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Abstract Background Hypoplastic left heart syndrome (HLHS) covers a spectrum of rare congenital anomalies characterised by a non-apex forming left ventricle and stenosis/atresia of the mitral and aortic valves. Despite many studies, the causes of HLHS remain unclear and there are conflicting views regarding the role of flow, valvar or myocardial abnormalities in its pathogenesis, all of which were proposed prior to the description of the second heart field. Our aim was to re-evaluate the patterns of malformation in HLHS in relation to recognised cardiac progenitor populations, with a view to providing aetiologically useful sub-groupings for genomic studies. Results We examined 78 hearts previously classified as HLHS, with subtypes based on valve patency, and re-categorised them based on their objective ventricular phenotype. Three distinct subgroups could be identified: slit-like left ventricle (24%); miniaturised left ventricle (6%); and thickened left ventricle with endocardial fibroelastosis (EFE; 70%). Slit-like ventricles were always found in combination with aortic atresia and mitral atresia. Miniaturised left ventricles all had normally formed, though smaller aortic and mitral valves. The remaining group were found to have a range of aortic valve malformations associated with thickened left ventricular walls despite being described as either atresia or stenosis. The degree of myocardial thickening was not correlated to the degree of valvar stenosis. Lineage tracing in mice to investigate the progenitor populations that form the parts of the heart disrupted by HLHS showed that whereas Nkx2–5-Cre labelled myocardial and endothelial cells within the left and right ventricles, Mef2c-AHF-Cre, which labels second heart field-derived cells only, was largely restricted to the endocardium and myocardium of the right ventricle. However, like Nkx2–5-Cre, Mef2c-AHF-Cre lineage cells made a significant contribution to the aortic and mitral valves. In contrast, Wnt1-Cre made a major contribution only to the aortic valve. This suggests that discrete cardiac progenitors might be responsible for the patterns of defects observed in the distinct ventricular sub-groups. Conclusions Only the slit-like ventricle grouping was found to map to the current nomenclature: the combination of mitral atresia with aortic atresia. It appears that slit-like and miniature ventricles also form discrete sub-groups. Thus, reclassification of HLHS into subgroups based on ventricular phenotype, might be useful in genetic and developmental studies in investigating the aetiology of this severe malformation syndrome.

Background Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs). Aims We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms. Method This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n = 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or

Aims Suicide and substance use all contribute significantly to the global burden of mortality and morbidity. While existing evidence establishes the association between substance use and suicidal behaviour in Lower- and Middle-Income Countries (LMICs), only a few studies illustrate how substance use affected deceased people's lifestyles and suicide attempts. The study addresses this gap by exploring the role of substance use (particularly, alcohol and drug use) in overall lifestyles and suicides of deceased with substance use in Pakistan – an underexplored and under-researched country regarding suicide and substance use. Methods We conducted in-depth qualitative interviews (N = 11) with close relatives and friends of those who died by suicide and have a history of substance use. The topic guide was comprised of a narrative part exploring the circumstances that surrounded the suicidal death of the deceased and a problem-focused part collecting comprehensive details about the deceased's personal, family, psychological, and social context and the role of substance use in the lifestyles and the suicide of the deceased. Results The content analysis of interviews revealed five key themes: 1) Reasons for suicide, 2) Personality traits, 3) Psychological distress, 4) Initiation of substance use, and 5) Suicidal tendencies. Most of the participants reported the reason for their loved one's suicide was either an overdose of drugs or alcohol, family dynamics, or societal attitudes such as difficulty in building trust and finding acceptance within the family or society. Deceased individuals were perceived as impulsive with low control over their emotional states. Participants highlighted the underlying psychological distress in the deceased, emphasising the complexity of mental health and substance use problems. Participants reported that the deceased initiated drugs at an early age; had suicidal ideations; and overdosed themselves as a means of suicide. Conclusion This study provides valuable insights into the role of substance use in suicide. The findings highlight the need for a holistic approach to understanding the multifaceted factors that may influence suicidal behaviours in individuals with substance use. Understanding these factors can help develop targeted suicide prevention and intervention strategies, particularly in low-resource settings such as Pakistan.

