Dec 2010

PNN Quarterly File—Fourth Quarter 2010

PNN Pharmacotherapy Line
Oct. 1, 2010 * Vol. 17, No. 190
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Oct. issue of Pharmacotherapy (2010; 30).
Acid-Suppressing Drugs Before Ischemic Events: Many patients use acid-suppressing drugs before ischemic events occur, researchers report, presenting ìan unmeasured and uncontrolledî confounding factor in observational studies of potential interactions between clopidogrel and proton-pump inhibitors (pp. 985–93). Population-based, nested case-control analysis of Saskatchewan administrative databases revealed these patterns among patients aged 40 years or older who began antihypertensive drug therapy in 1994–2003 and were hospitalized for myocardial infarction (1,002 patients) or unstable angina (610 patients) and matched controls (8,060 patients): ìWithin the case and control groups, we calculated exposure to acid-suppressing therapy, defined as proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2RAs), within 90 days leading up to the event. Exposure to acid-suppressing therapy was higher among cases than controls (15.3% [246/1612] vs 10.4% [837/8060], adjusted odds ratio [AOR] 1.26, 95% confidence interval [CI] 1.06–1.49, p < 0.009). Exposure to each acid suppressant was similarly higher among cases than controls: H2RA users (11.7% [188/1612] vs 8.4% [678/8060], AOR 1.21, 95% CI 1.00–1.46, p < 0.048) and PPI users (4.0% [64/1612] vs 2.2% [179/8060], AOR 1.32, 95% CI 0.95–1.84, p = 0.094). Use of other drugs was also significantly increased during this period.î (D. Blackburn, d.blackburn@usask.ca)
Postoperative Acquired Coagulopathy: Coagulopathy following surgery, a complication that is not always recognized, produces lengths of hospital stay 3 times those of unaffected patients, a case–control study shows (pp. 994–1003).Included in the analysis were 26 patients who developed coagulopathy after surgery and 26 matched controls. Results showed: ìCase patients had a minimum of two postoperative consecutively drawn episodes of prothrombin time (PT) or activated partial thromboplastin time (aPTT) elevated to greater than 20% above the upper limit of normal. Patients with inherited clotting disorders or other identifiable causes of coagulopathy were excluded. Case patients underwent the following surgeries: 12 orthopedic (46%), six cardiovascular (23%), four gastrointestinal (15%), and four neurosurgical (15%). Mean values of the first elevated PT and aPTT were 19.7 and 50.8 seconds, respectively. Mean postoperative stay was 31.5 days for cases versus 9.8 days for controls (p < 0.05). Mean cost (2008 U.S. dollars) of resources used was $112,280 for cases versus $38,357 for controls (p < 0.001). Costs incurred between the onset of coagulopathy and discharge constituted 67% of postoperative costs. Physician reimbursement expenditures were minimal.î (E. B. Devine, bdevine@uw.edu)
International Travel & Mosquito-Borne Illnesses: People traveling internationally should, when appropriate, receive vaccinations and chemoprophylaxis against mosquito-borne diseases such as yellow fever and malaria, authors of a review article remind pharmacists (pp. 1031–43; E. Mirzaian).
Pharmacists & Health Care Reform: After analyzing the opportunities for pharmacists in the health care reform law, an editorialist concludes (pp. 967–72): ìHealth reform cannot meet its full potential without pharmacists. But only pharmacists can decide what the profession’s roles will be under the new law. It is a defining moment for the profession, and the opportunities will never be greater for pharmacists to be in the lead with other professionals, as together, they move the nation’s health care agenda forward. For this author, who is a health policy specialist and pharmacist advocate, it would be a great disservice to the nation’s health if this opportunity were lost. My recommendation? Go for it!î (H. L. Lipton, liptonh@pharmacy.ucsf.edu)

>>>PNN NewsWatch
* Unapproved oral dosage forms of single-ingredient colchicine have been ordered off the U.S. market by FDA. The action follows last year’s approval of Colcrys. The availability of an approved product means that grandfathered formulations that have never been approved by FDA can be declared misbranded. Companies affected by the FDA action have 45 days to stop manufacturing these products and 90 days to stop shipping them. Product in distribution channels at those points, including drugs on pharmacy shelves, can be retained and sold.

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 © 2010, 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. 4, 2010 * Vol. 17, No. 191
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 2 issue of Lancet (2010; 376).
Treatment of Metastatic Castration-Resistant Prostate Cancer: In men with metastatic castration-resistant prostate cancer whose disease has progressed despite docetaxel-based therapy, cabazitaxel plus prednisone may provide a new option, according to a study that looked at overall survival rates (pp. 1147–54). The open-label, Phase III trial provided participants with oral prednisone daily and, in randomized fashion, intravenous mitoxantrone or cabazitaxel every 3 weeks. Results showed: ì755 men were allocated to treatment groups (377 mitoxantrone, 378 cabazitaxel) and were included in the intention-to-treat analysis. At the cutoff for the final analysis (Sept 25, 2009), median survival was 15.1 months (95% CI 14.1–16.3) in the cabazitaxel group and 12.7 months (11.6–13.7) in the mitoxantrone group. The hazard ratio for death of men treated with cabazitaxel compared with those taking mitoxantrone was 0.70 (95% CI 0.59—0.83, p < 0.0001). Median progression-free survival was 2.8 months (95% CI 2.4–3.0) in the cabazitaxel group and 1.4 months (1.4–1.7) in the mitoxantrone group (HR 0.74, 0.64–0.86, p < 0.0001). The most common clinically significant grade 3 or higher adverse events were neutropenia (cabazitaxel, 303 [82%] patients vs mitoxantrone, 215 [58%]) and diarrhoea (23 [6%] vs one [<1%]). 28 (8%) patients in the cabazitaxel group and five (1%) in the mitoxantrone group had febrile neutropenia.î (J. S. de Bono, johann.de-bono@icr.ac.uk)
Rituximab for Chronic Lymphocytic Leukemia: Addition of rituximab to chemotherapy for chronic lymphocytic leukemia improved progression-free and overall survival among 817 patients, researchers report (pp. 1164–74). Previously untreated patients with CD20-positive CLL received six courses of intravenous fludarabine and cyclophosphamide with or without rituximab, with these results: ìAt 3 years after randomisation, 65% of patients in the chemoimmunotherapy group were free of progression compared with 45% in the chemotherapy group (hazard ratio 0.56 [95% CI 0.46–0.69], p < 0.0001); 87% were alive versus 83%, respectively (0.67 [0.48–0.92]; p = 0.01). Chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia (136 [34%] of 404 vs 83 [21%] of 396; p < 0.0001) and leucocytopenia (97 [24%] vs 48 [12%]; p < 0.0001). Other side-effects, including severe infections, were not increased. There were eight (2%) treatment-related deaths in the chemoimmunotherapy group compared with ten (3%) in the chemotherapy group.î (M. Hallek, michael.hallek@uni-koeln.de)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 341).
Prevention of Frequent Migraine: A combination of beta-blocker plus behavioral therapy was more effective than either intervention separately in prevention of migraine in 232 adult patients with frequent attacks, a study shows (c4871): ìThe addition of combined beta-blocker and behavioural migraine management (−3.3 migraines/30 days, 95% confidence interval −3.2 to −3.5), but not the addition of beta-blocker alone (−2.1 migraines/30 days, −1.9 to −2.2) or behavioural migraine management alone (−2.2 migraines migraines/30 days, −2.0 to −2.4), improved outcomes compared with optimised acute treatment alone (−2.1 migraines/30 days, −1.9 to −2.2). For a clinically significant (50% reduction) in migraines/30 days, the number needed to treat for optimised acute treatment plus combined beta-blocker and behavioural migraine management was 3.1 compared with optimised acute treatment alone, 2.6 compared with optimised acute treatment plus beta-blocker, and 3.1 compared with optimised acute treatment plus behavioural migraine management.î (K. A. Holroyd, holroyd@ohio.edu)

>>>PNN JournalWatch
* Rare Chromosomal Deletions and Duplications in Attention-Deficit Hyperactivity Disorder: A Genome-wide Analysis, in Lancet, doi: 10.1016/S0140-6736(10)61109-9. (N. G. Williams, williamsnm@cf.ac.uk)
* Unintended Effects of a Computerized Physician Order Entry Nearly Hard-Stop Alert to Prevent a Drug Interaction, in
Archives of Internal Medicine, 2010; 170: 1578–83. (B. L. Strom, bstrom@exchange.upenn.edu)
* Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments, in
Diabetes Care, 2010; 33: 2285–93. (S. Tesfaye, solomon.tesfaye@sth.nhs.uk)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 192
Providing news and information about medications and their proper use

>>>Health Affairs Highlights
Source:
Oct. issue of Health Affairs, a theme issue on comparative effectiveness research (2010; 29).
CER on Prescription Drugs: As comparative effectiveness research is conducted on prescription drugs, policymakers and researchers should focus on studies with proper comparators, optimal endpoints and time frames, and applicability to real-world practice, authors write (pp. 1842–8). After offering policy recommendations, the group concludes: ìComparative effectiveness research is gaining prominence as the foundation of clinical practice and the basis for a more-rational allocation of scarce health care resources in the developed world. Government agencies worldwide require or coordinate studies of new drugs against clinically relevant comparators, and such findings are used to help make national treatment recommendations or set pricing for public insurance programs. To date, the US experience suggests that comparative effectiveness studies might not be ready to fully support such broad national goals.
ìWe have observed here many cases of comparative effectiveness research that have led to results that would not promote better medical practice, which can often be traced to a study design that does not reflect real-world conditions. The absence of an express link between comparative effectiveness research and US health care delivery may explain these disappointing results. A guiding national commitment, now under way, should fortify the process of developing and marshalling evidence systematically in support of improved patient outcomes.î (A. S. Kesselheim,
akesselheim@partners.org)
CER & Personalized Medicine: Despite seemingly opposed viewpoints, ìcomparative effectiveness research can help discern the appropriate role of personalized medicine in improving health care outcomes and rationalizing costs,î authors write (pp. 1783–7): ìWithout comparative effectiveness research, we would not have been able to show that genetic testing can discern which patients will not manifest a hypersensitivity reaction to abacavir. Without this research and its flexible and cost-efficient methods, we will not be able to process the deluge of molecular diagnostic information and properly assess its place in therapeutics.
ìTherefore, comparative effectiveness research may be more compatible with personalized medicine than initially realized. It may even be necessary, if we are to discover all of the benefits that personalized medicine may bring patients.
ìComparative effectiveness research can at least augment other research methods by exploring the crevices where discoveries lie and other methods cannot reach, and thereby extend the potential applications of personalized medicine. Having been applied to the effectiveness of leeches two centuries ago, comparative effectiveness research can now be applied to contemporary forms of personalized medicine.î (R. Epstein,
Robert_Epstein@medco.com)
Political Fighting Over CER: Comparative effectiveness research is just the latest chapter in ìAmerica’s on-again, off-again support for determining what works in health care,î an author maintains (pp. 1757–60): ìMany threshold questions remain. Will physicians actually change their practices based on comparative effectiveness research findings, or will additional incentives be necessary to alter their professional behavior? Will private insurers and federal programs—especially Medicare—apply these findings to their coverage decisions, even though the Affordable Care Act stipulates that its language should not be construed as permitting institute-funded research to ‘mandate coverage, reimbursement, or other policies for any public or private payer’?
ìThese questions and others are likely to play out over many years—assuming that the Affordable Care Act and the [Patient-Centered Outcomes Research Institute] survive a possibly difficult period just ahead. With some twenty states suing in court to overturn provisions of health reform law, and House Republicans vowing to try to repeal the legislation if they win a majority in the November 2010 elections, the debate over the role of comparative effectiveness research in US health care is clearly far from over.î (J. K. Iglehart,
jiglehart@projecthope.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 © 2010, 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, 2010 * Vol. 17, No. 193
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 6 issue of JAMA (2010; 304).
Atypical Fractures with Long-term Bisphosphonates: The case of a 58-year-old woman with a nonhealing subtrochanteric left hip fracture during bisphosphonate therapy provides a springboard for discussion of atypical fractures associated with use of these drugs (pp. 1480–4): ìCase reports and limited clinical series over the past 5 years have raised concern that prolonged bisphosphonate therapy may suppress bone remodeling to the extent that normal bone repair is impaired, resulting in increased fracture risk. Fractures potentially resulting from suppressed bone turnover have been described as ‘atypical,’ affecting sites such as the subtrochanteric femur that are infrequently affected by osteoporotic fractures. A prodrome of thigh pain, lack of trauma prior to the fracture, and specific radiological characteristics have also been reported. Data are limited on the prevalence of, risk factors for, and treatment of this potential problem. Current strategies include fracture risk assessment, targeting bisphosphonate therapy appropriately to individuals at increased risk of fracture, considering a 12-month interruption in therapy after 5 years in patients who are clinically stable, and considering teriparatide treatment in individuals who experience an atypical fracture while receiving bisphosphonate therapy.î (D. E. Sellmeyer, dsellme1@jhmi.edu)

>>>Pediatrics Report
Source:
Oct. issue of Pediatrics (2010; 126).
Cost-effectiveness of Medications for Bronchiolitis: The combination of nebulized epinephrine plus oral dexamethasone proved more cost-effective in treatment of bronchiolitis than either agent alone or no treatment in infants aged 6 weeks to 12 months (pp. 623–31). From the societal and health care perspectives, investigators considered duration of symptoms of feeding problems, sleeping problems, coughing, and noisy breathing in their analysis, which showed the following: ìThe combination of nebulized epinephrine plus oral dexamethasone was dominant over the other 3 comparators in that it was both the most effective and least costly. Average societal costs were $1,115 (95% credible interval [CI]: 919–1,325) for the combination therapy, $1,210 (95% CI: 1,004–1,441) for no active treatment, $1,322 (95% CI: 1,093–1,571) for epinephrine alone, and $1,360 (95% CI: 1,124–1,624) for dexamethasone alone. The average time to curtailment of all symptoms was 12.1 days (95% CI: 11–13) for the combination therapy, 12.7 days (95% CI: 12–13) for no active treatment, 13.0 days (95% CI: 12–14) for epinephrine alone, and 12.6 days (95% CI: 12–13) for dexamethasone alone.î (A. Sumner)
Increasing Influenza Vaccinations in Pediatrics: More infants and young children would be vaccinated against influenza each season if pediatricians scheduled visits in October through January and had evening and weekend vaccine clinics, a study shows (pp. 665–73). In three U.S. counties, researchers found that greater proportions of children aged 6–23 months with complete influenza vaccination in practices with these characteristics: suburban location, lower patient volume, and vaccination strategies of evening/weekend vaccine clinics. Characteristics of children with complete vaccination were younger age, existing high-risk conditions, six well visits to the practice by 3 years of age, and any practice visit from October through January. (K. A. Poehling)

>>>PNN NewsWatch
* Greater responsibilities for nurses in direct patient care, residency training for nurses, and increased numbers with baccalaureate and doctoral degrees are among the recommendations of ìThe Future of Nursing: Leading Change, Advancing Health,î an Institute of Medicine report released yesterday. Developed by a committee chaired by former HHS Secretary Donna E. Shalala of the U. Miami, the report says that the more than 3 million nurses in the U.S. are the single largest group of health professionals, spend the greatest proportion of their time in direct patient care, and have ìvaluable insights and unique abilities to contribute as partners with other health care professionals in improving the quality and safety of care as envisioned in the Affordable Care Act enacted this year.î

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 194
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 7 issue of the New England Journal of Medicine (2010; 363).
Pluripotent Stem Cells for Long-QT Syndrome: Functional cardiac myocytes grown in the laboratory from pluripotent stem cells reversed the electrophysiologic problems associated with long-QT syndrome in two affected family members, researchers report (pp. 1397–409). A father and son with an autosomal dominant missense mutation (R190Q) in the KCNQ1 gene provided dermal fibroblasts, as did two healthy control patients. The fibroblasts were infected with retroviruses with four human transcription factors, converting them to pluripotent stem cells. Those were then directed to differentiate into cardiac myocytes.
The authors provide these details about the results of the effort: ìInduced pluripotent stem cells maintained the disease genotype of long-QT syndrome type 1 and generated functional myocytes. Individual cells showed a ‘ventricular,’ ‘atrial,’ or ‘nodal’ phenotype, as evidenced by the expression of cell-type–specific markers and as seen in recordings of the action potentials in single cells. The duration of the action potential was markedly prolonged in ‘ventricular’ and ‘atrial’ cells derived from patients with long-QT syndrome type 1, as compared with cells from control subjects. Further characterization of the role of the R190Q–KCNQ1 mutation in the pathogenesis of long-QT syndrome type 1 revealed a dominant negative trafficking defect associated with a 70 to 80% reduction in I
Ks current and altered channel activation and deactivation properties. Moreover, we showed that myocytes derived from patients with long-QT syndrome type 1 had an increased susceptibility to catecholamine-induced tachyarrhythmia and that beta-blockade attenuated this phenotype.î (K-L Laugwitz, klaugwitz@med1.med.tum.de)
After acknowledging that ìrealizing the full potential of this approach will itself be challenging,î an editorialist is positive about this new ìtool for the study of human diseaseî (
pp. 1471–2): ìIn the case of research on cardiac conditions, in which the availability and viability of human cardiomyocytes have been limiting factors, induced pluripotent stem cells provide an unprecedented opportunity to study disease mechanisms and potential therapies in a human cellular context, shining a new and powerful light on some of the very processes we hope to understand.î (A. Rosenzweig)
Rolofylline for Acute Heart Failure: The adenosine A1-receptor antagonist rolofylline showed ìno promiseî in treatment of acute heart failure in a clinical trial of 2,033 patients (pp. 1419–28). Randomized in 2:1 proportions to daily intravenous rolofylline 30 mg or placebo for up to 3 days, patients had these outcomes of treatment: ìRolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P = 0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P = 0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P = 0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A1-receptor antagonists.î (B. M. Massie, barry.massie@va.gov)
Autoimmunity in Duchenne’s Muscular Dystrophy: During the process of ìdelivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy,î investigators encountered unexpected problems with autoimmunity (pp. 1429–37): ìDystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease.î (C. M. Walker, christopher.walker@nationwidechildrens.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 © 2010, 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, 2010 * Vol. 17, No. 195
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Oct. 12 issue of the Journal of the American College of Cardiology (2010; 56).
Testosterone for Women with Chronic Heart Failure: In 36 older women with stable chronic heart failure, transdermal testosterone patches improved functional capacity, insulin resistance, and muscle strength, researchers report (pp. 1310–6). Based on baseline and 6-month measurements of 6-min walking test (6MWT), cardiopulmonary exercise test, echocardiogram, quadriceps maximal isometric voluntary contraction, dynamic quadriceps isokinetic strength (peak torque), and insulin resistance assessment by homeostasis model, the investigators found: ìDistance walked at 6MWT as well as peak oxygen consumption significantly improved in the [testosterone (T)] group, whereas they were unchanged in the [placebo (P)] group (p < 0.05 for all comparisons). The homeostasis model was significantly reduced in the T group in comparison with the P group (–16.5% vs. +5%, respectively; p < 0.05). Maximal voluntary contraction and peak torque increased significantly in the T group but did not change in the P group. Increase in distance walked at 6MWT was related to the increase in free testosterone levels (r = 0.593, p = 0.01). No significant changes in echocardiographic parameters were observed in either group. No side effects requiring discontinuation of T were detected.î (F. Iellamo, iellamo@med.uniroma2.it)
Noting that the evidence for testosterone efficacy is limited to plasma/tissue signals, target organ effects, and patient symptoms and quality of life, editorialists make these recommendations (
pp. 1317–9): ìWith this ‘bottom-up approach,’ we have arbitrarily scored the evidence acquired from the innovative and interesting work of Iellamo et al., which represents a promising start for this new therapeutic direction. However, we have travelled down the path of potential new treatments for heart failure many times and been disappointed more often than pleased. To that end, more work needs to be done. We require further understanding of the optimal degree of androgen replacement—physiologic or supraphysiologic—and how best to identify those requiring it; we also need to know which clinically available metric is the best gauge to follow. Hence, future studies should systematically examine both differing doses and routes of administration of testosterone, include much larger patient populations of both sexes, explore other correlates that would provide insight into the mechanism and benefit, and finally collect meaningful clinical outcome data that can establish its role and its potential promise in clinical practice.î (P. W. Armstrong, paul.armstrong@ualberta.ca)

>>>Circulation Report
Source:
Oct. 5 issue of Circulation (2010; 122).
Hemodynamic Factors in Systolic Blood Pressure: Greater forward pressure waves are the primary cause of elevations in pulse pressure at any age and in those of advanced age, according to noninvasive assessments of 6,417 Framingham Heart Study Third Generation and Offspring participants (pp. 1379–86). Seeking to provide data that would help resolve whether elevations in systolic blood pressure are caused by elevated pulse wave velocity and premature wave reflection, the researchers ìfound that forward wave amplitude is the predominant hemodynamic correlate of pulse pressure across the adult age spectrum and accounts for an overwhelming majority of the accelerated increase in pulse pressure after 50 years of age.î (G. F. Mitchell, GaryFMitchell@mindspring.com)

>>>PNN NewsWatch
* DEA said that Americans turned in 121 tons of prescription drugs at more than 4,000 locations during the first national Take-Back Campaign, held on Sept. 25. The agency added that Congress this week passed legislation for the President’s signature that would create a permanent framework for safe and proper disposal of unused or expired prescription medications.
* DEA also this week recognized
nurses in long-term care facilities as physician agents, thereby allowing them to communicate medication orders for Schedule III, IV, and V substances to pharmacies. ASCP said in an e-mail blast to members that it had been seeking this change ìfor many years.î
*
PNN will not be published on Mon., Oct. 11, 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 © 2010, 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, 2010 * Special alert
Providing news and information about medications and their proper use

Abbott Laboratories is pulling its antiobesity agent Meridia (sibutramine) off the U.S. market, FDA announced today. The action was taken at the request of FDA, which had reviewed data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT). It showed a 16% increase in risk of serious cardiovascular events in patients on the drug, compared with placebo. These events included nonfatal myocardial infarction, nonfatal stroke, cardiac arrest requiring resuscitation, and death.

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 © 2010, 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. 12, 2010 * Vol. 17, No. 196
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 11 issue of the Archives of Internal Medicine (2010; 170).
Pharmacists & Patient Care: Two research articles report on the impact of pharmacists in collaborative patient care, and a commentary explores the articles’ implications.
At five Iowa City primary care clinics, collaborative management of hypertension by pharmacists and physicians was significantly more effective than usual care, a study shows (
pp. 1634–9). Improved outcomes were seen with 24-hour ambulatory blood pressures and rates of BP control. Over a 9-month period, pharmacists ìhelped patients to identify barriers to BP control, counseled on lifestyle and dietary modifications, and adjusted antihypertensive therapy in collaboration with the patients’ primary care providers,î the investigators explain, with these results: ìBaseline and end-of-study ambulatory BP profiles were evaluated for 175 patients. Mean (SD) ambulatory systolic BPs (SBPs), reported in millimeters of mercury, were reduced more in the intervention group than in the control group: daytime change in SBP, 15.2 (11.5) vs 5.5 (13.5) (P < .001); nighttime change in SBP, 12.2 (14.8) vs 3.4 (13.3) (P < .001); and 24-hour change in SBP, 14.1 (11.3) vs 5.5 (12.5) (P < .001). More patients in the intervention group than in the control group had their BP controlled at the end of the study (75.0% vs 50.7%) (P < .001), as defined by overall 24-hour ambulatory BP monitoring.î (M. E. Ernst, michael-ernst@uiowa.edu)
In a study of smoking cessation efforts, physicians and pharmacists had higher perceived ability, confidence, and intention (ACI) to address smoking with patients, but only the physicians were successful in incorporating that knowledge into their practices, according to a study from 16 Texas communities (
pp. 1640–6). In a group-randomized trial of 87 physicians and 83 pharmacists, smoking cessation training was provided to the intervention group, while those in the control arm were trained in skin cancer prevention. Patient entrance and exit interviews were conducted, and results showed: ìThere was a significant increase in the percentage of physicians with a high ACI index in the intervention group from pretraining to posttraining (27% to 73%; P < .001) vs the control group (27% to 34%; P = .42) and for pharmacists (4% to 60%; P < .001) vs the control group (10% to 14%; P = .99). Similar results were seen from pretraining to extended follow-up. At baseline, fewer pharmacy patients reported being asked about smoking compared with patients seen by physicians (7% vs 33%; P = .001). There was an increase in assisting patients to quit (6% to 36%; P = .002) by physicians (baseline vs 12 months) in the intervention group, but not in the control group.î (A. V. Prokhorov, aprokhor@mdanderson.org)
Noting that pharmacists in hospitals are more frequently practicing ìat the top of their trainingî while those in community pharmacy lag, the author of a commentary article describes these possible ways to address the discrepancy (
pp. 1646–7): ìThe new federal health care reform bill will provide medical coverage for an additional 32 million US citizens, but access to health care remains bureaucratic and limited. There is a projected shortage of primary care providers. Pharmacists practicing in community pharmacies, which are widely distributed throughout the United States, could potentially expand access to care, particularly in the areas of preventative medicine and chronic disease management. However, an economic model that is solely driven by prescriptions filled per day will not unleash the full potential of these well-trained but clinically underused professionals. Limited access to medical records, contact with other health care providers, and reimbursement policies remain major impediments. Web-based efforts to improve accessibility of medical records, such as those being piloted with Google Health and Microsoft HealthVault, suggest a future in which such records could be available to the practicing community pharmacist. However, wide adoption of this technology is many years away.î (B. J. Guglielmo, gugliemoj@pharmacy.ucsf.edu)

>>>PNN JournalWatch
* Oral Sucrose as an Analgesic Drug for Procedural Pain in Newborn Infants: A Randomised Controlled Trial, in Lancet, 2010; 376: 1225–32. (R. Slater, r.slater@ucl.ac.uk)
* The Hippocampal Formation in Schizophrenia, in
American Journal of Psychiatry, 2010; 167: 1178–93. (C. A. Tamminga)

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 © 2010, 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, 2010 * Vol. 17, No. 197
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 13 issue of JAMA (2010; 304).
Managing Medications in the Elderly: The role of the pharmacist is part of a broad discussion of medication management in clinically complex elderly patients (pp. 1592–601). Using the case of an 84-year-old man in a Clinician’s Corner contribution, authors write: ìFor many physicians, ideal medication reviews and adherence assessments are an improbable reality given the time pressures of office-based practice. In this setting, focusing on the highest-risk and highest-benefit drugs can yield good return on a limited time investment. Better yet is sharing these responsibilities with other health care professionals. Contacting community pharmacists regarding concerns about patients can help engage their expertise in identifying and crafting solutions to problems with adherence or medication regimens. Where health systems permit, nurses and clinic-based pharmacists should share medication management responsibilities as articulated in the patient-centered medical home model of care. Some medication management programs are available through pharmacy benefit management plans serving Medicare Part D patients [a list of resources is provided with the article]. Eligibility criteria and scope of these programs are often limited, although more widespread benefits are mandated for implementation by 2013.î (M. A. Steinman, mike.steinman@ucsf.edu)
In an accompanying commentary, an author further expands on the need for a better system for elder care (
pp. 1606–7): ìAlthough the 2010 health care legislation did not reform the delivery system, it did provide for small pilot studies of ‘medical homes’ that could address the fragmentation of care that so often defeats the provision of integrated, coherent drug regimens for elderly patients with complex health care needs. Solutions could be designed-in as these systems develop in several ways. Pharmacists and nurses could work with physicians to develop, implement, and monitor drug regimens. Coordinated care could allocate funds to allow a clinician to spend more than 10 to 15 minutes for a patient visit. These steps could facilitate coordination and ‘pruning’ of the drug regimen—a difficult activity when several specialists share a patient’s care across practices and institutions. Coordination of drug regimens could minimize unnecessary complexity, maximize affordability, and permit action on non-adherence and overlapping prescribing.î (J. Avorn, javorn@medsoc.harvard.edu)
Buprenorphine Implants for Opioid Dependence: In 163 adult patients with opioid dependence, buprenorphine implants decreased opioid use over a 16-week period, compared with placebo, according to urine-sample data obtained in a 6-month clinical trial (pp. 1576–83). At 18 sites in 2007–08, patients received either buprenorphine 80-mg implants or placebo (in a 2:1 ratio), with these results following induction with sublingual buprenorphine–naloxone tablets: ìThe buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%–46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%–36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P < .001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P < .001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P < .001) and on the clinician global ratings of improvement (P < .001) than those who received placebo implants. Minor implant site reactions were the most common adverse events: 61 patients (56.5%) in the buprenorphine group and 29 (52.7%) in the placebo group.î (W. Ling, lwalter@ucla.edu)

>>>PNN NewsWatch
* FDA has approved an extended-release formulation of naltrexone, Vivitrol (Alkermes), for use in opioid-dependent patients after detoxification.

