Dec 2013

PNN October–December 2013

PNN Pharmacotherapy Line
Oct. 1, 2013 * Vol. 20, No. 189
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 1 issue of the Annals of Internal Medicine (2013; 159).
Underreporting of High-Risk Prescribing by Medicare Advantage Plans: In required reports based on Healthcare Effectiveness Data and Information Set (HEDIS) quality indicators, Medicare Advantage plans underreport high-risk prescribing, according to an analysis of beneficiaries in 172 plans during 2006 and 2007 (pp. 456–62). Investigators compared plan-reported HEDIS measures with rates calculated from Medicare Part D claims for older patients, with these results: “The mean rate of high-risk prescribing derived from Part D claims was 26.9% (95% CI, 25.9% to 28.0%), whereas the mean plan-reported rate was 21.1% (CI, 20.0% to 22.3%). Approximately 95% of plans underreported rates of high-risk prescribing relative to calculated rates derived from Part D claims. The differences in the calculated and reported rates negatively affected quality rankings for the plans that most accurately reported rates. For example, the 9 plans that reported rates of high-risk prescribing within 1 percentage point of calculated rates were ranked 43.4 positions lower when reported rates were used instead of calculated rates. Among 103,680 individuals present in both the sample of Part D claims and HEDIS data in 2006, Medicare Advantage plans incorrectly excluded 10.3% as ineligible for the HEDIS high-risk prescribing measure. Among those correctly included in the high-risk prescribing denominator, the reported rate of high-risk prescribing was 21.9% and the calculated rate was 26.2%.” (A. N. Trivedi, amal_trivedi@brown.edu)
Long-Term Dual- v. Single-Antiplatelet Therapy in Ischemic Stroke: Dual-antiplatelet therapy, continued for more than 1 year in patients with ischemic stroke, showed more harm than benefits in a systematic review and meta-analysis of seven randomized controlled trials of 38,574 patients (pp. 463–70). Looking at risk for recurrent stroke and intracranial hemorrhage (ICH) associated with long-term dual- and single-antiplatelet therapy among patients with ischemic stroke and transient ischemic attack, the investigators found: “Recurrent stroke risk did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (relative risk [RR], 0.89 [95% CI, 0.78 to 1.01]) or clopidogrel monotherapy (RR, 1.01 [CI, 0.93 to 1.08]). Risk for ICH did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (RR, 0.99 [CI, 0.70 to 1.42]) but was greater among patients receiving dual-antiplatelet therapy than among those receiving clopidogrel monotherapy (RR, 1.46 [CI, 1.17 to 1.82]).” (B. Ovbiagele)
Obstructive Sleep Apnea Clinical Practice Guideline: Using literature from 1966–2010 with additional articles through 2012, an American College of Physicians (ACP) clinical practice guideline makes these recommendations for management of obstructive sleep apnea (OSA) in adults (pp. 471–83; A. Qaseem):
* ACP recommends that all overweight and obese patients diagnosed with OSA should be encouraged to lose weight. (Grade: strong recommendation; low-quality evidence)
* ACP recommends continuous positive airway pressure treatment as initial therapy for patients diagnosed with OSA. (Grade: strong recommendation; moderate-quality evidence)
* ACP recommends mandibular advancement devices as an alternative therapy to continuous positive airway pressure treatment for patients diagnosed with OSA who prefer mandibular advancement devices or for those with adverse effects associated with continuous positive airway pressure treatment. (Grade: weak recommendation; low-quality evidence)

>>>PNN NewsWatch
* FDA yesterday approved vortioxetine (Brintellix, Takeda) to treat adults with major depressive disorder. Six clinical studies of adults with major depressive disorder demonstrated efficacy of vortioxetine for preventing recurrence of depression. The most common adverse effects reported by participants taking vortioxetine in clinical trials included nausea, constipation, and vomiting.
*
FDA also granted accelerated approval to pertuzumab (Perjeta, Genentech) for neoadjuvant (presurgical) treatment of patients with high-risk, HER2-positive, early-stage breast cancer.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 2, 2013 * Vol. 20, No. 190
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 2 issue of JAMA (2013; 310).
Long-Term Outcomes From Women’s Health Initiative: Thirteen-year follow-up from the Women’s Health Initiative (WHI) shows that menopausal hormonal therapy is “appropriate for symptom management in some women” but not for chronic disease prevention (pp. 1353–68). Among 27,347 postmenopausal women, a placebo-controlled evaluation of conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) in those with an intact uterus over a median of 5.6 years and CEE alone in those with prior hysterectomy over a median of 7.2 years: “During the CEE plus MPA intervention phase, the numbers of [coronary heart disease (CHD)] cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95–1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01–1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged ≥65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11–1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78–1.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61–1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65–0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50–59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age). Absolute risks of adverse events (measured by the global index) per 10,000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of 50–59 years to 38 for ages of 70–79 years; for women taking CEE alone, from 19 fewer cases for ages of 50–59 years to 51 excess cases for ages of 70–79 years. Quality-of-life outcomes had mixed results in both trials.” (J. E. Manson, jmanson@rics.bwh.harvard.edu)
Delivering a message particularly appropriate during a federal government shutdown, an editorialist concludes (
pp. 1349–50): “The WHI underscores the decisive importance of taxpayer-funded research conducted by the NIH. Further reductions in the NIH budget virtually ensure that vitally important studies like the WHI will not be conducted, and hence, US society will be poorly served. The fact that the public sector undertook this historic project (and that the researchers whose work is now reported have taken it to its next stage) has moved medical science forward by the most effective means of doing so—shattering prior dogma. For that, women and all patients whose health depends on sound science are grateful.” (E. G. Nabel, enabel@partners.org)
Opioid Therapy Before and After Bariatric Surgery: Better pain management is needed for patients undergoing bariatric surgery, according to a study showing frequent continuation of opioid therapy for up to 1 year after surgery at higher doses than those used for chronic pain preoperatively (pp. 1369–76). Retrospective analysis of 11,719 patients undergoing bariatric surgery in 2005–09 in a distributed health network showed these patterns of analgesic use: “Before surgery, 8% (95% CI, 7%–8%; n = 933) of bariatric patients were chronic opioid users. Of these individuals, 77% (95% CI, 75%–80%; n = 723) continued chronic opioid use in the year following surgery. Mean daily morphine equivalents for the 933 bariatric patients who were chronic opioid users before surgery were 45.0 mg (95% CI, 40.0–50.1) preoperatively and 51.9 mg (95% CI, 46.0–57.8) postoperatively (P < .001). For this group with chronic opiate use prior to surgery, change in morphine equivalents before vs after surgery did not differ between individuals with loss of more than 50% excess BMI vs those with 50% or less (>50% BMI loss: adjusted incidence rate ratio [adjusted IRR, 1.17; 95% CI, 1.07–1.28] vs ≤50% BMI loss [adjusted IRR, 1.03; 95% CI, 0.93–1.14] model interaction, P = .06).” (M. A. Raebel, marsha.a.raebel@kp.org)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 3, 2013 * Vol. 20, No. 191
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 3 New England Journal of Medicine (2013; 369).
Gliptins & CVD: Two research articles and an editorial explore the cardiovascular safety of antidiabetic drugs in the gliptin class.
Among 16,492 patients with type 2 diabetes and histories of or risk factors for cardiovascular events, treatment with the dipeptidyl peptidase 4 (DPP-4) inhibitor saxagliptin “did not increase or decrease the rate of ischemic events, though the rate of hospitalization for heart failure was increased,” SAVOR-TIMI 53 investigators write (
pp. 1317–26). During a median of 2.1 years of therapy, a primary composite end point of cardiovascular death, myocardial infarction, or ischemic stroke “occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group (7.3% and 7.2%, respectively, according to 2-year Kaplan–Meier estimates; hazard ratio with saxagliptin, 1.00; 95% confidence interval [CI], 0.89 to 1.12; P = 0.99 for superiority; P < 0.001 for noninferiority).” (D. L. Bhatt, dlbhattmd@post.harvard.edu)
Among 5,380 patients with type 2 diabetes and a recent acute myocardial infarction or unstable angina requiring hospitalization, “rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo,” report EXAMINE researchers (
pp. 1327–35). Treatment lasted a median of 18 months, and a primary end point included a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results showed: “A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P < 0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, −0.36 percentage points; P < 0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo.” (W. B. White, wwhite@nso1.uchc.edu)
Reflecting on experiences with rosiglitazone, editorialists make these comparisons with DPP-4 inhibitors (
pp. 1285–7): “Patients with type 2 diabetes and their physicians currently have numerous treatment options, and additional drugs are in development. Perhaps the recent experience with rosiglitazone will allow the FDA to become more targeted in its adjudication of the cardiovascular safety of new diabetes drugs, focusing the considerable resources needed to rule out a cardiovascular concern only on drugs with clinical or preclinical justification for that expenditure. New therapies targeting glycemic control may have cardiovascular benefit, but this has yet to be shown. The optimal approach to the reduction of cardiovascular risk in diabetes should focus on aggressive management of the standard cardiovascular risk factors rather than on intensive glycemic control.” (W. R. Hiatt)
Drug Choices in Type 2 Diabetes: “Many questions related to the comparative efficacy and safety of DPP-4 inhibitors, sulfonylureas, GLP-1 receptor agonists, and insulin will be answered within the next few years,” note authors of a Clinical Decisions article that focuses on optimal glycemic control in patients with type 2 diabetes (pp. 1370–2). One of two responding authors explores use of DPP-4 inhibitors in “Agnes,” a 51-year-old, making these observations: “There has been concern recently about a possible association of DPP-4 inhibitors with pancreatitis, pancreatic cancer, and pancreatic neuroendocrine tumors. However, the Committee for Medicinal Products for Human Use of the European Medicines Agency and later the U.S. Food and Drug Administration found no justification for this new concern, although acute pancreatitis has been noted in postmarketing reports. Furthermore, a recent analysis of autopsy results suggested that the concern about pancreatic cancer is ‘overstated and a misrepresentation of the information available.’” (I. B. Hirsch; M. E. Molitch)

>>>PNN NewsWatch
* October is American Pharmacists Month, APhA notes on its website. Branded materials reflecting the “Know Your Pharmacist, Know Your Medicine” theme are available there. Photos of celebrations should be emailed to aphm@aphanet.org.
* Join a
worldwide #Pharmacist tweet-a-thon today on Twitter. The goal is to highlight the positive impact pharmacists have on patients, communities, and health care in general.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 4, 2013 * Vol. 20, No. 192
Providing news and information about medications and their proper use

>>>Psychiatry Highlights
Source:
Oct. issue of the American Journal of Psychiatry (2013; 170).
Ketamine as Antidepressant: Antagonism of the glutamate N-methyl-d-aspartate (NMDA) receptor is a potential “novel mechanism” for achieving rapid improvement in severe and chronic depression, according to a study of ketamine in 73 patients (pp. 1134–42). Patients had treatment-resistant major depression when they were randomized to ketamine infusion or an active control (midazolam). Changes in depression severity after 24 hours, as measured on the Montgomery-Åsberg Depression Rating Scale (MADRS), were as follows: “The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively.” (S. J. Mathew, sjmathew@bcm.edu)
“How certain and generalizable are the findings from this report?” asks an editorialist (
pp. 1079–81). “The internal validity of the study might be challenged since the subjective effects of midazolam are likely to be quite different than those of ketamine. If blinding was incomplete, the [number needed to treat] might be larger. On the other hand, the overall study results were comparable at the two individual sites. Furthermore, as [the authors] note, additional studies of ketamine in treatment-resistant depression that provide similar response rates or effect sizes have been reported.…
“While insufficient to recommend a wholesale change in practice presently, these results certainly provide substantial hope for patients with treatment-resistant depression, insight into the biology of this condition, and a major obligation by clinician scientists and funding agencies to answer this next set of important clinical questions for our patients with refractory depression.” (A. J. Rush,
john.rush@duke-nus.edu.sg)

>>>Pediatrics Report
Source:
Oct. issue of Pediatrics (2013; 132).
Psychotropic Medication Use in Young Children: Between 1994 and 2009, use of psychotropic medications in children ages 2–5 years peaked in 2002–05, researchers report (pp. 615–23). Based on data from the National Ambulatory and National Hospital Ambulatory Medical Care Surveys for those years showed these patterns: “Psychotropic prescription rates were 0.98% from 1994–1997, 0.83% from 1998–2001, 1.45% from 2002–2005, and 1.00% from 2006–2009. The likelihood of preschool psychotropic use was highest in 2002–2005 (1994–1997 adjusted odds ratio [AOR] versus 2002–2005: 0.67; 1998–2001 AOR versus 2002–2005: 0.63; 2006–2009 AOR versus 2002–2005: 0.64), then diminished such that the 2006–2009 probability of use did not differ from 1994–1997 or from 1998–2001. Boys (AOR versus girls: 1.64), white children (AOR versus other race: 1.42), older children (AOR for 4 to 5 vs 2 to 3 year olds: 3.87), and those lacking private insurance (AOR versus privately insured: 2.38) were more likely than children from other groups to receive psychotropic prescriptions.” (V. Chirdkiatgumchai)
Pertussis Clusters & Nonmedical Vaccine Exemptions: During the 2010 pertussis resurgence in California, clustering of nonmedical exemptions (NMEs) from childhood vaccinations may have been one of the causative factors, a study shows (pp. 624–30). Analysis of NMEs for children entering kindergarten in 2005–10 showed these relationships with spatial and temporal clusters of pertussis infections: “Kulldorff’s scan statistics identified 39 statistically significant clusters of high NME rates and 2 statistically significant clusters of pertussis cases in this time period. Census tracts within an exemptions cluster were 2.5 times more likely to be in a pertussis cluster (odds ratio = 2.47, 95% confidence interval: 2.22–2.75). More cases occurred within as compared with outside exemptions clusters (incident rate ratios = 1.20, 95% confidence interval: 1.10–1.30). The association remained significant after adjustment for demographic factors. NMEs clustered spatially and were associated with clusters of pertussis cases.” (J. E. Atwell)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 7, 2013 * Vol. 20, No. 193
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 5 issue of Lancet (2013; 382).
Internet-Based Training on Antibiotic Prescribing Rates: In a study of six European countries, Internet-based training of physicians and patients about point-of-care testing for C-reactive protein (CRP) reduced antibiotic prescribing for respiratory-tract infections (pp. 1175–82). Baseline audit and patient recruitment in 2010–11 produced these results for groups assigned to usual care, Internet CRP training, enhanced communication skills, or both CRP and enhanced communication: “The antibiotic prescribing rate was lower with CRP training than without (33% vs 48%, adjusted risk ratio 0.54, 95% CI 0.42–0.69) and with enhanced-communication training than without (36% vs 45%, 0.69, 0.54–0.87). The combined intervention was associated with the greatest reduction in prescribing rate (CRP risk ratio 0.53, 95% CI 0.36–0.74, p < 0.0001; enhanced communication 0.68, 0.50—0.89, p = 0.003; combined 0.38, 0.25—0.55, p < 0.0001).” (P. Little, p.little@soton.ac.uk)
Antiretroviral Therapy in Serodiscordant Couples: Reduced HIV transmission resulted from antiretroviral therapy administered to HIV-positive partners in serodiscordant couples, researchers report (pp. 1195–203). A retrospective observational cohort study performed in China showed these results for patients seen in 2003–11: “Based on data from 38,862 serodiscordant couples, with 101,295.1 person–years of follow-up for the seronegative partners, rates of HIV infection were 2.6 per 100 person–years (95% CI 2.4–2.8) among the 14,805 couples in the treatment-naive cohort (median baseline CD4 count for HIV-positive partners 441 cells per µl [IQR 314–590]) and 1.3 per 100 person–years (1.2–1.3) among the 24,057 couples in the treated cohort (median baseline CD4 count for HIV-positive partners 168 cells per µl [62–269]). We calculated a 26% relative reduction in HIV transmission (adjusted hazard ratio 0.74, 95% CI 0.65–0.84) in the treated cohort. The reduction in transmission was seen across almost all demographic subgroups and was significant in the first year (0.64, 0.54–0.76), and among couples in which the HIV-positive partner had been infected by blood or plasma transfusion (0.76, 0.59–0.99) or heterosexual intercourse (0.69, 0.56–0.84), but not among couples in which the HIV-positive partner was infected by injecting drugs (0.98, 0.71–1.36).” (Y. Shao, yshao08@gmail.com)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2013; 347).
Mortality Effects of Exercise v. Drugs: Used for secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes, exercise and many drugs show similar benefits, according to a random-effects network meta-analysis (f5577): “We included 16 (four exercise and 12 drug) meta-analyses. Incorporating an additional three recent exercise trials, our review collectively included 305 randomised controlled trials with 339,274 participants. Across all four conditions with evidence on the effectiveness of exercise on mortality outcomes (secondary prevention of coronary heart disease, rehabilitation of stroke, treatment of heart failure, prevention of diabetes), 14,716 participants were randomised to physical activity interventions in 57 trials. No statistically detectable differences were evident between exercise and drug interventions in the secondary prevention of coronary heart disease and prediabetes. Physical activity interventions were more effective than drug treatment among patients with stroke (odds ratios, exercise v anticoagulants 0.09, 95% credible intervals 0.01 to 0.70 and exercise v antiplatelets 0.10, 0.01 to 0.62). Diuretics were more effective than exercise in heart failure (exercise v diuretics 4.11, 1.17 to 24.76). Inconsistency between direct and indirect comparisons was not significant.” (H. Naci, h.naci@lse.ac.uk)

>>>PNN JournalWatch
* Blood Pressure Lowering and Major Cardiovascular Events in People With and Without Chronic Kidney Disease: Meta-Analysis of Randomised Controlled Trials, in
BMJ, 2013; 347: f5680. (V. Perkovic, VPerkovic@george.org.au)
* Medication Adherence and Health Care Utilization in Pediatric Chronic Illness: A Systematic Review, in
Pediatrics, 2013; 132: 730–40. (M. E. McGrady)
* Air Travel: Effects of Sleep Deprivation and Jet Lag, in
Chest, 2013; 144: 1394–401. (J. A. Weingarten, jaw9031@nyp.org)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 8, 2013 * Vol. 20, No. 194
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Oct. 15 issue of the Journal of the American College of Cardiology (2013; 62).
Antioxidant Reinforcement & Postoperative Atrial Fibrillation: A low-cost regimen of n-3 fatty acids plus vitamins C and E supplements “favorably affected postoperative atrial fibrillation, increased antioxidant potential, and attenuated oxidative stress and inflammation,” according to results of the Prevention of Postoperative Atrial Fibrillation: Pathophysiological Characterization of a Pharmacological Intervention Based on a Novel Model of Nonhypoxic Pre-Conditioning trial (pp. 1457–65). A total of 203 patients who were undergoing on-pump cardiac surgery randomly received placebo or n-3 polyunsaturated fatty acids 2 g/d, vitamin C 1 g/d, and vitamin E 400 IU/d, with these results: “Postoperative atrial fibrillation occurred in 10 of 103 patients (9.7%) in the supplemented group versus 32 of 100 patients (32%) in the placebo group (p < 0.001). Early after surgery, placebo patients presented with increased levels of biomarkers of inflammation and oxidative stress, which were markedly attenuated by antioxidant supplementation. The activity of catalase, superoxide dismutase, and glutathione peroxidase in atrial tissue of the supplemented patients was 24.0%, 17.1%, and 19.7% higher than the respective placebo values (p < 0.05). The atrial tissue of patients who developed atrial fibrillation showed NADPH oxidase p47-phox subunit protein and mRNA expression 38.4% and 35.7% higher, respectively, than patients in sinus rhythm (p < 0.05).” (R. Rodrigo)

>>>Circulation Report
Source:
Oct. 8 issue of Circulation (2013; 128).
Antiplatelet Therapy for Ischemic Stroke, TIA: Dual antiplatelet therapy is more effective than monotherapy for prevention of early recurrent stroke and cardiovascular outcomes in patients with acute ischemic stroke and transient ischemic attack (TIA), authors of a systematic review and meta-analysis report (pp. 1656–66). Studies published through Nov. 2012 plus the CHANCE trial (Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events), reported these outcomes in adult patients with acute noncardioembolic ischemic stroke or TIA with treatment initiated within 3 days of ictus: “In total, 14 studies of 9,012 patients were included in the systematic review and meta-analysis. Dual antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio, 0.69; 95% confidence interval, 0.60–0.80; P < 0.001) and the composite outcome of stroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95% confidence interval, 0.63–0.81; P < 0.001) when compared with monotherapy, and nonsignificantly increased risk of major bleeding (risk ratio, 1.35; 95% confidence interval, 0.70–2.59, P = 0.37). Analyses restricted to the CHANCE Trial or the 7 double-blind randomized, controlled trials showed similar results.” (Y. Wang, yongjunwang1962@gmail.com)

>>>Chest Highlights
Source:
Oct. issue of Chest (2013; 144).
Bisphosphonates & AF: Use of bisphosphonates is associated with increased risk of atrial fibrillation (AF) requiring hospitalization, a meta-analysis shows, but risks of stroke or cardiovascular mortality are not increased (pp. 1311–22). Results from six randomized controlled trials (RCTs) and six observational studies show the following: “On pooling observational studies, there was an increased risk of AF (OR, 1.27; 95% CI, 1.16-–1.39) among bisphosphonate users. Further, analysis of RCTs revealed a statistically significant increase in the risk of serious AF (OR, 1.40; 95% CI, 1.02–1.93) and no increase in the risk of stroke (OR, 1.07; 95% CI, 0.85–1.34) or cardiovascular mortality (OR, 0.92; 95% CI, 0.68–1.26) with the use of bisphosphonates.” (A. Sharma, abhisheksharma4mamc@gmail.com)
Thrombocytopenia & Thromboprophylaxis: In critically ill patients, thromboprophylaxis with low-molecular-weight heparin (LMWH) is associated with lower risks of thrombocytopenia, a study of 3,746 patients reports (pp. 1207–15). Predictors of higher risk of thrombocytopenia in the study of heparin versus LMWHs were high severity of illness, prior surgery, use of inotropes or vasopressors, renal replacement therapy, and liver dysfunction. Patients developing thrombocytopenia were more likely to bleed, receive transfusions, and die, the authors add. (D. R. Williamson, david.williamson@umontreal.ca)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 9, 2013 * Vol. 20, No. 195
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 9 issue of JAMA (2013; 310).
Adjuvant Chemotherapy in Resected Pancreatic Cancer: Gemcitabine therapy in patients with resected pancreatic cancer yielded significantly higher overall and disease-free survival rates, researchers report (pp. 1473–81). In the open-label, Phase III CONKO-001 (Charité Onkologie 001) trial, patients were randomized to gemcitabine for 6 months or observation following complete pancreatic tumor resection. Results showed: “A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%–90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%–92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6–15.3) months in the treatment group compared with 6.7 (95% CI, 6.0–7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44–0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61–0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%–26.6%) vs 10.4% (95% CI, 5.9%–15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%–17.2%) vs 7.7% (95% CI, 3.6%–11.8%).” (H. Oettle, helmut.oettle@charite.de)
Surveillance Bias & VTE Quality Measure: Increased use of imaging to detect postoperative venous thromboembolism (VTE) results in higher VTE event rates in high-performing hospitals, a study shows, and this results in “surveillance bias” that “limits the usefulness of the VTE quality measure for hospitals working to improve quality and patients seeking to identify a high-quality hospital” (pp. 1482–9). Data from 2009–10 showed these patterns of VTE imaging and event rates for 954,926 surgical discharges at 2,796 hospitals: “Greater hospital VTE prophylaxis adherence rates were weakly associated with worse risk-adjusted VTE event rates (r2 = 4.2%; P = .03). Hospitals with increasing structural quality scores had higher VTE prophylaxis adherence rates (93.3% vs 95.5%, lowest vs highest quality quartile; P < .001) but worse risk-adjusted VTE rates (4.8 vs 6.4 per 1,000, lowest vs highest quality quartile; P < .001). Mean VTE diagnostic imaging rates ranged from 32 studies per 1,000 in the lowest imaging use quartile to 167 per 1,000 in the highest quartile (P < .001). Risk-adjusted VTE rates increased significantly with VTE imaging use rates in a stepwise fashion, from 5.0 per 1,000 in the lowest quartile to 13.5 per 1,000 in the highest quartile (P < .001).” (K. Y. Bilimoria, k-bilimoria@northwestern.edu)
Pain Medication Abuse Leads to Heroin Abuse: The resurgence of heroin abuse is being driven partially by patients who first abuse prescription pain medications, according to a news article on a recent Substance Abuse and Mental Health Services Administration (SAMHSA) report (pp. 1433–4): “Using data collected from 2002 to 2011 for the National Survey on Drug Use and Health, an annual anonymous survey of a nationally representative sample of 70,000 US individuals, scientists found that the incidence of heroin use is 19 times higher among individuals who have abused prescription pain medications than among those who have not. Although the overall incidence of heroin use in the population is low, there was a substantial difference in heroin use rates between the groups, with 0.39% of those with a history of pain medication abuse reporting heroin use compared with 0.02% of those who reported that they had never used prescription opioid medications for nonmedical purposes.” (B. M. Kuehn)

>>>PNN NewsWatch
* Using its priority review program, FDA yesterday approved the first soluble guanylate cyclase stimulator, riociguat (Adempas, Bayer), for treatment of adults with either of two forms of pulmonary hypertension—persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH and pulmonary arterial hypertension (WHO Group 1). The product carries a boxed warning cautioning against use in pregnant women; female patients can only receive the drug through the Adempas REMS program.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 10, 2013 * Vol. 20, No. 196
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 10 issue of the New England Journal of Medicine (2013; 369).
Edoxaban v. Warfarin in Venous Thromboembolism: In a “broad spectrum of patients with venous thromboembolism,” the oral factor Xa inhibitor edoxaban was noninferior to warfarin and possibly safer, researchers report (pp. 1406–15). Participants had initially received heparin for symptomatic venous thromboembolism; some patients had severe pulmonary embolism. Edoxaban 30–60 mg/d or warfarin for 3–12 months produced these changes in a primary efficacy outcome of recurrent symptomatic venous thromboembolism and a principal safety outcome of major or clinically relevant nonmajor bleeding: “A total of 4,921 patients presented with deep-vein thrombosis, and 3,319 with a pulmonary embolism. Among patients receiving warfarin, the time in the therapeutic range was 63.5%. Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome, which occurred in 130 patients in the edoxaban group (3.2%) and 146 patients in the warfarin group (3.5%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.70 to 1.13; P < 0.001 for noninferiority). The safety outcome occurred in 349 patients (8.5%) in the edoxaban group and 423 patients (10.3%) in the warfarin group (hazard ratio, 0.81; 95% CI, 0.71 to 0.94; P = 0.004 for superiority). The rates of other adverse events were similar in the two groups. A total of 938 patients with pulmonary embolism had right ventricular dysfunction, as assessed by measurement of N-terminal pro–brain natriuretic peptide levels; the rate of recurrent venous thromboembolism in this subgroup was 3.3% in the edoxaban group and 6.2% in the warfarin group (hazard ratio, 0.52; 95% CI, 0.28 to 0.98).” (H. R. Büller, h.r.buller@amc.uva.nl)
HIV Care in Africa: Two Perspective articles examine implications of reduced U.S. funding for HIV care in sub-Saharan Africa.
South Africa, recipient of the largest amount of U.S. dollars under the decade-old President’s Emergency Plan for AIDS Relief (PEPFAR), faces two realities that must be addressed, authors note (
pp. 1385–7): “How can the South African government provide comparable care with fewer resources? And what is the United States’ responsibility for the nearly 2 million South African patients currently receiving treatment? As South Africa transitions away from PEPFAR’s model of HIV care, dedicated resources will be required to assess rates of treatment initiation, retention, medication adherence, and virologic suppression. Ideally, the transition would involve efforts to strengthen the health system that are measurable and the introduction of a centrally monitored reporting system to provide data on all patients receiving care. In addition, support is necessary to retain health care workers trained in PEPFAR programs so that they can provide supervision and mentorship, since community-based clinicians often have limited training in HIV care. PEPFAR should continue to collaborate with the South African government to fund research evaluating innovative methods for retaining patients in care.” (I. T. Katz)
“PEPFAR has succeeded partly because it has benefited the entire health care system in ways that vaccination drives, maternal health initiatives, and other public health interventions hadn’t done,” writes the author of the second article (
pp. 1388–9). “Addressing defects and holes in Africa’s overall health systems, PEPFAR funded training for 140,000 new health care workers and the development of programs that used peer educators and community health workers to diagnose and treat patients with HIV at hard-to-reach rural sites. It was because of PEPFAR that [a patient discussed in the article] could undergo testing, be picked up at home and shepherded to the district hospital, and survive [extensively drug-resistant] tuberculosis. In less than a decade, PEPFAR has created health care systems in regions where people had never even seen a doctor.…
“Now I believe we have two options: improving the clinic further . . . or backtracking to the funeral parlor next door.” (P. Babaria)
Cardiac-Resynchronization Therapy in Heart Failure: A study of cardiac-resynchronization therapy in patients with systolic heart failure was stopped for futility, investigators report, adding that the use of an implanted device may have increased mortality (pp. 1395–405; J. Holzmeister, johannes.holzmeister@usz.ch).