Aims Bipolar disorder (BD) leads to marked disability, morbidity, and premature death. Although pharmacological agents are an essential part of BD treatment, psychosocial interventions have played an important role in enhancing treatment adherence, functioning and quality of life in patients with BD. Building on a successful pilot randomised controlled trial (RCT) of a Culturally adapted PsychoEducation (CaPE) intervention for BD, CaPE is currently being evaluated in a large multicenter RCT for its clinical and cost-effectiveness across Pakistan. However, innovations are urgently needed due to limited human resources and disproportionately high clinical needs to bring effective interventions to scale. This study aims to develop and test a mHealth iteration of CaPE, digital CaPE (dCaPE), to be delivered via a mobile app. Methods The study will utilise a two-phased approach to i) develop a user-centred dCaPE mobile application and ii) assess the feasibility and preliminary efficacy of dCaPE for people with BD in a randomised controlled trial in Pakistan. For application development, we have conducted discussion groups with stakeholders i.e., mental health professionals (psychiatrists, psychologists, nurses) (n = 8) and patients and carers (n = 10) to gauge their valuable insights for app design, visual elements, cultural sensitivity, motivational and mood-monitoring features, and app functionality to improve user experience. Results The findings from discussion groups informed the importance of visual elements, specifically font size and style. Participants recommended the use of soft and soothing colours like white, grey, and soft shades of pink to prevent overstimulation. Additionally, participants highlighted the need for culturally and linguistically inclusive features, including emojis and audio messages for effective engagement and to address the challenge of low literacy. The mHealth approach was deemed highly valuable, especially given the prevalence of mental health challenges and associated stigma. Endorsed by participants, the dCaPE application will offer customized psychoeducation messages along with daily 5-item (mood, energy, sleep, medication, and irritability) screening, a weekly comprehensive test for manic and depressive episodes based on DSM–5 criteria; weekly reminders to regulate sleep and eating habits, and visual representations of weekly mood monitoring reports with the incentive of badges or rewards for goal achievers. Conclusion This research has the potential to enhance clinical outcomes, social and occupational functioning, and the overall quality of life for BD patients while addressing substantial mental health treatment gaps with impact and implications extending to various low-resource settings.

Aims The burden of mental health difficulties is a global problem and preventing them from childhood is paramount. Children living in challenged and underserved settings can suffer various harmful lifelong consequences including alcohol and substance abuse, low self-esteem, health issues, poor school performance, self-harm and suicide. This study aims to assess the feasibility, acceptability and efficacy of the culturally adapted Strong Families program in improving child behaviour and family functioning in families living in a challenged setting i.e. Gilgit-Baltistan (GB), Pakistan. Methods This is a two-arm, multisite feasibility randomised controlled trial with 90 families (n = 45 in intervention, and n = 45 in waitlist group) including a female primary caregiver (mostly mother) and at least one of their children between the age of 8–15 years in three districts of GB. There will be three raters’ blind assessments: at baseline, week 2, and 6 weeks after Strong Families Program sessions. Results Strong Families Program is a brief evidence-based prevention programme designed to improve parenting skills, child well-being and family mental health. The primary outcome measures include the feasibility of Strong Families, as determined by families' recruitment, attendance rates, and program completeness (mean number of sessions attended, attrition rates). Additionally, purposefully selected participants, including up to 5 caregivers from each study site, researchers, and facilitators delivering the intervention, will be interviewed. Descriptive statistics will be used to analyse primary and secondary outcomes. The process evaluation will be conducted in terms of program context, reach, fidelity, dose delivered and received, implementation, and recruitment. Conclusion The findings from this feasibility trial hold the potential to carry out the large multicentre trial of clinical and cost-effectiveness and scale-up across Pakistan and other similar settings to meaningfully impact child behaviour and family dynamics in culturally diverse contexts.

