. March)

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 © 2009, 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, 2009 * Vol. 16, No. 192
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Oct. 6 issue of the Annals of Internal Medicine (2009; 151).
Extended-Duration Chemoprophylaxis Against Influenza: Use of neuraminidase inhibitors (NAIs) for prolonged time periods is a safe and effective way of preventing symptomatic influenza among immunocompetent white and Japanese adults, according to results of a systematic review (pp. 464–73). Extended-duration oseltamivir was associated with increased nausea and vomiting, the authors report, adding these details: “Of 1,876 potentially relevant citations, 7 trials involving 7,021 unique participants met inclusion criteria. Data were pooled by using random-effects models. Chemoprophylaxis with NAIs decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], –3.9 percentage points [CI, –5.8 to –1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, –0.4 percentage point [CI, –1.6 to 0.9 percentage point]). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, –0.2 to 0.4 percentage point]), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir.” (N. Khazeni)
A/H5N1 Influenza Pandemic Vaccination Strategies: Using a model to predict spread of avian influenza (A/H5N1), researchers find that expanded use of adjuvanted vaccines would be an effective and cost-effective means of containing a pandemic (early release). Expanded use of antiviral prophylaxis would delay the pandemic while additional strategies are being implemented, they add. Three strategies were compared: stockpiling of vaccination and antiviral drugs; an expanded prophylaxis strategy that combined the stockpiled strategy with expanded distribution of antiviral agents; and an expanded vaccination strategy that used stockpiled strategy plus adjuvanted vaccine. “Expanded vaccination was the most effective and cost-effective of the 3 strategies, averting 68% of infections and deaths and gaining 404,030 [quality-adjusted life-years (QALYs] at $10,844 per QALY gained relative to the stockpiled strategy,” the authors write. (N. Khazeni)
Early A/H1N1 Influenza Pandemic Vaccination Strategies: The advantages of early vaccination against influenza A/H1N1 include fewer deaths and lower costs, conclude researchers who used a compartmental model analysis to gauge the effects of vaccination in mid-October versus mid-November for a U.S. city of 8.3 million people (early release). Based on quality-adjusted life-years (QALYs) and other outcome measures, the investigators found these results using a societal perspective: “Assuming each primary infection causes 1.5 secondary infections, vaccinating 40% of the population in October or November would be cost-saving. Vaccination in October would avert 2,051 deaths, gain 69,679 QALYs, and save $469 million compared with no vaccination; vaccination in November would avert 1,468 deaths, gain 49,422 QALYs, and save $302 million.” Sensitivity analysis showed greater benefits if the pandemic peak were delayed by longer incubation periods, lower rates of infectiousness, or increased implementation of nonpharmaceutical interventions. (N. Khazeni)
Commenting on the utility of influenza forecasting with mathematical modeling as used in this and the above study, editorialists write (
early release): “Despite its limitations, the model demonstrates an important conclusion: The population health benefit of administering even a vaccine of low efficacy (50%) can be substantial if the proportion of the population receiving the vaccine is high. Although heightened public awareness of H1N1 this year and H5N1 in the last few years has increased attention to influenza, vaccination rates for seasonal influenza have been disappointing. Seasonal influenza kills more than 36,000 people every year, but fewer than 50% of high-risk adults aged 18 to 64 years received a vaccination last year. Health care professionals must take advantage of this heightened public awareness to educate and vaccinate a larger proportion of the population, not only for H1N1 this season, but especially for seasonal influenza, which has thus far killed far more people.” (S. M. Kansagra)

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 © 2009, 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, 2009 * Vol. 16, No. 193
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 7 issue of JAMA (2009; 302).
Supplements for Preventing Sepsis in Neonates: Among neonates with very low birth weights, lactoferrin/probiotic supplementation during the first 30–45 days of life reduced the incidence of first episodes of late-onset sepsis, compared with placebo, researchers report (pp. 1421–8). Bovine lactoferrin (BLF), alone or in combination with the probiotic Lactobacillus rhamnosus GG (LGG) yielded these results in 11 Italian tertiary neonatal intensive care units: “Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17–0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12–0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred.” (P. Manzoni, paolomanzoni@hotmail.com)
Pharmacogenetics of Tamoxifen in Breast Cancer: Presence of a pair of alleles in women with breast cancer predicted better outcomes during treatment with tamoxifen, according to a study of 1,325 patients in 1986–2005 (pp. 1429–36). Retrospective analysis plus genotyping tumor tissue or blood for CYP2D6 variants associated with reduced (*10, *41) or absent (*3, *4, *5) enzyme activity showed these patterns among women with extensive (n = 609), heterozygous extensive/intermediate (n = 637), or poor (n = 79) CYP2D6 metabolism: “Median follow-up was 6.3 years. At 9 years of follow-up, the recurrence rates were 14.9% for extensive metabolizers, 20.9% for heterozygous extensive/intermediate metabolizers, and 29.0% for poor metabolizers, and all-cause mortality rates were 16.7%, 18.0%, and 22.8%, respectively. Compared with extensive metabolizers, there was a significantly increased risk of recurrence for heterozygous extensive/intermediate metabolizers (time to recurrence adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.04-–1.90) and for poor metabolizers (time to recurrence HR, 1.90; 95% CI, 1.10–3.28). Compared with extensive metabolizers, those with decreased CYP2D6 activity (heterozygous extensive/intermediate and poor metabolism) had worse event-free survival (HR, 1.33; 95% CI, 1.06–1.68) and disease-free survival (HR, 1.29; 95% CI, 1.03–1.61), but there was no significant difference in overall survival (HR, 1.15; 95% CI, 0.88–1.51).” (H. Brauch, hiltrud.brauch@ikp-stuttgart.de)
National Public Insurance Assessments of Effectiveness: Both comparative effectiveness and cost-effectiveness can be used along with other factors by national public insurance programs to support decisions about drugs, authors of a research study conclude (pp. 1437–43). The bodies in Australia, Canada, and Great Britain—Common Drug Review (CDR) of Canada, National Institute for Health and Clinical Excellence (NICE) in Britain, and Pharmaceutical Benefits Advisory Committee (PBAC) of Australia—”face common issues with respect to the quality and strength of the experimental evidence in support of a clinically meaningful effect.” (B. J. Manns, braden.manns@albertahealthservices.ca)

>>>PNN NewsWatch
* This is Get Smart About Antibiotics Week, and the CDC has engaged pharmacists in educating consumers during this influenza season. CDC last week hosted its first-ever community pharmacy summit, bringing together Rite-Aid, Kroger, Giant Eagle, and Giant/Stop and Shop, and nonprofit and advocacy groups committed to decreasing the spread of antibiotic resistance and strengthening the important role of pharmacists in educating patients about remedies for colds and flu.
*
FDA has now approved 100 antiretroviral drugs for use in the President’s Emergency Plan for AIDS Relief, including 29 new products and 71 generic versions of existing agents. Under PEPFAR, FDA and other HHS agencies cooperate with the State Department’s Office of the U.S. Global AIDS Coordinator, U.S. Department of Defense, other federal agencies, host country governments, and many other international partners in an effort to support treatment of at least 3 million people, prevent 12 million new infections, and provide care for more than 12 million HIV-infected and affected people by 2013.

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 © 2009, 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, 2009 * Vol. 16, No. 194
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 8 issue of the New England Journal of Medicine (2009; 361).
MicroRNA Expression & Interferon Response: Expression patterns of microRNAs from liver tissue differ between men and women with hepatocellular carcinoma, and tumors with miR-26 expression were associated with lower survival but better responses to interferon alfa, researchers report (pp. 1437–47). Among three independent cohorts of 455 patients with hepatocellular carcinoma who had radical tumor resection between 1999 and 2003, microRNA expression was profiled in 241 of the patients, while survival and response to adjuvant interferon alfa was assessed in 214 patients. Results showed: “In patients with hepatocellular carcinoma, the expression of miR-26a and miR-26b in nontumor liver tissue was higher in women than in men. Tumors had reduced levels of miR-26 expression, as compared with paired noncancerous tissues, which indicated that the level of miR-26 expression was also associated with hepatocellular carcinoma. Moreover, tumors with reduced miR-26 expression had a distinct transcriptomic pattern, and analyses of gene networks revealed that activation of signaling pathways between nuclear factor B and interleukin-6 might play a role in tumor development. Patients whose tumors had low miR-26 expression had shorter overall survival but a better response to interferon therapy than did patients whose tumors had high expression of the microRNA.” (X. W. Wang, xw3u@nih.gov)
An editorialist writes of “micromanaging cancer” (
pp. 1500–1): “[Another] study … illustrates the potential promise of manipulating microRNA expression in cancer therapy. Because microRNAs suppress hundreds of genes to regulate whole programs of gene expression, it may be difficult for tumors to escape from the effect of microRNA drugs by mutating a few sequences. Since miR-26 is expressed by most normal cells, such replacement therapy is unlikely to be toxic to normal cells. The major obstacle to therapies that are based on RNA interference is delivering these oligonucleotides inside cells. Because of its filtering role, the liver traps and internalizes both small RNA drugs and gene-therapy viruses, making it an ideal testing ground for this new approach to treating cancer.” (J. Lieberman)
Doxycycline for Mansonella perstans Infection: In an open-label, randomized trial of patients with Mansonella perstans infection, doxycycline proved an effective treatment for eliminating microfilaremia (pp. 1448–58). Studying patients from Mali, some of whom also had Wuchereria bancrofti infection, investigators found: “At 12 months, 67 of 69 subjects who had received treatment with doxycycline only (97%) had no detectable M. perstans microfilariae per 60 mcL of blood, as compared with 10 of 63 subjects who had received no treatment (16%) (relative risk, 6.18; 95% confidence interval, 3.63 to 11.89; P < 0.001). At 36 months, M. perstans microfilaremia remained suppressed in 48 of 64 subjects who had received treatment with doxycycline only (75%), a finding that was consistent with a macrofilaricidal effect of doxycycline. Vomiting was more frequent in the doxycycline-treated group than in the untreated group (17% vs. 4%).” (A. D. Klion, aklion@nih.gov)
Baucus Brand of Health Care Reform: The health care reform bill introduced by Senate Finance Committee Chair Max Baucus (D-MT) succeeded in aggravating both the right and the left, but yesterday’s projection that the bill would cut the federal deficit over 10 years gave the measure an important boost. In this issue, Baucus’s political balancing act, especially regarding the public option, is recounted and prospects for passage assessed (e27): “Baucus’s proposal would require that as of 2013, all legal residents carry health insurance—or face an income-based financial penalty. Also beginning in 2013, small businesses and persons without access to employer-based coverage could purchase health benefits through new insurance exchanges, in which public subsidies would be provided to individuals and families with incomes between 133% and 400% of the federal poverty level. Instead of creating a public insurance option, the proposal would provide start-up funds to encourage the creation of nonprofit cooperative insurance plans that would be offered through the exchanges. This provision may not survive, however, because both Democratic and Republican members of the Finance Committee oppose it.” (J. K. Iglehart)

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 © 2009, 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, 2009 * Vol. 16, No. 195
Providing news and information about medications and their proper use

>>>Psychiatry Highlights
Source:
Oct. issue of the American Journal of Psychiatry (2009; 166).
Antidepressant Treatment of Adolescents: In the Treatment for Adolescents with Depression Study (TADS), long-term therapy with antidepressants improved measures of depression and suicidality among 327 patients aged 12–17 with major depressive disorder (pp. 1141–9). The findings from this 1-year naturalistic follow-up stand in contrast with those of short-term studies, about which increased suicidality has been a major concern over the past several years. Persistent benefits were evident among the 66% of eligible study participants who completed at least one assessment during this period. (TADS Team; J. March, john.march@duke.edu)
Binge Drinking in Older Adults: Middle-aged and older adults should be screened for binge drinking and concomitant use of other substances of abuse, conclude authors who analyzed 2005–06 data from the National Survey on Drug Use and Health (pp. 1162–9). In 10,953 respondents aged 50 or older, these results were noted: “Overall, 66% of male respondents and 55% of female respondents reported alcohol use during the past year. At-risk alcohol use and binge drinking were more frequent among respondents 50 to 64 years of age relative to respondents aged 65 years or older. In the 65 years old age group, 13% of men and 8% of women reported at-risk alcohol use, and more than 14% of men and 3% of women reported binge drinking. Among male subjects, binge drinking compared with no alcohol use was associated with higher income and being separated, divorced, or widowed, while being employed and nonmedical use of prescription drugs were associated with binge drinking compared with no alcohol use among women. For all respondents, binge drinking relative to no alcohol use was associated with the use of tobacco and illicit drugs. Among women who reported using alcohol, being African American and less educated were associated with binge drinking, but race/ethnicity and educational level were not associated with binge drinking in men who reported using alcohol.” (D. G. Blazer, blaze001@mc.duke.edu)

>>>Geriatrics Highlights
Source:
Oct. issue of the Journal of the American Geriatrics Society (2009; 57).
Effects of Alcohol Use on Mobility: Among 3,061 adults aged 70–79 without mobility disability at baseline, moderate alcohol use was associated with lower risks of functional decline over time, researchers report (pp. 1767–75). Lifestyle-related characteristics accounted for much of the association over the 6.5 years of follow-up, the group said, adding these details: “Adjusting for demographic characteristics, moderate alcohol intake was associated with lower risk of mobility limitation (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.55–0.89) and mobility disability (HR = 0.66, 95% CI = 0.45–0.95) than never or occasional consumption. Additional adjustment for lifestyle-related variables substantially reduced the strength of the associations (HR = 0.85, 95% CI = 0.66–1.08 and HR = 0.81, 95% CI = 0.56–1.18, respectively). Adjustment for diseases and health status indicators did not affect the strength of the associations, suggesting that lifestyle is most important in confounding this relationship.” (C. Maraldi, mrlcnz@unife.it)

>>>PNN NewsWatch
* The Senate Finance Committee will convene on Tuesday morning for the final vote on its health care reform bill. If approved by the panel, the legislation would become one of five bills that must be combined into House and Senate versions for floor votes. On pharmacist.com, APhA has provided links to background videos on how bills move through Congress and a diagram of the process, testimonials provided by pharmacists to Congress and the Obama administration, and an interactive map that shows state-by-state activity in medication therapy management.
* Patients are being immunized against seasonal
influenza in greater numbers this year than during past seasons, CDC is reporting. The agency will update numbers on cases and disease patterns in a media briefing later today. Thus far, most cases of influenza are testing positive for the novel A/H1N1 strain, whose vaccine is now reaching patients through local health departments and other providers.
*
PNN will not be published on Mon., Oct. 12, 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 © 2009, 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. 13, 2009 * Vol. 16, No. 196
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 339).
Cost-Effectiveness of Papillomavirus Vaccination in Boys: Inclusion of boys in routine human papillomavirus vaccination programs is not cost-effective from a societal perspective, conclude authors who analyzed cost per quality adjusted life year (QALY) gained for girls and boys aged 12 years in the U.S. (b3884). The study showed: “With 75% vaccination coverage and an assumption of complete, lifelong vaccine efficacy, routine HPV vaccination of 12 year old girls was consistently less than $50,000 per QALY gained compared with screening alone. Including preadolescent boys in a routine vaccination programme for preadolescent girls resulted in higher costs and benefits and generally had cost effectiveness ratios that exceeded $100,000 per QALY across a range of HPV related outcomes, scenarios for cervical cancer screening, and assumptions of vaccine efficacy and duration. Vaccinating both girls and boys fell below a willingness to pay threshold of $100,000 per QALY only under scenarios of high, lifelong vaccine efficacy against all HPV related diseases (including other non-cervical cancers and genital warts), or scenarios of lower efficacy with lower coverage or lower vaccine costs.” (J. J. Kim, jkim@hsph.harvard.edu)

>>>Lancet Highlights
Source:
Oct. 10 issue of Lancet (2009; 374).
Nortriptyline & Gabapentin for Neuropathic Pain: For treating neuropathic pain, the combination of nortriptyline plus gabapentin proved more efficacious than either drug alone, according to results of a Canadian study of 56 patients with diabetic polyneuropathy or postherpetic neuralgia (pp. 1252–61). In a crossover trial that used 6-week treatment periods, investigators found: “45 patients completed all three treatment periods; 47 patients completed at least two treatment periods and were analysed for the primary outcome. Mean daily pain (0–10; numerical rating scale) was 5.4 (95% CI 5.0 to 5.8) at baseline, and at maximum tolerated dose, pain was 3.2 (2.5 to 3.8) for gabapentin, 2.9 (2.4 to 3.4) for nortriptyline, and 2.3 (1.8 to 2.8) for combination treatment. Pain with combination treatment was significantly lower than with gabapentin (–0.9, 95% CI –1.4 to –0.3, p = 0.001) or nortriptyline alone (–0.6, 95% CI –1.1 to −0.1, p = 0.02). At maximum tolerated dose, the most common adverse event was dry mouth, which was significantly less frequent in patients on gabapentin than on nortriptyline (p < 0.0001) or combination treatment (p < 0.0001). No serious adverse events were recorded for any patients during the trial.” (I. Gilron, gilroni@queensu.ca)

>>>PNN NewsWatch
* C1-inhibitor (C1-INH) concentrate (Berinert, CSL Behring) has been approved by FDA for treatment of acute abdominal or facial attacks of hereditary angioedema (HAE). In the Phase II/III International Multi-center Prospective Angioedema C1-Inhibitor Trial (I.M.P.A.C.T.), C1-INH was effective and safe in rapidly treating acute abdominal and facial skin swellings in 124 adults and adolescents with HAE, with a median time to symptom relief of 30 minutes, compared with 1.5 hours with placebo. The most serious adverse reaction reported with the plasma-derived agents has been an increase in the severity of pain associated with HAE. The most common adverse reactions observed in more than 4% of patients receiving C1-INH were headache, abdominal pain, nausea, muscle spasms, pain, diarrhea, and vomiting.

>>>PNN JournalWatch
* Oestrogen plus Progestin and Lung Cancer in Postmenopausal Women (Women’s Health Initiative Trial): A Post-Hoc Analysis of a Randomised Controlled Trial, in Lancet, 2009; 374: 1243–51. (R. T. Chlebowski, rchlebowski@gmail.com)
* Statins for the Prevention and Treatment of Infections: A Systematic Review and Meta-analysis, in
Archives of Internal Medicine, 2009; 169: 1658–67. (I. M. Tleyjeh, tleyjeh.imad@mayo.edu)
* Thrombotic Events in Patients With Cancer Receiving Antiangiogenesis Agents, in
Journal of Clinical Oncology, 2009; 27: 4865–73. (M. Zangari, maurizio.zangari@hsc.utah.edu)
* Effect of the Management of Patients with Chronic Cough by Pulmonologists and Certified Respiratory Educators on Quality of Life: A Randomized Trial, in
Chest, 2009; 136: 1021–8. (S. K. Field, sfield@ucalgary.ca)
* Molecular Mechanisms of Combination Therapy with Inhaled Corticosteroids and Long-Acting Beta-Agonists, in
Chest, 2009; 136: 1095–100. (J. L. Black, judblack@med.usyd.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 © 2009, 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, 2009 * Vol. 16, No. 197
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release articles from JAMA (2009; 302).
H1N1 Influenza in Canada & Mexico: Two research reports, released in advance of print, detail experiences with 2009 A/H1N1 influenza viral infections in Canada and Mexico. These 28- and 90-day outcomes are reported for Canadian patients (doi:10.1001/jama.2009.1496): “Critical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2–7 days) and from hospitalization to ICU admission was 1 day (IQR, 0–2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao2 to fraction of inspired oxygen [Fio2] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6–20 days) and ICU stay was 12 days (IQR, 5–20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%–24.0%; n = 29).” (A. Kumar, akumar61@yahoo.com)
Results from Mexico showed a high frequency of critical illness in young people, with associated severe acute respiratory distress syndrome and shock, and a high case-fatality rate (
doi:10.1001/jama.2009.1536; R. Fowler, rob.fowler@sunnybrook.ca).
Editorialists write of how hospitals should be “preparing for the sickest patients with 2009 influenza A(H1N1)” (
doi:10.1001/jama.2009.1539): “The large proportion of critically ill patients with H1N1 [in the above reports] who survived is an important reminder that the medical response to a respiratory pandemic is very different today than it was for the 1918 influenza pandemic. The widespread availability of antibiotics, antiviral agents, vasopressors, and mechanical ventilation makes it possible to save many patients who would not have survived in 1918. With this potential comes an obligation for hospitals and public health systems to collaboratively develop strategies to ensure that, if there is a resurgence of 2009 influenza A(H1N1), the benefits of intensive care medicine can be offered to the maximum number of patients. Although guidelines and recommendations exist for augmenting hospital surge capacity, their implementation in individual hospitals is far from complete. The investigators from both Mexico and Canada noted that the health care systems struggled to meet the demands created by the increased patient volume, a sobering observation given that the absolute number of excess ICU admissions was modest.” (D. B. White, whitedb@upmc.edu)

>>>PNN NewsWatch
* Medication therapy management and other pharmacy-related provisions have survived the committee process as the nation debates health care reform. With yesterday’s passage of the fifth and final HCR bill in the Senate Finance Committee, the action now moves to merger of the various versions and floor debate, pharmacist.com reports.
* Four companies must cease marketing
unapproved codeine sulfate tablets, FDA announced yesterday. Warning letters have gone out to Lehigh Valley Technologies, Cerovene Inc., Dava International Inc., and Glenmark Generics Inc.
* McNeil Consumer Healthcare is working with
FDA and other officials to recover cases of two Tylenol products allegedly stolen from a Jacksonville (FL) Port Authority cargo terminal (lot 09XMC112 of Tylenol Arthritis Pain Caplets and lot 09XMC110 of Tylenol PM Caplets).

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 © 2009, 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, 2009 * Vol. 16, No. 198
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 15 issue of the New England Journal of Medicine (2009; 361).
Interleukin-2 Therapy in Patients with HIV Infection: Added to antiretroviral therapy, interleukin-2 therapy in patients with HIV infection yielded no clinical benefits in either of two studies despite producing a substantial, sustained increase in CD4+ cell count (pp. 1548–59). The trials were the Subcutaneous Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy (SILCAAT) study and the Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT). Patients in these studies had HIV and respective CD4+ cell counts of 50–299 or more than 300 cells/cu mm. Interleukin-2 cycles of 5 consecutive days administered every 8 weeks showed these effects: “In the SILCAAT study, 1,695 patients (849 receiving interleukin-2 plus antiretroviral therapy and 846 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 202 cells per cubic millimeter were enrolled; in ESPRIT, 4,111 patients (2,071 receiving interleukin-2 plus antiretroviral therapy and 2,040 receiving antiretroviral therapy alone) who had a median CD4+ cell count of 457 cells per cubic millimeter were enrolled. Over a median follow-up period of 7 to 8 years, the CD4+ cell count was higher in the interleukin-2 group than in the group receiving antiretroviral therapy alone—by 53 and 159 cells per cubic millimeter, on average, in the SILCAAT study and ESPRIT, respectively. Hazard ratios for opportunistic disease or death from any cause with interleukin-2 plus antiretroviral therapy (vs. antiretroviral therapy alone) were 0.91 (95% confidence interval [CI], 0.70 to 1.18; P = 0.47) in the SILCAAT study and 0.94 (95% CI, 0.75 to 1.16; P = 0.55) in ESPRIT. The hazard ratios for death from any cause and for grade 4 clinical events were 1.06 (P = 0.73) and 1.10 (P = 0.35), respectively, in the SILCAAT study and 0.90 (P = 0.42) and 1.23 (P = 0.003), respectively, in ESPRIT.” (J. D. Neaton, jim@ccbr.umn.edu)
Contaminated Dietary Supplements: Undisclosed amphetamines in a Brazilian dietary supplement cost a cop his job when they were detected on a drug screen, writes the author of a Perspective article (pp. 1523–5). Calling on Congress to correct the deficiencies in the 1994 Dietary Supplement Health and Education Act (DSHEA), the author reports: “Recent events involving dietary supplements marketed for weight loss, which have been consumed by an estimated 15% of U.S. adults, illustrate [a] growing problem. In July 2009, the FDA expanded its alert to include 75 tainted weight-loss products that contain undeclared medications. Analyses by the FDA have found the stimulant sibutramine in weight-loss supplements at levels amounting to three times the maximum recommended daily dose. Several of the unapproved anorectic ingredients detected in dietary supplements have been linked to serious adverse events: rimonabant to suicide and fenproporex to both addiction and suicide. The inclusion of furosemide and other diuretics in some of these supplements may result in dehydration and hypokalemia; other contaminants, such as benzodiazepines and antidepressants, mask the side effects of stimulants while conferring an increased risk of dependence. Some weight-loss pills, including many from Brazil, combine multiple medications in a single formulation.” (P. A. Cohen)

>>>PNN NewsWatch
* FDA yesterday launched a new page on its website for consumers on safe medication-disposal procedures. Other than high-potency opioids and select controlled substances for which the agency continues to recommend flushing down the sink or toilet, FDA advises consumers to discard other drug products in household trash after they are mixed with an unpalatable substance such as coffee grounds and sealing them in a bag or other container. Another option is to dispose of them through drug take back programs, when federal and state laws permit. FDA noted that all medicines listed on the site have disposal instructions in their professional prescribing information; this Web page provides clear instructions for consumers on whether a medicine should be flushed or disposed of in the trash.
* Following the death of a patient,
FDA has warned against reconstituting and administering zanamivir (Relenza, GlaxoSmithKline) by nebulizer or mechanical ventilator.

