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Kristin Kostka,1,2 Talita Duarte-Salles,3 Albert Prats-Uribe,4 Anthony G Sena,5,6 Andrea Pistillo,3 Sara Khalid,4 Lana YH Lai,7 Asieh Golozar,8,9 Thamir M Alshammari,10 Dalia M Dawoud,11 Fredrik Nyberg,12 Adam B Wilcox,13,14 Alan Andryc,5 Andrew Williams,15 Anna Ostropolets,16 Carlos Areia,17 Chi Young Jung,18 Christopher A Harle,19 Christian G Reich,1,2 Clair Blacketer,5,6 Daniel R Morales,20 David A Dorr,21 Edward Burn,3,4 Elena Roel,3,22 Eng Hooi Tan,4 Evan Minty,23 Frank DeFalco,5 Gabriel de Maeztu,24 Gigi Lipori,19 Hiba Alghoul,25 Hong Zhu,26 Jason A Thomas,13 Jiang Bian,19 Jimyung Park,27 Jordi Martínez Roldán,28 Jose D Posada,29 Juan M Banda,30 Juan P Horcajada,31 Julianna Kohler,32 Karishma Shah,33 Karthik Natarajan,16,34 Kristine E Lynch,35,36 Li Liu,37 Lisa M Schilling,38 Martina Recalde,3,22 Matthew Spotnitz,14 Mengchun Gong,39 Michael E Matheny,40,41 Neus Valveny,42 Nicole G Weiskopf,21 Nigam Shah,29 Osaid Alser,43 Paula Casajust,42 Rae Woong Park,27,44 Robert Schuff,21 Sarah Seager,1 Scott L DuVall,35,36 Seng Chan You,45 Seokyoung Song,46 Sergio Fernández-Bertolín,3 Stephen Fortin,5 Tanja Magoc,19 Thomas Falconer,16 Vignesh Subbian,47 Vojtech Huser,48 Waheed-Ul-Rahman Ahmed,33,49 William Carter,38 Yin Guan,50 Yankuic Galvan,19 Xing He,19 Peter R Rijnbeek,6 George Hripcsak,16,34 Patrick B Ryan,5,16 Marc A Suchard,51 Daniel Prieto-Alhambra4 1IQVIA, Cambridge, MA, USA; 2OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, USA; 3Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain; 4Centre for Statistics in Medicine, NDORMS, University of Oxford, Oxford, UK; 5Janssen Research & Development, Titusville, NJ, USA; 6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands; 7School of Medical Sciences, University of Manchester, Manchester, UK; 8Regeneron Pharmaceuticals, Tarrytown, NY, USA; 9Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 10College of Pharmacy, Riyadh Elm University, Riyadh, Saudi Arabia; 11National Institute for Health and Care Excellence, London, UK; 12School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 13Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA; 14Unviersity of Washington Medicine, Seattle, WA, USA; 15Tufts Institute for Clinical Research and Health Policy Studies, Boston, MA, USA; 16Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA; 17Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 18Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea; 19University of Florida Health, Gainesville, FL, USA; 20Division of Population Health and Genomics, University of Dundee, Dundee, UK; 21Department of Medical Informatics & Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA; 22Universitat Autònoma de Barcelona, Barcelona, Spain; 23O’Brien Institute for Public Health, Faculty of Medicine, University of Calgary, Calgary, Canada; 24IOMED, Barcelona, Spain; 25Faculty of Medicine, Islamic University of Gaza, Gaza, Palestine; 26Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 27Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, South Korea; 28Director of Innovation and Digital Transformation, Hospital del Mar, Barcelona, Spain; 29Department of Medicine, School of Medicine, Stanford University, Redwood City, CA, USA; 30Georgia State University, Department of Computer Science, Atlanta, GA, USA; 31Department of Infectious Diseases, Hospital del Mar, Institut Hospital del Mar d’Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona, Universitat Pompeu Fabra, Barcelona, Spain; 32United States Agency for International Development, Washington, DC, USA; 33Botnar Research Centre, NDORMS, University of Oxford, Oxford, UK; 34New York-Presbyterian Hospital, New York, NY, USA; 35VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, USA; 36Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; 37Biomedical Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 38Data Science to Patient Value Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 39Institute of Health Management, Southern Medical University, Guangzhou, People’s Republic of China; 40Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, USA; 41Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA; 42Real-World Evidence, TFS, Barcelona, Spain; 43Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 44Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea; 45Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea; 46Department of Anesthesiology and Pain Medicine, Catholic University of Daegu, School of Medicine, Daegu, South Korea; 47College of Engineering, The University of Arizona, Tucson, AZ, USA; 48National Library of Medicine, National Institutes of Health, Bethesda, MD, USA; 49College of Medicine and Health, University of Exeter, St Luke’s Campus, Exeter, UK; 50DHC Technologies Co. Ltd., Beijing, People’s Republic of China; 51Departments of Biostatistics, Computational Medicine, and Human Genetics, University of California, Los Angeles, CA, USACorrespondence: Daniel Prieto-Alhambra, Botnar Research Centre, Windmill Road, Oxford, OX37LD, UK, Email daniel.prietoalhambra@ndorms.ox.ac.ukPurpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD.Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test, 886,193 hospitalized with COVID-19, and 113,627 hospitalized with COVID-19 requiring intensive services.Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed.Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance.Keywords: OHDSI, OMOP CDM, descriptive epidemiology, real world data, real world evidence, open science

