An audit of clinical laboratory data of 25OHD at Aga Khan University as reflecting Vitamin D deficiency in Pakistan

Objectives: To estimate the burden of Vitamin D deficiency in people from different geographical areas of Pakistan. Methods: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised specimens of subjects tested for 25-hydroxy D at the clinical laboratory between September 2010 and September 2011. Serum samples received from the phlebotomy centres all over Pakistan and the main laboratory in Karachi were included. SPSS 19 was used for statistical analysis. Results: Of the 60937 specimens in the study, 18721(30.7%) related to men. The overall mean age was 40.5±19.7 years, and median 25-hydroxy D level was 13.5ng/ml (interquartile range: 25.1-7.4 ng/ml).Overall, mean log 25-hydroxy D was 1.14±0.39ng/ml (median: 13.5ng/ml; interquartile range: 25.1-7.4 ng/ml). Out of the total, 40279(66.1%) subjects were vitamin D-deficient

Peer-taught virtual research workshops for surgical residents: Protocol for a novel and sustainable solution to improving surgical research in Pakistan

Objective: To generate a protocol describing the methodology for a study assessing the effectiveness of a comprehensive series of peer-taught online research workshops for surgical residents across Pakistan in terms of improving research-related knowledge and skills, and long-term research involvement and output.Methods: The quasi-experimental study will consist of a series of six online research workshops conducted over Zoom for surgical residents across Pakistan. An online sign-up form will be circulated on social media to current surgical residents throughout Pakistan. Curricular content covered in the workshops will be developed in collaboration with experienced research faculty at the Departments of Surgery and Community Health Sciences at the Aga Khan University Hospital, Karachi. Facilitators of the workshops will be current surgical residents with a solid track record of research involvement at the hospital. Improvement in research-related knowledge and skills will be assessed through pre- and post-tests for each workshop. A post-series feedback form will assess satisfaction with the organisation, content relevance, peer-teaching and online delivery of the workshops. Long-term research involvement and output will be assessed by follow-up surveys at 6 months and 1 year post-workshop. All data-collection will be done via Google Forms. For ethical purposes, informed consent will be taken from participants prior to enrolment; data will be collected using a unique identifier number to maintain anonymity; and the only incentive provided to participants will be a Certificate of Completion for the research workshop series.Results: We expect that surgical trainees participating in the series of six research workshops will demonstrate a highly significant percentage improvement (p80%) to rate the overall organisation, effectiveness of online mode of instruction, and relevance to surgical training of the workshops as excellent/good. We also expect that most participants (\u3e80%) would strongly agree/agree that peer-education is an effective model of teaching in research workshops. Finally, we expect statistically significant improvement (pConclusions: In light of the ever-growing need for academic surgeons in Pakistan, this research protocol details a comprehensive strategy for research capacity-building among surgical trainees across the country. By equipping trainees with the knowledge and skills to conduct high-quality research, virtual research workshops provide a novel, grassroots-level and sustainable solution for addressing the surgical research crisis in Pakistan

Knowledge & Awareness about COVID-19 and the Practice of Respiratory Hygiene and Other Preventive Measures among Patients with Diabetes Mellitus in Pakistan

COVID-19 is a global pandemic that has emerged and it is rapidly spreading throughout the world and subsequently causing great damage to the global economy and health-care. Patients with diabetes or other comorbidities are at a greater risk of developing severe illness. Knowledge and awareness are key elements to stimulate practice of preventive measures. The present study evaluated the level of knowledge and awareness about COVID-19 among individuals with diabetes and their compliance with the preventive measures against it. A total of 242 individuals who were diagnosed with diabetes mellitus and were 18 years or older participated in the study. The data was collected using an interview based questionnaire. Data was analyzed using Statistical Package for Social Sciences(SPSS) version 24. The mean age ± SD of the study population was 50.78 ± 11.24 years. In this study, 215 (88.8%) participants were aware that COVID-19 is caused by a virus and the disease is spread through droplets after sneezing or touching and shaking hands with an infected person (78.5%). However, only half the study populace regularly monitored their glucose level and complied with the “sick day rules” that is applicable during this pandemic. The present study indicates that despite the adequate knowledge and awareness about the coronavirus disease, the study participants were non-compliant with the practice of preventive and precautionary measures against the pandemic

