Globally, burns are responsible for around 11 million injuries and 180 000 burn-related deaths yearly. Unfortunately, 9 of 10 burn injuries and deaths happen in low-and-middle-income countries (LMICs) such as Pakistan. One in three people admitted to hospitals with burn injuries die within three weeks, and survivors face serious lifelong physical, emotional and psychosocial problems. This may result in anxiety, depression, post-traumatic stress disorder, increased mortality and social disintegration. This study aims to evaluate if implementation of a culturally adapted multidisciplinary rehabilitation programme for burn survivors is clinically and cost-effective, sustainable and scalable across Pakistan.

• - To understand lived experiences of burn survivors, families, and other stakeholders including the experience of care and impact of burns To work together with key stakeholders (such as burn survivors, family members) to adapt a culturally appropriate affordable burn rehabilitation programme

• - To undertake social media campaigns to promote burn prevention and risk assessment at communities, workplaces/industries/households; improve first aid; and address burn related stigma

• - To work with policy makers/parliamentarians to develop national guidelines for burns care and prevention in Pakistan

There are 6 work-packages (WPs). WP1 is to co-adapt a culturally appropriate burn care and rehabilitation programme. WP2 will develop and implement national burn registry on WHO’s initiative. WP3 is a cluster randomised controlled trial to determine clinical and cost-effectiveness in Pakistan. WP4 will evaluate social media campaigns for burn prevention and reduce stigma. WP5 involves working with key-stakeholders for burns-related care and policy and WP6 offers sustainable capacity and capability for burns treatment and rehabilitation.

A clinical and cost-effective burn care quality and rehabilitation programme may have a huge potential to save lives and contribute health and socio-economic benefits for patients, families, and the healthcare system in Pakistan. The nation-wide implementation and involvement of burn centres across all provinces offer an excellent opportunity to overcome the problem of burn care access experienced in LMICs.

To date, burns prevention, care and rehabilitation have not received sufficient attention in policy initiatives in Pakistan and other LMICs. This study is an excellent opportunity to evaluate culturally adapted burn care and rehabilitation programmes that can be implemented across LMICs. We will disseminate our findings widely, using a variety of approaches, supported by our stakeholder and patient advisory groups.

None Declared

Low and middle-income countries (LMICs) hold the majority of disease burden attributed to major depressive disorder (MDD). Despite this, there remains a substantial gap for access to evidence-based treatments for MDD in LMICs like Pakistan. Measurement-based care (MBC) incorporates systematic administration of validated outcome measures to guide treatment decision making and is considered a low-cost approach to optimise better clinical outcomes for individuals with MDD but there is a paucity of evidence on the efficacy of MBC in LMICs.

This protocol highlights a randomized trial which will include Pakistani outpatients with moderate to severe major depression.

Participants will be randomised to either MBC (guided by schedule), or standard treatment (guided by clinicians’ judgement), and will be prescribed with paroxetine (10–60mg/day) or mirtazapine (7.5–45mg/day) for 24 weeks. Outcomes will be evaluated by raters blind to study protocol and treatment.

National Bioethics Committee (NBC) of Pakistan has given full ethics approval. The trial is being conducted and reported as per recommendation of the CONSORT statement for RCTs.

With increasing evidence from high-income settings supporting the effectiveness of MBC for MDD, it is now necessary to explore its feasibility, utility. and efficacy in low-resource settings. The results of the proposed trial could inform the development of a low-cost and scalable approach to efficiently optimise outcomes for individuals with MDD in Pakistan.

None Declared

Suicide is a leading cause of death among young people and most deaths by suicide occur in low and middle-income countries. School is the best place where we can identify and respond to youth suicide risk. School-based interventions for suicide prevention in young people have been successful across US, Europe and Australia, but require adaptations to be acceptable and feasible in Pakistan.

To develop and test culturally adapted preventative interventions for suicidal behaviours among pupils in secondary schools in Pakistan. The qualitative component aimed at exploring the views of students, parents, teachers and general practitioners on cultural adaptation, experience of participation, areas of improvement and suggestions for scale-up of the school-based suicide prevention program (SEPAK).

A clustered randomised controlled trial. The four culturally modified interventions 1) Linking Education and Awareness of Depression and Suicide Awareness (LEADS) Training for pupils (students=260) 2) the Question, Persuade, and Refer (QPR) for teachers (students=203) 3) QPR for parents (students=445); 4) Screening by Professionals (Profscreen) (students=260) were compared against control intervention (educational posters) (students=227). Structured questionnaires were administered at baseline and 1-month post-intervention to assess suicidal behaviours, psychological well-being and quality of life. A total of 8 focus groups (FGs) were conducted at pre and post intervention stage with each stakeholders.

