Developing shared understanding of pre-eclampsia in Haiti and Zimbabwe using Theory of Change.

Pre-eclampsia, a complex and multi-system disorder specific to pregnancy, is a leading cause of preventable maternal and perinatal deaths in low-resource settings. Early detection and appropriate intervention with management of hypertension, prevention of eclampsia and timely delivery are effective at reducing mortality and morbidity. Outcomes can be greatly improved with the provision and uptake of good quality care. Cultural contexts of maternal care, social practices and expectations around pregnancy and childbirth profoundly shape understanding and prioritisation when it comes to seeking out care. Few studies have addressed health education specifically targeting pre-eclampsia in low resource settings. The existing literature has limited descriptions of contextual barriers to care or of the intervention development processes employed. More engaging, holistic approaches to pre-eclampsia education for women and families that recognise the challenges they face and that support a shared understanding of the disorder, are needed. We describe our experience of developing a Theory of Change (ToC) as part of the co-production of educational resources for pre-eclampsia in Haiti and Zimbabwe.

Pills and prayers: a comparative qualitative study of community conceptualisations of pre-eclampsia and pluralistic care in Ethiopia, Haiti and Zimbabwe.

BACKGROUND: Pre-eclampsia is a leading cause of preventable maternal and perinatal deaths globally. While health inequities remain stark, removing financial or structural barriers to care does not necessarily improve uptake of life-saving treatment. Building on existing literature elaborating the sociocultural contexts that shape behaviours around pregnancy and childbirth can identify nuanced influences relating to pre-eclampsia care. METHODS: We conducted a cross-cultural comparative study exploring lived experiences and understanding of pre-eclampsia in Ethiopia, Haiti and Zimbabwe. Our primary objective was to examine what local understandings of pre-eclampsia might be shared between these three under-resourced settings despite their considerable sociocultural differences. Between August 2018 and January 2020, we conducted 89 in-depth interviews with individuals and 17 focus group discussions (n = 106). We purposively sampled perinatal women, survivors of pre-eclampsia, families of deceased women, partners, older male and female decision-makers, traditional birth attendants, religious and traditional healers, community health workers and facility-based health professionals. Template analysis was conducted to facilitate cross-country comparison drawing on Social Learning Theory and the Health Belief Model. RESULTS: Survivors of pre-eclampsia spoke of their uncertainty regarding symptoms and diagnosis. A lack of shared language challenged coherence in interpretations of illness related to pre-eclampsia. Across settings, raised blood pressure in pregnancy was often attributed to psychosocial distress and dietary factors, and eclampsia linked to spiritual manifestations. Pluralistic care was driven by attribution of causes, social norms and expectations relating to alternative care and trust in biomedicine across all three settings. Divergence across the contexts centred around nuances in religious or traditional practices relating to maternal health and pregnancy. CONCLUSIONS: Engaging faith and traditional caregivers and the wider community offers opportunities to move towards coherent conceptualisations of pre-eclampsia, and hence greater access to potentially life-saving care.

Large B cell lymphoma presenting as an adnexal mass in an HIV positive patient: a case report.

We present a 34-year-old HIV positive woman who presented with a 2-month history of abdominal pain, abdominal distension, night sweats and fever. She had a firm, immobile and irregular abdominopelvic mass of about 30 weeks uterine size. Investigations showed a haemoglobin of 6.5g/dl, (NR 12-14) cancer antigen 125 of 44U/ml (NR 0-35), serum beta human chorionic gonadotropin (HCG) of 0.258mIU/ml (NR 0-5) and alpha fetoprotein of 7ng/ml (NR <10). Her CD4 count was 63cells/mm3. At laparotomy there was a left ovarian mass and the rest of the abdomen and omentum looked grossly normal, leading to the conclusion that the primary was in the ovaries. A total abdominal hysterectomy, bilateral adnexectomy and infracolic omentectomy were done. Sigmoidectomy and Hartmann's procedure were also performed. Histology of the specimens showed a large B cell lymphoma. She has since been commenced on chemotherapy and antiretroviral therapy and has been doing well.

