Mar 2015

PNN January–March 2015

PNN Pharmacotherapy Line
Jan. 5, 2015 * Vol. 22, No. 1
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 1 issue of the New England Journal of Medicine (2015; 372).
Intraarterial Thrombolysis for Acute Ischemic Stroke: Intraarterial interventions in patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion proved safe and effective in a trial of 500 patients at 16 medical centers in the Netherlands, researchers report (pp. 11–20). Clinicians used approved microcatheters to access the clot site and, at their discretion, administer alteplase 90 mg or urokinase 1.2 million units and/or perform mechanical thrombectomy within 6 hours of symptom onset. Based on a primary outcome of modified Rankin scale scores at 90 days, the MR CLEAN investigators found these results in comparison with usual care: “The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage.” (D. W. J. Dippel, d.dippel@erasmusmc.nl)
This study is “a step in the right direction” for interventional thrombectomy of major stroke, an editorialist writes (
pp. 76–7). While “it is premature to conclude that there is no longer equipoise regarding thrombectomy,” several ongoing trials will either “confirm or refute the results of MR CLEAN but also to look at effects in subgroups (according to stroke severity, occlusion site, or time to treatment initiation), for which most single trials are underpowered.” (W. Hacke)
Combination Treatment of Melanoma: Compared with vemurafenib 960 mg twice daily used alone, the combination of dabrafenib 150 mg twice daily plus trametinib 2 mg once daily “significantly improved overall survival in previously untreated patients with metastatic melanoma with BRAF V600E or V600K mutations, without increased overall toxicity,” an open-label Phase III trial shows (pp. 30–9). Results based on a primary outcome of overall survival showed the following: “At the preplanned interim overall survival analysis, which was performed after 77% of the total number of expected events occurred, the overall survival rate at 12 months was 72% (95% confidence interval [CI], 67 to 77) in the combination-therapy group and 65% (95% CI, 59 to 70) in the vemurafenib group (hazard ratio for death in the combination-therapy group, 0.69; 95% CI, 0.53 to 0.89; P = 0.005). The prespecified interim stopping boundary was crossed, and the study was stopped for efficacy in July 2014. Median progression-free survival was 11.4 months in the combination-therapy group and 7.3 months in the vemurafenib group (hazard ratio, 0.56; 95% CI, 0.46 to 0.69; P <0.001). The objective response rate was 64% in the combination-therapy group and 51% in the vemurafenib group (P <0.001). Rates of severe adverse events and study-drug discontinuations were similar in the two groups. Cutaneous squamous-cell carcinoma and keratoacanthoma occurred in 1% of patients in the combination-therapy group and 18% of those in the vemurafenib group.” (C. Robert, caroline.robert@gustaveroussy.fr)

>>>PNN JournalWatch
* Disorders of Plasma Sodium—Causes, Consequences, and Correction, in
New England Journal of Medicine, 2015; 372: 55–65. (R. H. Sterns, richard.sterns@rochesterregional.org)
* Antimicrobial Stewardship in Pediatrics: A Good Beginning But We Have a Long Way to Go, in
Pediatrics, 2015; 135: 180–1. (W. Mason)
* Rapid Normalization of Vitamin D Levels: A Meta-Analysis, in
Pediatrics, 2015; 135: e152–66. (J. D. McNally)
* Vitamin D in Fetal Development: Findings From a Birth Cohort Study, in
Pediatrics, 2015; 135: e167–73. (P.H. Hart)
* Hypercalcemia and “Primary” Hyperparathyroidism During Lithium Therapy, in
American Journal of Psychiatry, 2015; 172: 12–5. (H. I. Shapiro)
* Treatment of Multidrug-Resistant
Pseudomonas aeruginosa Using Extended-Infusion Antimicrobial Regimens, in Pharmacotherapy, 2015; 35: 10.1002/phar.1514. (E. L. Heil, eheil@umm.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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 6, 2015 * Vol. 22, No. 2
Providing news and information about medications and their proper use

>>>Internal Medicine Report I
Source:
Jan. issue of JAMA Internal Medicine (2015; 175).
Outpatient MTM: Authors of a systematic review and meta-analysis conclude that medication therapy management (MTM) interventions “may reduce the frequency of some medication-related problems, including nonadherence, and lower some health care use and costs, but the evidence is insufficient with respect to improvement in health outcomes” (pp. 76–87). The group attributed their grading to available evidence as “insufficient” because of “inconsistency and imprecision that stem in part from underlying heterogeneity in populations and interventions.”
Review of 44 studies meeting inclusion criteria led the group to these specific results: “The evidence was insufficient to determine the effect of MTM interventions on most evaluated outcomes (eg, drug therapy problems, adverse drug events, disease-specific morbidity, disease-specific or all-cause mortality, and harms). The interventions improved a few measures of medication-related problems and health care use and costs (low strength of evidence) when compared with usual care. Specifically, MTM interventions improved medication appropriateness (4.9 vs 0.9 points on the medication appropriateness index, P < .001), adherence (approximately 4.6%), and percentage of patients achieving a threshold adherence level (odds ratios [ORs] ranged from 0.99 to 5.98) and reduced medication dosing (mean difference, −2.2 doses; 95% CI, −3.738 to −0.662). Medication therapy management interventions reduced health plan expenditures on medication costs, although the studies reported wide CIs. For patients with diabetes mellitus or heart failure, MTM interventions lowered the odds of hospitalization (diabetes: OR, 0.91 to 0.93 based on type of insurance; adjusted hazard rate for heart failure: 0.55; 95% CI, 0.39 to 0.77) and hospitalization costs (mean differences ranged from −$363.45 to −$398.98). The interventions conferred no benefit for patient satisfaction and most measures of health-related quality of life (low strength).” (M. Viswanathan)

>>>Internal Medicine Report II
Source:
Jan. 6 issue of the Annals of Internal Medicine (2015; 162).
Valganciclovir After Stem-Cell Transplant: Compared with polymerase chain reaction–guided preemptive therapy with ganciclovir, prophylactic valganciclovir “was not superior in reducing the composite end point of [cytomegalovirus (CMV)] disease, invasive bacterial or fungal disease, or death” among 184 recipients of hematopoietic cell transplantation (HCT) who were at high risk for late CMV disease, researchers report (pp. 1–10). Study participants received valganciclovir 900 mg/d or placebo for 6 months, and those with high positive or rapidly increasing results on polymerase chain reaction tests for serum CMV DNA received ganciclovir or valganciclovir. Based on a composite primary end point of death, CMV disease, or other invasive infections by 270 days after HCT, results showed: “The primary composite outcome occurred in 20% of valganciclovir recipients versus 21% of placebo-preemptive therapy recipients (treatment difference, −0.01 [95% CI, −0.13 to 0.10]; P = 0.86). There was no difference in the primary end point or its components 640 days after HCT. The incidence of a CMV DNAemia level of 1000 copies/mL or greater or a 5-fold increase over baseline was reduced in the valganciclovir group (11% vs. 36%; P < 0.001). Neutropenia was not significantly different at the absolute neutrophil count of less than 0.5 × 109 cells/L (P = 0.57); however, more patients received hematopoietic growth factors in the valganciclovir group (25.3% vs. 12.4%; P = 0.026). No significant differences were seen in other secondary outcomes.” (M. Boeckh)
Multitarget Lupus Nephritis Induction Treatment: Compared with intravenous cyclophosphamide every 4 weeks as induction therapy for lupus nephritis, multitarget therapy provided “superior efficacy” based on complete remission at 24 weeks (pp. 18–26). Both groups were pretreated with pulse methylprednisolone. The participants in the multitarget treatment group received tacrolimus 4 mg/d, and mycophenolate mofetil 1.0 g/d. “More patients in the multitarget group (45.9%) than in the intravenous cyclophosphamide group (25.6%) showed complete remission (difference, 20.3 percentage points [95% CI, 10.0 to 30.6 percentage points]; P < 0.001)” at 24 weeks, the group reports. (Z. Liu, liuzhihong@nju.edu.cn)

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 7, 2015 * Vol. 22, No. 3
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 7 issue of JAMA (2015; 313).
Mortality in Type 1 Diabetes: Two studies and an editorial examine long-term mortality in patients with type 1 diabetes.
In a follow-up to the Diabetes Control and Complications Trial (DCCT), “6.5 years of initial intensive diabetes therapy was associated with a modestly lower all-cause mortality rate when compared with conventional therapy,” researchers report (
pp. 45–53). DCCT, conducted in 1983–93 at 27 U.S. and Canadian academic clinical centers, was followed by an observational phase of 1,441 healthy volunteers with type 1 diabetes. Through the end of 2012, these outcomes were noted in this group: “Vital status was ascertained for 1,429 (99.2%) participants. There were 107 deaths, 64 in the conventional and 43 in the intensive group. The absolute risk difference was −109 per 100,000 patient–years (95% CI, −218 to −1), with lower all-cause mortality risk in the intensive therapy group (hazard ratio [HR] = 0.67 [95% CI, 0.46–0.99]; P = .045). Primary causes of death were cardiovascular disease (24 deaths; 22.4%), cancer (21 deaths; 19.6%), acute diabetes complications (19 deaths; 17.8%), and accidents or suicide (18 deaths; 16.8%). Higher levels of glycated hemoglobin (HbA1c) were associated with all-cause mortality (HR = 1.56 [95% CI, 1.35–1.81 per 10% relative increase in HbA1c]; P < .001), as well as the development of albuminuria (HR = 2.20 [95% CI, 1.46–3.31]; P < .001).” (T. J. Orchard, tjo@pitt.edu)
In Scotland, men and women who live to age 20 can expect 11 and 13 fewer years of life, respectively, if they have type 1 diabetes, according to a prospective cohort study conducted in 2008–10 (
pp. 37–44). Included in the analysis were all individuals with type 1 diabetes in a nationwide registry who were 20 years or older in 2008. Among these 24,691 patients (67,712 person–years and 1,043 deaths during the study), results differed from a cohort without the disease: “Life expectancy at an attained age of 20 years was an additional 46.2 years among men with type 1 diabetes and 57.3 years among men without it, an estimated loss in life expectancy with diabetes of 11.1 years (95% CI, 10.1–12.1). Life expectancy from age 20 years was an additional 48.1 years among women with type 1 diabetes and 61.0 years among women without it, an estimated loss with diabetes of 12.9 years (95% CI, 11.7–14.1). Even among those with type 1 diabetes with an estimated glomerular filtration rate of 90 mL/min/1.73 m2 or higher, life expectancy was reduced (49.0 years in men, 53.1 years in women) giving an estimated loss from age 20 years of 8.3 years (95% CI, 6.5–10.1) for men and 7.9 years (95% CI, 5.5–10.3) for women. Overall, the largest percentage of the estimated loss in life expectancy was related to ischemic heart disease (36% in men, 31% in women) but death from diabetic coma or ketoacidosis was associated with the largest percentage of the estimated loss occurring before age 50 years (29.4% in men, 21.7% in women).” (S. J. Livingstone)
Editorialists note the continuing conundrum in diabetes therapy, with lack of progress despite use of intensive insulin therapy and contemporary tools for managing the disease (
pp. 35–6): “In the middle of the 20th century, there was still a 20-year reduction in life expectancy for those diagnosed with type 1 diabetes; 50% of individuals with youth-onset disease failed to reach the age of 55 years. A half century later, in the current era, intensive insulin therapy has become the standard of care and advances in insulin delivery and glucose monitoring assist in the management of type 1 diabetes. Yet glycemic control remains suboptimal for the majority of patients with type 1 diabetes, and acute and chronic diabetes complications persist, reducing life expectancy for many patients.” (M. Katz)
HPV Vaccine & Multiple Sclerosis: Administration of quadrivalent human papillomavirus (qHPV) vaccine was not associated with development of multiple sclerosis or other demyelinating diseases in an assessment of nationwide registries in Denmark and Sweden (pp. 54–61). Among nearly 4 million girls and women, including 789,082 who received 1.9 million qHPV doses, “there was no increased risk of multiple sclerosis (crude incidence rates, 6.12 events/100,000 person–years [95% CI, 4.86–7.69] and 21.54 events/100,000 person–years [95% CI, 20.90–22.20] for the vaccinated and unvaccinated periods.…” (N. M. Scheller)

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 8, 2015 * Vol. 22, No. 4
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 8 New England Journal of Medicine (2015; 372).
Treatment of Node-Negative, HER2-Positive Breast Cancer: In an uncontrolled study of 406 women with small, node-negative, human epidermal growth factor receptor type 2 (HER2)–positive breast cancers, the risk of early recurrence was 2% with adjuvant paclitaxel and trastuzumab, researchers report (pp. 134–41). Patients with these stage 1 tumors have generally been ineligible for pivotal trials of adjuvant trastuzumab, and thus clinicians have had no firm guidance on whether to add this agent to adjuvant paclitaxel. Patients received weekly treatment with paclitaxel and trastuzumab for 12 weeks followed by 9 months of trastuzumab monotherapy.
Results showed: “The median follow-up period was 4.0 years. The 3-year rate of survival free from invasive disease was 98.7% (95% confidence interval [CI], 97.6 to 99.8). Among the 12 relapses seen, 2 were due to distant metastatic breast cancer. Excluding contralateral HER2-negative breast cancers and nonbreast cancers, 7 disease-specific events were noted. A total of 13 patients (3.2%; 95% CI, 1.7 to 5.4) reported at least one episode of grade 3 neuropathy, and 2 had symptomatic congestive heart failure (0.5%; 95% CI, 0.1 to 1.8), both of whom had normalization of the left ventricular ejection fraction after discontinuation of trastuzumab. A total of 13 patients had significant asymptomatic declines in ejection fraction (3.2%; 95% CI, 1.7 to 5.4), as defined by the study, but 11 of these patients were able to resume trastuzumab therapy after a brief interruption.” (E. P. Winer,
ewiner@partners.org)
Carfilzomib in Relapsed Multiple Myeloma: In a study of 792 patients with relapsed multiple myeloma, “addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk–benefit profile,” investigators write (pp. 142–52). Compared with lenalidomide and dexamethasone alone, addition of carfilzomib produced these results: “Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P = 0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan–Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = 0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P <0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life.” (A. K. Stewart, stewart.keith@mayo.edu)
Tetravalent Dengue Vaccine in Latin American Children: Based on efficacy against symptomatic, virologically confirmed dengue (VCD), a recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) prevented disease and led to fewer hospitalizations in a Phase III trial of 20,869 healthy children (pp. 113–23): “At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person–years at risk) in the vaccine group and 221 VCD cases (with 5,809 person–years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events.” (G. H. Dayan, gustavo.dayan@sanofipasteur.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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 9, 2015 * Vol. 22, No. 5
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
Jan. issue of Pediatrics (2015; 135).
E-Cigarette & Tobacco Use in Adolescents: A school-based study from Hawaii shows that medium-risk adolescents are particularly susceptible to begin using e-cigarettes when they would not likely take up use of tobacco products (pp. e43–51). Among 1,941 high school students in 2013, these use statistics were reported: “Prevalence for the categories was 17% (e-cigarettes only), 12% (dual use), 3% (cigarettes only), and 68% (nonusers). Dual users and cigarette-only users were highest on risk status (elevated on risk factors and lower on protective factors) compared with other groups. E-cigarette only users were higher on risk status than nonusers but lower than dual users. E-cigarette only users and dual users more often perceived e-cigarettes as healthier than cigarettes compared with nonusers.” (T. A. Wills)
Drug Interactions Among Patients in Children’s Hospitals: Exposure to potential drug–drug interactions (PDDI) is common in U.S. children’s hospitals, according to a retrospective cohort analysis based on information from the MicroMedex DRUG-REAX system (pp. e99–108): “Of 498,956 hospitalizations in 2011, 49% were associated with ≥1 PDDI, with a ‘contraindicated’ PDDI occurring in 5% of all hospitalizations, a ‘major’ PDDI present in 41%, a ‘moderate’ PDDI in 28%, and a ‘minor’ PDDI in 11%. Opioids were involved in 25% of all PDDIs, followed by antiinfective agents (17%), neurologic agents (15%), gastrointestinal agents (13%), and cardiovascular agents (13%). One-half of all PDDI exposures were due to specific drug pairs occurring in ≤3% of patients per hospital day. The most common potential adverse drug events included additive respiratory depression (in 21% of PDDIs), bleeding risk (5%), QT interval prolongation (4%), reduced iron absorption/availability (4%), central nervous system depression (4%), hyperkalemia (3%), and altered diuretic effectiveness (3%).” (J. Feinstein)

>>>Psychiatry Report
Source:
Jan. issue of the American Journal of Psychiatry (2015; 172).
Treatment of Resistant Bipolar Depression: Neither electroconvulsive therapy (ECT) nor algorithm-based pharmacologic treatment produced remission among the majority of patients with treatment-resistant bipolar depression, researchers report (pp. 41–51). While ECT is “regarded by many clinicians as the most effective treatment for treatment-resistant bipolar depression,” a randomized controlled trial comparing the two approaches in 73 patients found improved scores with ECT but equivocal remission rates: “Linear mixed-effects modeling analysis revealed that ECT was significantly more effective than algorithm-based pharmacological treatment. The mean scores at the end of the 6-week treatment period were lower for the ECT group than for the pharmacological treatment group: by 6.6 points on the Montgomery–Åsberg Depression Rating Scale (SE = 2.05, 95% CI = 2.5–10.6), by 9.4 points on the 30-item version of the Inventory of Depressive Symptomatology–Clinician-Rated (SE = 2.49, 95% CI = 4.6–14.3), and by 0.7 points on the Clinical Global Impression for Bipolar Disorder (SE = 0.31, 95% CI = 0.13–1.36). The response rate was significantly higher in the ECT group than in the group that received algorithm-based pharmacological treatment (73.9% versus 35.0%), but the remission rate did not differ between the groups (34.8% versus 30.0%).” (H. K. Schoeyen)

>>>PNN NewsWatch
* FDA yesterday approved edoxaban (Savaysa, Daiichi Sankyo), an oral, once-daily selective factor Xa-inhibitor, for reducing risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) and for treatment of deep vein thrombosis and pulmonary embolism following 5–10 days of initial therapy with a parenteral anticoagulant. In the ENGAGE AF-TIMI 48 trial, edoxaban was noninferior to warfarin in the overall study population for the primary efficacy endpoint of stroke or systemic embolism. A boxed warning cautions that the drug should not be used in patients with NVAF whose creatinine clearance levels are more than 95 mL/min because in that population there is an increased risk of ischemic stroke compared with warfarin therapy. Common adverse effects in clinical trials were bleeding and anemia; as with anticlotting agents in general, life-threatening bleeding can occur.

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 12, 2015 * Vol. 22, No. 6
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 10 issue of Lancet (2015; 385).
Global Burden of Disease 2013: Worldwide causes of death are shifting “towards a larger share of the remaining deaths caused by non-communicable disease and injuries,” researchers report for the 1990–2013 period (pp. 117–71). “Age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries,” the group writes, based on these results for 188 countries: “Global life expectancy for both sexes increased from 65.3 years (UI 65.0–65.6) in 1990, to 71.5 years (UI 71.0–71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8–48.2) to 54.9 million (UI 53.6–56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100,000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.” (GBD 2013 Mortality and Causes of Death Collaborators)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2015; 350).
Dosing Schedule for HPV Vaccine: A cost-effectiveness study finds that the two-dose schedule for human papillomavirus vaccine is best if it provides protection for at least 20 years (g7584). Compared with a three-dose schedule, the investigators calculated the following from the perspective of a health care provider in the U.K.: “Giving at least two doses of vaccine seems to be highly cost effective across the entire range of scenarios considered at the quadrivalent vaccine list price of £86.50 (109.23 euros; $136.00) per dose. If two doses give only 10 years’ protection but adding a third dose extends this to lifetime protection, then the third dose also seems to be cost effective at £86.50 per dose (median incremental cost effectiveness ratio £17 000, interquartile range £11 700-£25 800). If two doses protect for more than 20 years, then the third dose will have to be priced substantially lower (median threshold price £31, interquartile range £28-£35) to be cost effective. Results are similar for a bivalent vaccine priced at £80.50 per dose and when the same scenarios are explored by parameterising a Canadian model (HPV-ADVISE) with economic data from the United Kingdom.” (M. Jit, mark.jit@phe.gov.uk)

>>>PNN JournalWatch
* Mechanisms and Clinical Consequences of Untreated Central Sleep Apnea in Heart Failure, in
Journal of the American College of Cardiology, 2015; 65: 72–84. (M. R. Costanzo)
* American Heart Association Cardiovascular Genome-Phenome Study: Foundational Basis and Program, in
Circulation, 2015; 131: 100–12. (J. Loscalzo, jloscalzo@partners.org)
* “Pills” and the Air Passages: A Continuum, in
Chest, 2015; 147: 242–50. (A. C. Mehta, Mehtaa1@ccf.org)
* Medical Marijuana: Policy Topic for 2015 APhA House of Delegates, in
Journal of the American Pharmacists Association, 2015; 55: 10–16.

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 13, 2015 * Vol. 22, No. 7
Providing news and information about medications and their proper use

>>>Internal Medicine Report I
Source:
Early-release article from the Annals of Internal Medicine (2015; 162).
Long-Term Opioid Therapy for Chronic Pain: Long-term opioid therapy is not supported by sufficient evidence of improved chronic pain and function, according to results of a systematic review conducted for an NIH Pathways to Prevention workshop (doi: 10.7326/M14-2559). Studies indicate a dose-dependent risk for harms, the authors conclude, based on these findings: “No study of opioid therapy versus no opioid therapy evaluated long-term (>1 year) outcomes related to pain, function, quality of life, opioid abuse, or addiction. Good- and fair-quality observational studies suggest that opioid therapy for chronic pain is associated with increased risk for overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction, although there are few studies for each of these outcomes; for some harms, higher doses are associated with increased risk. Evidence on the effectiveness and harms of different opioid dosing and risk mitigation strategies is limited.” (R. Chou, chour@ohsu.edu)

>>>Internal Medicine Report II
Source:
Early-release article from JAMA Internal Medicine (2015; 175).
Overtreatment of Intensive Antidiabetic Therapy in Older Adults: “Although the harms of intensive treatment likely exceed the benefits for older patients with complex/intermediate or very complex/poor health status,” such adults with A1c levels in the National Health and Nutrition Examination Survey (NHANES) in 2001–10 often were treated to tight glycemic targets, a study shows (doi: 10.1001/jamainternmed.2014.7345). Insulin or sulfonylureas were most often used in these patients, and both therapies are associated with severe hypoglycemia, the authors note. “Our findings suggest that a substantial proportion of older adults with diabetes were potentially overtreated,” the group concludes. (K. J. Lipska, kasia.lipska@yale.edu)

>>>Infectious Diseases Report
Source:
Jan. 15 issue of Clinical Infectious Diseases (2015; 60).
Antiviral Therapy in Herpes Simplex Virus Meningitis: Immunocompromised patients with herpes simplex virus (HSV) meningitis had better outcomes when treated with acyclovir, researchers report, but symptomatic therapy is generally sufficient for immunocompetent patients (pp. 237–42). In a retrospective, observational study, review of medical records for 42 patients with cerebrospinal fluid specimens positive for HSV-1 or HSV-2 in 2000–12 showed these outcomes: “In 6 episodes (14.3%), patients with meningitis received no antivirals, whereas the remaining episodes were treated with an oral antiviral (n = 11 [26.2%]), combination intravenous and oral therapy (n = 22 [52.4%]), or intravenous acyclovir alone (n = 3 [7.1%]). Six patients had recurrent episodes of meningitis and all recovered without any neurologic sequelae. Neurologic outcomes were significantly improved with antiviral therapy in immunocompromised patients with herpes meningitis (P < .05), but not in the 27 patient-episodes among immunocompetent patients (P = 1.0), as no neurologic sequelae were noted in this group.” (A. Noska, anoska@lifespan.org)
Neutropenia With Piperacillin–Tazobactam in Children: Courses of piperacillin–tazobactam (P/T) lasting longer than 2 weeks place children at a greater risk of neutropenia, compared with ticarcillin–clavulanate (T/C), according to Canadian authors who analyzed a series of 299 episodes of therapy with either combination in 2008–11 (pp. 203–7): “Among those episodes, 213 had data allowing complete white blood cell count analysis and were included in the final analysis. Thirteen cases of neutropenia were observed during the study period. The average time to onset was 17.6 days and all patients were aged <13 years. Seven cases (10.8%) occurred in the P/T group and 6 (2.6%) in the T/C group (unadjusted odds ratio, 4.59; 95% confidence interval, 1.48–14.17). Although a statistically significant correlation was observed between age, treatment duration, and total dose and the development of neutropenia (r = −0.121, P = .037; r = 0.267, P < .001; r = 0.260, P < .001, respectively), this was not the case for sex, indications, neutrophil count at initiation, and concomitant drug treatments.” (P. Lemieux, pierre.lemieux.1@ulaval.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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 14, 2015 * Vol. 22, No. 8
Providing news and information about medications and their proper use

>>>JAMA Report
Source:
Jan. 14 issue of JAMA (2015; 313).
CVD Prevention & Health Outcomes: In a county in Maine over a 40-year period, hospitalizations and mortality rates were reduced through “sustained, community-wide programs targeting cardiovascular risk factors and behavior changes,” compared with the rest of Maine, researchers report (pp. 147–55). Franklin County is in a rural part of the state and had a population of 22,444 in 1970. Community-wide programs targeting hypertension, cholesterol, and smoking had these effects through 2010: “More than 150,000 individual county resident contacts occurred over 40 years. Over time, as cardiovascular risk factor programs were added, relevant health indicators improved. Hypertension control had an absolute increase of 24.7% (95% CI, 21.6%–27.7%) from 18.3% to 43.0%, from 1975 to 1978; later, elevated cholesterol control had an absolute increase of 28.5% (95% CI, 25.3%–31.6%) from 0.4% to 28.9%, from 1986 to 2010. Smoking quit rates improved from 48.5% to 69.5%, better than state averages (observed − expected [O − E], 11.3%; 95% CI, 5.5%–17.7%; P < .001), 1996–2000; these differences later disappeared when Maine’s overall quit rate increased. Franklin County hospitalizations per capita were less than expected for the measured period, 1994–2006 (O − E, −17 discharges/1,000 residents; 95% CI −20.1 to −13.9; P < .001). Franklin was the only Maine county with consistently lower adjusted mortality than predicted over the time periods 1970–1989 and 1990–2010 (O − E, −60.4 deaths/100 000; 95% CI, −97.9 to −22.8; P < .001, and −41.6/100,000; 95% CI, −77.3 to −5.8; P = .005, respectively).” (N. B. Record)
““The Franklin County, Maine, program demonstrates significant accomplishments in one northern U.S. rural community that have made a difference in cardiovascular outcomes,” editorialists write (
pp. 139–40). “The experience deserves consideration as a model for other communities to emulate, adapt, and implement.” (D. R. Labarthe)
Asthma & Obstructive Sleep Apnea: Data collected since 1988 in the Wisconsin Sleep Cohort Study show that asthma is associated with an increased risk of new-onset obstructive sleep apnea (OSA) (pp. 156–64): “Twenty-two of 81 participants (27% [95% CI, 17%-37%]) with asthma experienced incident OSA over their first observed 4-year follow-up interval compared with 75 of 466 participants (16% [95% CI, 13%-19%]) without asthma. Using all 4-year intervals, participants with asthma experienced 45 cases of incident OSA during 167 4-year intervals (27% [95% CI, 20%-34%]) and participants without asthma experienced 160 cases of incident OSA during 938 4-year intervals (17% [95% CI, 15%-19%]); the corresponding adjusted relative risk (RR) was 1.39 (95% CI, 1.06-1.82), controlling for sex, age, baseline and change in body mass index, and other factors. Asthma was also associated with new-onset OSA with habitual sleepiness (RR, 2.72 [95% CI, 1.26-5.89], P = .045). Asthma duration was related to both incident OSA (RR, 1.07 per 5-year increment in asthma duration [95% CI, 1.02-1.13], P = .01) and incident OSA with habitual sleepiness (RR, 1.18 [95% CI, 1.07-1.31], P = .02).” (M. Teodorescu)

>>>PNN NewsWatch
* “Pharmacists’ roles are evolving beyond dispensing medication to providing direct care to patients as part of an integrated team of health care providers,” the National Governors Association said yesterday in a news release. NGA has released a report, “The Expanding Role of Pharmacists in a Transformed Health Care System,” which explores ways states can better integrate pharmacists into the health care delivery system, including amending existing laws and regulations to allow them to practice to the full scope of their profession. “Integrating pharmacists into chronic-care delivery teams, in particular, has the potential to improve health outcomes because of the critical role medication management plays in treating chronic disease,” the news release noted. “A limited number of studies indicate that pharmacists who provide medication therapy management services can improve outcomes and reduce costs.” This is the fourth in a series of NGA issue briefs on the health care workforce; the others cover physician assistants, dental hygienists, and nurse practitioners.

