Search

Abstract Background Despite success in HIV treatment, diagnosis and management of hypertension (HTN) and cardiovascular disease (CVD) remains suboptimal among people living with HIV (PLWH) in Botswana, with an overall HTN control of only 19% compared to 98% HIV viral suppressed. These gaps persist despite CVD primary care national guidelines and availability of free healthcare including antihypertensive medications. Our study aims to develop and test strategies to close the HTN care gap in PLWH, through integration into HIV care, leveraging the successful national HIV care and treatment program and strategies. Methods The InterCARE trial is a cluster randomized controlled hybrid type 2 effectiveness-implementation trial at 14 sites designed to enroll 4652 adults living with HIV and HTN plus up to 2326 treatment partners. Primary outcomes included effectiveness (HTN control) and implementation outcomes using the Reach Effectiveness Adoption Implementation and Maintenance framework, with explanatory mixed methods used to understand variability in outcomes. InterCARE trial’s main strategies include healthcare worker HTN and CVD care training plus long-term practice facilitation, electronic health record (EHR) documentation of key indicators and use of reminders, and use of treatment partners to provide social support to people living with HIV and HTN. InterCARE started with formative research to identify contextual factors influencing care gaps using the Consolidated Framework for Implementation Research. Results were used to adapt initial and develop additional implementation strategies to address barriers and leverage facilitators. The package was pilot tested in two clinics, with findings used to further adapt or add strategies for the clinical trial. Discussion If successful, the InterCARE model can be scaled up to HIV clinics nationwide to improve diagnosis, management, and support in Botswana. The trial will provide insights for scale-up of HTN integration into HIV care in the region. Trial registration ClinicalTrials.gov reference NCT05414526. Registered 18 May 2022, https://clinicaltrials.gov/study/NCT05414526?term=NCT05414526.&rank=1 .

Abstract Background Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain. Study design The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel-coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplasty are mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, including cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. Discussion The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting. Trial registration Registered on clinicaltrial.gov (NCT04561739).

Abstract Background Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. Methods The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. Discussion The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB. Trial registration ClinicalTrials.gov identifier: NCT04971356.

Abstract Background Abnormal blood potassium levels are associated with an increased risk of cardiometabolic diseases and mortality in the general population; however, evidence regarding the association between dyskalemia and mortality among patients with cardiovascular disease (CVD) remains inconclusive. This study aimed to evaluate the association of potassium levels with all-cause and cardiovascular mortality among patients with CVD. Methods PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to August 2023 to identify relevant cohort studies among patients with CVD, such as myocardial infarction, stroke, and heart failure. Abnormal potassium levels were considered as hypokalemia or hyperkalemia. The primary outcomes were all-cause mortality based on follow-up length (including in-hospital, short-term and long-term mortality) and cardiovascular mortality. The methodological quality of included studies was assessed by using the Newcastle-Ottawa Scale. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Restricted cubic splines were applied to explore the dose-response relationship. Results Thirty-one cohort studies involving 227,645 participants with an average age of 68.3 years were included in the meta-analysis, all of which achieved moderate to high quality. Hyperkalemia was significantly associated with an approximately 3.0-fold increased risk of all-cause in-hospital mortality (RR:2.78,95CI%:1.92,4.03), 1.8-fold of all-cause short-term mortality (RR:1.80, 95CI%:1.44,2.27), 1.3-fold of all-cause long-term mortality (RR:1.33, 95CI%:1.19,1.48) and 1.2-fold of cardiovascular mortality (RR:1.19, 95CI%:1.04,1.36). Similar positive associations were also observed between hypokalemia and risk of all-cause mortality and cardiovascular mortality. The RRs of all-cause in-hospital, short-term, long-term mortality and cardiovascular mortality with hyperkalemia were attenuated to 2.21 (95CI%:1.60,3.06), 1.46(95CI%:1.25,1.71), 1.23 (95CI%:1.09,1.39) and 1.13 (95CI%:1.00,1.27) when treating hypokalemia together with normokalemia as the reference group. A U-shaped association was observed between potassium levels and mortality, with the lowest risk at around 4.2 mmol/L. Conclusions Both hypokalemia and hyperkalemia were positively associated with the risk of mortality in patients with CVD. Our results support the importance of potassium homeostasis for improving the CVD management. Registration PROSPERO, CRD42022324337.

Abstract Background The social disparities in obesity may originate in early life or in adulthood, and the associations of socioeconomic position (SEP) with obesity could alter over time. It is unclear how lifetime-specific and life-course SEP influence adult obesity development in China. Methods Based on the China Health and Nutrition Survey (CHNS), three SEP-related indicators, including the father’s occupational position and the participant’s education and occupational position, were obtained. The life-course socioeconomic changes and a cumulative SEP score were established to represent the life-course SEP of the participants in the study. The growth mixture modeling was used to identify BMI trajectories in adulthood. Multinomial logistic regression was adopted to assess the associations between SEP and adult BMI trajectories. Results A total of 3,138 participants were included in the study. A positive correlation was found between the paternal occupational position, the participants’ occupational position, education, and obesity in males, whereas an inverse correlation was observed among females. Males who experienced social upward mobility or remained stable high SEP during the follow-up had 2.31 and 2.52-fold risks of progressive obesity compared to those with a stable-low SEP. Among females, stable high SEP in both childhood and adulthood was associated with lower risks of progressive obesity (OR = 0.63, 95% CI: 0.43–0.94). Higher risks of obesity were associated with the life-course cumulative SEP score among males, while the opposite relationship was observed among females. Conclusions The associations between life-course SEP and BMI development trajectories differed significantly by gender. Special emphasis should be placed on males experiencing upward and stable high socioeconomic change.