Waheed-Ul-Rahman Ahmed,1,* Emily Mills2,* 1College of Medicine and Health, University of Exeter, Exeter, UK; 2Brighton and Sussex Medical School, Brighton, UK *These authors contributed equally to this workWe read the recent article by Kothari et al1 with great interest. We thank the authors for shedding light on an ever-important topic that resonates with medical students such as ourselves, around the world. The rigorous nature of medical education compounds depression and anxiety;2 this is further complicated by the appreciably low uptake of mental health services by students.3 Kothari et al1 outline approaches to tackling mental health barriers among medical students, principally the use of personal academic tutors. In this manuscript, we wish to provide our experience on the efficacy of the proposed strategies and suggest further solutions to tackle the mounting problem of medical students accessing mental health care.View the original paper by Kothari and colleagues

Cancer is a complex disease driven by the dysregulation of multiple signaling pathways and cellular processes. The development of compounds capable of exerting multitarget actions against these key pathways involved in cancer progression is a promising therapeutic approach. Here, a series of novel ( E / Z )- N -(4-(2-(2-(substituted)hydrazineyl)-2-oxoethyl)thiazol-2-yl)-1 H -indole-2-carboxamide derivatives ( 6a - 6z ) were designed, synthesized, and evaluated for their biological activity. Compounds 6e , 6i , 6q , 6v , 7a , and 7b exhibited exceptional cytotoxicity against various cancer cell lines, particularly 6i (IC 50 = 6.10 ± 0.4 μM against MCF-7 cell lines) and 6v (IC 50 = 6.49 ± 0.3 μM against MCF-7 cell lines). These potent compounds inhibited key protein kinases like EGFR, HER2, VEGFR-2, and CDK2, induced cell cycle arrest at the G2/M phase, and promoted apoptosis. Docking studies revealed improved binding affinity of 6i and 6v with target proteins compared to reference drugs. These findings highlight the promising potential of 6i and 6v as multitarget cancer therapeutics deserving further development., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background : Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods : We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results : The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion : COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes., Competing Interests: Competing interests: Dr. Verhamme works for a research department who received/receives unconditional research grants from Pfizer/Boehringer Ingelheim, Yamanouchi, Novartis, GSK, Chiesi, Amgen, UCB, J&J none of which are related to the content of this work; Ms. Kostka reports consulting fees from National Institutes of Health NCATS, outside the submitted work; and during the 36 months prior to publication, Ms. Kostka was an employee of IQVIA Inc (a commercial entity); Dr. Prieto-Alhambra reports grants and other from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department and open for external participants; Dr. Blacketer reports and full-time employee of Janssen R&D and a stockholder of Johnson & Johnson; Dr. DuVall reports grants from Anolinx, LLC, grants from Astellas Pharma, Inc, grants from AstraZeneca Pharmaceuticals LP, grants from Boehringer Ingelheim International GmbH, grants from Celgene Corporation, grants from Eli Lilly and Company, grants from Genentech Inc., grants from Genomic Health, Inc., grants from Gilead Sciences Inc., grants from GlaxoSmithKline PLC, grants from Innocrin Pharmaceuticals Inc., grants from Janssen Pharmaceuticals, Inc., grants from Kantar Health, grants from Myriad Genetic Laboratories, Inc., grants from Novartis International AG, grants from Parexel International Corporation through the University of Utah or Western Institute for Veteran Research, outside the submitted work; Dr. Nyberg reports other from AstraZeneca, outside the submitted work; Dr. Posada reports grants from National Library of Medicine, during the conduct of the study; Dr. Rijnbeek reports grants from Innovative Medicines Initiative, from Janssen Research and Development, during the conduct of the study; Dr. Sena reports and full-time employee of Janssen R&D and a stockholder of Johnson & Johnson; Dr. Shah reports grants from National Library of Medicine, during the conduct of the study; Dr. Suchard reports grants from US National Institutes of Health, grants from US Department of Veterans Affairs, during the conduct of the study; grants from US Food & Drug Administration, personal fees from Janssen Research & Development, outside the submitted work; Dr. Hripcsak reports grants from US National Institutes of Health, during the conduct of the study; grants from Janssen Research, outside the submitted work; Dr. Ryan reports and is employee of Janssen Research and Development and shareholder of Johnson & Johnson; Dr. Morales is supported by a Wellcome Trust Clinical Research Development Fellowship (Grant 214588/Z/18/Z) and reports grants from Chief Scientist Office (CSO), grants from Health Data Research UK (HDR-UK), grants from National Institute of Health Research (NIHR), and Tenovus outside the submitted work., (Copyright: © 2023 Moreno-Martos D et al.)

