Protocol for process evaluation of ARTEMIS cluster randomised controlled trial: an intervention for management of depression and suicide among adolescents living in slums in India.

INTRODUCTION: There are around 250 million adolescents (10-19 years) in India. The prevalence of mental health-related morbidity among adolescents in India is approximately 7.3%. Vulnerable subpopulations among adolescents such as those living in slum communities are particularly at risk due to poor living conditions, financial difficulty and limited access to support services. Adolescents' Resilience and Treatment nEeds for Mental Health in Indian Slums (ARTEMIS) is a cluster randomised controlled trial of an intervention that intends to improve the mental health of adolescents living in slum communities in India. The aim of this paper is to describe the process evaluation protocol for ARTEMIS trial. The process evaluation will help to explain the intervention outcomes and understand how and why the intervention worked or did not work. It will identify contextual factors, intervention barriers and facilitators and the adaptations required for optimising implementation. METHODS: Case study method will be used and the data will include a mix of quantitative metrics and qualitative data. The UK Medical Research Council's guidance on evaluating complex interventions, the Reach, Efficacy, Adoption, Implementation and Maintenance Framework and the Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Safety/Side Effects and, Equity criteria will be used to develop a conceptual framework and a priori codes for qualitative data analysis. Quantitative data will be analysed using descriptive statistics. Implementation fidelity will also be measured. DISCUSSION: The process evaluation will provide an understanding of outcomes and causal mechanisms that influenced any change in trial outcomes. ETHICS AND DISSEMINATION: Ethics Committee of the George Institute for Global Health India (project number 17/2020) and the Research Governance and Integrity Team, Imperial College, London (ICREC reference number: 22IC7718) have provided ethics approval. The Health Ministry's Screening Committee has approved to the study (ID 2020-9770). TRIAL REGISTRATION NUMBER: CTRI/2022/02/040307.

Pea protein extraction method impacts the protein (micro)structural organisation and in vitro digestion kinetics.

There is increasing interest in including pulse proteins into food products due to their nutrient-rich and sustainable character. However, little is known regarding the consequences of different extraction approaches on the pulse protein structure and the subsequent protein (micro)structural organization and protein digestion kinetics. Therefore, three green pea protein extracts were created: (i) cooking followed by cotyledon cell isolation, (ii) alkaline extraction followed by isoelectric precipitation, or (iii) salt extraction, and compared to the original pea flour as well as to sodium caseinate. The results showed that encapsulated, denatured protein inside pea cotyledon cells presented the (s)lowest digestion, while accessible and more native protein (e.g., pea flour, pea protein salt extract) presented much faster and higher digestion. Moreover, the alkali extracted pea protein was denatured to some extent, significantly lowering in vitro digestion kinetics. In the second part, three different in vitro approaches were applied to digest the salt extracted pea protein. Semi-dynamic gastric digestion approaches simulate in vivo conditions more closely which especially impacted the rate of digestion.

Using formative research to inform a mental health intervention for adolescents living in Indian slums: the ARTEMIS study.

BACKGROUND: Adolescents are vulnerable to stressors because of the rapid physical and mental changes that they go through during this life period. Young people residing in slum communities experience additional stressors due to living conditions, financial stress, and limited access to healthcare and social support services. The Adolescents' Resilience and Treatment nEeds for Mental Health in Indian Slums (ARTEMIS) study, is testing an intervention intended to improve mental health outcomes for adolescents living in urban slums in India combining an anti-stigma campaign with a digital health intervention to identify and manage depression, self-harm/suicide risk or other significant emotional complaints. METHODS: In the formative phase, we developed tools and processes for the ARTEMIS intervention. The two intervention components (anti-stigma and digital health) were implemented in purposively selected slums from the two study sites of New Delhi and Vijayawada. A mixed methods formative evaluation was undertaken to improve the understanding of site-specific context, assess feasibility and acceptability of the two components and identify required improvements to be made in the intervention. In-depth interviews and focus groups with key stakeholders (adolescents, parents, community health workers, doctors, and peer leaders), along with quantitative data from the digital health platform, were analysed. RESULTS: The anti-stigma campaign methods and materials were found to be acceptable and received overall positive feedback from adolescents. A total of 2752 adolescents were screened using the PHQ9 embedded into a digital application, 133 (4.8%) of whom were identified as at high-risk of depression and/or suicide. 57% (n = 75) of those at high risk were diagnosed and treated by primary health care (PHC) doctors, who were guided by an electronic decision support tool based on WHO's mhGAP algorithm, built into the digital health application. CONCLUSION: The formative evaluation of the intervention strategy led to enhanced understanding of the context, acceptability, and feasibility of the intervention. Feedback from stakeholders helped to identify key areas for improvement in the intervention; strategies to improve implementation included engaging with parents, organising health camps in the sites and formation of peer groups. TRIAL REGISTRATION: The trial has been registered in the Clinical Trial Registry India, which is included in the WHO list of Registries, Reference number: CTRI/2022/02/040307. Registered 18 February 2022.

