Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Global fertility in 204 countries and territories, 1950–2021, with forecasts to 2100: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background Accurate assessments of current and future fertility—including overall trends and changing population age structures across countries and regions—are essential to help plan for the profound social, economic, environmental, and geopolitical challenges that these changes will bring. Estimates and projections of fertility are necessary to inform policies involving resource and health-care needs, labour supply, education, gender equality, and family planning and support. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 produced up-to-date and comprehensive demographic assessments of key fertility indicators at global, regional, and national levels from 1950 to 2021 and forecast fertility metrics to 2100 based on a reference scenario and key policy-dependent alternative scenarios. Methods To estimate fertility indicators from 1950 to 2021, mixed-effects regression models and spatiotemporal Gaussian process regression were used to synthesise data from 8709 country-years of vital and sample registrations, 1455 surveys and censuses, and 150 other sources, and to generate age-specific fertility rates (ASFRs) for 5-year age groups from age 10 years to 54 years. ASFRs were summed across age groups to produce estimates of total fertility rate (TFR). Livebirths were calculated by multiplying ASFR and age-specific female population, then summing across ages 10–54 years. To forecast future fertility up to 2100, our Institute for Health Metrics and Evaluation (IHME) forecasting model was based on projections of completed cohort fertility at age 50 years (CCF50; the average number of children born over time to females from a specified birth cohort), which yields more stable and accurate measures of fertility than directly modelling TFR. CCF50 was modelled using an ensemble approach in which three sub-models (with two, three, and four covariates variously consisting of female educational attainment, contraceptive met need, population density in habitable areas, and under-5 mortality) were given equal weights, and analyses were conducted utilising the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. To capture time-series trends in CCF50 not explained by these covariates, we used a first-order autoregressive model on the residual term. CCF50 as a proportion of each 5-year ASFR was predicted using a linear mixed-effects model with fixed-effects covariates (female educational attainment and contraceptive met need) and random intercepts for geographical regions. Projected TFRs were then computed for each calendar year as the sum of single-year ASFRs across age groups. The reference forecast is our estimate of the most likely fertility future given the model, past fertility, forecasts of covariates, and historical relationships between covariates and fertility. We additionally produced forecasts for multiple alternative scenarios in each location: the UN Sustainable Development Goal (SDG) for education is achieved by 2030; the contraceptive met need SDG is achieved by 2030; pro-natal policies are enacted to create supportive environments for those who give birth; and the previous three scenarios combined. Uncertainty from past data inputs and model estimation was propagated throughout analyses by taking 1000 draws for past and present fertility estimates and 500 draws for future forecasts from the estimated distribution for each metric, with 95% uncertainty intervals (UIs) given as the 2·5 and 97·5 percentiles of the draws. To evaluate the forecasting performance of our model and others, we computed skill values—a metric assessing gain in forecasting accuracy—by comparing predicted versus observed ASFRs from the past 15 years (2007–21). A positive skill metric indicates that the model being evaluated performs better than the baseline model (here, a simplified model holding 2007 values constant in the future), and a negative metric indicates that the evaluated model performs worse than baseline. Findings During the period from 1950 to 2021, global TFR more than halved, from 4·84 (95% UI 4·63–5·06) to 2·23 (2·09–2·38). Global annual livebirths peaked in 2016 at 142 million (95% UI 137–147), declining to 129 million (121–138) in 2021. Fertility rates declined in all countries and territories since 1950, with TFR remaining above 2·1—canonically considered replacement-level fertility—in 94 (46·1%) countries and territories in 2021. This included 44 of 46 countries in sub-Saharan Africa, which was the super-region with the largest share of livebirths in 2021 (29·2% [28·7–29·6]). 47 countries and territories in which lowest estimated fertility between 1950 and 2021 was below replacement experienced one or more subsequent years with higher fertility; only three of these locations rebounded above replacement levels. Future fertility rates were projected to continue to decline worldwide, reaching a global TFR of 1·83 (1·59–2·08) in 2050 and 1·59 (1·25–1·96) in 2100 under the reference scenario. The number of countries and territories with fertility rates remaining above replacement was forecast to be 49 (24·0%) in 2050 and only six (2·9%) in 2100, with three of these six countries included in the 2021 World Bank-defined low-income group, all located in the GBD super-region of sub-Saharan Africa. The proportion of livebirths occurring in sub-Saharan Africa was forecast to increase to more than half of the world's livebirths in 2100, to 41·3% (39·6–43·1) in 2050 and 54·3% (47·1–59·5) in 2100. The share of livebirths was projected to decline between 2021 and 2100 in most of the six other super-regions—decreasing, for example, in south Asia from 24·8% (23·7–25·8) in 2021 to 16·7% (14·3–19·1) in 2050 and 7·1% (4·4–10·1) in 2100—but was forecast to increase modestly in the north Africa and Middle East and high-income super-regions. Forecast estimates for the alternative combined scenario suggest that meeting SDG targets for education and contraceptive met need, as well as implementing pro-natal policies, would result in global TFRs of 1·65 (1·40–1·92) in 2050 and 1·62 (1·35–1·95) in 2100. The forecasting skill metric values for the IHME model were positive across all age groups, indicating that the model is better than the constant prediction. Interpretation Fertility is declining globally, with rates in more than half of all countries and territories in 2021 below replacement level. Trends since 2000 show considerable heterogeneity in the steepness of declines, and only a small number of countries experienced even a slight fertility rebound after their lowest observed rate, with none reaching replacement level. Additionally, the distribution of livebirths across the globe is shifting, with a greater proportion occurring in the lowest-income countries. Future fertility rates will continue to decline worldwide and will remain low even under successful implementation of pro-natal policies. These changes will have far-reaching economic and societal consequences due to ageing populations and declining workforces in higher-income countries, combined with an increasing share of livebirths among the already poorest regions of the world

