Youth Culturally adapted Manual Assisted Problem Solving Training (YCMAP) in Pakistani adolescent with a history of self-harm: protocol for multicentre clinical and cost-effectiveness randomised controlled trial

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

X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin

The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca2+ release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient

Efficacy and tolerability of tegaserod in constipation dominant irritable bowel syndrome

Objective: To determine the efficacy and tolerability of tegaserod in the treatment of symptoms of irritable bowel syndrome (IBS) IBS-C patients.Design: An open label (quasi interventional) study.PLACE AND DURATION OF STUDY: Patients were enrolled between October 2000 and August 2001 at 4 centres (AKUH, Karachi; Mayo Hospital, Lahore; PIMS, Islamabad; Hayatabad Teaching Complex, Peshawar).PATIENTS AND Methods: Tegaserod was administered in a dose of 6 mg (twice-a-day) orally for a period of 6 weeks. Symptoms were assessed before and during treatment using a questionnaire.Results: The mean age of patients was 37.5 years and 81(69.2%) were males. The study enrolled 117 patients and 101 patients completed the study. Number of bowel movements, symptoms of straining at defecation, stool consistency, bloating, urgency and abdominal pain improved significantly following treatment (p\u3c0.05). Analysis of data in both genders separately showed statistically significant improvement in symptoms of urgency, straining at defecation, abdominal pain and number of bowel movements following treatment. Side effects of diarrhoea and vertigo (6 and 1 patients respectively) necessitating discontinuation of treatment were infrequent.CONCLUSION: Tegaserod given in a dose of 6 mg b.d. is effective and well tolerated in IBS-C patients. It is equally effective in males and females in relieving the symptoms of abdominal pain, bloating, straining at defecation as well as increased in the mean number of bowel movements per week

Career intentions of medical students in the UK: a national, cross-sectional study (AIMS study)

Objective To determine current UK medical students’ career intentions after graduation and on completing the Foundation Programme (FP), and to ascertain the motivations behind these intentions.Design Cross-sectional, mixed-methods survey of UK medical students, using a non-random sampling method.Setting All 44 UK medical schools recognised by the General Medical Council.Participants All UK medical students were eligible to participate. The study sample consisted of 10 486 participants, approximately 25.50% of the medical student population.Outcome measures Career intentions of medical students postgraduation and post-FP, motivations behind these career intentions, characterising the medical student population and correlating demographic factors and propensity to leave the National Health Service (NHS).Results The majority of participating students (8806/10 486, 83.98%) planned to complete both years of the FP after graduation, with under half of these students (4294/8806, 48.76%) intending to pursue specialty training thereafter. A subanalysis of career intentions after the FP by year of study revealed a significant decrease in students’ intentions to enter specialty training as they advanced through medical school. Approximately a third of surveyed students (3392/10 486, 32.35%) intended to emigrate to practise medicine, with 42.57% (n=1444) of those students not planning to return. In total, 2.89% of students intended to leave medicine altogether (n=303). Remuneration, work-life balance and working conditions were identified as important factors in decision-making regarding emigration and leaving the profession. Subgroup analyses based on gender, type of schooling, fee type and educational background were performed. Only 17.26% of surveyed students were satisfied or very satisfied with the overall prospect of working in the NHS.Conclusions The Ascertaining the career Intentions of UK Medical Students study highlights UK students’ views and career intentions, revealing a concerning proportion of those surveyed considering alternative careers or emigration. Addressing factors such as remuneration, work-life balance and working conditions may increase retention of doctors and improve workforce planning efforts

The role of medical schools in UK students’ career intentions: findings from the AIMS study

Abstract Objectives To investigate differences in students’ career intentions between UK medical schools. Design Cross-sectional, mixed-methods online survey. Setting The primary study included all 44 UK medical schools, with this analysis comprising 42 medical schools. Participants Ten thousand four hundred eighty-six UK medical students. Main outcome measures Career intentions of medical students, focusing on differences between medical schools. Secondary outcomes included variation in medical students’ satisfaction with a prospective career in the NHS, by medical school. Results 2.89% of students intended to leave medicine altogether, with Cambridge Medical School having the highest proportion of such respondents. 32.35% of respondents planned to emigrate for practice, with Ulster medical students being the most likely. Of those intending to emigrate, the University of Central Lancashire saw the highest proportion stating no intentions to return. Cardiff Medical School had the greatest percentage of students intending to assume non-training clinical posts after completing FY2. 35.23% of participating medical students intended to leave the NHS within 2 years of graduating, with Brighton and Sussex holding the highest proportion of these respondents. Only 17.26% were satisfied with the prospect of working in the NHS, with considerable variation nationally; Barts and the London medical students had the highest rates of dissatisfaction. Conclusions This study reveals variability in students’ career sentiment across UK medical schools, emphasising the need for attention to factors influencing these trends. A concerning proportion of students intend to exit the NHS within 2 years of graduating, with substantial variation between institutions. Students’ intentions may be shaped by various factors, including curriculum focus and recruitment practices. It is imperative to re-evaluate these aspects within medical schools, whilst considering the wider national context, to improve student perceptions towards an NHS career. Future research should target underlying causes for these disparities to facilitate improvements to career satisfaction and retention. </jats:sec