The Cotton Plant.

This essay describes the author's experience when her father had cardiac arrest.

Evaluation of bone mineral density (BMD) and trabecular bone score (TBS) in pheochromocytoma and paraganglioma; a multi-centric case-control study from India.

Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) due to excess sympathetic system stimulation. Our study revealed low BMD and TBS (trabecular bone score) in cases compared to matched controls. Plasma-free nor-metanephrine and hypertension duration found to be most consistent predictive factors. PURPOSE: Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) and increased fracture risks. Sympathetic nervous system stimulation has been shown to increase bone resorption and decrease bone formation via ß2 receptors. Chronic inflammation and increased cytokine production add to more bone loss. TBS (trabecular bone score) is an established surrogate marker for bone histomorphometry. BMD and TBS data in pheochromocytoma and PPGL are scarce. The aim was to assess the BMD and TBS in pheochromocytoma and PPGL and look for clinical and biochemical predictors. METHODS: This case-control study had sample size of 58 (29 cases and controls each). BMI-, age-, and sex-matched controls were taken for comparison. Both cases and controls had undergone DXA scan and BMD {Z-scores and bone mineral concentration (BMC) in g/cm2} and TBS were analyzed. Detailed clinical histories and relevant biochemistry values were noted. RESULTS: The mean age of our case population was 29.5 ± 9.4 years with a mean age of HTN onset at 26.86 ± 6.6 years. Lumbar spine BMC (0.86 ± 0.14 vs 0.96 ± 0.15; p = 0.036), femoral neck Z-score (- 1.23 ± 1.07 vs - 0.75 ± 0.97; p = 0.003), and whole body BMC (0.91 ± 0.14 vs 1.07 ± 0.11; p = 0.000) were significantly low in cases compared to controls. Similarly, TBS was significantly lower in cases compared to controls (1.306 ± 0.113 vs 1.376 ± 0.083; p = 0.001). CONCLUSION: This study establishes both low bone mass and poor bone quality in an Indian pheochromocytoma and PPGL patient's cohort. Plasma-free nor-metanephrine and duration of hypertension were found to be most consistent predictive factors in multivariate regression analysis.

Internet and Telephone Support for Discontinuing Long-Term Antidepressants: The REDUCE Cluster Randomized Trial.

Importance: There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. Objective: To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practitioner review alone. Design, Setting, and Participants: In this cluster randomized clinical trial, 131 UK family practices were randomized between December 1, 2018, and March 31, 2022, with remote computerized allocation and 12 months of follow-up. Participants and researchers were aware of allocation, but analysis was blind. Participants were adults who were receiving antidepressants for more than 1 year for a first episode of depression or more than 2 years for recurrent depression who were currently well enough to consider discontinuation and wished to do so and who were at low risk of relapse. Of 6725 patients mailed invitations, 330 (4.9%) were eligible and consented. Interventions: Internet and telephone self-management support, codesigned and coproduced with patients and practitioners. Main Outcomes and Measures: The primary (safety) outcome was depression at 6 months (prespecified complete-case analysis), testing for noninferiority of the intervention to under 2 points on the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes (testing for superiority) were antidepressant discontinuation, anxiety, quality of life, antidepressant withdrawal symptoms, mental well-being, enablement, satisfaction, use of health care services, and adverse events. Analyses for the main outcomes were performed on a complete-case basis, and multiple imputation sensitivity analysis was performed on an intention-to-treat basis. Results: Of 330 participants recruited (325 eligible for inclusion; 178 in intervention practices and 147 in control practices; mean [SD] age at baseline, 54.0 [14.9] years; 223 women [68.6%]), 276 (83.6%) were followed up at 6 months, and 240 (72.7%) at 12 months. The intervention proved noninferior; mean (SD) PHQ-9 scores at 6 months were slightly lower in the intervention arm than in the control arm in the complete-case analysis (4.0 [4.3] vs 5.0 [4.7]; adjusted difference, -1.1; 95% CI, -2.1 to -0.1; P = .03) but not significantly different in an intention-to-treat multiple imputation sensitivity analysis (adjusted difference, -0.9 (95% CI, -1.9 to 0.1; P = .08). By 6 months, antidepressants had been discontinued by 66 of 145 intervention arm participants (45.5%) who provided discontinuation data and 54 of 129 control arm participants (41.9%) (adjusted odds ratio, 1.02; 95% CI, 0.52-1.99; P = .96). In the intervention arm, antidepressant withdrawal symptoms were less severe, and mental well-being was better compared with the control arm; differences were small but significant. There were no significant differences in the other outcomes; 28 of 179 intervention arm participants (15.6%) and 22 of 151 control arm participants (14.6%) experienced adverse events. Conclusions and Relevance: In this cluster randomized clinical trial of adding internet and telephone support to a practitioner review for possible antidepressant discontinuation, depression was slightly better with support, but the rate of discontinuation of antidepressants did not significantly increase. Improvements in antidepressant withdrawal symptoms and mental well-being were also small. There were no significant harms. Family practitioner review for possible discontinuation of antidepressants appeared safe and effective for more than 40% of patients willing and well enough to discontinue. Trial Registration: ISRCTN registry Identifiers: ISRCTN15036829 (internal pilot trial) and ISRCTN12417565 (main trial).