Determinants of stillbirths in sub-Saharan Africa: A systematic review.

BACKGROUND: Sub-Saharan African (SSA) countries have high stillbirth rates compared with high-income countries, yet research on risk factors for stillbirth in SSA remain scant. OBJECTIVES: To identify the modifiable risk factors of stillbirths in SSA and investigate their strength of association using a systematic review. SEARCH STRATEGY: CINAHL Plus, EMBASE, Global Health and MEDLINE databases were searched for literature. SELECTION CRITERIA: Observational population- and facility-level studies exploring stillbirth risk factors, published in 2013-2019 were included. DATA COLLECTION AND ANALYSIS: A narrative synthesis of data was undertaken and the potential risk factors were classified into subgroups. MAIN RESULTS: Thirty-seven studies were included, encompassing 20 264 stillbirths. The risk factors were categorised as: maternal antepartum factors (0-4 antenatal care visits, multiple gestations, hypertension, birth interval of >3 years, history of perinatal death); socio-economic factors (maternal lower wealth index and basic education, advanced maternal age, grand multiparity of ≥5); intrapartum factors (direct obstetric complication); fetal factors (low birthweight and gestational age of <37 weeks) and health systems factors (poor quality of antenatal care, emergency referrals, ill-equipped facility). The proportion of unexplained stillbirths remained very high. No association was found between stillbirths and body mass index, diabetes, distance from the facility or HIV. CONCLUSIONS: The overall quality of evidence was low, as many studies were facility based and did not adjust for confounding factors. This review identified preventable risk factors for stillbirth. Focused programmatic strategies to improve antenatal care, emergency obstetric care, maternal perinatal education, referral and outreach systems, and birth attendant training should be developed. More population-based, high-quality research is needed.

Mental health related stigma, service provision and utilization in Northern India: situational analysis.

Stigma, discrimination, poor help seeking, dearth of mental health professionals, inadequate services and facilities all adversely impact the mental health treatment gap. Service utilization by the community is influenced by cultural beliefs and literacy levels. We conducted a situational analysis in light of the little information available on mental health related stigma, service provision and utilization in Haryana, a state in Northern India. This involved: (a) qualitative key informant interviews; (b) health facility records review; and (c) policy document review to understand the local context of Faridabad district in Northern India. Ethical approvals for the study were taken before the study commenced. Phone call in-depth interviews were carried out with a purposive sample of 13 participants (Mean = 38.07 years) during the COVID-19 pandemic, which included 4 community health workers, 4 people with mental illness, 5 service providers (primary health care doctors and mental health specialists). Data for health facility review was collected from local primary health and specialist facilities while key policy documents were critically analysed for service provision and stigma alleviation activities. Thematic analysis was used to analyse patterns within the interview data. We found poor awareness and knowledge about mental illnesses, belief in faith and traditional healers, scarcity of resources (medicines, trained professionals and mental health inpatient and outpatient clinics), poor access to appropriate mental health facilities, and high costs for seeking mental health care. There is a critical gap between mental health related provisions in policy documents and its implementation at primary and district level.

The value of process evaluation for public health interventions: field-case studies for non-communicable disease prevention and management in five countries.