The task of gathering data from nodes within mobile ad hoc wireless sensor networks presents an enduring challenge. Conventional strategies employ customized routing protocols tailored to these environments, with research focused on refining them for improved efficiency in terms of throughput and energy utilization. However, these elements are interconnected, and enhancements in one often come at the expense of the other. An alternative data collection approach involves the use of unmanned aerial vehicles (UAVs). In contrast to traditional methods, UAVs directly collect data from mobile nodes, bypassing the need for routing. While existing research predominantly addresses static nodes, this paper proposes an evolutionary based, innovative path selection approach based on future position prediction of caching enabled mobile ad hoc wireless sensor network nodes for UAV data collection, aimed at maximizing node encounters and gathering the most valuable information in a single trip. The proposed technique is evaluated for different movement models and parameter configurations.

Abstract Background Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan. Method A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety). Conclusions A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP. Trial registration NCT05814913.

Background Suicidal ideation and attempts are growing public health concerns globally. Evidence from high-income countries suggests that individuals with psychosis and bipolar disorder are at increased risk of suicidal ideation and attempts, but there is a scarcity of evidence from South Asia. Aims To estimate the prevalence of suicidal ideation and attempts in individuals with psychosis and bipolar disorder in South Asia. Method In this systematic review and meta-analysis, four databases (PsycINFO, Web of Science, EMBASE and Medline) were searched until December 2022. Pooled prevalence was estimated with random-effects models. Heterogeneity was quantified with the I2-statistic. Results The pooled sample size across the 21 studies was 3745 participants, 1941 (51.8%) of which were male. The pooled prevalence of suicide attempts in South Asian people with either psychosis or bipolar disorder was 22% (95% CI 17–27; n = 15). The pooled prevalence of suicidal ideation with psychosis or bipolar disorder combined was 38% (95% CI 27–51; n = 10). Meta-regression, subgroup and sensitivity analysis showed that the pooled prevalence estimates for both suicide attempt and ideation remained unaffected by variations in critical appraisal ratings and study designs. Only one study reported data on suicide-related deaths. Conclusions One in four individuals diagnosed with psychosis or bipolar disorder have reported suicide attempts, whereas up to one in three have experienced suicidal ideation. These findings underscore the urgent need for clinicians to regularly assess and monitor suicidal ideation and attempts among individuals with these disorders in South Asia.

Objective: The diagnosis and treatment of breast cancer is associated with significant distress that has huge impact on survivors’ quality of life. The objective of this study is to assess the effectiveness of an integrated intervention “Moving on After Breast Cancer (ABC) Plus culturally adapted Cognitive Behavior Therapy” (Moving on ABC Plus). Method: This is a randomized controlled trial that aims to recruit 354 breast cancer survivors from the inpatient and outpatient oncology departments in public and private hospitals in Karachi, Hyderabad, Lahore, Multan, and Rawalpindi in Pakistan. Patients scoring 10 or above on either the Patient Health Questionnaire—9 and/or the Generalized Anxiety Disorder scale (GAD-7) will be recruited. Baseline assessments will include Functional Assessment of Cancer Therapy—Breast; EuroQol-5D; Multidimensional Scale for Perceived Social Support; Intrusive Thoughts Scale; and Rosenberg Self-Esteem Scale. Participants randomized into intervention arm, Moving on ABC Plus, will receive 12 individual therapy sessions over 4 months. Follow-up will be completed at 4- and 6-month post-randomization, using all baseline instruments along with the Client Satisfaction Questionnaire (CSQ-8). We will also explore the participants’, their family members’, and the therapists’ experiences of the trial and intervention. Results: We will be assessing the effectiveness of intervention in reducing depression and anxiety in breast cancer survivors as a primary outcome of the trial. The secondary outcomes will include effectiveness of intervention in terms of reduction in intrusive thoughts and improvement in health-related quality of life, self-esteem, and perceived social support. Conclusion: The results of the study will inform the design of a future larger randomized control trial with long-term follow-up.