Abstract Background The lack of trained mental health professionals is a key barrier to scale-up of evidence-based psychological interventions in low and middle-income countries. We have developed an app that allows a peer with no prior experience of health-care delivery to deliver the cognitive therapy-based intervention for perinatal depression, the Thinking Healthy Programme (THP). This trial aims to assess the effectiveness and cost-effectiveness of this Technology-assisted peer-delivered THP versus standard face-to-face Thinking Healthy Programme delivered by trained health workers. Methods We will employ a non-inferiority stratified cluster randomized controlled trial design comparing the two formats of intervention delivery. A total of 980 women in the second or third trimester of pregnancy with a diagnosis of Major Depressive Episode, evaluated with the Structured Clinical Interview for DSM-V Disorders (SCID), will be recruited into the trial. The unit of randomization will be 70 village clusters randomly allocated in a 1:1 ratio to the intervention and control arms. The primary outcome is defined as remission from major depressive episode at 3 months postnatal measured with the SCID. Data will also be collected on symptoms of anxiety, disability, quality of life, service use and costs, and infant-related outcomes such as exclusive breastfeeding and immunization rates. Data will be collected on the primary outcome and selected secondary outcomes (depression and anxiety scores, exclusive breastfeeding) at 6 months postnatal to evaluate if the improvements are sustained in the longer-term. We are especially interested in sustained improvement (recovery) from major depressive episode. Discussion This trial will evaluate the effectiveness and cost-effectiveness of a technology-assisted peer-delivered cognitive behavioral therapy-based intervention in rural Pakistan. If shown to be effective, the novel delivery format could play a role in reducing the treatment gap for perinatal depression and other common mental disorders in LMIC. Trial registration The trial was registered at Clinicaltrials.gov (NCT05353491) on 29 April 2022.

Abstract Background Infections are one of the leading causes of death in the neonatal period. This trial aims to evaluate if the provision of alcohol-based hand rub (ABHR) to pregnant women for postnatal household use prevents severe infections (including sepsis, diarrhoea, pneumonia, or death) among infants during the first three postnatal months. Methods Through a cluster-randomised trial in eastern Uganda, 72 clusters are randomised in a 2-arm design with rural villages as units of randomisation. We estimate to include a total of 5932 pregnant women at 34 weeks of gestation. All women and infants in the study are receiving standard antenatal and postnatal care. Women in the intervention group additionally receive six litres of ABHR and training on its use. Research midwives conduct follow-up visits at participants’ homes on days 1, 7, 28, 42, and 90 after birth and telephone calls on days 14, 48, and 60 to assess the mother and infant for study outcomes. Primary analyses will be by intention to treat. Discussion This study will provide evidence on the effectiveness of a locally available and low-cost intervention in preventing neonatal sepsis and early infant infections. If ABHR is found effective, it could be implemented by adding it to birthing kits. Trial registration Pan African Clinical Trial Registry, PACTR202004705649428. Registered 1 April 2020, https://pactr.samrc.ac.za/ .

Abstract Background Waist circumference (WC), visceral adiposity index (VAI), lipid accumulation product (LAP), and Chinese visceral adiposity index (CVAI) are considered surrogate indicators of abdominal fat deposition, but the longitudinal association of these indices with cardiovascular (CV) events in adults with type 2 diabetes (T2D) remains unclear. Our study aimed to examine the associations between abdominal obesity indices and incident CV events among people with T2D and to compare their predictive performance in risk assessment. Methods The present study included 2328 individuals with T2D from the Xinjiang Multi-Ethnic Cohort. Multivariable Cox regression analyses were applied to assess the associations between abdominal obesity indices and CV events. Harrell's concordance statistic (C-statistic), net reclassification improvement (NRI) index, and integrated discrimination improvement (IDI) index were utilized to evaluate the predictive performance of each abdominal obesity index. Results At a median follow-up period of 59 months, 289 participants experienced CV events. After multivariable adjustment, each 1-SD increase in WC, VAI, LAP, and CVAI was associated with a higher risk of CV events in people with T2D, with adjusted hazard ratios (HRs) being 1.57 [95% CI (confidence interval): 1.39–1.78], 1.11 (95% CI 1.06–1.16), 1.46 (95% CI 1.36–1.57), and 1.78 (95% CI 1.57–2.01), respectively. In subgroup analyses, these positive associations appeared to be stronger among participants with body mass index (BMI)

Abstract Background Child and adolescent mental health problems are a global public mental health priority. However, there is a lack of evidence-based scalable psychological interventions for adolescents living in low resource settings. This trial was designed to evaluate the feasibility and acceptability of delivering the World Health Organization’s Early Adolescent Skills for Emotions (EASE) intervention at public schools in a rural sub-district in Rawalpindi, Pakistan. Methods A two arm, single blinded, feasibility cluster randomized controlled trial with mixed-methods evaluation was conducted with 59 adolescents and their caregivers from 8 public schools. In the 4 intervention arm schools, 6 non-specialist facilitators delivered the culturally-adapted EASE group sessions to the adolescents (n = 29) and their caregivers with desired fidelity under the supervision of in-country supervisors. Results The participation rate of adolescents in the intervention sessions was 83%. The intervention strategies were implemented by the adolescents. However, attending biweekly sessions at schools was challenging for caregivers with only 50% caregivers attending the sessions. Conclusions The results of this study support the feasibility and acceptability of delivering this culturally adapted intervention through non-specialist facilitators in school settings in Pakistan and pave the way to conduct a fully powered cluster randomized controlled trial to test the effectiveness of intervention to improve psychological outcomes in adolescents. Trial registration Trial registered with Clinicaltrials.gov prospectively; NCT04254393.