Complex interventions are needed to effectively tackle non-communicable diseases. However, complex interventions can contain a mix of effective and ineffective actions. Process evaluation (PE) in public health research is of great value as it could clarify the mechanisms and contextual factors associ-ated with variation in the outcomes, better identify effective components, and inform adaptation of the intervention. The aim of this paper is to demonstrate the value of PE through five case studies that span the research cycle. The interven-tions include using digital health, salt reduction strategies, use of fixed dose combinations, and task shifting. Insights of the methods used, and the implications of the PE findings to the project, were discussed. PE of complex interventions can refute or confirm the hypothesized mechanisms of action, thereby enabling intervention refinement, and identifying implementation strategies that can address local contextual needs, so as to improve service delivery and public health outcomes.

Operational challenges in the pre-intervention phase of a mental health trial in rural India: reflections from SMART Mental Health.

BACKGROUND: Availability of mental health services in low- and middle-income countries is largely concentrated in tertiary care with limited resources and scarcity of trained professionals at the primary care level. SMART Mental Health is a strategy that combines a community anti-stigma campaign with a primary health care workforce strengthening initiative, using electronic decision support with the goal of better identifying and supporting people with common mental disorders in India. METHODS: We describe the challenges faced and lessons learnt during the pre-intervention phase of SMART Mental Health cluster Randomised Controlled Trial. Pre-intervention phase includes preliminary activities for setting-up the trial and research activities prior to delivery of the intervention. Field notes from project site visit, project team meetings and detailed follow-up discussions with members of the project team were used to document operational challenges and strategies adopted to overcome them. The socio-ecological model was used as the analytical framework to organise the findings. RESULTS: Key challenges included delays in government approvals, addressing community health worker needs, and building trust in the community. These were addressed through continuous communication, leveraging support of relevant stakeholders, and addressing concerns of community health workers and community. Issues related to use of digital platform for data collection were addressed by a dedicated technical support team. The COVID-19 pandemic and political unrest led to significant and unexpected challenges requiring important adaptations to successfully implement the project. CONCLUSION: Setting up of this trial has posed challenges at a combination of community, health system and broader socio-political levels. Successful mitigating strategies to overcome these challenges must be innovative, timely and flexibly delivered according to local context. Systematic ongoing documentation of field-level challenges and subsequent adaptations can help optimise implementation processes and support high quality trials. TRIAL REGISTRATION: The trial is registered with Clinical Trials Registry India (CTRI/2018/08/015355). Registered on 16th August 2018. http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=23254&EncHid=&userName=CTRI/2018/08/015355.

An intervention to reduce stigma and improve management of depression, risk of suicide/self-harm and other significant emotional or medically unexplained complaints among adolescents living in urban slums: protocol for the ARTEMIS project.

BACKGROUND: There are around 250 million adolescents in India. Adolescents are vulnerable to common mental disorders with depression and self-harm accounting for a major share of the burden of death and disability in this age group. Around 20% of children and adolescents are diagnosed with/ or live with a disabling mental illness. A national survey has found that suicide is the third leading cause of death among adolescents in India. The authors hypothesise that an intervention involving an anti-stigma campaign co-created by adolescents themselves, and a mobile technology-based electronic decision support system will help reduce stigma, depression, and suicide risk and improve mental health for high-risk adolescents living in urban slums in India. METHODS: The intervention will be implemented as a cluster randomised control trial in 30 slum clusters in each of the cities of Vijayawada and New Delhi in India. Adolescents aged 10 to 19 years will be screened for depression and suicide ideation using the Patient Health Questionnaire (PHQ-9). Two evaluation cohorts will be derived-a high-risk cohort with an elevated PHQ-9 score ≥ 10 and/or a positive response (score ≥ 2) to the suicide risk question on the PHQ-9, and a non-high-risk cohort comprising an equal number of adolescents not at elevated risk based on these scores. DISCUSSION: The key elements that ARTEMIS will focus on are increasing awareness among adolescents and the slum community on these mental health conditions as well as strengthening the skills of existing primary healthcare workers and promoting task sharing. The findings from this study will provide evidence to governments about strategies with potential for addressing the gaps in providing care for adolescents living in urban slums and experiencing depression, other significant emotional or medically unexplained complaints or increased suicide risk/self-harm and should have relevance not only for India but also for other low- and middle-income countries. TRIAL STATUS: Protocol version - V7, 20 Dec 2021 Recruitment start date: tentatively after 15th July 2022 Recruitment end date: tentatively 14th July 2023 (1 year after the trial start date) TRIAL REGISTRATION: The trial has been registered in the Clinical Trial Registry India, which is included in the WHO list of Registries ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries ) Reference No. CTRI/2022/02/040307 . Registered on 18 February 2022. The tentative start date of participant recruitment for the trial will begin after 15th July 2022.