Introduction 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. Objectives 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. Methods 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. Results 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. Conclusions 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. Disclosure of Interest None Declared

Introduction 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. Objectives 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). Methods 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. Results 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. Conclusions 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 Disclosure of Interest None Declared

Introduction 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. Objectives 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. Methods 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. Results 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. Conclusions 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. Disclosure of Interest None Declared

Introduction 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. Objectives - 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 Methods 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. Results 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. Conclusions 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. Disclosure of Interest None Declared

Abstract Background Prevalence of post-traumatic stress disorder (PTSD) is high in Pakistan both due to natural disasters and ongoing conflicts. Offspring of trauma survivors are at increased risk for mental and physical illnesses. Parental PTSD has been linked to troubled parent–child relationships, behaviour problems, trauma symptoms, and depression in children. This study aims to explore the acceptability, feasibility and indications of the effectiveness of group learning through play plus trauma-focused cognitive behaviour therapy (LTP Plus TF-CBT) for parents experiencing PTSD. Methods/Design This is a two-arm pilot cluster randomised controlled trial (RCT). We aim to recruit 300 parents with a diagnosis of PTSD. The screening will be done using the Impact of Event Scale-Revised. Diagnosis of PTSD will be confirmed using the Clinician-Administered PTSD Scale-5 (CAPS-5). Union Councils from Peshawar and Karachi will be randomised into either group LTP Plus TF CBT arm or treatment as usual (TAU). The intervention includes 12 sessions of LTP Plus TF-CBT delivered weekly in the first 2 months and then fortnightly in a group setting by trained psychologists. The groups will be co-facilitated by the community health workers (CHWs). Parents will be assessed at baseline and 4th month (end of the intervention), using the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder (GAD-7) Scale, Client Service Receipt Inventory (CSRI), and Ages and Stages Questionnaire (ASQ-3) Discussion This trial would help build an understanding of the acceptability, feasibility and indications of the effectiveness of a low-cost parenting intervention.

Background Bipolar disorder is a source of marked disability, morbidity and premature death. There is a paucity of research on personalised psychosocial interventions for bipolar disorder, especially in low-resource settings. A pilot randomised controlled trial (RCT) of a culturally adapted psychoeducation intervention for bipolar disorder (CaPE) in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes regarding bipolar disorder, and improvement in mood symptom scores and health-related quality of life measures compared with treatment as usual (TAU). Aims The current protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan. Trial registration: NCT05223959. Method A multicentre individual, parallel-arm RCT of CaPE in 300 Pakistani adults with bipolar disorder. Participants over the age of 18, with a diagnosis of bipolar I or II disorder who are currently euthymic, will be recruited from seven sites: Karachi, Lahore, Multan, Rawalpindi, Peshawar, Hyderabad and Quetta. Time to recurrence will be the primary outcome assessed using the Longitudinal Interval Follow-up Evaluation (LIFE). Secondary measures will include mood symptoms, quality of life and functioning, adherence to psychotropic medications, and knowledge and attitudes regarding bipolar disorder. Results This trial will assess the effectiveness of the CaPE intervention compared with TAU in reducing the time to recurrence for people with bipolar disorder currently in remission in Pakistan and determine the effect on clinical outcomes, quality of life and functioning. Conclusions A successful trial might 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 group patients with bipolar disorder.

Introduction Suicide is a global health concern. Sociocultural factors have an impact on self-harm and suicide rates. In Pakistan, both self-harm and suicide are considered as criminal offence’s and are condemned on both religious and social grounds. The proposed intervention ‘Youth Culturally Adapted Manual Assisted Problem Solving Training (YCMAP)’ is based on principles of problem-solving and cognitive–behavioural therapy. YCMAP is a brief, culturally relevant, scalable intervention that can be implemented in routine clinical practice if found to be effective.Method and analysis A multicentre rater blind randomised controlled trial to evaluate the clinical and cost-effectiveness of YCMAP including a sample of 652 participants, aged 12–18 years, presenting to general physicians/clinicians, emergency room after self harm or self referrals. We will test the effectiveness of 8–10 individual sessions of YCMAP delivered over 3 months compared with treatment as usual. Primary outcome measure is repetition of self-harm at 12 months. The seconday outcomes include reduction in suicidal ideation, hopelessness and distress and improvement in health related quality of life. Assessments will be completed at baseline, 3, 6, 9 and 12 months postrandomisation. The nested qualitative component will explore perceptions about management of self-harm and suicide prevention among adolescents and investigate participants’ experiences with YCMAP. The study will be guided by the theory of change approach to ensure that the whole trial is centred around needs of the end beneficiaries as key stakeholders in the process.Ethics and dissemination Ethics approval has been obtained from the Ethics Committee of University of Manchester, the National Bioethics Committee in Pakistan. The findings of this study will be disseminated through community workshops, social media, conference presentations and peer-reviewed journals.Trial registration number NCT04131179.