Exploring the effect of implementation and context on a stepped-wedge randomised controlled trial of a vital sign triage device in routine maternity care in low-resource settings.

BACKGROUND: Interventions aimed at reducing maternal mortality are increasingly complex. Understanding how complex interventions are delivered, to whom, and how they work is key in ensuring their rapid scale-up. We delivered a vital signs triage intervention into routine maternity care in eight low- and middle-income countries with the aim of reducing a composite outcome of morbidity and mortality. This was a pragmatic, hybrid effectiveness-implementation stepped-wedge randomised controlled trial. In this study, we present the results of the mixed-methods process evaluation. The aim was to describe implementation and local context and integrate results to determine whether differences in the effect of the intervention across sites could be explained. METHODS: The duration and content of implementation, uptake of the intervention and its impact on clinical management were recorded. These were integrated with interviews (n = 36) and focus groups (n = 19) at 3 months and 6-9 months after implementation. In order to determine the effect of implementation on effectiveness, measures were ranked and averaged across implementation domains to create a composite implementation strength score and then correlated with the primary outcome. RESULTS: Overall, 61.1% (n = 2747) of health care providers were trained in the intervention (range 16.5% to 89.2%) over a mean of 10.8 days. Uptake and acceptability of the intervention was good. All clusters demonstrated improved availability of vital signs equipment. There was an increase in the proportion of women having their blood pressure measured in pregnancy following the intervention (79.2% vs. 97.6%; OR 1.30 (1.29-1.31)) and no significant change in referral rates (3.7% vs. 4.4% OR 0.89; (0.39-2.05)). Availability of resources and acceptable, effective referral systems influenced health care provider interaction with the intervention. There was no correlation between process measures within or between domains, or between the composite score and the primary outcome. CONCLUSIONS: This process evaluation has successfully described the quantity and quality of implementation. Variation in implementation and context did not explain differences in the effectiveness of the intervention on maternal mortality and morbidity. We suggest future trials should prioritise in-depth evaluation of local context and clinical pathways. TRIAL REGISTRATION: Trial registration: ISRCTN41244132 . Registered on 2 Feb 2016.

Incidence of eclampsia and related complications across 10 low- and middle-resource geographical regions: Secondary analysis of a cluster randomised controlled trial.

BACKGROUND: In 2015, approximately 42,000 women died as a result of hypertensive disorders of pregnancy worldwide; over 99% of these deaths occurred in low- and middle-income countries. The aim of this paper is to describe the incidence and characteristics of eclampsia and related complications from hypertensive disorders of pregnancy across 10 low- and middle-income geographical regions in 8 countries, in relation to magnesium sulfate availability. METHODS AND FINDINGS: This is a secondary analysis of a stepped-wedge cluster randomised controlled trial undertaken in sub-Saharan Africa, India, and Haiti. This trial implemented a novel vital sign device and training package in routine maternity care with the aim of reducing a composite outcome of maternal mortality and morbidity. Institutional-level consent was obtained, and all women presenting for maternity care were eligible for inclusion. Data on eclampsia, stroke, admission to intensive care with a hypertensive disorder of pregnancy, and maternal death from a hypertensive disorder of pregnancy were prospectively collected from routine data sources and active case finding, together with data on perinatal outcomes in women with these outcomes. In 536,233 deliveries between 1 April 2016 and 30 November 2017, there were 2,692 women with eclampsia (0.5%). In total 6.9% (n = 186; 3.47/10,000 deliveries) of women with eclampsia died, and a further 51 died from other complications of hypertensive disorders of pregnancy (0.95/10,000). After planned adjustments, the implementation of the CRADLE intervention was not associated with any significant change in the rates of eclampsia, stroke, or maternal death or intensive care admission with a hypertensive disorder of pregnancy. Nearly 1 in 5 (17.9%) women with eclampsia, stroke, or a hypertensive disorder of pregnancy causing intensive care admission or maternal death experienced a stillbirth or neonatal death. A third of eclampsia cases (33.2%; n = 894) occurred in women under 20 years of age, 60.0% in women aged 20-34 years (n = 1,616), and 6.8% (n = 182) in women aged 35 years or over. Rates of eclampsia varied approximately 7-fold between sites (range 19.6/10,000 in Zambia Centre 1 to 142.0/10,000 in Sierra Leone). Over half (55.1%) of first eclamptic fits occurred in a health-care facility, with the remainder in the community. Place of first fit varied substantially between sites (from 5.9% in the central referral facility in Sierra Leone to 85% in Uganda Centre 2). On average, magnesium sulfate was available in 74.7% of facilities (range 25% in Haiti to 100% in Sierra Leone and Zimbabwe). There was no detectable association between magnesium sulfate availability and the rate of eclampsia across sites (p = 0.12). This analysis may have been influenced by the selection of predominantly urban and peri-urban settings, and by collection of only monthly data on availability of magnesium sulfate, and is limited by the lack of demographic data in the population of women delivering in the trial areas. CONCLUSIONS: The large variation in eclampsia and maternal and neonatal fatality from hypertensive disorders of pregnancy between countries emphasises that inequality and inequity persist in healthcare for women with hypertensive disorders of pregnancy. Alongside the growing interest in improving community detection and health education for these disorders, efforts to improve quality of care within healthcare facilities are key. Strategies to prevent eclampsia should be informed by local data. TRIAL REGISTRATION: ISRCTN: 41244132.

