Expanding EMC foldopathies: Topogenesis deficits alter the neural crest.

The endoplasmic reticulum (ER) membrane protein complex (EMC) is essential for the insertion of a wide variety of transmembrane proteins into the plasma membrane across cell types. Each EMC is composed of Emc1-7, Emc10, and either Emc8 or Emc9. Recent human genetics studies have implicated variants in EMC genes as the basis for a group of human congenital diseases. The patient phenotypes are varied but appear to affect a subset of tissues more prominently than others. Namely, craniofacial development seems to be commonly affected. We previously developed an array of assays in Xenopus tropicalis to assess the effects of emc1 depletion on the neural crest, craniofacial cartilage, and neuromuscular function. We sought to extend this approach to additional EMC components identified in patients with congenital malformations. Through this approach, we determine that EMC9 and EMC10 are important for neural crest development and the development of craniofacial structures. The phenotypes observed in patients and our Xenopus model phenotypes similar to EMC1 loss of function likely due to a similar mechanism of dysfunction in transmembrane protein topogenesis.

Effectiveness and implementation of psychological interventions for depression in people with non-communicable diseases in South Asia: Systematic review and meta-analysis.

We evaluate the effectiveness of psychological interventions for depression in people with NCDs in South Asia and explore the individual, organizational, and policy-level barriers and facilitators for the implementation and scaling up of these interventions. Eight databases (and local web pages) were searched in May 2022. We conducted random effects models to evaluate the pooled effect of psychological interventions on depression in people with NCDs. We extracted the individual, organizational, and policy level barriers and facilitators. We found five randomized control trials, nine qualitative studies, and 35 policy documents that fitted the inclusion criteria. The pooled standardized mean difference in depression comparing psychological interventions with usual care was -2.31 (95% CI, -4.16 to -0.45; p = .015, I2 = 96.0%). We found barriers and facilitators to intervention delivery, mental health appears in the policy agenda in Bangladesh and Pakistan. However, there is a lack of policies relating to training in mental health for NCD health providers and a lack of integration of mental health care with NCD care. All of the psychological interventions reported to be effective in treating depression in this population. There are important delivery and policy barriers to the implementation and scaling up of psychological interventions for people with NCDs.

Excessive Daytime Sleepiness and Sleep Quality and their Impact on Health-Related Quality of Life in People with Epilepsy: A study from Pakistan.

BACKGROUND: Epilepsy is one of the most common but manageable neurological disorder. The relation between epilepsy, sleep, and health-related quality of life (HRQoL) in culturally distinct environment of Pakistan remains unclear. The purpose of this study was to determine prevalence and predictors of excessive daytime sleepiness (EDS), poor sleep quality (SQ), and to analyze their association with HRQoL in people with epilepsy (PWE). METHODS: A study was conducted among PWE attending two tertiary care hospitals of Islamabad and Rawalpindi, Pakistan. The EDS, SQ, and HRQoL were evaluated by Urdu versions of Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Quality of Life in Epilepsy-31 (QOLIE-31). RESULTS: The study included 200 PWE and 51 healthy controls with mean (SD) ages of 33.1 ±â€¯13.9, 32.9 ±â€¯10.9, and a disease duration of 5.01 ±â€¯6.17, respectively. The majority of the respondents (n = 130, 65%) had poor seizure control, and most of these (n = 88, 68%) were on combination antiepileptic drug (AED) therapy. In comparison to controls, a higher number of PWE had EDS by ESS (score ≥ 11, 10% vs. 40%, p-value 0.00), and poor SQ by PSQI (score > 5, 9% vs. 71%, p-value 0.00). A multiple logistic regression analysis reveals that the factors significantly associated with EDS were: female gender; increasing age; seizure control; duration of epilepsy; and combination AED therapy. A second multiple binary logistic regression analysis suggests that factors significantly associated with poor SQ were: increasing age; female gender; poor seizure control; and combination therapy. The Hierarchical multivariate analysis suggests that poor seizure control, EDS, and poor SQ were significant predictors of low HRQoL. CONCLUSION: The findings suggest high prevalence of EDS and poor SQ in PWE in Pakistan. A significant negative association exists between sleep complaints and HRQoL. During routine clinical consultations, awareness about sleep hygiene practices must be provided to enhance HRQoL.

Interventions for preventing type 2 diabetes in adults with mental disorders in low- and middle-income countries.