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 11, 2013 * Vol. 20, No. 197
Providing news and information about medications and their proper use

>>>Infectious Diseases Report
Source:
Nov. 1 issue of Clinical Infectious Diseases (2013; 57).
Bundled Care for Staph aureus Septicemia: Improved management and lower mortality resulted from a bundle-oriented approach to Staphylococcus aureus bacteremia (SAB), researchers report (pp. 1225–33). Six evidence-based quality-of-care indicators (QCIs) for management of SAB were identified through a systematic literature review and implemented in a quasi-experimental fashion at 12 Spanish tertiary hospitals, with these results: “A total of 287 and 221 patients were included in the preintervention and intervention periods, respectively. After controlling for potential confounders, the intervention was independently associated with improved adherence to follow-up blood cultures (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.78–4.49), early source control (OR, 4.56; 95% CI, 2.12–9.79), early intravenous cloxacillin for methicillin-susceptible isolates (OR, 1.79; 95% CI, 1.15–2.78), and appropriate duration of therapy (OR, 2.13; 95% CI, 1.24–3.64). The intervention was independently associated with a decrease in 14-day and 30-day mortality (OR, 0.47; 95% CI, 0.26–0.85 and OR, 0.56; 95% CI, 0.34–0.93, respectively).” (J. Rodríguez-Baño, jesusrb@us.es)
While promising, this approach is not “ready for prime time,” writes an editorialist (
pp. 1234–6): “The feasibility of each quality indicator and whether it could have a measurable impact alone without [infectious disease (ID)] consultation should be assessed. Some hospitals may not have access to ID consultation for all patients with SAB, making a measure such as early source identification and control difficult to implement consistently and effectively. In addition, it will be essential to consider the ease of data measurement and collection by hospitals. For example, information regarding treatment duration according to complexity of infection cannot be easily gathered as most patients are discharged from the hospital prior to completing their course of antibiotic therapy. Furthermore, data abstractors will need a method to distinguish between ‘uncomplicated’ and ‘complicated’ SAB as there are no ICD-9 codes for either. Finally, careful attention is required to determine which patients should be included and excluded from the metrics and compliance monitoring. For example, patients with ‘complicated bacteremia or predisposing condition for endocarditis’ must be clearly defined to determine those in whom echocardiography should be performed.” (C. Liu, catherine.liu@ucsf.edu)

>>>Oncology Highlights
Source:
Oct. 10 issue of the Journal of Clinical Oncology (2013; 31).
Response-Guided Neoadjuvant Chemotherapy for Breast Cancer: Compared with adjuvant chemotherapy, response-guided adjuvant chemotherapy has the potential to improve disease-free survival (DFS) and overall survival (OS) in women with early breast cancer, according to results of an exploratory analysis (pp. 3623–30). Early responders to two cycles of docetaxel, doxorubicin, and cyclophosphamide (TAC) were randomly assigned to four (n = 704) or six (n = 686) additional TAC cycles or to four cycles of TAC (n = 321) or vinorelbine and capecitabine (NX; n = 301) before surgery, with these results: “DFS was longer in early responders receiving TAC × 8 than in those receiving TAC × 6 (hazard ratio [HR], 0.78; 95% CI, 0.62 to 0.97; P = .026), and in early nonresponders receiving TAC-NX than in those receiving TAC × 6 (HR, 0.59; 95% CI, 0.49 to 0.82; P = .001). Exploratory analysis showed that DFS after response-guided chemotherapy (TAC × 8 or TAC-NX) was significantly longer (HR, 0.71; 95% CI, 0.60 to 0.85; P < .003), as was OS (HR, 0.79; 95% CI, 0.63 to 0.99; P = .048), than on conventional chemotherapy (TAC × 6). DFS was longer after response-guided chemotherapy in all hormone receptor–positive tumors (luminal A HR = 0.55, luminal B [human epidermal growth factor receptor 2 (HER2) negative] HR = 0.40, and luminal B [HER2 positive] HR = 0.56), but not in hormone receptor–negative tumors (HER2 positive [nonluminal] HR = 1.01 and triple negative HR = 0.87).… pCR predicted an improved DFS in triple-negative (HR = 6.67), HER2-positive (nonluminal; HR 5.24), or luminal B (HER2-negative) tumors (HR = 3.74).” (G. von Minckwitz, gunter.vonminckwitz@germanbreastgroup.de)

>>>PNN NewsWatch
* PNN will not be published on Mon., Oct. 14, Columbus Day.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 15, 2013 * Vol. 20, No. 198
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 15 issue of the Annals of Internal Medicine (2013; 159).
Lifestyle Interventions in Type 2 Diabetes: The incidence of type 2 diabetes can be reduced in high-risk patients through comprehensive lifestyle interventions, according to a systematic review and meta-analysis of 20 randomized controlled trials (pp. 543–51). Once the disease occurs, however, evidence is lacking, authors report: “Seven studies reported that lifestyle interventions decreased the risk for diabetes from the end of intervention up to 10 years after it. In patients with diabetes, 2 randomized, controlled trials (which included pharmacotherapy) reported no improvement in all-cause mortality (risk ratio, 0.75 [95% CI, 0.53 to 1.06]). Composite outcomes for cardiovascular disease were too heterogeneous to pool. One trial reported improvement in microvascular outcomes at 13-year follow-up.” (C. Korownyk, cpoag@ualberta.ca)

>>>Internal Medicine Report
Source:
Oct. 14 issue of the JAMA Internal Medicine (2013; 173).
Cholecalciferol in Isolated Systolic Hypertension: In older patients with isolated systolic hypertension, vitamin D supplementation failed to improve blood pressure or markers of vascular health, researchers report (pp. 1672–9). Patients at primary care and hospital clinics who were 70 years or older with supine systolic blood pressure >140 mm Hg and supine diastolic blood pressure <90 mm Hg and baseline 25-hydroxyvitamin D levels less than 30 ng/mL, oral cholecalciferol 100,000 IU or placebo every 3 months for 1 year produced these outcomes: “A total of 159 participants were randomized (mean age, 77 years). Mean baseline office systolic blood pressure was 163/78 mm Hg. Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group (+8 ng/mL at 1 year, P < .001). No significant treatment effect was seen for mean (95% CI) office blood pressure (−1 [−6 to 4]/−2 [−4 to 1] mm Hg at 3 months and 1 [−2 to 4]/0 [−2 to 2] mm Hg overall treatment effect). No significant treatment effect was evident for any of the secondary outcomes (24-hour blood pressure, arterial stiffness, endothelial function, cholesterol level, glucose level, and walking distance). There was no excess of adverse events in the treatment group, and the total number of falls was nonsignificantly lower in the group receiving vitamin D (36 vs 46, P = .24).” (M. D. Witham, m.witham@dundee.ac.uk)

>>>Lancet Highlights
Source:
Oct. 12 issue of Lancet (2013; 382).
VEGF Inhibition in Age-Related Choroidal Neovascularisation: In a head-to-head 2 X 2 factorial comparison, ranibizumab and bevacizumab were similarly effective in 628 patients with active, previously untreated neovascular age-related macular degeneration (pp. 1258–67). “Reduction in the frequency of retreatment resulted in a small loss of efficacy irrespective of drug,” the investigators conclude. “Safety was worse when treatment was administered discontinuously. These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought.” (U. Chakravarthy, u.chakravarthy@qub.ac.uk)

>>>PNN NewsWatch
* FDA on Friday approved Nasacort Allergy 24HR (triamcinolone acetonide) nasal spray for nonprescription treatment of nasal allergy symptoms (nasal congestion, runny nose, sneezing, and itchy nose) in children 2 years of age and older, adolescents, and adults.

>>>PNN JournalWatch
* Smoking Cessation Treatment and Risk of Depression, Suicide, and Self Harm in the Clinical Practice Research Datalink: Prospective Cohort Study, in
BMJ, 2013; 347: f5704. (K. H. Thomas, kyla.thomas@bristol.ac.uk)
* Primary Care Interventions to Prevent Tobacco Use in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement, in
Annals of Internal Medicine, 2013; 159: 552–7. (www.uspreventiveservicestaskforce.org)
* Advanced Wound Care Therapies for Nonhealing Diabetic, Venous, and Arterial Ulcers: A Systematic Review, in
Annals of Internal Medicine, 2013; 159: 532–42. (N. Greer, nancy.greer@va.gov)
* Optimizing Care for HIV-Infected People Who Use Drugs: Evidence-Based Approaches to Overcoming Healthcare Disparities, in
Clinical Infectious Diseases, 2013; 57: 1309–17. (J. P. Meyer, jaimie.meyer@yale.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 16, 2013 * Vol. 20, No. 199
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 16 issue of JAMA (2013; 310).
Universal Precautions & Antibiotic-Resistant Bacteria: In a cluster-randomized trial of 20 medical and surgical intensive care units (ICUs), authors report that “the use of gloves and gowns for all patient contact compared with usual care among patients in medical and surgical ICUs did not result in a difference in the primary outcome of acquisition of [methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE)]” (pp. 1571–80). Comparing intervention and usual-care ICUs, the investigators found these changes in a primary outcome of acquisition of MRSA or VRE: “From the 26,180 patients included, 92,241 swabs were collected for the primary outcome. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1,000 patient–days (95% CI, 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1,000 patient–days (95% CI, 14.09 to 20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1,000 patient–days (95% CI, 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1,000 patient–days (95% CI, 13.48 to 19.68) in the study period, a difference in changes that was not statistically significant (difference, −1.71 acquisitions per 1,000 person–days, 95% CI, −6.15 to 2.73; P = .57). ” (A. D. Harris, aharris@epi.umaryland.edu)
Metoclopramide in Pregnancy: Safety data from a Danish registry shows that “metoclopramide use in pregnancy was not associated with increased risk of major congenital malformations overall, any of … 20 individual malformation categories assessed, spontaneous abortion, or stillbirth” (pp. 1601–11). Metoclopramide-exposed and -unexposed women matched in a 1:4 ratio from a cohort of 1.2 million pregnancies had these congenital outcomes: “Among 28,486 women exposed to metoclopramide in the first trimester, 721 had an infant with a major congenital malformation (25.3 [95% CI, 23.5–27.1] cases per 1,000 births), compared with 3,024 among 113,698 unexposed women (26.6 [95% CI, 25.7–27.5] per 1,000 births). There were no significant associations between metoclopramide use and malformations overall (prevalence odds ratio, 0.93 [95% CI, 0.86–1.02]) or any of the 20 individual malformation categories, eg, neural tube defects, transposition of great vessels, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of the aorta, cleft lip, cleft palate, anorectal atresia/stenosis, and limb reduction (upper limit of 95% CI below 2.0 for 17 of 20 categories). Metoclopramide was not associated with increased risk of spontaneous abortion (757 cases [20.0 {95% CI, 18.5–21.4} per 1,000] among 37,946 metoclopramide-exposed women and 9,414 cases [62.1 {95% CI, 60.9–63.3} per 1,000] among 151,661 unexposed women; HR, 0.35 [95% CI, 0.33–0.38]) and stillbirth (142 cases [3.5 {95% CI, 2.9–4.1} per 1,000] among 40,306 metoclopramide-exposed women and 634 cases [3.9 {95% CI, 3.6–4.2} per 1,000] among 161,098 unexposed women; HR, 0.90 [95% CI, 0.74–1.08]).” (B. Pasternak, bjp@ssi.dk)
Antiretroviral Therapy in HIV-Discordant Couples: Treatment of the infected partner in HIV-discordant couples lowers the rate of HIV transmission, according to authors of a JAMA Clinical Evidence Synopsis (pp. 1619–20): “In each [HIV Prevention Trials Network Study 052] group, 14% of participants had 1 or more severe or life-threatening events…, suggesting no increased risk associated with antiretroviral therapy in this setting. The most frequent adverse events were infections and gastrointestinal, metabolic, nutritional, psychiatric, and nervous system disorders. In contrast, grade 3 or 4 laboratory abnormalities (most frequently neutropenia, hyperphosphatemia, and hyperbilirubinemia) were more common in participants receiving early antiretroviral therapy (27%) than among those receiving delayed treatment (18%).” (A. Anglemyer, andrew.anglemyer@ucsf.edu)

>>>PNN NewsWatch
* FDA is investigating an increasing frequency of reports of serious and life-threatening blood clots and severe narrowing of arteries and veins of patients taking ponatinib (Icusig, ARIAD Pharmaceuticals). Patients taking ponatinib should seek immediate medical attention if they experience symptoms suggesting a heart attack or stroke, FDA said.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 17, 2013 * Vol. 20, No. 200
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 17 issue of the New England Journal of Medicine (2013; 369).
Safety of Tiotropium Respimat Inhaler: In patients with chronic obstructive pulmonary disease (COPD), tiotropium 2.5 or 5 µg delivered using the soft-mist Respimat Inhaler produced noninferior efficacy and safety outcomes in a comparison with 18-µg doses of the drug delivered by the dry-powder HandiHaler device, researchers report (pp. 1491–501). The randomized, double-blind, parallel-group study included 17,135 patients with COPD and produced these results: “During a mean follow-up of 2.3 years, Respimat was noninferior to HandiHaler with respect to the risk of death (Respimat at a dose of 5 µg vs. HandiHaler: hazard ratio, 0.96; 95% confidence interval [CI], 0.84 to 1.09; Respimat at a dose of 2.5 µg vs. HandiHaler: hazard ratio, 1.00; 95% CI, 0.87 to 1.14) and not superior to HandiHaler with respect to the risk of the first exacerbation (Respimat at a dose of 5 µg vs. HandiHaler: hazard ratio, 0.98; 95% CI, 0.93 to 1.03). Causes of death and incidences of major cardiovascular adverse events were similar in the three groups.” (R. A. Wise, rwise@jhmi.edu)
This study provides “more than just reassurance on tiotropium safety,” an editorialist writes (
pp. 1555–6): “The rigor, careful conduct, scrupulous follow-up of patients, and use of clinically appropriate entry criteria in this study will reassure many clinicians who may have had concerns about the narrow focus of some COPD trials. The global recruitment, fast completion, and clear outcomes of the trial should also encourage all those who fear that real-world studies enrolling patients who truly reflect typically heterogeneous populations and phenotypes will produce messy, uninterpretable results. This study clears the air regarding the safety of tiotropium delivered by Respimat and at the same time establishes a high standard for clinical trials involving patients with COPD, particularly studies that focus on patient safety.” (C. R. Jenkins)
Colchicine in Acute Pericarditis: Added to conventional anti-inflammatory therapy with aspirin or ibuprofen in patients with acute pericarditis, colchicine reduces the frequency of incessant or recurrent disease, a study shows (pp. 1522–8). The trial enrolled adult patients with acute pericarditis and compared colchicine 0.5 mg once or twice daily for 3 months with placebo: “A total of 240 patients were enrolled, and 120 were randomly assigned to each of the two study groups. The primary outcome [of incessant or recurrent pericarditis] occurred in 20 patients (16.7%) in the colchicine group and 45 patients (37.5%) in the placebo group (relative risk reduction in the colchicine group, 0.56; 95% confidence interval, 0.30 to 0.72; number needed to treat, 4; P < 0.001). Colchicine reduced the rate of symptom persistence at 72 hours (19.2% vs. 40.0%, P = 0.001), the number of recurrences per patient (0.21 vs. 0.52, P = 0.001), and the hospitalization rate (5.0% vs. 14.2%, P = 0.02). Colchicine also improved the remission rate at 1 week (85.0% vs. 58.3%, P < 0.001). Overall adverse effects and rates of study-drug discontinuation were similar in the two study groups. No serious adverse events were observed.” (M. Imazio, massimo_imazio@yahoo.it)
Calcium Supplements & Fracture Prevention: The need for calcium supplements should be assessed based on patients’ dietary intake, according to a Clinical Practice article that examines the case of a 62-year-old healthy postmenopausal woman (pp. 1537–43): “Since her calcium intake is substantially greater than the [Institute of Medicine] recommendation of 1,200 mg per day for postmenopausal women, I would recommend that she increase her dietary calcium intake [of 1,040 mg per day] by 200 mg per day and discontinue her calcium supplements. If increasing her dietary intake is not feasible, she can reduce her calcium carbonate supplementation to one 500-mg tablet each day.” (D. C. Bauer, dbauer@psg.ucsf.edu)

>>>PNN NewsWatch
* Workers furloughed during the federal government shutdown in the U.S. return to their offices this morning. Parts of FDA and CMS continued working during the shutdown, but notices on the agencies’ websites have cautioned that information might not be up to date. Many CDC employees will need to catch up since they were out during the critical start-up of the influenza-vaccination season.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 18, 2013 * Vol. 20, No. 201
Providing news and information about medications and their proper use

>>>Rheumatology Report
Source:
Oct. issue of Arthritis & Rheumatism (2013; 65).
TNF Inhibitors in Ankylosing Spondylitis: In 334 patients with ankylosing spondylitis (AS), disease progression as measured through radiography of the spine was slowed by treatment with tumor necrosis factor alpha (TNF-alpha) inhibitors, with results better when therapy began early and was continued longer (pp. 2645–54). The longitudinal study included patients with at least two sets of spinal radiographs taken a minimum of 1.5 years apart. All received standard therapy with NSAIDs and TNF-alpha inhibitors. Statistical examination of times of initiation and duration of TNF-alpha therapy yielded these findings: “TNF-alpha inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30–0.88, P = 0.02). Patients with a delay of >10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09–5.3], P = 0.03). In [a zero-inflated negative binomial (ZINB)] model, the use of TNF-alpha inhibitors significantly reduced disease progression when the gap between radiographs was >3.9 years. The protective effect of TNF-alpha inhibitors was stronger after propensity score matching.” (N. Haroon, Nigil.Haroon@uhn.ca)
Sirukumab in Lupus Erythematosus: Sirukumab, a human anti–interleukin-6 monoclonal antibody, was well tolerated in a Phase I study of patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE) (pp. 2661–71). The dose-ranging study provided these insights into the safety and pharmacokinetics of the investigational drug: “We treated 31 CLE patients (23 with sirukumab, 8 with placebo) and 15 SLE patients (10 with sirukumab, 5 with placebo). Adverse events (AEs) occurred more often with sirukumab than placebo in CLE patients (91% versus 63%) and in SLE patients (90% versus 80%). Sirukumab led to sustained, dose-independent decreases in white blood cell counts, absolute neutrophil counts (neutropenia), and platelet counts (thrombocytopenia) and to minor elevations in total cholesterol levels. The majority of infections were mild respiratory infections. which were reported similarly across CLE cohorts but more often in sirukumab-treated than in placebo-treated SLE patients. Two serious AEs of infection occurred (pneumonia in the 10 mg/kg–treated group and iatrogenic wound infection in the 4 mg/kg–treated group). Sirukumab showed linear pharmacokinetics in CLE patients. Systemic exposure and half-life were comparable between CLE and SLE patients. No patient developed antibodies to sirukumab through 22 weeks. C-reactive protein and serum amyloid A mean concentrations were suppressed with sirukumab from week 1 to week 14.” (J. C. Szepietowski, jacek.szepietowski@umed.wroc.pl)

>>>JAPhA Highlights
Source:
Early-release article from the Journal of the American Pharmacists Association (2013; 53).
‘Newest Vital Sign’ in Older Adults: In older adults, utility of a commonly used health-literacy tool, the Newest Vital Sign (NVS), “is limited because of a floor effect that hinders its predictive power for medication adherence,” researchers report (pp. e198–204). The NVS instrument was “originally validated in a relatively young population (mean age 41.3 years),” the authors note, and “few studies have evaluated the performance of health literacy instruments in older patients.” Among 100 white community-dwelling older adults in Lisbon, Portugal, these results were noted when the NVS and Single Item Literacy Screener (SILS) were administered and results compared with self-reported Measure of Adherence to Therapy (MAT) scores: “The mean (± SD) age of the respondents was 73.3 ± 7.8 years and 71% were women. The NVS score was 0.81 ± 0.10 (of 6 possible points), and 95% of the respondents scored in the three lowest possible scores, indicating a notable floor effect. Age was found to be inversely correlated with NVS score ( P = 0.003). The MAT score was 36.2 ± 4.7 (range 17–42). No statistically significant association between the NVS and level of education ( P = 0.059 [Kruskal–Wallis]), gender ( P = 0.700 [Mann–Whitney]), SILS ( P = 0.167), or MAT ( P = 0.379) was identified.” (F. Fernandez-Llimos, f-llimos@ff.ul.pt)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 21, 2013 * Vol. 20, No. 202
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release article from BMJ (2013; 347).
Advanced Kidney Disease & Psoriasis: Patients with moderate-to-severe cases of psoriasis are at increased risk of developing chronic kidney disease irrespective of other common risk factors, according to a population-based cohort study and nested cross-sectional study (f5961). Using electronic medical records from the U.K., adult patients ages 18–90 with psoriasis were matched with up to five patients without psoriasis in the cohort study; in the nested analysis, patients ages 25–62 with the disease were matched with up to 10 patients without psoriasis. Results showed: “136,529 patients with mild psoriasis and 7,354 patients with severe psoriasis based on treatment patterns were matched to 689,702 unaffected patients. The adjusted hazard ratios (95% confidence intervals) for incident chronic kidney disease were 1.05 (1.02 to 1.07), 0.99 (0.97 to 1.02), and 1.93 (1.79 to 2.08) in the overall, mild, and severe psoriasis groups, respectively. Age was a significant effect modifier in the severe psoriasis group, with age specific adjusted hazard ratios (95% confidence intervals) of 3.82 (3.15 to 4.64) and 2.00 (1.86 to 2.17) for patients aged 30 and 60, respectively. In the nested analysis of 8,731 patients with psoriasis with measurements of affected body surface area matched to 87,310 patients without psoriasis, the adjusted odds ratios (95% confidence intervals) for chronic kidney disease were 0.89 (0.72 to 1.10), 1.36 (1.06 to 1.74), and 1.58 (1.07 to 2.34) in the mild, moderate, and severe psoriasis groups, respectively.” (J. M. Gelfand, joel.gelfand@uphs.upenn.edu)

>>>Allergy/Immunology Report
Source:
Oct. Journal of Allergy and Clinical Immunology (2013; 132).
H3 Antagonism in Allergen-Induced Nasal Congestion: In a proof-of-concept study, the selective H3-receptor antagonist JNJ-39220675 relieved allergen-induced nasal congestion but showed only a trend for increasing nasal patency, compared with pseudoephedrine, researchers report (pp. 838–46.e6). The single-dose, patient-blind, double-dummy, Phase IIa crossover study included 53 participants with ragweed allergy who received JNJ-39220675, pseudoephedrine, or placebo before exposure to ragweed allergen, with these results: “Smaller decreases in minimal cross-sectional area [of the nasal cavity] were observed after JNJ-39220675 (least square mean difference, −0.126; P = .06) and pseudoephedrine (least square mean difference, −0.195; P = .004) treatment compared with placebo. The means for the baseline-adjusted area under the curve of [total nasal symptom scores (TNSSs)] were significantly smaller for JNJ-39220675 (P = .0003) and pseudoephedrine (P = .04) versus placebo. JNJ-39220675 was significantly effective in treating all 4 individual symptoms (P ≤ .05 for all scores) compared with placebo, whereas pseudoephedrine only showed a trend for improvement in individual symptom scores of the TNSS. Insomnia was the most frequent adverse event (17.3%) associated with JNJ-39220675 treatment.” (W. T. Barchuk, wbarchuk@its.jnj.com)

>>>PNN NewsWatch
* FDA has approved macitentan (Opsumit, Actelion) for treatment of adults with pulmonary arterial hypertension. In a 742-participant study, macitentan delayed disease progression. Similar to other members of its drug class, macitentan is contraindicated in pregnant women; female patients can receive the drug only through the Opsumit Risk Evaluation and Mitigation Strategy (REMS) Program. Common adverse effects of the drug include anemia, nasopharyngitis, sore throat, bronchitis, headache, and influenza and urinary tract infections.

