A scoping review on laboratory surveillance in the WHO Southeast Asia Region: Past, present and the future.

Background: The South-East Asia (SEA) region bears a significant proportion of the world's communicable disease burden. The onset of the COVID-19 pandemic has further affected the situation. A well-established laboratory-based surveillance (LBS) can reduce the burden of infectious diseases. In light of this, the review collated the existing literature on LBS system in the region and the modifications adopted by the surveillance systems during the pandemic. Methodology: We followed the guidelines for scoping review as prescribed by Arskey and O'Malley. We comprehensively searched three databases (PubMed, Scopus and CINAHL) and supplemented it with grey literature search. The screening of the articles was conducted at the title and abstract followed by full-text screening. This was followed by data extraction using a pre-tested data extraction tool by two independent reviewers. The results were presented narratively. Results: Including 75 relevant articles and documents, we compiled a list of surveillance systems. A shift from paper to dual (paper and electronic) modalities was identified across the countries. This largely low- and middle-income countries (LMIC) area face challenges in reporting, resources, and collaboration-related issues. While some countries have well-established National Reference Laboratories; others have more private than public-owned laboratories. Given the COVID-19 pandemic, modifications to the existing laboratory capacities to enable real-time surveillance was identified. Laboratory capacity complemented with genomic surveillance can indubitably aid in disease detection and control. Limitations due to inaccessible government portals, and language barriers are acknowledged. This review identified a comprehensive list of surveillance systems in the region, challenges faced in using these surveillance systems and inform the decision makers about the benefits of integrating fragmented surveillance systems. Conclusion: Regionally and nationally integrated genomic and laboratory surveillance systems justify capital investments, as their payoffs rationalise such costs owing to economies of scale over time. Further, as data flows are harmonized and standardized, algorithm- and computing-based pattern recognition methods allow for targeted and accurate disease prediction when integrated with, potentially, climate and weather systems data. Trained human resources are a sine qua non to optimize such investments, but in the medium to long run, such investments will buttress initiatives in other arenas at the regional level.

Measuring the Burden of Infodemics: Summary of the Methods and Results of the Fifth WHO Infodemic Management Conference.

Background: An infodemic is excess information, including false or misleading information, that spreads in digital and physical environments during a public health emergency. The COVID-19 pandemic has been accompanied by an unprecedented global infodemic that has led to confusion about the benefits of medical and public health interventions, with substantial impact on risk-taking and health-seeking behaviors, eroding trust in health authorities and compromising the effectiveness of public health responses and policies. Standardized measures are needed to quantify the harmful impacts of the infodemic in a systematic and methodologically robust manner, as well as harmonizing highly divergent approaches currently explored for this purpose. This can serve as a foundation for a systematic, evidence-based approach to monitoring, identifying, and mitigating future infodemic harms in emergency preparedness and prevention. Objective: In this paper, we summarize the Fifth World Health Organization (WHO) Infodemic Management Conference structure, proceedings, outcomes, and proposed actions seeking to identify the interdisciplinary approaches and frameworks needed to enable the measurement of the burden of infodemics. Methods: An iterative human-centered design (HCD) approach and concept mapping were used to facilitate focused discussions and allow for the generation of actionable outcomes and recommendations. The discussions included 86 participants representing diverse scientific disciplines and health authorities from 28 countries across all WHO regions, along with observers from civil society and global public health-implementing partners. A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used throughout the conference to frame and contextualize discussions. Five key areas for immediate action were identified. Results: The 5 key areas for the development of metrics to assess the burden of infodemics and associated interventions included (1) developing standardized definitions and ensuring the adoption thereof; (2) improving the map of concepts influencing the burden of infodemics; (3) conducting a review of evidence, tools, and data sources; (4) setting up a technical working group; and (5) addressing immediate priorities for postpandemic recovery and resilience building. The summary report consolidated group input toward a common vocabulary with standardized terms, concepts, study designs, measures, and tools to estimate the burden of infodemics and the effectiveness of infodemic management interventions. Conclusions: Standardizing measurement is the basis for documenting the burden of infodemics on health systems and population health during emergencies. Investment is needed into the development of practical, affordable, evidence-based, and systematic methods that are legally and ethically balanced for monitoring infodemics; generating diagnostics, infodemic insights, and recommendations; and developing interventions, action-oriented guidance, policies, support options, mechanisms, and tools for infodemic managers and emergency program managers.