BACKGROUND: The prevalence of type 2 diabetes is increased in individuals with mental disorders. Much of the burden of disease falls on the populations of low- and middle-income countries (LMICs). OBJECTIVES: To assess the effects of pharmacological, behaviour change, and organisational interventions versus active and non-active comparators in the prevention or delay of type 2 diabetes among people with mental illness in LMICs. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register, CENTRAL, MEDLINE, Embase and six other databases, as well as three international trials registries. We also searched conference proceedings and checked the reference lists of relevant systematic reviews. Searches are current up to 20 February 2020. SELECTION CRITERIA: Randomized controlled trials (RCTs) of pharmacological, behavioural or organisational interventions targeting the prevention or delay of type 2 diabetes in adults with mental disorders in LMICs. DATA COLLECTION AND ANALYSIS: Pairs of review authors working independently performed data extraction and risk of bias assessments. We conducted meta-analyses using random-effects models. MAIN RESULTS: One hospital-based RCT with 150 participants (99 participants with schizophrenia) addressed our review's primary outcome of prevention or delay of type 2 diabetes onset. Low-certainty evidence from this study did not show a difference between atypical and typical antipsychotics in the development of diabetes at six weeks (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.03 to 7.05) (among a total 99 participants with schizophrenia, 68 were in atypical and 31 were in typical antipsychotic groups; 55 participants without mental illness were not considered in the analysis). An additional 29 RCTs with 2481 participants assessed one or more of the review's secondary outcomes. All studies were conducted in hospital settings and reported on pharmacological interventions. One study, which we could not include in our meta-analysis, included an intervention with pharmacological and behaviour change components. We identified no studies of organisational interventions. Low- to moderate-certainty evidence suggests there may be no difference between the use of atypical and typical antipsychotics for the outcomes of drop-outs from care (RR 1.31, 95% CI 0.63 to 2.69; two studies with 144 participants), and fasting blood glucose levels (mean difference (MD) 0.05 lower, 95% CI 0.10 to 0.00; two studies with 211 participants). Participants who receive typical antipsychotics may have a lower body mass index (BMI) at follow-up than participants who receive atypical antipsychotics (MD 0.57, 95% CI 0.33 to 0.81; two studies with 141 participants; moderate certainty of evidence), and may have lower total cholesterol levels eight weeks after starting treatment (MD 0.35, 95% CI 0.27 to 0.43; one study with 112 participants). There was moderate certainty evidence suggesting no difference between the use of metformin and placebo for the outcomes of drop-outs from care (RR 1.22, 95% CI 0.09 to 16.35; three studies with 158 participants). There was moderate-to-high certainty evidence of no difference between metformin and placebo for fasting blood glucose levels (endpoint data: MD -0.35, 95% CI -0.60 to -0.11; change from baseline data: MD 0.01, 95% CI -0.21 to 0.22; five studies with 264 participants). There was high certainty evidence that BMI was lower for participants receiving metformin compared with those receiving a placebo (MD -1.37, 95% CI -2.04 to -0.70; five studies with 264 participants; high certainty of evidence). There was no difference between metformin and placebo for the outcomes of waist circumference, blood pressure and cholesterol levels. Low-certainty evidence from one study (48 participants) suggests there may be no difference between the use of melatonin and placebo for the outcome of drop-outs from care (RR 1.00, 95% CI 0.38 to 2.66). Fasting blood glucose is probably reduced more in participants treated with melatonin compared with placebo (endpoint data: MD -0.17, 95% CI -0.35 to 0.01; change from baseline data: MD -0.24, 95% CI -0.39 to -0.09; three studies with 202 participants, moderate-certainty evidence). There was no difference between melatonin and placebo for the outcomes of waist circumference, blood pressure and cholesterol levels. Very low-certainty evidence from one study (25 participants) suggests that drop-outs may be higher in participants treated with a tricyclic antidepressant (TCA) compared with those receiving a selective serotonin reuptake inhibitor (SSRI) (RR 0.34, 95% CI 0.11 to 1.01). It is uncertain if there is no difference in fasting blood glucose levels between these groups (MD -0.39, 95% CI -0.88 to 0.10; three studies with 141 participants, moderate-certainty evidence). It is uncertain if there is no difference in BMI and depression between the TCA and SSRI antidepressant groups. AUTHORS' CONCLUSIONS: Only one study reported data on our primary outcome of interest, providing low-certainty evidence that there may be no difference in risk between atypical and typical antipsychotics for the outcome of developing type 2 diabetes. We are therefore not able to draw conclusions on the prevention of type 2 diabetes in people with mental disorders in LMICs. For studies reporting on secondary outcomes, there was evidence of risk of bias in the results. There is a need for further studies with participants from LMICs with mental disorders, particularly on behaviour change and on organisational interventions targeting prevention of type 2 diabetes in these populations.

