BackgroundLeishmaniasis is a neglected tropical parasitic disease endemic in South Asia, East Africa, Latin America and the Middle East. It is associated with low socioeconomic status (SES) and responsible for considerable mortality and morbidity. Reports suggest that patients with leishmaniasis may have a higher risk of mental illness (MI), psychosocial morbidity (PM) and reduced quality of life (QoL), but this is not well characterised. The aim of this study was to conduct a systematic review to assess the reported impact of leishmaniasis on mental health and psychosocial wellbeing.MethodsA systematic review of the literature was carried out. Pre-specified criteria were applied to identify publications including observational quantitative studies or systematic reviews. Two reviewers screened all of the titles, abstracts and full-studies and a third reviewer was consulted for disagreements. Data was extracted from papers meeting the criteria and quality appraisal of the methods was performed using the Newcastle-Ottawa Scale or the Risk of Bias in Systematic Review tool.ResultsA total of 14 studies were identified from 12,517 records. Nine cross-sectional, three case-control, one cohort study and one systematic review were included. Eleven assessed MI outcomes and were measured with tools specifically designed for this; nine measured PM and 12 measured QoL using validated measurement tools. Quality appraisal of the studies showed that six were of good quality. Cutaneous leishmaniasis and post kala-azar dermal leishmaniasis showed evidence of associated MI and PM including depression, anxiety and stigma, while all forms of disease showed decreased QoL. The findings were used to inform a proposed model and conceptual framework to show the possible links between leishmaniasis and mental health outcomes.ConclusionThere is evidence that leishmaniasis has an impact on MI, PM or QoL of patients and their families and this occurs in all the main subtypes of the disease. There are however large gaps in the evidence. Further research is required to understand the full extent of this problem and its mechanistic basis.

MGMT downregulation in high-grade gliomas (HGG) has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP) or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA). By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation) and genetic (monosomy, locus deletion) changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

BackgroundDepression is common in people with non-communicable diseases (NCDs) such as cardiovascular disease, diabetes, cancer, and chronic respiratory conditions. The co-existence of depression and NCDs may a ect health behaviours, compliance with treatment, physiological factors, and quality of life. This in turn is associated with worse outcomes for both conditions. Behavioural activation is not currently indicated for the treatment of depression in this population in the UK, but is increasingly being used to treat depression in adults. ObjectivesTo examine the e ects of behavioural activation compared with any control group for the treatment of depression in adults with NCDs.To examine the e ects of behavioural activation compared with each control group separately (no treatment, waiting list, other psychological therapy, pharmacological treatment, or any other type of treatment as usual) for the treatment of depression in adults with NCDs. Search methodsWe searched CCMD-CTR, CENTRAL, Ovid MEDLINE, Embase, four other databases, and two trial registers on 4 October 2019 to identify randomised controlled trials (RCTs) of behavioural activation for depression in participants with NCDs, together with grey literature and reference checking. We applied no restrictions on date, language, or publication status to the searches. Selection criteriaWe included RCTs of behavioural activation for the treatment of depression in adults with one of four NCDs: cardiovascular disease, diabetes, cancer, and chronic respiratory conditions. Only participants with a formal diagnosis of both depression and an NCD were eligible. Studies were included if behavioural activation was the main component of the intervention. We included studies with any comparator that was not behavioural activation, and regardless of reported outcomes. Behavioural activation therapy for depression in adults with non-communicable diseases (Review)

19Background: Leishmaniasis is a neglected tropical parasitic disease endemic in South 20 Asia, East Africa, South America and the Middle East. It is associated with low 21 socioeconomic status (SES) and responsible for considerable mortality and morbidity. 22Reports suggest that patients with leishmaniasis may have a higher risk of mental illness 23 (MI), psychosocial morbidity (PM) and reduced quality of life (QoL), but this is not 24 well characterised. The aim of this study was to conduct a systematic review to assess 25 the reported impact of leishmaniasis on mental health and psychosocial wellbeing. 26Methods: A systematic review of the literature was carried out. Pre-specified criteria 27 were applied to identify publications including observational quantitative studies or 28 systematic reviews. Two reviewers screened all of the titles, abstracts and full-studies 29 and a third reviewer was consulted for disagreements. Data was extracted from papers 30 meeting the criteria and quality appraisal of the methods was performed using the 31 Newcastle-Ottowa Scale or the Risk of Bias in Systematic Review tool. 32Results: A total of 14 studies were identified from 12,517 records. Nine cross-sectional, 33 three case-control, one cohort study and one systematic review were included. Eleven 34 assessed MI outcomes and were measured with tools specifically designed for this; nine 35 measured PM and 12 measured QoL using validated measurement tools. Quality 36 appraisal of the studies showed that six were of good quality. Cutaneous leishmaniasis 37 and post kala-azar dermal leishmaniasis showed evidence of associated MI and PM 38 including depression, anxiety and stigma, while all forms of disease showed decreased 39 QoL. The findings were used to inform a proposed model and conceptual framework to 40 show the possible links between leishmaniasis and mental health outcomes. 3 41 Conclusion: There is evidence that leishmaniasis has an impact on MI, PM or QoL of 42 patients and their families and this occurs in all the main subtypes of the disease. There 43 are however large gaps in the evidence. Further research is required to understand the 44 full extent of this problem and its mechanistic basis. 45 46 AUTHOR SUMMARY 47 Leishmaniasis is a parasitic disease prevalent in many low-and middle-income countries 48 worldwide. In this study the authors looked for evidence as to whether leishmaniasis 49 affected the mental health and quality of life of patients. To conduct the review, a wide 50 search of the literature was conducted, where a total of 14 full articles were included 51 and analysed. It was found that different forms of leishmaniasis (visceral leishmaniasis, 52 cutaneous leishmaniasis and post kala-azar dermal leishmaniasis) do cause a significant 53 impact on patients' mental health and quality of life through societal factors such as 54 stigma, lack of knowledge, culture and low self-esteem among others. However, no 55 evidence of biological mechanisms was found linking leishmaniasis to mental i...

