Showing papers in "PLOS Medicine in 2020"

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis.

Abstract: BACKGROUND There is disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a living systematic review and meta-analysis to address three questions: (1) Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? (3) What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection or presymptomatic? METHODS AND FINDINGS We searched PubMed, Embase, bioRxiv, and medRxiv using a database of SARS-CoV-2 literature that is updated daily, on 25 March 2020, 20 April 2020, and 10 June 2020. Studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up or modelling studies were included. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with an adapted checklist for case series, and the relevance and credibility of modelling studies were assessed using a published checklist. We included a total of 94 studies. The overall estimate of the proportion of people who become infected with SARS-CoV-2 and remain asymptomatic throughout infection was 20% (95% confidence interval [CI] 17-25) with a prediction interval of 3%-67% in 79 studies that addressed this review question. There was some evidence that biases in the selection of participants influence the estimate. In seven studies of defined populations screened for SARS-CoV-2 and then followed, 31% (95% CI 26%-37%, prediction interval 24%-38%) remained asymptomatic. The proportion of people that is presymptomatic could not be summarised, owing to heterogeneity. The secondary attack rate was lower in contacts of people with asymptomatic infection than those with symptomatic infection (relative risk 0.35, 95% CI 0.10-1.27). Modelling studies fit to data found a higher proportion of all SARS-CoV-2 infections resulting from transmission from presymptomatic individuals than from asymptomatic individuals. Limitations of the review include that most included studies were not designed to estimate the proportion of asymptomatic SARS-CoV-2 infections and were at risk of selection biases; we did not consider the possible impact of false negative RT-PCR results, which would underestimate the proportion of asymptomatic infections; and the database does not include all sources. CONCLUSIONS The findings of this living systematic review suggest that most people who become infected with SARS-CoV-2 will not remain asymptomatic throughout the course of the infection. The contribution of presymptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention measures, with enhanced hand hygiene, masks, testing tracing, and isolation strategies and social distancing, will continue to be needed.

CINeMA: An approach for assessing confidence in the results of a network meta-analysis.

Abstract: BACKGROUND The evaluation of the credibility of results from a meta-analysis has become an important part of the evidence synthesis process. We present a methodological framework to evaluate confidence in the results from network meta-analyses, Confidence in Network Meta-Analysis (CINeMA), when multiple interventions are compared. METHODOLOGY CINeMA considers 6 domains: (i) within-study bias, (ii) reporting bias, (iii) indirectness, (iv) imprecision, (v) heterogeneity, and (vi) incoherence. Key to judgments about within-study bias and indirectness is the percentage contribution matrix, which shows how much information each study contributes to the results from network meta-analysis. The contribution matrix can easily be computed using a freely available web application. In evaluating imprecision, heterogeneity, and incoherence, we consider the impact of these components of variability in forming clinical decisions. CONCLUSIONS Via 3 examples, we show that CINeMA improves transparency and avoids the selective use of evidence when forming judgments, thus limiting subjectivity in the process. CINeMA is easy to apply even in large and complicated networks.

Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis

Abstract: Background Circulating lipoprotein lipids cause coronary heart disease (CHD). However, the precise way in which one or more lipoprotein lipid-related entities account for this relationship remains unclear. Using genetic instruments for lipoprotein lipid traits implemented through multivariable Mendelian randomisation (MR), we sought to compare their causal roles in the aetiology of CHD. Methods and findings We conducted a genome-wide association study (GWAS) of circulating non-fasted lipoprotein lipid traits in the UK Biobank (UKBB) for low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoprotein B to identify lipid-associated single nucleotide polymorphisms (SNPs). Using data from CARDIoGRAMplusC4D for CHD (consisting of 60,801 cases and 123,504 controls), we performed univariable and multivariable MR analyses. Similar GWAS and MR analyses were conducted for high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. The GWAS of lipids and apolipoproteins in the UKBB included between 393,193 and 441,016 individuals in whom the mean age was 56.9 y (range 39–73 y) and of whom 54.2% were women. The mean (standard deviation) lipid concentrations were LDL cholesterol 3.57 (0.87) mmol/L and HDL cholesterol 1.45 (0.38) mmol/L, and the median triglycerides was 1.50 (IQR = 1.11) mmol/L. The mean (standard deviation) values for apolipoproteins B and A-I were 1.03 (0.24) g/L and 1.54 (0.27) g/L, respectively. The GWAS identified multiple independent SNPs associated at P < 5 × 10−8 for LDL cholesterol (220), apolipoprotein B (n = 255), triglycerides (440), HDL cholesterol (534), and apolipoprotein A-I (440). Between 56%–93% of SNPs identified for each lipid trait had not been previously reported in large-scale GWASs. Almost half (46%) of these SNPs were associated at P < 5 × 10−8 with more than one lipid-related trait. Assessed individually using MR, LDL cholesterol (odds ratio [OR] 1.66 per 1-standard-deviation–higher trait; 95% CI: 1.49–1.86; P < 0.001), triglycerides (OR 1.34; 95% CI: 1.25–1.44; P < 0.001) and apolipoprotein B (OR 1.73; 95% CI: 1.56–1.91; P < 0.001) had effect estimates consistent with a higher risk of CHD. In multivariable MR, only apolipoprotein B (OR 1.92; 95% CI: 1.31–2.81; P < 0.001) retained a robust effect, with the estimate for LDL cholesterol (OR 0.85; 95% CI: 0.57–1.27; P = 0.44) reversing and that of triglycerides (OR 1.12; 95% CI: 1.02–1.23; P = 0.01) becoming weaker. Individual MR analyses showed a 1-standard-deviation–higher HDL cholesterol (OR 0.80; 95% CI: 0.75–0.86; P < 0.001) and apolipoprotein A-I (OR 0.83; 95% CI: 0.77–0.89; P < 0.001) to lower the risk of CHD, but these effect estimates attenuated substantially to the null on accounting for apolipoprotein B. A limitation is that, owing to the nature of lipoprotein metabolism, measures related to the composition of lipoprotein particles are highly correlated, creating a challenge in making exclusive interpretations on causation of individual components. Conclusions These findings suggest that apolipoprotein B is the predominant trait that accounts for the aetiological relationship of lipoprotein lipids with risk of CHD.

Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: A federated electronic medical record analysis.

Abstract: Background At the beginning of June 2020, there were nearly 7 million reported cases of coronavirus disease 2019 (COVID-19) worldwide and over 400,000 deaths in people with COVID-19. The objective of this study was to determine associations between comorbidities listed in the Charlson comorbidity index and mortality among patients in the United States with COVID-19. Methods and findings A retrospective cohort study of adults with COVID-19 from 24 healthcare organizations in the US was conducted. The study included adults aged 18–90 years with COVID-19 coded in their electronic medical records between January 20, 2020, and May 26, 2020. Results were also stratified by age groups (<50 years, 50–69 years, or 70–90 years). A total of 31,461 patients were included. Median age was 50 years (interquartile range [IQR], 35–63) and 54.5% (n = 17,155) were female. The most common comorbidities listed in the Charlson comorbidity index were chronic pulmonary disease (17.5%, n = 5,513) and diabetes mellitus (15.0%, n = 4,710). Multivariate logistic regression analyses showed older age (odds ratio [OR] per year 1.06; 95% confidence interval [CI] 1.06–1.07; p < 0.001), male sex (OR 1.75; 95% CI 1.55–1.98; p < 0.001), being black or African American compared to white (OR 1.50; 95% CI 1.31–1.71; p < 0.001), myocardial infarction (OR 1.97; 95% CI 1.64–2.35; p < 0.001), congestive heart failure (OR 1.42; 95% CI 1.21–1.67; p < 0.001), dementia (OR 1.29; 95% CI 1.07–1.56; p = 0.008), chronic pulmonary disease (OR 1.24; 95% CI 1.08–1.43; p = 0.003), mild liver disease (OR 1.26; 95% CI 1.00–1.59; p = 0.046), moderate/severe liver disease (OR 2.62; 95% CI 1.53–4.47; p < 0.001), renal disease (OR 2.13; 95% CI 1.84–2.46; p < 0.001), and metastatic solid tumor (OR 1.70; 95% CI 1.19–2.43; p = 0.004) were associated with higher odds of mortality with COVID-19. Older age, male sex, and being black or African American (compared to being white) remained significantly associated with higher odds of death in age-stratified analyses. There were differences in which comorbidities were significantly associated with mortality between age groups. Limitations include that the data were collected from the healthcare organization electronic medical record databases and some comorbidities may be underreported and ethnicity was unknown for 24% of participants. Deaths during an inpatient or outpatient visit at the participating healthcare organizations were recorded; however, deaths occurring outside of the hospital setting are not well captured. Conclusions Identifying patient characteristics and conditions associated with mortality with COVID-19 is important for hypothesis generating for clinical trials and to develop targeted intervention strategies.