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

Dietary Supplementation of Brown Seaweed and/or Nucleotides Improved Shrimp Performance, Health Status and Cold-Tolerant Gene Expression of Juvenile Whiteleg Shrimp during the Winter Season

This study was aimed to evaluate the efficiency of Sargassumpolycystum and nucleotides- supplemented diets to improve immune response and cold-tolerance of juvenile Litopenaeus vannamei. Four treatments were evaluated: T1, the control, shrimp received only a basal diet; T2, a basal diet with 500 ppm nucleotides; T3, a basal diet with 500 ppm S.polycystum powdered; T4, a basal diet with 500 ppm nucleotides and 500 ppm S.polycystum powdered. Shrimp were fed experimental diets for 56 days. Results revealed shrimp fed T4 diet exhibited the best significant improvement in water quality, survival, growth, and feed utilization indices followed by T2, and T3, while T1 showed the worst values. Additionally, nonspecific immune responses (phagocytosis (%), lysozyme, phenoloxidase, super oxide dismutase (SOD) activity, total nitric oxide) were improved with 1.7–3.2-fold in T4 higher than T1. Histomorphology of hepatopancreas in T4 showed the most increased activation of the hepatic glandular duct system compared with the other treatments. Moreover, nucleotides/seaweed-supplemented diets upregulated relative expression of cMnSOD, Penaeidin4, and heat shock protein70 (HSP70) genes, while translationally controlled tumor protein (TCTP) was downregulated. In conclusion, the synergistic effects of both S. polycystum and nucleotides have many advantages as a growth promoter, immunostimulant, antimicrobial, and cold-tolerant stimulant to L. vannamei

Effect of dietary bile acids : Growth performance, immune response, genes expression of fatty acid metabolism, intestinal, and liver morphology of striped catfish (Pangasianodon hypophthalmus)

Seven isonitrogenous (31.70% protein) and isolipidic (5.20%) experimental diets were made by supplementing a control diet (BA0) with 0.25, 0.50, 0.75, 1.0, 1.25, and 1.5 g bile acid (BA) kg−1 diet, respectively. The diets were fed to striped catfish (Pangasianodon hypophthalmus) to monitor the effects on the growth, non-specific immune response, gene expression of fatty acids metabolism, liver, and their intestinal morphology. The average initial fish weight was 10.3 ± 0.20 (SD) g. The diets were randomly assigned to 21 hapas, each stocked with 10 fish and fed for 70 days. Supplementing BA1.0 and BA1.25 significantly improved growth and nutrient utilization (P < 0.05) compared to BA0 and other treatments. Additionally, the hematological analyses red blood cell count (RBC), haemoglobin, packed cell volume (PCV) and white blood cell count (WBC) amplified in the subsequent order: BA1.0, BA1.25, BA0.75, BA1.50, and BA0.50 g kg−1 diet and finally BA0.25 g kg−1 diet compared to the control diet. The rates of serum lysozyme activity, biochemical parameters, phagocytic index, phagocytic activity, and antioxidants parameters were considerably improved (P ≤ 0.05) in fish fed diets BA1.0 and BA1.25. In the intestinal measurement and liver histomorphometricall, the highest values were observed on BA1.0 and BA1.25. Among the five genes assayed in the liver tissues, peritoneal fat, and musculature levels of ATGL, HSL, and CPT-1, genes expression increased in fish fed diets with increasing levels of bile acid added to the diet while, the expression of PPARα and FAS decreased. Consequently, bile acids are recommended at levels of 1.0–1.25 g kg−1 diet to improve the growth performance and immune status of striped catfish

