265 results on '"S Khan"'
Search Results
2. Association of fasting glucose with lifetime risk of incident heart failure: the Lifetime Risk Pooling Project
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Faraz S. Ahmad, Matthew J. O’Brien, Hongyan Ning, Michael P. Bancks, John T. Wilkins, Arjun Sinha, Norrina B. Allen, Donald M. Lloyd-Jones, Sadiya S. Khan, and Mercedes R. Carnethon
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Blood Glucose ,Male ,Risk ,Adult ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Population ,Risk Assessment ,White People ,Prediabetic State ,Sex Factors ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Diabetes Mellitus ,Hypoglycemic Agents ,Humans ,Prediabetes ,education ,Angiology ,Original Investigation ,Aged ,Heart Failure ,education.field_of_study ,business.industry ,Proportional hazards model ,Incidence ,Hazard ratio ,Fasting ,Competing risk ,Middle Aged ,medicine.disease ,Lifetime risk ,Race Factors ,Black or African American ,lcsh:RC666-701 ,Heart failure ,Commentary ,Female ,Morbidity ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers - Abstract
Background Given the rising prevalence of dysglycemia and disparities in heart failure (HF) burden, we determined race- and sex-specific lifetime risk of HF across the spectrum of fasting plasma glucose (FPG). Methods Individual-level data from adults without baseline HF was pooled from 6 population-based cohorts. Modified Kaplan–Meier analysis, Cox models adjusted for the competing risk of death, and Irwin’s restricted mean were used to estimate the lifetime risk, adjusted hazard ratio (aHR), and years lived free from HF in middle-aged (40–59 years) and older (60–79 years) adults with FPG Results In 40,117 participants with 638,910 person-years of follow-up, 4846 cases of incident HF occurred. The lifetime risk of HF was significantly higher among middle-aged White adults and Black women with prediabetes (range: 6.1% [95% CI 4.8%, 7.4%] to 10.8% [95% CI 8.3%, 13.4%]) compared with normoglycemic adults (range: 3.5% [95% CI 3.0%, 4.1%] to 6.5% [95% CI 4.9%, 8.1%]). Middle-aged Black women with diabetes had the highest lifetime risk (32.4% [95% CI 26.0%, 38.7%]) and aHR (4.0 [95% CI 3.0, 5.4]) for HF across race-sex groups. Middle-aged adults with prediabetes and diabetes lived on average 0.9–1.6 and 4.1–6.0 fewer years free from HF, respectively. Findings were similar in older adults except older Black women with prediabetes did not have a higher lifetime risk of HF. Conclusions Prediabetes was associated with higher lifetime risk of HF in middle-aged White adults and Black women, with the association attenuating in older Black women. Black women with diabetes had the highest lifetime risk of HF compared with other race-sex groups.
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- 2021
3. Missed myocardial infarction in a vicenarian with malignant anomalous right coronary artery causing acute coronary syndrome: a case report
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Paramanand Maharaj, Nafeesah Ali, Kandace Baggan, Shari S Khan, and Ronan G Ali
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Adult ,Male ,Acute coronary syndrome ,medicine.medical_specialty ,Chest Pain ,Coronary Vessel Anomalies ,Coronary anomaly ,lcsh:Medicine ,Case Report ,030204 cardiovascular system & hematology ,Chest pain ,Sudden cardiac death ,Coronary artery disease ,03 medical and health sciences ,Anomalous right coronary artery ,0302 clinical medicine ,Internal medicine ,medicine.artery ,Medicine ,Humans ,Myocardial infarction ,Acute Coronary Syndrome ,business.industry ,lcsh:R ,General Medicine ,medicine.disease ,Coronary arteries ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Right coronary artery ,Pulmonary artery ,Cardiology ,medicine.symptom ,business - Abstract
Background Traditional coronary artery disease risk factors are well established and help risk stratify most patients presenting with chest pain syndromes. Young patients (under age 30 years) without other risk factors are thought to be at very low risk of coronary artery disease and acute coronary syndromes. Case presentation We highlight the case of a 27-year-old Afro-Caribbean male who presented to hospital with chest pain and was discharged from the emergency room because he was thought to be low risk for ischemic heart disease. Laboratory investigations subsequently confirmed acute coronary syndrome. He was found to have an anomalous right coronary artery with a malignant origin running between the aorta and pulmonary artery eventually requiring surgical correction. Anomalous origins of the coronary arteries are rare causes of acute coronary syndromes, chest pain, and sudden cardiac death. Conclusion Our patient could have easily had an adverse outcome as his diagnosis was missed by the initial treating physician. It is important to consider anomalous coronary artery origin in the evaluation of young symptomatic patients who may be otherwise low risk and not have traditional risk factors for ischemic heart disease.
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- 2021
4. Association of cardiovascular health and epigenetic age acceleration
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Matthew A. Allison, Aladdin H. Shadyab, Wei Zhang, Philip Greenland, Hilary A. Tindle, Gretchen L. Wells, Sadiya S. Khan, Donald M. Lloyd-Jones, Rami Nassir, Lisa W. Martin, Andrea A. Baccarelli, Lifang Hou, Eric A. Whitsel, JoAnn E. Manson, Yinan Zheng, and Tess D. Pottinger
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0301 basic medicine ,Aging ,Younger age ,Health Status ,Women’s health initiative (WHI) ,Disease ,030204 cardiovascular system & hematology ,Cardiovascular ,Epigenesis, Genetic ,Cohort Studies ,0302 clinical medicine ,Genetics (clinical) ,media_common ,Cause of death ,DNA methylation ,Women's health initiative ,Women's Health Initiative ,Longevity ,Simple seven ,American Heart Association ,Middle Aged ,Postmenopause ,Cardiovascular Diseases ,Cohort ,Female ,medicine.medical_specialty ,Cardiovascular health (CVH) ,media_common.quotation_subject ,Cardiovascular health ,Clinical Sciences ,Epigenetic age acceleration ,Acceleration ,Paediatrics and Reproductive Medicine ,03 medical and health sciences ,Genetic ,Internal medicine ,Genetics ,medicine ,Humans ,Epigenetics ,Molecular Biology ,Aged ,business.industry ,Research ,United States ,Good Health and Well Being ,030104 developmental biology ,Cross-Sectional Studies ,Women's Health ,Women’s health initiative ,CpG Islands ,business ,Epigenesis ,Developmental Biology - Abstract
Background Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age. Methods and results We performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women’s Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score. We examined the association between CVH score and EAA using linear regression modeling adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, 50% were white and mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (~ 6 months younger age per 1 point higher CVH score, p p Conclusions These cross-sectional observations suggest a possible mechanism by which ideal CVH is associated with greater longevity.
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- 2021
5. ICU admission body composition: skeletal muscle, bone, and fat effects on mortality and disability at hospital discharge—a prospective, cohort study
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John Fantauzzi, Ria Itty, Hau Chieng, Malik M H S Khan, Camille L. Dumas, Ariel Jaitovich, Paul J. Feustel, Ali Naqvi, Marc A. Judson, and Jesse B. Hall
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Male ,medicine.medical_specialty ,Bone density ,Skeletal muscle ,Adipose tissue ,Critical Care and Intensive Care Medicine ,Bone and Bones ,law.invention ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,law ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Mortality ,Prospective cohort study ,Muscle, Skeletal ,Aged ,Retrospective Studies ,business.industry ,Research ,Confounding ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,lcsh:RC86-88.9 ,Middle Aged ,medicine.disease ,Intensive care unit ,Obesity ,Patient Discharge ,Intensive Care Units ,medicine.anatomical_structure ,030228 respiratory system ,Cohort ,Body Composition ,Abdomen ,Female ,business ,Critical illness ,Cohort study - Abstract
Background Reduced body weight at the time of intensive care unit (ICU) admission is associated with worse survival, and a paradoxical benefit of obesity has been suggested in critical illness. However, no research has addressed the survival effects of disaggregated body constituents of dry weight such as skeletal muscle, fat, and bone density. Methods Single-center, prospective observational cohort study of medical ICU (MICU) patients from an academic institution in the USA. Five hundred and seven patients requiring CT scanning of chest or abdomen within the first 24 h of ICU admission were evaluated with erector spinae muscle (ESM) and subcutaneous adipose tissue (SAT) areas and with bone density determinations at the time of ICU admission, which were correlated with clinical outcomes accounting for potential confounders. Results Larger admission ESM area was associated with decreased odds of 6-month mortality (OR per cm2, 0.96; 95% CI, 0.94–0.97; p 2, 0.98; 95% CI, 0.96–0.99; p = 0.012). Higher bone density was similarly associated with lower odds of mortality (OR per 100 HU, 0.69; 95% CI, 0.49–0.96; p = 0.027) and disability at discharge (OR per 100 HU, 0.52; 95% CI, 0.37–0.74; p Conclusion In our cohort, ICU admission skeletal muscle mass measured with ESM area and bone density were associated with survival and disability at discharge, although muscle area was the only component that remained significantly associated with survival after multivariable adjustments. SAT had no association with the analyzed outcome measures.
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- 2020
6. External validation, update and development of prediction models for pre-eclampsia using an Individual Participant Data (IPD) meta-analysis: the International Prediction of Pregnancy Complication Network (IPPIC pre-eclampsia) protocol
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Asma Khalil, Lucilla Poston, Kym I E Snell, Jenny Myers, Claire L Chan, Karel G.M. Moons, Ben W.J. Mol, Asif Ahmed, Louise C. Kenny, Richard D Riley, Khalid S. Khan, Liona C. Poon, Lucy C Chappell, Julie Dodds, Ewelina Rogozińska, John Allotey, Peter von Dadelszen, Shakila Thangaratinam, Marcus Green, Basky Thilaganathan, and Richard Hooper
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Individual participant data ,medicine.medical_specialty ,Maternal ,030204 cardiovascular system & hematology ,Q1 ,Fetal ,03 medical and health sciences ,0302 clinical medicine ,Prediction model ,medicine ,Protocol ,030212 general & internal medicine ,Intensive care medicine ,Protocol (science) ,lcsh:R5-920 ,Pregnancy ,Eclampsia ,business.industry ,medicine.disease ,Prognosis ,R1 ,IPD ,Identification (information) ,Systematic review ,Aggregate data ,lcsh:Medicine (General) ,Complication ,business ,RA ,Pre-eclampsia ,Predictive modelling ,Biomedical engineering - Abstract
Background Pre-eclampsia, a condition with raised blood pressure and proteinuria is associated with an increased risk of maternal and offspring mortality and morbidity. Early identification of mothers at risk is needed to target management. Methods/design We aim to systematically review the existing literature to identify prediction models for pre-eclampsia. We have established the International Prediction of Pregnancy Complication Network (IPPIC), made up of 72 researchers from 21 countries who have carried out relevant primary studies or have access to existing registry databases, and collectively possess data from more than two million patients. We will use the individual participant data (IPD) from these studies to externally validate these existing prediction models and summarise model performance across studies using random-effects meta-analysis for any, late (after 34 weeks) and early (before 34 weeks) onset pre-eclampsia. If none of the models perform well, we will recalibrate (update), or develop and validate new prediction models using the IPD. We will assess the differential accuracy of the models in various settings and subgroups according to the risk status. We will also validate or develop prediction models based on clinical characteristics only; clinical and biochemical markers; clinical and ultrasound parameters; and clinical, biochemical and ultrasound tests. Discussion Numerous systematic reviews with aggregate data meta-analysis have evaluated various risk factors separately or in combination for predicting pre-eclampsia, but these are affected by many limitations. Our large-scale collaborative IPD approach encourages consensus towards well developed, and validated prognostic models, rather than a number of competing non-validated ones. The large sample size from our IPD will also allow development and validation of multivariable prediction model for the relatively rare outcome of early onset pre-eclampsia. Trial registration The project was registered on Prospero on the 27 November 2015 with ID: CRD42015029349 .