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 © 2009, 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, 2009 * Vol. 16, No. 199
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Oct. 20 issue of the Journal of the American College of Cardiology (2009; 54).
Genetic Variant Associated with Statin Adverse Effects: Mild adverse effects associated with statin therapy occurred more frequently in women and in those with a genetic variation in a clearance gene, researchers report (pp. 1609–16). In the STRENGTH (Statin Response Examined by Genetic Haplotype Markers) study, 509 participants received atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg followed by 80 mg, 80 mg, and 40 mg, respectively. Patients’ genomes were sequenced for CYP2D6, CYP2C8, CYP2C9, CYP3A4, and SLCO1B1 and seven reduced-function alleles for association with a composite adverse event (CAE) of any side effect, myalgia, or creatine kinase (CK) of more than 3 times the upper limit of normal. Results showed: “The CAE occurred in 99 subjects (54 discontinuations, 49 myalgias, and 9 CK elevations). Sex was associated with CAE (percent female in CAE vs. no CAE groups, 66% vs. 50%, p < 0.01). SLCO1B1*5 was associated with CAE (percent with ≥1 allele in CAE vs. no CAE groups, 37% vs. 25%, p = 0.03) and those with CAE with no significant CK elevation (p ≤ 0.03). Furthermore, there was evidence for a gene–dose effect (percent with CAE in those with 0, 1, or 2 alleles: 19%, 27%, and 50%, trend p = 0.01). Finally, the CAE risk appeared to be greatest in those carriers assigned to simvastatin.” (G. S. Ginsburg, geoffrey.ginsburg@duke.edu)

>>>Chest Highlights
Source:
Oct. issue of Chest (2009; 136).
Steroids in COPD: In a systematic review of studies of chronic obstructive pulmonary disorder, the combination of long-acting beta-agonists (LABAs) and inhaled corticosteroids (ICS) was beneficial but not enough to counter serious adverse effects, compared with LABAs alone, authors write (pp. 1029–38). Focusing on primary outcomes of COPD exacerbations and mortality, the investigators found: “Eighteen randomized controlled trials (12,446 participants) were selected. Therapy with LABAs/ICSs did not decrease the number of severe exacerbations (relative risk [RR], 0.91; 95% CI, 0.82 to 1.01; I2 = 1%), or all-cause mortality (RR, 0.90; 95% CI, 0.76 to 1.06; I2 = 0%), respiratory mortality (RR, 0.80; 95% CI, 0.61 to 1.05; I2 = 0%), and cardiovascular mortality (RR, 1.22; 95% CI, 0.88 to 1.71; I2 = 0%). To the contrary, the number of moderate exacerbations (RR, 0.84; 95% CI, 0.74 to 0.96; I2 = 50%) and the St. George respiratory questionnaire total score (weighted mean difference, −1.88; 95% CI, −2.44 to −1.33; I2 = 29%) were significantly reduced with LABA/ICS therapy. Although therapy with LABAs/ICSs increases FEV1 significantly (0.06 and 0.04 L, respectively), they were associated with an increased risk of pneumonia (RR, 1.63; 95% CI, 1.35 to 1.98; I2 = 20%).” (G. J. Rodrigo, gurodrig@adinet.com.uy)
Warfarin for Atrial Fibrillation in Patients on Dialysis: In a review article, authors assess the utility of warfarin anticoagulation for atrial fibrillation in patients on hemodialysis (pp. 1128–33): “Little evidence exists for patients with end-stage renal disease (ESRD) about whether the extrapolation of [general population] guidelines is appropriate. In patients with ESRD who are undergoing hemodialysis, the rates for both stroke and bleeding are 3 to 10 times higher than that for the general population. Furthermore, the proportion of hemorrhagic to ischemic strokes has increased, making the decision of whether to initiate anticoagulation problematic. In this commentary, we discuss the existing literature for stroke in atrial fibrillation, stroke type, risk reduction with anticoagulation, and bleeding risks in the hemodialysis population. We comment on validated risk stratification models of stroke prevention and bleeding and their applicability to patients undergoing hemodialysis. Finally, we recommend treatment strategies that are based on the existing state of knowledge.” (M. M. Sood, msood@sbgh.mb.ca)

>>>PNN NewsWatch
* FDA is warning consumers to use extreme care when purchasing any products over the Internet that claim to diagnose, prevent, treat, or cure the H1N1 influenza virus. The warning comes after the FDA recently purchased and analyzed several products represented online as oseltamivir (Tamiflu) that may pose risks to patients.

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 © 2009, 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. 19, 2009 * Vol. 16, No. 200
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 17 issue of Lancet (2009; 374).
Acetaminophen & Vaccinations: Antibody responses to vaccinations are reduced by prophylactic administration of acetaminophen, researchers report (pp. 1339–50). Two consecutive open-label trials of 459 healthy infants in the Czech Republic showed these effects of three prophylactic paracetamol (acetaminophen) doses in the first 24 hours after primary and booster pneumococcal vaccination versus no prophylaxis: “Fever greater than 39.5°C was uncommon in both groups (after primary: one of 226 participants [<1%] in prophylactic paracetamol group vs three of 233 [1%] in no prophylactic paracetamol group; after booster: three of 178 [2%] vs two of 172 [1%]). The percentage of children with temperature of 38°C or greater after at least one dose was significantly lower in the prophylactic paracetamol group (94/226 [42%] after primary vaccination and 64/178 [36%] after booster vaccination) than in the no prophylactic paracetamol group (154/233 [66%] after primary vaccination and 100/172 [58%] after booster vaccination). Antibody geometric mean concentrations (GMCs) were significantly lower in the prophylactic paracetamol group than in the no prophylactic paracetamol group after primary vaccination for all ten pneumococcal vaccine serotypes, protein D, antipolyribosyl-ribitol phosphate, antidiphtheria, antitetanus, and antipertactin. After boosting, lower antibody GMCs persisted in the prophylactic paracetamol group for antitetanus, protein D, and all pneumococcal serotypes apart from 19F.” (R. Prymula, prymula@pmfhk.cz)
Paclitaxel & Carboplatin for Advanced Ovarian Cancer: In a study of women with advanced epithelial ovarian cancer, dose-dense weekly paclitaxel plus carboplatin improves survival, compared with the conventional regimen (pp. 1331–8). Patients in Japan had stage II to IV epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer, and these results were noted using a primary endpoint of progression-free survival: “631 of the 637 enrolled patients were eligible for treatment and were included in the [intention to treat] population (dose-dense regimen, n = 312; conventional regimen, n = 319). Median progression-free survival was longer in the dose-dense treatment group (28.0 months, 95% CI 22.3—35.4) than in the conventional treatment group (17.2 months, 15.7—21.1; hazard ratio [HR] 0.71; 95% CI 0.58—0.88; p = 0.0015). Overall survival at 3 years was higher in the dose-dense regimen group (72.1%) than in the conventional treatment group (65.1%; HR 0.75, 0.57—0.98; p = 0.03). 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early. Reasons for participant dropout were balanced between the groups, apart from withdrawal because of toxicity, which was higher in the dose-dense regimen group than in the conventional regimen group (n = 113 vs n = 69). The most common adverse event was neutropenia (dose-dense regimen, 286 [92%] of 312; conventional regimen, 276 [88%] of 314). The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group (214 [69%]) than in the conventional treatment group (137 [44%]; p < 0.0001). The frequencies of other toxic effects were similar between groups.” (N. Katsumata, N. Katsumata, nkatsuma@ncc.go.jp)

>>>PNN NewsWatch
* Anaphylactic-type reactions, including fatalities, following parenteral administration of iron dextran injection are the focus of a recently added boxed warning in product labeling, according to FDA and American Regent.
* Indications for Merck’s
Gardasil have been expanded to include prevention of genital warts in boys and men ages 9–26.

>>>PNN JournalWatch
* Explaining the Rise in Antidepressant Prescribing: A Descriptive Study Using the General Practice Research Database, in BMJ, 2009: b3999. (M. Moore, mvm198@soton.ac.uk)
* Women and Ischemic Heart Disease: Evolving Knowledge, in
Journal of the American College of Cardiology, 2009; 54: 1561–75. (C. N. Bairey Merz, merz@cshs.org)
* New Technologies in Atrial Fibrillation Ablation, in
Circulation, 2009; 120: 1533–41. (A. Natale, dr.natale@gmail.com)
* Recommendations for Appropriate Sublingual Immunotherapy Clinical Trials, in
Journal of Allergy and Clinical Immunology, 2009; 124: 665–70. (T. B. Casale, tbcasale@creighton.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 © 2009, 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, 2009 * Vol. 16, No. 201
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from the Annals of Internal Medicine.
Management of Erectile Dysfunction: Phosphodiesterase-5 inhibitors should remain the mainstay of therapy of erectile dysfunction, the American College of Physicians recommends in a clinical practice guideline (early release). Citing lack of evidence, the group takes no position on use of tests for or supplements providing hormones such as testosterone and prolactin. Specific recommendations include the following (A. Qaseem, aqaseem@acponline.org):
* The American College of Physicians recommends that clinicians initiate therapy with a PDE-5 inhibitor in men who seek treatment for erectile dysfunction and who do not have a contraindication to PDE-5 inhibitor use (Grade: strong recommendation; high-quality evidence).
* The American College of Physicians recommends that clinicians base the choice of a specific PDE-5 inhibitor on the individual preferences of men with erectile dysfunction, including ease of use, cost of medication, and adverse effects profile (Grade: weak recommendation; low-quality evidence).
* The American College of Physicians does not recommend for or against routine use of hormonal blood tests or hormonal treatment in the management of patients with erectile dysfunction (Grade: insufficient evidence to determine net benefits and harms).
Treatment of Erectile Dysfunction: For treating erectile dysfunction, any of the available oral phosphodiesterase-5 inhibitors are fine, improving erectile functioning and having similar efficacy and safety profiles, according to a systematic review and meta-analysis (early release). Evidence on hormonal treatments are inconclusive, the authors write, adding these details: “Data primarily from short-term trials (≤12 weeks) indicate that PDE-5 inhibitors were more effective than placebo in improving sexual intercourse success (69.0% vs. 35.0%). The proportion of men with improved erections was significantly greater among those treated with PDE-5 inhibitors (range, 67.0% to 89.0%) than with placebo (range, 27.0% to 35.0%). The PDE-5 inhibitors were associated with increased risk for any adverse events compared with placebo (for example, relative risk with sildenafil, 1.72 [95% CI, 1.53 to 1.93]). In 4 head-to-head RCTs comparing sildenafil, vardenafil, and tadalafil, improvement of ED and adverse events did not differ among treatments. Results from 15 RCTs evaluating hormonal treatment of ED were inconsistent on whether treatment improved outcomes. Evidence was insufficient regarding whether men with ED had a higher prevalence of hypogonadism than men without ED.” (H. A. Fink, howard.fink@va.gov)
ACEs, ARBs for Ischemic Heart Disease: In some patients with stable ischemic heart disease and preserved ventricular function, addition of an ACE inhibitor to standard medical therapy improves outcomes, but the combination of ACE inhibitors plus an angiotensin II receptor blocker provides no additional benefit and increases risks of adverse effects, researchers report (early release). A systematic review provides this analysis of existing literature: “41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32 559 participants) showed that ACE inhibitors reduce the relative risk (RR) for total mortality (RR, 0.87 [95% CI, 0.81 to 0.94]) and nonfatal myocardial infarction (RR, 0.83 [CI, 0.73 to 0.94]) but increase the risk for syncope (RR, 1.24 [CI, 1.02 to 1.52]) and cough (RR, 1.67 [CI, 1.22 to 2.29]) compared with placebo. Low-strength evidence (1 trial; 5926 participants) suggested that ARBs reduce the RR for the composite end point of cardiovascular mortality, nonfatal myocardial infarction, or stroke (RR, 0.88 [CI, 0.77 to 1.00]) but not for the individual components. Moderate-strength evidence (1 trial; 25 620 participants) showed similar effects on total mortality (RR, 1.07 [CI, 0.98 to 1.16]) and myocardial infarction (RR, 1.08 [CI, 0.94 to 1.23]) but an increased risk for discontinuations because of hypotension (P < 0.001) and syncope (P = 0.035) with combination therapy compared with ACE inhibitors alone.” (C. M. White, cmwhite@harthosp.org)

>>>PNN NewsWatch
* The antiangiogenesis agent pazopanib (Votrient, GlaxoSmithKline) has been approved by FDA for treatment of advanced renal cell carcinoma.

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 © 2009, 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, 2009 * Vol. 16, No. 202
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 21 issue of JAMA (2009; 302).
Omega-3 Fatty Acids in Depression, Coronary Heart Disease: Omega-3 fatty acids were no more effective for treating symptoms of major depression than a corn oil placebo in a 10-week trial of patients who also had coronary heart disease, researchers report (pp. 1651–7). All patients received sertraline 50 mg/day plus either eicosapentaenoic acid 930 mg and docosahexaenoic acid 750 mg or corn oil capsules, with effects on Beck and Hamilton Depression Inventories: “There were no differences in weekly BDI-II scores (treatment x time interaction = 0.02; 95% confidence interval [CI], –0.33 to 0.36; t112 = 0.11; P = .91), pre–post BDI-II scores (placebo, 14.8 vs omega-3, 16.1; 95% difference-in-means CI, –4.5 to 2.0; t116 = –0.77; P = .44), or HAM-D scores (placebo, 9.4 vs omega-3, 9.3; 95% difference-in-means CI, –2.2 to 2.4; t115 = 0.12; P = .90). The groups did not differ on predefined indicators of depression remission (BDI-II 8: placebo, 27.4% vs omega-3, 28.3%; odds ratio [OR], 0.96; 95% CI, 0.43-2.15; t113 = –0.11; P = .91) or response (>50% reduction in BDI-II from baseline: placebo, 49.0% vs omega-3, 47.7%; OR, 1.06; 95% CI, 0.51-2.19; t112 = 0.15; P = .88).” (R. M. Carney, carneyr@bmc.wustl.edu)
Aldosterone Antagonists in Heart Failure: Few patients hospitalized with heart failure are being treated in accordance with guideline-recommended aldosterone therapy, according to a study of 43,625 patients admitted with HF and discharged home from 241 hospitals in the Get With The Guidelines–HF quality improvement registry in 2005–07 (pp. 1658–65). The observational study showed: “Among 12,565 patients eligible for aldosterone antagonist therapy, 4,087 (32.5%) received an aldosterone antagonist at discharge, and treatment increased modestly from 28% to 34% over the study period. There was also wide variation in aldosterone antagonist use among hospitals (0%-90.6%). Aldosterone antagonist use in eligible patients was associated with younger age (adjusted odds ratio [OR], 0.85; 95% confidence interval [CI], 0.82–0.88), African American race/ethnicity (adjusted OR, 1.17; 95% CI, 1.04–1.32), lower systolic blood pressure (adjusted OR, 0.94; 95% CI, 0.92–0.95), history of implantable cardioverter-defibrillator use (adjusted OR, 1.51; 95% CI, 1.34–1.69), depression (adjusted OR, 1.15; 95% CI, 1.01–1.30), alcohol use (adjusted OR, 1.23; 95% CI, 1.02–1.50), and pacemaker implantation (adjusted OR, 1.21; 95% CI, 1.06–1.38), and with having no history of renal insufficiency (adjusted OR, 0.85; 95% CI, 0.75–0.96). Applying serum creatinine and potassium appropriateness criteria, inappropriate and potentially inappropriate use of aldosterone antagonist therapy was low and did not change over the 3-year study period.” (N. M. Albert, albertn@ccf.org)
Physician Workforce Projections: A younger, smaller physician workforce is predicted for coming years, based on analysis of data for 1979–2008 from the AMA’s Physician Masterfile and estimates and projections from the U.S. Census Bureau Current Population Survey (CPS) (pp. 1674–80): “In an average year in the sample period, the CPS estimated 67,000 (10%) fewer active physicians than did the Masterfile (95% confidence interval [CI], 57,000–78,000; P < .001), almost entirely due to fewer active physicians aged 55 years or older. The CPS estimated more young physicians (ages 25–34 years) than did the Masterfile, with the difference increasing to an average of 17,000 (12%) during the final 15 years (95% CI, 13,000–22,000; P < .001). The CPS estimates of more young physicians were consistent with historical growth observed in the number of first-year residents, and the CPS estimates of fewer older physicians were consistent with lower Medicare billing by older physicians. Projections based on both the CPS and the Masterfile data indicate that the number of active physicians will increase by approximately 20% between 2005 and 2020. However, projections for 2020 using CPS data estimate nearly 100,000 (9%) fewer active physicians than projections using the Masterfile data (957,000 vs 1,050,000), and estimate that a smaller proportion of active physicians will be 65 years or older (9% vs 18%). The increasing proportion of female physicians had little effect on physician supply projections because, unlike male physicians, female physicians were found to maintain their work activity after age 55 years.” (D. O. Staiger, doug.staiger@dartmouth.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 © 2009, 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, 2009 * Vol. 16, No. 203
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release articles from and Oct. 22 issue of New England Journal of Medicine (2009; 361).
HIV-1 Vaccination: A modest benefit was evident in tests of an HIV-1 vaccine in a largely heterosexual population in Thailand, according to results with a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E) (10.1056/NEJMoa0908492). In healthy men and women aged 18–30 years, the immunization strategy showed these effects on HIV-1 infection and early viremia: “In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], –4.0 to 47.9; P = 0.08). In the per-protocol analysis involving 12,452 subjects, the vaccine efficacy was 26.2% (95% CI, –13.3 to 51.9; P = 0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 51.2; P = 0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed.” (J. H. Kim, jkim@hivresearch.org)
Noting that these results “have important implications for future directions in vaccine research,” an editorialist comments (
10.1056/NEJMe0909972): “The possible vaccine efficacy observed was modest and indicates that the vaccine regimen studied is unlikely to be a public health control measure for HIV-1 infection, as the authors themselves acknowledge. The most important contribution of the study is most likely the opportunity to investigate possible host–response correlates of protection against infection. The establishment of such correlates is the central question in HIV vaccine development and will have a profound effect on the designs of vaccines and clinical trials to assess their efficacy. Given the lack of detection of conventional immune responses in earlier studies of these vaccine components, as well as the divergence between the vaccine’s effect on the infection and the effect on viral load, the correlates of protection may, indeed, reflect new concepts of host response. This should be the focus of intense research using the most current research techniques. Ultimately, it is the results of such studies that will most likely determine the significance of this clinical trial to the field of HIV vaccine development.” (R. Dolin)
A/H1N1 Influenza Vaccine: A single dose of nonadjuvanted vaccine against novel influenza A/H1N1 virus is immunogenic in patients ranging in age from 3 to 77 years, researchers report (10.1056/NEJMoa0908535). The dose-ranging study reports: “A total of 2,200 subjects received one dose, and 2,103 (95.6%) received the second dose, of vaccine or placebo. No severe adverse side effects associated with the vaccine were noted. In the nonadjuvanted-vaccine groups, injection-site or systemic reactions, most mild in nature, were noted in 5.5 to 15.9% of subjects. Among the subjects receiving 15 mcg of nonadjuvanted vaccine, a hemagglutination-inhibition titer of 1:40 or more was achieved by day 21 in 74.5% of subjects between 3 and 11 years of age, 97.1% of subjects between 12 and 17 years, 97.1% of subjects between 18 and 60 years, and 79.1% of subjects 61 years of age or older; by day 35, the titer had been achieved in 98.1%, 100%, 97.1%, and 93.3% of subjects, respectively. The proportion with a titer of 1:40 or more was generally highest among the subjects receiving 30 mcg of vaccine, with or without adjuvant. Vaccine without adjuvant was associated with fewer local reactions and greater immune responses than was vaccine with adjuvant.” (F-C Zhu, jszfc@vip.sina.com)
Public Option in HCR: Cooperatives, proposed by Sen. Finance Chair Max Baucus (D–MT), and triggers as envisioned by Maine Republican Sen. Olympia Snowe, are both “poor substitutes” for a public option in a reformed health care system, an author claims (pp. 1617–9): “Rather than developing fig leaves to provide political cover, congressional leaders and the President should push for a national public plan that competes on a level playing field with private insurance to provide coverage to people who are uninsured and workers in the smallest firms. Such competition is the key to creating greater choice and accountability in increasingly consolidated insurance markets.” (J. S. Hacker)

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 © 2009, 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, 2009 * Vol. 16, No. 204
Providing news and information about medications and their proper use

>>>Rheumatology Highlights
Source:
Oct. issue of Arthritis & Rheumatism (2009; 60).
Obesity, OA, & Leptin: An editorialist, commenting on a mouse study published in this issue (pp. 2935–44; F. Guilak, guilak@duke.edu), discusses future research possibilities into the relationship among obesity, osteoarthritis, and serum leptin concentrations (pp. 2858–60): “It will be very informative to conditionally knock out leptin and other adipokines, such as resistin, in a joint-, bone-, or cartilage-specific manner, because when mice develop without leptin, as in the mutants used in the study by Griffin et al, other events may take place that affect overall physiology. It will also be interesting to induce traumatic OA in leptin-knockout mice to determine whether their response to injury is different from that of normal mice on the C57BL/6J background or another background that is more or less resistant to OA. Investigating the response of cartilage and chondrocytes to leptin in the leptin-deficient mice would be helpful, but these studies will remain for the future. In contrast to such changes in genetically deficient mice, changing levels of leptin and obesity in ‘normal’ mice may help to shed light on the complex relationship between obesity and OA. For certain, the role of leptin in physiology and metabolism is a balancing act, with local and systemic factors playing a role…. Via the study conducted by Griffin and colleagues, one more piece of the puzzle is put in place, however; without leptin, mice appear to be protected from OA. Thus, the balance is tipped to a pro-degenerative function for leptin in cartilage.” (L. J. Sandell, sandelll@wudosis.wustl.edu)
Adenosine Receptor Up-regulation in Early RA: Up-regulation of two subtypes of adenosine receptors in lymphocytes and neutrophils may be a factor in early rheumatoid arthritis (ERA), according to results of a study of anti-tumor necrosis factor alpha and methotrexate (pp. 2880–91). The investigators used A2A and A3 agonists to produce cAMP in control patients, those with ERA, and RA patients being treated with MTX or anti-TNF-alpha, with these results: “In ERA patients, we found a high density and altered functionality of A2A and A3 receptors. The binding and functional parameters of A2A and A3 receptors normalized after anti-TNF-alpha, but not MTX, treatment. TNF-alpha release was increased in ERA patients and in MTX-treated RA patients, whereas in anti-TNF-alpha-treated RA patients, release was comparable to that in the controls. NF-kappa-B activation was elevated in ERA patients and in MTX-treated RA patients. Anti-TNF-alpha treatment mediated decreased levels of NF-kappa-B activation.” (P. A. Borea, bpa@unife.it)

>>>Gastroenterology Report
Source:
Oct. issue of Gastroenterology (2009; 137).
Endoscopist-Directed Administration of Propofol: Mortality rates for endoscopist-directed propofol sedation (EDP) were lower than those with benzodiazepines and opioids administered by those specialists and comparable to rates for general anesthesia administered by anesthesiologists, a review article concludes (pp. 1229–37): “A total of 646,080 (223,656 published and 422,424 unpublished) EDP cases were identified. Endotracheal intubations, permanent neurologic injuries, and deaths were 11, 0, and 4, respectively. Deaths occurred in 2 patients with pancreatic cancer, a severely handicapped patient with mental retardation, and a patient with severe cardiomyopathy. The overall number of cases requiring mask ventilation was 489 (0.1%) of 569,220 cases with data available. For sites specifying mask ventilation risk by procedure type, 185 (0.1%) of 185,245 patients and 20 (0.01%) of 142,863 patients required mask ventilation during their esophagogastroduodenoscopy or colonoscopy, respectively (P < .001). The estimated cost per life-year saved to substitute anesthesia specialists in these cases, assuming they would have prevented all deaths, was $5.3 million.” (D. K. Rex, drex@iupui.edu)

>>>PNN NewsWatch
* A voluntary recall of all lots of Ketorolac Tromethamine Injection, USP 30 mg/mL has been initiated, FDA and American Regent announced yesterday. Vials of 1 and 2 mL of the product may contain particulate matter caused by crystallization. The product should be immediately quarantined for return. This recall does not include other concentrations of American Regent Ketorolac Tromethamine Injection.

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 © 2009, 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. 26, 2009 * Vol. 16, No. 205
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 24 issue of Lancet (2009; 374).
Darusentan in Treatment-Resistant Hypertension: In 379 patients with elevated systolic blood pressures not responsive to treatment with multidrug therapy, the selective endothelin-receptor antagonist darusentan lowered SBP (pp. 1423–31). SBPs were 140 mm Hg or more (130 mm Hg or more for those with diabetes or chronic kidney disease) while patients were taking a diuretic plus at least two other hypotensive agents at full or maximally tolerated doses. Addition of darusentan showed these effects: “The mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg (SD 14/8) with placebo, 17/10 mm Hg (15/9) with darusentan 50 mg, 18/10 mm Hg (16/9) with darusentan 100 mg, and 18/11 mm Hg (18/10) with darusentan 300 mg (p < 0.0001 for all effects). The main adverse effects were related to fluid accumulation. Oedema or fluid retention occurred in 67 (27%) patients given darusentan compared with 19 (14%) given placebo. One patient in the placebo group died (sudden cardiac death), and five patients in the three darusentan dose groups combined had cardiac-related serious adverse events.” (M. A. Weber, michaelwebermd@cs.com)
Maintenance Pemetrexed for Non–Small-Cell Lung Cancer: Progression-free and overall survival was improved in patients with advanced non–small-cell lung cancer continued on maintenance doses of pemetrexed, researchers report (pp. 1432–40). In 663 patients with stage IIIB or IV disease who had not progressed during four cycles of platinum-based chemotherapy, pemetrexed plus supportive care provided these benefits: “Pemetrexed significantly improved progression-free survival (4.3 months [95% CI 4.1–4.7] vs 2.6 months [1.7–2.8]; hazard ratio [HR] 0.50, 95% CI 0.42–0.61, p < 0.0001) and overall survival (13.4 months [11.9–15.9] vs 10.6 months [8.7—12.0]; HR 0.79, 0.65–0.95, p = 0.012) compared with placebo. Treatment discontinuations due to drug-related toxic effects were higher in the pemetrexed group than in the placebo group (21 [5%] vs three [1%]). Drug-related grade three or higher toxic effects were higher with pemetrexed than with placebo (70 [16%] vs nine [4%]; p < 0.0001), specifically fatigue (22 [5%] vs one [1%], p = 0.001) and neutropenia (13 [3%] vs 0, p = 0.006). No pemetrexed-related deaths occurred. Relatively fewer patients in the pemetrexed group than in the placebo group received systemic post-discontinuation therapy (227 [51%] vs 149 [67%]; p = 0.0001).” (C. P. Belani, cbelani@psu.edu)

>>>PNN NewsWatch
* An emergency use authorization (EUA) has been issued by FDA for the investigational antiviral drug peramivir intravenous (IV) in certain adult and pediatric patients with confirmed or suspected 2009 H1N1 influenza infection who are admitted to a hospital. The action came the day before President Obama signed an emergency declaration for H1N1 influenza, which allows health facilities to petition the Dept. of Health and Human Services for Section 1135 waivers that respond to particular needs within their areas. Responding to a request from the CDC, FDA authorized use of IV peramivir only in hospitalized adult and pediatric patients for whom therapy with an IV drug is clinically appropriate because (1) the patient is not responding to either oral or inhaled antiviral therapy or (2) drug delivery by a route other than an intravenous route (e.g., oral or inhaled) is not expected to be dependable or feasible. FDA added that for adults only, the drug can be used when the clinician judges IV therapy to be appropriate because of other circumstances. Health professionals using peramivir under this EUA are required to report all associated adverse drug events and medication errors, FDA added. Within 7 calendar days of the onset of symptoms possibly related to unintended effects of peramivir, health professionals are required to report deaths and other serious adverse events.