Objectives: Chronic obstructive pulmonary disease contributes to substantial health and economic burden worldwide. Co-morbid depression and anxiety are highly prevalent in patients with chronic obstructive pulmonary disease. Depressive symptoms in chronic obstructive pulmonary disease are associated with poorer survival, longer hospitalisation and impaired quality of life. Literature on chronic obstructive pulmonary disease is largely derived from high-income countries; yet 90% of deaths related to chronic obstructive pulmonary disease occur in low- and middle-income countries. We aimed to establish the prevalence of anxiety and depression in patients with chronic obstructive pulmonary disease, as well as the association with psychosocial outcomes. Methods: This was a cross-sectional study of chronic obstructive pulmonary disease patients attending outpatient primary care clinics in Karachi, Pakistan. The Patient Health Questionnaire-9 was used to assess depression and the Generalised Anxiety Disorder-7 scale was used for the assessment of anxiety. Health-related quality of life was assessed with EuroQol–Five Dimensions, social support with Oslo-3 and social stress with Life Events Checklist. We recruited 293 subjects. Results: The prevalence of depression and anxiety in the sample was 51% ( n = 149) and 20% ( n = 59), respectively. Depressed chronic obstructive pulmonary disease patients reported significantly lower health-related quality of life scores as compared to non-depressed patients. Participants with depression had significantly higher levels of anxiety, less social support, higher social stress and more subjective impairment in quality of life. Conclusion: Given the association with reduced social support and increased perceived stress, the role of psychosocial interventions must be explored in improving outcomes of chronic obstructive pulmonary disease patients in Pakistan.

BackgroundThe evidence base for stigma in mental health largely originates from high-income countries.AimsThis study from Pakistan aimed to address the gap in literature on stigma from low- and middle-income countries.MethodThis cross-sectional study surveyed 1470 adults from Karachi, Pakistan. Participants from three groups (healthcare professionals, healthcare students and the general public) completed the adapted Bogardus Social Distance Scale (SDS) as a measure of stigma.ResultsAll three groups reported higher scores of stigma toward mental disorders compared with physical disorders. SDS scores for mental illness in the general public were significantly higher than in healthcare students (mean difference (MD) 6.93, 95% CI 5.45–8.45, P < 0.001) and healthcare professionals (MD 6.93, 95% CI 5.48–8.38, P < 0.001). However, SDS scores between healthcare students and healthcare professionals were not significantly different (MD 0.003, 95% CI −1.14–1.14, P > 0.99). Being female was associated with lower stigma scores and being over the age of 30 years was associated with higher stigma scores.ConclusionsStigma campaigns in Pakistan need to target the general population. However, evidence of negative attitudes toward mental illness in healthcare students and healthcare professionals supports the need for stronger emphasis on psychiatric education within undergraduate and postgraduate training in Pakistan.

