Predictors, moderators, and mediators of psychological therapies for perinatal depression in low- and middle-income countries:A systematic review

Psychological interventions have demonstrated effectiveness in treating perinatal depression (PND), but understanding for whom, how and under what conditions they improve symptoms in low- and middle-income countries (LMICs) is largely unknown. This review aims to synthesise current knowledge about predictors, moderators and mediators of psychological therapies to treat PND in LMICs. Five databases were searched for studies quantitatively examining the effects of at least one mediator, moderator or predictor of therapies for PND in LMICs. The review sampled seven publications evaluating findings from randomised trials conducted in Asia and sub-Saharan Africa. The small number of included studies limited generalisability of findings. Analyses of trials with acceptable quality suggest that patient activation in Pakistan and social support in both India and Pakistan may mediate psychotherapy effectiveness, higher baseline depression severity may moderate treatment response in South Africa, and shorter depression duration at baseline may moderate intervention response in India. This review highlights current gaps in evidence quality and the need for future trials exploring PND psychotherapy effectiveness in LMICs to follow reporting guidelines to facilitate appropriate predictor, moderator and mediator analyses

Understanding the effects of a complex psychological intervention on symptoms of depression in Goa, India: findings from a causal mediation analysis

BACKGROUND: Understanding how and under what circumstances a highly effective psychological intervention, improved symptoms of depression is important to maximise its clinical effectiveness. AIMS: To address this complexity, we estimate the indirect effects of potentially important mediators to improve symptoms of depression (measured with the Patient Health Questionnaire (PHQ-9)) in the Healthy Activity Program trial. METHOD: Interventional in(direct) effects were used to decompose the total effect of the intervention on PHQ-9 scores into the direct and indirect effects. The following indirect effects were considered: characteristics of sessions, represented by the number of sessions and homework completed; behavioural activation, according to an adapted version of the Behavioural Activation for Depression Scale - Short Form; and extra sessions offered to participants who did not respond to the intervention. RESULTS: Of the total effect of the intervention measured through the difference in PHQ-9 scores between treatment arms (mean difference: -2.1, bias-corrected 95% CI -3.2 to -1.5), 34% was mediated through improved levels of behavioural activation (mean difference: -0.7, bias-corrected 95% CI -1.2 to -0.4). There was no evidence to support the mediating role of characteristics of the sessions nor the extra sessions offered to participants who did not respond to the treatment. CONCLUSIONS: Findings from our robust mediation analyses confirmed the importance of targeting behavioural activation. Contrary to published literature, our findings suggest that neither the number of sessions nor proportion of homework completed improved outcomes. Moreover, in this context, alternative treatments other than extra sessions should be considered for patients who do not respond to the intervention

Maternal infection and risk of intrapartum death: a population based observational study in South Asia.

BACKGROUND: Approximately 1.2 million stillbirths occur in the intrapartum period, and a further 717,000 annual neonatal deaths are caused by intrapartum events, most of which occur in resource poor settings. We aim to test the 'double-hit' hypothesis that maternal infection in the perinatal period predisposes to neurodevelopmental sequelae from an intrapartum asphyxia insult, increasing the likelihood of an early neonatal death compared with asphyxia alone. This is an observational study of singleton newborn infants with signs of intrapartum asphyxia that uses data from three previously conducted cluster randomized controlled trials taking place in rural Bangladesh and India. METHODS: From a population of 81,778 births in 54 community clusters in rural Bangladesh and India, we applied mixed effects logistic regression to data on 3890 singleton infants who had signs of intrapartum asphyxia, of whom 769 (20%) died in the early neonatal period. Poor infant condition at five minutes post-delivery was our proxy measure of intrapartum asphyxia. We had data for two markers of maternal infection: fever up to three days prior to labour, and prolonged rupture of membranes (PROM). Cause-specific verbal autopsy data were used to validate our findings using previously mentioned mixed effect logistic regression methods and the outcome of a neonatal death due to intrapartum asphyxia. RESULTS: Signs of maternal infection as indicated by PROM, combined with intrapartum asphyxia, increased the risk of an early neonatal death relative to intrapartum asphyxia alone (adjusted odds ratio (AOR) 1.28, 95% CI 1.03 - 1.59). Results from cause-specific verbal autopsy data verified our findings where there was a significantly increased odds of a early neonatal death due to intrapartum asphyxia in newborns exposed to both PROM and intrapartum asphyxia (AOR: 1.52, 95% CI 1.15 - 2.02). CONCLUSIONS: Our data support the double-hit hypothesis for signs of maternal infection as indicated by PROM. Interventions for pregnant women with signs of infection, to prevent early neonatal deaths and disability due to asphyxia, should be investigated further in resource-poor populations where the chances of maternal infection are high

