Characteristics and result reporting of registered COVID-19 clinical trials of Chinese and Indian traditional medicine: A comparative analysis.

Objective: To assess the main characteristics and result reporting of registered COVID-19 interventional trials of traditional Chinese medicine and traditional Indian medicine. Materials and methods: We assessed design quality and result reporting of COVID-19 trials of traditional Chinese medicine (TCM) and traditional Indian medicine (TIM) registered before 10 February 2021, respectively, on Chinese Clinical Trial Registry (ChiCTR) and Clinical Trial Registry-India (CTRI). Comparison groups included registered COVID-19 trials of conventional medicine conducted in China (WMC), India (WMI), and in other countries (WMO). Cox regression analysis was used to assess the association between time from trial onset to result reporting and trial characteristics. Results: The proportion of COVID-19 trials investigating traditional medicine was 33.7% (130/386) among trials registered on ChiCTR, and 58.6% (266/454) on CTRI. Planned sample sizes were mostly small in all COVID-19 trials (median 100, IQR: 50-200). The proportion of trials that were randomized was 75.4 and 64.8%, respectively, for the TCM and TIM trials. Blinding measures were used in 6.2% of the TCM trials, and 23.6% of the TIM trials. Cox regression analysis revealed that planned COVID-19 clinical trials of traditional medicine were less likely to have results reported than trials of conventional medicine (hazard ratio 0.713, 95% confidence interval: 0.541-0.939; p = 0.0162). Conclusion: There were considerable between-country and within-country differences in design quality, target sample size, trial participants, and reporting of trial results. Registered COVID-19 clinical trials of traditional medicine were less likely to report results than trials of conventional medicine.

A health systems intervention to strengthen the integration of tuberculosis and COVID-19 detection: Outcomes of a quasi-experimental study in a high burden tuberculosis district in KwaZulu Natal, South Africa.

OBJECTIVES: The adverse effects of the COVID-19 pandemic on tuberculosis (TB) detection have been well documented. Despite shared symptoms, guidance for integrated screening for TBand COVID-19 are limited, and opportunities for health systems strengthening curtailed by lockdowns. We partnered with a high TB burden district in KwaZulu-Natal, South Africa, to co-develop an integrated approach to assessing COVID-19 and TB, delivered using online learning and quality improvement, and evaluated its performance on TB testing and detection. METHODS: We conducted a mixed methods study incorporating a quasi-experimental design and process evaluation in 10 intervention and 18 control clinics. Nurses in all 28 clinics were all provided access to a four-session online course to integrate TB and COVID-19 screening and testing, which was augmented with some webinar and in-person support at the 10 intervention clinics. We estimated the effects of exposure to this additional support using interrupted time series Poisson regression mixed models. Process evaluation data comprised interviews before and after the intervention. Thematic coding was employed to provide explanations for effects of the intervention. RESULTS: Clinic-level support at intervention clinics was associated with a markedly higher uptake (177 nurses from 10 intervention clinics vs. 19 from 18 control clinics). Lack of familiarity with online learning, and a preference for group learning hindered the transition from face-to-face to online learning. Even so, any exposure to training was initially associated with higher rates of GeneXpert testing (adjusted incidence ratio [IRR] 1.11, 95% confidence interval 1.07-1.15) and higher positive TB diagnosis (IRR 1.38, 1.11-1.71). CONCLUSIONS: These results add to the knowledge base regarding the effectiveness of interventions to strengthen TB case detection during the COVID-19 pandemic. The findings support the feasibility of a shift to online learning approaches in low-resource settings with appropriate support and suggest that even low-intensity interventions are capable of activating nurses to integrate existing disease control priorities during pandemic conditions.

"I have travelled along on my own"-Experiences of seeking help for serious non-COVID health problems during the COVID-19 pandemic: A qualitative study.

OBJECTIVES: During COVID-19 the UK general population has been given strong messages to stay at home. Concurrently unprecedented changes occurred in healthcare access with moves to remote/triage systems. Data have shown that the number of people accessing healthcare services decreased and there are significant concerns that the pandemic has negatively affected help-seeking for serious conditions, with potentially increased morbidity and mortality. An understanding of help-seeking is urgently needed to inform public campaigns. We aimed to develop an in-depth, theory-based understanding of how, when and why people sought help for potentially serious symptoms (e.g., related to major cardiovascular events or cancer diagnoses) during the pandemic, and what influenced their decisions. DESIGN: Qualitative semi-structured interviews. METHODS: We interviewed 25 adults recruited through a targeted social media campaign. Interviews were conducted via telephone or online platform. Our topic guide was informed by the Model of Pathways to Treatment and the Capability-Opportunity-Motivation-Behaviour model. RESULTS: The analysis identified four main themes: Delay in recognition, Holding on to concerns, Weighing it up and Long-term impacts. Multiple societal and environmental factors influenced participants' help-seeking and motivation, capability and opportunity to seek help, with long-term impacts on well-being and future help-seeking. CONCLUSIONS: There is a need for clear guidance about pathways to raise concerns about symptoms and gain advice while usual healthcare contacts are paused or stopped. Recommendations for future interventions to support help-seeking during pandemics include clearer messaging, co-produced with end-users, on when, where and how to seek help.