>>>PNN JournalWatch
* Salicylates and Pandemic Influenza Mortality, 1918–1919 Pharmacology, Pathology, and Historic Evidence, in Clinical Infectious Diseases, 2009; 49: 1405–10. (K. M. Starko, karenstarko@gmail.com)
* Forced Euvolemic Diuresis with Mannitol and Furosemide for Prevention of Contrast-Induced Nephropathy in Patients With CKD Undergoing Coronary Angiography: A Randomized Controlled Trial, in
American Journal of Kidney Diseases, 2009; 54: 602–9. (S. R. Majumdar, me2.majumdar@ualberta.ca)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2009, 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, 2009 * Vol. 16, No. 206
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 26 issue of the Archives of Internal Medicine (2009; 170).
Reporting of Safety Results in RCTs: In randomized controlled trials published in 2006–07 in six high impact-factor journals, reporting of adverse events was highly variable and heterogeneous, researchers report (pp. 1756–61): “Adverse events were mentioned in 88.7% of the 133 reports. No information on severe adverse events and withdrawal of patients owing to an adverse event was given in 27.1% and 47.4% of articles, respectively. Restrictions in the reporting of harm-related data were noted in 43 articles (32.3%) with a description of the most common adverse events only (n = 17), severe adverse events only (n = 16), statistically significant events only (n = 5), and a combination of restrictions (n = 5). The population considered for safety analysis was clearly reported in 65.6% of articles.” (P. Ravaud, philippe.ravaud@bch.aphp.fr)
Describing reporting of adverse events in RCTs as “neglected, restricted, distorted, and silenced,” an editorialist writes (
pp. 1737–9): “Poor reporting may sometimes reflect that collection of information on harms was not included in study design or was neglected during study conduct. Trials for some interventions (eg, psychotherapies) almost never report any harms. Then, information on toxic effects may be explicitly collected as planned, but authors may not report it or may report it in a fragmented or restricted fashion. The usual argument in such a case is printed space limitations. However, Web supplements can cater to any amount of information. It should also be acknowledged that safety data may sometimes cause information overload from routine but unnecessary measurements. Nevertheless, careful consideration of what data are useful to collect may avoid this deluge and eliminate the need for spurious post hoc restrictions in presenting results.” (J. P. A. Ioannidis, jioannid@cc.uoi.gr)
Vitamin D Deficiency, Supplementation: Ergocalciferol (vitamin D2) 50,000 IU weekly for 8 weeks and then every other week for up to 6 years was an effective treatment for vitamin D deficiency in patients whose 2006–07 medical records were reviewed retrospectively (pp. 1806–8). Of 86 patients whose serum 25-hydroxyvitamin D levels were checked, 79 (92%) were below the lower limit of normal, 30 mg/mL. The authors report these results with their supplementation regimens: “Of the 86 patients studied, 41 who were vitamin D deficient or insufficient received 8 weeks of 50,000 IU of ergocalciferol weekly prior to starting maintenance therapy. For those patients, the mean (SD) pretreatment 25(OH)D level was 19.3 (6.2) ng/mL, which increased to 37.2 (13.0) ng/mL after 8 weeks of weekly therapy (P < .001). These patients were then treated with 50,000 IU of ergocalciferol every other week and had a mean (SD) final 25(OH)D level of 46.9 (18.6) ng/mL (P < .001).
“For the 45 patients who received only maintenance therapy of 50,000 IU of ergocalciferol every 2 weeks, the mean (SD) pretreatment 25(OH)D level was 26.9 (10.6) ng/mL, and the mean (SD) final level was 47.1 (18.0) ng/mL (P < .001). Mean (SD) serum calcium levels did not change (pretreatment, 9.5 [0.7] mg/dL; final, 9.6 [0.6] mg/dL [to convert to millimoles per liter, multiply by 0.25]; P = .20). There were no incidents of kidney stones or evidence of vitamin D intoxication.” (M. F. Holick,
mfholick@bu.edu)
Off-Label Prescribing: Commentary authors present a framework for analyzing the appropriateness of prescribing of medications for uses not approved by FDA (pp. 1745–7): “Off-label use is an important area of practice in which evidence gaps should trigger more reflection and scrutiny. Four characteristics of off-label use signal to physicians the need for a higher level of scrutiny: new drugs, novel off-label uses, drugs with known serious adverse effects, and high-cost drugs. By classifying off-label uses as supported, suppositional, or investigational, this conceptual framework grounds recommendations for prescribing practices in a judgment of the strength of the evidence for net health benefit. This elevates the role of evidence in the otherwise unregulated realm of off-label prescribing and will help physicians in exercising their responsibility for applying evidence in practice in a rigorous fashion.” (S. D. Pearson, pearsonsd@cc.nih.gov)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2009, 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, 2009 * Vol. 16, No. 207
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 28 issue of JAMA (2009; 302).
Antipsychotic Drug Risk in Pediatrics: Significant weight gain was associated with first use of all four second-generation antipsychotic agents in children and adolescents, a research study shows, while changes in cardiometabolic risk factors varied (pp. 1765–73). In 272 patients with at least one postbaseline assessment and 15 patients who refused participation or were nonadherent (comparison group), results showed these changes in cardiometabolic risk factors: “After a median of 10.8 weeks (interquartile range, 10.5–11.2 weeks) of treatment, weight increased by 8.5 kg (95% confidence interval [CI], 7.4 to 9.7 kg) with olanzapine (n = 45), by 6.1 kg (95% CI, 4.9 to 7.2 kg) with quetiapine (n = 36), by 5.3 kg (95% CI, 4.8 to 5.9 kg) with risperidone (n = 135), and by 4.4 kg (95% CI, 3.7 to 5.2 kg) with aripiprazole (n = 41) compared with the minimal weight change of 0.2 kg (95% CI, –1.0 to 1.4 kg) in the untreated comparison group (n = 15). With olanzapine and quetiapine, respectively, mean levels increased significantly for total cholesterol (15.6 mg/dL [95% CI, 6.9 to 24.3 mg/dL] P < .001 and 9.1 mg/dL [95% CI, 0.4 to 17.7 mg/dL] P = .046), triglycerides (24.3 mg/dL [95% CI, 9.8 to 38.9 mg/dL] P = .002 and 37.0 mg/dL [95% CI, 10.1 to 63.8 mg/dL] P = .01), non–high-density lipoprotein (HDL) cholesterol (16.8 mg/dL [95% CI, 9.3 to 24.3 mg/dL] P < .001 and 9.9 mg/dL [95% CI, 1.4 to 18.4 mg/dL] P = .03), and ratio of triglycerides to HDL cholesterol (0.6 [95% CI, 0.2 to 0.9] P = .002 and (1.2 [95% CI, 0.4 to 2.0] P = .004). With risperidone, triglycerides increased significantly (mean level, 9.7 mg/dL [95% CI, 0.5 to 19.0 mg/dL]; P = .04). Metabolic baseline-to-end-point changes were not significant with aripiprazole or in the untreated comparison group.” (C. U. Correll, ccorrell@lij.edu)
The observed weight gain has these implications, editorialists write (
pp. 1811–2): “Pronounced weight gain early in life and significant changes in lipid profiles have ominous long-term health implications. Children and adolescents with mental health problems often have multiple risk factors, including poor nutrition, inadequate exercise, substance abuse, and lack of adequate health care monitoring.… Research is needed to establish whether dietary interventions or the addition of medications targeting obesity or glucose regulation (eg, metformin) mitigate metabolic adverse effects. A careful cost-benefit analysis needs to accurately gauge both short-term and long-term risks. Anticipating these risks is necessary because longitudinal data will not be available until a generation of children and adolescents who are exposed to these medications potentially experiences the metabolic consequences of their treatment.” (C. K. Varley, chris.varley@seattlechildrens.org)

>>>JAPhA Highlights
Source:
Early-release article from and Sept/Oct issue of the Journal of the American Pharmacists Association (2009; 49).
Pharmacist Interventions in Family Medicine Clinic Medication therapy review and intervention by a pharmacist resulted in identification of medication-related problems in 90% of 92 patients, and interventions produced better care in 45% of patients, researchers report (pp. 623–7). Prospective cohort analysis during 2000–01 showed: “Significant improvement in status was found for hypertension (P = 0.007), dyslipidemia (P = 0.002), and asthma (P = 0.011). Significant improvement was seen for aspirin use for myocardial infarction prevention (50% vs. 93%, P = 0.031) and inhaled steroids for asthma (36% vs. 64%, P = 0.031). The number of medications was reduced from an average of 3.92 to 3.04 (P < 0.001) per patient.” (I. M Harris, iharris@umphysicians.umn.edu)
MTM Impact in 2007: Experiences of 73,793 Medicare Part D patients qualifying for medication therapy management services in 2007 are reported by one of the two large MTM providers (e163–70). Local pharmacists saw 9,140 patients face-to-face and contacted 12,196 patients by telephone. Another 3,436 patients were phoned by call-center pharmacists, and the remainder—49,021 patients—received an educational mailing with patient-specific medication-related information, a personal medication record, and tips on saving money on prescriptions. Drug costs decreased between 2007 and 2008 by up to $40 per patient per month, with decreases higher for local pharmacist care. (S. Winston, swinston@mirixa.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 © 2009, 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, 2009 * Vol. 16, No. 208
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 29 New England Journal of Medicine (2009; 361).
Complex Insulin Regimens: Addition of a basal or prandial insulin-based regimen to oral hypoglycemic therapy produced better indicators of diabetes control than did a biphasic insulin-based regimen, researchers report (pp. 1736–47). In the open-label Treating to Target in Type 2 Diabetes (4-T) study, 708 patients with type 2 diabetes uncontrolled by metformin and sulfonylureas were randomized to biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once (twice if required) daily. Sulfonylurea therapy was replaced with a second type of insulin if glycemic control declined. Results over 3 years showed: “Median glycated hemoglobin levels were similar for patients receiving biphasic (7.1%), prandial (6.8%), and basal (6.9%) insulin-based regimens (P = 0.28). However, fewer patients had a level of 6.5% or less in the biphasic group (31.9%) than in the prandial group (44.7%, P = 0.006) or in the basal group (43.2%, P = 0.03), with 67.7%, 73.6%, and 81.6%, respectively, taking a second type of insulin (P = 0.002). Median rates of hypoglycemia per patient per year were lowest in the basal group (1.7), higher in the biphasic group (3.0), and highest in the prandial group (5.7) (P < 0.001 for the overall comparison). The mean weight gain was higher in the prandial group than in either the biphasic group or the basal group. Other adverse event rates were similar in the three groups.” (R. R. Holman, rury.holman@dtu.ox.ac.uk)
“Optimal insulin treatment in type 2 diabetes” is discussed in an editorial (
pp. 1801–3): “Safety issues such as mitogenic and antiapoptotic effects, which have been observed with insulin analogues in cell culture, require further exploration. However, neither the pharmaceutical industry nor other sponsors are likely to fund long-term trials comparing regular human insulin with analogue insulin. Furthermore, 18 to 32% of patients in the 4-T study continued to receive sulfonylurea after one year, although its combination with insulin has no physiological rationale and may have increased the risk of hypoglycemia.” (M. Roden)
Pediatric Recurrent UTI Prophylaxis: Among children predisposed to urinary tract infections, long-term, low-dose trimethoprim–sulfamethoxazole decreased the number of UTIs, compared with placebo (pp. 1748–59). Use of daily trimethoprim 2 mg–sulfamethoxazole 10 mg per kilogram for 12 months showed: “From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim–sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P ≥ 0.20 for all interactions).” (J. C. Craig)
“A one-size-fits-all approach may not be appropriate,” editorialists write (
pp. 1804–6). “The treatment effect of prophylaxis did not differ significantly between children with [vesicoureteral] reflux and those without reflux, although not all participating children underwent voiding cystourethrography. Furthermore, the trial was not powered to detect clinically meaningful effects in subgroups of children, and the reduction in the absolute risk of symptomatic urinary tract infection was greatest for children with grade III through V reflux (6.8 percentage points), as compared with that for children with grade I or II reflux (5.4 percentage points) or those with no reflux (1.8 percentage points), although this trend was not significant. Early diagnosis and treatment of urinary tract infection and treatment of dysfunctional voiding, which predisposes many children to urinary tract infection, are likely to go a long way toward preventing long-term renal damage. Ongoing randomized, controlled trials in Sweden and the United States in children with a wide range of grades of vesicoureteral reflux may tell us whether the diagnosis and treatment of such reflux provide any incremental benefit.” (A. Hoberman)

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 © 2009, 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, 2009 * Vol. 16, No. 209
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Nov. issue of Diabetes Care (2009; 32).
Diet, Supplements, & Diabetes: Two studies fail to support a relationship between improved intake of nutrients and lowered risk of diabetes.
Low levels of 25-hydroxy vitamin D were not associated with new-onset or ongoing type 1 diabetes, although researchers found uniformly suboptimal concentrations of the vitamin (
pp. 1977–9). The investigators were seeking to replicate findings of a vitamin D link with diabetes identified in other geographic regions, especially northern Europe, in sun-rich Florida. Serum samples from 153 controls, 46 patients with new-onset type 1 diabetes, 110 patients with established type 1 diabetes, and 106 first-degree relatives of the patients with diabetes showed the following: “In this study, 25-OH vitamin D levels (median, range, interquartile range [IQR]) were similar among control subjects (20.1, below detection [bd]–163.5, 13.0–37.4 ng/ml), new-onset type 1 diabetic patients (21.2, bd–48.6, 12.2–30.2 ng/ml), established type 1 diabetic patients (23.2, bd–263.8, 13.8–33.9 ng/ml), and first-degree relatives (22.2, bd–59.9, 12.7–33.1 ng/ml) (P = 0.87). Mean 25-OH vitamin D levels were less than the optimal World Health Organization level of 30 ng/ml in all study groups.” (M. Atkinson, atkinson@ufl.edu)
Risk of type 2 diabetes was not reduced by increased consumption of fish or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a population-based cohort analysis (
pp. 2021–6). Among 4,472 Dutch participants aged 55 years or older and without type 2 diabetes at baseline, food-frequency questionnaires revealed these findings: “After 15 years of follow-up, 463 participants developed type 2 diabetes. Median fish intake, mainly lean fish (81%), was 10 g/day. Total fish intake was associated positively with risk of type 2 diabetes; the RR was 1.32 (95% CI 1.02–1.70) in the highest total fish group (≥28 g/day) compared with that for non–fish eaters (Ptrend = 0.04). Correspondingly, lean fish intake tended to be associated positively with type 2 diabetes (RR highest group ]≥23 g/day] 1.30 [95% CI 1.01–1.68]; Ptrend = 0.06), but fatty fish was not. No association was observed between EPA and DHA intake and type 2 diabetes (RR highest group [≥149.4 mg/day] 1.22 [0.97–1.53]). With additional adjustment for intake of selenium, cholesterol, and vitamin D, this RR decreased to 1.05 (0.80–1.38; Ptrend = 0.77).” (G. J. van Woudenbergh, truus.vanwoudenbergh@wur.nl)

>>>PNN NewsWatch
* Ofatumumab (Arzerra; GlaxoSmithKline, Genmab) has been approved on an accelerated basis by FDA for treatment of patients with chronic lymphocytic leukemia that is refractory to fludarabine and alemtuzumab. In a pivotal study, 42% of such patients responded to ofatumumab treatment. Median duration of response was 6.5 months. Adverse reactions seen in 10% or more of patients on the monoclonal antibody were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. The most common serious adverse reactions were infections (including pneumonia and sepsis), neutropenia, and pyrexia.
* An expansion of
FDA’s partnership with WebMD focuses on allergies/asthma, children’s health, diabetes, heart health, and vitamins and supplements, the agency announced yesterday. This second phase of the partnership includes expanded content and multimedia tools at www.webmd.com/fda.
*
Pharmacist-provided medication therapy management services are included in the final health care reform bill released yesterday by House Democrats, APhA reports. On the Senate side, Majority Leader Harry Reid of Nevada earlier this week sent a “health insurance reform bill” to the Congressional Budget Office for scoring but has not released its text or specified a schedule for voting. The House bill, due up for a vote late next week, provides for grants that will examine innovative ways of treating chronic diseases in a collaborative fashion. It would be funded by a 5.4% tax on those earning more than $500,000 per year and cost-saving reforms such as creation of accountable care organizations and medical homes, elimination of the “donut hole” in Medicare Part D, and elimination of nontaxable reimbursements for nonprescription medications.

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 © 2009, 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. 2, 2009 * Vol. 16, No. 210
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 31 issue of Lancet (2009; 374).
Delaying Onset of MS with Glatiramer: In patients presenting with clinically isolated syndrome and brain lesions visualized with magnetic resonance imaging, early treatment with glatiramer acetate delays conversion to clinically definite multiple sclerosis, reports the PreCISe study group (pp. 1503–11). At 80 sites in 16 countries, this Teva-sponsored trial randomized 481 patients to subcutaneous glatiramer acetate 20 mg/day or placebo for up to 36 months or until conversion to clinically definite MS, whichever was first. Results showed: “All randomly assigned participants were analysed for the primary outcome. Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo (hazard ratio 0.55, 95% CI 0.40–0.77; p = 0.0005). The time for 25% of patients to convert to clinically definite disease was prolonged by 115%, from 336 days for placebo to 722 days for glatiramer acetate. The most common adverse events in the glatiramer acetate group were injection-site reactions (135 [56%] glatiramer acetate vs 56 [24%] placebo) and immediate post-injection reactions (47 [19%] vs 12 [5%]).” (G. Comi, g.comi@hsr.it)
High-Dose Cytarabine for Primary CNS Lymphoma: Addition of high-dose cytarabine to high-dose methotrexate improves outcomes with acceptable toxicity in patients aged 75 years or younger with primary CNS lymphoma, researchers report (pp. 1512–20). The International Extranodal Lymphoma Study Group (IELSG) conducted an open-label, Phase II trial of 79 patients with non-Hodgkin lymphoma exclusively localized in the CNS, cranial nerves, or eyes. At 24 centers in 6 countries, the adult patients experienced these outcomes following four courses of either methotrexate alone or methotrexate plus cytarabine: “All randomly assigned participants were analysed. After chemotherapy, seven patients given methotrexate and 18 given methotrexate plus cytarabine achieved a complete remission, with a complete remission rate of 18% (95% CI 6–30) and 46% (31–61), respectively, (p = 0.006). Nine patients receiving methotrexate and nine receiving methotrexate plus cytarabine achieved a partial response, with an overall response rate of 40% (25–55) and 69% (55–83), respectively, (p = 0.009). Grade 3–4 haematological toxicity was more common in the methotrexate plus cytarabine group than in the methotrexate group (36 [92%] vs six [15%]). Four patients died of toxic effects (three vs one).” (A. J. M. Ferreri, andres.ferreri@hsr.it)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 339).
Acceptance of H1N1 Vaccination in Hong Kong: Without more and better information about the effectiveness and safety of the vaccine for the 2009 novel A/H1N1 influenza virus, people in Hong Kong would be unlikely to get immunized, especially if the product were not free, according to a telephone survey of 301 adults (b4164). Responses from 80% of those surveyed during early stages of the pandemic showed: “45% (n = 135) of the participants reported that they would be highly likely take up vaccination if it was free. When vaccination incurred a cost, however, the prevalence of uptake decreased: 36% (n = 108) would take up vaccination if it cost less than $HK100, 24% (n = 72) if it cost $HK101–200, and 15% (n = 45) if it cost more than $HK200; and in absence of proved efficacy and safety decreased to 5% (n = 14). Moreover, 32% (n = 95) considered universal A/H1N1 vaccination unnecessary. Overall, 39% (n = 117) of participants believed that A/H1N1 vaccination would prevent the virus being contracted; 63% (n = 189) erroneously believed that efficacy of the vaccine had been confirmed by clinical trials, and 16% (n = 49) believed that it is necessary for everyone in Hong Kong to take up vaccination against influenza A/H1N1.” (J. T. F. Lau, jlau@cuhk.edu.hk)

>>>PNN JournalWatch
* Pathogenesis, Treatment, and Prevention of Pneumococcal Pneumonia, in Lancet, 2009; 374: 1543–56. (T. van der Poll, t.vanderpoll@amc.uva.nl)
* The Potency of Team-Based Care Interventions for Hypertension: A Meta-analysis, in
Archives of Internal Medicine, 2009; 169: 1748–55. (B. L. Carter, barry-carter@uiowa.edu)
* Alcohol as a Risk Factor for Type 2 Diabetes: A Systematic Review and Meta-analysis, in
Diabetes Care, 2009; 32: 2123–32. (D. Baliunas, dolly.baliunas@utoronto.ca)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2009, 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, 2009 * Vol. 16, No. 211
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release article from and Nov. 3 issue of the Annals of Internal Medicine (2009; 151).
Cost-Effectiveness of Early RA Treatment: Early treatment of rheumatoid arthritis is cost justified when disease-modifying antirheumatic drugs are used, but the more expensive biologic agents produce uncertain results when assessing cost-effectiveness using objective measures of RA progression (pp. 612–21). Researchers used published patient and hospital data and a lifetime horizon to assess cost-effectiveness in patients with RA symptoms for 3 months or less. Taking the perspective of the health care provider or society, three management strategies (symptomatic or “pyramid” strategy with initial NSAIDs, patient education, pain management, and low-dose glucocorticoids, and DMARDs; early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate at 1 year for nonresponders) produced these effects on cost per quality-adjusted life-year (QALY) gained: “By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4,849 per QALY (95% CI, $0 to $16,354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater.” (A. Finckh)
Monotherapy v. Combination Therapy for Dyslipidemia: Evidence for combination therapy in management of dyslipidemias is limited or of low quality, write authors of a systematic review (pp. 622–30). Looking at studies of statins and bile-acid sequestrants, fibrates, ezetimibe, niacin, or omega-3 fatty acids with statin monotherapy, the group found: “102 studies met eligibility criteria. The main analysis compared combination therapy with high-dose statin monotherapy in high-risk patients. Very-low-strength evidence showed that statin–ezetimibe (2 trials; n = 439) and statin–fibrate (1 trial; n = 166) combinations did not reduce mortality more than high-dose statin monotherapy. No trials compared the effect of combination therapy versus high-dose statin monotherapy on the incidence of myocardial infarction, stroke, or revascularization procedures. Two statin–ezetimibe trials (n = 295) demonstrated higher low-density lipoprotein cholesterol goal attainment with combination therapy (odds ratio, 7.21 [95% CI, 4.30 to 12.08]). Trials in lower-risk patients did not show a difference in mortality.” (M. Sharma)
Family History & Improving Health: The importance of family history information as a means of predicting disease and improving individual health outcomes is emphasized in two early-release articles in this issue. An NIH state-of-the-science conference statement details expert analysis of six questions on family history (early release; www.consensus.nih.gov; 888/644-2667). The second article, a systematic review of family history in risk assessment for common diseases, concludes (early release): “Insufficient evidence evaluates how to collect family history information accurately in the primary care setting and the effects of taking family history on patient outcomes. Patients seem to correctly report the absence of disease in relatives more often than the presence of disease.” (B. J. Wilson, bwilson@uottawa.ca)

>>>PNN NewsWatch
* Guidelines for pharmacies to use in compounding limited amounts of oseltamivir oral suspension from Tamiflu (Roche) capsules were released yesterday by FDA. Commercially available Tamiflu for Oral Suspension is in short supply because of the A/H1N1 influenza pandemic. The FDA guidance provides both specifics on compounding and storage procedures as well as an assurance that the agency does not consider advance preparation of a 24-hour supply to be manufacturing as defined in federal statutes.
* Possible renal function problems, including renal failure, are the topics of new warnings added to the labeling of
exenatide (Byetta, Amylin), FDA said yesterday. Patients with pre-existing renal disease or at risk for renal disease have been affected.

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 © 2009, 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, 2009 * Vol. 16, No. 212
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 4 JAMA, an issue on A/H1N1 influenza (2009; 302).
Respiratory Protection Against Influenza: Among 478 nurses, surgical masks were noninferior to N95 respirators for protection against laboratory-confirmed cases of influenza (pp. 1865–71). During the 2008–09 influenza season, nurses in emergency departments, medical units, and pediatric units at eight Ontario tertiary care hospitals were randomly assigned to masks or respirators when caring for patients with febrile respiratory illness, with these results: “Influenza infection occurred in 50 nurses (23.6%) in the surgical mask group and in 48 (22.9%) in the N95 respirator group (absolute risk difference, –0.73%; 95% CI, –8.8% to 7.3%; P = .86), the lower confidence limit being inside the noninferiority limit of –9%.” (M. Loeb, loebm@mcmaster.ca)
Editorialists emphasize that respiratory protection is just one way to prevent influenza transmission to health care providers (HCPs), with vaccination and hand hygiene also important (
pp. 1903–4): “Chief among these is the annual vaccination of HCP against influenza, which has been shown to protect both patients and HCP, decrease patient mortality, and minimize worker absenteeism. Although this recommendation is relevant every flu season, it is especially important during pandemics, as the population has increased susceptibility to infection. However, HCP adherence with annual flu vaccination remains poor at around 45%. Also important is the implementation of a multifaceted approach designed to reduce the risks of HCP exposures to patients infected with influenza. These include ‘administrative controls,’ including plans to exclude ill visitors, rapidly and effectively triage patients with febrile respiratory illness into effective isolation, develop engineering measures to increase spatial separation and provide physical barriers, and implement respiratory hygiene/cough etiquette programs. Recent data demonstrate the important role that masking of an incubating or ill patient could have on transmission of virus and underscore the importance of this simple strategy, not just in waiting rooms, but even after patients have been admitted to facilities.” (A. Srinivasan, beu8@cdc.gov)
Preparing for the Sickest Patients with A/H1N1: Responding to three descriptions of patient types and outcomes as A/H1N1 influenza virus spread in Canada (pp. 1872–9; A. Kumar, akumar61@yahoo.com), Mexico (pp. 1880–7; R. Fowler, rob.fowler@sunnybrook.ca), and Australia/New Zealand (pp. 1888–95; A. R. Davies, a.davies@alfred.org.au), editorialists note the critical importance of pandemic planning and preparation (pp. 1905–6): “Hospitals must develop explicit policies to equitably determine who will and will not receive life support should absolute scarcity occur. The controversy that erupted around triage decisions during Hurricane Katrina highlights the importance of advance planning and clear guidelines. Several groups have provided recommendations for allocating scarce therapies during the influenza pandemic. Any deaths from 2009 influenza A(H1N1) will be regrettable, but those that result from insufficient planning and inadequate preparation will be especially tragic.” (D. B. White, whitedb@upmc.edu)
New Solutions, Old Problems with Influenza: A former director of CDC editorializes that the answers to questions posed to a 1941 influenza commission “remain incomplete, at best” (pp. 1907–8): “For clinicians, the most urgent gaps are those related to the prediction, treatment, and supportive care of individuals at increased risk for serious complications of infection.… Clinicians should not be falsely reassured by previous good health, young age, and absence of major comorbidities because these characteristics do not exclude the potential for respiratory failure and death. Likewise, major comorbidities, tobacco use, pregnancy, and possibly obesity may increase the risk. On the other hand, a majority of patients can survive intensive care for this illness, even if antiviral treatment was not initiated within 48 hours of clinical onset. Meticulous attention to complicating conditions including bacterial superinfection, pulmonary embolism, and adverse events associated with prolonged mechanical ventilation is essential. Respiratory isolation also remains an important priority, given that nosocomial transmission was the source of infection in 10% of the Canadian patients who required intensive care.” (J. L. Gerberding, JulieGerberdingMD.LLC@gmail.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 © 2009, 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, 2009 * Vol. 16, No. 213
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release articles from and Nov. 5 issue of the New England Journal of Medicine (2009; 361).
Darbepoetin Alfa in Type 2 Diabetes & Chronic Kidney Disease: Treatment of moderate anemia with darbepoetin alfa is ineffective and increases stroke risk in patients with type 2 diabetes and chronic kidney disease, researchers report (doi: 10.1056/NEJMoa0907845). In 4,038 patients in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), darbepoetin alfa or placebo produced these changes in primary composite end points of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease: “Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P = 0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P = 0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P < 0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P < 0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group.” (M. A. Pfeffer, mpfeffer@rics.bwh.harvard.edu)
An editorialist calls for “strategies based on evidence” in erythropoiesis-stimulating agent (ESA) treatment of anemia of chronic kidney disease (
doi: 10.1056/NEJMe0909664): “The TREAT data may not be applicable to other populations, especially patients who are undergoing dialysis. Alternative dosing strategies, such as those to achieve unique rates of change, absolute levels of hemoglobin, or both, may alleviate the risk of stroke yet conserve the modest benefits observed in quality of life. Naysayers will point to differences in baseline characteristics of the patients as confounders in this study. The randomization procedure created a nominally significant imbalance in the baseline cardiovascular history, especially heart failure. Patients who received placebo had previously received ESA treatment; in fact, approximately 10% of randomly assigned patients had received an ESA 12 weeks or more before randomization. Moreover, during the study, 46% of patients assigned to placebo received at least one dose of darbepoetin alfa. Some people may argue that the investigators have discounted the differences between the two groups in the number of red-cell transfusions received; they may have a point. A substantial proportion of candidates for kidney transplantation continue to require periodic blood transfusions that carry a risk of allosensitization.” (P. A. Marsden)
Oncoprotein HPV-16 Vaccination: A synthetic long-peptide vaccine against the human papillomavirus (HPV) type 16 oncoproteins E6 and E7 produced clinical responses in 20 women with HPV-16–positive, grade 3 vulvar intraepithelial neoplasia (pp. 1838–47). After three or four vaccinations, results showed: “The most common adverse events were local swelling in 100% of the patients and fever in 64% of the patients; none of these events exceeded grade 2 of the Common Terminology Criteria for Adverse Events of the National Cancer Institute. At 3 months after the last vaccination, 12 of 20 patients (60%; 95% confidence interval [CI], 36 to 81) had clinical responses and reported relief of symptoms. Five women had complete regression of the lesions, and HPV-16 was no longer detectable in four of them. At 12 months of follow-up, 15 of 19 patients had clinical responses (79%; 95% CI, 54 to 94), with a complete response in 9 of 19 patients (47%; 95% CI, 24 to 71). The complete-response rate was maintained at 24 months of follow-up. All patients had vaccine-induced T-cell responses, and post hoc analyses suggested that patients with a complete response at 3 months had a significantly stronger interferon-–associated proliferative CD4+ T-cell response and a broad response of CD8+ interferon- T cells than did patients without a complete response.” (G. G. Kenter, g.g.kenter@lumc.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 © 2009, 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, 2009 * Vol. 16, No. 214
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Nov. issue of Pharmacotherapy (2009; 29).
Liraglutide v. Glimepiride for Type 2 Diabetes: Liraglutide 1.2- and 1.8-mg monotherapies provide better long-term projected survival, diabetes complications, and costs, compared with glimepiride, in patients with type 2 diabetes, researchers report (pp. 1280–8). In a mathematical simulation using the validated Center for Outcomes Research (CORE) Diabetes Model, data from the short-term Liraglutide Effect and Action in Diabetes (LEAD)-3 trial, and data from long-term outcomes studies, the group found: “The impact of the three treatments for type 2 diabetes on survival and cumulative incidence of cardiovascular, ocular, or renal events and costs were estimated at three time periods: 10, 20, and 30 years. Simulations predicted improved survival for liraglutide 1.8 and 1.2 mg at all three time points compared with glimepiride. Survival benefits were greatest after 30 years of follow-up: 16.5%, 13.6%, and 7.3%, respectively. The frequency of nonfatal renal and ocular events was lower for both liraglutide doses than for glimepiride. The rate of neuropathies leading to first or recurrent amputation was higher for glimepiride compared with both liraglutide doses. The average cumulative cost/patient was higher for glimepiride compared with liraglutide 1.2 mg and liraglutide 1.8 mg.” (S. D. Sullivan, sdsull@u.washington.edu)
Safety of Prenatal, Perinatal Protease Inhibitor Use: No negative effects of protease inhibitors on prematurity, birth weight, or weight at 2 years were found in a retrospective cohort analysis of patients at a Montreal tertiary hospital (pp. 1289–96). The study included 206 pairs of mothers with HIV and their infants. Comparison of 176 infants exposed to highly active antiretroviral therapy with protease inhibitors and 206 unexposed infants in 1997–2005 showed these results: “In infants exposed to HAART, the 10.6% rate of prematurity (11.1% with and 7.1% without protease inhibitors) was not significantly higher than that in the control group (7.8%). Moreover, the 9.9% rate for small for gestational age (9.8% with and 10.3% without protease inhibitors) was also not significantly higher than that in the control group (5.3%). The 176 mothers and infants exposed to protease inhibitors had a median follow-up of 5 years. Stillbirth or death was not observed. At delivery, the weight, length, and head circumference of the 176 infants exposed to protease inhibitors were similar to those of the control group. During the first 2 years of life, premature infants were in the lower percentiles of growth; however, they followed normal Centers for Disease Control and Prevention growth curves matched for age and sex.” (E. Ferreira, ema.ferreira@umontreal.ca)
Simplified Gentamicin Dosing in Critically Ill Neonates: In 644 critically ill neonates less than 7 days old, a simplified, weight-based, extended-interval gentamicin dosing protocol for critically ill neonates performed well and minimized risk of toxicity, a study shows (pp. 1297–305). Initiated on the first day of life for suspected sepsis, the protocol showed these results: “Mean gentamicin peak and trough concentrations were 9.38 mg/L (95% confidence interval [CI] 9.24–9.52 mg/L) and 1.00 mg/L (95% CI 0.96–1.04 mg/L), respectively. With use of the protocol, 361 neonates (56.1%) achieved gentamicin peak plasma concentrations in the range defined as successful and 610 neonates (94.7%) achieved successful trough concentrations. The mean gentamicin apparent volume of distribution and half-life were 0.48 L/kg (95% CI 0.47–0.49 L/kg) and 8.31 hours (95% CI 8.09–8.52 hrs), respectively.” (D. S. Hoff, david.hoff@childrensmn.org)