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 © 2010, 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, 2010 * Vol. 17, No. 198
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 14 issue of the New England Journal of Medicine (2010; 363).
Antiretroviral Therapies After Peripartum Nevirapine: Two studies and an editorial examine use of antiretroviral drugs following peripartum nevirapine exposure, which selects for resistant strains.
Ritonavir-boosted lopinavir proved a useful antiretroviral regimen in women who were exposed during childbirth to single-dose nevirapine, a study shows (
pp. 1499–509). In Africa, women with HIV-1 infection and CD4+ T-cell counts of less than 200 per cubic millimeter were included in the trial according to whether they had or had not taken single-dose nevirapine at least 6 months before enrollment. Participants received either tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir, with these results: ìA total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P = 0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died.î (S. Lockman, slockman@hsph.harvard.edu)
For children with HIV-1 infections who were exposed during the peripartum period to single-dose nevirapine, zidovudine and lamivudine plus ritonavir-boosted lopinavir produced better outcomes than a regimen of zidovudine and lamivudine plus nevirapine (
pp. 1510–20). The authors concluded that alternative strategies for preventing mother-to-child HIV transmission are ìurgently required,î based on these results in African children aged 6–36 months who had or had not been exposed to single-dose nevirapine and a primary end point of virologic failure or discontinuation of treatment by week 24: ìA total of 164 children were enrolled. The median percentage of CD4+ lymphocytes was 19%; a total of 56% of the children had WHO stage 3 or 4 disease. More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point (39.6% vs. 21.7%; weighted difference, 18.6 percentage-points; 95% confidence interval, 3.7 to 33.6; nominal P = 0.02). Baseline resistance to nevirapine was detected in 18 of 148 children (12%) and was predictive of treatment failure. No significant between-group differences were seen in the rate of adverse events.î (P. Palumbo, paul.e.palumbo@dartmouth.edu)
Editorialists write that ìthese studies help equip us with strategies to deal with the current imperfections in our scale-up effortsî to prevent perinatal HIV transmission (
pp. 1570–2): ìWith the new WHO guidelines calling for increased access to therapy and prophylaxis for both immunocompromised and nonimmunocompromised pregnant women and timely provision of maternal and infant antiretroviral prophylaxis throughout pregnancy, delivery, and breast-feeding, the goal of eradication of pediatric HIV is within sight. Reaching that goal will require long-term investment in health systems, integration of strategies for the prevention of mother-to-child transmission into maternal and child health programs and national HIV treatment programs, access to laboratory monitoring, and second-line and third-line regimens. It is remarkable that despite the economic downturn, major international agencies and nongovernmental organizations have committed themselves to this ambitious goal.î (M. Lallemant)

>>>PNN NewsWatch
* Following up on recent information about atypical fractures in patients taking bisphosphonates (see PNN, Sept. 15), FDA yesterday announced additional warnings for product labeling of these drugs.

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 © 2010, 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, 2010 * Vol. 17, No. 199
Providing news and information about medications and their proper use

>>>Neurology Highlights
Source:
Oct. 12 issue of Neurology (2010; 75).
Antiplatelet Therapy at Time of Intracerebral Hemorrhage: Increased mortality but no significant differences in poor functional outcomes were found in a systematic review and meta-analysis of studies of antiplatelet therapy (APT) at the time of intracerebral hemorrhage (ICH) (pp. 1333–42). Of 2,873 studies that included mortality or functional outcomes during pre-ICH APT, 10 met inclusion criteria. Data from these were combined with unpublished information from 15 cohort studies published by the authors. Results showed: ìWe obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29).î (E. E. Smith, eesmith@ucalgary.ca)
Editorialists provide this assessment of use of APT in patients at risk for ICH (
pp. 1314–5): ìThe [above] study Ö has confirmed that prior antiplatelet therapy use is frequent among patients with ICH. Their review of the current literature demonstrates that more convincing evidence for an adverse effect of antiplatelet therapy on ICH outcomes is needed before further research into reversing the effects of antiplatelet drugs is planned. However, a clinically important effect of antiplatelet therapy on ICH outcomes cannot be discounted yet.î (C.E. Lovelock, cloveloc@sgul.ac.uk)

>>>Rheumatology Report
Source:
Oct. issue of Arthritis & Rheumatism (2010; 62).
Comparative Efficacy of Agents for RA: Based on studies showing that disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, biologic agents, and combinations of these drugs are equally effective in patients with rheumatoid arthritis, investigators conclude that biologic agents should be reserved for patients whose conditions do not respond to DMARDs (pp. 2852–63). The authors used data from 70 comparative trials of 16 total interventions to conduct 21 meta-analyses, with these results on the percentage of annual radiographic progression rates (PARPRs): ìCompared with placebo, the PARPR was 0.65% smaller in the single-DMARD group (P < 0.002) and 0.54% smaller in the glucocorticoid group (P < 0.00001). Compared with single-DMARD treatment, the PARPR was 0.62% smaller in the combination-DMARD group (P < 0.001) and 0.61% smaller in the biologic agent plus methotrexate (MTX) group (P < 0.00001). The effect of a combination of 2 DMARDs plus step-down glucocorticoids did not differ from the effect of a biologic agent plus MTX (percentage mean difference –0.07% [95% confidence interval –0.25, 0.11]) (P = 0.44).î (N. Graudal, graudal@dadlnet.dk)
Abatacept in SLE: In a 12-month, Phase IIb trial of abatacept, 175 patients with systemic lupus erythematosus had these changes in their scores of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of a steroid taper (pp. 3077–87): ìThe proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference −3.5 [95% CI −15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician-assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient-reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease-related events occurring during the first 6 months of the study (including the steroid taper period).î (J. T. Merrill, joan-merrill@omrf.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 © 2010, 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. 18, 2010 * Vol. 17, No. 200
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 16 issue of Lancet (2010; 376).
Pharmacogenetics of Clopidogrel, Prasugrel: Patients with genetic variants of the P-glycoprotein gene (ABCB1) have reduced platelet inhibition and are thus at increased risk for ischemic events during clopidogrel treatment, a study shows (pp. 1312–9). Combined with cytochrome 2C19 variants found in 2,932 patients with acute coronary syndromes, the investigators concluded that about one-half of the population has a genotype that places them at increased risk of cardiovascular events during treatment with standard doses of clopidogrel. No such associations were found with prasugrel, however, as noted in these results: ìIn patients treated with clopidogrel, ABCB1 3435C—>T genotype was significantly associated with the risk of cardiovascular death, myocardial infarction, or stroke (p = 0.0064). TT homozygotes had a 72% increased risk of the primary endpoint compared with CT/CC individuals (Kaplan–Meier event rates 12.9% [52 of 414] vs 7.8% [80 of 1,057 participants]; HR 1.72, 95% CI 1.22—2.44, p = 0.002). ABCB1 3435C—>T and CYP2C19 genotypes were significant, independent predictors of the primary endpoint, and 681 (47%) of the 1,454 genotyped patients taking clopidogrel who were either CYP2C19 reduced-function allele carriers, ABCB1 3435 TT homozygotes, or both were at increased risk of the primary endpoint (HR 1.97, 95% CI 1.38–2.82, p = 0.0002). In healthy participants, 3,435 TT homozygotes had an absolute reduction in maximum platelet aggregation with clopidogrel that was 7.3 percentage points less than for CT/CC individuals (p = 0.0127). ABCB1 genotypes were not significantly associated with clinical or pharmacological outcomes in patients with an acute coronary syndrome or healthy individuals treated with prasugrel, respectively.î (J. L. Mega, jmega@partners.org)
Ticagrelor v. Clopidogrel for ACS: Ticagrelor both is more effective than clopidogrel for treating acute coronary syndromes and avoids the need for genetic pretesting, a study shows (pp. 1320–8). In the PLATO trial, ìticagrelor reduced the composite outcome of cardiovascular death, myocardial infarction, and stroke, but increased events of major bleeding related to non-coronary artery bypass graft,î the authors write. In a genetic analysis of CYP2C19 and ABCB1 alleles, the investigators found these results with respect to a primary efficacy composite endpoint of cardiovascular death, myocardial infarction, or stroke after up to 12 months’ treatment with ticagrelor or clopidogrel: ì10,285 patients provided samples for genetic analysis. The primary outcome occurred less often with ticagrelor versus clopidogrel, irrespective of CYP2C19 genotype: 8.6% versus 11.2% (hazard ratio 0.77, 95% CI 0.60—0.99, p = 0.0380) in patients with any loss-of-function allele; and 8.8% versus 10.0% (0.86, 0.74–1.01, p = 0.0608) in those without any loss-of-function allele (interaction p = 0.46). For the ABCB1 genotype, event rates for the primary outcome were also consistently lower in the ticagrelor than in the clopidogrel group for all genotype groups (interaction p = 0.39; 8.8% vs 11.9%; 0.71, 0.55–0.92 for the high-expression genotype). In the clopidogrel group, the event rate at 30 days was higher in patients with than in those without any loss-of-function CYP2C19 alleles (5.7% vs 3.8%, p = 0.028), leading to earlier separation of event rates between treatment groups in patients with loss-of-function alleles. Patients on clopidogrel who had any gain-of-function CYP2C19 allele had a higher frequency of major bleeding (11.9%) than did those without any gain-of-function or loss-of-function alleles (9.5%; p = 0.022), but interaction between treatment and genotype groups was not significant for any type of major bleeding.î (L. Wallentin, lars.wallentin@ucr.uu.se)

>>>PNN NewsWatch
* FDA on Friday approved onabotulinumtoxinA (Botox, Allergan) for prevention of chronic migraine.

>>>PNN JournalWatch
* Reboxetine for Acute Treatment of Major Depression, in BMJ, 2010; 341: c4737. (B Wieseler, beate.wieseler@iqwig.de)
* Safety of Proton Pump Inhibitor Exposure, in
Gastroenterology, 2010; 139: 1115–27. (Y-X Yang, yangy@mail.med.upenn.edu)
* Asthma in the Elderly: Diagnosis and Management, in
Journal of Allergy and Clinical Immunology, 2010; 126: 681–7. (C. E. Reed, cereed@centurytel.net)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 201
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Oct. 19 issue of the Annals of Internal Medicine (2010; 153).
Reciprocal Peer Support for Diabetes Care: Compared with nurse care management (NCM) at two VA facilities, a reciprocal peer-support (RPS) program significantly improved indicators of diabetes care in 244 men with initial hemoglobin A1c levels greater than 7.5% (pp. 507–15). Participants assigned to the RPS group attended an initial group session where they received education and were paired with another patient. Peers were encouraged to talk weekly, and patients could attend subsequent voluntary group sessions. NCM included usual care plus a 1.5-hour educational session. Over 6 months, these results were obtained: ìOf the 244 patients enrolled, 216 (89%) completed the HbA1c assessments and 231 (95%) completed the survey assessments at 6 months. Mean HbA1c level decreased from 8.02% to 7.73% (change, −0.29%) in the RPS group and increased from 7.93% to 8.22% (change, 0.29%) in the NCM group. The difference in HbA1c change between groups was 0.58% (P = 0.004). Among patients with a baseline HbA1c level greater than 8.0%, those in the RPS group had a mean decrease of 0.88%, compared with a 0.07% decrease among those in the NCM group (between-group difference, 0.81%; P < 0.001). Eight patients in the RPS group started insulin therapy, compared with 1 patient in the NCM group (P = 0.020). Groups did not differ in blood pressure, self-reported medication adherence, or diabetes-specific distress, but the RPS group reported improvement in diabetes social support.î (M. Heisler, mheisler@umich.edu)
Drug-Resistant Tuberculosis in Health Care Workers: In HIV-endemic South Africa, health care workers have a significantly higher risk of being hospitalized with multidrug-resistant or extensively drug-resistant tuberculosis (MDR-TB, XDR-TB) than non–health care workers, a study shows (pp. 516–22). At a public TB referral hospital, these data were gathered for 231 health care workers and 4,151 non–health care workers admitted for initiation of MDR-TB or XDR-TB treatment: ìEstimated incidence of MDR-TB hospitalization was 64.8 per 100,000 health care workers versus 11.9 per 100,000 non–health care workers (incidence rate ratio, 5.46 [95% CI, 4.75 to 6.28]). Estimated incidence of XDR-TB hospitalizations was 7.2 per 100,000 health care workers versus 1.1 per 100,000 non–health care workers (incidence rate ratio, 6.69 [CI, 4.38 to 10.20]). A higher percentage of health care workers than non–health care workers with MDR-TB or XDR-TB were women (78% vs. 47%; P < 0.001), and health care workers were less likely to report previous tuberculosis treatment (41% vs. 92%; P < 0.001). HIV infection did not differ between health care workers and non–health care workers (55% vs. 57%); however, among HIV-infected patients, a higher percentage of health care workers were receiving antiretroviral medications (63% vs. 47%; P < 0.001).î (M. R. O’Donnell, max.odonnell@einstein.yu.edu)
Content of Placebos: The composition of placebo formulations is an important omission from most reports of controlled clinical trials, according to an analysis of data from four general and internal medicine journals in 2008–09 (pp. 532–5). Three reviewers independently abstracted data from the introduction and methods sections of randomized, placebo-controlled trials. They found that 8.2% of studies of solid oral dosage forms described the contents of placebo formulation, while 26.7% did so for injections and other formulations. The authors conclude, ìBecause the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.î (B. A. Golomb, bgolomb@ucsd.edu)
Medical Residents & Duty Hours: Two early-release articles are critical of new duty-hour standards that will limit medical residents’ shifts to 16 hours beginning in July 2011. Authors of one article argue that ìa more flexible, dynamic policy that emphasizes ongoing testing and evaluation would be more likely to achieve improvements in clinical and educational outcomesî (J. H. Silber, silber@email.chop.edu). Efforts to enhance efficiency based on the not-necessarily-correct assumption that productivity will improve ìhave sucked out much of the joy that brought us to internal medicine in the first place,î a second author writes (M. B. Edmond, medmond@vcu.edu).

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 202
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 20 issue of JAMA (2010; 304).
Effects of DHA During Pregnancy: A controlled clinical trial of fish oil capsules fails to support epidemiologic evidence of benefits in mothers and children of increased intake of docosahexaenoic acid (DHA) during pregnancy (pp. 1675–83). In the DHA to Optimize Mother Infant Outcome (DOMInO) trial, 2,399 women at five Australian maternity hospitals received DHA-rich fish oil capsules (800 mg/d) or matched vegetable oil capsules from study entry (at less than 21 weeks’ gestation) to birth: ìThe percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups (9.67% vs 11.19%; adjusted relative risk, 0.85; 95% confidence interval [CI], 0.70–1.02; P = .09). Mean cognitive composite scores (adjusted mean difference, 0.01; 95% CI, –1.36 to 1.37; P = .99) and mean language composite scores (adjusted mean difference, –1.42; 95% CI, –3.07 to 0.22; P = .09) of children in the DHA group did not differ from children in the control group.î (M. Makrides, maria.makrides@health.sa.gov.au)
Editorialists are conservative in their recommendations (
pp. 1717–8): ìThe results of the large randomized trial by Makrides et al suggest that consumption of DHA-rich fish oil supplements during pregnancy does not reduce postpartum depression in mothers or improve cognitive or language outcomes in their children at up to 18 months. Other investigations are ongoing and will provide additional data about these and other outcomes, although it appears that many women may have already made decisions about using fish oil–containing products. For instance, almost one-third of women who were screened for recruitment into the DOMInO trial were ineligible because they were already taking a supplement that included DHA. Fish oil supplements are safe, well tolerated, and reduce risks for early preterm birth, which is associated with poor neurocognitive outcomes and maternal depression. Whether fish consumption during pregnancy will confer similar or perhaps even greater benefits for mothers and their children requires more investigation, including large randomized trials such as the DOMInO trial. For now, pregnant women should take care to get the recommended intake of 200 mg/d of DHA, either by including low-mercury, high-DHA fish in their diets or by taking a daily n-3 PUFA supplement. The benefit of higher intakes remains unclear.î (E. Oken, emily_oken@hphc.org)
Hormones & Breast Cancer: Commenting on an analysis of Women’s Health Initiative data that shows an increased incidence of breast cancer in women on estrogen/progestin therapy (pp. 1684–92; R. T. Chlebowski, rchlebowski@gmail.com), an editorialist describes hormonal therapy as ìan uncertain trade-offî (pp. 1719–20): ìThe available data dictate caution in the current approach to use of hormone therapy, particularly because one of the lessons from the WHI is that physicians are ill-equipped to anticipate the effect of hormone therapy on long-term health. Clinicians who prescribe brief courses of hormone therapy for relief of menopausal symptoms should be aware that this approach has not been proven in rigorous clinical trials and that the downstream negative consequences for their patients are of uncertain magnitude.î (P. B. Bach, bachp@mskcc.org)

>>>PNN NewsWatch
* FDA has approved dabigatran etexilate (Pradaxa, Boehringer-Ingelheim) for stroke risk reduction in patients with nonvalvular atrial fibrillation. In the RE-LY (Randomized Evaluation of Long term anticoagulant therapY) trial, 18,113 patients had reductions in stroke risk with dabigatran that were 35% lower than those achieved with warfarin. Reductions in risk of intracranial bleeding were also observed. Adverse effects of dabigatran include bleeding, including life-threatening and fatal bleeding, gastrointestinal symptoms, including dyspepsia, stomach pain, nausea, heartburn, and bloating. The oral direct thrombin inhibitor can be dosed at 150 mg twice daily in most patients; those with severe renal impairment (15–30 mL/min) should receive 75 mg twice daily. Monitoring is not required. An analysis of dabigatran data, posted on the ClotCare Online Resource, shows that patients well controlled with warfarin likely do better when maintained on that drug, but poorly controlled patients might do better on alternative agents such as dabigatran.

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 © 2010, 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, 2010 * Vol. 17, No. 203
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 21 issue of the New England Journal of Medicine (2010; 363).
Home Testing of INRs: Weekly at-home monitoring of international normalized ratios in patients taking warfarin did not improve clinical outcomes, compared with monthly high-quality testing in a clinic, researchers report (pp. 1608–20). ìThese results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy,î conclude the authors, adding these details for 2,922 patients with mechanical heart valves or atrial fibrillation: ìThe patients were followed for 2.0 to 4.75 years, for a total of 8,730 patient–years of follow-up. The time to the first primary event [stroke, major bleeding episode, or death] was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P = 0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P < 0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P = 0.002) and quality of life (P < 0.001).î (D. B. Matchar, david.matchar@duke-nus.edu.sg)
FSH Receptors in Cancer Cells: Follicle-stimulating hormone receptors are selectively expressed on the surfaces of a wide variety of tumor-feeding blood vessels, a study shows, and this could help clinicians identify the margins of tumors through imaging (pp. 1621–30). Using immunohistochemical and immunoblotting techniques and in situ hybridization, investigators analyzed tissue samples from a wide variety of human tumors, looking for the presence of FSH receptors and the specific epitopes that were involved. Mouse tumors were also analyzed. The researchers found: ìIn all 1,336 patients examined, FSH receptor was expressed by endothelial cells in tumors of all grades, including early T1 tumors. The tumors were located in the prostate, breast, colon, pancreas, urinary bladder, kidney, lung, liver, stomach, testis, and ovary. In specimens obtained during surgery performed to remove tumors, the FSH receptor was not expressed in the normal tissues located more than 10 mm from the tumors. The tumor lymphatic vessels did not express FSH receptor. The endothelial cells that expressed FSH receptor were located at the periphery of the tumors in a layer that was approximately 10 mm thick; this layer extended both into and outside of the tumor. Immunoelectron microscopy in mice with xenograft tumors, after perfusion with anti–FSH-receptor antibodies coupled to colloidal gold, showed that the FSH receptor is exposed on the luminal endothelial surface and can bind and internalize circulating ligands.î Based on these findings, the authors wrote, ìIf it becomes possible to exploit FSH-receptor expression for imaging purposes, the location of the FSH-receptor signal at the boundary between the tumoral and the normal tissues should make it useful for defining the target volume for radiation therapy or surgery.î (N. Ghinea, nicolae.ghinea@inserm.fr)
Ranibizumab for Macular Degeneration: Neovascular age-related macular degeneration in a 66-year-old man provides the basis for discussion of the use of monoclonal antibodies in treatment (pp. 1648–55). Either ranibizumab or bevacizumab could be used, the authors conclude, although only the former agent is approved by FDA for this indication. Initial injection would be done in a minor surgery unit, the group notes, and follow-up injections would be provided until the retina became dry. (E. M. Stone, edwin-stone@uiowa.edu)

>>>PNN NewsWatch
* Men taking gonadotropin-releasing hormone (GnRH) agonists have increased risk of heart disease and diabetes, and product labeling of the drugs is being updated to reflect these risks, FDA said yesterday. Brand names of involved products are Eligard, Lupron, Synarel, Trelstar, Vantas, Viadur, and Zoladex. Most of the increases in risk have been small but statistically significant, FDA had reported in May (see PNN, May 4).

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 © 2010, 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, 2010 * Vol. 17, No. 204
Providing news and information about medications and their proper use

>>>Infectious Disease Report
Source:
Nov. 15 issue of Clinical Infectious Diseases (2010; 51).
Laninamivir for Treatment of Influenza: A single dose of the long-acting neuraminidase inhibitor laninamivir is effective for treatment of seasonal influenza, a study shows, including cases caused by oseltamivir-resistant strains (pp. 1167–75). In a double-blind trial, 1,003 adults with febrile symptoms for no more than 36 hours received laninamivir octanoate 20 or 40 mg or oseltamivir, with these results: ìA total of 996 patients were included in the primary analysis (40-mg laninamivir octanoate, n = 334; 20-mg laninamivir octanoate, n = 326; and oseltamivir, n = 336). The median time to illness alleviation in the 40-mg laninamivir octanoate, 20-mg laninamivir octanoate, and oseltamivir groups was 73.0, 85.8, and 73.6 h, respectively. The difference between laninamivir octanoate and oseltamivir was −0.6 h (95% confidence interval, −9.9 to 6.9 h) for the 40-mg group and 12.2 h (95% confidence interval, −1.5 to 17.2 h) for the 20-mg group. The upper limits of the 95% confidence intervals were less than the prespecified noninferiority margin (18 h). The proportion of patients shedding virus at day 3 was significantly lower in the 40-mg laninamivir octanoate group than in the oseltamivir group (P = .006).î (A. Watanabe, akiwa@idac.tohoku.ac.jp)
A/H1N1 Influenza Attack Rates & Severity: In Hong Kong during the 2009 A/H1N1 influenza pandemic, nearly one-half of school-age children were infected with the virus during the first wave of infections, and older adults aged 50–59 years had significantly greater risk of intensive care and death if infected, compared with school children, researchers report (pp. 1184–91). Analysis of serum samples from various times during Apr. through Dec. 2009 show the following patterns: ì3.3% and 14% of persons aged 5–59 years had antibody titers 1:40 before and after the first wave, respectively. The overall attack rate was 10.7%, with age stratification as follows: 43.4% in persons aged 5–14 years, 15.8% in persons aged 15–19 years, 11.8% in persons aged 20–29 years, and 4%–4.6% in persons aged 30–59 years. Case-hospitalization rates were 0.47%–0.87% among persons aged 5–59 years. Case-ICU rates were 7.9 cases per 100,000 infections in persons aged 5–14 years and 75 cases per 100,000 infections in persons aged 50–59 years, respectively. Case-fatality rates were 0.4 cases per 100,000 infections in persons aged 5–14 years and 26.5 cases per 100,000 infections in persons aged 50–59 years, respectively.î (J. T. Wu, joewu@hku.hk)

>>>Oncology Highlights
Source:
Oct. 20 issue of the Journal of Clinical Oncology (2010; 28).
Rofecoxib as Adjuvant Agent in Colorectal Cancer: In 2,434 patients with stage II or III colorectal cancer (CRC), adjuvant rofecoxib did not improve overall survival (OS), or protect from recurrence, and COX-2 expression did not correlate with overall prognosis or predict effectiveness of COX-2 inhibitors, according to final results of the VICTOR trial (pp. 4575–80). Patients received the drug in doses of 20 mg/day, with these results: ìThe trial was terminated early because of the worldwide withdrawal of rofecoxib. At this point, 1,167 patients had received rofecoxib and 1,160 patients had received placebo for median treatment durations of 7.4 and 8.2 months, respectively. For the rofecoxib and placebo arms, median follow-up times were 4.84 and 4.85 years, with 241 and 246 deaths and 297 and 329 recurrences, respectively. No difference was demonstrated in OS (hazard ratio [HR] = 0.97; 95% CI, 0.81 to 1.16; P = .75) or recurrence (HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) comparing the two groups. Tumor COX-2 expression by immunohistochemistry was assessed for 871 patients, but neither prognostic nor predictive effects were observed.î (R. S. Midgley, rachel.midgley@clinpharm.ox.ac.uk)
Combination Phase I Trials: Journal editors provide characteristics of what they consider high-priority Phase I trials of combinations of oncolytic drugs (pp. 4545–6). These include compelling rationale based on preclinical data, novelty of the drug combination, determination of pharmacokinetics with attention to interactions, and drug tolerability at maximal doses. (J. Verweij)

>>>PNN NewsWatch
* FDA yesterday mandated new safety warnings for saquinavir (Invirase, Genentech) regarding PR prolongation when the drug is used concomitantly with ritonavir.

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 © 2010, 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. 25, 2010 * Vol. 17, No. 205
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Early-release article from Lancet (2010; 376).
Aspirin & Colorectal Cancer Prevention: The 20-year incidence of colorectal cancer, particularly in the difficult-to-diagnose proximal colon, can be reduced by aspirin prophylaxis at doses of 75 mg/d, an analysis shows (doi: 10.1016/S0140-6736(10)61543-7). Investigators combined data from four randomized comparative trials of aspirin for primary (Thrombosis Prevention Trial, British Doctors Aspirin Trial) and secondary (Swedish Aspirin Low Dose Trial, UK-TIA Aspirin Trial) prevention, as follows: ìIn the four trials of aspirin versus control (mean duration of scheduled treatment 6.0 years), 391 (2.8%) of 14,033 patients had colorectal cancer during a median follow-up of 18.3 years. Allocation to aspirin reduced the 20-year risk of colon cancer (incidence hazard ratio [HR] 0.76, 0.60–0.96, p = 0.02; mortality HR 0.65, 0.48–0.88, p = 0.005), but not rectal cancer (0.90, 0.63–1.30, p = 0.58; 0.80, 0.50–1.28, p = 0.35). Where subsite data were available, aspirin reduced risk of cancer of the proximal colon (0.45, 0.28–0.74, p = 0.001; 0.34, 0.18–0.66, p = 0.001), but not the distal colon (1.10, 0.73–1.64, p = 0.66; 1.21, 0.66–2.24, p = 0.54; for incidence difference p = 0.04, for mortality difference p = 0.01). However, benefit increased with scheduled duration of treatment, such that allocation to aspirin of 5 years or longer reduced risk of proximal colon cancer by about 70% (0.35, 0.20–0.63; 0.24, 0.11–0.52; both p < 0.0001) and also reduced risk of rectal cancer (0.58, 0.36–0.92, p = 0.02; 0.47, 0.26–0.87, p = 0.01). There was no increase in benefit at doses of aspirin greater than 75 mg daily, with an absolute reduction of 1.76% (0.61—2.91; p = 0.001) in 20-year risk of any fatal colorectal cancer after 5-years scheduled treatment with 75–300 mg daily. However, risk of fatal colorectal cancer was higher on 30 mg versus 283 mg daily on long-term follow-up of the Dutch TIA trial (odds ratio 2.02, 0.70—6.05, p = 0.15).î (P. M. Rothwell, peter.rothwell@clneuro.ox.ac.uk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 341).
Tricyclic Antidepressants & Headaches: Compared with SSRIs, tricyclic antidepressants are more effective for prevention of migraine and tension-type headaches, a meta-analysis of 37 studies shows (c5222). While adverse effects were worse with tricyclics, the drugs’ efficacy seemed to improve over time: ìTricyclics significantly reduced the number of days with tension-type headache and number of headache attacks from migraine than placebo (average standardised mean difference −1.29, 95% confidence interval −2.18 to −0.39 and −0.70, −0.93 to −0.48) but not compared with selective serotonin reuptake inhibitors (−0.80, −2.63 to 0.02 and −0.20, −0.60 to 0.19). The effect of tricyclics increased with longer duration of treatment (beta =−0.11, 95% confidence interval −0.63 to −0.15; P < 0.0005).î (J. L. Jackson, Jeffrey.jackson6@va.gov)

>>>PNN NewsWatch
* Hyland’s Teething Tablets, a homeopathic product containing small amounts of belladonna, is being recalled from the market, FDA announced on Saturday. The agency said its analysis showed inconsistent amounts of belladonna in these tablets, and reports of serious adverse effects in children were ìconsistent with belladonna toxicity.î An ongoing inspection at the manufacturer, Standard Homeopathic Co., indicated substandard control of the manufacturing operation, FDA added.