- Published
- 2017
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7. Tuberculosis active case finding in Cambodia: a pragmatic, cost-effectiveness comparison of three implementation models
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Pichenda Koeut, Keovathanak Khim, Lydia Boudarene, Richard James, Joanne Yoong, Saly Saint, Richard Coker, Chea Phalla, Tan Eang Mao, and Mishal S Khan
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Pathology ,medicine.medical_specialty ,Tuberculosis ,Case finding ,Cost effectiveness ,Cost-Benefit Analysis ,030231 tropical medicine ,Psychological intervention ,03 medical and health sciences ,0302 clinical medicine ,Poverty Areas ,Medicine ,National Policy ,Humans ,Mass Screening ,030212 general & internal medicine ,Activity-based costing ,Tuberculosis, Pulmonary ,Mass screening ,Retrospective Studies ,Strategic planning ,Cost–benefit analysis ,business.industry ,Health Plan Implementation ,Middle Aged ,medicine.disease ,Infectious Diseases ,Family medicine ,Cost-effectiveness ,business ,Cambodia ,Research Article - Abstract
BACKGROUND: Globally, almost 40% of tuberculosis (TB) patients remain undiagnosed, and those that are diagnosed often experience prolonged delays before initiating correct treatment, leading to ongoing transmission. While there is a push for active case finding (ACF) to improve early detection and treatment of TB, there is extremely limited evidence about the relative cost-effectiveness of different ACF implementation models. Cambodia presents a unique opportunity for addressing this gap in evidence as ACF has been implemented using different models, but no comparisons have been conducted. The objective of our study is to contribute to knowledge and methodology on comparing cost-effectiveness of alternative ACF implementation models from the health service perspective, using programmatic data, in order to inform national policy and practice. METHODS: We retrospectively compared three distinct ACF implementation models - door to door symptom screening in urban slums, checking contacts of TB patients, and door to door symptom screening focusing on rural populations aged above 55 - in terms of the number of new bacteriologically-positive pulmonary TB cases diagnosed and the cost of implementation assuming activities are conducted by the national TB program of Cambodia. We calculated the cost per additional case detected using the alternative ACF models. RESULTS: Our analysis, which is the first of its kind for TB, revealed that the ACF model based on door to door screening in poor urban areas of Phnom Penh was the most cost-effective (249 USD per case detected, 737 cases diagnosed), followed by the model based on testing contacts of TB patients (308 USD per case detected, 807 cases diagnosed), and symptomatic screening of older rural populations (316 USD per case detected, 397 cases diagnosed). CONCLUSIONS: Our study provides new evidence on the relative effectiveness and economics of three implementation models for enhanced TB case finding, in line with calls for data from 'routine conditions' to be included in disease control program strategic planning. Such cost-effectiveness comparisons are essential to inform resource allocation decisions of national policy makers in resource constraint settings. We applied a novel, pragmatic methodological approach, which was designed to provide results that are directly relevant to policy makers, costing the interventions from Cambodia's national TB program's perspective and using case finding data from implementation activities, rather than experimental settings.
- Published
- 2017
8. The CROWN initiative: journal editors invite researchers to develop core outcomes in women’s health
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Khalid S. Khan and José M. Belizán
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Research design ,medicine.medical_specialty ,Evidence-based medicine ,Consensus ,CIENCIAS MÉDICAS Y DE LA SALUD ,Women's health ,Alternative medicine ,Specialty ,Reproductive medicine ,Psychological intervention ,Ciencias de la Salud ,Guidelines ,purl.org/becyt/ford/3.3 [https] ,Clinical trials ,Nursing ,Outcome Assessment, Health Care ,Obstetrics and Gynaecology ,medicine ,Humans ,Treatment outcome ,Salud Ocupacional ,business.industry ,Public health ,Obstetrics and Gynecology ,Systematic reviews ,Research Personnel ,Clinical trial ,Editorial ,Treatment Outcome ,Systematic review ,Reproductive Medicine ,Research Design ,Bias (Epidemiology) ,Women's Health ,Endpoint determination/standards ,Female ,purl.org/becyt/ford/3 [https] ,Research design/standards ,business - Abstract
Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a "core outcomes set" - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CROWN (CoRe Outcomes in WomeN's health) Initiative. Fil: Khan, Khalid. CROWN Initiative; Estados Unidos Fil: Belizan, Jose. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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- 2014
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9. The effectiveness of a clinically integrated e-learning course in evidence-based medicine: A cluster randomised controlled trial
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Amanda Burls, Sjors F.P.J. Coppus, Regina Kulier, Julie Hadley, Berrit Meyerrose, Gianni Zanrei, Tamás Decsi, Kausik Das, Katarzyna Stawiarz, Susanne Weinbrenner, Ben W.J. Mol, Theodoros N. Arvanitis, Jose I. Emparanza, Andrea R. Horvath, Eva Nagy, Javier Zamora, Sadia Malick, Marcin Kaczor, Khalid S. Khan, Karen Pierer, Regina Kunz, Juan B. Cabello, Amsterdam Public Health, Center for Reproductive Medicine, and Obstetrics and Gynaecology
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Program evaluation ,medicine.medical_specialty ,E-learning (theory) ,education ,Alternative medicine ,lcsh:Medicine ,Education ,X900 ,Medicine ,Cluster Analysis ,Humans ,Learning ,X200 ,Cluster randomised controlled trial ,X300 ,Netherlands ,Reino unido ,Medicine(all) ,Medical education ,lcsh:LC8-6691 ,Internet ,Evidence-Based Medicine ,lcsh:Special aspects of education ,business.industry ,lcsh:R ,General Medicine ,Evidence-based medicine ,United Kingdom ,Obstetrics ,Gynecology ,LB ,business ,RA ,Program Evaluation ,Research Article - Abstract
Background: To evaluate the educational effects of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduates compared to a traditional lecture-based course of equivalent content. Methods: We conducted a cluster randomised controlled trial in the Netherlands and the UK involving postgraduate trainees in six obstetrics and gynaecology departments. Outcomes (knowledge gain and change in attitude towards EBM) were compared between the clinically integrated e-learning course (intervention) and the traditional lecture based course (control). We measured change from pre- to post-intervention scores using a validated questionnaire assessing knowledge (primary outcome) and attitudes (secondary outcome). Results: There were six clusters involving teaching of 61 postgraduate trainees (28 in the intervention and 33 in the control group). The intervention group achieved slightly higher scores for knowledge gain compared to the control, but these results were not statistically significant (difference in knowledge gain: 3.5 points, 95% CI -2.7 to 9.8, p = 0.27). The attitudinal changes were similar for both groups. Conclusion: A clinically integrated e-learning course was at least as effective as a traditional lecture based course and was well accepted. Being less costly than traditional teaching and allowing for more independent learning through materials that can be easily updated, there is a place for incorporating e-learning into postgraduate EBM curricula that offer on-the-job training for just-in-time learning. Trial registration: Trial registration number: ACTRN12609000022268.
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- 2009
10. Core outcomes set for studies on primary prevention of preterm birth
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Shireen Meher, James Duffy, George R. Saade, Janneke van 't Hooft, Khalid S. Khan, Zarko Alfirevic, and Ben W.J. Mol
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medicine.medical_specialty ,Cochrane collaboration ,business.industry ,Alternative medicine ,Medicine (miscellaneous) ,3. Good health ,Nonprobability sampling ,Systematic review ,Family medicine ,Primary prevention ,Poster Presentation ,Medicine ,Pharmacology (medical) ,business ,Set (psychology) ,Selection (genetic algorithm) ,Patient organisations - Abstract
Materials and methods Between May and November 2014 we went through the process of identification and selection of outcomes. All possible outcomes were drawn from systematic reviews, interviews and questionnaires. From this initial list, a selection process was performed using an online 2-round Delphic survey and a consultation meeting. Target stakeholders were approached to contribute in this selection (parents, midwives, obstetricians, neonatologists and methodologists) through purposive sampling in relevant networks: patient organisations, midwife networks, Global Obstetrics Network (GONet), the Cochrane collaboration and journal editors from the Core Outcomes in Women’s health (CROWN) initiative.
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- 2015
11. Prevalence and risk factors of kidney disease in urban Karachi: baseline findings from a community cohort study
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Ashar Alam, Ismat Lotia-Farrukh, Naila Baig-Ansari, Farhana Amanullah, and Faisal S. Khan
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Population ,Renal function ,Disease ,South Asia ,Severity of Illness Index ,General Biochemistry, Genetics and Molecular Biology ,Cohort Studies ,Diabetes Complications ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Chronic kidney disease ,medicine ,Prevalence ,Diabetes Mellitus ,Humans ,Pakistan ,Renal Insufficiency, Chronic ,education ,Intensive care medicine ,Aged ,Medicine(all) ,education.field_of_study ,Biochemistry, Genetics and Molecular Biology(all) ,business.industry ,urogenital system ,Age Factors ,General Medicine ,Middle Aged ,medicine.disease ,Cohort ,Hypertension ,Microalbuminuria ,Female ,business ,Cohort study ,Kidney disease ,Research Article ,Glomerular Filtration Rate - Abstract
Background Chronic kidney disease (CKD) is being increasingly recognized as a leading public health problem. However, there are limited data available with respect to prevalence of CKD in Pakistan, a developing South Asian country. The study presents the baseline findings of prevalence and risk factors for adult kidney disease in a Pakistani community cohort. Methods A total of 667 households were enrolled between March 2010 and August 2011 including 461 adults, aged 15 and older. Mild kidney disease was defined as estimated Glomerular Filtration Rate (eGFR) ≥60 ml/min with microalbuminuria ≥ 30 mg/dl and moderate kidney disease was defined as eGFR
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- 2014
12. The development of pharmacy brief intervention practice: overview of a research program
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Ranjita Dhital, Ian Norman, Jim McCambridge, Natasha S Khan, and Peter Milligan
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business.industry ,Service delivery framework ,Pharmacist ,Pharmacy ,General Medicine ,law.invention ,Clinical pharmacy ,Nursing ,Randomized controlled trial ,law ,Meeting Abstract ,Medicine ,Job satisfaction ,Pharmacy practice ,Brief intervention ,business - Abstract
Brief intervention (BI) delivered in pharmacies is not currently routine practice, nor is there evidence regarding its efficacy. Community pharmacies attract a large and diverse range of people to a health-care environment that is promising for BI research. Work undertaken by this research group included semi-structured interviews with pharmacy service users to obtain their views on potential pharmacy BI; a five-month cohort study with 134 participants conducted in 28 pharmacies that assessed feasibility issues; and focus-group studies with “active” and “less active” pharmacists to identify barriers and facilitators of implementing BI. Pharmacy service users were positive about participating in BI, which was found to be feasible. Training and staff support were identified as important factors influencing service delivery, and there are preliminary indications of effectiveness including an impressive reduction in overall consumption among those who completed follow-up. Pharmacist motivation has been evaluated with the Short Alcohol and Alcohol Problems Perception Questionnaire (SAAPPQ), and role adequacy and work satisfaction improved among “active” pharmacists. These outcomes are currently being used to inform the development of a randomized controlled trial of BI delivered in the pharmacy, due to begin soon. It is hoped that findings from the trial will contribute to current knowledge and promote interest in the area. Unanswered questions include how pharmacy BI can be implemented in routine practice if trial results demonstrate effectiveness, and how SBI fits with the needs of a changing pharmacy profession.
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- 2012
13. Comparison of cellular and humoral immune responses induced by primary, consensus or mosaic HIV-1 Env DNA vaccines
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DB Weiner, Amir S. Khan, Jian Yan, Niranjan Y. Sardesai, and Panyupa Pankhong
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lcsh:Immunologic diseases. Allergy ,biology ,business.industry ,Electroporation ,Human immunodeficiency virus (HIV) ,RNA ,medicine.disease_cause ,DNA vaccination ,Immune system ,Infectious Diseases ,Antigen ,Virology ,Immunology ,Poster Presentation ,biology.protein ,Medicine ,Antibody ,business ,lcsh:RC581-607 - Abstract
Background The genomic variability of HIV viruses has impeded the development of globally relevant HIV vaccines with ability to induce strong and broad cellular and humoral immune responses. Many strategies, such as codon/ RNA optimization, addition of highly efficient leader sequences, use of consensus or mosaic antigens, and electroporation (EP) have all been applied to enhance the breadth and magnitude of immune responses induced by DNA vaccines.
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- 2012
14. Optimization of chemical induction for evaluation of endogenous retroviruses in different species
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Hailun Ma, Dhanya K. Williams, Teresa A. Galvin, Arifa S. Khan, Wenbin Ma, Yunkun Ma, and Syed Shaheduzzaman
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lcsh:Immunologic diseases. Allergy ,biology ,Rodent ,viruses ,Endogenous retrovirus ,biology.organism_classification ,Bioinformatics ,Cell biology ,Infectious Diseases ,Retrovirus ,Cell culture ,Virology ,biology.animal ,Poster Presentation ,biology.protein ,Vero cell ,Inducer ,African Green Monkey ,Antibody ,lcsh:RC581-607 - Abstract
Background Chemical inducers such as 5-azacytidine (AzaC) and 5’iodo-2’deoxyuridine (lUdR) have been used to discover and characterize endogenous retroviruses from rodent and avian speciecs, for example KBALB mouse cells. We found that induction conditions that have been optimized for mouse cells were not successful in inducing retrovirus from cell lines of other species, including nonhuman primates. Therefore, we developed a stepwise strategy based upon identification of critical parameters for endogenous retrovirus induction in mouse cells for optimizing induction conditions for non-murine cells. Using this approach, we have determined optimum conditions for investigating inducible endogenous retroviruses from Vero cells, which are of African green monkey (AGM) origin, a species that has never been reported to produce endogenous retroviruses [1].