Effect of a novel vital sign device on maternal mortality and morbidity in low-resource settings: a pragmatic, stepped-wedge, cluster-randomised controlled trial.

BACKGROUND: In 2015, an estimated 303 000 women died in pregnancy and childbirth. Obstetric haemorrhage, sepsis, and hypertensive disorders of pregnancy account for more than 50% of maternal deaths worldwide. There are effective treatments for these pregnancy complications, but they require early detection by measurement of vital signs and timely administration to save lives. The primary aim of this trial was to determine whether implementation of the CRADLE Vital Sign Alert and an education package into community and facility maternity care in low-resource settings could reduce a composite of all-cause maternal mortality or major morbidity (eclampsia and hysterectomy). METHODS: We did a pragmatic, stepped-wedge, cluster-randomised controlled trial in ten clusters across Africa, India, and Haiti, introducing the device into routine maternity care. Each cluster contained at least one secondary or tertiary hospital and their main referral facilities. Clusters crossed over from existing routine care to the CRADLE intervention in one of nine steps at 2-monthly intervals, with CRADLE devices replacing existing equipment at the randomly allocated timepoint. A computer-generated randomly allocated sequence determined the order in which the clusters received the intervention. Because of the nature of the intervention, this trial was not masked. Data were gathered monthly, with 20 time periods of 1 month. The primary composite outcome was at least one of eclampsia, emergency hysterectomy, and maternal death. This study is registered with the ISRCTN registry, number ISRCTN41244132. FINDINGS: Between April 1, 2016, and Nov 30, 2017, among 536 223 deliveries, the primary outcome occurred in 4067 women, with 998 maternal deaths, 2692 eclampsia cases, and 681 hysterectomies. There was an 8% decrease in the primary outcome from 79·4 per 10 000 deliveries pre-intervention to 72·8 per 10 000 deliveries post-intervention (odds ratio [OR] 0·92, 95% CI 0·86-0·97; p=0·0056). After planned adjustments for variation in event rates between and within clusters over time, the unexpected degree of variability meant we were unable to judge the benefit or harms of the intervention (OR 1·22, 95% CI 0·73-2·06; p=0·45). INTERPRETATION: There was an absolute 8% reduction in primary outcome during the trial, with no change in resources or staffing, but this reduction could not be directly attributed to the intervention due to variability. We encountered unanticipated methodological challenges with this trial design, which can provide valuable learning for future research and inform the trial design of future international stepped-wedge trials. FUNDING: Newton Fund Global Research Programme: UK Medical Research Council; Department of Biotechnology, Ministry of Science & Technology, Government of India; and UK Department of International Development.

Evaluation of a novel vital sign device to reduce maternal mortality and morbidity in low-resource settings: a mixed method feasibility study for the CRADLE-3 trial.