The global burden of disease attributable to high body mass index in 195 countries and territories, 1990-2017: An analysis of the Global Burden of Disease Study

Abstract: Background Obesity represents an urgent problem that needs to be properly addressed, especially among children. Public and global health policy- and decision-makers need timely, reliable quantitative information to develop effective interventions aimed at counteracting the burden generated by high body mass index (BMI). Few studies have assessed the high-BMI-related burden on a global scale. Methods and findings Following the methodology framework and analytical strategies used in the Global Burden of Disease Study (GBD) 2017, the global deaths and disability-adjusted life years (DALYs) attributable to high BMI were analyzed by age, sex, year, and geographical location and by Socio-demographic Index (SDI). All causes of death and DALYs estimated in GBD 2017 were organized into 4 hierarchical levels: level 1 contained 3 broad cause groupings, level 2 included more specific categories within the level 1 groupings, level 3 comprised more detailed causes within the level 2 categories, and level 4 included sub-causes of some level 3 causes. From 1990 to 2017, the global deaths and DALYs attributable to high BMI have more than doubled for both females and males. However, during the study period, the age-standardized rate of high-BMI-related deaths remained stable for females and only increased by 14.5% for males, and the age-standardized rate of high-BMI-related DALYs only increased by 12.7% for females and 26.8% for males. In 2017, the 6 leading GBD level 3 causes of high-BMI-related DALYs were ischemic heart disease, stroke, diabetes mellitus, chronic kidney disease, hypertensive heart disease, and low back pain. For most GBD level 3 causes of high-BMI-related DALYs, high-income North America had the highest attributable proportions of age-standardized DALYs due to high BMI among the 21 GBD regions in both sexes, whereas the lowest attributable proportions were observed in high-income Asia Pacific for females and in eastern sub-Saharan Africa for males. The association between SDI and high-BMI-related DALYs suggested that the lowest age-standardized DALY rates were found in countries in the low-SDI quintile and high-SDI quintile in 2017, and from 1990 to 2017, the age-standardized DALY rates tended to increase in regions with the lowest SDI, but declined in regions with the highest SDI, with the exception of high-income North America. The study's main limitations included the use of information collected from some self-reported data, the employment of cutoff values that may not be adequate for all populations and groups at risk, and the use of a metric that cannot distinguish between lean and fat mass. Conclusions In this study, we observed that the number of global deaths and DALYs attributable to high BMI has substantially increased between 1990 and 2017. Successful population-wide initiatives targeting high BMI may mitigate the burden of a wide range of diseases. Given the large variations in high-BMI-related burden of disease by SDI, future strategies to prevent and reduce the burden should be developed and implemented based on country-specific development status.

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.

Abstract: BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.

The prevalence of mental illness in refugees and asylum seekers: A systematic review and meta-analysis

Abstract: Background Globally, the number of refugees and asylum seekers has reached record highs. Past research in refugee mental health has reported wide variation in mental illness prevalence data, partially attributable to methodological limitations. This systematic review aims to summarise the current body of evidence for the prevalence of mental illness in global refugee populations and overcome methodological limitations of individual studies. Methods and findings A comprehensive search of electronic databases was undertaken from 1 January 2003 to 4 February 2020 (MEDLINE, MEDLINE In-Process, EBM Reviews, Embase, PsycINFO, CINAHL, PILOTS, Web of Science). Quantitative studies were included if diagnosis of mental illness involved a clinical interview and use of a validated assessment measure and reported at least 50 participants. Study quality was assessed using a descriptive approach based on a template according to study design (modified Newcastle-Ottawa Scale). Random-effects models, based on inverse variance weights, were conducted. Subgroup analyses were performed for sex, sample size, displacement duration, visa status, country of origin, current residence, type of interview (interpreter-assisted or native language), and diagnostic measure. The systematic review was registered with PROSPERO (CRD) 42016046349. The search yielded a result of 21,842 records. Twenty-six studies, which included one randomised controlled trial and 25 observational studies, provided results for 5,143 adult refugees and asylum seekers. Studies were undertaken across 15 countries: Australia (652 refugees), Austria (150), China (65), Germany (1,104), Italy (297), Lebanon (646), Nepal (574), Norway (64), South Korea (200), Sweden (86), Switzerland (164), Turkey (238), Uganda (77), United Kingdom (420), and the United States of America (406). The prevalence of posttraumatic stress disorder (PTSD) was 31.46% (95% CI 24.43–38.5), the prevalence of depression was 31.5% (95% CI 22.64–40.38), the prevalence of anxiety disorders was 11% (95% CI 6.75–15.43), and the prevalence of psychosis was 1.51% (95% CI 0.63–2.40). A limitation of the study is that substantial heterogeneity was present in the prevalence estimates of PTSD, depression, and anxiety, and limited covariates were reported in the included studies. Conclusions This comprehensive review generates current prevalence estimates for not only PTSD but also depression, anxiety, and psychosis. Refugees and asylum seekers have high and persistent rates of PTSD and depression, and the results of this review highlight the need for ongoing, long-term mental health care beyond the initial period of resettlement.

An evaluation of Chile's Law of Food Labeling and Advertising on sugar-sweetened beverage purchases from 2015 to 2017: A before-and-after study.

Abstract: Bloomberg Philanthropies International Development Research Center 108180 107731 Population Research Infrastructure Program P2C HD050924

Impact of self-imposed prevention measures and short-term government-imposed social distancing on mitigating and delaying a COVID-19 epidemic: A modelling study.

Abstract: Background The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every country in the world since it first emerged in China in December 2019. Many countries have implemented social distancing as a measure to "flatten the curve" of the ongoing epidemics. Evaluation of the impact of government-imposed social distancing and of other measures to control further spread of COVID-19 is urgent, especially because of the large societal and economic impact of the former. The aim of this study was to compare the individual and combined effectiveness of self-imposed prevention measures and of short-term government-imposed social distancing in mitigating, delaying, or preventing a COVID-19 epidemic. Methods and findings We developed a deterministic compartmental transmission model of SARS-CoV-2 in a population stratified by disease status (susceptible, exposed, infectious with mild or severe disease, diagnosed, and recovered) and disease awareness status (aware and unaware) due to the spread of COVID-19. Self-imposed measures were assumed to be taken by disease-aware individuals and included handwashing, mask-wearing, and social distancing. Government-imposed social distancing reduced the contact rate of individuals irrespective of their disease or awareness status. The model was parameterized using current best estimates of key epidemiological parameters from COVID-19 clinical studies. The model outcomes included the peak number of diagnoses, attack rate, and time until the peak number of diagnoses. For fast awareness spread in the population, self-imposed measures can significantly reduce the attack rate and diminish and postpone the peak number of diagnoses. We estimate that a large epidemic can be prevented if the efficacy of these measures exceeds 50%. For slow awareness spread, self-imposed measures reduce the peak number of diagnoses and attack rate but do not affect the timing of the peak. Early implementation of short-term government-imposed social distancing alone is estimated to delay (by at most 7 months for a 3-month intervention) but not to reduce the peak. The delay can be even longer and the height of the peak can be additionally reduced if this intervention is combined with self-imposed measures that are continued after government-imposed social distancing has been lifted. Our analyses are limited in that they do not account for stochasticity, demographics, heterogeneities in contact patterns or mixing, spatial effects, imperfect isolation of individuals with severe disease, and reinfection with COVID-19. Conclusions Our results suggest that information dissemination about COVID-19, which causes individual adoption of handwashing, mask-wearing, and social distancing, can be an effective strategy to mitigate and delay the epidemic. Early initiated short-term government-imposed social distancing can buy time for healthcare systems to prepare for an increasing COVID-19 burden. We stress the importance of disease awareness in controlling the ongoing epidemic and recommend that, in addition to policies on social distancing, governments and public health institutions mobilize people to adopt self-imposed measures with proven efficacy in order to successfully tackle COVID-19.

Dietary fibre and whole grains in diabetes management: Systematic review and meta-analyses.