Calcium transport and phytate hydrolysis during chemical hardening of common bean seeds.

In this study, two chemical bean seed hardening methods were used to investigate the changes in cooking behavior associated with Ca2+ transport and phytate hydrolysis to better understand their role in the pectin-cation-phytate hypothesis. The texture evolution of fresh and hardened red kidney beans was evaluated, hardening being induced by soaking or in a CaCl2 solution (0.01 M, 0.05 M, 0.1 M) or sodium acetate buffer (0.1 M, pH 4.4, 41 °C). The beans soaked in a CaCl2 solution at higher concentrations or in sodium acetate buffer for a longer time exhibited a delayed cooking behavior. This study also explored the bio-chemical changes (calcium content in different bean substructures, phytate content and the pectin degree of methylesterification (DM) in the cotyledons) occurring in the beans during chemical hardening and cooking. The Ca2+ concentrations in the whole beans and cotyledons of beans soaked and cooked in CaCl2 solutions significantly increased while inositol hexaphosphate IP6 content showed no significant changes. This indicates that the delayed texture drop in this case results from the influx of exogenous Ca2+ in the cotyledons and seed coats during cooking while the IP6 was not hydrolyzed and did not release endogenous Ca2+. For beans soaked in sodium acetate buffer, phytate profiling showed increased hydrolysis of IP6 with longer soaking time, suggesting the migration of endogenous Ca2+ released from phytate hydrolysis contributing to the delayed cooking of these beans. These results indicate that both an exogenous Ca2+ influx during soaking and cooking and an endogenous Ca2+ replacement resulting from phytate hydrolysis can play an important role in the hardening of beans. In neither of the cases, a significant change in pectin DM was observed during chemical hardening, therefore limiting the delayed cooking to the role of Ca2+ transport. The outcome of both cases is inline with the basic principles of the pectin-cation-phytate hypothesis whereby pectin DM changes are hardly involved and different mechanisms of release/transport are involved.

Protocol for process evaluation of SMART Mental Health cluster randomised control trial: an intervention for management of common mental disorders in India.

INTRODUCTION: In India about 95% of individuals who need treatment for common mental disorders like depression, stress and anxiety and substance use are unable to access care. Stigma associated with help seeking and lack of trained mental health professionals are important barriers in accessing mental healthcare. Systematic Medical Appraisal, Referral and Treatment (SMART) Mental Health integrates a community-level stigma reduction campaign and task sharing with the help of a mobile-enabled electronic decision support system (EDSS)-to reduce psychiatric morbidity due to stress, depression and self-harm in high-risk individuals. This paper presents and discusses the protocol for process evaluation of SMART Mental Health. METHODS AND ANALYSIS: The process evaluation will use mixed quantitative and qualitative methods to evaluate implementation fidelity and identify facilitators of and barriers to implementation of the intervention. Case studies of six intervention and two control clusters will be used. Quantitative data sources will include usage analytics extracted from the mHealth platform for the trial. Qualitative data sources will include focus group discussions and interviews with recruited participants, primary health centre doctors, community health workers (Accredited Social Health Activits) who participated in the project and local community leaders. The design and analysis will be guided by Medical Research Council framework for process evaluations, the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework, and the normalisation process theory. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee of the George Institute for Global Health, India and the Institutional Ethics Committee, All India Institute of Medical Sciences (AIIMS), New Delhi. Findings of the study will be disseminated through peer-reviewed publications, stakeholder meetings, digital and social media platforms. TRIAL REGISTRATION NUMBER: CTRI/2018/08/015355.

