Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Impact of COVID‐19 in cognitively unimpaired individuals and dementia caregivers from the Peruvian Alzheimer Disease Initiative (PeADI)

Abstract Background The COVID‐19 pandemic has profoundly affected people’s lives worldwide. Stress and social restriction have a negative physical and psychological effect on people with dementia and their caregivers. Peru was one of the countries that experienced social restrictions and high rates of COVID‐19 morbidity and mortality. Methods We assessed the NIA‐NIH COVID‐19 impact survey for unrelated cognitively unimpaired (CU) individuals and caregivers from the PeADI cohort (case‐control genetic study for Alzheimer’s disease and related dementias) from five different regions across Peru. Results We analyzed 249 COVID‐19 impact surveys,65 dementia patient caregivers and 184 older CU individuals. Among caregivers, 86% felt isolated and 55.3% less connected with friends and family. 87.6% felt disrupted in everyday life, and 83% could not control the important things in their life. 44.6% found more difficult to provide care. The limitations on care include:physician appointments 64.6%,respite by family or friends 36.9%,day activity programs 32.35%, and overnight or extended‐stay respite care 16.9%. About 61.5% of them significantly reduced their household income. Almost 51% negatively changed their willingness to participate in clinical research if it required in‐person visits. Among the 184 CU individuals (mean age: 69.5± 3.8 years; 58.2% women). About 40.2% had new or worsening symptoms while thinking they had COVID‐19.About 60% were tested for Covid‐19 at least once, 29.3% were diagnosed with COVID‐19, and 2.1% were hospitalized. About 70% felt worried about getting or being reinfected by COVID‐19, 68.5% felt isolated from family and friends, 84.2% felt disrupted daily life, and 68.4% felt unable to control the important things in their life. About 60% had significantly reduced household income.About 52% of the CU noticed health changes (memory and thinking 31.2%, depression 42.7%, anxiety 51%, or behavior 46.8%).About 58% changed their willingness to participate in clinical research if it required in‐person visits. Conclusions Our results suggest that the COVID‐19 pandemic has affected dementia patient caregivers and CU individuals, both experienced variable changes in their mental health and significantly reduced household income.Caregivers have significant concerns regarding limited access to healthcare for their patients.CU individuals experienced fear of COVID‐19 reinfection.Further longitudinal surveys are required to explore changes in neuropsychiatric symptoms over time

The Peruvian Alzheimer Disease Initiative (PeADI): An international effort model to increase diversity in AD research

Background Peru is one of the five largest countries in Latin America and harboring a high Amerindian ancestry component in this population. The Latin American population, including Peruvians, are underrepresented in research studies of Alzheimer disease (AD).We have developed an international collaborative research initiative to ascertain a Peruvian cohort for AD and other related dementias for genetic studies of Amerindian individuals. Methods The Peruvian Alzheimer Disease initiative (PeADI) was developed to recruit and enroll Peruvian adults aged 65 and older to a comprehensive genetic AD study. Individuals will get whole genome sequencing and plasma biomarkers. Participants included cases with AD and ADD,healthy controls as well as multiplex AD families. Since 2019, we have established a multisource ascertainment approach including recruitment at main hospitals, outreach community activities and more recently due to the COVID19 pandemic remote recruitment and home visits. Our recruitment has expanded since our initial efforts in which we enrolled individuals from Lima, the capital city. We are now ascertaining participants in three regions from the Andes highlands (Puno,Huancayo, and Cusco) and one region from the southern coast (Tacna).All participants are enrolled using a standard protocol administered by neurologists and neuropsychologists. This protocol includes clinical interviews and neurocognitive assessment. Results As of December 2021, we have enrolled 103 AD and other dementia cases, 202 controls and 4 multiplex AD families. While the majority of participants are from Lima, 25% controls and 1% of cases have been recruited in regions outside Lima. We have confirmed a significant association between APOE and AD in Peruvian Population higher than we have observed in non‐Hispanics. In addition to ascertainment activities, we are working closely with the respective sites to develop a network for AD research across Peru. To date, we have developed local research capacities within each region,including training opportunities for investigators, coordinators and lab technicians. In addition, we are developing resources for health and medical support and basic equipment for all regions. Conclusion The PeADI study shows the importance of equitable international north‐south cooperation and local network cooperation to increase representation of understudied admixed populations to help us understand Amerindian ancestry in drug target discovery

A new risk locus on chromosome 1 is suggested by genome‐wide association study in Peruvians for Alzheimer disease

Abstract Background Increasing ethnic/ancestral diversity in genetic studies is critical for defining the genetic architecture of Alzheimer disease (AD). Amerindian (AI) populations are substantially underrepresented in AD genetic studies. The Peruvian (PE) population, with up to ∼80% of AI ancestry, provides a unique opportunity to assess the role of AI ancestry in AD. We performed the first genome‐wide association study (GWAS) in the PE population to identify novel AD susceptibility loci and characterize known AD genetic risk loci. Method The PE dataset includes array‐genotype and phenotype data from 542 individuals (189 cases; 353 controls), imputed to the NHLBI TOPMedv5 haplotype reference panel. We used a generalized linear mixed‐model (SAIGE software) for the GWAS analysis. We analyzed two separate models; the first model accounted for sex, age, and population substructure, while the second model also included the dosage of APOEe4. In both models, we included a genetic relationship matrix as a random effect to account for any potential relatedness. To determine if the associations are specific to specific ancestries, we employed ancestry‐aware approaches using the RFMix software. Result APOE was significantly associated with AD with an effect size comparable to that found in non‐Hispanic white (NHW) populations (OR = 3.3(2.2‐4.8),pv = 8.0×10 −10 ). Two additional known AD loci, TREML2 (pv = 0.008) and CLU (pv = 0.012), showed nominal significance Variants at three additional loci reached suggestive significance (pv<1×10 −6 ): NFASC (pv = 9.4×10 −8 ;chromosome 1), STK32A (pv = 9.3×10 −7 ; chromosome 5), and LOC100132830 (pv = 6.7×10 −7 ;chromosome 6). The NFASC locus neared genome‐wide significance in the APOE adjusted model (pv = 6.7×10 −8 ). The haplotypes associated with AD at the NFASC locus were found to be of European origin. Additionally, the STK32A locus was found to have a protective effect specifically among individuals of AI background. We did not observe significant heterogeneity of effect at the APOE and LOC100132830 loci across different ancestral backgrounds. Conclusion PE GWAS identified a novel, promising AD susceptibility locus in the NFASC gene of European origin. We also detected a potential protective effect in the STK32A locus on AI background, emphasizing the importance of incorporating ancestry‐aware approaches in gene discovery in admixed populations