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Brain Eating Amoeba: Alarming Rise of Naegleriasis in Pakistan

Naegleriasis also known as primary amoebic meningoencephalitis (PAM) is a fulminant brain infection is caused by a single-celled, ameboflagellate known as Naegleria fowleri. Naegleria fowleri has been difficult to eradicate since its growth is typically found in bodies of warm freshwater, unchlorinated, piped water, swimming pools and moist soil. This letter focuses on characteristics and route of spread of infection caused by Naegleria Fowleri and preventative measures that can be taken to limit its spread. A thorough literature review was performed to identify different route of spread of Naegleria Fowleri infection and specific measures that should be taken to limit its spread. We found that Naegleria follows a nasal route of infection, migrating along the olfactory nerve, through the cribriform plate into the brain where it evokes a substantial immune response causing a widespread inflammation, hemorrhage and necrosis eventually leading to death. The at-risk population includes individuals associated with swimming, diving and water skiing in freshwater and poorly chlorinated swimming pools and individuals performing ablution. Therefore, specific measures should be taken to limit the spread of Naegleria Fowleri infection which includes education and awareness of the public as well as of the health professionals regarding Naegleriasis and its preventative measures

Atypical presentation of a rare gestational trophoblastic neoplasm: a case report

A 34-year-old woman had a history of 3 miscarriages and presented with symptoms of an unproductive cough and rising serum beta-human chorionic gonadotropin (B-hCG) levels. There were no gynaecological symptoms. A diagnosis of Choriocarcinoma with pulmonary metastasis was made. In Pakistan, the incidence of Choriocarcinoma remains exceedingly rare, accounting for less than 0.3% of all gynaecologic tumours. Though rare, if managed appropriately, it has a reasonably good prognosis, as demonstrated by the outcome of the current case. Keywords: Choriocarcinoma, EMA-CO Chemotherapy, Pulmonary Metastasis, Thoracotom

Genome Sequence of Exiguobacterium antarcticum B7, Isolated from a Biofilm in Ginger Lake, King George Island, Antarctica

Exiguobacterium antarcticum is a psychotropic bacterium isolated for the first time from microbial mats of Lake Fryxell in Antarctica. Many organisms of the genus Exiguobacterium are extremophiles and have properties of biotechnological interest, e. g., the capacity to adapt to cold, which make this genus a target for discovering new enzymes, such as lipases and proteases, in addition to improving our understanding of the mechanisms of adaptation and survival at low temperatures. This study presents the genome of E. antarcticum B7, isolated from a biofilm sample of Ginger Lake on King George Island, Antarctic peninsula.National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e TecnologicoCNPq)National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq)Brazilian Federal Agency for the Support and Evaluation of Graduate Education (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-CAPES)Brazilian Federal Agency for the Support and Evaluation of Graduate Education (Coordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorCAPES)Paraense Amazonia Foundation (Fundacao Amazonia ParaenseFAPESPA)Paraense Amazonia Foundation (Fundacao Amazonia Paraense-FAPESPA)Amazon Center of Excellence in Genomics of Microorganisms (Nucleo Amazonico de Excelencia em Genomica de Microorganismos)Centers of Excellence Support Program (Programa de apoio a Nucleo de Excelencia) Pronex/CNPq/FAPESPAAmazon Center of Excellence in Genomics of Microorganisms (Nucleo Amazonico de Excelencia em Genomica de Microorganismos)-Centers of Excellence Support Program (Programa de apoio a Nucleo de Excelencia) Pronex/CNPq/FAPESPANational Program for Academic Cooperation (Programa Nacional de Cooperacao Academica) PROCAD/CAPESNational Program for Academic Cooperation (Programa Nacional de Cooperacao Academica) PROCAD/CAPESStudies and Projects Funding Agency (Financiadora de Estudos e ProjetosFINEP)Studies and Projects Funding Agency (Financiadora de Estudos e Projetos-FINEP)Minas Gerais Research Fund (Fundacao de Amparo a Pesquisa do estado de Minas Gerais-FAPEMIG)Minas Gerais Research Fund (Fundacao de Amparo a Pesquisa do estado de Minas GeraisFAPEMIG