Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratory-confirmed COVID-19 infections among healthcare workers: a multicentre, parallel-group randomised controlled trial from India.

OBJECTIVES: To determine whether hydroxychloroquine when used with personal protective equipment reduces the proportion of laboratory-confirmed COVID-19 among healthcare workers in comparison to the use of personal protective equipment alone. DESIGN: Multicentre, parallel-group, open-label randomised trial. Enrolment started on 29 June 2020 and stopped on 4 February 2021. Participants randomised in HydrOxychloroquine Prophylaxis Evaluation were followed for 6 months. SETTING: 9 hospitals across India. PARTICIPANTS: Healthcare workers in an environment with exposure to COVID-19 were randomised in a 1:1 ratio to hydroxychloroquine plus use of personal protective equipment or personal protective equipment alone. 886 participants were screened and 416 randomised (213 hydroxychloroquine arm and 203 personal protective equipment). INTERVENTION: Participants in intervention arm received 800 mg of hydroxychloroquine on day of randomisation and then 400 mg once a week for 12 weeks in addition to the use of personal protective equipment. In the control arm, participants continued to use personal protective equipment alone. MAIN OUTCOME: Proportion of laboratory-confirmed COVID-19 in the 6 months after randomisation. RESULTS: Participants were young (mean age 32.1 years, SD 9.1 years) with low-comorbid burden. 47.4% were female. In the 6 months after randomisation (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary endpoint (5.2% vs 5.9%; OR 0.85, 95% CI 0.35 to 2.07, p=0.72). There was no heterogeneity of treatment effect in any prespecified subgroup. There were no significant differences in 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. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine along with personal protective equipment was not superior to personal protective equipment alone on the proportion of laboratory-confirmed COVID-19. Definitive conclusions are precluded as the trial stopped early for futility, and hence was underpowered. TRIAL REGISTRATION NUMBER: CTRI/2020/05/025067.

Applying systems thinking to identify enablers and challenges to scale-up interventions for hypertension and diabetes in low-income and middle-income countries: protocol for a longitudinal mixed-methods study.

INTRODUCTION: There is an urgent need to reduce the burden of non-communicable diseases (NCDs), particularly in low-and middle-income countries, where the greatest burden lies. Yet, there is little research concerning the specific issues involved in scaling up NCD interventions targeting low-resource settings. We propose to examine this gap in up to 27 collaborative projects, which were funded by the Global Alliance for Chronic Diseases (GACD) 2019 Scale Up Call, reflecting a total funding investment of approximately US$50 million. These projects represent diverse countries, contexts and adopt varied approaches and study designs to scale-up complex, evidence-based interventions to improve hypertension and diabetes outcomes. A systematic inquiry of these projects will provide necessary scientific insights into the enablers and challenges in the scale up of complex NCD interventions. METHODS AND ANALYSIS: We will apply systems thinking (a holistic approach to analyse the inter-relationship between constituent parts of scaleup interventions and the context in which the interventions are implemented) and adopt a longitudinal mixed-methods study design to explore the planning and early implementation phases of scale up projects. Data will be gathered at three time periods, namely, at planning (TP), initiation of implementation (T0) and 1-year postinitiation (T1). We will extract project-related data from secondary documents at TP and conduct multistakeholder qualitative interviews to gather data at T0 and T1. We will undertake descriptive statistical analysis of TP data and analyse T0 and T1 data using inductive thematic coding. The data extraction tool and interview guides were developed based on a literature review of scale-up frameworks. ETHICS AND DISSEMINATION: The current protocol was approved by the Monash University Human Research Ethics Committee (HREC number 23482). Informed consent will be obtained from all participants. The study findings will be disseminated through peer-reviewed publications and more broadly through the GACD network.

An intervention package for supporting the mental well-being of community health workers in low, and middle-income countries during the COVID-19 pandemic.