>>>PNN NewsWatch
* The House Committee on Rules meets this afternoon to discuss this weekend’s floor vote on HR 3962, the Affordable Health Care for America Act. House members are scheduled to begin debate on Saturday, and a final vote could come later that day or on Sunday.
*
Safe Use Initiative is a new FDA effort to reduce the likelihood of preventable harm from medication use. Announced this week, the program includes collaboration with health professionals and other stakeholders to identify drugs and drug classes that are linked to preventable harm. A list of specific problems, cross-sector interventions for reducing harm from these problems, and the metrics for success will be developed, the agency said.

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 © 2009, 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. 9, 2009 * Vol. 16, No. 215
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 7 issue of Lancet (2009; 374).
Liraglutide for Obesity: In a 20-week trial, liraglutide helped patients with obesity lose weight, and the drug improved some obesity-related risk factors and reduced the onset of prediabetes, researchers report (pp. 1606–16). The open-label trial included 564 patients with body mass index of 30–40 kg/sq m. They received one of four liraglutide doses or placebo once daily subcutaneously or oral orlistat 120 mg three times daily, with these results: “Participants on liraglutide lost significantly more weight than did those on placebo (p = 0.003 for liraglutide 1.2 mg and p < 0.0001 for liraglutide 1.8–3.0 mg) and orlistat (p =0 .003 for liraglutide 2.4 mg and p < 0.0001 for liraglutide 3.0 mg). Mean weight loss with liraglutide 1.2–3.0 mg was 4.8 kg, 5.5 kg, 6.3 kg, and 7.2 kg compared with 2.8 kg with placebo and 4.1 kg with orlistat, and was 2.1 kg (95% CI 0.6–3.6) to 4.4 kg (2.9–6.0) greater than that with placebo. More individuals (76%, n = 70) lost more than 5% weight with liraglutide 3.0 mg that with placebo (30%, n = 29) or orlistat (44%, n = 42). Liraglutide reduced blood pressure at all doses, and reduced the prevalence of prediabetes (84–96% reduction) with 1.8–3.0 mg per day. Nausea and vomiting occurred more often in individuals on liraglutide than in those on placebo, but adverse events were mainly transient and rarely led to discontinuation of treatment.” (A. Astrup, ast@life.ku.dk)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2009; 339).
Insulin Options for Nonobese Patients with Type 2 Diabetes: Insulin plus metformin provided glycemic control equivalent to that with insulin plus repaglinide in 97 nonobese patients with type 2 diabetes who were poorly controlled on oral hypoglycemic agents alone, and it did so with less weight gain (b4324). Biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months was used by all patients, and they were randomized to repaglinide 6 mg or metformin 2,000 mg. Results showed: “At the end of treatment, HbA1c concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA1c 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P = 0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments –2.51 kg, 95% confidence interval –4.07 to –0.95).” (S. S. Lund, sqrl@steno.dk)
Aspirin for Primary Cardiovascular Prevention in Diabetes: In patients with diabetes, aspirin is not clearly beneficial for primary prevention of cardiovascular disease, according to authors of a meta-analysis of six clinical trials with 10,117 participants (b4531): “When aspirin was compared with placebo there was no statistically significant reduction in the risk of major cardiovascular events (five studies, 9,584 participants; relative risk 0.90, 95% confidence interval 0.81 to 1.00), cardiovascular mortality (four studies, n = 8,557, 0.94; 0.72 to 1.23), or all cause mortality (four studies, n = 8,557; 0.93, 0.82 to 1.05). Significant heterogeneity was found in the analysis for myocardial infarction (I2 = 62.2%; P = 0.02) and stroke (I2 = 52.5%; P = 0.08). Aspirin significantly reduced the risk of myocardial infarction in men (0.57, 0.34 to 0.94) but not in women (1.08, 0.71 to 1.65; P for interaction = 0.056). Evidence relating to harms was inconsistent.” (A. Nicolucci, nicolucci@negrisud.it)

>>>PNN NewsWatch
* The health care reform bill that passed the House on Saturday night included pharmacist-provided medication therapy management provisions and other favorable pharmacy language. Observers are predicting a rough road for the comprehensive package in the Senate.

>>>PNN JournalWatch
* Bipolar II Postpartum Depression: Detection, Diagnosis, and Treatment, in American Journal of Psychiatry, 2009; 166: 1217–21. (V. Sharma)
* Defining Vitamin D Deficiency in Children: Beyond 25-OH Vitamin D Serum Concentrations, in
Pediatrics, 2009; 124: 1471–3. (F. R. Greer, frgreer@pediatrics.wisc.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 © 2009, 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, 2009 * Vol. 16, No. 216
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 9 issue of the Archives of Internal Medicine (2009; 170).
Thiazides at 50: The effects of thiazides, now in use since the late 1950s, on cardiovascular disease are reviewed (pp. 1851–6): “Thiazide diuretics have stood the test of time for more than 50 years in the management of hypertension. Their use as monotherapy or in combination with other antihypertensive agents has resulted in dramatic decreases not only in cerebrovascular but also in [cardiovascular] events. Comparative data with other antihypertensive medications with different mechanisms of action indicate that diuretics are as, and in some instances more, effective in event reduction than other antihypertensive drugs. We hope that better understanding of the transport mechanisms in the kidneys and more recent advances in our understanding of the molecular mechanisms and genetic traits that underlie variations in [blood pressure] in the population will lead to improved diuretics and, possibly, to improved treatment of hypertension.” (M. Moser, moserbp@aol.com)
Diagnostic Errors in Medicine: Drug reactions and overdoses and poor management of laboratory orders are two common causes of diagnostic errors in medicine, according to a survey of physicians (pp. 1881–7). The 6-item questionnaire was distributed by mail at two institutions and during grand rounds at 20 institutions. Results showed: “A total of 669 cases were reported by 310 clinicians from 22 institutions. After cases without diagnostic errors or lacking sufficient details were excluded, 583 remained. Of these, 162 errors (28%) were rated as major, 241 (41%) as moderate, and 180 (31%) as minor or insignificant. The most common missed or delayed diagnoses were pulmonary embolism (26 cases [4.5% of total]), drug reactions or overdose (26 cases [4.5%]), lung cancer (23 cases [3.9%]), colorectal cancer (19 cases [3.3%]), acute coronary syndrome (18 cases [3.1%]), breast cancer (18 cases [3.1%]), and stroke (15 cases [2.6%]). Errors occurred most frequently in the testing phase (failure to order, report, and follow-up laboratory results) (44%), followed by clinician assessment errors (failure to consider and overweighing competing diagnosis) (32%), history taking (10%), physical examination (10%), and referral or consultation errors and delays (3%).” (G. D. Schiff, gschiff@partners.org)
Hospital Adverse Events: Disclosure of adverse events increases hospitalized patients’ ratings of quality during their stays, researchers report (pp. 1888–94). Among a random sample of 603 medical and surgical acute care adult patients in Massachusetts hospitals in 2003, 845 AEs occurred, and 40% of these were disclosed to patients. Higher-quality ratings were two times as likely when preventable and nonpreventable AEs were disclosed. Patients were also about twice as likely to say they felt they could protect themselves when the AEs were disclosed. When events were preventable, caused discomfort, or continued to affect the patient adversely at the time of the survey, quality ratings were lower. (L. López, llopez1@partners.org)
Patient Safety Movement at 10: Reflecting on the above hospital adverse events study and considering the 10 years that have passed since the Institute of Medicine released its landmark To Err Is Human study, an author writes (pp. 1894–6): “Getting providers to disclose errors to patients and to discuss diagnostic errors openly requires the creation of supportive, safe environments, coupled with appropriate training. For error disclosure, such safe environments are bolstered by evidence that malpractice risk is not raised by disclosure, by laws that protect apologies from being used against physicians in litigation, by training programs in effective disclosure techniques, and by findings such as those of López and colleagues demonstrating that patients rate the quality of care higher when adverse events are disclosed.” (R. M. Wachter, bobw@medicine.ucsf.edu)

>>>PNN NewsWatch
* Romidepsin (Istodax, Gloucester Pharmaceuticals) has been approved for treatment of cutaneous T-cell lymphoma, FDA announced yesterday.
* Possible presence of particulate matter has led to the recall of 85 lots of
Liposyn II 10%, Liposyn II 20%, Liposyn III 10%, Liposyn III 20%, and Liposyn III 30%, and 73 lots of Propofol Injectable Emulsion 1% products. Affected lots have numbers beginning with 79 or 80, Hospira and FDA said.

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 © 2009, 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, 2009 * Vol. 16, No. 217
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 11 issue of JAMA (2009; 302).
Persistent Pain After Breast Cancer Surgery: In a study of Danish women who had breast cancer surgery in 2005–06, pain and sensory disturbances persisted 2–3 years later (pp. 1985–92). Responses to a questionnaire sent in the first 4 months of 2008 showed the following: “By June 2008, 3,253 of 3,754 eligible women (87%) returned the questionnaire. A total of 1,543 patients (47%) reported pain, of whom 201 (13%) had severe pain, 595 (39%) had moderate pain, and 733 (48%) had light pain. Factors associated with chronic pain included young age (18–39 years: OR, 3.62; 95% confidence interval [CI], 2.25–5.82; P < .001) and adjuvant radiotherapy (OR, 1.50; 95% CI, 1.08–2.07; P = .03), but not chemotherapy (OR, 1.01; 95% CI, 0.85–1.21; P = .91). Axillary lymph node dissection (ALND) was associated with increased likelihood of pain (OR, 1.77; 95% CI, 1.43–2.19; P < .001) compared with sentinel lymph node dissection. Risk of sensory disturbances was associated with young age (18–39 years: OR, 5.00; 95% CI, 2.87–8.69; P < .001) and ALND (OR, 4.97; 95% CI, 3.92–6.30; P < .001). Pain complaints from other parts of the body were associated with increased risk of pain in the surgical area (P < .001). A total of 306 patients (20%) with pain had contacted a physician within the prior 3 months for pain complaints in the surgical area.” (R. Gärtner, runegartner@gmail.com)
Editorialists offer this advice: (
pp. 2034–5): “Chronic pain after breast cancer surgery is an important clinical issue that demands careful attention. In addition to nerve injury from breast surgery and axillary procedures, other etiologies of pain should be considered, including brachial plexus infiltration by tumor; compression injury to the brachial plexus from lymphedema; radiation-induced ischemic plexopathy, injury, and fibrosis; carpal tunnel syndrome; and second primary tumors. Patients at high risk for the development of postsurgical pain syndrome should be identified, should have therapy initiated early, and the effects of early intervention should be assessed. Management requires a multidisciplinary approach that includes evaluation by surgeons, medical oncologists, radiation oncologists, pain management specialists, psychologists and psychiatrists, social workers, and experts in rehabilitation medicine. Thus, the findings reported by Gärtner et al should prove helpful in the search for achieving effective relief of pain after breast cancer surgery.” (L. S. Loftus, loretta.loftus@moffitt.org)
Statins & Gallstones: Patients on long-term statin therapy have decreased risks of gallstone disease requiring cholecystectomy, researchers report (pp. 2001–7). A case–control analysis of the U.K. General Practice Research Database for incident cases of gallstone disease between 1994 and 2008 showed the following: “A total of 27,035 patients with cholecystectomy and 106,531 matched controls were identified, including 2,396 patients and 8,868 controls who had statin use. Compared with nonuse, current statin use (last prescription recorded within 90 days before the first-time diagnosis of the disease) was 1.0% for patients and 0.8% for controls (AOR, 1.10; 95% CI, 0.95–1.27) for 1 to 4 prescriptions; 2.6% vs 2.4% (AOR, 0.85; 95% CI, 0.77–0.93) for 5 to 19 prescriptions, and 3.2% vs 3.7% (AOR, 0.64; 95% CI, 0.59–0.70) for 20 or more prescriptions. The AORs for current use of statins defined as 20 or more prescriptions were similar (around 0.6) across age, sex, and body mass index categories, and across the statin class.” (C. R. Meier, meierch@uhbs.ch)

>>>PNN NewsWatch
* In a letter to health care professionals, Commissioner of Food and Drugs Margaret A. Hamburg seeks to allay concerns and provide talking points about A/H1N1 influenza disease and vaccines. She explains that the process used in development of the H1N1 vaccines was “similar in every respect to that which is employed every year for the preparation of seasonal influenza vaccines.” In addition, “FDA and other agencies are looking for any unexpected, rare, serious adverse events and are quickly investigating concerns,” she said.
* A
Washington State nurse was sentenced for tampering with meperidine by opening ampules, removing the contents, refilling with saline, and using Super Glue to put the ampules back together before returning them to stock.

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 © 2009, 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, 2009 * Vol. 16, No. 218
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Nov. 12 issue of the New England Journal of Medicine (2009; 361).
H1N1 Influenza: Three articles and an editorial discuss 2009 novel A/H1N1 influenza virus.
During this year’s winter season in Australia and New Zealand, intensive-care units were inundated with patients with 2009 pandemic influenza A (H1N1) virus (
pp. 1925–34). Among 722 patients with confirmed H1N1, the investigators reported: “669 (92.7%) were under 65 years of age and 66 (9.1%) were pregnant women; of the 601 adults for whom data were available, 172 (28.6%) had a body-mass index … greater than 35. Patients infected with the 2009 H1N1 virus were in the ICU for a total of 8,815 bed-days (350 per million inhabitants). The median duration of treatment in the ICU was 7.0 days (interquartile range, 2.7 to 13.4); 456 of 706 patients (64.6%) with available data underwent mechanical ventilation for a median of 8 days (interquartile range, 4 to 16). The maximum daily occupancy of the ICU was 7.4 beds (95% CI, 6.3 to 8.5) per million inhabitants. As of September 7, 2009, a total of 103 of the 722 patients (14.3%; 95% CI, 11.7 to 16.9) had died, and 114 (15.8%) remained in the hospital.” (S. A. R. Webb, sarwebb@cyllene.uwa.edu.au)
During April through mid-June 2009 in the U.S., severe cases of A/H1N1 influenza requiring intensive care was seen, with some deaths, reports a second article (
pp. 1935–44): “Of the 272 patients we studied, 25% were admitted to an intensive care unit and 7% died. Forty-five percent of the patients were children under the age of 18 years, and 5% were 65 years of age or older. Seventy-three percent of the patients had at least one underlying medical condition; these conditions included asthma; diabetes; heart, lung, and neurologic diseases; and pregnancy. Of the 249 patients who underwent chest radiography on admission, 100 (40%) had findings consistent with pneumonia. Of the 268 patients for whom data were available regarding the use of antiviral drugs, such therapy was initiated in 200 patients (75%) at a median of 3 days after the onset of illness. Data suggest that the use of antiviral drugs was beneficial in hospitalized patients, especially when such therapy was initiated early.” (S. Jain, bwc8@cdc.gov)
Patterns of cross-reactivity among patients receiving prior influenza vaccines or with possible previous exposure to the H1N1 influenza virus are described in the third paper (
pp. 1945–52). Using stored serum samples from people who had donated blood or been vaccinated with either seasonal or the 1976 H1N1 swine influenza vaccines, researchers determined: “A total of 4 of 107 persons (4%) who were born after 1980 had preexisting cross-reactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults.” (J. M. Katz, jkatz@cdc.gov)
While acknowledging that the number of deaths from H1N1 thus far does not approach the numbers typically encountered with seasonal influenza, editorialists provide this assessment of possible impact (
pp. 1991–3): “In the United States, there are approximately 6,000 ICUs with 66,000 beds for adults and 20,000 for children. An estimated 90,000 respirators for mechanical ventilation are available. Recently, Zilberberg and colleagues analyzed data from Mexico and the United States to explore the potential effect of 2009 H1N1 influenza on ICUs by using Monte Carlo simulations. They estimated that ICUs in the United States would need to handle more than 330,000 episodes of mechanical ventilation, an increase in volume of 23 to 45% over current use. However, the preliminary data from the [Webb et al.] study show a small fraction of that estimate: if the findings from Australia and New Zealand are extrapolated to the United States, they would indicate a need for only 5,433 episodes of mechanical ventilation and 62,400 ventilation-days over a 3-month period.” (R. P. Wenzel)

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 © 2009, 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, 2009 * Vol. 16, No. 219
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Nov. 17 issue of the Journal of the American College of Cardiology (2009; 54).
Gender Considerations with Clopidogrel Therapy: In both men and women, clopidogrel reduces the risk of cardiovascular events, researchers report (pp. 1935–45). The current findings differ from previous studies showing gender-related difference in clopidogrel therapy: “Overall, clopidogrel was associated with a highly significant 14% proportional reduction in the risk of cardiovascular events (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93), with no significant differences in treatment effect between women and men. Among the 23,533 women enrolled, there were fewer cardiovascular events in the clopidogrel group compared with the placebo group (11.0% vs. 11.8%; OR: 0.93; 95% CI: 0.86 to 1.01). In women the risk reduction with clopidogrel seemed to be greatest for MI (OR: 0.81; 95% CI: 0.70 to 0.93), with the effects on stroke (OR: 0.91; 95% CI: 0.69 to 1.21) or total death (OR: 0.99; 95% CI: 0.90 to 1.08) not statistically significant. Among the 56,091 men enrolled, there were fewer cardiovascular events in those receiving clopidogrel compared with placebo (7.8% vs. 9.0%; OR: 0.84; 95% CI: 0.78 to 0.91), and the risk reduction was significant for MI (OR: 0.83; 95% CI: 0.76 to 0.92), stroke (OR: 0.83; 95% CI: 0.71 to 0.96), and total death (OR: 0.91; 95% CI: 0.84 to 0.97). Clopidogrel increased the risk of major bleeding in both women (OR: 1.43; 95% CI: 1.15 to 1.79) and men (OR: 1.22; 95% CI: 1.05 to 1.42).” (J. S. Berger, jeffrey.berger@nyumc.org)
“Women are like men … sometimes,” writes an editorialist (
pp. 1946–8): “The cumulative evidence continues to show that women with coronary artery disease differ from men in many important ways, including the response to antiplatelet therapy. The good news is that clopidogrel is an exception. It is also critically important that future studies are designed to adequately address the responses to therapy in women because outcomes cannot be predicted by mostly male-dominated trials. Only then can treatment be optimized for the growing population of women with cardiovascular disease.” (D. P. Faxon, dfaxon@partners.org)
Adult Complications of Kawasaki Disease: A subset of adult patients who had Kawasaki disease as children require treatment for life, write authors of a state-of-the-art paper (pp. 1911–20): “Kawasaki disease (KD) is an acute, self-limited vasculitis that typically occurs in young children and was first described by Japanese pediatrician Tomisaku Kawasaki in 1967. Although originally thought to be a rare condition, KD has become the most common cause of acquired heart disease in the pediatric age group in developed countries. The majority of patients with KD appear to have a benign prognosis, but a subset of patients with coronary artery aneurysms are at risk for ischemic events and require lifelong treatment. In the 4 decades that have passed since the initial recognition of KD, the number of patients reaching adulthood has continued to grow. Adult cardiologists will be increasingly involved in the management of these patients. Currently, there are no established guidelines for the evaluation and treatment of adult patients who have had KD. We review here the current literature that may be helpful to clinicians who care for adults who experienced KD in childhood.” (J. B. Gordon, AdultKD@gmail.com)

>>>PNN NewsWatch
* FDA yesterday expanded the approved indications of CSL’s 2009 A/H1N1 influenza vaccine to include children and adolescents ages 6 months to 18 years. This vaccine was previously approved only for use in adults. The approval was based on a study of the company’s seasonal flu vaccine in children showing the vaccine’s safety and efficacy in inducing antibodies to protect against influenza. Common adverse events experienced by children after administration of seasonal and H1N1 vaccines typically include pain, redness and swelling at the injection site as well as, in some cases, irritability, loss of appetite, and drowsiness.
*
APhA today dedicates the new addition to its historic home on the National Mall in Washington, DC. An annex built around 1960 was replaced with a six-story structure that expanded the group’s square footage 10-fold, to 359,026 square feet.