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- 2011
15. P03-11. DNA vaccination with IL-12 lowers viral replication following SIVmac251 challenge
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Ling Wu, Julie A. Karl, Nancy Miller, Betts, David H. O’Connor, David I. Watkins, Lauren A. Hirao, Anlan Dai, Niranjan Y. Sardesai, DB Weiner, Amir S. Khan, Jean D. Boyer, Roger W. Wiseman, and Simon M. Lank
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lcsh:Immunologic diseases. Allergy ,biology ,business.industry ,Bioinformatics ,Virology ,DNA vaccination ,Infectious Diseases ,Viral replication ,Poster Presentation ,Interleukin 12 ,biology.protein ,Medicine ,Antibody ,lcsh:RC581-607 ,business - Published
- 2009
16. P14-08. Intramuscular DNA delivery by electroporation leads to greatly enhanced systemic and mucosal immune responses and control of SIVmac251 challenge
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Rashmi Jalah, Vainav Patel, Cristina Bergamaschi, Ruxandra Draghia-Akli, A Valentin, Amir S. Khan, Viraj Kulkarni, K. K. A. Van Rompay, G.N. Pavlakis, Claes Ohlen, Margherita Rosati, Barbara K. Felber, and A von Gegerfelt
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lcsh:Immunologic diseases. Allergy ,Dna delivery ,biology ,business.industry ,Electroporation ,Viremia ,medicine.disease ,Bioinformatics ,Phenotype ,Infectious Diseases ,Immune system ,Antigen ,Virology ,Immunology ,Poster Presentation ,medicine ,biology.protein ,Antibody ,lcsh:RC581-607 ,business ,CD8 - Abstract
Results DNA delivery using EP led to greatly enhanced expression of SIV antigens and increased cellular responses (up 3% of total T cells) that were broad, long-lasting (up to 45 weeks post vaccination) and included cells of multifunctional phenotype. SIV-specific cellular responses were found both in blood, BAL and rectal mucosa. Interestingly, compared to blood, the responses in BAL were consistently higher (up to 2 log) and included a higher frequency of polyfunctional cells. The cellular responses were characterized as predominantly EM CD4+ and CD8+ T cells in BAL and as both CM and EM T cells in blood. EP DNA delivery elicited both systemic and mucosal humoral immune responses, including the induction of Gag-specific IgA. Upon high dose SIVmac251 challenge, the vaccinated animals showed statistically significant lower VL peak in acute (1 log10) and in chronic viremia (1.7 log10).
- Published
- 2009
17. Knowledge and beliefs concerning evidence-based practice amongst complementary and alternative medicine health care practitioners and allied health care professionals: A questionnaire survey
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Julie Hadley, Khalid S. Khan, Ismail Hassan, HADLEY, Julie, Hassan, Ismail, and Khan, Khalid
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Adult ,Complementary Therapies ,Male ,medicine.medical_specialty ,Health Knowledge, Attitudes, Practice ,Evidence-based practice ,Attitude of Health Personnel ,MEDLINE ,Alternative medicine ,Allied Health Personnel ,B300 ,X900 ,Nursing ,Surveys and Questionnaires ,Health care ,medicine ,Medical Staff ,Humans ,X200 ,Staff Development ,Curriculum ,Evidence-Based Medicine ,business.industry ,Professional development ,Questionnaire ,lcsh:Other systems of medicine ,General Medicine ,Evidence-based medicine ,Middle Aged ,lcsh:RZ201-999 ,United Kingdom ,Complementary and alternative medicine ,Health Care Surveys ,Female ,Clinical Competence ,business ,Research Article - Abstract
Background Evidence-based practice (EBP) has become an important competency in many allied and complementary and alternative medicine (CAM) health care practitioners' professional standards of proficiency. Methods To compliment an EBP course for allied health care professionals and CAM practitioners, we undertook a questionnaire survey to assess learning needs. We developed a questionnaire to measure allied health care professionals and CAM practitioners' basic knowledge, skills and beliefs concerning the main principles of EBP. The questionnaires were administered to all attendees of one-day EBP workshops. Results During 2004–5 we surveyed 193 allied health care professionals and CAM practitioners who attended one-day EBP courses prior to commencement of teaching. Of the respondents 121 (62.7%) were allied health care professionals and 65 (33.7%) practitioners stated that they work in the CAM field Our survey found that the majority of the respondents had not previously attended a literature appraisal skills workshop (87.3%) or received formal training in research methods (69.9%), epidemiology (91.2%) or statistics (80.8%). Furthermore, 67.1% of practitioners specified that they felt that they had not had adequate training in EBM and they identified that they needed more training and education in the principles of EBM (86.7%). Differences in knowledge and beliefs concerning EBP amongst allied and CAM practitioners were found and length of time since qualification was also found to be an important factor in practitioner's beliefs. More CAM practitioners compared to allied health professionals accessed educational literature via the Internet (95.3% v 68.1%, p = 0.008). Whilst, practitioners with more than 11 years experience felt that original research papers were far more confusing (p = 0.02) than their less experienced colleagues. Conclusion The results demonstrate that practitioner's learning needs do vary according to the type of profession, time since graduation and prior research experience. Our survey findings are exploratory and will benefit from further replication, however, we do believe that they warrant consideration by allied health care and CAM tutors and trainers when planning EBP teaching curricula as it is important to tailor teaching to meet the needs of specific subgroups of trainees to ensure that specific learning needs are met.
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- 2008
18. Human infrapatellar fat pad-derived stem cells express the pericyte marker 3G5 and show enhanced chondrogenesis after expansion in fibroblast growth factor-2
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Simon R. Tew, Timothy E. Hardingham, Adetola B Adesida, and Wasim S. Khan
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Pathology ,medicine.medical_specialty ,Cellular differentiation ,Immunology ,Cell- and Tissue-Based Therapy ,Biology ,Fibroblast growth factor ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Rheumatic Diseases ,medicine ,Articular cartilage repair ,Immunology and Allergy ,Humans ,Growth Substances ,Cells, Cultured ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,Infrapatellar fat pad ,Mesenchymal stem cell ,Antibodies, Monoclonal ,Cell Differentiation ,Mesenchymal Stem Cells ,Patella ,Chondrogenesis ,Cell biology ,medicine.anatomical_structure ,Adipose Tissue ,Fibroblast Growth Factor 2 ,Pericyte ,Stem cell ,Pericytes ,030217 neurology & neurosurgery ,Research Article - Abstract
Introduction Infrapatellar fat pad (IPFP) is a possible source of stem cells for the repair of articular cartilage defects. In this study, adherent proliferative cells were isolated from digests of IPFP tissue. The effects of the expansion of these cells in fibroblast growth factor-2 (FGF-2) were tested on their proliferation, characterisation, and chondrogenic potential. Methods IPFP tissue was obtained from six patients undergoing total knee replacement, and sections were stained with 3G5, alpha smooth muscle actin, and von Willebrand factor to identify different cell types in the vasculature. Cells were isolated from IPFP, and both mixed populations and clonal lines derived from them were characterised for cell surface epitopes, including 3G5. Cells were expanded with and without FGF-2 and were tested for chondrogenic differentiation in cell aggregate cultures. Results 3G5-positive cells were present in perivascular regions in tissue sections of the IPFP, and proliferative adherent cells isolated from the IPFP were also 3G5-positive. However, 3G5 expression was on only a small proportion of cells in all populations and at all passages, including the clonally expanded cells. The cells showed cell surface epitope expression similar to adult stem cells. They stained strongly for CD13, CD29, CD44, CD90, and CD105 and were negative for CD34 and CD56 but were also negative for LNGFR (low-affinity nerve growth factor receptor) and STRO1. The IPFP-derived cells showed chondrogenic differentiation in cell aggregate cultures, and prior expansion with FGF-2 enhanced chondrogenesis. Expansion in FGF-2 resulted in greater downregulation of many cartilage-associated genes, but on subsequent chondrogenic differentiation, they showed stronger upregulation of these genes and this resulted in greater matrix production per cell. Conclusion These results show that these cells express mesenchymal stem cell markers, but further work is needed to determine the true origin of these cells. These results suggest that the expansion of these cells with FGF-2 has important consequences for facilitating their chondrogenic differentiation.
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- 2008
19. WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity
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Khalid S. Khan, Pallavi Latthe, Lale Say, Metin Gülmezoglu, and Manish Latthe
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medicine.medical_specialty ,Population ,Global Health ,Pelvic Pain ,World Health Organization ,Dysmenorrhea ,Pelvic inflammatory disease ,Epidemiology ,Prevalence ,Medicine ,Humans ,education ,Developing Countries ,Disease burden ,Response rate (survey) ,education.field_of_study ,business.industry ,lcsh:Public aspects of medicine ,Pelvic pain ,Developed Countries ,Public Health, Environmental and Occupational Health ,lcsh:RA1-1270 ,Epidemiologic Studies ,Dyspareunia ,Reproductive Medicine ,Sample size determination ,Chronic Disease ,Physical therapy ,Regression Analysis ,Female ,Biostatistics ,medicine.symptom ,business ,Research Article ,Pelvic Inflammatory Disease - Abstract
Background Health care planning for chronic pelvic pain (CPP), an important cause of morbidity amongst women is hampered due to lack of clear collated summaries of its basic epidemiological data. We systematically reviewed worldwide literature on the prevalence of different types of CPP to assess the geographical distribution of data, and to explore sources of variation in its estimates. Methods We identified data available from Medline (1966 to 2004), Embase (1980 to 2004), PsycINFO (1887 to 2003), LILACS (1982 to 2004), Science Citation index, CINAHL (January 1980 to 2004) and hand searching of reference lists. Two reviewers extracted data independently, using a piloted form, on participants' characteristics, study quality and rates of CPP. We considered a study to be of high quality (valid) if had at least three of the following features: prospective design, validated measurement tool, adequate sampling method, sample size estimation and response rate >80%. We performed both univariate and multivariate meta-regression analysis to explore heterogeneity of results across studies. Results There were 178 studies (459975 participants) in 148 articles. Of these, 106 studies were (124259 participants) on dysmenorrhoea, 54 (35973 participants) on dyspareunia and 18 (301756 participants) on noncyclical pain. There were only 19/95 (20%) less developed and 1/45 (2.2%) least developed countries with relevant data in contrast to 22/43 (51.2%) developed countries. Meta-regression analysis showed that rates of pain varied according to study quality features. There were 40 (22.5%) high quality studies with representative samples. Amongst them, the rate of dysmenorrhoea was 16.8 to 81%, that of dyspareunia was 8 to 21.8%, and that for noncyclical pain was 2.1 to 24%. Conclusion There were few valid population based estimates of disease burden due to CPP from less developed countries. The variation in rates of CPP worldwide was due to variable study quality. Where valid data were available, a high disease burden of all types of pelvic pain was found.
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- 2006
20. Knowledge of modifiable risk factors of heart disease among patients with acute myocardial infarction in Karachi, Pakistan: a cross sectional study
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Azhar Faruqui, Syed Ishtiaq Rasool, Nish Chaturvedi, Muhammad S Khan, Tazeen H. Jafar, Fahim H. Jafary, and Juanita Hatcher
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Male ,medicine.medical_specialty ,lcsh:Diseases of the circulatory (Cardiovascular) system ,Health Knowledge, Attitudes, Practice ,Heart disease ,Heart Diseases ,Cross-sectional study ,Myocardial Infarction ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Surveys and Questionnaires ,medicine ,Humans ,Pakistan ,030212 general & internal medicine ,Risk factor ,Nuclear family ,2. Zero hunger ,030505 public health ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,3. Good health ,Cross-Sectional Studies ,lcsh:RC666-701 ,Family medicine ,Physical therapy ,Population study ,Female ,0305 other medical science ,business ,Cardiology and Cardiovascular Medicine ,Research Article - Abstract
Background Knowledge is an important pre-requisite for implementing both primary as well as secondary preventive strategies for cardiovascular disease (CVD). There are no estimates of the level of knowledge of risk factor of heart disease in patients with CVD. We estimated the level of knowledge of modifiable risk factors and determined the factors associated with good level of knowledge among patients presenting with their first acute myocardial infarction (AMI) in a tertiary care hospital in Karachi, Pakistan. Methods A hospital based cross-sectional study was conducted at the National Institute of Cardiovascular Disease, a major tertiary care hospital in Karachi Pakistan. Patients admitted with their first AMI were eligible to participate. Standard questionnaire was used to interview 720 subjects. Knowledge of four modifiable risk factors of heart disease: fatty food consumption, smoking, obesity and exercise were assessed. The participants knowing three out of four risk factors were regarded as having a good level of knowledge. A multiple logistic regression model was constructed to identify the determinants of good level of knowledge. Results The mean age (SD) was 54 (11.66) years. A mere 42% of our study population had a good level of knowledge. In multiple logistic regression analysis, independent predictors of "good" level of knowledge were (odds ratio [95% confidence interval]) more than ten years of schooling were 2.5 [1.30, 4.80] (verses no schooling at all) and nuclear family system (verses extended family system) 2.54 [1.65, 3.89]. In addition, Sindhi ethnicity OR [3.03], higher level of exercise OR [2.76] and non user of tobacco OR [2.53] were also predictors of good level of knowledge. Conclusion Our findings highlight the lack of good level of knowledge of modifiable risk factors for heart disease among subjects admitted with AMI in Pakistan. There is urgent need for aggressive and targeted educational strategies in the Pakistani population.