Effect of a task-shared, collaborative care psychosocial intervention to improve depressive symptomatology among older adults in socioeconomically deprived areas of Brazil (PROACTIVE):cluster randomised controlled trial

BACKGROUND: There is an urgent need to reduce the burden of depression among older adults in low-income and middle-income countries (LMICs). We aimed to evaluate the efficacy of a task-shared, collaborative care psychosocial intervention for improving recovery from depression in older adults in Brazil. METHODS: PROACTIVE was a pragmatic, two-arm, parallel-group, cluster-randomised controlled trial conducted in Guarulhos, Brazil. Primary care clinics (clusters) were stratified by educational level and randomly allocated (1:1) to either enhanced usual care alone (control group) or to enhanced usual care plus the psychosocial intervention (intervention group), which involved a 17-week psychosocial programme based on psychoeducation and behavioural activation approaches. Individuals approached for the initial screening assessment were selected randomly from a list of individuals provided by the Health Secretariat of Guarulhos. Face-to-face baseline assessments were conducted among adults aged 60 years or older registered with one of the primary care clinics and identified with clinically significant depressive symptomatology (9-item Patient Health Questionnaire [PHQ-9] score ≥10). Community health workers delivered the programme through home sessions, supported by a dedicated tablet application. Masking of clinic staff and community health workers who delivered the intervention was not feasible; however, research assistants conducting recruitment and follow-up assessments were masked to trial allocation. The primary outcome was recovery from depression (PHQ-9 score <10) at 8-month follow-up. All primary analyses were performed by intention to treat with imputed data. Adaptations to the protocol were made due to the COVID-19 pandemic; recruitment and intervention home sessions were stopped, and follow-up assessments were conducted by telephone. This trial is registered with the ISRCTN registry, ISRCTN57805470. FINDINGS: We identified 24 primary care clinics in Guarulhos that were willing to participate, of which 20 were randomly allocated to either the control group (ten [50%] clusters) or to the intervention group (ten [50%] clusters). The four remaining eligible clusters were kept as reserves. Between May 23, 2019, and Feb 21, 2020, 8146 individuals were assessed for eligibility, of whom 715 (8·8%) participants were recruited: 355 (49·7%) in the control group and 360 (50·3%) in the intervention group. 284 (80·0%) participants in the control group and 253 (70·3%) in the intervention group completed follow-up at 8 months. At 8-month follow-up, 158 (62·5%) participants in the intervention group showed recovery from depression (PHQ-9 score <10) compared with 125 (44·0%) in the control group (adjusted odds ratio 2·16 [95% CI 1·47–3·18]; p<0·0001). These findings were maintained in the complete case analysis. No adverse events related to the intervention were observed. INTERPRETATION: Although the COVID-19 pandemic altered delivery of the intervention, the low-intensity psychosocial intervention delivered mainly by non-mental health professionals was highly efficacious in improving recovery from depression in older adults in Brazil. Our results support a low-resource intervention that could be useful to reduce the treatment gap for depression among older people in other LMICs. FUNDING: São Paulo Research Foundation and Joint Global Health Trials (UK Department for International Development, Medical Research Council, and the Wellcome Trust)

Protocol for intervention development to improve adolescent perinatal mental health in Kenya and Mozambique: The INSPIRE project

Introduction: Mental health interventions have traditionally been developed by clinicians and researchers without the meaningful engagement and partnership with those who would receive, deliver, and fund them. Recent progress has highlighted the importance of the co-design of interventions, through stakeholder participation, as a means of increasing the integration of mental health interventions into existing health, education, and social care systems. This protocol describes the pre-implementation phase of the INSPIRE (Innovative approaches to adolescent perinatal wellbeing) project which aims to identify challenges, and design and test interventions to promote mental wellbeing and good mental health of adolescent girls during pregnancy and the year after birth with local stakeholders in Kenya and Mozambique. Methods: A participatory approach that blends human-centred design, systems thinking, and implementation science methods will be used to engage adolescents (aged 15–19 years), their families, and other stakeholders who can influence implementation efforts, in planning and preparing interventions. First, an understanding of context, barriers, and opportunities related to adolescent perinatal mental health will be elicited through individual interviews, focus group discussions, and observations. This will be complemented by a scoping review of relevant interventions. The research team will identify contextual insights relating to adolescent and system characteristics, strengths, and challenges. These will be shared with and refined by stakeholders. Thematic analysis will be conducted to describe the experiences of adolescent girls, and barriers and enablers to maintaining good mental health. The former will be triangulated with the Context and Implementation of Complex Intervention (CICI) framework. Causal loop diagrams will be developed to illustrate the individual and system-level variables which influence adolescent perinatal mental health. Stakeholder workshops will be used to identify priorities, brainstorm potential interventions, develop a program theory, and prototype an intervention and implementation strategies. Intervention acceptability, appropriateness, and feasibility will be assessed, and a theory of change map finalized. Results: To date the study has recruited 169 participants to complete individual interviews, focus group discussions and observation activities. Conclusions: It is anticipated that the use of a participatory and systematic approach to the development of an intervention to improve mental health, will improve its perceived appropriateness, acceptability, and feasibility among key stakeholders. This may, in turn, significantly improve its availability, uptake, and sustainability

Determinants and consequences of short birth interval in rural Bangladesh: a cross-sectional study.