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 © 2009, 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. 16, 2009 * Vol. 16, No. 220
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 14 issue of Lancet (2009; 374).
Persistence of Lifestyle, Drug Interventions To Delay Diabetes: In a long-term follow-up on the Diabetes Prevention Program (DPP) patients, researchers found that lifestyle interventions and metformin effects persisted for at least 10 years (pp. 1677–86). The original randomized trial, conducted over 2.8 years, showed a 58% reduction in diabetes incidence among those in the intensive lifestyle intervention group and 31% among those taking metformin. During a median additional follow-up of 5.7 years, these trends were observed in 2,766 DPP patients: “During the 10.0-year (IQR 9.0–10.5) follow-up since randomisation to DPP, the original lifestyle group lost, then partly regained weight. The modest weight loss with metformin was maintained. Diabetes incidence rates during the DPP were 4.8 cases per 100 person–years (95% CI 4.1–5.7) in the intensive lifestyle intervention group, 7.8 (6.8–8.8) in the metformin group, and 11.0 (9.8–12.3) in the placebo group. Diabetes incidence rates in this follow-up study were similar between treatment groups: 5.9 per 100 person-years (5.1–6.8) for lifestyle, 4.9 (4.2–5.7) for metformin, and 5.6 (4.8–6.5) for placebo. Diabetes incidence in the 10 years since DPP randomisation was reduced by 34% (24–42) in the lifestyle group and 18% (7–28) in the metformin group compared with placebo.” (Diabetes Prevention Program Research Group, dppmail@biostat.bsc.gwu.edu)
Killed Whole-Cell Cholera Vaccine: In India, children aged 1.0 to 4. 9 years were protected against clinically significant cholera by a killed whole-cell oral vaccine, researchers report (pp. 1694–702). The study included nearly 108,000 nonpregnant resident who were cluster-randomized to receive orally either the test vaccine or a heat-killed Escherichia coli K12 placebo. Results showed: “There were 20 episodes of cholera in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%; one-tailed 99% CI, lower bound 35%, p < 0.0001). The vaccine protected individuals in age-groups 1.0–4.9 years, 5.0–14.9 years, and 15 years and older, and protective efficacy did not differ significantly between age-groups (p = 0.28). We recorded no vaccine-related serious adverse events.” (A. L. Lopez, anlopez@ivi.int)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 339).
Metformin v. Repaglinide in Nonobese Patients with Type 2 Diabetes: In 97 nonobese patients with type 2 diabetes who had preserved beta-cell function, supplementation of insulin therapy with metformin yielded equivalent glycemic control and less weight gain than did insulin plus repaglinide (b4324). Patients had glycosylated hemoglobin levels of 6.5% or more at randomization to repaglinide 6 mg or metformin 2,000 mg with biphasic insulin aspart 70/30 6 units once daily before dinner. Twelve-month results showed the following: “At the end of treatment, HbA1c concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA1c 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P = 0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments –2.51 kg, 95% confidence interval –4.07 to –0.95).” (S. S. Lund, sqrl@steno.dk)

>>>PNN JournalWatch
* Genome-wide Association Studies and Human Disease: From Trickle to Flood, in JAMA, 2009; 302: 2028–9. (P. M. Visscher, peter.visscher@qimr.edu.au)
* Why We Don’t Have an HIV Vaccine, and How We Can Develop One, in
Health Affairs, 2009; 28: 1642–54. (J. Harris, jeffrey@mit.edu)
* Acute Pancreatitis and Critical Illness: A Pancreatic Tale of Hypoperfusion and Inflammation, in
Chest, 2009; 136: 1413–9. (K. W. Burchard, Kenneth.W.Burchard@Hitchcock.org)
* Does Left Atrial Appendage Occlusion Eliminate the Need for Warfarin? [point/counterpoint], in
Circulation, 2009; 120: 1919–26; 1927–32. (D. R. Holmes, Jr, holmes.david@mayo.edu; R. Whitlock, richard.whitlock@phri.ca)
* Histone Deacetylase Inhibitors in Cancer Therapy, in
Journal of Clinical Oncology, 2009; 27: 5459–68. (B. A. Chabner, bchabner@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 © 2009, 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, 2009 * Vol. 16, No. 221
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Nov. 17 issue of the Annals of Internal Medicine (2009; 151).
Self-management in Hypertension Control: Compared with usual care, a 24-month program of home blood pressure monitoring with telephone intervention enabled patients to achieve better control of hypertension, researchers report (pp. 687–95). At two university-affiliated primary care clinics, patients received either usual care, a behavioral intervention (bimonthly tailored, nurse-administered telephone intervention targeting hypertension-related behaviors), home BP monitoring 3 times weekly, or behavioral intervention plus home BP monitoring, with these results: “475 patients (75%) completed the 24-month BP follow-up. At 24 months, improvements in the proportion of patients with BP control relative to the usual care group were 4.3% (95% CI, −4.5% to 12.9%) in the behavioral intervention group, 7.6% (CI, −1.9% to 17.0%) in the home BP monitoring group, and 11.0% (CI, 1.9%, 19.8%) in the combined intervention group. Relative to usual care, the 24-month difference in systolic BP was 0.6 mm Hg (CI, −2.2 to 3.4 mm Hg) for the behavioral intervention group, −0.6 mm Hg (CI, −3.6 to 2.3 mm Hg) for the BP monitoring group, and −3.9 mm Hg (CI, −6.9 to −0.9 mm Hg) for the combined intervention group; patterns were similar for diastolic BP.” (H. B. Bosworth, hayden.bosworth@duke.edu)
Eszopiclone in CPAP Adherence: Administered during the first 2 weeks of continuous positive airway pressure therapy, eszopiclone improved 24-week CPAP adherence (pp. 696–702). In 160 patients newly diagnosed with obstructive sleep apnea, eszopiclone 3 mg or placebo for the first 14 nights of CPAP therapy yielded these results: “Patients in the eszopiclone group used CPAP for 20.8% more nights (95% CI, 7.2% to 34.4%; P = 0.003), 1.3 more hours per night for all nights (CI, 0.4 to 2.2 hours; P = 0.005), and 1.1 more hours per night of CPAP use (CI, 0.2 to 2.1 hours; P = 0.019). The hazard ratio for discontinuation of CPAP was 1.90 (CI, 1.1 to 3.4; P = 0.033) times higher in the placebo group. Side effects were reported in 7.1% of patients and did not differ between groups.” (C. J. Lettieri, christopher.lettieri@us.army.mil)
Prevention of Breast Cancer: Three medications reduce the risk of breast cancer, according to a comparative-effectiveness systematic review, but adverse-effect profiles must be considered (pp. 703–15). Tamoxifen and to some degree raloxifene increase the risk of thromboembolic events; tamoxifen increases risks of endometrial cancer and cataracts; and tibolone carries a stroke risk in older women. (H. Nelson, nelsonh@ohsu.edu)
Family History in Medical Care: Despite the assumption that taking a good family history should be a core element in medical care, little concrete evidence supports the practice and patient recall is somewhat suspect, according to an NIH conference report and systematic review (early release). The NIH document concludes by emphasizing these research challenges: “Family history was a core element of clinical care long before the evidence-based medicine paradigm was even proposed. Therefore, it comes as no surprise that the evidence base supporting family history for common diseases in primary care, as assessed in this state-of-the-science review, is weak in defining the key elements, assessing test performance, linking results to clinical conditions, acting on results in specific clinical scenarios, evaluating potential benefits and harms, and assessing factors encouraging and discouraging use of family history. For a systematically collected family history for common diseases to become an evidence-based tool in primary care clinical settings, substantial additional research is needed. Challenges include the number, complexity, and cost of rigorous studies that can adequately address the scientific questions outlined in this panel’s research recommendations. The relative priority of specific research questions on family history in the context of other health information and genetic technologies and interventions that might address the same clinical problems in different ways requires debate to ensure the best outcomes for improving health.” (www.consensus.nih.gov; 888-644-2667)

>>>PNN NewsWatch
* A fifth 2009 H1N1 influenza vaccine has been licensed by FDA. ID Biomedical Corp., owned by GlaxoSmithKline, will supply thimerosal-containing multidose vials.

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 © 2009, 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, 2009 * Vol. 16, No. 222
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 18 issue of JAMA (2009; 302).
Telephone-Delivered Collaborative Care: After 8 months of telephone-delivered collaborative care provided by nurses to 302 patients with depression following coronary artery bypass graft surgery, mental health-related quality of life (HRQL), physical functioning, and mood symptoms were better than in 151 patients who received usual care (pp. 2095–103). Nurses with primary care physicians were supervised by a study psychiatrist and primary care physician. The Short Form-36 Mental Component Summary (SF-36 MCS), Hamilton Rating Scale for Depression (HRS-D), physical HRQL (SF-36 PCS), and Duke Activity Status Index (DASI) showed: “The intervention patients reported greater improvements in mental HRQL (all P ≤ .02) (SF-36 MCS: change, 3.2 points; 95% confidence interval [CI], 0.5–6.0), physical functioning (DASI: change, 4.6 points; 95% CI, 1.9–7.3), and mood symptoms (HRS-D: change, 3.1 points; 95% CI, 1.3–4.9); and were more likely to report a 50% or greater decline in HRS-D score from baseline (50.0% vs 29.6%; number needed to treat, 4.9 [95% CI, 3.2–10.4]) than usual care patients (P < .001). Men with depression were particularly likely to benefit from the intervention (SF-36 MCS: change, 5.7 points; 95% CI, 2.2–9.2; P = .001). However, the mean HRQL and physical functioning of intervention patients did not reach that of the nondepressed comparison group.” (B. L. Rollman, rollmanbl@upmc.edu)
Mortality with Folate/B12 Treatment: Increased cancer risk related to B vitamin intake creates doubt about folic acid fortification of foods (pp. 2119–26). In two clinical trials from Norway, where foods are not supplemented with folic acid, 6,837 patients with ischemic heart disease were treated with B vitamins or placebo, with these results: “After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B12 vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03–1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B12 vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07–1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B12 vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04–1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B12.” (M. Ebbing, marta.ebbing@helse-bergen.no)

>>>PNN NewsWatch
* The anticlotting effects of clopidogrel are reduced by almost half by concomitant administration of omeprazole, FDA said yesterday. In contrast to a Lancet article that pronounced the combination acceptable (see PNN, Sept. 21), FDA says that omeprazole’s inhibition of CYP 2C19, which metabolizes clopidogrel, results in a 45% lower serum concentration of the drug’s active metabolite. The reduction occurs when doses are administered together or 12 hours apart. Similar effects can be expected from other 2C19 inhibitors, including cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, and ticlopidine.
* An
8% capsaicin patch, Qutenza (Lohmann Therapie-Systems AD; NeurogesX), has been approved as a prescription product by FDA for treatment of the pain of postherpetic neuralgia. Because placement of the patch can be painful, it must be applied by a health professional. Local topical anesthetics are used in the procedure, and patients sometimes receive ice treatments or opioid analgesics beforehand. In addition, patients should be observed for 1 hour after the patch is placed so that blood pressure can be monitored for elevations that sometimes occur. Pain, swelling, itching, redness, and bumps at the application site are the most common adverse effects of the new patch.
*
CNN, citing a study commissioned by AARP, reports that drug costs are up 9% over the past year. Since the pharmaceutical industry has pledged to contribute $80 billion in cost reductions over the next 10 years as part of the Obama Administration’s health care reform package, the observation that prices have been raised in advance will likely play into the debate about to begin in the Senate.

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 © 2009, 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, 2009 * Vol. 16, No. 223
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release article from and Nov. 19 issue of New England Journal of Medicine (2009; 361).
Antiviral Treatment of Hospitalized Patients with Influenza: Data on use of neuraminidase inhibitors in patients hospitalized for H1N1 influenza come only from observational studies, writes a CDC official in a brief review article (early release): “Taken together, although data are limited, findings of observational studies all point in the same direction, suggesting benefit of early neuraminidase inhibitor treatment for hospitalized influenza patients as well as for patients presenting >48 hours after illness onset. In the setting of 2009 pandemic influenza A (H1N1) virus activity in a community, empiric neuraminidase inhibitor treatment should be started as soon as possible for any hospitalized patient who presents with influenza that is suspected (e.g., acute respiratory illness, acute exacerbation of chronic conditions, or other complications) or confirmed, in addition to initiating antibiotic treatment as indicated for suspected bacterial coinfection.” (T. Uyeki)
IBD & the Interleukin-10 Receptor: A possible molecular cause of inflammatory bowel disease is identified in a study of nine patients, and disease remission in one patient with allogeneic stem-cell transplantation is reported (pp. 2033–45). In two families described as unrelated but of common ancestry who had children with early-onset IBD and an additional six patients with this condition, genetic-linkage analysis and candidate-gene sequencing revealed these patterns: “In four of nine patients with early-onset colitis, we identified three distinct homozygous mutations in genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively, which form a heterotetramer to make up the interleukin-10 receptor. The mutations abrogate interleukin-10–induced signaling, as shown by deficient STAT3 (signal transducer and activator of transcription 3) phosphorylation on stimulation with interleukin-10. Consistent with this observation was the increased secretion of tumor necrosis factor and other proinflammatory cytokines from peripheral-blood mononuclear cells from patients who were deficient in IL10R subunit proteins, suggesting that interleukin-10–dependent ‘negative feedback’ regulation is disrupted in these cells. The allogeneic stem-cell transplantation performed in one patient was successful.” (C. Klein, klein.christoph@mh-hannover.de)
Advances in IBD Therapy: While inhibitors of tumor necrosis factor alpha provided an important advance in treatment of inflammatory bowel disease, their use is limited by loss of efficacy, write authors of a review article (pp. 2066–78). Under investigation are several novel therapies, the authors explain: “Anti-p40 monoclonal antibodies have been reported to be effective in psoriasis and Crohn’s disease. The p40 cytokine subunit is common to both interleukin-23 and interleukin-12, and monoclonal antibodies against p40 inhibit both pathways. Selective blockade of interleukin-23 can be achieved by targeting the p19 subunit, and this approach has been reported to be effective in many, although not all, animal models of inflammatory bowel disease. Selective inhibition of interleukin-23 may, however, deregulate other, cross-regulated pathways and T-cell subgroups, with unintended consequences. Moreover, some Th17 cytokines may also have protective features; for example, interleukin-22 ameliorates disease in an animal model of colitis. A major question that remains to be resolved is whether selective interleukin-23 blockade will be more or less effective than combined interleukin-12–interleukin-23 blockade in the treatment of inflammatory bowel disease.” (J. H. Cho, judy.cho@yale.edu)

>>>PNN NewsWatch
* Pharmacist-delivered medication management services are included in the Patient Protection and Affordable Care Act introduced yesterday by Senate Majority Leader Harry Reid of Nevada. The measure contains provisions needed for political cover by moderate Democrats from conservative Southern states such as Arkansas and Louisiana but also an opt-out version of the public plan sought by many members of the party. Whether the bill can the votes of all 58 Democrats and 2 independent Senators who caucus with them—or possibly attract the support of Maine’s pair of moderate Republican Senators—could well determine the fate of health care reform in this session.

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 © 2009, 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, 2009 * Vol. 16, No. 224
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Nov. issue of the Journal of Allergy and Clinical Immunology (2009; 124).
Etanercept for Psoriasis: The mechanism of action of etanercept is explored in patients with psoriasis vulgaris (pp. 1022–30.e395). While 11 responders and 4 nonresponders were all found to inactivate sepsis cascade cytokines, researchers determined, “Response to etanercept is dependent on inactivation of myeloid dendritic cell genes and inactivation of the Th17 immune response.” Genomic profiling of the participants showed: “In responders, 4 clusters of downregulated genes and 3 clusters of upregulated genes were identified. Genes downmodulated most rapidly reflected direct inhibition of myeloid lineage immune genes. Upregulated genes included the stable dendritic cell population genes CD1c and CD207 (langerin). Comparison of responders and nonresponders revealed rapid downmodulation of innate IL-1-beta and IL-8 sepsis cascade cytokines in both groups, but only responders downregulated IL-17 pathway genes to baseline levels.” (J. G. Krueger, jgk@rockefeller.edu)

>>>Neurology Highlights
Source:
Nov. issue of Neurology (2009; 73).
Gene Therapy for Parkinson Disease: Infusion of the gene for aromatic l-amino acid decarboxylase (AADC) improved mean scores on the Unified Parkinson’s Disease Rating Scale by approximately 30% in the on and off states among 10 patients with moderately advanced disease, but the procedure was not without risks, researchers report (pp. 1662–9). Patients received low or high doses of a bilateral intraputaminal infusion of adeno-associated viral type 2 vector containing the human AADC gene, with these results: “The gene therapy was well tolerated, but 1 symptomatic and 2 asymptomatic intracranial hemorrhages followed the operative procedure. Total and motor rating scales improved in both cohorts. Motor diaries also showed increased on-time and reduced off-time without increased ‘on’ time dyskinesia. At 6 months, [radionuclide PET imaging] showed a 30% increase of putaminal uptake in the low-dose cohort and a 75% increase in the high-dose cohort.” (M. J. Aminoff, aminoffm@neurology.ucsf.edu)

>>>Geriatrics Highlights
Source:
Nov. issue of the Journal of the American Geriatrics Society (2009; 57).
Cardiovascular Medication Use After ACS: Among patients recently discharged with a diagnosis of acute coronary syndrome, older adults are less likely to persist with medication therapy than those in other age groups, researchers report (pp. 1990–6). Addressing the reasons that patients cite in explaining their discontinuance of evidence-based cardiovascular medications (EBCMs) is important in practice, the group maintains, citing these results: “At 3-month follow-up, overall persistence was 71.2%. There was a significant trend toward lower overall persistence with prescribed EBCMs in older adults than in the other age groups (74.9% for <60, 71.0% for 60–69, 64.5% for ≥70; P = .02). Overall, 112 (10.6%) patients discontinued EBCMs with provider advice, and 178 (16.9%) self-discontinued. Provider discontinuation increased across age groups (9.1%, 10.4%, and 13.6%, respectively). A similar trend was observed for EBCM self-discontinuation (15.2%, 17.0%, and 19.9%, respectively). Reasons for self-discontinuation included adverse effects, cost, and perception that the medication was not needed.” (R. C. Ali, robin.ali@duke.edu)
Bradycardia in Patients on Cholinesterase Inhibitors: Patients with dementia who are being treated with cholinesterase inhibitors have an increased risk of bradycardia, according to an analysis of data from the New England Veterans Affairs Healthcare System (pp. 1997–2003). The risk with donepezil appeared to be dose-related, as follows: “A greater risk for bradycardia was found in patients taking any ChE-Is than in the no-treatment group (adjusted hazard ratio (HR) = 1.4, 95% confidence interval (CI) = 1.1–1.6). A dose–response effect was observed for donepezil, with the highest-dose group at greatest risk (HR = 2.1, 95% CI = 1.5–2.9). Results were consistent regardless of bradycardia definition. Patients with bradycardia were more likely to fall, experience syncope, or need a pacemaker implantation than those without.” (E. V. Lawler, Elizabeth.Lawler@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 © 2009, 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. 23, 2009 * Vol. 16, No. 225
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 21 issue of Lancet (2009; 374).
Forming a Temporary Skin Substitute for Large Burns: Human embryonic stem cells (hESCs) can be used to form temporary skin substitutes that could be useful in initial management of patients with large burns—while awaiting autologous grafts to be cultured from the patient’s own cells—researchers report (pp. 1745–53). Using two lines of hESCs, the investigators cultured cells and found they could be differentiated into basal kerotinocytes that were fully functional, as described here: “From hESCs, we generated a homogeneous population of cells that showed phenotypic characteristics of basal keratinocytes. Expression levels of genes encoding keratin 14, keratin 5, integrin alpha-6, integrin beta-4, collagen VII, and laminin 5 in these cells were similar to those in basal keratinocytes. After seeding on an artificial matrix, keratinocytes derived from hESCs (K-hESCs) formed a pluristratified epidermis. Keratin-14 immunostaining was seen in the basal compartment, with keratin 10 present in layers overlying the basal layer. Involucrin and filaggrin, late markers of epidermal differentiation, were detected in the uppermost layers only. 12 weeks after grafting onto five immunodeficient mice, epidermis derived from K-hESCs had a structure consistent with that of mature human skin. Human involucrin was appropriately located in spinous and granular layers and few Ki67-positive cells were detected in the basal layer.” (C. Baldeschi, cbaldeschi@istem.genethon.fr)
Genotypes in Asthma Management: B16 genotypes (Arg/Arg or Gly/Gly) in patients with asthma do not affect responses to combination treatment with salmeterol and inhaled corticosteroids, according to results of the long-acting beta-2 agonist in asthma (LARGE) trial (pp. 1754–64). Genotyping in the open-label study showed these results based on peak expiratory flow (PEF) as measured by patients each morning: “After 18 weeks of treatment, mean morning PEF in Arg/Arg participants was 21.4 L/min (95% CI 11.8—31.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p < 0.0001). In Gly/Gly participants, morning PEF was 21.5 L/min (11.0—32.1) higher when participants were assigned to receive salmeterol than when assigned to receive placebo (p < 0.0001). The improvement in PEF did not differ between genotypes (difference [Arg/Arg—Gly/Gly] −0.1, −14.4 to 14.2; p = 0.99). In Gly/Gly participants, methacholine PC20 (20% reduction in forced expiratory volume in 1 s; a prespecified secondary outcome) was 2.4 times higher when participants were assigned to salmeterol than when assigned to placebo (p < 0.0001). Responsiveness to methacholine did not differ between salmeterol and placebo in Arg/Arg participants (p = 0.87). The 2.5 times higher genotype-specific difference in responsiveness to methacholine was significant (1.32 doubling dose difference between genotypes, 0.43—2.21, p = 0.0038). Seven Arg/Arg participants (placebo, n = 5; salmeterol, n = 2) and six Gly/Gly participants (placebo, n=3; salmeterol, n = 3) had an asthma exacerbation.” (M. E. Wechsler, mwechsler@partners.org)

>>>PNN NewsWatch
* While major hurdles remain to be cleared with regard to public-option and abortion-coverage provisions, the health care reform bill remains on track in Congress as a result of Saturday’s Senate vote to begin debate. APhA reports on pharmacist.com that the bill includes numerous favorable pharmacy provisions in its 2,074 pages.

>>>PNN JournalWatch
* The Economy-wide Impact of Pandemic Influenza on the UK: A Computable General Equilibrium Modelling Experiment, in BMJ, 2009; 339: b4571. (R. D. Smith, richard.smith@lshtm.ac.uk)
* Management of Chronic Obstructive Pulmonary Disease: Moving Beyond the Asthma Algorithm, in
Journal of Allergy and Clinical Immunology, 2009; 124: 873–80. (S. C. Lazarus, lazma@ucsf.edu)
* Translating Clinical Guidelines into Clinical Practice: Role of the Pharmacist in Type 2 Diabetes Management, in
Journal of the American Pharmacists Association, 2009; 49: e152–e162. (S. Drab, drab@pitt.edu)
* Antimicrobial Susceptibility Testing: A Review of General Principles and Contemporary Practices, in
Clinical Infectious Diseases, 2009; 49: 1749–55. (J. H. Jorgensen, jorgensen@uthscsa.edu)
* Proteinuria in Kidney Transplant Recipients: Prevalence, Prognosis, and Evidence-Based Management, in
American Journal of Kidney Diseases, 2009; 54: 1131–44. (G. A. Knoll, gknoll@ottawahospital.on.ca)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2009, 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, 2009 * Vol. 16, No. 226
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release article from and Nov. 23 issue of the Archives of Internal Medicine (2009; 170).
Pharmacist–Physician Collaboration for BP Control: Blood pressure control rates were significantly better when pharmacists collaborated with physicians in the care of patients with uncontrolled hypertension at three Iowa clinics, compared with three control clinics (pp. 1996–2002). Clinical pharmacists used national guidelines for their recommendations to physicians, with these results: “The mean (SD) guideline adherence scores increased from 49.4 (19.3) at baseline to 53.4 (18.1) at 6 months (8.1% increase) in the control group and from 40.4 (22.6) at baseline to 62.8 (13.5) at 6 months (55.4% increase) in the intervention group (P = .09 for adjusted between-group comparison). The mean BP decreased 6.8/4.5 mm Hg in the control group and 20.7/9.7 mm Hg in the intervention group (P < .05 for between-group systolic BP comparison). The adjusted difference in systolic BP was –12.0 (95% confidence interval [CI], –24.0 to 0.0) mm Hg, while the adjusted difference in diastolic BP was –1.8 (95% CI, –11.9 to 8.3) mm Hg. The 24-hour BP levels showed similar effect sizes. Blood pressure was controlled in 29.9% of patients in the control group and in 63.9% of patients in the intervention group (adjusted odds ratio, 3.2; 95% CI, 2.0-5.1; P < .001).” (B. L. Carter, barry-carter@uiowa.edu)
Pharmacist-Facilitated Hospital Discharge Program: Pharmacist participation in the discharge process for patients at high risk for medication-related problems improved the identification and reconciliation of medication discrepancies at discharge but failed to reduce postdischarge resource utilization, according to a study of 724 patients (pp. 2003–10). Using a prospective, alternating-month quasi-experimental design involving the general medicine service and a faculty hospitalist service, a pharmacist provided medication therapy assessment, medication reconciliation, screening for adherence concerns, patient counseling and education, and postdischarge telephone follow-up. Results showed: “Medication discrepancies at discharge were identified in 33.5% of intervention patients and 59.6% of control patients (P < .001). Although all discrepancies were resolved in the intervention group prior to discharge, readmission rates did not differ significantly between groups at 14 days (12.6% vs 11.5%; P = .65) and 30 days (22.1% vs 18%; P = .17), nor did emergency department visits (2.8% vs 2.2%, respectively; P = .60).” (P. C. Walker, pcwalker@umich.edu)
Commenting on the above two studies plus another on the impact of nurse and dietitian cardiovascular care (
pp. 1988–95; R. S. Stafford, rstafford@stanford.edu), an editorialist advocates team-based care in chronic disease management (pp. 1945–8): “While most existing medical home teams do not include pharmacists, Bates calls for their inclusion, and a recent [Institute of Medicine] report includes pharmacists in new practice team-based models for the future. Given the mounting evidence of pharmacists’ contributions in improving patient quality of care in team-based practices, a comprehensive effort should be undertaken, before the medical home is broadened further, to ensure that pharmacists and other appropriate clinicians are included on the team and receive reasonable reimbursement.” (H. L. Lipton, Helene.Lipton@ucsf.edu)
Falls & Drugs in the Elderly: Use of sedatives and hypnotics, antidepressants, and benzodiazepines is associated with falls in elderly individuals, according to a meta-analysis of 22 studies, 9 drug classes, and 79,081 participants (pp. 1952–60). “It is hoped that future research in this area can be completed with larger sample sizes in both community and long-term care facility settings and thus improve the quality of information about fall risks that is available to physicians and pharmacists when they are deciding which types of pharmacotherapy to provide,” the authors conclude. (C. A. Marra, carlo.marra@ubc.ca)
Eliminating Consultation Codes: Billing by physicians for consultation rather than new patient evaluation and management is costing the Medicare system more than half a billion dollars each year, according to an author writing about health care reform (early release). He maintains that these consultation codes should be reevaluated in view of the need to reduce costs and create more parity for cognitive services for primary care physicians. (J. I. Shalowitz, j-shalowitz@kellogg.northwestern.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2009, 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, 2009 * Vol. 16, No. 227
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 25 issue of JAMA (2009; 302).
Chronic Pain & Falls in the Elderly: Among 749 community-dwelling older patients, chronic pain is associated with falls and fall-related injuries, researchers report (pp. 2214–21). Contrary to previous studies, the use of analgesics did not ameliorate the risk identified in the longitudinal Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) Boston Study: “There were 1,029 falls reported during the follow-up. A report of 2 or more locations of musculoskeletal pain at baseline was associated with greater occurrence of falls. The age-adjusted rates of falls per person–year were 1.18 (95% confidence interval [CI], 1.13–1.23) for the 300 participants with 2 or more sites of joint pain, 0.90 (95% CI, 0.87–0.92) for the 181 participants with single-site pain, and 0.78 (95% CI, 0.74–0.81) for the 267 participants with no joint pain. Similarly, more severe or disabling pain at baseline was associated with higher fall rates (P < .05). The association persisted after adjusting for multiple confounders and fall risk factors. The greatest risk for falls was observed in persons who had 2 or more pain sites (adjusted rate ratio [RR], 1.53; 95% CI, 1.17–1.99), and those in the highest tertiles of pain severity (adjusted RR, 1.53; 95% CI, 1.12–2.08) and pain interference with activities (adjusted RR, 1.53; 95%CI, 1.15–2.05), compared with their peers with no pain or those in the lowest tertiles of pain scores.” (S. G. Leveille, suzanne.leveille@umb.edu)
IV Drug Administration During Out-of-Hospital Cardiac Arrest: Short-term survival was increased in patients treated with intravenous medications during out-of-hospital cardiac arrest, but several key indicators were unchanged—survival to hospital discharge, quality of cardiopulmonary resuscitation (CPR), and long-term survival (pp. 2222–9). The study was conducted within the Oslo, Norway, emergency medical service system in 2003–08. Various elements in advanced cardiac life support (ACLS) showed these relationships with outcomes: “Of 1,183 patients for whom resuscitation was attempted, 851 were included; 418 patients were in the ACLS with intravenous drug administration group and 433 were in the ACLS with no access to intravenous drug administration group. The rate of survival to hospital discharge was 10.5% for the intravenous drug administration group and 9.2% for the no intravenous drug administration group (P = .61), 32% vs 21%, respectively, (P < .001) for hospital admission with return of spontaneous circulation, 9.8% vs 8.1% (P = .45) for survival with favorable neurological outcome, and 10% vs 8% (P = .53) for survival at 1 year. The quality of CPR was comparable and within guideline recommendations for both groups. After adjustment for ventricular fibrillation, response interval, witnessed arrest, or arrest in a public location, there was no significant difference in survival to hospital discharge for the intravenous group vs the no intravenous group (adjusted odds ratio, 1.15; 95% confidence interval, 0.69–1.91).” (T. M. Olasveengen, t.m.olasveengen@medisin.uio.no)
Failure Rate in Phase III Trials: Costs and increasingly risk-averse research processes are just two of the factors that are reducing the success of Phase III trials, a Commentary author writes (pp. 2254–6): “Although many factors play a role in the increasing failure rate in phase 3 clinical testing, decreasing control rates may be an indicator of a broader process of maturation. While the described adaptations can preserve control rates, permitting new treatments that undoubtedly may be of benefit, better understanding of the fundamental relationship between decreasing control rates and the marginal efficiency of innovation may permit wiser allocation of research resources.” (D. M. Kent, dkent1@tuftsmedicalcenter.org)