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- 2006
21. Bias associated with delayed verification in test accuracy studies: accuracy of tests for endometrial hyperplasia may be much higher than we think!
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Aravinthan Coomarasamy, Khalid S. Khan, Gerben ter Riet, T Justin Clark, and General practice
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medicine.medical_specialty ,Time Factors ,lcsh:Medicine ,Diagnostic accuracy ,Endometrium ,Bias ,Odds Ratio ,Medicine ,Humans ,Ultrasonography ,Gynecology ,Medicine(all) ,Study quality ,medicine.diagnostic_test ,business.industry ,lcsh:R ,Ultrasound ,General Medicine ,Odds ratio ,Reference Standards ,medicine.disease ,Endometrial hyperplasia ,Endometrial Hyperplasia ,Diagnostic odds ratio ,Regression Analysis ,Female ,Radiology ,business ,Endometrial biopsy ,Research Article - Abstract
Background To empirically evaluate bias in estimation of accuracy associated with delay in verification of diagnosis among studies evaluating tests for predicting endometrial hyperplasia. Methods Systematic reviews of all published research on accuracy of miniature endometrial biopsy and endometr ial ultrasonography for diagnosing endometrial hyperplasia identified 27 test accuracy studies (2,982 subjects). Of these, 16 had immediate histological verification of diagnosis while 11 had verification delayed > 24 hrs after testing. The effect of delay in verification of diagnosis on estimates of accuracy was evaluated using meta-regression with diagnostic odds ratio (dOR) as the accuracy measure. This analysis was adjusted for study quality and type of test (miniature endometrial biopsy or endometrial ultrasound). Results Compared to studies with immediate verification of diagnosis (dOR 67.2, 95% CI 21.7–208.8), those with delayed verification (dOR 16.2, 95% CI 8.6–30.5) underestimated the diagnostic accuracy by 74% (95% CI 7%–99%; P value = 0.048). Conclusion Among studies of miniature endometrial biopsy and endometrial ultrasound, diagnostic accuracy is considerably underestimated if there is a delay in histological verification of diagnosis.
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- 2004
22. A review of the methodological features of systematic reviews in maternal medicine.
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Sheikh, Lumaan, Johnston, Shelley, Thangaratinam, Shakila, Kilby, Mark D., and Khalid S. Khan
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MATERNAL health services ,DECISION making ,CLINICAL medicine ,MEDICAL research ,INFORMATION services - Abstract
Background: In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods: Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results: Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1-381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9-16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3- 10.8, p = 0.02). Conclusion: This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine. [ABSTRACT FROM AUTHOR]
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- 2007
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23. Gender: shaping personality, lives and health of women in Pakistan.
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Rizvi, Narjis, S Khan, Kausar, and Shaikh, Babar T
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Background: Gender norms determine the status of Pakistani women that influence their life including health. In Pakistan, the relationship between gender norms and health of women is crucial yet complex demanding further analysis. This paper: determines the reasons for reiteration of gender roles; describes the societal processes and mechanisms that reproduce and reinforce them; and identifies their repercussions on women's personality, lives and health especially reproductive health.Methods: As part of a six-country study titled 'Women's Empowerment in Muslim Contexts', semi-structured group discussions (n = 30) were conducted with women (n = 250) who were selected through snowballing from different age, ethnic and socio-economic categories. Discussion guidelines were used to collect participant's perceptions about Pakistani women's: characteristics, powers, aspirations, needs and responsibilities; circumstances these women live in such as opportunities, constraints and risks; and influence of these circumstances on their personality, lifestyle and health.Results: The society studied has constructed a 'Model' for women that consider them 'Objects' without rights and autonomy. Women's subordination, a prerequisite to ensure compliance to the constructed model, is maintained through allocation of lesser resources, restrictions on mobility, seclusion norms and even violence in cases of resistance. The model determines women's traits and responsibilities, and establishes parameters for what is legitimate for women, and these have implications for their personality, lifestyle and health, including their reproductive behaviours.Conclusion: There is a strong link between women's autonomy, rights, and health. This demands a gender sensitive and a, right-based approach towards health. In addition to service delivery interventions, strategies are required to counter factors influencing health status and restricting access to and utilization of services. Improvement in women's health is bound to have positive influences on their children and wider family's health, education and livelihood; and in turn on a society's health and economy. [ABSTRACT FROM AUTHOR]- Published
- 2014
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24. The role of autoantibodies in bridging obesity, aging, and immunosenescence.
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Valentino TR, Chen N, Makhijani P, Khan S, Winer S, Revelo XS, and Winer DA
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Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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25. Deep-m5U: a deep learning-based approach for RNA 5-methyluridine modification prediction using optimized feature integration.
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Noor S, Naseem A, Awan HH, Aslam W, Khan S, AlQahtani SA, and Ahmad N
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- Computational Biology methods, Algorithms, RNA chemistry, RNA genetics, Neural Networks, Computer, RNA, Messenger genetics, RNA, Messenger metabolism, Deep Learning, Uridine analogs & derivatives, Uridine chemistry
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Background: RNA 5-methyluridine (m5U) modifications play a crucial role in biological processes, making their accurate identification a key focus in computational biology. This paper introduces Deep-m5U, a robust predictor designed to enhance the prediction of m5U modifications. The proposed method, named Deep-m5U, utilizes a hybrid pseudo-K-tuple nucleotide composition (PseKNC) for sequence formulation, a Shapley Additive exPlanations (SHAP) algorithm for discriminant feature selection, and a deep neural network (DNN) as the classifier., Results: The model was evaluated using two benchmark datasets, i.e., Full Transcript and Mature mRNA. Deep-m5U achieved overall accuracies of 91.47% and 95.86% for the Full Transcript and Mature mRNA datasets with 10-fold cross-validation, and for independent samples, the model attained 92.94% and 95.17% accuracy., Conclusion: Compared to existing models, Deep-m5U showed approximately 5.23% and 3.73% higher accuracy on the training data and 3.95% and 3.26% higher accuracy on independent samples for the Full Transcript and Mature mRNA datasets, respectively. The reliability and effectiveness of Deep-m5U make it a valuable tool for scientists and a potential asset in pharmaceutical design and research., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that there is no conflict of interest regarding the publication of this paper., (© 2024. The Author(s).)
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- 2024
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26. The association between the stress hyperglycaemia ratio and mortality in cardiovascular disease: a meta-analysis and systematic review.
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Esdaile H, Khan S, Mayet J, Oliver N, Reddy M, and Shah ASV
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- Humans, Risk Assessment, Risk Factors, Aged, Middle Aged, Male, Prognosis, Female, Time Factors, Cardiovascular Diseases mortality, Cardiovascular Diseases diagnosis, Cardiovascular Diseases blood, Ischemic Stroke mortality, Ischemic Stroke blood, Ischemic Stroke diagnosis, Aged, 80 and over, Adult, Myocardial Infarction mortality, Myocardial Infarction blood, Myocardial Infarction diagnosis, Heart Failure mortality, Heart Failure diagnosis, Heart Failure blood, Hyperglycemia mortality, Hyperglycemia blood, Hyperglycemia diagnosis, Blood Glucose metabolism, Biomarkers blood, Cause of Death
- Abstract
Background: A raised stress hyperglycaemia ratio (SHR) has been associated with all-cause mortality and may better discriminate than an absolute glucose value. The aim of this meta analysis and systematic review is to synthesise the evidence assessing the relationship between the SHR and all-cause mortality across three common cardiovascular presentations., Methods: We undertook a comprehensive search of Medline, Embase, Cochrane CENTRAL and Web of Science from the date of inception to 1st March 2024, and selected articles meeting the following criteria: studies of patients hospitalised for acute myocardial infarction, ischaemic stroke or acute heart failure reporting the risk (odds ratio or hazard ratio) for all-cause mortality associated with the SHR. A random effects model was used for primary analysis. Subgroup analysis by diabetes status and of mortality in the short and long term was undertaken. Risk of bias assessment was performed using the Newcastle Ottawa quality assessment scale., Results: A total of 32 studies were included: 26 studies provided 31 estimates for the meta-analysis. The total study population in the meta analysis was 80,010. Six further studies were included in the systematic review. Participants admitted to hospital with cardiovascular disease and an SHR in the highest category had a significantly higher risk ratio of all-cause mortality in both the short and longer term compared with those with a lower SHR (RR = 1.67 [95% CI 1.46-1.91], p < 0.001). This finding was driven by studies in the myocardial infarction (RR = 1.75 [95% CI 1.52-2.01]), and ischaemic stroke cohorts (RR = 1.78 [95% CI 1.26-2.50]). The relationship was present amongst those with and without diabetes (diabetes: RR 1.49 [95% CI 1.14-1.94], p < 0.001, no diabetes: RR 1.85 [95% CI 1.49-2.30], p < 0.001) with p = 0.21 for subgroup differences, and amongst studies that reported mortality as a single outcome (RR of 1.51 ([95% CI 1.29-1.77]; p < 0.001) and those that reported mortality as part of a composite outcome (RR 2.02 [95% CI 1.58-2.59]; p < 0.001). On subgroup analysis by length of follow up, higher SHR values were associated with increased risk of mortality at 90 day, 1 year and > 1year follow up, with risk ratios of 1.84 ([95% CI 1.32-2.56], p < 0.001), 1.69 ([95% CI 1.32-2.16], p < 0.001) and 1.58 ([95% CI 1.34-1.86], p < 0.001) respectively., Conclusions: A raised SHR is associated with an increased risk of all-cause mortality following myocardial infarction and ischaemic stroke. Further work is required to define reference values for the SHR, and to investigate the potential effects of relative hypoglycaemia. Interventional trials targeting to the SHR rather than the absolute glucose value should be undertaken., Prospero Database Registration: CRD 42023456421 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023456421., Competing Interests: Declarations Competing interests Harriet Esdaile has received grant funding from Dexcom. Jamil Mayet has received a research award from the British Heart Foundation and grant funding from Dexcom. Nick Oliver has received grant funding from the National Institute for Health and Care Research, Diabetes UK, the Helmsley Trust, Dexcom, and Medtronic Diabetes, and has received speaker’s fees from Tandem Diabetes, Sanofi, Dexcom, Medtronic Diabetes, and Astra Zeneca. Nick Oliver participates on the advisory board of Medtronic Diabetes and Roche Diabetes. Monika Reddy has received grant funding from Dexcom and Medtronic Diabetes, has participated on the advisory board of Medtronic, and has received payment from Wiley for an invited manuscript. Anoop Shah and Shaila Khan have no potential conflicts relevant to this article., (© 2024. The Author(s).)
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- 2024
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27. Exploring plant-based dengue therapeutics: from laboratory to clinic.
