Assessing adherence to Antihypertensive therapy in primary health care in Namibia: findings and implications

Namibia has the highest burden and incidence of hypertension in sub-Sahara Africa. Though non-adherence to antihypertensive therapy is an important cardiovascular risk factor, little is known about potential ways to improve adherence in Namibia following universal access. The objective of this study is to validate the Hill-Bone compliance scale and determine the level and predictors of adherence to antihypertensive treatment in primary health care settings in sub-urban townships of Windhoek, Namibia

Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation. METHODS: ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks\u27 gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970. FINDINGS: From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks\u27 gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (\u3c34 \u3eweeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups. INTERPRETATION: In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development

Design and implementation of a community-based mother-to-mother peer support programme for the follow-up of low birthweight infants in rural western Kenya

Background: Globally, low birthweight (LBW) infants (<2,500 g) have the highest risk of mortality during the first year of life. Those who survive often have adverse health outcomes. Post-discharge outcomes of LBW infants in impoverished communities in Africa are largely unknown. This paper describes the design and implementation of a mother-to-mother peer training and mentoring programme for the follow-up of LBW infants in rural Kenya. Methods: Key informant interviews were conducted with 10 mothers of neonates (infants <28 days) from two rural communities in western Kenya. These data informed the identification of key characteristics required for mother-to-mother peer supporters (peer mothers) following up LBW infants post discharge. Forty potential peer mothers were invited to attend a 5-day training programme that focused on three main themes: supportive care using appropriate communication, identification of severe illness, and recommended care strategies for LBW infants. Sixteen peer mothers were mentored to conduct seven community follow-up visits to each mother-LBW infant pair with fifteen completing all the visits over a 6-month period. A mixed methods approach was used to evaluate the implementation of the programme. Quantitative data of peer mother socio-demographic characteristics, recruitment, and retention was collected. Two post-training focus group discussions were conducted with the peer mothers to explore their experiences of the programme. Descriptive statistics were generated from the quantitative data and the qualitative data was analysed using a thematic framework. Results: The median age of the peer mothers was 26 years (range 21–43). From March-August 2019, each peer mother conducted a median of 28 visits (range 7–77) with fourteen (88%) completing all their assigned follow-up visits. Post training, our interviews suggest that peer mothers felt empowered to promote appropriate infant feeding practices. They gave multiple examples of improved health seeking behaviours as a result of the peer mother training programme. Conclusion: Our peer mother training programme equipped peer mothers with the knowledge and skills for the post-discharge follow-up of LBW infants in this rural community in Kenya. Community-based interventions for LBW infants, delivered by appropriately trained peer mothers, have the potential to address the current gaps in post-discharge care for these infants

Safety of daily low-dose aspirin use during pregnancy in low-income and middle-income countries

BACKGROUND The daily use of low-dose aspirin may be a safe, widely available, and inexpensive intervention for reducing the risk of preterm birth. Data on the potential side effects of low-dose aspirin use during pregnancy in low- and middle-income countries are needed. OBJECTIVE This study aimed to assess differences in unexpected emergency medical visits and potential maternal side effects from a randomized, double-blind, multicountry, placebo-controlled trial of low-dose aspirin use (81 mg daily, from 6 to 36 weeks’ gestation). STUDY DESIGN This study was a secondary analysis of data from the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial, a trial of the Global Network for Women's and Children's Health conducted in India (2 sites), Pakistan, Guatemala, Democratic Republic of the Congo, Kenya, and Zambia. The outcomes for this analysis were unexpected emergency medical visits and the occurrence of the following potential side effects—overall and separately—nausea, vomiting, rash or hives, diarrhea, gastritis, vaginal bleeding, allergic reaction, and any other potential side effects. Analyses were performed overall and by geographic region. RESULTS Between the aspirin (n=5943) and placebo (n=5936) study groups, there was no statistically significant difference in the risk of unexpected emergency medical visits or the risk of any potential side effect (overall). Of the 8 potential side effects assessed, only 1 (rash or hives) presented a different risk by treatment group (4.2% in the aspirin group vs 3.5% in the placebo group; relative risk, 1.20; 95% confidence interval, 1.01–1.43; P=.042). CONCLUSION The daily use of low-dose aspirin seems to be a safe intervention for reducing the risk of preterm birth and well tolerated by nulliparous pregnant women between 6 and 36 weeks’ gestation in low- and middle-income countries

Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). INTERPRETATION: In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. FUNDING: UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust

Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing. Findings: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77–0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45–0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72–0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes. Interpretation: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Cost-Effectiveness of Low-Dose Aspirin for the Prevention of Preterm Birth: A Prospective Study of the Global Network for Women\u27s and Children\u27s Health Research

Background: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries. Methods: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In this analysis from a health-care sector perspective, we considered the costs and effects of LDA treatment, pregnancy outcomes, and neonatal health-care use. We did sensitivity analyses to understand the effect of the price of the LDA regimen, and the effectiveness of LDA in reducing both preterm birth and perinatal death. Findings: In model simulations, LDA was associated with 141 averted preterm births, 74 averted perinatal deaths, and 31 averted hospitalisations per 10 000 pregnancies. The reduction in hospitalisation resulted in a cost of US$248 per averted preterm birth,$471 per averted perinatal death, and $15·95 per disability-adjusted life year. Interpretation: LDA treatment in nulliparous, singleton pregnancies is a low-cost, effective treatment to reduce preterm birth and perinatal death. The low cost per disability-adjusted life year averted strengthens the evidence in support of prioritising the implementation of LDA in publicly funded health care in low-income and middle-income countries. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development

Cost-Effectiveness of Low-Dose Aspirin for the Prevention of Preterm Birth: A Prospective Study of the Global Network for Women’s and Children’s Health Research

Background: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries. Methods: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In this analysis from a health-care sector perspective, we considered the costs and effects of LDA treatment, pregnancy outcomes, and neonatal health-care use. We did sensitivity analyses to understand the effect of the price of the LDA regimen, and the effectiveness of LDA in reducing both preterm birth and perinatal death. Findings: In model simulations, LDA was associated with 141 averted preterm births, 74 averted perinatal deaths, and 31 averted hospitalisations per 10 000 pregnancies. The reduction in hospitalisation resulted in a cost of US$248 per averted preterm birth,$471 per averted perinatal death, and $15·95 per disability-adjusted life year. Interpretation: LDA treatment in nulliparous, singleton pregnancies is a low-cost, effective treatment to reduce preterm birth and perinatal death. The low cost per disability-adjusted life year averted strengthens the evidence in support of prioritising the implementation of LDA in publicly funded health care in low-income and middle-income countries. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development