Patient and public involvement and Engagement (PPIE) was strongly embedded in the project to ensure meaningful benefits for participants. A total of 40 schools were recruited from 8 cities across Pakistan. A total of 243 students attended LEADS intervention, 92 teachers and 304 parents completed QPR training, and 9 general practitioners were trained in ProfScreen. The retention rate at follow-up was 99% that shows feasibility of delivering intervention package in Pakistan. All participants marked SEPAK as effective in identifying risk of and preventing self-harm and suicide in young people and in improving pathways to treatment. Interventions were perceived as helpful in improving knowledge about mental health, impact of mental health difficulties on functioning, reducing stigma, equipping stakeholders to identify and signpost at-risk people. Improvement in clinical and teaching practice as well as understanding others behaviors were also reported.

This study suggest feasibility of integrating a suicide prevention program in existing educational system and highlights positive role of creating awareness about suicide in youth, introduction of school-based mental health programs, parental counseling and strengthening of the health system by training general practitioners in early identification of suicide risk and promoting suicide prevention strategies

None Declared

Bipolar disorder (BD) is a source of marked disability, morbidity, and premature death. There is a paucity of research on personalized psychosocial interventions for BD, especially in lowresource settings. A previously published pilot randomized controlled trial (RCT) of a Culturally adapted PsychoEducation (CaPE) intervention for BD in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes towards BD, and improvement in mood symptom scores and health-related quality of life measures compared to treatment-as-usual (TAU).

This protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan.

A multicentre individual, parallel arm, RCT of CaPE in 300Pakistani adults with BD. Participants over the age of 18, with adiagnosis of bipolar I and II and who are currently euthymic, will berecruited from seven sites including Karachi, Lahore, Multan, Rawalpindi,Peshawar, Hyderabad and Quetta. Time to recurrence will be the primaryoutcome assessed using Longitudinal Interval Follow-up Evaluation(LIFE). Secondary measures will include mood symptomatology, qualityof life and functioning, adherence to psychotropic medications, andknowledge and attitudes towards BD.

Full ethics approval has been received from National Bioethics Committee (NBC) of Pakistan and Centre for Addiction and Mental Health (CAMH), Toronto, Canada. The study has completed sixty-five screening across the seven centres, of which forty-eight participants have been randomised.

A successful trial will lead to rapid implementation of CaPE in clinical practice, not only in Pakistan, but also in other low-resource settings including those in high-income countries, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority patients with BD.

None Declared

Depression is the leading cause of disability worldwide and low and middle-income countries (LMICs) carry over 80% of this disease burden. Attempts have been made to address depression in LMICs, with improvements in the home environment and maternal knowledge. However paternal depression is a neglected and under-researched area. Since maternal depression is associated with depression in fathers there is a need for partner inclusive parenting programs to address parental mental health and improve child outcomes.

To evaluate the clinical and cost effectiveness of partner inclusive Learning through play plus (LTP+) intervention in reducing depression in fathers and mothers.

To evaluate the effectiveness of LTP + intervention in improving child outcomes.

To conduct process evaluation and identify challenges in transition to scale up of the intervention across Karachi, Pakistan from the perspective of fathers, mothers, and other stakeholders.

This is a cluster randomised controlled (cRCT) trial of partner inclusive group parenting program called (Learning Through Play (LTP+) across 18 towns in the city of Karachi. Over 5000 parents (fathers and partners) will participate in the study with a capacity building component of training 4000 Community Health Workers across Pakistan.

This large cRCT will confirm the clinical and cost-effectiveness of LTP+ in reducing depression in parents and improving child outcomes along with the barriers and facilitators to implement the LTP+ group parenting program and the possibilities to roll out the innovation at national level through engagement with policy makers.

Addressing depression in parents is hugely important because of its adverse effects both for child and parents. This low-cost group parenting program will help in scaling up the innovation across health services in Pakistan and other LMICs.

None Declared

Repeated self-harm represents the single strongest risk factor for suicide. Worldwide, suicide is the second leading cause of death in young people aged 15-29 year, and the leading cause of death in many Asian countries.

This qualitative study was nested in a multi-center effectiveness trial of a Youth Culturally-adapted Manual Assisted Problem-solving intervention (Y-CMAP) for prevention of self-harm in Pakistan and aimed to explore young people’s perspective on the intervention.

One-to-one in-depth qualitative interviews were conducted with 20 participants from 5 cities across Pakistan, using a semi-structured topic guide to explore their views about self-harm, Y-CMAP intervention content, perceived effectiveness and challenges. Interviews were conducted in Urdu language, digitally recorded, transcribed verbatim and translated into English. Thematic analysis was conducted by the trained qualitative researchers.