Background: Trigger finger and carpal tunnel syndrome are the two most common non-traumatic connective tissue disorders of the hand. Both of these conditions frequently co-occur, often in patients with rheumatoid arthritis. However, this phenotypic association is poorly understood. Hypothesising that the co-occurrence of trigger finger and carpal tunnel syndrome might be explained by shared germline predisposition, we aimed to identify a specific genetic locus associated with both diseases., Methods: In this genome-wide association study (GWAS), we identified 2908 patients with trigger finger and 436579 controls from the UK Biobank prospective cohort. We conducted a case-control GWAS for trigger finger, followed by co-localisation analyses with carpal tunnel syndrome summary statistics. To identify putative causal variants and establish their biological relevance, we did fine-mapping analyses and expression quantitative trait loci (eQTL) analyses, using fibroblasts from healthy donors (n=79) and tenosynovium samples from patients with carpal tunnel syndrome (n=77). We conducted a Cox regression for time to trigger finger and carpal tunnel syndrome diagnosis against plasma IGF-1 concentrations in the UK Biobank cohort., Findings: Phenome-wide analyses confirmed a marked association between carpal tunnel syndrome and trigger finger in the participants from UK Biobank (odds ratio [OR] 11·97, 95% CI 11·1-13·0; p<1 × 10 -300 ). GWAS for trigger finger identified five independent loci, including one locus, DIRC3 , that was co-localised with carpal tunnel syndrome and could be fine-mapped to rs62175241 (0·76, 0·68-0·84; p=5·03 × 10 -13 ). eQTL analyses found a fibroblast-specific association between the protective T allele of rs62175241 and increased DIRC3 and IGFBP5 expression. Increased plasma IGF-1 concentrations were associated with both carpal tunnel syndrome and trigger finger in participants from UK Biobank (hazard ratio >1·04, p<0·02)., Interpretation: In this GWAS, the DIRC3 locus on chromosome 2 was significantly associated with both carpal tunnel syndrome and trigger finger, possibly explaining their co-occurrence. The disease-protective allele of rs62175241 was associated with increased expression of long non-coding RNA DIRC3 and its transcriptional target, IGBP5 , an antagonist of IGF-1 signalling. These findings suggest a model in which IGF-1 is a driver of both carpal tunnel syndrome and trigger finger, and in which the DIRC3-IGFBP5 axis directly antagonises fibroblastic IGF-1 signalling., Funding: Wellcome Trust, National Institute for Health Research, Medical Research Council., Competing Interests: Declaration of interests DLB reports grants from Lilly and AstraZeneca, has acted as a consultant on behalf of Oxford Innovation for Amgen, Biointervene, Bristows, LatigoBio, GSK, Ionis, Lilly, Olipass, Orion, Regeneron, and Theranexus, and has a patent application “a method for the treatment or prevention of pain, or excessive neuronal activity, or epilepsy” (16/337,428). GB reports consultancy fees from Biocoding and Ivy Farm. JP is chair of Oz Single Cells and has stock or stock options in Sonic Healthcare. All other authors declare no competing interests.

Varicose veins affect one-third of Western society, with a significant subset of patients developing venous ulceration, costing $14.9 billion annually in the USA. Current management consists of either compression stockings, or surgical ablation for more advanced disease. Most varicose veins patients report a positive family history, and heritability is ~17%. We describe the largest two-stage genome-wide association study of varicose veins in 401,656 individuals from UK Biobank, and replication in 408,969 individuals from 23andMe (total 135,514 cases and 675,111 controls). Forty-nine signals at 46 susceptibility loci were discovered. We map 237 genes to these loci, several of which are biologically plausible and tractable to therapeutic targeting. Pathway analysis identified enrichment in extracellular matrix biology, inflammation, (lymph)angiogenesis, vascular smooth muscle cell migration, and apoptosis. Using a polygenic risk score (PRS) derived in an independent cohort, we demonstrate its predictive utility and correlation with varicose veins surgery., (© 2022. The Author(s).)

Background : Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods : We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a 'diagnosed' and 'hospitalized' cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results : The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients.   Conclusion : COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes., Competing Interests: Competing interests: Dr. Verhamme works for a research department who received/receives unconditional research grants from Pfizer/Boehringer Ingelheim, Yamanouchi, Novartis, GSK, Chiesi, Amgen, UCB, J&J none of which are related to the content of this work; Ms. Kostka reports consulting fees from National Institutes of Health NCATS, outside the submitted work; and during the 36 months prior to publication, Ms. Kostka was an employee of IQVIA Inc (a commercial entity); Dr. Prieto-Alhambra reports grants and other from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department and open for external participants; Dr. Blacketer reports and full-time employee of Janssen R&D and a stockholder of Johnson & Johnson; Dr. DuVall reports grants from Anolinx, LLC, grants from Astellas Pharma, Inc, grants from AstraZeneca Pharmaceuticals LP, grants from Boehringer Ingelheim International GmbH, grants from Celgene Corporation, grants from Eli Lilly and Company, grants from Genentech Inc., grants from Genomic Health, Inc., grants from Gilead Sciences Inc., grants from GlaxoSmithKline PLC, grants from Innocrin Pharmaceuticals Inc., grants from Janssen Pharmaceuticals, Inc., grants from Kantar Health, grants from Myriad Genetic Laboratories, Inc., grants from Novartis International AG, grants from Parexel International Corporation through the University of Utah or Western Institute for Veteran Research, outside the submitted work; Dr. Nyberg reports other from AstraZeneca, outside the submitted work; Dr. Posada reports grants from National Library of Medicine, during the conduct of the study; Dr. Rijnbeek reports grants from Innovative Medicines Initiative, from Janssen Research and Development, during the conduct of the study; Dr. Sena reports and full-time employee of Janssen R&D and a stockholder of Johnson & Johnson; Dr. Shah reports grants from National Library of Medicine, during the conduct of the study; Dr. Suchard reports grants from US National Institutes of Health, grants from US Department of Veterans Affairs, during the conduct of the study; grants from US Food & Drug Administration, personal fees from Janssen Research & Development, outside the submitted work; Dr. Hripcsak reports grants from US National Institutes of Health, during the conduct of the study; grants from Janssen Research, outside the submitted work; Dr. Ryan reports and is employee of Janssen Research and Development and shareholder of Johnson & Johnson; Dr. Morales is supported by a Wellcome Trust Clinical Research Development Fellowship (Grant 214588/Z/18/Z) and reports grants from Chief Scientist Office (CSO), grants from Health Data Research UK (HDR-UK), grants from National Institute of Health Research (NIHR), and Tenovus outside the submitted work., (Copyright: © 2022 Moreno-Martos D et al.)