Challenges in delivering primary care via telemedicine during COVID-19 pandemic in India: A review synthesis using systems approach.

Background: Countries, including India, were quick to adopt telemedicine for delivering primary care in response to the widespread disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. This expeditious adoption was critical and the challenges faced during this exigency could guide the design and delivery of future telemedicine applications toward strengthening primary healthcare services. Methods: To identify the challenges in delivering primary care via telemedicine technology in the Indian context, a scoping review was conducted. Drawing from the systems approach in healthcare delivery, the review findings are summarized at four levels, patient, provider, healthcare organizations, and policy. Results: The initial search yielded 247 articles and 13 met our inclusion criteria. This review highlighted that telemedicine facilitated the continuity of care during COVID-19 but not without challenges. Low levels of education and computer literacy along with the language barriers posed the predominant challenges at the patient level. Providers had concerns related to digital literacy, clinical process flows, legal liabilities, and unethical behavior of the patients. The policy-level challenges include data privacy and security, reimbursement models, unethical behavior by the patient, or provider, and regulating prescriptions of psychotropic drugs. A lack of an integrated telehealthcare model covering diagnostics, prescriptions, and medication supply mirrored the existing fragmentation of care delivery. Conclusion: Telemedicine has the potential to improve primary healthcare delivery even beyond COVID-19. Currently, telemedicine applications in India are only facilitating a remote consultation wherein an integrated person-centered care is lacking. There is a need to acknowledge and factor in the inter-connectedness of health system elements for ensuring an effective and efficient healthcare delivery via telemedicine.

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.

Telehealth as a Means of Enabling Health Equity.

OBJECTIVE: The goal of this paper is to provide a consensus review on telehealth delivery prior to and during the COVID-19 pandemic to develop a set of recommendations for designing telehealth services and tools that contribute to system resilience and equitable health. METHODS: The IMIA-Telehealth Working Group (WG) members conducted a two-step approach to understand the role of telehealth in enabling global health equity. We first conducted a consensus review on the topic followed by a modified Delphi process to respond to four questions related to the role telehealth can play in developing a resilient and equitable health system. RESULTS: Fifteen WG members from eight countries participated in the Delphi process to share their views. The experts agreed that while telehealth services before and during COVID-19 pandemic have enhanced the delivery of and access to healthcare services, they were also concerned that global telehealth delivery has not been equal for everyone. The group came to a consensus that health system concepts including technology, financing, access to medical supplies and equipment, and governance capacity can all impact the delivery of telehealth services. CONCLUSION: Telehealth played a significant role in delivering healthcare services during the pandemic. However, telehealth delivery has also led to unintended consequences (UICs) including inequity issues and an increase in the digital divide. Telehealth practitioners, professionals and system designers therefore need to purposely design for equity as part of achieving broader health system goals.

Regulatory Frameworks for Clinical Trial Data Sharing: Scoping Review.