Effect of fishmeal replacement with dried red wigglers (Eisenia fetida) worm meal on growth and feed utilization, production efficiency, and serum biochemistry in Nile tilapia (Oreochromis niloticus) fingerlings

This study investigated the effect of replacing fishmeal with red wigglers (Eisenia fetida) worm meal (RWWM) in the diet of Nile tilapia (Oreochromis niloticus) fingerlings. Red wigglers worms (RWW) were culture on a vegetable by-product medium, harvested and dried to obtain red wigglers worm meal. The fish (average weight ± SE: 7.70 ± 0.06 g) were fed with seven diets (30% crude protein and 7.5% crude lipid), in which fishmeal was replaced with 0%, 5%, 10%, 15%, 20%, 25%, and 30% RWWM. The fish was reared in 1000 L fiberglass tanks in a recirculating aquaculture system and were hand-fed twice daily for 90 days. At the end of the experiment, the growth, feed conversion ratio, and energy utilization improved when feeding 15% and 20% RWWM compared with the control diet (P < 0.05). Using broken line regression between growth efficiency and feed utilization, showed the optimum level of RWWM replacing FM in Nile tilapia fingerlings diet was around 21 – 22% of the diet. The whole-body crude protein and ash content were elevated in the fish fed with 10–25% RWWM, while crude lipid and energy contents were elevated in the fish fed with 5–25% RWWM compared with the control group (P < 0.05). The essential and non-essential amino acids profiles of the fish were improved by 15% and 20% RWWM compared with the control (P < 0.05). The plasma glucose was decreased by 15–20% and significantly enhanced in fish fed with 25–30% RWWM diets compared with the control (P < 0.05). The total protein, albumin and globulin increased in the fish fed 15–20% diets and decreased in fish fed the 30% RWWM (P < 0.05). Therefore, this study demonstrates that RWWM could replace 20% fishmeal in the diets of Nile tilapia fingerlings without negatively affecting fish growth and physiological performance

Assessment of zootechnical parameters, intestinal digestive enzymes, haemato-immune responses, and hepatic antioxidant status of Pangasianodon hypophthalmus fingerlings reared under different stocking densities

A 3-month experiment was designed to investigate the effects of different stocking densities on growth, stress markers, intestinal digestive enzymes, hepatic antioxidant biomarkers, serum immunity, and survivability of striped catfish, Pangasianodon hypophthalmus. The relationship between fish stocking densities and water quality parameters was also assessed. Healthy fish (n = 1260 individuals, 17.52 ± 0.20 g) were raised in twelve fiberglass tanks. Triplicate fish groups with stocking densities of 60, 90, 120, or 150 fish per 1 m3 were designed, further referred to as SD60, SD90, SD120, and SD150 groups. Fish feeding was done using a commercially purchased well-balanced diet three times per day with a feeding rate of 3% of the wet fish weight. Results revealed that un-ionized ammonia, nitrite, and pH were significantly elevated, and dissolved oxygen levels were decreased significantly with increasing the stocking densities. The survival rates and growth significantly decreased with increasing fish stocking densities. The intestinal lipase, protease, trypsin, and amylase enzymes decreased significantly (P < 0.05) along with increased stocking densities. Moreover, significant decreases were noticed in total protein, lysozyme activity, and globulin levels when the stocking density was higher than 60 fish/m3. Conversely, serum stress biomarkers (such as blood glucose and cortisol), transaminases, alkaline phosphatase, and blood urea nitrogen were significantly elevated with increasing stocking densities. Hepatic CAT, SOD, and T-AOC were decreased; meanwhile, hepatic MDA levels were significantly increased, together with the stocking rates. In the end, we found that the SD150 group recorded the lowest growth rates, immune responses, and antioxidant capacity and the highest stress markers as blood glucose and cortisol. In this context, we can conclude that the stocking 60 fish/m3 resulted in better growth, survival, immunity, antioxidant status, and overall performances of striped catfish. Graphical Abstract: [Figure not available: see fulltext.]