Abstract Background Recent guidelines recommended a systolic blood pressure (SBP) target of < 130 mmHg for patients with or without diabetes but without providing a lower bound. Our study aimed to explore whether additional clinical benefits remain at achieved blood pressure (BP) levels below the recommended target. Methods We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) among the non-diabetic population and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial among diabetic subjects. We used the propensity score method to match patients from the intensive BP group to those from the standard group in each trial. Individuals with different achieved BP levels from the intensive BP group were used as “reference.” For each stratum, the trial-specific primary outcome (i.e., composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death for SPRINT; non-fatal MI, non-fatal stroke, or cardiovascular death for ACCORD-BP) was compared by Cox regression. Results A non-linear association was observed between the mean achieved BP and incidence of composite cardiovascular events, regardless of treatment allocation. The significant treatment benefit for primary outcome remained at SBP 110–120 mmHg (hazard ratio, 0.59 [95% CI, 0.46, 0.76] for SPRINT; 0.67 [0.52, 0.88] for ACCORD-BP) and SBP 120–130 mmHg for SPRINT (0.47 [0.34, 0.63]) but not for ACCORD-BP (0.93 [0.70, 1.23]). The results were similar for the secondary outcomes including all-cause mortality, cardiovascular mortality, MI, stroke, and HF. Intensive BP treatment benefits existed among patients maintaining a diastolic BP of 60–70 mmHg but were less distinct. Conclusions The treatment benefit persists at as low as SBP 110–120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality.

Abstract Introduction Evidence on health-related quality of life (HRQoL) outcomes is limited for new antiretroviral therapies (ART). Dolutegravir-based treatment is being rolled out as the preferred first-line treatment for HIV in many low- and middle-income countries. We compared HRQoL between treatment-naïve pregnant women randomized to dolutegravir- or efavirenz-based ART in a clinical trial in Uganda and South Africa. Methods We gathered HRQoL data from 203 pregnant women of mean age 28 years, randomized to either dolutegravir- or efavirenz-based ART. We used the medical outcomes study-HIV health survey at baseline, 24 and 48 weeks between years 2018 and 2019. Physical health summary (PHS) and mental health summary (MHS) scores were the primary study outcomes, while the 11 MOS-HIV subscales were secondary outcomes. We applied mixed model analysis to estimate differences within and between-treatment groups. Multivariate regression analysis was included to identify associations between primary outcomes and selected variables. Results At 24 weeks postpartum, HRQoL scores increased from baseline in both treatment arms: PHS (10.40, 95% CI 9.24, 11.55) and MHS (9.23, 95% CI 7.35, 11.10) for dolutegravir-based ART; PHS (10.24, 95% CI 9.10, 11.38) and MHS (7.54, 95% CI 5.66, 9.42) for efavirenz-based ART. Increased scores for all secondary outcomes were significant at p

Abstract Background The purpose of this study is to assess the level of knowledge, attitudes, and willingness to organ donation among the general public in China. Methods The study population consisted of 4274 participants from Eastern, Central and Western China. The participants’ knowledge, attitudes and willingness to organ donation were collected by a self-designed questionnaire consisting of 30 items. Knowledge is measured by 10 items and presented as a 10 point score, attitudes is measured by 20 items using a 5-step Likert scale and total score ranged between 0 and 80; while the willingness to donate is assessed as binary variable (0 = No; 1 = Yes). A logistic regression model was used to assess the association of knowledge and attitudes with willingness to organ donation, controlling for demographic and socioeconomic confounders. Results The questionnaire response rate was 94.98%. The mean score (± SD) of the general public’s knowledge to organ donation was 6.84 ± 1.76, and the mean score (± SD) of attitudes to organ donation was 47.01 ± 9.07. The general public’s knowledge and attitudes were the highest in Eastern China, followed by West and Central China. The logistic regression model indicated a positive association between knowledge and the willingness to organ donation (OR = 1.12, 95%CI: 1.08, 1.17; P

Abstract Background Malnutrition amongst under-fives remains common in resource-poor countries and is resistant to current interventions. New opportunities have emerged to target “environmental enteric dysfunction” (EED) that refers to the abnormal gut structure and function that results from colonisation of the gut with pathogenic microbes and compromises nutrition and growth in early life. Although the gut microbiome may provide a defence against ingested gut pathogens through colonisation resistance, its development is adversely affected by multiple environmental factors. Dietary supplements of pro- or synbiotics may build the resilience of the gut microbiome against these environmental factors and boost colonisation resistance. We aim to assess whether dietary supplementation of newborns in rural Kenya with pro/synbiotics prevents or ameliorates EED and improves growth. Methods Six hundred newborns less than 4 days old will be recruited from Homa Bay County Teaching and Referral Hospital, western Kenya. Newborns will be randomly allocated, stratified by HIV exposure, in a 1:1:1:1 ratio to one of 4 study arms to receive either of two synbiotics, a probiotic or no supplement. Supplements will be given daily for 10 days and then weekly until 6 months of age. Participants will be followed until the age of 2 years. The primary outcome is systemic inflammation at 6 months assessed by plasma alpha-1-acid glycoprotein. Secondary outcomes include biomarkers of gut health and growth, anthropometric indices, morbidity and mortality. Discussion As dietary supplements with pro- or synbiotics may improve gut health and can be administered in early life, our findings may inform the package of interventions to prevent malnutrition and improve growth in Africa and similar low-resource settings. Trial registration Pan African Clinical Trials Registry, Trial number: PACTR202003893276712. Date: 02/03/2020 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9798

Abstract Background Previous studies have suggested that maternal stress could increase the risk of some adverse pregnancy outcomes, but evidence on congenital heart disease (CHD) is limited. We aimed to explore the association between maternal exposure to life events during pregnancy and CHD in offspring. Methods The data was based on an unmatched case-control study about CHD conducted in Shaanxi province of China from 2014 to 2016. We included 2280 subjects, 699 in the case group and 1581 in the control group. The cases were infants or fetuses diagnosed with CHD, and the controls were infants without any birth defects. The life events were assessed by the Life Events Scale for Pregnant Women, and were divided into positive and negative events for synchronous analysis. A directed acyclic graph was drawn to screen the confounders. Logistic regression was employed to estimate the odds ratio and 95% confidence interval for the effects of life events on CHD. Results After controlling for the potential confounders, the pregnant women experiencing the positive events during pregnancy had lower risk of CHD in offspring than those without positive events (OR = 0.38, 95%CI: 0.30 ~ 0.48). The risk of CHD in offspring could increase by 62% among the pregnant women experiencing the negative events compared to those without (OR = 1.62, 95%CI: 1.29 ~ 2.03). Both effects showed a certain dose-response association. Besides, the positive events could weaken the risk impact of negative events on CHD. Conclusion It may suggest that maternal exposure to negative life events could increase the risk of CHD in offspring, while experiencing positive events could play a potential protective role.