BACKGROUND: Short birth intervals are known to have negative effects on pregnancy outcomes. We analysed data from a large population surveillance system in rural Bangladesh to identify predictors of short birth interval and determine consequences of short intervals on pregnancy outcomes. METHODS: The study was conducted in three districts of Bangladesh - Bogra, Moulavibazar and Faridpur (population 282,643, 54,668 women of reproductive age). We used data between January 2010 and June 2011 from a key informant surveillance system that recorded all births, deaths and stillbirths. Short birth interval was defined as an interval between consecutive births of less than 33 months. Initially, risk factors of a short birth interval were determined using a multivariate mixed effects logistic regression model. Independent risk factors were selected using a priori knowledge from literature review. An adjusted mixed effects logistic regression model was then used to determine the effect of up to 21-, 21-32-, 33-44- and 45-month and higher birth-to-birth intervals on pregnancy outcomes controlling for confounders selected through a directed acyclic graph. RESULTS: We analysed 5,571 second or higher order deliveries. Average birth interval was 55 months and 1368/5571 women (24.6%) had a short birth interval (<33 months). Younger women (AOR 1.11 95% CI 1.08-1.15 per year increase in age), women who started their reproductive life later (AOR 0.95, 0.92-0.98 per year) and those who achieve higher order parities were less likely to experience short birth intervals (AOR 0.28, 0.19-0.41 parity 4 compared to 1). Women who were socioeconomically disadvantaged were more likely to experience a short birth interval (AOR 1.42, 1.22-1.65) and a previous adverse outcome was an important determinant of interval (AOR 2.10, 1.83-2.40). Very short birth intervals of less than 21 months were associated with increased stillbirth rate (AOR 2.13, 95% CI 1.28-3.53) and neonatal mortality (AOR 2.28 95% CI 1.28-4.05). CONCLUSIONS: Birth spacing remains a reproductive health problem in Bangladesh. Disadvantaged women are more likely to experience short birth intervals and to have increased perinatal deaths. Research into causal pathways and strategies to improve spacing between pregnancies should be intensified

Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001–12: a retrospective observational study

Background Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. Methods Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi’s Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children’s clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2–11 months of age, and 12–59 months of age using separate multivariable mixed eff ects logistic regression models. Findings Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92∧7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4–6·7). The case fatality rate signifi cantly decreased between 2001 (15·2% [13·4–17·1]) and 2012 (4·5% [4·1–4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors signifi cantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2–11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%). Interpretation Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specifi c subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of suffi cient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of eff ective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi

Contextual equipoise: a novel concept to inform ethical implications for implementation research using randomised controlled trials in low- and middle-income countries

The call for universal health coverage requires the urgent implementation and scale-up of interventions that are known to be effective, in resource-poor settings. Achieving this objective requires high-quality implementation research (IR) that evaluates the complex phenomenon of the influence of context on the ability to effectively deliver evidence-based practice. Nevertheless, IR for global health is failing to apply a robust, theoretically driven approach, leading to ethical concerns associated with research that is not methodologically sound. Inappropriate methods are often used in IR to address and report on context. This may result in a lack in understanding of how to effectively adapt the intervention to the new setting and a lack of clarity in conceptualising whether there is sufficient evidence to generalise findings from previous IR to a new setting, or if a randomised controlled trial (RCT) is needed. Some of the ethical issues arising from this shortcoming include poor-quality research that may needlessly expose vulnerable participants to research that has not been adapted to suit local needs and priorities, and the inappropriate use of RCTs that denies participants in the control arm access to treatment that is effective within the local context. To address these concerns, we propose a complementary approach to clinical equipoise for IR, known as contextual equipoise. We discuss challenges in the evaluation of context and also with assessing the certainty of evidence to justify an RCT. Finally, we describe methods that can be applied to improve the evaluation and reporting of context and to help understand if contextual equipoise can be justified or if significant adaptations are required. We hope our analysis offers helpful insight to better understand and ensure that the ethical principle of beneficence is upheld in the real-world contexts of IR in low-resource settings