BACKGROUND: Although well recognized for its scientific value, data sharing from clinical trials remains limited. Steps toward harmonization and standardization are increasing in various pockets of the global scientific community. This issue has gained salience during the COVID-19 pandemic. Even for agencies willing to share data, data exclusivity practices complicate matters; strict regulations by funders affect this even further. Finally, many low- and middle-income countries (LMICs) have weaker institutional mechanisms. This complex of factors hampers research and rapid response during public health emergencies. This drew our attention to the need for a review of the regulatory landscape governing clinical trial data sharing. OBJECTIVE: This review seeks to identify regulatory frameworks and policies that govern clinical trial data sharing and explore key elements of data-sharing mechanisms as outlined in existing regulatory documents. Following from, and based on, this empirical analysis of gaps in existing policy frameworks, we aimed to suggest focal areas for policy interventions on a systematic basis to facilitate clinical trial data sharing. METHODS: We followed the JBI scoping review approach. Our review covered electronic databases and relevant gray literature through a targeted web search. We included records (all publication types, except for conference abstracts) available in English that describe clinical trial data-sharing policies, guidelines, or standard operating procedures. Data extraction was performed independently by 2 authors, and findings were summarized using a narrative synthesis approach. RESULTS: We identified 4 articles and 13 policy documents; none originated from LMICs. Most (11/17, 65%) of the clinical trial agencies mandated a data-sharing agreement; 47% (8/17) of these policies required informed consent by trial participants; and 71% (12/17) outlined requirements for a data-sharing proposal review committee. Data-sharing policies have, a priori, milestone-based timelines when clinical trial data can be shared. We classify clinical trial agencies as following either controlled- or open-access data-sharing models. Incentives to promote data sharing and distinctions between mandated requirements and supportive requirements for informed consent during the data-sharing process remain gray areas, needing explication. To augment participant privacy and confidentiality, a neutral institutional mechanism to oversee dissemination of information from the appropriate data sets and more policy interventions led by LMICs to facilitate data sharing are strongly recommended. CONCLUSIONS: Our review outlines the immediate need for developing a pragmatic data-sharing mechanism that aims to improve research and innovations as well as facilitate cross-border collaborations. Although a one-policy-fits-all approach would not account for regional and subnational legislation, we suggest that a focus on key elements of data-sharing mechanisms can be used to inform the development of flexible yet comprehensive data-sharing policies so that institutional mechanisms rather than disparate efforts guide data generation, which is the foundation of all scientific endeavor.

Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial.

PURPOSE: We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. METHODS: We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. RESULTS: The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. CONCLUSION: We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days.

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.

The Pandemic, Infodemic, and People's Resilience in India: Viewpoint.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused widespread fear and stress. The pandemic has affected everyone, everywhere, and created systemic inequities, leaving no one behind. In India alone, more than 34,094,373 confirmed COVID-19 cases and 452,454 related deaths have been reported as of October 19, 2021. Around May 2021, the daily number of new COVID-19 cases crossed the 400,000 mark, seriously hampering the health care system. Despite the devastating situation, the public response was seen through their efforts to come forward with innovative ideas for potential ways to combat the pandemic, for instance, dealing with the shortage of oxygen cylinders and hospital bed availability. With increasing COVID-19 vaccination rates since September 2021, along with the diminishing number of daily new cases, the country is conducting preventive and preparatory measures for the third wave. In this article, we propose the pivotal role of public participation and digital solutions to re-establish our society and describe how Sustainable Development Goals (SDGs) can support eHealth initiatives and mitigate infodemics to tackle a postpandemic situation. This viewpoint reflects that the COVID-19 pandemic has featured a need to bring together research findings across disciplines, build greater coherence within the field, and be a driving force for multi-sectoral, cross-disciplinary collaboration. The article also highlights the various needs to develop digital solutions that can be applied to pandemic situations and be reprocessed to focus on other SDGs. Promoting the use of digital health care solutions to implement preventive measures can be enhanced by public empowerment and engagement. Wearable technologies can be efficiently used for remote monitoring or home-based care for patients with chronic conditions. Furthermore, the development and implementation of informational tools can aid the improvement of well-being and dissolve panic-ridden behaviors contributing toward infodemics. Thus, a call to action for an observatory of digital health initiatives on COVID-19 is required to share the main conclusions and lessons learned in terms of resilience, crisis mitigation, and preparedness.

Telehealth and the COVID-19 Pandemic: International Perspectives and a Health Systems Framework for Telehealth Implementation to Support Critical Response.

OBJECTIVES: Telehealth implementation is a complex systems-based endeavour. This paper compares telehealth responses to (COrona VIrus Disease 2019) COVID-19 across ten countries to identify lessons learned about the complexity of telehealth during critical response such as in response to a global pandemic. Our overall objective is to develop a health systems-based framework for telehealth implementation to support critical response. METHODS: We sought responses from the members of the International Medical Informatics Association (IMIA) Telehealth Working Group (WG) on their practices and perception of telehealth practices during the times of COVID-19 pandemic in their respective countries. We then analysed their responses to identify six emerging themes that we mapped to the World Health Organization (WHO) model of health systems. RESULTS: Our analysis identified six emergent themes. (1) Government, legal or regulatory aspects of telehealth; (2) Increase in telehealth capacity and delivery; (3) Regulated and unregulated telehealth; (4) Changes in the uptake and perception of telemedicine; (5) Public engagement in telehealth responses to COVID-19; and (6) Implications for training and education. We discuss these themes and then use them to develop a systems framework for telehealth support in critical response. CONCLUSION: COVID-19 has introduced new challenges for telehealth support in times of critical response. Our themes and systems framework extend the WHO systems model and highlight that telemedicine usage in response to the COVID-19 pandemic is complex and multidimensional. Our systems-based framework provides guidance for telehealth implementation as part of health systems response to a global pandemic such as COVID-19.