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Rehman B, Ahmed A, Khan S, Saleem N, Naseer F, and Ahmad S
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Dengue virus (DENV) is a mosquito-borne virus that causes dengue fever, a significant public health concern in many tropical and subtropical regions. Dengue is endemic in more than 100 countries, primarily in tropical and subtropical regions of the world. Each year, up to 400 million people get infected with dengue. Approximately 100 million people get sick from infection, and 40,000 die from severe dengue. Unfortunately, dengue vaccine development is also marred with various complicating factors, as the forefront candidate vaccine performed unsatisfactorily. Moreover, the only licensed vaccine (Dengvaxia) for children 9 through 16 years of age is available in just a few countries. The treatment difficulties are compounded by the absence of an effective antiviral agent. Exploring plant-based therapeutics for dengue from the laboratory to clinical application involves a multi-stage process, encompassing various scientific disciplines. Individual investigators have screened a wide range of plant extracts or compounds for potential antiviral activity against DENV. In vitro studies help identify candidates that exhibit inhibitory effects on viral replication. Some of the most promising medicinal plants showing in vitro activity against DENV include Andrographis paniculate, Acorus calamus, and Cladogynos orientalis. Further laboratory studies, both in vitro and in animal models (in vivo), elucidate the mechanisms of action by which the identified compounds exert antiviral effects. Medicinal plants such as Carica papaya, Cissampelos pareira, and Ipomea batata exhibited potent platelet-enhancing activities while Azadirachta indica and Curcuma longa showed promising effects in both in vitro and in vivo studies. Based on positive preclinical results, researchers design clinical trials. This involves careful planning of trial phases, patient recruitment criteria, ethical considerations, and endpoints. The most important medicinal plants showing efficacy and safety in clinical trials include Carica papaya and Cissampelos pareira. This review suggests that several promising medicinal plants exist that have the potential to be turned into clinical drugs to treat dengue infection. However, in addition to developing synthetic and plant-based therapies against dengue infection, vector management strategies should be made robust, emphasizing the need to focus on reducing disease incidence., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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28. Normative values and factors affecting saphenous nerve responses in a south Asian population: a cross-sectional neurophysiological study at a tertiary care hospital in Pakistan.
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Hameed S, Aziz B, Baig P, Malik MGR, Awan S, and Khan S
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- Humans, Female, Cross-Sectional Studies, Male, Pakistan epidemiology, Adult, Middle Aged, Young Adult, Reference Values, Body Mass Index, Neural Conduction physiology, Tertiary Care Centers
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Background: The saphenous nerve, a sensory branch of the femoral nerve, is not commonly included in routine lower extremity nerve conduction studies due to a high frequency of non-recordable responses in healthy subjects. However, saphenous nerve conduction studies are sometimes utilized for the diagnostic assessment of isolated lumbosacral plexus, femoral, or saphenous mononeuropathies. Our study aims to determine normative saphenous nerve response values in a healthy Pakistani population and to investigate their associations with patient body mass index, age, and gender., Methods: This cross-sectional descriptive study was undertaken over a 3‑month period (May to July 2021) at a neurophysiology department of a tertiary care center in Pakistan. Healthy subjects underwent neurological examination, anthropometric measurements, and bilateral SN nerve conduction studies, with recording of peak-latency, peak-to-peak amplitude and conduction velocity. Statistical analyses and linear regression were conducted to evaluate associations between nerve conduction study variables and patient characteristics. Statistical analyses were also run to assess patient characteristics affecting recordability of saphenous nerve responses. A p-value < 0.05 was considered statistically significant., Results: Among 117 subjects, 79.5% (n = 93) had recordable saphenous nerve responses. Median peak-latency, amplitude, and conduction velocity were 3.2 (3.0-3.3) m/s, 7.7 (5.8-9.9) uV, and 44.0 (42.0-47.0) m/s, respectively. Bilaterally absent responses were observed in 20.5% (n = 24) of subjects. Obese participants had a significantly higher number of absent saphenous responses (p = 0.033). Females had shorter peak-latency (p = 0.006) and higher conduction velocity (p = 0.012)., Conclusions: Saphenous nerve responses can be used to assess unilateral femoral and saphenous nerve pathologies, provided they are recordable on the asymptomatic side for comparison. Absent bilateral saphenous nerve responses should be interpreted with caution given their prevalence in healthy individuals. Patient characteristics should be taken into consideration when interpreting recordable and nonrecordable saphenous nerve responses., (© 2024. The Author(s).)
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- 2024
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29. Curcumin attenuates smoking and drinking activated NF-κB/IL-6 inflammatory signaling axis in cervical cancer.
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Kashyap VK, Nagesh PKB, Singh AK, Massey A, Darkwah GP, George A, Khan S, Hafeez BB, Zafar N, Kumar S, Sinha N, Yallapu MM, Jaggi M, and Chauhan SC
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Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation., Methods: The impact of benzo[a]pyrene (B[a]P) and/or ethanol (EtOH) exposure on cervical cancer cells was assessed by measuring changes in their cell migration and invasion characteristics. Expression of HPV16 E6/E7, NF-κB, cytokines, and inflammation mediators was determined using qRT-PCR, immunoblotting, ELISA, luciferase reporter assay, and confocal microscopy. Herein, we used curcumin (Cur), and PLGA nanoparticle formulation of curcumin (PLGA-Cur) and determined effectiveness of free Cur and PLGA-Cur formulation on smoking and drinking activated NF-κB/IL-6 mediated inflammatory signaling pathways using in vitro cervical cancer models., Results: Treatments with B[a]P and/or EtOH altered the expression of HPV16 E6/E7 oncogenes and EMT markers in cervical cancer cells; it also enhanced migration and invasion. In addition, B[a]P and/or EtOH exposure promoted inflammation pathways through TNF-α and NF-κB signaling, leading to IL-6 upregulation and activation of VEGF. The molecular effects caused by B[a]P and/or EtOH exposure were effectively attenuated by curcumin (Cur)/PLGA-Cur treatment., Conclusions: These data suggest a molecular link between smoking, drinking, and HPV infectivity in cervical carcinogenesis. In addition, attenuation of these effects by treatment with Cur/PLGA-Cur treatment, implies the role of curcumin in cervical cancer prevention and treatment., (© 2024. The Author(s).)
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- 2024
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30. Expanding the genetic spectrum of hereditary motor sensory neuropathies in Pakistan.
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Ahmed AN, Rawlins LE, Khan N, Jan Z, Ubeyratna N, Voutsina N, Azeem A, Khan S, Baple EL, Crosby AH, and Saleha S
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- Humans, Pakistan epidemiology, Male, Female, Adult, Adolescent, Child, Young Adult, Middle Aged, Child, Preschool, Hereditary Sensory and Motor Neuropathy genetics, Hereditary Sensory and Motor Neuropathy diagnosis, Hereditary Sensory and Motor Neuropathy epidemiology, Exome Sequencing methods, Pedigree
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Background: Hereditary motor and sensory neuropathy (HMSN) refers to a group of inherited progressive peripheral neuropathies characterized by reduced nerve conduction velocity with chronic segmental demyelination and/or axonal degeneration. HMSN is highly clinically and genetically heterogeneous with multiple inheritance patterns and phenotypic overlap with other inherited neuropathies and neurodegenerative diseases. Due to this high complexity and genetic heterogeneity, this study aimed to elucidate the genetic causes of HMSN in Pakistani families using Whole Exome Sequencing (WES) for variant identification and Sanger sequencing for validation and segregation analysis, facilitating accurate clinical diagnosis., Methods: Families from Khyber Pakhtunkhwa with at least two members showing HMSN symptoms, who had not previously undergone genetic analysis, were included. Referrals for genetic investigations were based on clinical features suggestive of HMSN by local neurologists. WES was performed on affected individuals from each family, with Sanger sequencing used to validate and analyze the segregation of identified variants among family members. Clinical data including age of onset were assessed for variability among affected individuals, and the success rate of genetic diagnosis was compared with existing literature using proportional differences and Cohen's h., Results: WES identified homozygous pathogenic variants in GDAP1 (c.310 + 4 A > G, p.?), SETX (c.5948_5949del, p.(Asn1984Profs*30), IGHMBP2 (c.1591 C > A, p.(Pro531Thr) and NARS1 (c.1633 C > T, p.(Arg545Cys) as causative for HMSN in five out of nine families, consistent with an autosomal recessive inheritance pattern. Additionally, in families with HMSN, a SETX variant was found to cause cerebellar ataxia, while a NARS1 variant was linked to intellectual disability. Based on American College of Medical Genetics and Genomics criteria, the GDAP1 variant is classified as a variant of uncertain significance, while variants in SETX and IGHMBP2 are classified as pathogenic, and the NARS1 variant is classified as likely pathogenic. The age of onset ranged from 1 to 15 years (Mean = 5.13, SD = 3.61), and a genetic diagnosis was achieved in 55.56% of families with HMSN, with small effect sizes compared to previous studies., Conclusions: This study expands the molecular genetic spectrum of HMSN and HMSN plus type neuropathies in Pakistan and facilitates accurate diagnosis, genetic counseling, and clinical management for affected families., (© 2024. The Author(s).)
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- 2024
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31. Surgical management and outcomes of renal tumors with inferior vena cava extension among children: a single center retrospective study from Pakistan.
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Halepota HF, Khan S, Irshad HA, and Arshad M
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- Humans, Female, Retrospective Studies, Male, Pakistan epidemiology, Child, Child, Preschool, Infant, Adolescent, Treatment Outcome, Neoplasm Invasiveness, Thrombectomy methods, Wilms Tumor surgery, Wilms Tumor pathology, Nephrectomy methods, Vena Cava, Inferior surgery, Vena Cava, Inferior pathology, Kidney Neoplasms surgery, Kidney Neoplasms pathology
- Abstract
Objective: The aim of this study was to assess management and determine outcomes of renal tumors with inferior vena cava (IVC) and intracardiac (IC) extension in a tertiary care center in Pakistan., Methods: A retrospective chart review was conducted at the Aga Khan University Hospital, Karachi, Pakistan. All patients from 1 to 18 years of age with renal tumors with intravascular extensions, surgically managed from January 1988 till June 2016, were included. Data was extracted by reviewing medical records, and the tumor details, treatment and outcomes were analyzed., Results: A total of 18 patients out of the total 61 patients with renal tumors, presented with IVC and/or IC extension, with the majority involving the right kidney. Mean age was 5.9 (SD:4.9) and a female preponderance (56%) was seen. Wilms tumor (77%) was the most common tumor type, with the level of tumor extension into IVC predominantly being below the diaphragm (55.5%). Fourteen patients received preoperative chemotherapy, with tumor regression, seen in 10. Most patients underwent thrombectomy through the renal vein (56%). Regarding outcomes, frequency of mortality and morbidity was 1 and 2, respectively, with 7 patients having no recurrent 5 years post-surgery., Conclusion: A greater incidence (29.5%) of IVC and or IC Tumor extension was found compared to existing literature, which could likely be due to a higher referral rate to the center. Moreover, this is a single-center study and so a multi-center study is crucial to form an assessment of surgical management in resource-limited settings. Our study is the first from Pakistan on this particular renal tumor presentation. Considering the varying case presentations and surgical techniques used, further studies are needed to standardize surgical management and optimize patient outcomes., (© 2024. The Author(s).)
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- 2024
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32. Efficacy of human interleukin-11 analogs for treating dengue fever-associated thrombocytopenia: a prospective cohort.
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Khan S, Muqtadir J, Abbas SA, Batool I, Zaidi SHM, Mahrukh, Wahab A, Ayoob K, Sameeullah F, and Vohra EA
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- Humans, Female, Male, Adult, Prospective Studies, Middle Aged, Platelet Count, Young Adult, Thrombocytopenia drug therapy, Thrombocytopenia etiology, Interleukin-11 therapeutic use, Dengue drug therapy, Dengue complications
- Abstract
Aim: Dengue fever (DF), carried by Aedes mosquitoes, affects millions worldwide. Platelet-inducing human IL-11 analogues may be effective in treating DF-associated thrombocytopenia., Methodology: A prospective study was done at Dr. Ziauddin Hospital, a tertiary care hospital in Karachi, Pakistan, from September 2023 to April 30, 2024., Results: This study recruited 300 DF patients characterized by thrombocytopenia (platelet count < 30,000), including 159 in the treatment and 141 in the control group. The median age of patients was 34 ± 11.05 years, with 187 males (62.3%) and 113 females (37.7%). The treatment group had a higher proportion of fever (80%, p < 0.0001) and headache (96%, p = 0.012) compared to the control group; however, no significant changes were observed in other clinical parameters between the two groups. Following treatment for 5 days, platelet counts of the treatment group increased significantly in response to IL-11 treatment compared to the control group at all time intervals (day 0, day 1, day 2, day 3, day 4, and day 5). Following treatment, males consistently exhibited higher platelet counts than females (all p < 0.05). In addition, patients admitted on day 3 of their course of illness showed a significantly slow response to the treatment compared to those admitted on day 5. Although young individuals exhibited a significant increase in platelet count, the age showed no significant intergroup differences., Conclusions: IL-11 analogs have promising potential for treating DF-associated thrombocytopenia. Additional investigation is necessary to refine administration protocols and examine the wider therapeutic ramifications of IL-11 in managing DF., (© 2024. The Author(s).)
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- 2024
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33. PSSM-Sumo: deep learning based intelligent model for prediction of sumoylation sites using discriminative features.