Objective: To characterise patients with and without prevalent hypertension and COVID-19 and to assess adverse outcomes in both inpatients and outpatients., Design and Setting: This is a retrospective cohort study using 15 healthcare databases (primary and secondary electronic healthcare records, insurance and national claims data) from the USA, Europe and South Korea, standardised to the Observational Medical Outcomes Partnership common data model. Data were gathered from 1 March to 31 October 2020., Participants: Two non-mutually exclusive cohorts were defined: (1) individuals diagnosed with COVID-19 (diagnosed cohort) and (2) individuals hospitalised with COVID-19 (hospitalised cohort), and stratified by hypertension status. Follow-up was from COVID-19 diagnosis/hospitalisation to death, end of the study period or 30 days., Outcomes: Demographics, comorbidities and 30-day outcomes (hospitalisation and death for the 'diagnosed' cohort and adverse events and death for the 'hospitalised' cohort) were reported., Results: We identified 2 851 035 diagnosed and 563 708 hospitalised patients with COVID-19. Hypertension was more prevalent in the latter (ranging across databases from 17.4% (95% CI 17.2 to 17.6) to 61.4% (95% CI 61.0 to 61.8) and from 25.6% (95% CI 24.6 to 26.6) to 85.9% (95% CI 85.2 to 86.6)). Patients in both cohorts with hypertension were predominantly >50 years old and female. Patients with hypertension were frequently diagnosed with obesity, heart disease, dyslipidaemia and diabetes. Compared with patients without hypertension, patients with hypertension in the COVID-19 diagnosed cohort had more hospitalisations (ranging from 1.3% (95% CI 0.4 to 2.2) to 41.1% (95% CI 39.5 to 42.7) vs from 1.4% (95% CI 0.9 to 1.9) to 15.9% (95% CI 14.9 to 16.9)) and increased mortality (ranging from 0.3% (95% CI 0.1 to 0.5) to 18.5% (95% CI 15.7 to 21.3) vs from 0.2% (95% CI 0.2 to 0.2) to 11.8% (95% CI 10.8 to 12.8)). Patients in the COVID-19 hospitalised cohort with hypertension were more likely to have acute respiratory distress syndrome (ranging from 0.1% (95% CI 0.0 to 0.2) to 65.6% (95% CI 62.5 to 68.7) vs from 0.1% (95% CI 0.0 to 0.2) to 54.7% (95% CI 50.5 to 58.9)), arrhythmia (ranging from 0.5% (95% CI 0.3 to 0.7) to 45.8% (95% CI 42.6 to 49.0) vs from 0.4% (95% CI 0.3 to 0.5) to 36.8% (95% CI 32.7 to 40.9)) and increased mortality (ranging from 1.8% (95% CI 0.4 to 3.2) to 25.1% (95% CI 23.0 to 27.2) vs from 0.7% (95% CI 0.5 to 0.9) to 10.9% (95% CI 10.4 to 11.4)) than patients without hypertension., Conclusions: COVID-19 patients with hypertension were more likely to suffer severe outcomes, hospitalisations and deaths compared with those without hypertension., Competing Interests: Competing interests: SLD reports grants from Anolinx. MAS reports grants from US National Institutes of Health, grants from Department of Veterans Affairs, during the conduct of the study; grants from IQVIA, personal fees from Janssen Research and Development, grants from US Food and Drug Administration, personal fees from Private Health Management, outside the submitted work. GH reports grants from NIH, during the conduct of the study; and grants from Janssen Research, outside the submitted work. FN reports being an employee of AstraZeneca until 2019 and holds some AstraZeneca shares, outside the submitted work. KK reports personal fees from the National Institutes of Health, outside the submitted work, and at the time of data analysis and initial drafting of the manuscript. KK was an employee of IQVIA. CRei reports he is an employee of IQVIA. GdM is an employee of IOMED. NV is an employee of TFS. AGS reports personal fees from Janssen R&D, outside the submitted work, and is a full-time employee of Janssen R&D and a Johnson and Johnson shareholder. CB reports personal fees from Janssen R&D, outside the submitted work, and is a full-time employee of Janssen R&D and a Johnson and Johnson shareholder. JDP reports grants from the National Library of Medicine, during the conduct of the study. AG is an employee of Regeneron Pharmaceuticals and reports stocks from Regeneron Pharmaceuticals. PRR reports having received research group grants from Innovative Medicine Initiative and Janssen Research and Development. PR reports being an employee of Janssen Research and Development and a shareholder of Johnson & Johnson. ER, SF-B, NS, LMS, DP, SCY, MR, AP-U, HA, KEL, MEM, AO, CA, CRey, TD-S, TMA, OA, W-U-RA, ILM, JMR, LSR, DD, LL and AP have nothing to declare. No other relationships or activities could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity., Methods: We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status., Results: We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8-40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0-33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity., Conclusion: We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies., (© 2021. The Author(s).)

