Pegfilgrastim vs. filgrastim for supportive care after autologous stem cell transplantation: Can we decide?

Granulocyte-colony-stimulating factors are helpful for the support of patients receiving autologous hematopoietic stem cell transplantation, resulting in faster neutrophil recovery and lower incidence of febrile neutropenia (FN). Our aim was to evaluate the use of pegfilgrastim vs. filgrastim with regard to absolute neutrophil count (ANC) recovery, risk, and duration of FN and length of hospital stay. Mean difference was the summary effect for continuous data, and odds ratio for binary data, using random-effects modeling. MEDLINE, EMBASE, and the Cochrane Registry of Randomized Controlled Trials were included in the search. Randomized controlled trials (RCTs), case-control studies, and studies with historical control group for filgrastim were eligible. Of the initial 114 studies screened, 12 studies were analyzed (four were RCTs, including one phase III trial). The use of pegfilgrastim resulted in a oned gain in ANC recovery (mean difference -0.82, 95% CI -1.07 to -0.57, p<0.001) and duration of FN (-0.67, 95% CI -1.28 to -0.06, p<0.001) but had no effect on the risk of FN or length of stay. Pegfilgrastim was more expensive (baseline marginal cost €116.97, p<0.001), which was largely determined by the treatment duration and pegfilgrastim cost. Non-randomized setting attenuated the effect on duration of FN whereas delayed onset of filgrastim injections (to pegfilgrastim) overestimated the protective effect on the risk of FN. Both drugs are at least equally effective, though methodology and disease stratification in published trials warrant further improvement. © 2011 John Wiley & Sons A/S

Effectiveness of Systemic Antifungal Prophylaxis in Patients With Neutropenia After Chemotherapy: A Meta-Analysis of Randomized Controlled Trials

Background: Invasive fungal infections are responsible for substantial morbidity and mortality among patients with neutropenia after chemotherapy. Objective: This meta-analysis was conducted to estimate the effect of systemic antifungal prophylaxis on the frequency of invasive fungal infections in patients with neutropenia and the mortality associated with these infections. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through September 15, 2010, for English-language publications of randomized controlled trials that compared systemic antifungal prophylaxis with placebo or no treatment in patients with neutropenia. Studies involving nonsystemic antifungal agents, direct comparisons of antifungal agents, and empirical, preemptive, or salvage treatment were excluded. Data were extracted according to European Organization for Research and Treatment of Cancer definitions of proven, possible, or probable fungal infections. Effect measures were reported as odds ratios (ORs) for fungal infection and mortality. Outcomes were pooled using random-effects meta-analysis. Study quality was assessed based on the study setting (single center or multicenter), institutional review board approval/informed consent, randomization, description of allocation concealment, double blinding, and reporting of dropouts. Results: Twenty-six trials including a total of 3979 patients were included in the meta-analysis. Antifungal prophylaxis was associated with significant reductions in proven fungal infections (OR = 0.43; 95% CI, 0.31-0.60; number needed to treat [NNT] = 20) and mortality attributed to fungal infections (OR = 0.49; 95% CI, 0.30-0.80; NNT = 53). Overall mortality was not affected by antifungal prophylaxis (OR = 0.92; 95% CI, 0.74-1.14). Antifungal prophylaxis was associated with a reduction in risk for proven Candida infections (OR = 0.28; 95% CI, 0.20-0.38), but not for aspergillosis or zygomycosis. Antifungal prophylaxis was also associated with a decreased need for antifungal therapy (OR = 0.64; 95% CI, 0.48-0.86). In an explanatory subgroup analysis of major outcomes, only recipients of a hematopoietic stem cell transplant (HSCT) had a significant likelihood of benefiting from antifungal prophylaxis in terms of reductions in risk for proven infections (OR = 0.27; 95% CI, 0.16-0.44) and mortality attributed to infections (OR = 0.41; 95% CI, 0.21-0.81). A metaregression analysis indicated that a multicenter (vs single-center) design and a double-blind (vs unblinded) design were significant moderators of the effect of antifungal prophylaxis on overall mortality and proven systemic fungal infections, respectively. Conclusions: Systemic antifungal prophylaxis was associated with a reduction in proven fungal infections and mortality attributed to these infections in patients with neutropenia after chemotherapy. In the setting of HSCT, antifungal prophylaxis was associated with reductions in both proven infections and mortality attributed to infections. There was no significant association between antifungal prophylaxis and overall mortality. © 2010 Elsevier HS Journals, Inc

Medicare part D prescribing for direct oral anticoagulants in the United States: Cost, use and the “Rubber Effect”

Introduction Direct oral anticoagulants (DOAC) have gained an increased share over warfarin for prevention and treatment of thromboembolic disease. We studied DOAC adoption across providers and medical specialties. Methods Retrospective, cross-sectional analysis of Medicare Part D public use files (PUF), 2013 to 2015. We summarized prescription data for claims and drug payment, stratified by drug class, specialty and calendar year. We treated DOAC claims as a count outcome and explored patterns of expansion across prescribers via a truncated negative binomial regression. We described dispersion and spread in DOAC prescribing, across hospital referral regions (HRRs), including the p90/p10 ratios, and the median absolute deviation from the median. Results In 2015 part D PUF, oral anticoagulant claims have climbed to approximately 24.4 million with a payment cost of approximately $3.3 billion. DOAC claims comprised 31.0$367.4 (interquartile range 323.9 to 445.9), as opposed to $12.3 (interquartile range 9.2 to 16.5) for warfarin. The median cost per standardized (30-day supply) prescription was$317.0 (interquartile range 303.8 to 324.3) and $8.0 (6.7 to 9.8) for DOACs and warfarin, respectively. DOAC adoption differs by specialty. Cardiologists, cardiac electrophysiologists and orthopedics had the highest predicted DOAC share per 100 claims (53.8, 72.9 and 71.5, respectively in 2015); nephrologists, family practitioners and geriatricians the lowest (22.3, 21.5 and 20.7, respectively in 2015). The p90/p10 ratio and the median absolute deviation from the median varied across HRRs and correlated positively with the prevalence of stroke and atrial fibrillation in the Medicare population. Conclusions DOACs have been increasing their share year-over-year, but adoption varies across specialties. In prevalent areas for stroke and atrial fibrillation, prescription dispersion magnifies, and this may signify a rapid adoption by top providers. © 2018 Ziakas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited