Correction: The cross-sectional association of stressful life events with depression severity among patients with hypertension and diabetes in Malawi.

[This corrects the article DOI: 10.1371/journal.pone.0279619.].

Implementation strategies to build mental health-care capacity in Malawi: a health-economic evaluation.

BACKGROUND: Depression is a major contributor to morbidity and mortality in sub-Saharan Africa. Due to low system capacity, three in four patients with depression in sub-Saharan Africa go untreated. Despite this, little attention has been paid to the cost-effectiveness of implementation strategies to scale up evidence-based depression treatment in the region. In this study, we investigate the cost-effectiveness of two different implementation strategies to integrate the Friendship Bench approach and measurement-based care in non-communicable disease clinics in Malawi. METHODS: The two implementation strategies tested in this study are part of a trial, in which ten clinics were randomly assigned (1:1) to a basic implementation package consisting of an internal coordinator acting as a champion (IC-only group) or to an enhanced package that complemented the basic package with quarterly external supervision, and audit and feedback of intervention delivery (IC + ES group). We included material costs, training costs, costs related to project-wide meetings, transportation and medication costs, time costs related to internal champion activities and depression screening or treatment, and costs of external supervision visits if applicable. Outcomes included the number of patients screened with the patient health questionnaire 2 (PHQ-2), cases of remitted depression at 3 and 12 months, and disability-adjusted life-years (DALYs) averted. We compared the cost-effectiveness of both packages to the status quo (ie, no intervention) using a micro-costing-informed decision-tree model. FINDINGS: Relative to the status quo, IC + ES would be on average US$10 387 ($1349-$17 365) more expensive than IC-only but more effective in achieving remission and averting DALYs. The cost per additional remission would also be lower with IC + ES than IC-only at 3 months ($119 vs $223) and 12 months ($210 for IC + ES; IC-only dominated by the status quo at 12 months). Neither package would be cost-effective under the willingness-to-pay threshold of $65 per DALY averted currently used by the Malawian Ministry of Health. However, the IC + ES package would be cost-effective in relation to the commonly used threshold of three times per-capita gross domestic product per DALY averted. INTERPRETATION: Investing in supporting champions might be an appropriate use of resources. Although not currently cost-effective by Malawian willingness-to-pay standards compared with the status quo, the IC + ES package would probably be a cost-effective way to build mental health-care capacity in resource-constrained settings in which decision makers use higher willingness-to-pay thresholds. FUNDING: National Institute of Mental Health.

Two implementation strategies to support the integration of depression screening and treatment into hypertension and diabetes care in Malawi (SHARP): parallel, cluster-randomised, controlled, implementation trial.

BACKGROUND: Although evidence-based treatments for depression in low-resource settings are established, implementation strategies to scale up these treatments remain poorly defined. We aimed to compare two implementation strategies in achieving high-quality integration of depression care into chronic medical care and improving mental health outcomes in patients with hypertension and diabetes. METHODS: We conducted a parallel, cluster-randomised, controlled, implementation trial in ten health facilities across Malawi. Facilities were randomised (1:1) by covariate-constrained randomisation to either an internal champion alone (ie, basic strategy group) or an internal champion plus external supervision with audit and feedback (ie, enhanced strategy group). Champions integrated a three-element, evidence-based intervention into clinical care: universal depression screening; peer-delivered psychosocial counselling; and algorithm-guided, non-specialist antidepressant management. External supervision involved structured facility visits by Ministry officials and clinical experts to assess quality of care and provide supportive feedback approximately every 4 months. Eligible participants were adults (aged 18-65 years) seeking hypertension and diabetes care with signs of depression (Patient Health Questionnaire-9 score ≥5). Primary implementation outcomes were depression screening fidelity, treatment initiation fidelity, and follow-up treatment fidelity over the first 3 months of treatment, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03711786, and is complete. FINDINGS: Five (50%) facilities were randomised to the basic strategy and five (50%) to the enhanced strategy. Between Oct 1, 2019, and Nov 30, 2021, in the basic group, 587 patients were assessed for eligibility, of whom 301 were enrolled; in the enhanced group, 539 patients were assessed, of whom 288 were enrolled. All clinics integrated the evidence-based intervention and were included in the analyses. Of 60 774 screening-eligible visits, screening fidelity was moderate (58% in the enhanced group vs 53% in the basic group; probability difference 5% [95% CI -38% to 47%]; p=0·84) and treatment initiation fidelity was high (99% vs 98%; 0% [-3% to 3%]; p=0·89) in both groups. However, treatment follow-up fidelity was substantially higher in the enhanced group than in the basic group (82% vs 20%; 62% [36% to 89%]; p=0·0020). Depression remission was higher in the enhanced group than in the basic group (55% vs 36%; 19% [3% to 34%]; p=0·045). Serious adverse events were nine deaths (five in the basic group and four in the enhanced group) and 26 hospitalisations (20 in the basic group and six in the enhanced group); none were treatment-related. INTERPRETATION: The enhanced implementation strategy led to an increase in fidelity in providers' follow-up treatment actions and in rates of depression remission, consistent with the literature that follow-up decisions are crucial to improving depression outcomes in integrated care models. These findings suggest that external supervision combined with an internal champion could offer an important advance in integrating depression treatment into general medical care in low-resource settings. FUNDING: The National Institute of Mental Health.

The longitudinal association of stressful life events with depression remission among SHARP trial participants with depression and hypertension or diabetes in Malawi.

Depressive disorders are leading contributors to morbidity in low- and middle-income countries and are particularly prevalent among people with non-communicable diseases (NCD). Stressful life events (SLEs) are risk factors for, and can help identify those at risk of, severe depressive illness requiring more aggressive treatment. Yet, research on the impact of SLEs on the trajectory of depressive symptoms among NCD patients indicated for depression treatment is lacking, especially in low resource settings. This study aims to estimate the longitudinal association of SLEs at baseline with depression remission achievement at three, six, and 12 months among adults with either hypertension or diabetes and comorbid depression identified as being eligible for depression treatment. Participants were recruited from 10 NCD clinics in Malawi from May 2019-December 2021. SLEs were measured by the Life Events Survey and depression remission was defined as achieving a Patient Health Questionaire-9 (PHQ-9) score <5 at follow-up. The study population (n = 737) consisted predominately of females aged 50 or higher with primary education and current employment. At baseline, participants reported a mean of 3.5 SLEs in the prior three months with 90% reporting ≥1 SLE. After adjustment, each additional SLE was associated with a lower probability of achieving depression remission at three months (cumulative incidence ratio (CIR) 0.94; 95% confidence interval: 0.90, 0.98, p = 0.002), six months (0.95; 0.92, 0.98, p = 0.002) and 12 months (0.96; 0.94, 0.99, p = 0.011). Re-expressed per 3-unit change, the probability of achieving depression remission at three, six, and 12 months was 0.82, 0.86, and 0.89 times lower per 3 SLEs (the median number of SLEs). Among NCD patients identified as eligible for depression treatment, recent SLEs at baseline were associated with lower probability of achieving depression remission at three, six, and 12 months. Findings suggest that interventions addressing SLEs during integrated NCD and depression care interventions (e.g., teaching and practicing SLE coping strategies) may improve success of depression treatment among adult patient populations in low-resource settings and may help identify those at risk of severe and treatment resistant depression.

Champion and audit and feedback strategy fidelity and their relationship to depression intervention fidelity: A mixed method study.