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Khan S, AlQahtani SA, Noor S, and Ahmad N
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- Support Vector Machine, Computational Biology methods, Algorithms, Humans, Position-Specific Scoring Matrices, Protein Processing, Post-Translational, Sumoylation, Deep Learning
- Abstract
Post-translational modifications (PTMs) are fundamental to essential biological processes, exerting significant influence over gene expression, protein localization, stability, and genome replication. Sumoylation, a PTM involving the covalent addition of a chemical group to a specific protein sequence, profoundly impacts the functional diversity of proteins. Notably, identifying sumoylation sites has garnered significant attention due to their crucial roles in proteomic functions and their implications in various diseases, including Parkinson's and Alzheimer's. Despite the proposal of several computational models for identifying sumoylation sites, their effectiveness could be improved by the limitations associated with conventional learning methodologies. In this study, we introduce pseudo-position-specific scoring matrix (PsePSSM), a robust computational model designed for accurately predicting sumoylation sites using an optimized deep learning algorithm and efficient feature extraction techniques. Moreover, to streamline computational processes and eliminate irrelevant and noisy features, sequential forward selection using a support vector machine (SFS-SVM) is implemented to identify optimal features. The multi-layer Deep Neural Network (DNN) is a robust classifier, facilitating precise sumoylation site prediction. We meticulously assess the performance of PSSM-Sumo through a tenfold cross-validation approach, employing various statistical metrics such as the Matthews Correlation Coefficient (MCC), accuracy, sensitivity, specificity, and the Area under the ROC Curve (AUC). Comparative analyses reveal that PSSM-Sumo achieves an exceptional average prediction accuracy of 98.71%, surpassing existing models. The robustness and accuracy of the proposed model position it as a promising tool for advancing drug discovery and the diagnosis of diverse diseases linked to sumoylation sites., (© 2024. The Author(s).)
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- 2024
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34. Sociodemographic and work-related factors associated with psychological resilience in South African healthcare workers: a cross-sectional study.
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Mcizana T, Adams S, Khan S, and Ntatamala I
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- Humans, Cross-Sectional Studies, Female, Male, South Africa, Adult, Middle Aged, Physicians psychology, Physicians statistics & numerical data, Sociodemographic Factors, Resilience, Psychological, Health Personnel psychology, Health Personnel statistics & numerical data
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Background: Psychological resilience facilitates adaptation in stressful environments and is an important personal characteristic that enables workers to navigate occupational challenges. Few studies have evaluated the factors associated with psychological resilience in healthcare workers., Objectives: To determine the prevalence and factors associated with psychological resilience in a group of South African medical doctors and ambulance personnel., Materials and Methods: This analytical cross-sectional study used secondary data obtained from two studies conducted among healthcare workers in 2019 and 2022. Self-reported factors associated with resilience, as measured by the Connor-Davidson Resilience Scale-10 (CD-RISC-10), were evaluated. R statistical software was used for analysing the data and performing statistical tests., Results: A total of 647 healthcare workers were included in the study, of which 259 were doctors and 388 were ambulance personnel. Resilience scores were low overall (27.6 ± 6.6) but higher for ambulance personnel (28.0 ± 6.9) than for doctors (27.1 ± 6.0) (p = 0.006). Female gender (OR 1.94, 95%CI 1.03-3.72, p = 0.043), job category (OR 6.94 95%CI 1.22-60.50, p = 0.044) and overtime work (OR 13.88, 95%CI 1.61-368.00, p = 0.044) significantly increased the odds of low resilience for doctors. Conversely, salary (OR 0.13, 95%CI 0.02-0.64, p = 0.024) and current smoking status (OR 0.16, 95%CI 0.02-0.66, p = 0.027) significantly reduced the odds of low resilience amongst doctors. In addition, only previous alcohol use significantly reduced the odds of low resilience for ambulance personnel (OR 0.44, 95%CI 0.20-0.94, p = 0.038) and overall sample (OR 0.52, 95%CI 0.29-0.91, p = 0.024)., Conclusions: Resilience was relatively low in this group of South African healthcare workers. The strong association between low resilience and individual and workplace factors provides avenues for early intervention and building resilience among healthcare workers., (© 2024. The Author(s).)
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- 2024
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35. Bile acid diarrhoea and metabolic changes after cholecystectomy: a prospective case-control study.
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Farrugia A, Williams N, Khan S, and P Arasaradnam R
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- Humans, Case-Control Studies, Prospective Studies, Female, Male, Middle Aged, Adult, Triglycerides blood, Cholecystectomy adverse effects, Gallbladder metabolism, Gallbladder surgery, Postoperative Complications etiology, Enterohepatic Circulation, Aged, Cholestenones blood, Diarrhea etiology, Diarrhea metabolism, Bile Acids and Salts blood, Bile Acids and Salts metabolism, Fibroblast Growth Factors blood, Fibroblast Growth Factors metabolism, PPAR alpha metabolism
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Introduction: Bile acid diarrhoea (BAD) can occur due to disruption to the enterohepatic circulation such as following cholecystectomy. However, the mechanism behind this is as yet unknown. The aim of this study was to determine the rate of post-cholecystectomy diarrhoea and to assess whether FGF19 within the gallbladder was associated with the development of BAD., Methods: This was a prospective case-control study in which patients were assessed pre- and post- cholecystectomy (study group) and compared with patients also having laparoscopic surgery but not cholecystectomy (control group). Their bowel habits and a GIQLI questionnaire was performed to compare the pre- and post-operative condition of the two groups. Gallbladder tissue sample was tested for FGF19 and PPARα in the study group patients. A subset had serum lipid levels, FGF19 and C4 measurements., Results: Gallbladder PPAR α was found to have a significant correlation with stool consistency, with the lower the PPARα concentration the higher the Bristol stool chart number (i.e. looser stool). There were no significant correlation when assessing the effect of gallbladder FGF19 concentration on bowel habit, stool consistency, lipid levels, BMI or smoking. The study group showed a significant increase in triglycerides post-operatively, however there were no changes in cholesterol, HDL and LDL levels. Correlation of the increased triglyceride levels with stool consistency and frequency showed no significant results DISCUSSION AND CONCLUSION: We did not find any direct evidence that FGF19 levels within the gallbladder impact the development of post-cholecystectomy diarrhoea. There was however a significant increase in triglycerides postoperatively. There was also no correlation of bowel habits with PPARα suggesting the observed rise is independent of this pathway. Further work is required particularly relating to the gut microbiome to further investigate this condition., (© 2024. The Author(s).)
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- 2024
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36. Arthroscopic assisted versus open non-vascularized bone grafting in delayed union and nonunion of the scaphoid: a systematic review and meta-analysis.
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Noori A, Persitz J, Khan S, Chan A, and Paul R
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- Humans, Treatment Outcome, Scaphoid Bone surgery, Scaphoid Bone injuries, Bone Transplantation methods, Fractures, Ununited surgery, Arthroscopy methods, Arthroscopy adverse effects, Fracture Healing
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Background: Delayed union and nonunion of the scaphoid is a common complication often requiring surgical reconstruction and bone grafting. Our goal was to systematically assess the healing time and clinical outcomes following arthroscopic-assisted versus open non-vascularized bone grafting of the scaphoid., Methods: A comprehensive search of the MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases was completed from inception to September 2023. We included randomized trials and observational studies that reported outcomes following scaphoid delayed union/nonunion comparing arthroscopic-assisted vs. open non-vascularized bone grafting. Two reviewers independently extracted data and assessed the risk of bias. One investigator assessed certainty of evidence and a senior investigator confirmed the assessment. We pooled effects using random-effects models, when possible, for all outcomes reported by more than 1 study., Results: Overall, 26 studies and 822 patients were included in the study. Very low certainty evidence demonstrated that arthroscopic-assisted surgery may decrease healing time compared to open surgery (weighted mean difference [WMD] -7.8 weeks; 95%CI -12.8 to -2.8). Arthroscopic bone grafting did not result in an improvement in union rate (relative risk 1.01; 95%CI 0.9 to 1.09). The pooled data in arthroscopic graft group showed mean time to union of 11.4 weeks (95%CI: 10.4 to 12.5) with union rate of 95% (95%CI 91-98%). A single comparative study reported very low certainty evidence that arthroscopy-assisted vs. open surgery may not have an effect on pain relief (MD 0 cm, 95%CI -0.4 to 0.5 on VAS 10 cm for pain) or improving function (MD -1.2, 95% CI -4.8 to 2.3 on 100 points DASH)., Conclusion and Future Directions: Our results suggest that arthroscopic-assisted non-vascularized bone grafting may be associated with improved average weeks to heal in comparison with open surgery for scaphoid delayed union/nonunion reconstruction with overall comparable union rates. There is insufficient evidence to assess the effects of arthroscopic-assisted reconstruction on union rate, time to union, and patient-reported outcomes in patients with other important nonunion characteristics such as established humpback deformity., (© 2024. The Author(s).)
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- 2024
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37. Impact of acidic beverages on composition and surface characteristics of human teeth: scanning electron microscopic, stereomicroscopic and energy dispersive x-ray analyses.
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Kumar N, Amin F, Dahri WM, Khan S, Zaidi H, Rahman S, Farhan T, Zafar MS, and Fareed MA
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- Humans, Acids analysis, Tooth Erosion, Tooth ultrastructure, Tooth chemistry, Hydrogen-Ion Concentration, Calcium analysis, Tooth Demineralization, Phosphorus analysis, Microscopy, Electron, Scanning, Spectrometry, X-Ray Emission, Beverages analysis, Surface Properties
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Objectives: The objective of this study was to evaluate the effect of acidic beverages on the surface topography and elemental composition of human teeth., Methods: A total of five highly acidic beverages (Red Bull, Pepsi, Apple Cidra, Tang Mosambi, and Tang Orange) were investigated. The tooth specimens of experimental groups were submerged in each beverage and incubated at 37 °C for 7 days, whereas, the tooth specimens of control groups were placed in distilled water. Afterwards, tooth specimens were analyzed using scanning electron microscopic (SEM), stereomicroscopic, and energy dispersive x-ray (EDX) techniques., Results: All experimental groups revealed a decline in the tooth elements compared to controls, however, such decline was not statistically significant. Nevertheless, comparing the experimental groups, the Red Bull beverage caused a marked reduction in the percentage of both calcium and phosphorus elements compared to the Pepsi, Apple Cidra, Tang Mosambi, and Tang Orange beverages but it was insignificant as well in contrast to its control counterpart. All five acidic beverages demonstrated erosive potential under SEM analysis; however, each group of specimens showed a diverse amount of demineralization. In addition, all experimental groups exhibited significant discoloration of tooth specimens compared to their respective control counterparts., Conclusions: Within the limitations of study, all five acidic beverages demonstrated erosive potential in the simulated in vitro conditions under SEM analysis; however, each group of specimens exhibited a different extent of demineralization. In addition, the overall effect of all beverages was insignificant under EDX analysis as no substantial difference was revealed between the elemental composition of experimental and control group specimens., (© 2024. The Author(s).)
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- 2024
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38. The C-terminal proline-rich repeats of Enteropathogenic E. coli effector EspF are sufficient for the depletion of tight junction membrane proteins and interactions with early and recycling endosomes.
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Ansari I, Mandal A, Kansal K, Walling P, Khan S, and Aijaz S
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Background: Enteropathogenic E. coli (EPEC) causes acute infantile diarrhea accounting for significant morbidity and mortality in developing countries. EPEC uses a type three secretion system to translocate more than twenty effectors into the host intestinal cells. At least four of these effectors, namely EspF, Map, EspG1/G2 and NleA, are reported to disrupt the intestinal tight junction barrier. We have reported earlier that the expression of EspF and Map in MDCK cells causes the depletion of the TJ membrane proteins and compromises the integrity of the intestinal barrier. In the present study, we have examined the role of the proline-rich repeats (PRRs) within the C-terminus of EspF in the depletion of the tight junction membrane proteins and identified key endocytosis markers that interact with EspF via these repeats., Results: We generated mutant EspF proteins which lacked one or more proline-rich repeats (PRRs) from the N-terminus of EspF and examined the effect of their expression on the cellular localization of tight junction membrane proteins. In lysates derived from cells expressing the mutant EspF proteins, we found that the C-terminal PRRs of EspF are sufficient to cause the depletion of TJ membrane proteins. Pull-down assays revealed that the PRRs mediate interactions with the TJ adaptor proteins ZO-1 and ZO-2 as well as with the proteins involved in endocytosis such as caveolin-1, Rab5A and Rab11., Conclusions: Our study demonstrates the direct role of the proline-rich repeats of EspF in the depletion of the TJ membrane proteins and a possible involvement of the PRRs in the endocytosis of host proteins. New therapeutic strategies can target these PRR domains to prevent intestinal barrier dysfunction in EPEC infections., (© 2024. The Author(s).)