Effect of Ramadan fasting on glucose level, lipid profile, HbA1c and uric acid among medical students in Karachi, Pakistan.

To assess the effect of Ramadan fasting on blood pressure, fasting glucose, lipid profile, uric acid, HbA1c, body mass index, body adiposity index and visceral adiposity index among fasting medical students, 35 students were recorded before, during and after Ramadan (August) 2011, for their blood pressure, anthropometric measurements, questionnaire response and blood sample. A blood sample was taken at each visit for glucose, lipid profile and HbA1c. Total physical activity, weight-to-height ratio, body adiposity index and visceral adiposity index were calculated for insulin sensitivity. Changes in anthropometric measurements were not statistically significant. However, physical activities increased significantly after Ramadan. Changes in blood pressure, fasting blood sugar, total cholesterol, HbA1c, uric acid and triglyceride were not statistically significant. Mean high density lipoprotein decreased significantly in Ramadan, while low density lipoprotein increased significantly.

Association Of Smoking With Recurrence Of Pulmonary Kochs; After Completion Of Antituberculous Treatment.

BACKGROUND: Smoking is one of the most important yet modifiable risk factors for incidence, morbidity, recurrence and mortality from Pulmonary Koch's or tuberculosis. This study attempted to demonstrate the association between smoking and recurrence risk of Pulmonary Koch's in Pakistani male population. METHODS: This case control study was conducted at Federal Government Tuberculosis Hospital, Rawalpindi from 2015 to 2016. It included 332 study participants; 166 recurrent cases of Pulmonary Tuberculosis within two years of completion of Anti-tuberculous therapy (ATT) and 166 non-recurrent controls. Smoking status of all study participants was assessed. RESULTS: Amongst 166 cases of recurrence, 75 (63.6%) had continued smoking after ATT compared to 43 (36.4%) controls who continued smoking (p-value 0.00, OR=2.35, 95% CI=1.48 to 3.74, NNH=4.75). Highly statistically significant associations of recurrence were observed with smoking>10 years (p-value 0.00, OR=3.67, CI=1.55-8.71 NNH=4.75) and if ever smoked in life (p-value 0.00, OR=2.05, CI=1.32-3.19, NNH=5.61). Mean duration of smoking in cases (12.37±8.72 years) was statistically different from controls (9.54±7.01 years), with p-value of 0.04. CONCLUSIONS: There is strong association of recurrence of Pulmonary Kochs with continuation of smoking within 2 years of completion of ATT, with ever smoking in life and smoking >10 years in life.

Sofosbuvir For The Treatment Of Hepatitis C Genotype 3 Infected Patients In Pakistan.

BACKGROUND: This study was conducted to determine the viral responses of patients with chronic infection of Hepatitis C virus treated with sofubuvir. METHODS: This Quasi experimental study was conducted at Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi from September 2014 to September 2016. 502 patients with HCV genotype 3 including treatment naive, non-responders or relapsers to previous interferon based therapy along with patients having decompensated cirrhosis (child class B or C) were included in the study. All patients were treated with Sofosbuvir 400 mg once daily along with Ribavirin for 6 months. Follow-up qualitative PCR (polymerase Chain Reaction) were performed at 4 weeks interval to assess RVR (Rapid virological Response), end of treatment to determine ETR (End of treatment response) and 3 months post treatment to determine SVR12 (Sustained viral response at 12 week). RESULTS: 91% of the patients had become PCR negative at completion of four weeks of treatment with Sofosbuvir, whereas at completion of treatment 96.5% had attained a negative PCR. Sustained virological response at 12 weeks post therapy (SVR12) was attained in 85.5% of patients. No statistically significant associations were found with attainment status of RVR, ETR and SVR based on previous treatment status or presence of Decompensated liver disease. However, attainment of SVR was slightly more in females (p value=0.03). The serological profiles of patients whether they attained PCR at week 4, 24 of treatment or 12 weeks' post treatment did not exhibit any statistically significant difference. CONCLUSION: Sofosbuvir is effective in eradicating hepatitis C virus irrespective of previous treatment or liver fibrosis status in genotype 3 HCV Pakistani patients.