Abstract Background Both pulmonary tuberculosis (PTB) and diabetes mellitus (DM) are major global public health problems. We estimated the global, regional, and national prevalence of diabetes mellitus in a population with PTB. Methods We searched for observational studies of DM in people with PTB using the PubMed and Embase electronic bibliographic databases, focusing on articles published in the English language from database inception until March 31, 2021. We included original research that reported the prevalence of DM in PTB or those that had sufficient data to compute these estimates. Studies were excluded if they did not provide primary data or were case studies or reviews. Two authors independently extracted the articles and collected detailed information using a predefined questionnaire. A country-specific random-effects meta-analysis was used for countries with two or more available studies, and a fractional response regression model was employed to predict the prevalence of DM in PTB for countries with one or no study. The study was registered with the International Prospective Register of Systematic Reviews, using the registration number CRD42018101989. Results We identified 22,658 studies, and 153, across 51 countries, were retained for data extraction. The global prevalence of DM among patients with PTB was estimated to be 13.73% (95% confidence interval [CI] 12.51–14.95). The prevalence rates were 19.32% (95% CI 13.18–25.46) in the region of the Americas, 17.31% (95% CI 12.48–22.14) in the European region, 14.62% (95% CI 12.05–17.18) in Southeast Asia, 13.59% (95% CI 7.24–19.95) in the western Pacific region, 9.61% (95% CI 4.55–14.68) in the eastern Mediterranean region, and 9.30% (95% CI 2.83–15.76) in the African region. The country with the highest estimated prevalence was the Marshall Islands (50.12%; 95% CI 4.28–95.76). Conclusion Comorbid PTB and DM remain prevalent worldwide.

Abstract Background Globally, there is a large documented gap between needs of families and children with developmental disorders and available services. We adapted the World Health Organization’s mental health Gap-Intervention Guidelines (mhGAP-IG) developmental disorders module into a tablet-based android application to train caregivers of children with developmental disorders. We aimed to evaluate the effectiveness of this technology-assisted, family volunteers delivered, parents’ skills training intervention to improve functioning in children with developmental disorders in a rural community of Rawalpindi, Pakistan. Methods In a single-blinded, cluster randomized controlled trial, 30 clusters were randomised (1:1 ratio) to intervention (n = 15) or enhanced treatment as usual (ETAU) arm (n = 15). After screening, 540 children (18 participants per cluster) aged 2–12 years, with developmental disorders and their primary caregivers were recruited into the trial. Primary outcome was child’s functioning, measured by Childhood Disability Assessment Schedule for Developmental Disorders (DD-CDAS) at 6-months post-intervention. Secondary outcomes were parents’ health related quality of life, caregiver-child joint engagement, socio-emotional well-being of children, family empowerment and stigmatizing experiences. Intention-to-treat analyses were done using mixed-models adjusted for covariates and clusters. Results At 6-months post-intervention, no statistically significant mean difference was observed on DD-CDAS between intervention and ETAU (mean [SD], 47.65 [26.94] vs. 48.72 [28.37], Adjusted Mean Difference (AMD), − 2.63; 95% CI − 6.50 to 1.24). However, parents in the intervention arm, compared to ETAU reported improved health related quality of life (mean [SD] 65.56 [23.25] vs. 62.17 [22.63], AMD 5.28; 95% CI 0.44 to 10.11). The results were non-significant for other secondary outcomes. Conclusions In the relatively short intervention period of 6 months, no improvement in child functioning was observed; but, there were significant improvements in caregivers’ health related quality of life. Further trials with a longer follow-up are recommended to evaluate the impact of intervention. Trial registration Clinicaltrials.gov, NCT02792894. Registered April 4, 2016, https://clinicaltrials.gov/ct2/show/NCT02792894

Abstract Background In many low resource settings, the provision of government mental health care services is limited to specialized psychiatry units in urban hospital care facilities, where the most common treatment for common mental disorders (CMDs) is pharmacotherapy, occasionally with adjunct nonspecific psychological support. We aimed to evaluate the effectiveness of adding a low intensity, psychological intervention, Problem Management Plus (PM+) for CMDs into routine care in a specialized mental health care facility in Pakistan. Methods A two arm, single-blind individual randomized controlled trial (RCT) was carried out with adults (N = 192), referred for psychological support by psychiatrists. The study participants were randomized (1:1) to PM + plus Treatment as Usual (TAU) (n = 96) or TAU only (n = 96). The primary outcomes were symptoms of anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS) and functional impairment as measured by WHO Disability Assessment Schedule (WHODAS 2.0) at 20 weeks after baseline. Results The analysis was done on intention-to-treat principle. The linear mixed model analysis showed that at 20 weeks after baseline, there was a significant reduction in symptoms of anxiety and depression (mean [SD], 16.23 [8.81] vs 19.79 [7.77]; AMD, − 3.10; 95% CI, − 0.26 to − 5.76); p = 0.03 and improvement in functioning (mean [SD], 22.94 [9.37] vs 27.37 [8.36]; AMD, − 4.35; 95% CI, − 1.45 to − 7.24); p = 0.004 in PM + plus TAU versus TAU arm. The follow-up rate was 67% at primary end-point. Conclusions Specialized care facilities in LMICs may consider adding brief, evidence-based psychological treatments for CMDs to their routine care. Trial Registration Australian New Zealand Clinical Trials Registry, ACTRN12616000381482. Registered March 23, 2016. Retrospectively registered, https://www.anzctr.org.au/Default.aspx/ ACTRN12616000381482