>>>PNN JournalWatch
* Review of Hepatitis B Therapeutics, in Clinical Infectious Diseases, 2010; 51: 1201–8. (D. Bhattacharya, debikab@mednet.ucla.edu)
* Cardiovascular Risk Factors and Morbidity in Long-Term Survivors of Testicular Cancer: A 20-Year Follow-Up Study, in
Journal of Clinical Oncology, 2010; 28: 4649–57. (H. S. Haugnes, hege.sagstuen.haugnes@uit.no)
* Screening in Frail Older People: An Ounce of Prevention or a Pound of Trouble?, in
Journal of the American Geriatrics Society, 2010; 58: 2016–21. (A. M. Clarfield, markclar@bgu.ac.il)
* Medical and Surgical Treatment of Acute Right Ventricular Failure, in
Journal of the American College of Cardiology, 2010; 56: 1435–46. (D. R. Meldrum, dmeldrum@iupui.edu)
* Omega-3 Polyunsaturated Fatty Acids in the Treatment of Kidney Disease, in
American Journal of Kidney Diseases, 2010; 56: 728–42. (R. G. Fassett, r.fassett@uq.edu.au)
* Pulmonary Complications of Hemoglobinopathies, in
Chest, 2010; 138: 973–83. (R. F. Machado, machador@uic.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 © 2010, 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, 2010 * Vol. 17, No. 206
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 25 issue of the Archives of Internal Medicine (2010; 170).
Recurrence Risk After VTE: In patients who have had symptomatic venous thromboembolism, risks of recurrence following cessation of anticoagulation are low when the VTE was provoked by surgery, intermediate if a nonsurgical risk factor was involved, and high in patients with unprovoked conditions, a review article concludes (pp. 1710–6). Authors looked at prospective cohort studies and randomized trials of patients with first-episode VTE, finding these annualized recurrence rates: ìAt 24 months, the rate of recurrence was 3.3% per patient–year (11 studies, 2,268 patients) for all patients with a transient risk factor, 0.7% per patient-year (3 studies, 248 patients) in the subgroup with a surgical factor, and 4.2% per patient-year (3 studies, 509 patients) in the subgroup with a nonsurgical factor. In the same studies, the rate of recurrence after unprovoked VTE was 7.4% per patient-year. The rate ratio for a nonsurgical compared with a surgical factor was 3.0 and for unprovoked thrombosis compared with a nonsurgical factor was 1.8 at 24 months.î (A. Lorio, iorioa@mcmaster.ca)
Content Variability of Red Yeast Rice Products: ìBuyer beware!î is the warning conveyed in the title of a research study reporting marked variation in monacolins and citrinin content among 12 proprietary red yeast rice (RYR) products (pp. 1722–7). RYR contains 14 monacolins, which lower cholesterol levels, the investigators explain, including lovastatin (monacolin K). The products also sometimes contain the nephrotoxic compound citrinin. In the study, products labeled as containing ì600 mg/capsuleî were analyzed, with these results: ìThere was marked variability in the 12 RYR products in total monacolins (0.31–11.15 mg/capsule), monacolin K (lovastatin) (0.10–10.09 mg/capsule), and monacolin KA (0.00–2.30 mg/capsule). Four products had elevated levels of citrinin.î (R. Y. Gordon, ram.gordon@gmail.com)

>>>Medical Care Highlights
Source:
Oct. and Nov. issues of Medical Care (2010; 48).
Pharmacist-Provided Direct Patient Care: Pharmacists involvement as health care team members in direct patient care provide ìa viable solution to help improve U.S. health care,î conclude investigators who conducted a meta-analysis of 298 studies that examined clinical and humanistic outcomes of pharmacist care (pp. 923–33): ìFavorable results were found in therapeutic and safety outcomes, and meta-analyses conducted for hemoglobin A1c, LDL cholesterol, blood pressure, and adverse drug events were significant (P < 0.05), favoring pharmacists’ direct patient care over comparative services. Results for humanistic outcomes were favorable with variability. Medication adherence, patient knowledge, and quality of life-general health meta-analyses were significant (P < 0.05), favoring pharmacists’ direct patient care.î (M. A. Chisholm-Burns, chisholm@pharmacy.arizona.edu)
That team of researchers also reported much more mixed economic outcomes from 126 studies in an analysis published in the Oct. 1
American Journal of Health-System Pharmacy (2010; 67: 1624–34): ìResults favoring pharmacist-provided care were found in 20 studies (15.9%), mixed results were seen in 53 studies (42.1%), no effect was found in 6 studies (4.8%), and unclear results were found in 47 studies (37.3%).î
Impact of Suicidality Warnings: Prescribing of antidepressants for youth with clinician-reported diagnoses of depression declined following FDA’s warnings of drug-related suicidality in 2004, a study shows, but those with major depressive disorder still received the agents (pp. 947–54). Analysis of a commercial insurance database showed these patterns in 2003–06 for 40,000 patients aged 2–17: ìCompared to youth with a new-onset diagnosis of depression in the pre-FDA warning period, youth with new-onset diagnosis of depression during the postwarning period had (1) A significantly lower likelihood of antidepressant use: (odds ratio [OR] = 0.85 [0.81–0.89]); when youth with the diagnosis of depression were separated into those with MDD and those with less severe depression diagnoses, only the latter had a significant postwarning antidepressant decline. (2) A significant increase in the odds of a psychotherapy visit (children, OR = 1.31 [1.23–1.40]; adolescents OR = 1.19 [1.15–1.24]).î (S. Valluri)

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 © 2010, 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, 2010 * Vol. 17, No. 207
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 27 issue of JAMA (2010; 304).
Pharmacogenetic Determinants of Cetuximab Effects in Colorectal Cancer: Based on findings of improved outcomes with cetuximab in patients with metastatic colorectal cancer who have KRAS codon 12– or KRAS codon 13–mutated tumors, investigators recommend prospective randomized trials of the drug (pp. 1812–20). Analysis of data from 579 patients treated for chemotherapy-refractory colorectal cancer treated with cetuximab between 2001 and 2008 showed these genetic associations: ìIn comparison with patients with other KRAS-mutated tumors, patients with p.G13D-mutated tumors (n = 32) treated with cetuximab had longer overall survival (median, 7.6 [95% confidence interval {CI}, 5.7–20.5] months vs 5.7 [95% CI, 4.9–6.8] months; adjusted hazard ratio [HR], 0.50; 95% CI, 0.31–0.81; P = .005) and longer progression-free survival (median, 4.0 [95% CI, 1.9–6.2] months vs 1.9 [95% CI, 1.8–2.8] months; adjusted HR, 0.51; 95% CI, 0.32–0.81; P = .004). There was a significant interaction between KRAS mutation status (p.G13D vs other KRAS mutations) and overall survival benefit with cetuximab treatment (adjusted HR, 0.30; 95% CI, 0.14–0.67; P = .003). In vitro and mouse model analysis showed that although p.G12V-mutated colorectal cells were insensitive to cetuximab, p.G13D-mutated cells were sensitive, as were KRAS wild-type cells.î (S. Tejpar, sabine.tejpar@uzleuven.be)
Pharmacogenetics of Clopidogrel: Patients with as few as 1 mutation of the CYP2C19 gene causing reduced enzyme function are at greater risk of major cardiovascular events during clopidogrel therapy, a meta-analysis concludes (pp. 1821–30). The researchers, some of whom authored a pharmacogenetic analysis in the Oct. 16 Lancet (see PNN, Oct. 18), obtained genotypic data from investigators in 9 studies of CYP2C19, finding the following: ìAmong 9,685 patients (91.3% who underwent percutaneous coronary intervention and 54.5% who had an acute coronary syndrome), 863 experienced the composite end point of cardiovascular death, myocardial infarction, or stroke; and 84 patients had stent thrombosis among the 5,894 evaluated for such. Overall, 71.5% were noncarriers, 26.3% had 1 reduced-function CYP2C19 allele, and 2.2% had 2 reduced-function CYP2C19 alleles. A significantly increased risk of the composite end point was evident in both carriers of 1 (HR, 1.55; 95% CI, 1.11–2.17; P = .01) and 2 (HR, 1.76; 95% CI, 1.24–2.50; P = .002) reduced-function CYP2C19 alleles, as compared with noncarriers. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of 1 (HR, 2.67; 95% CI, 1.69–4.22; P < .0001) and 2 (HR, 3.97; 95% CI, 1.75–9.02; P = .001) CYP2C19 reduced-function alleles, as compared with noncarriers.î (J. L. Mega, jmega@partners.org)
Editorialists describe this information on reduced-function
CYP2C19 genetic variants as ìa limited piece of the overall therapeutic puzzleî (pp. 1839–40): ìIn patients treated with clopidogrel, the best genome-guided strategy remains to be determined. The information obtained by CYP2C19 genetic testing may be particularly useful in patients at risk of poor outcomes, either because they have already had an adverse event (eg, stent thrombosis) or other at-risk characteristics such as diabetes mellitus, chronic renal failure, or angiographic high-risk features. Three ongoing studies (Genotyping Infarct patients to Adjust and Normalize Thienopyridine treatment [GIANT]; ClinicalTrials.gov identifier, NCT01134380), Genotype Guided Comparison of Clopidogrel and Prasugrel Outcomes Study (NCT00995514), and Thrombocyte Activity Reassessment and Genotyping for PCI (TARGET-PCI [NCT01177592]) are currently under way to find the best genome-guided strategy for these higher-risk patients. In the meantime, clopidogrel and CYP2C19 genetic testing appear to be only a limited piece of the overall therapeutic puzzle of clopidogrel therapy and personalized medicine.î (V. Fuster, valentin.fuster@mssm.edu)

>>>PNN NewsWatch
* GlaxoSmithKline yesterday agreed to a criminal fine and forfeiture totaling $750 million, the U.S. Dept. of Justice announced, including a $150 million criminal fine and $600 million civil settlement. At issue in the case was GSK’s failure to maintain Current Good Manufacturing Practices at a Puerto Rican plant in 2001–05.

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 © 2010, 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, 2010 * Vol. 17, No. 208
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 28 issue of the New England Journal of Medicine (2010; 363).
ALK Inhibition in Non–Small-Cell Lung Cancers: Crizotinib (PF-02341066), an orally available small-molecule inhibitor of the anaplastic lymphoma kinase (ALK) tyrosine kinase enzyme, produced tumor shrinkage and stable disease in 82 patients with advanced ALK-positive non–small-cell lung cancer, an early-phase study shows (pp. 1693–703). ALK and another oncogenic fusion gene, EML4, are present in 2–7% of NSCLC tumors. Study participants, selected based on screening of tumor samples from 1,500 patients, had generally been treated previously, and they received crizotinib 250 mg twice daily in 28-day cycles: ìPatients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects.î (E. L. Kwak, ekwak@partners.org)
Commenting on this study and two brief reports also published in this issue (
pp. 1727–33, G. D. Demetri, gdemetri@partners.org; pp. 1734–9, H. Mano, hmano@jichi.ac.jp), editorialists point out that ALK inhibition may be beneficial in a variety of other patients, including those with ALK-positive non-Hodgkin’s lymphoma or inflammatory myofibroblastic tumor (pp. 1760–2). They conclude: ìTogether, these three studies provide an optimistic view of the successful treatment of ALK-positive cancers. One positive offshoot is the potential use of crizotinib in treating neuroblastoma, a devastating childhood cancer, in which ALK gain-of-function mutations have been reported in approximately 10% of patients. Clearly, in groups of patients with cancers in which ALK is implicated, a standard genotyping approach will be important for a more personalized therapeutic protocol. Future clinical studies of crizotinib and other ALK inhibitors will tell us whether they will be the latest champions in the cancer wars.î (B. Hallberg)
Tiotropium Step-Up Therapy in Uncontrolled Asthma: In adults with uncontrolled asthma, step-up therapy with tiotropium bromide appears to be equivalent in its effects to salmeterol, researchers report (pp. 1715–26). In a 14-week, three-way crossover, comparative effectiveness study, tiotropium and salmeterol, both long-acting beta-agonists, were compared with doubled doses of inhaled glucocorticoids, with these results: ìThe use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P < 0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P < 0.001); the proportion of asthma-control days, with a difference of 0.079 (P = 0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P = 0.004); and daily symptom scores, with a difference of −0.11 points (P < 0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P = 0.003).î (S. P. Peters, sppeters@wfubmc.edu)
Two editorials provide commentary on this study. L. J. Smith (
pp. 1764–5) is critical of the ìlimited duration of this studyî but notes: ìSome clinicians have already begun substituting tiotropium for LABAs, such as salmeterol and formoterol, in patients who remain symptomatic on low doses of inhaled glucocorticoids, and the study by Peters et al. provides encouraging results with respect to lung function and symptoms in such patients.î Journal editors (p. 1763) are critical of GlaxoSmithKline for refusing to provide repackaged drug and matching placebo inhalers for this study, writing that manufacturers must be willing to put their ìproducts at riskî just as study participants put themselves at risk.

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 © 2010, 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, 2010 * Vol. 17, No. 209
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Nov. issue of Diabetes Care (2010; 33).
Effects of Baseline Renal Function on Aliskiren Therapy: Added to losartan in patients with diabetes, nephropathy, and hypertension, aliskiren reduced albuminuria and renal dysfunction, according to the Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) study (pp. 2304–9). A total of 599 patients in stages 1, 2, or 3 chronic kidney disease (CKD) received aliskiren 150–300 mg/d or placebo for 6 months. Patients also received losartan and optimal antihypertensive therapy. Results showed: ìThe antiproteinuric effects of aliskiren were consistent across CKD stages (19, 22, and 18% reduction). In the stage 3 CKD group, baseline serum creatinine levels were equal, but renal dysfunction, prespecified as a postrandomization serum creatinine elevation >176.8 µmol/l (2.0 mg/dl) occurred more frequently in the placebo group (29.2 vs. 13.6%, P = 0.032). Serum potassium elevations >5.5 mmol/l (based on a single measurement) were more frequent with aliskiren (22.5 vs. 13.6%) in stage 3 CKD. Adverse event rates were similar between treatments, irrespective of CKD stage.î (F. Persson, frip@steno.dk)
A1C Values Changed by Iron, Erythropoietin: Alternative means of assessing glycemic control must be used in patients receiving iron and/or erythropoietin therapy, researchers conclude (pp. 2310–3). In 30 patients with type 2 diabetes and chronic kidney disease IIIB or IV, A1C values, seven-point daily glucose three times weekly, and continuous glucose monitoring (CGM) were examined during therapy with intravenous iron (group A) or erythropoietin-stimulating agents (ESAs). To support their conclusion that ìregular capillary glucose measurements and the concurrent use of CGM remain the best alternative measurements of glycemic control in this patient group,î the authors provide these data: ìMean A1C (95% CI) values fell in both groups (7.40% [6.60–8.19] to 6.96% [6.27–7.25], P < 0.01, with intravenous iron and 7.31% [6.42–8.54] to 6.63% [6.03–7.36], P = 0.013, ESA). There was no change in mean blood glucose in group A (9.55 mmol/l [8.20–10.90] vs. 9.71 mmol/l [8.29–11.13], P = 0.07) and in group B (8.72 mmol/l [7.31–10.12] vs. 8.78 mmol/l [7.47–9.99], P = 0.61) over the study period. Hemoglobin and hematocrit values significantly increased following both treatments. There was no linear relationship found between the change in A1C values and the rise of hemoglobin following either treatment.î (J. M. Ng, ben.ng@hey.nhs.uk)

>>>PNN NewsWatch
* CDC reports in this week’s MMWR (2010; 59: 1361–6) that the incidence of end-stage renal disease in patients with diabetes declined significantly in the U.S. in 1996–2007. Overall, a 35% decline was found, from 304.5 to 199.1 cases per 100,000 persons with diagnosed diabetes. Possible reasons for the decline are reductions in risk factors for kidney disease and better treatment of kidney disease, especially increased use of ACE inhibitors and angiotensin-receptor blockers. This issue of MMWR also reminds readers that November is National Diabetes Month.
*
FDA yesterday approved a once-daily agent for schizophrenia in adults, lurasidone (Latuda, Sunovian). Efficacy and safety of the oral second-generation antipsychotic agent was established in four clinical trials of 6 weeks’ duration in adults with schizophrenia. Use for longer periods has not been studied adequately. Adverse effects of lurasidone are similar to those with other atypical antipsychotics, including drowsiness, akathisia, nausea, movement abnormalities, and agitation. Sunovian Pharmaceuticals is the new name of Sepracor following its 2009 acquisition by Japan’s Dainippon Sumitomo Pharma Co., Ltd.
* The oral kinase inhibitor
dasatinib (Sprycel, Bristol-Myers Squibb) was approved yesterday by FDA for first-line treatment of Philadelphia chromosome–positive chronic phase chronic myeloid leukemia (Ph+ CP-CML). The agent had been previously approved for use in adults with CP-CML with resistant disease or intolerant of other therapies, such as imatinib or nilotinib.
*
Correction: In Thursday’s PNN, the long-acting anticholinergic agent tiotropium bromide was incorrectly identified as a long-acting beta-agonist.

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 © 2010, 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. 1, 2010 * Vol. 17, No. 210
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 30 issue of Lancet (2010; 376).
Nucleoside Polymerase Inhibitor for Hepatitis C: RG7128, a nucleoside polymerase inhibitor, appeared useful when used in combination with the protease inhibitor danoprevir in treatment of patients with chronic hepatitis C virus infection, a study shows (pp. 1467–75). In New Zealand and Australia, patients received up to 13 days of oral combination therapy with RG7128 500 or 1,000 mg twice daily and danoprevir 100 or 200 mg every 8 hours or 600 or 900 mg twice daily, with these results: ì88 patients were randomly assigned to a study drug treatment regimen (n = 74 over seven treatment groups; 73 received at least one dose of study drug) or to placebo (n = 14, all of whom received at least one dose). The median change in HCV RNA concentration from baseline to day 14 ranged from −3.7 to −5.2 log10 IU/mL in the cohorts that received 13 days of combination treatment. At the highest combination doses tested (1,000 mg RG7128 and 900 mg danoprevir twice daily), the median change in HCV RNA concentration from baseline to day 14 was −5.1 log10 IU/mL (IQR −5.6 to −4.7) in treatment-naive patients and −4.9 log10 IU/mL in previous standard of care null responders (−5.2 to −4.5) compared with an increase of 0.1 log10 IU/mL in the placebo group. The combination of RG7128 and danoprevir was well tolerated with no treatment-related serious or severe adverse events, no grade 3 or 4 changes in laboratory parameters, and no safety-related treatment discontinuations.î (E. J. Gane, edgane@adhb.govt.nz)
Celiprolol for Vascular Ehlers–Danlos Syndrome: In patients with the rare condition vascular Ehlers–Danlos syndrome, celiprolol prevented major complications from arterial dissections and ruptures that can lead to early death, researchers report (pp. 1476–84). The agent, a beta-1 antagonist and beta-2 agonist, was provided to patients at centers in France and Belgium for 5 years. Results showed these effects on primary endpoints of arterial events (rupture or dissection; fatal or not): ì53 patients were randomly assigned to celiprolol (25 patients) or control groups (28). Mean duration of follow-up was 47 (SD 5) months, with the trial stopped early for treatment benefit. The primary endpoints were reached by five (20%) in the celiprolol group and by 14 (50%) controls (hazard ratio [HR] 0.36; 95% CI 0.15–0.88; p = 0.040). Adverse events were severe fatigue in one patient after starting 100 mg celiprolol and mild fatigue in two patients related to dose uptitration.î (P. Boutouyrie, pierre.boutouyrie@egp.aphp.fr)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 341).
Deaths During and After Opiate Substitution: ìClinicians and patients should be aware of the increased mortality risk at the start of opiate substitution treatment and immediately after stopping treatment,î conclude authors of a study of 5,577 primary care patients receiving methadone or buprenorphine in 1990–2005 (c5475): ìCrude mortality rates were 0.7 per 100 person years on opiate substitution treatment and 1.3 per 100 person years off treatment; standardised mortality ratios were 5.3 (95% confidence interval 4.0 to 6.8) on treatment and 10.9 (9.0 to 13.1) off treatment. Men using opiates had approximately twice the risk of death of women (morality rate ratio 2.0, 1.4 to 2.9). In the first two weeks of opiate substitution treatment the crude mortality rate was 1.7 per 100 person years: 3.1 (1.5 to 6.6) times higher (after adjustment for sex, age group, calendar period, and comorbidity) than the rate during the rest of time on treatment. The crude mortality rate was 4.8 per 100 person years in weeks 1–2 after treatment stopped, 4.3 in weeks 3–4, and 0.95 during the rest of time off treatment: 9 (5.4 to 14.9), 8 (4.7 to 13.7), and 1.9 (1.3 to 2.8) times higher than the baseline risk of mortality during treatment. Opiate substitution treatment has a greater than 85% chance of reducing overall mortality among opiate users if the average duration approaches or exceeds 12 months.î (M. Hickman, matthew.hickman@bristol.ac.uk)

>>>PNN JournalWatch
* Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes: A Meta-analysis, in Diabetes Care, 2010; 33: 2477–83. (F. B. Hu, frank.hu@channing.harvard.edu)
* Vancomycin-Resistant Enterococcal Urinary Tract Infections, in
Pharmacotherapy, 2010; 30: 1136–49. (B. Heintz, heintzb@pharmacy.ucsf.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 © 2010, 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, 2010 * Vol. 17, No. 211
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release article from and Nov. 2 issue of the Annals of Internal Medicine (2010; 153).
Dabigatran v. Warfarin for AF Stroke Prevention: In a cost-effectiveness model that included the expenses associated with warfarin monitoring and anticoagulation management, the newly approved oral direct thrombin inhibitor dabigatran compares favorably with the older drug (early release). Using data from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, investigators made these calculations regarding quality-adjusted life–years (QALYs) and costs in 2008 U.S. dollars based on a lifetime horizon and societal perspective: ìThe quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143,193 for warfarin, $164,576 for low-dose dabigatran, and $168,398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51,229 per QALY for low-dose dabigatran and $45,372 per QALY for high-dose dabigatran.î
Sensitivity analysis showed: ìThe model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50,000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85,000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage.î (M. Turakhia,
mintu@stanford.edu)
Pain at the End of Life: While the prevalence of pain increases among patients during their last 4 months of life, it is present in more than a fourth of patients during the last 2 years of life and is often caused by arthritis, an epidemiologic study shows (pp. 563–9). In the Health and Retirement Study—conducted in community-living older adults in 1994–2006—investigators found these patterns of clinically significant pain: ìThe sample included 4,703 decedents. Mean age (SD) of participants was 75.7 years (SD, 10.8); 83.1% were white, 10.7% were black, 4.7% were Hispanic; and 52.3% were men. The adjusted prevalence of pain 24 months before death was 26% (95% CI, 23% to 30%). The prevalence remained flat until 4 months before death (28% [CI, 25% to 32%]), then it increased, reaching 46% (CI, 38% to 55%) in the last month of life. The prevalence of pain in the last month of life was 60% among patients with arthritis versus 26% among patients without arthritis (P < 0.001) and did not differ by terminal diagnosis category (cancer [45%], heart disease [48%], frailty [50%], sudden death [42%], or other causes [47%]; P = 0.195).î (A. K. Smith, aksmith@ucsf.edu)
The importance of treating pain at the end of life is emphasized in an accompanying editorial (
pp. 612–3): ìAll physicians, regardless of specialty, should routinely assess for and be prepared to treat clinically significant pain. Like geriatricians, the numbers of pain management and palliative care specialists are insufficient to address the care needs of all older adults with complex pain problems. Educational interventions that seek to improve the pain management skills of other types of physicians are needed to address this gap. In light of several patient-level barriers to managing pain in later life, clinicians should ask patients not only whether they hurt but also about their preferences for treatment approaches. Coordination of pain care is absolutely critical to avoid the duplication that can result when several physicians prescribe pain medications or the neglect that can occur when one physician erroneously assumes that another physician is managing the patient’s pain.î (M.C. Reid, mcr2004@med.cornell.edu)

>>>PNN NewsWatch
* Everolimus (Afinitor, Novartis) has been approved by FDA for treatment of patients with subependymal giant cell astrocytoma (SEGA), a benign brain tumor associated with tuberous sclerosis, who require therapeutic intervention but are not candidates for curative surgical resection. Accelerated action on the drug was based on results of a 28-patient study. At 6 months, 9 patients had greater than 50% reduction in volume of their largest SEGA tumor. Duration of response in these patients was from 3 months to 2.5 years (median, 266 days), and 7 patients remained stable at last follow-up. Adverse effects of everolimus include upper respiratory tract infections, sinus and ear infections, mouth sores, and fever.

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 © 2010, 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, 2010 * Vol. 17, No. 212
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 3 issue of JAMA (2010; 304).
DHA in Alzheimer Disease: Compared with placebo, docosahexaenoic acid supplements had no significant effect on the rate of cognitive and functional decline in patients with Alzheimer disease in the Alzheimer’s Disease Cooperative Study (pp. 1903–11). Over an 18-month period, patients received DHA 2 g/d or placebo. Based on changes in the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) and the Clinical Dementia Rating (CDR) sum of boxes, the investigators found: ìA total of 402 individuals were randomized and a total of 295 participants completed the trial while taking study medication (DHA: 171; placebo: 124). Supplementation with DHA had no beneficial effect on rate of change on ADAS-cog score, which increased by a mean of 7.98 points (95% confidence interval [CI], 6.51–9.45 points) for the DHA group during 18 months vs 8.27 points (95% CI, 6.72–9.82 points) for the placebo group (linear mixed-effects model: P = .41). The CDR sum of boxes score increased by 2.87 points (95% CI, 2.44–3.30 points) for the DHA group during 18 months compared with 2.93 points (95% CI, 2.44–3.42 points) for the placebo group (linear mixed-effects model: P = .68). In the subpopulation of participants (DHA: 53; placebo: 49), the rate of brain atrophy was not affected by treatment with DHA. Individuals in the DHA group had a mean decline in total brain volume of 24.7 cm3 (95% CI, 21.4–28.0 cm3) during 18 months and a 1.32% (95% CI, 1.14%–1.50%) volume decline per year compared with 24.0 cm3 (95% CI, 20-28 cm3) for the placebo group during 18 months and a 1.29% (95% CI, 1.07%–1.51%) volume decline per year (P = .79).î (J. F. Quinn, quinnj@ohsu.edu)
ìBecause AD is such a devastating illness and current therapeutic choices are limited and only moderately effective, new treatment options are urgently needed,î writes an editorialist (
pp. 1952–3). ìRecently, almost every trial for treatment of AD has led to disappointing results, including several with beta-amyloid–modifying agents. If aging and AD is a complex adaptation to insults that begin decades before symptoms emerge, targeting one downstream mechanism may not be effective. In addition, while beta-amyloid most likely has a central role in the cascade of neuronal degeneration, there are also important contributions from tau protein, synaptic dysfunction, and vascular changes. The next steps in AD treatment may need to incorporate a combined regimen similar to the treatment approaches used for other chronic diseases. Another possibility is to combine pharmacologic strategies with behavioral interventions, an approach that has not been investigated.î (K. Yaffe, Kristine.Yaffe@ucsf.edu)

>>>PNN NewsWatch
* The forecast for Washington, DC, is for 2 years of gridlock and conflict, following yesterday’s Republican successes at ballot boxes across the country. Just what that means for health care reform between now and Inauguration Day 2013 is uncertain. With Democrats controlling the Senate and the White House, the near-certain GOP repeal of the Affordable Care Act in the House will mean little. But implementation of the law requires money, and the House has the power to cut that off. The key element in health care reform—the individual mandate to have health insurance—doesn’t take effect until 2014, but lots of other provisions kick in before that, including many important to pharmacy. Leaders are talking about working together this morning, but the pressure of presidential politics will soon take hold. It’s difficult to work together and run against each other at the same time.
*
FDA has approved the marketing of ceftaroline fosamil (Teflaro, Forest) for treatment of adults with community acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI), including methicillin-resistant Staphylococcus aureus. In two CABP trials, 1,231 adult patients received ceftaroline or ceftriaxone. Clinical response based on improvement in signs and symptoms of pneumonia on day 4 after starting therapy was similar with ceftaroline and ceftriaxone. In two ABSSSI trials, 1,396 adult patients received ceftaroline or vancomycin plus aztreonam. Clinical responses, including cessation of spread of the lesion and absence of fever on day 3, were similar with each therapy. Common adverse effects with ceftaroline are diarrhea, nausea, and rash.

