An SMS chatbot digital educational program to increase healthy eating behaviors in adolescence: A multifactorial randomized controlled trial among 7,890 participants in the Danish National Birth Cohort.

BACKGROUND: Few cost-effective strategies to shift dietary habits of populations in a healthier direction have been identified. We examined if participating in a chatbot health education program transmitted by Short Messages Service ("SMS-program") could improve adolescent dietary behaviors and body weight trajectories. We also explored possible added effects of maternal or peer involvement. METHODS AND FINDINGS: We conducted a randomized controlled trial (RCT) among adolescents from the Danish National Birth Cohort (DNBC). Eligible were adolescents who during 2015 to 2016 at age 14 years had completed a questionnaire assessing height, weight, and dietary habits. Two thirds were offered participation in an SMS-program, whereas 1/3 ("non-SMS group") received no offer. The SMS program aimed to improve 3 key dietary intake behaviors: sugar-sweetened beverages (SSBs), fruit and vegetables (FV), and fish. The offered programs had 3 factorially randomized schemes; the aims of these were to test effect of asking the mother or a friend to also participate in the health promotion program, and to test the effect of a 4-week individually tailored SMS program against the full 12-week SMS program targeting all 3 dietary factors. Height and weight and intakes of SSB, FV, and fish were assessed twice by a smartphone-based abbreviated dietary questionnaire completed at 6 months (m) and 18 m follow-up. Main outcome measures were (1) body mass index (BMI) z-score; and (2) an abbreviated Healthy Eating Index (mini-HEI, 1 m window, as mean of z-scores for SSB, FV, and fish). Among the 7,890 randomized adolescents, 5,260 were assigned to any SMS program; 63% (3,338) joined the offered program. Among the 7,890 randomized, 74% (5,853) and 68% (5,370) responded to follow-ups at 6 m and 18 m, respectively. Effects were estimated by intention-to-treat (ITT) analyses and inverse probability weighted per-protocol (IPW-PP) analyses excluding adolescents who did not join the program. Mean (standard deviation (SD)) mini-HEI at baseline, 6 m and 18 m was -0.01 (0.64), 0.01 (0.59), and -0.01 (0.59), respectively. In ITT-analyses, no effects were observed, at any time point, in those who had received any SMS program compared to the non-SMS group, on BMI z-score (6 m: -0.010 [95% confidence interval (CI) -0.035, 0.015]; p = 0.442, 18 m: 0.002 [95% CI -0.029, 0.033]; p = 0.901) or mini-HEI (6 m: 0.016 [95% CI -0.011, 0.043]; p = 0.253, 18m: -0.016 [95% CI -0.045, 0.013]; p = 0.286). In IPW-PP analyses, at 6 m, a small decrease in BMI z-score (-0.030 [95% CI -0.057, -0.003]; p = 0.032) was observed, whereas no significant effect was observed in mini-HEI (0.027 [95% CI -0.002, 0.056]; p = 0.072), among those who had received any SMS program compared to the non-SMS group. At 18 m, no associations were observed (BMI z-score: -0.006 [95% CI -0.039, 0.027]; p = 0.724, and mini-HEI: -0.005 [95% CI -0.036, 0.026]; p = 0.755). The main limitations of the study were that DNBC participants, though derived from the general population, tend to have higher socioeconomic status than average, and that outcome measures were self-reported. CONCLUSIONS: In this study, a chatbot health education program delivered through an SMS program had no effect on dietary habits or weight trajectories in ITT analyses. However, IPW-PP-analyses, based on those 63% who had joined the offered SMS program, suggested modest improvements in weight development at 6 m, which had faded at 18 m. Future research should focus on developing gender-specific messaging programs including "booster" messages to obtain sustained engagement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02809196 https://clinicaltrials.gov/study/NCT02809196.

Willingness to adopt wearable devices with behavioral and economic incentives by health insurance wellness programs: results of a US cross-sectional survey with multiple consumer health vignettes.

BACKGROUND: The number of health-related wearable devices is growing but it is not clear if Americans are willing to adopt health insurance wellness programs based on wearables and the incentives with which they would be more willing to adopt. METHODS: In this cross-sectional study we used a survey methodology, usage vignettes and a dichotomous scale to examine U.S. residents' willingness to adopt wearables (WTAW) in six use-cases where it was mandatory to use a wearable device and share the resulting data with a health insurance company. Each use-case was tested also for the influence of additional economic incentives on WTAW. RESULTS: A total of 997 Americans across 46 states participated in the study. Most of them were 25 to 34 years old (40.22%), 57.27% were female, and 74.52% were white. On average, 69.5% of the respondents were willing to adopt health-insurance use-cases based on wearable devices, though 77.8% of them were concerned about issues related to economic benefits, data privacy and to a lesser extent, technological accuracy. WTAW was 11-18% higher among consumers in use-cases involving health promotion and disease prevention. Furthermore, additional economic incentives combined with wearables increased WTAW overall. Notably, financial incentives involving providing healthcare credits, insurance premium discount, and/or wellness product discounts had particularly greater effectiveness for increasing WTAW in the consumer use-cases involving participation: for health promotion (RR = 1.06 for financial incentive, 95% CI: 1.01-1.11; P = 0.018); for personalized products and services (RR = 1.11 for financial incentive, 95% CI: 1.01-1.21; P = 0.018); and for automated underwriting discount at annual renewal (RR = 1.28 for financial incentive, 95% CI: 1.20-1.37; P < 0.001). CONCLUSIONS: Under the adequate economic, data privacy and technical conditions, 2 out of 3 Americans would be willing to adopt health insurance wellness programs based on wearable devices, particularly if they have benefits related to health promotion and disease prevention, and particularly with financial incentives.