Abstract Background Coronavirus Disease-2019 (COVID-19) pandemic has become a major health event that endangers people health throughout China and the world. Understanding the factors associated with COVID-19 disease severity could support the early identification of patients with high risk for disease progression, inform prevention and control activities, and potentially reduce mortality. This study aims to describe the characteristics of patients with COVID-19 and factors associated with severe or critically ill presentation in Jiangsu province, China. Methods Multicentre retrospective cohort study of all individuals with confirmed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections diagnosed at 24 COVID-19-designated hospitals in Jiangsu province between the 10th January and 15th March 2020. Demographic, clinical, laboratory, and radiological data were collected at hospital admission and data on disease severity were collected during follow-up. Patients were categorised as asymptomatic/mild/moderate, and severe/critically ill according to the worst level of COVID-19 recorded during hospitalisation. Results A total of 625 patients, 64 (10.2%) were severe/critically ill and 561 (89.8%) were asymptomatic/mild/moderate. All patients were discharged and no patients died. Patients with severe/critically ill COVID-19 were more likely to be older, to be single onset (i.e. not belong to a cluster of cases in a family/community, etc.), to have a medical history of hypertension and diabetes; had higher temperature, faster respiratory rates, lower peripheral capillary oxygen saturation (SpO2), and higher computer tomography (CT) image quadrant scores and pulmonary opacity percentage; had increased C-reactive protein, fibrinogen, and D-dimer on admission; and had lower white blood cells, lymphocyte, and platelet counts and albumin on admission than asymptomatic/mild/moderate cases. Multivariable regression showed that odds of being a severe/critically ill case were associated with age (year) (OR 1.06, 95%CI 1.03–1.09), lymphocyte count (109/L) (OR 0.25, 95%CI 0.08–0.74), and pulmonary opacity in CT (per 5%) on admission (OR 1.31, 95%CI 1.15–1.51). Conclusions Severe or critically ill patients with COVID-19 is about one-tenths of patients in Jiangsu. Age, lymphocyte count, and pulmonary opacity in CT on admission were associated with risk of severe or critically ill COVID-19.

Abstract Background Primiparous mothers who lack of experience and knowledge of child caring, are usually overwhelmed by multifarious stressors and challenges. Although professional support is needed for primiparas, there is a gap between the necessary high-quality services and the currently provided poor services. This study aimed to explore Chinese primiparous mothers’ views on professional services, identify barriers to utilizing professional support, and further understand mothers’ expectations of and preferences for the delivery of professional services. Method A descriptive phenomenological study design was utilized in this study, and semi-structured interviews were conducted with 28 primiparous mothers who had given birth in the first year period before the interview and were selected from two community health centres in Xi’an city, Shaanxi Province, Northwest China. Each conversational interview lasted between 20 and 86 min. Colaizzi’s seven-step phenomenological approach was used to analyse the data. Results Three major themes were identified: (a) dissatisfaction with current professional services for postpartum mothers, (b) likelihood of health care professional help-seeking behaviour, (c) highlighting the demands for new health care services. The related seven sub-themes included being disappointed with current hospital services; distrusting services provided by community health centres, private institutes and commercial online platforms; preferring not seeking help from professionals as their first choice; hesitating to express their inner discourse to professionals; following confinement requirement and family burden prevents mothers from seeking professional help; experiencing urgent needs for new baby-care-related services; and determining the importance of mothers’ needs. The necessity of professional support in the first month after childbirth was strongly emphasized by the participants. Online professional guidance and support were perceived as the best way to receive services in this study. Conclusion The results of this descriptive phenomenological study suggested that the current maternal and child health care services were insufficient and could not meet primiparous mothers’ need. The results also indicated that identifying barriers and providing services focused on mothers’ needs may be an effective strategy to enhance primiparous mothers’ well-being, and further suggested that feasibility, convenience, and the cultural adaptability of health care services should be considered during the delivery of postpartum interventions.

Abstract Background Continuum of care for maternal health services (CMHS) is a proven approach to improve health and safety for mothers and newborns. This study aims to explore the influence of China’s 2009 healthcare reform on improving the CMHS utilisation. Methods This population-based cross-sectional quantitative study included 2332 women drawn from the fourth and fifth National Health Service Surveys of Shaanxi Province, conducted in 2008 and 2013 respectively, before and after China’s 2009 healthcare reform. A generalised linear mixed model (GLMM) was applied to analyse the influence of this healthcare reform on utilisation of CMHS. Concentration curves, concentration indexes and its decomposition method were used to analyse the equity of changes in utilisation. Results This study showed post-reform CMHS utilisation was higher in both rural and urban women than the CMHS utilisation pre-reform (according to China’s policy defining CMHS). The rate of CMHS utilisation increased from 24.66 to 41.55% for urban women and from 18.31 to 50.49% for rural women (urban: χ2 = 20.64, P