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 © 2010, 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, 2010 * Vol. 17, No. 213
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release article from and Nov. 4 issue of the New England Journal of Medicine (2010; 363).
Recombinant Activated Factor VII for Bleeding: High-dose therapy with recombinant activated factor VII (rFVIIa), used off-label for life-threatening bleeding, is associated with an increased risk of arterial but not venous thromboembolic events, investigators report (pp. 1791–800). Analyzing data from 35 randomized clinical trials in which rFVIIa was used for off-label indications, the authors made these calculations about the frequency of thromboembolic events: ìAmong 4,468 subjects (4,119 patients and 349 healthy volunteers), 498 had thromboembolic events (11.1%). Rates of arterial thromboembolic events among all 4,468 subjects were higher among those who received rFVIIa than among those who received placebo (5.5% vs. 3.2%, P = 0.003). Rates of venous thromboembolic events were similar among subjects who received rFVIIa and those who received placebo (5.3% vs. 5.7%). Among subjects who received rFVIIa, 2.9% had coronary arterial thromboembolic events, as compared with 1.1% of those who received placebo (P = 0.002). Rates of arterial thromboembolic events were higher among subjects who received rFVIIa than among subjects who received placebo, particularly among those who were 65 years of age or older (9.0% vs. 3.8%, P = 0.003); the rates were especially high among subjects 75 years of age or older (10.8% vs. 4.1%, P = 0.02).î (M. Levi, m.m.levi@amc.uva.nl)
This research on off-label use of rFVIIa can serve as a model, an editorialist writes (
pp. 1853–4): ìThe authors appropriately warn readers that these data warrant scrutiny when rFVIIa is used on an off-label basis. The thrombotic sequelae reported here are not inconsequential. The risk is particularly notable among older patients. This article should serve as a template for pharmaceutical companies to report all studies involving the use of a given drug, on-label and off-label, so that physicians can fully appreciate the benefit and risks when making therapeutic decisions.î (L. M. Aledort)
Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis: Safety and efficacy of the recently approved everolimus (see PNN, Nov. 2) are reported in the trial that served as the basis for FDA action (pp. 1801–11). The agent, an inhibitor of the mammalian target of rapamycin, produced these effects in 28 patients with serial growth of subependymal giant-cell astrocytomas when used in open-label fashion: ìEverolimus therapy was associated with a clinically meaningful reduction in volume of the primary subependymal giant-cell astrocytoma, as assessed on independent central review (P < 0.001 for baseline vs. 6 months), with a reduction of at least 30% in 21 patients (75%) and at least 50% in 9 patients (32%). Marked reductions were seen within 3 months and were sustained. There were no new lesions, worsening hydrocephalus, evidence of increased intracranial pressure, or necessity for surgical resection or other therapy for subependymal giant-cell astrocytoma. Of the 16 patients for whom 24-hour video electroencephalography data were available, seizure frequency for the 6-month study period (vs. the previous 6-month period) decreased in 9, did not change in 6, and increased in 1 (median change, −1 seizure; P = 0.02). The mean (± SD) score on the validated Quality-of-Life in Childhood Epilepsy questionnaire (on which scores can range from 0 to 100, with higher scores indicating a better quality of life) was improved at 3 months (63.4 ± 12.4) and 6 months (62.1 ± 14.2) over the baseline score (57.8 ± 14.0). Single cases of grade 3 treatment-related sinusitis, pneumonia, viral bronchitis, tooth infection, stomatitis, and leukopenia were reported.î (D. N. Franz, tsclinic@cchmc.org)
Geographic Variation in the Quality of Prescribing: Higher spending on pharmaceuticals is not associated with better clinical outcomes, researchers report based on an analysis of Medicare Part D data from 2007 (early release). ìBecause spending on nondrug medical care is positively associated with a greater use of potentially harmful drugs, our results also do not suggest that more medical spending is associated with better health care overall,î the researchers add. ìOur results are consistent, however, with an association between lower-quality prescription patterns and more adverse drug events that may require additional expense to treat.î (Y. Zhang)

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 © 2010, 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, 2010 * Vol. 17, No. 214
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Nov. issue of Pharmacotherapy (2010; 30).
Treatment of Acute Severe Hypertension: A mixed bag of drugs are used when clinicians encounter patients with acute severe hypertension, a study shows, and the outcomes observed during hospitalization are equally heterogeneous (pp. 1087–96). Data from 25 hospitals recorded in the STAT registry were obtained, and investigators focused on 1,184 consecutive adults who presented with nonneurologically caused acute blood pressure elevations (systolic blood pressure, 180 mm Hg or more; diastolic blood pressure of 110 mm Hg or more). Results showed: ìPatients started intravenous antihypertensive therapy 1.3 (median [interquartile range (IQR) 0.5–3.2]) hours after the qualifying SBP (median 204 [IQR 190–221] mm Hg). Labetalol (27%), metoprolol (21%), and nitroglycerin (20%) were the most frequent initial intravenous choices. For the 43% of patients administered two or more intravenous agents sequentially, the 24% receiving three or more, and the 8% receiving four or more, median SBPs at the time of the second, third, and fourth additions were 186 (IQR 168–211), 176 (IQR 152–196), and 164 (IQR 143–193) mm Hg, respectively. Most common continuous intravenous infusions were nitroglycerin (30%), nicardipine (13%), and labetalol (7%). After the first intravenous agent, an SBP decrease of 10–25% was achieved at 1 and 6 hours in 48% and 72%, respectively. Of the 6% without at least a 10% decrease in SBP during the entire hospitalization, labetalol (28%), hydralazine (21%), and metoprolol (17%) were the most frequent initial intravenous choices. Hypotension (SBP 90 mm Hg) occurred in 5% and was most common with intravenous nitroglycerin (39%). Oral antihypertensives were started within 1 and 6 hours after the first intravenous therapy in 13% and 34% of patients, respectively, with many patients (61%) receiving three or more oral agents during hospitalization.î (J. W. Devlin, j.devlin@neu.edu)
Factors in Suboptimal Corticosteroid Use in Children with Asthma: Both poor prescribing patterns and patient nonadherence, often for noneconomic reasons, frequently lead to poor asthma control, researchers report (pp. 1109–16). A retrospective analysis of two Canadian administrative claims databases identified 2,355 children aged 5–15 years with persistent asthma who used more than 3 doses of short-acting beta-agonists per week during a 12-month period before inhaled corticosteroids were added. For 1997–2005, these patterns were noted using a ìnovel drug adherence measure,î the Proportion of Prescribed Days Covered (PPDC): ìThe PPDC measure was defined as the total days’ supply dispensed divided by the total days’ supply prescribed. During the 12-month follow-up period, 20% of the children received only one prescription for inhaled corticosteroids with no prescribed renewals. The mean number of prescriptions (including prescribed renewals) was 5.0, corresponding to only 152 days’ supply prescribed. Mean PPDC (drug adherence) was 62.4%. Only 25% of the patients had controlled asthma, based on the use of 3 or fewer doses/week of short-acting beta-2-agonists and absence of moderate-to-severe exacerbations.î (L. Blais, lucie.blais@umontreal.ca)
Effects of Collaboration on Cost of Cardiac Care: A retrospective cohort study shows that a Collaborative Cardiac Care Service (CCCS) reduced health care expenditures (pp. 1127–35): ìThere were 12 and 98 cardiac-related deaths and 16 and 188 all-cause deaths for the CCCS and No CCCS groups, respectively; mean and median total health care expenditures/day were $39 and $20, respectively, for the CCCS group, and $108 and $45, respectively, for the No CCCS group (all p < 0.001). After adjustment, total health care expenditures for patients in the CCCS group were approximately $60/day ($21,900/yr) lower than those for patients in the No CCCS group (p < 0.001; adjusted R2 = 0.29 with log-transformed expenditures).î (T. Delate, tom.delate@kp.org)

>>>PNN NewsWatch
* Patients with chronic musculoskeletal pain, including discomfort from osteoarthritis and chronic lower back pain, can now be treated with duloxetine (Cymbalta, Lilly), FDA announced yesterday. In approving the new indication for the antidepressant, FDA noted that results of four clinical trials supported efficacy and safety of duloxetine in patients with these pain syndromes.

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 © 2010, 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. 8, 2010 * Vol. 17, No. 215
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 6 issue of Lancet (2010; 376).
Vitamin D Receptor Activation & Diabetic Albuminuria: Added to renin–angiotensin–aldosterone system (RAAS) inhibitors, the selective vitamin D receptor activator paricalcitol lowered residual albuminuria in 281 patients with type 2 diabetes, researchers report (pp. 1543–51). For 24 weeks, patients received placebo or paricalcitol in doses of 1 or 2 µg/d. Using a primary endpoint of the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to last measurement during treatment, the investigators found: ìChange in UACR was: −3% (from 61 to 60 mg/mmol; 95% CI −16 to 13) in the placebo group; −16% (from 62 to 51 mg/mmol; −24 to −9) in the combined paricalcitol groups, with a between-group difference versus placebo of −15% (95% CI −28 to 1; p = 0.071); −14% (from 63 to 54 mg/mmol; −24 to −1) in the 1 µg paricalcitol group, with a between-group difference versus placebo of −11% (95% CI −27 to 8; p = 0.23); and −20% (from 61 to 49 mg/mmol; −30 to −8) in the 2 µg paricalcitol group, with a between-group difference versus placebo of −18% (95% CI −32 to 0; p = 0.053). Patients on 2 µg paricalcitol showed an early, sustained reduction in UACR, ranging from −18% to −28% (p = 0.014 vs placebo). Incidence of hypercalcaemia, adverse events, and serious adverse events was similar between groups receiving paricalcitol versus placebo.î (D. de Zeeuw, d.de.zeeuw@med.umcg.nl)
Quantifying Drug Harms: The drug causing the most harm in the U.K. is alcohol, a multicriteria decision analysis (MCDA) shows, while second- and third-place heroin and crack cocaine get the attention of regulators and the legal system (pp. 1558–65). The article demonstrates how a 16-criteria MCDA can be used to assess drug harms: ìMCDA modelling showed that heroin, crack cocaine, and metamfetamine were the most harmful drugs to individuals (part scores 34, 37, and 32, respectively), whereas alcohol, heroin, and crack cocaine were the most harmful to others (46, 21, and 17, respectively). Overall, alcohol was the most harmful drug (overall harm score 72), with heroin (55) and crack cocaine (54) in second and third places.î (D. J. Nutt, d.nutt@imperial.ac.uk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 341).
Vitamin E & Stroke: The risks of hemorrhagic and ischemic strokes are slightly reduced in patients taking vitamin E, authors of a meta-analysis report (c5702): ìVitamin E increased the risk for haemorrhagic stroke by 22% and reduced the risk of ischaemic stroke by 10%. This differential risk pattern is obscured when looking at total stroke. Given the relatively small risk reduction of ischaemic stroke and the generally more severe outcome of haemorrhagic stroke, indiscriminate widespread use of vitamin E should be cautioned against.î (M. Sch¸rks, mschuerks@rics.bwh.harvard.edu)

>>>PNN NewsWatch
* ASHP’s Pharmacy Practice Model Initiative Summit is under way in Dallas, TX, with some 100 voting participants and three dozen invited observers in attendance. Three speakers—the head of the Society of Hospital Medicine, a hospital administrator, and the ASHP exec—presented on Sunday evening, ASHP.org reports. Virtual participants can watch sessions online, comment on Twitter (#PPMI), and submit questions to speakers electronically.

>>>PNN JournalWatch
* A Systematic Review of Faces Scales for the Self-report of Pain Intensity in Children, in Pediatrics, 2010; 126: e1168–98. (D. Tomlinson)
* Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis, in
Pediatrics, 2010; 126: e1211–26. (O. J. Phung)
* Developing and Evaluating Complex Healthcare Interventions in Geriatrics: The Use of the Medical Research Council Framework Exemplified on a Complex Fall Prevention Intervention, in
Journal of the American Geriatrics Society, 2010; 58: 2212–21. (M. C. Faes, m.faes@ger.umcn.nl)
* Linking Molecules to Mood: New Insight into the Biology of Depression, in
American Journal of Psychiatry, 2010; 167: 1305–20. (V. Krishnan)
* Management of
Clostridium difficile Infection: Thinking Inside and Outside the Box, in Clinical Infectious Diseases, 2010; 51: 1306–13. (D. N. Gerding, dale.gerding2@va.gov)
* Health Care Workers and Researchers Traveling to Developing-World Clinical Settings: Disease Transmission Risk and Mitigation, in
Clinical Infectious Diseases, 2010; 51: 1298–305. (N. Aronson, naronson@usuhs.mil)

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 © 2010, 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, 2010 * Vol. 17, No. 216
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release article from and Nov. 8 issue of the Archives of Internal Medicine (2010; 170).
Heart Failure & Antihypertensives: For preventing heart failure in patients with hypertension, diuretics are the most effective class of blood-pressure-lowering agents, followed by renin–angiotensin inhibitors, according to a Bayesian network meta-analysis (doi: 10.1001/archinternmed.2010.427). Randomized controlled trials published in 1997–2009 of patients with hypertension or a high-risk population that included many patients with hypertension were analyzed, with these results: ìA total of 223,313 patients were enrolled in the selected studies. Network meta-analysis showed that diuretics (odds ratio [OR], 0.59; 95% credibility interval [CrI], 0.47–0.73), angiotensin-converting enzyme (ACE) inhibitors (OR, 0.71; 95% CrI, 0.59–0.85) and angiotensin II receptor blockers (ARBs) (OR, 0.76; 95% CrI, 0.62–0.90) represented the most efficient classes of drugs to reduce the heart failure onset compared with placebo. On the one hand, a diuretic-based therapy represented the best treatment because it was significantly more efficient than that based on ACE inhibitors (OR, 0.83; 95% CrI, 0.69–0.99) and ARBs (OR, 0.78; 95% CrI, 0.63–0.97). On the other hand, diuretics (OR, 0.71; 95% CrI, 0.60–0.86), ARBs (OR, 0.91; 95% CrI, 0.78–1.07), and ACE inhibitors (OR, 0.86; 95% CrI, 0.75–1.00) were superior to calcium channel blockers, which were among the least effective first-line agents in heart failure prevention, together with beta-blockers and alpha-blockers.î (M. Volpe, massimo.volpe@uniroma1.it)
Structured Exercise in Diabetes: In 691 sedentary patients with type 2 diabetes mellitus, a twice-weekly program of supervised aerobic and resistance training with structured exercise counseling was significantly more effective than counseling alone (pp. 1794–803). Over a 12-month period, the ìexercise intervention strategy was effective in promoting [physical activity] and improving HbA1c and cardiovascular risk profile. Conversely, counseling alone, though successful in achieving the currently recommended amount of activity, was of limited efficacy on cardiovascular risk factors, suggesting the need for a larger volume of [physical activity] in these high-risk subjects.î (G. Pugliese, giuseppe.pugliese@uniroma1.it)
Editorialists call for change based on the Italian Diabetes and Exercise Study (IDES) results (
pp. 1790–1): ìThis trial Ö supports the addition of supervised, facility-based exercise training to standard therapy for T2DM, just as exercise-based cardiac rehabilitation is considered part of the optimal treatment of patients with acute cardiac events.Ö Supervised exercise training should be offered as an evidence-based therapy and supported by payers in the same way as nutritional therapy and medications. The cost of delivering such therapy would probably compare favorably with the costs of many diabetes medications, none of which would have the vast range of clinically beneficial effects demonstrated in the IDES supervised exercise group.î (R. J. Sigal, rsigal@ucalgary.ca)
More Chocolate, Please: More evidence that flavonoids in cocoa lower blood pressure and improve endothelial function comes from a calcium-supplement study of 1,216 women (pp. 1857–8). During the 5 years of the trial, chocolate intake was recorded using validated questionnaires, and those data were associated with cardiovascular events. Results showed: ìThere were 158 [atherosclerotic vascular disease (ASVD)] events (27.3%) in the group that rarely consumed chocolate, compared with 90 events (20.7%) in the group that consumed chocolate weekly, and 42 events (20.8%) in the group that consumed chocolate daily.Ö Results from ASVD event analyses showed that hospitalization or death was less common in participants who consumed chocolate frequently. Compared with women who rarely consumed chocolate, those who consumed chocolate frequently had a significantly lower risk of hospitalization for or death from ischemic heart disease and heart failure in both age and multivariable-adjusted analyses. Women who frequently consumed chocolate also had a significantly lower prevalence of carotid atherosclerotic plaques compared with women who consumed chocolate rarely, but there was no effect on the mean [common carotid artery intima-media thickness] by age or multivariable-adjusted analysis of variance.î (J. R. Lewis, josh.lewis@meddent.uwa.edu.au)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 217
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release articles from JAMA (2010; 304).
Remission Maintenance in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: Surprising results show that mycophenolate mofetil is less, not more, efficacious than azathioprine for maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) (doi: 10.1001/jama.2010.1658). In the open-label, randomized controlled International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides (IMPROVE) trial, European patients received azathioprine 2 mg/kg/d or mycophenolate mofetil 2,000 mg/d following induction of remission with cyclophosphamide and prednisolone, with these results: ìA total of 156 patients were assigned to azathioprine (n = 80) or mycophenolate mofetil (n = 76) and were followed up for a median of 39 months (interquartile range, 0.66–53.6 months). All patients were retained in the analysis by intention to treat. Relapses were more common in the mycophenolate mofetil group (42/76 patients) compared with the azathioprine group (30/80 patients), with an unadjusted hazard ratio (HR) for mycophenolate mofetil of 1.69 (95% confidence interval [CI], 1.06–2.70; P = .03). Severe adverse events did not differ significantly between groups. There were 22 severe adverse events in 13 patients (16%) in the azathioprine group and there were 8 severe adverse events in 8 patients (7.5%) in the mycophenolate mofetil group (HR, 0.53 [95% CI, 0.23–1.18]; P = .12). The secondary outcomes of Vasculitis Damage Index, estimated glomerular filtration rate, and proteinuria did not differ significantly between groups.î (T. F. Hiemstra, tfh24@cam.ac.uk)
An editorialist provides this perspective on therapeutic interventions for systemic vasculitis (
doi: 10.1001/jama.2010.1676): ìAt the dawn of the 21st century of vasculitis research, several key therapeutic findings are apparent. For patients with [Wegener granulomatosis] or [microscopic polyangiitis], chronic long-term cyclophosphamide therapy is no longer justified. Remission maintenance therapies (methotrexate, azathioprine) are as effective as prolonged cyclophosphamide and are much safer. Mycophenolate mofetil is associated with a higher relapse rate than azathioprine. Discontinuation of maintenance therapies appears to be associated with a higher rate of relapse than continuation of treatment. However, the risk-benefit formulas of long-term maintenance therapy vs discontinuation and treatment of relapses require further study. Ideally these questions can be addressed by clinical trials of similar quality and importance as the [above] report Ö and other major contributions of the [European Vasculitis Study Group].î (G. S. Hoffman, hoffmag@ccf.org)

>>>PNN NewsWatch
* Imagine a world where pharmacists have delegated every possible distributive task to certified pharmacy technicians, all of whom have completed accredited training programs before sitting for the certification exam. All pharmacists providing drug therapy management services have completed accredited residencies, or have equivalent experience, and they are certified by the Board of Pharmacy Specialties in appropriate clinical areas. All patients in health systems have access to the clinical services of pharmacists. With an eye on fiscal realities, pharmacists triage care based on a patient medication acuity or complexity index. If those voting at the just-completed ASHP Pharmacy Practice Model Initiative Summit have their way, those scenarios will be reality in just a few years—with tech training being required as early as 2015. The group pushed to attain consensus on all but a handful of some 200 statements on overarching principles, specific services, use of technology and technicians, and paths for implementing change. An 80% vote was required to adopt statements, and attendees required two or even three votes on items to achieve this level of agreement. While many statements are specific to hospitals and health systems, others, such as changes in state laws, would have professionwide implications. In closing the Dallas conference, former ASHP staffer Bill Zellmer called for ìnew bold actions,î ones that would implement a ìclear, inspiring vision for practiceî through an ìassertive program.î The Society’s president, Diane Ginsburg of U. Texas, said the conference ìwas just the beginning--just one piece of this entire movementî and ìASHP and the ASHP Foundation are committed to move this forward.î

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 218
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Nov. 11 issue of the New England Journal of Medicine (2010; 363).
Romiplostim in Immune Thrombocytopenia: Compared with standard care in 234 adult patients with immune thrombocytopenia, the thrombopoietin mimetic romiplostim produced a higher rate of a platelet response, lower incidence of treatment failure and splenectomy, less bleeding and fewer blood transfusions, and a higher quality of life, researchers report (pp. 1889–99). Used open label over a 52-week period, weekly subcutaneous romiplostim injections produced these results: ìThe rate of a platelet response in the romiplostim group was 2.3 times that in the standard-of-care group (95% confidence interval [CI], 2.0 to 2.6; P < 0.001). Patients receiving romiplostim had a significantly lower incidence of treatment failure (18 of 157 patients [11%]) than those receiving the standard of care (23 of 77 patients [30%], P < 0.001) (odds ratio with romiplostim, 0.31; 95% CI, 0.15 to 0.61). Splenectomy also was performed less frequently in patients receiving romiplostim (14 of 157 patients [9%]) than in those receiving the standard of care (28 of 77 patients [36%], P < 0.001) (odds ratio, 0.17; 95% CI, 0.08 to 0.35). The romiplostim group had a lower rate of bleeding events, fewer blood transfusions, and greater improvements in the quality of life than the standard-of-care group. Serious adverse events occurred in 23% of patients (35 of 154) receiving romiplostim and 37% of patients (28 of 75) receiving the standard of care.î (D. J. Kuter, kuter.david@mgh.harvard.edu)
Two things are certain about treatment of immune thrombocytopenia, an editorialist writes (
pp. 1959–61): ìFirst, the availability of the thrombopoietin-mimetic agents has been a great advance for patients with immune thrombocytopenia. Thrombopoietin-mimetic agents can be effective in inducing safe platelet counts when all other treatments, including splenectomy and rituximab, have failed, providing hope for patients with the most severe thrombocytopenia. Second, active discussion of the proper place for thrombopoietin-mimetic agents in the sequence of immune thrombocytopenia treatments will continue. For patients with immune thrombocytopenia, an orphan disease, this attention is both new and welcome. Patients with immune thrombocytopenia will feel less isolated, and their care will be better.î (J. N. George)
$4 Generics & Quality Assurance: Because pharmacy claims data have become so important in improving ìthe effectiveness of pharmaceutical care in large populations,î the availability of low-cost generics that patients pay for out of pocket presents challenges, authors write, offering this solution (pp. 1885–7): ìThe simplest strategy is to ensure that pharmacists submit to pharmacy benefit managers all claims for beneficiaries, including those for drugs that are paid for in cash, thereby exploiting the current system of information flow. However, pharmacists will need incentives to submit such documentation, and these incentives must not violate conflict-of-interest and kickback regulations, given the established relationships between pharmacy benefit managers and pharmaceutical manufacturers.î (N. K. Choudhry)

>>>PNN NewsWatch
* FDA yesterday announced its approval of tesamorelin for injection (Egrifta, EMD Serono) for treatment of HIV-infected patients with abdominal lipohypertrophy. The growth hormone releasing factor, administered in a once-daily injection, was evaluated in two Phase III trials of 26 weeks’ duration. Compared with placebo, tesamorelin demonstrated significant decreases in visceral adipose tissue and waist circumference in 816 HIV-infected patients with excess abdominal fat associated with lipodystrophy. Since the long-term cardiovascular safety and potential long-term cardiovascular benefit of tesamorelin have not been studied and are not known, product labeling advises careful consideration about use of the drug in patients who do not show a clear efficacy response as judged by the degree of reduction in visceral adipose tissue measured by waist circumference or CT scan. The most commonly reported adverse effects in clinical studies included arthralgia, erythema and pruritus at the injection site, stomach pain, swelling, and myalgia. Worsening blood glucose control occurred more often in patients treated with tesamorelin than with placebo.

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 © 2010, 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, 2010 * Vol. 17, No. 219
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Nov. 16 issue of the Journal of the American College of Cardiology (2010; 56).
Telmisartan in Hemodialysis Patients with Heart Failure: Added to standard therapy with ACE inhibitors, telmisartan significantly reduced all-cause mortality, cardiovascular death, and heart failure hospital stays in hemodialysis patients with chronic heart failure (CHF) and left ventricular ejection fraction (LVEF) of 40% or less, a study shows (pp. 1701–8). In a 3-year trial at 30 Italian clinics, 332 patients were titrated to target doses of telmisartan of 80 mg, or received placebo, in addition to standard therapy that included an ACE inhibitor. During a median of 35.5 months of follow-up, these results were recorded: ìAt 3 years, telmisartan significantly reduced all-cause mortality (35.1% vs. 54.4%; p < 0.001), cardiovascular death (30.3% vs. 43.7%; p < 0.001), and hospital admission for CHF (33.9% vs. 55.1%; p < 0.0001). With Cox proportional hazards analysis, telmisartan was an independent determinant of all-cause mortality (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.32 to 0.82; p < 0.01), cardiovascular mortality (HR: 0.42; 95% CI: 0.38 to 0.61; p < 0.0001), and hospital stay for deterioration of heart failure (HR: 0.38; 95% CI: 0.19 to 0.51; p < 0.0001). Adverse effects, mainly hypotension, occurred in 16.3% of the telmisartan group versus 10.7% in the placebo group.î (G. Cice, gennarocice@hotmail.com)
Editorialists write that clinicians are ìfinally getting some evidenceî regarding use of renin–angiotensin system (RAS) antagonists in this patient population (
pp. 1709–11): ìAll things considered, the findings of Cice et al. are important and, like all important studies, should lead to further investigation. Given the grim prognosis of hemodialyzed patients with HF and the premise for improved longevity with aggressive RAS inhibition in the current study, it would be reassuring to see another larger trial of add-on angiotensin-receptor blockade in this patient population with similar findings. These investigators should be given credit for paving the way to providing the clinician an evidence base from which to make relevant therapeutic decisions in this complex and mortal disease state. For now, clinicians should carefully evaluate the choice of agents in the treatment of HF when it complicates dialysis and make sure that drugs that antagonize both the RAS and adrenergic axes are considered.î (J. C. Fang, james.fang@uhhospitals.org)
Bisphosphonates & Valvular/Vascular Calcification: In the Multi-Ethnic Study of Atherosclerosis (MESA), nitrogen-containing bisphosphonate (NCBP) therapy was associated with decreased prevalence of cardiovascular calcification in older women but increased rates in younger women (pp. 1752–9). These age-related effects were observed in 3,710 women with the following prevalences of aortic valve, aortic valve ring, mitral annulus, thoracic aorta, and coronary artery calcification (AVC, AVRC, MAC, TAC, and CAC, respectively): ìAnalyses were age-stratified, because of a significant interaction between age and NCBP use (interaction p values: AVC p < 0.0001; AVRC p < 0.0001; MAC p = 0.002; TAC p < 0.0001; CAC p = 0.046). After adjusting for age; body mass index; demographic data; diabetes; smoking; blood pressure; cholesterol levels; and statin, hormone replacement, and renin–angiotensin inhibitor therapy, NCBP use was associated with a lower prevalence of cardiovascular calcification in women 65 years of age (prevalence ratio: AVC 0.68 [95% confidence interval (CI): 0.41 to 1.13]; AVRC 0.65 [95% CI: 0.51 to 0.84]; MAC 0.54 [95% CI: 0.33 to 0.93]; TAC 0.69 [95% CI: 0.54 to 0.88]; CAC 0.89 [95% CI: 0.78 to 1.02]), whereas calcification was more prevalent in NCBP users among the 2,181 women <65 years of age (AVC 4.00 [95% CI: 2.33 to 6.89]; AVRC 1.92 [95% CI: 1.42 to 2.61]; MAC 2.35 [95% CI: 1.12 to 4.84]; TAC 2.17 [95% CI: 1.49 to 3.15]; CAC 1.23 [95% CI: 0.97 to 1.57]).î (S. Elmariah, selmariah@partners.org)

>>>PNN NewsWatch
* An attorney for GlaxoSmithKline has been charged with obstruction and making false statements, according to media reports and a Dept. of Justice news release. Lauren Stevens of Durham, NC, signed and sent a series of letters from the company to FDA that falsely denied that the company had promoted a drug for off-label uses, the indictment alleges, pointing to 511 talks given by one physician and 488 by another in 2001–02.