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 15, 2015 * Vol. 22, No. 9
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 15 issue of the New England Journal of Medicine (2015; 372).
U.S. Opioid Analgesic Abuse and Mortality: Diversion and abuse of opioid analgesics plateaued or decreased between 2011 and 2013, researchers report, after climbing from 2002 to 2010 (pp. 241–8). The results may indicate “progress in controlling the abuse of opioid analgesics” in the U.S., the authors conclude. Data from five programs from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System were used to generate these results for all products and formulations of six agents: “RADARS System programs reported large increases in the rates of opioid diversion and abuse from 2002 to 2010, but then the rates flattened or decreased from 2011 through 2013. The rate of opioid-related deaths rose and fell in a similar pattern. Reported nonmedical use did not change significantly among college students.” (R. C. Dart, richard.dart@rmpdc.org)
Treatment of Hyperkalemia: Two research studies and an editorial examine clinical management of hyperkalemia.
Patiromer, a nonabsorbed potassium binder, was effective in lowering serum potassium and reducing recurrence of hyperkalemia in patients with chronic kidney disease who were taking renin–angiotensin–aldosterone system (RAAS) inhibitors (
pp. 211–21). In the OPAL-HK trial, participants had serum potassium levels of 5.1 to less than 6.5 mmol/L. They received patiromer for 4 weeks followed by randomization of responders to continued therapy or placebo for 8 weeks, with these results: “In the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium measurement at a scheduled visit after day 3, the mean (± SE) change in the serum potassium level was −1.01 ± 0.03 mmol per liter (P <0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase. The median increase in the potassium level from baseline of that phase was greater with placebo than with patiromer (P <0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P <0.001). Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%.” (M. R. Weir, mweir@medicine.umaryland.edu)
In 753 patients with hyperkalemia, sodium zirconium cyclosilicate (ZS-9) reduced serum potassium levels within 48 hours, a study shows (
pp. 222–31). The two-stage, Phase III trial treated participants with the “novel selective cation exchanger” or placebo for 48 hours and then randomized responders to ZS-9 or placebo on days 3–14. Results showed: “At 48 hours, the mean serum potassium level had decreased from 5.3 mmol per liter at baseline to 4.9 mmol per liter in the group of patients who received 2.5 g of ZS-9, 4.8 mmol per liter in the 5-g group, and 4.6 mmol per liter in the 10-g group, for mean reductions of 0.5, 0.5, and 0.7 mmol per liter, respectively (P <0.001 for all comparisons) and to 5.1 mmol per liter in the 1.25-g group and the placebo group (mean reduction, 0.3 mmol per liter). In patients who received 5 g of ZS-9 and those who received 10 g of ZS-9, serum potassium levels were maintained at 4.7 mmol per liter and 4.5 mmol per liter, respectively, during the maintenance phase, as compared with a level of more than 5.0 mmol per liter in the placebo group (P <0.01 for all comparisons). Rates of adverse events were similar in the ZS-9 group and the placebo group (12.9% and 10.8%, respectively, in the initial phase; 25.1% and 24.5%, respectively, in the maintenance phase). Diarrhea was the most common complication in the two study groups.” (D. K. Packham, dmpackham@netspace.net.au)
“Whether either or both of these agents will permit long-term administration of renoprotective and cardioprotective agents that block the RAAS will require more investigation,” an editorialist writes (
pp. 275–7). “Neither study included cases of markedly elevated levels of potassium (>6.5 mmol per liter). However, both agents appear to offer some promise for the treatment of hyperkalemia in patients with chronic kidney and cardiac disease.” (J. R. Ingelfinger)

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 16, 2015 * Vol. 22, No. 10
Providing news and information about medications and their proper use

>>>Cardiology Highlights
Source:
Jan. 20 issue of the Journal of the American College of Cardiology (2015; 65).
Aspirin in Primary CVD Prevention: Aspirin is used inappropriately for primary prevention of cardiovascular disease (CVD) in many Americans, according to an analysis of the National Cardiovascular Disease Registry’s Practice Innovation and Clinical Excellence registry (pp. 111–21). Among 68,808 unique patients seen in 119 U.S. primary care practices, these frequencies of inappropriate use (defined as use in patients with less than 6% risk of CVD over next 10 years) were observed: “Inappropriate aspirin use frequency was 11.6% (7,972 of 68,808) in the overall cohort. There was significant practice-level variation in inappropriate use (range 0% to 71.8%; median 10.1%; interquartile range 6.4%) for practices; adjusted [median rate ratio (MRR)] was 1.63 (95% confidence interval [CI]: 1.47 to 1.77). Results remained consistent after excluding 21,052 women age ≥65 years (inappropriate aspirin use 15.2%; median practice-level inappropriate aspirin use 13.8%; interquartile range 8.2%; adjusted MRR 1.61 [95% CI: 1.46 to 1.75]) and after excluding patients with diabetes (inappropriate aspirin use 13.9%; median practice-level inappropriate aspirin use 12.4%; interquartile range 7.6%; adjusted MRR 1.55 [95% CI: 1.41 to 1.67]).” (R. S. Hira)

>>>Circulation Report
Source:
Jan. 13 issue of Circulation (2015; 131).
Dabigatran in Nonvalvular Atrial Fibrillation: Compared with warfarin, dabigatran used in primary care practices for treating nonvalvular atrial fibrillation “was associated with reduced risk of ischemic stroke, intracranial hemorrhage, and death and increased risk of major gastrointestinal hemorrhage,” researchers report (pp. 157–64). “These associations were most pronounced in patients treated with dabigatran 150 mg twice daily, whereas the association of 75 mg twice daily with study outcomes was indistinguishable from warfarin except for a lower risk of intracranial hemorrhage with dabigatran,” the group adds. The study included new-user cohorts of older Medicare beneficiaries (n = 134,414). Based on 2,715 events during 37,587 person–years of follow-up, these results were observed: “The hazard ratios (95% confidence intervals) comparing dabigatran with warfarin (reference) were as follows: ischemic stroke, 0.80 (0.67–0.96); intracranial hemorrhage, 0.34 (0.26–0.46); major gastrointestinal bleeding, 1.28 (1.14–1.44); acute myocardial infarction, 0.92 (0.78–1.08); and death, 0.86 (0.77–0.96). In the subgroup treated with dabigatran 75 mg twice daily, there was no difference in risk compared with warfarin for any outcome except intracranial hemorrhage, in which case dabigatran risk was reduced. Most patients treated with dabigatran 75 mg twice daily appeared not to have severe renal impairment, the intended population for this dose. In the dabigatran 150-mg twice daily subgroup, the magnitude of effect for each outcome was greater than in the combined-dose analysis.” (D. J. Graham, david.graham1@fda.hhs.gov)

>>>Allergy/Immunology Report
Source:
Jan. issue of the Journal of Allergy and Clinical Immunology (2015; 135).
Asthma Treatment During Pregnancy: Two commonly used treatments for asthma produced similar and low rates of birth defects in babies born to women with asthma, a study shows (pp. 123–30.e2). Cohorts of women who were exposed to inhaled corticosteroids (ICSs) during the first trimester of pregnancy in 1990–2009 showed these outcomes for those on low-dose ICSs plus long-acting beta-2 agonists (LABAs) or increased ICS doses: “In one subcohort there were 643 women who used a LABA plus low-dose ICS and 305 who used a medium-dose ICS; the other subcohort included 198 users of a LABA plus medium-dose ICS and 156 users of a high-dose ICS. The prevalence of major malformations was 6.9% and 7.2%, respectively. The adjusted odds ratio for major malformations was 1.1 (95% CI, 0.6-1.9) when a LABA plus low-dose ICS was used compared with a medium-dose ICS and 1.2 (95% CI, 0.5-2.7) when a LABA plus medium-dose ICS was used compared with a high-dose ICS.” (L. Blais, lucie.blais@umontreal.ca)

>>>PNN NewsWatch
* PNN will not be published on Mon., Jan. 19, King 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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 20, 2015 * Vol. 22, No. 11
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 17 issue of Lancet (2015; 385).
Avoiding Premature Deaths: Achieving a U.N. goal of avoiding 40% of premature deaths by 2030 is feasible, an analysis of 1970–2010 data shows (pp. 239–52). The goal—avoiding in each country under-70 deaths that would be seen in the 2030 population at 2010 death rates and to improve health care at all ages—has these global subtargets for 2030: avoiding two-thirds of child and maternal deaths; two-thirds of tuberculosis, HIV, and malaria deaths; a third of premature deaths from noncommunicable diseases (NCDs); and a third of those from other causes (other communicable diseases, undernutrition, and injuries). The authors find these patterns from the past 40 years, including acceleration of premature-death avoidance in 2000–10: “Throughout the world, except in countries where the effects of HIV or political disturbances predominated, mortality decreased substantially from 1970–2010, particularly in childhood. From 2000–10, under-70 age-standardised mortality rates decreased 19% (with the low-income and lower-middle-income countries having the greatest absolute gains). The proportional decreases per decade (2000–10) were: 34% at ages 0–4 years; 17% at ages 5–49 years; 15% at ages 50–69 years; 30% for communicable, perinatal, maternal, or nutritional causes; 14% for NCDs; and 13% for injuries (accident, suicide, or homicide).” (O. F. Norheim, Ole.norheim@igs.uib.no)

>>>Internal Medicine Report
Source:
Jan. 20 issue of the Annals of Internal Medicine (2015; 162).
Combination Therapy for Invasive Aspergillosis: Higher survival resulted when patients with invasive aspergillosis (IA) were treated with the combination of voriconazole and anidulafungin, compared with voriconazole alone, researchers report (pp. 81–9). Among 454 patients with hematologic malignancies or hematopoietic cell transplantation at 93 international sites, these effects on a primary outcome of 6-week mortality were observed: “Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, −8.2 percentage points [95% CI, −19.0 to 1.5]; P = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, −11.5 percentage points [CI, −22.7 to −0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different.” (K. A. Marr, kmarr4@jhmi.edu)
Factors Associated With Lack of HIV Suppression: When pregnant women living with HIV start antiretroviral therapy and how well they adhere to the regimen are important predictors of lack of viral suppression at delivery, according to an analysis from 67 U.S. AIDS clinical research sites (pp. 90–9). Participants were pregnant women who initiated highly active antiretroviral therapy (HAART) during pregnancy. Results showed: “Between 2002 and 2011, 671 women met inclusion criteria and 13.1% had detectable [viral load (VL)] at delivery. Factors associated with detectable VL included multiparity (16.4% vs. 8.0% nulliparity; P = 0.002), black ethnicity (17.6% vs. 6.6% Hispanic and 6.6% white; P < 0.001), 11th grade education or less (17.6% vs. 12.1% had a high school diploma; P = 0.013), initiation of HAART in the third trimester (23.9% vs. 12.3% and 8.6% in the second and trimesters, respectively; P = 0.003), having an HIV diagnosis before the current pregnancy (16.1% vs. 11.0% during the current pregnancy; P = 0.051), and having the first prenatal visit in the third trimester (33.3% vs. 14.3% and 10.5% in the second and third trimesters, respectively; P = 0.002). Women who had treatment interruptions or reported poor medication adherence were more likely to have detectable VL at delivery.” (I. T. Katz, ikatz2@partners.org)

>>>PNN JournalWatch
* Do Human Extraintestinal
Escherichia coli Infections Resistant to Expanded-Spectrum Cephalosporins Originate From Food-Producing Animals? A Systematic Review, in Clinical Infectious Diseases, 2015; 60: 439–52. (B. A. Rogers, benrogers@uq.edu.au)

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 21, 2015 * Vol. 22, No. 12
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 20 issue of JAMA (2015; 313).
Surgery for Drug-Resistant Focal Epilepsy: Compared with continued drug treatment, resective epilepsy surgery reduced seizure activity in patients with drug-resistant focal epilepsy, according to a review of 55 published articles (pp. 285–93): “Two randomized clinical trials enrolling 118 patients with temporal lobe epilepsy found greater freedom from seizures with surgery when compared with continued medical treatment (58% vs 8% [n = 80] and 73% vs 0% [n = 38], P <.001). Nine systematic reviews and 2 large case series of medically refractory patients treated with surgery reported seizure-free outcomes in 34% to 74% of patients (median, 62.4%). The remainder of systematic reviews and meta-analyses examined subpopulations. Epilepsy surgery was less effective when there were extratemporal lesions, the epilepsy was not associated with a structural lesion, or both. Seizure-free outcomes were similar between children and adults. Hippocampal sclerosis and benign tumors were associated with better outcomes relative to other pathologies. Similar procedures such as selective amygdalohippocampectomy and temporal lobectomy for temporal lobe epilepsy were associated with subtle differences in seizure and neuropsychological outcome. There is low perioperative mortality (0.1%–0.5%) from epilepsy surgery. The most frequent neurologic complication is visual field defect occurring from temporal lobe resection. Quality of life improved after surgery but improved the most in patients who were seizure-free after surgery.” (B. C. Jobst)
Pneumonia Hospitalizations & Later Cardiovascular Disease: Pneumonia may be a risk factor for cardiovascular disease (CVD), according to authors who found an association between hospitalization for this condition and short- and long-term risks of new CVD (pp. 264–74). Data from the Cardiovascular Health Study (CHS, n = 5,888) and the Atherosclerosis Risk in Communities study (ARIC, n = 1,5 79) were examined for hospitalizations for pneumonia and incident CVD over the ensuing 10 years. Results for cases and matched controls showed the following: “Of 591 pneumonia cases in CHS, 206 had CVD events over 10 years after pneumonia hospitalization. CVD risk after pneumonia was highest in the first year. CVD occurred in 54 cases and 6 controls in the first 30 days (HR, 4.07; 95% CI, 2.86–5.27); 11 cases and 9 controls between 31 and 90 days (HR, 2.94; 95% CI, 2.18–3.70); and 22 cases and 55 controls between 91 days and 1 year (HR, 2.10; 95% CI, 1.59–2.60). Additional CVD risk remained elevated into the tenth year, when 4 cases and 12 controls developed CVD (HR, 1.86; 95% CI, 1.18–2.55). In ARIC, of 680 pneumonia cases, 112 had CVD over 10 years after hospitalization. CVD occurred in 4 cases and 3 controls in the first 30 days (HR, 2.38; 95% CI, 1.12–3.63); 4 cases and 0 controls between 31 and 90 days (HR, 2.40; 95% CI, 1.23–3.47); 11 cases and 8 controls between 91 days and 1 year (HR, 2.19; 95% CI, 1.20–3.19); and 8 cases and 7 controls during the second year (HR, 1.88; 95% CI, 1.10–2.66). After the second year, the HRs were no longer statistically significant.” (V. F. Corrales–Medina)
Stem-Cell Transplant in Multiple Sclerosis: In a preliminary communication, researchers report that “nonmyeloablative hematopoietic stem cell transplantation was associated with improvement in neurological disability and other clinical outcomes” in 123 patients with relapsing–remitting multiple sclerosis (pp. 275–84; R. K. Burt).
Medical Student Collaboration & Diagnostic Performance: Medical students who worked in pairs were more accurate in diagnosing simulated patient cases compared with students who worked alone, a study shows (pp. 303–4). “Similar to other studies, collaboration may have helped correct errors, fill knowledge gaps, and counteract reasoning flaws,” the authors write. Participants evaluated six simulated cases of difficult breathing on a computer. Of 88 students recruited, 28 worked individually and 60 in pairs. Pairs of students were more accurate than individuals in selecting a correct diagnosis (68% vs. 50%) despite having comparable knowledge about the topic and selecting an equal number of diagnostic tests. Pairs needed more time than individuals to reach a diagnosis, but the tests they selected would have taken less time in a real clinical setting. Pairs were more confident with their selected diagnoses than were individuals. (W. E. Hautz)

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 22, 2015 * Vol. 22, No. 13
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 22 issue of the New England Journal of Medicine (2015; 372).
Nivolumab in Hodgkin’s Lymphoma, Melanoma: Two research articles and an editorial examine use of the programmed death 1 (PD-1) blocking antibody nivolumab in patients with two common cancers.
In 23 patients with heavily treated relapsed or refractory Hodgkin’s lymphoma, nivolumab “had substantial therapeutic activity and an acceptable safety profile,” researchers report (
pp. 311–9). The ongoing study used doses of 3 mg/kg every 2 weeks until patients had complete remission, tumor progression, or excessive toxic effects. The researchers also tested for PDL1 and PDL2 loci and PD-L1 and PD-L2 protein expression, with these results: “Of the 23 study patients, 78% were enrolled in the study after a relapse following autologous stem-cell transplantation and 78% after a relapse following the receipt of brentuximab vedotin. Drug-related adverse events of any grade and of grade 3 occurred in 78% and 22% of patients, respectively. An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease. The rate of progression-free survival at 24 weeks was 86%; 11 patients were continuing to participate in the study. Reasons for discontinuation included stem-cell transplantation (in 6 patients), disease progression (in 4 patients), and drug toxicity (in 2 patients). Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these ligands.” (S. M. Ansell, ansell.stephen@mayo.edu)
This monoclonal antibody also yielded positive results in a group of previously untreated patients with melanoma that lacked the
BRAF mutation, a second study shows (pp. 320–30). Results in 418 patients who received nivolumab or dacarbazine showed the following: “At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P <0.001). The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P <0.001). The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P <0.001). The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 (PD-L1). Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drug-related adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with nivolumab and 17.6% of those treated with dacarbazine.” (C. Robert, caroline.robert@gustaveroussy.fr)
“With recent data showing impressive clinical activity of PD-1 or PD-[ligand 1] antagonists in subgroups of patients with a variety of different cancers, the critical and foundational role of immune interventions in cancer treatment is no longer deniable,” editorialists write (
pp. 374–5). “The success that has been achieved to date was accomplished with agents directed against only two of the many potentially important immune targets, which also include a large number of coinhibitory and costimulatory ligand–receptor pairs. The substantial investment in immunology and tumor immunobiology by the National Institutes of Health and the National Cancer Institute is paying off, and the clinical data that were sampled in these two studies presage the substantial additional gains that could be possible from continued investment in this field.” (M. Sznol)

>>>PNN NewsWatch
* FDA yesterday approved secukinumab (Cosentyx, Novartis) for treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. The first approved interleukin (IL) 17A antagonist, secukinumab produced clear or almost clear skin in clinical trials of 3,990 adults with the disease. A medication guide warns patients of greater risk of infection while on the drug.

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 23, 2015 * Vol. 22, No. 14
Providing news and information about medications and their proper use

>>>Health Affairs Highlights
Source:
Jan. issue of Health Affairs (2015; 34).
Medicare Annual Preventive Care Visits: Medicare fee-for-service patients are more frequently getting preventive care since provisions of the Affordable Care Act (ACA) have been begun requiring coverage of an annual preventive care visit, a study shows (pp. 11–20). Patients at the Palo Alto Medical Foundation whose ages make them Medicare-eligible had these experiences in 2007–13 (204,388 patient–years): “Among Medicare fee-for-service patients, the annual use of preventive visits rose from 1.4 percent before the implementation of the ACA to 27.5 percent afterward. This increase was significantly larger than was seen for patients in the other insurance groups. Nevertheless, rates of annual preventive care visit use among Medicare fee-for-service patients remained 10–20 percentage points lower than was the case for people with private coverage (43–44 percent) or those in a Medicare HMO (53 percent). ACA policy changes led to increased preventive service use by Medicare fee-for-service beneficiaries, which suggests that Medicare coverage expansion is an effective way to increase seniors’ use of preventive services.” (S. Chung, chungs@pamfri.org)
Patient-Centered Medical Homes In Louisiana: Patient-centered medical homes have had “minimal impact” on use of acute care and costs among the state’s Medicaid population, a study shows (pp. 87–94). Seeking to evaluate effects of the new model on quality and costs over time in this patient population, the investigators conducted a pre–post analysis of Louisiana primary care clinics that had been certified as medical homes: “We found no impact on acute care use and modest support for reduced costs and primary care use among medical homes serving higher proportions of chronically ill patients. These findings provide preliminary results related to the ability of the patient-centered medical home model to improve outcomes for Medicaid beneficiaries. The findings support a case-mix-adjusted payment policy for medical homes going forward.” (E. S. Cole, ecole@gsu.edu)

>>>Medical Care Report
Source:
Feb. issue of Medical Care (2015; 53).
Medical Homes & Medication Adherence: In a study of Medicaid beneficiaries in North Carolina who had multiple chronic conditions (MCCs), medication adherence was greater among those enrolled in medical homes (pp. 168–76). Longitudinal cohorts of Community Care of North Carolina medical home enrollees were compared with nonenrollees retrospectively for proportion of days covered (PDC) over 12 months and a dichotomous measure of adherence (PDC >0.80) among new users of antidepressants (n = 9,303), antihypertensive agents (n = 12,595), oral diabetic agents (n = 6,409), and statins (n = 9,263): “Compared with nonenrollees, medical home enrollees exhibited higher PDC by 4.7, 6.0, 4.8, and 5.1 percentage points for depression, hypertension, diabetes, and hyperlipidemia, respectively (P’s <0.001). The dichotomous adherence measure showed similar increases, with absolute differences of 4.1, 4.5, 3.5, and 4.6 percentage points, respectively (P’s <0.001).” (C. A. Beadles)
Receipt of Pandemic Influenza Vaccine: Among American children during the 2009–10 influenza pandemic, subgroups of patients were underserved, researchers report, based on receipt of the A(H1N1) vaccine (pp. 191–8). Clinical and demographic characteristics of these patients can be used by public health officials during future pandemics to increase vaccination rates: “Receipt of a seasonal influenza vaccination in the 12 months before October 2009 as well as race/ethnicity, family structure, and various measures representing family socioeconomic status were statistically significant correlates of receipt of the first pH1N1 dose, whereas children’s asthma and chronic condition status were not.” (D. L. Blackwell)

>>>PNN NewsWatch
* More than one-third of reproductive-aged women enrolled in Medicaid, and more than one-quarter of those with private insurance, had a prescription filled for an opioid analgesic each year during 2008–12, according to a report in this week’s MMWR. The prescribing rates varied geographically, with highest rates in the South and lowest rates in the Northeast.

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 26, 2015 * Vol. 22, No. 15
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Jan. 24 issue of Lancet (2015; 385).
Statins & Diabetes: Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) “at least partially” explains the increase in odds of new-onset type diabetes in patients taking statins, researchers report (pp. 351–61). In 43 genetic studies of 223,463 individuals, these patterns of single nucleotide polymorphisms were found in the HMGCR gene, rs17238484 and rs12916: “Each additional rs17238484-G allele was associated with a mean 0.06 mmol/L (95% CI 0.05–0.07) lower LDL cholesterol and higher body weight (0.30 kg, 0.18–0.43), waist circumference (0.32 cm, 0.16–0.47), plasma insulin concentration (1.62%, 0.53–2.72), and plasma glucose concentration (0.23%, 0.02–0.44). The rs12916 SNP had similar effects on LDL cholesterol, body weight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1.02, 95% CI 1.00–1.05); the rs12916-T allele association was consistent (1.06, 1.03–1.09). In 129,170 individuals in randomised trials, statins lowered LDL cholesterol by 0.92 mmol/L (95% CI 0.18–1.67) at 1-year of follow-up, increased body weight by 0.24 kg (95% CI 0.10–0.38 in all trials; 0.33 kg, 95% CI 0.24–0.42 in placebo or standard care controlled trials and −0.15 kg, 95% CI −0.39 to 0.08 in intensive-dose vs moderate-dose trials) at a mean of 4.2 years (range 1.9–6.7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1.12, 95% CI 1.06–1.18 in all trials; 1.11, 95% CI 1.03–1.20 in placebo or standard care controlled trials and 1.12, 95% CI 1.04–1.22 in intensive-dose vs moderate dose trials).” (D. I. Swerdlow, d.swerdlow@ucl.ac.uk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2015; 350).
Treating Gestational Diabetes: Based on a systematic review and meta-analysis of 15 articles with 2,509 participants, investigators conclude that “glibenclamide should not be used for the treatment of women with gestational diabetes if insulin or metformin is available” (h102; R. Corcoy, rcorcoy@santpau.cat).

>>>PNN NewsWatch
* Bexsera (Novartis Vaccines) on Friday became the second FDA-licensed meningococcal serogroup B vaccine, indicated for prevention of meningococcal disease caused by Neisseria meningitidis serogroup B in individuals 10 through 25 years of age. Safety and effectiveness was established in clinical trials of 2,600 adolescents and young adults; safety was also monitored during use of the product in 15,000 college students during outbreaks at two U.S. universities.
*
FDA on Friday approved parathyroid hormone (Natpara, NPS Pharmaceuticals) as an adjunct to calcium and vitamin D to control hypocalcemia in patients with hypoparathyroidism. Injected subcutaneously into the thigh using a pen device, parathyroid hormone reduced calcium and vitamin D doses needed to maintain normal calcium levels.
*
FDA also on Friday allowed marketing of the first set of mobile medical apps that allow people with diabetes to automatically and securely share data from a continuous glucose monitor (CGM) with other people in real-time using an Apple mobile device such as an iPhone. The Dexcom Share system displays data from the G4 Platinum CGM System using two apps: one installed on the patient’s mobile device and one installed on the mobile device of another person. Using Dexcom Share’s mobile medical app, the user can designate people (“followers&rdquoWinking with whom to share their CGM data.