Longitudinal trends in the health outcomes among children of the North Eastern States of India: a comparative analysis using national DHS data from 2006 to 2020.

BACKGROUND/OBJECTIVES: Northeastern Indian region has a high density of marginalised populations with a concerning quality of health services. We observed the trends in prevalence of infectious diseases and nutritional disorders among children under-five years from 2006 to 2020 in the Northeastern states. We also assessed the distribution of their burden by place of residence. METHODS: A secondary data analysis of select indicators on infectious diseases and nutritional disorders in seven Northeastern states across three rounds of the National Family Health Survey (2005-06, 2015-16, 2019-20) was undertaken. We calculated outcome indicator mean prevalence, relative change and average annual rates of reduction of the indicators. RESULTS: A significant relative reduction between 2006-2020 in the prevalence of diarrhoea (0.4 [95CI:0.7,0.1]) at p < 0.05; acute respiratory illness (ARI) (0.7 [95CI:0.1,0.4]), stunting (0.3 [95CI: 0.3,0.12]) and underweight (0.3 [95CI:0.5,0.2]) at p < 0.001 were noted. However, overweight prevalence increased (10.1[95CI:4.3,16.0, p < 0.001]) due to a low annual reduction rate. The highest annual reduction rates were observed in Sikkim and Tripura for diarrhoea and ARI respectively (>10.0%), and in Meghalaya for wasting and severely wasting (6.3%). Rural areas had a higher burden of stunting, wasting (including severe), underweight, anaemia and diarrhoea; overweight was seen in both rural and urban settings. CONCLUSION: Significant reductions were observed in ARI, diarrhoea, stunting and underweight prevalence between 2006-2020, with sub-regional variations and a greater burden in rural areas. During this period, overweight prevalence worsened; and anaemia showed a large increase from 2016. To reduce the equity-gap, programmes should be adapted to meet the differential needs of the Northeastern states.

An economical strategy towards the managing of selenium pollution from contaminated water: A current state-of-the-art review.

During the last few decades, contamination of selenium (Se) in groundwater has turned out to be a major environmental concern to provide safe drinking water. The content of selenium in such contaminated water might range from 400 to 700 µg/L, where bringing it down to a safe level of 40 µg/L for municipal water supply employing appropriate methodologies is a major challenge for the global researcher communities. The current review focuses mostly on the governing selenium remediation technologies such as coagulation-flocculation, electrocoagulation, bioremediation, membrane-based approaches, adsorption, electro-kinetics, chemical precipitation, and reduction methods. This study emphasizes on the development of a variety of low-cost adsorbents and metal oxides for the selenium decontamination from groundwater as a cutting-edge technology development along with their applicability, and environmental concerns. Moreover, after the removal, the recovery methodologies using appropriate materials are analyzed which is the need of the hour for the reutilization of selenium in different processing industries for the generation of high valued products. From the literature survey, it has been found that hematite modified magnetic nanoparticles (MNP) efficiently adsorb Se (IV) (25.0 mg/g) from contaminated groundwater. MNP@hematite reduced Se (IV) concentration from 100 g/L to 10 g/L in 10 min at pH 4-9 using a dosage of 1 g/L. In 15 min, the magnetic adsorbent can be recycled and regenerated using a 10 mM NaOH solution. The adsorption and desorption efficiencies were over 97% and 82% for five consecutive cycles, respectively. To encourage the notion towards scale-up, a techno-economic evaluation with possible environmentally sensitive policy analysis has been introduced in this article to introspect the aspects of sustainability. This type of assessment is anticipated to be extremely encouraging to convey crucial recommendations to the scientific communities in order to produce high efficiency selenium elimination and further recovery from contaminated groundwater.

An integrated community and primary healthcare worker intervention to reduce stigma and improve management of common mental disorders in rural India: protocol for the SMART Mental Health programme.