Objective: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza., Methods: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization., Results: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%)., Conclusion: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza., Methods: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes., Results: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%-18% and 1%-14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza ( n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events., Conclusions: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent., Impact: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies., (©2021 The Authors; Published by the American Association for Cancer Research.)

Objectives: To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children and adolescents diagnosed or hospitalized with coronavirus disease 2019 (COVID-19) and to compare them in secondary analyses with patients diagnosed with previous seasonal influenza in 2017-2018., Methods: International network cohort using real-world data from European primary care records (France, Germany, and Spain), South Korean claims and US claims, and hospital databases. We included children and adolescents diagnosed and/or hospitalized with COVID-19 at age <18 between January and June 2020. We described baseline demographics, comorbidities, symptoms, 30-day in-hospital treatments, and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome, multisystem inflammatory syndrome in children, and death., Results: A total of 242 158 children and adolescents diagnosed and 9769 hospitalized with COVID-19 and 2 084 180 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were more common among those hospitalized with versus diagnosed with COVID-19. Dyspnea, bronchiolitis, anosmia, and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital prevalent treatments for COVID-19 included repurposed medications (<10%) and adjunctive therapies: systemic corticosteroids (6.8%-7.6%), famotidine (9.0%-28.1%), and antithrombotics such as aspirin (2.0%-21.4%), heparin (2.2%-18.1%), and enoxaparin (2.8%-14.8%). Hospitalization was observed in 0.3% to 1.3% of the cohort diagnosed with COVID-19, with undetectable ( n < 5 per database) 30-day fatality. Thirty-day outcomes including pneumonia and hypoxemia were more frequent in COVID-19 than influenza., Conclusions: Despite negligible fatality, complications including hospitalization, hypoxemia, and pneumonia were more frequent in children and adolescents with COVID-19 than with influenza. Dyspnea, anosmia, and gastrointestinal symptoms could help differentiate diagnoses. A wide range of medications was used for the inpatient management of pediatric COVID-19., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: To study the efficacy of 100 μg intravenous shot of carbetocin compared to 20 IU oxytocin intravenous infusion to prevent placental retention in second trimester medical termination of pregnancy., Methods: A double-blinded randomized controlled trial was conducted at Ain Shams University Maternity Hospital from 1 April 2013 to 30 November 2013. A total of 132 women between 14 and 24 weeks gestation indicated for termination were randomized to receive either 20 IU oxytocin infusion (n = 66) or 100 μg carbetocin shot (n = 66) after fetal expulsion. Patients were observed for time elapsed between fetal and placental expulsion, presence of placental retention and blood loss., Results: Third stage was 33.4 ± 20.4 min in oxytocin group & 23.1 ± 16.8 min in carbetocin group (p = 0.002). Eight patients (12.1%) in oxytocin group had complete placental retention versus two patients (3.0%) in carbetocin group (p = 0.05). Eight patients (13.8%) received oxytocin had remnants of placenta compared to four patients (6.2%) received carbetocin (p = 0.04). Sixteen patients (24.2%) received oxytocin and six patients (9%) received carbetocin needed surgical curettage (p = 0.04). Third stage blood loss was 87.2 ± 33.7 ml in carbetocin and 206.9 ± 35.2 ml in oxytocin groups (p = 0.001)., Conclusion: Carbetocin is superior to oxytocin infusion for management of placental delivery in second trimester abortion.

Recommended treatment of chronic Hepatitis C virus (HCV) infection is interferon and ribavirin. Most patients develop side effects during treatment. Weight loss is one of the side effects of interferon therapy. Present study was conducted at Pakistan Medical and Research Centre (PMRC), Jinnah Postgraduate Medical Centre (JPMC), Karachi from January 1998 - December 2010, to find out the frequency, extent of weight loss, its recovery after interferon therapy and the impact of weight loss on treatment response. Body weight was recorded on regular outpatient visits i.e initially, then at 1, 3 and 6 months of treatment and six months post treatment. Out of 260 patients, 176 (67.7%) observed statistically significant weight loss (p<0.05), on completion of therapy as compared to initial visit. Weight loss during interferon therapy was found to be independent of age, gender, treatment outcome, serum albumin, haemoglobin, white blood cell (WBC) and platelet count. Body weight returned to baseline within six months after completion of treatment in most cases.

Glomerular podocytes are highly specialized cells with a complex cytoarchitecture. Their most prominent features are interdigitated foot processes with filtration slits in between. These are bridged by the slit diaphragm, which plays a major role in establishing the selective permeability of the glomerular filtration barrier. We searched Medline and Pubmed using the combination of keywords "NPHS2", "podocin", "steroid-resistant nephrotic syndrome," and "genetics" to identify studies describing an association between NPHS2 gene and renal disease. The highly dynamic foot processes contain an actin-based contractile apparatus comparable to that of smooth muscle cells. Mutations affecting several podocyte proteins lead to rearrangement of the cytoskeleton, disruption of the filtration barrier, and subsequent renal disease. The fact that the dynamic regulation of the podocyte cytoskeleton is vital to kidney function has led to podocytes emerging as an excellent model system for studying actin cytoskeleton dynamics in a physiological context. Injury to podocytes leads to proteinuria, a hallmark of most glomerular diseases. Recent studies have led to a considerable increase in our understanding of podocyte biology including composition and arrangement of the cytoskeleton involved in the control of ultrafiltration. Moreover, disturbances of podocyte architecture resulting in the retraction of foot processes and proteinuria appear to be a common theme in the progression of an acquired glomerular disease. In hereditary nephrotic syndromes identified over the last few years, all mutated gene products were localized in podocytes. This review integrates our recent physiological and molecular understanding of the role of podocytes during the maintenance and failure of the glomerular filtration barrier.