>>>PNN JournalWatch
* Disease Mechanisms in Rheumatology—Tools and Pathways: Defining Functional Genetic Variants in Autoimmune Diseases, in
Arthritis & Rheumatology, 2015; 67: 1–10. (P. M. Gaffney, gaffneyp@omrf.org)
* American Geriatrics Society Abstracted Clinical Practice Guideline for Postoperative Delirium in Older Adults, in
Journal of the American Geriatrics Society, 2015; 63: 142–50. (M. Samuel, mjsamuel@americangeriatrics.org)
* American Society of Clinical Oncology Policy Statement Update: The Critical Role of Phase I Trials in Cancer Research and Treatment, in
Journal of Clinical Oncology, 2015; 33: 278–84. (J. S. Weber, jeffrey.weber@moffitt.org)
* Lenalidomide Monotherapy as Salvage Treatment for Recurrent Primary CNS Lymphoma, in
Neurology, 2015; 84: 325–6. (K. Hoang-Xuan, khe.hoang-xuan@psl.aphp.fr)

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 27, 2015 * Vol. 22, No. 16
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Jan. issue of the Journal of the American Geriatrics Society (2015; 63).
Anticoagulation for AF in Nursing Homes: Oral anticoagulants were prescribed to fewer than one-half of nursing home residents with atrial fibrillation (AF) in a study of patient characteristics and physician attitudes conducted in the south of France (pp. 71–6). Overall, 10.1% of nursing home residents had AF; mean age was 87. “Recurrent falls (47%), cognitive impairment (22.6%), and advanced age (16.4%) were the main reasons for not prescribing anticoagulants,” the authors report, concluding, “Physicians caring for those residents wrongly thought that paroxysmal AF caused fewer thromboembolic events than permanent AF, which explains lower rates of anticoagulant prescription in individuals with paroxysmal AF.” (O. Bahri, arda.bahri@chu-rouen.fr">oarda.bahri@chu-rouen.fr)
Drug–Disease Interactions Among Nursing Home Residents: Among older residents of 15 VA nursing homes who have dementia or cognitive impairment or a history of falls or fractures, drug–disease interactions (DDIs) are common but predictable based on clinical characteristics, a study shows (pp. 77–84). Using the 2012 Beers criteria to evaluate medication regimens, the authors found these results in 696 residents, 361 (51.9%) of whom had DDIs: “None [of the DDIs] involved residents with a history of [peptic ulcer disease], one involved a resident with [chronic kidney disease], and four occurred in residents with [heart failure]. Of 540 residents with dementia or cognitive impairment, 50.7% took a drug that could exacerbate these conditions; the most commonly involved medications were antipsychotics (35.4%) and benzodiazepines (14.4%). Of 267 with a history of falls or hip fracture, 67.8% received an interacting medication, with selective serotonin reuptake inhibitors (33.1%), antipsychotics (30.7%), and anticonvulsants (25.1%) being most commonly involved. Using separate multivariable logistic regression models, factors associated with DDIs in dementia or cognitive impairment and falls or fractures included age 85 and older (adjusted odds ratio (aOR) = 0.38, 95% confidence interval (CI) = 0.24–0.60 and aOR = 0.48, 95% CI = 0.24–0.96, respectively), taking five to eight medications (aOR = 2.06, 95% CI = 1.02–4.16 and aOR = 4.76, 95% CI = 1.68–13.5, respectively), taking nine or more medications (aOR = 1.99, 95% CI = 1.03–3.85 and aOR = 3.68, 95% CI = 1.41–9.61, respectively), and being a long-stay resident (aOR = 1.80, 95% CI = 1.04–3.12 and aOR = 2.35, 95% CI = 1.12–4.91, respectively).” (S. L. Aspinall, sherrie.aspinall@va.gov)
Utility of Anticholinergic Risk Scales: Among 537,387 individuals in New Zealand, estimation of anticholinergic burden exposure varied widely when nine different scales were used, but scores from each scale were associated with one or more “adverse clinical outcomes of interest” (pp. 85–90). The Pharmaceutical Claims Data Mart data set for 2011 provided estimations of medication exposure, and National Minimum Datasets detailed hospital admissions, hospitalizations for falls, hospital length of stay (LOS), and visits to general practitioners (GP): “Prevalence of exposure to anticholinergic medicines ranged from 22.8% to 55.9% according to the different scales. Multivariate regression analysis showed that anticholinergic burden scores quantified according to all nine scales were significantly associated with hospital admissions, hospitalizations for falls, LOS, and GP visits (P < .001). The strongest predictors of these outcomes were the Drug Burden Index—Anticholinergic component scores, aged 85 and older, female sex, and polypharmacy.” (P. S. Nishtala, prasad.nishtala@otago.ac.nz)

>>>PNN NewsWatch
* Ivax Pharmaceuticals, a Teva subsidiary, will market the first generic version of Nexium (esomeprazole magnesium delayed-release capsules) to treat gastroesophageal reflux disease (GERD) in adults and children ages 1 and older, FDA said yesterday. Esomeprazole capsules are also approved to reduce the risk of gastric ulcers associated with use of NSAIDs, treat Helicobacter pylori in combination with certain antibiotics, and to treat gastric hypersecretory conditions, including Zollinger–Ellison syndrome. Generic esomeprazole capsules will be dispensed with a patient Medication Guide that provides important information about the medication’s use and risks, FDA added.

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 28, 2015 * Vol. 22, No. 17
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Jan. 27 issue of JAMA (2015; 313).
Treating C. difficile: Based on a review of 196 articles on Clostridium difficile infection (CDI), authors confirm first-line use of vancomycin for severe or complicated disease and the utility of metronidazole in mild CDI (pp. 398–408). “Fidaxomicin is a therapeutic option for patients with recurrent CDI or a high risk of recurrence,” the group writes. “Fecal microbiota transplantation is associated with symptom resolution of recurrent CDI but its role in primary and severe CDI is not established.” Those conclusions were reached based on these findings from the literature: “Vancomycin and metronidazole are first-line therapies for most patients, although treatment failures have been associated with metronidazole in severe or complicated cases of CDI. Recent data demonstrate clinical success rates of 66.3% for metronidazole vs 78.5% for vancomycin for severe CDI. Newer therapies show promising results, including fidaxomicin (similar clinical cure rates to vancomycin, with lower recurrence rates for fidaxomicin, 15.4% vs vancomycin, 25.3%; P = .005) and fecal microbiota transplantation (response rates of 83%-94% for recurrent CDI).” (N. Bagdasarian)
Chlorhexidine Bathing & Nosocomial Infections: Incidence of a variety of nosocomial infections was not reduced by daily bathing of critically ill patients with chlorhexidine cloths, a study shows (pp. 369–78). Looking at occurrence of central line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonia (VAP), and Clostridium difficile infections, investigators found these patterns in a pragmatic cluster randomized, crossover study of 9,340 patients in five adult ICUs that compared chlorhexidine and nonantimicrobial cloths for once-daily bathing: “During the chlorhexidine bathing period, 55 infections occurred: 4 CLABSI, 21 CAUTI, 17 VAP, and 13 C difficile. During the control bathing period, 60 infections occurred: 4 CLABSI, 32 CAUTI, 8 VAP, and 16 C difficile. The primary outcome rate was 2.86 per 1,000 patient–days during the chlorhexidine and 2.90 per 1,000 patient–days during the control bathing periods (rate difference, −0.04; 95% CI, −1.10 to 1.01; P = .95). After adjusting for baseline variables, no difference between groups in the rate of the primary outcome was detected. Chlorhexidine bathing did not change rates of infection-related secondary outcomes including hospital-acquired bloodstream infections, blood culture contamination, or clinical cultures yielding multidrug-resistant organisms. In a prespecified subgroup analysis, no difference in the primary outcome was detected in any individual intensive care unit.” (M. J. Noto)
Pediatric Sedation Protocol for Ventilation: In critically ill children with acute respiratory failure, a sedation protocol did not reduce the duration of mechanical ventilation, compared with usual care, researchers report (pp. 379–89). The study included 2,449 children with a mean age of 4.7 years in 31 U.S. pediatric ICUs. The protocol included targeted sedation, arousal assessments, extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. The investigators found: “Duration of mechanical ventilation was not different between the 2 groups (intervention: median, 6.5 [IQR, 4.1–11.2] days; control: median, 6.5 [IQR, 3.7–12.1] days). Sedation-related adverse events including inadequate pain and sedation management, clinically significant iatrogenic withdrawal, and unplanned endotracheal tube/invasive line removal were not significantly different between the 2 groups. Intervention patients experienced more postextubation stridor (7% vs 4%; P = .03) and fewer stage 2 or worse immobility-related pressure ulcers (<1% vs 2%; P = .001). In exploratory analyses, intervention patients had fewer days of opioid administration (median, 9 [IQR, 5–15] days vs 10 [IQR, 4–21] days; P = .01), were exposed to fewer sedative classes (median, 2 [IQR, 2–3] classes vs 3 [IQR, 2–4] classes; P < .001), and were more often awake and calm while intubated (median, 86% [IQR, 67%–100%] of days vs 75% [IQR, 50%–100%] of days; P = .004) than control patients, respectively; however, intervention patients had more days with any report of a pain score ≥4 (median, 50% [IQR, 27%–67%] of days vs 23% [IQR, 0%–46%] of days; P < .001) and any report of agitation (median, 60% [IQR, 33%–80%] vs 40% [IQR, 13%–67%]; P = .003), respectively.” (M. A. Q. Curley)

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 29, 2015 * Vol. 22, No. 18
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Jan. 29 issue of the New England Journal of Medicine (2015; 372).
Degree of Blood Pressure Control in Pregnancy: Pregnant women with hypertension had similar outcomes when managed with tight- versus less-tight control of hypertension, researchers report, but severe hypertension developed more often with less-tight control (pp. 407–17). Risk of pregnancy loss, high-level neonatal care, or overall maternal complications were statistically similar with the two approaches, which were tested in 987 women in an open, international trial. Target diastolic blood pressures of 85 and 100 mm Hg were used in the two trials. Based on a composite primary outcome of pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days, results showed: “Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-outcome rates were similar among 493 women assigned to less-tight control and 488 women assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7% and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4). Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-control group and 27.5% of the women in the tight-control group (P <0.001).” (L. A. Magee, LMagee@cw.bc.ca)
“The current study showed that tight control of hypertension conferred no apparent benefits to the fetus and only a moderate benefit (a lower rate of progression to severe hypertension) for the mother,” editorialists write (
pp. 475–6). “It does, however, provide valuable reassurance that tight control, as targeted in this study, does not carry major risks for the fetus or newborn.” (C. G. Solomon)
Cost-effectiveness of Hypertension Control: Lives could be saved and costs averted through implementation of 2014 guidelines on hypertension control from the Eighth Joint National Committee, a study shows (pp. 447–55). The Cardiovascular Disease Policy Model was used “to simulate drug-treatment and monitoring costs, costs averted for the treatment of cardiovascular disease, and quality-adjusted life–years (QALYs) gained by treating previously untreated adults between the ages of 35 and 74 years from 2014 through 2024,” with these results: “The full implementation of the new hypertension guidelines would result in approximately 56,000 fewer cardiovascular events and 13,000 fewer deaths from cardiovascular causes annually, which would result in overall cost savings. The projections showed that the treatment of patients with existing cardiovascular disease or stage 2 hypertension would save lives and costs for men between the ages of 35 and 74 years and for women between the ages of 45 and 74 years. The treatment of men or women with existing cardiovascular disease or men with stage 2 hypertension but without cardiovascular disease would remain cost-saving even if strategies to increase medication adherence doubled treatment costs. The treatment of stage 1 hypertension was cost-effective (defined as <$50,000 per QALY) for all men and for women between the ages of 45 and 74 years, whereas treating women between the ages of 35 and 44 years with stage 1 hypertension but without cardiovascular disease had intermediate or low cost-effectiveness.” (A. E. Moran, aem35@cumc.columbia.edu)
Drug Formularies as Discrimination Tools: Some insurers in the federal marketplace have categorized all medications for HIV infections in their highest tier, thus discouraging people living with HIV from joining their plans, authors of a Perspectives article write (pp. 389–402). “The ACA has already made major inroads in designing a more equitable health care system for people with chronic conditions, but the struggle is far from over,” the article notes. (D. B. Jacobs)

>>>PNN NewsWatch
* Legislation recognizing pharmacists as Medicare Part B providers in medically underserved areas was reintroduced yesterday into the House of Representatives, pharmacist.com reports. H.R. 592, the Pharmacy and Medically Underserved Areas Enhancement Act, is supported by the multidisciplinary and broad-based Patient Access to Pharmacists’ Care Coalition.

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 844/270-0717 (fax). Copyright © 2015, 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
Jan. 30, 2015 * Vol. 22, No. 19
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Feb. issue of Diabetes Care (2015; 38).
Incretins & CHF: In a nested case–control analysis, incretin-based therapy treatment of type 2 diabetes was not associated with development of congestive heart failure (pp. 277–84). In 2007–12, conditional logistic regression of data from the U.K. Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database, showed: “The cohort consisted of 57,737 patients followed for a mean 2.4 years, during which time 1,118 incident cases of hospitalized CHF were identified (incidence rate 8.1/1,000 person–years). Current use of incretin-based drugs was not associated with an increased risk of CHF (adjusted OR 0.85 [95% CI 0.62–1.16]). Secondary analyses revealed no duration–response relationship (P trend = 0.39).” (S. Suissa, samy.suissa@mcgill.ca)
This analysis provides “welcome reassurance about GLP-1 drugs,” an editorialist writes, “but they are still young and not fully grown” (
pp. 183–5). “Like people, therapeutic agents come in families with individual members and a typical life history. A new class of drugs begins as a pathophysiological insight, a gleam in a scientist’s eye. A new drug’s childhood consists of testing in animal (preclinical) studies and small human (phase 1 and 2) studies. Moving into larger clinical studies (phase 3), an adolescent drug must show consistent therapeutic effects and a lack of alarming side effects over 6 to 12 months of use in a broader population of people. Good results can lead to approval for clinical practice after which further (phase 4) studies and observation of clinical experience may explore specific clinical indications and safety during more prolonged use. Because drugs are, by necessity, launched when young and without long-term experience, there can be distressing surprises that lead to later restriction of usage. Full understanding of any drug’s best uses requires years of experience after its introduction.” (M. C. Riddle, riddle@ohsu.edu)
Metformin & Glucose During Exercise: Glucose homeostasis during exercise is improved when the patient is taking metformin, a study shows (pp. 293–301). Isotope tracers were used to determine glucose kinetics during 45 minutes of exercise at 60% VO2max in patients with type 2 diabetes who were (DM2+Met) or were not (DM2) taking metformin and in control participants (CON). Results showed: “Plasma glucose concentration was unchanged during exercise in CON but decreased in DM2. No significant change was found in DM2+Met. Hormones and metabolites showed no differences among the groups except for elevated exercise-induced concentrations of lactate in DM2 (area under the curve [AUC] 31 ± 1% vs. CON) and glucagon in DM2 (AUC 5 ± 1% vs. DM2+Met). Free fatty acid levels were lower in DM2+Met than in DM2 (AUC −14 ± 1%). Absolute values of the baseline glucose rate of appearance (Ra) were elevated in DM2 and DM2+Met, but the increase in glucose Ra relative to baseline was blunted in DM2 (19 ± 1%) and DM2+Met (18 ± 4%) compared with CON (46 ± 4%). Glucose rate of disappearance relative to baseline increased more in CON (31 ± 3%) than in DM2 (6 ± 1%) and DM2+Met (21 ± 2%), showing a small increase caused by metformin. Glucose metabolic clearance rate relative to baseline was similar during exercise in DM2 (33 ± 1%) and CON (35 ± 3%) but was improved in DM2+Met (37 ± 3%) compared with DM2.” (M. Hansen, hansen.merethe@gmail.com)

>>>PNN NewsWatch
* A pharmacist provider status companion bill was introduced yesterday into the U.S. Senate, just a day after the House bill dropped (see yesterday’s PNN), pharmacist.com reports. Those introducing the two bills are members of the committees with jurisdiction over the legislation, an important element that increases the likelihood of getting hearings on the proposals and ultimately passage.
* The Obama administration today is unveiling details about the
Precision Medicine Initiative, described by the White House as “a bold new research effort to revolutionize how we improve health and treat disease.” Launched with a proposed $215 million investment, the Precision Medicine Initiative “will pioneer a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients,” according to a White House statement.

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 2, 2015 * Vol. 22, No. 20
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2015; 350).
Financial Incentives for Smoking Cessation in Pregnancy: Paying pregnant women to stop smoking appears to be an effective strategy, according to a Phase II trial conducted in the west of Scotland (h134). Routine care provided to control and intervention groups included an in-person discussion of smoking and cessation, free nicotine-replacement therapy for 10 weeks, and four weekly support telephone calls. The intervention group could also receive up to £800 for meeting various milestones, including validated abstinence based on exhaled carbon monoxide levels.
Results showed: “Recruitment was extended from 12 to 15 months to achieve the target sample size. Follow-up continued until September 2013. Of the 306 women randomised, three controls opted out soon after enrolment; these women did not want their data to be used, leaving 306 intervention and 303 control group participants in the intention to treat analysis. No harms of financial incentives were documented. Significantly more smokers in the incentives group than control group stopped smoking: 69 (22.5%) versus 26 (8.6%). The relative risk of not smoking at the end of pregnancy was 2.63 (95% confidence interval 1.73 to 4.01) P <0.001. The absolute risk difference was 14.0% (95% confidence interval 8.2% to 19.7%). The number needed to treat (where financial incentives need to be offered to achieve one extra quitter in late pregnancy) was 7.2 (95% confidence interval 5.1 to 12.2). The mean birth weight was 3,140 g (SD 600 g) in the incentives group and 3,120 (SD 590) g in the control group (P = 0.67).” (D. Tappin,
david.tappin@glasgow.ac.uk)
Postmenopausal Weight & Fracture Risk: Fracture-site patterns differ in postmenopausal women who gain or lose weight, or who lose weight unintentionally, according to a post-hoc analysis of data from the Women’s Health Initiative (h25). Conducted at 40 U.S. clinical center, the study included 120,566 postmenopausal women who were 50–79 years of age at baseline in 1993–98. Incident self-reported fractures showed these patterns during a mean of 11 years of follow-up: “Mean participant age was 63.3. Mean annualized percent weight change was 0.30% (95% confidence interval 0.28 to 0.32). Overall, 79,279 (65.6%) had stable weight; 18,266 (15.2%) lost weight; and 23,021 (19.0%) gained weight. Compared with stable weight, weight loss was associated with a 65% higher incidence rates of fracture in hip (adjusted hazard ratio 1.65, 95% confidence interval 1.49 to 1.82), upper limb (1.09, 1.03 to 1.16), and central body (1.30, 1.20 to 1.39); weight gain was associated with higher incidence rates of fracture in upper limb (1.10, 1.05 to 1.18) and lower limb (1.18, 1.12 to 1.25). Compared with stable weight, unintentional weight loss was associated with a 33% higher incidence rates of hip fracture (1.33, 1.19 to 1.47) and increased incidence rates of vertebral fracture (1.16, 1.06 to 1.26); intentional weight loss was associated with increased incidence rates of lower limb fracture (1.11, 1.05 to 1.17) and decreased incidence of hip fracture (0.85, 0.76 to 0.95).” (C. J. Crandall, ccrandall@mednet.ucla.edu)

>>>PNN NewsWatch
* FDA last week approved new indications for two drugs: lisdexamfetamine dimesylate (Vyvanse, Shire) to treat binge-eating disorder in adults (the first FDA-approved medication for this use) and ibrutinib (Imbruvica; Pharmacyclics, Janssen Biotech) for treating patients with Waldenström’s macroglobulinemia, a rare form of non-Hodgkin lymphoma.

>>>PNN JournalWatch
* Exercises To Improve Function of the Rheumatoid Hand (SARAH): A Randomised Controlled Trial, in
Lancet, 2015; 385: 421–9. (S. E. Lamb, sarah.lamb@ndorms.ox.ac.uk)
* Duration of Pertussis Immunity After DTaP Immunization: A Meta-analysis, in
Pediatrics, 2015; 135: 331–43. (A. McGirr)
* Treatment of Psychosis and Mania in the Postpartum Period, in
American Journal of Psychiatry, 2015; 172: 115–23. (V. Bergink)
* Identifying Predictors, Moderators, and Mediators of Antidepressant Response in Major Depressive Disorder: Neuroimaging Approaches, in
American Journal of Psychiatry, 2015; 172: 124–38. (M. L. Phillips)
* Early Childhood Gut Microbiomes Show Strong Geographic Differences Among Subjects at High Risk for Type 1 Diabetes, in
Diabetes Care, 2015; 38: 329–32. (E. W. Triplett, ewt@ufl.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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 3, 2015 * Vol. 22, No. 21
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 3 issue of the Annals of Internal Medicine (2015; 162).
Adult Immunization Schedule: The 2015 recommended adult immunization schedule, as approved by the Advisory Committee on Immunization Practices (ACIP) in Oct. 2014, is published in this issue of Annals (pp. 214–23). “Changes in the 2015 adult immunization schedule from the 2014 schedule include the September 2014 recommendation for routine administration of the 13-valent pneumococcal conjugate vaccine in series with the 23-valent pneumococcal polysaccharide vaccine for all adults aged 65 years or older, the August 2014 revision on contraindications and precautions for the live attenuated influenza vaccine, and the October 2014 approval by the U.S. Food and Drug Administration to expand the approved age for use of recombinant influenza vaccine,” the authors write on behalf of ACIP. “The 2015 adult immunization schedule was also reviewed and approved by the American College of Physicians, American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and American College of Nurse-Midwives.” (D. K. Kim, dkim@cdc.gov)
Blood Pressure Reduction in Mild Hypertension: Treatment of patients with mild hypertension (140–159 over 90–99 mm Hg) is likely beneficial in reducing stroke and mortality risk, conclude investigators who conducted a systematic review and meta-analysis (pp. 184–91). Released in advance of print (see PNN, Dec. 23), the article provides these details: “Individual-patient data involved 10 comparisons from trials where most patients had diabetes, and aggregate data involved 3 comparisons from trials of patients without diabetes. The average blood pressure reduction was about 3.6/2.4 mm Hg. Over 5 years, odds ratios were 0.86 (95% CI, 0.74 to 1.01) for total cardiovascular events, 0.72 (CI, 0.55 to 0.94) for strokes, 0.91 (CI, 0.74 to 1.12) for coronary events, 0.80 (CI, 0.57 to 1.12) for heart failure, 0.75 (CI, 0.57 to 0.98) for cardiovascular deaths, and 0.78 (CI, 0.67 to 0.92) for total deaths. Results were similar in secondary analyses. Withdrawal from treatment due to adverse effects was more common in the active groups.” (J. Sundström)
Nutritional Formula for Pressure Ulcers: Healing of pressure ulcers (PUs) was improved when malnourished patients received 8 weeks of therapy with a nutritional formula enriched with arginine, zinc, and antioxidants, researchers report (pp. 167–74). The randomized controlled trial included 200 patients in long-term or home care with stage II, III, or IV PUs. Compared with an isocaloric, isonitrogenous formula over 8 weeks, the energy-dense, protein-rich formula 400 mL/d yielded these effects: “Supplementation with the enriched formula (n = 101) resulted in a greater reduction in PU area (mean reduction, 60.9% [95% CI, 54.3% to 67.5%]) than with the control formula (n = 99) (45.2% [CI, 38.4% to 52.0%]) (adjusted mean difference, 18.7% [CI, 5.7% to 31.8%]; P = 0.017). A more frequent reduction in area of 40% or greater at 8 weeks was also seen (odds ratio, 1.98 [CI, 1.12 to 3.48]; P = 0.018). No difference was found in terms of the other secondary end points.” (E. Cereda, e.cereda@smatteo.pv.it)
End-of-Life Symptom Trends: Pain and other alarming symptoms increased in frequency in patients in their last year of life between 1998 and 2010, according to a cohort study of community-dwelling Americans aged 51 years or older (pp. 175–83). The HRS (Health Retirement Study) included 7,204 participants who died while enrolled and family members who provided input. Results for proxy-reported pain and other symptoms for at least 1 month during the last year of life showed these trends: “Between 1998 and 2010, proxy reports of the prevalence of any pain increased for all decedents from 54.3% (95% CI, 51.6% to 57.1%) to 60.8% (CI, 58.2% to 63.4%), an increase of 11.9% (CI, 3.1% to 21.4%). Reported prevalences of depression and periodic confusion also increased for all decedents by 26.6% (CI, 14.5% to 40.1%) and 31.3% (CI, 18.6% to 45.1%), respectively. Individual symptoms increased in prevalence among specific decedent categories, except in cancer, which showed no significant changes. The prevalence of moderate or severe pain did not change among all decedents or in any specific decedent category.” (A. E. Singer, asinger@rand.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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 4, 2015 * Vol. 22, No. 22
Providing news and information about medications and their proper use

>>>Pediatrics Highlights
Source:
Feb. issue of Pediatrics (2015; 135).
Geographic Clusters in Vaccine Refusal: Spatial scan statistics may be a useful method for identifying geographic clusters of underimmunization related to vaccine refusals and using focused interventions with parents, a study concludes (pp. 280–9). Analysis of 154,424 children born in 2000–11 in 13 northern California counties showed these geographic clusters of underimmunization (missing one or more vaccines by 36 months of age) and vaccine refusals: “We identified 5 statistically significant clusters of underimmunization among children who turned 36 months old during 2010–2012. The underimmunization rate within clusters ranged from 18% to 23%, and the rate outside them was 11%. Children in the most statistically significant cluster had 1.58 (P < .001) times the rate of underimmunization as others. Underimmunization with measles, mumps, rubella vaccine and varicella vaccines clustered in similar geographic areas. Vaccine refusal also clustered, with rates of 5.5% to 13.5% within clusters, compared with 2.6% outside them.” (T. A. Lieu)
Safety of Measles Vaccines: No new safety concerns were identified in a study of 2000–12 data from the Vaccine Safety Datalink for products containing measles antigen, researchers report (pp. e321–9). Among more than 700,000 doses of measles–mumps–rubella–varicella (MMRV) vaccine and the separate measles–mumps–rubella (MMR) and varicella (MMR + V) vaccine, immune thrombocytopenia purpura risk and ataxia risk was lower was higher with both approaches, and the combination had greater risks of seizure and fever 7–10 days after vaccination. (N. P. Klein)
Emergent Treatment of Migraine: Retrospective analysis of visits to 35 pediatric emergency departments (EDs) for migraine showed that prochlorperazine is superior to metoclopramide in preventing revisits, while “diphenhydramine use is associated with increased rates of return” (pp. 232–8). The study included children aged 7–18 years who visited one of the EDs in 2009–12 and used a primary outcome of revisits within 3 days. Results showed: “The study identified 32,124 children with migraine; 27,317 (85%) were discharged, and 5.5% had a return ED visit within 3 days. At the index visit, the most common medications included nonopioid analgesics (66%), dopamine antagonists (50%), diphenhydramine (33%), and ondansetron (21%). Triptans and opiate medications were administered infrequently (3% each). Children receiving metoclopramide had a 31% increased odds for an ED revisit within 3 days compared with prochlorperazine. Diphenhydramine with dopamine antagonists was associated with 27% increased odds of an ED revisit compared with dopamine antagonists alone. Children receiving ondansetron had similar revisit rates to those receiving dopamine antagonists.” (R. G. Bachur)
Post-Tonsillectomy Analgesia: Ibuprofen is a safe and effective analgesic for children following tonsillectomy, a study shows, and morphine use in this situation “should be limited, as it may be unsafe in certain children” (pp. 307–13). Parents used a pulse oximeter to measure oxygen saturation and apnea events before and the night after tonsillectomy with or without adenoidectomy. Pain was managed with acetaminophen plus oral morphine 0.2–0.5 mg/kg or ibuprofen 10 mg/kg, with these results: “A total of 91 children aged 1 to 10 years were randomized. On the first postoperative night, with respect to oxygen desaturations, 86% of children did not show improvement in the morphine group, whereas 68% of ibuprofen patients did show improvement (14% vs 68%; P < .01). The number of desaturation events increased substantially in the morphine group, with an average increase of 11.17 ± 15.02 desaturation events per hour (P < .01). There were no differences seen in analgesic effectiveness, tonsillar bleeding, or adverse drug reactions.” (L. E. Kelly)

>>>PNN NewsWatch
* A cyclin-dependent kinase 4 and 6 inhibitor, palbociclib (Ibrance, Pfizer), was granted accelerated approval yesterday by FDA. The new agent’s approved indication is treatment in combination with letrozole of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer as initial endocrine-based therapy for metastatic disease. The product is available immediately through select specialty pharmacies, the company said in a news release.

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 5, 2015 * Vol. 22, No. 23
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 5 issue of the New England Journal of Medicine (2015; 372).
Tenofovir-Based Preexposure HIV Prophylaxis: In clinical trial complicated by low rates of adherence, tenofovir-based preexposure regimens failed to reduce rates of HIV-1 acquisition among African women, researchers report (pp. 509–19). VOICE study investigators assigned participants to daily oral tenofovir disoproxil fumarate (TDF), oral tenofovir–emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel, with these results: “Of 12,320 women who were screened, 5,029 were enrolled in the study. The rate of retention in the study was 91% during 5,509 person–years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person–years. In the modified intention-to-treat analysis, the effectiveness was −49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), −4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P = 0.004). We observed no significant differences in the frequencies of other adverse events.” (J. M. Marrazzo, jmm2@uw.edu)
This study “indicates that much more work is needed, not so much in the realm of understanding the biologic basis of preexposure prophylaxis as a preventive treatment but rather in the realm of understanding behavioral barriers in the setting of strong social stigma,” editorialists write (
pp. 564–6). After quoting from the 1848 “Declaration of Sentiments” that marked the formal beginning of the women’s rights movement, the authors note: “As in the fight for women to find their voice in the United States against strong social stigma so long ago, victory in the battle to prevent HIV will require the women at risk for infection to find ‘a position different from that which they have hitherto occupied’ in order for them to find their VOICE.” (M. S. Saag)
Neuroprotective Effects of Prehospital Magnesium Sulfate: Paramedic administration of magnesium sulfate to patients with suspected stroke was safe in the FAST-MAG study, but 90-day disability outcomes were unchanged in a comparison with placebo (pp. 528–36). Using Rankin scale scores to determine degree of disability at 90 days, the investigators report these results for 1,700 patients with a mean age of 69 ± 13 years: “The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P = 0.28 by the Cochran–Mantel–Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P = 1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P = 0.95) or all serious adverse events.” (J. L. Saver, ajsaver@mednet.ucla.edu)

>>>PNN NewsWatch
* FDA Commissioner Margaret Hamburg will step down in March, the Washington Post and other media are reporting. “Stephen Ostroff, the FDA’s chief scientist and a former official at the Centers for Disease Control and Prevention, will take over in the top post until President Obama names a successor for Hamburg,” the Post notes.