Abstract: Background Fibre is promoted as part of a healthy dietary pattern and in diabetes management. We have considered the role of high-fibre diets on mortality and increasing fibre intake on glycaemic control and other cardiometabolic risk factors of adults with prediabetes or diabetes. Methods and findings We conducted a systematic review of published literature to identify prospective studies or controlled trials that have examined the effects of a higher fibre intake without additional dietary or other lifestyle modification in adults with prediabetes, gestational diabetes, type 1 diabetes, and type 2 diabetes. Meta-analyses were undertaken to determine the effects of higher fibre intake on all-cause and cardiovascular mortality and increasing fibre intake on glycaemic control and a range of cardiometabolic risk factors. For trials, meta regression analyses identified further variables that influenced the pooled findings. Dose response testing was undertaken; Grading of Recommendations Assessment, Development and Evaluation (GRADE) protocols were followed to assess the quality of evidence. Two multicountry cohorts of 8,300 adults with type 1 or type 2 diabetes followed on average for 8.8 years and 42 trials including 1,789 adults with prediabetes, type 1, or type 2 diabetes were identified. Prospective cohort data indicate an absolute reduction of 14 fewer deaths (95% confidence interval (CI) 4-19) per 1,000 participants over the study duration, when comparing a daily dietary fibre intake of 35 g with the average intake of 19 g, with a clear dose response relationship apparent. Increased fibre intakes reduced glycated haemoglobin (HbA1c; mean difference [MD] -2.00 mmol/mol, 95% CI -3.30 to -0.71 from 33 trials), fasting plasma glucose (MD -0.56 mmol/L, 95% CI -0.73 to -0.38 from 34 trials), insulin (standardised mean difference [SMD] -2.03, 95% CI -2.92 to -1.13 from 19 trials), homeostatic model assessment of insulin resistance (HOMA IR; MD -1.24 mg/dL, 95% CI -1.72 to -0.76 from 9 trials), total cholesterol (MD -0.34 mmol/L, 95% CI -0.46 to -0.22 from 27 trials), low-density lipoprotein (LDL) cholesterol (MD -0.17 mmol/L, 95% CI -0.27 to -0.08 from 21 trials), triglycerides (MD -0.16 mmol/L, 95% CI -0.23 to -0.09 from 28 trials), body weight (MD -0.56 kg, 95% CI -0.98 to -0.13 from 18 trials), Body Mass Index (BMI; MD -0.36, 95% CI -0·55 to -0·16 from 14 trials), and C-reactive protein (SMD -2.80, 95% CI -4.52 to -1.09 from 7 trials) when compared with lower fibre diets. All trial analyses were subject to high heterogeneity. Key variables beyond increasing fibre intake were the fibre intake at baseline, the global region where the trials were conducted, and participant inclusion criteria other than diabetes type. Potential limitations were the lack of prospective cohort data in non-European countries and the lack of long-term (12 months or greater) controlled trials of increasing fibre intakes in adults with diabetes. Conclusions Higher-fibre diets are an important component of diabetes management, resulting in improvements in measures of glycaemic control, blood lipids, body weight, and inflammation, as well as a reduction in premature mortality. These benefits were not confined to any fibre type or to any type of diabetes and were apparent across the range of intakes, although greater improvements in glycaemic control were observed for those moving from low to moderate or high intakes. Based on these findings, increasing daily fibre intake by 15 g or to 35 g might be a reasonable target that would be expected to reduce risk of premature mortality in adults with diabetes.

Correction: Variation in racial/ethnic disparities in COVID-19 mortality by age in the United States: A cross-sectional study

Abstract: Background In the United States, non-Hispanic Black (NHB), Hispanic, and non-Hispanic American Indian/Alaska Native (NHAIAN) populations experience excess COVID-19 mortality, compared to the non-Hispanic White (NHW) population, but racial/ethnic differences in age at death are not known. The release of national COVID-19 death data by racial/ethnic group now permits analysis of age-specific mortality rates for these groups and the non-Hispanic Asian or Pacific Islander (NHAPI) population. Our objectives were to examine variation in age-specific COVID-19 mortality rates by racial/ethnicity and to calculate the impact of this mortality using years of potential life lost (YPLL). Methods and findings This cross-sectional study used the recently publicly available data on US COVID-19 deaths with reported race/ethnicity, for the time period February 1, 2020, to July 22, 2020. Population data were drawn from the US Census. As of July 22, 2020, the number of COVID-19 deaths equaled 68,377 for NHW, 29,476 for NHB, 23,256 for Hispanic, 1,143 for NHAIAN, and 6,468 for NHAPI populations; the corresponding population sizes were 186.4 million, 40.6 million, 2.6 million, 19.5 million, and 57.7 million. Age-standardized rate ratios relative to NHW were 3.6 (95% CI 3.5, 3.8; p < 0.001) for NHB, 2.8 (95% CI 2.7, 3.0; p < 0.001) for Hispanic, 2.2 (95% CI 1.8, 2.6; p < 0.001) for NHAIAN, and 1.6 (95% CI 1.4, 1.7; p < 0.001) for NHAP populations. By contrast, NHB rate ratios relative to NHW were 7.1 (95% CI 5.8, 8.7; p < 0.001) for persons aged 25–34 years, 9.0 (95% CI 7.9, 10.2; p < 0.001) for persons aged 35–44 years, and 7.4 (95% CI 6.9, 7.9; p < 0.001) for persons aged 45–54 years. Even at older ages, NHB rate ratios were between 2.0 and 5.7. Similarly, rate ratios for the Hispanic versus NHW population were 7.0 (95% CI 5.8, 8.7; p < 0.001), 8.8 (95% CI 7.8, 9.9; p < 0.001), and 7.0 (95% CI 6.6, 7.5; p < 0.001) for the corresponding age strata above, with remaining rate ratios ranging from 1.4 to 5.0. Rate ratios for NHAIAN were similarly high through age 74 years. Among NHAPI persons, rate ratios ranged from 2.0 to 2.8 for persons aged 25–74 years and were 1.6 and 1.2 for persons aged 75–84 and 85+ years, respectively. As a consequence, more YPLL before age 65 were experienced by the NHB and Hispanic populations than the NHW population—despite the fact that the NHW population is larger—with a ratio of 4.6:1 and 3.2:1, respectively, for NHB and Hispanic persons. Study limitations include likely lag time in receipt of completed death certificates received by the Centers for Disease Control and Prevention for transmission to NCHS, with consequent lag in capturing the total number of deaths compared to data reported on state dashboards. Conclusions In this study, we observed racial variation in age-specific mortality rates not fully captured with examination of age-standardized rates alone. These findings suggest the importance of examining age-specific mortality rates and underscores how age standardization can obscure extreme variations within age strata. To avoid overlooking such variation, data that permit age-specific analyses should be routinely publicly available.

Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies.

Abstract: Background Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. Methods and findings We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83–2.76, p 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12–1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome. Conclusions In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease. Trial registration PROSPERO CRD42018115459.

Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial

Abstract: Background There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity. Methods and findings FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild–moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus −3% ± 32% in placebo group, mean difference 9%, 95% CI −5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI −0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference −0.1 kg, 95% CI −1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI −0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention. Conclusions Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study. Trial registration ClinicalTrials.gov NCT02530385.

Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis.