BACKGROUND: Around 1 in 7 people in India are impacted by mental illness. The treatment gap for people with mental disorders is as high as 75-95%. Health care systems, especially in rural regions in India, face substantial challenges to address these gaps in care, and innovative strategies are needed. METHODS: We hypothesise that an intervention involving an anti-stigma campaign and a mobile-technology-based electronic decision support system will result in reduced stigma and improved mental health for adults at high risk of common mental disorders. It will be implemented as a parallel-group cluster randomised, controlled trial in 44 primary health centre clusters servicing 133 villages in rural Andhra Pradesh and Haryana. Adults aged ≥ 18 years will be screened for depression, anxiety and suicide based on Patient Health Questionnaire (PHQ-9) and Generalised Anxiety Disorders (GAD-7) scores. Two evaluation cohorts will be derived-a high-risk cohort with elevated PHQ-9, GAD-7 or suicide risk and a non-high-risk cohort comprising an equal number of people not at elevated risk based on these scores. Outcome analyses will be conducted blinded to intervention allocation. EXPECTED OUTCOMES: The primary study outcome is the difference in mean behaviour scores at 12 months in the combined 'high-risk' and 'non-high-risk' cohort and the mean difference in PHQ-9 scores at 12 months in the 'high-risk' cohort. Secondary outcomes include depression and anxiety remission rates in the high-risk cohort at 6 and 12 months, the proportion of high-risk individuals who have visited a doctor at least once in the previous 12 months, and change from baseline in mean stigma, mental health knowledge and attitude scores in the combined non-high-risk and high-risk cohort. Trial outcomes will be accompanied by detailed economic and process evaluations. SIGNIFICANCE: The findings are likely to inform policy on a low-cost scalable solution to destigmatise common mental disorders and reduce the treatment gap for under-served populations in low-and middle-income country settings. TRIAL REGISTRATION: Clinical Trial Registry India CTRI/2018/08/015355 . Registered on 16 August 2018.

Impact of the COVID-19 pandemic on the human resources for health in India and key policy areas to build a resilient health workforce.

The COVID-19 pandemic has disrupted the already low resourced, fragmented and largely unregulated health systems in countries like India. It has only further exacerbated the stress on human resources for health (HRH) in many unanticipated ways. We explored the effect of COVID-19 pandemic on the health workforce in India, and analytically extrapolated the learnings to draw critical components to be addressed in the HRH policies, which can further be used to develop a detailed 'health workforce resilience' policy. We examined the existing literature and media reports published during the pandemic period, covering the gaps and challenges that impeded the performance of the health workers. Recommendations were designed by studying the learnings from various measures taken within India and in some other countries. We identified seven key areas that could be leveraged and improved for strengthening resilience among the health workforce. The system-level factors (at macro level) include developing a health workforce resilience policy, planning and funding for emergency preparedness, stakeholder engagement and incentivization mechanisms; the organization-level factors (meso level) include identifying HRH bench strength, mobilizing the health workforce, psycho-social support, protection from disease; and the individual-level factors (micro level) include measures around self-care by health workers. In keeping with the interdisciplinary nature of the associated factors, we emphasize on developing a future-ready health workforce using a multi-sectoral approach for building its strength and resilience.

Structure of indole···imidazole heterodimer in a supersonic jet: a gas phase study on the interaction between the aromatic side chains of tryptophan and histidine residues in proteins.

In this study, we have investigated the binding motifs between the aromatic side chains of tryptophan and histidine residues in proteins by studying the indole···imidazole heterodimer in a supersonic jet. Different spectroscopic techniques including resonant two-photon ionization (R2PI), UV-UV hole-burning, and resonant ion dip infrared (RIDIR) spectroscopy merged with quantum chemistry calculations have been used for this work. UV-UV hole-burning spectroscopy has been used to confirm the presence of only one structure of the dimer in the experiment. From the comparison of the RIDIR spectrum of the observed dimer with the theoretical IR spectra of different structures of the dimer, it is found that the dimer present in the experiment has a V-shaped structure held by N-H···N hydrogen bond, C-H···π, and weakly present π···π stacking interactions. The most important finding of the present study is that the noncovalent interactions present in the observed dimer have a close resemblance with those present between tryptophan and histidine residues in a nonfluorescent flavoprotein. The present spectroscopic investigation on the indole···imidazole dimer has also immense pharmaceutical significance as this imparts molecular level understanding about the binding motifs of the imidazole drugs with the indole chromophore present in proteins.