Patient-reported outcome measures for monitoring primary care patients with depression: the PROMDEP cluster RCT and economic evaluation.

Background: Guidelines on the management of depression recommend that practitioners use patient-reported outcome measures for the follow-up monitoring of symptoms, but there is a lack of evidence of benefit in terms of patient outcomes. Objective: To test using the Patient Health Questionnaire-9 questionnaire as a patient-reported outcome measure for monitoring depression, training practitioners in interpreting scores and giving patients feedback. Design: Parallel-group, cluster-randomised superiority trial; 1 : 1 allocation to intervention and control. Setting: UK primary care (141 group general practices in England and Wales). Inclusion criteria: Patients aged ≥ 18 years with a new episode of depressive disorder or symptoms, recruited mainly through medical record searches, plus opportunistically in consultations. Exclusions: Current depression treatment, dementia, psychosis, substance misuse and risk of suicide. Intervention: Administration of the Patient Health Questionnaire-9 questionnaire with patient feedback soon after diagnosis, and at follow-up 10-35 days later, compared with usual care. Primary outcome: Beck Depression Inventory, 2nd edition, symptom scores at 12 weeks. Secondary outcomes: Beck Depression Inventory, 2nd edition, scores at 26 weeks; antidepressant drug treatment and mental health service contacts; social functioning (Work and Social Adjustment Scale) and quality of life (EuroQol 5-Dimension, five-level) at 12 and 26 weeks; service use over 26 weeks to calculate NHS costs; patient satisfaction at 26 weeks (Medical Informant Satisfaction Scale); and adverse events. Sample size: The original target sample of 676 patients recruited was reduced to 554 due to finding a significant correlation between baseline and follow-up values for the primary outcome measure. Randomisation: Remote computerised randomisation with minimisation by recruiting university, small/large practice and urban/rural location. Blinding: Blinding of participants was impossible given the open cluster design, but self-report outcome measures prevented observer bias. Analysis was blind to allocation. Analysis: Linear mixed models were used, adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering including practice as random effect. Quality of life and costs were analysed over 26 weeks. Qualitative interviews: Practitioner and patient interviews were conducted to reflect on trial processes and use of the Patient Health Questionnaire-9 using the Normalization Process Theory framework. Results: Three hundred and two patients were recruited in intervention arm practices and 227 patients were recruited in control practices. Primary outcome data were collected for 252 (83.4%) and 195 (85.9%), respectively. No significant difference in Beck Depression Inventory, 2nd edition, score was found at 12 weeks (adjusted mean difference -0.46, 95% confidence interval -2.16 to 1.26). Nor were significant differences found in Beck Depression Inventory, 2nd Edition, score at 26 weeks, social functioning, patient satisfaction or adverse events. EuroQol-5 Dimensions, five-level version, quality-of-life scores favoured the intervention arm at 26 weeks (adjusted mean difference 0.053, 95% confidence interval 0.013 to 0.093). However, quality-adjusted life-years over 26 weeks were not significantly greater (difference 0.0013, 95% confidence interval -0.0157 to 0.0182). Costs were lower in the intervention arm but, again, not significantly (-£163, 95% confidence interval -£349 to £28). Cost-effectiveness and cost-utility analyses, therefore, suggested that the intervention was dominant over usual care, but with considerable uncertainty around the point estimates. Patients valued using the Patient Health Questionnaire-9 to compare scores at baseline and follow-up, whereas practitioner views were more mixed, with some considering it too time-consuming. Conclusions: We found no evidence of improved depression management or outcome at 12 weeks from using the Patient Health Questionnaire-9, but patients' quality of life was better at 26 weeks, perhaps because feedback of Patient Health Questionnaire-9 scores increased their awareness of improvement in their depression and reduced their anxiety. Further research in primary care should evaluate patient-reported outcome measures including anxiety symptoms, administered remotely, with algorithms delivering clear recommendations for changes in treatment. Study registration: This study is registered as IRAS250225 and ISRCTN17299295. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/42/02) and is published in full in Health Technology Assessment; Vol. 28, No. 17. See the NIHR Funding and Awards website for further award information.