Abstract: Background Numerous clinical trials and observational studies have investigated various pharmacological agents as potential treatment for Coronavirus Disease 2019 (COVID-19), but the results are heterogeneous and sometimes even contradictory to one another, making it difficult for clinicians to determine which treatments are truly effective. Methods and findings We carried out a systematic review and network meta-analysis (NMA) to systematically evaluate the comparative efficacy and safety of pharmacological interventions and the level of evidence behind each treatment regimen in different clinical settings. Both published and unpublished randomized controlled trials (RCTs) and confounding-adjusted observational studies which met our predefined eligibility criteria were collected. We included studies investigating the effect of pharmacological management of patients hospitalized for COVID-19 management. Mild patients who do not require hospitalization or have self-limiting disease courses were not eligible for our NMA. A total of 110 studies (40 RCTs and 70 observational studies) were included. PubMed, Google Scholar, MEDLINE, the Cochrane Library, medRxiv, SSRN, WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched from the beginning of 2020 to August 24, 2020. Studies from Asia (41 countries, 37.2%), Europe (28 countries, 25.4%), North America (24 countries, 21.8%), South America (5 countries, 4.5%), and Middle East (6 countries, 5.4%), and additional 6 multinational studies (5.4%) were included in our analyses. The outcomes of interest were mortality, progression to severe disease (severe pneumonia, admission to intensive care unit (ICU), and/or mechanical ventilation), viral clearance rate, QT prolongation, fatal cardiac complications, and noncardiac serious adverse events. Based on RCTs, the risk of progression to severe course and mortality was significantly reduced with corticosteroids (odds ratio (OR) 0.23, 95% confidence interval (CI) 0.06 to 0.86, p = 0.032, and OR 0.78, 95% CI 0.66 to 0.91, p = 0.002, respectively) and remdesivir (OR 0.29, 95% CI 0.17 to 0.50, p < 0.001, and OR 0.62, 95% CI 0.39 to 0.98, p = 0.041, respectively) compared to standard care for moderate to severe COVID-19 patients in non-ICU; corticosteroids were also shown to reduce mortality rate (OR 0.54, 95% CI 0.40 to 0.73, p < 0.001) for critically ill patients in ICU. In analyses including observational studies, interferon-alpha (OR 0.05, 95% CI 0.01 to 0.39, p = 0.004), itolizumab (OR 0.10, 95% CI 0.01 to 0.92, p = 0.042), sofosbuvir plus daclatasvir (OR 0.26, 95% CI 0.07 to 0.88, p = 0.030), anakinra (OR 0.30, 95% CI 0.11 to 0.82, p = 0.019), tocilizumab (OR 0.43, 95% CI 0.30 to 0.60, p < 0.001), and convalescent plasma (OR 0.48, 95% CI 0.24 to 0.96, p = 0.038) were associated with reduced mortality rate in non-ICU setting, while high-dose intravenous immunoglobulin (IVIG) (OR 0.13, 95% CI 0.03 to 0.49, p = 0.003), ivermectin (OR 0.15, 95% CI 0.04 to 0.57, p = 0.005), and tocilizumab (OR 0.62, 95% CI 0.42 to 0.90, p = 0.012) were associated with reduced mortality rate in critically ill patients. Convalescent plasma was the only treatment option that was associated with improved viral clearance rate at 2 weeks compared to standard care (OR 11.39, 95% CI 3.91 to 33.18, p < 0.001). The combination of hydroxychloroquine and azithromycin was shown to be associated with increased QT prolongation incidence (OR 2.01, 95% CI 1.26 to 3.20, p = 0.003) and fatal cardiac complications in cardiac-impaired populations (OR 2.23, 95% CI 1.24 to 4.00, p = 0.007). No drug was significantly associated with increased noncardiac serious adverse events compared to standard care. The quality of evidence of collective outcomes were estimated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The major limitation of the present study is the overall low level of evidence that reduces the certainty of recommendations. Besides, the risk of bias (RoB) measured by RoB2 and ROBINS-I framework for individual studies was generally low to moderate. The outcomes deducted from observational studies could not infer causality and can only imply associations. The study protocol is publicly available on PROSPERO (CRD42020186527). Conclusions In this NMA, we found that anti-inflammatory agents (corticosteroids, tocilizumab, anakinra, and IVIG), convalescent plasma, and remdesivir were associated with improved outcomes of hospitalized COVID-19 patients. Hydroxychloroquine did not provide clinical benefits while posing cardiac safety risks when combined with azithromycin, especially in the vulnerable population. Only 29% of current evidence on pharmacological management of COVID-19 is supported by moderate or high certainty and can be translated to practice and policy; the remaining 71% are of low or very low certainty and warrant further studies to establish firm conclusions.

Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: systematic review and component network meta-analysis

Abstract: Background Complex traumatic events associated with armed conflict, forcible displacement, childhood sexual abuse, and domestic violence are increasingly prevalent. People exposed to complex traumatic events are at risk of not only posttraumatic stress disorder (PTSD) but also other mental health comorbidities. Whereas evidence-based psychological and pharmacological treatments are effective for single-event PTSD, it is not known if people who have experienced complex traumatic events can benefit and tolerate these commonly available treatments. Furthermore, it is not known which components of psychological interventions are most effective for managing PTSD in this population. We performed a systematic review and component network meta-analysis to assess the effectiveness of psychological and pharmacological interventions for managing mental health problems in people exposed to complex traumatic events. Methods and findings We searched CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Published International Literature on Traumatic Stress, PsycINFO, and Science Citation Index for randomised controlled trials (RCTs) and non-RCTs of psychological and pharmacological treatments for PTSD symptoms in people exposed to complex traumatic events, published up to 25 October 2019. We adopted a nondiagnostic approach and included studies of adults who have experienced complex trauma. Complex-trauma subgroups included veterans; childhood sexual abuse; war-affected; refugees; and domestic violence. The primary outcome was reduction in PTSD symptoms. Secondary outcomes were depressive and anxiety symptoms, quality of life, sleep quality, and positive and negative affect. We included 116 studies, of which 50 were conducted in hospital settings, 24 were delivered in community settings, seven were delivered in military clinics for veterans or active military personnel, five were conducted in refugee camps, four used remote delivery via web-based or telephone platforms, four were conducted in specialist trauma clinics, two were delivered in home settings, and two were delivered in primary care clinics; clinical setting was not reported in 17 studies. Ninety-four RCTs, for a total of 6,158 participants, were included in meta-analyses across the primary and secondary outcomes; 18 RCTs for a total of 933 participants were included in the component network meta-analysis. The mean age of participants in the included RCTs was 42.6 ± 9.3 years, and 42% were male. Nine non-RCTs were included. The mean age of participants in the non-RCTs was 40.6 ± 9.4 years, and 47% were male. The average length of follow-up across all included studies at posttreatment for the primary outcome was 11.5 weeks. The pairwise meta-analysis showed that psychological interventions reduce PTSD symptoms more than inactive control (k = 46; n = 3,389; standardised mean difference [SMD] = −0.82, 95% confidence interval [CI] −1.02 to −0.63) and active control (k-9; n = 662; SMD = −0.35, 95% CI −0.56 to −0.14) at posttreatment and also compared with inactive control at 6-month follow-up (k = 10; n = 738; SMD = −0.45, 95% CI −0.82 to −0.08). Psychological interventions reduced depressive symptoms (k = 31; n = 2,075; SMD = −0.87, 95% CI −1.11 to −0.63; I2 = 82.7%, p = 0.000) and anxiety (k = 15; n = 1,395; SMD = −1.03, 95% CI −1.44 to −0.61; p = 0.000) at posttreatment compared with inactive control. Sleep quality was significantly improved at posttreatment by psychological interventions compared with inactive control (k = 3; n = 111; SMD = −1.00, 95% CI −1.49 to −0.51; p = 0.245). There were no significant differences between psychological interventions and inactive control group at posttreatment for quality of life (k = 6; n = 401; SMD = 0.33, 95% CI −0.01 to 0.66; p = 0.021). Antipsychotic medicine (k = 5; n = 364; SMD = –0.45; –0.85 to –0.05; p = 0.085) and prazosin (k = 3; n = 110; SMD = −0.52; −1.03 to −0.02; p = 0.182) were effective in reducing PTSD symptoms. Phase-based psychological interventions that included skills-based strategies along with trauma-focused strategies were the most promising interventions for emotional dysregulation and interpersonal problems. Compared with pharmacological interventions, we observed that psychological interventions were associated with greater reductions in PTSD and depression symptoms and improved sleep quality. Sensitivity analysis showed that psychological interventions were acceptable with lower dropout, even in studies rated at low risk of attrition bias. Trauma-focused psychological interventions were superior to non-trauma-focused interventions across trauma subgroups for PTSD symptoms, but effects among veterans and war-affected populations were significantly reduced. The network meta-analysis showed that multicomponent interventions that included cognitive restructuring and imaginal exposure were the most effective for reducing PTSD symptoms (k = 17; n = 1,077; mean difference = −37.95, 95% CI −60.84 to −15.16). Our use of a non-diagnostic inclusion strategy may have overlooked certain complex-trauma populations with severe and enduring mental health comorbidities. Additionally, the relative contribution of skills-based intervention components was not feasibly evaluated in the network meta-analysis. Conclusions In this systematic review and meta-analysis, we observed that trauma-focused psychological interventions are effective for managing mental health problems and comorbidities in people exposed to complex trauma. Multicomponent interventions, which can include phase-based approaches, were the most effective treatment package for managing PTSD in complex trauma. Establishing optimal ways to deliver multicomponent psychological interventions for people exposed to complex traumatic events is a research and clinical priority.

Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: A modeling study in Hubei, China, and six regions in Europe.

Abstract: Background As of 16 May 2020, more than 4.5 million cases and more than 300,000 deaths from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. Reliable estimates of mortality from SARS-CoV-2 infection are essential for understanding clinical prognosis, planning healthcare capacity, and epidemic forecasting. The case–fatality ratio (CFR), calculated from total numbers of reported cases and reported deaths, is the most commonly reported metric, but it can be a misleading measure of overall mortality. The objectives of this study were to (1) simulate the transmission dynamics of SARS-CoV-2 using publicly available surveillance data and (2) infer estimates of SARS-CoV-2 mortality adjusted for biases and examine the CFR, the symptomatic case–fatality ratio (sCFR), and the infection–fatality ratio (IFR) in different geographic locations. Method and findings We developed an age-stratified susceptible-exposed-infected-removed (SEIR) compartmental model describing the dynamics of transmission and mortality during the SARS-CoV-2 epidemic. Our model accounts for two biases: preferential ascertainment of severe cases and right-censoring of mortality. We fitted the transmission model to surveillance data from Hubei Province, China, and applied the same model to six regions in Europe: Austria, Bavaria (Germany), Baden-Wurttemberg (Germany), Lombardy (Italy), Spain, and Switzerland. In Hubei, the baseline estimates were as follows: CFR 2.4% (95% credible interval [CrI] 2.1%–2.8%), sCFR 3.7% (3.2%–4.2%), and IFR 2.9% (2.4%–3.5%). Estimated measures of mortality changed over time. Across the six locations in Europe, estimates of CFR varied widely. Estimates of sCFR and IFR, adjusted for bias, were more similar to each other but still showed some degree of heterogeneity. Estimates of IFR ranged from 0.5% (95% CrI 0.4%–0.6%) in Switzerland to 1.4% (1.1%–1.6%) in Lombardy, Italy. In all locations, mortality increased with age. Among individuals 80 years or older, estimates of the IFR suggest that the proportion of all those infected with SARS-CoV-2 who will die ranges from 20% (95% CrI 16%–26%) in Switzerland to 34% (95% CrI 28%–40%) in Spain. A limitation of the model is that count data by date of onset are required, and these are not available in all countries. Conclusions We propose a comprehensive solution to the estimation of SARS-Cov-2 mortality from surveillance data during outbreaks. The CFR is not a good predictor of overall mortality from SARS-CoV-2 and should not be used for evaluation of policy or comparison across settings. Geographic differences in IFR suggest that a single IFR should not be applied to all settings to estimate the total size of the SARS-CoV-2 epidemic in different countries. The sCFR and IFR, adjusted for right-censoring and preferential ascertainment of severe cases, are measures that can be used to improve and monitor clinical and public health strategies to reduce the deaths from SARS-CoV-2 infection.

Impact of the announcement and implementation of the UK Soft Drinks Industry Levy on sugar content, price, product size and number of available soft drinks in the UK, 2015-19: A controlled interrupted time series analysis.

Abstract: Background Dietary sugar, especially in liquid form, increases risk of dental caries, adiposity, and type 2 diabetes. The United Kingdom Soft Drinks Industry Levy (SDIL) was announced in March 2016 and implemented in April 2018 and charges manufacturers and importers at £0.24 per litre for drinks with over 8 g sugar per 100 mL (high levy category), £0.18 per litre for drinks with 5 to 8 g sugar per 100 mL (low levy category), and no charge for drinks with less than 5 g sugar per 100 mL (no levy category). Fruit juices and milk-based drinks are exempt. We measured the impact of the SDIL on price, product size, number of soft drinks on the marketplace, and the proportion of drinks over the lower levy threshold of 5 g sugar per 100 mL. Methods and findings We analysed data on a total of 209,637 observations of soft drinks over 85 time points between September 2015 and February 2019, collected from the websites of the leading supermarkets in the UK. The data set was structured as a repeat cross-sectional study. We used controlled interrupted time series to assess the impact of the SDIL on changes in level and slope for the 4 outcome variables. Equivalent models were run for potentially levy-eligible drink categories (‘intervention’ drinks) and levy-exempt fruit juices and milk-based drinks (‘control’ drinks). Observed results were compared with counterfactual scenarios based on extrapolation of pre-SDIL trends. We found that in February 2019, the proportion of intervention drinks over the lower levy sugar threshold had fallen by 33.8 percentage points (95% CI: 33.3–34.4, p < 0.001). The price of intervention drinks in the high levy category had risen by £0.075 (£0.037–0.115, p < 0.001) per litre—a 31% pass through rate—whilst prices of intervention drinks in the low levy category and no levy category had fallen and risen by smaller amounts, respectively. Whilst the product size of branded high levy and low levy drinks barely changed after implementation of the SDIL (−7 mL [−23 to 11 mL] and 16 mL [6–27ml], respectively), there were large changes to product size of own-brand drinks with an increase of 172 mL (133–214 mL) for high levy drinks and a decrease of 141 mL (111–170 mL) for low levy drinks. The number of available drinks that were in the high levy category when the SDIL was announced was reduced by 3 (−6 to 12) by the implementation of the SDIL. Equivalent models for control drinks provided little evidence of impact of the SDIL. These results are not sales weighted, so do not give an account of how sugar consumption from drinks may have changed over the time period. Conclusions The results suggest that the SDIL incentivised many manufacturers to reduce sugar in soft drinks. Some of the cost of the levy to manufacturers and importers was passed on to consumers as higher prices but not always on targeted drinks. These changes could reduce population exposure to liquid sugars and associated health risks.

Estimating progress towards meeting women's contraceptive needs in 185 countries: A Bayesian hierarchical modelling study.

Abstract: Background Expanding access to contraception and ensuring that need for family planning is satisfied are essential for achieving universal access to reproductive healthcare services, as called for in the 2030 Agenda for Sustainable Development. Monitoring progress towards these outcomes is well established for women of reproductive age (15–49 years) who are married or in a union (MWRA). For those who are not, limited data and variability in data sources and indicator definitions make monitoring challenging. To our knowledge, this study is the first to provide data and harmonised estimates that enable monitoring for all women of reproductive age (15–49 years) (WRA), including unmarried women (UWRA). We seek to quantify the gaps that remain in meeting family-planning needs among all WRA. Methods and findings In a systematic analysis, we compiled a comprehensive dataset of family-planning indicators among WRA from 1,247 nationally representative surveys. We used a Bayesian hierarchical model with country-specific time trends to estimate these indicators, with 95% uncertainty intervals (UIs), for 185 countries. We produced estimates from 1990 to 2019 and projections from 2019 to 2030 of contraceptive prevalence and unmet need for family planning among MWRA, UWRA, and all WRA, taking into account the changing proportions that were married or in a union. The model accounted for differences in the prevalence of sexual activity among UWRA across countries. Among 1.9 billion WRA in 2019, 1.11 billion (95% UI 1.07–1.16) have need for family planning; of those, 842 million (95% UI 800–893) use modern contraception, and 270 million (95% UI 246–301) have unmet need for modern methods. Globally, UWRA represented 15.7% (95% UI 13.4%–19.4%) of all modern contraceptive users and 16.0% (95% UI 12.9%–22.1%) of women with unmet need for modern methods in 2019. The proportion of the need for family planning satisfied by modern methods, Sustainable Development Goals (SDG) indicator 3.7.1, was 75.7% (95% UI 73.2%–78.0%) globally, yet less than half of the need for family planning was met in Middle and Western Africa. Projections to 2030 indicate an increase in the number of women with need for family planning to 1.19 billion (95% UI 1.13–1.26) and in the number of women using modern contraception to 918 million (95% UI 840–1,001). The main limitations of the study are as follows: (i) the uncertainty surrounding estimates for countries with little or no data is large; and (ii) although some adjustments were made, underreporting of contraceptive use and needs is likely, especially among UWRA. Conclusions In this study, we observed that large gaps remain in meeting family-planning needs. The projected increase in the number of women with need for family planning will create challenges to expand family-planning services fast enough to fulfil the growing need. Monitoring of family-planning indicators for all women, not just MWRA, is essential for accurately monitoring progress towards universal access to sexual and reproductive healthcare services—including family planning—by 2030 in the SDG era with its emphasis on ‘leaving no one behind.’