>>>PNN JournalWatch
* Comparison of Global Estimates of Prevalence and Risk Factors for Peripheral Artery Disease in 2000 and 2010: A Systematic Review and Analysis, in
Lancet, 2013; 382: 1329–40. (F. G. R. Fowkes, gerry.fowkes@ed.ac.uk)
* Out-of-Hospital Use of Proton Pump Inhibitors and Hypomagnesemia at Hospital Admission: A Nested Case-Control Study, in
American Journal of Kidney Diseases, 2013; 62: 730–7. (B. L. Jaber, bertrand.jaber@steward.org)
* Poor Oral Health and Quality of Life in Older U.S. Adults With Diabetes Mellitus, in
Journal of the American Geriatrics Society, 2013; 61: 1782–8. (D. L. Huang, huangdx@u.washington.edu)
* Optimizing Care for HIV-Infected People Who Use Drugs: Evidence-Based Approaches to Overcoming Healthcare Disparities, in
Clinical Infectious Diseases, 2013; 57: 1309–17. (J. P. Meyer, jaimie.meyer@yale.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 22, 2013 * Vol. 20, No. 203
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Oct. Journal of the American Geriatrics Society (2013; 61).
SNF Admissions of NH Residents With Advanced Dementia: Insertion of a percutaneous endoscopic gastrostomy (PEG) during hospitalization is strongly associated with admission of nursing home residents with advanced dementia to skilled-nursing facilities (SNFs), report authors who used a cohort design to analyze information from the Minimum Data Set, Medicare claims, and the On-line Survey Certification of Automated Records (pp. 1645–50). Data from 2000–06 in the U.S. show these patterns: “Sixty-one percent of residents with advanced dementia were admitted to a SNF after their hospitalization. [PEG] tube placement during hospitalization was strongly associated with SNF admission (adjusted odds ratio (AOR) = 2.31, 95% confidence interval (CI) = 1.85–2.88), as was better functional status (AOR = 1.21, 95% CI = 1.05–1.38). The presence of diabetes mellitus was associated with lower likelihood of SNF admission (AOR = 0.85, 95% CI = 0.73–0.99). Facility features significantly associated with SNF admission included more than 100 beds (AOR = 1.25, 95% CI = 1.07–1.46), being part of a chain (AOR = 1.31, 95% CI = 1.14–1.50), urban location (AOR = 1.21, 95% CI = 1.03–1.41), and for-profit status (AOR = 1.28, 95% CI = 1.09–1.51).” (J. L. Givens, JaneGivens@hsl.harvard.edu)
Practice-Based Learning for Improving Osteoporosis Care: Physicians who participated in the American Board of Internal Medicine Osteoporosis Practice Improvement Module showed improved patterns of osteoporosis care, researchers report (pp. 1651–60). In a retrospective cohort study, care provided by 850 U.S. board-certified internists or other specialists had these results for 23 process measures and 7 practice system domains of osteoporosis care: “Variability in performance on measures was found, with observed differences between general internists, geriatricians, and rheumatologists. Some practice system elements were modestly associated with measure performance; the largest association was between providing patient-centered self-care support and documentation of calcium intake and vitamin D estimation and counseling (correlation coefficients from 0.20 to 0.28, Ps < .002). For all practice types, the most commonly selected measure targeted for improvement was documentation of vitamin D level (38% of physicians). On average, physicians reported significant and large increases in performance on measures targeted for improvement.” (B. J. Hess, brianhessconsulting@gmail.com)

>>>Gastroenterology Report
Source:
Nov. issue of Gastroenterology (2013; 145).
Dietary Fiber & Inflammatory Bowel Disease Risk: The risk of Crohn’s disease (CD) but not ulcerative colitis (UC) can be lowered by long-term adequate intake of fiber, particularly from fruit, the Nurses’ Health Study shows (pp. 970–7). These patterns were noted among 170,776 women followed for 26 years (3.3 million person–years): “We confirmed 269 incident cases of CD (incidence, 8/100,000 person–years) and 338 cases of UC (incidence, 10/100,000 person–years). Compared with the lowest quintile of energy-adjusted cumulative average intake of dietary fiber, intake of the highest quintile (median of 24.3 g/day) was associated with a 40% reduction in risk of CD (multivariate HR for CD, 0.59; 95% confidence interval, 0.39–0.90). This apparent reduction appeared to be greatest for fiber derived from fruits; fiber from cereals, whole grains, or legumes did not modify risk. In contrast, neither total intake of dietary fiber (multivariate HR, 0.82; 95% confidence interval, 0.58–1.17) nor intake of fiber from specific sources appeared to be significantly associated with risk of UC.” (A. N. Ananthakrishnan, aananthakrishnan@partners.org)
Thiopurines & Lymphoma in Ulcerative Colitis: Patients with ulcerative colitis (UC) have a gradually increasing risk of developing lymphoma during treatment with thiopurines, according to a nationwide retrospective cohort study (pp. 1007–15.e3). VA data on 4,734 patients with UC show that 13% received thiopurine treatment for a median of 1 year. Per 1,000 person–years, incidence rates of lymphoma were 0.60, 2.31, and 0.28 among those who, respectively, had not been treated with thiopurines, had been treated with thiopurines, and had discontinued thiopurine treatment. (N. Kahn, nkhan2@tulane.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 23, 2013 * Vol. 20, No. 204
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Oct. 23/30 issue of JAMA (2013; 310).
Statins in Ventilator-Associated Pneumonia: Testing the theory that statins improve outcomes in various infections, investigators report that the drugs failed to improve 28-day mortality in a controlled trial of patients with ventilator-associated pneumonia (VAP) (pp. 1692–700). At 26 intensive-care units in France in 2010–13, patients received either simvastatin 60 mg or placebo beginning when antibiotic therapy started and administered until discharge, death, or day 28: “The study was stopped for futility at the first scheduled interim analysis after enrollment of 300 patients, of whom all but 7% in the simvastatin group and 11% in the placebo group were naive to statin therapy at ICU admission. Day-28 mortality was not lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95% CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, −3.0% to 14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to 29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054) (between-group difference, 7.7% [95%CI, −1.8% to 16.8%). There were no significant differences regarding day-14, ICU, or hospital mortality rates; duration of mechanical ventilation; or changes in [Sequential Organ Failure Assessment] score.” (L. Papazian, laurent.papazian@ap-hm.fr)
An editorialist writes of the need for testing of seemingly promising interventions in critically ill patients (
pp. 1567–8): “Although it is appealing to believe there is a simple approach to what should and should not be done to prevent infection in the ICU, best practices are more nuanced and unfortunately, one size does not fit all. The final approach must be adapted to fit the epidemiology of specific ICUs and should also consider the type of resources available. The study by Harris et al serves as a poignant reminder that many questions remain for what constitutes best practice in the care of critically ill patients. Ongoing investment in these sorts of resource-intensive trials is essential for continued progress.” (P. N. Malani, pmalani@umich.edu)
Influenza Vaccination & Cardiovascular Outcomes:
According to a meta-analysis of clinical trials, administration of influenza vaccination is associated with a lowering of risk for cardiovascular events, with the greatest protection seen in those at highest risk because of active coronary disease (pp. 1711–20). A large multicenter trial is warranted, the authors conclude, based on these findings: “Five published and 1 unpublished randomized clinical trials of 6,735 patients (mean age, 67 years; 51.3% women; 36.2% with a cardiac history; mean follow-up time, 7.9 months) were included. Influenza vaccine was associated with a lower risk of composite cardiovascular events (2.9% vs 4.7%; RR, 0.64 [95% CI, 0.48–0.86], P = .003) in published trials. A treatment interaction was detected between patients with (RR, 0.45 [95% CI, 0.32–0.63]) and without (RR, 0.94 [95% CI, 0.55–1.61]) recent [acute coronary syndrome] (P for interaction = .02). Results were similar with the addition of unpublished data.” (J. A. Udell, jay.udell@utoronto.ca)
Findings such as these reinforce the need to vaccinate all possible people, writes an editorialist (
pp. 1681–2): “There are proven ways to increase vaccination coverage, including expanding access through nontraditional settings (eg, pharmacy, workplace, school venues), improving the use of evidence-based practices at medical sites (eg, standing orders, reminder or recall notification), and using immunization registries. One of the most consistent and relevant findings of operational research is that recommendation for vaccination from physicians and other health care professionals is a strong predictor of vaccine acceptance and receipt among patients. While few are in a position to develop new influenza vaccines, all health care practitioners can recommend influenza vaccine to their patients. Doing so will help achieve the goal of 100% vaccination for the 2013–2014 influenza season.” (K. M. Neuzil, kneuzil@path.org)

>>>PNN NewsWatch
* APhA is supporting passage of the compounding bill now before the Senate. While concerns remain, APhA said the bill “would protect the public from harm while maintaining access for consumers to important and often life-saving compounded preparations,” pharmacist.com reports.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 24, 2013 * Vol. 20, No. 205
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Oct. 24 issue of the New England Journal of Medicine (2013; 369).
Fungal Infections & Contaminated Methylprednisolone Injections: A year after the outbreak of fungal infections from contaminated methylprednisolone injections produced by the New England Compounding Center, two articles describe public-health aspects of the situation and clinical aspects of affected patients.
Beginning with a CDC investigation in Sept. 2012, “a large, multistate outbreak of fungal infections” was quickly linked to “injection of a contaminated glucocorticoid medication from a single compounding pharmacy,” write members of the Multistate Fungal Infection Outbreak Response Team (
pp. 1598–609). “Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians,” the authors write, adding these details: “By October 19, 2012, more than 99% of 13,534 potentially exposed persons had been contacted. As of July 1, 2013, there were 749 reported cases of infection in 20 states, with 61 deaths (8%). Laboratory evidence of Exserohilum rostratum was present in specimens from 153 case patients (20%). Additional data were available for 728 case patients (97%); 229 of these patients (31%) had meningitis with no other documented infection. Case patients had received a median of 1 injection (range, 1 to 6) of implicated methylprednisolone acetate. The median age of the patients was 64 years (range, 15 to 97), and the median incubation period (the number of days from the last injection to the date of the first diagnosis) was 47 days (range, 0 to 249); 40 patients (5%) had a stroke.” (B. J. Park, bpark1@cdc.gov)
While initially identified patients in the outbreak had fungal meningitis, clinical experience in the ensuing months demonstrates “a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors,” Multistate Fungal Infection Clinical Investigation Team members write in a second article (
pp. 1610–9): “Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P < 0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P < 0.001), and such infections developed in patients with and in those without meningitis.” (J. A. Jernigan, jqj9@cdc.gov)
Dapsone Hypersensitivity & Genetics: HLA-B and HLA-C genotyping may be useful in identifying risk for the frequently fatal dapsone hypersensitivity syndrome, researchers report (pp. 1620–8). The syndrome occurs in 0.5–3.5% of patients taking dapsone and has a mortality rate of 9.9%, the authors explain. A genomewide study of 872 patients who received dapsone for leprosy showed these associations: “Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P = 3.84 × 10−13). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P = 6.84 × 10−25). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans.” (J-J Liu, liuj3@gis.a-star.edu.sg)
Randomized Registry Trials: “The randomized registry trial represents a disruptive technology, a technology that transforms existing standards, procedures, and cost structures,” Perspective authors write (pp. 1579–81). “Today we … have registries and other powerful digital platforms. Today it may be possible to design and conduct megatrials with what we have: bigger data and smaller budgets.” (M. S. Lauer)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 25, 2013 * Vol. 20, No. 206
Providing news and information about medications and their proper use

>>>Health Affairs Highlights
Source:
Oct. issue of Health Affairs (2013; 32).
Delayed Aging & Medical Research: With slowing of the aging process “now a realistic goal,” medical researchers should examine the implications of people living longer and healthier lives, write authors (pp. 1698–705): “Most medical research remains focused on combating individual diseases. Using the Future Elderly Model—a microsimulation of the future health and spending of older Americans—we compared optimistic ‘disease specific’ scenarios with a hypothetical ‘delayed aging’ scenario in terms of the scenarios’ impact on longevity, disability, and major entitlement program costs. Delayed aging could increase life expectancy by an additional 2.2 years, most of which would be spent in good health. The economic value of delayed aging is estimated to be $7.1 trillion over fifty years. In contrast, addressing heart disease and cancer separately would yield diminishing improvements in health and longevity by 2060—mainly due to competing risks. Delayed aging would greatly increase entitlement outlays, especially for Social Security. However, these changes could be offset by increasing the Medicare eligibility age and the normal retirement age for Social Security. Overall, greater investment in research to delay aging appears to be a highly efficient way to forestall disease, extend healthy life, and improve public health.” (D. P. Goldman, dana.goldman@usc.edu)
Living Longer With Cardiovascular Disease: Opposing trends—less smoking but more obesity and diabetes combined with longer lives—have increased the overall number of people living with cardiovascular disease, researchers report (pp. 1706–14). Based on analysis of data from the nine National Health and Nutrition Examination Survey waves from 1973 to 2010, the authors project cardiovascular prevalence rates from 2015 to 2030:” We found that continued improvements in cardiovascular disease treatment and declining smoking rates will not outweigh the influence of increasing population age and obesity on cardiovascular disease risk. Given an aging population, an obesity epidemic, and declining mortality from the disease, the United States should expect to see a sharp rise in the health care costs, disability, and reductions in quality of life associated with increased prevalence of cardiovascular disease. Policies that target the treatment of high blood pressure and cholesterol and the reduction of obesity will be necessary to curb the imminent spike in cardiovascular disease prevalence.” (A. Pandya, anp2042@med.cornell.edu)

>>>Neurology Report
Source:
Oct. issue of Neurology (2013; 81).
Omega-3 Fatty Acids & Cognitive Function: Levels of omega-3 fatty acids in red blood cells (RBCs) showed no relationship with age-associated cognitive decline in a trial of 2,157 women (pp. 1484–91). Participants had normal cognition when enrolled in a postmenopausal hormone therapy study and followed over a median of 5.9 years. In a retrospective cohort analysis, investigators found these patterns among prerandomization RBC docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels and changes in cognition over time: “After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time.” (E. Ammann, eric-ammann@uiowa.edu)

>>>PNN NewsWatch
* Drug products such as Vicodin and Lortab would be moved to Schedule II if, as expected, DEA accepts an FDA recommendation made yesterday, report the New York Times and the Washington Post. The recommendation covers products containing hydrocodone plus acetaminophen or aspirin and would place a 90-day limit on days supply of a single prescription order. Medical and pharmacy organizations had opposed the move, and FDA had blocked DEA on the issue for years. The change in FDA’s position comes in the wake of a growing number of Americans dying each year from excessive use and abuse of opioid analgesics and hepatotoxicity from those products containing acetaminophen.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 28, 2013 * Vol. 20, No. 207
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Oct. 26 issue of Lancet (2013; 382).
Linagliptin in Older Patients With Type 2 Diabetes: The dipeptidyl peptidase-4 inhibitor linagliptin is effective and safe for treating poorly controlled type 2 diabetes, results of a placebo-controlled Phase III trial show (pp. 1413–23). Participants were aged 70 years or older and had glycated hemoglobin A1c (HbA1c) of 7.0% or more despite treatment with metformin, sulfonylureas, and/or basal insulin. Stratified randomization to linagliptin 5 mg or matching placebo for 24 weeks produced these outcomes: “241 community-living outpatients were randomised (162 linagliptin, 79 placebo). Mean age was 74.9 years (SD 4.3). Mean HbA1c was 7.8% (SD 0.8). At week 24, placebo-adjusted mean change in HbA1c with linagliptin was –0.64% (95% CI –0.81 to –0.48, p < 0.0001). Overall safety and tolerability were much the same between the linagliptin and placebo groups; 75.9% of patients in both groups had an adverse event (linagliptin n = 123, placebo n = 60). No deaths occurred. Serious adverse events occurred in 8.6% (14) of patients in the linagliptin group and 6.3% (five) patients in the placebo group; none were deemed related to study drug. Hypoglycaemia was the most common adverse event in both groups, but did not differ between groups (24.1% [39] in the linagliptin group, 16.5% [13] in the placebo group; odds ratio 1.58, 95% CI 0.78–3.78, p = 0.2083).” (A. H. Barnett, anthony.barnett@heartofengland.nhs.uk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2013; 347).
Analgesia & Steam Inhalation in Respiratory Tract Infections: In patients 3 years or older with acute respiratory tract infections, treatment with steam inhalation and analgesics—standard advice in primary care—is ineffective, according to results of an open, pragmatic, parallel-group, factorial randomized trial (f6041). A total of 889 primary-care patients in the U.K. were advised to use paracetamol (acetaminophen), ibuprofen, or both; take analgesics regularly or as needed; and use or do not use steam inhalation. Results based on mean symptom severity on days 2–4 showed: “Neither advice on dosing nor on steam inhalation was significantly associated with changes in outcomes. Compared with paracetamol, symptom severity was little different with ibuprofen (adjusted difference 0.04, 95% confidence interval −0.11 to 0.19) or the combination of ibuprofen and paracetamol (0.11, −0.04 to 0.26). There was no evidence for selective benefit with ibuprofen among most subgroups defined before analysis (presence of otalgia; previous duration of symptoms; temperature >37.5°C; severe symptoms), but there was evidence of reduced symptoms severity benefit in the subgroup with chest infections (ibuprofen −0.40, −0.78 to −0.01; combination −0.47; −0.84 to −0.10), equivalent to almost one in two symptoms rated as a slight rather than a moderately bad problem. Children might also benefit from treatment with ibuprofen (ibuprofen: −0.47, −0.76 to −0.18; combination: −0.04, −0.31 to 0.23). Reconsultations with new/unresolved symptoms or complications were documented in 12% of those advised to take paracetamol, 20% of those advised to take ibuprofen (adjusted risk ratio 1.67, 1.12 to 2.38), and 17% of those advised to take the combination (1.49, 0.98 to 2.18). Mild thermal injury with steam was documented for four patients (2%) who returned full diaries, but no reconsultations with scalding were documented.” (P. Little, p.little@soton.ac.uk)

>>>PNN NewsWatch
* FDA on Friday approved Zohydro ER, an extended-release formulation of hydrocodone bitartrate.

>>>PNN JournalWatch
* Comparative Effectiveness of Renin-Angiotensin System Blockers and Other Antihypertensive Drugs in Patients With Diabetes: Systematic Review and Bayesian Network Meta-Analysis, in
BMJ, 2013; 347: f6008. (Y-K Tu, yukangtu@ntu.edu.tw)
* Thirty Years of Disparities Intervention Research: What Are We Doing To Close Racial and Ethnic Gaps in Health Care?, in
Medical Care, 2013; 51: 1020–6. (A. R. Clarke)
* A New Option for Glycemic Control: Insulin Degludec, a New-Generation Basal Insulin with an Ultralong Duration of Action, in
Pharmacotherapy, 2013; 33: 10.1002/phar.1361. (S. R. Drab, drab@pitt.edu)
* Long-Acting Reversible Contraception: A Review in Special Populations, in
Pharmacotherapy, 2013; 33: 10.1002/phar.1358. (G. M. Prescott, gmzurick@buffalo.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 29, 2013 * Vol. 20, No. 208
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Oct. 28 issue of JAMA Internal Medicine (2013; 173).
Predicting Kidney Failure, Mortality in Rhabdomyolysis: In patients with rhabdomyolysis, the risk of severe acute kidney injury requiring continuous renal replacement therapy (RRT) or leading to death can be predicted on admission using commonly available demographic, clinical, and laboratory information, researchers report (pp. 1821–7). In a retrospective cohort study of 2,371 patients admitted to 2 large Boston teaching hospitals in 2000–11, patients with creatine phosphokinase levels in excess of 5,000 U/L within 3 days of admission had these outcomes based on a composite of RRT or in-hospital mortality: “The causes and outcomes of rhabdomyolysis were similar between the derivation and validation cohorts. In total, the composite outcome occurred in 19.0% of patients (8.0% required RRT and 14.1% died during hospitalization). The highest rates of the composite outcome were from compartment syndrome (41.2%), sepsis (39.3%), and following cardiac arrest (58.5%). The lowest rates were from myositis (1.7%), exercise (3.2%), and seizures (6.0%). The independent predictors of the composite outcome were age, female sex, cause of rhabdomyolysis, and values of initial creatinine, creatine phosphokinase, phosphate, calcium, and bicarbonate. We developed a risk-prediction score from these variables in the derivation cohort and subsequently applied it in the validation cohort. The C statistic for the prediction model was 0.82 (95% CI, 0.80-0.85) in the derivation cohort and 0.83 (0.80-0.86) in the validation cohort. The Hosmer-Lemeshow P values were .14 and .28, respectively. In the validation cohort, among the patients with the lowest risk score (<5), 2.3% died or needed RRT. Among the patients with the highest risk score (>10), 61.2% died or needed RRT.” (G. M. McMahon, gearoidmm@gmail.com)
“While the new McMahon rhabdomyolysis score has the potential to be an immediate classic, especially if validated in independent and diverse settings, it shares properties of risk calculators past that do not exploit the capabilities of modern-day electronic health records systems,” editorialists write (
pp.1828–9). “Nowadays, it is possible to embed code into these systems that calculates patient risk in real time from data continuously streaming into a patient’s hospital record.… Clinicians can be provided with real-time risk probabilities with an accuracy that may exceed the already impressive predictive capability of the McMahon score. If real-time prediction of rhabdomyolysis risk is the future, McMahon and colleagues will have provided crucial feasibility data and established an already excellent starting point for system-based practice that may improve the outcomes of patients with rhabdomyolysis and facilitate efficient resource use in their care.” (W. C. Winkelmayer, wcw1@stanford.edu)
Secondary Uses of Electronic Health Information: Patients presented with 18 scenarios of use of their electronic health information for secondary purposes (including pharmaceutical marketing) “cared most about the specific purpose for using their health information” and were not as sensitive as to who was using the information, a study shows (pp. 1798–806). A total of 3,336 adult participants gave these responses to various uses, users, and data sensitivity: “The use of data was a more important factor in the conjoint analysis (importance weight, 64.3%) than the user (importance weight, 32.6%) and data sensitivity (importance weight, 3.1%). In unadjusted linear regression models, marketing uses (beta = −1.55), quality improvement uses (beta = −0.51), drug company users (beta = −0.80), and public health department users (beta = −0.52) were associated with less willingness to share health information than research uses and university hospital users (all P < .001). Hispanics and African Americans differentiated less than whites between uses.” (D. Grande, dgrande@wharton.upenn.edu)
An editorialist proposes an alternative with regard to secondary use of patient information (
pp. 1806–7): “‘Why is our first obligation not to ensure that our patients’ data are used for research as they wish and expect them to be used?’ … Additional studies … should be pursued to determine whether the preferences they report are consistent across different populations and whether they hold up not only in response to theoretical questions but also post hoc in actual experience.” (I. S. Kohane, isaac_kohane@harvard.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 30, 2013 * Vol. 20, No. 209
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Nov. issue of the Diabetes Care (2013; 36).
Nutrigenetics of Metabolic Syndrome: In patients with a genetic variant located near an allele associated with metabolic syndrome (MetS), high-fat, calorically restricted diets may be more effective than low-fat diets for condition management, the POUNDS LOST study shows (pp. 3442–7). The trial included 738 patients with overweight/obesity whose average age was 60. Before random assignment to one of four weight-loss diets for a 2-year period, patients were genotyped for two variants located near the allele, IRS1. All diets had a 750-kcal/d deficit; they varied by fat content (40% v. 20% of calories as fat). Results showed: “Among rs1522813 A-allele carriers, the reversion rates of the MetS were higher in the high-fat diet group than those in the low-fat diet group over the 2-year intervention (P = 0.002), while no significant difference between diet groups was observed among noncarriers (P = 0.27). The genetic modulation on dietary effect was independent of weight changes. The odds ratio (OR) for the 2-year reversion of the MetS was 2.88 (95% CI 1.25–6.67) comparing the high-fat and low-fat diets among rs1522813 A-allele carriers, while the corresponding OR was 0.83 (0.36–1.92) in noncarriers. The variant rs2943641 was not observed to modulate dietary effects on the MetS status.” (L. Qi, nhlqi@channing.harvard.edu)
More than 20 loci associated with MetS have been identified at the genomewide level, an editorialist notes (
pp. 3379–81): “The inclusion of only variants near IRS1 and the modest effect sizes reported in the current study should be viewed with healthy skepticism. Furthermore, the POUNDS LOST group itself has reported elsewhere that variation in at least six different genes modulates the association between dietary composition and changes in metabolic traits. Thus, it is clear that no single gene or variant is likely responsible for interindividual differences in the response of MetS and its components to dietary interventions.” (C. Bouchard, claude.bouchard@pbrc.edu)
Benchmarking in Type 2 Diabetes: Among patients with type 2 diabetes cared for by primary-care physicians in Europe, benchmarking was associated with improved clinical outcomes in a 12-month, prospective randomized study (pp. 3388–95). Compared with standard care, provision of feedback benchmarked against other centers in each of six countries yielded these changes in clinical indicators: “Of 4,027 patients enrolled, 3,996 patients were evaluable and 3,487 completed 12 months of follow-up. Primary end point of HbA1c target was achieved in the benchmarking group by 58.9 vs. 62.1% in the control group (P = 0.398) after 12 months; 40.0 vs. 30.1% patients met the SBP target (P < 0.001); 54.3 vs. 49.7% met the LDL cholesterol target (P = 0.006). Percentages of patients meeting all three targets increased during the study in both groups, with a statistically significant increase observed in the benchmarking group. The percentage of patients achieving all three targets at month 12 was significantly larger in the benchmarking group than in the control group (12.5 vs. 8.1%; P < 0.001).” (M. P. Hermans, michel.hermans@uclouvain.be)
Clinical Inertia in Type 2 Diabetes: Clinicians lag for years in intensifying antidiabetic therapies, a retrospective cohort study shows, even when patients’ glycemic control is clearly suboptimal (pp. 3411–7). Data for 81,573 patients with type 2 diabetes in the U.K. Clinical Practice Research Datalink for 2004–06 with follow-up through 2011 show the following patterns: “In people with HbA1c ≥7.0, ≥7.5, or ≥8.0% (≥53, ≥58, or ≥64 mmol/mol), median time from above HbA1c cutoff to intensification with an additional [oral antidiabetic drug (OAD)] was 2.9, 1.9, or 1.6 years, respectively, for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years for those taking one, two, or three OADs. Mean HbA1c at intensification with an OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%. In patients taking one, two, or three OADs, median time from treatment initiation to intensification with an OAD or insulin exceeded the maximum follow-up time of 7.2 years. The probability of patients with poor glycemic control taking one, two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1–43.6% and with insulin 5.1–12.0%.” (K. Khunti, kk22@leicester.ac.uk)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Oct. 31, 2013 * Vol. 20, No. 210
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release article from and Oct. 31 issue of the New England Journal of Medicine (2013; 369).
Early Stem-Cell Transplantation in Aggressive Non-Hodgkin’s Lymphoma: In patients with high-intermediate-risk or high-risk diffuse, aggressive non-Hodgkin’s lymphoma who had a response to rituximab–CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) induction therapy, early autologous stem-cell transplantation improved progression-free survival but not overall survival, researchers report (pp. 1681–90). A total of 397 patients received five cycles of CHOP or CHOP-rituximab, and those responding randomly received three additional induction cycles of chemotherapy or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation.
Based on primary end points of 2-year progression-free survival and overall survival, results showed: “Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression-free survival rates of 69 and 55%, respectively (hazard ratio in the control group vs. the transplantation group, 1.72; 95% confidence interval [CI], 1.18 to 2.51; P = 0.005). Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively (hazard ratio, 1.26; 95% CI, 0.82 to 1.94; P = 0.30). Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P = 0.04 for interaction) and overall survival (P = 0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group.” (P. J. Stiff)
“Early myeloablative therapy, a 20th-century therapeutic innovation, remains an option for patients carefully selected with the use of 21st-century risk criteria,” an editorialist concludes (
pp. 1750–1). “The targeting of immune checkpoints used by tumors to actively evade immune destruction could … prove useful, as has been shown in the treatment of chemoresistant solid tumors. It remains to be proved that these targeting agents will challenge myeloablative therapies for the … patients with a poor prognosis, and obtaining proof will necessitate clinical trials in which patients should be encouraged to participate.” (N. Milpied)
nab-Paclitaxel & Gemcitabine in Pancreatic Cancer: In a Phase III trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine in patients with metastatic pancreatic adenocarcinoma, the combination significantly improved overall survival, progression-free survival, and response rate, but with increased frequencies of peripheral neuropathy and myelosuppression, compared with gemcitabine alone (pp. 1691–703): “A total of 861 patients were randomly assigned to nab-paclitaxel plus gemcitabine (431 patients) or gemcitabine (430). The median overall survival was 8.5 months in the nab-paclitaxel–gemcitabine group as compared with 6.7 months in the gemcitabine group (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.62 to 0.83; P < 0.001). The survival rate was 35% in the nab-paclitaxel–gemcitabine group versus 22% in the gemcitabine group at 1 year, and 9% versus 4% at 2 years. The median progression-free survival was 5.5 months in the nab-paclitaxel–gemcitabine group, as compared with 3.7 months in the gemcitabine group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.58 to 0.82; P < 0.001); the response rate according to independent review was 23% versus 7% in the two groups (P < 0.001). The most common adverse events of grade 3 or higher were neutropenia (38% in the nab-paclitaxel–gemcitabine group vs. 27% in the gemcitabine group), fatigue (17% vs. 7%), and neuropathy (17% vs. 1%). Febrile neutropenia occurred in 3% versus 1% of the patients in the two groups. In the nab-paclitaxel–gemcitabine group, neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days.” (D. D. Von Hoff, dvh@tgen.org)
Education Bubbles: Pharmacy graduates with increasing debt-to-income ratios could be instructive to medical educators as this trend worsens for graduating physicians, according to a Perspective article on a possible “medical-education bubble.” (10.1056/NEJMp1310778; D. A. Asch)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 1, 2013 * Vol. 20, No. 211
Providing news and information about medications and their proper use

