PLoS Medicine

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ISSN / EISSN : 15491277 / 15491676
Current Publisher: Public Library of Science (PLoS) (10.1371)
Total articles ≅ 4,170
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Anita Lal, Ana Maria Mantilla-Herrera, Lennert Veerman, Kathryn Backholer, Gary Sacks, Marjory Moodie, Mohammad Siahpush, Rob Carter, Anna Peeters
PLOS Medicine, Volume 17; doi:10.1371/journal.pmed.1003310

Marcela Reyes, Lindsey Smith Taillie, Barry Popkin, Rebecca Kanter, Stefanie Vandevijvere, Camila Corvalán
PLOS Medicine, Volume 17; doi:10.1371/journal.pmed.1003220

Abstract:
In June 2016, the first phase of the Chilean Food Labelling and Advertising Law that mandated front-of-package warning labels and marketing restrictions for unhealthy foods and beverages was implemented. We assess foods and beverages reformulation after this initial implementation. A data set with the 2015 to 2017 nutritional information was developed collecting the information at 2 time periods: preimplementation (T0: January–February 2015 or 2016; n = 4,055) and postimplementation (T1: January–February 2017; n = 3,025). Quartiles of energy and nutrients of concern (total sugars, saturated fats, and sodium, per 100 g/100 mL) and the proportion of products with energy and nutrients exceeding the cutoffs of the law (i.e., products “high in”) were compared pre- and postimplementation of the law in cross-sectional samples of products with sales >1% of their specific food or beverage groups, according to the Euromonitor International Database; a longitudinal subsample (i.e., products collected in both the pre- and postimplementation periods, n = 1,915) was also analyzed. Chi-squared, McNemar tests, and quantile regressions (simple and multilevel) were used for comparing T0 and T1. Cross-sectional analysis showed a significant decrease (T0 versus T1) in the proportion of product with any “high in” (from 51% [95% confidence interval (CI) 49–52] to 44% [95% CI 42–45]), mostly in food and beverage groups in which regulatory cutoffs were below the 75th percentile of the nutrient or energy distribution. Most frequent reductions were in the proportion of “high in” sugars products (in beverages, milks and milk-based drinks, breakfast cereals, sweet baked products, and sweet and savory spreads; from 80% [95% CI 73–86] to 60% [95% CI 51–69]) and in “high in sodium” products (in savory spreads, cheeses, ready-to-eat meals, soups, and sausages; from 74% [95% CI 69–78] to 27% [95% CI 20–35]). Conversely, the proportion of products “high in” saturated fats only decreased in savory spreads (p < 0.01), and the proportion of “high in” energy products significantly decreased among breakfast cereals and savory spreads (both p < 0.01). Quantile analyses showed that most of the changes took place close to the cutoff values, with only few exceptions of overall left shifts in distribution. Longitudinal analyses showed similar results. However, it is important to note that the nonexperimental nature of this study does not allow to imply causality of these findings. Our results show that, after initial implementation of the Chilean Law of Food Labelling and Advertising, there was a significant decrease in the amount of sugars and sodium in several groups of packaged foods and beverages. Further studies should clarify how food reformulation will impact dietary quality of the population.
Yan-Ting Wu, Jun Liu, Jing-Jing Xu, Yan-Fen Chen, Wen Yang, Yang Chen, Cheng Li, Yu Wang, Han Liu, Chen Zhang, et al.
PLOS Medicine, Volume 17; doi:10.1371/journal.pmed.1003195

Abstract:
As of June 1, 2020, coronavirus disease 2019 (COVID-19) has caused more than 6,000,000 infected persons and 360,000 deaths globally. Previous studies revealed pregnant women with COVID-19 had similar clinical manifestations to nonpregnant women. However, little is known about the outcome of neonates born to infected women. In this retrospective study, we studied 29 pregnant women with COVID-19 infection delivered in 2 designated general hospitals in Wuhan, China between January 30 and March 10, 2020, and 30 neonates (1 set of twins). Maternal demographic characteristics, delivery course, symptoms, and laboratory tests from hospital records were extracted. Neonates were hospitalized if they had symptoms (5 cases) or their guardians agreed to a hospitalized quarantine (13 cases), whereas symptom-free neonates also could be discharged after birth and followed up through telephone (12 cases). For hospitalized neonates, laboratory test results and chest X-ray or computed tomography (CT) were extracted from hospital records. The presence of antibody of SARS-CoV-2 was assessed in the serum of 4 neonates. Among 29 pregnant COVID-19-infected women (13 confirmed and 16 clinical diagnosed), the majority had higher education (56.6%), half were employed (51.7%), and their mean age was 29 years. Fourteen women experienced mild symptoms including fever (8), cough (9), shortness of breath (3), diarrhea (2), vomiting (1), and 15 were symptom-free. Eleven of 29 women had pregnancy complications, and 27 elected to have a cesarean section delivery. Of 30 neonates, 18 were admitted to Wuhan Children’s Hospital for quarantine and care, whereas the other 12 neonates discharged after birth without any symptoms and had normal follow-up. Five hospitalized neonates were diagnosed as COVID-19 infection (2 confirmed and 3 suspected). In addition, 12 of 13 other hospitalized neonates presented with radiological features for pneumonia through X-ray or CT screening, 1 with occasional cough and the others without associated symptoms. SARS-CoV-2 specific serum immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in 4 neonates and 2 were positive. The limited sample size limited statistical comparison between groups. In this study, we observed COVID-19 or radiological features of pneumonia in some, but not all, neonates born to women with COVID-19 infection. These findings suggest that intrauterine or intrapartum transmission is possible and warrants clinical caution and further investigation. Chinese Clinical Trial Registry, ChiCTR2000031954 (Maternal and Perinatal Outcomes of Women with coronavirus disease 2019 (COVID-19): a multicenter retrospective cohort study).
Tom Wiggins, Nadia Guidozzi, Richard Welbourn, Ahmed R. Ahmed, Sheraz R. Markar
PLOS Medicine, Volume 17; doi:10.1371/journal.pmed.1003206

