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

Adequacy of blood pressure control and level of adherence with antihypertensive therapy

Objectives: To determine the adequacy of blood pressure (BP) control and level of adherence to pharmacotherapy in hypertensive out-patients.Design: Cross-sectional study.Setting: General medical outpatient clinics at a tertiary referral hospital, Kenyatta National Hospital.Subjects: Hypertensive with at least one documented renewal of prescription. Main outcome measure: Adequacy of BP control and level of adherence by the Hill- Bone score.Results: Of 783 patients screened over a six month period, 575 (73%) met the inclusion criteria and 264 were randomly recruited; 67% were female; mean age was 57.3 years; mean duration of hypertension was 6.75 years (range six months to 31 years);21.6% had normal BMI. Knowledge of lifestyle measures for BP control was weight loss 50%, exercise 54% and salt restriction 80%. Number of antihypertensives prescribed were 35.2% two drugs, 36.6% three drugs and 14.9% on four or more drugs; with drugs class being thiazide diuretics 64.1%, B-blockers 55.7%, calcium channel blockers 55.3% and angiotensin system inhibitors at 50.4%. Sixty eight (26%) had adequate BP control and 114 (58.5%) of those with inadequate BP control had BP of > 160/l00mmHg. Eightyfour (31.8%) of the patients were fully adherent to antihypertensive therapy. Non adherence was not significantly associated with any socio-demographic factors. Poor BP control was significantly associated with non adherence (p=0.006, r2=0.54 SBP, 0.63 DBP), obesity (p=0.03), and increasing number of medications (p=0.012 DBP and 0.038 SBP);other factors included obesity, suboptimal dosing and suboptimal therapeuticcombinations. Conclusion: We document poor BP control in 75% of our treated hypertensive patients and this is largely due to non adherence, with other associated factors being obesity, suboptimal drug combinations and doses

A Comparative Study of Cellular Diversity between the Xenopus Pronephric and Mouse Metanephric Nephron

The kidney is an essential organ that ensures bodily fluid homeostasis and removes soluble waste products from the organism. Nephrons, the functional units of the kidney, comprise a blood filter, the glomerulus or glomus, and an epithelial tubule that processes the filtrate from the blood or coelom and selectively reabsorbs solutes, such as sugars, proteins, ions, and water, leaving waste products to be eliminated in the urine. Genes coding for transporters are segmentally expressed, enabling the nephron to sequentially process the filtrate. The Xenopus embryonic kidney, the pronephros, which consists of a single large nephron, has served as a valuable model to identify genes involved in nephron formation and patterning. Therefore, the developmental patterning program that generates these segments is of great interest. Prior work has defined the gene expression profiles of Xenopus nephron segments via in situ hybridization strategies, but a comprehensive understanding of the cellular makeup of the pronephric kidney remains incomplete. Here, we carried out single-cell mRNA sequencing of the functional Xenopus pronephric nephron and evaluated its cellular composition through comparative analyses with previous Xenopus studies and single-cell mRNA sequencing of the adult mouse kidney. This study reconstructs the cellular makeup of the pronephric kidney and identifies conserved cells, segments, and associated gene expression profiles. Thus, our data highlight significant conservation in podocytes, proximal and distal tubule cells, and divergence in cellular composition underlying the capacity of each nephron to remove wastes in the form of urine, while emphasizing the Xenopus pronephros as a model for physiology and disease

Plasma proteomic signatures of enteric permeability among hospitalized and community children in Kenya and Pakistan

We aimed to establish if enteric permeability was associated with similar biological processes in children recovering from hospitalization and relatively healthy children in the community. Extreme gradient boosted models predicting the lactulose-rhamnose ratio (LRR), a biomarker of enteric permeability, using 7,500 plasma proteins and 34 fecal biomarkers of enteric infection among 89 hospitalized and 60 community children aged 2–23 months were built. The R2 values were calculated in test sets. The models performed better among community children (R2: 0.27 [min-max: 0.19, 0.53]) than hospitalized children (R2: 0.07 [min-max: 0.03, 0.11]). In the community, LRR was associated with biomarkers of humoral antimicrobial and cellular lipopolysaccharide responses and inversely associated with anti-inflammatory and innate immunological responses. Among hospitalized children, the selected biomarkers had few shared functions. This suggests enteric permeability among community children was associated with a host response to pathogens, but this association was not observed among hospitalized children

Plasma proteomic signatures associated with enteric permeability among hospitalized and community children under two years of age in Kenya and Pakistan

