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

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 middle-income 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 low-income 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 low-income, 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

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

Burden of hypertension and associated risks for cardiovascular mortality in Cuba: a prospective cohort study

Background In Cuba, hypertension control in primary care has been prioritised as a cost-effective means of addressing premature death from cardiovascular disease (CVD). However, there is little large-scale evidence on the prevalence and management of hypertension in Cuba, and no direct evidence on the expected benefit of such efforts on CVD mortality. Methods Between Jan 1, 1996, and Nov 24, 2002, 146,556 men and women in Cuba were interviewed, measured and followed up for certified causes of death to Jan 1, 2017; 24,345 participants were resurveyed between Jul 14, 2006, and Oct 19, 2008. We calculated the prevalence of hypertension at recruitment (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or receiving treatment for hypertension) and the proportion of hypertensives who were diagnosed, treated and controlled (systolic Findings After exclusion of those with incomplete data, there were 136 111 participants aged 35-79 at recruitment (mean age 54 [SD 12] and 75 947 [56%] women). Overall, one-third of these participants were hypertensive (34%). Of those with hypertension, two-thirds were diagnosed (67%); of those diagnosed, three-quarters were treated (76%); and, of those treated, about one-third had controlled blood pressure (36%). During 1.7 million person-years of follow-up, there were 5707 CVD deaths. Uncontrolled hypertension at baseline was associated with RRs of 2.15 (95%CI 1.88-2.46), 1.86 (1.69-2.05) and 1.41 (1.32-1.52) at ages 35-59, 60-69 and 70-79, respectively, and accounted for ~20% of premature CVD deaths. Interpretation In this Cuban population, one-third had hypertension. The proportion of hypertensives that were diagnosed and treated was high, and commensurate with some high-income countries. However, the proportion of treated hypertensives with controlled blood pressure was low. In addition to measures to reduce hypertension prevalence, public health programs should address the need for improved blood pressure control among treated hypertensives in Cuba.</p

Burden of hypertension and associated risks for cardiovascular mortality in Cuba: a prospective cohort study

Background In Cuba, hypertension control in primary care has been prioritised as a cost-effective means of addressing premature death from cardiovascular disease (CVD). However, there is little large-scale evidence on the prevalence and management of hypertension in Cuba, and no direct evidence on the expected benefit of such efforts on CVD mortality. Methods Between Jan 1, 1996, and Nov 24, 2002, 146,556 men and women in Cuba were interviewed, measured and followed up for certified causes of death to Jan 1, 2017; 24,345 participants were resurveyed between Jul 14, 2006, and Oct 19, 2008. We calculated the prevalence of hypertension at recruitment (systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or receiving treatment for hypertension) and the proportion of hypertensives who were diagnosed, treated and controlled (systolic &lt;140 mmHg and diastolic &lt;90 mmHg). Cox regressions relate CVD mortality rate ratios (RRs) at ages 35-79 among participants with, versus those without, uncontrolled hypertension. RRs were used to estimate the fraction of CVD deaths attributable to hypertension. Findings After exclusion of those with incomplete data, there were 136 111 participants aged 35-79 at recruitment (mean age 54 [SD 12] and 75 947 [56%] women). Overall, one-third of these participants were hypertensive (34%). Of those with hypertension, two-thirds were diagnosed (67%); of those diagnosed, three-quarters were treated (76%); and, of those treated, about one-third had controlled blood pressure (36%). During 1.7 million person-years of follow-up, there were 5707 CVD deaths. Uncontrolled hypertension at baseline was associated with RRs of 2.15 (95%CI 1.88-2.46), 1.86 (1.69-2.05) and 1.41 (1.32-1.52) at ages 35-59, 60-69 and 70-79, respectively, and accounted for ~20% of premature CVD deaths. Interpretation In this Cuban population, one-third had hypertension. The proportion of hypertensives that were diagnosed and treated was high, and commensurate with some high-income countries. However, the proportion of treated hypertensives with controlled blood pressure was low. In addition to measures to reduce hypertension prevalence, public health programs should address the need for improved blood pressure control among treated hypertensives in Cuba.</p

Alcohol consumption and cause-specific mortality in Cuba: prospective study of 120 623 adults

Background The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba. Methods In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35–79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08. Findings After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (<1 bottle/week), but this association was almost completely attenuated on exclusion of early follow-up. Interpretation In this large prospective study in Cuba, weekly alcohol consumption was continuously related to premature mortality. Reverse causality is likely to account for much of the apparent excess risk among non-drinkers. The findings support limits to alcohol consumption that are lower than present recommendations in Cuba. Funding Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen)

Isoenzymatic variability among five Anopheles species belonging to the Nyssorhynchus and Anopheles subgenera of the Amazon region, Brazil

An isoenzymatic comparative analysis of the variability and genetics differentiation among Anopheles species was done in populations of An. (Nys.) intermedius and An. (Ano.) mattogrossensis of the Anopheles subgenus, and of An. darlingi, An. albitarsis and An. triannulatus of the Nyssorhynchus subgenus, with the aim of detecting differences between both subgenera and of estimating the degree of genetic intere specific divergence. Samples from Macapá, State of Amapá and Janauari Lake, near Manaus, State of Amazonas, were analyzed for eight isoenzymatic loci. Analysis revealed differences in the average number of alleles per locus (1.6-2.3) and heterozygosity (0.060-0.284). However, the proportion of polymorphic loci was the same for An. (Nys.) darlingi, An. (Nys.) triannulatus and An. (Ano.) mattogrossensis (50%), but differed for An. (Nys.) albitarsis (62.5%) and An. (Ano.) intermedius (25%). Only the IDH1 (P > 0.5) locus in all species studied was in Hardy-Weinberg equilibrium. The fixation index demonstrated elevated genetic structuring among species, based on values of Fst = 0.644 and genetic distance (0.344-0.989). Genetic difference was higher between An. (Nys.) triannulatus and An. (Ano.) intermedius (0.989) and smaller between An. (Nys.) albitarsis sensu lato and An. (Nys.) darlingi (0.344). The data show interspecific genetic divergence which differs from the phylogenetic hypothesis based on morphological characters