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 6, 2015 * Vol. 22, No. 24
Providing news and information about medications and their proper use

>>>Circulation Report
Source:
Feb. 3 issue of Circulation (2015; 131).
Bridging in AF During Anticoagulation Interruptions: Data emanating from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry do not support routine use of bridging anticoagulation during interruptions in therapy for those with atrial fibrillation, as the common practice “is associated with higher risk for bleeding and adverse events” (pp. 488–94). The registry, which includes prospective, observational data on U.S. outpatients with atrial fibrillation, shows the following: “Of 7,372 patients treated with oral anticoagulation, 2,803 overall interruption events occurred in 2,200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n = 665), predominantly low-molecular-weight heparin (73%, n = 487) and unfractionated heparin (15%, n = 97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P = 0.0003) and mechanical valve replacements (9.6% versus 2.4%; P <0.0001); however, there was no difference in CHA2DS2-VASc scores (scores ≥2 in 94% versus 95%; P = 0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84; P <0.0001). The incidence of myocardial infarction, stroke or systemic embolism, major bleeding, hospitalization, or death within 30 days was also significantly higher in patients receiving bridging (13% versus 6.3%; adjusted odds ratio, 1.94; P = 0.0001).” (B. A. Steinberg, benjamin.steinberg@duke.edu)

>>>Cardiology Highlights
Source:
Feb. 10 issue of the Journal of the American College of Cardiology (2015; 65).
Cost-effectiveness of Ticagrelor: In an economic analysis from the perspective of the U.S. health care system, ticagrelor therapy increased life expectancy, compared with dual antiplatelet therapy, at an “incremental cost well within accepted benchmarks of good value for money,” researchers report (pp. 465–76). This investigation assessed 547 patients with acute coronary syndrome (ACS) from the PLATO (Platelet Inhibition and Patient Outcomes) trial who were receiving low-dose aspirin and projected costs and cost-effectiveness for ticagrelor and clopidogrel. Results showed: “One year of ticagrelor therapy, relative to that of generic clopidogrel, cost $29,665/quality-adjusted life–year gained, with 99% of bootstrap estimates falling under a $100,000 willingness-to-pay threshold. Results were robust to extensive sensitivity analyses, including variations in clopidogrel cost, exclusion of costs in extended years of life, and a recalibrated estimate of survival reflecting a lower underlying mortality risk in the United States.” (P. A. Cowper)
“With time, a better understanding of the effectiveness of ticagrelor in the real world, particularly compared with contemporary alternatives such as prasugrel or genotype-tailored strategies, will help identify the most cost-effective strategy for managing antiplatelet therapy after ACS,” writers add in an accompanying comment on this article (
pp. 477–9). “The cardiovascular community is justifiably proud of its commitment to evidence-based medicine and is now starting to consider value as well as efficacy in developing clinical guidelines. Evaluation of long-term effectiveness alongside lifetime cost in systematic cost-effectiveness studies can enhance the quality of health care and health policy decisions, as well as identify the critical gaps in knowledge that need to be addressed. The analysis by Cowper et al. suggests that a 1-year course of ticagrelor and aspirin among PLATO-eligible patients with ACS appears to provide a reasonable value for the money spent, at least from the U.S. health care perspective.” (D. S. Kazi)
Jogging Dose & Mortality: In the Copenhagen City Heart Study, mortality among joggers followed a U-shaped curve, with light or moderate joggers having the lowest mortality rates (pp. 411–9). The mortality rate among strenuous joggers was statistically equivalent to that of sedentary people. (P. Schnohr)

>>>PNN NewsWatch
* Adult vaccination coverage remained low in 2013 for most routinely recommended vaccines and below Healthy People 2020 targets, CDC reports yesterday in this week’s MMWR. Modest increases in Tdap, herpes zoster, and HPV (among young men) vaccines were noted, while rates for other vaccines did not improve.

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 9, 2015 * Vol. 22, No. 25
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2015; 350).
Systolic Blood Pressure Targets & Outcomes: Retrospective cohort analysis of 88,756 adults with hypertension shows the importance of “timely medical management and follow-up” in decreasing risk of acute cardiovascular event or death, a study shows (h158). “Systolic intensification thresholds higher than 150 mm Hg, delays of greater than 1.4 months before medication intensification after systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up after antihypertensive medication intensification were associated with increased risk of an acute cardiovascular event or death,” the group reports based on these experiences at primary care practices in the U.K.: “During a median follow-up of 37.4 months after the treatment strategy assessment period, 9,985 (11.3%) participants had an acute cardiovascular event or died. No difference in risk of the outcome was seen between systolic intensification thresholds of 130–150 mm Hg, whereas systolic intensification thresholds greater than 150 mm Hg were associated with progressively greater risk (hazard ratio 1.21, 95% confidence interval 1.13 to 1.30; P <0.001 for intensification threshold of 160 mm Hg). Outcome risk increased progressively from the lowest (0–1.4 months) to the highest fifth of time to medication intensification (hazard ratio 1.12, 1.05 to 1.20; P = 0.009 for intensification between 1.4 and 4.7 months after detection of elevated blood pressure). The highest fifth of time to follow-up (>2.7 months) was also associated with increased outcome risk (hazard ratio 1.18, 1.11 to 1.25; P <0.001).” (A. Turchin, aturchin@partners.org)
Warfarin-Related Bleeding in Patients With CKD & AF: Risks of bleeding are particularly high in the first 30 days of warfarin therapy for atrial fibrillation in older patients with reduced kidney function, researchers report (h246). The study, conducted among patients aged 66 or older in Alberta, looked at outcomes in those with atrial fibrillation who began warfarin treatment in 2003–10. The Chronic Kidney Disease Epidemiology Collaboration equation was used to estimate kidney function, and participants were categorized based on resulting estimated glomerular filtration rates (eGFRs), as follows: “Of 12,403 participants, 45% had an eGFR <60 mL/min/1.73m2. Overall, 1,443 (11.6%) experienced a major bleeding episode over a median follow-up of 2.1 (interquartile range: 1.0–3.8) years. During the first 30 days of warfarin treatment, unadjusted and adjusted rates of major bleeding were higher at lower eGFR (P for trend <0.001 and 0.001, respectively). Adjusted bleeding rates per 100 person years were 63.4 (95% confidence interval 24.9 to 161.6) in participants with eGFR <15 mL/min/1.73m2 compared with 6.1 (1.9 to 19.4) among those with eGFR >90 mL/min/1.73m2 (adjusted incidence rate ratio 10.3, 95% confidence interval 2.3 to 45.5). Similar associations were observed at more than 30 days after starting warfarin, although the magnitude of the increase in rates across eGFR categories was attenuated. Across all eGFR categories, adjusted rates of major bleeding were consistently higher during the first 30 days of warfarin treatment compared with the remainder of follow-up. Increases in major bleeding rates were largely due to gastrointestinal bleeding (3.5-fold greater in eGFR <15 mL/min/1.73m2 compared with ≥90 mL/min/1.73m2). Intracranial bleeding was not increased with worsening kidney function.” (B. Hemmelgarn, Brenda.Hemmelgarn@albertahealthservices.ca)

>>>PNN NewsWatch
* FDA on Friday expanded the approved use for ranibizumab injection) 0.3 mg (Lucentis, Genentech) to treat diabetic retinopathy in patients with diabetic macular edema. Approved with a breakthrough designation, the product is administered once monthly as an ocular injection by a physician.

>>>PNN JournalWatch
* Integration of Palliative Care in the Context of Rapid Response: A Report From the Improving Palliative Care in the ICU Advisory Board, in
Chest, 2015; 147: 560–9. (K. S. Mathews, kusum.mathews@mssm.edu)
* Sleep-Disordered Breathing in Down Syndrome, in
Chest, 2015; 14: 570–9. (C. Lal, lalch@musc.edu)
* Challenges and Opportunities in Pediatric Heart Failure and Transplantation—Pharmacogenomics: Personalizing Pediatric Heart Transplantation, in
Circulation, 2015; 131:503–12. (S. A. Webber, steve.a.webber@Vanderbilt.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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 10, 2015 * Vol. 22, No. 26
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. issue of JAMA Internal Medicine (2015; 175).
Statins & Fractures: Contrary to the results of observational studies, the JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial shows no effect on fracture risks among men and women with elevated high-sensitivity C-reactive protein (hs-CRP), researchers report (pp. 171–7). JUPITER participants were men older than 50 and women older than 60 with hs-CRP levels of 2 mg/L or more. Among the 17,802 trial participants, these effects of rosuvastatin calcium 20 mg/d or placebo on fracture rates were found: “During the study, 431 incident fractures were reported and confirmed. Among participants allocated to rosuvastatin, 221 fractures were confirmed, compared with 210 among those allocated to placebo, such that the incidence of fracture in the rosuvastatin and placebo groups was 1.20 and 1.14 per 100 person–years, respectively (adjusted HR, 1.06 [95% CI, 0.88–1.28]; P = .53). Overall, increasing baseline hs-CRP level was not associated with an increased risk of fractures (adjusted HR for each unit increase in hs-CRP tertile, 1.06 [95% CI, 0.94–1.20]; P for trend, .34).” (J. M. Peña)
Tramadol & Hospitalization for Hypoglycemia: Patients using tramadol for noncancer pain are at increased risk of hypoglycemia requiring hospitalization, a study shows, and authors conclude that “additional studies are needed to confirm this rare but potentially fatal adverse event” (pp. 186–93). Linking the United Kingdom Clinical Practice Research Datalink with the Hospital Episodes Statistics database for all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012, investigators obtained these results using nested case–control analysis: “The cohort included 334,034 patients, of whom 1,105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1,000 per year) and matched to 11,019 controls. Compared with codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (OR, 1.52 [95% CI, 1.09–2.10]), particularly elevated in the first 30 days of use (OR, 2.61 [95% CI, 1.61–4.23]). This 30-day increased risk was confirmed in the cohort (HR, 3.60 [95% CI, 1.56–8.34]) and case–crossover analyses (OR, 3.80 [95% CI, 2.64–5.47]).” (J-P Fournier)
Tobacco Cessation & Socioeconomic Status: Proactive-outreach facilitated with interactive voice response (IVR) techniques was effective in engaging people of lower socioeconomic status for smoking cessation in a study of 707 patients (pp. 218–26). Patients contacted through IVR and managed with a multidimensional cessation program (motivational counseling by phone, free nicotine-replacement therapy for 6 weeks, access to community-based referrals, and integrated care through electronic health records) had higher quit rates (17.8% vs. 8.1%) than those engaged through IVR and managed with usual care. (J. S. Haas)

>>>PNN NewsWatch
* Seniors would have more convenient access to discounted or preferred copayments for prescription drugs at their pharmacy of choice under H.R. 793, the National Community Pharmacists Association (NCPA) said yesterday. The “Ensuring Seniors Access to Local Pharmacies Act of 2015” would allow seniors in medically underserved areas to access lower copays at any pharmacy willing to accept the Medicare Part D drug plan’s “preferred pharmacy” terms and conditions (pricing), NCPA said. The Pharmaceutical Care Management Association (PCMA) countered the bill “would undermine the availability of lower cost, preferred pharmacies and increase Medicare spending by $21 billion over the next 10 years,” citing research from The Moran Company based on analysis the same legislative language introduced during the last Congress. PCMA said the Moran study shows “there is not necessarily a relationship between the underserved areas targeted in the legislation and pharmacy access. The targeted underserved areas are identified by primary medical care, dental or mental health providers, without regard to pharmacy access.”
*
NCPA also spoke out yesterday in praise of a CMS final regulation issued last week for the Medicare Part D benefit in the 2016 fiscal year. NCPA said the rule would “discourage Medicare Part D prescription drug plans from paying long-term care pharmacies lower, prorated dispensing fees for ‘short-cycle’ prescriptions.”

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 11, 2015 * Vol. 22, No. 27
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 11 issue of JAMA (2015; 313).
Oral Iron Supplementation After Blood Donation: In both iron-depleted and -replete individuals, oral doses of the element can speed recovery from blood donation, a study shows (pp. 575–83). Ferrous gluconate tablets containing 37.5 mg of elemental iron or no iron for 24 weeks produced these changes in time to recovery of 80% of donation-reduced hemoglobin levels and ferritin stores: “The mean baseline hemoglobin levels were comparable in the iron and no-iron groups and declined from a mean (SD) of 13.4 (1.1) g/dL to 12.0 (1.2) g/dL after donation in the low-ferritin group and from 14.2 (1.1) g/dL to 12.9 (1.2) g/dL in the higher-ferritin group. Compared with participants who did not receive iron supplementation, those who received iron supplementation had shortened time to 80% hemoglobin recovery in both the low-ferritin (mean, 32 days, interquartile range [IQR], 30–34, vs 158 days, IQR, 126–>168) and higher-ferritin groups (31 days, IQR, 29–33, vs 78 days, IQR, 66–95). Median time to recovery to baseline ferritin levels in the low-ferritin group taking iron was 21 days (IQR, 12–84). For participants not taking iron, recovery to baseline was longer than 168 days (IQR, 128–>168). Median time to recovery to baseline in the higher-ferritin group taking iron was 107 days (IQR, 75–141), and for participants not taking iron, recovery to baseline was longer than 168 days (IQR, >168–>168). Recovery of iron stores in all participants who received supplements took a median of 76 days (IQR, 20–126); for participants not taking iron, median recovery time was longer than 168 days (IQR, 147–>168 days; P < .001). Without iron supplements, 67% of participants did not recover iron stores by 168 days.” (J. E. Kiss, jkiss@itxm.org)
Creatine Effects in Parkinson Disease: In a 5-year study, clinical outcomes were not improved through creatine supplementation in patients with early and treated Parkinson disease, researchers report (pp. 584–93). Participants in the Long-term Study 1 received placebo or creatine 10 g/d as the monohydrate salt and had these outcomes based on monitoring with five measures: “The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2,360 (95% CI, 2249–2470) and for creatine was 2,414 (95% CI, 2304–2524). The global statistical test yielded t1865.8  = −0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system.” (Writing Group for the NINDS Exploratory Trials in Parkinson Disease [NET-PD] Investigators)
Blood Pressure Lowering in Type 2 Diabetes: Use of hypotensive agents in patients with type 2 diabetes and baseline systolic blood pressures above 140 mm Hg is supported by results of a systematic review and meta-analysis of 40 trials with 100,354 participants (pp. 603–15). Mortality was decreased and other clinical outcomes improved with blood pressure treatments, the authors noted, adding these details: “Each 10–mm Hg lower systolic BP was associated with a significantly lower risk of mortality (relative risk [RR], 0.87; 95% CI, 0.78–0.96); absolute risk reduction (ARR) in events per 1,000 patient–years (3.16; 95% CI, 0.90–5.22), cardiovascular events (RR, 0.89 [95% CI, 0.83–0.95]; ARR, 3.90 [95% CI, 1.57–6.06]), coronary heart disease (RR, 0.88 [95% CI, 0.80–0.98]; ARR, 1.81 [95% CI, 0.35–3.11]), stroke (RR, 0.73 [95% CI, 0.64–0.83]; ARR, 4.06 [95% CI, 2.53–5.40]), albuminuria (RR, 0.83 [95% CI, 0.79–0.87]; ARR, 9.33 [95% CI, 7.13–11.37]), and retinopathy (RR, 0.87 [95% CI, 0.76–0.99]; ARR, 2.23 [95% CI, 0.15–4.04]). When trials were stratified by mean baseline systolic BP at greater than or less than 140 mm Hg, RRs for outcomes other than stroke, retinopathy, and renal failure were lower in studies with greater baseline systolic BP (P interaction <0.1). The associations between BP-lowering treatments and outcomes were not significantly different, irrespective of drug class, except for stroke and heart failure. Estimates were similar when all trials, regardless of risk of bias, were included.” (C. A. Emdin)

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 12, 2015 * Vol. 22, No. 28
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 12 issue of the New England Journal of Medicine (2015; 372).
Lenvatinib in Radioiodine-Refractory Thyroid Cancer: In a Phase III trial of 392 patients with iodine-131–refractory thyroid cancer, lenvatinib improved progression-free survival and response rates, compared with placebo, but with more adverse effects and several deaths attributed to the drug, researchers report (pp. 621–30). The new drug is an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor alpha, RET, and KIT. Administered in 28-day cycles, lenvatninib produced these changes in primary and secondary end points: “The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 to 0.31; P <0.001). A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups. The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P <0.001). The median overall survival was not reached in either group. Treatment-related adverse effects of any grade, which occurred in more than 40% of patients in the lenvatinib group, were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%), and nausea (in 41.0%). Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib (14.2%) and 3 patients who received placebo (2.3%). In the lenvatinib group, 6 of 20 deaths that occurred during the treatment period were considered to be drug-related.” (M. Schlumberger, martin.schlumberger@gustaveroussy.fr)
Asthma, Exercise & Athletes: Authors of a review article examine current management of asthma and exercise-induced bronchoconstriction in athletes with a focus on endurance sports and recommendations for high-level performers (pp. 641–8). “The prevalence of asthma and exercise-induced bronchoconstriction among athletes is uncertain but has been estimated to be between 30% and 70% among elite athletes, depending on the type of sports performed; however, much remains to be learned about the reasons for this and how to reduce the risk,” the writers conclude. “Asthma and exercise-induced bronchoconstriction can usually be well managed in athletes, most often with the use of maintenance inhaled glucocorticoids and occasional inhaled short-acting beta-2-agonists before exercise. Knowledge of and adherence to antidoping regulations regarding asthma drugs are important for developing an asthma-management plan for competitive athletes. The approach outlined here is based largely on expert opinion. We need better data from controlled trials on ways to manage asthma and exercise-induced bronchoconstriction in athletes, who undertake frequent and intense efforts, often in challenging environmental conditions.” (L-P Boulet, lpboulet@med.ulaval.ca)
Emerging Smoking-Related Diseases: Looking at causes of mortality among smokers, researchers find in five U.S. cohort studies that “a substantial portion of the excess mortality among current smokers between 2000 and 2011 was due to associations with diseases that have not been formally established as caused by smoking” (pp. 631–40). Pooling a study data for 421,378 men and 532,651 women aged 55 or older showed the following: “During the follow-up period, there were 181,377 deaths, including 16,475 among current smokers. Overall, approximately 17% of the excess mortality among current smokers was due to associations with causes that are not currently established as attributable to smoking. These included associations between current smoking and deaths from renal failure (relative risk, 2.0; 95% confidence interval [CI], 1.7 to 2.3), intestinal ischemia (relative risk, 6.0; 95% CI, 4.5 to 8.1), hypertensive heart disease (relative risk, 2.4; 95% CI, 1.9 to 3.0), infections (relative risk, 2.3; 95% CI, 2.0 to 2.7), various respiratory diseases (relative risk, 2.0; 95% CI, 1.6 to 2.4), breast cancer (relative risk, 1.3; 95% CI, 1.2 to 1.5), and prostate cancer (relative risk, 1.4; 95% CI, 1.2 to 1.7). Among former smokers, the relative risk for each of these outcomes declined as the number of years since quitting increased.” (B. D. Carter, brian.carter@cancer.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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 13, 2015 * Vol. 22, No. 29
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Feb. issue of the Journal of Allergy and Clinical Immunology (2015; 135).
Asthma Phenotypes & Biologic Medications: “Further refinement of type 2 therapies to specific type 2 phenotypes and novel approaches for patients without type 2 inflammation are needed for asthma and allergic disease treatment,” conclude authors of a review article (pp. 299–310). Describing these refinements in the use of biologic medications as “the next steps toward personalized care” of asthma and allergic disease, the investigators write: “Traditionally, asthma and allergic diseases have been defined by broad definitions and treated with nonspecific medications, including corticosteroids and bronchodilators. There is an increasing appreciation of heterogeneity within asthma and allergic diseases based primarily on recent cluster analyses, molecular phenotyping, biomarkers, and differential responses to targeted and nontargeted therapies. These pioneering studies have led to successful therapeutic trials of molecularly targeted therapies in defined phenotypes. This review analyzed randomized double-blind, placebo-controlled trials of molecularly targeted therapies in defined allergic disease and asthma phenotypes. IgE was the first successful biological target used in patients with allergic disease and asthma. This review shows that therapies targeting the canonical type 2 cytokines IL-4, IL-5, and IL-13 have shown consistent efficacy, especially in asthmatic patients with evidence of Th2/type 2 inflammation (‘type 2 high&rsquoWinking. As of yet, there are no successful trials of targeted therapies in asthmatic patients without evidence for type 2 inflammation.” (M. L. Fajt, fajtml@upmc.edu)

>>>Oncology Highlights
Source:
Feb. 10 issue of the Journal of Clinical Oncology (2015; 33).
Readmissions After Major Cancer Surgery: Inpatient readmissions following major cancer surgery are common, a study shows, and this results “in substantially poorer patient outcomes and higher costs” (pp. 455–64). Among SEER–Medicare patients diagnosed in 2001–07 with bladder, lung, pancreas, or esophagus cancer who underwnt extirpative surgery, these outcomes were noted: “Four thousand nine hundred forty cystectomies, 1,573 esophagectomies, 20,362 lung resections, and 2,844 pancreatectomies were included. Thirty- and 90-day readmission rates ranged from 13% to 29% and 23% to 43%, respectively, based on tumor type. Predictors of readmission were discharge to somewhere other than home, longer length of stay, comorbidities, higher stage at diagnosis, and longer travel distance (P < .001 for each). Patients who lived farther from the index hospital also had increased emergency room visits and were more likely to be readmitted to a hospital other than the index hospital (P < .001). Of readmitted patients, 31.9% were readmitted more than once. Long-term survival was worse and costs of care higher for patients who were readmitted (P < .001 for all).” (K. B. Stitzenberg, stitz@med.unc.edu)

>>>Infectious Disease Report
Source:
Feb. 15 issue of Clinical Infectious Diseases (2015; 60).
Moxifloxacin Pharmacokinetics in Children with MDRTB: South African children with multidrug-resistant tuberculosis had altered moxifloxacin pharmacokinetics, compared with adults, in a 23-patient study (pp. 549–56). Compared with data from adults receiving moxifloxacin 400 mg/d, the children had lower-than-expected maximum serum concentration, area under the curve from 0 to 8 hours, time to maximum concentration, and half-life. (S. Thee, stephanie.thee@charite.de)

>>>PNN NewsWatch
* Jerome A. Halperin, former Executive Vice President and Chief Executive Officer of USP from 1990 to 2000, died on Feb. 10. During his tenure at the helm of USP, he “expanded USP’s horizons and built relationships that helped lay the groundwork for USP’s international expansion,” according to a blog posted on the organization’s site. A pharmacist, Halperin was instrumental in instigating and planning the first Pharmacy in the 21st Century conference. That meeting and three subsequent P21 conferences in many ways led to the “current vision for pharmacy practice expressed by the Joint Commission of Pharmacy Practitioners,” ASHP Historian Bill Zellmer said.
*
PNN will not be published on Mon., Feb. 16, Presidents 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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 17, 2015 * Vol. 22, No. 30
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Feb. 17 issue of the Annals of Internal Medicine (2015; 162).
Estimating Cardiovascular Risk: Available tools for estimating cardiovascular risks—including the controversial method released in 2013 by the American Heart Association (AHA) and American College of Cardiology (ACC)—typically overstate patients’ risk of an atherosclerotic cardiovascular disease (ASCVD) event, a study shows (pp. 266–75). Of five risk scores, four “showed overestimation of risk (25% to 115%) in a modern, multiethnic cohort without baseline clinical ASCVD,” MESA (Multi-Ethnic Study of Atherosclerosis) investigators report based on 10.2 years of follow-up for 4,227 participants: “The new AHA-ACC-ASCVD and 3 older Framingham-based risk scores overestimated cardiovascular events by 37% to 154% in men and 8% to 67% in women. Overestimation was noted throughout the continuum of risk. In contrast, the Reynolds Risk Score overestimated risk by 9% in men but underestimated risk by 21% in women. Aspirin, lipid-lowering or antihypertensive therapy, and interim revascularization did not explain the overestimation.” (A. P. DeFilippis, APDeFi01@louisville.edu)

>>>Lancet Highlights
Source:
Feb. 14 issue of Lancet (2015; 385).
Managing Blood Pressure After Stroke: Transdermal nitroglycerin lowered blood pressure but did not improve functional outcomes when administered following stroke in patients with high blood pressure, researchers report (pp. 617–28). Patients hospitalized with acute ischemic or hemorrhagic stroke and systolic blood pressure of 140–220 mm Hg had these outcomes after 7 days of transdermal nitroglycerin 5 mg or no nitroglycerin: “Between July 20, 2001, and Oct 14, 2013, we enrolled 4,011 patients. Mean blood pressure was 167 (SD 19) mm Hg/90 (13) mm Hg at baseline (median 26 h [16–37] after stroke onset), and was significantly reduced on day 1 in 2,000 patients allocated to glyceryl trinitrate compared with 2,011 controls (difference −7.0 [95% CI −8.5 to −5.6] mm Hg/–3.5 [–4.4 to −2.6] mm Hg; both p <0.0001), and on day 7 in 1,053 patients allocated to continue antihypertensive drugs compared with 1,044 patients randomised to stop them (difference −9.5 [95% CI −11.8 to −7.2] mm Hg/–5.0 [–6.4 to −3.7] mm Hg; both p <0.0001). Functional outcome at day 90 did not differ in either treatment comparison—the adjusted common odds ratio (OR) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1.01 (95% CI 0.91–1.13; p = 0.83), and with continue versus stop antihypertensive drugs OR was 1.05 (0.90–1.22; p = 0.55).” (ENOS Trial Investigators)

>>>PNN NewsWatch
* FDA on Friday granted expedited approval to lenvatinib mesylate (Lenvima, Eisai) as a treatment for locally recurrent or metastatic, progressive, radioactive iodine–refractory differentiated thyroid cancer. The orally administered molecular targeted agent selectively inhibits several molecules, Eisai reported, including VEGFR, FGFR, RET, KIT and PDGFR. X-ray crystal structural analysis has shown that lenvatinib is the first compound to demonstrate a new binding mode (Type V) to VEGFR2, and exhibits rapid and potent inhibition of kinase activity, the company added.
*
FDA has issued five new draft documents regarding compounding of human drugs in pharmacies, federal facilities, outsourcing facilities, and physician offices. The draft guidances, available for public comment for 90 days, cover registration as outsourcing facilities, repackaging of some human drug products by pharmacies and outsourcing facilities, mixing/diluting and repackaging biological products, and adverse event reporting for compounded products. A draft memorandum of understanding between states and FDA was also released; it is open for comment for 120 days.

>>>PNN JournalWatch
* Allergic Reactions After Egg-Free Recombinant Influenza Vaccine: Reports to the US Vaccine Adverse Event Reporting System, in
Clinical Infectious Diseases, 2015; 60: 777–80. (E. J. Woo, jane.woo@fda.hhs.gov)
* Insulin-like Growth Factors and Kidney Disease, in
American Journal of Kidney Diseases, 2015; 65: 327–36. (L. A. Bach, leon.bach@monash.edu)
* Discrepancies in Liver Disease Labeling in the Package Inserts of Commonly Prescribed Medications, in
Gastroenterology, 2015; 148: 269–73. (E. S. Bjornsson)

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 18, 2015 * Vol. 22, No. 31
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 17 issue of JAMA (2015; 313).
Corticosteroids & Treatment Failure With Severe CAP: Treatment failure was decreased with use of corticosteroids in patients with severe community-acquired pneumonia and high initial inflammatory response, a study shows (pp. 677–86). At three Spanish teaching hospitals, patients received intravenous methylprednisolone 0.5 mg/kg or placebo as a bolus every 12 hours for 5 days for CAP complicated by high C-reactive protein levels. Results showed: “There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, −6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34).” (A. Torres)
“A more important question is what exactly are steroids preventing?” writes an editorialist (
pp. 673–4). “Because radiographic progression during the period between 72 hours and 5 days was the primary driver of treatment differences, understanding what this clinical finding represents is key to acceptance of the findings. The 2 logical explanations for radiographic progression are uncontrolled pneumonia and development of acute respiratory distress syndrome. Although the latter is supported by a body of literature, a beneficial effect on uncontrolled pneumonia is less logical. A more intriguing possibility is that corticosteroids block a Jarisch–Herxheimer-like reaction to initiation of antibiotics in patients with high genomic bacterial load.” (R. G. Wunderink)
Varenicline & Smoking Reduction: Varenicline may offer “a treatment option for smokers whose needs are not addressed by clinical guidelines recommending abrupt smoking cessation,” conclude authors who found increased cessation rates when the drug was used to reduce cigarette consumption gradually over a 3-month period (pp. 687–94). At 61 centers in 10 countries, 1,510 study participants received varenicline 1 mg/d or placebo for 24 weeks with reduction goals of 50% by 4 weeks, 75% by 8 weeks, and a quit attempt by 12 weeks. Results showed: “The varenicline group (n = 760) had significantly higher continuous abstinence rates during weeks 15 through 24 vs the placebo group (n = 750) (32.1% for the varenicline group vs 6.9% for the placebo group; risk difference (RD), 25.2% [95% CI, 21.4%–29.0%]; relative risk (RR), 4.6 [95% CI, 3.5–6.1]). The varenicline group had significantly higher continuous abstinence rates vs the placebo group during weeks 21 through 24 (37.8% for the varenicline group vs 12.5% for the placebo group; RD, 25.2% [95% CI, 21.1%–29.4%]; RR, 3.0 [95% CI, 2.4–3.7]) and weeks 21 through 52 (27.0% for the varenicline group vs 9.9% for the placebo group; RD, 17.1% [95% CI, 13.3%–20.9%]; RR, 2.7 [95% CI, 2.1–3.5]). Serious adverse events occurred in 3.7% of the varenicline group and 2.2% of the placebo group (P = .07).” (J. O. Ebbert)
Fondaparinux v. LMWHs in NSTEMI: In-hospital and 6-month rates of major bleeding events and death were reduced by use of fondaparinux rather than low-molecular-weight heparins (LMWHs) in patients with non–ST-segment elevation myocardial infarction (NSTEMI), researchers report (pp. 707–16). In Sweden in 2006–10, these outcomes were recorded in a prospective cohort study: “In total, 14,791 patients (36.4%) were treated with fondaparinux and 25,825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42–0.70). A total of 394 patients (2.7%) in the fondaparinux group died while in the hospital vs 1,022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63–0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups.” (K. Szummer)

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 19, 2015 * Vol. 22, No. 32
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 19 issue of the New England Journal of Medicine (2015; 372).
Efficacy of 9-Valent HPV Vaccine: An investigational 9-valent human papillomavirus (HPV) vaccine prevented infections of target HPV types and generated noninferior antibody responses against oncogenic HPV types, researchers report (pp. 711–23). The vaccine—active against the types included in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58)—or the qHPV vaccine was administered to 14,215 women on day 1 and at months 2 and 6, with these results: “The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1,000 person–years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1,000 person–years in the 9vHPV group and 1.6 per 1,000 person–years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group.” (E. A. Joura, elmar.joura@meduniwien.ac.at)
The challenge with HPV vaccines is higher rates of vaccination, writes an editorialist, not vaccine efficacy (
pp. 775–6): “Even with the availability of another HPV vaccine targeting additional cancer-causing virus types, vaccination of a much higher proportion of preteens is needed. Otherwise, decades from now oncologists will still be talking about HPV-associated cancers with thousands of new patients every year. Instead, I hope that in a few decades we will be able to tell a generation of adults who never had HPV-associated cancers or precancers that when they were teenagers, we had them covered.” (A. Schuchat)
Addition of Pertuzumab in HER2-Positive Metastatic Breast Cancer: The addition of of pertuzumab to trastuzumab–docetaxel therapy of human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer improved progression-free survival by 56.5 months in a new study, extending “the results of previous analyses showing the efficacy of this drug combination” (pp. 724–34): “The median overall survival was 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving the pertuzumab combination, as compared with 40.8 months (95% CI, 35.8 to 48.3) in the group receiving the placebo combination (hazard ratio favoring the pertuzumab group, 0.68; 95% CI, 0.56 to 0.84; P <0.001), a difference of 15.7 months.… Pertuzumab extended the median duration of response by 7.7 months, as independently assessed. Most adverse events occurred during the administration of docetaxel in the two groups, with long-term cardiac safety maintained.” (S. M. Swain, sandra.m.swain@medstar.net)
Eradicating Yaws: A strategy being used by the World Health Organization to eradicate the infectious disease yaws is supported by results of a trial of mass treatment with single-dose azithromycin (pp. 703–10). In Papua New Guinea, 13,302 of 16,092 residents received a single oral dose of azithromycin, which is active against the causative organism, Treponema pallidum subspecies pertenue. “The prevalence of active infectious yaws was reduced from 2.4% before mass treatment to 0.3% at 12 months (difference, 2.1 percentage points; P <0.001),” the authors report. “The prevalence of high-titer latent yaws among children was reduced from 18.3% to 6.5% (difference, 11.8 percentage points; P <0.001) with a near-absence of high-titer seroreactivity in children 1 to 5 years of age. Adverse events identified within 1 week after administration of the medication occurred in approximately 17% of the participants, included nausea, diarrhea, and vomiting, and were mild in severity. No evidence of emergence of resistance to macrolides against Treponema pallidum subspecies pertenue was seen.” (O. Mitjà, riolmitja@hotmail.com">oriolmitja@hotmail.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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 20, 2015 * Vol. 22, No. 33
Providing news and information about medications and their proper use

>>>Medical Care Highlights
Source:
Mar. issue of Medical Care (2015; 53).
Timing of Influenza Vaccination: An analysis of the economic value and quality-of-life impact of earlier influenza vaccination concludes that, despite many people being immunized well after the initial September/October period, “they likely are still vaccinated early enough to provide substantial cost-savings” (pp. 218–29). Investigators used data from Allegheny County, PA, and two models to assess the timing of influenza vaccination. Results showed: “Applying the current timing of vaccinations averted 223,761 influenza cases, $16.3 million in direct health care costs, $50.0 million in productivity losses, and 804 in [quality-adjusted life-years (QALYs)], compared with no vaccination (February peak, R0 1.2). When the population does not have preexisting immunity and the influenza season peaks in February (R0 1.2–1.6), moving individuals who currently received the vaccine after September to the end of September could avert an additional 9,634–17,794 influenza cases, $0.6–$1.4 million in direct costs, $2.1–$4.0 million in productivity losses, and 35–64 QALYs. Moving the vaccination of just children to September (R0 1.2–1.6) averted 11,366–1660 influenza cases, $0.6–$0.03 million in direct costs, $2.3–$0.2 million in productivity losses, and 42–8 QALYs. Moving the season peak to December increased these benefits, whereas increasing preexisting immunity reduced these benefits.” (B. Y. Lee)
Burnout During Primary Care Transformation: Clinicians and health-system staff members can experience emotional exhaustion (EE) during periods of radical change in care models, a study shows (pp. 253–60). During the initial phase of national primary care transformation in the Veterans Health Administration, these indicators of EE were identified among 515 primary care clinicians (PCCs) and staff in 5 health-care systems using the Maslach Burnout Inventory: “In total, 53% of PCCs and 43% of staff had high EE. PCCs (vs. other primary care staff), female (vs. male), and non-Latino (vs. Latino) respondents reported higher EE. Respondents reporting higher efficacy for change and participatory decision making had lower EE scores, adjusting for sex and race.” (L. S. Meredith)

>>>Health Affairs Report
Source:
Feb. issue of Health Affairs, a theme issue on Biomedical Innovation (2015; 34).
Biotechnology Evolution & Health Care: A review article recounts, “For more than three decades the field of biotechnology has had an extraordinary impact on science, health care, law, the regulatory environment, and business” (pp. 210–9): “During this time more than 260 novel biotechnology products were approved for over 230 indications. Global sales of these products exceeded $175 billion in 2013 and have helped sustain a vibrant life sciences sector that includes more than 4,600 biotech companies worldwide. In this article we examine the evolution of biotechnology during the past three decades and the profound impact that it has had on health care through four interrelated and interdependent tracks: innovations in science, government activity, business development, and patient care. The future impact of biotechnology is promising, as long as the public and private sectors continue to foster policies and provide funds that lead to scientific breakthroughs; governments continue to offer incentives for private-sector biotech innovation; industry develops business models for cost-effective research and development; and all stakeholders establish policies to ensure that the therapeutic advances that mitigate or cure medical conditions that currently have inadequate or no available therapies are accessible to the public at a reasonable cost.” (R. Evens, medaff4biopharma@aol.com)
Pharmacotherapy of Age-Related Macular Degeneration: The VA and Medicare systems could “adopt more value-conscious treatment patterns” in the drug therapy of age-related macular degeneration, researchers report (pp. 229–38). Compared with $50 for bevacizumab, ranibizumab costs about $2,000 per injection, yet it was the predominant agent used in 2007–09 among Medicare patients. The less expensive drug became predominant in that system in 2009, but the two agents were used approximately equally in the VA system during this time period. (M. K. Bundorf, bundorf@stanford.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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 23, 2015 * Vol. 22, No. 34
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2015; 350).
Tailored Prevention of Diabetes: Using data from the Diabetes Prevention Program, investigators find in a post-hoc analysis that patients at high risk of diabetes have “substantial variation in their likelihood of receiving benefit from diabetes prevention treatments” (h454). Among 3,060 participants without diabetes but with impaired glucose metabolism, these outcomes were noted for drug (metformin) and nonpharmacologic (weight loss and exercise) preventive interventions: “655 (21%) [participants] progressed to diabetes over a median 2.8 years’ follow-up. The diabetes risk model had good discrimination (C statistic = 0.73) and calibration. Although the lifestyle intervention provided a sixfold greater absolute risk reduction in the highest risk quarter than in the lowest risk quarter, patients in the lowest risk quarter still received substantial benefit (three year absolute risk reduction 4.9% v 28.3% in highest risk quarter; numbers needed to treat of 20.4 and 3.5, respectively). The benefit of metformin, however, was seen almost entirely in patients in the top quarter of risk of diabetes. No benefit was seen in the lowest risk quarter. Participants in the highest risk quarter averaged a 21.4% three year absolute risk reduction (number needed to treat 4.6).” (J. B. Sussman, jeremysu@med.umich.edu)
Antidepressant Use & Suicidal Ideation: In an observational analysis of 283,963 patients aged 20–64 years seen in U.K. general practices, “rates of suicide and attempted suicide or self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic and related antidepressants,” researchers conclude (h517). Using cohort analysis, the authors found the highest rate of suicidality among those taking mirtazapine, venlafaxine, and trazodone, as noted in these results: “During follow-up, 87.7% (n=209,476) of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days (interquartile range 79–590 days). During the first five years of follow-up 198 cases of suicide and 5,243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant (adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50), but the suicide rate was significantly increased during periods of treatment with other antidepressants (2.64, 1.74 to 3.99). The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram (3.70, 2.00 to 6.84). Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants (0.96, 0.87 to 1.08) compared with selective serotonin reuptake inhibitors, but the rate of attempted suicide or self harm was significantly higher for other antidepressants (1.80, 1.61 to 2.00). The adjusted hazard ratios for attempted suicide or self harm were significantly increased for three of the most commonly prescribed drugs compared with citalopram: venlafaxine (1.85, 1.61 to 2.13), trazodone (1.73, 1.26 to 2.37), and mirtazapine (1.70, 1.44 to 2.02), and significantly reduced for amitriptyline (0.71, 0.59 to 0.85). The absolute risks of attempted suicide or self harm over one year ranged from 1.02% for amitriptyline to 2.96% for venlafaxine. Rates were highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment.” (C. Coupland, carol.coupland@nottingham.ac.uk)
Divorce Among Health Professionals: Divorce was least common among pharmacists in a study of health professionals in the U.S., with 22.9% reporting ever being divorced, statistically equivalent to figures for physicians (24.3%) and dentists 25.2% and significantly lower than rates for nurses (33.0%), health executives (30.9%), and the non-health-care professionals (35.0%) (h706). Physicians and dentists had the highest percentage of men in the study (68.3% and 75.9%, respectively), while nurses and pharmacists had the lowest (8.5% and 47.7%, respectively). (A. B. Jena, jena@hcp.med.harvard.edu)

>>>PNN JournalWatch
* Editorial: Inflammation, Disease-Modifying Antirheumatic Drugs, Lipids, and Cardiovascular Risk in Rheumatoid Arthritis, in
Arthritis & Rheumatology, 2015; 67: 327–9. (K. P. Liao, kliao@partners.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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 24, 2015 * Vol. 22, No. 35
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Feb. issue of the Journal of the American Geriatrics Society (2015; 63).
Metabolic Syndrome & Functional Decline: In the Lifestyle Interventions and Independence for Elders (LIFE) study, community-dwelling sedentary adults aged 70–89 years often had metabolic syndrome (MetS), but changes in their physical function were not consistently associated with presence of the syndrome, researchers report (pp. 222–32). In a cross-sectional analysis, 1,535 participants at high risk of mobility disability showed these outcomes for physical capacity, disability, and self-rated health: “The prevalence of MetS was 49.8% in the overall sample (83.2% of those with diabetes mellitus, 38.1% of those without). MetS was associated with stronger grip strength (mean difference (∆) = 1.2 kg, P = .01) in the overall sample and in participants without diabetes mellitus and with poorer self-rated health (∆ = 0.1 kg, P < .001) in the overall sample only. No significant differences were found in 400-m walk time, [Short Physical Performance Battery] score, or disability score between participants with and without MetS, in the overall sample or diabetes mellitus subgroups.” (A. Botoseneanu, andabm@umich.edu)
Inclusion of Seniors With Pneumonia in Antibiotic Trials: The evidence on antibiotic treatment of older patients with pneumonia is lacking because of frequent exclusion of this group because of comorbidities, according to a systematic review of 43 randomized controlled trials (RCTs) of community-acquired (CAP), health-care-associated (HCAP), hospital-acquired (HAP), or ventilator-associated (VAP) pneumonia (pp. 233–43): “No RCT reported exclusion based on an upper age limit; 100% of community CAP trials, 90% of hospitalized CAP trials, and 76% of HAP and VAP trials excluded individuals based on comorbidities. None of the RCTs reported a subgroup analysis for mortality according to age. The RR for the pooled difference in treatment failure rates between participants younger than 65 and those aged 65 and older was 1.25 (95% CI = 0.94–1.65, 12 RCTs) and between participants younger than 75 and aged 75 and older was 1.43 (95% CI = 0.98–2.09, 7 RCTs). RCT participants were significantly younger (54.0 ± 9.6) than those in observational studies of CAP (66.2 ± 8.1, P < .001). Age differences were not significant for HCAP, HAP, and VAP.” (T. Avni, tomerav@clalit.org.il)
Marketing Influence on Nursing Home Use of Antipsychotics: At 41 Connecticut nursing homes (NHs), influence of pharmaceutical marketing on use of second-generation antipsychotic agents was unclear, a study shows (pp. 297–301). “NH leaders frequently encounter pharmaceutical marketing through a variety of ways,” according to 93 NH administrators, directors of nursing, and medical directors who shared experiences in the mixed-methods, cross-sectional study: “Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader.” (C. B. Pimentel, Camilla.Pimentel@umassmed.edu)

>>>JAPhA Highlights
Source:
Early-release article from the Journal of the American Pharmacists Association (2015; 55).
Communication Needs of Patients With Altered Hearing Ability: “Deaf and [hard-of-hearing (HOH)] patients have unique needs that pharmacists must understand and address,” conclude authors based on focus groups with 20 such patients (pp. e92–9). In 2013–14, Deaf/HOH patients reported these perceptions and experiences: “Many of the Deaf/HOH still perceived community pharmacists in a dispensing role and lacked an understanding of other services being offered in this setting. In addition, pharmacists who demonstrated a lack of sensitivity and patience towards the Deaf/HOH risk weakening the relationship between patient and provider. As a result, safe use of medications is compromised.” (M. C. Ferguson, mcfergu@siue.edu)

>>>PNN NewsWatch
* FDA yesterday approved panobinostat (Farydak, Novartis) for treatment of multiple myeloma. This is the first inhibitor of histone deacetylase approved for this indication. A boxed warning describes severe diarrhea and severe and fatal cardiac events with the drug.

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 25, 2015 * Vol. 22, No. 36
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Feb. 25 issue of JAMA (2015; 313).
NSAIDs & Antithrombotic Agents After MI: NSAIDs used after myocardial infarction (MI) in patients on antithrombotic drugs—even for short time periods—are associated with increased risk of bleeding and excess thrombotic events, according to an analysis of nationwide registries in Denmark (pp. 805–14). Patients aged 30 years or older hospitalized in 2002–11 for a first MI and alive at 30 days were included in the study. Results for prescription drug use after MI showed the following: “We included 61,971 patients (mean age, 67.7 [SD, 13.6] years; 63% men); of these, 34% filled at least 1 NSAID prescription. The number of deaths during a median follow-up of 3.5 years was 18,105 (29.2%). A total of 5,288 bleeding events (8.5%) and 18,568 cardiovascular events (30.0%) occurred. The crude incidence rates of bleeding (events per 100 person–years) were 4.2 (95% CI, 3.8–4.6) with concomitant NSAID treatment and 2.2 (95% CI, 2.1–2.3) without NSAID treatment, whereas the rates of cardiovascular events were 11.2 (95% CI, 10.5–11.9) and 8.3 (95% CI, 8.2–8.4). The multivariate-adjusted Cox regression analysis found increased risk of bleeding with NSAID treatment compared with no NSAID treatment (hazard ratio, 2.02 [95% CI, 1.81–2.26]), and the cardiovascular risk was also increased (hazard ratio, 1.40 [95% CI, 1.30–1.49]). An increased risk of bleeding and cardiovascular events was evident with concomitant use of NSAIDs, regardless of antithrombotic treatment, types of NSAIDs, or duration of use.” (A-M Schjerning Olsen)
It’s “time for more than gut check” on indiscriminate use of NSAIDs with antithrombotic agents following MI, editorialists write (
pp. 801–2): “The cumulative evidence available is an important reminder that the while NSAIDs can be helpful and at times necessary medications for satisfactory quality of life, use of these medications among patients with a history of a recent MI is likely to be associated with clinically meaningful bleeding and ischemic risks. Because the present study tracked only prescription NSAID use, it is plausible that an even greater health care effect might occur in many countries, such as the United States, where NSAIDs are widely available as over-the-counter medications and physicians may be unaware whether their patients are taking NSAIDs.” (C. L. Campbell)
Genetic Variant Linked to Vincristine Peripheral Neuropathy: Among 222 children with acute lymphoblastic leukemia (ALL), an “inherited polymorphism in the promoter region of CEP72 was associated with increased risk of and severity of vincristine-related peripheral neuropathy,” researchers report (pp. 815–23). “Grade 2 to 4 vincristine-induced neuropathy during continuation therapy occurred in 28.8% of patients (64/222) in the St Jude cohort and in 22.2% (22/99) in the [Children’s Oncology Group] cohort. A [single-nucleotide polymorphism (SNP)] in the promoter region of the CEP72 gene, which encodes a centrosomal protein involved in microtubule formation, had a significant association with vincristine neuropathy (meta-analysis P = 6.3×10−9). This SNP had a minor allele frequency of 37% (235/642), with 50 of 321 patients (16%; 95% CI, 11.6%–19.5%) homozygous for the risk allele (TT at rs924607). Among patients with the high-risk CEP72 genotype (TT at rs924607), 28 of 50 (56%; 95% CI, 41.2%–70.0%) developed at least 1 episode of grade 2 to 4 neuropathy, a higher rate than in patients with the CEP72 CC or CT genotypes (58/271 patients [21.4%; 95% CI, 16.9%–26.7%]; P = 2.4×10−6). The severity of neuropathy was greater in patients homozygous for the TT genotype compared with patients with the CC or CT genotype (2.4-fold by Poisson regression [P <.0001] and 2.7-fold based on mean grade of neuropathy: 1.23 [95% CI, 0.74–1.72] vs 0.45 [95% CI, 0.3–0.6]; P = .004 by t test). Reducing CEP72 expression in human neurons and leukemia cells increased their sensitivity to vincristine.” (B. Diouf)
While “it is not clear that vincristine can be removed from the treatment options for a child with CEP72 variants,” an editorialist writes that “this study suggests that the resulting increase in leukemia cellular sensitivity makes vincristine dose reductions possible without compromising antileukemic effect” (
pp. 803–4). In addition, availability of this information can inform discussion of relative “risks and benefits of [vincristine] therapy with patients and their family members.”

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 26, 2015 * Vol. 22, No. 37
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Feb. 26 issue of the New England Journal of Medicine (2015; 372).
C. difficile Burden in U.S.: Nearly 30,000 Americans died in 2011 from infections of Clostridium difficile, according to a CDC report released yesterday and reported in today’s NEJM (pp. 825–34). Surveillance of 10 geographic areas served as the basis for estimates that nearly 500,000 cases of C. difficile infections occurred that year: “A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care–associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 strain was more prevalent among health care–associated infections than among community-associated infections (30.7% vs. 18.8%, P <0.001).” (F. C. Lessa, flessa@cdc.gov)
Pediatric CAP in U.S.: Population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age show that the very young are most often affected and that respiratory viruses are usually the causative pathogens, CDC reports (pp. 835–45). Analysis of data from hospitals in Memphis, Nashville, and Salt Lake City provide these insights: “From January 2010 through June 2012, we enrolled 2,638 of 3,803 eligible children (69%), 2,358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2,358 children (21%) required intensive care, and 3 (<1%) died. Among 2,222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1,802 (81%), one or more viruses in 1,472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%).” (S. Jain, bwc8@cdc.gov)
Nosocomial Transmission of MERS-CoV: One-fifth of those infected during last year’s outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jeddah, Saudi Arabia, were health care workers, a study shows, and nearly all the rest had contact with health care facilities, infected individuals, or both, within 14 days of the onset of illness (pp. 846–54). Review of 255 patients with confirmed MERS-CoV infections shows these patterns: “Of the 191 symptomatic patients, 40 (20.9%) were health care personnel. Among the 151 symptomatic patients who were not health care personnel, 112 (74.2%) had data that could be assessed, and 109 (97.3%) of these patients had had contact with a health care facility, a person with a confirmed case of MERS-CoV infection, or someone with severe respiratory illness in the 14 days before the onset of illness. The remaining 3 patients (2.7%) reported no such contacts.” (T. A. Madani, tmadani@kau.edu.sa)

>>>PNN NewsWatch
* Following priority review, FDA has approved a combination product with a new non-beta-lactam beta-lactamase inhibitor, avibactam, and ceftazidime (Avycaz, Forest). The fixed-dose product is indicated for treatment of adults with complicated intra-abdominal infections, in combination with metronidazole, and complicated urinary tract infections including pyelonephritis caused by designated susceptible bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa.