Abstract Background The prevalence of perinatal depression in China ranges from 15 to 20% and the vast majority of prenatally depressed women do not receive the intervention they require. Recent research evidence shows that evidence based, culturally–adapted psychosocial interventions are effective in reducing mental health problems. The World Health Organization (WHO) has endorsed the Thinking Healthy Programme (THP), which is an evidence based psychosocial intervention that can be delivered by non-mental health specialists. The aim of this study was to translate and adapt THP for the Chinese population and to establish its acceptability when delivered by non-specialists to a group of mothers with perinatal depression. Methods The study was conducted in two phases. The THP manual, handbook, and health calendar was translated and adapted based on 8 domains of the Bernal framework (language, metaphors, content, concepts, goals, context, people and methods). Pre-testing was done using cognitive interviewing in the first phase. In second phase of field-testing, THP sessions were delivered to the depressed women by local THP trained nurses. Post intervention, programme survey was used for evaluation. Results This study showed that the core structure, process and techniques of the THP were culturally compatible with the target Chinese population and did not require major changes. It was found that the adapted version of THP manual, handbook, and health calendar were acceptable, understandable, and culturally relevant to the Chinese women and their family members. Nurses were found as a suitable delivery agent by the mothers and their families. Conclusion The Thinking Healthy Programme is acceptable and transferable to the Chinese cultural and healthcare context and nurses are a suitable delivery agent. The translated and adapted version of THP can be used for further implementation and evaluation studies in the Chinese context. Further evaluation can help establish the effectiveness of the programme and barriers to scale-up in China.

Abstract Background The World Health Organization (WHO) End TB Strategy has established a milestone to reduce the number of tuberculosis (TB)- affected households facing catastrophic costs to zero by 2020. The role of active case finding (ACF) in reducing patient costs has not been determined globally. This study therefore aimed to compare costs incurred by TB patients diagnosed through ACF and passive case finding (PCF), and to determine the prevalence and intensity of patient-incurred catastrophic costs in Nepal. Methods The study was conducted in two districts of Nepal: Bardiya and Pyuthan (Province No. 5) between June and August 2018. One hundred patients were included in this study in a 1:1 ratio (PCF: ACF, 25 consecutive ACF and 25 consecutive PCF patients in each district). The WHO TB patient costing tool was applied to collect information from patients or a member of their family regarding indirect and direct medical and non-medical costs. Catastrophic costs were calculated based on the proportion of patients with total costs exceeding 20% of their annual household income. The intensity of catastrophic costs was calculated using the positive overshoot method. The chi-square and Wilcoxon-Mann-Whitney tests were used to compare proportions and costs. Meanwhile, the Mantel Haenszel test was performed to assess the association between catastrophic costs and type of diagnosis. Results Ninety-nine patients were interviewed (50 ACF and 49 PCF). Patients diagnosed through ACF incurred lower costs during the pre-treatment period (direct medical: USD 14 vs USD 32, P = 0.001; direct non-medical: USD 3 vs USD 10, P = 0.004; indirect, time loss: USD 4 vs USD 13, P

Abstract Background Ensuring equal access to preventive care has always been given a priority in health system throughout world. This study aimed to decompose inequality in utilization of preventive care services into its contributing factors and then explore its changes over the period of China’s 2009–2015 health system reform. Methods The concentration index (CI) and decomposition of the CI was performed to capture income-related inequalities in preventive services utilization and identify contribution of various determinants to such inequality using data from China Health and Nutrition Survey. Then, changes in inequality from 2009 to 2015 were estimated using Oaxaca-type decomposition technique. Results The CI for preventive services utilization dropped from 0.2240 in 2009 to 0.1825 in 2015. Residential location and household income made the biggest contributions to income-related inequalities in these two years. Oaxaca decomposition revealed changes in residential location, regions and medical insurance made positive contributions to decline in inequality. However, alternation in household income, age and medical services utilization pushed the equality toward deterioration. Conclusion The pro-rich inequality in preventive healthcare services usage is evident in China despite a certain decline in such inequality during observation period. Policy actions on eliminating urban-rural and income disparity should be given the priority to equalize preventive healthcare.

Abstract Background Adolescent girls in sub-Saharan Africa are disproportionally vulnerable to sexual and reproductive health (SRH) harms. In western Kenya, where unprotected transactional sex is common, young females face higher rates of school dropout, often due to pregnancy, and sexually transmitted infections (STIs), including HIV. Staying in school has shown to protect girls against early marriage, teen pregnancy, and HIV infection. This study evaluates the impact of menstrual cups and cash transfer interventions on a composite of deleterious outcomes (HIV, HSV-2, and school dropout) when given to secondary schoolgirls in western Kenya, with the aim to inform evidence-based policy to improve girls’ health, school equity, and life-chances. Methods Single site, 4-arm, cluster randomised controlled superiority trial. Secondary schools are the unit of randomisation, with schoolgirls as the unit of measurement. Schools will be randomised into one of four intervention arms using a 1:1:1:1 ratio and block randomisation: (1) menstrual cup arm; (2) cash transfer arm, (3) cups and cash combined intervention arm, or (4) control arm. National and county agreement, and school level consent will be obtained prior to recruitment of schools, with parent consent and girls’ assent obtained for participant enrolment. Participants will be trained on safe use of interventions, with all arms receiving puberty and hygiene education. Annually, the state of latrines, water availability, water treatment, handwashing units and soap in schools will be measured. The primary endpoint is a composite of incident HIV, HSV-2, and all-cause school dropout, after 3 years follow-up. School dropout will be monitored each term via school registers and confirmed through home visits. HIV and HSV-2 incident infections and risk factors will be measured at baseline, mid-line and end-line. Intention to treat analysis will be conducted among all enrolled participants. Focus group discussions will provide contextual information on uptake of interventions. Monitoring for safety will occur throughout. Discussion If proved safe and effective, the interventions offer a potential contribution toward girls’ schooling, health, and equity in low- and middle-income countries. Trial registration ClinicalTrials.gov NCT03051789, 15th February 2017.

