Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings. Methods and findings Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 μg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87–1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%–0.1%) and 0.01% (95% CI 0.00%–0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites. Conclusions In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severi...

OBJECTIVES While anthracycline-based treatment can cure diffuse large B-cell lymphoma, most patients over age 80 do not receive doxorubicin due to toxicity concerns. This study evaluated this practice, as patients age 80 and older are largely excluded from clinical trials. The primary outcome of interest was overall survival. Secondary outcomes included treatment-related mortality and anthracycline dose intensity. MATERIALS AND METHODS We assembled a cohort of 530 newly diagnosed diffuse large B-cell lymphoma patients age 80 or older diagnosed within United States Veterans Health Administration. Treatment and survival information were obtained to determine associations between anthracycline use, dose intensity, treatment-related mortality and overall survival. RESULTS Of the 530 patients, 285 received systemic treatment and 193 received an anthracycline. After controlling for potential confounders, rituximab decreased mortality (hazard ratio, 0.62; 95% confidence interval [CI]: 0.44 – 0.88), while doxorubicin was not significantly associated with mortality (hazard ratio, 0.87; 95% CI: 0.64 – 1.17). Completion of treatment with anthracycline dose intensity ≥85% of expected was only 14%. Patients treated with anthracycline dose intensity <85% had better one year survival compared to those treated at ≥85% (70% vs. 59%, p = 0.029). CONCLUSION These results suggest that full dose anthracycline therapy may be less important in the treatment of diffuse large B-cell lymphoma patients over age 80. The low frequency of completion of full dose intensity treatment suggests standard doses are an unrealistic standard of care for patients this age. Alternate treatment strategies and risk stratification should be considered for these patients.

The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have activity in one of the pathways influenced by nitrogen-containing bisphosphonates, which are associated with improved survival in multiple myeloma (MM). To understand the benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of patients with MM. Patients and MethodsFrom the Veterans Administration Central Cancer Registry, we identified patients diagnosed with MM between 1999 and 2013. We defined statin use as the presence of any prescription for a statin within 3 months before or any time after MM diagnosis. Cox proportional hazards regression assessed the association of statin use with mortality, while controlling for known MM prognostic factors. ResultsWe identified a cohort of 4,957 patients, of whom 2,294 received statin therapy. Statin use was associated with a 21% decrease in all-cause mortality (adjusted hazard ratio, 0.79; 95% CI, 0.73 to 0.86; P , .001) as well as a 24% decrease in MM-specific mortality (adjusted hazard ratio, 0.76; 95% CI, 0.67 to 0.86; P , .001). This association remained significant across all sensitivity analyses. In addition to reductions in mortality, statin use was associated with a 31% decreased risk of developing a skeletal-related event. ConclusionIn this cohort study of US veterans with MM, statin therapy was associated with a reduced risk of both all-cause and MM-specific mortality. Our findings suggest a potential role for statin therapy in patients with MM. The putative benefit of statin therapy in MM should be corroborated in prospective studies.

Background Multiple myeloma (MM) is one of the most common hematologic malignancies in the United States and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Methods A retrospective cohort of patients in the U.S. Veterans Health Administration database diagnosed with MGUS between 1, October, 1999 and 31, December, 2009 and diabetes mellitus prior to their MGUS diagnosis was identified and followed through 6, August, 2013. Patient-level clinical data were reviewed to verify diagnoses and to abstract data on size of baseline M-protein and type of MGUS, i.e., immunoglobulin (Ig) subtype or light-chain, when available. Metformin users were defined as patients that were prescribed metformin for at least 4 years, with no single break between consecutive prescriptions ≥6 months. Kaplan-Meier curves and Cox models were used to analyze the association between metformin use and the progression of MGUS to MM. Findings The analytic cohort consisted of 2,003 MGUS patients with a median follow-up time of 69 months. Within the analytic cohort, 463 metformin users (23·1%) were identified. Among the metformin users, 13 patients progressed to MM, while 74 patients progressed to MM among the non-metformin users. Metformin use was associated with a reduced risk of transformation to MM (Hazard ratio, HR: 0·47; 95% confidence interval, CI: 0·25–0·87). Interpretation For diabetics diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of transformation of MGUS to MM. Prospective studies are required to determine whether this association is causal and whether these results can be extrapolated to non-diabetics.

Obesity and black race are risk factors for transformation of MGUS to MM. Future clinical trials should examine whether weight loss is a way to prevent the progression to MM in MGUS patients.