Background: Globally, mental health disorders rank as the greatest cause of disability. Low and middle-income countries (LMICs) hold a disproportionate share of the mental health burden, especially as it pertains to depression. Depression is highly prevalent among those with non-communicable diseases (NCDs), creating a barrier to successful treatment. While some treatments have proven efficacy in LMIC settings, wide dissemination is challenged by multiple factors, leading researchers to call for implementation strategies to overcome barriers to care provision. However, implementation strategies are often not well defined or documented, challenging the interpretation of study results and the uptake and replication of strategies in practice settings. Assessing implementation strategy fidelity (ISF), or the extent to which a strategy was implemented as designed, overcomes these challenges. This study assessed fidelity of two implementation strategies (a 'basic' champion strategy and an 'enhanced' champion + audit and feedback strategy) to improve the integration of a depression intervention, measurement based care (MBC), at 10 NCD clinics in Malawi. The primary goal of this study was to assess the relationship between the implementation strategies and MBC fidelity using a mixed methods approach. Methods: We developed a theory-informed mixed methods fidelity assessment that first combined an implementation strategy specification technique with a fidelity framework. We then created corresponding fidelity indicators to strategy components. Clinical process data and one-on-one in-depth interviews with 45 staff members at 6 clinics were utilized as data sources. Our final analysis used descriptive statistics, reflexive-thematic analysis (RTA), data merging, and triangulation to examine the relationship between ISF and MBC intervention fidelity. Results: Our mixed methods analysis revealed how ISF may moderate the relationship between the strategies and MBC fidelity. Leadership engagement and implementation climate were critical for clinics to overcome implementation barriers and preserve implementation strategy and MBC fidelity. Descriptive statistics determined champion strategy fidelity to range from 61 to 93% across the 10 clinics. Fidelity to the audit and feedback strategy ranged from 82 to 91% across the 5 clinics assigned to that condition. MBC fidelity ranged from 54 to 95% across all clinics. Although correlations between ISF and MBC fidelity were not statistically significant due to the sample of 10 clinics, associations were in the expected direction and of moderate effect size. A coefficient for shared depression screening among clinicians had greater face validity compared to depression screening coverage and functioned as a proximal indicator of implementation strategy success. Conclusion: Fidelity to the basic and enhanced strategies varied by site and were influenced by leadership engagement and implementation climate. Champion strategies may benefit from the addition of leadership strategies to help address implementation barriers outside the purview of champions. ISF may moderate the relationship between strategies and implementation outcomes.

Assessing suicidality during the SARS-CoV-2 pandemic: Lessons learned from adaptation and implementation of a telephone-based suicide risk assessment and response protocol in Malawi.

The SARS-CoV-2 pandemic led to the rapid transition of many research studies from in-person to telephone follow-up globally. For mental health research in low-income settings, tele-follow-up raises unique safety concerns due to the potential of identifying suicide risk in participants who cannot be immediately referred to in-person care. We developed and iteratively adapted a telephone-delivered protocol designed to follow a positive suicide risk assessment (SRA) screening. We describe the development and implementation of this SRA protocol during follow-up of a cohort of adults with depression in Malawi enrolled in the Sub-Saharan Africa Regional Partnership for Mental Health Capacity Building (SHARP) randomized control trial during the COVID-19 era. We assess protocol feasibility and performance, describe challenges and lessons learned during protocol development, and discuss how this protocol may function as a model for use in other settings. Transition from in-person to telephone SRAs was feasible and identified participants with suicidal ideation (SI). Follow-up protocol monitoring indicated a 100% resolution rate of SI in cases following the SRA during this period, indicating that this was an effective strategy for monitoring SI virtually. Over 2% of participants monitored by phone screened positive for SI in the first six months of protocol implementation. Most were passive risk (73%). There were no suicides or suicide attempts during the study period. Barriers to implementation included use of a contact person for participants without personal phones, intermittent network problems, and pre-paid phone plans delaying follow-up. Delays in follow-up due to challenges with reaching contact persons, intermittent network problems, and pre-paid phone plans should be considered in future adaptations. Future directions include validation studies for use of this protocol in its existing context. This protocol was successful at identifying suicide risk levels and providing research assistants and participants with structured follow-up and referral plans. The protocol can serve as a model for virtual SRA development and is currently being adapted for use in other contexts.

The cross-sectional association of stressful life events with depression severity among patients with hypertension and diabetes in Malawi.

Depressive disorders are a leading cause of global morbidity and remain disproportionately high in low- and middle-income settings. Stressful life events (SLEs) are known risk factors for depressive episodes and worsened depressive severity, yet are under-researched in comparison to other depression risk factors. As depression is often comorbid with hypertension, diabetes, and other noncommunicable diseases (NCDs), research into this relationship among patients with NCDs is particularly relevant to increasing opportunities for integrated depression and NCD care. This study aims to estimate the cross-sectional association between SLEs in the three months preceding baseline interviews and baseline depressive severity among patients with at least mild depressive symptoms who are seeking NCD care at 10 NCD clinics across Malawi. SLEs were measured by the Life Events Survey and depressive severity (mild vs. moderate to severe) was measured by the Patient Health Questionnaire-9. The study population (n = 708) was predominately currently employed, grand multiparous (5-8 children) women with a primary education level. Two thirds (63%) had mild depression while 26%, 8%, and 3% had moderate, moderately severe, and severe depression, respectively. Nearly all participants (94%) reported at least one recent SLE, with the most common reported SLEs being financial stress (48%), relationship changes (45%), death of a family member or friend (41%), or serious illness of a family member or friend (39%). Divorce/separation, estrangement from a family member, losing source of income, and major new health problems were significant predictors of greater (moderate or severe) depressive severity compared to mild severity. Having a major new health problem or experiencing divorce/separation resulted in particularly high risk of more severe depression. After adjustment, each additional SLE was associated with a 9% increased risk of moderate or worse depressive severity compared to mild depressive severity (RR: 1.09; (95% CI: 1.05, 1.13), p<0.0001). Among patients with NCDs with at least mild depressive symptoms, SLEs in the prior 3 months were associated with greater depressive severity. While many SLEs may not be preventable, this research suggests that assessment of SLEs and teaching of positive coping strategies when experiencing SLEs may play an important role in integrated NCD and depression treatment models.

Qualitative Perceptions of Dapivirine VR Adherence and Drug Level Feedback Following an Open-Label Extension Trial.

BACKGROUND: There continues to be a need for HIV prevention options that women can initiate and use autonomously. The dapivirine vaginal ring (VR) has been shown to have a favorable safety profile and reduce the risk of HIV-1 acquisition. We report on women's experiences with VR adherence during the MTN-025/HIV Open-label Prevention Extension (HOPE) study and responses to Residual Drug Level (RDL) results. SETTING: Ten women at each of the 6 HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were randomly selected (n = 60). METHODS: After confirmation of eligibility criteria, in-depth interviews were conducted where available RDL results were presented. RESULTS: Many women with low RDL release measurements deflected blame onto other factors (the ring, the drug, and faulty testing machines) and distrust of the testing method. The disclosure of RDL results enabled some users to discuss their challenges experienced (fear of partner objections, perceived side effects, and removals during menses). Consistent users reported important motivators (support from others, protection from HIV, and enhanced sexual experiences from the VR). CONCLUSION: The VR provided a sense of security for some women; however, adherence was still challenging for others regardless of it being a female controlled, long-acting HIV prevention technology. Adherence measurements may not be sustainable in the real-world implementation of the VR, although they can be seen as a benefit as they provide a better understanding of actual product use and provide women with a platform to discuss their experiences.

The Sub-Saharan Africa Regional Partnership (SHARP) for Mental Health Capacity-Building Scale-Up Trial: Study Design and Protocol.

BACKGROUND: Depression is a leading cause of death and disability worldwide, including in low- and middle-income countries (LMICs). Depression often coexists with chronic medical conditions and is associated with worse clinical outcomes. This confluence has led to calls to integrate mental health treatment with chronic disease care systems in LMICs. This article describes the rationale and protocol for a trial comparing the clinical effectiveness and cost-effectiveness of two different intervention packages to implement evidence-based antidepressant management and psychotherapy into chronic noncommunicable disease (NCD) clinics in Malawi. METHODS: Using constrained randomization, the Sub-Saharan Africa Regional Partnership (SHARP) for mental health capacity building will assign five Malawian NCD clinics to a basic implementation strategy via an internal coordinator, a provider within the chronic care clinic who champions depression services by providing training, supervision, operations, and reporting. Another five clinics will be assigned to depression services implementation via an internal coordinator along with an external quality assurance committee, which will provide a quarterly audit of intervention component delivery with feedback to providers and the health management team. RESULTS: The authors will compare key implementation outcomes (fidelity to intervention), clinical effectiveness outcomes (patient health), and cost-effectiveness and will assess characteristics of clinics that may influence uptake and fidelity. NEXT STEPS: This trial will provide key information to guide the Malawi Ministry of Health in scaling up depression management in existing NCD settings. The SHARP trial is anticipated to substantially contribute to enhancing both mental health treatment and implementation science research capacity in Malawi and the wider region.

