The Cost-Effectiveness and Value of Information of Three Influenza Vaccination Dosing Strategies for Individuals with Human Immunodeficiency Virus

Influenza vaccine immunogenicity is diminished in patients living with HIV/AIDS. We evaluated the cost-effectiveness and expected value of perfect information (EVPI) of three alternative influenza vaccine dosing strategies intended to increase immunogenicity in those patients.A randomized, multi-centered, controlled, vaccine trial was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine were used in HIV infected adults: two standard doses over 28 days (Strategy A), two double doses over 28 days (Strategy B) and a single standard dose of influenza vaccine (Strategy C), administered prior to the 2008 influenza season. The comparator in our analysis was practice in the previous year, in which 82.8% of HIV/AIDS received standard-dose vaccination (Strategy D). A Markov cohort model was developed to estimate the monthly probability of Influenza-like Illness (ILI) over one influenza season. Costs and quality-adjusted life years, extrapolated to the lifetime of the hypothetical study cohorts, were estimated in calculating incremental cost-effectiveness ratios (ICER) and EVPI in conducting further research.298 patients with median CD4 of 470 cells/µl and 76% with viral load suppression were randomized. Strategy C was the most cost-effective strategy for the overall trial population and for suppressed and unsuppressed individuals. Mean ICERs for Strategy A for unsuppressed patients could also be considered cost-effective. The level of uncertainty regarding the decision to implement strategy A versus C for unsuppressed individuals was high. The maximum acceptable cost of reducing decision uncertainty in implementing strategy A for individuals with unsuppressed pVL was $418,000--below the cost of conducting a larger-scale trial.Our results do not support a policy to implement increased antigen dose or booster dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine for individuals with HIV in Canada.ClinicalTrials.gov NCT00764998

Circuit-based interrogation of sleep control.

Sleep is a fundamental biological process observed widely in the animal kingdom, but the neural circuits generating sleep remain poorly understood. Understanding the brain mechanisms controlling sleep requires the identification of key neurons in the control circuits and mapping of their synaptic connections. Technical innovations over the past decade have greatly facilitated dissection of the sleep circuits. This has set the stage for understanding how a variety of environmental and physiological factors influence sleep. The ability to initiate and terminate sleep on command will also help us to elucidate its functions within and beyond the brain

Pulse Pressure is a Stronger Predictor Than Systolic Blood Pressure for Severe Eye Diseases in Diabetes Mellitus

Background: Evidence of the role of systolic blood pressure (SBP) in development of severe diabetic retinopathy is not strong, although the adverse effect of low diastolic blood pressure has been a partial explanation. We assessed the predictive ability of incident severe diabetic retinopathy between pulse pressure (PP) which considers both SBP and diastolic blood pressure, compared with SBP. Methods and Results: Eligible patients (12 242, 83% men) aged 19 to 72 years from a nationwide claims database were analyzed for a median observational 4.8‐year period. Severe diabetic retinopathy was defined as vision‐threatening treatment‐required diabetic eye diseases. Multivariate Cox regression analysis revealed that hazard ratios (95% CI) of treatment‐required diabetic eye diseases for 1 increment of standard deviation and the top tertile compared with the bottom tertile were 1.39 (1.21–1.60) and 1.72 (1.17–2.51), respectively, for PP and 1.22 (1.05–1.41) and 1.43 (0.97–2.11), respectively, for SBP adjusted for age, sex, body mass index, hemoglobin A1c, fasting plasma glucose, lipids, and smoking status. In a model with SBP and PP simultaneously as covariates, the hazard ratios of only PP (hazard ratios [95% CI], 1.57 [1.26–1.96]) but not SBP (0.85 [0.68–1.07]) were statistically significant. Delong test revealed a significant difference in the area under the receiver operating characteristic curve between PP and SBP (area under the receiver operating characteristic curve [95% CI], 0.58 [0.54–0.63] versus 0.54 [0.50–0.59]; P=0.03). The strongest predictor remained as hemoglobin A1c (area under the receiver operating characteristic curve [95% CI], 0.80 [0.77–0.84]). Conclusions: After excluding the significant impact of glycemic control, PP in comparison with SBP is a better predictor of severe diabetic retinopathy, suggesting a role of diastolic blood pressure and arterial stiffness in pathology

Predictive factors associated with bleeding in atrial fibrillation patients treated with anti-coagulant drugs using a large claims database.

ObjectiveTo identify risk factors for bleeding in atrial fibrillation (AF) patients treated with anti-coagulants such as warfarin, apixaban, edoxaban, dabigatran, rivaroxaban using a large claims database.MethodsA claims database for 8926 AF patients from 2004 to 2016 was obtained from JMDC. Inc. We performed a retrospective cohort study in 2796 Japanese AF patients with 4-month screening and 12-month observation periods. Polypharmacy was defined as prescription of over six drugs. Logistic regression analysis was conducted after stratification based on the presence and absence of cerebrovascular diseases to detect the predictive factors for bleeding.ResultsPolypharmacy was observed in 815 of 2796 (29.1%) patients. A total of 371 AF patients (13.3%) experienced bleeding in the 12-month observation period. Bleeding risk assessment using multiple logistic regression analysis revealed that the odds ratio for the number of co-administered drugs in the elderly (age for ≥60, ≤74) was not significant in those without and with cerebrovascular diseases (1.05 [0.99-1.12], N.S. and 1.10 [0.96-1.27], N.S.). In contrast, in the young (age for ConclusionWe determined the bleeding risk in the clinical setting using a large claims database. Physicians and pharmacists need to monitor patients for the initial bleeding signs, particularly in those with these predictive risk factors