BackgroundA cluster randomised trial of mHealth and participatory learning and action (PLA) community mobilisation interventions showed that PLA significantly reduced the prevalence of intermediate hyperglycaemia and type 2 diabetes mellitus (T2DM) and the incidence of T2DM among adults in rural Bangladesh; mHealth improved knowledge but showed no effect on glycaemic outcomes. We explore the equity of intervention reach and impact.MethodsIntervention reach and primary outcomes of intermediate hyperglycaemia and T2DM were assessed through interview surveys and blood fasting glucose and 2-hour oral glucose tolerance tests among population-based samples of adults aged ≥30 years. Age-stratified, gender-stratified and wealth-stratified intervention effects were estimated using random effects logistic regression.ResultsPLA participants were similar to non-participants, though female participants were younger and more likely to be married than female non-participants. Differences including age, education, wealth and marital status were observed between individuals exposed and those not exposed to the mHealth intervention.PLA reduced the prevalence of T2DM and intermediate hyperglycaemia in all age, gender and wealth strata. Reductions in 2-year incidence of T2DM of at least 51% (0.49, 95% CI 0.26 to 0.92) were observed in all strata except among the oldest and least poor groups. mHealth impact on glycaemic outcomes was observed only among the youngest group, where a 47% reduction in the 2-year incidence of T2DM was observed (0.53, 95% CI 0.28 to 1.00).ConclusionLarge impacts of PLA across all strata indicate a highly effective and equitable intervention. mHealth may be more suitable for targeting higher risk, younger populations.Trial registration numberISRCTN41083256.

Background An estimated 463 million people globally have diabetes, with the prevalence growing in low-and middle-income settings, such as Bangladesh. Given the need for context-appropriate interventions to prevent type 2 diabetes mellitus (T2DM), the ‘Diabetes: Community-led Awareness, Response and Evaluation’ (D:Clare) trial will rigorously evaluate the replication and scale-up of a participatory learning and action (PLA) cycle intervention in Bangladesh, to inform policy on population-level T2DM prevention and control. Methods This is a stepped-wedge cluster randomised controlled trial, with integrated process and economic evaluations, conducted from March 2020 to September 2022. The trial will evaluate a community-based four-phase PLA cycle intervention focused on prevention and control of T2DM implemented over 18 months, against a control of usual care. Twelve clusters will be randomly allocated (1:1) to implement the intervention at project month 1 or 12. The intervention will be evaluated through three cross-sectional surveys at months 1, 12 and 24. The trial will be conducted in Alfadanga Upazila, Faridpur district, with an estimated population of 120,000. Clusters are defined as administrative geographical areas, with approximately equal populations. Each of the six unions in Alfadanga will be divided into two clusters, forming 12 clusters in total. Given the risk of inter-cluster contamination, evaluation surveys will exclude villages in border areas. Participants will be randomly sampled, independently for each survey, from a population census conducted in January 2020. The primary outcome is the combined prevalence of intermediate hyperglycaemia and T2DM, measured through fasting and 2-h post-glucose load blood tests. A total of 4680 participants provide 84% power to detect a 30% reduction in the primary outcome, assuming a baseline of 30% and an ICC of 0.07. The analysis will be by intention-to-treat, comparing intervention and control periods across all clusters, adjusting for geographical clustering. Discussion This study will provide further evidence of effectiveness for community-based PLA to prevent T2DM at scale in a rural Bangladesh setting. However, we encountered several challenges in applying the stepped-wedge design to our research context, with particular consideration given to balancing seasonality, timing and number of steps and estimation of partial versus full effect. Trial registration ISRCTN: ISRCTN42219712. Registered on 31 October 2019

Comprehensive meta-analysis of excess mortality in depression in the general community versus patients with specific illnesses.

Background Engaging communities is an important component of multisectoral action to address the growing burden of non-communicable diseases (NCDs) in low- and middle-income countries. We conducted research with non-communicable disease stakeholders in Bangladesh to understand how a community-led intervention which was shown to reduce the incidence of type 2 diabetes in rural Bangladesh could be scaled-up. Methods We purposively sampled any actor who could have an interest in the intervention, or that could affect or be affected by the intervention. We interviewed central level stakeholders from donor agencies, national health policy levels, public, non-governmental, and research sectors to identify scale-up mechanisms. We interviewed community health workers, policy makers, and non-governmental stakeholders, to explore the feasibility and acceptability of implementing the suggested mechanisms. We discussed scale-up options in focus groups with community members who had attended a community-led intervention. We iteratively developed our data collection tools based on our analysis and re-interviewed some participants. We analysed the data deductively using a stakeholder analysis framework, and inductively from codes identified in the data. Results Despite interest in addressing NCDs, there was a lack of a clear community engagement strategy at the government level, and most interventions have been implemented by non-governmental organisations. Many felt the Ministry of Health and Family Welfare should lead on community engagement, and NCD screening and referral has been added to the responsibilities of community health workers and health volunteers. Yet there remains a focus on reproductive health and NCD diagnosis and referral instead of prevention at the community level. There is potential to engage health volunteers in community-led interventions, but their present focus on engaging women for reproductive health does not fit with community needs for NCD prevention. Conclusions Research highlighted the need for a preventative community engagement strategy to address NCDs, and the potential to utilise existing cadres to scale-up community-led interventions. It will be important to work with key stakeholders to address gender issues and ensure flexibility and responsiveness to community concerns. We indicate areas for further implementation research to develop scaled-up models of community-led interventions to address NCDs.