>>>Pharmacotherapy Report
Source:
Nov. issue of Pharmacotherapy, a theme issue on anticoagulation (2013; 33).
Clinical Outcomes With New Warfarin Management Method: In the STORM2, trial of long-term warfarin therapy, 55 patients had a significant increase in time spent in therapeutic range, and pharmacogenetic testing demonstrated a need for higher-than-usual doses in those with certain gene patterns (pp. 1136–46; previously reported in PNN on Aug. 30 based on early online publication). Use of the STORM2 intervention and analysis of polymorphisms in the genes for vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 isoenzyme produced these results: “The percentage of time that the INR is within the time in therapeutic range (TTR) improved from 56% before the intervention to 81% after the intervention (p < 0.0001), and time spent at extreme INR values of lower than 1.5 or higher than 5 was reduced from 3.1% to 0.4% (p = 0.01). Clinician time was less than 10 minutes per four patient visits per month. Genetic polymorphisms did not correlate with INR stability or the increase in warfarin dose after vitamin K supplementation. The content of the vitamin K product, however, was only 34–76% of the labeled amount. Patients with the GG VKORC1 genotype required a higher warfarin dose than predicted by the genomic-based dosing chart in the warfarin package insert.” (H. I. Bussey, bussey@gcresearch.com)
Reacting to this and other articles on anticoagulation in this issue, an editorialist writes that “changes in the anticoagulation landscape are coming that may significantly impact the roles of anticoagulation clinics in the future” (
pp. 1133–5): “These include an increased role for patient self-testing and self-management, availability of pharmacogenomic information and automated dosing algorithms, and approval of novel oral anticoagulants as alternatives to warfarin. However, with each of these advances, a role for a highly educated and well-trained anticoagulation specialist is evident. The need exists for educating patients and caregivers about emerging self-monitoring technologies, aiding in interpretation and utilization of pharmacogenomic information, and appropriately selecting and monitoring new oral anticoagulants. These services will continue to be in high demand. The anticoagulation specialist will also need to provide other antithrombotic functions such as formulary management, management of bleeding and anticoagulant reversal, periprocedural antithrombotic recommendations, coordination during transitions of care, and health care team education. The face of anticoagulation services has become brighter as tremendous opportunities continue to evolve for fruitful collaboration and research.” (W. L. Baker, wbaker@uchc.edu)
Comprehensive Warfarin Pharmacogenetics Service: At the University of Illinois at Chicago, a comprehensive warfarin pharmacogenetics service has successfully implemented routine genotype-guided warfarin dosing, authors report, “with most genotypes available prior to the second warfarin dose and good adherence to genotype-guided dose recommendations by the medical staff” (pp. 1156–64). Based on analysis of 80 patients who began warfarin therapy managed through the service, these results were identified: “Of 436 genotype orders placed during the first 6 months of the service, 190 (44%) were deemed appropriate. For the 80 patients on the service who consented to data collection, 76% of the genotypes were available prior to the second warfarin dose. The median (range) time from genotype order to genotype result was 26 hours (7–80 hrs), and the time to genotype-guided dose recommendation was 30 hours (7–80 hrs). A total of 73% of warfarin doses ordered by the medical staff were within 0.5 mg of the daily dose recommended by the pharmacogenetics consult service.” (L. H. Cavallari, humma@uic.edu)

>>>PNN NewsWatch
* Acting to further stem the number of drug shortages in the U.S., FDA yesterday announced a strategic plan that would improve the agency’s response to imminent or existing shortages and proposed a rule requiring new manufacturer notifications of permanent or temporary actions that could create or worsen shortages. Following the President’s 2011 Executive Order on reducing drug shortages, the number of new shortages in 2012 was 117, down from 251 in 2011, FDA said.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 4, 2013 * Vol. 20, No. 212
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 2 issue of Lancet (2013; 382).
Octreotide in Polycystic Kidney Disease: Large randomized controlled trials of somatostatin analogues are merited in patients with autosomal-dominant polycystic kidney disease, investigators conclude, based on a single-blind controlled trial of octreotide long-acting release (LAR) (pp. 1485–95). The parallel-group study, conducted at five Italian hospitals, assigned participants to two injections of octreotide-LAR 20 mg or placebo every 28 days. The trial used a primary endpoint of change in total kidney volume (TKV), measured by MRI, at 1- and 3-year follow-up in adult patients with initial glomerular filtration rates of 40 mL/min or more: “Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up; at this timepoint, mean TKV increased significantly less in the octreotide-LAR group (46.2 mL, SE 18.2) compared with the placebo group (143.7 mL, 26.0; p = 0.032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220.1 mL, 49.1) was numerically smaller than in the placebo group (454.3 mL, 80.8), but the difference was not significant (p = 0.25). 37 (92.5%) participants in the octreotide-LAR group and 32 (82.1%) in the placebo group had at least one adverse event (p = 0.16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related.” (G. Remuzzi, giuseppe.remuzzi@marionegri.it)
End Game for AIDS: “HIV is a wily beast,” an editorialist writes while pondering “an AIDS end game” (pp. 1462–4), “but recent insights seem to offer tangible clues about how to begin to consign the AIDS pandemic to the dustbin of history.” (K. H. Mayer, khmayer@gmail.com)

>>>PNN NewsWatch
* FDA on Friday made its first approval of a “breakthrough” new drug, indicating substantial improvement over available therapies for a serious or life-threatening disease. Obinutuzumab (Gazyva, Genentech) was approved for use with chlorambucil in patients with previously untreated chronic lymphocytic leukemia. In an open-label study of 356 patients, obinutuzumab plus chlorambucil yielded progression-free survival of 23 months, significantly longer than 11.1 months with chlorambucil alone, FDA said.
* Marketing and sales of
ponatinib (Iclusig, Ariad Pharmaceuticals) have been suspended because of a risk of life-threatening blood clots and severe narrowing of blood vessels, FDA announced late Thursday. Earlier in October, the agency said it was investigating reports of such problems (see PNN, Oct. 16). Patients currently taking the drug and not responding should discontinue therapy, FDA said, and no new patients should be started on ponatinib. Those already taking and responding to the drug and who have a positive benefit:risk ratio can be continued on therapy under a single-patient IND or expanded-access registry program.
*
FDA has approved changes to the product labeling of ezogabine (Potiga; GlaxoSmithKline, Valeant) warning of risks of abnormalities to the retina in the eye, potential vision loss, and skin discoloration, all of which may become permanent.

>>>PNN JournalWatch
* Management of Nocturnal Enuresis, in
BMJ, 2013; 347: f6259. (P. H. Y. Caldwell, patrina.caldwell@health.nsw.gov.au)
* The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders, in
American Journal of Psychiatry, 2013; 170: 1249–62. (E. Vieta, evieta@clinic.ub.es)
* Lamotrigine Dosing for Pregnant Patients With Bipolar Disorder,
American Journal of Psychiatry, 2013; 170: 1240–7. (C. T. Clark, crystal.clark@northwestern.edu)
* Rare Bleeding Disorders in Children: Identification and Primary Care Management, in
Pediatrics, 2013; 132: 882–92. (S. S. Acharya)
* Use of a Medication Reconciliation Tool in an Outpatient Geriatric Clinic, in
Journal of the American Pharmacists Association, 2013; 53: 652–8. (S. M. Vouri, scott.vouri@stlcop.edu)
* COPD 2013: An Update on Treatment and Newly Approved Medications for Pharmacists, in
Journal of the American Pharmacists Association, 2013; 53: e219–e231. (K. Meyer, kmeyer@acuityhealthcare.net)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 5, 2013 * Vol. 20, No. 213
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 5 issue of the Annals of Internal Medicine (2013; 159).
Opioid Overdose After Prison Release: In a cohort study from Washington State, opioid overdose was a common reason for mortality among those released from prisons, leading researchers to conclude that “innovation is needed to reduce the risk for overdose among former prisoners” (pp. 592–600). Data on 76,208 people released from prisons showed these relationships among death and opioid and other causes of death: “The all-cause mortality rate was 737 per 100,000 person–years (95% CI, 708 to 766) (n = 2,462 deaths). Opioids were involved in 14.8% of all deaths. Overdose was the leading cause of death (167 per 100,000 person-years [CI, 153 to 181]), and overdose deaths in former prisoners accounted for 8.3% of the overdose deaths among persons aged 15 to 84 years in Washington from 2000 to 2009. Women were at increased risk for overdose (HR, 1.38 [CI, 1.12 to 1.69]) and opioid-related deaths (HR, 1.39 [CI, 1.09 to 1.79]).” (I. A. Binswanger, ingrid.binswanger@ucdenver.edu)
Patient-Driven Pharyngitis Care: Based on research into participatory medicine conducted at a national chain of retail health clinics, patients could use new scoring criteria to determine whether to seek care for sore throats (pp. 577–83). The retrospective cohort study included 71,776 patients aged 15 years or older who had pharyngitis and visited clinics in 2006–08. A score derived by the investigators to identify those at low risk of group A streptococcal (GAS) pharyngitis performed as follows in comparison with the Centor score and other traditional scores that require clinician evaluation and input: “If patients aged 15 years or older with sore throat did not visit a clinician when the new score estimated the likelihood of GAS pharyngitis to be less than 10% instead of having clinicians manage their symptoms following guidelines that use the Centor score, 230,000 visits would be avoided in the United States each year and 8,500 patients with GAS pharyngitis who would have received antibiotics would not be treated with them.” (A. M. Fine, andrew.fine@childrens.harvard.edu)
Midlife Dietary Patterns & Healthy Aging: Better dietary patterns during midlife are associated with greater health and well-being in women surviving to older ages, according to findings from the Nurses’ Health Study (pp. 584–91). Focusing on 10,670 women in the study who were in their late 50s and early 60s in 1984–86, investigators found these patterns between Alternative Healthy Eating Index-2010 (AHEI-2010) and Alternate Mediterranean diet scores and “healthy” aging (survival to 70 years or older with no major chronic diseases or major impairments in cognitive or physical function or mental health): “After multivariable adjustment, greater adherence to the AHEI-2010 (upper vs. lower quintiles) in midlife was related to 34% (95% CI, 9% to 66%; P for trend < 0.001) greater odds of healthy versus usual aging. Greater adherence to Alternate Mediterranean diet was related to 46% (CI, 17% to 83%; P for trend = 0.002) greater odds of healthy aging. When … 4 components of healthy aging were analyzed separately, the AHEI-2010 and Alternate Mediterranean diet were significantly associated with greater likelihood of no major limitations in physical function and mental health.” (C. Samieri, cecilia.samieri@channing.harvard.edu)
Pediatric Screening for Primary Hypertension: In an update to 2003 recommendations, the U.S. Preventive Services Task Force (USPSTF) concludes that “the current evidence is insufficient to assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease in childhood or adulthood” (pp. 613–9). In its report, USPSTF presents its rationale and makes recommendations for clinical practice and research. (www.uspreventiveservicestaskforce.org)

>>>PNN NewsWatch
* Janssen Pharmaceuticals will pay a $400 million criminal fine for introducing a misbranded drug, Risperdal (risperidone), into interstate commerce, and also $1.25 billion under a separate civil settlement concerning the same drug, FDA and the Dept. of Justice said yesterday. The fine and settlement relate to alleged marketing of the drug for agitation associated with dementia in older patients, an off-label use.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.


PNN Pharmacotherapy Line
Nov. 6, 2013 * Vol. 20, No. 214
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 6 issue of JAMA (2013; 310).
Colloids v. Crystalloids in Hypovolemic Shock: Mortality at 28 days was unaffected by the choice of colloids or crystalloids in critically ill patients, according to results of the Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial (pp. 1809–17). Colloid therapy resulted in lower 90-day mortality rates, but this finding should be considered exploratory, authors conclude. A total of 2,857 patients received colloids (gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (isotonic or hypertonic saline or Ringer lactate solution), with these results: “Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, −0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, −0.04 to 2.10] days; P = .03).” (D. Annane, djillali.annane@rpc.aphp.fr)
“There may be no definitive answer to the question of whether patients with hypovolemic shock should preferentially receive colloids or crystalloids,” editorialists write (
pp. 1803–4). “Rather, there are a number of complexities, including the type of shock requiring resuscitation, the resuscitation targets, and the use of adjunctive vasoactive therapies. In addition, any given fluid choice could have both beneficial and harmful effects, with trade-offs that vary depending on the other complexities listed above. Thus, perhaps the most important message from the latest round of trials is that simply performing larger 2-group trials with greater rigor will not bring the field to consensus. Instead, alternative study designs should be considered, perhaps with multiple study interventions and use of adaptive trial design methods, such as response-adaptive randomization, to better capture the complexity of modern resuscitation options.” (C. W. Seymour, seymourcw@upmc.edu)
Adverse Outcomes & Testosterone Therapy: In a retrospective cohort study, men in the VA system who were on testosterone replacement therapy had higher rates of a composite measure of all-cause mortality, myocardial infarction (MI), and stroke, researchers report (pp. 1829–36). The analysis included those with low testosterone levels who had coronary angiography in 2005–11. Results showed: “Of the 8,709 men with a total testosterone level lower than 300 ng/dL, 1,223 patients started testosterone therapy after a median of 531 days following coronary angiography. Of the 1,710 outcome events, 748 men died, 443 had MIs, and 519 had strokes. Of 7,486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. Among 1,223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, −1.4% to 13.1%) at 3 years after coronary angiography. In Cox proportional hazards models adjusting for the presence of coronary artery disease, testosterone therapy use as a time-varying covariate was associated with increased risk of adverse outcomes (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). There was no significant difference in the effect size of testosterone therapy among those with and without coronary artery disease (test for interaction, P = .41).” (P. M. Ho, Michael.Ho@va.gov)
Given the “high volume of prescriptions and aggressive marketing by testosterone manufacturers,” this study adds to “mounting evidence of a signal of cardiovascular risk” with replacement therapy, writes an editorialist (
pp. 1805–6). “This signal warrants both cautious testosterone prescribing and additional investigation.” (A. R. Cappola, acappola@mail.med.upenn.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 7, 2013 * Vol. 20, No. 215
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Nov. 7 issue of the New England Journal of Medicine (2013; 369).
Ponatinib in Philadelphia Chromosome–Positive Leukemias: In a Phase II trial of patients with chronic myeloid leukemia (CML) or Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph-positive ALL), ponatinib demonstrated “significant antileukemic activity” but also produced serious arterial thrombotic events, researchers report (pp. 1783–96). In 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation, ponatinib at initial doses of 45 mg daily produced these results: “Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event.” (J. E. Cortes, jcortes@mdanderson.org)
While an editorialist writes that “this practice-changing trial of ponatinib will have a major impact on the future of cancer-drug discovery” (
pp. 1852–3; J. H. Doroshow), authors of a Perspectives article counter that “the next chapter of the CML story has yet to unfold” (pp. 1779–81): “In addition to considering the risks of toxic effects, one must also weigh financial costs in choosing a BCR-ABL inhibitor for first-line treatment of CML. Economic incentives for using newer tyrosine kinase inhibitors as first-line therapies in CML should not be overlooked. The patent on imatinib will expire in the United States in 2015 and in European countries in 2016, which will reduce its currently extraordinary cost (estimated at $92,000 per year in the United States). On the other hand, even more expensive, patent-protected, newer agents are competing with imatinib for the lucrative position of first-line therapy for CML.” (J. D. Groarke)
Dolutegravir Plus Abacavir–Lamivudine for HIV-1: Compared in a 48-week trial with efavirenz–tenofovir disoproxil fumarate (DF)–emtricitabine (EFV–TDF–FTC), the combination of dolutegravir and abacavir–lamivudine (DTG–ABC–3TC) had a better safety profile and was more effective in 833 patients with HIV-1 infection (pp. 1807–18): “The proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG–ABC–3TC group than in the EFV–TDF–FTC group (88% vs. 81%, P = 0.003), thus meeting the criterion for superiority. The DTG–ABC–3TC group had a shorter median time to viral suppression than did the EFV–TDF–FTC group (28 vs. 84 days, P < 0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P < 0.001).” (S. L. Walmsley, sharon.walmsley@uhn.ca)

>>>PNN NewsWatch
* Labeling of low molecular weight heparins will be updated to reflect new FDA recommendations that health professionals carefully consider the timing of spinal catheter placement and removal in patients taking anticoagulant drugs and delay dosing of anticoagulant medications for some time interval after catheter removal to decrease the risk of spinal column bleeding and subsequent paralysis after spinal injections, including epidural procedures and lumbar punctures.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 8, 2013 * Vol. 20, No. 216
Providing news and information about medications and their proper use

>>>Chest Highlights

Source: Nov. issue of Chest (2013; 144).
Sleep Apnea Treatment & Blood Pressure in Resistant Hypertension: In patients with resistant hypertension (HTN) and obstructive sleep apnea (OSA), treatment of the latter condition with continuous positive airway pressure (CPAP) significantly reduces daytime blood pressure (BP), researchers report (pp. 1487–94). This “reinforces the importance of recognizing and treating OSA in patients with resistant HTN,” the authors conclude, based on these findings in 40 patients who were randomized to medical therapy or medical therapy plus CPAP for 6 months and evaluated using 24-hour ambulatory BP monitoring (ABPM): “Thirty-five patients (77% men; age, 56 ± 1 years; BMI, median 32 kg/m2 [25%-75%, 28-39 kg/m2]; apnea-hypopnea index, 29 events/h [24-48 events/h]; Epworth Sleepiness Scale, 10 ± 1; systolic/diastolic office BP, 162 ± 4/97 ± 2 mm Hg; taking four [four to five] antihypertensive drugs) completed the study. CPAP was used for 6:01 ± 0:20 h/night (3:42-7:44 h/night). Compared with the control group, awake systolic/diastolic ABPM decreased significantly in the CPAP group (∆: +3.1 ± 3.3 /+2.1 ± 2.7 mm Hg vs −6.5 ± 3.3/−4.5 ± 1.9 mm Hg, respectively, P < .05). Interestingly, the BP changes were observed only while patients were awake, but not during nocturnal ABPM (∆: +2.8 ± 4.5/+1.8 ± 3.5 mm Hg vs +1.6 ± 3.5/+0.8 ± 2.9 mm Hg, P = NS).” (G. Lorenzi-Filho, geraldo.lorenzi@incor.usp.br)
Pharmacists in ICUs: “The addition of a pharmacist to an interprofessional critical care team should be encouraged as health-care systems focus on improving the quality and efficiency of care delivered to improve patient outcomes,” conclude authors of a Recent Advances in Chest Medicine article (pp. 1687–95): “Critical care pharmacy services in the ICU have expanded from traditional dispensing responsibilities to being recognized as an essential component of multidisciplinary care for critically ill patients. Augmented by technology and resource utilization, this shift in roles has allowed pharmacists to provide valuable services in the form of assisting physicians and clinicians with pharmacotherapy decision-making, reducing medication errors, and improving medication safety systems to optimize patient outcomes. Documented improvements in the management of infections, anticoagulation therapy, sedation, and analgesia for patients receiving mechanical ventilation and in emergency response help to justify the need for clinical pharmacy services for critically ill patients. Contributions to quality improvement initiatives, scholarly and research activities, and the education and training of interdisciplinary personnel are also valued services offered by clinical pharmacists. Partnering with physician and nursing champions can garner support from hospital administrators for the addition of clinical pharmacy critical care services.” (I. Lat, ishaq.lat@uchospitals.edu)

>>>Pediatrics Report
Source: Nov. issue of Pediatrics (2013; 132).
Nonmedical Opioid, Sedative Use by Adolescents: In the emergency department (ED), adolescents should be screened for nonmedical prescription opioid and sedative use (NPOU and NPSU, respectively), according to investigators who found 10–15% of patients in this age group reporting such use (pp. 825–32). At the U. Michigan Med. Ctr., patients aged 14–20 presenting to the ED in 2010–11 reported the following on computerized surveys: “Of the 2,135 participants (86.0% response rate), 222 (10.4%) reported either NPOU or NPSU. Among the 185 (8.7%) participants that reported NPOU, 14.6% had a current home prescription for an opioid and among the 115 (5.4%) with NPSU, 12.3% had a current home prescription for a sedative. After controlling for demographics (age, gender, race, public assistance), correlates of NPOU or NPSU included other substance use, and drinking and driving or riding with a drinking driver. Additional correlates of NPOU included receiving an intravenous opioid in the ED and for NPSU, dating violence, presenting to the ED for a noninjury complaint, and previous ED visit in the past year.” (L. K. Whiteside)

>>>PNN NewsWatch
* Partially hydrogenated oils—
trans fat—are not generally recognized as safe, FDA has proposed. If the ruling is finalized, added oils would need to be removed from foods in the U.S.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 11, 2013 * Vol. 20, No. 217
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 9 issue of Lancet (2013; 382).
Early Time-Limited Antiretroviral Therapy: In the Children with HIV Early Antiretroviral (CHER) trial, early time-limited antiretroviral therapy (ART) produced better clinical and immunological outcomes than did deferred therapy (pp. 1555–63). Conducted in asymptomatic infants younger than 12 weeks in South Africa, the trial used an open-label, randomized design with three groups: deferred ART (ART-Def), immediate ART for 40 weeks (ART-40W), or immediate ART for 96 weeks (ART-96W). Results showed: “377 infants were enrolled, with a median age of 7.4 weeks, CD4% of 35%, and HIV RNA log 5.7 copies per mL. Median follow-up was 4.8 years; 34 infants (9%) were lost to follow-up. Median time to ART initiation in the ART-Def group was 20 weeks (IQR 16–25). Time to restarting of ART after interruption was 33 weeks (26–45) in ART-40W and 70 weeks (35–109) in ART-96W; at the end of the trial, 19% of patients in ART-40W and 32% of patients in ART-96W remained off ART. Proportions of follow-up time spent on ART were 81% in the ART-Def group, 70% in the ART-40W group, and 69% in the ART-96W group. 48 (38%) of 125 children in the ART-Def group, 32 (25%) of 126 in the ART-40W group, and 26 (21%) of 126 in the ART-96W group reached the primary endpoint. The hazard ratio, relative to ART-Def, was 0.59 (95% CI 0.38–0.93, p = 0.02) for ART-40W and 0.47 (0.27–0.76, p = 0.002) for ART-96W. Three children in ART-Def, three in ART-40W, and one in ART-96W switched to second-line ART.” (M. F. Cotton, mcot@sun.ac.za)
Global Burden of Disease From Illicit Drug Use: Increased efforts are needed to reduce the global burden of disease related to opioid dependence and injecting drug use, authors conclude, including delivery of opioid substitution treatment and needle and syringe programs (pp. 1564–74). A systematic review of the epidemiology of drug use was combined with results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to make these determinations about years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life–years (DALYs): “Illicit drug dependence directly accounted for 20.0 million DALYs (95% UI 15.3–25.4 million) in 2010, accounting for 0.8% (0.6–1.0) of global all-cause DALYs. Worldwide, more people were dependent on opioids and amphetamines than other drugs. Opioid dependence was the largest contributor to the direct burden of DALYs (9.2 million, 95% UI 7.1–11.4). The proportion of all-cause DALYs attributed to drug dependence was 20 times higher in some regions than others, with an increased proportion of burden in countries with the highest incomes. Injecting drug use as a risk factor for HIV accounted for 2.1 million DALYs (95% UI 1.1–3.6 million) and as a risk factor for hepatitis C accounted for 502,000 DALYs (286,000–891,000). Suicide as a risk of amphetamine dependence accounted for 854,000 DALYs (291,000–1,791,000), as a risk of opioid dependence for 671,000 DALYs (329,000–1,730,000), and as a risk of cocaine dependence for 324,000 DALYs (109,000–682,000). Countries with the highest rate of burden (>650 DALYs per 100,000 population) included the USA, UK, Russia, and Australia.” (L. Degenhardt, l.degenhardt@unsw.edu.au)

>>>PNN NewsWatch
* Use of certain OxyElite Pro dietary supplement products (USPlabs LLC) has been linked to liver illnesses, FDA said yesterday. The products are being recalled.