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 © 2010, 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. 15, 2010 * Vol. 17, No. 220
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 13 issue of Lancet (2010; 376).
Bivalent Oral Poliovirus Vaccine: Bivalent types 1 and 3 oral poliovirus vaccine (bOPV) was superior to trivalent oral poliovirus vaccine (tOPV) and was not inferior to monovalent types 1 and 3 (mOPV1, mOPV3) in a study conducted at three centers in India (pp. 1682–8). Using random allocation in permuted blocks of 10 and a level of significance of 0.01 that accounted for multiple comparisons, the investigators found: ì900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8%) discontinued, leaving 830 (92%) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20% for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15% for tOPV (25 of 168; p > 0.01), to poliovirus type 2 was 21% (35 of 170) for mOPV2 compared with 25% (42 of 168) for tOPV (p > 0.01), and to poliovirus type 3 was 12% (20 of 165) for mOPV3 and 7% (11 of 159) for bOPV compared with 4% (7 of 168) for tOPV (mOPV3 vs tOPV p = 0.01; bOPV vs tOPV; p > 0.01). Cumulative two-dose seroconversion to poliovirus type 1 was 90% (151 of 168) for mOPV1 and 86% (136 of 159) for bOPV compared with 63% (106 of 168) for tOPV (p < 0.0001), to poliovirus type 2 was 90% (153 of 170) for mOPV2 compared with 91% (153 of 168) for tOPV (p > 0.01), and to poliovirus type 3 was 84% (138 of 165) for mOPV3 and 74% (117 of 159) for bOPV compared with 52% (87 of 168) for tOPV (p < 0.0001). The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions.î (R. W. Sutter, sutterr@who.int)
Focusing on the Politics of Chronic Diseases: In the first of a series, the need for change in global and national policies is discussed in relation to the prevention of chronic diseases (pp. 1689–98). Authors propose three strategies: ìReframe the debate to emphasise the societal determinants of disease and the interrelation between chronic disease, poverty, and development; mobilise resources through a cooperative and inclusive approach to development and by equitably distributing resources on the basis of avoidable mortality; and build on emerging strategic and political opportunities, such as the World Health Assembly 2008–13 Action Plan and the high-level meeting of the UN General Assembly in 2011 on chronic disease. Until the full set of threats—which include chronic disease—that trap poor households in cycles of debt and illness are addressed, progress towards equitable human development will remain inadequate.î (R. Geneau, rgeneau@bruyere.org)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 341).
Suicidality with Isotretinoin: Patients who have taken isotretinoin for severe acne should be monitored for suicidality for 1 year after treatment cessation, according to a 21-year analysis from Sweden (c5812). Despite an increase in suicidality seen during drug therapy, the investigators note that ìthe risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established. As patients with a history of suicide attempts before treatment made new attempts to a lesser extent than did patients who started such behaviour in connection with treatment, patients with severe acne should not automatically have isotretinoin treatment withheld because of a history of attempted suicide.î The analysis included 5,756 patients aged 15–49 years who received isotretinoin in 1980–2001. The authors noted: ìTwelve (38%) of 32 patients who made their first suicide attempt before treatment made a new attempt or committed suicide thereafter. In contrast, 10 (71%) of the 14 who made their first suicide attempt within six months after treatment stopped made a new attempt or committed suicide during follow-up (two sample test of proportions, P = 0.034). The number needed to harm was 2,300 new six month treatments per year for one additional first suicide attempt to occur and 5,000 per year for one additional repeat attempt.î (A. Sundstrˆm, Anders.Sundstrom@Ki.se)

>>>PNN JournalWatch
* Antithrombotic Therapy in the Elderly, in Journal of the American College of Cardiology, 2010; 56: 1683–92. (D. J. Angiolillo, dominick.angiolillo@jax.ufl.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 221
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 16 issue of the Annals of Internal Medicine (2010; 153).
Testosterone Effects in Middle-Aged Men: The wisdom of long-term testosterone supplementation in men is called into question by a study that shows no prostate benefits and some decreases in bone mineral density with transdermal administration (pp. 621–32). Testing the hypothesis that transdermal testosterone can reduce late-life prostate growth in asymptomatic men older than 50, the investigators provided transdermal dihydrotestosterone (DHT) or placebo to 114 men for 2 years, with these results: ìOver 24 months, there was an increase in total (29% [95% CI, 23% to 34%]) and central (75% [CI, 64% to 86%]; P < 0.01) prostate volume and serum prostate-specific antigen level (15% [CI, 6% to 24%]) with time on study, but DHT had no effect (P > 0.2). Dihydrotestosterone treatment decreased spinal BMD (1.4% [CI, 0.6% to 2.3%]; P < 0.001) at 24 months but not hip BMD (P > 0.2) and increased serum aminoterminal propeptide of type I procollagen in the second year of the study compared with placebo. Dihydrotestosterone increased serum DHT levels and its metabolites (5-alpha-androstane-3-alpha,17-beta-diol and 5-alpha-androstane-3-beta, 17-beta diol) and suppressed serum testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels. Dihydrotestosterone increased hemoglobin levels (7% [CI, 5% to 9%]), serum creatinine levels (9% [CI, 5% to 11%]), and lean mass (2.4% [CI, 1.6% to 3.1%) but decreased fat mass (5.2% [CI, 2.6% to 7.7%]) (P <0.001 for all). Protocol-specific discontinuations due to DHT were asymptomatic increased hematocrit (n = 8), which resolved after stopping treatment, and increased prostate-specific antigen levels (n = 3; none with prostate cancer) in the DHT group. No serious adverse effects due to DHT occurred.î (D. J. Handelsman, djh@anzac.edu.au)
Prescription Abandonment in Community Pharmacy: In a CVS Caremark study, researchers found that the number of prescriptions not picked up by patients was small, totaling just over 3% of prescriptions (pp. 633–40). But these abandoned prescriptions ìhighlight important opportunities to intervene and thereby improve medication taking,î the group writes. The study analyzed data from the third quarter of 2008. Covered patients were included, and prescriptions were placed in one of three mutually exclusive categories: filled, returned to stock (RTS), or RTS with later fill for another agent in the same medication class. Results showed: ì10,349,139 index prescriptions were filled by 5,249,380 patients. Overall, 3.27% of index prescriptions were abandoned; 1.77% were RTS and 1.50% were RTS with fill. Patients were least likely to abandon opiate prescriptions. Prescriptions with copayments of $40 to $50 and prescriptions costing more than $50 were 3.40 times and 4.68 times more likely, respectively, to be abandoned than prescriptions with no copayment (P < 0.001 for both comparisons). New users of medications had a 2.74 times greater probability of abandonment than prevalent users (P < 0.001), and prescriptions delivered electronically were 1.64 times more likely to be abandoned than those that were not electronic (P < 0.001).î (W. H. Shrank, wshrank@partners.org)

>>>PNN NewsWatch
* FDA has approved eribulin mesylate (Halaven, Eisai) injection for treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included, an anthracycline and a taxane for early or advanced breast cancer. The nontaxane, microtubule dynamics inhibitor was studied in EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus Eribulin), which showed that patients treated with eribulin survived a median of 2.5 months longer than patients who received a single-agent therapy chosen by their physician (13.12 versus 10.65 months). The most common adverse effects of eribulin were neutropenia, anemia, asthenia/fatigue, alopecia, peripheral neuropathy, nausea, and constipation.
* Coinciding with
Get Smart about Antibiotics Week, FDA launched a campaign to educate consumers about skipping doses, sharing these drugs with others, and saving antibiotics for later use.

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 © 2010, 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, 2010 * Vol. 17, No. 222
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release article from and the Nov. 17 issue of JAMA (2010; 304).
Prescription Omega-3 Fatty Acids in AF: Twenty-four weeks of treatment with prescription omega-3 fatty acids failed to affect the number of recurrent atrial fibrillation episodes in a study of 663 outpatients (doi: 10.1001/jama.2010.1735). Study participants had confirmed symptomatic paroxysmal (n = 542) or persistent (n = 121) AF, with no substantial structural heart disease, and were in normal sinus rhythm when they were recruited between Nov. 2006 and July 2009. Prescription omega-3 in doses of 8 g/d for the first 7 days and 4 g/d thereafter or placebo produced these results: ìAt 24 weeks, in the paroxysmal AF stratum, 129 of 269 participants (48%) in the placebo group and 135 of 258 participants (52%) in the prescription group had a recurrent symptomatic AF or flutter event. In the persistent AF stratum, 18 participants (33%) in the placebo group and 32 (50%) in the prescription group had documented symptomatic AF or flutter events. There was no difference between treatment groups for recurrence of symptomatic AF in the paroxysmal stratum (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.90–1.46; P = .26), in the persistent stratum (HR, 1.64; 95% CI, 0.92–2.92; P = .09), and both strata combined (HR, 1.22; 95% CI, 0.98–1.52; P = .08). Other, secondary end points were supportive of the primary result. A total of 5% of those receiving placebo and 4% of those receiving prescription omega-3 discontinued due to adverse events. Eicosapentaenoic and docosahexaenoic acid blood levels were significantly higher in the prescription group than in the placebo group at weeks 4 and 24.î (P. R. Kowey, KoweyP@mlhs.org)
Doxorubicin–Sorafenib for Advanced Hepatocellular Carcinoma: The combination of doxorubicin plus sorafenib increased median time to progression, overall survival, and progression-free survival in patients with advanced hepatocellular carcinoma, compared with doxorubicin alone, researchers report (pp. 2154–60). This Phase II, multinational study included 96 patients, mostly men, who received doxorubicin 60 mg/sq m intravenously every 21 days plus either sorafenib 400 mg or placebo orally twice daily. The results, which form the basis for further testing of this combination in a Phase III trial, show the following: ìFollowing complete accrual, an unplanned early analysis for efficacy was performed by the independent data monitoring committee, so the trial was halted. The 2 patients remaining in the placebo group at that time were offered sorafenib. Based on 51 progressions, 63 deaths, and 70 events for progression-free survival, median time to progression was 6.4 months in the sorafenib–doxorubicin group (95% confidence interval [CI], 4.8–9.2), and 2.8 months (95% CI, 1.6–5) in the doxorubicin-placebo monotherapy group (P = .02). Median overall survival was 13.7 months (95% CI, 8.9–not reached) and 6.5 months (95% CI, 4.5–9.9; P = .006), and progression-free survival was 6.0 months (95% CI, 4.6–8.6) and 2.7 months (95% CI, 1.4–2.8) in these groups, respectively (P = .006). Toxicity profiles were similar to those for the single agents.î (G. K. Abou–Alfa, abou-alg@mskcc.org)
Acute Otitis Media in Children: In acute otitis media, antibiotics ìare modestly more effective than no treatment but cause adverse effects in 4% to 10% of children,î conclude authors who conducted a systematic review of AOM diagnosis, treatment, and the association of heptavalent pneumococcal conjugate vaccine (PCV7) use with AOM microbiology (pp. 2161–9): ìIn the few available studies, prevalence of Streptococcus pneumoniae decreased (eg, 33%–48% vs 23%–31% of AOM isolates), while that of Haemophilus influenzae increased (41%–43% vs 56%–57%) pre- vs post-PCV7. Short-term clinical success was higher for immediate use of ampicillin or amoxicillin vs placebo (73% vs 60%; pooled rate difference, 12% [95% CI, 5%–18%]; number needed to treat, 9 [95% CI, 6–20]), while increasing the rate of rash or diarrhea by 3% to 5%. Two of 4 studies showed greater clinical success for immediate vs delayed antibiotics (95% vs 80%; rate difference, 15% [95% CI, 6%–24%] and 86% vs 70%; rate difference, 16% [95% CI, 6%–26%]). Data are absent on long-term effects on antimicrobial resistance. Meta-analyses in general showed no significant differences in antibiotic comparative effectiveness.î (T. R. Coker, tcoker@mednet.ucla.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 © 2010, 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, 2010 * Vol. 17, No. 223
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Nov. 18 New England Journal of Medicine (2010; 363).
VX-770 in Cystic Fibrosis: Improvements in cystic fibrosis transmembrane conductance regulator (CFTR) and lung function were noted in patients taking the CFTR potentiator VX-770, a study shows (pp. 1991–2003). The trial, which focused on safety and adverse events, found these changes in 39 adults with cystic fibrosis and at least one G551D-CFTR allele: ìAt day 28, in the group of subjects who received 150 mg of VX-770, the median change in the nasal potential difference (in response to the administration of a chloride-free isoproterenol solution) from baseline was −3.5 mV (range, −8.3 to 0.5; P = 0.02 for the within-subject comparison, P = 0.13 vs. placebo), and the median change in the level of sweat chloride was −59.5 mmol per liter (range, −66.0 to −19.0; P = 0.008 within-subject, P = 0.02 vs. placebo). The median change from baseline in the percent of predicted forced expiratory volume in 1 second was 8.7% (range, 2.3 to 31.3; P = 0.008 for the within-subject comparison, P = 0.56 vs. placebo). None of the subjects withdrew from the study. Six severe adverse events occurred in two subjects (diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes). All severe adverse events resolved without the discontinuation of VX-770.î (F. J. Accurso, accurso.frank@tchden.org)
An editorialist summarizes progress in ìtargeting the basic defect in cystic fibrosisî (
pp. 2056–7): ìScreening of newborns for CFTR mutations, which is now universal in the United States, provides a tremendous opportunity to intervene early and thus heightens the urgency in understanding relationships between CFTR function and disease. Given that infants have a defect in pulmonary host defense that allows bacterial infection to initiate a cascade of inflammation and remodeling, an ideal scenario would be to begin therapeutically targeting CFTR soon after birth. However, if we are to commit babies to a lifetime of treatment, we must have quantitative metrics to guide factors such as dosing, continuous or intermittent administration, and intervals between treatments. Even the treatment of patients with established disease would benefit from more sensitive and quantitative biomarkers. Acquiring knowledge of the pathophysiology of cystic fibrosis and developing new assays with the use of that knowledge should be priorities. One hope is that studies of the use of agents such as VX-770 will advance these goals. The reaching of this milestone along the pathway of discovery leaves me optimistic for people who have cystic fibrosis.î (M. J. Welsh)
Fatty Acids in CVD: In patients on ìstate-of-the-art antihypertensive, antithrombotic, and lipid-modifying therapy,î low-dose supplementation of marine n-3 or plant-derived fatty acids failed to add clinical advantage relative to cardiovascular disease (pp. 2015–26). The 4,837 participants were mostly men (78%), aged 60–80, and had had a myocardial infarction. Use of margarine containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and/or alpha-linolenic acid (ALA) produced these results: ìThe patients consumed, on average, 18.8 g of margarine per day, which resulted in additional intakes of 226 mg of EPA combined with 150 mg of DHA, 1.9 g of ALA, or both, in the active-treatment groups. During the follow-up period, a major cardiovascular event occurred in 671 patients (13.9%). Neither EPA–DHA nor ALA reduced this primary end point (hazard ratio with EPA–DHA, 1.01; 95% confidence interval [CI], 0.87 to 1.17; P = 0.93; hazard ratio with ALA, 0.91; 95% CI, 0.78 to 1.05; P = 0.20). In the prespecified subgroup of women, ALA, as compared with placebo and EPA–DHA alone, was associated with a reduction in the rate of major cardiovascular events that approached significance (hazard ratio, 0.73; 95% CI, 0.51 to 1.03; P = 0.07). The rate of adverse events did not differ significantly among the study groups.î (D. Kromhout, daan.kromhout@wur.nl)

>>>PNN NewsWatch
* Certain needleless glass syringes, especially those containing adenosine or amiodarone, can break, become clogged, or otherwise malfunction, FDA warned yesterday. A letter to stakeholders advises, ìIn some cases, the syringe may damage the IV tubing and/or the needleless connector and require reestablishment of intravenous access. These failures can cause a delay in administration of the medication.î

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 224
Providing news and information about medications and their proper use

>>>Heart Highlights
Source:
Presentations at the Am. Heart Assoc. Scientific Sessions, Nov. 14–16, Chicago.
Seven ìHealth Factorsî: Ideal levels of cholesterol, blood sugar, and blood pressure, nonsmoking, and appropriate weight, physical activity, and diet—those are ìlife’s simple seven,î according to the AHA, that can provide the path toward less cardiovascular disease and fewer strokes. Introducing the concept in his presidential address on Sunday, Ralph Sacco, MD, said, ìWe’re not only urging the avoidance of risk factors, in fact, we’re calling them ‘health factors,’ not risk factors. It may seem like semantics, but we believe that will motivate people to understand and embrace the benefits of healthy living.Ö I believe diet will be the toughest to achieve. In fact, our nutritionist and epidemiologist experts struggled to identify a realistic approach to diet.î
Sacco is the first neurologist to head the heart association.
Anacetrapib for Dyslipidemia: Results reported at AHA for a new Merck drug are so far beyond those of existing drugs, ìit’s like a rocket to Jupiter versus one to the moon,î Robert Eckel, MD, of U. Colorado, told the Associated Press. During 6 months of treatment, anacetrapib lowered LDL cholesterol levels from 81 to 45 mg/dL and raised HDL cholesterol from 41 to 101 mg/dL among 1,623 people with prior myocardial infarction, diabetes, or other cardiovascular risk factors. Those receiving placebo had cholesterol changes of 82 to 77 mg/dL for LDL and 40 to 46 mg/dL for HDL. In the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) trial, active therapy was associated with fewer deaths, myocardial infarctions, cardiovascular events, and procedures for clogged arteries. But the study had insufficient power to detect whether these decreases were significant.
Patients in the study were already on statins and/or other lipid-lowering drugs and had met their LDL goals. Results were released early on the website of the
New England Journal of Medicine.
Anacetrapib is an inhibitor of the cholesterylester transfer protein (CETP), which transfers cholesterol particles from HDL to LDL. Through 76 weeks of the study, blood pressures were not changed by the new drug, an important observation in view of Pfizer’s discontinuance of development of another CETP inhibitor, torcetrapib, because of adverse effects on blood pressure.
ìAnacetrapib has a knock-your-socks-off effect on HDL and a jaw-dropping effect on LDL,î said Christopher P. Cannon, MD, senior investigator of the TIMI Study Group in the cardiovascular division of Brigham and Women’s Hospital in Boston. ìThese changes are striking because virtually all the patients in the study were already taking cholesterol-lowering drugs and achieved previously unattainable levels of good and bad cholesterol.î
Anacetrapib will now be evaluated in a Phase III trial, Cannon said.
Acetylcysteine for Renoprotection: Acetylcysteine, commonly used to protect the kidneys from contrast dyes, does not work, according to data reported by Otavio Berwanger, MD, PhD, director of the Research Institute at the Hospital do CoraÁ„o in Sao Paulo, Brazil.
Among 2,308 patients seen in 46 centers in this South American country, acetylcysteine or placebo were administered before and after coronary arteriograms and angiography procedures in which contrast dyes were used. About 75% of patients were given the more protective low-osmolar dye. Iso-osmolar dye was used in about 3% of the patients.
Patients who received acetylcysteine had the same incidence of kidney damage, 13%, as those who took placebo.
The Brazilian researchers are planning a study of 4,800 patients that will explore the effectiveness of saline and bicarbonate for protecting kidneys during contrast-dye procedures.
Rivaroxaban in AF: Yet another new agent provides an alternative to warfarin, according to data presented in Chicago. Rivaroxaban produced significantly fewer strokes and emboli than did warfarin among 14,264 patients in the Stroke Prevention Using the Oral Direct Factor Xa Inhibitor Rivaroxaban Compared With Warfarin in Patients with Nonvalvular Atrial Fibrillation (ROCKET AF) trial. Major bleeding complications were similar in the two groups, with 3.60 and 3.45 events per 100 patient–years for rivaroxaban and warfarin, respectively.

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 © 2010, 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, 2010 * Special alert
Providing news and information about medications and their proper use

Propoxyphene is being withdrawn from the U.S. market, FDA just announced. Xanodyne Pharmaceuticals Inc., which makes Darvon and Darvocet, has agreed to withdraw the medication from the U.S. market at the request of the U.S. Food and Drug Administration. FDA has also informed generic manufacturers of Xanodyne's decision, and the agency says they will be removing their propoxyphene-containing products from the market as well.
More information is available on the
FDA website.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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. 22, 2010 * Vol. 17, No. 225
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 20 issue of Lancet (2010; 376).
Injections in Tendinopathy: Injections of corticosteroids and other agents help with lateral epicondylalgia (tennis elbow) and other forms of tendinopathy, a systematic review and meta-analysis of 41 clinical trials shows (pp. 1751–67). Steroids, sodium hyaluronate, botulinum toxin, and prolotherapy (injections that stimulate the body’s reparative systems) were studied: ìWe showed consistent findings between many high-quality randomised controlled trials that corticosteroid injections reduced pain in the short term compared with other interventions, but this effect was reversed at intermediate and long terms. For example, in pooled analysis of treatment for lateral epicondylalgia, corticosteroid injection had a large effect (defined as {standardised mean differences [SMDs]} > 0.8) on reduction of pain compared with no intervention in the short term (SMD 1.44, 95% CI 1.17–1.71, p < 0.0001), but no intervention was favoured at intermediate term (−0.40, −0.67 to −0.14, p < 0.003) and long term (−0.31, −0.61 to −0.01, p = 0.05). Short-term efficacy of corticosteroid injections for rotator-cuff tendinopathy is not clear. Of 991 participants who received corticosteroid injections in studies that reported adverse events, only one (0.1%) had a serious adverse event (tendon rupture). By comparison with placebo, reductions in pain were reported after injections of sodium hyaluronate (short [3.91, 3.54–4.28, p < 0.0001], intermediate [2.89, 2.58–3.20, p < 0.0001], and long [3.91, 3.55–4.28, p < 0.0001] terms), botulinum toxin (short term [1.23, 0.67–1.78, p < 0.0001]), and prolotherapy (intermediate term [2.62, 1.36–3.88, p < 0.0001]) for treatment of lateral epicondylalgia. Lauromacrogol (polidocanol), aprotinin, and platelet-rich plasma were not more efficacious than was placebo for Achilles tendinopathy, while prolotherapy was not more effective than was eccentric exercise.î (B. Vicenzino, b.vicenzino@uq.edu.au)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2010; 341).
Economics of Antiretroviral Therapy in Africa: While reductions in price of antiretroviral drugs have improved medication access in 13 African countries, future progress may depend more on foreign assistance and national public health expenditures, researchers conclude (c6218). A price index of first-line antiretroviral therapy showed: ìBetween 2003 and 2008 the annual price of first line antiretroviral therapy decreased from $1,177 (733 British pounds; 844 euros) to $96 and foreign assistance for HIV per capita increased from $0.4 to $13.8. At an annual price of $100, a $10 decrease was associated with a 0.16% adjusted increase in coverage (95% confidence interval 0.11% to 0.20%; 0.19% unadjusted, 0.14% to 0.24%). Each additional $1 per capita in foreign assistance for HIV was associated with a 1.0% adjusted increase in coverage (0.7% to 1.2%; 1.4% unadjusted, 1.1% to 1.6%). If the annual price of antiretroviral therapy stayed at $100, foreign assistance would need to quadruple to $64 per capita to be associated with universal coverage. Government effectiveness and national public health expenditures were also positively associated with increasing coverage.î (E. Bendavid, ebd@stanford.edu)

>>>PNN JournalWatch
* Is It Time to Move to Active Comparator Trials in Juvenile Idiopathic Arthritis?: A Review of Current Study Designs, in Arthritis & Rheumatism, 2010; 62: 3131–9. (N. Ruperto, nicolaruperto@ospedale-gaslini.ge.it)
* Chronic Macrolide Therapy in Inflammatory Airways Diseases, in
Chest, 2010; 138: 1202–12. (A. L. Friedlander, Adam.Friedlander@UCDenver.edu)
* Pathogenesis of Cholestatic Liver Disease and Therapeutic Approaches, in
Gastroenterology, 2010; 139: 1481–96. (M. E. Gershwin, megershwin@ucdavis.edu)
* A Computerized Provider Order Entry Intervention for Medication Safety During Acute Kidney Injury: A Quality Improvement Report, in
American Journal of Kidney Diseases, 2010; 56: 832–41. (A. B. McCoy, allison.mccoy@vanderbilt.edu)
* Small Is Beautiful: Insulin-Like Growth Factors and Their Role in Growth, Development, and Cancer, in
Journal of Clinical Oncology, 2010; 28: 4985–95. (R. G. Maki, makir@mskcc.org)
* Enzymatic Pathways in the Pathogenesis of Hereditary Angioedema: The Role of C1 Inhibitor Therapy, in
Journal of Allergy and Clinical Immunology, 2010; 126: 918–25. (A. P. Kaplan, kaplana@musc.edu)
* Closer Look at Autism and the Measles–Mumps–Rubella Vaccine, in
Journal of the American Pharmacists Association, 2010; 50: 736–41. (E. Hensley, emily.ann.hensley@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 © 2010, 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, 2010 * Vol. 17, No. 226
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release article from and Nov. 22 issue of the Archives of Internal Medicine (2010; 170).
ìTraining Patientsî in Cardiovascular Device Studies: Inclusion of data on the first individuals in whom physicians use investigational cardiovascular devices—termed ìtraining patientsî in the industry—would provide a more realistic look at safety and efficacy outcomes of the devices, authors maintain (doi: 10.1001/archinternmed.2010.445). Based on information abstracted from the Summary of Safety and Effectiveness Data for cardiovascular device premarket applications approved by the FDA from 2000 through 2007, investigators determined: ìThere were 78 cardiovascular device summaries in this 8-year period, of which 17 (22%) involved training patients. Of the 123 studies in the summaries, 20 (16%) used training patients. All studies excluded training patients from efficacy analyses and 19 of 20 (95%) excluded them from safety analyses. Sixteen of 20 (80%) did not provide any outcome data, and 15 of 20 (75%) did not check for outcome differences between training and nontraining treatment patients. Eighteen of 20 (90%) did not provide demographic information on training patients, and 14 of 20 (70%) did not prespecify guidelines for their enrollment.î
These findings led the authors to conclude: ìTraining patients comprise a considerable proportion of patients receiving investigational cardiovascular devices, but their results are excluded from FDA submissions. Their exclusion from analyses means that safety and efficacy outcomes may look better than actual results. Guidelines on the use and inclusion of results for training patients would improve accuracy on results reporting.î (R. F. Redberg,
redberg@medicine.ucsf.edu)
Metformin & Cardiovascular Conditions: Metformin, normally avoided in patients with cardiovascular disease, ìmay decrease mortality among patients with diabetes when used as a means of secondary prevention, including subsets of patients in whom metformin use is not now recommended,î an analysis concludes (pp. 1892–9). Among 19,691 patients with diabetes and established atherothrombosis who were in the Reduction of Atherothrombosis for Continued Health (REACH) Registry in 2003–04, these patterns were noted using a main outcome measure of 2-year mortality: ìThe mortality rates were 6.3% (95% confidence interval [CI], 5.2%–7.4%) with metformin and 9.8% (8.4%–11.2%) without metformin; the adjusted hazard ratio (HR) was 0.76 (0.65–0.89; P < .001). Association with lower mortality was consistent among subgroups, noticeably in patients with a history of congestive heart failure (HR, 0.69; 95% CI, 0.54–0.90; P = .006), patients older than 65 years (0.77; 0.62–0.95; P = .02), and patients with an estimated creatinine clearance of 30 to 60 mL/min/1.73 m2 (0.64; 95% CI, 0.48–0.86; P = .003) (to convert creatinine clearance to mL/s/m2, multiply by 0.0167).î (R. Roussel, ronan.roussel@bch.aphp.fr)
ED Visits for Anticlotting-Associated Bleeding: While the frequency of emergency department visits for bleeding is lower with dual antiplatelet therapy (DAT) than with warfarin, the risk is ìclinically significantî and should be recognized and anticipated by patients and practitioners, researchers report (pp. 1926–33). Adverse events (AEs) related to bleeding showed these rates in data from national databases in 2006–08 ìBased on 384 cases, there were an estimated 7,654 (95% confidence interval [CI], 3,325–11,983) ED visits annually for hemorrhage-related AEs from DAT compared with 2,926 cases and an estimated 60,575 (36,117–85,033) ED visits from warfarin. Approximately 60% of ED visits for DAT consisted of epistaxis or other minor hemorrhages (eg, bleeding from small cuts). The risk of hospitalization for ED visits involving acute hemorrhages was not significantly different between DAT and warfarin (risk ratio, 0.73; 95% CI, 0.38–1.08). The estimated rate of ED visits involving acute hemorrhages from DAT was 1.2 per 1,000 outpatient prescription visits vs 2.5 per 1,000 outpatient prescription visits for warfarin (risk ratio, 0.49; 95% CI, 0.15–0.83).î (N. Shehab, nshehab@cdc.gov)

>>>PNN NewsWatch
* The dietary supplement Vigor-25 contains undeclared sildenafil, FDA says, and should not be purchased or used. The Piston Corp. product is sold primarily on the Internet but possibly in some retail outlets, the agency notes.

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 © 2010, 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, 2010 * Vol. 17, No. 227
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 24 issue of JAMA (2010; 304).
Exercise & A1c in Diabetes: Both aerobic and resistance exercise are needed to improve hemoglobin A1c levels in patients with type 2 diabetes, researchers report, as either type of exercise alone does not work (pp. 2253–62). During a 9-month exercise program conducted in Louisiana, 262 sedentary men and women had these outcomes when they engaged in resistance training 3 days/wk, expended 12 kcal/kg/wk, or expended 10 kcal/kg/wk and engaged in resistance training 2 days/wk: ìThe study included 63.0% women and 47.3% nonwhite participants who were a mean (SD) age of 55.8 years (8.7 years) with a baseline HbA1c level of 7.7% (1.0%). Compared with the control group, the absolute mean change in HbA1c in the combination training exercise group was –0.34% (95% confidence interval [CI], –0.64% to –0.03%; P = .03). The mean changes in HbA1c were not statistically significant in either the resistance training (–0.16%; 95% CI, –0.46% to 0.15%; P = .32) or the aerobic (–0.24%; 95% CI, –0.55% to 0.07%; P = .14) groups compared with the control group. Only the combination exercise group improved maximum oxygen consumption (mean, 1.0 mL/kg per min; 95% CI, 0.5-1.5, P < .05) compared with the control group. All exercise groups reduced waist circumference from –1.9 to –2.8 cm compared with the control group. The resistance training group lost a mean of –1.4 kg fat mass (95% CI, –2.0 to –0.7 kg; P < .05) and combination training group lost a mean of –1.7 (–2.3 to –1.1 kg; P < .05) compared with the control group.î (T. S. Church, tim.church@pbrc.edu)
Supervision of exercise programs is an important and necessary element in interventions like these, editorialists write (
pp. 2298–9): ìThe results obtained in these trials may be better than what can be expected if patients attempt these interventions at home because prior studies of home-based resistance training did not demonstrate improved glycemic control. Likewise, supervised interventions tend to be more effective than unsupervised ones. This is a common theme for lifestyle interventions. Obesity is indeed treatable if supervised diet and exercise programs are provided at no cost to patients, whereas these types of interventions appear to be less successful when implemented by patients by themselves.î (R. J. Sigal, rsigal@ucalgary.ca)

>>>NEJM Highlights
Source:
Early-release articles from the New England Journal of Medicine (2010; 363).
Pre-exposure Chemoprophylaxis for HIV: Daily administration of emtricitabine and tenofovir disoproxil fumarate (FTC–TDF) is effective for preventing HIV infection in high-risk patients, report authors of an early-release article (10.1056/NEJMoa1011205). The study of 2,499 HIV-seronegative men or transgender women who have sex with men showed these results: ìThe study subjects were followed for 3,324 person–years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P < 0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P < 0.001). The two groups had similar rates of serious adverse events (P = 0.57).î (R. M. Grant, robert.grant@ucsf.edu)
An editorialist describes these potential risks with this approach (
10.1056/NEJMe1012929): ìThe risks of daily FTC–TDF use include the troubling development of secondary antiretroviral resistance in treated persons with undiagnosed acute HIV infection and a low but measurable degree of renal toxicity. Adherence to a daily regimen was low, nondurable, and difficult to assess without pharmacologic testing, which has substantial implications for research that uses this measure of behavior for medication compliance.î (N. L. Michael)

>>>PNN NewsWatch
* PNN will not published on these dates in the upcoming holiday season: Nov. 25–26, Thanksgiving; Dec. 24, Christmas Eve; Dec. 31, New Year’s Eve.