BACKGROUND: The CRADLE-3 trial is a stepped-wedge randomised controlled trial aiming to reduce maternal mortality and morbidity by implementing a novel vital sign device (CRADLE Vital Sign Alert) and training package into routine maternity care in 10 low-income sites. The MRC Guidance on complex interventions proposes that interventions and implementation strategies be shaped by early phase piloting and development work. We present the findings of a three-month mixed-methodology feasibility study for this trial, describe how this was informed by the MRC guidance and the study design was refined. METHODS: The fidelity, dose, feasibility and acceptability of implementation and training materials were assessed in three representative non-trial sites (Zimbabwe, Ethiopia, India) using multiple-choice questionnaires, evaluation of clinical management (action log), healthcare provider (HCP) semi-structured interviews and focus groups 4-10 weeks after implementation. Simultaneously, the 10 sites included in the main trial (eight countries) collected primary outcome data to inform the power calculation and randomisation allocation and assess the feasibility of data collection. RESULTS: The package was implemented with high fidelity (85% of HCP trained, n = 204). The questionnaires indicated a good understanding of device use with 75% of participants scoring > 75% (n = 97; 90% of those distributed). Action logs were inconsistently completed but indicated that the majority of HCP responded appropriately to abnormal results. From 18 HCP interviews and two focus groups it was widely reported that the intervention improved capacity to make clinical decisions, escalate care and make appropriate referrals. Nine of the ten main trial sites achieved ethical approval for pilot data collection. Intensive care was an inconsistent marker of morbidity and stroke an infrequent outcome and therefore they were removed from the main trial composite outcome. Tools and methods of data collection were optimized and event rates used to inform randomisation. CONCLUSIONS: This feasibility study demonstrates that the components of the intervention were acceptable, methods of implementing were successful and the main trial design would be feasible. Qualitative work identified key moderators that informed the main trial process evaluation. Changes to the training package, implementation strategy, study design and processes were identified to refine the implementation in the main trial. TRIAL REGISTRATION: ISRCTN41244132 ; Registered 24/11/2015.

Microbiology and clinical outcomes of puerperal sepsis: a prospective cohort study.

The objectives of this study were to determine the identity and antibacterial susceptibility profiles of bacteria colonising the female genital tract and blood stream and their association with clinical outcomes in women with puerperal sepsis. A prospective descriptive cohort study was conducted at two tertiary hospitals in Zimbabwe. Endocervical swabs and blood were collected for culture and susceptibility testing from 151 consecutive women who met the World Health Organisation criteria for puerperal sepsis. Medical records were reviewed for assessment of clinical outcomes. The commonest bacterial isolates were Escherichia coli (30.6%) and Klebsiella pneumoniae (15.3%). Multidrug-resistant organisms (MDRO) accounted for 10.9% of all isolates. MDRO were associated with prolonged hospital stay, 23.0 days compared to 10.5 days in women without MDRO (p = .009). Puerperal sepsis case fatality rate was 7.3%. Clinical culture surveillance to monitor epidemiologic trends, identify MDRO, robust infection control strategies and emphasis on rational drug use are recommended. Impact statement What is already known? Puerperal sepsis is often a polymicrobial infection. Escherichia coli has been reported as a common cause of severe maternal sepsis originating from the genital tract. Other bacteria include Group A Streptococcus, S. aureus, Streptococcus spp. Klebsiellae spp, Pseudomonas spp. and anaerobes. What does this study add? This study confirms Escherichia coli as the commonest cause of sepsis in Harare. There is high level resistance to first-line antibiotic regimens on most Gram-negative isolates from the endocervix among women with puerperal sepsis. Emerging resistance to carbapenems is demonstrated. MDRO significantly increased length of hospital stay, and there was a clinically important trend towards higher rates of pelvic abscess, septic shock, death, need for laparotomy and ICU admission specific to puerperal sepsis. What are the implications for clinical practice and further research? Clinical culture surveillance to monitor epidemiologic trends in conjunction with robust infection control strategies and rational drug use may assist in prevention of community acquired and nosocomial multidrug-resistant infections.