>>>PNN JournalWatch
* Tamsulosin Treatment for Benign Prostatic Hyperplasia and Risk of Severe Hypotension in Men Aged 40–85 Years in the United States: Risk Window Analyses Using Between and Within Patient Methodology, in
BMJ, 2013; 347: f6320. (M. Etminan, metminan@popi.ubc.ca)
* Colchicine and the Heart: Pushing the Envelope, in
Journal of the American College of Cardiology, 2013; 62: 1817–25. (S. Deftereos)
* Omega-3 Fatty Acid Blood Levels: Clinical Significance and Controversy, in
Circulation, 2013; 128: 2154–61. (H. Robert Superko, HighHDL@mac.com)
* Managing Transmission of Carbapenem-Resistant Enterobacteriaceae in Healthcare Settings: A View From the Trenches, in
Clinical Infectious Diseases, 2013; 57: 1593–9. (D. K. Henderson, dkh@nih.gov)
* Delivering High-Quality and Affordable Care Throughout the Cancer Care Continuum, in
Journal of Clinical Oncology, 2013; 31: 4151–7. (Y-C T. Shih, tinashih@uchicago.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 12, 2013 * Vol. 20, No. 218
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 11 issue of JAMA Internal Medicine (2013; 173).
Intensive Glycemic Control in Hyperglycemic Acute Coronary Syndrome: In patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), intensive glucose regulation failed to reduce infarct size, report researchers with the Randomized BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome–2 (BIOMArCS-2) Glucose Trial (pp. 1896–904). In this open-label randomized controlled trial, 294 patients with admission glucose levels of 140–288 mg/dL received intensive glucose management using intravenous insulin with a target plasma glucose level of 85 to 110 mg/dL or to conventional expectative glucose management. Results based on a primary end point of high-sensitivity troponin T value 72 hours after admission (hsTropT72) and secondary end points of area under the curve of creatine kinase, myocardial band (AUC–CK-MB), release and myocardial perfusion scintigraphy findings at 6 weeks showed: “In the intensive management arm, median hsTropT72 was 1,197 ng/L (25th and 75th percentiles of distribution, 541–2,296 ng/L) vs 1,354 ng/L (530–3,057 ng/L) in the conventional arm (P = .41). Median AUC–CK-MB was 2,372 U/L (1,242–5,004 U/L) vs 3,171 U/L (1,620–5,337 U/L) (P = .18). The difference in median extent of myocardial injury measured by myocardial perfusion scintigraphy was not significant (2% vs 4%) (P = .07). Severe hypoglycemia (<50 mg/dL) was rare and occurred in 13 patients. Before discharge, death or a spontaneous second myocardial infarction occurred in 8 patients (5.7%) vs 1 (0.7%) (P = .04).” (V. A. Umans, v.umans@mca.nl)
Combined with results of previous studies, these findings provide an important lesson, editorialists write (
pp. 1905–6): “The most remarkable [observation] is the fact that initiating a [glucose-insulin-potassium] infusion within an hour after the onset of symptoms, as in the IMMEDIATE study, provides a profound benefit despite the induction of hyperglycemia. A large, prospective, randomized study with major adverse clinical events as the primary end point, based on normalization of blood glucose concentrations to less than 140 mg/dL with low-dose insulin infusion, needs to be carried out to address these critically important but as yet unanswered questions. Until then, observations derived from smaller, underpowered trials keep the embers of scientific interest in insulin therapy for hyperglycemic patients with ACS smoldering, which is surely sufficient for generating smoke—but not fire.” (W. E. Boden, william.boden@va.gov)
Patient-Centered Medical Home: In a multipayer patient-centered medical home, quality rose and care utilization declined during a 2-year pilot program (pp. 1907–13): “The mean National Committee for Quality Assurance recognition scores of the pilot practices increased from 42 to 90 points of a possible 100 points. The pilot and comparison practices had statistically indistinguishable baseline patient characteristics and practice patterns, except for higher numbers of attributed member months per year in the pilot practices (31,130 per practice vs 14,779, P = .01) and lower rates of cervical cancer screening in the comparison practices. Although estimates of the emergency department visits and inpatient admissions of patients in the pilot practices trended toward lower utilization, the only significant difference was a lower rate of ambulatory care sensitive emergency department visits in the pilot practices. The Chronic Care Sustainability Initiative pilot program was associated with a reduction in ambulatory care–sensitive emergency department visits of approximately 0.8 per 1,000 member months or approximately 11.6% compared with the baseline rate of 6.9 for emergency department visits per 1,000 member months (P = .002). No significant improvements were found in any of the quality measures.” (M. B. Rosenthal, meredith_rosenthal@harvard.edu)

>>>PNN NewsWatch
* Eslicarbazepine acetate (Aptiom, Sunovion) has been approved by FDA for adjunctive therapy of partial-onset epilepsy. Pivotal trials included patients whose partial-onset seizures were not controlled by concomitant therapy with up to three antiepileptic drugs, including carbamazepine, lamotrigine, valproic acid, and/or levetiracetam. The product will be available in second quarter 2014.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 13, 2013 * Vol. 20, No. 219
Providing news and information about medications and their proper use

>>>Lipids Guidelines Replace LDL With Risk Assessment
The long-awaited revisions to the ATP-3 and Obesity-1 guidelines were released yesterday by the American College of Cardiology and the American Heart Association. For management of patients with hypercholesterolemia, the lipds guideline takes a vastly different and more complicated approach than the LDL-centered ones clinicians have relied on for years.
Four full guidelines were published in manuscript form by the
Journal of the American College of Cardiology, and links below are to that site. The guidelines are also on the Circulation website and the website of the Journal of the American Pharmacists Association, the only pharmacy organization endorsing the guidelines.
Cholesterol: The revised lipids guidelines identifies four major groups of patients for whom cholesterol-lowering HMG-CoA reductase inhibitors have the greatest chance of preventing stroke and heart attacks:
* Patients who have cardiovascular disease
* Patients with an LDL cholesterol level of 190 mg/dL or higher
* Patients with type 2 diabetes who are 40–75 years of age
* Patients with an estimated 10-year risk of cardiovascular disease of 7.5% or higher who are 40–75 years of age (see the Risk Assessment guidelines for details on this calculation)
The guideline also emphasizes the importance of adopting a heart-healthy lifestyle to prevent and control high blood cholesterol (see Lifestyle guidelines for details).
In addition to identifying patients most likely to benefit from statins, the guideline outlines the recommended intensity of statin therapy for different patient groups. Rather than use a “lowest is best” approach that combines a low dose of a statin drug along with several other cholesterol-lowering drugs, the panel found that it can be preferable to focus instead on a healthy lifestyle along with a higher dose of statins, eliminating the need for additional medications.
Risk Assessment: The previous guideline relied primarily on data from the Framingham study, which was a white population, and did not include risk of stroke in its calculation. The revised risk assessment guideline corrects both of these deficiencies in a broadened assessment for risk of stroke as well as heart attack and with new gender- and ethnicity-specific formulas for predicting risk in black and white women and men. The recommendations also help clinicians and patients look beyond traditional short-term (10-year) risk estimates to predict an individual’s lifetime risk of developing heart disease and having a stroke.
The calculation of risk is complex, however, and a spreadsheet will be made available for clinicians’ use. In the long run, electronic health records are expected to provide the risk assessment automatically.
The work group was also charged with making recommendations about the clinical usefulness of new markers of risk. While existing evidence did not support using of new risk measures routinely in risk assessment, four markers stood out as potentially helpful to use when patients or providers are uncertain about risk-based treatment after the quantitative risk has been calculated using the pooled equations: family history of premature cardiovascular disease; coronary artery calcium score; high-sensitivity C-reactive protein levels; and ankle brachial index, the ratio of the blood pressure in the ankle compared to blood pressure in the arm.
Lifestyle: The lifestyle guideline recommends limiting intake of saturated and trans fats to lower blood cholesterol, restricting sodium intake to 2,400 mg/d to lower blood pressure (or to 1,500 mg/d to achieve greater reductions), and eating a heart-healthy diet that emphasizes fruits, vegetables, and whole grains, while including low-fat dairy products, poultry, fish and nuts, and limiting red meat, sweets, and sugar-sweetened beverages. The guideline advises moderate- to vigorous-intensity aerobic exercise for an average of 40 minutes three to four times a week.
Obesity: The obesity guideline largely stuck with existing cut points for BMI definitions of obesity and overweight and endorsed bariatric surgery for the morbidly obese. The guideline did not answer a critical question about use of medications in management of weight disorders, saying simply that efficacy and safety evidence is insufficient to make a recommendation.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 14, 2013 * Vol. 20, No. 220
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Nov. 14 issue of the New England Journal of Medicine (2013; 369).
ACE/ARB Therapy in Diabetic Nephropathy: While combination therapy with ACE inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria, a clinical trial of the drugs for slowing progression of diabetic proteinuria was terminated because of excess adverse events, VA NEPHRON-D Investigators report (pp. 1892–903). In patients with type 2 diabetes, losartan 100 mg/d was given with either lisinopril 10–40 mg/d or placebo, with these effects on estimated glomerular filtration rates: “The study was stopped early owing to safety concerns. Among 1,448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P = 0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = 0.10) decreased with time (P = 0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P = 0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person–years, vs. 2.6 events per 100 person–years with monotherapy; P < 0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person–years, P < 0.001).” (L. F. Fried, linda.fried@va.gov)
This study could mark the “end of dual therapy with renin–angiotensin–aldosterone system [RAAS] blockade," an editorialist writes (
pp. 1960–2): “The results of the VA NEPHRON-D study add to available data and make it clear that dual RAAS blockade for the treatment of patients with diabetes cannot currently be recommended. Importantly, the VA NEPHRON-D study adjusted the dosing of the RAAS blockade on the basis of serum potassium levels and the degree of renal failure. However, the trial did not alter the dosage of losartan or lisinopril to improve control of either blood pressure or albuminuria.…
“In the future, studies will probably measure and integrate multiple drug responses to predict the chance of obtaining positive hard outcomes. For now, dual RAAS blockade can be resuscitated only if we can show renal and cardiovascular protection in a defined group of patients in whom the desired decreases in blood pressure, albuminuria, or both are achieved without major increases in potassium levels or other side effects.” (D. de Zeeuw)
Low-Intensity Therapy in Burkitt’s Lymphoma: Low-intensity therapy was “highly effective” in an uncontrolled prospective study of 30 patients with sporadic or immunodeficiency-associated Burkitt’s lymphoma (pp. 1915–25). Two regimens of infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (EPOCH-R) were tested: a standard dose-adjusted combination in HIV-negative patients (DA-EPOCH-R group) and a lower-dose short-course combination with a double dose of rituximab in HIV-positive patients (SC-EPOCH-RR group). Results showed: “The principal toxic events, fever and neutropenia, were observed during 22% of the DA-EPOCH-R treatment cycles and 10% of the SC-EPOCH-RR treatment cycles. The tumor lysis syndrome developed in 1 patient; no treatment-related deaths occurred. The median cumulative doses of doxorubicin–etoposide and cyclophosphamide administered in the SC-EPOCH-RR group were 47% and 57% lower, respectively, than those administered in the DA-EPOCH-R group. With median follow-up times of 86 months in the DA-EPOCH-R group and 73 months in the SC-EPOCH-RR group, the rates of freedom from progression of disease and overall survival were, respectively, 95% and 100% with DA-EPOCH-R and 100% and 90% with SC-EPOCH-RR. None of the patients died from Burkitt’s lymphoma.” (W. H. Wilson, wilsonw@mail.nih.gov)

>>>PNN NewsWatch
* FDA yesterday approved its second “breakthrough” drug, ibrutinib (Imbruvica, Pharmacyclics and Janssen Biotech), for use in previously treated patients with mantle cell lymphoma, a rare and aggressive type of non-Hodgkin lymphoma. Tumors shrank or disappeared in two thirds of 111 patients treated with ibrutinib.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 15, 2013 * Vol. 20, No. 221
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Nov. issue of the Journal of the American Geriatrics Society (2013; 61).
Adverse Drug Events After Hospital Discharge: Adverse drug events (ADEs) were common among older patients discharged from acute-care facilities to their homes in a retrospective review of 1,000 consecutive discharges and 45-day postdischarge experiences (pp. 1894–9). Medications in the Beers list were rarely involved, indicating success in changing prescribing patterns. Review of records from a Massachusetts health plan showed these results: “At least one ADE was identified during the 45-day period in 18.7% (n = 187) of the 1,000 discharges. Of the 242 ADEs identified, 35% (n = 84) were deemed preventable, of which 32% (n = 27) were characterized as serious, and 5% (n = 4) as life threatening. More than half of all ADEs occurred within the first 14 days after hospitalization. The percentage of ADEs in which Beers Criteria medications were implicated was 16.5% (n = 40). Beers criteria medications with both a high quality of evidence and strong strength of recommendation were implicated in 6.6% (n = 16) of the ADEs.” (A. O. Kanaan, abir.kanaan@mcphs.edu)
Osteoporosis Care Quality & Fragility Fractures: Analysis of Medicare claims shows that patients older than 67 who had fragility fractures frequently did not receive postfracture treatment for osteoporosis, particularly if they were men or black (pp. 1855–62). Inpatient and outpatient claims in 2003–10 and drug claims from 2006–10 showed these patterns among beneficiaries who survived at least 12 months after a fracture of the hip, radius, or humerus: “In 61,832 individuals with fractures, mean age was 80.6, 87.0% were female, 88.5% were white, 2.6% were black, and 62.1% were attention naïve at the time of fracture; 21.8% received testing, pharmacotherapy, or both in the 6 months after fracture. In adjusted models, factors associated with significantly lower likelihood of receiving this care were black race, male sex, and an upper extremity fracture (vs hip). In models restricted to attention-naïve participants, the same factors were associated with lower relative risk of receiving care. Adjusted [hospital referral region]-level care rates ranged from 14.7% to 22.9% (10th to 90th percentile). The proportion receiving care increased from 2006 to 2009.” (S. K. Liu, stephen.k.liu@hitchcock.org)

>>>Allergy/Immunology Report
Source:
Nov. issue of the Journal of the Allergy and Clinical Immunology (2013; 132).
Glucocorticoid-Induced Osteoporosis: “Glucocorticoid-induced osteoporosis (GIO) is the most common iatrogenic cause of secondary osteoporosis and an issue of concern for physicians treating patients with inhaled or oral glucocorticoids either continuously or intermittently,” write authors of a review article (pp. 1019–30): “Patients with GIO experience fragility fractures at better dual-energy x-ray absorptiometry T-scores than those with postmenopausal or age-related osteoporosis. This might be explained, at least in part, by the effects of glucocorticoids not only on osteoclasts but also on osteoblasts and osteocytes. Effective options to detect and manage GIO exist, and a management algorithm has been published by the American College of Rheumatology to provide treatment guidance for clinicians. This review will summarize GIO epidemiology and pathophysiology and assess the role of inhaled and oral glucocorticoids in asthmatic adults and children, with particular emphasis on the effect of such therapies on bone health. Lastly, we will review the American College of Rheumatology GIO guidelines and discuss diagnostic and therapeutic strategies to mitigate the risk of GIO and fragility fractures.” (B. Buehring, bbuehring@medicine.wisc.edu)

>>>PNN NewsWatch
* The RNS Stimulator (Neuropace), approved yesterday by FDA for reducing seizure frequency in medication-resistant epilepsy, is a small neurotransmitter that is placed under the skull and connected by wires to epileptogenic regions of the brain. When abnormal activity occurs, the neurotransmitter electrically stimulates that part of the brain and normalizes activity before symptoms occur. In a 3-month clinical trial, 191 patients with drug-resistant epilepsy had a 38% reduction in mean number of seizures per month when the device was turned on, compared with a 17% reduction when it was off.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 18, 2013 * Vol. 20, No. 222
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 16 issue of Lancet (2013; 382).
E-cigarettes for Smoking Cessation: In a pragmatic randomized controlled trial, e-cigarettes with or without nicotine were modestly effective for smoking cessation, compared with nicotine patches, researchers report (pp. 1629–37). The trial, conducted in New Zealand in 2011–13, provided low-intensity telephone support for all participants and used block randomization to assign adult smokers to e-cigarettes with nicotine 16 mg, nicotine patches 21 mg once daily, or e-cigarettes without nicotine, with these results: “657 people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes) and were included in the intention-to-treat analysis. At 6 months, verified abstinence was 7.3% (21 of 289) with nicotine e-cigarettes, 5.8% (17 of 295) with patches, and 4.1% (three of 73) with placebo e-cigarettes (risk difference for nicotine e-cigarette vs patches 1.51 [95% CI –2.49 to 5.51]; for nicotine e-cigarettes vs placebo e-cigarettes 3.16 [95% CI –2.29 to 8.61]). Achievement of abstinence was substantially lower than we anticipated for the power calculation, thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes. We identified no significant differences in adverse events, with 137 events in the nicotine e-cigarettes group, 119 events in the patches group, and 36 events in the placebo e-cigarettes group. We noted no evidence of an association between adverse events and study product.” (C.Bullen, c.bullen@nihi.auckland.ac.nz)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2013; 347).
Physical Activity & Inflammatory Bowel Disease: In the Nurses’ Health Study and Nurses’ Health Study II, the risk of developing Crohn’s disease was inversely related to women’s levels of physical activity, but the association was not found for ulcerative colitis (f6633). Conducted in the U.S. in 1984–2010, the studies showed these patterns: “During 3,421,972 person years of follow-up, we documented 284 cases of Crohn’s disease and 363 cases of ulcerative colitis. The risk of Crohn’s disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn’s disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn’s disease compared with sedentary women with <3 MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn’s disease among women in the highest fifth of physical activity was 8 and 6 events per 100,000 person years compared with 11 and 16 events per 100,000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn’s disease (all P for interaction >0.35).” (A. T. Chan, achan@partners.org)

>>>PNN NewsWatch
* To reduce the risk of infection with improper OTC topical antiseptic use and the possibility of these products becoming contaminated with bacteria during use, FDA is requesting that manufacturers package products indicated for preoperative or preinjection skin preparation in single-use containers.

>>>PNN JournalWatch
* IgE-Mediated Food Allergy in Children, in
Lancet, 2013; 382: 1656–64. (E. Barbi, ebarbi@libero.it)
* Potentially Inappropriate Medication Use in Veterans Residing in Community Living Centers: Have We Gotten Better?, in
Journal of the American Geriatrics Society, 2013; 61: 1994–9. (D. Dosa, david_dosa@brown.edu)
* New Kids on the Block: Group 2 Innate Lymphoid Cells and Type 2 Inflammation in the Lung, in
Chest, 2013; 144: 1681–6. (T. Y. F. Halim, thalim@mrc-lmb.cam.ac.uk)
* Membranous Nephropathy and Nonsteroidal Anti-inflammatory Agents, in
American Journal of Kidney Diseases, 2013; 62: 1012–7. (M. L. Troxell, troxellm@ohsu.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 19, 2013 * Vol. 20, No. 223
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 19 issue of the Annals of Internal Medicine (2013; 159).
Arsenic & Cardiovascular Disease: In the Strong Heart Study, long-term exposure to low to moderate arsenic levels was associated with development of cardiovascular disease and related mortality in 2,575 American Indian adults in Arizona, Oklahoma, and the Dakotas (pp. 649–59). The prospective cohort study collected baseline data in 1989–91 and followed up through 2008. Urine inorganic and methylated arsenic levels and incident cardiovascular events showed the following: “A total of 1,184 participants developed fatal and nonfatal cardiovascular disease. When the highest and lowest quartiles of arsenic concentrations (>15.7 vs. <5.8 µg/g creatinine) were compared, the hazard ratios for cardiovascular disease, coronary heart disease, and stroke mortality after adjustment for sociodemographic factors, smoking, body mass index, and lipid levels were 1.65 (95% CI, 1.20 to 2.27; P for trend < 0.001), 1.71 (CI, 1.19 to 2.44; P for trend < 0.001), and 3.03 (CI, 1.08 to 8.50; P for trend = 0.061), respectively. The corresponding hazard ratios for incident cardiovascular disease, coronary heart disease, and stroke were 1.32 (CI, 1.09 to 1.59; P for trend = 0.002), 1.30 (CI, 1.04 to 1.62; P for trend = 0.006), and 1.47 (CI, 0.97 to 2.21; P for trend = 0.032). These associations varied by study region and were attenuated after further adjustment for diabetes, hypertension, and kidney disease measures.” (A. Navas-Acien, anavas@jhsph.edu)
Statins & Cognition: While published data do not demonstrate that statins have adverse effects on cognition, the strength of the evidence is weak, especially for high-dose statins, according to a systematic review (pp. 688–97). “Larger and better-designed studies are needed to draw unequivocal conclusions about the effect of statins on cognition,” the authors conclude based on these findings in published literature and FDA databases from 1986 through 2012: “Among statin users, low-quality evidence suggested no increased incidence of Alzheimer disease and no difference in cognitive performance related to procedural memory, attention, or motor speed. Moderate-quality evidence suggested no increased incidence of dementia or mild cognitive impairment or any change in cognitive performance related to global cognitive performance scores, executive function, declarative memory, processing speed, or visuoperception. Examination of the FDA postmarketing surveillance databases revealed a low reporting rate for cognitive-related adverse events with statins that was similar to the rates seen with other commonly prescribed cardiovascular medications.” (E. M. deGoma, Emil.deGoma@uphs.upenn.edu)
Drugs for Reducing Risk of Primary Breast Cancer: In an update to its 2002 recommendations, the U.S. Preventive Services Task Force (USPSTF) recommends use of medications for reducing the risk of primary breast cancer in women only for those with increased risk of the disease and low risk for adverse medication effects (pp. 698–708). The selective estrogen receptor modulators tamoxifen and raloxifene have been used for this indication, USPSTF notes. In making the following recommendations, the Task Force reviewed evidence regarding the medications and a meta-analysis of placebo-controlled trials (www.uspreventiveservicestaskforce.org):
* The USPSTF recommends that clinicians engage in shared, informed decision making with women who are at increased risk for breast cancer about medications to reduce their risk. For women who are at increased risk for breast cancer and at low risk for adverse medication effects, clinicians should offer to prescribe risk-reducing medications, such as tamoxifen or raloxifene. (B recommendation)
* The USPSTF recommends against the routine use of medications, such as tamoxifen or raloxifene, for risk reduction of primary breast cancer in women who are not at increased risk for breast cancer. (D recommendation)

>>>PNN NewsWatch
* Controversy over recently released lipids guidelines and an online risk calculator in particular (see PNN, Nov. 13) has engulfed the American Heart Association meeting in Dallas, reports the New York Times. AHA also released a new algorithm for hypertension on Monday, but it doesn’t appear to be the long-awaited eighth revision of the Joint National Committee, or JNC8.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 20, 2013 * Vol. 20, No. 224
Providing news and information about medications and their proper use

>>>AHA Meeting Highlights
The American Heart Association Scientific Sessions 2013 conclude today in Dallas. Numerous articles have been released early to coincide with presentations at the meeting.
Pharmacogenetics of Warfarin: A genotype-guided approach to warfarin dosing failed to improve anticoagulation control during the first 4 weeks of treatment, according to the first of three articles released by the New England Journal of Medicine (doi: 10.1056/NEJMoa1310669). Among 1,015 patients assigned during the first 5 days of treatment to care based on clinical variables only or clinical variables plus genotype, international normalized ratio (INR) results through day 28 of therapy showed the following: “At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], −0.2; 95% confidence interval, −3.4 to 3.1; P = 0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P = 0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.” (S. E. Kimmel, stevek@mail.med.upenn.edu)
A second
NEJM study shows the opposite results: “Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy” (doi: 10.1056/NEJMoa1311386). Using a point-of-care genotyping test, results were as follows for 455 patients whose care in the first 5 days was guided by genetics versus standard care: “The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P < 0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥ 4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P < 0.001).” (M. Pirmohamed, munirp@liverpool.ac.uk)
“Despite the variation in trial design, these trials indicate that this pharmacogenetic testing has either no usefulness in the initial dosing of vitamin K antagonists or, at best, marginal usefulness, given the cost and effort required to perform this testing,” an editorialist adds (
doi: 10.1056/NEJMe1313682, B. Furie).
Edoxaban Versus Warfarin: In 21,105 patients with moderate-to-high-risk atrial fibrillation followed over a median of 2.8 years, the direct oral factor Xa inhibitor edoxaban was noninferior to warfarin (doi: 10.1056/NEJMoa1310907). Two once-daily edoxaban regimens were tested, and the higher-dose one showed a trend toward greater efficacy, compared with warfarin. Major bleeding occurred significantly less often with the Xa inhibitor. (R. P. Giugliano, rgiugliano@partners.org)
Hypertension Treatment Protocol: Commenting on a hypertension algorithm released by the journal Hypertension, CDC officials write in JAMA that the Million Hearts initiative “is now making available sample protocols that are being used successfully around the country, as well as a customizable template for blood pressure control” (doi: 10.1001/jama.2013.282615): “There should be no debate about the need to improve performance and the important role of protocol-driven care, which has been well documented for more than 30 years. Every physician, other health care practitioner, and health care organization should adopt one of the posted protocols or create their own customized evidence-based protocol. Which protocol is selected is less important than the decision to select, adopt, implement, and evaluate implementation of any evidence-based protocol. Standardized treatment will help clinicians, teams, and patients achieve and maintain healthy blood pressures and thereby prevent myocardial infarction and stroke.” (T. R. Frieden, tfrieden@cdc.gov)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 21, 2013 * Vol. 20, No. 225
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release article from and Nov. 21 issue of the New England Journal of Medicine (2013; 369).
Racial Differences in Vitamin D–Binding Protein: Genetic polymorphisms that produce lower levels of vitamin D–binding protein in black Americans should be considered when assessing the need for vitamin D supplementation, according to researchers who analyzed data from the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort (pp. 1991–2000). Black Americans generally have lower levels of total vitamin D than do whites, the authors note. Among 2,085 study participants, genotyping for two common polymorphisms in the vitamin D–binding protein gene (rs7041 and rs4588) and estimation of bioavailable vitamin D showed these patterns: “Mean (± SE) levels of both total 25-hydroxyvitamin D and vitamin D–binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.6 ± 0.2 ng per milliliter vs. 25.8 ± 0.4 ng per milliliter, P < 0.001; vitamin D–binding protein, 168 ± 3 µg per milliliter vs. 337 ± 5 µg per milliliter, P < 0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D–binding protein and total 25-hydroxyvitamin D, respectively. [Bone mineral density] was higher in blacks than in whites (1.05 ± 0.01 g per square centimeter vs. 0.94 ± 0.01 g per square centimeter, P < 0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P < 0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxyvitamin D overall (2.9 ± 0.1 ng per milliliter and 3.1 ± 0.1 ng per milliliter, respectively; P=0.71) and within quintiles of parathyroid hormone concentration.” (M. K. Evans, rthadhani@mgh.harvard.edu)
“More research is needed to fully appreciate what bioavailable versus total vitamin D status means — for 25-hydroxyvitamin D as well as 1,25-dihydroxyvitamin D,” an editorialist writes (
pp. 2047–8). Evolutionary drivers that affected blacks who moved from equatorial Africa can be combined with bioavailability analyses to hypothesize why blacks have low vitamin D levels but high bone mineral densities: “The higher blood calcium levels observed in blacks as compared with whites may result from higher bioavailable levels of 1,25-dihydroxyvitamin D due to the observed lower levels of vitamin D–binding protein. Bioavailability may be relative regarding vitamin D and its metabolites. Megalin serves to transport the bioavailable 25-hydroxyvitamin D bound to the vitamin D–binding protein and albumin. However, the liver prefers unbound vitamin D3. Immune and other cells lack megalin and thus may be able to use only unbound 25-hydroxyvitamin D.” (M. F. Holick)
Next-Generation DNA Sequencers Approved by FDA: Commenting on Tuesday’s authorization by FDA for marketing of four diagnostic high-throughput gene-sequencing devices, NIH officials describe possible clinical implications of widespread availability of this technology (DOI: 10.1056/NEJMp1314561): “The marketing authorization for the first next-generation genome sequencer represents a significant step forward in the ability to generate genomic information that will ultimately improve patient care. Yet it is only one step. There are many challenges ahead before personalized medicine can be considered truly embedded in health care. We need to continue to uncover variants within the genome that can be used to predict disease onset, affect progression, and modulate drug response. New genomic findings need to be validated before they can be integrated into medical decision making. Doctors and other health care professionals will need support in interpreting genomic data and their meaning for individual patients. Patients will want to be able to talk about their genetic information with their doctor. With the right information and support, patients will be able to participate alongside their doctors in making more informed decisions. Reimbursement issues need to be resolved to assure that patients have access to the best tests and that manufacturers have incentives to develop them.” (F. S. Collins)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 22, 2013 * Vol. 20, No. 226
Providing news and information about medications and their proper use

>>>Health Affairs Highlights
Source:
Nov. issue of Health Affairs, a theme issue on redesigning the health care workforce (2013; 32).
Pharmacists in ACOs & Integrated Care Teams: Pharmacists will be an important part of the health care equation as reform progresses, authors write in an article on accountable care organizations and integrated care teams (pp. 1963–70): “Effective health care workforce development requires the adoption of team-based care delivery models, in which participating professionals practice at the full extent of their training in pursuit of care quality and cost goals. The proliferation of such new models as medical homes, accountable care organizations, and community-based care teams is creating new opportunities for pharmacists to assume roles and responsibilities commensurate with their capabilities. Some challenges to including pharmacists in team-based care delivery models, including the lack of payment mechanisms that explicitly provide for pharmacist services, have yet to be fully addressed by policy makers and others. Nevertheless, evolving models and strategies reveal a variety of ways to draw on pharmacists’ expertise in such critical areas as medication management for high-risk patients. As Affordable Care Act provisions are implemented, health care workforce projections need to consider the growing number of pharmacists expected to play an increasing role in delivering primary care services.” (M. Smith, marie.smith@uconn.edu)
New Roles for Pharmacists & Technicians: “Optimal deployment of the pharmacy workforce will require the closer alignment of pharmacy practice and policy with each other and with the nation’s health care priorities,” authors write in describing new models of care (pp. 1956–62). “Of particular concern are inconsistent state-level scope-of-practice laws, the lack of mechanisms to reimburse pharmacists for services provided, the need to recognize pharmacists as health care providers, and the need to establish national standards for the preparation of pharmacy technicians.” (L. Maine, lmaine@aacp.org)
Linking Education, Training & Care Delivery: In an overview article, authors write that “neither regulatory policies nor market forces are keeping up with a rapidly changing delivery system and … training and education should be connected more closely to the actual delivery of care” (pp. 1874–80): “There is growing consensus that the health care workforce in the United States needs to be reconfigured to meet the needs of a health care system that is being rapidly and permanently redesigned. Accountable care organizations and patient-centered medical homes, for instance, will greatly alter the mix of caregivers needed and create new roles for existing health care workers. The focus of health system innovation, however, has largely been on reorganizing care delivery processes, reengineering workflows, and adopting electronic technology to improve outcomes. Little attention has been paid to training workers to adapt to these systems and deliver patient care in ever more coordinated systems, such as integrated health care networks that harmonize primary care with acute inpatient and postacute long-term care.” (T. C. Ricketts, tom_ricketts@unc.edu)

>>>Medical Care Report
Source:
Dec. issue of Medical Care (2013; 51).
“Withdrawal of Care” With Thrombolytics in Stroke: After identifying individual and institutional factors associated with “withdrawal of care” in patients with acute ischemic stroke, researchers conclude that a more evidence-based policy is needed (pp. 1094–100). National Inpatient Sample data for 2002–10 showed: “‘Withdrawal of care’ during hospitalization was instituted in 4,287 (3.3%) of the 130,437 acute ischemic stroke patients treated with thrombolytics. In the stepwise logistic regression analysis, women [odds ratio (OR) 1.2, 95% confidence interval (CI), (1.0–1.5)], presence of atrial fibrillation [OR 1.2, 95% CI, (1.0–1.5)], hemiplegia/hemiparesis [OR 1.4, 95% CI, (1.1–1.7)], aphasia [OR 1.2, 95% CI, (1.0–1.5)], and postthrombolytic intracerebral hemorrhage (OR 1.5, 95% CI, 1.1–1.8) were significant predictors of ‘withdrawal of care’ among thrombolytic-treated ischemic stroke patient. Hospitals located in the west region [OR 1.7, 95% CI, (1.2–2.4)], and teaching hospitals [OR 1.4, 95% CI, (1.0–1.8)] were more likely to use withdrawal of care. In-hospital mortality (61% vs. 9.0%, P ≤ 0.0001) were higher among those with ‘withdrawal of care.’” (A. I. Qureshi)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 25, 2013 * Vol. 20, No. 227
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Nov. 23 issue of Lancet (2013; 382).
Secukinumab in Ankylosing Spondylitis: The anti-IL-17A monoclonal antibody secukinumab “rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated” in a proof-of-concept trial conducted in Europe (pp. 1705–13). Using Bayesian analysis of a primary efficacy endpoint of the percentage of patients with a 20% response at 6 weeks on Assessment of SpondyloArthritis international Society criteria (ASAS20), investigators found these effects of two doses of intravenous secukinumab or placebo given 3 weeks apart: “37 patients with moderate-to-severe ankylosing spondylitis were screened, and 30 were randomly assigned to receive either intravenous secukinumab (n=24) or placebo (n=6). The final efficacy analysis included 23 patients receiving secukinumab and six patients receiving placebo, and the safety analysis included all 30 patients. At week 6, ASAS20 response estimates were 59% on secukinumab versus 24% on placebo (99.8% probability that secukinumab is superior to placebo). One serious adverse event (subcutaneous abscess caused by Staphylococcus aureus) occurred in the secukinumab-treated group.” (W. Hueber, wolfgang.hueber@novartis.com)
Dual Antiplatelet Therapy Cessation: Among patients discharged on dual antiplatelet therapy (DAPT) who had had percutaneous coronary interventions (PCI), cessation of the drugs carries a risk of early cardiac events, researchers report, but one that “attenuates over time” (pp. 1714–22). In the prospective, observational Patterns of Non-Adherence to Dual Anti-Platelet Regimen In Stented Patients (PARIS) trial, patients undergoing PCI at 15 clinical sites in the U.S. and Europe in 2009–10 were followed for up to 2 years after stent implantation. Results for those whose DAPT was stopped were as follows: “We enrolled 5,031 patients undergoing PCI, including 5,018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57.3%. Rate of any discontinuation was 40.8%, of interruption was 10.5%, and of disruption was 14.4%. The corresponding overall 2 year [composite rate of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularization (MACE)] rate was 11.5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1.41 (95% CI 0.94–2.12; p = 0.10) and to disruption was 1.50 (1.14–1.97; p = 0.004). Within 7 days, 8–30 days, and more than 30 days after disruption, adjusted HRs were 7.04 (3.31–14.95), 2.17 (0.97–4.88), and 1.3 (0.97–1.76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0.63 [0.46–0.86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation.” (R. Mehran, roxana.mehran@mountsinai.org)

>>>PNN NewsWatch
* FDA on Friday licensed Influenza A (H5N1) Virus Monovalent Vaccine, Adjuvanted, for use in people 18 years of age and older who are at increased risk of exposure to the avian influenza virus. This is the first adjuvanted product licensed for this use.
* The agency also approved
simepravir (Olysio, Janssen) for use in treatment-naive and -experienced patients with chronic hepatitis C virus infection. The third protease inhibitor approved by FDA for HCV, simepravir is intended for use in those with compensated liver function, including cirrhosis.