Abstract Objective The aim of the present study is to identify the average effect across different time points and to specify the time effects of maternal pre-pregnancy BMI and weekly gestational weight gain on the mental development and physical growth of infants. Methods The present cohort study used a repeated measures study design that began in 2004 with follow up at 3, 6, 12, 18, and 24 months of age. The participants were a subset from a controlled, cluster-randomized, double-blind trial. Bayley Scales of Infant Development (BSID) were used to estimate the mental development of infants. A generalized estimating equation linear model was used to estimate the effects of maternal BMI and weight gain. Results The average effect of maternal BMI and weight gain on the weight for age Z scores (WAZ), length for age Z scores (LAZ) and mental development index (MDI) across the different time points of infants was significant. In addition, the maternal BMI and weight gain were positively and significantly associated with the WAZ and LAZ in infants of different ages. However, the effect of weekly gestational weight gain was significant only during the earlier period of life (3 months, Coefficient: 11.15, 95%CI: 4.89–17.41). Conclusions Our results indicate positive effects of pre-pregnancy and prenatal nutrition on the physical growth of infants. Weekly gestational weight gain of the pregnant women had a positive effect on the mental development of the infants, but this effect appears to decline over time.

Abstract Background Children hospitalised with severe anaemia in malaria endemic areas in Africa are at high risk of readmission or death within 6 months post-discharge. Currently, no strategy specifically addresses this period. In Malawi, 3 months of post-discharge malaria chemoprevention (PMC) with monthly treatment courses of artemether-lumefantrine given at discharge and at 1 and 2 months prevented 30% of all-cause readmissions by 6 months post-discharge. Another efficacy trial is needed before a policy of malaria chemoprevention can be considered for the post-discharge management of severe anaemia in children under 5 years of age living in malaria endemic areas. Objective We aim to determine if 3 months of PMC with monthly 3-day treatment courses of dihydroartemisinin-piperaquine is safe and superior to a single 3-day treatment course with artemether-lumefantrine provided as part of standard in-hospital care in reducing all-cause readmissions and deaths (composite primary endpoint) by 6 months in the post-discharge management of children less than 5 years of age admitted with severe anaemia of any or undetermined cause. Methods/design This is a multi-centre, two-arm, placebo-controlled, individually randomised trial in children under 5 years of age recently discharged following management for severe anaemia. Children in both arms will receive standard in-hospital care for severe anaemia and a 3-day course of artemether-lumefantrine at discharge. At 2 weeks after discharge, surviving children will be randomised to receive either 3-day courses of dihydroartemisinin-piperaquine at 2, 6 and 10 weeks or an identical placebo and followed for 26 weeks through passive case detection. The trial will be conducted in hospitals in malaria endemic areas in Kenya and Uganda. The study is designed to detect a 25% reduction in the incidence of all-cause readmissions or death (composite primary outcome) from 1152 to 864 per 1000 child years (power 80%, α = 0.05) and requires 520 children per arm (1040 total children). Results Participant recruitment started in May 2016 and is ongoing. Trial registration ClinicalTrials.gov, NCT02671175. Registered on 28 January 2016.

Abstract Background Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretroviral therapy (ART). Mortality is driven in part by limited availability of amphotericin-based treatment, drug-induced toxicities of amphotericin B deoxycholate and prolonged hospital admissions. A single, high-dose of liposomal amphotericin (L-AmB, Ambisome) on a fluconazole backbone has been reported as non-inferior to 14 days of standard dose L-AmB in reducing fungal burden. This trial examines whether single, high-dose L-AmB given with high-dose fluconazole and flucytosine is non-inferior to a seven-day course of amphotericin B deoxycholate plus flucytosine (the current World Health Organization [WHO] recommended treatment regimen). Methods An open-label phase III randomised controlled non-inferiority trial conducted in five countries in sub-Saharan Africa: Botswana, Malawi, South Africa, Uganda and Zimbabwe. The trial will compare CM induction therapy with (1) a single dose (10 mg/kg) of L-AmB given with 14 days of fluconazole (1200 mg/day) and flucytosine (100 mg/kg/day) to (2) seven days amphotericin B deoxycholate (1 mg/kg/day) given alongside seven days of flucytosine (100 mg/kg/day) followed by seven days of fluconazole (1200 mg/day). The primary endpoint is all-cause mortality at ten weeks with a non-inferiority margin of 10% and 90% power. Secondary endpoints are early fungicidal activity, proportion of grade III/IV adverse events, pharmacokinetic parameters and pharmacokinetic/pharmacodynamic associations, health service costs, all-cause mortality within the first two and four weeks, all-cause mortality within the first ten weeks (superiority analysis) and rates of CM relapse, immune reconstitution inflammatory syndrome and disability at ten weeks. A total of 850 patients aged ≥ 18 years with a first episode of HIV-associated CM will be enrolled (425 randomised to each arm). All patients will be followed for 16 weeks. All patients will receive consolidation therapy with fluconazole 800 mg/day to complete ten weeks of treatment, followed by fluconazole maintenance and ART as per local guidance. Discussion A safe, sustainable and easy to administer regimen of L-AmB that is non-inferior to seven days of daily amphotericin B deoxycholate therapy may reduce the number of adverse events seen in patients treated with amphotericin B deoxycholate and shorten hospital admissions, providing a highly favourable and implementable alternative to the current WHO recommended first-line treatment. Trial registration ISRCTN, ISRCTN72509687. Registered on 13 July 2017.