Association of bariatric surgery with all-cause mortality and incidence of obesity-related disease at a population level: A systematic review and meta-analysis.

Abstract: Background Previous clinical trials and institutional studies have demonstrated that surgery for the treatment of obesity (termed bariatric or metabolic surgery) reduces all-cause mortality and the development of obesity-related diseases such as type 2 diabetes mellitus (T2DM), hypertension, and dyslipidaemia. The current study analysed large-scale population studies to assess the association of bariatric surgery with long-term mortality and incidence of new-onset obesity-related disease at a national level. Methods and findings A systematic literature search of Medline (via PubMed), Embase, and Web of Science was performed. Articles were included if they were national or regional administrative database cohort studies reporting comparative risk of long-term mortality or incident obesity-related diseases for patients who have undergone any form of bariatric surgery compared with an appropriate control group with a minimum follow-up period of 18 months. Meta-analysis of hazard ratios (HRs) was performed for mortality risk, and pooled odds ratios (PORs) were calculated for discrete variables relating to incident disease. Eighteen studies were identified as suitable for inclusion. There were 1,539,904 patients included in the analysis, with 269,818 receiving bariatric surgery and 1,270,086 control patients. Bariatric surgery was associated with a reduced rate of all-cause mortality (POR 0.62, 95% CI 0.55 to 0.69, p < 0.001) and cardiovascular mortality (POR 0.50, 95% CI 0.35 to 0.71, p < 0.001). Bariatric surgery was strongly associated with reduced incidence of T2DM (POR 0.39, 95% CI 0.18 to 0.83, p = 0.010), hypertension (POR 0.36, 95% CI 0.32 to 0.40, p < 0.001), dyslipidaemia (POR 0.33, 95% CI 0.14 to 0.80, p = 0.010), and ischemic heart disease (POR 0.46, 95% CI 0.29 to 0.73, p = 0.001). Limitations of the study include that it was not possible to account for unmeasured variables, which may not have been equally distributed between patient groups given the non-randomised design of the studies included. There was also heterogeneity between studies in the nature of the control group utilised, and potential adverse outcomes related to bariatric surgery were not specifically examined due to a lack of available data. Conclusions This pooled analysis suggests that bariatric surgery is associated with reduced long-term all-cause mortality and incidence of obesity-related disease in patients with obesity for the whole operated population. The results suggest that broader access to bariatric surgery for people with obesity may reduce the long-term sequelae of this disease and provide population-level benefits.

The potential impact of COVID-19 in refugee camps in Bangladesh and beyond: A modeling study.

Abstract: Background COVID-19 could have even more dire consequences in refugees camps than in general populations. Bangladesh has confirmed COVID-19 cases and hosts almost 1 million Rohingya refugees from Myanmar, with 600,000 concentrated in the Kutupalong-Balukhali Expansion Site (mean age, 21 years; standard deviation [SD], 18 years; 52% female). Projections of the potential COVID-19 burden, epidemic speed, and healthcare needs in such settings are critical for preparedness planning. Methods and findings To explore the potential impact of the introduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Kutupalong-Balukhali Expansion Site, we used a stochastic Susceptible Exposed Infectious Recovered (SEIR) transmission model with parameters derived from emerging literature and age as the primary determinant of infection severity. We considered three scenarios with different assumptions about the transmission potential of SARS-CoV-2. From the simulated infections, we estimated hospitalizations, deaths, and healthcare needs expected, age-adjusted for the Kutupalong-Balukhali Expansion Site age distribution. Our findings suggest that a large-scale outbreak is likely after a single introduction of the virus into the camp, with 61%-92% of simulations leading to at least 1,000 people infected across scenarios. On average, in the first 30 days of the outbreak, we expect 18 (95% prediction interval [PI], 2-65), 54 (95% PI, 3-223), and 370 (95% PI, 4-1,850) people infected in the low, moderate, and high transmission scenarios, respectively. These reach 421,500 (95% PI, 376,300-463,500), 546,800 (95% PI, 499,300-567,000), and 589,800 (95% PI, 578,800-595,600) people infected in 12 months, respectively. Hospitalization needs exceeded the existing hospitalization capacity of 340 beds after 55-136 days, between the low and high transmission scenarios. We estimate 2,040 (95% PI, 1,660-2,500), 2,650 (95% PI, 2,030-3,380), and 2,880 (95% PI, 2,090-3,830) deaths in the low, moderate, and high transmission scenarios, respectively. Due to limited data at the time of analyses, we assumed that age was the primary determinant of infection severity and hospitalization. We expect that comorbidities, limited hospitalization, and intensive care capacity may increase this risk; thus, we may be underestimating the potential burden. Conclusions Our findings suggest that a COVID-19 epidemic in a refugee settlement may have profound consequences, requiring large increases in healthcare capacity and infrastructure that may exceed what is currently feasible in these settings. Detailed and realistic planning for the worst case in Kutupalong-Balukhali and all refugee camps worldwide must begin now. Plans should consider novel and radical strategies to reduce infectious contacts and fill health worker gaps while recognizing that refugees may not have access to national health systems.

Social distancing to slow the US COVID-19 epidemic: Longitudinal pretest-posttest comparison group study.

Abstract: Background Social distancing measures to address the US coronavirus disease 2019 (COVID-19) epidemic may have notable health and social impacts. Methods and findings We conducted a longitudinal pretest–posttest comparison group study to estimate the change in COVID-19 case growth before versus after implementation of statewide social distancing measures in the US. The primary exposure was time before (14 days prior to, and through 3 days after) versus after (beginning 4 days after, to up to 21 days after) implementation of the first statewide social distancing measures. Statewide restrictions on internal movement were examined as a secondary exposure. The primary outcome was the COVID-19 case growth rate. The secondary outcome was the COVID-19-attributed mortality growth rate. All states initiated social distancing measures between March 10 and March 25, 2020. The mean daily COVID-19 case growth rate decreased beginning 4 days after implementation of the first statewide social distancing measures, by 0.9% per day (95% CI −1.4% to −0.4%; P < 0.001). We did not observe a statistically significant difference in the mean daily case growth rate before versus after implementation of statewide restrictions on internal movement (0.1% per day; 95% CI −0.04% to 0.3%; P = 0.14), but there is substantial difficulty in disentangling the unique associations with statewide restrictions on internal movement from the unique associations with the first social distancing measures. Beginning 7 days after social distancing, the COVID-19-attributed mortality growth rate decreased by 2.0% per day (95% CI −3.0% to −0.9%; P < 0.001). Our analysis is susceptible to potential bias resulting from the aggregate nature of the ecological data, potential confounding by contemporaneous changes (e.g., increases in testing), and potential underestimation of social distancing due to spillover effects from neighboring states. Conclusions Statewide social distancing measures were associated with a decrease in the COVID-19 case growth rate that was statistically significant. Statewide social distancing measures were also associated with a decrease in the COVID-19-attributed mortality growth rate beginning 7 days after implementation, although this decrease was no longer statistically significant by 10 days.

Antibiotic prescription practices in primary care in low- And middle-income countries: A systematic review and meta-analysis

Abstract: Background The widespread use of antibiotics plays a major role in the development and spread of antimicrobial resistance. However, important knowledge gaps still exist regarding the extent of their use in low- and middle-income countries (LMICs), particularly at the primary care level. We performed a systematic review and meta-analysis of studies conducted in primary care in LMICs to estimate the prevalence of antibiotic prescriptions as well as the proportion of such prescriptions that are inappropriate. Methods and findings We searched PubMed, Embase, Global Health, and CENTRAL for articles published between 1 January 2010 and 4 April 2019 without language restrictions. We subsequently updated our search on PubMed only to capture publications up to 11 March 2020. Studies conducted in LMICs (defined as per the World Bank criteria) reporting data on medicine use in primary care were included. Three reviewers independently screened citations by title and abstract, whereas the full-text evaluation of all selected records was performed by 2 reviewers, who also conducted data extraction and quality assessment. A modified version of a tool developed by Hoy and colleagues was utilized to evaluate the risk of bias of each included study. Meta-analyses using random-effects models were performed to identify the proportion of patients receiving antibiotics. The WHO Access, Watch, and Reserve (AWaRe) framework was used to classify prescribed antibiotics. We identified 48 studies from 27 LMICs, mostly conducted in the public sector and in urban areas, and predominantly based on medical records abstraction and/or drug prescription audits. The pooled prevalence proportion of antibiotic prescribing was 52% (95% CI: 51%-53%), with a prediction interval of 44%-60%. Individual studies' estimates were consistent across settings. Only 9 studies assessed rationality, and the proportion of inappropriate prescription among patients with various conditions ranged from 8% to 100%. Among 16 studies in 15 countries that reported details on prescribed antibiotics, Access-group antibiotics accounted for more than 60% of the total in 12 countries. The interpretation of pooled estimates is limited by the considerable between-study heterogeneity. Also, most of the available studies suffer from methodological issues and report insufficient details to assess appropriateness of prescription. Conclusions Antibiotics are highly prescribed in primary care across LMICs. Although a subset of studies reported a high proportion of inappropriate use, the true extent could not be assessed due to methodological limitations. Yet, our findings highlight the need for urgent action to improve prescription practices, starting from the integration of WHO treatment recommendations and the AWaRe classification into national guidelines. Trial registration PROSPERO registration number: CRD42019123269.