BACKGROUND: As the COVID-19 pandemic continues, there is an increasing reliance on community health workers (CHWs) to achieve its control especially in low, and middle-income countries (LMICs). An increase in the demand for their services and the challenges they already face make them prone to mental health illness. Therefore, there is a need to further support the mental health and well-being of CHWs during the COVID-19 pandemic. METHODS: We organised a workshop on Zoom to deliberate on relevant components of an intervention package for supporting the mental health of CHWs in LMICs during the COVID-19 pandemic. We used a thematic analysis approach to summarise deliberations from this workshop. OUTCOMES: Participants identified the need for a hub for coordinating CHW activities, a care coordination team to manage their health, training programs aimed at improving their work performance and taking control of their health, a communication system that keeps them in touch with colleagues, family, and the communities they serve. They cautioned against confidentiality breaches while handling personal health information and favoured tailoring interventions to the unique needs of CHWs. Participants also advised on the need to ensure job security for CHWs and draw on available resources in the community. To measure the impact of such an intervention package, participants encouraged the use of mixed methods and a co-designed approach. INTERPRETATION: As CHWs contribute to the pandemic response in LMICs, their mental health and well-being need to be protected. Such protection can be provided by using an intervention package that harnesses inputs from members of the broader health system, their families, and communities.

Effects of a Lifestyle Intervention to Prevent Deterioration in Glycemic Status Among South Asian Women With Recent Gestational Diabetes: A Randomized Clinical Trial.

Importance: Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. Objective: To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. Design, Setting, and Participants: This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021. Interventions: A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care. Main Outcomes and Measures: The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight. Results: A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome. Conclusions and Relevance: This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry Identifier: SLCTR/2017/001; and ClinicalTrials.gov Identifier: NCT03305939.

Do mentoring programmes influence women's careers in the health and medical research sector? A mixed-methods evaluation of Australia's Franklin Women Mentoring Programme.

OBJECTIVES: It is known that women are under-represented in senior positions within the health and medical research sector. The Franklin Women Mentoring Programme (Programme) is a professionally facilitated, cross-organisational initiative designed to support career development for mid-career women. The objective of this study was to evaluate Programme outcomes reported by participants 12 months following its formal conclusion. DESIGN: Explanatory sequential mixed-methods study design using a cross-sectional survey and semi-structured interviews. SETTING: Health and medical research institutes in Sydney, Australia. PARTICIPANTS: Health and medical researchers from the 2018 Programme. PRIMARY AND SECONDARY OUTCOME MEASURES: Changes in knowledge, skills, behaviours and research metrics directly attributed to Programme participation. RESULTS: A total of 50 mentors and mentees participated in the cross-sectional survey (68% of the total cohort) and 14 mentors and mentees participated in the interviews. All reported changes to their knowledge, skills, behaviours and research metrics which were directly attributed to participation in the Programme. This included changes in knowledge and skills to be more inclusive (96% mentees, 83% mentors), resilience (88% mentees, 67% mentors), ability to have difficult workplace conversations (88% mentees, 71% mentors) and improvements in supervisory and team management (82% mentees, 75% mentors) skills. Positive impacts on promotions and grant opportunities were also reported. All evaluation participants believed this Programme was a worthwhile initiative for their workplaces to invest in. CONCLUSION: Participation in this cross-organisational, professionally facilitated, structured mentoring programme has led to positive outcomes for mentees, as well as mentors. Reported outcomes indicate the Programme is meeting its aims to support the career development of mid-career women in health and medical research, while facilitating a more inclusive workforce.

Reformulation and strengthening of return-of-service (ROS) schemes could change the narrative on global health workforce distribution and shortages in sub-Saharan Africa.

Despite policies for addressing shortages and maldistribution of health professionals, sub-Saharan Africa continues to experience shortages and maldistribution of skilled health professionals. Policies such as return-of-service schemes or state-funded educational initiatives do not seem to be achieving their intended objectives, potentially due to poor design, implementation; and lack of monitoring and evaluation of the strategies. A focus by global health experts on strengthening and reformulating educational initiatives offers potential for producing, retaining and recruiting health professionals.