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 844/270-0717 (fax). Copyright © 2015, 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
Feb. 27, 2015 * Vol. 22, No. 38
Providing news and information about medications and their proper use

>>>Diabetes Report
Source:
Mar. issue of Diabetes Care (2015; ).
Canagliflozin in Type 2 Diabetes: In a 104-week trial of 1,450 patients with type 2 diabetes treated with metformin, the sodium–glucose cotransporter 2 inhibitor canagliflozin “provided durable glycemic improvements compared with glimepiride and was generally well tolerated,” researchers report (pp. 355–64). Results were as follows for canagliflozin 100 mg or 300 mg or glimepiride titrated to 6 or 8 mg daily: “At week 104, reductions from baseline in A1C were −0.65%, −0.74%, and −0.55% (−7.1, −8.1, and −6.0 mmol/mol) with canagliflozin 100 and 300 mg and glimepiride, respectively. Durability analyses showed sustained A1C lowering with both canagliflozin doses versus glimepiride. Reductions in body weight (−4.1%, −4.2%, and 0.9%, respectively) and systolic blood pressure (−2.0, −3.1, and 1.7 mm Hg, respectively) were seen with canagliflozin 100 and 300 mg compared with glimepiride at week 104. The overall adverse event (AE) incidence was 73.3%, 77.9%, and 78.4% with canagliflozin 100 and 300 mg and glimepiride; the incidence of AE-related discontinuations was low across groups (6.2%, 9.5%, and 7.3%, respectively). Incidences of genital mycotic infections, urinary tract infections, and osmotic diuresis–related AEs were higher with canagliflozin than glimepiride; these were generally mild to moderate in intensity and led to few discontinuations. Fewer patients had hypoglycemia episodes with canagliflozin 100 and 300 mg than glimepiride (6.8%, 8.2%, and 40.9%).” (L. A. Leiter, leiterl@smh.ca)
Dapagliflozin in Type 2 Diabetes: “Dapagliflozin was well tolerated and effective over 24 weeks as add-on to metformin plus sulfonylurea,” conclude investigators who studied 218 patients with type 2 diabetes (pp. 365–72). Participants had baseline A1C levels of 7.0% to 10.%; results showed: “HbA1c (baseline: dapagliflozin 8.08% [65 mmol/mol]; placebo 8.24% [67 mmol/mol]) and fasting plasma glucose (baseline: dapagliflozin 167.4 mg/dL [9.29 mmol/L]; placebo 180.5 mg/dL [10.02 mmol/L]) significantly improved from baseline with dapagliflozin (placebo-subtracted change –0.69% [–7.5 mmol/mol], P < 0.0001; –33.5 mg/dL [–1.86 mmol/L], P < 0.0001, respectively). More patients achieved a therapeutic glycemic response (HbA1c <7.0% [53 mmol/mol]) with dapagliflozin (31.8%) versus placebo (11.1%) (P < 0.0001). Body weight and systolic blood pressure were significantly reduced from baseline over 24 and 8 weeks, respectively, with dapagliflozin (placebo-subtracted change –2.1 kg, P < 0.0001; –3.8 mmHg, P = 0.0250). Patients receiving dapagliflozin showed placebo-subtracted increases in total, LDL, and HDL cholesterol (11.4 mg/dL, P = 0.0091; 11.4 mg/dL, P = 0.0030; 2.2 mg/dL, P = 0.0172, respectively) with no change in LDL/HDL cholesterol ratio (0.1; P = 0.2008) or triglycerides (–16.5 mg/dL; P = 0.1755). Adverse events occurred in 48.6% of patients receiving dapagliflozin and 51.4% receiving placebo. Significantly more patients with dapagliflozin compared with placebo experienced hypoglycemia (12.8 vs. 3.7%; P = 0.024) and genital infections (5.5 vs. 0%; P = 0.029). Events of urinary tract infection were reported by 6.4% of patients in both groups.” (S. Matthaei, s.matthaei@ckq-gmbh.de)
Empagliflozin/Linagliptin in Type 2 Diabetes: In 686 patients with type 2 diabetes poorly controlled on metformin, the addition of empagliflozin plus linagliptin significantly reduced A1C levels, compared with individual components, a study shows (pp. 384–93). Patients also tolerated the combination well, with no hypoglycemic events. Other results showed: “At week 24, reductions in HbA1c (mean baseline 7.90–8.02% [62.8–64.1 mmol/mol]) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin; adjusted mean (SE) changes from baseline were −1.19% (0.06) (−13.1 mmol/mol [0.7]) with empagliflozin 25 mg/linagliptin 5 mg, −1.08% (0.06) (−11.8 mmol/mol [0.7]) with empagliflozin 10 mg/linagliptin 5 mg, −0.62% (0.06) (−6.8 mmol/mol [0.7]) with empagliflozin 25 mg, −0.66% (0.06) (−7.2 mmol/mol [0.7]) with empagliflozin 10 mg, and −0.70% (0.06) (−7.6 mmol/mol [0.7]) with linagliptin 5 mg (P < 0.001 for all comparisons). In these groups, respectively, 61.8, 57.8, 32.6, 28.0, and 36.1% of subjects with baseline HbA1c ≥7% (≥53 mmol/mol) had HbA1c <7% (<53 mmol/mol) at week 24.” (R. A. DeFronzo, defronzo@uthscsa.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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 2, 2015 * Vol. 22, No. 39
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Feb. 28 issue of Lancet (2015; 385).
Extended-Duration Dual Antiplatelet Therapy: In a systematic review and meta-analysis of studies of patients with coronary stents, aspirin alone after 12 months or short-term dual antiplatelet therapy for 6 months or less produced mortality rates similar to those with dual therapy beyond 12 months, researchers report (pp. 792–8). Including the Dual Antiplatelet Therapy (DAPT) study and 13 other trials with 69,644 participants in all, the authors identified these effects of treatments on all-cause, cardiovascular, or noncardiovascular death: “Compared with aspirin alone or short duration dual antiplatelet therapy (≤6 months), continued treatment was not associated with a difference in all-cause mortality (hazard ratio [HR] 1.05, 95% credible interval [CrI] 0.96–1.19; p = 0.33). Similarly, cardiovascular (1.01, 0.93–1.12; p = 0.81) and non-cardiovascular mortality (1.04, 0.90–1.26; p = 0.66) were no different with extended duration versus short duration dual antiplatelet therapy or aspirin alone.” (R. W. Yeh, ryeh@mgh.harvard.edu)

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2015; 350).
Standardized Company Dossier for New Drugs: Information required from pharmaceutical companies in Germany since 2011 is more complete than publicly available information in other European countries, a study shows (h796). Assessment of the company-supplied dossier (AMNOG) yields information on a drug’s added benefit using patient-relevant outcomes, the authors note. Comparison of AMNOG information with other sources from 2011 through early 2013 provided these results: “15 out of 27 dossiers were eligible for inclusion and contained 22 studies. The 15 dossier assessments contained 28 individual assessments of 15 total study populations and 13 approved subpopulations. European public assessment reports were available for all drugs. Journal publications were available for 14 out of 15 drugs and 21 out of 22 studies. A registry report in ClinicalTrials.gov was available for all drugs and studies; however, only 11 contained results. In the analysis of total study populations, the AMNOG documents reached the highest grade of completeness, with about 90% of methods and results items completely reported. In non-AMNOG documents, the rate was 75% for methods and 52% for results items; journal publications achieved the best rates, followed by European public assessment reports and registry reports. The analysis of approved subpopulations showed poorer complete reporting of results items, particularly in non-AMNOG documents (non-AMNOG versus AMNOG: 11% v 71% for overall results items and 5% v 70% for patient relevant outcomes). The main limitation of our analysis is the small sample size.” (B. Wieseler, beate.wieseler@iqwig.de)
Remifentanil During Labor: Compared with epidural analgesia during labor, patient-controlled analgesia using remifentanil was not equivalent based on satisfaction with pain relief scores, according to a crossover trial of 1,414 women (h846). The drug, a mu opioid-receptor agonist, was tested in women with intermediate to high likelihood of delivering vaginally, with these results: “Of women primarily treated with remifentanil, 13% (53/402) converted to epidural analgesia, while in women primarily treated with epidural analgesia 1% (3/296) converted to remifentanil. The area under the curve for total satisfaction with pain relief was 30.9 in the remifentanil group versus 33.7 in the epidural analgesia group (mean difference −2.8, 95% confidence interval −6.9 to 1.3). For who actually received pain relief the area under the curve for satisfaction with pain relief after the start of pain relief was 25.6 in the remifentanil group versus 36.1 in the epidural analgesia group (mean difference −10.4, −13.9 to −7.0). The rate of caesarean section was 15% in both groups.” (L. M. Freeman, l.m.freeman@lumc.nl)

>>>PNN JournalWatch
* Serum 25-Hydroxyvitamin D: A Predictor of Macrovascular and Microvascular Complications in Patients With Type 2 Diabetes, in
Diabetes Care, 2015; 38: 521–8. (A. C. Keech, fieldtrial@ctc.usyd.edu.au)
* Sleep Duration and Risk of Type 2 Diabetes: A Meta-analysis of Prospective Studies, in
Diabetes Care, 2015; 38: 529–37. (L. Liu, lgliu@mails.tjmu.edu.cn)
* Nonpharmacologic Treatment of Functional Abdominal Pain Disorders: A Systematic Review, in
Pediatrics, 2015; 135: 522–35. (J. M. T. M. Rutten)

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 3, 2015 * Vol. 22, No. 40
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 2 issue of the Annals of Internal Medicine (2015; 162).
Need for Smoking Cessation Among Patients With HIV: Tobacco screening and cessation strategies are important in the care of patients with HIV, conclude authors who found a high use in this group (pp. 335–44). Nationally representative cross-sectional surveys of 4,217 American adults with HIV and 27,731 general-population adults showed these patterns: “Of the estimated 419 945 adults with HIV receiving medical care, 42.4% (95% CI, 39.7% to 45.1%) were current cigarette smokers, 20.3% (CI, 18.6% to 22.1%) were former smokers, and 37.3% (CI, 34.9% to 39.6%) had never smoked. Compared with the U.S. adult population, in which an estimated 20.6% of adults smoked cigarettes in 2009, adults with HIV were nearly twice as likely to smoke (adjusted prevalence difference, 17.0 percentage points [CI, 14.0 to 20.1 percentage points]) but were less likely to quit smoking (quit ratio, 32.4% vs. 51.7%). Among adults with HIV, factors independently associated with greater smoking prevalence were older age, non-Hispanic white or non-Hispanic black race, lower educational level, poverty, homelessness, incarceration, substance use, binge alcohol use, depression, and not achieving a suppressed HIV viral load.” (M. Y. Sutton, msutton@cdc.gov)
Treatment of Pressure Ulcers: Evidence regarding the options for treating pressure ulcers is weak, the American College of Physicians reports in making three recommendations in a clinical practice guideline (pp. 370–9). The recommendations, all of them “weak,” advocate use of protein/amino acid supplements (low-quality evidence), hydrocolloid or foam dressings (low-quality evidence), and electrical stimulation as adjunctive therapy (moderate-quality evidence). (A. Qaseem, aqaseem@acponline.org)

>>>Internal Medicine Report
Source:
Mar. issue of JAMA Internal Medicine (2015; 175).
Overtreatment of Diabetes: A “substantial proportion” of older Americans with diabetes were overtreated in the 2001–10 decade, according to an analysis of data for 1,288 adults with the disease from the National Health and Nutrition Examination Survey (NHANES) (pp. 356–62). About one-half of participants were relatively healthy (representing 3.1 million Americans), one-quarter had intermediate/complex health (representing 1.7 million Americans), and one-fifth had very complex/poor health (representing 1.3 million Americans). Results showed the following: “Of the older adults with an HbA1c level of less than 7%, 54.9% (95% CI, 50.4%–59.3%) were treated with either insulin or sulfonylureas; this proportion was similar across health status categories (50.8% [95% CI, 45.1%–56.5%] were relatively healthy, 58.7% [95% CI, 49.4%–67.5%] had complex/intermediate health, and 60.0% [95% CI, 51.4%–68.1%] had very complex/poor health; P = .14). During the 10 study years, there were no significant changes in the proportion of older adults with an HbA1c level of less than 7% (P = .34), the proportion with an HbA1c level of less than 7% who had complex/intermediate or very complex/poor health (P = .27), or the proportion with an HbA1c level of less than 7% who were treated with insulin or sulfonylureas despite having complex/intermediate or very complex/poor health (P = .65).” (K. J. Lipska)
Strong Anticholinergics & Incident Dementia: “Higher cumulative anticholinergic use is associated with an increased risk for dementia,” the Seattle-based Adult Changes in Thought study in Group Health shows (pp. 401–7). Among 3,434 participants aged 65 or older at study entry in 1994–96 (with later continuous replacement for deaths), pharmacy records and biennial follow-up showed: “The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P <.001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74–1.16) for [total standardized daily doses (TSDDs)] of 1 to 90; 1.19 (95% CI, 0.94–1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94–1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21–1.96) for TSDDs greater than 1,095.” (S. L. Gray)

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 4, 2015 * Vol. 22, No. 41
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 3 issue of JAMA (2015; 313).
Sedatives Before General Anesthesia: Based on patients’ self-reports the day following elective surgeries, use of lorazepam as a sedative premedication had no significant effects compared with placebo or no medication, researchers report (pp. 916–25). In the PremedX study, 1,062 adults younger than 70 years were randomized to lorazepam 2.5 mg, no premedication, or placebo. Results on the Evaluation du Vécu de l’Anesthésie Generale (EVAN-G) questionnaire administered 24 hours after surgery showed the following: “Premedication with lorazepam did not improve the EVAN-G mean global index for overall level of patient satisfaction (72 [95% CI, 70–73]; n = 330) compared with no premedication (73 [95% CI, 71–74]; n = 319) or placebo (71 [95% CI, 70–73]; n = 322) (P = .38). Among patients with heightened preoperative anxiety, there were no significant differences found in the EVAN-G mean global index between the lorazepam group (68 [95% CI, 65–72]; n = 87) and the no premedication group (73 [95% CI, 69–77]; n = 57) or the placebo group (70 [95% CI, 67–72]; n = 87) (P = .18). Time to extubation was 17 minutes (95% CI, 14–20 minutes) in the lorazepam group, 12 minutes (95% CI, 11–13 minutes) for the no premedication group, and 13 minutes (95% CI, 12–14 minutes) for the placebo group (P < .001) and the rate of early cognitive recovery was 51% (95% CI, 45%–56%), 71% (95% CI, 66%–76%), and 64% (95% CI, 59%–69%), respectively (P < .001).” (A. Maurice-Szamburski)
Managing Irritable Bowel Syndrome: An “individualized, holistic approach”—with dietary, lifestyle, medical, and behavioral interventions—optimizes management of patients with irritable bowel syndrome (IBS), according to authors of a review article (pp. 949–58). Analysis of results of 139 articles led to this summary of diagnosis and management of the condition: “IBS is not a single disease but rather a symptom cluster resulting from diverse pathologies. Factors important to the development of IBS include alterations in the gut microbiome, intestinal permeability, gut immune function, motility, visceral sensation, brain-gut interactions, and psychosocial status. The diagnosis of IBS relies on symptom-based criteria, exclusion of concerning features (symptom onset after age 50 years, unexplained weight loss, family history of selected organic gastrointestinal diseases, evidence of gastrointestinal blood loss, and unexplained iron-deficiency anemia), and the performance of selected tests (complete blood cell count, C-reactive protein or fecal calprotectin, serologic testing for celiac disease, and age-appropriate colorectal cancer screening) to exclude organic diseases that can mimic IBS. Determining the predominant symptom (IBS with diarrhea, IBS with constipation, or mixed IBS) plays an important role in selection of diagnostic tests and treatments. Various dietary, lifestyle, medical, and behavioral interventions have proven effective in randomized clinical trials.” (W. D. Chey)
Medicaid Policies on Antipsychotic Prescribing to Children: With a concern about inappropriate prescribing of antipsychotic medications to children, 31 states have implemented prior authorization policies for second-generation antipsychotic prescribing, mostly within the past 5 years, and with most states applying their policies to children younger than 7 years of age, a study shows (pp. 966–8). Review of Medicaid prior-authorization policies showed that 31 states have implemented prior authorization policies for atypical antipsychotic prescribing to children, mostly within the past 5 years. Most states apply their policies to children younger than 5, 6, or 7 years of age. Only 7 states (Alabama, Kentucky, Maryland, Nevada, North Carolina, Pennsylvania, Tennessee) apply their policies to Medicaid-insured youth up to age 18 years. Seven other states (California, Colorado, Georgia, Mississippi, Nebraska, New York, Washington) have age-restriction criteria that vary by drug entity. Of the 31 states, 15 have incorporated a peer-review process, wherein the adjudication process usually involves a psychiatrist or other physician specialty. The programs without a peer-review process use automated systems or non-physician manual reviews for adjudication. (I. Schmid)

>>>PNN NewsWatch
* FDA is requiring changes to the labeling of testosterone products to warn of potentially increased risks of heart attacks and stroke.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 5, 2015 * Vol. 22, No. 42
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 5 issue of the New England Journal of Medicine (2015; 372).
Hepatitis E Vaccine: In China, a hepatitis E vaccine showed long-term efficacy in a trial of 112,604 adult patients younger than 66 years, researchers report (pp. 914–22). Participants received either hepatitis E vaccine or hepatitis B vaccine (control) at months 0, 1, and 6. They were followed initially for 19 months and then for 4.5 years on a double-blind basis, with these results: “During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person–years), and 53 cases in the control group (2.1 cases per 10,000 person–years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups.” (J. Zhang, zhangj@xmu.edu.cn)
Given this sustained response to hepatitis E vaccination, “now is the time to answer … remaining questions and establish the public health applications of a hepatitis E vaccine,” editorialists write (
pp. 899–901). “A hepatitis E vaccine could become a powerful new tool in the prevention and control of [hepatitis E virus (HEV)] transmission and disease. Most immediately, it can have a role in curbing outbreaks of hepatitis E in humanitarian crises. The benefits of broad adoption of hepatitis E vaccine could be far-reaching, if studies reveal that vaccination protects against all HEV genotypes and is safe and effective when used in people at highest risk for hepatitis E–related illness and death, including pregnant women.” (E. Teshale)
Goserelin During Breast-Cancer Adjuvant Chemotherapy: The gonadotropin-releasing hormone agonist goserelin, given during adjuvant therapy of 257 women with breast cancer, protected against ovarian failure, thereby “reducing the risk of early menopause and improving prospects for fertility,” investigators conclude (pp. 923–32). The study used a primary end point of rate of ovarian failure (absence of menses in preceding 6 months and levels of follicle-stimulating hormone [FSH] in the postmenopausal range) at 2 years. Results for 135 patients with complete data showed the following: “The ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P = 0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P = 0.03); women in the goserelin group also had improved disease-free survival (P = 0.04) and overall survival (P = 0.05).” (H. C. F. Moore, mooreh1@ccf.org)
Valganciclovir in Congenital CMV: Longer-term outcomes were better with 6 months of valganciclovir treatment of congenital cyclomegalovirus (CMV), compared with 6 weeks of therapy, even though short-term outcomes were equivocal, a study shows (pp. 933–43). Among 96 neonates, best-ear hearing function was improved at 24 months with longer therapy, as were neurodevelopmental scores and results on the receptive-communication scale. Grade 3 or 4 neutropenia occurred in 19% of patients during the first 6 weeks of therapy and in 21% of those on the drug for 6 months; the adverse effect was more common (27%) after the drug was stopped in the 6-week group. (D. W. Kimberlin, adkimberlin@peds.uab.edu)

>>>PNN NewsWatch
* FDA yesterday expanded the approved use of nivolumab (Opdivo, Bristol-Myers Squibb) to include treatment of patients with advanced squamous non-small-cell lung cancer with progression on or after platinum-based chemotherapy.
* An
FDA Drug Shortages app was launched yesterday, the agency said. The app identifies current drug shortages, resolved shortages and discontinuations of drug products.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 6, 2015 * Vol. 22, No. 43
Providing news and information about medications and their proper use

>>>Psychiatry Highlights
Source:
Mar. issue of the American Journal of Psychiatry (2015; 172).
Initial Schizophrenia Therapy: Insurance status was a significant predictor of medication choice for 404 patients with first-episode schizophrenia, a study shows (pp. 237–48). Based on findings in the nationwide Recovery After an Initial Schizophrenia Episode Project’s Early Treatment Program (RAISE-ETP), authors concluded, “Besides prescriber education, policy makers may need to consider not only patient factors but also service delivery factors in efforts to improve prescription practices for first-episode schizophrenia patients.” They report, “Nearly 40% of the sample “might [have benefited] from changes in their psychotropic prescriptions. Of these, 8.8% received prescriptions for recommended antipsychotics at higher than recommended dosages; 32.1% received prescriptions for olanzapine (often at high dosages), 23.3% for more than one antipsychotic, 36.5% for an antipsychotic and also an antidepressant without a clear indication, 10.1% for psychotropic medications without an antipsychotic, and 1.2% for stimulants. Multivariate analysis showed evidence for sex, age, and insurance status effects on prescription practices. Racial and ethnic effects consistent with effects reported in previous studies of multiepisode patients were found in univariate analyses. Despite some regional variations in prescription practices, no region consistently had different practices from the others. Diagnosis had limited and inconsistent effects.” (D. G. Robinson)
In treating schizophrenia, “the use of principles of shared decision making, in which patients and their families are engaged in a comprehensive discussion of the risks and benefits of different medication choices, is essential,” editorialists write (
pp. 209–11). “Only in this context can individuals make well-informed decisions about whether to take medications, which medication to take, and at what dosage and for how long. Unfortunately, the available information, particularly about medication choice, dosage, and duration, is limited. Further research on how best to provide services and prescribe medications for individuals early in the course of psychotic illness is direly needed.” (L. B. Dixon)

>>>Pediatric Reports
Source:
Mar. issue of Pediatrics (2015; 135).
Medication-Related Pediatric ED Visits: One of every 12 visits by pediatric patients to emergency departments (EDs) is medication related, Canadian researchers report (pp. 435–43). Over a 12-month period, authors, report that “2,028 patients were enrolled (mean age, 6.1 ± 5.0 years; girls, 47.4%). [A medication-related visit (MRV)] was found in 163 patients (8.0%; 95% confidence interval [CI]: 7.0%–9.3%) of which 106 (65.0%; 95% CI: 57.2%–72.3%) were deemed preventable. Severity was classified as mild in 14 cases (8.6%; 95% CI: 4.8%–14.0%), moderate in 140 cases (85.9%; 95% CI: 79.6%–90.8%), and severe in 9 cases (5.5%; 95% CI: 2.6%–10.2%). The most common events were related to adverse drug reactions 26.4% (95% CI: 19.8%–33.8%), subtherapeutic dosage 19.0% (95% CI: 13.3%–25.9%), and nonadherence 17.2% (95% CI: 11.7%–23.9%). The probability of hospital admission was significantly higher among patients with an MRV compared with those without an MRV (odds ratio, 6.5; 95% CI: 4.3–9.6) and, if admitted, the median (interquartile range) length of stay was longer (3.0 [5.0] days vs 1.5 [2.5] days, P = .02).” (P. J. Zed)
Vaccines & Invasive Pneumococcal Disease: Invasive pneumococcal diseases (IPD) producing mortality in children are often caused by serotypes not in either vaccine or serotypes in the 23-valent product not in the 13-valent vaccine, a study shows (pp. 495–503). From 2002 to 2014 in Massachusetts, surveillance yielded 1,052 IPD cases with these characteristics: “Immunocompromising conditions (32.7%) and chronic respiratory diseases (22.4%) were [the] most common [comorbidities]. Children with comorbidities were older at the time of IPD diagnosis (median 54 vs 23 months, P < .001), had higher hospitalization (odds ratio 2.5; 95% confidence interval 1.7–3.6) and case-fatality rates (odds ratio 3.7; 95% confidence interval 1.5–8.9).… During the last 2 years of the study, IPD among children with comorbidities was caused by non–pneumococcal conjugate vaccine 13 serotypes in 23-valent polysaccharide pneumococcal vaccine (6/12, 50%) or serotypes that are not included in any of the vaccines (6/12; 50%).” (I. Yildirim)

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 9, 2015 * Vol. 22, No. 44
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 7 issue of Lancet (2015; 385).
Roflumilast in COPD: In 1,945 high-risk patients with chronic obstructive pulmonary disease (COPD), use of roflumilast reduced exacerbations and hospital admissions, compared with placebo, in the REACT trial (pp. 857–66). Participants had severe COPD and were at risk of exacerbations despite inhaled corticosteroid and long-acting beta-2 agonist treatment. Therapy with oral roflumilast 500 mcg or placebo once daily with fixed-dose inhaled corticosteroid and long-acting beta-2 agonist showed these outcomes: “The rate of moderate-to-severe chronic obstructive pulmonary disease exacerbations was 13.2% lower in the roflumilast group than in the placebo group according to a Poisson regression analysis (roflumilast 0.805 vs placebo 0.927; rate ratio [RR] 0.868 [95% CI 0.753–1.002], p = 0.0529), and 14.2% lower according to a predefined sensitivity analysis using negative binomial regression (0.823 vs 0.959; 0.858 [0.740–0.995], p = 0.0424). Adverse events were reported by 648 (67%) of 968 patients receiving roflumilast and by 572 (59%) of 967 patients in the placebo group; adverse event-associated patient withdrawal from the study was also more common in the roflumilast group (104/968 [11%]) than in the placebo group (52/967 [5%]). The most frequently reported serious adverse events were chronic obstructive pulmonary disease exacerbations and pneumonia, and 17 (1.8%) deaths occurred in the roflumilast group compared with 18 (1.9%) in the placebo group.” (F. J Martinez, fmartine@med.umich.edu)
Antibiotic Duration for Vertebral Osteomyelitis: In an open-label noninferiority trial, 6 weeks of antibiotics worked just as well as 12 weeks for treating 359 patients with pyogenic vertebral osteomyelitis, researchers report (pp. 875–82). At 71 French medical centers, these results were produced: “160 (90.9%) of 176 patients in the 6-week group and 159 (90.9%) of 175 of those in the 12-week group met the criteria for clinical cure. The difference between the groups (0.05%, 95% CI −6.2 to 6.3) showed the non-inferiority of the 6-week regimen when compared with the 12-week regimen. 50 patients in the 6-week group and 51 in the 12-week group had adverse events, the most common being death (14 [8%] in the 6-week group vs 12 [7%] in the 12-week group), antibiotic intolerance (12 [7%] vs 9 [5%]), cardiorespiratory failure (7 [4%] vs 12 [7%]), and neurological complications (7 [4%] vs 3 [2%]).” (L. Bernard, lbernard@univ-tours.fr)

>>>PNN NewsWatch
* FDA on Friday approved its first biosimilar product. Filgrastim-sndz (Zarxio, Sandoz) is biosimilar to Neupogen (Amgen), FDA said, and is therefore approved for the same indications as that product. FDA has not yet decided how biosimilar products will be named generically; “filgrastim-sndz” is a “placeholder nonproprietary name,” the agency said.
*
Isavuconazonium sulfate (Cresemba, Astellas) on Friday became the sixth agent approved by FDA and designated as a Qualified Infectious Disease Product. The azole antifungal drug product is indicated for treatment of adults with invasive aspergillosis and invasive mucormycosis. The agent, a prodrug for isavuconazole, is effective orally or intravenously for these life-threatening infections.

>>>PNN JournalWatch
* A Proposal to Incorporate Trial Data Into a Hybrid ACC/AHA Algorithm for the Allocation of Statin Therapy in Primary Prevention, in
Journal of the American College of Cardiology, 2015; 65: 942–8. (P. M. Ridker)
* Back to the Future: Improving Use of Guidelines-Recommended Coronary Disease Secondary Prevention at the Dawn of the Precision Medicine Era, in
Circulation, 2015; 10.1161/circulationaha.115.015707. (K. Newby, kristin.newby@duke.edu)
* KDOQI US Commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD, in
American Journal of Kidney Diseases, 2015; 65: 354–66. (M. J. Sarnak, msarnak@tuftsmedicalcenter.org)
* Bronchoconstriction and Airway Biology: Potential Impact and Therapeutic Opportunities, in
Chest, 2015; 147: 798–803. (R. Gosens, r.gosens@rug.nl)
* Tools for Assessing Outcomes in Studies of Chronic Cough: CHEST Guideline and Expert Panel Report, in
Chest, 2015; 147: 804–14. (L-P Boulet, lpboulet@med.ulaval.ca)
* Ovarian Hormone Fluctuation, Neurosteroids, and HPA Axis Dysregulation in Perimenopausal Depression: A Novel Heuristic Model, in
American Journal of Psychiatry, 2015; 172: 227–36. (J. L. Gordon)

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 10, 2015 * Vol. 22, No. 45
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Early-release articles from JAMA Internal Medicine (2015; 175).
Stepped-Care for Veterans With Chronic Pain: In 241 veterans of the Iraqi and Afghan conflicts, a stepped-care intervention using “analgesics, self-management strategies, and brief cognitive behavioral therapy resulted in statistically significant reductions in pain-related disability, pain interference, and pain severity in veterans with chronic musculoskeletal pain,” a study shows (doi: 10.1001/jamainternmed.2015.97). The two-step intervention included 12 weeks of analgesic treatment with optimization based on patient self-reports followed by 12 weeks of cognitive behavioral therapy. Nurse care managers delivered the interventions, and results were compared with usual care in randomized fashion.
Results showed: “The primary analysis included 121 patients receiving the stepped-care intervention and 120 patients receiving usual care. At 9 months, the mean decrease from baseline in the Roland Morris Disability Scale score was 1.7 (95% CI, −2.6 to −0.9) points in the usual care group and 3.7 (95% CI, −4.5 to −2.8) points in the intervention group (between-group difference, −1.9 [95% CI, −3.2 to −0.7] points; P = .002). The mean decrease from baseline in the Pain Interference subscale score of the Brief Pain Inventory was 0.9 points in the usual care group and 1.7 points in the intervention group (between-group difference, −0.8 [95% CI, −1.3 to −0.3] points; P = .003). The Graded Chronic Pain Scale severity score was reduced by 4.5 points in the usual care group and 11.1 points in the intervention group (between-group difference, −6.6 [95% CI, −10.5 to −2.7] points; P = .001).” (M. J. Bair,
Matthew.Bair@va.gov)
Cognitive Decline in Older Patients with Low Blood Pressure During Antihypertensive Therapy: In a cohort study of 172 older patients with dementia or mild cognitive impairment (MCI), the decline in mental acuity was greater in those treated with antihypertensive drugs (AHDs) (doi: 10.1001/jamainternmed.2014.8164): “Patients in the lowest tertile of daytime systolic blood pressure (SBP) (≤128 mm Hg) showed a greater [Mini-Mental State Examination (MMSE)] score change (mean [SD], −2.8 [3.8]) compared with patients in the intermediate tertile (129–144 mm Hg) (mean [SD], −0.7 [2.5]; P = .002) and patients in the highest tertile (≥145 mm Hg) (mean [SD], −0.7 [3.7]; P = .003). The association was significant in the dementia and MCI subgroups only among patients treated with AHDs.” (E. Mossello)

>>>Kidney Disease Highlights
Source:
Mar. issue of the American Journal of Kidney Diseases (2015; 65).
3% Sodium Chloride Treatment of Hyponatremic Encephalopathy: Administered in the emergency department, adult patients presenting with hyponatremic encephalopathy (sodium levels <130 meq/L) with neurologic symptoms indicating increased intracranial pressure were effectively treated with continuous infusions of 500 mL of 3% sodium chloride injection over a 6-h period, researchers report (pp. 435–42). In a case series analysis of 71 episodes of hyponatremic encephalopathy in 64 patients, the authors found these outcomes: “Baseline mean serum sodium level was 114.1 ± 0.8 (SEM) mEq/L and increased to 117.9 ± 1.3, 121.2 ± 1.2, 123.9 ± 1.0, and 128.3 ± 0.8 mEq/L at 3, 12, 24, and 48 hours following the initiation of 3% sodium chloride solution treatment, respectively. There was a marked improvement in central nervous system symptoms within hours of therapy in 69 of 71 (97%) episodes. There were 12 deaths, all of which occurred following the resolution of hyponatremic encephalopathy and were related to comorbid conditions, with 75% of deaths related to sepsis. No patient developed neurologic symptoms consistent with cerebral demyelination at any point during the 6-month follow-up period.” (J. C. Ayus, carlosayus@yahoo.com)

