Comparative analysis of chromogenic vs clot based CDC modified, Nijmegen-Bethesda assay for detection of factor viii inhibitor titre

Background:-Inhibitors to infused factor VIII are the most significant complication of hemophilia treatment. These inhibitors are usually IgG antibodies, that react with FVIII in a time and temperature dependent manner. Coagulation factor VIII inhibitors can be detected by Chromogenic, clot based and immunological assays. However, there is lack of consensus as to what constitutes a positive inhibitor, including the appropriate cut-off for inhibitor measurement The main objective of this study is to compare the sensitivity and specificity of chromogenic Nijmegen Bethesda assay (CNBA) with Centre for disease control modified Nijmegen Bethesda (CDC-NBA) assay against the Reference control method (RCM).Materials and Methods: The Coagulometer used for inhibitor titre  quantification is Sysmex CS-5100. APTT reagent used isPathromtin SL supplied by seimensSeimens. All data were expressed as Mean ± SD. Statistical formulae were used for sensitivity and specificity calculations. Unpaired students t test was used whereever necessary and a P value of <0.05 is considered as statistical significanceResults: A total of 150 cases were tested for inhibitor titre using CNBA vs CDC-NBA. For low titre Inhibitor (<2 NBU), CNBA has 92% and 86% and CDC-NBA has 80 and 60% sensitivity and specificity respectively. These results show that CDC-NBA shows false positive results at low inhibitor titre. For High titre Inhibitor ( >2 NBU) CNBA has 88% and 80% and CDC-NBA has 85 and 70 % sensitivity and specificity respectively.Conclusion :- These results shows that CNBA is more sensitive and specific than CDC-NBA at both low and high inhibitor titre. Moreover chromogenic assays can differentiate factor specific inhibitor from nonspecific inhibitors like lupus anticoagulant and unfractionated heparin therapy.Keywords: Hemophilia, Bethesda assay, ELISA, Factor VIII, Inhibitor, Mixing studyAbbrevations: APLA- Antiphospholipid antibody syndrome, CDC:NBA- Centers for Disease Control and Prevention - Nijmegen-BethesdaAssay, CNBA:- chromogenic Nijmegen Bethesda assa

Comprehensive Analysis to Uncover Determinants of Patient Appointment Compliance in Ophthalmology at the Kresge Eye Institute

Introduction: Appointment compliance (AC) has a significant impact on physician-patient relationship and overall patient care. However, determinants of AC in Ophthalmology and its subspecialties remains elusive. Methods: We performed a five-year retrospective analysis across Kresge Eye Institute (KEI) and its affiliated Michigan locations. A total of 597,364 appointments across \u3e13 subspecialties were included. AC was the primary outcome of interest. Compliant (CO) and non-compliant (NC) groups were compared to the following variables: patient characteristics (gender, race, age, insurance), appointment rank (relative to patient history), scheduling location, month, and ophthalmic specialty, in regard to arrival and no-show. Results: Among all appointments, 59.77% were associated with a female patient and 79.16% of the total number of appointments were compliant. AC differed concerning specialty, with retina representing the highest compliance across all appointments. Among 200+ insurance providers, Medicare was most frequently used and represented the highest share of CO appointments. African Americans were the primary ethnicity served by KEI and had the highest number of NC appointments. Conclusion: Our study demonstrates the impact of patient demographics, appointment characteristics, and ophthalmic subspecialty on AC. A better understanding of these determinants could allow for an increased CO for Ophthalmology practices

Preparing for low surface brightness science with the Vera C. Rubin Observatory: A Comparison of Observable and Simulated Intracluster Light Fractions