>>>PNN JournalWatch
* Effect of Beta Blockers on Mortality After Myocardial Infarction in Adults With COPD: Population Based Cohort Study of UK Electronic Healthcare Records, in
BMJ, 2013; 347: f6650. (J. K. Quint, Jennifer.quint@lshtm.ac.uk)
* Glycemic Index, Glycemic Load, Carbohydrates, and Type 2 Diabetes: Systematic Review and Dose–Response Meta-Analysis of Prospective Studies, in
Diabetes Care, 2013; 36: 4166–71. (D. C. Greenwood, d.c.greenwood@leeds.ac.uk)
* Temporal Trends in New Exposure to Antiepileptic Drug Monotherapy and Suicide-Related Behavior, in
Neurology, 2013; 10.1212/01.wnl.0000436614.51081.2e. (M. J. V. Pugh, maryjo.pugh2@va.gov)
* Acute Decompensated Heart Failure: Evolving Literature and Implications for Future Practice, in
Pharmacotherapy, 2013; DOI: 10.1002/phar.1369. (J. D. Cicci, jdcicci@gmail.com)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 26, 2013 * Vol. 20, No. 228
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Nov. 25 issue of JAMA Internal Medicine (2013; 173).
Placebo Effects in Migraines: In trials of prophylactic interventions for migraine, sham acupuncture and sham surgery are associated with higher responder ratios than oral pharmacological placebos, according to a systematic review of randomized controlled trials (pp. 1941–51). Researchers looked at studies that lasted at least 8 weeks after randomization and compared an experimental treatment with a placebo control. They found the following: “Of the 102 eligible trials, 23 could not be included in the meta-analyses owing to insufficient data. Sham acupuncture (proportion of responders, 0.38 [95% CI, 0.30–0.47]) and sham surgery (0.58 [0.37–0.77]) were associated with a more pronounced reduction of migraine frequency than oral pharmacological placebos (0.22 [0.17–0.28]) and were the only significant predictors of response in placebo groups in multivariable analyses (P = .005 and P = .001, respectively). Network meta-analysis confirmed that more patients reported response in sham acupuncture groups than in oral pharmacological placebo groups (odds ratio, 1.88 [95% CI, 1.30–2.72]). Corresponding analyses for continuous outcomes showed similar findings.” (K. Meissner, karin.meissner@med.lmu.de)

>>>Rheumatology Report
Source:
Nov. issue of Arthritis & Rheumatism (2013; 65).
Classification Criteria for Systemic Sclerosis: The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) present revised classification criteria for systemic sclerosis (SSc), which they report perform “better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease” (pp. 2737–47). Seeking to develop a more sensitive scheme for early detection of SSc and detection of limited cutaneous SSc, an ACR/EULAR committee reports the following: “It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud’s phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc.” (F. van den Hoogen, F.vandenHoogen@maartenskliniek.nl)
Imaging Outcome Measures in Osteoarthritis Clinical Trials: Authors debate the adequacy of FDA-accepted radiography of the knee for assessing the adequacy of treatments for osteoarthritis (OA) (pp. 2748–58). “Originally developed for epidemiologic reasearch, [radiographic measures of knee OA severity] were repurposed to measure structural progression.… However, demonstrating structural modification by a pharmacologic therapy has proved to be a substantial and costly challenge in [disease-modifying OA drug] trials, with most trials, if not all, exhibiting null results. A question arises as to whether this failure is a consequence of poor measurement properties of the outcome technology, or lack of biologic efficacy of the putative therapy.” (A. Guermazi, guermazi@bu.edu; K. D. Brandt, kenbrandt@yahoo.com)

>>>PNN NewsWatch
* Citing new information on cardiovascular risks, FDA yesterday removed some restrictions for rosiglitazone (Avandia, GlaxoSmithKline). Results from the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) clinical trial showed no elevated risk of heart attack or death in patients being treated with rosiglitazone when compared with standard-of-care antidiabetic agents, FDA said. These data therefore do not confirm the signal of increased risk of heart attacks that was found in a meta-analysis of clinical trials first reported in 2007.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Nov. 27, 2013 * Vol. 20, No. 229
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Nov. 27 issue of JAMA (2013; 310).
Thalidomide in Pediatric Crohn Disease: Improved clinical remission resulted from 8 weeks of therapy and longer open-label treatment with thalidomide in a group of 56 children and adolescents with refractory Crohn disease, researchers report (pp. 2164–73). At tertiary-care centers in Italy, patients received thalidomide 1.5–2.5 mg/kg/d or placebo once daily for 8 weeks. Responders continued therapy for 52 weeks or more, with these results: “Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2–12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2–12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1–3.9]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4–14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49 (65.3%) achieved 75% response. Mean duration of clinical remission in the thalidomide group was 181.1 weeks (95% CI, 144.53–217.76) vs 6.3 weeks (95% CI, 3.51–9.15) in the placebo group (P < .001). Cumulative incidence of severe adverse events was 2.1 per 1000 patient–weeks, with peripheral neuropathy the most frequent severe adverse event.” (M. Lazzerini, marzia.lazzerini@burlo.trieste.it)
Oral Fluoroquinolones & Retinal Detachment: A population-based cohort study from Denmark finds no association between use of oral fluoroquinolones and retinal detachment (pp. 2184–90). Based on the nationwide analysis, a risk of more than 3-fold is ruled out. (B. Pasternak, bjp@ssi.dk)

>>>PNN NewsWatch
* Pres. Obama will sign the pharmacy compounding bill this afternoon in the Oval Office, the White House has announced. H.R. 3204, the Drug Quality and Security Act, creates outsourcing facilities, a new classification of pharmacies conducting large-scale compounding of sterile drugs. After voluntary registration, these facilities would be regulated by FDA and would be subject to risk-based inspections, pharmacist.com reports. Most pharmacy groups supported the bill, which is not expected to affect most pharmacies. In a letter to the Senate before that body gave final approval to the bill, APhA wrote, “Our members were concerned about being forced to register with the FDA, and this legislation would allow traditional pharmacies to continue to be regulated by state boards of pharmacy while creating outsourcing facilities that would be subject to FDA oversight.” The Academy of Managed Care Pharmacy has criticized the bill, saying its “limited scope” prevents it from achieving its main goal of “protect[ing] the public from the unauthorized compounding of drugs.” AMCP wrote in a media release, “Only those facilities that volunteer to register will be subject to the FDA, which will leave the public no better off. Facilities that compound drugs, are not licensed pharmacies and choose not to register with the FDA will continue to ‘escape’ regulation and oversight.” AMCP added that a licensed pharmacy that also registers as an outsourcing facility will be subject to dual regulation that “will lead to administration and regulatory confusion, creating opportunities for gaps in responsibility and accountability.” Another section of the new law requires use of track-and-trace technology for drug products at the unit level within 10 years.
* Labeling for a European emergency contraceptive identical to
Plan B One-Step will have new labeling in 2014 saying that the product is not effective in women weighing more than 176 pounds, according to articles in Mother Jones and on other news outlets. BMI has previously been reported to decrease the effectiveness of contraceptives. A good discussion of previous studies is on the Emergency Contraception Website, hosted by Princeton U. It suggests that ulipristal is a better emergency contraceptive choice for women with BMIs of 30 or more than progestin-only products.
*
PNN will not be published on Thurs. and Fri, Nov. 28 and 29, Thanksgiving holidays.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 2, 2013 * Vol. 20, No. 230
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release article from BMJ (2013; 347).
Cardiovascular Events & Sodium-Containing Drug Products: Compared with standard formulations, drugs in sodium-containing effervescent, dispersible, and soluble formulations are associated with significantly increased odds of cardiovascular events, according to a nested case–control study of 1.3 million patients in the U.K. Clinical Practice Research Datalink who were followed for a mean of 7.23 years (f6954). The analysis included adult primary-care patients who were prescribed sodium-containing formulations or matched standard formulations of the same drug in 1987–2010: “A total of 61,072 patients with an incident cardiovascular event were matched with controls. For the primary endpoint of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death the adjusted odds ratio for exposure to sodium-containing drugs was 1.16 (95% confidence interval 1.12 to 1.21). The adjusted odds ratios for the secondary endpoints were 1.22 (1.16 to 1.29) for incident non-fatal stroke, 1.28 (1.23 to 1.33) for all cause mortality, 7.18 (6.74 to 7.65) for hypertension, 0.98 (0.93 to 1.04) for heart failure, 0.94 (0.88 to 1.00) for incident non-fatal myocardial infarction, and 0.70 (0.31 to 1.59) for vascular death. The median time from date of first prescription (that is, date of entry into cohort) to first event was 3.92 years.” (T. MacDonald, tom@memo.dundee.ac.uk)
>>>Lancet Highlights
Source:
Nov. 30 issue of Lancet, which contains six papers from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) in the U.K. (2013; 382).
Sexually Transmitted Diseases: Among members of a probability sample in 2010–12 in Britain, sexually transmitted infections (STIs) “were distributed heterogeneously, requiring general and infection-specific interventions,” Natsal researchers report (pp. 1795–806). Among 4,828 participants who provided a urine sample that was tested for STIs, results showed: “Chlamydia prevalence was 1.5% (95% CI 1.1–2.0) in women and 1.1% (0.7–1.6) in men. Prevalences in individuals aged 16–24 years were 3.1% (2.2–4.3) in women and 2.3% (1.5–3.4) in men. Area-level deprivation and higher numbers of partners, especially without use of condoms, were risk factors. However, 60.4% (45.5–73.7) of chlamydia in women and 43.3% (25.9–62.5) in men was in individuals who had had one partner in the past year. Among sexually active 16–24-year-olds, 54.2% (51.4–56.9) of women and 34.6% (31.8–37.4) of men reported testing for chlamydia in the past year, with testing higher in those with more partners. High-risk HPV was detected in 15.9% (14.4–17.5) of women, similar to in Natsal-2. Coverage of HPV catch-up vaccination was 61.5% (58.2–64.7). Prevalence of HPV types 16 and 18 in women aged 18–20 years was lower in Natsal-3 than Natsal-2 (5.8% [3.9–8.6] vs 11.3% [6.8–18.2]; age-adjusted odds ratio 0.44 [0.21–0.94]). Gonorrhoea (<0.1% prevalence in women and men) and HIV (0.1% prevalence in women and 0.2% in men) were uncommon and restricted to participants with recognised high-risk factors. Since Natsal-2, substantial increases were noted in attendance at sexual health clinics (from 6.7% to 21.4% in women and from 7.7% to 19.6% in men) and HIV testing (from 8.7% to 27.6% in women and from 9.2% to 16.9% in men) in the past 5 years.” (P. Sonnenberg, p.sonnenberg@ucl.ac.uk)
Unplanned Pregnancies: “Increasing intervals between first sexual intercourse, cohabitation, and childbearing means that, on average, women in Britain spend about 30 years of their life needing to avert an unplanned pregnancy,” Natsal-3 results show (pp. 1807–16; K. Wellings, kaye.wellings@lshtm.ac.uk)

>>>PNN JournalWatch
* Trimethoprim-Associated Hyponatremia, in
American Journal of Kidney Diseases, 2013; 62: 1188–92. (R. Babayev, rn2032@columbia.edu)
* Kidney Disease in the Setting of Liver Failure: Core Curriculum 2013, in
American Journal of Kidney Diseases, 2013; 62: 1198–212. (T. A. Gonwa, gonwa.thomas@mayo.edu)
* Pharmacists’ Role in Addressing Opioid Abuse, Addiction, and Diversion, in
Journal of the American Pharmacists Association, 2013; 2013: e5–15. (J. A. Owen, jowen@aphanet.org)
* Seizure Prophylaxis in Neurocritical Care: A Review of Evidence-Based Support, in
Pharmacotherapy, 2013; doi: 10.1002/phar.1374. (H. E. Goodwin, hgoodwi3@jhmi.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 3, 2013 * Vol. 20, No. 231
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Dec. 3 issue of the Annals of Internal Medicine (2013; 159).
Pegylated Interferon for HCV in Patients on Hemodialysis: Compared with pegylated interferon-alpha-2a monotherapy, pegylated interferon plus low-dose ribavirin produced greater sustained virologic responses in treatment-naive patients with hepatitis C virus (HCV) infection who were on hemodialysis, researchers report (pp. 729–38). In an open-label trial at eight centers in Taiwan, 205 patients received 48 weeks of monotherapy or combination therapy, with these results: “Compared with monotherapy, combination therapy had a greater sustained virologic response rate (64% vs. 33%; relative risk, 1.92 [95% CI, 1.41 to 2.62]; P < 0.001). More patients receiving combination therapy had hemoglobin levels less than 8.5 g/dL than those receiving monotherapy (72% vs. 6%; risk difference, 66% [CI, 56% to 76%]; P < 0.001). Patients receiving combination therapy required a higher dosage (mean, 13,946 IU per week [SD, 6449] vs. 5,833 IU per week [SD, 1169]; P = 0.006) and longer duration (mean, 29 weeks [SD, 9] vs. 18 weeks [SD, 7]; P = 0.004) of epoetin-beta than patients receiving monotherapy. The adverse event–related withdrawal rates were 7% in the combination therapy group and 4% in the monotherapy group (risk difference, 3% [CI, −3% to 9%]).” (J-H Kao, kaojh@ntu.edu.tw)
Herpes Zoster Incidence & Childhood Varicella Vaccination: In the U.S., an increase in the rate of age-specific herpes zoster (HZ) incidence began before introduction of childhood varicella vaccinations in 1996, and the change in incidence was not noticeably affected by the vaccine’s introduction, a study shows (pp. 739–45). Describing their results as “reassuring,” the investigators report these patterns in Medicare data for 1992–2010 among 2.9 million beneficiaries: “281,317 incident cases of HZ occurred. Age- and sex-standardized HZ incidence increased 39% from 10.0 per 1,000 person–years in 1992 to 13.9 per 1,000 person–years in 2010 with no evidence of a statistically significant change in the rate of increase after introduction of the varicella vaccination program. Before introduction of this program, HZ incidence was higher in women (RR, 1.21 [95% CI, 1.19 to 1.24]) than men and was lower in black persons (RR, 0.51 [CI, 0.48 to 0.53]) and Hispanic persons (RR, 0.76 [CI, 0.72 to 0.81]) than white persons. In a model adjusted for sex, age, and calendar year from 1997 to 2010, HZ incidence did not vary by state varicella vaccination coverage (RR, 0.9998 [CI, 0.9993 to 1.0003]).” (C. M. Hales, chales@cdc.gov)
Weight & Metabolic Health: In a systematic review and meta-analysis, investigators found increased long-term risk of all-cause mortality and/or cardiovascular events in all patients with obesity, including a unique subgroup with normal metabolic features (pp. 758–69). Based on the following data, the group concluded that “there is no healthy pattern of increased weight”: “Eight studies (n = 61,386; 3,988 events) evaluated participants for all-cause mortality and/or cardiovascular events. Metabolically healthy obese individuals (relative risk [RR], 1.24; 95% CI, 1.02 to 1.55) had increased risk for events compared with metabolically healthy normal-weight individuals when only studies with 10 or more years of follow-up were considered. All metabolically unhealthy groups had a similarly elevated risk: normal weight (RR, 3.14; CI, 2.36 to 3.93), overweight (RR, 2.70; CI, 2.08 to 3.30), and obese (RR, 2.65; CI, 2.18 to 3.12).” (R. Retnakaran, rretnakaran@mtsinai.on.ca)

>>>PNN NewsWatch
* “The Drug Quality and Security Act is a significant step toward having new and stronger drug quality and safety laws,” FDA Commissioner Margaret A. Hamburg wrote in a blog posted yesterday. “Drugs produced by compounders that are not registered as outsourcing facilities must meet certain other conditions described in the law, or they will be regulated by FDA as conventional drug manufacturers,” she wrote in describing the pharmacy compounding bill signed into law last Wednesday by Pres. Obama. “Generally, the state boards of pharmacy will continue to have primary responsibility for the day-to-day oversight of state-licensed pharmacies, including traditional pharmacy compounding. And FDA will continue to cooperate with state authorities to address pharmacy compounding activities that may be in violation of the Federal Food Drug and Cosmetic Act.”

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 4, 2013 * Vol. 20, No. 232
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 4 issue of JAMA, a theme issue on graduate medical education (2013; 310).
Resident Handoff Bundle & Medical Errors: Medical errors and other preventable adverse events were significantly reduced following implementation of a resident handoff bundle consisting of standardized communication and handoff training, a verbal mnemonic, and a new team handoff structure (pp. 2262–70). At Boston Children’s Hospital, a prospective intervention study compared events before (July to Sept. 2009) and after (Nov. 2009 to Jan. 2010) implementation of the bundle during 1,255 patient admissions and 84 resident physicians. Results showed: “Medical errors decreased from 33.8 per 100 admissions (95% CI, 27.3–40.3) to 18.3 per 100 admissions (95% CI, 14.7–21.9; P < .001), and preventable adverse events decreased from 3.3 per 100 admissions (95% CI, 1.7–4.8) to 1.5 (95% CI, 0.51–2.4) per 100 admissions (P = .04) following the intervention. There were fewer omissions of key handoff elements on printed handoff documents, especially on [a] unit that received the computerized handoff tool (significant reductions of omissions in 11 of 14 categories with computerized tool; significant reductions in 2 of 14 categories without computerized tool). Physicians spent a greater percentage of time in a 24-hour period at the patient bedside after the intervention (8.3%; 95% CI 7.1%–9.8%) vs 10.6% (95% CI, 9.2%–12.2%; P = .03). The average duration of verbal handoffs per patient did not change. Verbal handoffs were more likely to occur in a quiet location (33.3%; 95% CI, 14.5%–52.2% vs 67.9%; 95% CI, 50.6%–85.2%; P = .03) and private location (50.0%; 95% CI, 30%–70% vs 85.7%; 95% CI, 72.8%–98.7%; P = .007) after the intervention.” (A. J. Starmer, amy.starmer@childrens.harvard.edu)
Efforts like this are important “as hospitals and residency programs seek to manage increasing complexity and fragmentation without reverting to an archaic model of round-the-clock care,” an editorialist writes (
pp. 2255–6; L. Horwitz, leora.horwitz@yale.edu)
Substance Use Among Anesthesiology Residents: Substance use disorder (SUD) among anesthesiology residents is rare, but when it occurs, risk of relapse is high, a study shows (pp. 2289–96). Records of the American Board of Anesthesiology for 1975–2009 showed these patterns among 44,612 residents during 177,848 resident–years: “Of the residents, 384 had evidence of SUD during training, with an overall incidence of 2.16 (95% CI, 1.95–2.39) per 1,000 resident–years (2.68 [95% CI, 2.41–2.98] men and 0.65 [95% CI, 0.44–0.93] women per 1,000 resident–years). During the study period, an initial rate increase was followed by a period of lower rates in 1996–2002, but the highest incidence has occurred since 2003 (2.87 [95% CI, 2.42–3.39] per 1,000 resident–years). The most common substance category was intravenous opioids, followed by alcohol, marijuana or cocaine, anesthetics/hypnotics, and oral opioids. Twenty-eight individuals (7.3%; 95% CI, 4.9%–10.4%) died during the training period; all deaths were related to SUD. The Kaplan–Meier estimate of the cumulative proportion of survivors experiencing at least 1 relapse by 30 years after the initial episode (based on a median follow-up of 8.9 years [interquartile range, 5.0–18.8 years]) was 43% (95% CI, 34%–51%). Rates of relapse and death did not depend on the category of substance used. Relapse rates did not change over the study period.” (D. O. Warner, warner.david@mayo.edu)

>>>PNN NewsWatch
* In three guidances released on Monday, FDA moved quickly and aggressively to implement the Drug Quality and Safety Act signed into law just last week, pharmacist.com reports. The guidances are not yet effective but will likely be formally proposed by FDA through publication in the Federal Register in a few days. In one guidance, FDA proposes that all compounding—nonsterile and sterile—follow USP Chapters <795> and <797>. If adopted, the requirement could apply in virtually every pharmacy nationwide for any compounding activity, including reconstitution of antibiotic powders, according to an attorney quoted in the pharmacist.com article.
*
Clobazam (Onfi, Lundbeck) can cause Stevens–Johnson syndrome and toxic epidermal necrolysis at any point during therapy, FDA warned yesterday, but such reactions are more common during the first 8 weeks of treatment or when the drug is stopped and restarted.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 5, 2013 * Vol. 20, No. 233
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 5 issue of the New England Journal of Medicine (2013; 369).
Bivalirudin During Emergency PCI Transport: Among 2,218 patients with ST-segment elevation myocardial infarction (STEMI) being emergently transported for primary percutaneous coronary intervention (PCI), bivalirudin administration significantly improved 30-day clinical outcomes with fewer episodes of major bleeding but produced more acute stent thrombosis, compared with unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (pp. 2207–17). Based on a primary outcome at 30 days of a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG) and a principal secondary outcome of a composite of death, reinfarction, or non-CABG major bleeding, the investigators found: “Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P = 0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P = 0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P < 0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P = 0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients.” (P. G. Steg, gabriel.steg@bch.aphp.fr)
An editorialist asks whether “the tradeoff of reduced procedural bleeding [is] worth the increased risk of acute stent thrombosis” and reaches this conclusion (
pp. 2263–5): “Few observers would dispute that stent thrombosis is a serious, albeit infrequent, event that results in either reinfarction or death in most cases. On the other hand, major bleeding occurs more frequently but varies widely in severity, depending on how the term is defined. Severe bleeding is prognostically more important but far less frequent than less serious bleeding, which has little or no long-term importance. Thus, it is critical that clinicians weigh the relative importance of these events before selecting an antithrombotic strategy for their patients.” (S. R. Mehta)
Fertility Treatments & Multiple Births: In the U.S., use of fertility treatments over the past four decades is responsible for one third of twin births and three fourths of triplet and higher-order births, but the rate of the latter is declining because of changes in in vitro fertilization (IVF) procedures, researchers report (pp. 2218–25). Birth data from 1962–66 served as a prefertility-treatment baseline. In 1971–2011, these patterns of multiple births were noted: “We estimated that by 2011, a total of 36% of twin births and 77% of triplet and higher-order births resulted from conception assisted by fertility treatments. The observed incidence of twin births increased by a factor of 1.9 from 1971 to 2009. The incidence of triplet and higher-order births increased by a factor of 6.7 from 1971 to 1998 and decreased by 29% from 1998 to 2011. This decrease coincided with a 70% reduction in the transfer of three or more embryos during IVF (P < 0.001) and a 33% decrease in the proportion of triplet and higher-order births attributable to IVF (P < 0.001).” (A. D. Kulkarni, eof0@cdc.gov)
Initiation of Obesity Prevention: “It is time to interrupt [the] vicious cycle” of obesity and chronic diseases being passed from mothers to children, write authors of a Perspective article describing obesity prevention care that begins during pregnancy (pp. 2173–5): “Even as we await the results of obesity-prevention trials, some recommendations are warranted because of their beneficial effects on other health outcomes. Pregnant women should not smoke. Treatment of gestational diabetes reduces macrosomia at birth, although such treatment hasn’t been proven to prevent obesity. U.S. rates of elective cesarean sections have apparently leveled off, but reducing these rates, especially of cesarean sections performed before 39 weeks of gestation, is a public health goal. Simple sleep-hygiene measures [for infants] are worth trying, even in early infancy. The ideal age, in terms of [infant] allergy prevention, for introducing solid foods appears to be 4 to 6 months, and further research may show that the same is true in terms of obesity prevention.” (M. W. Gillman)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 6, 2013 * Vol. 20, No. 234
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Dec. issue of Diabetes Care (2013; 36).
Long-Term Course of Young-Onset Diabetes: In patients with onset at 15–30 years of age, type 2 diabetes (T2DM) is more lethal than type 1 diabetes (T1DM), with “greater mortality, more diabetes complications, and unfavorable cardiovascular disease risk factors,” researchers report (pp. 3863–9). Australian data on 354 patients with young-onset T2DM and 470 patients with young-onset T1DM revealed these patterns: “For a median observation period of 21.4 (interquartile range 14–30.7) and 23.4 (15.7–32.4) years for the T2DM and T1DM cohorts, respectively, 71 of 824 patients (8.6%) died. A significant mortality excess was noted in T2DM15–30 (11 vs. 6.8%, P = 0.03), with an increased hazard for death (hazard ratio 2.0 [95% CI 1.2–3.2], P = 0.003). Death for T2DM15–30 occurred after a significantly shorter disease duration (26.9 [18.1–36.0] vs. 36.5 [24.4–45.4] years, P = 0.01) and at a relatively young age. There were more cardiovascular deaths in T2DM15–30 (50 vs. 30%, P < 0.05). Despite equivalent glycemic control and shorter disease duration, the prevalence of albuminuria and less favorable cardiovascular risk factors were greater in the T2DM15–30 cohort, even soon after diabetes onset. Neuropathy scores and macrovascular complications were also increased in T2DM15–30 (P < 0.0001).” (M. I. Constantino, maria.constantino@sswahs.nsw.gov.au)
Guidelines and goals on cardiovascular disease risk factors “clearly need to be revisited” based on these data, an editorialist writes (
pp. 3857–9). “Constantino et al. should serve not only as an alarm bell for the development of appropriate management strategies for young-onset type 2 diabetes but also—especially given the disappointing results of the TODAY study of management of adolescent type 2 diabetes—a call to further our prevention efforts in terms of type 2 diabetes and insulin resistance in general. While we can probably still conclude that those with type 1 diabetes and an onset in youth may have a normal life expectancy, particularly if micro- or macroalbuminuria is avoided, it seems doubtful that the same optimism can be extended to those developing type 2 diabetes at a similarly young age.” (T. J. Orchard, tjo@pitt.edu)