Diagnosis, Management And Prevention Of Hepatitis C In Pakistan 2017.

AIMS AND OBJECTIVES: Since the advent of direct acting antiviral agents, there is a revolutionary change in the management of HCV infection. Newer drugs with different mechanism of action are being introduced and are expected to be available in coming few months in Pakistan as well. The main purpose of the guideline is to review and induct the latest research in field of HCV infection in Pakistani perspective so that our healthcare professionals can apply the new recommendations in timely and judicial manner. Target groups of guidelines are general physicians treating hepatitis C, hepatologists and gastroenterologists. Other beneficiaries of these guidelines are public health institutions of Pakistan, which provide free treatment to deserving patients under National Hepatitis Prevention and Control Program and Pakistan Bait-ul- Mal Program. METHODOLOGY: These guidelines are based on the review of National consensus practice guidelines: Diagnosis, Management and Prevention of Hepatitis C Pakistan 2009. Published data in National and International Journals searched with the help of Google search and pub med, and 2015-16 guidelines of HCV by AASLD, EASL, APASL and WHO. Local studies are preferably added with references to enhance the Pakistani perspective. Evidence was also taken from published studies. Recommendations have been based upon evidence from national publications on the subject and scientific presentations at national liver meeting as well from experts' personal experience and opinion.

Living with depression and diabetes: A qualitative study in Bangladesh and Pakistan.

Diabetes and depression are both serious health conditions. While their relationship is bidirectional and each condition adversely affects outcomes for the other, they are treated separately. In low and middle income countries, such as Bangladesh and Pakistan, health systems are already stretched and the integration of diabetes and depression care is rarely a priority. Within this context through interviews with patients, healthcare workers and policy makers the study explored: lived experiences of people living with depression and diabetes, current practice in mental health and diabetes care and barriers and perspectives on integrating a brief psychological therapy into diabetes care. The findings of the study included: differing patient and practitioner understandings of distress/depression, high levels of stigma for mental health and a lack of awareness and training on treating depression. While it was apparent there is a need for more holistic care and the concept of a brief psychological intervention appeared acceptable to participants, many logistical barriers to integrating a mental health intervention into diabetes care were identified. The study highlights the importance of context and of recognising drivers and understandings of distress when planning for more integrated mental and physical health services, and specifically when adapting and implementing a new intervention into existing services.

Identification and analyses of exonic and copy number variants in spastic paraplegia.

Hereditary spastic paraplegias are a diverse group of degenerative disorders that are clinically categorized as isolated; with involvement of lower limb spasticity, or symptomatic, where spastic paraplegia is complicated by further neurological features. We sought to identify the underlying genetic causes of these disorders in the participating patients. Three consanguineous families with multiple affected members were identified by visiting special schools in the Punjab Province. DNA was extracted from blood samples of the participants. Exome sequencing was performed for selected patients from the three families, and the data were filtered to identify rare homozygous variants. ExomeDepth was used for the delineation of the copy number variants. All patients had varying degrees of intellectual disabilities, poor speech development, spasticity, a wide-based gait or an inability to walk and hypertonia. In family RDHR07, a homozygous deletion involving multiple exons and introns of SPG11 (NC000015.9:g.44894055_449028del) was found and correlated with the phenotype of the patients who had spasticity and other complex movement disorders, but not those who exhibited ataxic or indeterminate symptoms as well. In families ANMD03 and RDFA06, a nonsense variant, c.985C > T;(p.Arg329Ter) in DDHD2 and a frameshift insertion‒deletion variant of AP4B1, c.965-967delACTinsC;p.(Tyr322SerfsTer14), were identified which were homozygous in the patients while the obligate carriers in the respective pedigrees were heterozygous. All variants were ultra-rare with none, or very few carriers identified in the public databases. The three loss of function variants are likely to cause nonsense-mediated decay of the respective transcripts. Our research adds to the genetic variability associated with the SPG11 and AP4B1 variants and emphasizes the genetic heterogeneity of hereditary spastic paraplegia.

Health-related quality of life and medication adherence of people living with epilepsy in Pakistan: A cross-sectional study.