>>>PNN NewsWatch
* A higher number of cardiovascular events (myocardial infarction, stroke, resuscitated cardiac arrest, or death) associated with use of sibutramine is under study by FDA, the agency has announced. In the interim, use of sibutramine should be avoided in patients with a history of coronary artery disease, congestive heart failure, arrhythmias, or stroke.
* During the upcoming holiday season,
PNN will not be published on Nov. 26–27, Thanksgiving; Dec. 24–25, Christmas; and Dec. 31 and Jan. 1, 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 © 2009, 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. 30, 2009 * Vol. 16, No. 228
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 28 issue of Lancet, a theme issue on disability (2009; 374).
Losartan Doses in Heart Failure: Higher doses of losartan were significantly better than lower doses in terms of mortality and hospitalizations for heart failure among 3,846 patients with New York Heart Association class II through IV symptoms, left ventricular fractions of 40% or less, and intolerance to ACE inhibitors (pp. 1840–8). In the HEALL study, patients at 255 sites in 30 countries received either 50 or 150 mg doses of losartan each day, with these results: “With 4.7-year median follow-up in each group (IQR 3.7–5.5 for losartan 150 mg; 3.4–5.5 for losartan 50 mg), 828 (43%) patients in the 150 mg group versus 889 (46%) in the 50 mg group died or were admitted for heart failure (hazard ratio [HR] 0.90, 95% CI 0.82–0.99; p = 0.027). For the two primary endpoint components, 635 patients in the 150 mg group versus 665 in the 50 mg group died (HR 0.94, 95% CI 0.84–1.04; p = 0.24), and 450 versus 503 patients were admitted for heart failure (0.87, 0.76–0.98; p = 0.025). Renal impairment (n = 454 vs 317), hypotension (203 vs 145), and hyperkalaemia (195 vs 131) were more common in the 150 mg group than in the 50 mg group, but these adverse events did not lead to significantly more treatment discontinuations in the 150 mg group.” (M. A. Konstam, mkonstam@tuftsmedicalcenter.org)
Research Priorities in People with Disabilities: Using the priority-setting method of the Child Health and Nutrition Research Initiative, researchers examined opinions of 82 stakeholders about research priorities about the health of people with disabilities (pp. 1857–62): “The leading research priority was identification of barriers that people with disabilities have in accessing health services at different levels, and finding the best possible strategies to integrate their needs into primary health-care systems and ensure local delivery. Results showed that addressing specific impairments is secondary to ensuring that health systems provide adequately for all people with disabilities. Our findings are a call for urgent attention to the issue of access to appropriate health care for people with disabilities, especially in low-income and middle-income countries.” (M. Tomlinson, markt@sun.ac.za)

>>>NEJM Highlights
Source:
Nov. 26 issue of New England Journal of Medicine (2009; 361).
Niacin v. Ezetimibe for Lipid Modification: Among 208 patients with coronary heart disease or a CHD risk equivalent, extended-release niacin produced a significant regression in carotid intima–media thickness when combined with a statin, and niacin’s effect was larger than that of ezetimibe, researchers report (pp. 2113–22): “The mean HDL cholesterol level in the niacin group increased by 18.4% over the 14-month study period, to 50 mg per deciliter (P < 0.001), and the mean LDL cholesterol level in the ezetimibe group decreased by 19.2%, to 66 mg per deciliter (1.7 mmol per liter) (P < 0.001). Niacin therapy significantly reduced LDL cholesterol and triglyceride levels; ezetimibe reduced the HDL cholesterol and triglyceride levels. As compared with ezetimibe, niacin had greater efficacy regarding the change in mean carotid intima–media thickness over 14 months (P = 0.003), leading to significant reduction of both mean (P = 0.001) and maximal carotid intima–media thickness (P ≤ 0.001 for all comparisons). Paradoxically, greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima–media thickness (R = –0.31, P < 0.001). The incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group (1% vs. 5%, P = 0.04 by the chi-square test).” (A. J. Taylor, allen.taylor@medstar.net)

>>>PNN NewsWatch
* An additional brand of seasonal influenza vaccine has been licensed by FDA. Preservative-free Agriflu is manufactured in Italy by Novartis Vaccines and Diagnostics, which also produces the already-approved Fluvirin

>>>PNN JournalWatch
* Interventions for Muscular Dystrophy: Molecular Medicines Entering the Clinic, in Lancet, 2009; 374: 1849–56. (K. Bushby, kate.bushby@ncl.ac.uk)
* Use of Diuretics in Patients with Hypertension, in
New England Journal of Medicine, 2009; 361: 2153–64. (M. E. Ernst, michael-ernst@uiowa.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 © 2009, 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, 2009 * Vol. 16, No. 229
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Dec. 1 issue of the Annals of Internal Medicine (2009; 151).
Low-Dose Aspirin in Peptic Ulcer Bleeding: Continuing aspirin therapy at low cardioprotective doses during peptic ulcer bleeding increases patients’ risk of recurrent bleeding but lowers overall mortality rates, according to a 156-patient study (early release). Comparing aspirin 80 mg/day and placebo in patients who were also receiving pantoprazole, the investigators found these results in the 8 weeks after endoscopy: “Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points [95% CI, −3.6 to 13.4 percentage points]). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points [CI, 3.7 to 19.5 percentage points]).Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points [CI, 1.7 to 16.3 percentage points]).” (J. J. Y. Sung, joesung@cuhk.edu.hk)
Editorialists ask whether “we are harming patients” by withdrawing aspirin during acute peptic ulcer bleeding (
early release): “Perhaps of most importance, this trial forces us to reconsider the all-too-common paradigm that acutely focuses on the gut in upper gastrointestinal bleeding in these patients (even if this represents a vexing reality check for gastrointestinal endoscopists). The benefits of low-dose aspirin therapy must be weighed against its attendant risks in patients who develop peptic ulcer bleeding. Patients who receive antithrombotic therapy for primary prophylaxis should discontinue low-dose aspirin therapy unless the vascular risk profile worsens. On the basis of all available data, international consensus recommendations … concluded that patients with upper gastrointestinal bleeding who require secondary cardiovascular prophylaxis should resume low-dose aspirin therapy as soon as the cardiovascular risks outweigh the gastrointestinal risks (usually within 7 days).
“We must also not forget to tend to the long-term management of patients who have had gastrointestinal bleeding while receiving low-dose aspirin. In this case, the data are convincing that the combination of low-dose aspirin and proton-pump inhibitors results in less recurrent bleeding than a switch to clopidogrel alone during the following 12 months.” (A. N. Barkun,
alan.barkun@muhc.mcgill.ca)
Pharyngitis in Young People: Fusobacterium necrophorum should be added to the pharyngitis paradigm when treating adolescents and young adults aged 15–24 years, an author argues (pp. 812–5): “On the basis of published epidemiologic data, F. necrophorum is estimated to cause the Lemierre syndrome—a life-threatening suppurative complication—at a higher incidence than that at which group A streptococcus causes acute rheumatic fever. Moreover, these estimates suggest greater morbidity and mortality from the Lemierre syndrome.… Expanding the pharyngitis paradigm will have several important implications. Further epidemiologic research is needed on both F. necrophorum pharyngitis (especially clinical presentation) and the Lemierre syndrome. Clinicians need reliable diagnostic techniques for F. necrophorum pharyngitis. In the meantime, adolescents and young adults who develop bacteremic symptoms should be aggressively treated with antibiotics for F. necrophorum infection. Physicians should avoid macrolides if they choose to treat streptococcus-negative pharyngitis empirically. Finally, pediatricians, internists, family physicians, and emergency department physicians should know the red flags for adolescent and young adult pharyngitis: worsening symptoms or neck swelling (especially unilateral neck swelling). Adolescent and young adult pharyngitis is more complicated than previously considered.” (R. M. Centor, rcentor@uab.edu)

>>>PNN NewsWatch
* Today is World AIDS Day 2009. The theme is Universal Access and Human Rights. An estimated 33.4 million people are living with HIV, including 2.1 million children. Most people with HIV and AIDS live in lower- and middle-income countries. About one-half of people who acquire HIV do so before age 25 and die before reaching 35.

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 © 2009, 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, 2009 * Vol. 16, No. 230
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 2 issue of JAMA (2009; 302).
Infections in ICUs: A study of 1,265 intensive-care units in 75 countries shows the impact of infections: They are common, the risk of infection increases with ICU stay, and the risk of in-hospital death increases with infection (pp. 2323–9). The point-prevalence survey, which included 14,414 patients, showed these patterns on May 8, 2007: “On the day of the study, 7,087 of 13,796 patients (51%) were considered infected; 9,084 (71%) were receiving antibiotics. The infection was of respiratory origin in 4,503 (64%), and microbiological culture results were positive in 4,947 (70%) of the infected patients; 62% of the positive isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. Patients who had longer ICU stays prior to the study day had higher rates of infection, especially infections due to resistant staphylococci, Acinetobacter, Pseudomonas species, and Candida species. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25% [1,688/6,659] vs 11% [682/6,352], respectively; P < .001), as was the hospital mortality rate (33% [2,201/6,659] vs 15% [942/6,352], respectively; P < .001) (adjusted odds ratio for risk of hospital mortality, 1.51; 95% confidence interval, 1.36–1.68; P < .001).” (J-L Vincent, jlvincen@ulb.ac.be)
Reflecting on the above Extended Prevalence of Infection in Intensive Care (EPIC II) study, editorialists write (
pp. 2367–8): “Limiting use of antibiotics to patients with clear evidence of infection rather than colonization is essential, and discontinuation of antibiotics when their possible benefits have been obtained is also critical. New initiatives such as the use of biomarkers to aid clinicians in the decision to discontinue unnecessary antibiotic therapy should be encouraged. Immunotherapies and reduced reliance on invasive diagnostic and hemodynamic monitoring techniques might also be useful in the future. Development of novel classes of antimicrobial agents is sadly lacking and needs to be a major research priority. New drugs are needed to replace the increasingly obsolete classes of antibiotics that currently exist. A ‘postantibiotic era’ is difficult to contemplate but might become a reality unless the threat of progressive antibiotic resistance is taken seriously.” (S. M. Opal, Steven_Opal@brown.edu)

>>>Psychiatry Highlights
Source:
Dec. issue of the American Journal of Psychiatry (2009; 166).
Treating Aggression in ADHD: Addition of divalproex to optimized stimulant treatment increases the likelihood of remission of aggression in children with attention-deficit/hyperactivity disorder, researchers report (pp. 1392–401). The study included children with ADHD and a disruptive disorder whose aggression was not adequately responsive to stimulant therapy. Over 8 weeks, addition of divalproex or placebo with weekly family behavioral therapy showed these results: “A significantly higher proportion of children randomly assigned to divalproex met remission criteria (eight out of 14 [57%]) than those randomly assigned to placebo (two out of 13 [15%]). Divalproex was generally well tolerated.” (J. C. Blader, joseph.blader@stonybrook.edu)
Editorialists add this perspective (
pp. 1315–7): “The future of psychopharmacology in childhood aggression and its underlying disorders is an important area of great need for more work along the lines demonstrated in this study. It is unrealistic to assume, as we have been for some time, that complex behaviors, such as aggression (3), will respond robustly to single psychopharmacological agents in all patients and all types of comorbidity, and yet the bulk of clinical trials are done with single agents. A more realistic assumption is that a careful blend of activating (like stimulants) and inhibiting (arguably valproic acid) agents will ultimately result in controls of main and downstream effects of neurotransmitters that produce remission of symptoms. This is especially likely in children and adolescents in whom development generates rapid shifts in neurosystems underpinning instrumental behavior such as aggression.” (H. Steiner, steiner@stanford.edu)

>>>PNN NewsWatch
* The injectable agent ecallantide (Kalbitor, Dyax Corp.) has been approved by FDA for treatment of patients with hereditary angioedema.

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 © 2009, 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, 2009 * Vol. 16, No. 231
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 3 issue of and online article from the New England Journal of Medicine (2009; 361).
Antiretroviral Treatment of HIV-1 Infection: Significant differences were found among once-daily antiretroviral regimens, with abacavir–lamivudine performing best in a group of 1,858 patients with HIV-1 infection (pp. 2230–40). Also studied was tenofovir disoproxil fumarate (DF)–emtricitabine; patients also received either efavirenz or ritonavir-boosted atazanavir. Based on a primary efficacy end point of time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level ≥1,000 copies per milliliter at or after 16 weeks and before 24 weeks, or ≥200 copies per milliliter at or after 24 weeks), results showed: “A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the [nucleoside reverse-transcriptase inhibitor] combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir–lamivudine group than in the tenofovir DF–emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P < 0.001), with 57 virologic failures (14%) in the abacavir–lamivudine group versus 26 (7%) in the tenofovir DF–emtricitabine group. The time to the first adverse event was also shorter in the abacavir–lamivudine group (P < 0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.” (P. E. Sax, psax@partners.org)
Effects of Obesity and Smoking on U.S. Life Expectancy: The increasing rate of obesity in the U.S. threatens to reverse health gains from decreased smoking rates and other advances in care since the early 20th century, authors of a forecasting article write (pp. 2252–60). Life expectancy and quality-adjusted life expectancy were calculated for each year between 2005 and 2020 for a representative 18-year-old. Data sources included surveys of smoking trends, body mass index, and medical expenditures (as an indicator of health-related quality of life). Results showed: “The negative effects of increasing BMI overwhelmed the positive effects of declines in smoking in multiple scenarios. In the base case, increases in the remaining life expectancy of a typical 18-year-old are held back by 0.71 years or 0.91 quality-adjusted years between 2005 and 2020. If all U.S. adults became nonsmokers of normal weight by 2020, we forecast that the life expectancy of an 18-year-old would increase by 3.76 life–years or 5.16 quality-adjusted years.” (S. T. Stewart, sstewart@nber.org)
Emergency Use Authorization of Peramivir: Clinicians need to be aware of legal and clinical considerations when the investigational agent peramivir is used to treat H1N1 influenza under FDA’s Oct. 23 emergency use authorization, agency authors explain in a Perspective article (pp. 2204–7): “Under the EUA, the usual adult dose for peramivir is 600 mg administered intravenously once daily for 5 to 10 days. This dose was selected on the basis of findings of a treatment benefit at doses of 300 mg or 600 mg in acute, uncomplicated influenza; the expected proportionally greater exposure at 600 mg than at lower doses; and the consideration that patients with more severe disease may need a higher dose. The treatment duration was selected on the basis of the expected need for a longer duration in hospitalized patients and is consistent with the design of ongoing phase 3 trials in hospitalized patients. The available safety data, including data from the limited number of patients who received 600 mg daily for 5 or more days, supported the selection of this dose and duration under the EUA.” (D. Birnkrant)
Senate Debate on Health Care Reform: Americans can settle in for a long debate on health care reform in the Senate, journal national correspondent John K. Iglehart writes in a blog posted yesterday. Describing the Dec. 1 opening of the debate, he observes: “The first day of what promises to be a contentious weeks-long political war over health care reform underscored deep divisions between the parties. After weeks of twists and turns, one consensus that seems certain to survive is that the current spending trajectory is unsustainable, but changing it with so much money and market share at stake remains an unmet challenge.”

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 © 2009, 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, 2009 * Vol. 16, No. 232
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Dec. issue of Diabetes Care (2009; 32).
Economic v. Other Factors in Nonadherence: Pharmacists may be able to identify reasons that patients are not adhering to prescribed therapies based on whether they forgo all medications or just those for diabetes, based on a cross-sectional survey of 245 patients with both diabetes and chronic pain (pp. 2143–8). Researchers found that those who were nonadherent to both antidiabetic and analgesic medications were influenced by economic pressures, while those cutting back just on antidiabetic drugs were more likely affected by mood and beliefs about medications: “Of the patients, 9% cut back on medications for both conditions, 13% cut back on diabetes medications alone, and 9% cut back on pain medications alone. Income <20,000 USD (AOR = 5.7, P = 0.008) and monthly medication costs >50 USD (AOR = 3.9, P = 0.02) increased patients’ odds of [cost-related nonadherence] for both conditions versus neither. Low-income patients also were more likely to selectively forgo pain medications (AOR = 9.1, P = 0.001) but not diabetes medications (AOR = 2.1, P = 0.12). More depressive symptoms (AOR = 1.6, P = 0.006) and negative medication-related beliefs (AOR = 1.7, P = 0.02) increased patients’ odds of cutting back selectively on medications for diabetes but not pain.” (J. D. Piette, jpiette@umich.edu)
Treating Depression in Diabetes: Significant improvements in A1C and systolic blood pressure were noted after a low-income minority population with diabetes received drug treatment for depression (pp. 2156–60). Participants in the 6-month trial were screened for depression at a county diabetes clinic, and these changes were noted during monthly administrations of the Hamilton Depression Scale (HAM-D) in those assigned to sertraline or placebo therapy: “A total of 150 subjects answered positively to at least one question on Whooley’s questionnaire. The positive predictive value for depression diagnosed by [the Computerized Diagnostic Interview Survey] was 69, 67, and 84% for positive answers to question 1 only, question 2 only, or both, respectively. Of the 89 subjects who entered the study, 75 completed. An intention-to-treat analysis revealed significant differences between baseline and 6 months in HAM-D and pain scores, [quality of life], and A1C and systolic blood pressure levels in both groups, with no differences between groups for the first three but a significantly greater decrease with sertraline in A1C and systolic blood pressure levels. Changes in HAM-D scores and A1C levels were significantly correlated in all subjects (P = 0.45 [P < 10−6]).” (M. B. Davidson, mayerdavidson@cdrewu.edu)
Glucose Monitoring During Initiation of Pump Therapy: Glycemic control is better during initiation of pump therapy in patients with poorly controlled type 1 diabetes when continuous glucose monitoring (CGM) is used, compared with conventional pump therapy, researchers report (pp. 2245–50). In the 6-month RealTrend study, 132 adults and children with A1C values of 8% or more despite multiple daily insulin injections were randomized to the Medtronic MiniMed Paradigm REAL-Time system (PRT group), an insulin pump with integrated CGM, and instructed to wear CGM sensors at least 70% of the time, or to conventional insulin pump therapy. Results showed: “A total of 115 patients completed the study. Between baseline and trial end, A1C improved significantly in both groups (PRT group −0.81 ± 1.09%, P < 0.001; CSII group −0.57 ± 0.94%, P < 0.001), with no significant difference between groups. When the 91 patients who were fully protocol-compliant (including CGM sensor wear ≥70% of the time) were considered, A1C improvement was significantly greater in the PRT group (P = 0.004) (PRT group −0.96 ± 0.93%, P < 0.001; CSII group −0.55 ± 0.93%, P < 0.001). Hyperglycemia parameters decreased in line with improvements in A1C with no impact on hypoglycemia.” (D. Raccah, denis.raccah@mail.ap-hm.fr)
Beta-Cell Function in Long-Standing Diabetes: Among 20 patients who had had type 1 diabetes for an average of 21.3 years, surviving pancreatic beta-cells continued to secrete insulin in a physiologically regulated manner (pp. 2251–7). However, treatment with intensified insulin therapy, exenatide, and daclizumab failed to induce improved function of these cells. (Kristina I. Rother, kristina.rother@nih.gov)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2009, 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. 7, 2009 * Vol. 16, No. 233
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 5 issue of Lancet (2009; 374).
Perinatal Use of Chlorhexidine: Chlorhexidine intravaginal wipes and neonatal washes were ineffective for prevention of neonatal sepsis and vertical acquisition of pathogenic bacteria among neonates, researchers report (pp. 1909–16). In South Africa, chlorhexidine wipes were used in 8,011 during active labor, with some women having the wipes used intravaginally (intervention) and others only on the external genitalia (control). The agent was also used for full-body (intervention) or foot (control) washes of their 8,129 newborns. Results showed: “Rates of neonatal sepsis did not differ between the groups (chlorhexidine 141 [3%] of 4,072 vs control 148 [4%] of 4057; p = 0.6518). Rates of colonisation with group B streptococcus in newborn babies born to mothers in the chlorhexidine (217 [54%] of 401) and control groups (234 [55%] of 429] did not differ (efficacy −0.05%, 95% CI −9.5 to 7.9).” (C. L. Cutland, cutlandc@hivsa.com)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2009; 339).
Mortality Among Users of Oral Antidiabetic Agents: Metformin and pioglitazone had relatively favorable risk profiles, compared with sulfonylureas and rosiglitazone, respectively, in a retrospective cohort study of 91,521 people with diabetes (b4731). Pioglitazone also had a more favorable risk profile than did metformin in this analysis of data from the U. K. General Practice Research Database from 1990 through 2005: “3,588 incident cases of myocardial infarction, 6,900 of congestive heart failure, and 18,548 deaths occurred. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P < 0.001) and second generation sulphonylureas with an 18% to 30% excess risk for congestive heart failure (P = 0.01 and P < 0.001). The thiazolidinediones were not associated with risk of myocardial infarction; pioglitazone was associated with a significant 31% to 39% lower risk of all cause mortality (P = 0.02 to P < 0.001) compared with metformin. Among the thiazolidinediones, rosiglitazone was associated with a 34% to 41% higher risk of all cause mortality (P = 0.14 to P = 0.01) compared with pioglitazone. A large number of potential confounders were accounted for in the study; however, the possibility of residual confounding or confounding by indication (differences in prognostic factors between drug groups) cannot be excluded.” (P. Elliott, p.elliott@imperial.ac.uk)
Weight Loss as Treatment for Sleep Apnea: A low-energy diet improved symptoms of obstructive sleep apnea among 63 obese men, suggesting that long-term studies should assess weight loss as a primary treatment strategy of this condition (b4609). Study participants had body mass indices of 30–40 kg/sq m and apnea–hypopnea indices of 15 or more, which required treatment with continuous positive airway pressure. Comparing 7 weeks of a liquid very-low-energy diet with usual diet, the investigators found: “Both groups had a mean AHI of 37 events/h (SD 15) at baseline. At week 9, the intervention group’s mean body weight was 20 kg (95% confidence interval 18 to 21) lower than that of the control group, while its mean AHI was 23 events/h (15 to 30) lower. In the intervention group, five of 30 (17%) were disease free after the energy restricted diet (AHI <5), with 15 of 30 (50%) having mild disease (AHI 5–14.9), whereas the AHI of all patients in the control group except one remained at 15 or higher.” (K. Johansson, kari.johansson@ki.se)

>>>PNN JournalWatch
* Booster Vaccinations: Can Immunologic Memory Outpace Disease Pathogenesis?, in Pediatrics, 2009; 124: 1633–41. (M. E. Pichichero)
* Human Immunodeficiency Virus in an Aging Population, a Complication of Success, in
Journal of the American Geriatrics Society, 2009; 57: 2129–38. (M. B. Goetz, matthew.goetz@va.gov)
* Hypertension in Hemodialysis Patients: The Role of Antihypertensive Medications, in
American Journal of Kidney Diseases, 2009; 54: 996–99. (D. C. Miskulin, dmiskulin@tuftsmedicalcenter.org)
* Prasugrel: A Critical Comparison with Clopidogrel, in
Pharmacotherapy, 2009; 29: 1441–51. (W. L. Baker, wbaker01@harthosp.org)
* Transdermal Rotigotine: A Clinically Innovative Dopamine-Receptor Agonist for the Management of Parkinson’s Disease, in
Pharmacotherapy, 2009; 29: 1452–67. (J. J. Chen, jjchen@llu.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 © 2009, 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, 2009 * Vol. 16, No. 234
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Dec. issue of Pharmacotherapy (2009; 29).
Upper GI Complications with NSAIDs: NSAIDs vary in their upper gastrointestinal adverse effect profiles, a nested case–control study confirms (pp. 1397–407). Logistic regression of data from the administrative health care databases of Saskatchewan showed these patterns among 726 patients with first hospitalizations for upper gastrointestinal complications in 1999–2001 and 20,002 control patients: “Current rofecoxib and naproxen users had the highest risk for upper gastrointestinal complications with adjusted ORs of 3.6 (95% CI 2.2–5.7) and 3.4 (95% CI 1.8–6.7), respectively. No association was found between the risk of upper gastrointestinal complications and use of celecoxib (OR 1.1, 95% CI 0.7–1.8) or the use of diclofenac plus misoprostol (OR 0.7, 95% CI 0.3–1.8). A dose–response relationship was observed for rofecoxib and naproxen with ORs for high dose of 5.2 (95% CI 2.5–10.6) and 5.1 (95% CI 2.1–12.3), respectively. Short-term users of celecoxib and naproxen had a higher risk than long-term users, whereas among users of rofecoxib the risk was higher among long-term than short-term users.” (J. Castellsague, castellsague@rti.org)
Discontinuation of Initial Rhythm-Control Drug Therapy: In patients with atrial fibrillation, initial drug therapy used for rhythm control is often discontinued, and that is “likely have an impact on the effectiveness of disease management and the quality of care,” researchers write (pp. 1417–26). Data on 3,549 adults newly diagnosed with AF between 2002 and 2006 came from the PharMetrics Patient-Centric Database. (M.H. Kim, Michael.Kim@nmff.org)
Dexmedetomidine During Cardiac Surgery: In a large community teaching hospital with a fast-track cardiovascular recovery unit (CVRU) model, patients who received dexmedetomidine rather than propofol for perioperative sedation had lower postoperative opioid requirements, a 100-patient study shows (pp. 1427–32): “Opioid requirements were significantly lower during the sedative infusion period for dexmedetomidine-treated patients than for propofol-treated patients (median [range] 0 [0–10 mg] vs 4 mg [0–33 mg], p < 0.001), but not through the entire CVRU admission (median [range] 26 mg [0–119 mg] vs 30 mg (0–100 mg], p = 0.284). The proportion of patients who did not require opioids during the infusion was significantly higher in the dexmedetomidine group compared with the propofol group (32 [64%] vs 13 [26%], p < 0.001). No significant differences were noted between the groups for length of mechanical ventilation, quality of sedation, or adverse events. Sedation-related costs were significantly higher (~$50/patient higher) with dexmedetomidine (p < 0.001).” (J. F. Barletta, Jeffrey.barletta@spectrum-health.org)
Pharmaceutical Care in Hemodialysis: Decreased drug use and reduced hospitalization rates were among the benefits of pharmaceutical care in a group of 104 patients with end-stage renal disease who were undergoing hemodialysis (pp. 1433–40). In a prospective, randomized, longitudinal study, patients on pharmaceutical (one-on-one care, with in-depth drug therapy reviews conducted by a clinical pharmacist) or usual care had these economic outcomes: “At the end of the 2-year follow-up, pharmaceutical care was associated with a significant decrease of 14% fewer drugs compared with standard of care, as documented during each drug therapy review (p < 0.05). There were significantly fewer all-cause hospitalizations among patients assigned to pharmaceutical care compared with those receiving standard of care (mean ± SD 1.8 ± 2.4 vs 3.1 ± 3 hospitalizations, p = 0.02), and the cumulative time hospitalized was shorter in the pharmaceutical care group compared with the standard of care group (9.7 ± 14.7 vs 15.5 ± 16.3 days, p = 0.06). During the study period, 530 DRPs were identified and resolved.” (A. Barton Pai, amy.bartonpai@acphs.edu)

>>>PNN NewsWatch
* Actor Dennis Quaid was one of the 20,000 attendees at the ASHP Midyear Clinical Meeting when it opened in Las Vegas on Sunday. During his keynote address to the group on Monday, Quaid announced his support for ASHP’s Pharmacy Technician Initiative and a new National Alert Network for Serious Medication Errors. Quaid’s twin daughters nearly died when they were given too much medication in 2008.