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 © 2010, 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. 29, 2010 * Vol. 17, No. 228
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 27 issue of Lancet (2010; 376).
Rivastigmine for ICU Delirium: Rivastigmine performed poorly in a trial of critically ill patients with delirium, failing to improve symptoms and possibly increasing mortality, researchers report (pp. 1829–37). The cholinesterase inhibitor was used in doses of 1.5 mg to 6 mg twice daily as an adjunct to haloperidol, with these results: ìAlthough a sample size of 440 patients was planned, after inclusion of 104 patients with delirium who were eligible for the intention-to-treat analysis (n = 54 on rivastigmine, n = 50 on placebo), the [data safety and monitoring board] recommended that the trial be halted because mortality in the rivastigmine group (n = 12, 22%) was higher than in the placebo group (n = 4, 8%; p = 0.07). Median duration of delirium was longer in the rivastigmine group (5.0 days, IQR 2.7–14.2) than in the placebo group (3.0 days, IQR 1.0–9.3; p = 0.06).î (A. J. C. Slooter, a.slooter-3@umcutrecht.nl)
Texting as Adherence Tool: Mobile phones can be used effectively for improving patient adherence to medications, shows a study of short message service (SMS) interventions (pp. 1838–45). Patients on antiretroviral therapy (ART) received weekly texts from a clinic nurse. They were required to respond within 48 hours. Compared with standard care, the SMS intervention produced these changes in self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months: ìAdherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0.81, 95% CI 0.69–0.94; p = 0.006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0.84, 95% CI 0.71–0.99; p = 0.04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5.0–29.5) and the NNT to achieve viral load suppression was 11 (5.8–227.3).î (R. T. Lester, rlester.id@gmail.com)

>>>NEJM Highlights
Source:
Nov. 25 issue of the New England Journal of Medicine (2010; 363).
Teratogenicity of PPIs: Used in early pregnancy, proton-pump inhibitors are not associated with increased risk of major birth defects, a study shows (pp. 2114–23). Analysis of national registries and prescription drug use in Denmark between 1996 and 2008 showed these results: ìAmong 840,968 live births, 5,082 involved exposure to PPIs between 4 weeks before conception and the end of the first trimester of pregnancy. There were 174 major birth defects in infants whose mothers had been exposed to PPIs during this period (3.4%), as compared with 21,811 in the group whose mothers had not been exposed (2.6%) (adjusted prevalence odds ratio, 1.23; 95% confidence interval [CI], 1.05 to 1.44). In analyses limited to exposure during the first trimester, there were 118 major birth defects among 3,651 infants exposed to PPIs (3.2%), and the adjusted prevalence odds ratio was 1.10 (95% CI, 0.91 to 1.34). The risk of birth defects was not significantly increased in secondary analyses of exposure to individual PPIs during the first trimester or in analyses limited to the offspring of women who had filled PPI prescriptions and received enough doses to have a theoretical chance of first-trimester exposure.î (B. Pasternak, bjp@ssi.dk)

>>>PNN JournalWatch
* Temporal Trends in Rates of Patient Harm Resulting from Medical Care, in New England Journal of Medicine, 2010; 363: 2124–34. (C. P. Landrigan, clandrigan@partners.org)
* At Pitney Bowes, Value-Based Insurance Design Cut Copayments and Increased Drug Adherence, in
Health Affairs, 2010; 29: 1995–2001. (N. K. Choudhry, nchoudhry@partners.org)
* Copayment Reductions Generate Greater Medication Adherence in Targeted Patients, in
Health Affairs, 2010; 29: 2002–8. (M. L. Maciejewski, mlm34@duke.edu)
* The Economic Burden of Late Entry into Medical Care for Patients with HIV Infection, in
Medical Care, 2010; 48: 1071–9. (J. A. Fleishman)
* Intensive Glucose Lowering and Cardiovascular Disease Prevention in Diabetes: Reconciling the Recent Clinical Trial Data, in
Circulation, 2010; 122: 2201–11. (T. Mazzone, tmazzone@uic.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 © 2010, 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, 2010 * Vol. 17, No. 229
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Dec. issue of Pharmacotherapy (2010; 30).
Efficacy of Influenza Vaccine: Given within 4 months of annual seasonal influenza outbreaks, influenza vaccine ìprovided substantial protection against clinically diagnosed influenza,î according to an analysis of cases in the United Kingdom General Practice Research Database during 1996–2007 (pp. 1199–206). In a case–control study, experiences of 4,985 low-risk patients under age 80 who had influenza or influenza-like symptoms were compared with 19,940 matched control patients who were also at low risk of influenza. ìVaccination conferred an important protective effect (OR 0.74, 95% CI 0.60–0.91) when given within 4 months before seasonal influenza outbreaks,î the authors write. ìThis effect was similar for each calendar year and across all ages.î (H. Jick, hjick@bu.edu)
Echinocandins Efficacy in Candidal Infections: Compared with other antifungal agents, echinocandins are effective for the treatment of candidemia or invasive candidiasis due to Candida parapsilosis, a meta-analysis shows (pp. 1207–13). Analysis of five randomized, blinded, comparative trials indicated: ìAmong the 1,169 patients with invasive candidiasis or candidemia, 202 (17.3%) had C. parapsilosis. Among these C. parapsilosis cases, 102 received an echinocandin and 100 received a comparator drug. The success rates of treating C. parapsilosis were similar for the echinocandin group versus other antifungal treatment groups (76.5% [78/102] vs 73% [73/100]). A fixed-effects model was applied secondary to a low level of heterogeneity among the studies (I2 = 0%). The combined risk ratio demonstrated that echinocandins are not significantly different from other antifungal agents for the treatment of candidemia or invasive candidiasis due to C. parapsilosis (risk ratio 1.03, 95% confidence interval 0.88–1.21).î (P. Kale–Pradhan, pkale@wayne.edu)

>>>Diabetes Highlights
Source:
Dec. issue of Diabetes Care (2010; 33).
Antidepressants & Diabetes: Patients on continuous antidepressant therapy have significantly higher risk of developing diabetes, according to data from the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS) (pp. 2549–51). Metformin therapy reduced this risk, the authors report, adding these details from a median of 10 years’ follow-up in the DPP and DPPOS: ìControlled for factors associated with diabetes risk, continuous antidepressant use compared with no use was associated with diabetes risk in the placebo (adjusted hazard ratio 2.34 [95% CI 1.32–4.15]) and lifestyle (2.48 [1.45–4.22]) arms, but not in the metformin arm (0.55 [0.25–1.19]).î (R. R. Rubin, dppmail@biostat.bsc.gwu.edu)
Acute Pancreatitis in Diabetes: Patients with type 2 diabetes may be at increased risk of pancreatitis, a study shows, and insulin may reduce this risk (pp. 2580–5). In a population-based case–control analysis nested in a cohort of 85,525 patients with type 2 diabetes and 200,000 diabetes-free individuals from the general population using data from The Health Improvement Network database, findings showed: ìWe identified 419 cases of acute pancreatitis, 243 in the general population and 176 in the diabetes cohort. Incidence rates were 30.1 and 54.0 per 100,000 person–years in the general population and the diabetes cohort, respectively. In the cohort analysis, the adjusted incidence rate ratio of acute pancreatitis in diabetic patients versus that in the general population was 1.77 (95% CI 1.46–2.15). The magnitude of this association decreased with adjustment for multiple factors in the nested case-control analysis (adjusted odds ratio 1.37 [95% CI 0.99–1.89]). Furthermore, we found that the risk of acute pancreatitis was decreased among insulin-treated diabetic patients (0.35 [0.20–0.61]).î (A. Gonzalez–Perez, agonzalez@ceife.es)

>>>PNN NewsWatch
* A new Institute of Medicine report released today calls for daily limits of 4,000 IUs of vitamin D and 2,000–2,500 mg of calcium. In recommendations supported by the American Society for Bone and Mineral Research, IOM says that most adults need 600–800 IUs of vitamin D daily and 1,000–1,200 mg of calcium daily. ìIt’s important for patients and clinicians to understand that excessive amounts of over 4,000 IUs of vitamin D or over 2,000-2,500 mg of calcium could have adverse health effects,î ASBMR stated.

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 © 2010, 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, 2010 * Vol. 17, No. 230
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release articles from and Dec. 1 issue of JAMA (2010; 304).
Consistency of OTC Pediatric Dosing Devices: When FDA in Nov. 2009 released voluntary guidelines to the industry intended to improve consistency and clarity of nonprescription pediatric oral liquid medication dosing directions and measuring devices, the ìtop-selling pediatric OTC liquid medications contained highly variable and inconsistent dosing directions and measuring devices,î researchers report (doi: 10.1001/jama.2010.1797). A descriptive study of 200 analgesic, cough/cold, allergy, and gastrointestinal OTC oral liquid products was conducted through Oct. 30, 2009. Analysis of labeling and accompanying measuring devices showed the following: ìMeasuring devices were packaged with 148 of 200 products (74.0%). Within this subset of 148 products, inconsistencies between the medication’s dosing directions and markings on the device were found in 146 cases (98.6%). These included missing markings (n = 36, 24.3%) and superfluous markings (n = 120, 81.1%). Across all products, 11 (5.5%) used atypical units of measurement (eg, drams, cc) for doses listed. Milliliter, teaspoon, and tablespoon units were used for doses in 143 (71.5%), 155 (77.5%), and 37 (18.5%) products, respectively. A nonstandard abbreviation for milliliter (not mL) was used by 97 products. Of the products that included an abbreviation, 163 did not define at least 1 abbreviation.î (H. S. Yin, yinh02@med.nyu.edu)
While an editorialist ignores possible roles of pharmacists in helping address this problem, the role of the physician in improving the ìdismountî—îthe handoff of responsibility from the health care system to the patientî—is outlined (
doi: 10.1001/jama.2010.1844): ìAs physicians, most of our time in medical education and professional development is focused on getting the diagnosis and treatment plan right. All that work is meaningless without the dismount, which, in medicine, requires enabling the patient to understand and act in ways that maximize health outcomes. Several facets of health care delivery are affected: hospital discharge (readmission), outpatient visits, filling prescriptions at the pharmacy, and selling nonprescription medications. All parts of the health care system are involved. The traditional approach has been to assume that the patient understood. That may have worked decades ago, but the past 20 years have witnessed a rapid escalation in the complexity of medical care and the requirements of the patient. At the same time, the skill base in the population has not expanded. Because of the multiple missed opportunities and consequent adverse events, accountability for patient outcomes such as hospital readmission has emerged. Some current leading efforts to improve transitions of care and prevention of readmission are focused on improving the dismount.î (D. A. DeWalt, dewaltd@med.unc.edu)
Outcomes-Based Health Care: ìMaintaining health rather than delivering health care per se should be the goalî of a health care system over the long-term, authors write in discussing the U.K. National Health Service (pp. 2407–8). Three ìserious shortcomings in the NHS’s current approach to measuring qualityî are instructive: the tendency to ìfocus on process and proxies, not on outcomes that matter to patients,î ìonly viewing the tip of the quality iceberg,î and focusing ìon snapshots, not on the whole pathway.î The authors add, ìMany health care institutions and clinicians object that their business only encompasses a small section of the whole pathway. Although this is true, it is also precisely why a more holistic way of measuring quality is needed. A high-value health system not only deals effectively and efficiently with acute stroke, but also reduces the incidence of stroke (through risk stratification, targeted management, patient education, and primary care) and is also concerned with rehabilitation and secondary prevention. Focusing on the acute phase risks optimizing 1 part of a continuum, and missing the opportunity for prevention, which can obviate the need for expensive ‘rescue’ care. By contrast, a whole-pathway quality measurement approach, focused on relevant outcomes, will promote working arrangements (and payment systems) better aligned with the core purpose of the health system—health, not health care.î (J. Mountford, james.mountford@uclpartners.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 © 2010, 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, 2010 * Vol. 17, No. 231
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 2 issue of the New England Journal of Medicine (2010; 363).
Adjuvant Docetaxel in Breast Cancer: Adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) improved the rate of disease-free survival among 1,060 women with high-risk, node-negative breast cancer, compared with adjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC), a study shows (pp. 2200–10). Patients received one of the two regimens every 3 weeks for 6 cycles after surgery. These results were reported using a primary end point of disease-free survival after at least 5 years of follow-up: ìAt a median follow-up of 77 months, the proportion of patients alive and disease-free was higher among the 539 women in the TAC group (87.8%) than among the 521 women in the FAC group (81.8%), representing a 32% reduction in the risk of recurrence with TAC (hazard ratio, 0.68; 95% confidence interval [CI], 0.49 to 0.93; P = 0.01 by the log-rank test). This benefit was consistent, regardless of hormone-receptor status, menopausal status, or number of high-risk factors. The difference in survival rates (TAC, 95.2%; FAC, 93.5%) was not significant (hazard ratio, 0.76; 95% CI, 0.45 to 1.26); however, the number of events was small (TAC, 26; FAC, 34). Rates of grade 3 or 4 adverse events were 28.2% with TAC and 17.0% with FAC (P < 0.001). Toxicity associated with TAC was diminished when primary prophylaxis with granulocyte colony-stimulating factor was provided.î (M. MartÌn, mmartin@geicam.org)
BMI & Mortality: Fat kills, and being underweight might too, according to a study of body mass index values in 1.46 million white adults (pp. 2211–9). Using pooled data from 19 prospective studies, researchers found these associations between BMI and all-cause mortality: ìThe median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up.î (A. Berrington de Gonzalez, berringtona@mail.nih.gov)
FDA Status Report: In the Shattuck Lecture, the Commissioner of Food and Drugs assesses the status of innovation and regulation at FDA (pp. 2228–32). After reviewing the history of the agency and legal challenges to FDA’s authority, the Commissioner discusses the possibility of peer review as a supplement to premarket review of new therapeutic products and provides this assessment of regulatory science and innovation at the agency: ìTo truly leverage advances in science and technology, there must be a collaboration of all relevant stakeholders, including government, academia, and industry. The FDA must work with its partners to promote innovation and creativity at various points throughout the development process. For example, instead of simply waiting at the end of the pipeline to approve or reject a product, the FDA can help make clinical trials more efficient by identifying qualifying biomarkers that accurately predict outcomes and by encouraging investigators to use innovative trial designs that are as effective as standard designs but less burdensome and time-consuming. And instead of accepting that the only way to test for drug safety is to expose cadres of patients to new products, the FDA can help develop innovative assays for safety that can better predict toxic effects in the liver and kidney early on. The FDA can become more transparent, so that knowledge and insights can be shared and the field of drug discovery can move forward more quickly.î (M. A. Hamburg, margaret.hamburg@fda.hhs.gov)
Challenges with Pandemic Influenza: Authors discuss the need for faster production of influenza vaccine during pandemics and better ways of getting people to take the vaccines once they are produced (pp. 2183–5; K. M. Harris).

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 © 2010, 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, 2010 * Vol. 17, No. 232
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
Dec. issue of Pediatrics (2010; 126).
Acetaminophen & Liver Injury: Used in therapeutic doses in children, acetaminophen ìis not associated with liver injury,î authors report (e1430–44). A review of studies in which acetaminophen was used in doses of 75 mg/kg/day orally or intravenously or less, or of 100 mg/kg/day rectally or less, and case reports of liver injury after administration of therapeutic doses of the drug revealed the following: ìA total of 62 studies that enrolled 32,414 children were included. No child (0% [95% confidence interval: 0.000–0.009]) was reported to have exhibited signs or symptoms of liver disease, to have received an antidote or transplantation, or to have died. Major or minor hepatic [adverse events] were reported for 10 children (0.031% [95% confidence interval: 0.015–0.057]). The highest transaminase value reported was 600 IU/L. Naranjo scores (2–3) suggested ‘possible’ causation. Twenty-two case reports were identified. In 9 cases, the Naranjo score suggested ‘probable’ causation (5–6).î (E. J. Lavonas)
Medication Adverse Events Following Market Withdrawal: After market withdrawal of oral infant cough and cold medications (CCMs) in Oct. 2007, emergency department (ED) visits for CCM-related adverse events (AEs) fell significantly, according to a CDC analysis (pp. 1100–7). In a probabilistic sample of 63 U.S. EDs, the number of pediatric visits for CCM-related AEs showed these patterns in the 14 months before and after the market withdrawal: ìAfter withdrawal, the number and proportion of estimated ED visits for CCM-related AEs involving children <2 years of age were less than one-half of those in the prewithdrawal period (1,248 visits [13.3%] vs 2,790 visits [28.7%]; difference: –15.4% [95% confidence interval [CI]: –25.9% to –5.0%]), whereas the overall number of estimated ED visits for CCM-related AEs for children <12 years of age remained unchanged (9,408 visits [95% CI: 6,874–11,941 visits] vs 9,727 visits [95% CI: 6,649–12,805 visits]). During both periods, two-thirds of estimated ED visits involved unsupervised ingestions (ie, children finding and ingesting medications).î
The authors conclude: ìFurther reductions [in CCM-related AEs] likely will require packaging improvements to reduce harm from unsupervised ingestions and continued education about avoiding CCM use for young children. Monitoring of CCM-related harm should continue because recommendations were updated in October 2008 to avoid the use of CCMs for children <4 years of age.î (N. Shehab)

>>>Infectious Disease Report
Source:
Dec. 15 issue of Clinical Infectious Diseases (2010; 51).
Influenza Vaccine in Pregnancy: Infants whose mothers received influenza vaccine during pregnancy have fewer hospitalizations for influenza during their first 6 months of life, according to a case–control study at one hospital from 2000 to 2009 (pp. 1355–61). The authors calculated a vaccine effectiveness of 91.5%, as discussed here: ìThe mothers of 2 (2.2%) of 91 case subjects and 31 (19.9%) of 156 control subjects aged <6 months, and 1 (4.6%) of 22 case subjects and 2 (5.6%) of 36 control subjects aged 6 months, had received influenza vaccine during pregnancy. The effectiveness of influenza vaccine given to mothers during pregnancy in preventing hospitalization among their infants, adjusted for potential confounders, was 91.5% (95% confidence interval [CI], 61.7%–98.1%; P = .001) for infants aged <6 months. The unadjusted effectiveness was 90.7% (95% CI, 59.9%–97.8%; P = .001).î (M. V·zquez, marietta.vazquez@yale.edu)
Posaconazole for Chronic Pulmonary Aspergillosis: Retrospective analysis of 79 patients supports safety and partial effectiveness of posaconazole in treatment of chronic pulmonary aspergillosis (CPA) (pp. 1383–91): ìResponse to posaconazole was observed in 61% of patients at 6 months and in 46% at 12 months. Kaplan–Meier plots showed that the first response to posaconazole was observed in some patients only after approximately 1 year of therapy.Ö Adverse reactions were observed in 12 patients (15%) (nausea in 5, rash in 5, headache in 1, and lethargy in 1), leading to withdrawal of treatment for 9 patients.î Among 22 patients with cultured Aspergillus, treatment failed in all 4 patients whose pathogens had high minimum inhibitory posaconazole concentrations. (T. Felton, timothy.felton@manchester.ac.uk)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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. 6, 2010 * Vol. 17, No. 233
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 4 issue of Lancet (2010; 376).
Long-term Statin Therapy & Abnormal Liver Tests: In patients with mild-to-moderate changes in liver tests that may be caused by nonalcoholic fatty liver disease, continued statin therapy is safe, reduces mortality from coronary heart disease, and can potentially improve liver tests, report researchers from the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) study (pp. 1916–22). Post-hoc analysis of a random sample of 1,600 patients showed these results: ìOf 437 patients with moderately abnormal liver tests at baseline, which were possibly associated with non-alcoholic fatty liver disease, 227 who were treated with a statin (mainly atorvastatin 24 mg per day) had substantial improvement in liver tests (p < 0.0001) whereas 210 not treated with a statin had further increases of liver enzyme concentrations. Cardiovascular events occurred in 22 (10%) of 227 patients with abnormal liver tests who received statin (3.2 events per 100 patient–years) and 63 (30%) of 210 patients with abnormal liver tests who did not receive statin (10.0 events per 100 patient–years; 68% relative risk reduction, p < 0.0001). This cardiovascular disease benefit was greater (p = 0.0074) than it was in patients with normal liver tests (90 [14%] events in 653 patients receiving a statin [4.6 per 100 patient–years] vs 117 [23%] in 510 patients not receiving a statin [7.6 per 100 patient–years]; 39% relative risk reduction, p < 0.0001). Seven (<1%) of 880 participants who received a statin discontinued statin treatment because of liver-related adverse effects (transaminase concentrations more than three-times the upper limit of normal).î (D. P. Mikhailidis, mikhailidis@aol.com)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2010; 341).
Smokeless Tobacco & Varenicline: In patients using smokeless tobacco, varenicline was effective and had an acceptable safety profile, a study shows, and a high placebo response rate indicated that these users might be less resistant to treatment than smokers (c6549). In 413 patients treated for 12 weeks and followed for 14 weeks thereafter, these results were recorded: ìContinuous abstinence rate at week 9–12 was higher in the varenicline group than the placebo group (59% (125) v 39% (85); relative risk 1.60, 95% confidence interval 1.32 to 1.87, P < 0.001; risk difference 20%; number needed to treat 5). The advantage of varenicline over placebo persisted through 14 weeks of follow-up (continuous abstinence rate at week 9–26 was 45% (95) v 34% (73); relative risk 1.42, 1.08 to 1.79, P = 0.012; risk difference 11%; number needed to treat 9). The most common adverse events in the varenicline group compared with the placebo group were nausea (35% (74) v 6% (14)), fatigue (10% (22) v 7% (15)), headache (10% (22) v 9% (20)), and sleep disorder (10% (22) v 7% (15)). Few adverse events led to discontinuation of treatment (9% (19) and 4% (9), respectively), and serious adverse events occurred in two (1%) and three (1%) participants, respectively.î (K. Fagerstrˆm, Karl.fagerstrom@swipnet.se)
Teratogenicity of Carbamazepine: Spina bifida is the major congenital malformation associated with use of carbamazepine during pregnancy, and then the incidence is lower than with valproic acid, according to a systematic review of 8 studies and a case–control analysis (c6581): ìSpina bifida was the only specific major congenital malformation significantly associated with exposure to carbamazepine monotherapy (odds ratio 2.6 (95% confidence interval 1.2 to 5.3) compared with no antiepileptic drug), but the risk was smaller for carbamazepine than for valproic acid (0.2, 0.1 to 0.6). There was no evidence for an association with total anomalous pulmonary venous return (no cases with carbamazepine exposure), cleft lip (with or without palate) (0.2, 0.0 to 1.3), diaphragmatic hernia (0.9, 0.1 to 6.6), or hypospadias (0.7, 0.3 to 1.6) compared with no exposure to antiepileptic drugs.î (L. de Jong-van den Berg, l.t.w.de.jong-van.den.berg@rug.nl)

>>>PNN JournalWatch
* Health Professionals for a New Century: Transforming Education to Strengthen Health Systems in an Interdependent World, in Lancet, 2010; 376: 1923–58. (J. Frenk, jfrenk@hsph.harvard.edu)
* Probiotics and Prebiotics in Pediatrics, in
Pediatrics, 2010; 126: 1217–31. (D. W. Thomas)

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 © 2010, 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, 2010 * Vol. 17, No. 234
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from and Dec. 7 issue of the Annals of Internal Medicine (2010; 153).
Twice-Daily Exenatide with Basal Insulin: In 261 patients with uncontrolled type 2 diabetes who were on basal insulin glargine, twice-daily exenatide improved glycemic control without hypoglycemia or weight gain, a study shows (early release). At 59 centers in five countries, patients were started on twice-daily exenatide 10 mcg injections or placebo for 30 weeks, with these results: ìThe HbA1c level decreased by 1.74% with exenatide and 1.04% with placebo (between-group difference, −0.69% [95% CI, −0.93% to −0.46%]; P < 0.001). Weight decreased by 1.8 kg with exenatide and increased by 1.0 kg with placebo (between-group difference, −2.7 kg [CI, −3.7 to −1.7]). Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d. The estimated rate of minor hypoglycemia was similar between groups. Thirteen exenatide recipients and 1 placebo recipient discontinued the study because of adverse events (P < 0.010); rates of nausea (41% vs. 8%), diarrhea (18% vs. 8%), vomiting (18% vs. 4%), headache (14% vs. 4%), and constipation (10% vs. 2%) were higher with exenatide than with placebo.î (J. B. Buse, jbuse@med.unc.edu)
Achieving Universal Health Coverage in U.S.: Asking whether universal health coverage is ìslip, slidin’ awayî in the U.S., an author from the American College of Physicians discusses the polarized environment regarding health care reform and calls on Congress to ìseek a bipartisan accord on improving the lawî so that the opportunity to improve access for Americans is not lost (early release): ìThis debate is occurring even as the United States faces an unprecedented crisis in access to health insurance coverage, affecting nearly every demographic group, yet the uninsured have largely become an afterthought. Medical professionalism requires a commitment to improving access to care, and physicians could play a crucial role in informing lawmakers that providing all Americans with affordable health care coverage is a moral and medical imperative to prevent needless suffering and death, and must not be allowed to slip away.î (R. B. Doherty)
First-Line Prevention of AF: In a study that explores the ongoing controversy over the relative effects of beta-blockers and amiodarone for first-line prevention of atrial fibrillation, researchers found similar rates of AF in patients on each drug (pp. 703–9). However, statistical tests did not ensure equivalence, the group reports, adding these details for 316 consecutive patients who were hemodynamically stable and free of mechanical ventilation and AF within 24 hours after cardiac surgery: ìAtrial fibrillation occurred in 38 of 159 (23.9%) patients in the metoprolol group and 39 of 157 (24.8%) patients in the amiodarone group (P = 0.85). However, the difference (−0.9 percentage point [90% CI, −8.9 to 7.0 percentage points]) does not meet the prespecified equivalence margin of 5 percentage points. The adjusted hazard ratio of the metoprolol group compared with the amiodarone group was 1.09 (95% CI, 0.67 to 1.76).î (J. Halonen, jari.halonen@kuh.fi)
BNP Testing in HF: Testing of patients with acute dyspnea for B-type natriuretic peptide (BNP) in the emergency department reduces length of hospital stay by 1 day and may lower admission rates, but hospital mortality rates are not ìconclusively affected,î write investigators who conducted a meta-analysis (pp. 728–35): ìFive trials conducted in 5 countries and involving 2,513 patients met inclusion criteria. Study settings had differing emergency department staffing models and used various BNP testing protocols. The pooled estimate of effect of BNP testing on all-cause mortality had wide confidence bounds and was inconclusive (odds ratio, 0.96 [95% CI, 0.65 to 1.41]). Admission rates decreased in the tested group compared with the control group (odds ratio, 0.82 [CI, 0.67 to 1.01]), although this finding was not statistically significant. Length of hospital and critical care unit stay were both modestly reduced in the tested group compared with the control group, with a mean difference of −1.22 days (CI, −2.31 to −0.14 day) and −0.56 day (CI, −1.06 to −0.05 day), respectively.î (L. L. Lam, louisa.lam@monash.edu)

>>>PNN NewsWatch
* Videos from the ASHP Midyear Clinical Meeting, now under way in Anaheim, CA, are available at www.ashptv.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 © 2010, 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, 2010 * Vol. 17, No. 235
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 8 issue of JAMA (2010; 304).
Tobacco Cessation in Mental Health Care: Abstinence was longer among smokers with military-related posttraumatic stress disorder (PTSD) when tobacco cessation interventions were incorporated into mental health care, compared with referral to VA smoking cessation clinics (SCCs), researchers report (pp. 2485–93). At 10 VA medical centers in 2004–09, 943 smokers were recruited for the study, which used 12-month bioverified prolonged abstinence as its primary outcome. Results showed: ìIntegrated care was better than SCC on prolonged abstinence (8.9% vs 4.5%; adjusted odds ratio, 2.26; 95% confidence interval [CI], 1.30–3.91; P = .004). Differences between IC vs SCC were largest at 6 months for 7-day point prevalence abstinence (78/472 [16.5%] vs 34/471 [7.2%], P < .001) and remained significant at 18 months (86/472 [18.2%] vs 51/471 [10.8%], P < .001). Number of counseling sessions received and days of cessation medication used explained 39.1% of the treatment effect. Between baseline and 18 months, psychiatric status did not differ between treatment conditions. Posttraumatic stress disorder symptoms for quitters and nonquitters improved. Nonquitters worsened slightly on the Patient Health Questionnaire 9 relative to quitters (differences ranged between 0.4 and 2.1, P = .03), whose scores did not change over time.î (M. McFall, miles.mcfall@va.gov)
Integrated smoking cessation services should be explored further, writes an editorialist (
pp. 2534–5): ìThis multisite trial, with the advantages of large sample size and enhanced external validity, represents a significant advance in the evidence base on the effectiveness of treating tobacco dependence in smokers with mental disorders and integration of tobacco treatment services into mental health care settings. Critically, integrated care treatments are needed to reverse the clinical practices that have served to maintain the high rates of tobacco use and tobacco-related morbidity and mortality among individuals with mental illness. Future study needs include application in broader community mental health care settings and diagnostic patient groups. The study by McFall et al represents a major step forward on the path to abating the previously overlooked epidemic of tobacco dependence that has plagued persons with mental illness.î (J. J. Prochaska, jprochaska@ucsf.edu)
Occult Blood Tests & Low-Dose Aspirin: A pair of immunochemical fecal occult blood tests (iFOBTs) had a ìmarkedly higher sensitivityî in detection of advanced colorectal neoplasms when patients were taking low-dose aspirin, a study shows, and specificity declined only slightly (pp. 2513–20). iFOBTs are preferred over guaiac-based FOBTs because they are less likely to produce false-positive results in patients taking low-dose aspirin, the authors note. In 1,979 patients, including 233 regular users of low-dose aspirin, the group found these results of iFOBTs in 2005–09: ìAdvanced neoplasms were found in 24 users (10.3%) and 181 nonusers (10.4%) of low-dose aspirin. At the cut point recommended by the manufacturer, sensitivities of the 2 tests were 70.8% (95% confidence interval [CI], 48.9%–87.4%) for users compared with 35.9% (95% CI, 28.9%–43.4%) for nonusers and 58.3% (95% CI, 36.6%–77.9%) for users compared with 32.0% (95% CI, 25.3%–39.4%) for nonusers (P = .001 and P = .01, respectively). Specificities were 85.7% (95% CI, 80.2%–90.1%) for users compared with 89.2% (95% CI, 87.6%–90.7%) for nonusers and 85.7% (95% CI, 80.2%–90.1%) for users compared with 91.1% (95% CI, 89.5%–92.4%) for nonusers (P = .13 and P = .01, respectively). The areas under the [receiver operating characteristic (ROC)] curve were 0.79 (95% CI, 0.68–0.90) for users compared with 0.67 (95% CI, 0.62–0.71) for nonusers and 0.73 (95% CI, 0.62–0.85) for users compared with 0.65 (95% CI, 0.61–0.69) for nonusers (P = .05 and P = .17, respectively). Among men, who composed the majority of low-dose aspirin users, the areas under the ROC curve were 0.87 (95% CI, 0.76–0.98) for users compared with 0.68 (95% CI, 0.63–0.74) for nonusers and 0.81 (95% CI, 0.68–0.93) for users compared with 0.67 (95% CI, 0.61–0.72) for nonusers (P = .003 and P = .04, respectively).î (H. Brenner, h.brenner@dkfz.de)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 236
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release article from and Dec. 9 issue of the New England Journal of Medicine (2010; 363).
Neonatal Abstinence Syndrome After Methadone or Buprenorphine Exposure: Buprenorphine is an acceptable alternative to methadone in pregnant women, a study shows, one that avoids the neonatal abstinence syndrome (NAS) that follows methadone exposure (pp. 2320–31). In a study of 175 pregnant women, primary outcomes—the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference—showed these patterns: ìTreatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P < 0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P < 0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P < 0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events.î (H. E. Jones, hjones18@jhmi.edu)
Genomics, Diabetes, & Obesity: The value of recent genetic advances regarding common diseases is probably being underestimated, but expansion of personalized-medicine approaches to care remains years away, according to the author of a review article on type 2 diabetes and obesity (pp. 2339–50): ìAs yet, there are insufficient genetic data to support management decisions for common forms of type 2 diabetes and obesity. Although the TCF7L2 genotype is associated with variation in the response to sulfonylurea treatment, the effect is too modest to guide the care of individual patients. For the time being, the contribution of genetic information to therapy is most likely to come through the drug-discovery pipeline. Information from genetic studies could be used to identify new targets for pharmaceutical intervention that have validated effects on physiological characteristics, to provide information about new and existing targets (e.g., clues about the long-term safety of pathway intervention), and to characterize high-risk groups to enable more efficient clinical trials of agents designed to reduce the progression of type 2 diabetes or obesity or the risk of complications.î (M. I. McCarthy)
The Next Congress & Health Care Reform: Change in the way health care reform is implemented will likely come from the states, not Washington, according to an analysis of the 112th Congress (10.1056/NEJMp1012299). The writer adds this bottom-line assessment of rhetoric versus reality: ìDespite the talk of repeal, Congress will not pass any major health legislation over the next 2 years, and the health sector and private employers will be hard at work preparing for 2014, when many ACA provisions take effect. That does not make health care reform a fait accompli. Absent a miracle, the country will still face crushing budget deficits when the next president takes office. A Republican president, backed by a Republican Congress, would be wise to delay enrollment in the health insurance exchanges, using the time and money to develop a more targeted plan that closes off open-ended subsidies for health insurance and gets the economic incentives right. A Democratic president would do the same thing out of necessity—but it would take longer.î (J. R. Antos)

>>>PNN NewsWatch
* Testimony has concluded at a hearing in the case of the Oklahoma City pharmacist accused of murdering a robber, KFOR is reporting. But the judge in the case of Jerome Ersland is the one under scrutiny now, accused of making racist remarks. Other motions, including one to recuse the district attorney, will likely further delay the murder trial itself.
* Two students from
U. California, San Francisco—winners in ASHP’s Clinical Skills Competition—are interviewed in ashptv.org video reports from the Midyear Clinical Meeting in Anaheim.