Incidence of and trends in hip fracture among adults in urban China: A nationwide retrospective cohort study.

Abstract: Background Hip fracture is a public health concern because of its considerable morbidity, excess mortality, great risk of disability, and high societal healthcare costs. China has the largest population of older people in the world and is experiencing rapid population aging and facing great challenges from an increasing number of hip fractures. However, few studies reported the epidemiology, especially at a national level. We aimed to evaluate trends in hip fracture incidence and associated costs for hospitalization in China. Methods and findings We conducted a population-based study using data between 2012 and 2016 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China, covering about 480 million residents. Data from around 102.56 million participants aged 55 years and older during the study period were analyzed. A total of 190,560 incident hip fracture patients (mean age 77.05 years, standard deviation 8.94; 63.99% female) were identified. Primary outcomes included the age- and sex-specific incidences of hip fracture. Associated annual costs for hospitalization were also calculated. Incidence was described as per 100,000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. Hip fracture incidence overall in China did not increase during the study period despite rapid population aging. Incidence per 100,000 was 180.72 (95% CI 137.16, 224.28; P < 0.001) in 2012 and 177.13 (95% CI 139.93, 214.33; P < 0.001) in 2016 for females, and 121.86 (95% CI 97.30, 146.42; P < 0.001) in 2012 and 99.15 (95% CI 81.31, 116.99; P < 0.001) in 2016 for males. For both sexes, declines in hip fracture incidence were observed in patients aged 65 years and older, although incidence was relatively stable in younger patients. However, the total absolute number of hip fractures in those 55 years and older increased about 4-fold. The total costs for hospitalization showed a steep rise from US$60 million to US$380 million over the study period. Costs for hospitalization per patient increased about 1.59-fold, from US$4,300 in 2012 to US$6,840 in 2016. The main limitation of the study was the unavailability of data on imaging information to adjudicate cases of hip fracture. Conclusions Our results show that hip fracture incidence among patients aged 55 and over in China reached a plateau between 2012 and 2016. However, the absolute number of hip fractures and associated medical costs for hospitalization increased rapidly because of population aging.

Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis.

Abstract: Background Polycystic ovary syndrome (PCOS) is a common, complex genetic disorder affecting up to 15% of reproductive-age women worldwide, depending on the diagnostic criteria applied These diagnostic criteria are based on expert opinion and have been the subject of considerable controversy The phenotypic variation observed in PCOS is suggestive of an underlying genetic heterogeneity, but a recent meta-analysis of European ancestry PCOS cases found that the genetic architecture of PCOS defined by different diagnostic criteria was generally similar, suggesting that the criteria do not identify biologically distinct disease subtypes We performed this study to test the hypothesis that there are biologically relevant subtypes of PCOS Methods and findings Using biochemical and genotype data from a previously published PCOS genome-wide association study (GWAS), we investigated whether there were reproducible phenotypic subtypes of PCOS with subtype-specific genetic associations Unsupervised hierarchical cluster analysis was performed on quantitative anthropometric, reproductive, and metabolic traits in a genotyped cohort of 893 PCOS cases (median and interquartile range [IQR]: age = 28 [25–32], body mass index [BMI] = 354 [282–415]) The clusters were replicated in an independent, ungenotyped cohort of 263 PCOS cases (median and IQR: age = 28 [24–33], BMI = 357 [284–423]) The clustering revealed 2 distinct PCOS subtypes: a “reproductive” group (21%–23%), characterized by higher luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels with relatively low BMI and insulin levels, and a “metabolic” group (37%–39%), characterized by higher BMI, glucose, and insulin levels with lower SHBG and LH levels We performed a GWAS on the genotyped cohort, limiting the cases to either the reproductive or metabolic subtypes We identified alleles in 4 loci that were associated with the reproductive subtype at genome-wide significance (PRDM2/KAZN, P = 22 × 10−10; IQCA1, P = 28 × 10−9; BMPR1B/UNC5C, P = 97 × 10−9; CDH10, P = 12 × 10−8) and one locus that was significantly associated with the metabolic subtype (KCNH7/FIGN, P = 10 × 10−8) We developed a predictive model to classify a separate, family-based cohort of 73 women with PCOS (median and IQR: age = 28 [25–33], BMI = 343 [278–423]) and found that the subtypes tended to cluster in families and that carriers of previously reported rare variants in DENND1A, a gene that regulates androgen biosynthesis, were significantly more likely to have the reproductive subtype of PCOS Limitations of our study were that only PCOS cases of European ancestry diagnosed by National Institutes of Health (NIH) criteria were included, the sample sizes for the subtype GWAS were small, and the GWAS findings were not replicated Conclusions In conclusion, we have found reproducible reproductive and metabolic subtypes of PCOS Furthermore, these subtypes were associated with novel, to our knowledge, susceptibility loci Our results suggest that these subtypes are biologically relevant because they appear to have distinct genetic architecture This study demonstrates how phenotypic subtyping can be used to gain additional insights from GWAS data

Changes in the amount of nutrient of packaged foods and beverages after the initial implementation of the Chilean Law of Food Labelling and Advertising: A nonexperimental prospective study.

Abstract: Bloomberg Philanthropies IDRC 107731-002 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 3150183

Healthy lifestyle and life expectancy in people with multimorbidity in the UK Biobank: A longitudinal cohort study.

Abstract: Background Whether a healthy lifestyle impacts longevity in the presence of multimorbidity is unclear. We investigated the associations between healthy lifestyle and life expectancy in people with and without multimorbidity. Methods and findings A total of 480,940 middle-aged adults (median age of 58 years [range 38–73], 46% male, 95% white) were analysed in the UK Biobank; this longitudinal study collected data between 2006 and 2010, and participants were followed up until 2016. We extracted 36 chronic conditions and defined multimorbidity as 2 or more conditions. Four lifestyle factors, based on national guidelines, were used: leisure-time physical activity, smoking, diet, and alcohol consumption. A combined weighted score was developed and grouped participants into 4 categories: very unhealthy, unhealthy, healthy, and very healthy. Survival models were applied to predict life expectancy, adjusting for ethnicity, working status, deprivation, body mass index, and sedentary time. A total of 93,746 (19.5%) participants had multimorbidity. During a mean follow-up of 7 (range 2–9) years, 11,006 deaths occurred. At 45 years, in men with multimorbidity an unhealthy score was associated with a gain of 1.5 (95% confidence interval [CI] −0.3 to 3.3; P = 0.102) additional life years compared to very unhealthy score, though the association was not significant, whilst a healthy score was significantly associated with a gain of 4.5 (3.3 to 5.7; P < 0.001) life years and a very healthy score with 6.3 (5.0 to 7.7; P < 0.001) years. Corresponding estimates in women were 3.5 (95% CI 0.7 to 6.3; P = 0.016), 6.4 (4.8 to 7.9; P < 0.001), and 7.6 (6.0 to 9.2; P < 0.001) years. Results were consistent in those without multimorbidity and in several sensitivity analyses. For individual lifestyle factors, no current smoking was associated with the largest survival benefit. The main limitations were that we could not explore the consistency of our results using a more restrictive definition of multimorbidity including only cardiometabolic conditions, and participants were not representative of the UK as a whole. Conclusions In this analysis of data from the UK Biobank, we found that regardless of the presence of multimorbidity, engaging in a healthier lifestyle was associated with up to 6.3 years longer life for men and 7.6 years for women; however, not all lifestyle risk factors equally correlated with life expectancy, with smoking being significantly worse than others.

