Tolerability and Safety Profile of Cariprazine in Treating Psychotic Disorders, Bipolar Disorder and Major Depressive Disorder: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Cariprazine is a novel antipsychotic agent recently approved for treating schizophrenia and bipolar mania in the USA. The sample sizes of published randomized controlled trials (RCTs) of the drug are small; previous meta-analyses included few RCTs and did not specifically investigate the tolerability/safety profile of cariprazine. OBJECTIVE: Our objective was to conduct a meta-analysis of published RCTs to systematically review the tolerability and safety of cariprazine versus placebo. METHODS: We searched the clinical trial registers (the metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform) and electronic databases (PubMed, Embase, PsycINFO and Cochrane library) up to June 2016 to identify phase II/III RCTs of cariprazine in patients with schizophrenia, bipolar disorder or major depressive disorder. We conducted a meta-analysis to investigate outcomes, including risks of discontinuation due to adverse events (AEs), extrapyramidal side effects (EPS) or related events, metabolic syndrome and cardiovascular-related events. RESULTS: We included nine RCTs, with a total of 4324 subjects. The risk of discontinuation due to AEs for cariprazine was similar to that for placebo (risk ratio [RR] 1.13, 95 % confidence interval [CI] 0.77-1.66). Cariprazine was associated with higher risks of EPS-related events than was placebo, including risk of akathisia (RR 3.92, 95 % CI 2.83-5.43), tremor (RR 2.41, 95 % CI 1.53-3.79) and restlessness (RR 2.17, 95 % CI 1.38-3.40). The cariprazine treatment group was more likely to have clinically significant weight gain (RR 1.68, 95 % CI 1.12-2.52). No statistically significant differences in results were found in other metabolic parameters or cardiovascular-related events. CONCLUSION: There was a statistically significant higher risk of EPS-related AEs and a slight increase in mean body weight with cariprazine. There were no statistically significant effects on prolactin level or cardiovascular parameters. EPSs were the main short-term adverse reactions reported in the limited number of patients studied. Further clinical and post-marketing pharmacovigilance studies are needed to investigate the long-term safety of cariprazine

Cohort analysis of programme data to estimate HIV incidence and uptake of HIV-related services among female sex workers in Zimbabwe, 2009-14.

BACKGROUND: HIV epidemiology and intervention uptake among female sex workers (FSW) in sub-Saharan Africa remain poorly understood. Data from outreach programmes are a neglected resource. METHODS: Analysis of data from FSW consultations with Zimbabwe's National Sex Work programme, 2009-14. At each visit, data were collected on socio-demographic characteristics, HIV testing history, HIV tests conducted by the programme and antiretroviral (ARV) history. Characteristics at first visit and longitudinal data on programme engagement, repeat HIV testing and HIV sero-conversion were analysed using a cohort approach. RESULTS: Data were available for 13360 women, 31389 visits, 14579 reported HIV tests, 2750 tests undertaken by the programme and 2387 reported ARV treatment initiations. At first visit, 72% of FSW had tested for HIV; 50% of these reported being HIV-positive. Among HIV-positive women, 41% reported being on ARV. 56% of FSW attended the programme only once. FSW who had not previously had an HIV positive test had been tested within the last 6 months 27% of the time during follow up. After testing HIV-positive, women started on ARV at a rate of 23 / 100 person years of follow-up. Among those with two or more HIV tests, the HIV sero-conversion rate was 9.8 / 100 person years of follow-up (95% confidence interval 7.1-15.9). CONCLUSIONS: Individual-level outreach programme data can be used to estimate HIV incidence and intervention uptake among FSW in Zimbabwe. Current data suggest very high HIV prevalence and incidence among this group and help identify areas for programme improvement. Further methodological validation is required.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially.<br/

Attitudes and perceptions towards hypoglycaemia in patients with diabetes mellitus: A multinational cross-sectional study