Abstract:
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. 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. 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.
Anthony Hauser, Michel J. Counotte, Charles C. Margossian, Garyfallos Konstantinoudis, Nicola Low, Christian L. Althaus, Julien Riou
PLOS Medicine, Volume 17; doi:10.1371/journal.pmed.1003189

Abstract:
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. 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-Württemberg (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. 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.
Guozhi Jiang, Andrea O. Luk, Claudia H. T. Tam, Eric S. Lau, Risa Ozaki, Elaine Y. K. Chow, Alice P. S. Kong, Cadmon K. P. Lim, Ka Fai Lee, Shing Chung Siu, et al.
PLoS Medicine, Volume 17; doi:10.1371/journal.pmed.1003209

Abstract:
Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. In 1995–2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1–9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8–13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3–49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03–1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06–1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10−8) but not glycemic progression (HR: 1.01 [95% CI 0.96–1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.
M. Victoria Salgado, Joanne Penko, Alicia Fernandez, Jonatan Konfino, Pamela G. Coxson, Kirsten Bibbins-Domingo, Raul Mejia
PLoS Medicine, Volume 17; doi:10.1371/journal.pmed.1003224

Abstract:
Sugar-sweetened beverage (SSB) consumption is associated with obesity, diabetes, and hypertension. Argentina is one of the major consumers of SSBs per capita worldwide. Determining the impact of SSB reduction on health will inform policy debates. We used the Cardiovascular Disease Policy Model-Argentina (CVD Policy Model-Argentina), a local adaptation of a well-established computer simulation model that projects cardiovascular and mortality events for the population 35–94 years old, to estimate the impact of reducing SSB consumption on diabetes incidence, cardiovascular events, and mortality in Argentina during the period 2015–2024, using local demographic and consumption data. Given uncertainty regarding the exact amount of SSBs consumed by different age groups, we modeled 2 estimates of baseline consumption (low and high) under 2 different scenarios: a 10% and a 20% decrease in SSB consumption. We also included a range of caloric compensation in the model (0%, 39%, and 100%). We used Monte Carlo simulations to generate 95% uncertainty intervals (UIs) around our primary outcome measures for each intervention scenario. Over the 2015–2024 period, a 10% reduction in SSBs with a caloric compensation of 39% is projected to reduce incident diabetes cases by 13,300 (95% UI 10,800–15,600 [low SSB consumption estimate]) to 27,700 cases (95% UI 22,400–32,400 [high SSB consumption estimate]), i.e., 1.7% and 3.6% fewer cases, respectively, compared to a scenario of no change in SSB consumption. It would also reduce myocardial infarctions by 2,500 (95% UI 2,200–2,800) to 5,100 (95% UI 4,500–5,700) events and all-cause deaths by 2,700 (95% UI 2,200–3,200) to 5,600 (95% UI 4,600–6,600) for “low” and “high” estimates of SSB intake, respectively. A 20% reduction in SSB consumption with 39% caloric compensation is projected to result in 26,200 (95% UI 21,200–30,600) to 53,800 (95% UI 43,900–62,700) fewer cases of diabetes, 4,800 (95% UI 4,200–5,300) to 10,000 (95% UI 8,800–11,200) fewer myocardial infarctions, and 5,200 (95% UI 4,300–6,200) to 11,000 (95% UI 9,100–13,100) fewer deaths. The largest reductions in diabetes and cardiovascular events were observed in the youngest age group modeled (35–44 years) for both men and women; additionally, more events could be avoided in men compared to women in all age groups. The main limitations of our study are the limited availability of SSB consumption data in Argentina and the fact that we were only able to model the possible benefits of the interventions for the population older than 34 years. Our study finds that, even under conservative assumptions, a relatively small reduction in SSB consumption could lead to a substantial decrease in diabetes incidence, cardiovascular events, and mortality in Argentina.
Haijiang Dai, Tariq A. Alsalhe, Nasr Chalghaf, Matteo Riccò, Nicola Luigi Bragazzi, Jianhong Wu
PLoS Medicine, Volume 17; doi:10.1371/journal.pmed.1003198

Abstract:
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. 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. 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.
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