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- 2024
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39. Variants in HCFC1 and MN1 genes causing intellectual disability in two Pakistani families.
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Hussain SI, Muhammad N, Shah SA, Rehman AU, Khan SA, Saleha S, Khan YM, Muhammad N, Khan S, and Wasif N
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- Humans, Pakistan, Male, Female, Tumor Suppressor Proteins genetics, Trans-Activators genetics, Child, Exome Sequencing, Child, Preschool, Pedigree, Intellectual Disability genetics, Host Cell Factor C1 genetics
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Background: Intellectual disability (ID) is a neurodevelopmental condition affecting around 2% of children and young adults worldwide, characterized by deficits in intellectual functioning and adaptive behavior. Genetic factors contribute to the development of ID phenotypes, including mutations and structural changes in chromosomes. Pathogenic variants in the HCFC1 gene cause X-linked mental retardation syndrome, also known as Siderius type X-linked mental retardation. The MN1 gene is necessary for palate development, and mutations in this gene result in a genetic condition called CEBALID syndrome., Methods: Exome sequencing was used to identify the disease-causing variants in two affected families, A and B, from various regions of Pakistan. Affected individuals in these two families presented ID, developmental delay, and behavioral abnormalities. The validation and co-segregation analysis of the filtered variant was carried out using Sanger sequencing., Results: In an X-linked family A, a novel hemizygous missense variant (c.5705G > A; p.Ser1902Asn) in the HCFC1 gene (NM_005334.3) was identified, while in family B exome sequencing revealed a heterozygous nonsense variant (c.3680 G > A; p. Trp1227Ter) in exon-1 of the MN1 gene (NM_032581.4). Sanger sequencing confirmed the segregation of these variants with ID in each family., Conclusions: The investigation of two Pakistani families revealed pathogenic genetic variants in the HCFC1 and MN1 genes, which cause ID and expand the mutational spectrum of these genes., (© 2024. The Author(s).)
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- 2024
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40. Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa.
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Nisar MI, Kabole I, Khanam R, Shahid S, Bakari BA, Chowdhury NH, Qazi MF, Dutta A, Rahman S, Khalid J, Dhingra U, Hasan T, Ansari N, Deb S, Mitra DK, Mehmood U, Aftab F, Ahmed S, Khan S, Ali SM, Ahmed S, Manu A, Yoshida S, Bahl R, Baqui AH, Sazawal S, and Jehan F
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- Humans, Female, Pregnancy, Adult, United States epidemiology, Pakistan epidemiology, Cohort Studies, American Heart Association, Bangladesh epidemiology, Tanzania epidemiology, Young Adult, Blood Pressure, Infant, Newborn, Asia, Southern, Premature Birth epidemiology, Stillbirth epidemiology, Hypertension, Pregnancy-Induced diagnosis, Hypertension, Pregnancy-Induced epidemiology, Practice Guidelines as Topic
- Abstract
Background: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes., Methods: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group., Results: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes., Conclusion: The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension., (© 2024. The Author(s).)
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- 2024
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41. Psychiatric implications of anti-seizure medications in epileptic population.
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Khalid B, Waqar Z, Khan S, Ali I, Afzal N, Irfan A, Malik W, Muhammad Adil M, Saddiqa A, Khalil M, and Munawar Z
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- Humans, Male, Female, Adult, Young Adult, Middle Aged, Comorbidity, Adolescent, Pakistan epidemiology, Surveys and Questionnaires, Anticonvulsants therapeutic use, Epilepsy drug therapy, Epilepsy epidemiology, Epilepsy psychology, Mental Disorders epidemiology, Mental Disorders drug therapy
- Abstract
Background and Objective: Epilepsy is a prevalent neurological disorder that affects a significant number of individuals globally. This condition is associated with a high occurrence of psychiatric comorbidities, which can significantly affect the quality of life of individuals affected. The aim of this study was to investigate the association between antiseizure therapies and the likelihood of psychiatric comorbidities in individuals with epilepsy., Methodology: Data for this study was gathered from the Neurology referral center in Islamabad, Pakistan. A standardized questionnaire was utilized to gather data from 120 individuals diagnosed with epilepsy. The survey consisted of inquiries regarding the management of seizures, the utilization of anti-seizure medications, and the presence of psychiatric comorbidities. The data was analyzed using the Statistical Package for the Social Sciences (SPSS)., Results: The findings indicated that individuals who were using multiple antiseizure medications had a notably higher likelihood of having psychiatric comorbidities in comparison to those who were on mono therapy (p = 0.010). suggests that patients with unsuccessful seizure control are more probable to have psychiatric comorbidities as compared to those with good seizure control (p = 0.029)., Conclusion: To conclude poor seizure control and poly therapy are associated with increased risk of psychiatric comorbidities., (© 2024. The Author(s).)
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- 2024
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42. 'Nowhere and no one is safe': spatial analysis of damage to critical civilian infrastructure in the Gaza Strip during the first phase of the Israeli military campaign, 7 October to 22 November 2023.
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Asi Y, Mills D, Greenough PG, Kunichoff D, Khan S, Hoek JVD, Scher C, Halabi S, Abdulrahim S, Bahour N, Ahmed AK, Wispelwey B, and Hammoudeh W
- Abstract
Background: Since the Hamas attacks in Israel on 7 October 2023, the Israeli military has launched an assault in the Gaza Strip, which included over 12,000 targets struck and over 25,000 tons of incendiary munitions used by 2 November 2023. The objectives of this study include: (1) the descriptive and inferential spatial analysis of damage to critical civilian infrastructure (health, education, and water facilities) across the Gaza Strip during the first phase of the military campaign, defined as 7 October to 22 November 2023 and (2) the analysis of damage clustering around critical civilian infrastructure to explore broader questions about Israel's adherence to International Humanitarian Law (IHL)., Methods: We applied multi-temporal coherent change detection on Copernicus Sentinel 1-A Synthetic Aperture Radar (SAR) imagery to detect signals indicative of damage to the built environment through 22 November 2023. Specific locations of health, education, and water facilities were delineated using open-source building footprint and cross-checked with geocoded data from OCHA, OpenStreetMap, and Humanitarian OpenStreetMap Team. We then assessed the retrieval of damage at and with close proximity to sites of health, education, and water infrastructure in addition to designated evacuation corridors and civilian protection zones. The Global Moran's I autocorrelation inference statistic was used to determine whether health, education, and water facility infrastructure damage was spatially random or clustered., Results: During the period under investigation, in the entire Gaza Strip, 60.8% (n = 59) of health, 68.2% (n = 324) of education, and 42.1% (n = 64) of water facilities sustained infrastructure damage. Furthermore, 35.1% (n = 34) of health, 40.2% (n = 191) of education, and 36.8% (n = 56) of water facilities were functionally destroyed. Applying the Global Moran's I spatial inference statistic to facilities demonstrated a high degree of damage clustering for all three types of critical civilian infrastructure, with Z-scores indicating < 1% likelihood of cluster damage occurring by random chance., Conclusion: Spatial statistical analysis suggests widespread damage to critical civilian infrastructure that should have been provided protection under IHL. These findings raise serious allegations about the violation of IHL, especially in light of Israeli officials' statements explicitly inciting violence and displacement and multiple widely reported acts of collective punishment., (© 2024. The Author(s).)
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- 2024
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43. Organelle resolved proteomics uncovers PLA2R1 as a novel cell surface marker required for chordoma growth.
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Khan S, Zuccato JA, Ignatchenko V, Singh O, Govindarajan M, Waas M, Mejia-Guerrero S, Gao A, Zadeh G, and Kislinger T
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- Humans, Proteomics, Cell Membrane metabolism, Membrane Proteins, Organelles metabolism, Organelles pathology, Receptors, Phospholipase A2 metabolism, Chordoma genetics, Chordoma metabolism
- Abstract
Chordomas are clinically aggressive tumors with a high rate of disease progression despite maximal therapy. Given the limited therapeutic options available, there remains an urgent need for the development of novel therapies to improve clinical outcomes. Cell surface proteins are attractive therapeutic targets yet are challenging to profile with common methods. Four chordoma cell lines were analyzed by quantitative proteomics using a differential ultracentrifugation organellar fractionation approach. A subtractive proteomics strategy was applied to select proteins that are plasma membrane enriched. Systematic data integration prioritized PLA2R1 (secretory phospholipase A2 receptor-PLA2R1) as a chordoma-enriched surface protein. The expression profile of PLA2R1 was validated across chordoma cell lines, patient surgical tissue samples, and normal tissue lysates via immunoblotting. PLA2R1 expression was further validated by immunohistochemical analysis in a richly annotated cohort of 25-patient tissues. Immunohistochemistry analysis revealed that elevated expression of PLA2R1 is correlated with poor prognosis. Using siRNA- and CRISPR/Cas9-mediated knockdown of PLA2R1, we demonstrated significant inhibition of 2D, 3D and in vivo chordoma growth. PLA2R1 depletion resulted in cell cycle defects and metabolic rewiring via the MAPK signaling pathway, suggesting that PLA2R1 plays an essential role in chordoma biology. We have characterized the proteome of four chordoma cell lines and uncovered PLA2R1 as a novel cell-surface protein required for chordoma cell survival and association with patient outcome., (© 2024. The Author(s).)
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- 2024
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44. The impact of obesity on ventilator-associated pneumonia, a US nationwide study.
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El Labban M, Zeid Daou MA, Smaily H, Hammoud A, Hassan G, Khan S, and Bou Akl I
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- Adult, Female, Humans, Middle Aged, Male, Retrospective Studies, Obesity epidemiology, Intensive Care Units, Hospitalization, Respiration, Artificial, Pneumonia, Ventilator-Associated epidemiology
- Abstract
Background: Ventilator-associated pneumonia (VAP) is one of the leading causes of mortality in patients with critical care illness. Since obesity is highly prevalent, we wanted to study its impact on the outcomes of patients who develop VAP., Methods: Using the National Inpatient Sample (NIS) database from 2017 to 2020, we conducted a retrospective study of adult patients with a principal diagnosis of VAP with a secondary diagnosis with or without obesity according to 10th revision of the International Statistical Classification of Diseases (ICD-10) codes. Several demographics, including age, race, and gender, were analyzed. The primary endpoint was mortality, while the secondary endpoints included tracheostomy, length of stay in days, and patient charge in dollars. Multivariate logistic regression model analysis was used to adjust for confounders, with a p-value less than 0.05 considered statistically significant., Results: The study included 3832 patients with VAP, 395 of whom had obesity. The mean age in both groups was around 58 years, and 68% of the group with obesity were females compared to 40% in females in the group without obesity. Statistically significant comorbidities in the obesity group included a Charlson Comorbidity Index score of three and above, diabetes mellitus, hypertension, chronic kidney disease, and sleep apnea. Rates and odds of mortality were not significantly higher in the collective obesity group 39 (10%) vs. 336 (8.5%), p-value 0.62, adjusted odds ratio 1.2, p-value 0.61). The rates and odds of tracheostomy were higher in the obesity group but not statistically significant. Obese patients were also found to have a longer hospitalization. Upon subanalysis of the data, no evidence of racial disparities was found in the care of VAP for both the obese and control groups., Conclusions: Obesity was not found to be an independent risk factor for worse outcomes in patients who develop VAP in the intensive care unit., (© 2024. The Author(s).)
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- 2024
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45. Solanidine is a sensitive and specific dietary biomarker for CYP2D6 activity.
