Dry eye disease (DED) is a chronic and progressive multifactorial disorder of the tears and ocular surface, which results in symptoms of discomfort and visual disturbance. The aim of this systematic literature review was to evaluate the burden of DED and its components from an economic and health-related quality of life (HRQoL) perspective, and to compare the evidence across France, Germany, Italy, Spain, UK, USA, Japan, and China. PubMed, Embase, and six other resources were searched for literature published from January 1998 to July 2013. Of 76 titles/abstracts reviewed on the economic burden of DED and 263 on the HRQoL burden, 12 and 20 articles, respectively, were included in the review. The available literature suggests that DED has a substantial economic burden, with indirect costs making up the largest proportion of the overall cost due to a substantial loss of work productivity. In addition, DED has a substantial negative impact on physical, and potentially psychological, function and HRQoL across the countries examined. A number of studies also indicated that HRQoL burden increases with the severity of disease. Additional data are needed, particularly in Asia, in order to gain a better understanding of the burden of DED and help inform future health care resource utilization.

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BackgroundThe number of ambulatory patients seeking treatment for skin and skin structure infections (SSSI) are increasing. The objective of this study is to determine recent trends in hospital admissions and healthcare resource utilization and identify covariates associated with hospital costs and mortality for hospitalized adult patients with a primary SSSI diagnosis in the United States.MethodsWe performed a retrospective cross-sectional analysis (years 2005–2011) of data from the US Healthcare Cost and Utilization Project National Inpatient Sample. Recent trends, patient characteristics, and healthcare resource utilization for patients hospitalized with a primary SSSI diagnosis were evaluated. Descriptive and bivariate analyses were conducted to assess patient and hospital characteristics.ResultsA total of 1.8% of hospital admissions for the years 2005 through 2011 were for adult patients with a SSSI primary diagnosis. SSSI-related hospital admissions significantly changed during the study period (P < .001 for trend) ranging from 1.6% (in 2005) to 2.0% (in 2011). Mean hospital length of stay (LOS) decreased from 5.4 days in the year 2005 to 5.0 days in the year 2011 (overall change, P < .001) with no change in hospital costs. Patients with postoperative wound infections had the longest hospital stays (adjusted mean, 5.81 days; 95% confidence interval (CI), 5.80–5.83) and highest total costs (adjusted mean, $9388; 95% CI, $9366-$9410). Year of hospital admission was strongly associated with mortality; infection type, all patient refined diagnosis related group severity of illness level, and LOS were strongly associated with hospital costs.ConclusionsHospital admissions for adult patients in the United States with a SSSI primary diagnosis continue to increase. Decreasing hospital inpatient LOS and mortality rate may be due to improved early treatment. Future research should focus on identifying alternative treatment processes for patients with SSSI that could shift management from inpatient to outpatient treatment settings.

BackgroundA network meta-analysis can provide estimates of relative efficacy for treatments not directly studied in head-to-head randomized controlled trials. We estimated the relative efficacy and safety of dolutegravir (DTG) versus third agents currently recommended by guidelines, including ritonavir-boosted atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV), cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r), raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1–infected patients.MethodsA systematic review of published literature was conducted to identify phase 3/4 randomized controlled clinical trials (up to August 2013) including at least one third agent of interest in combination with a backbone nucleoside reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network meta-analysis models adjusting for the type of nucleoside reverse transcriptase inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid changes, adverse events, and discontinuations due to adverse events) of DTG relative to all other treatments. Sensitivity analyses assessing the impact of NRTI treatment adjustment and random-effects models were performed.ResultsThirty-one studies including 17,000 patients were combined in the analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir had better or equivalent changes in total cholesterol, LDL, triglycerides, and lower odds of adverse events and discontinuation due to adverse events compared to all treatments. Random-effects and unadjusted models resulted in similar conclusions.ConclusionThree clinical trials of DTG have demonstrated comparable or superior efficacy and safety to DRV, RAL, and EFV in HIV-1–infected treatment-naive patients. This network meta-analysis suggests DTG is also favorable or comparable to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).

Aim: To describe the epidemiologic, humanistic and economic burdens of hepatocellular carcinoma (HCC) in the USA. Materials & methods: Studies describing the epidemiology and economic burden from national cohorts, any economic models, or any humanistic burden studies published 2008–2018 were systematically searched. Results: HCC incidence was 9.5 per 100,000 person-years in most recent data, but was ∼100-times higher among patients with hepatitis/cirrhosis. Approximately a third of patients were diagnosed with advanced disease. Patients with HCC experienced poor quality of life. Direct costs were substantial and varied based on underlying demographics, disease stage and treatment received. Between 25–77% of patients did not receive surgical, locoregional or systemic treatment. Conclusion: Better treatments are needed to extend survival and improve quality of life for patients with HCC.