BACKGROUND: Preventing hypoglycaemia is an essential component of diabetes self-management that is affected by patients' attitudes and perceptions. This study aimed to explore the hypoglycaemia problem-solving ability of patients who have diabetes mellitus and factors that determine their attitudes and perceptions towards their previous events. METHODOLOGY: A cross-sectional study was conducted between October 2017 and May 2018 in three Arab countries (Jordan, Saudi Arabia and Kuwait) in patients with diabetes mellitus, who were prescribed antidiabetic therapy and had experienced hypoglycaemic events in the past six months. The Hypoglycaemia Problem-Solving Scale was used in this study. This scale contains two subscales, problem orientation (six questions) and problem-solving skills (eighteen questions), using a five-point Likert scale (range 0-4). Multiple linear regression analysis was used to identify predictors of hypoglycaemia problem-solving abilities. RESULTS: A total of 895 patients participated in this study from the three countries (300 in Jordan, 302 in Saudi Arabia, and 293 in Kuwait). The average age of the patients was 53.5 years (standard deviation = 13.7) and 52.4% (n = 469) were males. Patients had moderate overall problem-solving ability with a median score of 63.00 (interquartile range = 13.00). Patients' problem-solving skills score (68.1%) was better than their problem-orientation skills score (58.3%). The highest sub-scale scores were for detection control, setting problem-solving goals, and evaluating strategies, 75.0%. The lowest sub-scale score was for problem-solving perception and immediate management, 50.0%. Older age, being educated, being married, having T2DM, prescribed insulin therapy, and not having been admitted to hospital for hypoglycaemia were important predictors of patients' problem-solving ability (p < 0.05). CONCLUSIONS: Healthcare professionals are advised to provide more education to patients on how to self-manage hypoglycaemic events. Specifically, they should focus on the overall problem-solving perception of hypoglycaemia and its immediate management

Tin(iv) dopant removal through anti-solvent engineering enabling tin based perovskite solar cells with high charge carrier mobilities

We report the need for careful selection of anti-solvents for Sn-based perovskite solar cells fabricated through the commonly used anti-solvent method, compared to their Pb-based counterparts.</p

Impact of inhaled corticosteroids on growth in children with asthma: systematic review and meta-analysis

Background: Long-term inhaled corticosteroids (ICS) may reduce growth velocity and final height of children with asthma. We aimed to evaluate the association between ICS use of >12 months and growth. Methods: We initially searched MEDLINE and EMBASE in July 2013, followed by a PubMed search updated to December 2014. We selected RCTs and controlled observational studies of ICS use in patients with asthma. We conducted random effects meta-analysis of mean differences in growth velocity (cm/year) or final height (cm) between groups. Heterogeneity was assessed using the I2 statistic. Results: We found 23 relevant studies (twenty RCTs and three observational studies) after screening 1882 hits. Meta-analysis of 16 RCTs showed that ICS use significantly reduced growth velocity at one year follow-up (mean difference -0.48 cm/year (95% CI -0.66 to -0.29)). There was evidence of a dose-response effect in three RCTs. Final adult height showed a mean reduction of -1.20 cm (95% CI -1.90 cm to -0.50 cm) with budesonide versus placebo in a high quality RCT. Meta-analysis of two lower quality observational studies revealed uncertainty in the association between ICS use and final adult height, pooled mean difference -0.85 cm (95% CI -3.35 to 1.65). Conclusion: Use of ICS for >12 months in children with asthma has a limited impact on annual growth velocity. In ICS users, there is a slight reduction of about a centimeter in final adult height, which when interpreted in the context of average adult height in England (175 cm for men and 161 cm for women), represents a 0.7% reduction compared to non-ICS users

The HIV care cascade among female sex workers in Zimbabwe: results of a population-based survey from the Sisters Antiretroviral therapy Programme for Prevention of HIV, an Integrated Response (SAPPH-IRe) Trial.