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 © 2009, 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, 2009 * Vol. 16, No. 235
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 9 issue of JAMA (2009; 302).
Soy Foods & Breast Cancer Survival: In the Shanghai Breast Cancer Survival Study, consumption of soy foods was associated with decreased risk of death and tumor recurrence, researchers report (pp. 2347–43). Included in the population-based cohort study were 5,042 women who had survived breast cancer in China. Data collection over a 60-month period showed the following dietary and clinical trends: “During the median follow-up of 3.9 years (range, 0.5–6.2 years), 444 deaths and 534 recurrences or breast cancer–related deaths were documented in 5,033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54–0.92) for total mortality and 0.68 (95% CI, 0.54–0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor–positive or –negative breast cancer and was present in both users and nonusers of tamoxifen.” (X. O. Shu, xiao-ou.shu@vanderbilt.edu)
Concern About Artificially Sweetened Beverages: Diet drinks that rely on artificial sweeteners such as saccharin, aspartame, and sucralose may actually cause people to gain weight through disruption of biological and behavioral pathways, writes the author of a commentary article (pp. 2477–8): “Individuals who habitually consume artificial sweeteners may find more satiating but less intensely sweet foods (eg, fruit) less appealing and unsweet foods (eg, vegetables, legumes) less palatable, reducing overall diet quality in ways that might contribute to excessive weight gain.… Diet drinks have essentially no calories, unlike most artificially sweetened solid foods that typically contain other nutrients. Moreover, diet drinks are often consumed in the absence of other foods, producing a dissociation between sweet taste and calorie intake. One concern is that the dissociation of these physiological events might disrupt the hormonal and neurobehavioral pathways regulating hunger and satiety.” (D. S. Ludwig, david.ludwig@childrens.harvard.edu)
Contraindicated Drug Use in Dialysis Patients During PCI: Nearly a quarter of 22,778 patients on dialysis received contraindicated antithrombotic medications while undergoing percutaneous coronary interventions in 2004–08, according to data from 829 U.S. hospitals (pp. 2458–64). An increased risk of in-hospital major bleeding was associated with use of enoxaparin and eptifibatide, according to these study results: “Five thousand eighty-four patients (22.3%) received a contraindicated antithrombotic; of these patients, 2,375 (46.7%) received enoxaparin, 3,261 (64.1%) received eptifibatide, and 552 (10.9%) received both. Compared with patients who did not receive a contraindicated antithrombotic, patients who did had higher rates of in-hospital bleeding (5.6% vs 2.9%; odds ratio [OR], 1.93; 95% confidence interval [CI],1.66–2.23) and death (6.5% vs 3.9%; OR, 1.68; 95% CI, 1.46–1.95). After multivariable adjustment, patients receiving contraindicated antithrombotics had significantly higher risks of in-hospital bleeding (OR, 1.66; 95% CI, 1.43–1.92) and death (OR, 1.24; 95% CI, 1.04–1.48). In 10,158 patients matched by propensity scores, receipt of contraindicated antithrombotics remained significantly associated with in-hospital bleeding (OR, 1.63; 95% CI, 1.35–1.98) but not in-hospital death (OR, 1.15; 95% CI, 0.97–1.36).” (T. T. Tsai, thomas.tsai@va.gov)

>>>PNN NewsWatch
* New hepatic warnings have been added to the labeling of diclofenac sodium topical gel (Voltaren Gel, Endo; Novartis), FDA reports. Drug-induced hepatotoxicity, including severe reactions, have occurred in the first month of use of the product but can occur at any time during treatment.
*
FDA last week reminded health professionals about the risk of neural tube defects and other major malformations in infants exposed in utero to valproate.

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 © 2009, 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, 2009 * Vol. 16, No. 236
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 10 issue of the New England Journal of Medicine (2009; 361).
Cangrelor in PCI: Two research studies and a related editorial examine use of the nonthienopyridine adenosine triphosphate analogue cangrelor in patients undergoing percutaneous coronary interventions.
In a large international trial, intravenous cangrelor was not superior to oral clopidogrel in reducing the composite end point of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours (
pp. 2318–29). Investigators found: “We enrolled 8,877 patients, and 8,716 underwent PCI. At 48 hours, cangrelor was not superior to clopidogrel with respect to the primary composite end point, which occurred in 7.5% of patients in the cangrelor group and 7.1% of patients in the clopidogrel group (odds ratio, 1.05; 95% confidence interval [CI], 0.88 to 1.24; P = 0.59). Likewise, cangrelor was not superior at 30 days. The rate of major bleeding (according to Acute Catheterization and Urgent Intervention Triage Strategy criteria) was higher with cangrelor, a difference that approached statistical significance (3.6% vs. 2.9%; odds ratio, 1.26; 95% CI, 0.99 to 1.60; P = 0.06), but this was not the case with major bleeding (according to the Thrombolysis in Myocardial Infarction criteria) or severe or life-threatening bleeding (according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria). A secondary exploratory end point of death from any cause, Q-wave myocardial infarction, or ischemia-driven revascularization showed a trend toward a reduction with cangrelor, but it was not significant (0.6% vs. 0.9%; odds ratio, 0.67; 95% CI, 0.39 to 1.14; P = 0.14).” (R. A. Harrington, robert.harrington@duke.edu)
Cangrelor failed to outperform placebo in reducing complications of PCI in the second study (
pp. 2330–41). Using the same primary end point as in the first study, researchers reported these results: “The primary end point occurred in 185 of 2,654 patients receiving cangrelor (7.0%) and in 210 of 2,641 patients receiving placebo (8.0%) (odds ratio in the cangrelor group, 0.87; 95% confidence interval [CI], 0.71 to 1.07; P = 0.17) (modified intention-to-treat population adjusted for missing data). In the cangrelor group, as compared with the placebo group, two prespecified secondary end points were significantly reduced at 48 hours: the rate of stent thrombosis, from 0.6% to 0.2% (odds ratio, 0.31; 95% CI, 0.11 to 0.85; P = 0.02), and the rate of death from any cause, from 0.7% to 0.2% (odds ratio, 0.33; 95% CI, 0.13 to 0.83; P = 0.02). There was no significant difference in the rate of blood transfusion (1.0% in the cangrelor group and 0.6% in the placebo group, P = 0.13), though major bleeding on one scale was increased in the cangrelor group, from 3.5% to 5.5% (P < 0.001), because of more groin hematomas.” (D. L. Bhatt, dlbhattmd@post.harvard.edu)
Despite the above findings, editorialists hold out hope of finding an advantage for cangrelor in future studies (
pp. 2382–4). “The most important lesson from the two CHAMPION trials is that in patients with acute coronary syndromes in whom the administration of an ADP-receptor antagonist was deferred until diagnostic angiography had established the indication for PCI, intravenous cangrelor did not provide additional advantages to those achieved with 600 mg of clopidogrel. However, cangrelor is a potent intravenous ADP-receptor antagonist with a rapid onset and offset of action. These valuable qualities certainly warrant further study aimed at identifying more suitable clinical niches for cangrelor and more appropriate approaches to its use.” (A. Kastrati)
Dabigatran for VT: Used in patients with acute venous thromboembolism, dabigatran holds several advantages over warfarin, researchers report (pp. 2342–52). Fixed doses of the oral thrombin inhibitor are as effective as warfarin, have a similar safety profile, and do not require laboratory monitoring, according to the RE-COVER study. Among 2,539 patients, recurrent VT occurred in 2.4% and 2.1% of those on dabigatran and warfarin, respectively. Major bleeding occurred in 20 (1.6%) patients on dabigatran and 24 (1.9%) patients on warfarin. One significant difference between the drugs was that more patients on dabigatran discontinued therapy because of adverse effects (9.0%, compared with 6.8% of those on warfarin). (S. Schulman, schulms@mcmaster.ca)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2009, 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, 2009 * Vol. 16, No. 237
Providing news and information about medications and their proper use

>>>Circulation Highlights
Source:
Dec. 8 issue of Circulation (2009; 120).
Clopidogrel & PPIs: No conclusive evidence of a clinically relevant interaction between clopidogrel and proton-pump inhibitors was found in an analysis of data on patients undergoing percutaneous coronary intervention or hospitalized for acute coronary syndrome (pp. 2322–9). Contrary to recent FDA pronouncements (see PNN, Nov. 18), this analysis shows these results based on a primary end point of myocardial infarction hospitalization or death: “We entered 18,565 clopidogrel users into our analysis. On a pooled basis, 2.6% of those who also initiated a PPI versus 2.1% of PPI nonusers had a myocardial infarction hospitalization; 1.5% versus 0.9% died; and 3.4% versus 3.1% underwent revascularization. The propensity score–adjusted rate ratio for the primary end point of myocardial infarction or death was 1.22 (95% confidence interval, 0.99 to 1.51); for death, 1.20 (95% confidence interval, 0.84 to 1.70); and for revascularization, 0.97 (95% confidence interval, 0.79 to 1.21). Matched analyses generally yielded similar results.” (J. A. Rassen, jrassen@post.harvard.edu)
An editorialist provides this analysis of this potential drug interaction (
pp. 2310–2): “There is no doubt that a pharmacodynamic interaction exists; at issue is its clinical relevance. For the majority of patients, the interaction likely poses no serious threat. However, for an unidentifiable subset of patients carrying the wrong mix of drugs, doses, comorbidities, and genetics, a clinically important drug interaction remains a real possibility. As we await further research on the phenomenon of drug-induced clopidogrel resistance, a cautious approach that exploits the basic pharmacology of these drugs is a sensible and easily achievable way to safely prescribe PPIs in patients taking clopidogrel.” (D. Juurlink, dnj@ices.on.ca)
Smoking, Clopidogrel, & Mortality: In smokers, clopidogrel may be more effective, but it also confers a higher risk of bleeding, according to the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial of 12,152 patients with established cardiovascular disease (pp. 2337–44): “Current smoking was associated with an increase in all-cause (adjusted hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.85 to 3.60), cardiovascular (HR 2.26, 95% CI 1.48 to 3.45), and cancer (HR 3.56, 95% CI 1.96 to 6.46) mortality compared with never smoking. The impact of clopidogrel on mortality differed by smoking status (P for interaction = 0.018 for current smokers). Among current smokers, clopidogrel was associated with a reduction in all-cause mortality (HR 0.68, 95% CI 0.49 to 0.94); clopidogrel did not reduce all-cause mortality among former smokers (HR 0.95, 95% CI 0.75 to 1.19) or never-smokers (HR 1.14, 95% CI 0.83 to 1.58). A similar pattern was noted for cardiovascular mortality. As expected, no relationship was observed between clopidogrel and cancer mortality by smoking status. The risk of bleeding appeared to differ according to smoking status; randomized clopidogrel was associated with a significantly increased risk of severe or moderate bleeding (HR 1.62, P = 0.04) among current smokers but a smaller and nonsignificant increase among never-smokers (HR 1.31, P = 0.15).” (D. L. Bhatt, dlbhattmd@post.harvard.edu)

>>>Cardiology Highlights
Source:
Dec. 8 issue of the Journal of the American College of Cardiology (2009; 54).
Platelet Therapy During Elective GI Endoscopy: A JACC white paper provides advice on management of patients with atherosclerotic coronary artery disease who are undergoing elective endoscopic gastrointestinal procedures (pp. 2261–76): “Platelet-directed pharmacotherapy with aspirin and, among patients experiencing [acute coronary syndromes] and/or those undergoing [percutaneous coronary intervention (PCI)] and stent placement, a thienopyridine represents the current standard of care. Existing guidelines … underscore the benefit of dual platelet antagonists in patients at high risk for thrombotic events and the potential detrimental effects of sudden drug cessation—particularly within the first 6 months after PCI with [drug-eluting stent] insertion. Accordingly, elective endoscopic procedures should be deferred during this time period and possibly up to 12 months, if clinically acceptable.” (R. C. Becker, becke021@mc.duke.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 © 2009, 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. 14, 2009 * Vol. 16, No. 238
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 12 issue of Lancet (2009; 374).
Polypharmacy with Antithrombotic Agents: For patients who have had myocardial infarctions, use of antithrombotic agents must be individualized, according to authors who report an increased risk of hospitalization for bleeding based on the number of such drugs being used concomitantly (pp. 1967–74). Triple therapy or dual therapy with clopidogrel plus vitamin K antagonist showed these outcomes among 40,812 patients in Denmark with first MIs in 2000–05: “During a mean follow-up of 476.5 days (SD 142.0), 1,891 (4.6%) patients were admitted to hospital with bleeding. The yearly incidence of bleeding was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios for bleeding were 1.33 (95% CI 1.11–1.59) for clopidogrel, 1.23 (0.94–1.61) for vitamin K antagonist, 1.47 (1.28–1.69) for aspirin plus clopidogrel, 1.84 (1.51–2.23) for aspirin plus vitamin K antagonist, 3.52 (2.42–5.11) for clopidogrel plus vitamin K antagonist, and 4.05 (3.08–5.33) for triple therapy. Numbers needed to harm were 81.2 for aspirin plus clopidogrel, 45.4 for aspirin plus vitamin K antagonist, 15.2 for clopidogrel plus vitamin K antagonist, and 12.5 for triple therapy. 702 (37.9%) of 1,852 patients with non-fatal bleeding had recurrent myocardial infarction or died during the study period compared with 7,178 (18.4%) of 38,960 patients without non-fatal bleeding (HR 3.00, 2.75–3.27, p < 0.0001).” (R. Sørensen, rs@heart.dk)
Human Papillomavirus Vaccine Sustained Efficacy: “Excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine [were demonstrated for] up to 6.4 years,” according to a research report (pp. 1975–85). In a study of 1,113 women aged 15–25 years, these results were noted for a primary objective of long-term vaccine efficacy in prevention of incident cervical infection with HPV 16, HPV 18, or both (based on according-to-protocol [ATP] cohort) and an analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) in the total vaccinated cohort (TVC): “For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95·3% (95% CI 87·4—98·7) and against 12-month persistent infection was 100% (81·8—100). Vaccine efficacy against CIN2+ was 100% (51·3—100) for lesions associated with HPV-16/18 and 71·9% (20·6—91·9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred.” (GlaxoSmithKline Vaccine HPV-007 Study Group)

>>>PNN JournalWatch
* How to Reduce Prescribing Errors [editorial], in Lancet, 2009; 374: 1945. (Lancet editors)
* Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults: Systematic Review and Meta-analysis, in
BMJ, 2009; 339: b5106. (C. Del Mar, cdelmar@bond.edu.au)
* Insurer and Out-of-Pocket Costs of Osteoarthritis in the US: Evidence from National Survey Data, in
Arthritis & Rheumatism, 2009; 60: 3546–53. (J. A. Rizzo, john.rizzo@stonybrook.edu)
* Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet, in
Journal of Clinical Oncology, 2009; 27: 6041–51. (M. Baccarani, michele.baccarani@unibo.it)
* Clinical Cancer Advances 2009: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report from the American Society of Clinical Oncology, in
Journal of Clinical Oncology, 2009; 27: 6052–69. (N. J. Petrelli, npetrelli@christianacare.org)
* Rapid Diagnostic Testing for Community-Acquired Pneumonia: Can Innovative Technology for Clinical Microbiology Be Exploited?, in
Chest, 2009; 136: 1618–21. (V. L. Yu, vly@pitt.edu)
* Celiac Disease: From Pathogenesis to Novel Therapies, in
Gastroenterology, 2009; 137: 1912–33. (D. Schuppan, dschuppa@bidmc.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 © 2009, 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, 2009 * Vol. 16, No. 239
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Dec. 15 issue of the Annals of Internal Medicine (2009; 151).
Timing and Impact of Influenza Vaccination in Pandemic: Earlier vaccination against pandemic (H1N1) 2009 influenza is preferable—it prevents deaths and reduces costs—and complete population coverage is not necessary to shorten the pandemic (pp. 829–39). Those conclusions are reached by researchers who used a compartmental epidemic model with a Markov model of disease progression to assess the lifetime, societal impact of H1N1 vaccination in mid-October versus mid-November. Base-case and sensitivity analyses showed these effects on quality-adjusted life–years (QALYs): “Assuming each primary infection causes 1.5 secondary infections, vaccinating 40% of the population in October or November would be cost-saving. Vaccination in October would avert 2,051 deaths, gain 69,679 QALYs, and save $469 million compared with no vaccination; vaccination in November would avert 1,468 deaths, gain 49,422 QALYs, and save $302 million.
“Vaccination is even more cost-saving if longer incubation periods, lower rates of infectiousness, or increased implementation of nonpharmaceutical interventions delay time to the peak of the pandemic. Vaccination saves fewer lives and is less cost-effective if the epidemic peaks earlier than mid-October.” (N. Khazeni)
Use of Adjuvants, Antiviral Agents in Influenza Pandemic: Authors of the above study also assessed the impact of adjuvanted vaccines and antiviral pharmacotherapy in a hypothetical avian (H5N1) influenza pandemic (pp. 840–53). Again focusing on the lifetime, societal impact in a compartmental epidemic model with a Markov model of disease progression, the investigators considered three scenarios: vaccination and antiviral pharmacotherapy in quantities similar to those currently available in the U.S. stockpile (stockpiled strategy), stockpiled strategy but with expanded distribution of antiviral agents (expanded prophylaxis strategy), and stockpiled strategy but with adjuvanted vaccine (expanded vaccination strategy). Base-case and sensitivity analyses showed these effects on quality-adjusted life–years (QALYs): “Expanded vaccination was the most effective and cost-effective of the 3 strategies, averting 68% of infections and deaths and gaining 404,030 QALYs at $10,844 per QALY gained relative to the stockpiled strategy.
“Expanded vaccination remained incrementally cost-effective over a wide range of assumptions.” (N. Khazeni)
Comorbidity, Glycemic Control, & Cardiovascular Outcomes in Diabetes: Because patients with diabetes and comorbidities do not respond to intensive glycemic control to the degree other patients do, the presence of other diseases should be factored in when this intervention is considered, researchers conclude (pp. 854–60). In a 5-year longitudinal study of 2,613 patients with type 2 diabetes, these outcomes were found when intensive glycemic control was used: “Attaining an HbA1c level of 6.5% or less at baseline was associated with lower 5-year incidence of cardiovascular events in the low-to-moderate comorbidity subgroup (adjusted HR, 0.60 [95% CI, 0.42 to 0.85]; P = 0.005) but not in the high comorbidity subgroup (adjusted HR, 0.92 [CI, 0.68 to 1.25]; P = 0.61; P for subgroup by HbA1c interaction = 0.048). Similarly, attaining a baseline HbA1c level of 7.0% predicted fewer cardiovascular events in the low-to-moderate comorbidity subgroup (adjusted HR, 0.61 (CI, 0.44 to 0.83; P = 0.001) but not in the high comorbidity subgroup (adjusted HR, 0.88 [CI, 0.66 to 1.17]; P = 0.38; P for subgroup by HbA1c interaction = 0.093).” (S. Greenfield, sgreenfi@uci.edu)
Primary Care Workforce Crisis for Underserved: The primary care workforce crisis and ways in which the underserved can achieve greater access are addressed in a proposal that focuses on primary care teaching health centers (early release): “[Expansion of services] can be achieved by establishing primary care teaching health centers in expanded community health centers, which have established a patient-centered medical home practice environment. Residents would receive their final year of training in these centers, and then have the incentive of National Health Service Corps debt repayment if they subsequently practice in an underserved area.” (R. E. Rieselbach, rer@medicine.wisc.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 © 2009, 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, 2009 * Vol. 16, No. 240
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 16 issue of JAMA (2009; 302).
Tarenflurbil for Mild Alzheimer Disease: Among 1,046 patients with mild symptoms of Alzheimer disease, tarenflurbil was statistically no different than placebo at slowing cognitive decline or loss of activities of daily living, researchers report (pp. 2557–64). Tarenflurbil, a selective amyloid-beta-42–lowering agent formerly known as R-flurbiprofen, was administered in doses of 800 mg twice daily, with these results on the Alzheimer Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) and Alzheimer Disease Cooperative Studies–activities of daily living (ADCS-ADL) scale: “Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, –0.9 to 1.1; P = .86 and –0.5 for ADCS-ADL; 95% CI, –1.9 to 0.9; P = .48) using an intent-to-treat analysis.… The ADAS-Cog score decreased by 7.1 points over 18 months. The tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections.” (R. C. Green, rcgreen@bu.edu)
Plasma Leptin Levels in Incident Alzheimer Disease: Circulating leptin levels proved important in development of dementia and incident Alzheimer’s disease in a study of 785 community-dwelling older patients (pp. 2565–72). The patients, all from the original Framingham cohort, were seen in the 22nd examination cycle in 1990–94. Results showed: “During a median follow-up of 8.3 years (range, 0–15.5 years), 111 participants developed incident dementia; 89 had AD. Higher leptin levels were associated with a lower risk of incident dementia and AD in multivariable models (hazard ratio per 1-SD increment in log leptin was 0.68 [95% confidence interval, 0.54–0.87] for all-cause dementia and 0.60 [95% confidence interval, 0.46–0.79] for AD). This corresponds to an absolute AD risk over a 12-year follow-up of 25% for persons in the lowest quartile (first quartile) vs 6% for persons in the fourth quartile of sex-specific leptin levels. In addition, a 1-SD elevation in plasma leptin level was associated with higher total cerebral brain volume and lower temporal horn volume, although the association of leptin level with temporal horn volume did not reach statistical significance.” (S. Seshadri, suseshad@bu.edu)
Commenting on this and the above tarenflurbil study, editorialists make these observations about late-life dementias (
pp. 2593–4): “The null outcome for the leading gamma-secretase modulator in a phase 3 trial and the surprisingly strong association between plasma leptin and incident Alzheimer disease underscore the need to broaden the current view of potential therapeutic approaches to cognitive impairment and dementia in older individuals. Research must seek a fuller understanding of the complex convergence of Alzheimer disease with vascular disease and Lewy body disease, the application of biomarkers and other surrogates to clinical trials to quantify specific pharmacologic effects, and a multimodal approach to prevention and treatment. Doing so could have profound effects on the increasing numbers of older persons and on the societies confronting the global challenge of late-life dementias in decades to come.” (E. B. Larson, larson.e@ghc.org)

>>>Neurology Highlights
Source:
Dec. 15 issue of Neurology (2009; 73).
Pharmacogenomics in Alzheimer Disease: A Phase II trial of bapineuzumab failed to show significant advantages for the anti-amyloid-beta monoclonal antibody in cognitive decline among 234 patients with Alzheimer disease (pp. 2061–70). However, responses differed among patients based on APOE epsilon-4 genotype, leading investigators to call for pharmacogenomic approaches to therapy in Phase III trials. These results were observed following six courses of bapineuzumab infusions administered 13 weeks apart: “No significant differences were found in the primary efficacy analysis. Exploratory analyses showed potential treatment differences (p < 0.05, unadjusted for multiple comparisons) on cognitive and functional endpoints in study ‘completers’ and APOE epsilon-4 noncarriers. Reversible vasogenic edema, detected on brain MRI in 12/124 (9.7%) bapineuzumab-treated patients, was more frequent in higher dose groups and APOE epsilon-4 carriers. Six vasogenic edema patients were asymptomatic; 6 experienced transient symptoms.” (S. Salloway, SSalloway@Butler.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 © 2009, 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, 2009 * Vol. 16, No. 241
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 17 issue of the New England Journal of Medicine (2009; 361).
Evaluating Pandemic Influenza Vaccine Policy: Commenting on three research articles (pp. 2405–13, M. E. Greenberg, michael.greenberg@csl.com.au; pp. 2414–23, F-C Zhu, jszfc@vip.sina.com; pp. 2424–35, I. Stephenson, iain.stephenson@uhl-tr.nhs.uk) on the efficacy of A/H1N1 influenza vaccine, two of which were published online in advance of print publication (see PNN, Sept. 17), an editorialist makes these observations about pandemic influenza vaccine policy (e59): “Both vaccines tested have generally acceptable side-effect and adverse-event profiles, with pain or tenderness at the injection site being the most common adverse event observed. The local reactions seen with the adjuvanted vaccines were moderately higher than those generally seen with nonadjuvanted vaccines. Any association of uncommon adverse events with the vaccine cannot be ascertained in studies of this size. It is reassuring that the manufacturing process for these vaccines is identical to that used for seasonal vaccines, which have a strong record of safety. Although concerns linger about the association of the 1976 swine influenza vaccine with the Guillain–Barré syndrome, the syndrome was rare, with approximately 1 case for every 100,000 persons vaccinated. The rate was even lower among persons under 25 years of age. One notable difference is that in 1976, we did not have a pandemic influenza virus that was spreading quickly throughout the world, and causing illness and death, as we do today. A plan for robust and comprehensive safety surveillance should be in place to detect uncommon events rapidly during the upcoming vaccination campaigns, so that risk–benefit ratios can be reassessed.” (Kathleen M. Neuzil)
Ferric Carboxymaltose in Patients with Heart Failure: Intravenous ferric carboxymaltose improves symptoms, functional capacity, and quality of life with an acceptable adverse effects profile in patients with chronic heart failure and iron deficiency, with or without anemia, researchers report (pp. 2436–48). A study included 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, left ventricular ejection fractions of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 mcg/L or if the transferrin saturation was less than 20%, 100–299 mcg/L), and a hemoglobin level of 95–135 g/L. Treatment with intravenous ferric carboxymaltose or placebo produced these effects on primary end points of self-reported Patient Global Assessment and NYHA functional class at week 24: “Among the patients receiving ferric carboxymaltose, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the Patient Global Assessment (odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75 to 3.61). Among the patients assigned to ferric carboxymaltose, 47% had an NYHA functional class I or II at week 24, as compared with 30% of patients assigned to placebo (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients with anemia and those without anemia. Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality-of-life assessments. The rates of death, adverse events, and serious adverse events were similar in the two study groups.” (S. D. Anker, s.anker@cachexia.de)
Despite this study’s limitations and the “unanswered questions” it raises, an editorialist strikes a positive note regarding its impact on care of patients with heart failure and iron deficiency (
pp. 2475–7): “This trial suggests a new avenue for therapeutic exploration. Improvement in the quality of life is increasingly important to patients with heart failure, and the approach taken in this study may have merit in patients with moderately symptomatic heart failure and documented iron deficiency. Additional controlled trials will help to better select the patients most likely to benefit, clarify the optimal route and duration of iron replacement, and provide insight into possible mechanisms of the benefit.” (G. W. Dec)

>>>PNN NewsWatch
* With the outcome of health care reform uncertain in the Senate, pharmacy-related provisions remain positive, APhA reports in news reports and blogs.