INTRODUCTION: The primary purpose of this study was to determine adherence and health-related quality of life (HRQoL) in PWE. Secondary aims were to assess association between adherence and HRQoL and determine predictors of HRQoL in PWE in Pakistan. METHODS: A descriptive cross-sectional study was conducted among PWE receiving treatment from two tertiary care hospitals of Pakistan. The HRQoL and adherence were assessed with Urdu versions of Quality of Life in Epilepsy-31 (QOLIE-31), and Medication Adherence Rating Scale (MARS). Relationship between HRQoL and adherence was assessed by Pearson's product-moment correlation coefficient. Forced entry multiple linear models were used to determine relationship of independent variables with HRQoL. RESULTS: 219 PWE with a mean (±standard deviation) age, 34.18 (± 13.710) years, participated in this study. The overall weighted mean HRQoL score was (51.60 ± 17.10), and mean score for adherence was 6.17 (± 2.31). There was significant association between adherence and HRQoL in PWE (Pearson's correlation = 0.820-0.930; p ≤ .0001). Multiple linear regression found adherence (B = 16.8; p ≤ .0001), male gender (B = 10.0; p = .001), employment status (employed: B = 7.50; p = .030), level of education (Tertiary: B = 0.910; p = .010), duration of epilepsy (>10 years: B = -0.700; p ≤ .0001), and age (≥46 years: B = -0.680; p ≤ .0001), and ASM therapy (polypharmacy: B = 0.430; p = .010) as independent predictors of HRQoL in PWE from Pakistan. CONCLUSIONS: The findings suggest PWE from our center have suboptimal adherence which affects HRQoL. Independent factors such as male gender, employment status and duration of epilepsy are predictors of HRQoL.

Genome Sequencing of Consanguineous Family Implicates Ubiquitin-Specific Protease 53 (USP53) Variant in Psychosis/Schizophrenia: Wild-Type Expression in Murine Hippocampal CA 1-3 and Granular Dentate with AMPA Synapse Interactions.

Psychosis is a severe mental disorder characterized by abnormal thoughts and perceptions (e.g., hallucinations) occurring quintessentially in schizophrenia and in several other neuropsychiatric disorders. Schizophrenia is widely considered as a neurodevelopmental disorder that onsets during teenage/early adulthood. A multiplex consanguineous Pakistani family was afflicted with severe psychosis and apparent autosomal recessive transmission. The first-cousin parents and five children were healthy, whereas two teenage daughters were severely affected. Structured interviews confirmed the diagnosis of DSM-V schizophrenia. Probands and father underwent next-generation sequencing. All available relatives were subjected to confirmatory Sanger sequencing. Homozygosity mapping and directed a priori filtering identified only one rare variant [MAF < 5(10)-5] at a residue conserved across vertebrates. The variant was a non-catalytic deubiquitinase, USP53 (p.Cys228Arg), predicted in silico as damaging. Genome sequencing did not identify any other potentially pathogenic single nucleotide variant or structural variant. Since the literature on USP53 lacked relevance to mental illness or CNS expression, studies were conducted which revealed USP53 localization in regions of the hippocampus (CA 1-3) and granular dentate. The staining pattern was like that seen with GRIA2/GluA2 and GRIP2 antibodies. All three proteins coimmunoprecipitated. These findings support the glutamate hypothesis of schizophrenia as part of the AMPA-R interactome. If confirmed, USP53 appears to be one of the few Mendelian variants potentially causal to a common-appearing mental disorder that is a rare genetic form of schizophrenia.

Correction: Addressing TB multimorbidity in policy and practice: An exploratory survey of TB providers in 27 high-TB burden countries.

[This corrects the article DOI: 10.1371/journal.pgph.0001205.].

Prevalence of physical health conditions and health risk behaviours in people with severe mental illness in South Asia: multi-country cross-sectional survey.