Objective: To determine factors influencing response of interferon therapy in chronic hepatitis C patients., Study Design: Descriptive, analytical study., Place and Duration of Study: Pakistan Medical Research Centre, Jinnah Postgraduate Medical Centre, Karachi, from January 1998 to December 2009., Methodology: Patients of chronic hepatitis C treated with conventional interferon were retrospectively analyzed. End treatment response at 6 months for genotype 2 and 3 and one-year for genotype 1 and 4 was assessed. Sustained virological response was checked after 6 months of cessation of therapy. Non-compliant and incomplete follow-up cases were excluded. Factors influencing the response to therapy were analyzed by univariate and multivariate logistic regression analysis., Results: A total of 932 cases received interferon therapy 103 were lost to follow-up and were excluded. Treatment was completed in 829 cases end treatment response was 74% (615 out of 829 cases). Six months post-treatment follow-up was available in 492 cases. Sustained virological response was seen in 63% (308 out of 492 cases). Univariate logistic regression analysis showed significantly better response in patients with <40 years of age, body weight>70 kg, normal platelet count, serum albumin>4.0 grams, non diabetic patients and those with a normal alanine aminotransferase (ALT) at 1st month of therapy. Multiple logistic regression analysis showed that only age<40 years was significantly important for sustained virological response., Conclusion: For conventional interferon therapy, age<40 years is the best predictor for sustained virological response, however, better response can be achieved in patients with <70 kg weight, normal platelet count, serum albumin>4.0 grams, non-diabetics and patients having normal ALT at 1st month of therapy.

Objective: To determine the frequency of super infection of hepatitis C and D in patients with hepatitis B related complex liver disorders and the distribution of HBV genotypes in these patients., Study Design: Descriptive study., Place and Duration of Study: The Gastroenterology Unit of PMRC in JPMC, Karachi, from July 2006 to June 2007., Methodology: All patients registered for HBV associated infections were selected. Blood was drawn from 180 patients who fulfilled the inclusion criteria. Those with an incomplete test profile were excluded. All clinical conditions were investigated through liver function tests, coagulation profile, and findings at abdominal ultrasonography, upper gastrointestinal endoscopy and liver biopsy. Liver cirrhosis and hepatocellular carcinoma (HCC) were diagnosed either on the basis of histology, or on a combination of radiological, endoscopic and laboratory data. Hepatitis B virus DNA was extracted from serum, and subjected to a nested PCR using the type specific primers for HBV genotype. Descriptive statistics were used for frequency and mean determination., Results: The 129 patients finally selected for statistical analysis included 108 (84%) males and 21 (16%) females. The age ranged from 6- 68 years (mean=31.5 +/-12.39 years). There were 70 (54.2%) patients of non-cirrhotic, chronic hepatitis (CLD), 38 (29.4%) carriers, 12 (9.3%) cirrhotics and 9 (6.9%) HCC patients. Among the 129 patients, 45 (34.9%) were positive for double infection with HDV. These included 35 CLD cases, 7 cirrhotic and 3 carriers, 4 (3.1%) patients were positive for double infection with HCV including one with CLD, 2 with cirrhosis and one with HCC. Triple infection with HBV/HDV/HCV was present in 4 (3.1%) patients who had CLD. Approximately 59% (n=76) patients were not coinfected, though 9 had developed HCC. The genotype distribution of HBV was observed as D in 98 (76%) patients, A in 24 (18.6%), and AD mix in 7 (5.4%). Genotypes B, C, E or F were not found. Accordingly, genotype D strains were the predominant strains among all categories., Conclusion: The frequency of super infection of hepatitis C and D was found to be highest in HBV cirrhosis patients compared to patients having chronic liver disease (non-cirrhotics) and carriers. Genotype D of hepatitis B virus was found dominant in all hepatitis B related complex liver disorders.

Objective: To study the presentation of Achalasia and compare the response of pneumatic dilatation with surgery., Methods: Retrospective analysis of patient's records (January 2000-December 2005) from outpatients department of Pakistan Medical Research Council), Jinnah Postgraduate Medical Centre, Karachi was done. All patients with Achalasia were analyzed. As a protocol endoscopy, esophageal manometry, esophageal transit time and barium swallow was done to establish the diagnosis. Surgery and endoscopic guided pneumatic dilatation were offered to these patients as treatment options. Patients undergoing surgery or pneumatic dilatation were later followed to assess the efficacy and those not responding to second dilatation were also operated and follow up of all these cases were noted., Results: Forty-six patients (24 males, 22 females) with a mean age of 39.8 +/- 15.9 years were analyzed. Dysphagia was the primary symptom in thirty eight patients (83%) followed by vomiting and epigastric pain. Pneumatic dilatation was performed in 32 out of forty-six patients. Out of these cases 22 (69%) had single, and 10 (31%) had two dilatations. Two patients (6%) had perforation, one required emergency surgery, another patient was managed conservatively and recovery was unremarkable. Six patients (19%) later required surgery. Fourteen cases opted for surgery as a primary treatment. Out of 20 patients operated, four (20%) required post operative dilatation and one (5%) developed gastro-esophageal reflux., Conclusions: Achalasia is prevalent in young age, in both sexes almost equally. Pneumatic dilatation is safe and effective, as it can be managed on outpatient basis with little morbidity and 81% success rate. Surgery is still an effective procedure with comparable 80% success rate.