Depression is common, can be disabling and costs the nation billions. The National Health Service recommends general practitioners who treat people with depression use symptom questionnaires to help assess whether those people are getting better over time. A symptom questionnaire is one type of patient-reported outcome measure. Patient-reported outcome measures appear to benefit people having therapy and mental health care, but this approach has not been tested thoroughly in general practice. Most people with depression are treated in general practice, so it is important to test patient-reported outcome measures there, too. In this study, we tested whether using a patient-reported outcome measure helps people with depression get better more quickly. The study was a 'randomised controlled trial' in general practices, split into two groups. In one group, people with depression completed the Patient Health Questionnaire, or 'PHQ-9', patient-reported outcome measure, which measures nine symptoms of depression. In the other group, people with depression were treated as usual without the Patient Health Questionnaire-9. We fed the results of the Patient Health Questionnaire-9 back to the people with depression themselves to show them how severe their depression was and asked them to discuss the results with the practitioners looking after them. We found no differences between the patient-reported outcome measure group and the control group in their level of depression; their work or social life; their satisfaction with care from their practice; or their use of medicines, therapy or specialist care for depression. However, we did find that their quality of life was improved at 6 months, and the costs of the National Health Service services they used were lower. Using the Patient Health Questionnaire-9 can improve patients' quality of life, perhaps by making them more aware of improvement in their depression symptoms, and less anxious as a result. Future research should test using a patient-reported outcome measure that includes anxiety and processing the answers through a computer to give practitioners clearer advice on possible changes to treatment for depression.

Efficacy of Early Intervention for Infants With Cerebral Palsy in an LMIC: An RCT.

OBJECTIVE: To test efficacy of a parent-delivered multidomain early intervention (Learning through Everyday Activities with Parents [LEAP-CP]) for infants with cerebral palsy (CP) compared with equal-dose of health advice (HA), on (1) infant development; and (2) caregiver mental health. It was hypothesized that infants receiving LEAP-CP would have better motor function, and caregivers better mental health. METHODS: This was a multisite single-blind randomized control trial of infants aged 12 to 40 weeks corrected age (CA) at risk for CP (General Movements or Hammersmith Infant Neurologic Examination). Both LEAP-CP and HA groups received 15 fortnightly home-visits by a peer trainer. LEAP-CP is a multidomain active goal-directed intervention. HA is based on Key Family Practices, World Health Organization. Primary outcomes: (1) infants at 18 months CA: Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT mobility); and (2) caregiver: Depression Anxiety and Stress Scale. RESULTS: Of eligible infants, 153 of 165 (92.7%) were recruited (86 males, mean age 7.1±2.7 months CA, Gross Motor Function Classification System at 18 m CA: I = 12, II = 25, III = 9, IV = 18, V = 32). Final data were available for 118 (77.1%). Primary (PEDI-CAT mobility mean difference = 0.8 (95% CI -1.9 to 3.6) P = .54) and secondary outcomes were similar between-groups. Modified-Intention-To-Treat analysis on n = 96 infants with confirmed CP showed Gross Motor Function Classification System I and IIs allocated to LEAP-CP had significantly better scores on PEDI-CAT mobility domain (mean difference 4.0 (95% CI = 1.4 to 6.5), P = .003) compared with HA. CONCLUSIONS: Although there was no overall effect of LEAP-CP compared with dose-matched HA, LEAP-CP lead to superior improvements in motor skills in ambulant children with CP, consistent with what is known about targeted goal-directed training.

Frequency of Maternal Anemia in Patients Presenting With Preterm Premature Rupture of Membranes.

BACKGROUND: Preterm premature rupture of membranes (PPROM) is the rupture of fetal membranes before 38 weeks of gestation. The etiology is multifactorial. Maternal anemia is one of the factors leading to PPROM. This study aims to determine the frequency of maternal anemia in patients presenting with PPROM. MATERIALS AND METHODS: This cross-sectional study was carried out at the Department of Obstetrics and Gynecology, Lady Reading Hospital, Peshawar. This study was conducted from July 1 to December 31, 2021. One hundred and twenty two patients with PPROM presenting to the Department of Obstetrics and Gynecology were included. The diagnosis of PPROM was made based on the history of the PV leak, followed by confirmation with the nitrazine litmus test, microscopic fern test, and ultrasonographic amniotic fluid index measurement. Anemia was determined by examination of hemoglobin levels in the maternal blood samples. Hb <11gm/dl was labeled as anemia. IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. was used for statistical analysis. RESULTS:  The age of the patients ranged from 20 to 40 years. The mean age was 29.14 ± 6.194 years. 63 patients (51.6%) were multiparous (parity 2 to 4). Maternal anemia was observed in 39 patients (32.0%). A significant association (p = 0.005) was observed between maternal anemia and grand multiparity (parity 2 to 4). CONCLUSION:  Maternal anemia significantly contributes to PPROM, especially in multiple pregnancies. Meticulous family planning and consistent obstetrical monitoring throughout pregnancy are key to addressing this, potentially reducing both maternal anemia risk and PPROM complications.