: Female sex workers (FSW) in sub-Saharan Africa have a higher prevalence of HIV than other women of reproductive age. Social, legal, and structural barriers influence their access to care. Little is known about the HIV diagnosis and care cascade in most countries in Southern Africa. We aimed to describe the HIV diagnosis and care cascade among FSW in Zimbabwe. : We conducted cross-sectional respondent driven sampling (RDS) surveys of FSW in 14 sites across Zimbabwe as the baseline for a cluster-randomised controlled trial investigating a combination HIV prevention and care package. We administered a questionnaire, tested women for HIV and measured viral load. We report the mean, minimum, and maximum respondent-driven sampling-2 weighted site values. : The survey included 2722 women, approximately 200 per site. The mean HIV prevalence was 57.5% (42.8-79.2 site minimum and maximum). Of HIV-positive women, 64.0% (51.6-73.7) were aware of their status, 67.7% (53.4-84.1) of these reported taking antiretroviral therapy, and 77.8% (64.4-90.8) of these had a suppressed HIV viral load (&lt;1000 copies/mL). Among all HIV-positive women, 49.5% had a viral load &lt; 1000 copies/mL. : Although most HIV-positive women aware of their status are accessing antiretroviral therapy, 36.0% of HIV-positive women are unaware of their status and 29.3% of all FSW have an unsuppressed HIV viral load. Investigation and investment into models of testing, treatment, and care are necessary to reach UNAIDS targets for HIV elimination.<br/

Temporal and Spatial Dynamics of Carbon Fixation by Moso Bamboo (Phyllostachys pubescens) in Subtropical China

To study the temporal and spatial dynamics of carbon fixation by Moso bamboo (Phyllostachys pubescens) in subtropical China, carbon fixation of leaves within the canopy of P. pubescens was measured with a LI-6400 portable photosynthesis system. The results showed that the capability of carbon fixation of P. pubescens leaves had obvious temporal and spatial dynamic variations. It was revealed that there were two peak periods and two low periods in the season variation of carbon fixation capability. Data also revealed that the capability of carbon fixation by five-year-old P. pubescens was more than that of one-year-old and three-year-old. Daily and seasonal carbon fixation showed a negative correlation with the CO2 concentration. The temporal and spatial dynamics of carbon fixation by P. pubescens described above provided a scientific basis for development of technologies in bamboo timber production

STORIES Statement: publication standards for healthcare education evidence synthesis

Fully copy of the STORIES statement - a checklist of reporting guidance for health education evidence synthesis Structured approach for Reporting In health education of Evidence Synthesis Background Evidence synthesis techniques in healthcare education have been enhanced through the activities of experts in the field and the Best Evidence Medical Education (BEME) collaborative. Despite this, significant heterogeneity in techniques and reporting of healthcare education systematic review still exist and limit the usefulness of such reports. The aim of this project was to produce the STORIES (STructured apprOach to the Reporting In healthcare education of Evidence Synthesis) statement to offer a guide for reporting evidence synthesis in health education for use by authors and journal editors. Methods A review of existing published evidence synthesis consensus statements was undertaken. A modified Delphi process was used. In stage one, expert participants were asked to state whether common existing items identified were relevant, to suggest relevant texts and specify any items they feel should be included. The results were analysed and a second stage commenced where all synthesised items were presented and participants asked to state whether they should be included or amend as needed. After further analysis, the full statement was sent for final review and comment. Results Nineteen experts participated in the panel from 35 invitations. Thirteen text sources were proposed, six existing items amended and twelve new items synthesised. After stage two, 25 amended consensus items were proposed for inclusion. The final statement contains several items unique to this context, including description of relevant conceptual frameworks or theoretical constructs, description of qualitative methodologies with rationale for their choice and presenting the implications for educators in practice of the results obtained. Conclusions An international expert panel has agreed upon a consensus statement of 25 items for the reporting of evidence synthesis within healthcare education. This unique set of items is focused on context, rather than a specific methodology. This statement can be used for those writing for publication and reviewing such manuscripts to ensure reporting supports and best informs the wider healthcare education community

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

© 2014 Haider et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options