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 © 2010, 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, 2010 * Vol. 17, No. 237
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Dec. 14/21 issue of the Journal of the American College of Cardiology (2010; 56).
Anticoagulants for Stroke Prevention in AF: The potential for dabigatran and other direct-acting oral anticoagulant drugs to replace agents such as warfarin in patients with atrial fibrillation (AF) is examined in a review article (pp. 2067–76): ìAntithrombotic therapy using aspirin or vitamin K antagonists (VKA) is currently prescribed for prevention [of] ischemic stroke in patients with AF. A narrow therapeutic range and the need [for] regular monitoring of its anticoagulatory effect impair effectiveness and safety of VKA, causing a need for alternative anticoagulant drugs. Recently developed anticoagulants include direct thrombin antagonists such as dabigatran or factor Xa inhibitors such as rivaroxaban, apixaban, betrixaban, and edoxaban. Currently, data from a phase III clinical trial are available for dabigatran only, which show the direct thrombin antagonist to be at least noninferior in efficacy to VKA for the prevention of stroke and systemic embolism in patients with AF.î (S. H. Schirmer, Stephan.Schirmer@uks.eu)
Smoking Cessation in Peripheral Artery Disease: Long-term smokers with peripheral artery disease (PAD) are good candidates for intensive cessation efforts, researchers report (pp. 2105–12). In outpatients with lower-extremity PAD who were identified in medical records as smokers, investigators implemented an intensive tailored PAD-specific counseling intervention or minimal intervention, with these results: ìIn all, 687 outpatients were identified as probable smokers with lower extremity PAD; 232 met study eligibility requirements; and 124 (53% of eligible) enrolled. Participants were receptive to counselor contact: the median number of sessions was 8.5 (range 0 to 18). Participants randomly assigned to the intensive intervention group were significantly more likely to be confirmed abstinent at 6-month follow-up: 21.3% versus 6.8% in the minimal intervention group (chi-square = 5.21, p = 0.023).î (D. Hennrikus, hennr001@umn.edu)
Editorialists suggest supplementary efforts to enhance the effects of intensive counseling and to differentiate among patient types (
pp. 2113–4): ìGiven the logistical and financial difficulties in creating an intensive program in practice, exploring other interventions such as social media and on-line programs to supplement face-to-face counseling is warranted. In addition, providing pharmacologic products free or at reduced cost is likely to assist in quit rates. These aspects of smoking cessation programs have to be addressed before the widespread translation of intensive intervention to the community. Among populations such as patients with PAD, the high rates of cardiovascular disease and the resulting morbidity and mortality suggest the worth of continued research in the area of smoking cessation. However, our idea that one size fits all is both naÔve and also biologically implausible.î (K. A. Eagle, keagle@umich.edu)

>>>Nephrology Report
Source:
Dec. issue of the American Journal of Kidney Diseases (2010; 56).
Cost-Effectiveness of ESAs: In one of three articles in this issue of AJKD on costs of drugs, authors calculate a high cost-effectiveness figure for use of erythropoiesis-stimulating agents (ESAs) in patients with chronic kidney disease (pp. 1050–61). Using a decision-analysis model and the perspective of the payer, these costs per quality-adjusted life–year (QALY) were identified over a patient’s lifetime: ìFor dialysis patients, compared with anemia management without ESAs, using ESAs to target a low hemoglobin level is associated with a cost per QALY of $96,270. Given a lack of direct trials comparing low and intermediate targets, significant uncertainty exists between these strategies. Treatment to a high hemoglobin target was always associated with worse clinical outcomes and higher costs compared with a low hemoglobin target. Results were similar in non–dialysis-dependent patients with CKD, with a cost per QALY for a low target compared with no ESA of $147,980.î (B. J. Manns, braden.manns@albertahealthservices.ca)

>>>PNN NewsWatch
* The rapid expansion in pharmacy schools could be affecting the quality of pharmacy education, APhA and ASHP argue in a white paper released this week. Lack of faculty and preceptors are two of the identified problems.

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 © 2010, 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. 13, 2010 * Vol. 17, No. 238
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 11 issue of Lancet (2010; 376).
Zoledronate in Multiple Myeloma: The bisphosphonate zoledronic acid should be used for ìimmediate treatment Ö in patients with newly diagnosed multiple myeloma, not only for prevention of skeletal-related events, but also for potential antimyeloma benefits,î according to investigators with the Medical Research Council Myeloma IX trial (pp. 1989–99). Used in comparison with clodronic acid 1600 mg daily, zoledronic acid 4 mg infused every 3–4 weeks produced these effects in 1,970 patients over a median of 3.7 years: ìZoledronic acid reduced mortality by 16% (95% CI 4–26) versus clodronic acid (hazard ratio [HR] 0.84, 95% CI 0.74–0.96; p = 0.0118), and extended median overall survival by 5.5 months (50.0 months, IQR 21.0 to not reached vs 44.5 months, IQR 16.5 to not reached; p = 0.04). Zoledronic acid also significantly improved progression-free survival by 12% (95% CI 2–20) versus clodronic acid (HR 0.88, 95% CI 0.80–0.98; p = 0.0179), and increased median progression-free survival by 2.0 months (19.5 months, IQR 9.0–38.0 vs 17.5 months, IQR 8.5–34.0; p = 0.07). Rates of complete, very good partial, or partial response did not differ significantly between the zoledronic acid and clodronic acid groups for patients receiving intensive induction chemotherapy (432 patients [78%] vs 422 [76%]; p = 0.43) or non-intensive induction chemotherapy (215 [50%] vs 195 [46%]; p = 0.18). Both bisphosphonates were generally well tolerated, with similar occurrence of acute renal failure and treatment-emergent serious adverse events, but zoledronic acid was associated with higher rates of confirmed osteonecrosis of the jaw (35 [4%]) than was clodronic acid (3 [<1%]).î (G. J Morgan, gareth.morgan@icr.ac.uk)
Predicting Chemotherapy Outcomes in Acute Myeloid Leukemia: A Web-based risk-assessment tool, used before intensive chemotherapy, predicts accurately the likelihood of a complete response (CR) or early death (ED) in patients with acute myeloid leukemia, a study shows (pp. 2000–8). Among 1,406 patients aged 60 years or older in the German Acute Myeloid Leukaemia Cooperative Group 1999 study, the tool provided these risk predictions: ìBody temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2, from 7% to 61%).î (U. Krug, utz.krug@ukmuenster.de)

>>>PNN JournalWatch
* Effect of Mitoxantrone on Outcome of Children with First Relapse of Acute Lymphoblastic Leukaemia (ALL R3): An Open-Label Randomised Trial, in Lancet, 2010; 376: 2009–17. (V. Saha, vaskar.saha@manchester.ac.uk)
* Denosumab Compared with Zoledronic Acid for the Treatment of Bone Metastases in Patients with Advanced Breast Cancer: A Randomized, Double-Blind Study, in
Journal of Clinical Oncology, 2010; 28: 5132–9. (A. T. Stopeck, astopeck@azcc.arizona.edu)
* Clinical Implications of the Cancer Genome, in
Journal of Clinical Oncology, 2010; 28: 5219–28. (L. A.Garraway, Levi_Garraway@dfci.harvard.edu)
* Genetics and Clinical Destiny: Improving Care in Hypertrophic Cardiomyopathy, in
Circulation, 2010; 122: 2430–40. (C. Y. Ho)
* Management of Pneumonia in the Nursing Home, in
Chest, 2010; 138: 1480–5. (A. El-Solh, solh@buffalo.edu)
* Juvenile Idiopathic Arthritis and Risk of Cancer: A Nationwide Cohort Study, in
Arthritis & Rheumatism, 2010; 62: 3776–82. (J. F. Simard, julia.simard@post.harvard.edu)
* Personalized Medicine for Depression: Can We Match Patients With Treatments?, in
American Journal of Psychiatry, 2010; 167: 1445–55. (G. E. Simon)
* The Role of the T Cell in Asthma, in
Journal of Allergy and Clinical Immunology, 2010; 126: 1081–91. (D. S. Robinson, dsrobinson@leti.com)
* Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report, in
Journal of Allergy and Clinical Immunology, 2010; 126: 1105–18.

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 © 2010, 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, 2010 * Vol. 17, No. 239
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Dec. 13/27 issue of the Archives of Internal Medicine (2010; 170).
Safety of Analgesics in Arthritis: Among older adults with arthritis, nonselective NSAIDs (nsNSAIDs) provide the best margin of safety, according to an analysis of analgesic use by Medicare beneficiaries in Pennsylvania and New Jersey (pp. 1968–78). Between 1999 and 2005, the risk of adverse events related to analgesic use were as follows in matched groups of patients, mostly women (85%), with a mean age of 80.0 years: ìCompared with nsNSAIDs, coxibs (HR, 1.28; 95% confidence interval [CI], 1.01–1.62) and opioids (1.77; 1.39–2.24) exhibited elevated relative risk for cardiovascular events. Gastrointestinal tract bleeding risk was reduced for coxib users (HR, 0.60; 95% CI, 0.35–1.00) but was similar for opioid users. Use of coxibs and nsNSAIDs resulted in a similar risk for fracture; however, fracture risk was elevated with opioid use (HR, 4.47; 95% CI, 3.12–6.41). Use of opioids (HR, 1.68; 95% CI, 1.37–2.07) but not coxibs was associated with an increased risk for safety events requiring hospitalization compared with use of nsNSAIDs. In addition, use of opioids (HR, 1.87; 95 CI, 1.39–2.53) but not coxibs raised the risk of all-cause mortality compared with use of nsNSAIDs.î (D. H. Solomon, dsolomon@partners.org)
The author of an invited commentary focuses on rheumatoid arthritis as an example of a painful condition whose underlying cause should be treated first, not second (
pp. 1976–8): ìAlthough controlling pain is of paramount importance, one must not forget to effectively treat any underlying condition responsible for the pain. For example, the study by Solomon and colleagues included patients with RA, who made up more than 9% of the group of patients receiving opioids. According to guidelines published by the American College of Rheumatology, analgesic and anti-inflammatory medications (including nsNSAIDs, acetaminophen, and opioids) may reduce pain and swelling but do not alter the course of disease and thus should not be used as a sole treatment for RA. More effective control of RA-related symptoms and prevention of future pain and disability are achieved when a diagnosis of RA is made as early as possible and treatment is initiated with a conventional disease-modifying antirheumatic drug. Unfortunately, this is not always the case in clinical practice, where delays in diagnosis are common and patients continue to be referred to rheumatologists only after RA has been inadequately controlled with analgesic medications alone.î (J. Graf)
Safety of Opioids in Nonmalignant Pain: Opioids differ in their relative safety when used in older adults, the investigators from the above study conclude in a second article (pp. 1979–86). Using propensity-matched cohort analysis for Medicare patients in two states during 1996–2005, the researchers found these patterns when various opioids were started: ìThe risk of cardiovascular events was similar across opioid groups 30 days after the start of opioid therapy, but it was elevated for codeine (RR, 1.62; 95% CI, 1.27–2.06) after 180 days. Compared with hydrocodone, after 30 days of opioid exposure the risk of fracture was significantly reduced for tramadol (RR, 0.21; 95% CI, 0.16–0.28) and propoxyphene (0.54; 0.44–0.66) users. The risk of gastrointestinal safety events did not differ across opioid groups. All-cause mortality was elevated after 30 days for oxycodone (RR, 2.43; 95% CI, 1.47–4.00) and codeine (2.05; 1.22–3.45) users compared with hydrocodone users.î (D. H. Solomon, dsolomon@partners.org)
In an invited commentary, authors note that bone health is an important consideration in making opioids safer in older adults (
pp. 1986–8): ìThat the weaker opioids tramadol and propoxyphene had a decreased risk of fracture compared with the stronger opioids hydrocodone and oxycodone suggests a direct relationship between potency of the opioid and risk of falling and possibly decreased bone mass, although we would expect the endocrinological effects of opioids to be more relevant in younger patients with longer exposure to these medications. With the increasingly widespread use of opioids, these data should bring enhanced attention to fall prevention and spur further research into the effects of opioids on bone health in the elderly.î (P. O’Connor, patrick.oconnor@yale.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 240
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Dec. issue of the Journal of Allergy and Clinical Immunology (2010; 126).
Prenatal Acetaminophen, Genes & Asthma: Prenatal exposure to acetaminophen and polymorphisms in maternal antioxidant genes may interact to increase the chances that offspring will develop asthma in childhood, a study shows (pp. 1141–8.e7). In the Avon Longitudinal Study of Parents and Children, researchers ìtyped a functional nuclear erythroid 2 p45-related factor 2 (Nrf2) polymorphism and glutathione S-transferase (GST) M1, T1, and P1 polymorphisms.î These patterns resulted when those genotypes were integrated with stratified prenatal and infant acetaminophen exposure and asthma phenotypes at 7 years: ìRisk of asthma and wheezing associated with early gestation acetaminophen exposure was increased when maternal copies of the minor T allele of Nrf2 were present (P interactions, .02 and .04, respectively). Risk of asthma associated with late gestation exposure was higher when maternal GSTT1 genotype was present rather than absent (P interaction, .006), and risk of wheezing was increased when maternal GSTM1 was present (P interaction, .04). Although acetaminophen use in infancy was associated with an increased risk of atopy, child antioxidant genotype did not modify associations between infant acetaminophen use and asthma phenotypes. However, the increased risk of asthma and wheezing associated with late gestation acetaminophen exposure in the presence of maternal GSTM1 was further enhanced when GSTM1 was also present in the child.î (S. O. Shaheen, s.shaheen@qmul.ac.uk)
Maternal Peanut Intake & Childhood Sensitization: Among infants with likely milk or egg allergy, peanut allergy is linked to maternal ingestion of peanuts during pregnancy, researchers report (pp.1191–7). The study included 503 infants ages 3–15 months, 308 of whom had immediate allergic reactions to cow’s milk and/or egg and others with severe atopic dermatitis and positive allergy tests to these foods. Testing for peanut allergy showed the following: ìA total of 140 (27.8%) infants had peanut IgE levels 5 kUA/L. Multivariate analysis including clinical, laboratory, and demographic variables showed frequent peanut consumption during pregnancy (odds ratio, 2.9; 95% CI, 1.7–4.9; P < .001), IgE levels to milk (P = .001) and egg (P < .001), male sex (P = .02), and nonwhite race (P = .02) to be the primary factors associated with peanut IgE 5 kUA/L. Frequency of peanut consumption during pregnancy and breast-feeding showed a dose-response association with peanut IgE 5 kUA/L, but only consumption during pregnancy was a significant predictor. Among 71 infants never breast-fed, frequent consumption of peanut during pregnancy was strongly associated with peanut IgE 5 kUA/L (odds ratio, 4.99, 95% CI, 1.69–14.74; P < .004).î (S. H. Sicherer, scott.sicherer@mssm.edu)

>>>Psychiatry Highlights
Source:
Dec. issue of the American Journal of Psychiatry (2010; 167).
Shift to Medications for Mental Health: In 1998 to 2007, similar numbers of patients were treated with psychotherapy over time, but increasing numbers of patients received psychotropic drugs, according to analysis of national survey data (pp. 1456–63): ìThe percentage of persons using outpatient psychotherapy was 3.37% in 1998 and 3.18% in 2007 (adjusted odds ratio = 0.95, 95% CI = 0.82–1.09). Among individuals receiving outpatient mental health care, use of only psychotherapy (15.9% and 10.5% in 1998 and 2007, respectively; adjusted odds ratio = 0.66, 95% CI = 0.48–0.90) as well as psychotherapy and psychotropic medication together (40.0% and 32.1%; adjusted odds ratio = 0.73, 95% CI = 0.59–0.90) declined while use of only psychotropic medication increased (44.1% and 57.4%; adjusted odds ratio = 1.63, 95% CI = 1.32–2.00).î (M. Olfson)

>>>PNN NewsWatch
* Citing seven deaths of children younger than 10 since 1982, FDA is cautioning parents and pharmacists that benzonatate capsules (Tessalon, Forest) should be dispensed and stored in child-resistant containers. Benzonatate may be attractive to children because of the product’s appearance (round liquid-filled gelatin capsules), FDA added. Symptoms can appear within 15–20 minutes after ingestion, or immediately if the capsules are chewed.

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 © 2010, 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, 2010 * Vol. 17, No. 241
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 16 issue of the New England Journal of Medicine (2010; 363).
Teriparatide & Jaw Osseous Regeneration: Localized bone defects in the jaw respond to teriparatide treatment, a study of patients with severe, chronic periodontitis shows (pp. 2396–405). For 6 weeks, 40 study participants received daily injections of teriparatide 20 mcg or placebo, along with oral calcium 1000 mg and vitamin D 800 IU. Results showed: ìRadiographic linear resolution of osseous defects was significantly greater after teriparatide therapy than after placebo beginning at 6 months, with a mean linear gain in bone at 1 year of 29% as compared with 3% (P < 0.001). Clinical improvement was greater in patients taking teriparatide than in those taking placebo, with a reduction in periodontal probing depth of 33% versus 20% (2.42 mm vs. 1.32 mm) and a gain in clinical attachment level of 22% versus 7% (1.58 mm vs. 0.42 mm) in target lesions at 1 year (P = 0.02 for both comparisons). No serious adverse events were reported; however, the number of patients in the study was small. No significant differences were noted with respect to the other variables that were assessed.î (L. K. McCauley, mccauley@umich.edu)
An editorialist questions whether a controlled trial of teriparatide is feasible with patients who have severe osteonecrosis of the jaw (
pp. 2458–9): ìIn reality, the incidence of the disorder among patients with nonmalignant skeletal disease is so low, at least currently, that performing such a trial would be difficult, if not impossible, in that population. Clinicians faced with managing cases of severe osteonecrosis of the jaw in patients who do not have cancer must rely on observational data and clinical judgment, including careful discussion with their patients about the uncertainties regarding optimal management. A similar caveat applies to the investigation of teriparatide for the treatment of atypical femoral fractures that occur at very low rates in patients receiving long-term bisphosphonate therapy.î (A. Grey)
Anacetrapib & Dyslipidemias: In 1,623 patients with dyslipidemias, anacetrapib raised HDL cholesterol levels and lowered those of LDL cholesterol, and it did so without the adverse effects that caused discontinuation of testing of a related drug, torcetrapib (pp. 2406–15). All patients had received statins without successfully reaching target levels of cholesterol fractions. During 18 months of anacetrapib 100 mg or placebo daily, these changes were noted: ìBy 24 weeks, the LDL cholesterol level had been reduced from 81 mg per deciliter (2.1 mmol per liter) to 45 mg per deciliter (1.2 mmol per liter) in the anacetrapib group, as compared with a reduction from 82 mg per deciliter (2.1 mmol per liter) to 77 mg per deciliter (2.0 mmol per liter) in the placebo group (P < 0.001) — a 39.8% reduction with anacetrapib beyond that seen with placebo. In addition, the HDL cholesterol level increased from 41 mg per deciliter (1.0 mmol per liter) to 101 mg per deciliter (2.6 mmol per liter) in the anacetrapib group, as compared with an increase from 40 mg per deciliter (1.0 mmol per liter) to 46 mg per deciliter (1.2 mmol per liter) in the placebo group (P < 0.001) — a 138.1% increase with anacetrapib beyond that seen with placebo. Through 76 weeks, no changes were noted in blood pressure or electrolyte or aldosterone levels with anacetrapib as compared with placebo. Prespecified adjudicated cardiovascular events occurred in 16 patients treated with anacetrapib (2.0%) and 21 patients receiving placebo (2.6%) (P = 0.40). The prespecified Bayesian analysis indicated that this event distribution provided a predictive probability (confidence) of 94% that anacetrapib would not be associated with a 25% increase in cardiovascular events, as seen with torcetrapib.î (C. P. Cannon, cpcannon@partners.org)

>>>PNN NewsWatch
* On Wednesday, FDA declared war on dietary supplements with undeclared or deceptively labeled ingredients. In letters to dietary supplement manufacturers, FDA emphasized that manufacturers and distributors are responsible for ensuring that their products comply with the law. FDA cited nearly 300 tainted products identified in recent years, especially among products used for weight loss, body building, and sexual enhancement. Five major trade associations have agreed to share the FDA letter widely within the industry.

PNN Pharmacotherapy Line is published via e-mail each business day except for federal holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2010, 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, 2010 * Vol. 17, No. 242
Providing news and information about medications and their proper use

>>>Gastroenterology Report
Source:
Dec. issue of Gastroenterology (2010; 139).
PPIs for Postnasal Drainage: Testing whether gastroesophageal reflux might be related to symptoms of postnasal drainage, researchers found that twice-daily proton-pump inhibitor therapy significantly reduced symptoms of chronic drainage occurring without sinusitis or allergies (pp. 1887–93.e1) However, typical GERD symptoms—heartburn, regurgitation, abnormal levels of esophageal acid, or nonacid reflux—were not good predictors of decreased drainage symptoms with lansoprazole 30 mg twice daily in 75 participants: ìPostnasal drainage symptoms improved significantly among patients given lansoprazole compared with placebo. After 8 and 16 weeks, participants given lansoprazole were 3.12-fold (1.28–7.59) and 3.50-fold (1.41–8.67) more likely to respond, respectively, than participants given placebo. After 16 weeks, median (interquartile) percent symptom improvements were 50.0% (10.0%–72.0%) for participants given lansoprazole and 5.0% (0.0%–40.0%) for participants given placebo (P = .006). Neither baseline presence of typical reflux symptoms nor esophageal physiologic parameters predicted response to therapy.î (M. F. Vaezi, michael.vaezi@vanderbilt.edu)
Long-Term Tenofovir for HIV/HBV Coinfection: Through 5 years of therapy in patients with HIV and hepatitis B infections, tenofovir was a potent anti-HBV agent with a good resistance profile, researchers report (pp. 1934–41). Results of a prospective study of 102 patients showed the following: ìAmong patients positive for hepatitis B e antigen (HBeAg) (n = 67), 92% had a virologic response (HBV DNA <20 IU/mL) after 5 years of treatment. There was no difference between patients with or without lamivudine resistance at baseline (P = .39). Loss rates of HBeAg and hepatitis B s antigen (HBsAg) were 46% and 12%, respectively. Among HBeAg-negative patients (n = 15), 100% had a virologic response after 4 years of treatment and 2 (13%) lost HBsAg. Twenty subjects (20%, all HBeAg-negative) had undetectable HBV DNA at baseline; during a median follow-up period of 52 months (interquartile range, 41–63 mo), 19 (95%) maintained a virologic response and 2 (10%) lost HBsAg. Overall, one patient acquired a combination of resistance mutations for anti-HBV drugs and experienced a virologic breakthrough. Three (3%) patients discontinued TDF because of increased serum creatinine levels. The estimated decrease in renal function after 5 years of TDF therapy was 9.8 mL/min/1.73 m2, which was most pronounced shortly after TDF therapy was initiated.î (T. E. M. S. de Vries-Sluijs, t.sluijs@erasmusmc.nl)

>>>Geriatrics Highlights
Source:
Dec. Journal of the American Geriatrics Society (2010; 58).
Reasons for Pneumococcal Vaccine Underuse by African Americans: Citing a strong association between influenza and pneumococcal vaccination among community-dwelling, Medicare-eligible older adults, investigators conclude that attitudes toward immunizations in general explains the underuse of pneumococcal vaccine among older African Americans, rather than traditional confounders (pp. 2323–8). In four U.S. states, 795 pairs of black and white adults self-reported these data: ìPneumococcal vaccination rates were 22% for African Americans and 28% for whites (unadjusted odds ratios (OR) for African Americans = 0.75; 95% confidence interval (CI) = 0.60–0.94; P = .01). This association remained significant despite adjustment for sociodemographic and clinical confounders, including education, income, chronic obstructive pulmonary disease, and prior pneumonia (OR = 0.74, 95% CI = 0.56–0.97; P = .03), but the association was no longer significant after additional adjustment for the receipt of influenza vaccination (OR = 0.79, 95% CI = 0.59–1.06; P = .12). Receipt of influenza vaccination was associated with higher odds of receiving pneumococcal vaccination (unadjusted OR = 6.43, 95% CI = 5.00–8.28; P < .001), and the association between race and pneumococcal vaccination lost significance when adjusted for influenza vaccination alone (OR = 0.81, 95% CI = 0.63–1.03; P = .09).î (A. Ahmed, aahmed@uab.edu)

>>>PNN NewsWatch
* Bevacizumab lacks safety and efficacy in treatment of breast cancer, FDA has ruled. The agency began the process of removing this indication from product labeling. Other indications for Genentech’s Avastin are not 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 © 2010, 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. 20, 2010 * Vol. 17, No. 243
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 18 issue of Lancet (2010; 376).
Bortezomib in Myeloma Induction Therapy: In patients with newly diagnosed multiple myeloma, addition of bortezomib to thalidomide–dexamethasone induction therapy significantly improved outcomes when used before double autologous stem-cell transplantation, researchers report (pp. 2075–85). Concluding that this is ìa new standard of careî in patients with this condition, the investigators provided these details from 73 Italian sites in 2006–08 for those treated with thalidomide plus dexamethasone (TD) or TD with bortezomib (VTD): ì480 patients were enrolled and randomly assigned to receive VTD (n = 241 patients) or TD (n = 239). Six patients withdrew consent before start of treatment, and 236 on VTD and 238 on TD were included in the intention-to-treat analysis. After induction therapy, complete or near complete response was achieved in 73 patients (31%, 95% CI 25.0–36.8) receiving VTD, and 27 (11%, 7.3–15.4) on TD (p < 0.0001). Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD (n = 132, 56%) than in those on TD (n = 79, 33%; p < 0.0001), with a higher occurrence of peripheral neuropathy in patients on VTD (n = 23, 10%) than in those on TD (n = 5, 2%; p = 0.0004). Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD, and in three of five patients on TD.î (M. Cavo, michele.cavo@unibo.it)
GFR & Proteinuria Used Jointly as Markers of Kidney Injury: Information on proteinuria should be combined with estimated glomerular filtration rate values in identifying patients at risk of acute kidney injury, a study shows (pp. 2096–103). A cohort of 920,985 adults in Alberta in 2002–07 were studied, all of whom had at least one outpatient measurement of both serum creatinine and proteinuria. None of those included were on chronic dialysis at baseline. Using hospital admission with acute kidney injury as the main outcome variable, the investigators determined: ìDuring median follow-up of 35 months (range 0–59 months), 6,520 (0.7%) participants were admitted with acute kidney injury. In those with eGFR 60 mL/min per 1.73 m2 or greater, the adjusted risk of admission with this disorder was about 4 times higher in those with heavy proteinuria measured by dipstick (rate ratio 4.4 vs no proteinuria, 95% CI 3.7–5.2). The adjusted rates of admission with acute kidney injury and kidney injury needing dialysis remained high in participants with heavy dipstick proteinuria for all values of eGFR. The adjusted rates of death and the composite renal outcome were also high in participants admitted with acute kidney injury, although the rise associated with this injury was attenuated in those with low baseline eGFR and heavy proteinuria.î (M. Tonelli, mtonelli-admin@med.ualberta.ca)

>>>PNN NewsWatch
* Injectable dolasetron (Anzemet, Sanofi Aventis) is now contraindicated in patients with nausea and vomiting associated with cancer chemotherapy, FDA announced on Friday. Citing data showing an increased risk of torsades de pointes in patients receiving the selective serotonin 5-HT3 receptor antagonist by injection, FDA took the unusual action of removing an indication and making it a contraindication. Oral dolasetron tablets can still be used in patients on chemotherapy (but a stronger warning about abnormal heart rhythms is being added to product labeling), and the injectable form of the drug can be used for postoperative nausea and vomiting since the dose is lower, FDA said.