Continuum of care for non-communicable diseases during COVID-19 pandemic in rural India: A mixed methods study.

BACKGROUND: COVID-19 pandemic has resulted in disruption to routine health services delivery as strict lockdowns were implemented in India and health workforce redeployed for COVID-19 focused responses. We assess the perceptions about COVID-19, the impact of the lockdown on access to health services and continuum of care for Non-communicable diseases (NCDs) among a cohort of adults in rural India. METHODOLOGY: Since 2018, we have been following up a cohort of persons with non-communicable diseases in a high NCD burden region in Srikakulam District of Andhra Pradesh under the STOP CKDu study. We conducted this mixed methods study, administered through a structured telephonic questionnaire and interview to determine the awareness, perceptions and their compliance to ongoing treatment schedules. RESULTS: Overall, 68% of the participants exhibited adequate knowledge of symptoms of COVID-19, while 43% were not aware of the mode of transmission of the virus. In all, 822 (36.1%) participants reported at least one NCD condition. Among them, 115 (14%) missed their follow-up visit, 110 (13.4%) reported facing challenges in medication procurement and 11.6% either developed new complaints or experienced worsening of pre-existing symptoms. A total of 233 (28.5%) used a telemedicine facility and took telephonic advice from (private) physicians. As the access to medicines was restricted due to the lockdown, majority of the respondents were depending on rural medical practitioners (RMPs) for the procurement of medication. CONCLUSION: Our finding implies the need for the future guidelines on adaptation of telehealth approaches within health systems to maintain the continuum of care, digital health tools to facilitate the patient's appointments including virtual follow-up visits for those with NCDs coupled with regular engagement by frontline healthcare workers at the local levels, evidence informed public health messaging taking into consideration the social and behavioural aspect and uninterrupted essential primary healthcare services.

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. METHODS: The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. DISCUSSION: The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. METHODS: This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. DISCUSSION: This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.

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).

An overview of mobile applications (apps) to support the coronavirus disease 2019 response in India.

BACKGROUND & OBJECTIVES: The potential benefits of mobile health (mHealth) initiatives to manage the coronavirus disease 2019 (COVID-19) pandemic have been explored. The Government of India, State governments, and healthcare organizations have developed various mobile apps for the containment of COVID-19. This study was aimed to systematically review COVID-19 related mobile apps and highlight gaps to inform the development of future mHealth initiatives. METHODS: Google Play and the Apple app stores were searched using the terms 'COVID-19', 'coronavirus', 'pandemic', and 'epidemic' in the first week of April 2020. A list of COVID-19-specific functions was compiled based on the review of the selected apps, the literature on epidemic surveillance, and national and international media reports. The World Health Organization guideline on Digital Health Interventions was used to classify the app functions under the categories of the general public, health workers, health system managers, and data services. RESULTS: The search yielded 346 potential COVID-19 apps, of which 50 met the inclusion criteria. Dissemination of untargeted COVID-19-related information on preventative strategies and monitoring the movements of quarantined individuals was the function of 27 (54%) and 19 (32%) apps, respectively. Eight (16%) apps had a contact tracing and hotspot identification function. INTERPRETATION & CONCLUSIONS: Our study highlights the current emphasis on the development of self-testing, quarantine monitoring, and contact tracing apps. India's response to COVID-19 can be strengthened by developing comprehensive mHealth solutions for frontline healthcare workers, rapid response teams and public health authorities. Among this unprecedented global health emergency, the Governments must ensure the necessary but least intrusive measures for disease surveillance.