Hydroxychloroquine plus personal protective equipment versus standard personal protective equipment alone for the prevention of COVID-19 infections among frontline healthcare workers: the HydrOxychloroquine Prophylaxis Evaluation(HOPE) trial: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: To evaluate the effect of the combination of hydroxychloroquine (HCQ) and standard personal protective equipment (PPE) compared to the use of standard personal protective equipment alone on the proportion of laboratory confirmed COVID-19 infections among frontline healthcare workers(HCWs) in India TRIAL DESIGN: HOPE is an investigator initiated multi-centre open-label parallel group randomized controlled trial. PARTICIPANTS: All HCWs currently working in an environment with direct exposure to patients with confirmed COVID-19 infection are eligible to participate in the trial. The trial aims to be conducted across 20-30 centres (public and private hospitals) in India. HCWs who decline consent, who have a confirmed COVID-19 infection, those who are already on chloroquine/HCQ for any indication, or if pregnant or breast-feeding, or have known QT prolongation or are on medications that when taken with HCQ can prolong the QTc will be excluded. INTERVENTION AND COMPARATOR: The interventions to be compared in this trial are standard practice (use of recommended PPE) and HCQ plus standard practice. In the standard practice arm, HCWs will use recommended PPE as per institutional guidelines and based on their roles. They will be discouraged from taking HCQ to prevent contamination and contacted every week for the duration of the study to ascertain if they have taken any HCQ. Any such use will be reported as a protocol violation. In the intervention arm, HCWs will be administered 800mg of HCQ as a loading dose on the day of randomization (as two 400mg doses 12hrs apart) and subsequently continued on 400mg once a week for 12 weeks. This will be in addition to the use of recommended PPE as per institutional guidelines and based on their roles. HCWs will collect the drug once every week from designated research and pharmacy staff at site. A weekly phone reminder will be provided to participants in this arm to ensure compliance. An ECG will be performed between 4-6 weeks in this arm and if the QTc is prolonged (greater than 450milliseconds), the drug will be stopped. Follow-up will however continue. Participants in both arms will receive a weekly phone call for evaluation of the primary outcome, to monitor protocol compliance and development of any adverse events (in the HCQ group). MAIN OUTCOMES: Participants will be followed on a weekly basis. The primary outcome is the proportion of HCWs developing laboratory confirmed COVID-19 infection within 6 months of randomization. We will also evaluate a number of secondary outcomes, including hospitalization related to suspected/confirmed COVID-19 infection, intensive care unit or high-dependency unit admission due to suspected/confirmed COVID-19 infection, all-cause mortality, need for organ support ( non-invasive or invasive ventilation, vasopressors and renal replacement therapy), ICU and hospital length of stay, readmission, days off work and treatment-related adverse events. RANDOMISATION: Randomisation will be conducted through a password-protected, secure website using a central, computer-based randomisation program. Randomisation will be stratified by participating institutions and by the role of HCW - nursing, medical and other. Participants will be randomised 1:1 to either standard practice only or HCQ plus standard practice. Allocation concealment is maintained by central web-based randomisation BLINDING (MASKING): This is an unblinded study: study assigned treatment will be known to the research team and participant. Bias will be mitigated through an objective end point (laboratory confirmed COVID-19 infection). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 6,950 HCWs will be enrolled (3475 to the intervention) and (3475 to the standard practice group) to detect a 25% relative reduction, or 2.5% absolute reduction, in the infection rate from an estimated baseline infection rate of 10%, with 80% statistical power using a two-sided test at 5% level of significance. Available data from China and Italy indicate that the rate of infection among frontline healthcare workers varies between 4% to 12%. We therefore assumed a baseline infection rate of 10% among HCWs. This sample size allows for a potential loss to follow-up rate of 10% and a potential non-compliance rate of 10% in both the treatment and control arms. TRIAL STATUS: HOPE protocol version 3.0 dated June 3rd 2020. Recruitment started on 29th June 2020 and currently 56 participants have been enrolled. Planned completion of enrolment is January 31st 2021. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2020/05/025067 (prospectively registered) Date of registration: 6th May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expedited dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).