Ultra-processed food intake in association with BMI change and risk of overweight and obesity: A prospective analysis of the French NutriNet-Santé cohort.

Abstract: Background: Ultra-processed food (UPF) consumption has increased drastically worldwide and already represents 50%–60% of total daily energy intake in several high-income countries. In the meantime, the prevalence of overweight and obesity has risen continuously during the last century. The objective of this study was to investigate the associations between UPF consumption and the risk of overweight and obesity, as well as change in body mass index (BMI), in a large French cohort. Methods and findings: A total of 110,260 adult participants (≥18 years old, mean baseline age = 43.1 [SD 14.6] years; 78.2% women) from the French prospective population-based NutriNet-Sante cohort (2009–2019) were included. Dietary intakes were collected at baseline using repeated and validated 24-hour dietary records linked to a food composition database that included >3,500 different food items, each categorized according to their degree of processing by the NOVA classification. Associations between the proportion of UPF in the diet and BMI change during follow-up were assessed using linear mixed models. Associations with risk of overweight and obesity were assessed using Cox proportional hazard models. After adjusting for age, sex, educational level, marital status, physical activity, smoking status, alcohol intake, number of 24-hour dietary records, and energy intake, we observed a positive association between UPF intake and gain in BMI (β Time × UPF = 0.02 for an absolute increment of 10 in the percentage of UPF in the diet, P < 0.001). UPF intake was associated with a higher risk of overweight (n = 7,063 overweight participants; hazard ratio (HR) for an absolute increase of 10% of UPFs in the diet = 1.11, 95% CI: 1.08–1.14; P < 0.001) and obesity (n = 3,066 incident obese participants; HR10% = 1.09 (1.05–1.13); P < 0.001). These results remained statistically significant after adjustment for the nutritional quality of the diet and energy intake. Study limitations include possible selection bias, potential residual confounding due to the observational design, and a possible item misclassification according to the level of processing. Nonetheless, robustness was tested and verified using a large panel of sensitivity analyses. Conclusions: In this large observational prospective study, higher consumption of UPF was associated with gain in BMI and higher risks of overweight and obesity. Public health authorities in several countries recently started to recommend privileging unprocessed/minimally processed foods and limiting UPF consumption.

Population ageing and mortality during 1990-2017: A global decomposition analysis.

Abstract: Background As the number of older people globally increases, health systems need to be reformed to meet the growing need for medical resources. A few previous studies reported varying health impacts of population ageing, but they focused only on limited countries and diseases. We comprehensively quantify the impact of population ageing on mortality for 195 countries/territories and 169 causes of death. Methods and findings Using data from the Global Burden of Disease Study 2017 (GBD 2017), this study derived the total number of deaths and population size for each year from 1990 to 2017. A decomposition method was used to attribute changes in total deaths to population growth, population ageing, and mortality change between 1990 and each subsequent year from 1991 through 2017, for 195 countries/territories and for countries grouped by World Bank economic development level. For countries with increases in deaths related to population ageing, we calculated the ratio of deaths attributed to mortality change to those attributed to population ageing. The proportion of people aged 65 years and older increased globally from 6.1% to 8.8%, and the number of global deaths increased by 9 million, between 1990 and 2017. Compared to 1990, 12 million additional global deaths in 2017 were associated with population ageing, corresponding to 27.9% of total global deaths. Population ageing was associated with increases in deaths in high-, upper-middle-, and lower-middle-income countries but not in low-income countries. The proportions of deaths attributed to population ageing in 195 countries/territories ranged from -43.9% to 117.4% for males and -30.1% to 153.5% for females. The 2 largest contributions of population ageing to disease-specific deaths globally between 1990 and 2017 were for ischemic heart disease (3.2 million) and stroke (2.2 million). Population ageing was related to increases in deaths in 152 countries for males and 159 countries for females, and decreases in deaths in 43 countries for males and 36 countries for females, between 1990 and 2017. The decreases in deaths attributed to mortality change from 1990 to 2017 were more than the increases in deaths related to population ageing for the whole world, as well as in 55.3% (84/152) of countries for males and 47.8% (76/159) of countries for females where population ageing was associated with increased death burden. As the GBD 2017 does not provide variances in the estimated death numbers, we were not able to quantify uncertainty in our attribution estimates. Conclusions In this study, we found that population ageing was associated with substantial changes in numbers of deaths between 1990 and 2017, but the attributed proportion of deaths varied widely across country income levels, countries, and causes of death. Specific preventive and therapeutic techniques should be implemented in different countries and territories to address the growing health needs related to population ageing, especially targeting the diseases associated with the largest increase in number of deaths in the elderly.

COVID-19 prevention and treatment: A critical analysis of chloroquine and hydroxychloroquine clinical pharmacology.

Abstract: Nicholas White and coauthors discuss chloroquine and hydroxychloroquine pharmacology in the context of possible treatment of SARS-CoV-2 infection.

Acute Kidney Injury Associated with COVID-19: A Retrospective Cohort Study

Abstract: Background Initial reports indicate a high incidence of acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19), but more data are required to clarify if COVID-19 is an independent risk factor for AKI and how COVID-19–associated AKI may differ from AKI due to other causes. We therefore sought to study the relationship between COVID-19, AKI, and outcomes in a retrospective cohort of patients admitted to 2 acute hospitals in Derby, United Kingdom. Methods and findings We extracted electronic data from 4,759 hospitalised patients who were tested for COVID-19 between 5 March 2020 and 12 May 2020. The data were linked to electronic patient records and laboratory information management systems. The primary outcome was AKI, and secondary outcomes included in-hospital mortality, need for ventilatory support, intensive care unit (ICU) admission, and length of stay. As compared to the COVID-19–negative group (n = 3,374), COVID-19 patients (n = 1,161) were older (72.1 ± 16.1 versus 65.3 ± 20.4 years, p < 0.001), had a greater proportion of men (56.6% versus 44.9%, p < 0.001), greater proportion of Asian ethnicity (8.3% versus 4.0%, p < 0.001), and lower proportion of white ethnicity (75.5% versus 82.5%, p < 0.001). AKI developed in 304 (26.2%) COVID-19–positive patients (COVID-19 AKI) and 420 (12.4%) COVID-19–negative patients (AKI controls). COVID-19 patients aged 65 to 84 years (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.11 to 2.50), needing mechanical ventilation (OR 8.74, 95% CI 5.27 to 14.77), having congestive cardiac failure (OR 1.72, 95% CI 1.18 to 2.50), chronic liver disease (OR 3.43, 95% CI 1.17 to 10.00), and chronic kidney disease (CKD) (OR 2.81, 95% CI 1.97 to 4.01) had higher odds for developing AKI. Mortality was higher in COVID-19 AKI versus COVID-19 patients without AKI (60.5% versus 27.4%, p < 0.001), and AKI was an independent predictor of mortality (OR 3.27, 95% CI 2.39 to 4.48). Compared with AKI controls, COVID-19 AKI was observed in a higher proportion of men (58.9% versus 51%, p = 0.04) and lower proportion with white ethnicity (74.7% versus 86.9%, p = 0.003); was more frequently associated with cerebrovascular disease (11.8% versus 6.0%, p = 0.006), chronic lung disease (28.0% versus 19.3%, p = 0.007), diabetes (24.7% versus 17.9%, p = 0.03), and CKD (34.2% versus 20.0%, p < 0.001); and was more likely to be hospital acquired (61.2% versus 46.4%, p < 0.001). Mortality was higher in the COVID-19 AKI as compared to the control AKI group (60.5% versus 27.6%, p < 0.001). In multivariable analysis, AKI patients aged 65 to 84 years, (OR 3.08, 95% CI 1.77 to 5.35) and ≥85 years of age (OR 3.54, 95% CI 1.87 to 6.70), peak AKI stage 2 (OR 1.74, 95% CI 1.05 to 2.90), AKI stage 3 (OR 2.01, 95% CI 1.13 to 3.57), and COVID-19 (OR 3.80, 95% CI 2.62 to 5.51) had higher odds of death. Limitations of the study include retrospective design, lack of urinalysis data, and low ethnic diversity of the region. Conclusions We observed a high incidence of AKI in patients with COVID-19 that was associated with a 3-fold higher odds of death than COVID-19 without AKI and a 4-fold higher odds of death than AKI due to other causes. These data indicate that patients with COVID-19 should be monitored for the development of AKI and measures taken to prevent this. Trial registration ClinicalTrials.gov NCT04407156