Depression follow-up monitoring with the PHQ-9: an open cluster-randomised controlled trial.

BACKGROUND: Outcome monitoring of depression treatment is recommended but there is a lack of evidence on patient benefit in primary care. AIM: To test monitoring depression using the Patient Health Questionnaire (PHQ-9) with patient feedback. DESIGN AND SETTING: An open cluster-randomised controlled trial was undertaken in 141 group practices. METHOD: Adults with new depressive episodes were recruited through record searches and opportunistically. The exclusion criteria were as follows: dementia; psychosis; substance misuse; and suicide risk. The PHQ-9 was administered soon after diagnosis, and 10-35 days later. The primary outcome was the Beck Depression Inventory (BDI-II) score at 12 weeks. The secondary outcomes were as follows: BDI-II at 26 weeks; Work and Social Adjustment Scale (WSAS) and EuroQol EQ-5D-5L quality of life at 12 and 26 weeks; antidepressant treatment; mental health and social service contacts; adverse events, and Medical Interview Satisfaction Scale (MISS) over 26 weeks. RESULTS: In total, 302 patients were recruited to the intervention arm and 227 to the controls. At 12 weeks, 254 (84.1%) and 199 (87.7%) were followed-up, respectively. Only 40.9% of patients in the intervention had a GP follow-up PHQ-9 recorded. There was no significant difference in BDI-II score at 12 weeks (mean difference -0.46; 95% confidence interval [CI] = -2.16 to 1.26; adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering by practice). EQ-5D-5L quality-of-life scores were higher in the intervention arm at 26 weeks (adjusted mean difference 0.053; 95% CI = 0.013 to 0.093. A clinically significant difference in depression at 26 weeks could not be ruled out. No significant differences were found in social functioning, adverse events, or satisfaction. In a per-protocol analysis, antidepressant use and mental health contacts were significantly greater in patients in the intervention arm with a recorded follow-up PHQ-9 (P = 0.025 and P = 0.010, respectively). CONCLUSION: No evidence was found of improved depression outcome at 12 weeks from monitoring. The findings of possible benefits over 26 weeks warrant replication, investigating possible mechanisms, preferably with automated delivery of monitoring and more instructive feedback.

COVID-19 risk mitigation in reopening mass cultural events: population-based observational study for the UK Events Research Programme in Liverpool City Region.

OBJECTIVES: To understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risks, perceived risks and the feasibility of risk mitigations from experimental mass cultural events before coronavirus disease 2019 (COVID-19) restrictions were lifted. DESIGN: Prospective, population-wide observational study. SETTING: Four events (two nightclubs, an outdoor music festival and a business conference) open to Liverpool City Region UK residents, requiring a negative lateral flow test (LFT) within the 36 h before the event, but not requiring social distancing or face-coverings. PARTICIPANTS: A total of 12,256 individuals attending one or more events between 28 April and 2 May 2021. MAIN OUTCOME MEASURES: SARS-CoV-2 infections detected using audience self-swabbed (5-7 days post-event) polymerase chain reaction (PCR) tests, with viral genomic analysis of cases, plus linked National Health Service COVID-19 testing data. Audience experiences were gathered via questionnaires, focus groups and social media. Indoor CO2 concentrations were monitored. RESULTS: A total of 12 PCR-positive cases (likely 4 index, 8 primary or secondary), 10 from the nightclubs. Two further cases had positive LFTs but no PCR. A total of 11,896 (97.1%) participants with scanned tickets were matched to a negative pre-event LFT: 4972 (40.6%) returned a PCR within a week. CO2 concentrations showed areas for improving ventilation at the nightclubs. Population infection rates were low, yet with a concurrent outbreak of >50 linked cases around a local swimming pool without equivalent risk mitigations. Audience anxiety was low and enjoyment high. CONCLUSIONS: We observed minor SARS-CoV-2 transmission and low perceived risks around events when prevalence was low and risk mitigations prominent. Partnership between audiences, event organisers and public health services, supported by information systems with real-time linked data, can improve health security for mass cultural events.

Investigating pathogenic SNP of PKCι in HCV-induced hepatocellular carcinoma.