Applying learning health systems thinking in codeveloping integrated tuberculosis interventions in the contexts of COVID-19.

The COVID-19 pandemic reversed much of global progress made in combatting tuberculosis, with South Africa experiencing one of the largest impacts on tuberculosis detection. The aim of this paper is to share our experiences in applying learning health systems (LHS) thinking to the codevelopment of an intervention improving an integrated response to COVID-19 and tuberculosis in a South African district. A sequential partially mixed-methods study was undertaken between 2018 and 2021 in the district of Amajuba in KwaZulu-Natal. Here, we report on the formulation of a Theory of Change, codesigning and refining proposed interventions, and piloting and evaluating codesigned interventions in primary healthcare facilities, through an LHS lens. Following the establishment and formalisation of a district Learning Community, diagnostic work and a codevelopment of a theory of change, intervention packages tailored according to pandemic lockdowns were developed, piloted and scaled up. This process illustrates how a community of learning can generate more responsive, localised interventions, and suggests that the establishment of a shared space of research governance can provide a degree of resilience to facilitate adaption to external shocks. Four main lessons have been gleaned from our experience in adopting an LHS approach in a South African district, which are (1) the importance of building and sustaining relationships, (2) the utility of colearning, coproduction and adaptive capacity, (3) the centrality of theory-driven systems strengthening and (4) reflections on LHS as a framework.

Prospective study of factors associated with asthma attack recurrence (ATTACK) in children from three Ecuadorian cities during COVID-19: a study protocol.

INTRODUCTION: Asthma is a growing health problem in children in marginalised urban settings in low-income and middle-income countries. Asthma attacks are an important cause of emergency care attendance and long-term morbidity. We designed a prospective study, the Asthma Attacks study, to identify factors associated with recurrence of asthma attacks (or exacerbations) among children and adolescents attending emergency care in three Ecuadorian cities. METHODS AND ANALYSIS: Prospective cohort study designed to identify risk factors associated with recurrence of asthma attacks in 450 children and adolescents aged 5-17 years attending emergency care in public hospitals in three Ecuadorian cities (Quito, Cuenca and Portoviejo). The primary outcome will be rate of asthma attack recurrence during up to 12 months of follow-up. Data are being collected at baseline and during follow-up by questionnaire: sociodemographic data, asthma history and management (baseline only); recurrence of asthma symptoms and attacks (monthly); economic costs of asthma to family; Asthma Control Test; Pediatric Asthma Quality of life Questionnaire; and Newcastle Asthma Knowledge Questionnaire (baseline only). In addition, the following are being measured at baseline and during follow-up: lung function and reversibility by spirometry before and after salbutamol; fractional exhaled nitric oxide (FeNO); and presence of IgG antibodies to SARS-CoV-2 in blood. Recruitment started in 2019 but because of severe disruption to emergency services caused by the COVID-19 pandemic, eligibility criteria were modified to include asthmatic children with uncontrolled symptoms and registered with collaborating hospitals. Data will be analysed using logistic regression and survival analyses. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Hospital General Docente de Calderon (CEISH-HGDC 2019-001) and Ecuadorian Ministry of Public Health (MSP-CGDES-2021-0041-O N° 096-2021). The study results will be disseminated through presentations at conferences and to key stakeholder groups including policy-makers, postgraduate theses, peer-review publications and a study website. Participants gave informed consent to participate in the study before taking part.

Vaccination against COVID-19 and society's return to normality in England: a modelling study of impacts of different types of naturally acquired and vaccine-induced immunity.