The objective was to see the efficacy of ursodeoxycholic acid in improving the ALT levels in patients suffering from chronic liver disease. Thirty patients suffering from chronic liver disease (either B or C) were given oral ursodeoxycholic acid in a dose of 250 mg twice a day for 4 months. Their blood biochemistry and haematology were repeated monthly for 7 months i.e. 4 months of therapy and 3 months post therapy to see the response. The mean ALT levels of 30 patients who completed the study was 101 +/- 47 IU/L. During therapy 24 cases (80%) showed lowering of their ALT levels while 6 (20%) either showed no response or worsening of ALT levels. Of 24 cases who showed an improvement in their ALT levels; over 25% drop in ALT levels was seen in 217 cases (70%) and less than 25% drop seen in 7 cases (30%). The mean ALT values during therapy were 75 IU/L showing an overall 25% reduction from the baseline values. Following cessation of therapy the mean ALT levels showed a rise to 90 IU/L which was almost similar to 101 IU/L value in the pre treatment period. The study showed some role of ursodeoxycholic acid in improving the ALT levels in chronic liver disease.

Aims: To study the oesophageal pressures in normal Pakistani subjects using oesophageal manometry and compare the results from the studies done abroad., Setting: Ziauddin Medical University Hospital, North Nazimabad Karachi., Subjects: Twenty-five healthy subjects were studied., Results: Of 25 subjects 19 were males and 6 females. Their ages ranged from 14 to 67 years with a mean age of 41+16 years. The mean resting pressure of the lower oesophageal sphincter was 13.43+/-7.1 mm Hg and relaxation was 96+/-4.1%, with a residual pressure of 0.74+/-1.2 mm Hg. Peristaltic amplitude of the oesophageal body was highest at the lower end of the oesophagus both for dry and wet swallows, the values being 56.23+/-7.9 mm Hg and 74.28+/-35.8 mm Hg respectively. Distal oesophageal peristaltic amplitude was 54.18+/-18.6 and 70.91+/-24.3 mm Hg for dry and wet swallows respectively. Duration of the peristalsis was lowest at the upper end of the oesophagus both for dry and wet swallows being 3.48+/-0.88 and 3.5+/-1.3 seconds respectively. Highest duration of peristaltic amplitude was noted at the lower end of the oesophagus, i.e. 4.43 seconds both for dry and wet swallows. The speed of progression of the peristaltic waves at the proximal end was 2.64+/-1.3 cms / sec and at the distal end 3.37+/-1.6 cms / sec. Mean resting pressure of the upper oesophageal sphincter was 49.84+/-22.4 mm Hg. Residual pressure was 5.2 +/-9.3 mm Hg., Conclusion: The results of this study are in accordance with the results reported from abroad.

Objective: To see the etiology and prognostic factors related to mortality of patients with stroke., Methods: Retrospective analysis of patients admitted with stroke in two hospitals of same locality over 8 years., Results: Of the 12,454 cases admitted in medical units of hospital 796 (6.4%) had stroke. Majority of cases were between 4th and 6th decades of life. Fifty percent (304/606) were hypertensive, 19% (113/606) had cardiac disease and 18% (112/606) diabetes mellitus. Four percent (27/606) had previous history of stroke and 17% (102/606) were smokers. Of the 144 cases who had CT Scan 99 (69%) had infarct and 45 (31%) haemorrhage; overall mortality was 30% (288/971) and it was significantly high in cases over 60 years of age, cases with history of unconciousness at the onset and those with severe hypertension. Mortality rate in the community hospital was significantly higher (33%) as compared to private hospital (13%) (p 0.001)., Conclusion: Cardiac disease is one of the precipitating factors of stroke with infarct being the major cause. Mortality increased with the advancement of age.

Between January, 1979 to August, 1990, 107 histologically proven cases of oesophageal carcinoma were seen. The ages of the patients ranged from 19-85 years (mean 55 +/- 14 years) with a male to female ratio of 1.2:1. Majority (70%) of the cases belonged to lower socioeconomic group and 56% were migrants from India. History of tobacco chewing or smoking was present in 78% cases. In 54%, the lesion was located in the middle third of the oesophagus, followed by lower third in 44%. Histology showed squamous cell carcinoma in 86% and adenocarcinoma in 10% cases. Of the 19 cases followed, 16 underwent surgery and 3 received chemotherapy. Two cases died within 7 months following surgery and in 6 carcinomas recurred. All cases receiving chemotherapy died within 8 months of treatment.