Hepatocellular carcinoma is a leading cause of cancer-related deaths due to its complexity in diagnosis, chemo-resistance, and aggressive nature. Identifying pathogenic single nucleotide polymorphism (SNP) in protein kinase C iota (PKCι) can be a potential biomarker in the prognosis and treatment of HCC. This study investigated the association between a SNP in PRKCI and the Pakistani population's hepatocellular carcinoma (HCC) risk. Obtained samples were first evaluated for ALT measurements and viral load quantification through reverse transcriptase-PCR. The PKCι nsSNP rs1199520604 was evaluated computationally by multiple consensus bioinformatics tools for predicting its potential deleterious effects. Its association with hepatitis C virus- (HCV) mediated HCC was then investigated through ARMS-PCR (Amplification Refractory Mutation System Polymerase Chain Reaction). SNP analysis of rs1199520604 was performed in 100 cases and 100 controls. Variant rs1199520604's homozygous T genotype is a risk factor allele for the HCV-induced HCC (odds ratio: 4.13, relative risk: 2.01, P-value < 0.0001). The heterozygous genotype is determined to protect HCV patients from HCC development (P < 0.001). The study highlighted the disease association of variant rs1199520604 with HCV-induced HCC in the Pakistani populations. This variant, after further validation through high-throughput investigation on a larger cohort, has the potential to be translated at the clinical level.

Health and socioeconomic resource provision for older people in South Asian countries: Bangladesh, India, Nepal, Pakistan and Sri Lanka evidence from NEESAMA.

BACKGROUND: The global population is ageing rapidly, with low- and middle-income countries (LMICs) undergoing a fast demographic transition. As the number of older adults in LMICs increases, services able to effectively address their physical and mental health needs will be increasingly important. OBJECTIVE: We review the health and socioeconomic resources currently available for older people in South Asian countries, Bangladesh, India, Nepal, Pakistan and Sri Lanka, to identify gaps in available resources and assess areas for improvement. METHODS: We conducted a search of grey and published literature via Google Search, Compendex, EBSCO, JSTOR, Medline, Ovid, ProQuest databases, Scopus and Web of Science. Data on population demographics, human resources, health funding and social protection for older people were extracted. Local informants were consulted to supplement and verify the data. RESULTS: In the study countries, the number of health professionals with expertise in elderly care was largely unknown, with minimal postgraduate training programmes available in elderly medicine or psychiatry. Older adults are therefore cared for by general physicians, nurses and community health workers, all of whom are present in insufficient numbers per capita. Total average healthcare expenditure was 2.5-5.5% of GDP, with 48.1-72.0% of healthcare costs covered by out-of-pocket payments. Pakistan did not have a social pension; only India and Nepal offered financial assistance to people with dementia; and all countries had disproportionately low numbers of care elderly homes. CONCLUSIONS: Inadequate healthcare funding, a shortage of healthcare professionals and insufficient government pension and social security schemes are significant barriers to achieving universal health coverage in LMICs. Governing bodies must expand training programmes for healthcare providers for older adults, alongside increasing social protection to improve access to those in need and to prevent catastrophic health expenditure.

Apoptosis evasion via long non-coding RNAs in colorectal cancer.

Long non-coding RNA (LncRNA) is a novel and diverse class of regulatory transcripts that are frequently dysregulated in numerous tumor types. LncRNAs are involved in a complicated molecular network, regulating gene expression, and modulating diverse cellular activities in different cancers including colorectal cancer (CRC). Evidence indicates that lncRNAs can be used as a potential biomarker for the prognosis and diagnosis of CRC as they are aberrantly expressed in CRC cells. The high expression or silencing of lncRNAs is associated with cell proliferation, invasion, metastasis, chemoresistance and apoptosis in CRC. LncRNAs exert both pro-apoptotic and anti-apoptotic functions in CRC. The expression of some oncogene lncRNAs is upregulated which leads to the inhibition of apoptotic pathways, similarly, the tumor suppressor lncRNAs are downregulated in CRC. In this review, we describe the function and mechanisms of lncRNAs to regulate the expression of genes that are involved directly or indirectly in controlling cellular apoptosis in CRC. Furthermore, we also discussed the different apoptotic pathways in normal cells and the mechanisms by which CRC evade apoptosis.

Impact of deleterious missense PRKCI variants on structural and functional dynamics of protein.