Abstract Background Evidence for efficacy of cognitive-behavioural therapy (CBT) in treatment of schizophrenia is growing. CBT is effective and cost efficient in treating positive and negative symptoms. To effectively meet the needs of diverse cultural groups, CBT needs to be adapted to the linguistic, cultural and socioeconomic context. We aimed to assess the feasibility, efficacy and acceptability of a culturally adapted CBT for treatment of psychosis (CaCBTp) in a low-income country. Methods Rater-blind, randomised, controlled trial of the use of standard duration CBT in patients with psychosis from a low-income country. Participants with a ICD-10 diagnosis of psychosis were assessed using Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Psychotic Symptom Rating Scales (PSYRATS), and the Schedule for Assessment of Insight (SAI) (baseline, 3 months and 6 months). They were randomized into the intervention group (n = 18) and Treatment As Usual (TAU) group (n = 18). The intervention group received 12 weekly sessions of CaCBTp. Results The CaCBTp group had significantly lower scores on PANSS Positive (p = 0.02), PANSS Negative (p = 0.045), PANSS General Psychopathology (p = 0.008) and Total PANSS (p = 0.05) when compared to TAU at three months. They also had low scores on Delusion Severity Total (p = 0.02) and Hallucination Severity Total (p = 0.04) of PSYRATS, as well as higher scores on SAI (p = 0.01) at the same time point. At six months only the improvement in PANSS positive scores (p = 0.045) met statistical significance.. Conclusions It is feasible to offer CaCBTp as an adjunct to TAU in patients with psychosis, presenting to services in a lower middle-income country. Trial registration Clinicaltrials.gov identifier NCT02202694 (Retrospectively registered).

BackgroundA 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.AimsTo 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).MethodAfter 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.ResultsThis 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.ConclusionsAs 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.Declaration of interestI.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.

Background: Globally, paternal depression is a neglected and under-researched area. Aims: To feasibility test Learning Through Play Plus Dads (LTP+ Dads), a group parenting psychoeducation program adapted for depressed Pakistani fathers of children under 3 years of age. Methods: Fathers with depression were recruited in Karachi, Pakistan, for a pre-post feasibility study. Ten sessions of group LTP+ Dads were offered over three months. Clinical assessments were administered at baseline, three (end of intervention), and six (follow-up) months and included the Edinburgh Postnatal Depression Scale, 17-item Hamilton Depression Rating Scale, Brief Disability Questionnaire, Multidimensional Scale of Perceived Social Support, Euro-Qol-5 Dimensions, Rosenberg Self-esteem Scale, Parenting Stress Index, and Knowledge, Attitude and Practices questionnaire. Results: Of the 78 fathers approached, 34 consented to screening and 18 were eligible to participate. Participants had a mean age of 33 years, with a mean of 3.61 children. Most were unemployed and were from low-income households with low education backgrounds. The intervention was feasible and acceptable based on a recruitment rate of 100% of eligible participants and a 100% attendance rate for five of the 10 sessions. Fathers showed, on average, a reduction in depressive symptoms, an increase in most areas of knowledge, and positive attitudes about child development. Perceived social support, self-esteem, and functioning scores also increased. Conclusions: A low-cost, culturally adapted group intervention was found to be feasible and acceptable. Changes in depression, parenting-related, and other outcomes are promising and inform a future larger trial. Trial Registration: The trial was registered on Clinicaltrials.gov on 9 December 2020 (identifier: NCT04660253).

Cephalosporins are among the most commonly prescribed antibiotic classes due to their wide clinical utility and general tolerability, with approximately 1−3% of the population reporting a cephalosporin allergy. However, clinicians may avoid the use of cephalosporins in patients with reported penicillin allergies despite the low potential for cross-reactivity. The misdiagnosis of β-lactam allergies and misunderstanding of cross-reactivity among β-lactams, including within the cephalosporin class, often leads to use of broader spectrum antibiotics with poor safety and efficacy profiles and represents a serious obstacle for antimicrobial stewardship. Risk factors for cephalosporin allergies are broad and include female sex, advanced age, and a history of another antibiotic or penicillin allergy; however, cephalosporins are readily tolerated even among individuals with true immediate-type allergies to penicillins. Cephalosporin cross-reactivity potential is related to the structural R1 side chain, and clinicians should be cognizant of R1 side chain similarities when prescribing alternate β-lactams in allergic individuals or when new cephalosporins are brought to market. Clinicians should consider the low likelihood of true cephalosporin allergy when clinically indicated. The purpose of this review is to provide an overview of the role of cephalosporins in clinical practice, and to highlight the incidence of, risk factors for, and cross-reactivity of cephalosporins with other antibiotics.