The role of patient-provider communication: a qualitative study of patient attitudes regarding co-occurring depression and chronic diseases in Malawi.

BACKGROUND: Globally, depression is a leading cause of morbidity and mortality particularly in Low and Middle-Income Countries (LMICs). The burden of non-communicable diseases (NCDs) are also increasing in LMICs, the conditions frequently co-occur and exacerbate NCD outcomes. Depression interventions alone are not effective at improving NCD outcomes, resulting in wide-reaching calls for integrated services. Integrated services are in a nascent phase in LMICs in general and in Malawi in particular. This manuscript serves to clarify Malawian patients' attitudes and perceptions towards depression integration into routine NCD services. METHODS: Ten District Hospitals were selected for data collection and 2 participants were interviewed from each site (N = 20). An iterative approach to concept-driven coding was applied to facilitate the formation of similarities, differences, and connections between codes. RESULTS: While patients infrequently described moderate depression as a medical condition, and held various attitudes regarding treatments, they agreed on the appropriateness of integrated services. Patients' respect for their providers led them to support integration. Patients discussed how medical knowledge is highly regarded, revealing a power dynamic with their providers. Patients further acknowledged the importance of a provider's communication in shaping a patient's feelings about depression. CONCLUSIONS: Training and interventions that facilitate providers' abilities to transfer their medical knowledge, use strategies to channel their power, and engage patients in a meaningful and collaborative relationship will be key to successfully integrating depression treatment into Malawian NCD clinics. TRIAL REGISTRATION: This work served as part of formative data collection for National Institute of Mental Health (NIMH) Trail NCT03711786 registered on 10th October, 2018.

Perspectives on HIV partner notification, partner HIV self-testing and partner home-based HIV testing by pregnant and postpartum women in antenatal settings: a qualitative analysis in Malawi and Zambia.

INTRODUCTION: HIV testing male partners of pregnant and postpartum women can lead to improved health outcomes for women, partners and infants. However, in sub-Saharan Africa, few male partners get HIV tested during their partner's pregnancy in spite of several promising approaches to increase partner testing uptake. We assessed stakeholders' views and preferences of partner notification, home-based testing and secondary distribution of self-test kits to understand whether offering choices for partner HIV testing may increase acceptability. METHODS: Interviewers conducted semi-structured interviews with HIV-negative (N = 39) and HIV-positive (N = 41) pregnant/postpartum women, male partners of HIV-negative (N = 14) and HIV-positive (N = 14) pregnant/postpartum women, healthcare workers (N = 19) and policymakers (N = 16) in Malawi and Zambia. Interviews covered views of each partner testing approach and preferred approaches; healthcare workers were also asked about perceptions of a choice-based approach. Interviews were transcribed, translated and analysed to compare perspectives across country and participant types. RESULTS: Most participants within each stakeholder group considered all three partner testing strategies acceptable. Relationship conflict was discussed as a potential adverse consequence for each approach. For partner notification, additional barriers included women losing letters, being fearful to give partners letters, being unable to read and men refusing to come to the clinic. For home-based testing, additional barriers included lack of privacy or confidentiality and fear of experiencing community-level HIV stigma. For HIV self-test kits, additional barriers included lack of counselling, false results and poor linkage to care. Preferred male partner testing options varied. Participants preferred partner notification due to their respect for clinical authority, home-based testing due to their desire to prioritize convenience and clinical authority, and self-test kits due to their desire to prioritize confidentiality. Less than half of couples interviewed selected the same preferred male partner testing option as their partner. Most healthcare workers felt the choice-based approach would be acceptable and feasible, but noted implementation challenges in personnel, resources or space. CONCLUSIONS: Most stakeholders considered different approaches to partner HIV testing to be acceptable, but concerns were raised about each. A choice-based approach may allow women to select their preferred method of partner testing; however, implementation challenges need to be addressed.