>>>PNN NewsWatch
* FDA yesterday approved the ResQCPR System (Advance Circulatory Systems), which consists of two devices for first responders to use in performing cardiopulmonary resuscitation (CPR) on people in cardiac arrest. The devices may improve the patient’s chances of surviving cardiac arrest, FDA said, by impeding airflow into the chest during chest decompressions. This increases oxygenated blood in circulation.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 11, 2015 * Vol. 22, No. 46
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 10 issue of JAMA (2015; 313).
Familial Hypercholesterolemia & Type 2 Diabetes: The genes causing familial hypercholesterolemia may be protective against type 2 diabetes, according to a cross-sectional analysis of all 63,320 individuals in the Netherlands who were screened using DNA testing (pp. 1029–36). These patterns of familial hypercholesterolemia and comorbidities were identified: “The prevalence of type 2 diabetes was 1.75% in familial hypercholesterolemia patients (n = 440/25,137) vs 2.93% in unaffected relatives (n = 1119/38,183) (P < .001; odds ratio [OR], 0.62 [95% CI, 0.55–0.69]). The adjusted prevalence of type 2 diabetes in familial hypercholesterolemia, determined using multivariable regression models, was 1.44% (difference, 1.49% [95% CI, 1.24%–1.71%]) (OR, 0.49 [95% CI, 0.41–0.58]; P < .001). The adjusted prevalence of type 2 diabetes by [apolipoprotein B] vs LDL receptor gene was 1.91% vs 1.33% (OR, 0.65 [95% CI, 0.48–0.87] vs OR, 0.45 [95% CI, 0.38–0.54]), and the prevalence for receptor-deficient vs receptor-negative mutation carriers was 1.44% vs 1.12% (OR, 0.49 [95% CI, 0.40–0.60] vs OR, 0.38 [95% CI, 0.29–0.49]), respectively (P for trend <.001 in both comparisons).” (J. J. P. Kastelein, j.j.kastelein@amc.nl)
“This report adds to the growing literature of a complex interplay between lipids, glycemia, and adiposity, in which statins and other lipid-modifying agents appear to affect diabetes risk,” editorialists write (
pp. 1016–7). “From a clinical perspective, the findings should allay any concerns about the potential diabetogenic effect of statins when treating patients with familial hypercholesterolemia from childhood or young adulthood given that these patients appear to be at a low risk for diabetes. Most intriguingly, the results suggest that the expression and function of LDL receptors may be important for glucose homeostasis.… The advent of potent LDL cholesterol–lowering agents such as PCSK9 inhibitors provides an important opportunity to further examine the link between LDL receptor expression and glycemia, adiposity, and diabetes risk.” (D. Preiss, david.preiss@glasgow.ac.uk)
Evaluating New Anticoagulant Recommendations: Noting that 60 years elapsed between approval of warfarin by FDA and understanding how to dose the drug optimally, an editorialist asks, “How long will it take clinicians to understand how to optimally dose the new thrombin and factor Xa inhibitors in all patients?” (pp. 1013–4). “Even though the one-size-fits-all [direct-acting oral anticoagulant (DOAC)] dosing may perform as well as or better than warfarin on average, evidence suggests that patient safety can be further improved through individualized dosing. It is not a coincidence that 3 US-marketed DOACs share the same strategy of 1 dose for all patients and no need for laboratory testing. This is in part the marketing profile each company used at the drug discovery phase that then guided development decisions through phase 3 trial design, execution, and New Drug Application submission. Consequently, the FDA decisions to approve the drugs and the labeled dosing guidelines usually conform to those used in the pivotal phase 3 trials.” (J. R. Powell, bob.powell49@gmail.com)

>>>PNN NewsWatch
* FDA yesterday approved dinutuximab (Unituxin, United Therapeutics) as part of first-line therapy for pediatric patients with high-risk neuroblastoma. The drug was approved for use in combination with granulocyte–macrophage colony-stimulating factor, interleukin-2, and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. An orphan drug, dinutuximab was evaluated in clinical trials of 226 pediatric participants with high-risk neuroblastoma whose tumors shrunk or disappeared after treatment with multiple-drug chemotherapy and surgery followed by additional intensive chemotherapy and who subsequently received bone marrow transplantation support and radiation therapy. After 3 years, 63% of those on dinutuximab were alive and disease-free, compared with 46% of those on RA. The product has a boxed warning cautioning of serious infusion reactions, neuropathy, and neuropathic pain, and offers guidance on how the drug should be administered and actions to take if serious reactions occur.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 12, 2015 * Vol. 22, No. 47
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 12 issue of the New England Journal of Medicine (2015; 372).
Retail Aspects of Legalized Marijuana: Two Perspective articles examine events in states with legalized recreational use of marijuana.
With names such as Munchy Way and Buddahfinger, edible marijuana products “mimic popular candies and other sweets” and “are likely to appeal children and young adults,” authors write, even though sale to those under 21 is illegal (
pp. 989–91). “Because legal channels are available to address the problems with marijuana edibles, such issues are not an argument against legalizing marijuana. Indeed, one potential advantage of legalization is that it provides more regulatory levers than are available under prohibition. Rather, the edibles problem is an argument against implementing legalization before an appropriate regulatory framework is in place. Though the ingenuity and swiftness with which manufacturers have formulated the new edibles have been surprising, the general problem was predictable. As legalization of marijuana spreads, new adopters should ensure that their regulatory scheme for marijuana edibles is fully baked.” (R. J. MacCoun)
Colorado is using the lessons learned during the years when medical marijuana was available to address public health concerns created by availability of retail marijuana, according to a second article (
pp. 991–3). Focusing on adverse effects of edible products and impaired driving, the authors note: “States where medical marijuana is legal have been shown to have higher rates of calls to poison-control centers for unintentional marijuana exposure in children under 9 years of age, and more patients sought care at a Denver-area children’s hospital because of unintentional marijuana use after medical marijuana became commercially available. These findings suggest that greater availability of marijuana, particularly in edible products, can increase risks to young children. Already, since retail sales began in 2014, the Rocky Mountain Poison and Drug Center has received over 70% more calls related to marijuana exposure than it did in 2013.…
“To address impaired driving, Colorado passed legislation setting a limit of 5 ng of delta-9 [tetrahydrocannabinol] per milliliter of blood at which drivers are considered to be operating under the influence. The Colorado Department of Transportation launched a public education campaign about impaired driving in 2014. In addition, Colorado has added questions on marijuana use during driving to population-based surveys on behaviors and is adding marijuana-use questions to its trauma registry to elucidate the impact of marijuana legalization on injuries related to impairment.” (T. S. Ghosh)
Timely Reports of Results to ClinicalTrials.gov: Most principal investigators of highly likely applicable clinical trials (HLACTs) did not meet legal and ethical obligations to report results promptly to the ClinicalTrials.gov website, researchers report (pp. 1031–9). Analysis of 13,327 HLACTs (77.4% of them drug trials) completed or terminated in 2008–13 showed these patterns of reports: “A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health and 9% of trials that were funded by other government or academic institutions.” (M. L. Anderson, monique.anderson@duke.edu)

>>>PNN NewsWatch
* A consent decree entered on Tuesday prohibits Specialty Compounding, LLC, of Cedar Park, TX, and its owners from manufacturing, holding, or distributing sterile drugs until they comply with the Federal Food, Drug, and Cosmetic Act and its regulations, in addition to other requirements, FDA said in a news release. The action stems from an Aug. 2013 incident in which FDA received reports from two Texas hospitals that 17 patients had developed bacterial bloodstream infections after receiving an infusion of the drug calcium gluconate manufactured by Specialty Compounding, 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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 13, 2015 * Vol. 22, No. 48
Providing news and information about medications and their proper use

>>>Infectious Diseases Report
Source:
Apr.1 issue of Clinical Infectious Diseases (2015; 60).
Micafungin in Invasive Fungal Infection After Liver Transplant: In posttransplant patients with liver grafts who were at high risk of invasive fungal infection (IFI), micafungin prophylaxis was noninferior to standard care, researchers report, and kidney function was better with micafungin (pp. 997–1006). The open-label trial used random allocation to i.v. micafungin 100 mg or center-specific standard care that included fluconazole, liposomal amphotericin B, or caspofungin. Results showed: “The full analysis set comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease score ≥20. At [end of prophylaxis (EOP)] (mean treatment duration, 17 days), clinical success was 98.6% for micafungin and 99.3% for standard care (∆ standard care – micafungin [95% confidence interval], 0.7% [−2.7% to 4.4%]) in the per protocol set and 96.5% and 93.6%, respectively (−2.9% [−8.0% to 1.9%]), in the full analysis set. Incidences of drug-related adverse events for micafungin and standard care were 11.6% and 16.3%, leading to discontinuation in 6.4% and 11.6% of cases, respectively. At EOP, liver function tests were similar but creatinine clearance was higher in micafungin- vs standard care–treated patients.” (F. Saliba, faouzi.saliba@pbr.aphp.fr)
Fatal Infection From Vaccine Strain Varicella-Zoster Virus: A situation in which varicella-zoster virus live attenuated vaccine should not be used is illustrated by a case of disseminated, persistent, and fatal zoster caused by the vaccine strain of the virus (pp. 1068–70): “A middle-aged [immunocompromised] man with non-Hodgkin lymphoma received chemotherapy and a stem cell transplant. He was vaccinated 4 years post-transplantation, despite diagnosis of a new low-grade lymphoma confined to the lymph nodes. Within 3 months of vaccination, he developed recurrent rashes with fever, malaise, weakness, hepatitis, weight loss, and renal failure. The syndrome was eventually determined to be associated with persistent disseminated zoster caused by the vaccine virus.” (A. A. Gershon, aag1@cumc.columbia.edu)

>>>Oncology Highlights
Source:
Mar. issue of the Journal of Clinical Oncology (2015; 33).
Electronic Nicotine Delivery Systems: In a policy statement, the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) support a number of measures for regulating and controlling access to electronic nicotine delivery systems (ENDS), including electronic cigarettes (pp. 952–63): “ENDS use by both adults and youth has increased rapidly, and some have advocated these products could serve as harm-reduction devices and smoking cessation aids. ENDS may be beneficial if they reduce smoking rates or prevent or reduce the known adverse health effects of smoking. However, ENDS may also be harmful, particularly to youth, if they increase the likelihood that nonsmokers or former smokers will use combustible tobacco products or if they discourage smokers from quitting. [AACR and ASCO] recognize the potential ENDS have to alter patterns of tobacco use and affect the health of the public; however, definitive data are lacking. The AACR and ASCO recommend additional research on these devices, including assessing the health impacts of ENDS, understanding patterns of ENDS use, and determining what role ENDS have in cessation. Key policy recommendations include supporting federal, state, and local regulation of ENDS; requiring manufacturers to register with the US Food and Drug Administration and report all product ingredients, requiring childproof caps on ENDS liquids, and including warning labels on products and their advertisements; prohibiting youth-oriented marketing and sales; prohibiting child-friendly ENDS flavors; and prohibiting ENDS use in places where cigarette smoking is prohibited.” (R. S. Herbst, roy.herbst@yale.edu)
Views on Medicare Cuts: In a survey of patients, physicians, and the public, most respondents thought costs could be reduced in the Medicare system without affecting quality of care (pp. 846–53). “Overall, respondents strongly favored not paying for more expensive treatments when cheaper ones are equally effective,” the authors report based on responses of 326 patients, 225 oncologists, and 891 members of the general public. (K. Gogineni, kgogineni1@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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 16, 2015 * Vol. 22, No. 49
Providing news and information about medications and their proper use

>>>BMJ Highlights
Source:
Early-release articles from BMJ (2015; 350).
TNF Inhibitors in Rheumatoid Arthritis: Noninferior results and lower costs are possible in patients with established rheumatoid arthritis treated with combinations of synthetic disease-modifying drugs in place of tumor-necrosis factor (TNF) inhibitors, according to an open-label pragmatic randomized trial (h1046). Over 12 months at 24 English rheumatology clinics, 205 patients had these results based on a primary outcome of patient-rated reduction in disability at 12 months: “The primary outcome showed mean falls in scores on the health assessment questionnaire of −0.30 with the tumour necrosis factor inhibitor strategy and −0.45 with the alternative combined drug strategy. The difference between groups in unadjusted linear regression analysis favoured the alternative strategy of combined drugs. The mean difference was −0.14, and the 95% confidence interval (−0.29 to 0.01) was below the prespecified non-inferiority boundary of 0.22. Improvements at 12 months in secondary outcomes, including quality of life and erosive progression, were similar with both strategies. Initial reductions in disease activity were greater with the biologic strategy, but these differences did not persist beyond six months. Remission was seen in 72 patients (44 with biologic strategy; 36 with alternative strategy); 28 patients had serious adverse events (18 and 10, respectively); six and 10 patients, respectively, stopped treatment because of toxicity. The alternative strategy reduced health and social care costs per patient by £3615 (4930 euros, $5585) for months 0-6 and £1930 for months 6-12.” (D. L. Scott, d.scott1@nhs.net)
Drug Interactions in NICE Guidelines: After reviewing drug–drug and drug–disease interactions produced by following clinical guidelines of the U.K. National Institute of Health and Care Excellence (NICE), authors conclude that “the extensive number of potentially serious interactions requires innovative interactive approaches to the production and dissemination of guidelines to allow clinicians and patients with multimorbidity to make informed decisions about drug selection” (h949). The authors also note that many interactions are premised on presence of chronic kidney disease and recommend that “guideline developers … consider a more systematic approach regarding the potential for drug–disease interactions, based on epidemiological knowledge of the comorbidities of people with the disease the guideline is focused on, and … particularly consider whether chronic kidney disease is common in the target population.” (B. Guthrie, B.Guthrie@dundee.ac.uk)
Neuropsychiatric Adverse Events With Varenicline: Systematic review and meta-analysis of 39 randomized controlled trials of 10,761 participants show that varenicline use is not associated with increased risk of “suicide or attempted suicide, suicidal ideation, depression, or death,” researchers report (h1109). Only the already-recognized problems with sleep and abnormal dreams emerged in the analysis, summarized as follows by the authors: “There was no evidence of an increased risk of suicide or attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57), suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22), irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users. Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29 to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77), and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to 0.93). Similar findings were observed when risk differences were reported. There was no evidence for a variation in depression and suicidal ideation by age group, sex, ethnicity, smoking status, presence or absence of psychiatric illness, and type of study sponsor (that is, pharmaceutical industry or other).” (K. H. Thomas, kyla.thomas@bristol.ac.uk)

>>>PNN JournalWatch
* The Path to an Angiotensin Receptor Antagonist-Neprilysin Inhibitor in the Treatment of Heart Failure, in
Journal of the American College of Cardiology, 2015; 65: 1029–41. (E. Braunwald)
* Secondary Prevention After Coronary Artery Bypass Graft Surgery: A Scientific Statement From the American Heart Association, in
Circulation, 2015; 131: 927–64. (A. Kulik)

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 17, 2015 * Vol. 22, No. 50
Providing news and information about medications and their proper use

>>>Internal Medicine Report
Source:
Mar. 17 issue of the Annals of Internal Medicine (2015; 162).
Cost-Effectiveness Analysis of Hepatitis C Therapies: Two studies examine the relative costs and benefits of hepatitis C virus (HCV) treatments.
Treatments for HCV are cost-effective in most patients, according to an analysis conducted from the perspective of a third-party payer with a lifetime horizon (
pp. 397–406). However, short-term expenditures would far exceed benefits if large numbers of patients were treated in the next 5 years, the study shows: “Sofosbuvir-based therapies added 0.56 [quality-adjusted life–year (QALY)] relative to the [old standard of care (oSOC)] at an [incremental cost-effectiveness ratio (ICER)] of $55,400 per additional QALY. The ICERs ranged from $9,700 to $284,300 per QALY depending on the patient’s status with respect to treatment history, HCV genotype, and presence of cirrhosis. At a willingness-to-pay threshold of $100,000 per QALY, sofosbuvir-based therapies were cost-effective in 83% of treatment-naive and 81% of treatment-experienced patients. Compared with the oSOC, treating eligible HCV-infected persons in the United States with the new drugs would cost an additional $65 billion in the next 5 years, whereas the resulting cost offsets would be $16 billion.” (J. Chhatwal, JChhatwal@mdanderson.org)
Taking a lifetime time horizon and societal perspective, treatments for HCV vary in their cost-effectiveness depending on genotype, researchers report (
pp. 407–19). “Novel treatments for HCV are cost-effective compared with usual care for genotype 1 and probably genotype 3 but not for genotype 2,” the group concludes based on these findings in the base-case and sensitivity analyses: “Assuming sofosbuvir, simeprevir, daclatasvir, and ledipasvir cost $7,000, $5,500, $5,500, and $875 per week, respectively, sofosbuvir–ledipasvir was cost-effective for genotype 1 and cost $12,825 more per QALY than usual care. For genotype 2, sofosbuvir–ribavirin and sofosbuvir–daclatasvir cost $110,000 and $691,000 per QALY, respectively. For genotype 3, sofosbuvir–ledipasvir–ribavirin cost $73,000 per QALY, sofosbuvir–ribavirin was more costly and less effective than usual care, and sofosbuvir–daclatasvir cost more than $396,000 per QALY at assumed prices.
“Sofosbuvir–ledipasvir was the optimal strategy in most simulations for genotype 1 and would be cost-saving if sofosbuvir cost less than $5,500. For genotype 2, sofosbuvir–ribavirin–PEG would be cost-saving if sofosbuvir cost less than $2,250 per week. For genotype 3, sofosbuvir–ledipasvir–ribavirin would be cost-saving if sofosbuvir cost less than $1,500 per week.” (N. K. Choudhry,
nchoudhry@partners.org)

>>>PNN NewsWatch
* At the American College of Cardiology’s 64th Annual Scientific Session in San Diego, investigators yesterday reported that patients with obesity and atrial fibrillation had a significantly greater chance of achieving control of their heart disorder when they lost at least 10% of their body weight. Among 355 participants in the study, 45% of patients who lost 10% or more of their body weight and 22% of patients who lost 3%–9% of their weight achieved freedom from atrial fibrillation symptoms without the use of any atrial fibrillation surgery or medication. Only 13% of patients who lost less than 3% of their body weight were free of symptoms without these treatments. Even with the use of surgery or medication, those who lost more weight were substantially more likely to achieve freedom from atrial fibrillation symptoms.
* Added to aspirin therapy after myocardial infarction (MI),
ticagrelor reduced the rate of subsequent death from cardiovascular causes, according to another paper presented at ACC. In the PEGASUS-TIMI 54 trial, 21,162 patients with MI in the prior 1–3 years were randomized to ticagrelor 60 or 90 mg twice daily or placebo. Both ticagrelor doses reduced the chances of cardiovascular death, MI, or stroke, the study’s primary endpoint, with a 15% reduction in the 90-mg group and a 16% reduction in the 60-mg group compared with the placebo group. Dyspnea was more common with ticagrelor than placebo. Bleeding led to discontinuation of ticagrelor in about 7% of patients on the study drug, and dyspnea led to discontinuation of the study drug in about 5% of patients on the drug.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 18, 2015 * Vol. 22, No. 51
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 17 issue of JAMA (2015; 313).
Genes & ASA/NSAID Chemoprevention of Colorectal Cancer: Risk of colorectal cancer was reduced among patients regularly taking aspirin and/or other nonsteroidal anti-inflammatory drugs (NSAIDs), a genomewide investigation shows, and associations varied based on two single-nucleotide polymorphisms (SNPs) on chromosomes 12 and 15 (pp. 1133–42). The analysis included people of European descent in five case–control and five cohort studies from the U.S., Canada, Australia, and Germany. Between 1976 and 2003, these associations were noted among 8,634 patients with colorectal cancer (cases) and 8.553 matched controls: “Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64–0.74]; P =  6.2 × 10−28) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 × 10−9 for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61–0.70]; P = 7.7 × 10−33) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27–2.81]; P =  .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 × 10−9 for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62–0.71]; P = 1.9 × 10−30) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78–1.20]; P = .76).” (L. Hsu, lih@fredhutch.org)
These findings shed light on the possibilities for genetic personalization of preventive therapies, an editorialist writes (
pp. 1111–2): “In the not-too-distant future it will be possible to affordably and efficiently conduct genetic testing in healthy individuals to more accurately define benefits and risks of interventions intended to decrease risk of disease. It will be important for primary care clinicians to understand genetic risk and to have informed, clear, literacy-adjusted, culturally competent discussions with their patients about how to use this information; otherwise, the goal of using genetic information to enhance decision making about prevention will remain elusive. Research needs to test different approaches to translating this complex information into practical methods to share information and improve clinical decisions. The ability to translate genetic profiling into tailored preventive care plans for individuals is still years away, but with the [above] study, the road, arduous as it may be, is more clearly illuminated.” (R. C. Wender, richard.wender@cancer.org)
People, Politics & Vaccines: Parents have a right to voice concern over vaccines, writes a Viewpoint author, but the state can enforce mandatory immunizations by exercising its police powers in the protection of public health (pp. 1099–100): “A small fraction of parents categorically oppose vaccinations, but many others are concerned primarily with state mandates. For these parents, a ‘nudge’ may be all that is required, such as being informed of the science and making exemptions for immunizations more difficult to obtain. The uptake of vaccines, moreover, is associated with perceived susceptibility to and severity of childhood diseases. The catch-22 is that because vaccines are such powerful tools of prevention, individuals are less inclined to vaccinate their children because they rarely see vaccine-preventable childhood diseases.” (L. O. Gostin)

>>>PNN NewsWatch
* FDA yesterday approved cholic acid (Cholbam, Asklepion Pharmaceuticals) capsules, the first FDA-approved treatment for pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders (including Zellweger spectrum disorders). The product, approved under a “rare pediatric disease priority review,” FDA said, can be used in children as young as 3 weeks and in adults.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 19, 2015 * Vol. 22, No. 52
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 19 New England Journal of Medicine (2015; 372).
Antibiotics for Uncomplicated Skin Infections: In 524 adults and children with community-acquired methicillin-resistant Staphylococcus aureus (MRSA), results were similar with 10 days of clindamycin or trimethoprim–sulfamethoxazole (TMP-SMX), researchers report (pp. 1093–103). Patients had cellulitis, large abscesses, or both. Based on a primary outcome of clinical cure at 7–10 days, the investigators found: “One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, −2.6 percentage points; 95% confidence interval [CI], −10.2 to 4.9; P = 0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, −1.2 percentage points; 95% CI, −7.6 to 5.1; P = 0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups.” (L. G. Miller, lgmiller@ucla.edu)
This study is “reassuring in showing that outcomes are good for the vast majority of patients with uncomplicated skin infections treated with either of two popular agents,” an editorialist writes (pp. 1164–6). He notes that no antibiotic is generally needed for abscesses that have been incised and drained. “For cellulitis, therapy should be directed primarily at beta-hemolytic streptococci,” the writer adds. “An earlier well-designed trial showed no benefit of adding TMP-SMX to cephalexin for the treatment of cellulitis, so targeting MRSA in such patients appears to be unnecessary.” (M. R. Wessels)
Mongersen for Crohn Disease: Compared with placebo, the oral SMAD7 antisense oligonucleotide mongersen produced significantly higher rates of remission and clinical response in 166 patients with active Crohn disease (pp. 1104–13). These primary outcomes (based on clinical remission at day 15) were recorded: “The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P <0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P = 0.04, P <0.001, and P <0.001, respectively). Most adverse events were related to complications and symptoms of Crohn’s disease.” (G. Monteleone, gi.monteleone@med.uniroma2.it)
An “intriguing finding” of this study “is that clinical remission was maintained for almost 3 months, even though the drug was administered for only 14 days,” notes an editorialist (
pp. 1166–7). “A total of 83% of patients completed follow-up at day 84; 62% and 67% of patients in the 40-mg and 160-mg groups, respectively, remained in clinical remission at day 84. This contrasts with the rapid recurrence of symptoms on withdrawal of existing antiinflammatory drugs. It is possible that unblocking TGF-beta-1 signaling with short cycles of mongersen treatment would be sufficient to restore immunoregulatory processes and bring about a durable remission. If confirmed in future studies, this durable effect of mongersen would be unprecedented and would represent a first step toward curing the disease.” (S. Vermeire)
Polysaccharide Conjugate Vaccine in Adults: Pneumococcal polysaccharide conjugate vaccines, used in infants, are antigenic in older adults, “preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not … preventing community-acquired pneumonia from any cause,” investigators report in a study of 84,406 adults aged 65 years or older (pp. 1114–25; M. J. M. Bonten, mbonten@umcutrecht.nl)

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 20, 2015 * Vol. 22, No. 53
Providing news and information about medications and their proper use

>>>Allergy/Immunology Report
Source:
Mar. issue of the Journal of Allergy and Clinical Immunology (2015; 135).
Annual Update on Pediatric Asthma: “Advances in pediatric asthma related to prenatal and postnatal factors altering the natural history of asthma, assessment of asthma control, and new insights regarding the management of asthma in children as indicated in Journal of Allergy and Clinical Immunology publications in 2014” are reviewed in an annual summary of this condition (pp. 644–52). The author emphasizes a population health perspective for improving care of pediatric asthma: “New research reports can be integrated into medical communication in a population health perspective to assist clinicians in asthma management. The asthma specialist is in a unique position to convey important messages to the medical community related to factors that influence the course of asthma, methods to assess and communicate levels of control, and new targets for intervention, as well as new immunomodulators. By enhancing communication among patients, parents, primary care physicians, and specialists within provider systems, the asthma specialist can provide timely information that can help to reduce asthma morbidity and mortality.” (S. J. Szefler, Stanley.Szefler@childrenscolorado.org)
Aspirin Exacerbations in Adult Asthma: Aspirin-exacerbated respiratory disease (AERD) is common in adults with asthma and more frequent in those with severe conditions, researchers report (pp. 676–81.e1). “Early identification of this syndrome is critical in view of the increased morbidity and costs associated with asthma exacerbations and the option to treat patients with AERD with long-term aspirin treatment after desensitization,” the group concludes. Using a systematic review and meta-analysis of 27 published articles, the authors found these patterns: “Prevalence rates of AERD ranged from 5.5% to 12.4% based on study type. Among all studies in asthmatic patients, regardless of method, the prevalence of AERD was 7.15% (95% CI, 5.26% to 9.03%). The prevalence of AERD was highest among patients with severe asthma (14.89% [95% CI, 6.48% to 23.29%]). Among patients with nasal polyps and chronic rhinosinusitis, the prevalence was 9.69% (95% CI, 2.16% to 17.22%) and 8.7% (95% CI, −1.02% to 18.34%), respectively.” (J. P. Rajan, jessicarajan@gmail.com)

>>>Rheumatology Highlights
Source:
Mar. issue of Arthritis & Rheumatology (2015; 67).
Certolizumab Pegol in Axial Spondyloarthritis: A 96-week trial confirms efficacy results of shorter studies that support use of certolizumab pegol (CZP) in patients with axial spondyloarthritis (SpA), including ankylosing spondylitis (AS) and nonradiographic axial SpA (pp. 668–77). In the RAPID-axSpA trial, therapy was double-blinded and placebo-controlled for 24 weeks, dose-blinded in weeks 25 to 48, and open-label through week 204. Assessments of disease activity showed these efficacy and safety results for therapy through week 96: “Of the 325 patients who were randomized, 218 received CZP from week 0. Of these, 93% completed week 24, 88% completed week 48, and 80% completed week 96. Improvements in [Assessment of SpondyloArthritis international Society (ASAS)] responses were maintained to week 96 (for ASAS20, 67.4%, 72.0%, and 62.8% at weeks 24, 48, and 96, respectively), as well as improvements in [other disease-activity scales]. Comparable improvements were observed with both dosing regimens (200 mg every 2 weeks or 400 mg every 4 weeks) and in patients with AS and those with nonradiographic axial SpA. In the safety set, adverse events occurred in 279 patients (88.6%) and serious adverse events in 41 (13.0%). No deaths or malignancies were reported.” (J. Sieper, joachim.sieper@charite.de)