Protein kinase C iota (PKCÉ©) is a novel protein containing 596 amino acids and is also a member of atypical kinase family. The role of PKCÉ© has been explored in neurodegenerative diseases, neuroblastoma, ovarian and pancreatic cancers. Single nucleotide polymorphisms (SNPs) have not been studied in PKCÉ© till date. The purpose of the current study is to scrutinize the deleterious missense variants in PKCÉ© and determine the effect of these variants on stability and dynamics of the protein. The structure of protein PKCÉ© was predicted for the first time and post translational modifications were determined. Genetic variants of PKCÉ© were retrieved from ENSEMBL and only missense variants were further analyzed because of its linkage with diseases. The pathogenicity of missense variants, effect on structure and function of protein, association with cancer and conservancy of the protein residues were determined through computational approaches. It is observed that C1 and the pseudo substrate region has the highest number of pathogenic SNPs. Variations in the kinase domain of the protein are predicted to alter overall phosphorylation of the protein. Molecular dynamic simulations predicted noteworthy change in structural and functional dynamics of the protein because of these variants. The study revealed that nine deleterious variants can possibly contribute to malfunctioning of the protein and can be associated with diseases. This can be useful in diagnostics and developing therapeutics for diseases related to these polymorphisms.

Autism spectrum disorder in a rural community in Bangladesh: A mid-childhood assessment.

Population-based studies employing standardized diagnostics are needed to determine the burden of autism spectrum disorder (ASD) in low-resource settings. A community-based study was conducted among 8-11 year old children in rural, northwestern Bangladesh to establish the prevalence of ASD. A standardized screening and diagnosis protocol was adapted and deployed comprising the social communication questionnaire (SCQ), and the autism diagnostic observation schedule 2, (ADOS-2), and the autism diagnostic interview, revised (ADI-R), respectively. A year-long research training was conducted for a clinical psychologist to be certified to administer ADOS-2 and ADI-R. Over 8000 children were visited at home and administered the SCQ leading to some, based on their score, being further evaluated using the ADOS-2 and ADI-R by the clinical psychologist. Based on ADOS-2 applying the diagnoses of autism or autism spectrum, the prevalence was 40 (95% CI: 27, 54) per 10,000. Autistic disorder using ADI-R was found at 12 (95% CI: 5, 20) per 10,000. Boys were at a higher risk than girls with the rates among boys being 46 (95% CI: 25, 67) using ADOS-2 and 19 (95% CI:6, 33) using ADI-R. Among girls the rates were 34 (95% CI:16, 52) and 5 (95% CI:0, 12) per 10,000, respectively. Challenges to undertaking ASD research in a rural South Asian context are discussed. There was a low-to-moderate prevalence of ASD in a rural, child population in Bangladesh. Future research is needed to estimate rates of ASD and its causes and socioeconomic consequences in rural and urban settings of South Asia. LAY SUMMARY: In a study of over 8000, 8-11 year old children in a rural area of Bangladesh, two to four out of 1000 had ASD. Boys more than girls had ASD. Conducting ASD assessment in this setting was difficult, but more such research is needed to understand what causes ASD and its consequences for the individual, families and the society in rural and urban areas of low-income countries.

Impact of emollient therapy for preterm infants in the neonatal period on child neurodevelopment in Bangladesh: an observational cohort study.

BACKGROUND: Topical treatment with sunflower seed oil (SSO) or Aquaphor® reduced sepsis and neonatal mortality in hospitalized preterm infants <33 weeks' gestational age in Bangladesh. We sought to determine whether the emollient treatments improved neurodevelopmental outcomes during early childhood. METHODS: 497 infants were randomized to receive SSO, Aquaphor®, or neither through the neonatal period or hospital discharge. 159 infant survivors were enrolled in the longitudinal follow-up study using a validated Rapid Neurodevelopmental Assessment tool and the Bayley Scales of Infant Development II (BSID II) administered at three-monthly intervals for the first year and thereafter at six-monthly intervals. Lowess smoothing was used to display neurodevelopmental status across multiple domains by age and treatment group, and Generalized Estimating Equations (GEE) were used to compare treatment groups across age points. RESULTS: 123 children completed at least one follow-up visit. Lowess graphs suggest that lower proportions of children who received massage with either SSO or Aquaphor® had neurodevelopmental delays than control infants in a composite outcome of disabilities. In GEE analysis, infants receiving SSO showed a significant protective effect on the development of fine motor skills [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.86-0.98, p=0.006]. The Psychomotor Development Index (PDI) in the BSID II showed significantly lower disability rates in the Aquaphor group (23.6%) compared to the control (55.2%) (OR 0.21, 95% CI 0.06-0.72, p=0.004). CONCLUSIONS: Emollient massage of very preterm, hospitalized newborn infants improved some child neurodevelopmental outcomes over the first 2 years of follow-up. Findings warrant further confirmatory research. TRIAL REGISTRATION: ClinicalTrials.gov (98-04-21-03-2) under weblink https://clinicaltrials.gov/ct2/show/NCT00162747.

