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Background Around 1 in 7 people in India are impacted by mental illness. The treatment gap for people with mental disorders is as high as 75–95%. Health care systems, especially in rural regions in India, face substantial challenges to address these gaps in care, and innovative strategies are needed. Methods We hypothesise that an intervention involving an anti-stigma campaign and a mobile-technology-based electronic decision support system will result in reduced stigma and improved mental health for adults at high risk of common mental disorders. It will be implemented as a parallel-group cluster randomised, controlled trial in 44 primary health centre clusters servicing 133 villages in rural Andhra Pradesh and Haryana. Adults aged ≥ 18 years will be screened for depression, anxiety and suicide based on Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorders (GAD-7) scores. Two evaluation cohorts will be derived—a high-risk cohort with elevated PHQ-9, GAD-7 or suicide risk and a non-high-risk cohort comprising an equal number of people not at elevated risk based on these scores. Outcome analyses will be conducted blinded to intervention allocation. Expected outcomes The primary study outcome is the difference in mean behaviour scores at 12 months in the combined ‘high-risk’ and ‘non-high-risk’ cohort and the mean difference in PHQ-9 scores at 12 months in the ‘high-risk’ cohort. Secondary outcomes include depression and anxiety remission rates in the high-risk cohort at 6 and 12 months, the proportion of high-risk individuals who have visited a doctor at least once in the previous 12 months, and change from baseline in mean stigma, mental health knowledge and attitude scores in the combined non-high-risk and high-risk cohort. Trial outcomes will be accompanied by detailed economic and process evaluations. Significance The findings are likely to inform policy on a low-cost scalable solution to destigmatise common mental disorders and reduce the treatment gap for under-served populations in low-and middle-income country settings. Trial registration Clinical Trial Registry India CTRI/2018/08/015355. Registered on 16 August 2018.

Purpose: To evaluate the psychological impact of the COVID 19 crisis on ophthalmologists-in-training and practising ophthalmologists during lockdown in India. Methods: An online survey was completed by ophthalmologists and ophthalmology trainees during the lockdown. The information collected included demographics (age, gender), domicile (state, union territory), current professional status (in training or practising), type of practice (solo, group, institutional, governmental, non-governmental), marital status (married, single), impact of COVID-19 on their training or practice, and impact on income and ability to meet living expenses. Psychological distress was assessed using the Patient Health Questionnaire-9 (PHQ-9). Results: In all, 2,355 ophthalmologists responded. Mean age was 42.5 (range, 25-82 years; SD, 12.05) years. Of these, 1,332 (56.7%) were males; 475 (20.2%) were still not in practice; 366 (15.5%) were single; 1,244 (52.8%) felt that COVID-19 would impact on their training or professional work; and 869 (37%) had difficulty in meeting their living expenses. The mean PHQ-9 score was 3.98 (range, 0-27; SD, 4.65). In terms of psychological impact, 768 (32.6%) had some degree of depression; mild in 504 (21.4%), moderate in 163 (6.9%), and severe in 101 (4.3%). Multivariable analysis showed that depression was significantly higher at younger age. The odds of depression decreased by 3% with 1 year increase in age. It was higher in non-practicing ophthalmologists, especially those who were considerably worried about their training or professional growth, and those with difficulty in meeting living expenses. Conclusion: A strikingly high proportion of ophthalmologists are psychologically affected and may require personalized mental health care.

Background: Healthcare workers (HCWs),particularly from lower-middle income countries (LMIC), are at high risk of acquiring COVID-19. Limited data exist on the effectiveness of hydroxychloroquine as prophylaxis. Our trial evaluated the effectiveness of a 12-week regimen of hydroxychloroquine among HCWs on the risk of laboratory-confirmed COVID-19 in the 6 months after randomization Methods: We conducted a multicentre parallel-group open-label randomized controlled trial in 9 centres across India. HCWs serving in an environment with exposure to COVID-19 were eligible and randomized in a 1:1 ratio to hydroxychloroquine plus standard practice or to standard practice alone (role-appropriate personal protective equipment). In the intervention arm, participants received 2 doses of 400mg hydroxychloroquine at randomization followed by a weekly dose for 12 weeks. The primary outcome was the proportion of laboratory-confirmed COVID-19 in the 6 months after randomization using an intention-to-treat analysis. The trial was registered on Clinical Trials Registry of India(CTRI/2020/05/025067). Findings: From 29th June 2020 to 4th February 2021, 886 participants were screened and 416 were randomized (203-standard practice and 213- hydroxychloroquine plus standard practice). In the 6 months after randomization (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary end point[ 5.1% vs 5.9%; OR 0.85, [95% CI 0.35-2.06] p=0.71]. There was no heterogeneity of treatment effect on the primary outcome in any of the pre-specified subgroups. There were no significant differences in any of the secondary outcomes. The adverse event rates were 9.9% and 6.9% in the hydroxychloroquine and standard practice arms respectively. There were no serious adverse events in either group. Interpretation: Hydroxychloroquine along with standard practice was not superior to standard practice alone on the proportion of lab-confirmed COVID-19. However, conclusions are limited by the premature trial cessation. Trial Registration: Clinical Trials Registry of India (CTRI/2020/05/025067). Funding: Wesley Medical Research, Australia Declaration of Interest: OJ reports being a member of the WHO R&D Blueprint Safety Monitoring Team, ACT Acclerator-R&D Digital Health working group and COVID-19 Clinical Research Coalition data sharing working group. Remaining authors have nothing to declare. Ethical Approval: Written informed consent was obtained from all participants. The trial was approved by the Ethics Committee at all participating sites (coordinating centre EC approval number: The George Institute Ethics Committee:08-2020)

