Maternal and fetal outcome of febrile morbidity in pregnancy at tertiary care level

Background: Fever in pregnancy is a common clinical problem worldwide. Effects of hyperthermia depends on the extent and duration of temperature elevation, timing of exposure in pregnancy and possibly on maternal nutritional status, comorbidities, medications, socio-economic background and several other factors. The exposure of maternal temperature has been reported to lead to cell disruptions, vascular disturbance and placental infarction which can lead to the risk of structural and functional defects in progeny. The underlying maternal cytokine polymorphism is strongly associated with both intrapartum fever and neonatal outcome. Hence there is a need to detect the various life-threatening medical complications of febrile morbidity leading to severe maternal morbidity and its impact on fetal outcome. Aim of study were to study the etiology of fever in pregnancy during the study period and to know the effect of fever on both the mother and the fetus. Methods: A prospective observational study. Results: Out of the 60 cases of fever in pregnancy, most common cause of fever was urinary tract infection (30%), followed by dengue fever (25%) and upper respiratory tract infection (23.3%). Fever was associated with complications as such PROM, PPROM, preterm labour, PPH, thrombocytopenia, anemia and abortions. Fetal outcome were preterm birth (25%), low birth weight (36%), neonatal sepsis (20%) and perinatal death (13.8%). Conclusions: Febrile morbidity in pregnancy leads to numerous maternal and fetal complications can occur due to fever in pregnancy from various causes. The most common cause of fever was UTI followed by dengue fever. The maternal and fetal complications can be avoidable if the cause for the fever is diagnosed and treated early

The influence of mode of anaesthesia on perioperative outcomes in people with hip fracture: a prospective cohort study from the National Hip Fracture Database for England, Wales and Northern Ireland

Background: Delirium is common after hip fracture surgery, affecting up to 50% of patients. The incidence of delirium may be influenced by mode and conduct of anaesthesia. We examined the effect of spinal anaesthesia (with and without sedation) compared with general anaesthesia on early outcomes following hip fracture surgery, including delirium. Methods: We used prospective data on 107,028 patients (2018 to 2019) from the National Hip Fracture Database, which records all hip fractures in patients aged 60 years and over in England, Wales and Northern Ireland. Patients were grouped by anaesthesia: general (58,727; 55%), spinal without sedation (31,484; 29%), and spinal with sedation (16,817; 16%). Outcomes (4AT score on post-operative delirium screening; mobilisation day one post-operatively; length of hospital stay; discharge destination; 30-day mortality) were compared between anaesthetic groups using multivariable logistic and linear regression models. Results: Compared with general anaesthesia, spinal anaesthesia without sedation (but not spinal with sedation) was associated with a significantly reduced risk of delirium (odds ratio (OR)=0.95, 95% confidence interval (CI)=0.92–0.98), increased likelihood of day one mobilisation (OR=1.06, CI=1.02–1.10) and return to original residence (OR=1.04, CI=1.00–1.07). Spinal without sedation (p<0.001) and spinal with sedation (p=0.001) were both associated with shorter hospital stays compared with general anaesthesia. No differences in mortality were observed between anaesthetic groups. Conclusions: Spinal and general anaesthesia achieve similar outcomes for patients with hip fracture. However, this equivalence appears to reflect improved perioperative outcomes (including a reduced risk of delirium, increased likelihood of mobilisation day one post-operatively, shorter length of hospital stay and improved likelihood of returning to previous residence on discharge) among the sub-set of patients who received spinal anaesthesia without sedation. The role and effect of sedation should be studied in future trials of hip fracture patients undergoing spinal anaesthesia

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

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

MOF-derived nickel and cobalt metal nanoparticles in a N-doped coral shaped carbon matrix of coconut leaf sheath origin for high performance supercapacitors and OER catalysis

