A prospective study of the incidence and outcomes of eclampsia in a tertiary care hospital and teaching institute in India

Background: Eclampsia is a common cause of maternal and foetal morbidity and mortality in India and the rest of the world accounting for nearly 10% of all maternal deaths. However, there is a relative scarcity of outcome data for patients with eclampsia in India. Our goal was to estimate the incidence of eclampsia, the maternal and foetal outcomes of patients presenting with eclampsia, and predictors of clinical outcomes in these patients. Objective of this study was to estimate the incidence of eclampsia in patients who delivered at a single tertiary care institution over a 2-year period and to study the maternal and perinatal outcomes in those patients.Methods: Prospective cohort study conducted from September 2008 to August 2010 on all patients with eclampsia admitted during the study period at Lok Nayak Hospital, New Delhi, India.Results: The incidence of eclampsia among total deliveries was 0.45%.  About 97% of these patients received parenteral magnesium sulphate as the primary anticonvulsant therapy. Caesarean section was performed in 22.7% and majorities were done for foetal distress. Maternal complications were encountered among 17% of patients. There were 2 maternal deaths (2.3%), 13 stillbirths (14.1%) and 7 early neonatal deaths (7.9%).Conclusions: The incidence of eclampsia among all deliveries over a 2-year period at a tertiary care centre in India was 0.45%. Parenteral magnesium sulphate was effective in the vast majority of these patients in controlling the seizures. Further studies to evaluate whether early registration for antepartum care improves maternal and foetal outcomes in patients with eclampsia are warranted

Association between clinical diagnosis of foetal distress with umbilical artery acidaemia at birth in women undergoing caesarean section for foetal distress

Background: The risks of maternal morbidity and mortality associated with a caesarean section may not be reasonably justified by the degree of neonatal compromise at birth associated with caesarean section done for clinically diagnosed foetal distress. The aim was to study the association of clinical diagnosis of non-reassuring foetal status with umbilical artery acidaemia at birth in women undergoing caesarean section for foetal distress and to evaluate outcomes in neonates born by caesarean section performed for foetal distress.Methods: Prospective observational study of all the women undergoing emergency caesarean section for foetal distress at a tertiary care teaching facility over 2 months. Criteria for diagnosis of foetal distress were thick meconium stained liquor only or foetal heart rate abnormality with or without meconium stained liquor. Testing for pH was done on arterial blood drawn from umbilical cord at the time of birth. Acidaemia was defined as cord blood pH less than 7.2.  Severe acidaemia was defined as cord blood pH less than 7.0.Results: Cord blood pH was analysed in 110 caesareans done for foetal distress. Incidence of neonatal acidaemia at birth in study population was 53.6%.Conclusions: Much lower incidence of actual acidaemia and low Apgar scores in neonates born by caesarean section done for clinical diagnosis of foetal distress than previously reported indicate the need for more stringent criteria and more objective tests for diagnosis of foetal distress

Perceived stress in relation to quality of life and resilience in patients with advanced chronic kidney disease undergoing hemodialysis

Patients with chronic kidney disease undergo various stages of therapeutic adaptation which involve lifestyle modifications, physical changes, and adjustment to renal replacement therapy. This process produces adaptive stress. Objective: To identify how resilience, healthrelated quality of life, and sociodemographic, clinical, and hemodialysis routine-related variables are related to perceived stress in patients with chronic kidney disease receiving hemodialysis for more than six months. Methods: This was a multicenter and cross-sectional study involving 144 patients from the Valencian Community (Spain). The assessment scales used for the study were the Perceived Stress Scale 10, the Kidney Disease Quality of Life 36, and the Connors–Davidson Resilience Scale. To identify variables with predictive power over Perceived Stress Scale 10 scores, multiple regression analyses were performed. Results: Employment status (p = 0.003), resilience (p < 0.001), and quality of life (p < 0.001) were shown to be significantly related to perceived stress. The regression models determined that health-related quality of life and resilience explained up to 27.1% of the variance of total PSS10 scores. Conclusions: Resilience was identified as one of the most important predictors of Perceived Stress Scale 10 scores. Thus, the development of interventions to promote resilience may have a positive impact on perceived stress in patients with chronic kidney disease

Clinical, histopathological and molecular characterization of hypoplastic myelodysplastic syndrome

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AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

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

Gaps in availability, utilization and expectations of people from health care services: A study of resettlement colony, Chandigarh

Introduction: Health care services cover a wide spectrum of community services for the treatment of disease, prevention of illness and promotion of health.[1] Aim and Objective: This study was aimed at assessing the gap in availability and utilization of health services in a resettlement Colony of Chandigarh. Material and methods: Dadu Majra was purposely selected to assess the gap in availability and utilization of health care services and expectations of people from public health sector. Using semi structured interview schedule, interviews were carried with all health care providers. Six focused group discussions and interviews were held 114 sampled service users. Results: Most of the users were utilizing services from private medical clinics (96.5%) for the treatment of acute illnesses. For antenatal checkup/delivery (95.6%), chronic diseases (99.1%), and emergency services (95.6%) Government Multi-Speciality Hospital, Chandigarh was being utilized. Utilization of services provided at civil dispensary of study area was low. The expectations of users were availability of at least one doctor and availability of free medicine & laboratory facilities. Conclusions: Public health services were preferred over by the private and therefore need to be strengthened

Immobilised TiO2 application for pesticides degradation using a solar still

Pesticides are recalcitrant contaminants, which are bioaccumulative in nature. A good number of pesticides, particularly organochlorines, have been listed among the Persistent Organic Pollutant list of Stockholm convention. Organochlorine pesticides were significantly used in the past, however, their footprints still exist in environmental matrices.In the present study, degradation of pesticides using a solar still, with immobilised TiO2, is performed. Existing solar remediation systems have a limitation of utilizing ultraviolet portion of solar energy and the thermal energy remains unutilized in most cases. Solar distillation with a TiO2 photocatalysis enhances the purification properties of the solar still in terms of treatment of recalcitrant pollutants.Organochlorine pesticides like isomers of Hexachlorocyclohexane (HCH), Endosulphan and Dichlorodiphenyltrichloroethane (DDT) can be significantly degraded using a thermo-photocatalytic solar still described in the study. Besides this, degradation of synthetic pyrethroids like fenpropathrin, cyhalothrin, cyfluthrin, cypermethrin and fenvalerate is also studied. Combination of solar distillation and photocatalysis was effective for the treatment of water contaminated with pesticides, achieving more than 21–82% degradation for the studied pesticides. For Organochlorine pesticides, pp DDE’ was the compound which showed least degradation (21.4%) and maximum degradation was achieved for Alpha HCH (82.9%). In the synthetic pyrethroid group, fenpropathrin showed least degradation among all the compounds (60.4%) and fenvalerate showed a maximum degradation (96.4%).Solar photocatalytic distillation can find application in recycling of wastewater generated from agriculture-intensive areas and pesticide manufacturing industries