Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Frecuencia y variables asociadas a estigma-discriminación percibido en víctimas del conflicto armado colombiano

Resumen: Se desconoce la frecuencia de complejo estigma-discriminación percibido en víctimas del conflicto armado colombiano. El objetivo del estudio fue establecer la frecuencia y variables asociadas al estigma-discriminación percibido en víctimas del conflicto armado, en municipios del Departamento del Magdalena, Colombia. Se realizó un estudio transversal con víctimas registradas en el Programa de Atención Psicosocial y Salud Integral a Víctimas. Los síntomas depresivos se cuantificaron con cuatro ítems dicotómicos (tres o más se clasificaron como alto nivel de síntomas depresivos) y el estigma-discriminación percibido se cuantificó con seis incisos dicotómicos (dos o más afirmaciones se categorizó como alto estigma-discriminación percibido). Participaron 943 adultos (M = 47,9; DE = 14,2); 67,4%, mujeres; 109 (11,6%) informaron alto nivel de síntomas depresivos y 217 (23%) presentaron alto estigma-discriminación percibido. El alto estigma-discriminación percibido se asoció a alto nivel de síntomas depresivos (OR = 6,47; IC95%: 4,23-9,88). Se concluye que un cuarto de las víctimas del conflicto armado en Magdalena informa alto estigma-discriminación percibido; éste se asocia significativamente a alto nivel de síntomas depresivos

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. METHODS: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. FINDINGS: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66-2·79) in 2000 to 2·31 (2·17-2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5-137·8) in 2000 to a peak of 139·6 million (133·0-146·9) in 2016. Global livebirths then declined to 135·3 million (127·2-144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4-27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8-67·6) in 2000 to 73·5 years (72·8-74·3) in 2019. The total number of deaths increased from 50·7 million (49·5-51·9) in 2000 to 56·5 million (53·7-59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1-10·3) in 2000 to 5·0 million (4·3-6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0-6·3) in 2000 to 7·7 billion (7·5-8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1-60·8) in 2000 to 63·5 years (60·8-66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. INTERPRETATION: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. FUNDING: Bill & Melinda Gates Foundation

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

Using a Hybrid Approach to Model Central Carbon Metabolism Across the Cell Cycle

International audienceMetabolism and cell cycle are two central processes in the life of a eukaryote cell. If they have been extensively studied in their own right, their interconnection remains relatively poorly understood. In this paper, we propose to use a differential model of the central carbon metabolism. After verifying the model accurately reproduces known metabolic variations during the cell cycle’s phases, we extend it into a hybrid system reproducing an imposed succession of the phases. This first hybrid approach qualitatively recovers observations made in the literature, providing an interesting first step towards a better understanding of the crosstalks between cell cycle and metabolism

Controlled Release of Dutasteride from Biodegradable Microspheres: In Vitro and In Vivo Studies

The aim of the present work was to study the in vitro/in vivo characteristics of dutasteride loaded biodegradable microspheres designed for sustained release of dutasteride over four weeks. An O/W emulsion-solvent evaporation method was used to incorporate dutasteride, which is of interest in the treatment of benign prostatic hyperplasia (BPH), into poly(lactide-co-glycolide) (PLGA). A response surface method (RSM) with central composite design (CCD) was employed to optimize the formulation variables. A prolonged in vitro drug release profile was observed, with a complete release of the entrapped drug within 28 days. The pharmacokinetics study showed sustained plasma drug concentration-time profile of dutasteride loaded microspheres after subcutaneous injection into rats. The in vitro drug release in rats correlated well with the in vivo pharmacokinetics profile. The pharmacodynamics evaluated by determination of the BPH inhibition in the rat models also showed a prolonged pharmacological response. These results suggest the potential use of dutasteride loaded biodegradable microspheres for the management of BPH over long periods