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 © 2009, 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, 2009 * Vol. 16, No. 242
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Dec. issue of the Journal of Allergy and Clinical Immunology (2009; 124).
Pharmacogenetics of Beta-2 Agonists in Asthma: A study of 1,182 young patients with asthma shows that genotypically based problems with beta-2–agonist therapy include albuterol as well as the previously recognized long-acting agent salmeterol (pp. 1188–94.e3). Those with the Arg16 genotype of the adrenergic beta-2-receptor agonist gene (ADRB2) were more likely to have exacerbations during 6 months of daily beta-2–agonist therapy, researchers report: “An increased risk of exacerbations per copy of he Arg16 allele was observed in asthmatic patients, regardless of treatment regimen (odds ratio [OR], 1.30; 95% CI, 1.09–1.55; P = .003). This appears to be largely due to exposure to beta-2-agonists because the risk of exacerbations observed in patients with the Arg16 allele was only observed in those receiving daily inhaled long- or short-acting beta-2-agonist treatment (OR, 1.64; 95% CI, 1.22–2.20; P = .001). In contrast, there was no genotypic risk for exacerbations in patients using inhaled beta-2-agonists less than once a day (OR, 1.08; 95% CI, 0.85–1.36; P = .525). The Arg16 genotype–associated risk for exacerbations was significantly different in those exposed to beta-2-agonists daily versus those that were not (test for interaction, P = .022).” (S. Mukhopadhyay, s.mukhopadhyay@bsms.ac.uk)
An editorialist calls for action based on patients’ genomes (
pp. 1195–6): “It becomes clear here that pharmacogenetics in the early 21st century will not primarily lead to the invention of individualized therapeutics but exclude certain groups of patients from established treatment regimens because of their genetic risk profile. This should (in theory) make treatment safer for the rest of the patients and initiate further drug developments. This is a general observation not restricted to the beta-2–agonist discussion. With the millions of polymorphisms we all are carrying, everybody will have personal risk profiles for drug interactions. This information becomes available rapidly. We need to start dealing with it in clinical practice whether we like it or not.” (M. Kabesch, kabesch.michael@mh-hannover.de)
Congenital Malformations with High-Dose Inhaled Corticosteroids: While supporting previous studies showing that use of low to moderate doses of inhaled corticosteroids (ICS) is safe during the first trimester, a cohort study of 13,280 pregnancies raises new concerns about teratogenic effects of high doses of the drugs (pp. 1229–34.e4). Data from three administrative databases in Quebec showed these patterns: “We identified 1,257 infants with a congenital malformation (9.5%) and 782 infants with a major malformation (5.9%). We found that women who used >1,000 mcg/d ICS (n = 154) were significantly more likely (63%) to have a baby with a malformation than the 4,392 women who used >0 to 1,000 mcg/d (adjusted risk ratio, 1.63; 95% CI, 1.02–2.60). On the other hand, women who used >0 to 1,000 µg/d were not found to be more at risk than women who did not use ICSs during the first trimester (n = 8,734). Nonsignificant trends of similar magnitude were found for major malformations.” (L. Blais, lucie.blais@umontreal.ca)

>>>Infectious Disease Report
Source:
Jan. 1 issue of Clinical Infectious Diseases (2010; 50).
Voriconazole Dosing in Children: Serum concentrations of voriconazole should be monitored and adjusted based on pharmacokinetic and pharmacodynamic variables, a study concludes (pp. 27–36). Patients with trough serum levels exceeding 1,000 ng/mL had significantly better survival in the study, and patients were shown to differ in their kinetic profiles: “A total of 207 voriconazole measurements were obtained from 46 patients (age, 0.8–20.5 years). A 2-compartment Michaelis–Menten pharmacokinetic model fit the data best but explained only 80% of the observed variability. The crude mortality rate was 28%, and each trough serum voriconazole concentration <1000 ng/mL was associated with a 2.6-fold increased odds of death (95% confidence interval, 1.6–4.8; ). Serum voriconazole concentrations were not associated with hepatotoxicity. Simulations predicted an intravenous dose of 7 mg/kg or an oral dose of 200 mg twice daily would achieve a trough >1000 ng/mL in most patients, but with a wide range of possible concentrations.” (M. Neely, mneely@usc.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 © 2009, 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. 21, 2009 * Vol. 16, No. 243
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 19 issue of Lancet (2009; 374).
Adjuvant Chemotherapy with Tamoxifen in Breast Cancer: In postmenopausal women with hormone-receptor–positive, node-positive breast cancer, chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) plus tamoxifen provided longer disease-free survival than did tamoxifen alone, researchers report (pp. 2055–63). CAF was given every 4 weeks for five cycles, while tamoxifen was administered daily for 5 years either concurrently (CAFT) or sequentially (CAF-T): “Of 1,558 randomised women, 1,477 (95%) were eligible for inclusion in the analysis. After a maximum of 13 years of follow-up (median 8.94 years), 637 women had a disease-free survival event (tamoxifen, 179 events in 361 patients; CAF-T, 216 events in 566 patients; CAFT, 242 events in 550 patients). For the first objective, therapy with the CAF plus tamoxifen groups combined (CAFT or CAF-T) was superior to tamoxifen alone for the primary endpoint of disease-free survival (adjusted Cox regression hazard ratio [HR] 0.76, 95% CI 0.64–0.91; p = 0.002) but only marginally for the secondary endpoint of overall survival (HR 0.83, 0.68–1.01; p = 0.057). For the second objective, the adjusted HRs favoured CAF-T over CAFT but did not reach significance for disease-free survival (HR 0.84, 0.70–1.01; p = 0.061) or overall survival (HR 0.90, 0.73–1.10; p = 0.30). Neutropenia, stomatitis, thromboembolism, congestive heart failure, and leukaemia were more frequent in the combined CAF plus tamoxifen groups than in the tamoxifen-alone group.” (K. S. Albain, kalbain@lumc.edu)
Directly Observed Antiretroviral Therapy: In adult patients with HIV infection, direct observation of highly active antiretroviral therapy provides no benefit over self-administered treatment, according to authors who studied available randomized controlled trials in a meta-analysis (pp. 2064–71): “12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n = 1,862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91–1.20, p = 0.55), and noted moderate heterogeneity between the studies (I2= 53.8%, 95% CI 0–75.7, p = 0.0247) for directly observed versus self-administered treatment.” (N. Ford, Nathan.ford@joburg.msf.org)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2009; 339).
Intranasal Steroids in Otitis Media: Topical intranasal corticosteroids provided no therapeutic advantage over placebo in a 217-patient trial of children with recurrent bilateral otitis media with effusion (b4984). Mometasone furoate 50 mcg spray once daily in each nostril for 3 months was no more effective than placebo at improving tympanometric indicators of cure, and diary symptoms did not differ between the groups, investigators noted. (I. Williamson, igw@soton.ac.uk)

>>>PNN NewsWatch
* Through a series of compromises, concessions, and deals, Senate Democrats have lined up the 60 votes needed to proceed on health care reform. Following a 1 a.m. cloture vote this morning in a late-night session, the Senate is on track for a final vote on the legislation at 7 p.m. on Christmas Eve. Pharmacy-related provisions, including coverage of pharmacist-provided medication therapy management services, have survived negotiations thus far. If the Senate passes the bill as expected, much work remains for January in reconciling major differences between its version and the bill that passed the House in early November, including financing mechanisms, abortion provisions, and the public option.

>>>PNN JournalWatch
* Linezolid in the Treatment of Multidrug-Resistant Tuberculosis, in Clinical Infectious Diseases, 2010; 50: 49–55. (G. F. Schecter, gisela.schecter@cdph.ca.gov)
* Recognition, Diagnosis, and Treatment of Histoplasmosis Complicating Tumor Necrosis Factor Blocker Therapy, in
Clinical Infectious Diseases, 2010; 50: 85–92. (C. A. Hage, chage@iupui.edu)
* Patient Safety at Ten: Unmistakable Progress, Troubling Gaps, in
Health Affairs, 2009; doi: 10.1377/hlthaff.2009.0785. (R. M. Wachter)
* Impact of Interpreters on the Receipt of New Prescription Medication Information Among Spanish-Speaking Latinos, in
Medical Care, 2009; 47: 1201–8. (G. Moreno)

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 © 2009, 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, 2009 * Vol. 16, No. 244
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Dec. 14/28 issue of the Archives of Internal Medicine (2009; 170).
Antidepressants & Cardiovascular Mortality: With respect to possible cardiovascular disease and mortality, the risk–benefit relationship of antidepressants is favorable, according to data from the Women’s Health Initiative (pp. 2128–39). While some increased risks were found with tricyclic antidepressants and SSRIs, the drugs did not increase the overall risk of coronary heart disease. The risks of CHD, stroke, and mortality did not differ in those on tricyclics versus SSRIs. During a mean follow-up period of 5.9 years, these data were recorded for 5,496 women starting new antidepressants and other women in the 136,293-patient group taking no antidepressants: “Antidepressant use was not associated with CHD. Selective serotonin reuptake inhibitor (SSRI) use was associated with increased stroke risk (hazard ratio [HR],1.45, [95% CI, 1.08–1.97]) and all-cause mortality (HR,1.32 [95% CI, 1.10–1.59]). Annualized rates per 1,000 person–years of stroke with no antidepressant use and SSRI use were 2.99 and 4.16, respectively, and death rates were 7.79 and 12.77. Tricyclic antidepressant (TCA) use was associated with increased risk of all-cause mortality (HR,1.67 [95% CI, 1.33–2.09]; annualized rate, 14.14 deaths per 1,000 person–years). There were no significant differences between SSRI and TCA use in risk of any outcomes. In analyses by stroke type, SSRI use was associated with incident hemorrhagic stroke (HR, 2.12 [95% CI, 1.10–4.07]) and fatal stroke (HR, 2.10 [95% CI, 1.15–3.81]).” (J. W. Smoller, jsmoller@hms.harvard.edu)
In an invited commentary, authors assess the chicken-versus-the-egg nature of depression, antidepressant use, and cardiovascular outcomes (
pp. 2140–1): “Depression remains an important and underrecognized risk factor for cardiovascular morbidity and mortality in men and women with existing heart disease and/or cardiovascular risk factors. Depression is known to be associated with lower quality of life, unhealthy lifestyle choices, poor adherence to medication regimens, and poor outcomes. Unfortunately, therapies used to alleviate depressive symptoms and depression have not been associated with clear-cut cardiovascular benefits. Cognitive behavioral therapy has been shown to not improve cardiovascular outcomes; in fact it potentially worsens outcomes in women. Although smaller studies of SSRIs in patients with cardiovascular disease have suggested that SSRIs are safe, these studies have been significantly underpowered and could not be used to evaluate cardiovascular outcomes. Therefore, an important step in this field would be to embark on a national effort to endorse a large-scale simple trial of antidepressant therapy in patients with cardiovascular disease and to evaluate the influence of this therapy on cardiovascular outcomes such as cardiovascular quality of life, nonfatal cardiovascular events, and mortality. Until then, we are left with the chicken or the egg dilemma.” (C. O’Connor, conn002@mc.duke.edu">oconn002@mc.duke.edu)
Drugs for Smoking Cessation: Provision of cessation therapies at no cost combined with use of a telephone quit line resulted in relatively high cessation rates among smokers seen in primary care clinics, researchers report (pp. 2148–55). Five active pharmacotherapies were compared, including three monotherapies (nicotine patch, nicotine lozenge, and bupropion hydrochloride sustained release [SR]) and two combination therapies (patch + lozenge and bupropion SR + lozenge), with these results: “Among 7,128 eligible smokers (10 cigarettes per day) attending routine primary care appointments, 1,346 (18.9%) were enrolled in the study. Six-month abstinence rates for the 5 active pharmacotherapies were the following: bupropion SR, 16.8%; lozenge, 19.9%; patch, 17.7%; patch + lozenge, 26.9%; and bupropion SR + lozenge, 29.9%. Bupropion SR + lozenge was superior to all of the monotherapies (odds ratio, 0.46-0.56); patch + lozenge was superior to patch and bupropion monotherapies (odds ratio, 0.56 and 0.54, respectively).” (S. S. Smith, sss@ctri.medicine.wisc.edu)
Coffee, Tea, & Diabetes: High intakes of coffee, decaffeinated coffee, or tea are associated with decreased risks of developing diabetes, according to a systematic review and meta-analysis of 18 studies (pp. 2053–63). Risks of diabetes fell by 7% for each additional cup of coffee. (R. Huxley, rhuxley@george.org.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 © 2009, 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, 2009 * Vol. 16, No. 245
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release articles from JAMA (2009; 302).
Immunogenicity of H1N1 Vaccine in Young Children: In a study of 370 infants and children younger than 9 years, a single dose of influenza A/H1N1 vaccine was immunogenic and produced only mild or moderate adverse reactions (doi:10.1001/jama.2009.1911). Participants were randomized to receive either 15 or 30 mcg of hemagglutinin antigen intramuscularly in a 2-dose regimen of the inactivated, split-virus 2009 influenza A(H1N1) vaccine. Results showed: “Following the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-mcg group (92.5%; 95% confidence interval [CI], 87.6%–95.6%) and in 168 of 172 infants and children in the 30-mcg group (97.7%; 95% CI, 94.2%–99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%–91.0%) and 94.2% (95% CI, 89.6%–96.8%), and factor increases in geometric mean titer were 13.6 (95% CI, 11.8–15.6) and 18.3 (95% CI, 15.7–21.4). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity.” (T. Nolan, t.nolan@unimelb.edu.au)
Editorialists advise caution in extending these study results too quickly (
doi:10.1001/jama.2009.1929): “The immunogenicity data presented by Nolan et al suggest that at least some children will be protected after a single 15-mcg dose of the H1N1 vaccine used in this study, but the findings cannot be generalized with confidence to all children, epidemiological circumstances in every country, or different vaccine formulations. In recent years, important gaps in influenza knowledge and pandemic preparedness have been addressed, but significant challenges remain. Among those challenges is development of an easily measurable correlate of immunity that can consistently predict clinical vaccine effectiveness in all age groups. Until that objective is achieved, it remains prudent to continue to follow current recommendations for administering 2 doses to infants and young children while awaiting definitive vaccine effectiveness data.” (A. E. Fiore, abf4@cdc.gov)

>>>PNN NewsWatch
* Patients taking Vytorin (simvastatin plus ezetimibe) or Zetia (ezetimibe) do not likely have an increased risk of cancer or cancer-related death, FDA announced yesterday. But FDA added that an association cannot be definitively ruled out. Completing a review begun in Aug. 2008, the agency said that it is not advising health professionals or consumers to stop using these medications, but to continue to evaluate the clinical benefits and potential risks of Vytorin or Zetia compared with other FDA-approved cholesterol lowering medications. FDA told consumers to talk with health professionals if they have any questions about simvastatin, ezetimibe, or the Simvastatin and Ezetimibe in Aortic Stenosis trial that reported cancer in 11.1% and 7.5% of patients taking Vytorin and placebo, respectively.
* Senate Democrats appear poised to push through a
health care reform (HCR) bill on Christmas Eve. The final vote has been moved to 8 a.m. Eastern time, and observers expect the vote to be identical to those on several procedural votes earlier this week, with 60 votes in support of moving the bill forward.
* In other HCR news,
APhA is supporting efforts of a group of 11 freshmen Senators to beef up medication therapy management (MTM) provisions of the Senate bill. Sponsored by North Carolina Democrat Kay Hagan, the MTM amendment puts into statutory language many of the provisions contained in the CMS 2010 Call Letter to Medicare Part D plans. Hagan cited the efforts of Tar Heel State pharmacists in addressing the needs of patients with diabetes in a news release announcing her amendment: “Through MTM programs, pharmacists spend considerable time and resources evaluating a person’s current drug regimen and educating them about their drugs. In 2007, the North Carolina Health and Wellness Trust Fund Commission launched Checkmeds NC to provide MTM services to North Carolina seniors. During the program’s first year, more than 15,000 North Carolina seniors and 285 pharmacists participated and the program saved an estimated $10 million.”
*
PNN will not be published on Thurs. and Fri., Dec. 24–25.

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 © 2009, 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. 28, 2009 * Vol. 16, No. 246
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 24 issue of the New England Journal of Medicine (2009; 361).
Early Influenza A/H1N1 Cases in China: Oseltamivir shortens the duration of illness associated with 2009 pandemic influenza A/H1N1 infection, according to an analysis of the initial cases of the disease in China (pp. 2507–17). Patients diagnosed with the infection between the first case on May 10 and the end of June 2009 showed these clinical characteristics: “The mean age of the 426 patients was 23.4 years, and 53.8% were male. The diagnosis was made at ports of entry (in 32.9% of the patients), during quarantine (20.2%), and in the hospital (46.9%). The median incubation period of the virus was 2 days (range, 1 to 7). The most common symptoms were fever (in 67.4% of the patients) and cough (69.5%). The incidence of diarrhea was 2.8%, and the incidence of nausea and vomiting was 1.9%. Lymphopenia, which was common in both adults (68.1%) and children (92.3%), typically occurred on day 2 (range, 1 to 3) and resolved by day 7 (range, 6 to 9). Hypokalemia was observed in 25.4% of the patients. Duration of fever was typically 3 days (range, 1 to 11). The median length of time during which patients had positive real-time RT-PCR test results was 6 days (range, 1 to 17). Independent risk factors for prolonged real-time RT-PCR positivity included an age of less than 14 years, male sex, and a delay from the onset of symptoms to treatment with oseltamivir of more than 48 hours.” (X-W Li, ditanlxw@yahoo.com.cn)
Commenting in an editorial, an official in the U.S. Department of Health and Human Services describes a “need for science in the practice of public health,” including better vaccination strategies (
pp. 2571–2): “The ultimate way to protect individual persons and populations from disease is with vaccination, and the rapid development and manufacture of the H1N1 vaccine represent a triumph of modern science. Even so, the United States, which was one of the first countries to mount a large-scale vaccination campaign, has not yet reached the aspirational goal articulated in the pandemic preparedness plan published in November 2005—that is, to attain within 5 years the domestic manufacturing capacity to produce sufficient pandemic vaccine for the U.S. population within 6 months of pandemic onset. Additional breakthroughs in the development of safe cell-based, plant-based, and recombinant vaccines, combined with large-scale manufacturing capacity, are needed to reach this goal. Analogous global goals—and plans for achieving them—are badly needed.” (N. Lurie)
Comparison of Senate, House Reform Bills: Published as the Senate approved its health care reform bill by a 60–39 vote (one Republican Senator was absent) on Christmas Eve, an article evaluates the two Senate and House bills that are now headed to conference committee (pp. 2497–9): “Some critics [argue] that the bills don’t do enough to control costs. This argument ignores fundamental reforms in the Senate bill in particular, which includes a four-pronged attack on health care costs. First, it imposes a tax on high-cost insurance plans that will put pressure on insurers and employers to keep the cost of insurance down, while delivering $234 billion in wage income to workers over the next decade. Second, it includes funds and a structure for comparative-effectiveness research that will provide the information necessary to guide our health care system toward care that works and away from care that doesn’t. Third, it establishes a Medicare advisory board with the power to set rates (subject to an up-or-down vote by Congress) if costs grow too rapidly. Finally, it sets up an innovation center within the Centers for Medicare and Medicaid Services and launches pilot projects to explore alternative reimbursement and organizational structures that could transform the delivery of care.” (J. Gruber)

>>>PNN JournalWatch
* Total Cardiovascular Disease Burden: Comparing Intensive with Moderate Statin Therapy, in Journal of the American College of Cardiology, 2009; 54: 2353–7. (M. J. Tikkanen, matti.j.tikkanen@helsinki.fi)
* Barrett’s Esophagus, in
New England Journal of Medicine, 2009; 361: 2548–56. (P. Sharma, psharma@kumc.edu)
* Drug Fever, in
Pharmacotherapy, 2010; 30: 57–69. (J. C. Gallagher, jason.gallagher@temple.edu)
* A Comparative Review of the Lipoglycopeptides: Oritavancin, Dalbavancin, and Telavancin, in
Pharmacotherapy, 2010; 30: 80–94. (B. T. Tsuji, btsuji@buffalo.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 © 2009, 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, 2009 * Vol. 16, No. 247
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Dec. issue of the Journal of the American Geriatrics Society (2009; 57).
Cardiovascular Exercise & Vaccine Seroprotection: Increased seroprotection from influenza vaccinations was evident among older adults who engaged in cardiovascular exercise, but not flexibility and balance training, researchers report (pp. 2183–91). The exercise group had less overall illness severity and sleep disturbance during an influenza season, compared with the other two groups, but no changes in reported respiratory infections were noted: “Of the 160 participants enrolled, 144 (90%) completed the 10-month intervention with excellent compliance (about 83%). Cardiovascular, but not flexibility, exercise intervention resulted in improvements in indices of cardiovascular fitness, including maximal oxygen uptake. Although not affecting peak (e.g., 3 and 6 weeks) postvaccine anti-influenza HI titers, cardiovascular exercise resulted in a significant increase in seroprotection 24 weeks after vaccination (30–100% dependent on vaccine variant), whereas flexibility training did not.” (J. A. Woods, woods1@illinois.edu)
Treating Dementia in Nursing Homes: Less than one-third of U.S. nursing home residents with dementia are receiving cholinesterase inhibitors (ChEIs), an analysis of data from the 2004 National Nursing Home Survey (NNHS) shows (pp. 2269–74). For residents in a stratified, random sample who were aged 65 or older and had a chart diagnosis of dementia, these patterns in drug use and characteristics were noted: “Almost half (49.1%) of NNHS participants had dementia, and 30.0% of those with dementia were receiving ChEIs. Donepezil accounted for 71% of all ChEI prescriptions. Multivariable logistic regression showed that ChEI use was independently associated with younger age (odds ratio (OR) = 0.42, 95% confidence interval (CI) = 0.28–0.64, aged ≥95 vs 65–74), less activity of daily living impairment (OR = 0.49, 95% CI = 0.42–0.58, severe vs mild impairment), greater use of antipsychotics (OR = 1.33, 95% CI = 1.16–1.54) and antidepressants (OR=1.38, 95% CI = 1.20–1.59), and residence in NHs with more beds (OR=1.52, 95% CI = 1.07–2.16, ≥200 beds vs <50 beds).” (D. Seitz, dallas_seitz@hotmail.com)

>>>Nephrology Report
Source:
Jan. issue of the American Journal of Kidney Diseases (2010; 55).
Lovastatin, Cardiovascular Disease, & Kidney Function Loss: In a post-hoc analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study, investigators find that lovastatin, while effective for primary prevention of cardiovascular disease in patients with chronic kidney disease, has no effect on the rate of loss of kidney function in such patients (pp. 42–9). Looking for first major acute cardiovascular events in participants with mild CKD or kidney function loss in persons with or without CKD, the researchers found: “At baseline, mean estimated glomerular filtration rate in participants with CKD (n = 304) was 53.0 ± 6.0 mL/min/1.73 m2. After an average follow-up of 5.3 ± 0.8 years, the incidence of a fatal and nonfatal CVD event was lower in participants with CKD receiving lovastatin than in those receiving placebo (adjusted relative risk [RR], 0.31; 95% CI, 0.13–0.72; P = 0.01). Tests for interaction suggested that the benefit of lovastatin was independent of the presence of CKD. Lovastatin did not reduce the annualized mean decrease in estimated glomerular filtration rate (−1.3 ± 0.07 vs −1.4 ± 0.07 mL/min/1.73 m2/y, respectively; P = 0.1) or the frequency of a ≥ 25% decrease in kidney function (adjusted RR, 1.10; 95% CI, 0.96–1.28; P = 0.2) or incident CKD (adjusted RR, 1.04; 95% CI, 0.86–1.27; P = 0.6).” (M. Chonchol, michel.chonchol@ucdenver.edu)
Adalimumab in Focal Segmental Glomerulosclerosis: Adalimumab may be useful as an antifibrotic agent in patients with primary focal segmental glomerulonephritis, according to results of a Phase I pharmacokinetics trial (pp. 50–60). “Pharmacokinetic assessment showed increased clearance of adalimumab in patients with resistant primary FSGS and validated the need to evaluate the disposition of novel therapies for this disease to define appropriate dosing regimens,” the authors write. “The study provides a rationale to evaluate the efficacy of adalimumab as an antifibrotic agent for resistant FSGS in phase 2/3 clinical trials.” (H. Trachtman, trachtma@lij.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 © 2009, 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, 2009 * Vol. 16, No. 248
Providing news and information about medications and their proper use

>>>PNN’s Top 10 for 2009
A fitting close to a challenging decade, 2009 offered pharmacists the expected as well as many surprises. Here’s how the year looked through the lens of PNN.
1. A/H1N1 Influenza: The 2009 A/H1N1 influenza pandemic started innocently enough, with a simple announcement that CDC was investigating seven patient cases in Texas and California (Apr. 24). Stories soon were coming almost daily, and the tales of influenza-related morbidity and mortality are still not all told (Nov. 4, 11, 12; Dec. 28).
2. Health Care Reform: Last year’s number 1 topic delivered as promised following the historic inauguration of Barack Obama (Jan. 20). A medical journal editor called on physicians to adopt the “selflessness” of the new President early on (Feb. 13). But by the time the House and Senate passed HCR legislation (Nov. 9, Dec. 28), the debate had degenerated into bitter partisan fighting and a war of confusing contortions at which Washington excels (Dec. 1).
3. Medication Therapy Management Hits Prime Time: Despite the acrimonious HCR debate, pharmacy was organized in promoting its principles for change (Feb. 13). Pharmacist-delivered medication therapy management was a particularly popular provision on Capitol Hill. It was included in the final versions of both the House and Senate bills, and this portends positively in conference committee. In the literature, pharmacists’ cognitive services were positively portrayed in numerous settings ranging from intensive-care units (July 10) to community pharmacy–based immunizations (July 30).
4. Exploring Medical Homes: If HCR becomes law, will medical homes be the new “place” where pharmacists practice evidence-based pharmacotherapy? Will pharmacists be physically present, or will virtual interactions with other health professionals and patients prevail? Questions such as those come to mind as one reads this year’s articles on medical homes and comparative effectiveness research (Jan. 7; Feb. 11; Mar. 12, 13, 25, 31; Apr. 22; May 7; June 24, 30; July 24; Aug. 4, 7, 28; Sept. 1; Nov. 18, 24).
5. Check the Genome: As human genome pioneer Francis S. Collins took the helm at NIH (July 9), the question is clearly not if but when will pharmacogenomics be incorporated into routine care. Genetics was central to discussions about warfarin (Feb. 19, Aug. 18), diseases such as Alzheimer disease (July 16, Dec. 16) and acute lymphoblastic leukemia (Jan. 28), and a clopidogrel–PPI interaction (Jan. 22, 26, 27; Mar. 4; Aug. 26; Nov. 18; Dec. 11). Gene therapy was investigated in patients with Parkinson disease (Nov. 20) and severe combined immunodeficiency (Jan. 29).
6. How’s the Vitamin D Level: While dietary supplements and complementary and alternative medicine continued their mixed performances in evaluative studies (Feb. 10, 20, 24; Mar. 2, 10, 30; Apr. 14; May 18; Jun. 16; July 14, 17; Aug. 18; Oct. 7, 30), the year clearly belonged to vitamin D and new recognition of the importance of adequate body stores of the nutrient (Feb. 24; Mar. 23, 27; June 5; Oct. 27).
7. Public Worries About Vaccines: The public’s love–fear relationship with vaccines continued. Authors offered suggestions for dealing vaccine refusals (May 7), even while clinical trials painted a favorable risk–benefit relationship for vaccines of many types (Jan. 15, Mar. 19; Aug. 19, Oct. 22).
8. Medication Safety & FDA: As newly installed Commissioner of Food and Drugs Margaret A. Hamburg set an ambitious agenda for FDA (Aug. 7), medication safety stayed at the top of the agency’s list all year (Oct. 1). Plans were introduced to manage medication risk for opioids (Feb. 11, May 29) and metoclopramide (Feb. 27).
9. New Drugs: After a few years of ho-hum drug approvals, some interesting agents reached market in 2009, including prasugrel (July 13), saxagliptin (Aug. 3), and asenapine (Aug. 17).
10. Time for E-prescribing: The “low hanging fruit” of health information technology (Mar. 11), e-prescribing and medical record technology are being pushed for adoption in the next few years, thanks to provisions and money in the economic stimulus bill passed in Feb. (Mar. 12, 26; May 27; Aug. 7; Sept. 14).

>>>PNN NewsWatch
* PNN will not be published on Thurs. and Fri., Dec. 31–Jan. 1, New Year’s Eve and 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 © 2009, 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.