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Kiiski JI, Neuvonen M, Kurkela M, Hirvensalo P, Hämäläinen K, Tarkiainen EK, Sistonen J, Korhonen M, Khan S, Orpana A, Filppula AM, Lehtonen M, and Niemi M
- Subjects
- Humans, Paroxetine pharmacology, Biomarkers, Genotype, Cytochrome P-450 CYP2D6 genetics, Genome-Wide Association Study, Diosgenin
- Abstract
Background: Individual assessment of CYP enzyme activities can be challenging. Recently, the potato alkaloid solanidine was suggested as a biomarker for CYP2D6 activity. Here, we aimed to characterize the sensitivity and specificity of solanidine as a CYP2D6 biomarker among Finnish volunteers with known CYP2D6 genotypes., Results: Using non-targeted metabolomics analysis, we identified 9152 metabolite features in the fasting plasma samples of 356 healthy volunteers. Machine learning models suggested strong association between CYP2D6 genotype-based phenotype classes with a metabolite feature identified as solanidine. Plasma solanidine concentration was 1887% higher in genetically poor CYP2D6 metabolizers (gPM) (n = 9; 95% confidence interval 755%, 4515%; P = 1.88 × 10
-11 ), 74% higher in intermediate CYP2D6 metabolizers (gIM) (n = 89; 27%, 138%; P = 6.40 × 10-4 ), and 35% lower in ultrarapid CYP2D6 metabolizers (gUM) (n = 20; 64%, - 17%; P = 0.151) than in genetically normal CYP2D6 metabolizers (gNM; n = 196). The solanidine metabolites m/z 444 and 430 to solanidine concentration ratios showed even stronger associations with CYP2D6 phenotypes. Furthermore, the areas under the receiver operating characteristic and precision-recall curves for these metabolic ratios showed equal or better performances for identifying the gPM, gIM, and gUM phenotype groups than the other metabolites, their ratios to solanidine, or solanidine alone. In vitro studies with human recombinant CYP enzymes showed that solanidine was metabolized mainly by CYP2D6, with a minor contribution from CYP3A4/5. In human liver microsomes, the CYP2D6 inhibitor paroxetine nearly completely (95%) inhibited the metabolism of solanidine. In a genome-wide association study, several variants near the CYP2D6 gene associated with plasma solanidine metabolite ratios., Conclusions: These results are in line with earlier studies and further indicate that solanidine and its metabolites are sensitive and specific biomarkers for measuring CYP2D6 activity. Since potato consumption is common worldwide, this biomarker could be useful for evaluating CYP2D6-mediated drug-drug interactions and to improve prediction of CYP2D6 activity in addition to genotyping., (© 2024. The Author(s).)- Published
- 2024
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46. Enhancing nitrogen use efficiency and yield of maize (Zea mays L.) through Ammonia volatilization mitigation and nitrogen management approaches.
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Dawar K, Dawar A, Tariq M, Mian IA, Muhammad A, Farid L, Khan S, Khan K, Fahad S, Danish S, Al-Ghamdi AA, Elshikh MS, and Tahzeeb-Ul-Hassan M
- Subjects
- Agriculture methods, Zea mays, Volatilization, Fertilizers analysis, Calcium Sulfate, Soil, Urea, Edible Grain chemistry, Sulfur, Ammonia analysis, Nitrogen analysis
- Abstract
Management of nitrogen (N) fertilizer is a critical factor that can improve maize (Zea mays L.) production. On the other hand, high volatilization losses of N also pollute the air. A field experiment was established using a silt clay soil to examine the effect of sulfur-coated urea and sulfur from gypsum on ammonia (NH
3 ) emission, N use efficiency (NUE), and the productivity of maize crop under alkaline calcareous soil. The experimental design was a randomized complete block (RCBD) with seven treatments in three replicates: control with no N, urea150 alone (150 kg N ha-1 ), urea200 alone (200 kg N ha-1 ), urea150 + S (60 kg ha-1 S from gypsum), urea200 + S, SCU150 (sulfur-coated urea) and SCU200 . The results showed that the urea150 + S and urea200 + S significantly reduced the total NH3 by (58 and 42%) as compared with the sole application urea200 . The NH3 emission reduced further in the treatment with SCU150 and SCU200 by 74 and 65%, respectively, compared to the treatment with urea200 . The maize plant biomass, grain yield, and total N uptake enhanced by 5-14%, 4-17%, and 7-13, respectively, in the treatments with urea150 + s and urea200 + S, relative to the treatment with urea200 alone. Biomass, grain yield, and total N uptake further increased significantly by 22-30%, 25-28%, and 26-31%, respectively, in the treatments with SCU150 and SCU200 , relative to the treatment with urea200 alone. The applications of SCU150 enhanced the nitrogen use efficiency (NUE) by (72%) and SCU200 by (62%) respectively, compared with the sole application of urea200 alone. In conclusion, applying S-coated urea at a lower rate of 150 kg N ha-1 compared with a higher rate of 200 kg N ha-1 may be an effective way to reduce N fertilizer application rate and mitigate NH3 emission, improve NUE, and increase maize yield. More investigations are suggested under different soil textures and climatic conditions to declare S-coated urea at 150 kg N ha-1 as the best application rate for maize to enhance maize growth and yield., (© 2024. The Author(s).)- Published
- 2024
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47. Thyroid abscess associated with thyrotoxicosis caused by Yersinia enterocolitica subsp. palearctica in a patient with follicular adenoma of the thyroid gland.
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Hashimoto T, Yahiro T, Takakura S, Khan S, Kimitsuki K, Hiramatsu K, and Nishizono A
- Subjects
- Male, Humans, Aged, 80 and over, Abscess diagnosis, Piperacillin, Tazobactam, Yersinia enterocolitica, Thyroid Neoplasms, Thyrotoxicosis complications, Thyrotoxicosis diagnosis, Adenoma
- Abstract
Background: Yersinia enterocolitica is a gram-negative zoonotic bacterial pathogen that is typically transmitted via the fecal-oral route. The most common clinical manifestation of a Y. enterocolitica infection is self-limited gastroenteritis. Although various extraintestinal manifestations of Y. enterocolitica infection have been reported, there are no reports of thyroid abscesses., Case Presentation: An 89-year-old Japanese man with follicular adenoma of the left thyroid gland was admitted to our hospital with a 2-day history of fever and left neck pain. Laboratory tests revealed low levels of thyroid stimulating hormone and elevated levels of free thyroxine 4. Contrast-enhanced computed tomography showed low-attenuation areas with peripheral enhancement in the left thyroid gland. He was diagnosed with thyroid abscess and thyrotoxicosis, and treatment with intravenous piperacillin-tazobactam was initiated after collecting blood, drainage fluid, and stool samples. The isolated Gram-negative rod bacteria from blood and drainage fluid cultures was confirmed to be Y. enterocolitica. He was diagnosed with thyroid abscess and thyrotoxicosis due to be Y. enterocolitica subsp. palearctica. The piperacillin-tazobactam was replaced with levofloxacin., Conclusion: We report a novel case of a thyroid abscess associated with thyrotoxicosis caused by Y. enterocolitica subsp. palearctica in a patient with a follicular thyroid adenoma., (© 2024. The Author(s).)
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- 2024
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48. Transcriptional profiling of human cartilage endplate cells identifies novel genes and cell clusters underlying degenerated and non-degenerated phenotypes.
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Kuchynsky K, Stevens P, Hite A, Xie W, Diop K, Tang S, Pietrzak M, Khan S, Walter B, and Purmessur D
- Subjects
- Humans, Cartilage metabolism, Chondrocytes metabolism, Stem Cells metabolism, Intervertebral Disc metabolism, Intervertebral Disc Degeneration genetics, Intervertebral Disc Degeneration metabolism
- Abstract
Background: Low back pain is a leading cause of disability worldwide and is frequently attributed to intervertebral disc (IVD) degeneration. Though the contributions of the adjacent cartilage endplates (CEP) to IVD degeneration are well documented, the phenotype and functions of the resident CEP cells are critically understudied. To better characterize CEP cell phenotype and possible mechanisms of CEP degeneration, bulk and single-cell RNA sequencing of non-degenerated and degenerated CEP cells were performed., Methods: Human lumbar CEP cells from degenerated (Thompson grade ≥ 4) and non-degenerated (Thompson grade ≤ 2) discs were expanded for bulk (N=4 non-degenerated, N=4 degenerated) and single-cell (N=1 non-degenerated, N=1 degenerated) RNA sequencing. Genes identified from bulk RNA sequencing were categorized by function and their expression in non-degenerated and degenerated CEP cells were compared. A PubMed literature review was also performed to determine which genes were previously identified and studied in the CEP, IVD, and other cartilaginous tissues. For single-cell RNA sequencing, different cell clusters were resolved using unsupervised clustering and functional annotation. Differential gene expression analysis and Gene Ontology, respectively, were used to compare gene expression and functional enrichment between cell clusters, as well as between non-degenerated and degenerated CEP samples., Results: Bulk RNA sequencing revealed 38 genes were significantly upregulated and 15 genes were significantly downregulated in degenerated CEP cells relative to non-degenerated cells (|fold change| ≥ 1.5). Of these, only 2 genes were previously studied in CEP cells, and 31 were previously studied in the IVD and other cartilaginous tissues. Single-cell RNA sequencing revealed 11 unique cell clusters, including multiple chondrocyte and progenitor subpopulations with distinct gene expression and functional profiles. Analysis of genes in the bulk RNA sequencing dataset showed that progenitor cell clusters from both samples were enriched in "non-degenerated" genes but not "degenerated" genes. For both bulk- and single-cell analyses, gene expression and pathway enrichment analyses highlighted several pathways that may regulate CEP degeneration, including transcriptional regulation, translational regulation, intracellular transport, and mitochondrial dysfunction., Conclusions: This thorough analysis using RNA sequencing methods highlighted numerous differences between non-degenerated and degenerated CEP cells, the phenotypic heterogeneity of CEP cells, and several pathways of interest that may be relevant in CEP degeneration., (© 2023. The Author(s).)
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- 2024
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49. Teamwork in community health committees: a case study in two urban informal settlements.
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Karuga R, Khan S, Kok M, Moraa M, Mbindyo P, Broerse J, and Dieleman M
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- Humans, Kenya, Qualitative Research, Community Participation, Public Health, Community Health Services
- Abstract
Background: Community health committees (CHCs) are mechanisms for community participation in decision-making and overseeing health services in several low-and middle-income countries (LMICs). There is little research that examines teamwork and internal team relationships between members of these committees in LMICs. We aimed to assess teamwork and factors that affected teamwork of CHCs in an urban slum setting in Nairobi, Kenya., Methods: Using a qualitative case-study design, we explored teamwork of two CHCs based in two urban informal settlements in Nairobi. We used semi-structured interviews (n = 16) to explore the factors that influenced teamwork and triangulated responses using three group discussions (n = 14). We assessed the interpersonal and contextual factors that influenced teamwork using a framework for assessing teamwork of teams involved in delivering community health services., Results: Committee members perceived the relationships with each other as trusting and respectful. They had regular interaction with each other as friends, neighbors and lay health workers. CHC members looked to the Community Health Assistants (CHAs) as their supervisor and "boss", despite CHAs being CHC members themselves. The lay-community members in both CHCs expressed different goals for the committee. Some viewed the committee as informal savings group and community-based organization, while others viewed the committee as a structure for supervising Community Health Promoters (CHPs). Some members doubled up as both CHPs and CHC members. Complaints of favoritism arose from CHC members who were not CHPs whenever CHC members who were CHPs received stipends after being assigned health promotion tasks in the community. Underlying factors such as influence by elites, power imbalances and capacity strengthening had an influence on teamwork in CHCs., Conclusion: In the absence of direction and support from the health system, CHCs morph into groups that prioritize the interests of the members. This redirects the teamwork that would have benefited community health services to other common interests of the team. Teamwork can be harnessed by strengthening the capacity of CHC members, CHAs, and health managers in team building and incorporating content on teamwork in the curriculum for training CHCs., (© 2023. The Author(s).)
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- 2023
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50. The role of diabetes distress in Diabulimia.
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Poos S, Faerovitch M, Pinto C, Jamalkhani N, Chaudhri F, Khan S, Lo DF, McGowan K, and Martin A
- Abstract
Importance: Diabulimia is a disordered eating behavior in which a person with type 1 diabetes withholds insulin injections to lose weight. It is thought that the psychosocial stress of managing this chronic disease, which is termed diabetes distress, may contribute to developing diabulimia., Objective: This paper explores links between diabetes distress and diabulimia and their relevance to the diagnosis and treatment of diabulimia by assessing whether people with diabulimia report measurable evidence of diabetes distress., Evidence Review: We evaluated studies examining the qualitative experiences of people with disordered eating behaviors in the setting of type 1 diabetes for themes of diabetes distress by identifying aspects of the patients' stories that matched the criteria in the Diabetes Distress Scale. Selected studies recorded primary data, analyzed qualitative data, examined lived experiences of individuals with diabulimia, and were made available in English-language peer-reviewed journals between January 1, 2000 and August 31, 2022. Exclusion criteria included partial articles, editorials, reviews, and abstracts along with studies of patients with type 2 diabetes., Findings: Over forty individual participants across twelve studies were found to have aspects of their experiences that met one or more criteria from the Diabetes Distress Scale. Participants reported experiences that matched criteria items from each of the seven subscales of the Diabetes Distress Scale. Participants in the twelve studies included 185 individuals with type 1 diabetes experiencing diabulimia, including 164 females (88.6%), 20 males (10.8%), and 1 non-reported gender (0.54%)., Conclusion: We believe this discovery warrants further research probing the prevalence of diabetes distress among people with diabulimia as well as other links between the two conditions. We advocate for a diabetes distress-informed approach to diabulimia treatment and for diabetes distress screening in every patient with type 1 diabetes., (© 2023. The Author(s).)
- Published
- 2023
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