>>>PNN NewsWatch
* Consumers should not rely on homeopathic products that make claims regarding asthma, FDA warned yesterday. Pharmacists might expect questions, as the agency advised patients to “speak to your health care provider if you think you or your child may have asthma.”
* Misperceptions about
tooth staining with doxycycline prevent children from receiving needed treatment for Rocky Mountain spotted fever, CDC said this week. A Journal of Pediatrics study finds that the drug can be used in short courses in those younger than 8 years and that outdated product labeling is doing more harm than good.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 23, 2015 * Vol. 22, No. 54
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 21 issue of Lancet (2015; 385).
Grazoprevir + Elbasvir for Hepatitis C Virus Infection: Short, oral courses for hepatitis C virus (HCV) are examined in Phase II trials.
The C-WORTHY trial used open-label, randomized design to test the effects of grazoprevir (HCV NS3/4A protease inhibitor) with elbasvir (HCV NS5A inhibitor) with or without ribavirin in patients with HCV genotype 1 infection. In one report, high sustained virologic response (HCV RNA less than 25 IU/mL) rates resulted from 12 or 18 weeks of therapy in 253 adult patients (
pp. 1075–86): “High SVR12 rates were achieved irrespective of the use of ribavirin or extension of the treatment duration from 12 to 18 weeks; SVR12 rates ranged from 90% (95% CI 74–98; 28/31; cohort 1, 12 weeks, ribavirin-containing) to 100% (95% CI 89–100; 33/33; cohort 2, 18 weeks, ribavirin-containing). Among patients treated for 12 weeks with grazoprevir plus elbasvir without ribavirin, 97% (95% CI 82–100, 28/29) of patients in cohort 1 and 91% (76–98, 30/33) of patients in cohort 2 achieved SVR12. Adverse events reported in more than 10% of patients were fatigue (66 patients, 26% [95% CI 21–32]), headache (58 patients, 23% [95% CI 18–29]), and asthenia (35 patients, 14% [95% CI 10–19]).” (E. Lawitz, lawitz@txliver.com)
The C-WORTHY investigators examine 8 weeks of therapy in a second report, finding that 12 weeks of therapy are needed for adequate SVRs (
pp. 1087–97): “218 patients with HCV mono-infection (n=159) and HIV/HCV co-infection (n=59) were enrolled. SVR12 for patients treated for 12 weeks with or without ribavirin ranged from 93–98% in mono-infected and 87–97% in co-infected patients. SVR12 rates in mono-infected and co-infected patients treated for 12 weeks without ribavirin were 98% (95% CI 88–100; 43/44) and 87% (95% CI 69–96; 26/30), respectively, and with ribavirin were 93% (95% CI 85–97; 79/85) and 97% (95% CI 82–100; 28/29), respectively. Among mono-infected patients with genotype 1a infection treated for 8 weeks, SVR12 was 80% (95% CI 61–92; 24/30). Five of six patients who discontinued early for reasons other than virological failure had HCV RNA less than 25 IU/mL at their last study visit. Virological failure among patients treated for 12 weeks occurred in seven patients (7/188, 4%) and was associated with emergence of resistance-associated variants to one or both drugs. The safety profile of grazoprevir plus elbasvir with or without ribavirin was similar in mono-infected and co-infected patients. No patient discontinued due to an adverse event or laboratory abnormality. The most common adverse events were fatigue (51 patients, 23%), headache (44, 20%), nausea (32, 15%), and diarrhoea (21, 10%).” (M. Sulkowski, msulkowski@jhmi.edu)
Sofosbuvir in HCV/HIV Coinfected Patients: The PHOTON-2 study team reports adequate cure rates after 12 weeks of sofosbuvir plus ribavirin in patients coinfected with HCV and HIV (pp. 1098–106). In a Phase III trial conducted in Europe and Australia, 262 patients received the drug combination in nonrandomized, uncontrolled, open-label fashion, with these results: “Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77–91) in patients with genotype-1 HCV, 88% (69–98) in patients with genotype-2 HCV, 89% (81–94) in patients with genotype-3 HCV, and 84% (66–95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67–99] and 91% [81–97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36–100] and 86% [73–94], respectively). There was no emergence of sofosbuvir-resistance mutations in patients with HCV viral relapse.” (J-M Molina, jean-michel.molina@sls.aphp.fr)

>>>PNN JournalWatch
* Self-Management Following an Acute Exacerbation of COPD: A Systematic Review, in
Chest, 2015; 147: 646–61. (S. L. Harrison, samantha.harrison@westpark.org)
* Health Care System–Level Factors Associated With Performance on Medicare STAR Adherence Metrics in a Large, Integrated Delivery System, in
Medical Care, 2015; 53: 332–7. (J. A. Schmittdiel)
* Necessary Steps: How Health Care Fails Older Patients, And How It Can Be Done Better, in
Health Affairs, 2015; 34: 528–32. (L. Aronson, Louise.Aronson@ucsf.edu)
* Relaxin: A Novel Agent for the Treatment of Acute Heart Failure, in
Pharmacotherapy, 2015; doi: 10.1002/phar.1548. (S. S. Wilson, swilson1@dmc.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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 24, 2015 * Vol. 22, No. 55
Providing news and information about medications and their proper use

>>>Health Affairs Report
Source:
Mar. issue of Health Affairs (2015; 34).
Intelligent Assignment in Medicare Part D: Among Medicare Part D beneficiaries with schizophrenia who receive low-income subsidies, “intelligent” prescription drug plan assignment by algorithm “could produce substantial savings” and should be the “default approach” in this population, a study concludes (pp. 455–60). The authors further suggest that such algorithms be an option for all Part D beneficiaries, regardless of income: “We simulated savings from replacing random assignment with an ‘intelligent assignment’ algorithm that would assign beneficiaries to the least expensive plan in 2010 based on their drug usage in the previous year. Doing so generated projected annual drug savings of $379 per dual-eligible (those enrolled in both Medicaid and Medicare) beneficiary with a low-income subsidy; $404 per non–dual eligible with the subsidy; and $604 per beneficiary for those without the subsidy who chose their own plans. This translates into savings of $466 per beneficiary with schizophrenia. Intelligent assignment could have saved about $150 million for Medicare and beneficiaries with schizophrenia combined in 2010.” (Y. Zhang, ytzhang@pitt.edu)
Drug-Cost Sharing in Employer and Federal Exchange Plans: Patients newly insured under the Affordable Care Act could use assistance in matching their prescription drug needs with plans’ benefit designs, researchers report (pp. 467–76). In a study that examined variability in drug coverage among employer-sponsored and federal exchange plans, authors found these results: “[In] federally facilitated exchanges, we found wide variation in enrollees’ out-of-pocket costs for generic, preferred brand-name, nonpreferred brand-name, and specialty drugs, not only across metal tiers but also within those tiers across plan types. Compared to employer-sponsored plans, exchange plans generally had lower premiums but provided less generous drug coverage. However, for low-income enrollees who are eligible for cost-sharing subsidies, the exchange plans may be more comparable to employer-based coverage.” (C. Buttorff, buttorff@rand.org)
MD Awareness of PDMPs: While primary care physicians are generally aware of state prescription drug monitoring programs, they find the data difficult to access and use, according to results of a nationally representative survey of 1,000 practitioners in 2014 (pp. 484–92). Responses from 420 eligible physicians showed these patterns: “72 percent were aware of their state’s prescription drug monitoring program, and 53 percent reported using one of the programs. We identified several barriers that may prevent greater use of the programs, including the time-consuming nature of information retrieval and the lack of an intuitive format for data provided by the programs. These results suggest that the majority of US primary care physicians are aware of and use prescription drug monitoring programs at least on occasion, although many did not access these programs routinely. To increase the use of the programs in clinical practice, states should consider implementing legal mandates, investing in prescriber education and outreach, and taking measures to enhance ease of access to and use of the programs.” (G. C. Alexander, galexand@jhsph.edu)
Mandatory Disclaimers On Dietary Supplements: Courts have suggested that FDA could replace unconstitutional bans on promotional statements by manufacturers with disclaimers to off-label uses, but a new analysis shows that these are ineffective (pp. 438–46). Based on a systematic review of studies of disclaimers on dietary supplements, investigators found that “many consumers were unaware of a disclaimer or reported that it did not affect their perceptions of a product.” (A. S. Kesselheim, akesselheim@partners.org)

>>>PNN NewsWatch
* After reviewing the cases of two patients who died 3–4 days after receiving Zyprexa Relprevv (Lilly) and were later found to have extremely elevated blood levels of olanzapine, FDA is unable to conclude that the levels were associated with the deaths. In fact, the agency said, the levels may have become elevated after death. “We are not recommending any changes to the current prescribing or use of Zyprexa Relprevv injection at this time,” FDA said. “Patients should not stop receiving treatment without first talking to their health care professionals.”

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 25, 2015 * Vol. 22, No. 56
Providing news and information about medications and their proper use

>>>JAMA Highlights
Source:
Mar. 24/31 issue of JAMA (2015; 313).
HCV/HIV Co-infection: Two studies and an editorial explore emerging therapies for co-infections of hepatitis C virus (HCV) and HIV.
An all-oral, three-drug regimen (3D) produced high rates of sustained virologic responses (SVRs; HCV RNA levels below 25 IU/mL) at 12 and 24 weeks in patients co-infected with HCV/HIV, according to results of the TORQUOISE-I study (
pp. 1223–31). The open-label trial tested ombitasvir, paritaprevir (co-dosed with ritonavir [paritaprevir/r]), dasabuvir, and ribavirin in patients with HCV genotype 1 and HIV-1, including some patients with cirrhosis. Results showed: “Among patients receiving 12 or 24 weeks of 3D and ribavirin, SVR12 was achieved by 29 of 31 (94%; 95% CI, 79%–98%) and 29 of 32 patients (91%; 95% CI, 76%–97%), respectively. Of the 5 patients who did not achieve SVR, 1 withdrew consent, 2 had confirmed virologic relapse or breakthrough, and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection. The most common treatment-emergent adverse events were fatigue (48%), insomnia (19%), nausea (18%), and headache (16%). Adverse events were generally mild, with none reported as serious or leading to discontinuation. No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment.” (M. S. Sulkowski, msulkowski@jhmi.edu)
In a second open-label study, oral ledipasvir–sofosbuvir for 12 weeks produced high rates of SVR at week 12 of therapy in co-infected patients (
pp. 1232–9). At the NIH Clinical Center, this pilot study included 50 patients with HCV genotype 1/HIV co-infections and yielded these results: “Forty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug.” (S. Kottilil, skottilil@ihv.umaryland.edu)
“The high SVR rates in these two studies suggest that future barriers to prevention of unnecessary deaths due to HCV may be related to failures of the health care system,” an editorialist writes (
pp. 1217–8). With liver disease now the second leading cause of death among patients with HIV infection, the editorialist notes the need for the currently expensive elimination of HCV: “Clinicians who care for patients with HIV infection are already skilled at selecting regimens, managing drug–drug interactions, optimizing adherence, and providing harm reduction counseling. These skills are exactly what is needed to treat patients with hepatitis C and to ensure that the successes seen in research trials are replicated in clinical practice. Many clinicians also have experience advocating for their patients, and this skill may be as valuable now as it was in the early days of HIV. With the current concern about the high price of these regimens, it is critical that the patients who are living with hepatitis C and the value of treating this disease remain front and center.” (C. S. Graham, cgraham@bidmc.harvard.edu)
Postexposure Prophylaxis With Ebola Vaccine: An investigational vaccine against Ebola virus was administered to a physician following a needlestick accident at a Sierra Leone facility, according to authors of a preliminary communication (pp. 1249–55). “Postexposure vaccination with VSV∆G-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected.” (M. J. Mulligan, mark.mulligan@emory.edu)

>>>PNN NewsWatch
* Patients taking sofosbuvir-containing regimens and amiodarone have had serious bradycardia, FDA said yesterday. FDA is adding information about symptomatic bradycardia to the Harvoni and Sovaldi labels and recommending that component and similar drugs not be used with amiodarone.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 26, 2015 * Vol. 22, No. 57
Providing news and information about medications and their proper use

>>>NEJM Highlights
Source:
Mar. 26 issue of the New England Journal of Medicine (2015; 372).
Drug Efficacy/Safety in Diabetic Macular Edema: Comparing the relative efficacy and safety of three available intravitreous agents for diabetic macular edema, investigators find no differences in patients with mild loss of visual acuity and that aflibercept is more effective in those with worse initial vision (pp. 1193–203). A total of 660 adults with diabetic macular edema involving the macular center received intravitreous aflibercept 2.0 mg, bevacizumab 1.25 mg, or ranibizumab 0.3 mg as often as every 4 weeks, with these results: “From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P <0.001 for aflibercept vs. bevacizumab and P = 0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P <0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P >0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P <0.001 for aflibercept vs. bevacizumab, P = 0.003 for aflibercept vs. ranibizumab, and P = 0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P = 0.40), hospitalization (P = 0.51), death (P = 0.72), or major cardiovascular events (P = 0.56).” (A. R. Glassman, drcrstat2@jaeb.org)
Three-fourths of patients with this condition present with visual acuity of 20/40 or better, editorialists write (
pp. 1260–1): “Given the large difference in cost to patients per dose among bevacizumab ($50), ranibizumab ($1,200), and aflibercept ($1,950), bevacizumab should be considered as first-line therapy in patients with a visual acuity of 20/40 or better.” (D. F. Martin)
Regulation of Genomic Testing: FDA is “exploring radical new approaches for cutting the Gordian helix in which genomic testing has been bound,” writes the author of a Perspective article (pp. 1185–6). “Troublingly, some firms are already peddling genotype-based pronouncements about whether a child is at significantly increased risk for suicide or autism, or about which treatments will most benefit a particular person with mental illness,” the author notes. “The massive amounts of data produced by ‘next-generation’ sequencing can be a great asset for confirming analytic validity.… The scientific community has launched pilot efforts to systematically sift the genetic evidence and create reliable databases of the genes and genetic variants underlying disease. A flagship example is the NIH-funded Clinical Genome Resource (ClinGen) project, which gathers and curates data about the strength of relationships among genes, variants, and diseases. If such efforts were scaled up, they could provide rigorous—and regularly updated—public databases for all key clinical needs. In principle, the FDA might offer a ‘safe harbor,’ whereby sponsors whose genomic tests used interpretations that are consistent with recognized databases would not need to submit additional validation.” (E. S. Lander)

>>>PNN NewsWatch
* The provider status coalition yesterday launched a major media initiative aimed at promoting the role of pharmacists in senior care. The 25-member Patient Access to Pharmacists’ Care Coalition is running print and digital advertising in Washington, DC, media outlets over the course of the Congressional calendar. The “Pharmacists Care, in more ways than you may know” ad, the first in a series, begins to educate readers about the role that pharmacists can play in filling the gap some patients face in accessing care.
* With chain pharmacists in the nation’s capital for an annual “fly-in,”
NACDS was represented yesterday at the White House when President Obama kicked off the Health Care Payment Learning and Action Network, which aims to tie an increasing percentage of Medicare fee-for-service payments to quality or value, reaching 90% by 2018.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 27, 2015 * Vol. 22, No. 58
Providing news and information about medications and their proper use

>>>Diabetes Highlights
Source:
Apr. issue of Diabetes Care (2015; 38).
Glycemic Control With New Insulin Glargine Product: In a pharmacokinetic (PK) study using euglycemic clamp technique, a recently approved insulin glargine formulation with 300 units/mL (Gla-300) provided more even steady-state PK and pharmacodynamic (PD) profiles and a longer duration of action than did insulin glargline 100 units/mL (Gla-100) (pp. 637–43). As part of an 8-day, multiple dose to steady state study, 30 patients were given 0.4 units/kg of each insulin glargine formulation once daily in crossover fashion. Radioimmunoassay and automated euglycemic clamp technique over a 36-h period on the last treatment day produced these findings: “At steady state, insulin concentration (INS) and glucose infusion rate (GIR) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer, as supported by the later time (~3 h) to 50% of the area under the serum INS and GIR time curves from time zero to 36 h post dosing. Tight blood glucose control (≤105 mg·dL−1) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100.” (R. H. A. Becker, reinhard.becker@sanofi.com)
This study is “a good step forward” in addressing the need for sound head-to-head studies of new long-acting insulin analogs, an editorialist writes (
pp. 541–3). Becker et al. “studied the right population (absent endogenous insulin secretion) in which the observed PK/PD after subcutaneous (s.c.) injection of an insulin preparation are specifically attributable to the injected insulin. When clamp studies are instead run in subjects without diabetes or with type 2 diabetes (T2D), the PK/PD results are confounded by endogenous insulin secretion. Becker et al. correctly studied the subjects after 1 week of treatment at ‘steady state.’ However, they did use a fixed dose of basal insulin (0.4 units/kg/day glargine, either Gla-300 or Gla-100). This approach has the advantage of simplicity but the disadvantage of inducing a pharmacological overinsulinization with risk of hypoglycemia as the previously daily basal insulin dose used by the subjects with [type 1 diabetes] was lower (mean 0.30 units/kg/day). Indeed, the majority of subjects needed a robust GIR during the 6 h prior to injection of glargine (time zero) to prevent hypoglycemia, and several subjects had baseline plasma insulin concentrations higher before than after glargine clamp dosing. These baseline conditions, partly due to the automated biostator for glucose clamping, make it more difficult to interpret PK and PD.” (J. H. DeVries, j.h.devries@amc.uva.nl)
Inpatient Glycemic Control: In 206 hospital inpatients with type 2 diabetes who were being treated with a basal–bolus regimen, use of insulin supplements for correction of bedtime hyperglycemia did not result in improved glycemic control, researchers report (pp. 568–74). Study participants were randomized to supplemental insulin at bedtime for blood glucose (BG) >7.8 mmol/L or no supplemental insulin except for BG >19.4 mmol/L. Point-of-care testing before meals, at bedtime, and at 3 am showed these results: “There were no differences in mean fasting BG for the intention-to-treat (8.8 ± 2.4 vs. 8.6 ± 2.2 mmol/L, P = 0.76) and as-treated (8.9 ± 2.4 vs. 8.8 ± 2.4 mmol/L, P = 0.92) analyses. Only 66% of patients in the supplement and 8% in the no supplement groups received bedtime supplemental insulin. Hypoglycemia (BG <3.9 mmol/L) did not differ between groups for either the intention-to-treat (30% vs. 26%, P = 0.50) or the as-treated (4% vs. 8%, P = 0.37) analysis.” (G. E. Umpierrez, geumpie@emory.edu)

>>>PNN NewsWatch
* APhA2015 opens today in San Diego. On the agenda of the group’s professionwide House of Delegates are policies on interoperability of communications among health care providers; integrated nationwide prescription drug monitoring program, and role of the pharmacist in care of patients using cannabis. A new business item on pharmacist participation in executions has also been introduced.
* FDA this week approved
Anthrax Immune Globulin Intravenous (Human) (Anthrasil, Cangene Corp.) to treat patients with inhalational anthrax in combination with appropriate antibacterial drugs and aflibercept injection (Eylea; Regeneron, Genentech) to treat diabetic retinopathy in patients with diabetic macular edema.

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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 30, 2015 * Vol. 22, No. 59
Providing news and information about medications and their proper use

>>>Lancet Highlights
Source:
Mar. 28 issue of Lancet (2015; 385).
Tonicity of Pediatric I.V. Fluids: In a randomized controlled trial, use of isotonic intravenous fluids for pediatric maintenance hydration lowered risk of hyponatremia compared with a hypotonic solution (pp. 1190–7). Participants received either 140 mmol/L (Na140) or 77 mmol/L of sodium (Na77) for 72 h or until their I.V. fluid rate decreased to lower than 50% of the standard maintenance rate: “Primary outcome data were available for 319 who received Na140 and 322 who received Na77. Fewer patients given Na140 than those given Na77 developed hyponatraemia (12 patients [4%] vs 35 [11%]; odds ratio [OR] 0.31, 95% CI 0.16–0.61; p = 0.001). No clinically apparent cerebral oedema occurred in either group. Eight patients in the Na140 group (two potentially related to intravenous fluid) and four in the Na77 group (none related to intravenous fluid) developed serious adverse events during the treatment period. One patient in the Na140 had seizures during the treatment period compared with seven who received Na77.” (S. McNab, sarah.mcnab@rch.org.au)
P2X3 Receptor Antagonist in Chronic Cough: P2X3 receptors in airway vagal afferent nerves may play “a key role in mediation of cough neuronal hypersensitivity,” according to a study of a P2X3 antagonist (pp. 1198–205). AF-219 or placebo was administered to patients with refractory chronic cough, with these results: “Of 34 individuals assessed between Sept 22, 2011, and Nov 29, 2012, we randomly assigned 24 patients (mean age 54.5 years; SD 11.1). In the observed case analysis, cough frequency was reduced by 75% when patients were allocated to AF-219 compared when allocated to placebo (p = 0.0003). Daytime cough frequency fell from a mean 37 coughs per h (SD 32) to 11 (8) coughs per h after AF-219 treatment versus 65 (163) coughs per h to 44 (51) coughs per h after placebo. Six patients withdrew before the end of the study because of taste disturbances, which were reported by all patients taking AF-219.” (J. A. Smith, jacky.smith@manchester.ac.uk)

>>>BMJ Highlights
Source:
Early-release article from BMJ (2015; 350).
Precision Medicine & Bleeding Avoidance: At 1,135 U.S. hospitals, patients provided with prospective, individualized estimates of bleeding risk had increased use of bleeding-avoidance strategies before and after undergoing percutaneous coronary interventions, researchers report (h1302): “In a comparison of 7,408 pre-intervention procedures with 3,529 post-intervention procedures, use of bleeding avoidance strategies within intervention sites increased with pre-procedural risk stratification (odds ratio 1.81, 95% confidence interval 1.44 to 2.27), particularly among higher risk patients (2.03, 1.58 to 2.61; 1.41, 1.09 to 1.83 in low risk patients, after adjustment for control sites; P for interaction=0.05). Bleeding rates within intervention sites were significantly lower after implementation of risk stratification (1.0% v 1.7%; odds ratio 0.56, 0.40 to 0.78; 0.62, 0.44 to 0.87, after adjustment); the reduction in bleeding was greatest in high risk patients. Marked variability in use of bleeding avoidance strategies was observed across sites and physicians, both before and after implementation.” (J. A. Spertu, spertusj@umkc.edu)

>>>PNN NewsWatch
* Addressing APhA2015 in San Diego on Saturday, the Tennessee physician–pharmacist team of Reid Blackwelder, MD, FAAFP, American Academy of Family Physicians Board Chair, and Brian Cross, PharmD, BCACP, CDE called for greater collaboration between the professions, pharmacist.com reports.

>>>PNN JournalWatch
* Insulin Pump Risks and Benefits: A Clinical Appraisal of Pump Safety Standards, Adverse Event Reporting, and Research Needs, in
Diabetes Care, 2015; 38: 716–22. (J. R. Petrie, john.petrie@glasgow.ac.uk)
* Pharmacist Calls to Older Adults with Cognitive Difficulties After Discharge in a Tertiary Veterans Administration Medical Center: A Quality Improvement Program, in
Journal of the American Geriatrics Society, 2015; 63: 571–7. (J. L. Rudolph, jrudolph@partners.org)
* Update on Vaccination Guidelines for Older Adults, in
Journal of the American Geriatrics Society, 2015; 63: 584–8. (H. K. Talbot, keipp.talbot@vanderbilt.edu)
* Initial Use of a Novel Noninvasive Vagus Nerve Stimulator for Cluster Headache Treatment, in
Neurology, 2015; 84: 1249–53. (P. J. Goadsby, peter.goadsby@kcl.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 844/270-0717 (fax). Copyright © 2015, 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
Mar. 31, 2015 * Vol. 22, No. 60
Providing news and information about medications and their proper use

>>>Geriatrics Highlights
Source:
Mar. Journal of the American Geriatrics Society (2015; 63).
Anticholinergic Drugs & Community-Acquired Pneumonia: Older patients taking anticholinergic medications are at increased risk of community-acquired pneumonia, according to results of a nested case–control study (pp. 476–85). Investigators compared 1,039 immunocompetent patients aged 65–94 years living in the community who developed pneumonia with 2,022 control patients, with these results: “Acute use of anticholinergics was observed in 59% of cases and 35% of controls (adjusted odds ratio (aOR) = 2.55, 95% confidence interval (CI) = 2.08–3.13) and past use in 17% of cases and 23% of controls (aOR = 1.19, 95% CI = 0.92–1.53). Chronic use of anticholinergics was observed in 53% of cases and 36% of controls (aOR 2.07, 95% CI = 1.68–2.54). Results were not different for high- and low-potency anticholinergic medications.” The authors conclude that the study “[adds] to substantial evidence suggesting that these medications are high risk.” (S. Dublin, dublin.s@ghc.org)
Inappropriate Medication Use in Older Adults: Based on the 2012 Beers criteria, investigators found high but declining rates of use of potentially inappropriate medication (PIM) among participants in the 2006–2010 Medical Expenditure Panel Survey (MEPS) (pp. 486–500). Data for a community-dwelling sample of 18,475 U.S. adults showed these patterns: “Of older adults with prescription medications, 42.6% had at least one medication fill that met the broad definition, with nonsteroidal anti-inflammatory drugs (NSAIDs) having the highest prevalence (10.9%). The rate declined from 45.5% in 2006–2007 to 40.8% in 2009–2010. The categories with the largest absolute decline were NSAIDs, selected sulfonylureas, and estrogens. PIM prevalence was 30.9% using the qualified definition.” (A. J. Davidoff, amy.davidoff@yale.edu)
Antipsychotics & Mortality: A cohort study “adds to the body of evidence rejecting explanations other than causality for the greater mortality risk associated with conventional antipsychotics than with atypical antipsychotics,” researchers conclude (pp. 516–23). A merged data set of Medicaid, Medicare, Minimum Data Set (MDS), Online Survey Certification and Reporting system, and National Death Index for 2001–05 for 75,445 dual-eligible individuals aged 65 and older who initiated antipsychotic treatment in a nursing home showed the following: “Each risk score showed moderate discrimination for 6-month mortality, with c-statistics ranging from 0.61 to 0.63. There was no evidence of lack of fit. Imbalances in risk scores between conventional and atypical antipsychotic users, suggesting potential confounding, were much lower within PS deciles than the imbalances in the full cohort. Accounting for each score in the Cox model did not change the relative risk estimates: 2.24 with PS-only adjustment versus 2.20, 2.20, and 2.22 after further adjustment for the three risk scores.” (Y. Park, yop121@mail.harvard.edu)
Back Pain in Older Adults: Among 5,211 adults aged 65 or older who presented with back pain, symptoms persisted in most patients 12 months later, researchers report, as did disability and interference with activities (pp. 524–30). Data from the Back pain Outcomes using Longitudinal Data (BOLD) registry show that “most improvement occurred within the first 3 months. The number and proportion with 30% improvement in back pain increased from 1,950 (42.3%) at 3 months to 1,994 (44.8%) by 12 months, and 1,331 (28.8%) and 1,576 (35.4%) had 30% improvement in disability at 3 and 12 months. Only 23.0% reported that their back pain had resolved at 12 months.” (S. Rundell, srundell@uw.edu)

>>>PNN NewsWatch
* APhA2015 wrapped up in San Diego yesterday. In the House of Delegates, the profession debated a controversial policy on medical marijuana and passed language supporting the pharmacists’ role when science supports cannabis use and laws allow it. Policies on interoperability of communications among health care providers and integrated nationwide prescription drug monitoring program were also passed. Consumer media widely covered passage of this new business item: “The American Pharmacists Association discourages pharmacist participation in executions on the basis that such activities are fundamentally contrary to the role of pharmacists as providers of health 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 844/270-0717 (fax). Copyright © 2015, 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.