Case Report: Primary Duodenal Melanoma with Brain Metastasis.

Malignant duodenal tumors can be primary or secondary. Although the most common primary tumor involving the duodenum is an adenocarcinoma, primary malignant melanomas arising in the small intestine are exceedingly rare and remain a controversial clinical entity. In this report, we present a unique case of primary duodenal melanoma with brain metastasis managed successfully by surgical excision, stereotactic radiation, and adjuvant immunotherapy.

Duodenal Metastasis in Triple-Negative Invasive Ductal Breast Carcinoma With Negative Mammography: A Case Report and Review of the Literature.

Breast cancer metastasis to the gastrointestinal tract is uncommon, and duodenal involvement is exceptionally rare. Those cases that do metastasize are reported to be lobular, with ductal carcinomas comprising only a small percentage of reported cases. Furthermore, these invasive carcinomas are typically estrogen receptor-, progesterone receptor-positive ± human epidermal growth factor receptor 2 malignancies. We present a unique case of a patient with duodenal metastasis as the first sign of metastatic breast cancer. The rarity of this case is highlighted by the fact that the patient had no known breast malignancy, and pathological findings revealed triple-negative invasive ductal carcinoma consistent with primary breast cancer. Diagnostic mammogram and ultrasound were negative for any lesions.

Lay-therapist-delivered, low-intensity, psychosocial intervention for refugees and asylum seekers (PROSPER): protocol for a pilot randomised controlled trial.

BACKGROUND: Asylum seekers and refugees (AS&Rs) experience impaired mental health and wellbeing, related to stresses in their country of origin, experiences in transit and reception on arrival, including significant barriers to accessing mainstream services. Their contact with health care is often crisis-driven and mediated through non-governmental organisations (NGOs). Problem Management Plus (PM+) is a psychosocial intervention recommended by the World Health Organisation to address distress experienced by adults affected by humanitarian crises. We are investigating its application for the first time in a high-income country. METHODS: In a pilot randomised controlled trial (RCT), PM+ will be delivered to AS&Rs in contact with NGOs in Liverpool City Region, UK by lay therapists who have lived experience of forced migration. Following systematic review and stakeholder engagement, PM+ has been adapted to the local context, and lay therapists have been trained in its delivery. We will assess the feasibility of conducting a three-arm RCT of five 90-min sessions of PM+, delivered individually or in groups by lay therapists to AS&Rs experiencing emotional distress and functional impairment, compared with each other and with usual support offered by local NGOs. Distress and impairment at baseline will be measured by the Hospital Anxiety and Depression Scale (HADS) and the WHO Disability Assessment Schedule (WHO-DAS). We aim to recruit 105 participants, 35 per arm. Primary health outcomes are anxiety and depressive symptoms at 3 months, measured by HADS. Secondary outcomes include subjective wellbeing, functional status, progress on identified problems, presence of post-traumatic stress disorder and depressive disorder and service usage. Longer-term impact will be assessed at 6 months post baseline, on the same parameters. We will assess the feasibility of conducting a full RCT in relation to the following elements: recruitment and retention of lay therapists and study participants; fidelity of delivery of PM+; and suitability of the study measures, including any linguistic or cultural barriers. DISCUSSION: We will use these findings to specify the parameters for a full RCT to test the effectiveness and cost-effectiveness of PM+ in reducing emotional distress and health inequalities, and improving functional ability and wellbeing, amongst asylum seekers and refugees. TRIAL REGISTRATION: ISRCTN, ID: ISRCTN15214107. Registered on 10 September 2019.

The clinical effectiveness of sertraline in primary care and the role of depression severity and duration (PANDA): a pragmatic, double-blind, placebo-controlled randomised trial.