Interpersonal conflicts including relationship difficulties, financial problems, and lack of social support were highlighted as precipitating factors of self-harm. Participants reported that Y-CMAP intervention is structured and easy to understand. They acknowledged the role of distraction techniques, cost-benefit analysis, discussion on thinking pattern, problem-solving and anger management in improving their mental health and wellbeing and reduce self-harm. Participants also shared their initial fears regarding the intervention, such as fear of disclosure of information to media. School and job timings were described as potential challenges for participation in the intervention.

Exploring the perspectives of young people about culturally-appropriate intervention is imperative in their journey towards preventing suicide, which is a preventable cause of premature death. Findings are particularly relevant for Pakistan, one of the youngest nations in the world with limited resources for suicide prevention.

None Declared

There has been increased interest in repurposing anti-inflammatories for the treatment of bipolar depression. Evidence from high-income countries suggests that these agents may work best for specific depressive symptoms in a subset of patients with biochemical evidence of inflammation but data from lower-middle income countries (LMICs) is scarce. This secondary analysis explored the relationship between pretreatment inflammatory markers and specific depressive symptoms, clinical measures, and demographic variables in participants with bipolar depression in Pakistan.

The current study is a cross-sectional secondary analysis of a randomized controlled trial of two anti-inflammatory medications (minocycline and celecoxib) for bipolar depression (n = 266). A series of logistic and linear regression models were completed to assess the relationship between C-reactive protein (CRP) (CRP > or < 3 mg/L and log10CRP) and clinical and demographic features of interest and symptoms of depression. Baseline clinical trial data was used to extract clinical and demographic features and symptoms of depression were assessed using the 24-item Hamilton Depression Rating Scale.

The prevalence of low-grade inflammation (CRP > 3 mg/L) in the sample was 70.9%. After adjusting for baseline body mass index, socioeconomic status, age, gender, symptoms related to anhedonia, fatigue, and motor retardation were most associated with low-grade inflammation.

Bipolar disorder (BD) patients from LMICs may experience higher rates of peripheral inflammation than have been reported in Western populations with BD. Future trials of repurposed anti-inflammatory agents that enrich for participants with these symptom profiles may inform the development of personalized treatment for bipolar depression in LMICs.

The rates of postnatal depression (PND) in British South Asian (BSA) women are higher than the general population. PND is known to cause disability and suffering in women and negative consequences for their infants and their family with huge costs to society. Due to linguistic and cultural barriers, BSA women do not access health care services.

To conduct an exploratory trial to test the feasibility and acceptability of a culturally adapted group Cognitive Behavioural Therapy (CBT) intervention (Positive Health Programme (PHP).

We aimed to determine if depressed BSA women receiving the PHP intervention will show significant improvements in terms of severity of depression, marital support, and social support as compared to the control group.

We used a two-arm pragmatic single-blind randomised controlled design. Women meeting the inclusion criteria were randomised either to the experimental group receiving PHP or treatment as usual (TAU) that is standard care usually provided by the GP.

A total of 615 mothers were screened for participation in the trial, of these 137 were assessed further to determine eligibility. Eighty-three mothers were randomized to receive either PHP (n = 42) or treatment as usual (TAU) (n = 41). Mothers found the intervention to be acceptable and felt an overall positive change in their attitudes, behaviour and confidence level.

The recruitment and retention figures (70%) highlight the ability of the research team to engage with the population. The findings suggest the acceptability of the culturally adapted PHP intervention for British South Asian women with postnatal depression.

The authors have not supplied their declaration of competing interest.

A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.

To report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744).

After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery–Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12.

This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action.

As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.

I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.

Depression is common in Pakistan but no research on this subject has been reported from the North West Frontier Province (NWFP), host to numerous Afghan refugees.

To measure depressive symptoms and associated features in a population-based sample.

A Pushto translation of the Self Reporting Questionnaire (SRQ) was administered to 471 adults living in a village in one of the federally administered tribal areas. Respondents were also assessed with a life events checklist for social problems, a social support questionnaire and the Brief Disability Questionnaire.

Sixty per cent (95/158) of women and 45% (140/313) of men scored 9 or more on the SRQ. High SRQ score was associated with few years of education, higher social problem score, less social support and greater disability. High social problem score was the strongest correlate.

This population reports more depressive symptoms than other communities in Pakistan and this probably reflects the very high degree of social stress experienced in the NWFP, which has been affected by years of turmoil in neighbouring Afghanistan.