BACKGROUND AND OBJECTIVES: Neuropathy is a common complication of kidney disease that lacks proven disease-modifying treatments. Hemodiafiltration improves clearance of uremic toxins and is associated with better nerve function than hemodialysis. We aimed to determine whether hemodiafiltration reduces the progression of neuropathy in people receiving hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Filtration in the Neuropathy of End-Stage Kidney Disease Symptom Evolution (FINESSE) study was an open-label, blinded end point assessment, controlled trial that randomized maintenance hemodialysis recipients to hemodiafiltration or high-flux hemodialysis for 48 months or until death or cessation of dialysis at four study centers. The primary outcome was the mean change in the yearly modified total neuropathy score from baseline, with time points weighted equally. RESULTS: A total of 124 participants were randomized and followed for a mean of 41 months. At baseline, neuropathy was present in 91 (73%) participants (modified total neuropathy score greater than or equal to two), and 38 (31%) had moderate to severe neuropathy (modified total neuropathy score 9–28). Convection volume in the hemodiafiltration arm was a median of 24.7 (interquartile range, 22.4–26.5) L. The mean modified total neuropathy score (SEM) worsened by 1.7 (0.4)/28 and 1.2 (0.4)/28 in the hemodiafiltration and hemodialysis groups, respectively, with a mean difference of 0.5 (95% confidence interval, −0.7 to 1.7; P=0.37). There was no difference in survival (hazard ratio, 1.24; 95% confidence interval, 0.61 to 2.51; log rank P=0.55) or any of the prespecified adverse events. There was no difference between groups in the number of participants who suffered an adverse event adjusted by follow-up time (relative risk, 1.05; 95% confidence interval, 0.83 to 1.32; P=0.68). CONCLUSIONS: Neuropathy is still a common complication of kidney disease without disease-altering therapy. Hemodiafiltration did not affect neuropathy progression compared with hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Filtration in the Neuropathy of End-Stage Kidney Disease Symptom Evolution (FINESSE), ACTRN12609000615280

Background Obesity is characterized by inflammation, caused by increase in proinflammatory cytokines, a key factor for the development of insulin resistance. SR141716A, a cannabinoid receptor 1 (CB1) antagonist, shows significant improvement in clinical status of obese/diabetic patients. Therefore, we studied the effect of SR141716A on human adipocyte inflammatory profile and differentiation. Methods Adipocytes were obtained from liposuction. Stromal vascular cells were extracted and differentiated into adipocytes. Media and cells were collected for secretory (ELISA) and expression analysis (qPCR). Triglyceride accumulation was observed using oil red-O staining. Cholesterol was assayed by a fluorometric method. 2-AG and anandamide were quantified using isotope dilution LC-MS. TLR-binding experiments have been conducted in HEK-Blue cells. Results In LPS-treated mature adipocytes, SR141716A was able to decrease the expression and secretion of TNF-a. This molecule has the same effect in LPS-induced IL-6 secretion, while IL-6 expression is not changed. Concerning MCP-1, the basal level is down-regulated by SR141716A, but not the LPS-induced level. This effect is not caused by a binding of the molecule to TLR4 (LPS receptor). Moreover, SR141716A restored adiponectin secretion to normal levels after LPS treatment. Lastly, no effect of SR141716A was detected on human pre-adipocyte differentiation, although the compound enhanced adiponectin gene expression, but not secretion, in differentiated pre-adipocytes. Conclusion We show for the first time that some clinical effects of SR141716A are probably directly related to its anti-inflammatory effect on mature adipocytes. This fact reinforces that adipose tissue is an important target in the development of tools to treat the metabolic syndrome.