>>>Pharmacotherapy Report
Source:
Early-release articles from Pharmacotherapy (2013; 33).
Economics of Medication Errors: Analysis of 779 medication errors provides information on medication errors and a decision model based for estimating costs (doi: 10.1002/phar.1370). Data came from the Medication Error Detection, Amelioration and Prevention (MEDAP) study, which documented medication errors observed by clinical pharmacists during a consecutive 14-day period. Analysis of rates, outcomes, and interventions were determined, and a decision model was developed: “In the base case, the mean expected cost of a medication error was $88.57. In the Monte Carlo simulation, the mean cost was $89.35 (± $30.17 SD). One-way sensitivity analysis revealed that changes in the probability of medication errors causing hospitalization and the cost of hospitalization had the greatest variability on the outcome ($50.44–$155.81 [probability of hospitalization], $32.59–$136.40 [cost of hospitalization]).” (D. R. Touchette, drtouche@uic.edu)
Panresistant Cytomegalovirus in Kidney Transplant: The case of a patient with panresistant cytomegalovirus (CMV) is described (doi: 10.1002/phar.1373): “Resistance of CMV to antiviral agents is becoming more common but with few treatment strategies. Two specific mutations in the CMV genome—the UL97 and UL54 genes—correlate with antiviral drug resistance. We describe a 49-year-old, CMV-seronegative woman who received a CMV-seropositive donor kidney transplant and appropriate CMV prophylaxis. Approximately 1 month after transplantation, the patient developed CMV viremia that responded to valganciclovir. She was later diagnosed with recurrent CMV infection, CMV resistance, and both the UL97 and UL54 gene mutations. The patient responded to foscarnet and significant reduction of immunosuppression; she was negative for CMV viremia for the next 12 months. This case illustrates the importance of having heightened awareness for the possibility of panresistant CMV early and decreasing immunosuppression as the cornerstone of treatment.” (S. E. Yost, Sarah.yost@uahealth.com)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 9, 2013 * Vol. 20, No. 235
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release article from BMJ (2013; 347).
Respiratory Function & Probiotics in Pregnancy/Infancy: Randomized controlled trials do not support recommendations for use of probiotics during pregnancy and infancy for prevention of asthma and wheezing, according to a systematic review and meta-analysis (f6471): “Trials were heterogeneous in the type and duration of probiotic supplementation, and duration of follow-up. Only five trials conducted follow-up beyond participants’ age of 6 years (median 24 months), and none were powered to detect asthma as the primary outcome. The overall rate of doctor diagnosed asthma was 10.7%; overall rates of incident wheeze and lower respiratory tract infection were 33.3% and 13.9%, respectively. Among 3,257 infants enrolled in nine trials contributing asthma data, the risk ratio of doctor diagnosed asthma in participants randomised to receive probiotics was 0.99 (95% confidence interval 0.81 to 1.21, I2 = 0%). The risk ratio of incident wheeze was 0.97 (0.87 to 1.09, I2 = 0%, 9 trials, 1949 infants). Among 1364 infants enrolled in six trials, the risk ratio of lower respiratory tract infection after probiotic supplementation was 1.26 (0.99 to 1.61, I2 = 0%). We adjudicated most trials to be of high (ten trials) or unclear (nine trials) risk of bias, mainly due to attrition.” (M. B. Azad, meghan.azad@ualberta.ca)

>>>Pediatrics Highlights
Source:
Dec. issue of Pediatrics (2013; 132).
Neuraminidase Inhibitors in Critically Ill Children: A study of 784 critically ill pediatric patients with influenza shows that prompt institution of neuraminidase inhibitor (NAI) therapy can improve survival (pp. e1539–45). The patients, all younger than 18 years, had these outcomes when hospitalized in intensive-care units (ICUs): “Ninety percent (532 of 591) of cases during the 2009 H1N1 pandemic (April 3, 2009–August 31, 2010) received NAI treatment compared with 63% (121 of 193) of cases in the postpandemic period (September 1, 2010–September 30, 2012; P < .0001). Of 653 cases NAI-treated, 38 (6%) died compared with 11 (8%) of 131 untreated cases (odds ratio = 0.67, 95% confidence interval: 0.34–1.36). In a multivariate model that included receipt of mechanical ventilation and other factors associated with disease severity, the estimated risk of death was reduced in NAI-treated cases (odds ratio 0.36, 95% confidence interval: 0.16–0.83). Treatment within 48 hours of illness onset was significantly associated with survival (P = .04). Cases with NAI treatment initiated earlier in illness were less likely to die.” (J. K. Louie)
Probiotics for Late-Onset Sepsis in Very Preterm Infants: In infants born before 32 weeks’ gestation and weighing less than 1,500 g, probiotic therapy was safe and significantly reduced necrotizing enterocolitis (NEC) of Bell stage 2 or more, but the intervention did not affect rates of late-onset sepsis or mortality (pp. 1055–62). Infants received a probiotic combination of Bifidobacterium infantis, Streptococcus thermophilus, and Bifidobacterium lactis, with these results: “Rates of definite late-onset sepsis (16.2%), NEC of Bell stage 2 or more (4.4%), and mortality (5.1%) were low in controls, with high breast milk feeding rates (96.9%). No significant difference in definite late-onset sepsis or all-cause mortality was found, but this probiotic combination reduced NEC of Bell stage 2 or more (2.0% versus 4.4%; relative risk 0.46, 95% confidence interval 0.23 to 0.93, P = .03; number needed to treat 43, 95% confidence interval 23 to 333).” (S. E. Jacobs)
Pediatric Drugs & Emergency Departments: Two studies of emergency departments show that pediatric critical care telemedicine consults can reduce physician-related medication errors (pp. 1090–7; M. Dharmar) and that visits related to OTC cough-and-cold products declined among young children after voluntary market withdrawals and labeling revisions (pp. 1047–54; L. M. Hampton).

>>>PNN NewsWatch
* FDA has approved sofosbuvir (Sovaldi, Gilead) for treatment of chronic hepatitis C virus infection and a new indication for collagenase clostridium histolyticum (Xiaflex, Auxilium), nonsurgical treatment of bothersome penile curvature deformity (Peyronie’s disease).

>>>PNN JournalWatch
* Varenicline, Smoking Cessation, and Neuropsychiatric Adverse Events, in
American Journal of Psychiatry, 2013; 170: 1460–7. (R. D. Gibbons)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 10, 2013 * Vol. 20, No. 236
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Dec. 9/23 issue of JAMA Internal Medicine (2013; 173).
Health Care–Associated Infections: Savings to hospitals from reductions in complications of health care–associated infections (HAIs) should be reinvested in quality improvement initiatives to continue this progress, authors conclude (pp. 2039–46). Using a systematic review of HAIs, meta-analysis of their costs, and cost simulation, the investigators identified these results: “Using Monte Carlo simulation, we generated point estimates and 95% CIs for attributable costs and length of hospital stay. On a per-case basis, central line–associated bloodstream infections were found to be the most costly HAIs at $45,814 (95% CI, $30,919–$65,245), followed by ventilator-associated pneumonia at $40,144 (95% CI, $36,286–$44,220), surgical site infections at $20,785 (95% CI, $18,902–$22,667), Clostridium difficile infection at $11,285 (95% CI, $9,118–$13,574), and catheter-associated urinary tract infections at $896 (95% CI, $603–$1,189). The total annual costs for the 5 major infections were $9.8 billion (95% CI, $8.3–$11.5 billion), with surgical site infections contributing the most to overall costs (33.7% of the total), followed by ventilator-associated pneumonia (31.6%), central line–associated bloodstream infections (18.9%), C difficile infections (15.4%), and catheter-associated urinary tract infections (<1%).” (E. Zimlichman, ezimlichman@partners.org)
“In the past, one of the challenges in motivating system change through demonstrating the costs of health care–associated infections was that insurers paid hospitals for the additional costs owing to the infection,” according to an editor’s note accompanying this article (
p. 2046). “Under this perverse payment scheme, a hospital that invested money to decrease infections would pay ‘twice’: once for the intervention and once through not getting the additional money for treating the patient for the additional complication. This began to change in 2009 when Medicare stopped paying for hospital-acquired infections.
“Not paying for hospital-acquired infections or errors is an important part of the movement toward paying for quality, not quantity, of care. As physicians, we should embrace the opportunity that these new payment schemes offer for bringing higher-quality care—including fewer infections—to our patients.” (M. H. Katz)
Insurance Status & End-of-Life Care: Among nursing home residents with advanced dementia, those in Medicare managed-care programs receive more appropriate, less burdensome, and affordable care, compared with traditional fee-for-service Medicare programs, researchers report (pp. 2047–53). Medicare data and figures on 323 residents of 32 Boston-area nursing homes who participated in the Choices, Attitudes, and Strategies for Care of Advanced Dementia at the End-of-Life (CASCADE) prospective cohort study showed the following: “Residents enrolled in managed care (n = 133) were more likely to have do-not-hospitalize orders compared with those in traditional Medicare fee for service (n = 158) (63.7% vs 50.9%; adjusted odds ratio, 1.9; 95% CI, 1.1–3.4), were less likely to be transferred to the hospital for acute illness (3.8% vs 15.7%; adjusted odds ratio, 0.2; 95% CI, 0.1–0.5), had more primary care visits per 90 days (mean [SD], 4.8 [2.6] vs 4.2 [5.0]; adjusted rate ratio, 1.3; 95% CI, 1.1–1.6), and had more nurse practitioner visits (3.0 [2.1] vs 0.8 [2.6]; adjusted rate ratio, 3.0; 95% CI, 2.2–4.1). Survival, comfort, and other treatment outcomes did not differ significantly across groups.” (K. S. Goldfeld, keith.goldfeld@nyumc.org)

>>>PNN NewsWatch
* ASHP’s 48th Midyear Clinical Meeting is under way this week in Orlando (#ashpmidyear on Twitter; educational presentations are online during the meeting at connect.ashp.org/MCM13). The keynote address of Gen. Colin L. Powell (Ret.) energized the world’s largest gathering of pharmacists on Monday morning. Powell recounted interactions with pharmacists during hospitalizations in and visits to military health care facilities. To help Americans understand how pharmacists can help them, more interactions like those need to be created in the public space of community pharmacies, Powell said. Addressing pharmacy’s efforts to achieve provider status, Powell said the profession has its “work cut out” but has “a great vision and plan” for working together toward this goal.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 11, 2013 * Vol. 20, No. 237
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 11 issue of JAMA (2013; 310).
Acid Blockers & Vitamin B12 Deficiency: Among Kaiser Permanente Northern California patients, deficiencies of vitamin B12 were associated with current or previous use of gastric acid inhibitors, researchers report (pp. 2435–42). This risk of PPIs and H2 receptor antagonists (H2RAs) needs to be balanced against benefits of the drugs, the group concludes. A group of 25,956 patients with incident vitamin B12 deficiency was compared with 184,199 patients without deficiency. Results showed: “Among patients with incident diagnoses of vitamin B12 deficiency, 3,120 (12.0%) were dispensed a 2 or more years’ supply of PPIs, 1,087 (4.2%) were dispensed a 2 or more years’ supply of H2RAs (without any PPI use), and 21,749 (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients without vitamin B12 deficiency, 13,210 (7.2%) were dispensed a 2 or more years’ supply of PPIs, 5,897 (3.2%) were dispensed a 2 or more years’ supply of H2RAs (without any PPI use), and 165,092 (89.6%) had not received prescriptions for either PPIs or H2RAs. Both a 2 or more years’ supply of PPIs (OR, 1.65 [95% CI, 1.58–1.73]) and a 2 or more years’ supply of H2RAs (OR, 1.25 [95% CI, 1.17–1.34]) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77–2.15]) than were doses less than 0.75 pills/d (OR, 1.63 [95% CI, 1.48–1.78]; P = .007 for interaction).” (D. A. Corley, douglas.corley@kp.org)
Pruritus in Older Patients: When older patients present with itching, a number of dermatological, systemic, and neurological etiologies need to be considered, according to findings in a review article (pp. 2443–50): “More than 50% of elderly patients have xerosis (dry skin). Xerosis treatment should be included in the initial therapy for pruritus in all elderly patients. Calcium channel blockers and hydrochlorothiazide are important causes of pruritic skin eruptions in older patients. Neuropathic pruritus is infrequently considered but may cause localized itching (especially in the genital area) and generalized truncal pruritus (especially in patients with diabetes mellitus). Certain skin conditions are more common in elderly patients, including scabies, bullous pemphigoid, transient acantholytic dermatosis, and mycosis fungoides, and should be considered in elderly patients with pruritus.” (T. G. Berger, bergert@derm.ucsf.edu)
Statins for Primary Prevention: “When used for primary prevention, statins are associated with lower rates of all-cause mortality, major vascular events, and revascularizations compared with placebo,” authors of a JAMA Clinical Evidence Synopsis write, adding that use of the drugs is not associated with life-threatening adverse effects such as cancer (pp. 2451–2). Areas in need of study with regard to statin therapy include the following: “Cost-effectiveness estimates for statins in low-risk people are needed to inform guidelines in light of new evidence of benefits. New studies of the cost-effectiveness of alternative nonpharmacological CVD prevention strategies are needed. Further evidence on unintended adverse effects of statins from large-scale observational data and from unreported trial data is required to evaluate potential hazards of type 2 diabetes, adverse quality of life, and hemorrhagic stroke.” (F. C. Taylor, fiona.taylor@lshtm.ac.uk)
Weight Change After Bariatric Surgery: Three years after undergoing Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB), most patients achieve substantial weight loss and improved but variable outcomes in diabetes, blood pressure, and lipids, according to findings of the Longitudinal Assessment of Bariatric Surgery (LABS) Consortium (pp. 2416–25). Results for 2,458 patients (79% women) showed these results: “Median actual weight loss for RYGB participants was 41 kg (IQR, 31–52), corresponding to a percentage of baseline weight lost of 31.5% (IQR, 24.6%–38.4%). For LAGB participants, actual weight loss was 20 kg (IQR, 10–29), corresponding to 15.9% (IQR, 7.9%–23.0%).… The incidence of diabetes was 0.9% after RYGB and 3.2% after LAGB. Dyslipidemia resolved in 237 RYGB participants (61.9%) and 39 LAGB participants (27.1%); remission of hypertension occurred in 269 RYGB participants (38.2%) and 43 LAGB participants (17.4%).” (A. P. Courcoulas, courcoulasap@upmc.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 12, 2013 * Vol. 20, No. 238
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Dec. 12 New England Journal of Medicine (2013; 369).
Genomics & Warfarin: Five articles, including two research articles and an editorial covered previously in PNN (see Nov. 20), discuss integration of pharmacogenomics into warfarin therapy management.
A genotype-guided approach to warfarin dosing failed to improve anticoagulation control during the first 4 weeks of treatment, researchers report (
pp. 2283–93). Among 1,015 patients assigned during the first 5 days of treatment to care based on clinical variables only or clinical variables plus genotype, international normalized ratio (INR) results through day 28 of therapy showed the following: “At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], −0.2; 95% confidence interval, −3.4 to 3.1; P = 0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P = 0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.” (S. E. Kimmel, stevek@mail.med.upenn.edu)
A second study shows the opposite results: “Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy” (
pp. 2294–303). Using a point-of-care genotyping test, results were as follows for 455 patients whose care in the first 5 days was guided by genetics versus standard care: “The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P < 0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥ 4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P < 0.001).” (M. Pirmohamed, munirp@liverpool.ac.uk)
During the first 12 weeks of treatment, genotype-guided dosing did not improve time in therapeutic INR ranges, a study of 548 patients on acenocoumarol or phenprocoumon shows (
pp. 2304–12). Patients on genotype-guided dosing were in therapeutic range 61.6% of the time, versus 60.2% with algorithm-based dosing. Analysis of time in therapeutic range in the first 4 weeks was significantly better but not clinically relevant with genotyping (52.8% versus 47.5%). (A. H. Maitland-van der Zee, a.h.maitland@uu.nl)
“Despite the variation in trial design, these trials indicate that this pharmacogenetic testing has either no usefulness in the initial dosing of vitamin K antagonists or, at best, marginal usefulness, given the cost and effort required to perform this testing,” an editorialist writes (
pp. 2345–6, B. Furie).
In a Perspective article, two FDA pharmacists and the FDA commissioners seek to “recalibrate dosing” of warfarin based on pharmacogenetics and propose these guidelines for future research (
pp. 2273–5): “Methodologic rigor is critical in evidence assessment, and it is equally important to design experiments to definitively clarify issues of public health relevance. Randomization, in and of itself, does not accomplish this end. Rather, the choice of control, the treatment setting, characteristics of the population tested, the analytic approach, and end-point definition are likely to be the key considerations that determine the public health relevance of pharmacogenetic trials in the future. Future trials should use various methods to assess the clinical usefulness of pharmacogenetic interventions; these may include designs focused on assessing efficacy (emphasis on internal validity), effectiveness (emphasis on generalizability), and implementation effectiveness (emphasis on adoption and uptake). These approaches are not mutually exclusive and, if combined, may expedite assessment of the effects of pharmacogenetic interventions on patients, providers, and health systems.” (I. Zineh)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 13, 2013 * Vol. 20, No. 239
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Dec. 17 issue of the Journal of the American College of Cardiology (2013; 62).
Insulin Status, Vascular Responses & Weight Loss: In patients with overweight or obesity, reversal of insulin resistance and endothelial function is an important therapeutic target for reducing cardiovascular risks, a study shows (pp. 2297–305). Over a median of 11.7 months, 208 patients with BMIs of 25 or more received medical/dietary (48%) or bariatric surgical (52%) therapy. Results showed: “Patients age 45 ± 1 years, with BMI 45 ± 9 kg/m2, experienced 14 ± 14% weight loss during the study period. In individuals with higher baseline plasma insulin levels (above median >12 µIU/ml; n = 99), ≥10% weight loss (compared with <10%) significantly improved brachial artery macrovascular flow-mediated vasodilation and microvascular reactive hyperemia (p < 0.05 for all). By contrast, vascular function did not change significantly in the lower insulin group (≤12 µIU/ml; n = 109) despite a similar degree of weight loss. In analyses using a 5% weight loss cut point, only microvascular responses improved in the higher insulin group (p = 0.02).” (S. J. Bigornia)
Allopurinol in Diabetes & Hypertrophy: In patients type 2 diabetes (T2DM) and left ventricular hypertrophy (LVH), allopurinol therapy “may become useful” for improving cardiovascular (CV) mortality and morbidity, researchers report (pp. 2284–93). Allopurinol 600 mg/d or placebo over a 9-month period produced these changes in LVH and left ventricular mass (LVM): “Allopurinol significantly reduced absolute LVM (−2.65 ± 5.91 g vs. placebo group +1.21 ± 5.10 g [p = 0.012]) and LVM indexed to body surface area (−1.32 ± 2.84 g/m2 vs. placebo group +0.65 ± 3.07 g/m2 [p = 0.017]). No significant changes were seen in either flow-mediated dilation or augmentation index.” (B. R. Szwejkowski)

>>>Chest Highlights
Source:
Dec. issue of Chest (2013; 144).
Antibiotic Duration in Ventilator-Associated Pneumonia: Short- versus long-duration antibiotic therapy in ventilator-associated pneumonia (VAP) is examined in a systematic review and meta-analysis of four randomized controlled trials (pp. 1759–67). “Short-course treatment of VAP was associated with more antibiotic-free days” and “a strong trend for fewer relapses … in favor of the long-course treatment,” but the latter result was “mostly driven by one study in which the observed relapses were probably more microbiologic than clinical.” Details were as follows: “No difference in mortality was found between the compared arms (fixed effect model [FEM]: OR = 1.20; 95% CI, 0.84-1.72; P = .32). There was an increase in antibiotic-free days in favor of the short-course treatment with a pooled weighted mean difference of 3.40 days (random effects model: 95% CI, 1.43-5.37; P < .001). There was no difference in relapses between the compared arms, although a strong trend to lower relapses in the long-course treatment was observed (FEM: OR = 1.67; 95% CI, 0.99-2.83; P = .06).” (D. K. Matthaiou, d.matthaiou@gmail.com)
Treatment of Chronic Cough: “Opioid and certain nonopioid and nonanesthetic antitussives demonstrated efficacy for treating chronic cough in adults,” conclude authors of a systematic review and meta-analysis of 49 studies of 3,067 patients treated with 68 regimens (pp. 1827–38): “Compared with placebo, effect sizes (standardized mean differences for cough severity and rate ratios for cough frequency) for opioids were 0.55 (95% CI, 0.38–0.72; P < .0001) and 0.57 (95% CI, 0.36–0.91; P = .0260), respectively. For dextromethorphan, effect sizes were 0.37 (95% CI, 0.19–0.56; P = .0008) and 0.40 (95% CI, 0.18–0.85; P = .0248), respectively. The overall strength of evidence was limited by inconsistency and imprecision of results and by small numbers of direct comparisons. Nonpharmacologic therapies and the management of cough in children were infrequently studied.” (W. S. Yancy Jr., yancy006@mc.duke.edu)

>>>PNN NewsWatch
* The effort to gain provider status for pharmacists is on, APhA CEO Thomas E. Menighan blogged yesterday. Senators Grassley (R–IA) and Carper (D–DE) were ready to propose an amendment to the doc-fix bill in the Senate Finance Committee, but a large number of proposals resulted in most not being addressed, including this one.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 16, 2013 * Vol. 20, No. 240
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 14 issue of Lancet (2013; 382).
Cangrelor in PCI: In a pooled analysis of trial data, cangrelor reduced thrombotic complications of percutaneous coronary intervention (PCI), compared with placebo or clopidogrel), but “at the expense of increased bleeding,” researchers report (pp. 1981–92). Patient-level data from CHAMPION-PCI, CHAMPION-PLATFORM, and CHAMPION-PHOENIX were combined. Patients were undergoing PCI for ST-elevation myocardial infarction (11.6%), non–ST-elevation acute coronary syndromes (57.4%), and stable coronary artery disease (31.0%). Results showed: “Cangrelor reduced the odds of the primary outcome by 19% (3.8% for cangrelor vs 4.7% for control; odds ratio [OR] 0.81, 95% CI 0.71–0.91, p = 0.0007), and stent thrombosis by 41% (0.5% vs 0.8%, OR 0.59, 95% CI 0.43–0.80, p = 0.0008). Cangrelor reduced the odds of the secondary triple composite (all-cause death, myocardial infarction, or ischaemia-driven revascularisation at 48 h) by 19% (3.6% vs 4.4%, OR 0.81, 95% CI 0.71–0.92, p = 0.0014). Efficacy outcomes were consistent across the trials and main patient subsets. These benefits were maintained at 30 days. There was no difference in the primary safety outcome (0.2% in both groups), in GUSTO moderate bleeding (0.6% vs 0.4%), or in transfusion (0.7% vs 0.6%), but cangrelor increased GUSTO mild bleeding (16.8% vs 13.0%, p < 0.0001).” (P. G. Steg, gabriel.steg@bch.aphp.fr)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2013; 347).
Diabetes Risk With Cardiovascular Drugs: Use of diuretics or statins is associated with increased risk of diabetes in patients with impaired glucose tolerance or other cardiovascular risk factors, but beta-blockers do not carry this risk, report investigators who reanalyzed data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial (f6745). Among patients who were treatment-naive at baseline to beta-blockers (n = 6,346), diuretics (n = 6,346), statins (n = 6,146), and calcium-channel blockers (controls; n = 6,294), these patterns of medication use and incident diabetes were noted: “During the median five years of follow-up, beta blockers were started in 915 (16.2%) patients, diuretics in 1,316 (20.7%), statins in 1,353 (22.0%), and calcium channel blockers in 1,171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas beta blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively).” (H. Krum, henry.krum@monash.edu)
Chocolates on Hospital Wards: In addition to the James Bond study in the news since Thursday (f7255; P. Davies, patrick.davies@nuh.nhs.uk), BMJ’s annual Christmas issue of quirky research provides this observational study of the survival time of chocolates placed on four wards at three U.K. hospitals (f7198): “191 out of 258 (74%) chocolates were observed being eaten. The mean total observation period was 254 minutes (95% confidence interval 179 to 329). The median survival time of a chocolate was 51 minutes (39 to 63). The model of chocolate consumption was non-linear, with an initial rapid rate of consumption that slowed with time. An exponential decay model best fitted these findings (model R2 = 0.844, P < 0.001), with a survival half life (time taken for 50% of the chocolates to be eaten) of 99 minutes. The mean time taken to open a box of chocolates from first appearance on the ward was 12 minutes (95% confidence interval 0 to 24). Quality Street chocolates survived longer than Roses chocolates (hazard ratio for survival of Roses v Quality Street 0.70, 95% confidence interval 0.53 to 0.93, P = 0.014). The highest percentages of chocolates were consumed by healthcare assistants (28%) and nurses (28%), followed by doctors (15%).” (P. R. Gajendragadkar, gajendragadkar@gmail.com)

>>>PNN JournalWatch
* Role of Vitamin D in Atherosclerosis, in
Circulation, 2013; 128: 2517–31. (A. G. Papavassiliou, papavas@med.uoa.gr)
* An Update on Pulmonary Complications of Hematopoietic Stem Cell Transplantation, in
Chest, 2013; 144: 1913–22. (A. Chi, achi@tuftsmedicalcenter.org)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 17, 2013 * Vol. 20, No. 241
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Dec. 17 issue of the Annals of Internal Medicine (2013; 159).
High-Dose Vitamins After MI: One of four articles in this issue on vitamin therapy, a study of 1,708 patients 50 years or older with myocardial infarction (MI) shows that “high-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications” (pp. 797–805). Results were “tempered by the nonadherence rate.” Results for an oral high-dose multivitamin and mineral mixture with 28 components showed: “The median age was 65 years, and 18% of patients were women. The qualifying MI occurred a median of 4.6 years (interquartile range [IQR], 1.6 to 9.2 years) before enrollment. Median follow-up was 55 months (IQR, 26 to 60 months). Patients received vitamins for a median of 31 months (IQR, 13 to 59 months) in the vitamin group and 35 months (IQR, 13 to 60 months) in the placebo group (P = 0.65). Totals of 645 (76%) and 646 (76%) patients in the vitamin and placebo groups, respectively, completed at least 1 year of oral therapy (P = 0.98), and 400 (47%) and 426 (50%) patients, respectively, completed at least 3 years (P = 0.23). Totals of 394 (46%) and 390 (46%) patients in the vitamin and placebo groups, respectively, discontinued the vitamin regimen (P = 0.67), and 17% of patients withdrew from the study. The primary end point [of time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina] occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group (hazard ratio, 0.89 [95% CI, 0.75 to 1.07]; P = 0.21). No evidence suggested harm from vitamin therapy in any category of adverse events.” (G. A. Lamas, gervasio.lamas@msmc.com)
Long-Term Multivitamins & Cognition in Older Men: In the Physicians’ Health Study II, 5,947 men aged 65 years or older had no cognitive benefits from use of a daily multivitamin used for 12 years (pp. 806–14). During four cognitive assessments, researchers found these results based on a global composite score averaging five tests of global cognition, verbal memory, and category fluency: “No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessments. Specifically, for the global composite score, the mean difference in cognitive change over follow-up was −0.01 SU (95% CI, −0.04 to 0.02 SU) when treatment was compared with placebo. Similarly, cognitive performance did not differ between the multivitamin and placebo groups on the secondary outcome, verbal memory (mean difference in cognitive change over follow-up, −0.005 SU [CI, −0.04 to 0.03 SU]).” (F. Grodstein, phfrg@channing.harvard.edu)
Vitamins & Primary Prevention of CVD, Cancers: “Limited evidence” supports use of vitamin and mineral supplements for prevention of cardiovascular disease (CVD) and cancers, according to an updated systematic evidence review from the Agency for Healthcare Research and Quality (pp. 824–34). Only two trials found any benefit, and then the difference was “small, borderline-significant,” the group concludes, with differences limited to men: “Two large trials (n = 27,658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324,653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor beta-carotene prevented CVD or cancer, and beta-carotene increased lung cancer risk in smokers.” (AHRQ, www.ahrq.gov)
Editorialists responding to these articles urge U.S. adults to stop wasting their money on dietary supplements (
pp. 850–1). “Enough is enough,” the authors title their article, adding: “Evidence is sufficient to advise against routine supplementation, and we should translate null and negative findings into action. The message is simple: Most supplements do not prevent chronic disease or death, their use is not justified, and they should be avoided. This message is especially true for the general population with no clear evidence of micronutrient deficiencies, who represent most supplement users in the United States and other countries.” (E. Guallar).