Abstract Background Rural infant growth failure has been highlighted as a priority for action in China’s national nutrition and child development policies. The aim of this paper was to evaluate the effect of community-based intervention project on child feeding, child health care and child growth. Methods From 2001 to 2005, UNICEF and China’s Ministry of Health worked together to develop holistic strategies for child health care. All the interventions were implemented through the three-tier (county-township-village) rural health care network.In this study, 34 counties were included in both surveys in 2001 and 2005. Among these 34 counties, nine were subjected to the intervention and 25 counties were used as controls. In nine intervention counties, leaflets containing information of supplemental feeding of infants and young children were printed and distributed to women during hospital delivery or visit to newborn by village doctors. Two cross-sectional surveys were both conducted from July to early September in 2001 and 2005. We calculated Z-scores of height-for-age (HAZ), weight-for-age (WAZ) and weight-for-height (WHZ), with the new WHO growth standard. HAZ

Abstract Background Methodological research into the design, conduct, analysis and reporting of trials is essential to optimise the process. UK specialists in the field have established a set of top priorities in aid of this research. These priorities, however, may not be reflected in the needs of similar research in low- to middle-income countries (LMICs) with different healthcare provision, resources and research infrastructure. The aim of the study was to identify the top priorities for methodological research in LMICs to inform further research and ultimately to improve clinical trials in these regions. Methods An online, two-round survey was conducted from December 2016 to April 2017 amongst researchers and methodologists working on trials in LMICs. The first round required participants to suggest between three and six topics which they felt were priorities for trial methodological research in LMICs. The second round invited participants to grade the importance of a compulsory list of topics suggested by four or more individuals, and an optional list of the remaining topics. Findings Rounds 1 and 2 were completed by 412 and 314 participants, respectively. A wide spread of years of experience, discipline, current country of residence, origin of trials training and area of involvement in trials was reported. The topics deemed most important for methodological research were: choosing appropriate outcomes to measure and training of research staff. Conclusion By presenting these top priorities we have the foundations of a global health trials methodological research agenda which we hope will foster future research in specific areas in order to increase and improve trials in LMICs.

Abstract Background Early first-trimester medical abortion (MA) service (≤ 63 days) has been provided by doctors and nurses under doctors’ supervision since 2009 in Nepal. This paper assesses whether MA services provided by specifically trained and certified nurses and auxiliary nurse-midwives independently from doctors’ supervision, is considered as satisfactory by women as those provided by doctors. Methods The data come from a multi-center, randomized, controlled equivalence trial conducted between April 2009 and March 2010 in five district hospitals in Nepal. Women seeking MA were randomly assigned to doctors or nurses and auxiliary nurse-midwives(ANMs).Eligible women were administered 200 mg mifepristone orally followed by 800 μg misoprostol vaginally two days later by their assigned providers and followed up 10–14 days later. At the follow-up visit women’s reported satisfaction with MA service they received was measured. Results Of 1295 women screened for eligibility, 535 were randomly assigned to a doctor and 542 to a nurse or ANM. Nineteen women were lost-to-follow up in the former group and 27 were lost-to-follow up or did not complete the acceptability interview in the latter group. This study is, therefore, based on516womenin the doctor’s group and 515 women in the nurse or ANM group. All women in the nurse or ANM group reported being satisfied or highly satisfied by MA compared to 99% in the doctor’s group. Satisfaction was similar regardless of the type of provider; 38% among nurse or ANM and 35% among the doctor group were “highly satisfied”, and 62% and 64%, respectively, were “satisfied”. Women’s experiences such as ‘less than expected amount or duration of bleeding following MA’, ‘shorter than expected duration of the abortion process’, and ‘able to manage symptoms’, were found to be associated with women’s higher satisfaction with MA. Counseling and information on the method, potential complications of MA and post-abortion contraception was nearly universal. No statistically significant differences were found in the level of satisfaction by age, parity, marital status, education or occupation of women. Conclusions Women’s satisfaction with MA service provided by trained nurses or auxiliary nurse-midwives was similar to that provided by doctors. The findings, therefore, provide support for extending safe and accessible medical abortion services by government-trained nurses and auxiliary nurse midwives to women seeking early first trimester pregnancy termination. Trial registration The trial was retrospectively registered with ClinicalTrials.gov (identifier: NCT01186302 ). Registered August 20, 2010.

Abstract Background The impact of humanitarian disasters upon mental health is well recognised. The evidence for psychological interventions for mental health is mounting, but few interventions have been rigorously tested in humanitarian settings. To be sustainable in humanitarian settings interventions need to be short, simple, deliverable by nonspecialists under supervision, and adopt a transdiagnostic approach where an array of mental health outcomes are addressed simultaneously. These elements have been incorporated into the newly developed WHO Problem Management Plus (PM+) Group intervention. The aim of this trial is to evaluate the locally adapted PM+ Group intervention for women in Swat, Pakistan. Methods This PM+ Group trial is a two-arm, single-blind, cluster randomised controlled trial conducted in a community-based setting with women in rural Pakistan. PM+ is delivered in partnership with the Lady Health Worker (LHW) Programme which provides community-based health care to women in Pakistan. Thirty-four LHW clusters will be randomised in a 1:1 allocation ratio using a permuted-block randomisation method. Participants screened and found to meet the inclusion criteria will be allocated to either the PM+ intervention group (n = 306), or the control arm (n = 306). The manualised PM+ intervention involves five sessions, each lasting 3 h, and introduces four strategies applied by participants to problems that they are facing. It is delivered by local female facilitators with a minimum of 16 years of education who are provided with targeted training and supervision. The primary outcome is individual psychological distress, measured by levels of anxiety and depression on the Hospital Anxiety and Depression Scale at 20 weeks after baseline. Secondary outcomes include major depression, post-traumatic stress disorder, levels of social support, levels of functioning, and economic effectiveness. Intervention acceptability will be explored through an embedded qualitative study. Discussion The PM+ Group trial will provide important evidence on the effectiveness of an empirically supported psychological treatment delivered by nonspecialists in a humanitarian setting. If proven effective, the qualitative component will inform strategies for PM+ Group scale-up in health systems in other humanitarian settings. Trial registration Australian New Zealand Clinical Trials Registry, identifier: ACTRN12616000037404. Registered on 19 January 2016; WHO Protocol ID RPC705, v.4, 2 November 2015.

Following publication of the original article [1], we have been notified that one of the author names was listed incorrectly. Both incorrect and correct author names are presented below. The original publication has been corrected.