BACKGROUND: People with severe mental illness (SMI) die earlier than the general population, primarily because of physical disorders. AIMS: We estimated the prevalence of physical health conditions, health risk behaviours, access to healthcare and health risk modification advice in people with SMI in Bangladesh, India and Pakistan, and compared results with the general population. METHOD: We conducted a cross-sectional survey in adults with SMI attending mental hospitals in Bangladesh, India and Pakistan. Data were collected on non-communicable diseases, their risk factors, health risk behaviours, treatments, health risk modification advice, common mental disorders, health-related quality of life and infectious diseases. We performed a descriptive analysis and compared our findings with the general population in the World Health Organization (WHO) 'STEPwise Approach to Surveillance of NCDs' reports. RESULTS: We recruited 3989 participants with SMI, of which 11% had diabetes, 23.3% had hypertension or high blood pressure and 46.3% had overweight or obesity. We found that 70.8% of participants with diabetes, high blood pressure and hypercholesterolemia were previously undiagnosed; of those diagnosed, only around half were receiving treatment. A total of 47% of men and 14% of women used tobacco; 45.6% and 89.1% of participants did not meet WHO recommendations for physical activity and fruit and vegetable intake, respectively. Compared with the general population, people with SMI were more likely to have diabetes, hypercholesterolemia and overweight or obesity, and less likely to receive tobacco cessation and weight management advice. CONCLUSIONS: We found significant gaps in detection, prevention and treatment of non-communicable diseases and their risk factors in people with SMI.

Tobacco use in people with severe mental illness: Findings from a multi-country survey of mental health institutions in South Asia.

INTRODUCTION: People with severe mental illness (SMI) tend to die early due to cardiovascular and respiratory diseases, which may be linked to tobacco use. There is limited information on tobacco use in people with SMI in low- and middle-income countries where most tobacco users reside. We present novel data on tobacco use in people with SMI and their access to tobacco cessation advice in South Asia. METHODS: We conducted a multi-country survey of adults with SMI attending mental health facilities in Bangladesh, India, and Pakistan. Using data collected with a standardized WHO STEPS survey tool, we estimated the prevalence and distribution of tobacco use and assessed receipt of tobacco cessation advice. RESULTS: We recruited 3874 participants with SMI; 46.8% and 15.0% of men and women consumed tobacco, respectively. Smoking prevalence in men varied by country (Bangladesh 42.8%, India 20.1% and Pakistan 31.7%); <4% of women reported smoking in each country. Smokeless tobacco use in men also varied by country (Bangladesh 16.2%, India 18.2% and Pakistan 40.8%); for women, it was higher in Bangladesh (19.1%), but similar in India (9.9%) and Pakistan (9.1%). Just over a third of tobacco users (38.4%) had received advice to quit tobacco. Among smokers, 29.1% (n=244) made at least one quit attempt in the past year. There was strong evidence for the association between tobacco use and the severity of depression (OR=1.29; 95% CI: 1.12-1.48) and anxiety (OR=1.29; 95% CI: 1.12-1.49). CONCLUSIONS: As observed in high-income countries, we found higher tobacco use in people with SMI, particularly in men compared with rates reported for the general population in South Asia. Tobacco cessation support within mental health services offers an opportunity to close the gap in life expectancy between SMI and the general population. STUDY REGISTRATION: ISRCTN88485933; https://doi.org/10.1186/ISRCTN88485933 39.

IMPACT smoking cessation support for people with severe mental illness in South Asia (IMPACT 4S): A protocol for a randomised controlled feasibility trial of a combined behavioural and pharmacological support intervention.

INTRODUCTION: The prevalence of smoking is high among people living with severe mental illness (SMI). Evidence on feasibility, acceptability and effectiveness of smoking cessation interventions among smokers with SMI is lacking, particularly in low- and middle-income countries. We aim to test the feasibility and acceptability of delivering an evidence-based intervention,i.e., the IMPACT smoking cessation support for people with severe mental illness in South Asia (IMPACT 4S) intervention that is a combination of behavioural support and smoking cessation pharmacotherapies among adult smokers with SMI in India and Pakistan. We will also test the feasibility and acceptability of evaluating the intervention in a randomised controlled trial. METHODS: We will conduct a parallel, open label, randomised controlled feasibility trial among 172 (86 in each country) adult smokers with SMI in India and Pakistan. Participants will be allocated 1:1 to either Brief Advice (BA) or the IMPACT 4S intervention. BA comprises a single five-minute BA session on stopping smoking. The IMPACT 4S intervention comprises behavioural support delivered in upto 15 one-to-one, face-to-face or audio/video, counselling sessions, with each session lasting between 15 and 40 minutes; nicotine gum and/or bupropion; and breath carbon monoxide monitoring and feedback. Outcomes are recruitment rates, reasons for ineligibility/non-participation/non-consent of participants, length of time required to achieve required sample size, retention in study and treatments, intervention fidelity during delivery, smoking cessation pharmacotherapy adherence and data completeness. We will also conduct a process evaluation. RESULTS: Study will address- uncertainty about feasibility and acceptability of delivering smoking cessation interventions, and ability to conduct smoking cessation trials, among adult smokers with SMI in low- and middle-income countries. CONCLUSIONS: This is to inform further intervention adaptation, and the design and conduct of future randomised controlled trials on this topic. Results will be disseminated through peer-review articles, presentations at national, international conferences and policy-engagement forums. TRIAL REGISTRATION: ISRCTN34399445 (Updated 22/03/2021), ISRCTN Registry https://www.isrctn.com/.