>>>PNN JournalWatch
* Effect on Gastric Function and Symptoms of Drinking Wine, Black Tea, or Schnapps with a Swiss Cheese Fondue: Randomised Controlled Crossover Trial, from the annual Christmas issue of BMJ, 2010; 341: c6731. (M Fox, dr.mark.fox@gmail.com)
* Review of the Literature and Proposed Guidelines for the Use of Oral Ribavirin as Postexposure Prophylaxis for Lassa Fever, in
Clinical Infectious Diseases, 2010; 51: 1435–41. (D. G. Bausch, dbausch@tulane.edu)
* Pandemic Influenza’s 500th Anniversary, in
Clinical Infectious Diseases, 2010; 51: 1442–4. (D. M. Morens, dm260q@nih.gov)
* A Model for Integrating Independent Physicians into Accountable Care Organizations, in
Health Affairs, 2010; 29: 10.1377/hlthaff.2010.0824. (M. C. Shields, mark.shields@advocatehealth.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 © 2010, 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, 2010 * Vol. 17, No. 244
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Dec. 21 issue of the Annals of Internal Medicine (2010; 153).
Echinacea for Common Colds: In a trial conducted in 719 adolescents and adults with new-onset common cold, echinacea failed to affect illness duration or severity (pp. 769–77). Study participants, ages 12 to 80 years, were assigned to one of four groups: no treatment, blinded placebo or echinacea, or unblinded echinacea, with these results based on twice-daily self-reports using the Wisconsin Upper Respiratory Symptom Survey: ìMean global severity was 236 and 258 for the blinded and unblinded echinacea groups, respectively; 264 for the blinded placebo group; and 286 for the no-pill group. A comparison of the 2 blinded groups showed a 28-point trend (95% CI, −69 to 13 points) toward benefit for echinacea (P = 0.089). Mean illness duration in the blinded and unblinded echinacea groups was 6.34 and 6.76 days, respectively, compared with 6.87 days in the blinded placebo group and 7.03 days in the no-pill group. A comparison of the blinded groups showed a nonsignificant 0.53-day (CI, −1.25 to 0.19 days) benefit (P = 0.075). Median change in interleukin-8 levels and neutrophil counts were also not statistically significant (30 ng/L and 1 cell/high-power field [hpf] in the no-pill group, 39 ng/L and 1 cell/hpf in the blinded placebo group, 58 ng/L and 2 cells/hpf in the blinded echinacea group, and 70 ng/L and 1 cell/hpf in the open-label echinacea group).î (B. Barrett)
Costs of Expanded HIV Screening, Treatment: Expansion of HIV screening and antiretroviral treatment (ART) simultaneously provides the greatest benefit and is cost-effective, researchers report, but ìeven substantial expansion of HIV screening and treatment programs is not sufficient to markedly reduce the U.S. HIV epidemic without substantial reductions in risk behaviorî (pp. 778–89). Using data from the published literature to assess risks and outcomes in high-risk and low-risk Americans ages 15 to 64 years, the investigators made these calculations for 20-year and lifetime costs and quality-adjusted life–years (QALYs): ìOne-time HIV screening of low-risk persons coupled with annual screening of high-risk persons could prevent 6.7% of a projected 1.23 million new infections and cost $22,382 per QALY gained, assuming a 20% reduction in sexual activity after screening. Expanding ART utilization to 75% of eligible persons prevents 10.3% of infections and costs $20,300 per QALY gained. A combination strategy prevents 17.3% of infections and costs $21,580 per QALY gained.Ö With no reduction in sexual activity, expanded screening prevents 3.7% of infections. Earlier ART initiation when a CD4 count is greater than 0.350 109 cells/L prevents 20% to 28% of infections. Additional efforts to halve high-risk behavior could reduce infections by 65%.î (E. F. Long, elisa.long@yale.edu)
Trans-Palmitoleic Acid & Diabetes: Consumption of whole milk—and the resulting increase in levels of circulating trans-palmitoleic acid—might be good for people, according to a prospective cohort study in four U.S. communities (pp. 790–9). Analysis of anthropometric and clinical measures and dietary intake of 3,736 adults over 3 years showed the following: ìIn multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (−19.0%; P < 0.001), a lower total cholesterol–HDL cholesterol ratio (−4.7%; P < 0.001), lower C-reactive protein levels (−13.8%; P = 0.05), and lower insulin resistance (−16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort.î (D. Mozaffarian, dmozaffa@hsph.harvard.edu)

>>>PNN NewsWatch
* Medicaid reimbursement formulas defined in the health care reform law are reasonable, lowering pharmacy reimbursements but still exceeding acquisition costs, the Government Accountability Office said in a report released last week.

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 © 2010, 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, 2010 * Vol. 17, No. 245
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 22/29 issue of JAMA (2010; 304).
Weight-Lifting by Breast Cancer Survivors: While women surviving breast cancer without lymphedema have generally been advised to avoid upper-body exercise, a program of slowly progressive weight lifting did not result in increased risk of this clinical problem, a study shows (pp. 2699–705). A total of 154 women who were 1 to 5 years postunilateral breast cancer were assigned to gym membership with 13 weeks of supervised instruction followed by 9 months of unsupervised exercise or no exercise, with these effects on breast cancer–related lymphedema (BCRL): ìA total of 134 participants completed follow-up measures at 1 year. The proportion of women who experienced incident BCRL onset was 11% (8 of 72) in the weight lifting intervention group and 17% (13 of 75) in the control group (cumulative incidence difference [CID], −6.0%; 95% confidence interval [CI], −17.2% to 5.2%; P for equivalence = .04). Among women with 5 or more lymph nodes removed, the proportion who experienced incident BCRL onset was 7% (3 of 45) in the weight lifting intervention group and 22% (11 of 49) in the control group (CID, −15.0%; 95% CI, −18.6% to −11.4%; P for equivalence = .003). Clinician-defined BCRL onset occurred in 1 woman in the weight lifting intervention group and 3 women in the control group (1.5% vs 4.4%, P for equivalence = .12).î (K. H. Schmitz, schmitz@mail.med.upenn.edu)
Prenatal Iron/Folic Acid, Zinc Supplementation: In Nepal, an area where iron deficiency is prevalent, prenatal supplements containing iron/folic acid significantly improved working memory, inhibitory control, and fine motor functioning of offspring (pp. 2716–23). Addition of zinc to the supplements yielded no measured benefits on intellectual or motor skill development, the researchers report, adding these details about their cohort follow-up of 676 children aged 7–9 years in 2007–09: ìThe difference across outcomes was significant (Bonferroni-adjusted P < .001) for iron/folic acid vs control but not for other supplement groups. The mean [Universal Nonverbal Intelligence Test] T score in the iron/folic acid group was 51.7 (SD, 8.5) and in the control group was 48.2 (SD, 10.2), with an adjusted mean difference of 2.38 (95% confidence interval [CI], 0.06–4.70; P = .04). Differences were not significant between the control group and either the iron/folic acid/zinc (0.73; 95% CI, −0.95 to 2.42) or multiple micronutrient (1.00; 95% CI, −0.55 to 2.56) groups. In tests of executive function, scores were better in the iron/folic acid group relative to the control group for the Stroop test (adjusted mean difference in proportion who failed, −0.14; 95% CI, −0.23 to −0.04) and backward digit span (adjusted mean difference, 0.36; 95% CI, 0.01–0.71) but not for the go/no-go test. The [Movement Assessment Battery for Children] score was lower (better) in the iron/folic acid group compared with the control group but not after adjustment for confounders (mean difference, −1.47; 95% CI, −3.06 to 0.12; P = .07). Finger-tapping test scores were higher (mean difference, 2.05; 95% CI, 0.87–3.24; P = .001) in the iron/folic acid group.î (P. Christian, pchristi@jhsph.edu)
Physicians Leading in Health Care Reform: Growth in the number of multispecialty physician groups is documented in a Commentary article by a former editor of the New England Journal of Medicine (pp. 2740–1): ìStabilizing and integrating the new group practices into a national system would require help from government, such as loans or grants to subsidize start-up costs, protection from antitrust action, and reinsurance against adverse selection. To help control costs and fully realize the advantages of having group practices functioning as [accountable care organizations], their payment should be capitated and include the cost of services in hospitals and other facilities. Medical groups that did not own a hospital could choose the facility to which their patients would be sent, and initially could use their global payment to reimburse the hospitals. Major reform of the hospital payment system might then become the logical next step taken by Congress, and this legislation would determine whether a national insurance plan would pay for hospital care directly or through the groups.î (A. S. Relman, arelman@rics.bwh.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 © 2010, 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, 2010 * Vol. 17, No. 246
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 23 issue of the New England Journal of Medicine (2010; 363).
Oral Factor Xa Inhibitors: Two studies and an editorial report on oral factor Xa inhibitors.
Compared with enoxaparin, apixaban produced lower rates of venous thromboembolism without increased rates of bleeding in 5,407 patients undergoing total hip replacement, a study shows (
pp. 2487–98). Apixaban 2.5 mg orally twice daily or enoxaparin 40 mg subcutaneously every 24 hours produced these results over 35 days postsurgery: ìThe primary efficacy outcome [composite of asymptomatic or symptomatic deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause] occurred in 27 patients in the apixaban group (1.4%) and in 74 patients in the enoxaparin group (3.9%) (relative risk with apixaban, 0.36; 95% confidence interval [CI], 0.22 to 0.54; P < 0.001 for both noninferiority and superiority; absolute risk reduction, 2.5 percentage points; 95% CI, 1.5 to 3.5). The composite outcome of major and clinically relevant nonmajor bleeding occurred in 129 of 2,673 patients assigned to apixaban (4.8%) and 134 of 2,659 assigned to enoxaparin (5.0%) (absolute difference in risk, −0.2 percentage points; 95% CI, −1.4 to 1.0).î (M. R. Lassen, mirula@noh.regionh.dk)
A second study shows benefits of rivaroxaban in 3,449 patients with acute symptomatic deep-vein thrombosis (
pp. 2499–510). The open-label trial reports these results in comparison with enoxaparin followed by a vitamin K antagonist for 3, 6, or 12 months: ìRivaroxaban had noninferior efficacy with respect to the primary outcome [recurrent VT] (36 events [2.1%], vs. 51 events with enoxaparin–vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome [major or clinically relevant nonmajor bleeding during initial treatment and major bleeding during maintenance] occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P < 0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P = 0.11).î (H. R. Buller, h.r.buller@amc.uva.nl)
Exploring the therapeutic potential of oral factor Xa inhibitors, an editorialist writes (
pp. 2559–61): ìAlternatives to warfarin have been long awaited. The oral factor Xa inhibitors show great promise. The reversibility of the drugs’ effects and the ability to measure the anticoagulant effect in specific situations will continue to be highly desirable features and will help to allay physicians’ concerns. If these novel, breakthrough, oral anticoagulant drugs prove to be effective across the broad spectrum of patients in routine care and are conscientiously priced, the worldwide impact will be huge.î (E. M. Hylek)

>>>PNN NewsWatch
* An increased mortality risk in a French study of somatropin (recombinant human growth hormone) for short stature has led to an FDA drug safety communication. Using data from a mandatory registry, the long-term epidemiological study SAGhE (SantÈ Adulte GH Enfant) found a 30% increase in mortality among patients who received the drug as children for idiopathic growth hormone deficiency or idiopathic or gestational short stature. The absolute mortality rate was very low, 93 observed deaths, compared with 70 expected deaths in the general French population. Bone tumors and cardiovascular and cerebrovascular diseases, especially subarachnoid or intracerebral hemorrhage, were frequent causes of death.
* In a major recall,
Abbott Diabetes Care is asking consumers and professionals to return as many as 359 million glucose test strips marketed as Precision Xceed Pro, Precision Xtra, Medisense Optium, Optium, OptiumEZ, and ReliOn Ultima. Recalled test strips, which are used in health facilities and have been sold in stores and online, may give falsely low blood glucose results.
*
Gardasil has been approved for prevention of anal cancer and associated precancerous lesions caused by human papillomavirus types 6, 11, 16, and 18, FDA said yesterday. The Merck vaccine is licensed for use in patients ages 9 to 26 years.
*
PNN will not be published on Fri., Dec. 24, Christmas Eve.

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 © 2010, 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. 27, 2010 * Vol. 17, No. 247
Providing news and information about medications and their proper use

>>>Neurology Highlights
Source:
Dec. 14 issue of Neurology (2010; 75).
Hydroxyurea in Spinal Muscular Atrophy: In 55 patients with types 2 and 3 spinal muscular atrophy, hydroxyurea (HU) produced no improvements but was associated with development of neutropenia, according to results of a double-blind, placebo-controlled trial from Taiwan (pp. 2190–7). The HU regimen used initial doses of 10 mg/kg/d followed by titration over 8 weeks to 20 mg/kg/d. Using primary outcome measures of Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA, and secondary outcome measures of Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC), the investigators determined: ìExcept for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had −1.88 for GMFM (p = 0.11), −0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function. (Y-J Jong, yjjong@kmu.edu.tw)
Complementary Therapy in Gliomas: Given the common use of complementary and alternative therapies by those with the generally incurable gliomas, neuro-oncologists should ìencourage an open but critical dialogue with their patients,î researchers conclude (pp. 2229–35). Patients with grades II to IV gliomas at German centers completed 621 questionnaires, making these comments about ìmethods or compounds not used in routine clinical practice and not scientifically evaluatedî: ìForty percent of the responding patients reported the use of complementary therapies. Significant differences between the group of complementary therapy users and nonusers were seen with respect to age (younger > older), gender (female > male), and education (high education level > low education level). The motivation for complementary therapy use was not driven by unsatisfactory clinical care by the neuro-oncologists, but by the wish to add something beneficial to the standard of care.î (O. Heese, heese@uke.uni-hamburg.de)

>>>Circulation Highlights
Source:
Dec. 21 issue of Circulation (2010; 122).
Glucose-Lowering Targets in Inpatients with Acute Coronary Syndromes: The evidence on what glucose levels to target in patients hospitalized for myocardial infarction/acute coronary syndromes (MI/ACS) is weak, consisting of epidemiological observations, mechanistic hypotheses, and expert consensus, concludes a review article (pp. 2736–44): ìReflecting this uncertainty, in 2008 the American Heart Association published an update on its position relative to glucose targets for ACS/MI patients, which substantially liberalized previous recommendations. This American Heart Association position advocates for a glucose treatment threshold of >180 mg/dL. A similar position was adopted by the 2009 focused update of ST-segment elevation MI guidelines and was also endorsed by the revised American Association of Clinical Endocrinologists/American Diabetes Association guidelines. These guidelines now recommend the same glucose threshold for therapeutic intervention in critically ill patients of >180 mg/dL, with the suggested therapeutic target of glucose control specified at 140 to 180 mg/dL, a substantially more liberal approach than prior documents. Although even these targets represent an expert consensus, it is likely the most prudent approach in the presence of the accumulated data.î (M. Kosiborod, mkosiborod@cc-pc.com)

>>>PNN JournalWatch
* Molecular Pathways Underlying Cardiac Remodeling During Pathophysiological Stimulation, in Circulation, 2010; 122: 2727–35. (J. D. Molkentin, jeff.molkentin@cchmc.org)
* The Aging Heart and Post-Infarction Left Ventricular Remodeling, in
Journal of the American College of Cardiology, 2011; 57: 9–17. (A. J. Boyle, aboyle@medicine.ucsf.edu)
* The Vulnerability of Middle-Aged and Older Adults in a Multiethnic, Low-Income Area: Contributions of Age, Ethnicity, and Health Insurance, in
Journal of the American Geriatrics Society, 2010; 58: 2416–22. (K. Odom Walker, domwalkerk@fcm.ucsf.edu">odomwalkerk@fcm.ucsf.edu)
* Physical and Mental Health of Homebound Older Adults: An Overlooked Population, in
Journal of the American Geriatrics Society, 2010; 58: 2423–8. (W. W. Q. Qiu, wqiu67@bu.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 © 2010, 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, 2010 * Vol. 17, No. 248
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Jan. issue of Pharmacotherapy (2011; 31).
Pharmacist Support in Diabetes Care: In a network of primary care practices with pharmacist support, diabetes care ìappears satisfactory, but improvements are necessary if [National Committee for Quality Assurance (NCQA)] recognition is the goal,î researchers conclude (pp. 23–30). Data on 1,309 adults seen at 17 practices in the first half of 2008 showed these outcomes using measures from the NCQA Diabetes Recognition Program (DRP): ìThe DRP outcome measures were satisfactory: mean ± SD A1C 7.6% ± 1.9%, LDL level 99.1 ± 35.1 mg/dl, and systolic and diastolic blood pressures 130.2 ± 18.1 and 74.4 ± 10.8 mm Hg, respectively. Five practices (29%) achieved a sufficient score for NCQA recognition. No significant relationships were noted between DRP measures and participation in quality improvement, type of clinical pharmacy services, or use of electronic medical records (p > 0.05). In a regression analysis, only electronic medical record use was significantly related to DRP measures (p = 0.02).î (L. M. Dickerson, macfarll@musc.edu)
Hypertension Care for Veterans: At a tertiary-care VA facility and associated clinics, veterans with uncontrolled hypertension achieved significant improvements in outcomes after receiving pharmacist-managed care, a study shows (pp. 31–8). A total of 573 veterans were referred to the program in 2007–08. Clinical pharmacists met with patients individually, orchestrated drug therapy, and provided patient counseling, the authors report, adding these details regarding the primary study outcome of the difference between systolic and diastolic blood pressure measurements at the final pharmacist care management visit versus the initial pharmacist visit: ìSystolic blood pressure decreased from a mean ± SD of 141.3 ± 18.5 mm Hg at the initial pharmacist visit to 130.1 ± 13.8 mm Hg at the final pharmacist visit, and diastolic blood pressure decreased from 79.1 ± 12.2 to 74.5 ± 10.3 mm Hg (p < 0.001 for both comparisons). The secondary outcome was the proportion of patients reaching blood pressure treatment goals at the final visit compared with the initial pharmacist visit. Of the 573 patients, 431 (75.2%) reached blood pressure treatment goals at the final visit (p 0.001) compared with 221 (38.6%) at the initial visit. The study patients had several comorbid diseases, including diabetes mellitus (196 patients [34.2%]) and chronic kidney disease (43 patients [7.5%]). Both study outcomes were also assessed for these subgroups.î (A. J. Zillich, azillich@purdue.edu)
Pushing for Payment for Clinical Pharmacy Services: Editorialists argue that the time has come to ìchart the course to ensure widespread [direct] payment for clinical pharmacy services in the near futureî and call for provider recognition under Medicare (pp. 1–8): ìFor decades, pharmacists have been arguing for payment for clinical pharmacy services. This is not a new concept. With a new generation of pharmacists that is managing more complicated drug therapy to a population that is growing older, we need to ensure these well-trained pharmacists are receiving payment for the services they are trained to perform. Although the Affordable Care Act represents a major achievement toward recognition of the role of the pharmacist in medication management, provider status under Medicare Part B should still be pharmacy’s goal. Like optometry, Medicare Part B provider status will cement pharmacy’s unique role in primary care and offer legislative recognition of this role. Pharmacists can become medication gatekeepers with responsibility for MTM as part of a health care team. Specialty credentialing can provide the framework for payment for clinical pharmacy services. Pharmacists will have ample opportunity to demonstrate their contribution through the patient-centered medical home, MTM grants, and other models and projects proposed in the Affordable Care Act.î (J. Stubbings)

>>>PNN NewsWatch
* Specific lots of American Regent’s Dexamethasone Sodium Phosphate Injection, USP 4 mg/mL, 30 mL Multiple Dose Vial are being recalled because some vials contain particulates or have the potential to form particulates before their expiration dates, FDA announced.

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 © 2010, 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, 2010 * Vol. 17, No. 249
Providing news and information about medications and their proper use

>>>Medical Care Highlights
Source:
Jan. issue of Medical Care (2011; 49).
Medical Homes & Specialty Care: Researchers find that specialists spend a ìnontrivialî amount of time following up with patients about chronic diseases, and this will need to be factored into medical homes directed by primary care physicians (pp. 4–9). Using data from the 2007 National Ambulatory Medical Care Survey, the study identified visits for adult ambulatory visits for chronic obstructive pulmonary disease/asthma, low back pain, diabetes mellitus, coronary artery disease/congestive heart failure, chronic kidney disease, and depression. ìMost specialty visits (76.8%; 95% confidence interval [CI]: 73.6%–79.7%) were made by established patients,î the authors found. ìSpecialists spent 552,844 (95% CI: 454,660–651,029) and 108,113 (95% CI: 86,103–130,122) cumulative work weeks providing direct and indirect follow-up care, respectively. Reallocating half of this care would generate 3.2 (95% CI: 2.6–3.8) additional work weeks for each [primary care physician].î In their conclusion, the group notes that ìmultidimensional efforts to expand the primary care workforceî may be needed if this specialist care is to be reassigned to primary care providers.î (J. M. Hollingsworth)
Stopping Medications: Getting prescribers to stop unneeded medications is a complicated process, researchers report, one that needs to be studied further with attention to improved outcomes (pp. 24–36). A systematic review of experimental/quasi-experimental research showed the following: ìOf 1,306 articles reviewed, 12 were assessed to be of relevant, high-quality research. A variety of drugs were examined in the included studies with benzodiazepines the most common. Studies included in the review tested 9 different types of interventions. Effective interventions included patient-mediated interventions, manual reminders to prescribers, educational materials given to patients, a face-to-face intervention with prescribers, and a case of regulatory intervention. Partially effective interventions included audit and feedback, electronic reminders, educational materials alone sent to prescribers, and distance communication combined with educational materials sent to prescribers.î (R. Ostini)

>>>Health Affairs Report
Source:
Early-release article from and Dec. issue of Health Affairs (2010; 29).
Integrating Independent Physicians into ACOs: Processes used for integrating independent physicians into accountable care organizations (ACOs)may provide insights as to how independent and chain pharmacies will be handled. In an article proposing a model for independent physicians, authors write (10.1377/hlthaff.2010.0824): ìThe Affordable Care Act encourages the formation of [ACOs] as a new part of Medicare. Pending forthcoming federal regulations, though, it is unclear precisely how these ACOs will be structured. Although large integrated care systems that directly employ physicians may be most likely to evolve into ACOs, few such integrated systems exist in the United States. This paper demonstrates how Advocate Physician Partners in Illinois could serve as a model for a new kind of accountable care organization, by demonstrating how to organize physicians into partnerships with hospitals to improve care, cut costs, and be held accountable for the results. The partnership has signed its first commercial ACO contract effective January 1, 2011, with the largest insurer in Illinois, Blue Cross Blue Shield. Other commercial contracts are expected to follow. In a health care system still dominated by small, independent physician practices, this may constitute a more viable way to push the broader health care system toward accountable care.î (M. C. Shields, mark.shields@advocatehealth.com)
Technology & Trust: An article uses the case of dying patient to illustrate problems in the existing health care system (pp. 2343–6). ìPreventing future patients from shuttling back and forth between hospitals and skilled nursing facilities will require attacking each component of what, in effect, is a complex ecosystem of economics, ideology, and medical culture. They all reinforce each other to maintain the status quo. Only by reforming medical education, increasing consumers’ understanding of the roles of both medical treatment and palliative care, and altering how physician practices are organized and financed can we hope to bring about change.î (M. R. Gillick, muriel_gillick@vmed.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 © 2010, 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, 2010 * Vol. 17, No. 250
Providing news and information about medications and their proper use

>>>PNN’s Top 10 for 2010
A year of extremes, 2010 provided glimpses of a promising future but also highlighted difficult problems from the past. Here’s PNN’s annual effort to summarize the past 12 months in 10 easy trends.
1 Health Care Reform: Barring a court or Congressional action that stops the cogs at CMS from turning, President Obama’s signing of the health care reform law certainly fulfills his campaign promise of change for this huge sector of American life (see PNN, Mar. 25, 26). Despite partisan bickering over the mandatory insurance plank, much of health care—including pharmacy (Oct. 1)—seems hopeful about the law.
2 Medication Quality: Massive recalls by major pharmaceutical companies (Jan. 6, May 3). A never-ending stream of warnings by FDA of contaminated dietary supplements (Apr. 8 and many others), punctuated by a year’s end declaration to go after those involved (Dec. 16). Heists of pharmaceuticals by the truckload (Mar. 21, Apr. 29). It’s been a strange year, one in which pharmacists, other health professionals, and consumers had to have doubts about the quality of the medications in the nation’s supply chain.
3 Cool New Drugs: After a few years when most newly approved entities seemed to be monoclonal antibodies for orphan diseases, several innovative medications with broader indications cleared the FDA approval gauntlet this year: orally active dalfampridine (Jan. 26) and fingolimod, the first sphingosine 1-phosphate receptor modulator (Sept. 23), both for multiple sclerosis; prostate cancer vaccine sipuleucel-T (Apr. 30); denosumab, the first RANK ligand inhibitor, for osteoporosis (Jun. 2); and dabigatran, an orally active direct thrombin inhibitor for prevention of stroke in patients with nonvalvular atrial fibrillation (Oct. 20).
4 FDA Deals with Problems: Beyond the above medication-quality challenges, FDA dealt with companies that have failed to perform promised postmarketing studies (Aug. 17), fraudulently marketed medications (Sept. 16), and violated good manufacturing practices (Oct. 27). Gemtuzumab (June 21) and sibutramine (Oct. 8) were pulled from the market, and use of rosiglitazone was restricted (Sept. 26).
5 MTM Scores: Pharmaceutical care pioneer Doug Hepler spoke of ìa dream deferredî (June 9), but pharmacy continued to stake its future on that concept’s successor, medication therapy management (MTM). Studies were published in both the pharmacy and medical literature (Jan. 22, Feb. 26, July 28, Oct. 26, Dec. 28), and the lay media picked up on the trend (Aug. 20).
6 Bumps in the Pharmacy Practice Road: ASHP convened a summit on the future pharmacy practice model (Nov. 8, 10), but on the front lines, pharmacists hit a few bumps. Not long after an Ohio pharmacist was released from prison for involuntary manslaughter in a case involving a medication error (Feb. 17), an article noted the difficulty in moving from a ìculture of blameî to one of ìsafetyî (Mar. 10).
7 A Future in Health IT: The introduction of the iPad by Apple’s Steve Jobs (Jan. 28) could well have been the most important health IT event of 2010, if trends involving e-prescribing and telemedicine continue as predicted (Apr. 13, July 14).
8 Genetics & Genomics: Personalized medicine based on each patient’s unique genetic imprint made the news all year long (Feb. 12; July 8, 22; Oct. 18, 27). APhA (Mar. 19) and ACCP (June 6) established baselines for pharmacists.
9 Vaccination Lessons: A late wave of spring cases of A/H1N1 influenza caused illness and deaths in states with low vaccination rates (Apr. 5), providing another teachable moment for public health authorities. Earlier, CDC had called for near-universal flu vaccines for Americans (Feb. 25). Twelve years after it was published, the controversial Wakefield article on vaccine safety was retracted in full (Feb. 3), but parents continue to fret (Apr. 2).
10 Vitamin D Peaking? While dozens of studies continued to surprise many about the range of benefits of vitamin D (Jan. 25; Mar. 2; Apr. 2; May 12; June 8; July 13, 19, 23; Aug. 20, Sept. 29, Nov. 6), the Institute of Medicine called for a limit on daily doses (Nov. 30).

>>>PNN NewsWatch
* Specific lots of Sodium Bicarbonate Injection, USP, 7.5% and 8.4%, in 50-mL single-dose vials are being recalled by American Regent because of presence of particulate matter, FDA said.
*
PNN will not be published on Fri., Dec. 31, New Year’s Eve.

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 © 2010, 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.