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 18, 2013 * Vol. 20, No. 242
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Dec. 18 issue of JAMA (2013; 310).
Duration of Dual Antiplatelet Therapy After Zotarolimus-Eluting Stents: In patients with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents, 3 months of dual antiplatelet therapy appears to be just as effective as 12 months in preventing adverse effects (pp. 2510–22). In the open-label noninferiority OPTIMIZE trial, 3,119 patients at 33 Brazilian sites received aspirin 100–200 mg and clopidogrel 75 mg daily for 3 or 12 months. Based on a primary end point of net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction [MI], stroke, or major bleeding) and secondary end points of major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization), results showed: “NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 [95% CI, −1.52 to 1.86]; P = .002 for noninferiority). Kaplan–Meier estimates demonstrated MACE rates at 1 year of 8.3% (128) in the short-term group and 7.4% (114) in the long-term group (HR, 1.12 [95% CI, 0.87–1.45]). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 [2.6%] vs 38 [2.6%] for the short- and long-term groups, respectively; HR, 1.03 [95% CI, 0.66–1.60]), MACE (78 [5.3%] vs 64 [4.3%]; HR, 1.22 [95% CI, 0.88–1.70]), or stent thrombosis (4 [0.3%] vs 1 [0.1%]; HR, 3.97 [95% CI, 0.44–35.49]).” (F. Feres, fferes@lee.dante.br)
Nonsurgical Periodontal Therapy in Type 2 Diabetes: In patients with type 2 diabetes and moderate to advanced chronic periodontitis, scaling and root planing plus chlorhexidine oral rinse did not improve glycemic control, compared with no treatment over a 6-month period (pp. 2523–32). The Diabetes and Periodontal Therapy Trial (DPTT), designed based on “limited evidence that periodontal therapy may improve glycemic control,” included 514 patients and looked for change in glycosylated hemoglobin and secondary outcomes, including the Homeostasis Model Assessment (HOMA2) score: “Enrollment was stopped early because of futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, −0.05% [95% CI, −0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all).” (S. P. Engebretson, spe2002@nyu.edu)
Treatment of Acute Heart Failure With Renal Dysfunction: “Neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy” in a group of patients with acute heart failure and renal dysfunction, researchers report (pp. 2533–43). Open allocation to the two treatments in 241 patients yielded these findings: “Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8,524 mL; 95% CI, 7,917–9,131 vs placebo, 8,296 mL; 95% CI, 7,762–8,830 ; difference, 229 mL; 95% CI, −714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06–0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06–0.16; difference, 0.01; 95% CI, −0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8,574 mL; 95% CI, 8,014–9,134 vs placebo, 8,296 mL; 95% CI, 7,762–8,830; difference, 279 mL; 95% CI, −618 to 1,176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01–0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06–0.16; difference, −0.04; 95% CI, −0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes.” (H. H. Chen, chen.horng@mayo.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 19, 2013 * Vol. 20, No. 243
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Early-release articles from JAMA (2013; 310).
JNC 8: Long-awaited hypertension treatment guidelines were released yesterday on the JAMA website (doi: 10.1001/jama.2013.284427). The Eighth Joint National Committee (JNC 8) recommended a higher systolic blood pressure trigger point for patients 60 years or older and focused on diastolic levels only in younger patients: “There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes.” (P. A. James, paul-james@uiowa.edu)
In one of three related editorials (
doi: 10.1001/jama.2013.284430, E. D. Peterson; doi: 10.1001/jama.2013.284432, H. Bauchner), a writer offers four questions for evaluating the “trustworthiness” of the JNC 8 guidelines and describes why that is needed (doi:10.1001/jama.2013.284429): “Physicians and other readers are confronted with an important report that, although it has undergone extensive review, has not been evaluated by the specialty societies that the NHLBI designated to take responsibility for the guidelines program. The panel’s departure from usual practice leads to 4 questions. First, what are the key elements of trustworthiness in a guideline? Second, how does this guideline measure up? Third, what is the role of expert review of guidelines? Fourth, what is the pathway to guidelines that the public can trust?” (H. C. Sox)

>>>NEJM Highlights
Source:
Dec. 19 issue of the New England Journal of Medicine (2013; 369).
SSRIs in Pregnancy: Among all live births in Denmark in 1996–2005, maternal use of SSRIs during pregnancy was not associated with autism spectrum disorder in offspring, researchers report (pp. 2406–15). The cohort study of nearly 627,000 births showed these relationships: “During 5,057,282 person–years of follow-up, we identified 3,892 cases of autism spectrum disorder (incidence rate, 77.0 per 100,000 person–years). A total of 52 cases during 42,400 person–years of follow-up involved offspring of women who were exposed to SSRIs during their pregnancy (incidence rate, 122.6 per 100,000 person–years). As compared with no use of SSRIs both before and during pregnancy, use during pregnancy was not associated with a significantly increased risk of autism spectrum disorders (fully adjusted rate ratio, 1.20; 95% confidence interval [CI], 0.90 to 1.61). Among women who received SSRIs before pregnancy but not during pregnancy, the corresponding fully adjusted rate ratio was 1.46 (95% CI, 1.17 to 1.81).” (A. Hviid, aii@ssi.dk)

>>>PNN NewsWatch
* Umeclidinium and vilanterol inhalation powder (Anoro Ellipta, GlaxoSmithKline) was approved yesterday by FDA for once-daily, long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). The product, with two long-acting bronchodilators, is the first dual product approved for once-daily use in COPD.
* Use of
methylphenidate is rarely associated with priapism, FDA warned this week. As with other drugs, patients experiencing painful erections for more than 4 hours should seek medical care.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 20, 2013 * Vol. 20, No. 244
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Dec. issue of the Journal of the American Geriatrics Society (2013; 61).
Critically Ill Older Adults With Infection: More than half of patients with infections in intensive-care units are older than 65, and those older than 85 have high mortality rates, according to the international, observational Extended Prevalence of Infection in Intensive Care (EPIC II) study (pp. 2065–71). At 1,265 ICUs in 75 countries, these data were collected for adults on May 8, 2007: “Of the 13,796 adults enrolled in EPIC II, 7,087 (51.4%) had an infection. Of these, 330 (4.7%) were aged 85 and older, 1,405 (19.8%) were 75 to 84, 1,713 (24.2%) were 65 to 74, 2,358 (33.3%) were 45 to 64, and 1,281 (18.1%) were 18 to 44. Severity of illness did not differ between groups. Those aged 85 and older had fewer bloodstream infections than those younger than 75, fewer central nervous system infections than those who were younger than 65, and more abdominal infections than those who were younger than 45. A microbiological diagnosis was established less frequently in participants aged 85 and older than in younger participants. Gram-negative microorganisms were more frequently isolated in those aged 85 and older than in other groups. ICU and hospital mortality were significantly higher in participants aged 85 and older than in those who were younger than 65.” (G. Dimopoulos, gdimop@med.uoa.gr)
Hypertension Management in Older Adults With CKD: Older patients in China with chronic kidney disease (CKD) often have uncontrolled hypertension, primarily with elevated systolic blood pressures, according to the Survey of Prevalence, Awareness, and Treatment Rates in Chronic Kidney Disease Patients with Hypertension in China (PATRIOTIC) (pp. 2160–7). The nationwide study showed these patterns of disease among 2,414 participants older than 60: “The prevalence, awareness, and treatment of hypertension in elderly adults with CKD were 82.0%, 90.7%, and 87.3%, respectively. The control of hypertension at BP less than 140/90 mmHg was 29.6% and at BP less than 130/80 mmHg it was 12.1%. No significant differences were noted in the prevalence, awareness, treatment, or control of hypertension in individuals with CKD divided into the age groups of 60 to 69, 70 to 79, and 80 and older (P > .05). With increasing age, the proportion of isolated systolic hypertension in elderly adults with CKD with uncontrolled hypertension increased (P = .02). Obesity (P = .01), CKD Stages 4 and 5 (P < .001), and concomitant diabetes mellitus (P = .002) were significantly associated with uncontrolled hypertension in elderly adults with CKD, using the goal of BP less than 140/90 mmHg.” (X. Chen, xmchen301@126.com)

>>>Allergy/Immunology Report
Source:
Dec. issue of the Journal of Allergy and Clinical Immunology (2013; 132).
House Dust Mite Allergen Immunotherapy: More rigorous clinical studies are needed of immunotherapy for allergic rhinitis (AR) and allergic asthma (AA) induced by house dust mites (HDMs), according to authors who conducted an evidence-based analysis (pp. 1322–36). Based on 44 studies that met inclusion criteria, the group wrote that “there is no consensus on basic treatment parameters (eg, dose and duration)” in HDM subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT), adding these details: “Some studies tested both SLIT and SCIT or scored both AA and AR outcomes; therefore we reviewed 35 treatment arms in patients with AA (20 for SCIT and 15 for SLIT) and 23 treatment arms in patients with AR (7 for SCIT and 16 for SLIT). The treatment duration ranged from 6 weeks to 3 years. For SCIT, the dose of Der p 1 major allergen (when reported) ranged from 7 to 30 µg for maintenance doses and 60 to 420 µg for cumulative doses. For SLIT, the doses of Der p 1 (when reported) were 0.8 to 70 µg for maintenance doses and 60 to 23,695 µg for cumulative doses. Safety data were often absent or poorly reported. A statistically significant active versus placebo symptom score was observed more frequently for SCIT than for SLIT.” (P. Demoly, pascal.demoly@inserm.fr)

>>>PNN NewsWatch
* Abrams Royal Pharmacy in Dallas is voluntarily recalling all unexpired lots of sterile products dispensed nationwide due to lack of sterility assurance, FDA said.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 23, 2013 * Vol. 20, No. 245
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Dec. 21 issue of Lancet (2013; 382).
Dextrose Gel for Neonatal Hypoglycemia: In late preterm and term babies with hypoglycemia, dextrose gel is inexpensive and simple to administer and should be considered for first-line therapy in the first 48 hours after birth, investigators with the Sugar Babies study conclude (pp. 2077–83). At a New Zealand tertiary-care facility in 2008–10, at-risk neonates born at 35–42 weeks’ gestation and younger than 48 hours received 40% dextrose gel 200 mg/kg or placebo, with these results: “Of 514 enrolled babies, 242 (47%) became hypoglycaemic and were randomised. Five babies were randomised in error, leaving 237 for analysis: 118 (50%) in the dextrose group and 119 (50%) in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (16 [14%] vs 29 [24%]; relative risk 0.57, 95% CI 0.33–0.98; p = 0.04). We noted no serious adverse events. Three (3%) babies in the placebo group each had one blood glucose concentration of 0.9 mmol/L. No other adverse events took place.” (J. E. Harding, j.harding@auckland.ac.nz)
Algorithm-Based Management of Pelvic Radiation GI Symptoms: In patients with gastrointestinal symptoms following pelvic radiotherapy, an algorithm that can be used by trained nurses is significantly better than usual care, according to results of the ORBIT trial (pp. 2084–92). Adult patients at clinics in London were randomly assigned to usual care (a detailed self-help booklet), gastroenterologist-led algorithm-based treatment, or nurse-led algorithm-based treatment. Based on a primary endpoint of change in Inflammatory Bowel Disease Questionnaire–Bowel subset score (IBDQ-B) at 6 months, the authors found: “Between Nov 26, 2007, and Dec 12, 2011, we enrolled and randomly allocated 218 patients to treatment: 80 to the nurse group, 70 to the gastroenterologist group, and 68 to the booklet group. Most had a baseline IBDQ-B score indicating moderate-to-severe symptoms. We recorded the following pair-wise mean difference in change in IBDQ-B score between groups: nurse versus booklet 4.12 (95% CI 0.04–8.19; p = 0.04), gastroenterologist versus booklet 5.47 (1.14–9.81; p = 0.01). Outcomes in the nurse group were not inferior to outcomes in the gastroenterologist group (mean difference 1.36, one sided 95% CI −1.48).” (H. J. N. Andreyev, j@andreyev.demon.co.uk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2013; 347).
A Statin a Day: In a “comparative proverb assessment modeling study,” authors writing in the BMJ’s annual Christmas issue of quirky research find that an apple a day is nearly as effective as a statin a day for reducing mortality in adults older than 50 (f7267). Based on meta-analyses of the relationships among statins, apples, and health, the group finds: “The estimated annual reduction in deaths from vascular disease of a statin a day, assuming 70% compliance and a reduction in vascular mortality of 12% (95% confidence interval 9% to 16%) per 1.0 mmol/L reduction in low density lipoprotein cholesterol, is 9,400 (7,000 to 12,500). The equivalent reduction from an apple a day, modelled using the PRIME model (assuming an apple weighs 100 g and that overall calorie consumption remains constant) is 8,500 (95% credible interval 6,200 to 10,800).” (A. D. M. Briggs, adam.briggs@dph.ox.ac.uk)

>>>PNN NewsWatch
* PNN will not be published on Tues. and Wed., Dec. 24 and 25, Christmas Eve and Day.

>>>PNN JournalWatch
* Community-Acquired Bacterial Bloodstream Infections in HIV-Infected Patients: A Systematic Review, in
Clinical Infectious Diseases, 2014; 58: 79–92. (M. P. Grobusch, m.p.grobusch@amc.uva.nl)
* Evaluating Many Treatments and Biomarkers in Oncology: A New Design, in
Journal of Clinical Oncology, 2013; 31: 4562–8. (R. Kaplan, r.kaplan@ctu.mrc.ac.uk)
* Recommendations for Screening and Detection of Connective Tissue Disease–Associated Pulmonary Arterial Hypertension, in
Arthritis & Rheumatism, 2013; 65: 3194–201. (D. Khanna, khannad@med.umich.edu)
* Molecular Medicine and the Art of Brain Repair, in
Neurology, 2013; 81: 2143–4. (S. T. Carmichael, scarmichael@mednet.ulca.edu)
* Protocol-Driven Emergency Department Observation Units Offer Savings, Shorter Stays, and Reduced Admissions, in
Health Affairs, 2013; 32: 2149–56. (M. A. Ross, maross@emory.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 26, 2013 * Vol. 20, No. 246
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Early-release article from and Dec. 26 issue of the New England Journal of Medicine (2013; 369).
Quadrivalent Vaccine Prevention of Influenza in Children: In a multinational, Phase III, observer-blinded study, quadrivalent influenza vaccine (QIV) provided protection against influenza infection among 4,963 children ages 3–8 years (pp. 2481–91). Using a primary end point of influenza A or B confirmed by real-time polymerase chain reaction (rt-PCR), investigators found these results in those vaccinated with QIV or hepatitis A vaccine (control): “In the total vaccinated cohort, 62 children in the QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR–confirmed influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI], 45.2 to 69.7), with efficacy against culture-confirmed influenza of 59.1% (97.5% CI, 41.2 to 71.5). For moderate-to-severe rt-PCR–confirmed influenza, the attack rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per-protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI, 47.1 to 86.3). The QIV was associated with reduced risks of a body temperature above 39°C and lower respiratory tract illness, as compared with the control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to 0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic against all four strains. Serious adverse events occurred in 36 children in the QIV group (1.4%) and in 24 children in the control group (0.9%).” (G. Dbaibo, gdbaibo@aub.edu.lb)
Inclusion of two B antigens in influenza vaccines should prove valuable, an editorialist writes (
pp. 2547–9). “Constant reevaluation to identify the influenza strains that are the likeliest threats is important in determining the most effective strategy for preventing disease from influenza. Rapid development and wide use of vaccines with antigens that match the circulating strains are important for an effective response. Ongoing careful safety assessments of any new therapy, including these vaccines, is essential. In the United States, a quadrivalent influenza vaccine with both B-lineage antigens has been introduced this season as an alternative to the traditional trivalent vaccine. Over the next few influenza seasons we hope to see the value of the two Bs.” (L. R. Baden)
Gaps in DQSA: “The Drug Quality and Security Act may have been a good first step, but patients will not be protected unless states, the FDA, and health care providers and plans act quickly to fill in the gaps left by Congress,” concludes the author of a Perspective article on the new pharmacy compounding law (doi: 10.1056/NEJMp1314691). Few compounders will eagerly embrace the new “outsourcing facility” license, the writer predicts: “The more disappointing provision of the new law is found in Section 503B, which creates an optional new license for sterile compounders, to be known as ‘outsourcing facilities.’ This new license applies tougher standards than those applied to traditional compounders but is less stringent than the full rules applied to drug manufacturers. In the Senate bill, the outsourcing-facility license was mandatory, but the final act followed the House bill, making the license entirely voluntary. Over the past year, most of the debate in Congress has centered on how to draw the line between traditional compounding and activities that require the new license. The legislative compromise leaves that choice up to the compounder.” (K. Outterson)

>>>PNN NewsWatch
* FDA has approved Coagulation Factor XIII A-Subunit (Recombinant) (Tretten, Novo Nordisk), the first recombinant product for use in the routine prevention of bleeding in adults and children with congenital Factor XIII A-subunit deficiency. The product is administered once monthly and features a short infusion time.
* Consumers should not use
Mass Destruction (Blunt Force Nutrition), a product marketed as a dietary supplement for muscle growth, FDA said on Monday. The product is labeled to contain at least one synthetic anabolic steroid and has been linked to at least one reported serious illness, a case of liver failure requiring transplant.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 27, 2013 * Vol. 20, No. 247
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Jan. issue of Diabetes Care (2014; 37), with summary findings marking the 30th anniversary of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC).
DCCT/EDIC Is “Gift” That Keeps on Giving: Recalling the impact of the Kennedy assassination on a generation of Americans, authors describe similar effects of the presentation of DCCT results at the 1993 American Diabetes Association Scientific Sessions (pp. 5–7): “During the session, the significance of the findings was quite apparent. We realized there was no more guessing on what our standards of treatment were to be…now we had data! But, to be honest, we clearly did not appreciate the fact that 20 years later, we would be reflecting on that moment as just the beginning of a long and rewarding story. We agreed that the initial results at the time ushered in a new paradigm of treatment, but not one of us in attendance that day could have predicted what was to come of the DCCT and that the study would be as relevant today as it was then and continue to inform and provide new information In short, the study continues to evolve to the point that 20 years later the ‘gift’ of new information continues. Thus, in celebration of the 30th anniversary of the DCCT and [the] follow-up … EDIC, our editorial team is honored to feature the summary findings to date of the DCCT/EDIC in this issue.” (William T. Cefalu, cefaluwt@pbrc.edu)
DCCT/EDIC at 30: “DCCT/EDIC has demonstrated the effectiveness of [intensive therapy (INT)] in reducing the long-term complications of [type 1 diabetes (T1DM)] and improving the prospects for a healthy life span,” an author writes on behalf of the DCCT/EDIC Research Group (pp. 9–16). Recalling the DCCT and its 1,441 participants in 1982–93, the author provides this summary of study results: “The DCCT followed >99% of the cohort for a mean of 6.5 years and demonstrated a 35–76% reduction in the early stages of microvascular disease with INT, with a median HbA1c of 7%, compared with [conventional therapy], with a median HbA1c of 9%. The major adverse effect of INT was a threefold increased risk of hypoglycemia, which was not associated with a decline in cognitive function or quality of life. EDIC showed a durable effect of initial assigned therapies despite a loss of the glycemic separation (metabolic memory) and demonstrated that the reduction in early-stage complications during the DCCT translated into substantial reductions in severe complications and [cardiovascular disease].” (D. M. Nathan, dnathan@mgh.harvard.edu)

>>>JAPhA Report
Source:
Early-release articles from the Journal of the American Pharmacists Association (2014; 54).
Drug Information Resources at the National Library of Medicine: Five recently developed drug information resources for pharmacists are hosted on the National Library of Medicine website, authors write (doi: 10.1331/JAPhA.2014.13123): “[These include] a repository of current product labeling/package inserts, with automated search links to associated information resources; a portal to drug information that allows pharmacists to search multiple databases simultaneously and link to related medication and health care information resources; authoritative information on the effects of medications, herbal remedies, and dietary supplements in nursing infants and their mothers; comprehensive information, including a case registry, on the potential for liver toxicity due to drugs, herbal remedies, and dietary supplements; and a pill identification system with two intuitive search methodologies.” (J. E. Knoben, james.knoben@nih.hhs.gov)
Iterative Interviews for Collaboration: “Bringing physicians and pharmacists together for a face-to-face interaction that was informed by information gained in previous individual interviews successfully stimulated conversation on ways in which each profession could help the other provide optimal patient care,” conclude authors of a research study on iterative interviews (doi: 10.1331/JAPhA.2014.13104). “This interaction appeared to dispel assumptions and build trust. The results of this project may provide pharmacists with the confidence to reach out to their physician colleagues.” (M. A. Chui, mchui@pharmacy.wisc.edu)

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.

PNN Pharmacotherapy Line
Dec. 30, 2013 * Vol. 20, No. 248
Providing news and information about medications and their proper use

>>>PNN’s Top 10 for 2013
Pharmacy began 2013 under intense scrutiny after a nationwide outbreak of fungal infections caused by contaminated compounded products. Congress has given FDA new authority in that realm, and now the profession is headed back to Capitol Hill seeking something more positive: provider status.
1 Congress, FDA Act on Pharmacy Compounding: Pharmacy struggled with a compounding-quality conundrum (Apr. 8). A few days after Pres. Obama signed what some felt was a weak Drug Quality and Safety Act (Nov. 27), FDA issued aggressive guidances (Dec. 4) that could keep compounding in the news. If so, the profession will need to self-regulate to avoid the kind of morbidity and mortality caused by last year’s outbreak of fungal infections (Feb. 10, June 19 and 27, Oct. 24).
2 Pharmacists Seek Recognition as Obamacare Is Implemented: Health care is increasingly regulated and regimented, and medications are the prime mode of treatment of many diseases (especially chronic ones). To survive in the health care system now on the horizon, pharmacists need formal provider status recognition of the clinical services they can provide, and APhA (Jan. 8), ASHP (Jan. 4), ACCP (May 3), and other groups are out to attain it.
3 Pharmacists Excel in Clinical Roles: Nonadherence should be treated like a disease (May 23), but a polypill that addresses adherence is no solution if polypharmacy is the problem (Sept. 4), authors wrote. The medication expert on the health care team can help with such problems. In 2013, studies demonstrated pharmacists’ impact in care transitions and medication reconciliation (Jan. 23, Mar. 5, Aug. 23), on clinical care teams (Sept. 17), in critical care units (Nov. 8), and in accountable care organizations (Nov. 22).
4 Guidelines, No Longer Official, Lead to Controversy: When NIH bailed out of the guideline business (Aug. 14), an association-driven process seemed a natural answer. Within months, advice was published for lipids and obesity management, risk assessment, lifestyle changes (Nov. 13), and then not one but two guidelines for hypertension came out (Nov. 20 and Dec. 19). Controversy ensued, with a risk-assessment calculator criticized and confusion among clinicians about which guidelines to adopt.
5 New Drugs, New OTCs: New drugs for COPD (May 13 and Dec. 19) and hepatitis C virus (Dec. 9) were approved this year. Key agents made the Rx-to-OTC switch, including a court-driven Plan B One Step (June 6, 12, 21) and Nasacort Allergy 24 HR (Oct. 15).
6 Misused Opioids, Other Meds: The “opioid epidemic” continues, with abuse of these drugs the largest contributor to the global burden of illicit drug use (Nov. 11) and American adolescents in emergency departments needing to be screened for nonmedical opioid or sedative use (Nov. 8). Paradoxically, FDA announced one day that it wanted to move Vicodin and Lortab to Schedule II (Oct. 25) and then approved non-tamper-resistant Zohydro ER the next (Oct. 28).
7 Genomics & Personalized Care: This may have been the year FDA approved a new drug with a companion gene-mutation test (July 15), but those hoping genomics could recharge anticoag clinics were disappointed by results presented at the Am. Heart Assoc. meeting (Nov. 20 and Dec. 12).
8 Antibiotic Stewardship: Efforts to make better use of antibiotics continued, with emphasis on pathways (Jan. 11), care bundles (Feb. 8), decision support (Feb. 26), nursing homes (Apr. 23), pediatrics (June 12), class-specific changes (July 30), and electronic health records (Sept. 14).
9 Vitamin D Interests, Other Supplements Fade: Studies of vitamin D yielded mixed results during 2013 (Feb. 1, Apr. 1, May 1, July 19, Aug. 16), but uncovering of racial differences in levels, effects, and binding proteins proved fascinating. Other supplements continued to disappoint (Jan. 25, Oct. 25), and Americans heard an absolute recommendation to stop wasting money on vitamins (Dec. 17).
10 Economics Paint Picture: Medicare Part D provided interesting data for evaluating the costs of pharmacotherapy (Jan. 25, July 16). Payer-agnostic care was explored at a children’s hospital (Aug. 8), and some worried about physicians leaving the cost cutting to others (July 24).

>>>PNN NewsWatch
* PNN will not be published on Tues. and Wed., Dec. 31 and Jan. 1, New Year’s Eve and Day.

PNN Pharmacotherapy Line is published via e-mail each business day except U.S. holidays by PNN Pharmacotherapy News Network, P.O. Box 6565, Athens, GA 30604; 706/613-0100 or 706/613-0200 (fax). Copyright © 2013, Pharmacy Editorial & News Services, Inc. All rights reserved. L. Michael Posey, MA, Editor and Publisher. E-mail PNNInfo@mac.com or call 706/613-0100 to request missing copies of PNN. Quarterly files archived at www.PharmacotherapyNewsNetwork.com.