We aimed to establish if enteric permeability was associated with similar biological processes in children recovering from hospitalization and relatively healthy children in the community. Extreme gradient boosted models predicting the lactulose-rhamnose ratio (LRR), a biomarker of enteric permeability, using 7,500 plasma proteins and 34 fecal biomarkers of enteric infection among 89 hospitalized and 60 community children aged 2–23 months were built. The R2 values were calculated in test sets. The models performed better among community children (R2 : 0.27 [min-max: 0.19, 0.53]) than hospitalized children (R2 : 0.07 [min-max: 0.03, 0.11]). In the community, LRR was associated with biomarkers of humoral antimicrobial and cellular lipopolysaccharide responses and inversely associated with anti-inflammatory and innate immunological responses. Among hospitalized children, the selected biomarkers had few shared functions. This suggests enteric permeability among community children was associated with a host response to pathogens, but this association was not observed among hospitalized children

Beyond tipping points: risks, equity, and the ethics of intervention

Earth system tipping points pose existential threats to current and future generations, both human and non-human, with those least responsible for causing them facing the greatest risks. “Positive” social tipping points (that we shorten to positive tipping points, or PTPs) are often deliberate interventions into social systems with the aim of rapidly mitigating the risks of Earth system tipping. However, the desire to intervene should neither increase risks nor perpetuate unjust or inequitable outcomes through the creation of sacrifice zones. In this paper, we argue that considerations of what needs to change, who is being asked to change, and where and by whom the impacts of change will be felt are fundamental and normative questions that require reflexivity and systemic understanding of decision-making across scales. All actors have a role to play in ensuring that justice, equity, and ethics are carefully considered before any intervention. Enabling positive tipping points for radical transformations would thus benefit from more diverse perspectives, with a particular emphasis on the inclusion of marginalized voices in offering solutions. We conclude that taking a cautious approach to positive tipping interventions, including careful consideration of distributional and unintended consequences, and stepping back to explore all options, not just those appearing to offer a quick fix, could lead to more equitable and sustainable outcomes

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

The impact of risk factors on aspirin's efficacy for the prevention of preterm birth

BACKGROUND: The Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial was a landmark study that demonstrated a reduction in preterm birth and hypertensive disorders of pregnancy in nulliparous women who received low-dose aspirin. All women in the study had at least 1 moderate-risk factor for preeclampsia (nulliparity). Unlike current US Preventative Service Task Force guidelines, which recommend low-dose aspirin for ≥2 moderate-risk factors, women in this study were randomized to receive low-dose aspirin regardless of the presence or absence of an additional risk factor. OBJECTIVE: This study aimed to compare how low-dose aspirin differentially benefits nulliparous women with and without additional preeclampsia risk factors for the prevention of preterm birth and hypertensive disorders of pregnancy. STUDY DESIGN: This was a non-prespecified secondary analysis of the Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas trial that randomized nulliparous women with singleton pregnancies from 6 low-middle-income countries to receive low-dose aspirin or placebo. Our primary exposure was having an additional preeclampsia risk factor beyond nulliparity. Our primary outcome was preterm birth before 37 weeks of gestation, and our secondary outcomes included preterm birth before 34 weeks of gestation, preterm birth before 28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality. RESULTS: Among 11,558 nulliparous women who met the inclusion criteria, 66.8% had no additional risk factors. Low-dose aspirin similarly reduced the risk of preterm birth at &lt;37 weeks of gestation in women with and without additional risk factors (relative risk: 0.75 vs 0.85; P=.35). Additionally for our secondary outcomes, low-dose aspirin similarly reduced the risk of preterm birth at &lt;28 weeks of gestation, hypertensive disorders of pregnancy, and perinatal mortality in women with and without additional risk factors. The reduction of preterm birth at &lt;34 weeks of gestation with low-dose aspirin was significantly greater in women without additional risk factors than those with an additional risk factor (relative risk: 0.69 vs 1.04; P=.04). CONCLUSION: Low-dose aspirin's ability to prevent preterm birth, hypertensive disorders of pregnancy, and perinatal mortality was similar in nulliparous women with and without additional risk factors. Professional societies should consider recommending low-dose aspirin to all nulliparous women

Corrigendum to The impact of risk factors on aspirin's efficacy for the prevention of preterm birth. American Journal of Obstetrics & Gynecology MFM. Volume 5, Issue 10, October 2023, 101095

Corrigendum to The impact of risk factors on aspirin's efficacy for the prevention of preterm birth. American Journal of Obstetrics &amp; Gynecology MFM. Volume 5, Issue 10, October 2023, 10109