Effectiveness of interventions to address obesity and health risk behaviours among people with severe mental illness in low- and middle-income countries (LMICs): a systematic review and meta analysis.

Introduction: People with severe mental illness (SMI) are more likely to have obesity and engage in health risk behaviours than the general population. The aims of this study are (1) evaluate the effectiveness of interventions that focus on body weight, smoking cessation, improving sleeping patterns, and alcohol and illicit substance abuse; (2) Compare the number of interventions addressing body weight and health risk behaviours in low- and middle-income countries (LMICs) v. those reported in published systematic reviews focusing on high-income countries (HICs). Methods: Intervention studies published up to December 2020 were identified through a structured search in the following database; OVID MEDLINE (1946-December 2020), EMBASE (1974-December 2020), CINAHL (1975-2020), APA PsychoINFO (1806-2020). Two authors independently selected studies, extracted study characteristics and data and assessed the risk of bias. and risk of bias was assessed using the Cochrane risk of bias tool V2. We conducted a narrative synthesis and, in the studies evaluating the effectiveness of interventions to address body weight, we conducted random-effects meta-analysis of mean differences in weight gain. We did a systematic search of systematic reviews looking at cardiometabolic and health risk behaviours in people with SMI. We compared the number of available studies of LMICs with those of HICs. Results: We assessed 15 657 records, of which 9 met the study inclusion criteria. Six focused on healthy weight management, one on sleeping patterns and two tested a physical activity intervention to improve quality of life. Interventions to reduce weight in people with SMI are effective, with a pooled mean difference of -4.2 kg (95% CI -6.25 to -2.18, 9 studies, 459 participants, I 2 = 37.8%). The quality and sample size of the studies was not optimal, most were small studies, with inadequate power to evaluate the primary outcome. Only two were assessed as high quality (i.e. scored 'low' in the overall risk of bias assessment). We found 5 reviews assessing the effectiveness of interventions to reduce weight, perform physical activity and address smoking in people with SMI. From the five systematic reviews, we identified 84 unique studies, of which only 6 were performed in LMICs. Conclusion: Pharmacological and activity-based interventions are effective to maintain and reduce body weight in people with SMI. There was a very limited number of interventions addressing sleep and physical activity and no interventions addressing smoking, alcohol or harmful drug use. There is a need to test the feasibility and cost-effectiveness of context-appropriate interventions to address health risk behaviours that might help reduce the mortality gap in people with SMI in LMICs.

Molecular Characterization of Toxoplasma gondii in Cats and Its Zoonotic Potential for Public Health Significance.

Toxoplasmosis is a globally distributed disease of warm-blooded animals. It is caused by the opportunistic parasite Toxoplasma gondii (T. gondii). One-third of the global human population is believed to be infected with T. gondii. Cats serve as final host of T. gondii and are the main source of contamination of soil and water. This study aimed to detect genotypes of T. gondii in cats. Fecal samples (n = 400) were collected from districts of South Punjab (Khanewal and Sahiwal), and were processed by polymerase chain reaction (PCR) followed by sequencing and phylogenetic analysis. The obtained oligonucleotide sequences (T. gondii) were submitted to the GenBank database, and the evolutionary tree was constructed using MEGA-X software. Seven fecal samples (3.5%) from cats were positive. Five out of thirteen fecal samples (38.46%) found to be positive for T. gondii with microscopy were confirmed by PCR. After phylogenetic analysis with 3 clonal types and atypical strains, isolates of T. gondii in current study were more closely linked to a typical strain (AF249696). Besides genotyping from cats, seroprevalence from humans and ruminants is still considered to be the best and easiest way to identify the Toxoplasma. Blood samples were collected from sheep and goats (n = 2000 each), and human blood samples (n = 400) were collected from the same vicinity. Seroprevalence was determined using a commercial enzyme-linked immunosorbent assay (ELISA) kit. In Khanewal, the blood samples of 292 goats (29.2%) and 265 sheep (26.5%), and 6 fecal samples from cats (3%) were positive. Out of 200 human blood samples, 52 were positive, with a seroprevalence of 26%. In the Sahiwal district, the blood samples from 49 humans, 235 sheep and 348 goats were positive, with seroprevalence of 24.5%, 23.5% and 34.8%, respectively. The present study revealed the current circulating genotype of T. gondii from cats in the districts Khanewal and Sahiwal and the seroprevalence of the organism in small ruminants and humans living in the same vicinity. Further genotype analyses of the organism from ruminants and humans are needed.