BACKGROUND: Depression is usually managed in primary care, but most antidepressant trials are of patients from secondary care mental health services, with eligibility criteria based on diagnosis and severity of depressive symptoms. Antidepressants are now used in a much wider group of people than in previous regulatory trials. We investigated the clinical effectiveness of sertraline in patients in primary care with depressive symptoms ranging from mild to severe and tested the role of severity and duration in treatment response. METHODS: The PANDA study was a pragmatic, multicentre, double-blind, placebo-controlled randomised trial of patients from 179 primary care surgeries in four UK cities (Bristol, Liverpool, London, and York). We included patients aged 18 to 74 years who had depressive symptoms of any severity or duration in the past 2 years, where there was clinical uncertainty about the benefit of an antidepressant. This strategy was designed to improve the generalisability of our sample to current use of antidepressants within primary care. Patients were randomly assigned (1:1) with a remote computer-generated code to sertraline or placebo, and were stratified by severity, duration, and site with random block length. Patients received one capsule (sertraline 50 mg or placebo orally) daily for one week then two capsules daily for up to 11 weeks, consistent with evidence on optimal dosages for efficacy and acceptability. The primary outcome was depressive symptoms 6 weeks after randomisation, measured by Patient Health Questionnaire, 9-item version (PHQ-9) scores. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission (PHQ-9 and Beck Depression Inventory-II), generalised anxiety symptoms (Generalised Anxiety Disorder Assessment 7-item version), mental and physical health-related quality of life (12-item Short-Form Health Survey), and self-reported improvement. All analyses compared groups as randomised (intention-to-treat). The study is registered with EudraCT, 2013-003440-22 (protocol number 13/0413; version 6.1) and ISRCTN, ISRCTN84544741, and is closed to new participants. FINDINGS: Between Jan 1, 2015, and Aug 31, 2017, we recruited and randomly assigned 655 patients-326 (50%) to sertraline and 329 (50%) to placebo. Two patients in the sertraline group did not complete a substantial proportion of the baseline assessment and were excluded, leaving 653 patients in total. Due to attrition, primary outcome analyses were of 550 patients (266 in the sertraline group and 284 in the placebo group; 85% follow-up that did not differ by treatment allocation). We found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks. The mean 6-week PHQ-9 score was 7·98 (SD 5·63) in the sertraline group and 8·76 (5·86) in the placebo group (adjusted proportional difference 0·95, 95% CI 0·85-1·07; p=0·41). However, for secondary outcomes, we found evidence that sertraline led to reduced anxiety symptoms, better mental (but not physical) health-related quality of life, and self-reported improvements in mental health. We observed weak evidence that depressive symptoms were reduced by sertraline at 12 weeks. We recorded seven adverse events-four for sertraline and three for placebo, and adverse events did not differ by treatment allocation. Three adverse events were classified as serious-two in the sertraline group and one in the placebo group. One serious adverse event in the sertraline group was classified as possibly related to study medication. INTERPRETATION: Sertraline is unlikely to reduce depressive symptoms within 6 weeks in primary care but we observed improvements in anxiety, quality of life, and self-rated mental health, which are likely to be clinically important. Our findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder. FUNDING: National Institute for Health Research.

Detecting Developmental Delay and Autism Through Machine Learning Models Using Home Videos of Bangladeshi Children: Development and Validation Study.

BACKGROUND: Autism spectrum disorder (ASD) is currently diagnosed using qualitative methods that measure between 20-100 behaviors, can span multiple appointments with trained clinicians, and take several hours to complete. In our previous work, we demonstrated the efficacy of machine learning classifiers to accelerate the process by collecting home videos of US-based children, identifying a reduced subset of behavioral features that are scored by untrained raters using a machine learning classifier to determine children's "risk scores" for autism. We achieved an accuracy of 92% (95% CI 88%-97%) on US videos using a classifier built on five features. OBJECTIVE: Using videos of Bangladeshi children collected from Dhaka Shishu Children's Hospital, we aim to scale our pipeline to another culture and other developmental delays, including speech and language conditions. METHODS: Although our previously published and validated pipeline and set of classifiers perform reasonably well on Bangladeshi videos (75% accuracy, 95% CI 71%-78%), this work improves on that accuracy through the development and application of a powerful new technique for adaptive aggregation of crowdsourced labels. We enhance both the utility and performance of our model by building two classification layers: The first layer distinguishes between typical and atypical behavior, and the second layer distinguishes between ASD and non-ASD. In each of the layers, we use a unique rater weighting scheme to aggregate classification scores from different raters based on their expertise. We also determine Shapley values for the most important features in the classifier to understand how the classifiers' process aligns with clinical intuition. RESULTS: Using these techniques, we achieved an accuracy (area under the curve [AUC]) of 76% (SD 3%) and sensitivity of 76% (SD 4%) for identifying atypical children from among developmentally delayed children, and an accuracy (AUC) of 85% (SD 5%) and sensitivity of 76% (SD 6%) for identifying children with ASD from those predicted to have other developmental delays. CONCLUSIONS: These results show promise for using a mobile video-based and machine learning-directed approach for early and remote detection of autism in Bangladeshi children. This strategy could provide important resources for developmental health in developing countries with few clinical resources for diagnosis, helping children get access to care at an early age. Future research aimed at extending the application of this approach to identify a range of other conditions and determine the population-level burden of developmental disabilities and impairments will be of high value.