OBJECTIVES: To project impacts of mass vaccination against COVID-19, and investigate possible impacts of different types of naturally acquired and vaccine-induced immunity on future dynamics of SARS-CoV-2 transmission from 2021 to 2024 in England. DESIGN: Deterministic, compartmental, discrete-time Susceptible-Exposed-Infectious-Recovered (SEIR) modelling. PARTICIPANTS: Population in England. INTERVENTIONS: Mass vaccination programmes. OUTCOME MEASURES: Daily and cumulative number of deaths from COVID-19. RESULTS: If vaccine efficacy remains high (85%), the vaccine-induced sterilising immunity lasts ≥182 days, and the reinfectivity is greatly reduced (by ≥60%), annual mass vaccination programmes can prevent further COVID-19 outbreaks in England. Under optimistic scenarios, with annual revaccination programmes, the cumulative number of COVID-19 deaths is estimated to be from 130 000 to 150 000 by the end of 2024. However, the total number of COVID-19 deaths may be up to 431 000 by the end of 2024, under scenarios with compromised vaccine efficacy (62.5%), short duration of natural and vaccine immunity (365/182 days) and small reduction in reinfectivity (30%). Under the assumed scenarios, more frequent revaccinations are associated with smaller total numbers and lower peaks of daily deaths from COVID-19. CONCLUSIONS: Under optimistic scenarios, mass immunisation using efficacious vaccines may enable society safely to return to normality. However, under plausible scenarios with low vaccine efficacy and short durability of immunity, COVID-19 could continue to cause recurrent waves of severe morbidity and mortality despite frequent vaccinations. It is crucial to monitor the vaccination effects in the real world, and to better understand characteristics of naturally acquired and vaccine-induced immunity against SARS-CoV-2.

Effect of COVID-19 lockdown on hospital admissions and mortality in rural KwaZulu-Natal, South Africa: interrupted time series analysis.

OBJECTIVE: To assess the effect of lockdown during the 2020 COVID-19 pandemic on daily all-cause admissions, and by age and diagnosis subgroups, and the odds of all-cause mortality in a hospital in rural KwaZulu-Natal (KZN). DESIGN: Observational cohort. SETTING: Referral hospital for 17 primary care clinics in uMkhanyakude District. PARTICIPANTS: Data collected by the Africa Health Research Institute on all admissions from 1 January to 20 October: 5848 patients contributed to 6173 admissions. EXPOSURE: Five levels of national lockdown in South Africa from 27 March 2020, with restrictions decreasing from levels 5 to 1, respectively. OUTCOME MEASURES: Changes and trends in daily all-cause admissions and risk of in-hospital mortality before and at each stage of lockdown, estimated by Poisson and logistic interrupted time series regression, with stratification for age, sex and diagnosis. RESULTS: Daily admissions decreased during level 5 lockdown for infants (incidence rate ratio (IRR) compared with prelockdown 0.63, 95% CI 0.44 to 0.90), children aged 1-5 years old (IRR 0.43, 95% CI 028 to 0.65) and respiratory diagnoses (IRR 0.57, 95% CI 0.36 to 0.90). From level 4 to level 3, total admissions increased (IRR 1.17, 95% CI 1.06 to 1.28), as well as for men >19 years (IRR 1.50, 95% CI 1.17 to 1.92) and respiratory diagnoses (IRR 4.26, 95% CI 2.36 to 7.70). Among patients admitted to hospital, the odds of death decreased during level 5 compared with prelockdown (adjusted OR 0.48, 95% CI 0.28 to 0.83) and then increased in later stages. CONCLUSIONS: Level 5 lockdown is likely to have prevented the most vulnerable population, children under 5 years and those more severely ill from accessing hospital care in rural KZN, as reflected by the drop in admissions and odds of mortality. Subsequent increases in admissions and in odds of death in the hospital could be due to improved and delayed access to hospital as restrictions were eased.

Post-lockdown SARS-CoV-2 nucleic acid screening in nearly ten million residents of Wuhan, China.

Stringent COVID-19 control measures were imposed in Wuhan between January 23 and April 8, 2020. Estimates of the prevalence of infection following the release of restrictions could inform post-lockdown pandemic management. Here, we describe a city-wide SARS-CoV-2 nucleic acid screening programme between May 14 and June 1, 2020 in Wuhan. All city residents aged six years or older were eligible and 9,899,828 (92.9%) participated. No new symptomatic cases and 300 asymptomatic cases (detection rate 0.303/10,000, 95% CI 0.270-0.339/10,000) were identified. There were no positive tests amongst 1,174 close contacts of asymptomatic cases. 107 of 34,424 previously recovered COVID-19 patients tested positive again (re-positive rate 0.31%, 95% CI 0.423-0.574%). The prevalence of SARS-CoV-2 infection in Wuhan was therefore very low five to eight weeks after the end of lockdown.