Knowledge and Response to the COVID-19 Pandemic in People With Severe Mental Illness in Bangladesh and Pakistan: A Cross-Sectional Survey.

BACKGROUND: People with severe mental illnesses (SMIs) are likely to face disproportionate challenges during a pandemic. They may not receive or be able to respond to public health messages to prevent infection or to limit its spread. Additionally, they may be more severely affected, particularly in low- and middle-income countries. METHODS: We conducted a telephone survey (May-June 2020) in a sample of 1,299 people with SMI who had attended national mental health institutes in Bangladesh and Pakistan before the pandemic. We collected information on top worries, socioeconomic impact of the pandemic, knowledge of COVID-19 (symptoms, prevention), and prevention-related practices (social distancing, hygiene). We explored the predictive value of socio-demographic and health-related variables for relative levels of COVID-19 knowledge and practice using regularized logistic regression models. FINDINGS: Mass media were the major source of information about COVID-19. Finances, employment, and physical health were the most frequently mentioned concerns. Overall, participants reported good knowledge and following advice. In Bangladesh, being female and higher levels of health-related quality of life (HRQoL) predicted poor and better knowledge, respectively, while in Pakistan being female predicted better knowledge. Receiving information from television predicted better knowledge in both countries. In Bangladesh, being female, accessing information from multiple media sources, and better HRQoL predicted better practice. In Pakistan, poorer knowledge of COVID-19 prevention measures predicted poorer practice. CONCLUSION: Our paper adds to the literature on people living with SMIs and their knowledge and practices relevant to COVID-19 prevention. Our results emphasize the importance of access to mass and social media for the dissemination of advice and that the likely gendered uptake of both knowledge and practice requires further attention.

Addressing TB multimorbidity in policy and practice: An exploratory survey of TB providers in 27 high-TB burden countries.

In people with TB, co-existence of long-term conditions (e.g., depression, diabetes and HIV) and risk factors (e.g.,alcohol misuse, malnutrition, and smoking) are associated with increased mortality and poor treatment outcomes including delayed recovery, TB treatment failure and relapse. However, it is unclear as to what extent these comorbidities are addressed in TB policy and practice. Between August and October 2021, we conducted an online cross-sectional survey in high-TB burden countries. We recruited a purposive sample of TB health workers, managers, policy makers, advisors and advocates from these countries. The survey enquired about the extent to which various comorbid conditions are: (a) mentioned in TB policies, plans, and guidelines; (b) screened, diagnosed, treated or referred to specialist services by TB healthcare workers. We summarised using descriptive analysis. Of the 1100 potential respondents contacted in 33 countries, 543 responded but only 446 (41%) from 27 countries provided sufficient data for inclusion in the study. We found no notable differences between these providing insufficient data and those completing the survey. HIV, diabetes mellitus, depression and tobacco and alcohol use disorders were identified as the most common and concerning comorbid conditions in TB. HIV was screened for and managed by TB services in most countries. Screening for diabetes and/or tobacco and alcohol use disorders was offered by almost half of all TB services but only a few offered relevant treatments. Depression was rarely screened for, almost never treated, and only infrequently referred to specialist services. Most respondents felt confident in screening/diagnosing these comorbid conditions but not in treating these conditions. With the exception of HIV, chronic comorbid conditions are only partially screened for and rarely managed within TB services. Mental health conditions are for the most part neglected. Given their adverse impact on TB outcomes, integrating screening and management of these comorbidities within TB programmes offers a significant opportunity to meet TB targets, address non-communicable diseases and improve patient well-being.