Coconut leaf sheath-derived nitrogen doped carbon framework is developed and incorporated with nickel and cobalt metal nanoparticles in the carbon matrix by a facile process of growing ZIF-67 metal organic framework particles on the graphitised carbon, followed by annealing it in inert atmosphere. Various parameters are modified to obtain three different samples. These samples are tested for high performance supercapacitors and oxygen evolution reaction (OER) catalysts. The optimised sample NiCo–C-1 gave a high specific capacity of 308 mAh g−1 at a current density of 1 A g−1 in a 2 M KOH electrolyte. An asymmetric supercapacitor assembly prepared from NiCo–C-1 as the positive electrode and the nitrogen-doped carbon as the negative electrode, exhibited an energy density of up to 31.8 Wh Kg−1 for a high power density of 6.2 kW kg−1 over a potential window of 0–1.55 V. Two of our best samples were also tested for OER, giving good water oxidation kinetics, revealed by their lower Tafel slopes of around 107 mV and a low over potential (η) of around 420 mV at a current density of 10 mA cm−2. Hence, this work opens great avenues for biomass-derived materials for high performance supercapacitors and catalysis.MOE (Min. of Education, S’pore

Geographical variation in surgical care and mortality following hip fracture in England: a cohort study using the National Hip Fracture Database (NHFD)

Summary: we describe variation across geographical regions of England in operations undertaken following presentation of hip fracture and in 30-day mortality. Some significant geographic variation in 30-day mortality was observed particularly for patients with trochanteric hip fractures and warrants further investigation of other aspects of post-hip fracture careIntroduction: mortality after hip fracture has improved considerably in the UK over recent decades. Our aim here was to describe geographical variation in type of operation performed and 30-day mortality amongst patients in England with hip fracture.Methods: the National Hip Fracture Database was used to carry out a prospective cohort study of nearly all over-60 year olds with hip fracture in England. These data were linked to Hospital Episode Statistics (HES), allowing us to explore regional variation in the operations performed for three fracture types (intracapsular, trochanteric and subtrochanteric), and use logistic regression models adjusted for demographic and clinical factors to describe associated 30-day mortality.Results: NHFD recorded data for 64,211 patients who underwent surgery in England during 2017. Most had an intracapsular (59%) or trochanteric fracture (35%), and we found significant geographical variation across regions of England in use of total hip replacement (THR) (ranging from 10.1 to 17.4%) for intracapsular fracture and in intermedullary nailing (ranging from 14.9 to 27.0%) of trochanteric fracture. Some geographical variation in mortality amongst intracapsular fracture patients was found, with slightly higher mortality in the East of England (adjusted odds ratio [aOR]: 1.22, 95% CI: 1.02–1.46). Trochanteric fractures showed slightly more variation, with higher 30-day mortality (aOR: 1.40, 95%CI: 1.05–1.88) in the East of England and significantly lower mortality in the North East (aOR: 0.65, 95%CI: 0.46–0.93).Conclusions: we have identified regional differences in operation type and 30-day mortality amongst hip fracture patients in England. The relationship between surgical approach and mortality has been explored, but the extent to which differential mortality reflects variation in approach to medical assessment, anaesthesia and other aspects of care warrants further investigation

Significance and applications of carbon dots in anti cancerous nanodrug conjugate development: A review

Carbon-based nanoparticles known as Carbon Dots (CDs) have attracted a lot of interest in the field of cancer therapy because of their special physicochemical characteristics and biocompatibility. They are attractive carriers for drug delivery systems due to their surface functional ability, superior water solubility, and size-dependent fluorescence. CDs are unique in that they have a large surface area, adjustable surface chemistry, and a remarkable ability to carry anticancer medications. Their lower systemic toxicity, regulated drug release, and capacity to get beyond biological barriers have completely changed the way that drugs are delivered. CDs have a variety of uses in the creation of anti-tumor nanodrug conjugates. CDs have been used in combination therapy, a multimodal strategy for cancer treatment that involves co-delivering various medications for synergistic benefits. The incorporation of CDs into anticancerous has-drug conjugates represents a noteworthy progression in the treatment of cancer medication delivery systems have been revolutionized by their capacity to improve medication stability, target specificity, and controlled release, which holds the promise of more effective and customized treatments. This review article deals with the synthesis of carbon dot-mediated nanodrug conjugate and their roles in cancer therapy

Tri- modality therapy in advanced esophageal carcinoma: long- term results and insights from a developing world, institutional cohort

Objective: To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). Methods: Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. Results: The median OS was 71.4 months (interquartile range: 19.6–∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89–0.98); 0.94 (0.89–0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09–0.53); 0.30 (0.12–0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01–1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08–6.57)] and adventitial involvement [2.54 (1.36–4.72)] also influenced OS, while involved margins [3.12 (1.24–7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44–0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57–0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the periesophageal and perigastric (greater and lesser curvature) regions, respectively. Conclusion: NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. Advances in knowledge: The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS