Factors modifying drug and placebo responses in randomized trials for bipolar mania

Factors modifying drug and placebo responses in randomized trials for bipolar mania. Yildiz A, Vieta E, Tohen M, Baldessarini RJ. Source Department of Psychiatry, Dokuz Eylül University, Izmir, Turkey. agul_yildiz@hotmail.com Abstract Randomized placebo-controlled trials (RCTs) are standard for assessing efficacy and safety of treatments. We pursued preliminary indications that some factors are associated differentially with responses to placebo or drugs in RCTs for bipolar mania. We meta-analysed data from RCTs to assess influences of study-site count, subjects' age, sex distribution, diagnostic subgroups, clinical features, trial-completion rates, and publication year on mean difference (MD) in mania ratings between intake and final assessments. In 38 RCTs involving 3812 placebo-treated and 6988 drug-treated patients, symptomatic improvement was similar in placebo arms of trials of effective (6.77, 95% CI 5.77-7.76) and ineffective (7.61, 95% CI 5.47-8.75) drugs. Lesser placebo responses (MD) and greater drug-placebo differences (Hedges' g) were associated with fewer study sites, younger patients' age, and male sex. More patients with initial psychotic features and more trial completion in drug arms were associated with greater drug-associated improvement (MD) and drug-placebo contrast (Hedges' g), whereas more mixed-state diagnoses decreased both measures. Identifying modifying factors can support more efficient and cost-effective designs of therapeutic trials. In trials for mania, fewer sites may limit placebo response and enhance drug-placebo contrasts.

High Prevalence of Signs of Renal Damage Despite Normal Renal Function in a Cohort of HIV-Infected Patients: Evaluation of Associated Factors

Renal disorders are an emerging problem in HIV-infected patients. We performed a cross-sectional study of the first 1000 HIV-infected patients attended at our HIV unit who agreed to participate. We determined the frequency of renal alterations and its related risk factors. Summary statistics and logistic regression were applied. The study sample comprised 970 patients with complete data. Most were white (94%) and men (76%). Median (IQR) age was 48 (42–53) years. Hypertension was diagnosed in 19%, dyslipidemia in 27%, and diabetes mellitus in 3%. According to the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation, 29 patients (3%) had an eGFR < 60 ml/min/1.73m2; 18 of them (62%) presented altered albumin/creatinine and protein/creatinine (UPC or UAC) ratios. Of the patients with eGFR> 60mL/min, it was present in 293 (30%), 38 of whom (7.1%) had UPC> 300mg/g. Increased risk of renal abnormalities was correlated with hypertension (OR, 1.821 [95%CI, 1.292;2.564]; p = 0.001), age (OR, 1.015 [95%CI, 1.001;1.030], per one year; p = 0.040), and use of tenofovir disoproxil fumarate (TDF) plus protease inhibitor (PI), (OR, 1.401 [95%CI, 1.078;1.821]; p = 0.012). Current CD4 cell count was a protective factor (OR, 0.9995 [95%CI, 0.9991;0.9999], per one cell; p = 0.035). A considerable proportion of patients presented altered UPC or UAC ratios, despite having an eGFR > 60mL/min. CD4 cell count was a protective factor; age, hypertension, and use of TDF plus PIs were risk factors for renal abnormalities. Based on our results, screen of renal abnormalities should be considered in all HIV-infected patients to detect these alterations early.

Environmental factors, spatial variation, and specific requirements of Chironomidae in Mediterranean reference streams

Chironomidae spatial distribution was investigated at 63 near-pristine sites in 22 catchments of the Iberian Mediterranean coast. We used partial redundancy analysis to study Chironomidae community responses to a number of environmental factors acting at several spatial scales. The percentage of variation explained by local factors (23.3%) was higher than that explained by geographical (8.5%) or regional factors(8%). Catchment area, longitude, pH, % siliceous rocks in the catchment, and altitude were the best predictors of Chironomidae assemblages. We used a k-means cluster analysis to classified sites into 3 major groups based on Chironomidae assemblages. These groups were explained mainly by longitudinal zonation and geographical position, and were defined as 1) siliceous headwater streams, 2) mid-altitude streams with small catchment areas, and 3) medium-sized calcareous streams. Distinct species assemblages with associated indicator taxa were established for each stream category using IndVal analysis. Species responses to previously identified key environmental variables were determined, and optima and tolerances were established by weighted average regression. Distinct ecological requirements were observed among genera and among species of the same genus. Some genera were restricted to headwater systems (e.g., Diamesa), whereas others (e.g., Eukiefferiella) had wider ecological preferences but with distinct distributions among congenerics. In the present period of climate change, optima and tolerances of species might be a useful tool to predict responses of different species to changes in significant environmental variables, such as temperature and hydrology.