The cytoprotective effect of misoprostol co-administered with non-steroidal anti-inflammatory drugs (NSAIDs) was assessed in a double blind, placebo controlled study. Thirty-seven patients with rheumatoid arthritis receiving NSAIDs, having upper gastrointestinal symptoms and endoscopically confirmed gastric and/or duodenal lesions, were randomised to receive either misoprostol 200 micrograms or placebo tablets twice daily for 4 weeks. Of 31 evaluable cases, 13 of 16 (81%) patients receiving misoprostol showed endoscopic improvement as compared to 10 of 15 (67%) receiving placebo (P:NS). A significant decrease in mean (+/- SEM) mucosal lesion score was observed with misoprostol (from 3.38 +/- 0.32 to 1.32 +/- 0.44; P less than 0.001) but no change was seen with placebo (from 2.80 +/- 0.42 to 1.60 +/- 0.53; P:NS). Symptomatic relief was similar in both groups, being 44% and 40% respectively. Two patients complained of diarrhea in each group and one developed menorrhagia with misoprostol. It is concluded that though misoprostol decreased the number of NSAID-induced mucosal lesions, it was unable to relieve gastrointestinal symptoms.

In a double-blind randomized placebo controlled trial, 50 patients with endoscopically confirmed duodenal ulcer were treated with either misoprostol 200 micrograms or placebo in q.i.d. doses for 4-8 weeks. Of 25 patients in the placebo group, four defaulted and two were withdrawn due to worsening of symptoms. Of 25 misoprostol-treated cases, 17 cases (68%) and 21 cases (84%) healed at 4 and 8 weeks respectively, compared with three (14%) and five (24%) of the 21 placebo-treated cases (P less than 0.001). Except for diarrhoea in 2 patients in each group and itching in one with misoprostol, no serious side effects were noted.

Two hundred and forty-five endoscopically proven or surgically treated duodenal ulcers were retrospectively evaluated to see if the site of ulcer has any influence on the clinical presentation, and healing and relapse rates. Anterior wall ulcer was present in 42%, posterior wall in 33%, lesser curve side of the cap in 12% and greater curve side in 13% cases. Ulcer site showed no correlation to age, sex, duration of illness, analgesic intake or smoking habits. Bleeding (116 cases) and perforation (15 cases) were the major complications encountered; of these perforation was invariably found on the anterior wall, while bleeding was more frequent in ulcers present on the lesser curve side of the cap. Better healing and high relapse rates were seen in ulcers situated on the greater curve, and low healing and relapse rates in lesser curve duodenal ulcers.

Surveillance of hospitalized cholera cases from 1970 to 1977 in Dhaka, a matched control study in 1974, and a neighbourhood control study in 1975 were carried out and show a change from classical cholera to the eltor biotype during this period. Of all the hospitalized cholera cases, 9.1% in 1972 and 99.9% in 1973 were due to the eltor biotype. In 1974 and 1975 the distribution of eltor cholera cases in the city was uniform, except for areas with modern sanitation whose residents were spared. The incidence rates of cholera per 1000 infants (under the age of 1 year) were 1.16 and 0.93 for 1974 and 1975, respectively. On the whole, children below 10 years and females between 15 and 44 years of age were the ones most affected with eltor cholera. Higher rates of diarrhoea and hospitalization were noted among the contacts with cholera cases, compared with non-cholera controls. Contracting cholera was significantly associated with eating in places away from home, especially at charitable feeding centres.

During an epidemic of cholera we simultaneously cultured water from 30 important ponds, tanks and rivers of Dhaka city, to determine the role of surface water as a reservoir of Vibrio cholerae and nonagglutinating (NAG) vibrios and whether their presence or absence can be used as an indicator of a cholera epidemic in the community. Out of 4.016 samples 1216 (30.3%) were positive for NAG vibrios and one (0.025%) for Vibrio cholerae. Ponds showed a higher rate of NAG isolation (31.6%) than did rivers (21.9%). NAG group II constituted 87% and group V 10% of all positives. There were mild-to-moderate seasonal variations in isolation rates. The NAG isolation rate from water was related to the incidence of hospitalized NAG diarrhoea cases, but not to simultaneous cholera cases. Surface water does not appear to be an efficient natural reservoir of Vibrio cholerae, as it is for NAG vibrios. The absence of V. cholerae or presence of NAG vibrios in public surface water sources has no relationship with the extent of cholera cases present in a community.

The incidence of shigellosis and the death rate have increased and the resistance of shigellae to antibiotics has changed in Dhaka during our experiences. In 1980, we investigated the secondary infection and case rates, infection to case ratio, duration of illness, excretion of shigellae and antibiotic sensitivity pattern in 100 families with cases of shigellosis, culturing rectal swabs obtained by home visits for a 10-day period. Standard methods were used for culture and sensitivity tests. The over-all secondary infection rate in contacts was 27.3% and the case rate 10.7%. The rates were higher for Shigella flexneri than for Sh. dysenteriae. When the index cases were nought to four years old the secondary infection and case rates were higher than when index cases were older. Contacts aged nought to four years had highest attack rates. The average duration of excretion of Sh. flexneri was 4.5 and Sh. dysenteriae 2.6 days. Illness was one day longer for Sh. dysenteriae than for Sh. flexneri. Cases of shigellosis in hospital had higher rates of fever and blood in stool than those who were not in-patients. 40% of Sh. dysenteriae and 14% of Sh. flexneri were sensitive to tetracycline, 0 to 5% to streptomycin and 100% to sulphamethoxazole, trimethoprim and gentamicin. Incidence of Sh. flexneri had increased in 1980 but that of Sh. dysenteriae remained the same as in 1973 although Sh. dysenteriae type 1 appeared to be less infective in 1980 than in 1973.