Beta-blockers are established drugs in heart failure with reduced ejection fraction, but their role in heart failure with preserved ejection fraction (HFpEF) is not established. Hence, we undertook a meta-analysis to evaluate the efficacy of beta-blockers on mortality and morbidity in HFpEF patients. A systematic search using PubMed, Embase, Scopus and Cochrane databases was performed to identify all relevant studies on beta-blockers and HFpEF. A random-effects model was performed to assess the role of beta-blockers on all-cause mortality and HF hospitalization. Overall 15 observational studies and two randomized control trial involving a total of 27,099 patients were included in the analysis. In the observational studies, beta-blocker therapy was associated with lower all-cause mortality [RR 0.81 (0.72-0.90), p < 0.001], but not HF hospitalization [RR 0.79 (0.57-1.10), p < 0.001]. However, in the two RCTs, the use of beta-blocker was not associated with all-cause mortality [RR 0.94 (0.67-1.32), p = 0.72] or HF hospitalization [0.90 (0.54-1.49), p = 0.68]. The results were consistent by geographic region (USA vs. rest of world) and ejection fraction subgroups. Subgroup analysis revealed that the beneficial survival effect of beta-blocker was limited to studies with mean age <75 years. Observational studies showed a significant benefit from the use of beta-blockers for all-cause mortality, but not for HF hospitalization. Beta-blockers in the two RCTs were not associated with significant reduction in all-cause mortality or HF hospitalization; however, both the trials were not adequately powered and had high loss to follow-up rates. Further large sampled well-conducted randomized trials are warranted to confirm the effects of beta-blockers on mortality and hospitalization.

BackgroundBisphenol-A (BPA) is a polymerizing agent used in plastic bottles and several routinely used consumer items. It is classified among endocrine disrupting chemicals suspected to cause adverse health effects in mammals ranging from infertility and cancer to behavioral disorders. Work with the invertebrate lab model Caenorhabditis elegans has shown that BPA affects germ cells by disrupting double-stranded DNA break repair mechanisms. The current study utilizes this model organism to provide insight into low-dose and long-term behavioral effects of BPA and bisphenol-S (BPS), a supposed safer replacement for BPA.FindingsExperiments presented in our report demonstrate that the effects of embryonic exposure to considerably low levels of BPA persist into adulthood, affecting neural functionality as assayed by measuring habituation to mechano-sensory stimuli in C. elegans. These results are noteworthy in that they are based on low-dose exposures, following the rationale that subtler effects that may not be morphologically apparent are likely to be discernible through behavioral changes. In addition, we report that embryonic exposure to BPS follows a pattern similar to BPA.ConclusionsBuilding upon previous observations using the C. elegans model, we have shown that exposure of embryos to BPA and BPS affects their behavior as adults. These long-term effects are in line with recommended alternate low-dose chemical safety testing approaches. Our observation that the effects of BPS are similar to BPA is not unexpected, considering their structural similarity. This, to our knowledge, is the first reported behavioral study on low-dose toxicity of any endocrine disrupting chemical in C. elegans.

Objective: To evaluate the cost-effectiveness of alemtuzumab compared with fingolimod, natalizumab, ocrelizumab, and generic glatiramer acetate 20 mg among patients with relapsing multiple sclerosis (RMS) in the United States. Study Design: Markov model with annual periods from payer perspective. Methods: The modeled population represented pooled patients from the CARE-MS I and II trials. Therapies' comparative efficacy at reducing relapses and slowing disability worsening was obtained from network meta-analyses. Safety information was extracted from package inserts. Withdrawal rates, treatment waning, resource use, cost, and utility inputs were derived from published studies and clinical expert opinion. To project the natural history of disease worsening, data from the British Columbia cohort was used. Results: Alemtuzumab dominated comparators by accumulating higher total qualityadjusted life-years (QALYs) (8.977) and lower total costs ($421 996) compared with fingolimod (7.955; $1 085 814), natalizumab (8.456; $1 048 599), ocrelizumab (8.478; $908 365), and generic glatiramer acetate (7.845; $895 661) over a 20-year time horizon. Alemtuzumab's dominance was primarily driven by savings in treatment costs because alemtuzumab has long-term duration of response and is initially administered as 2 annual courses, with 36.1% of patients requiring retreatment over 5 years, whereas comparators are used chronically. In model scenarios where alemtuzumab's long-term duration of response was assumed not to hold and therapy had to be administered annually, probabilistic sensitivity analyses showed that alemtuzumab remained cost-effective versus ocrelizumab at a willingness-to-pay threshold of $100 000/QALY in 74% to 100% of model runs. Conclusions: Alemtuzumab was a cost-effective therapy. Model results should be used to optimize clinical and managed care decisions for effective RMS treatment.