Intracluster Light (ICL) provides an important record of the interactions galaxy clusters have undergone. However, we are limited in our understanding by our measurement methods. To address this we measure the fraction of cluster light that is held in the Brightest Cluster Galaxy and ICL (BCG+ICL fraction) and the ICL alone (ICL fraction) using observational methods (Surface Brightness Threshold-SB, Non-Parametric Measure-NP, Composite Models-CM, Multi-Galaxy Fitting-MGF) and new approaches under development (Wavelet Decomposition-WD) applied to mock images of 61 galaxy clusters (14<log10 M_200c/M_solar <14.5) from four cosmological hydrodynamical simulations. We compare the BCG+ICL and ICL fractions from observational measures with those using simulated measures (aperture and kinematic separations). The ICL fractions measured by kinematic separation are significantly larger than observed fractions. We find the measurements are related and provide equations to estimate kinematic ICL fractions from observed fractions. The different observational techniques give consistent BCG+ICL and ICL fractions but are biased to underestimating the BCG+ICL and ICL fractions when compared with aperture simulation measures. Comparing the different methods and algorithms we find that the MGF algorithm is most consistent with the simulations, and CM and SB methods show the smallest projection effects for the BCG+ICL and ICL fractions respectively. The Ahad (CM), MGF and WD algorithms are best set up to process larger samples, however, the WD algorithm in its current form is susceptible to projection effects. We recommend that new algorithms using these methods are explored to analyse the massive samples that Rubin Observatory's Legacy Survey of Space and Time will provide.Comment: Submitted for publication in MNRAS, posted to arXiv after responding to two positive rounds of referee comments. Key results in Figs 3, 5, 6 and 1

Preparing for low surface brightness science with the Vera C. Rubin Observatory: a comparison of observable and simulated intracluster light fractions

Intracluster light (ICL) provides an important record of the interactions galaxy clusters have undergone. However, we are limited in our understanding by our measurement methods. To address this, we measure the fraction of cluster light that is held in the Brightest Cluster Galaxy and ICL (BCG+ICL fraction) and the ICL alone (ICL fraction) using observational methods (surface brightness threshold-SB, non-parametric measure-NP, composite models-CM, and multi-galaxy fitting-MGF) and new approaches under development (wavelet decomposition-WD) applied to mock images of 61 galaxy clusters (14 <log10M200c/M⊙ < 14.5) from four cosmological hydrodynamical simulations. We compare the BCG+ICL and ICL fractions from observational measures with those using simulated measures (aperture and kinematic separations). The ICL fractions measured by kinematic separation are significantly larger than observed fractions. We find the measurements are related and provide equations to estimate kinematic ICL fractions from observed fractions. The different observational techniques give consistent BCG+ICL and ICL fractions but are biased to underestimating the BCG+ICL and ICL fractions when compared with aperture simulation measures. Comparing the different methods and algorithms, we find that the MGF algorithm is most consistent with the simulations, and CM and SB methods show the smallest projection effects for the BCG+ICL and ICL fractions, respectively. The Ahad (CM), MGF, and WD algorithms are best set up to process larger samples; however, the WD algorithm in its current form is susceptible to projection effects. We recommend that new algorithms using these methods are explored to analyse the massive samples that Rubin Observatory’s Legacy Survey of Space and Time will provide

Educating and Informing Patients Receiving Psychopharmacological Medications: Are Family Physicians in Pakistan up to the Task?

Introduction: Studies have shown a high prevalence of psychiatric illnesses among Patients in primary health care settings. Family physicians have a fundamental role in managing psychiatric illness with psychopharmacological medications. Providing information about the disease, its management and the potential adverse effects of the medications is an important part of the management of mental illnesses. Our objective was to determine if Patients who were prescribed psychopharmacological drugs by family physicians at a community health center in Karachi, Pakistan were provided adequate education about their disease and its management. Methods: A cross-sectional study was conducted at the Community Health Centre (CHC), Aga Khan University Hospital Karachi, Pakistan. Details about the prescriptions and Patient education were acquired from the Patients after their consultations. Results: A total of 354 adult Patients were interviewed during 3 days. Among them, 73 (20.6%) were prescribed psychopharmacological medications. Among Patients receiving psychopharmacological medicines, 37 (50.7%) did not know their diagnosis, 50 (68.5%) were unaware of the disease process, 52 (71.2%) were unaware of alternative treatments, 63 (86.3%) were not cautioned about the potential adverse effects of the drugs, 24 (32.9%) were unaware of the duration of treatment and in 60 (82.2%) of the participants an appropriate referral had not been discussed. For all aspects of education, Patients prescribed psychopharmacological medications knew less as compared to those Patients that were prescribed other medications. Discussion: The practice of imparting information to Patients who receive psychopharmacological medications seems to be inadequate in Pakistan. We have hypothesized about the possible reasons for our findings, and identified a need for further research to determine the cause for such findings and to address them accordingly. At the same time there is a need to educate family physicians in Pakistan about the special importance of providing adequate information to such Patients

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

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

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

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

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

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

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

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