Global Mortality From Firearms, 1990-2016.

Importance: Understanding global variation in firearm mortality rates could guide prevention policies and interventions. Objective: To estimate mortality due to firearm injury deaths from 1990 to 2016 in 195 countries and territories. Design, Setting, and Participants: This study used deidentified aggregated data including 13 812 location-years of vital registration data to generate estimates of levels and rates of death by age-sex-year-location. The proportion of suicides in which a firearm was the lethal means was combined with an estimate of per capita gun ownership in a revised proxy measure used to evaluate the relationship between availability or access to firearms and firearm injury deaths. Exposures: Firearm ownership and access. Main Outcomes and Measures: Cause-specific deaths by age, sex, location, and year. Results: Worldwide, it was estimated that 251 000 (95% uncertainty interval [UI], 195 000-276 000) people died from firearm injuries in 2016, with 6 countries (Brazil, United States, Mexico, Colombia, Venezuela, and Guatemala) accounting for 50.5% (95% UI, 42.2%-54.8%) of those deaths. In 1990, there were an estimated 209 000 (95% UI, 172 000 to 235 000) deaths from firearm injuries. Globally, the majority of firearm injury deaths in 2016 were homicides (64.0% [95% UI, 54.2%-68.0%]; absolute value, 161 000 deaths [95% UI, 107 000-182 000]); additionally, 27% were firearm suicide deaths (67 500 [95% UI, 55 400-84 100]) and 9% were unintentional firearm deaths (23 000 [95% UI, 18 200-24 800]). From 1990 to 2016, there was no significant decrease in the estimated global age-standardized firearm homicide rate (-0.2% [95% UI, -0.8% to 0.2%]). Firearm suicide rates decreased globally at an annualized rate of 1.6% (95% UI, 1.1-2.0), but in 124 of 195 countries and territories included in this study, these levels were either constant or significant increases were estimated. There was an annualized decrease of 0.9% (95% UI, 0.5%-1.3%) in the global rate of age-standardized firearm deaths from 1990 to 2016. Aggregate firearm injury deaths in 2016 were highest among persons aged 20 to 24 years (for men, an estimated 34 700 deaths [95% UI, 24 900-39 700] and for women, an estimated 3580 deaths [95% UI, 2810-4210]). Estimates of the number of firearms by country were associated with higher rates of firearm suicide (P < .001; R2 = 0.21) and homicide (P < .001; R2 = 0.35). Conclusions and Relevance: This study estimated between 195 000 and 276 000 firearm injury deaths globally in 2016, the majority of which were firearm homicides. Despite an overall decrease in rates of firearm injury death since 1990, there was variation among countries and across demographic subgroups.

Body-mass index and mortality among adults with incident type 2 diabetes.

BACKGROUND: The relation between body weight and mortality among persons with type 2 diabetes remains unresolved, with some studies suggesting decreased mortality among overweight or obese persons as compared with normal-weight persons (an "obesity paradox"). METHODS: We studied participants with incident diabetes from the Nurses' Health Study (8970 participants) and Health Professionals Follow-up Study (2457 participants) who were free of cardiovascular disease and cancer at the time of a diagnosis of diabetes. Body weight shortly before diagnosis and height were used to calculate the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters). Multivariable Cox models were used to estimate the hazard ratios and 95% confidence intervals for mortality across BMI categories. RESULTS: There were 3083 deaths during a mean period of 15.8 years of follow-up. A J-shaped association was observed across BMI categories (18.5 to 22.4, 22.5 to 24.9 [reference], 25.0 to 27.4, 27.5 to 29.9, 30.0 to 34.9, and ≥35.0) for all-cause mortality (hazard ratio, 1.29 [95% confidence interval {CI}, 1.05 to 1.59]; 1.00; 1.12 [95% CI, 0.98 to 1.29]; 1.09 [95% CI, 0.94 to 1.26]; 1.24 [95% CI, 1.08 to 1.42]; and 1.33 [95% CI, 1.14 to 1.55], respectively). This relationship was linear among participants who had never smoked (hazard ratios across BMI categories: 1.12, 1.00, 1.16, 1.21, 1.36, and 1.56, respectively) but was nonlinear among participants who had ever smoked (hazard ratios across BMI categories: 1.32, 1.00, 1.09, 1.04, 1.14, and 1.21) (P=0.04 for interaction). A direct linear trend was observed among participants younger than 65 years of age at the time of a diabetes diagnosis but not among those 65 years of age or older at the time of diagnosis (P<0.001 for interaction). CONCLUSIONS: We observed a J-shaped association between BMI and mortality among all participants and among those who had ever smoked and a direct linear relationship among those who had never smoked. We found no evidence of lower mortality among patients with diabetes who were overweight or obese at diagnosis, as compared with their normal-weight counterparts, or of an obesity paradox. (Funded by the National Institutes of Health and the American Diabetes Association.).

Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. METHODS: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). FINDINGS: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. INTERPRETATION: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. FUNDING: Bill & Melinda Gates Foundation.

Teenage smoking behaviour following a high-school smoking ban in Chile: interrupted time-series analysis.

OBJECTIVE: To evaluate the effect of a smoking ban in high schools on smoking behaviour among Chilean students. METHODS: We conducted an interrupted time-series analysis, using repeated cross-sectional data from Chile's school population survey (2000-2011) for high-school students aged 12-18 years and a control group of persons aged 19-24 years. Poisson regression models were used to assess trends in smoking behaviour before and after the policy changes. The outcome measures were self-reported smoking prevalence (any smoking in the past month) and high frequency of smoking (smoking 15 days or more per month). FINDINGS: From 2005 to 2011, the prevalence of smoking declined among high-school students by 6.8% per year compared with 3.6% decline per year in the control group. The decline in the target group was 2.9% (95% confidence interval, CI: 0.18 to 5.00) greater. We estimated that 5-6 years after enforcing the law, smoking prevalence among high-school students was 13.7% lower as a result of the ban. The impact of the smoking ban was primarily driven by declines in smoking prevalence among students in grades 8 to 10. The smoking ban did not significantly alter the frequency of smoking. CONCLUSION: The 2005 school smoking ban reduced smoking prevalence among younger high-school students in Chile. Further interventions targeting older individuals and frequent smokers may be needed.

Leisure-time physical activity and endometrial cancer risk: dose-response meta-analysis of epidemiological studies.

Although considerable evidence suggests that leisure-time physical activity is associated with a reduced risk of endometrial cancer (EC), the shape of dose-response relationship has not been investigated and previous meta-analyses have not accounted for differences in measures of physical activity. To address such issues, we conducted linear and nonlinear dose-response meta-analyses by metabolic equivalent of task (MET)-hour/week and hour/week, respectively, based on observational studies published up to September 2013 identified from PubMed and Embase databases. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. In the linear dose-response analysis, an increase in leisure-time physical activity by 3 MET-hour/week was associated with an ∼2% reduced risk of EC (summary RR = 0.98, p = 0.02, 95% CI = 0.95-1.00, I(2) = 53%, p(heterogeneity) = 0.06, three case-control studies and three cohort studies, 3,460 cases, range of activity = 0-50 MET-hour/week) and an increase by an hour/week was associated with an ∼5% reduced risk of EC (summary RR = 0.95, p < 0.001, 95% CI = 0.93-0.98, I(2) = 31%, p(heterogeneity) = 0.20, four case-control studies and two cohort studies, 3,314 cases, range of activity = 0-12 hour/week). Nonlinear dose-response meta-analysis suggested that the curve may plateau at 10 MET-hour/week (p(change) in slope = 0.04) but this statistical significance was sensitive to one study. No evidence of a nonlinear association was indicated by hour/week (p(change) in slope > 0.69). In conclusion, an increase in leisure-time physical activity may continue to decrease EC risk, within the range of 0-50 MET-hour/week or 0-15 hour/week. Future studies should evaluate possible independent role of intensity of physical activity and effect modification by obesity.

Comparison of paper- and web-based dietary records: a pilot study.

BACKGROUND/AIMS: Paper-based dietary records (Paper-DR) can be replaced by web-based dietary records (Web-DR) in both epidemiological studies and clinical practice to reduce the time and logistic burden. We aimed to compare Paper-DR and Web-DR. METHODS: We compared the matching of different food items (n = 1,103) from Paper-DR and Web-DR for energy and 48 nutrients among 16 pregnant volunteers, with DR for the same individuals matched for the same 4 days. Paper-DR were coded into the web-based version (referred to as Paper-Web-DR) independently by the same research dietitian. The Wilcoxon signed-rank test comparing mean rank differences, Spearman's ρ to measure associations and Bland-Altman limits of agreement to evaluate the level of agreement between the two dietary methods across the range of parameters were used. Volunteers also completed an evaluation questionnaire regarding the user acceptability of Paper-DR and Web-DR. RESULTS: A high correlation between Paper-DR and Web-DR was noted. There were statistically insignificant differences among 45 nutrients, except for free sugars (p < 0.001), α-linolenic acid (p = 0.041), folate (p = 0.036) and pantothenic acid (p = 0.023). Volunteers found the Paper-DR equally time-consuming as the Web-DR. The majority of the volunteers (75%) preferred the Web-DR. CONCLUSIONS: Paper-DR and Web-DR were comparable across a range of nutritional parameters, with a few exceptions. The Web-DR was more convenient for the majority and has substantial logistic and cost advantages.

Social network enhanced behavioral interventions for diabetes and obesity: A 3 arm randomized trial with 2 years follow-up in Jordan.

While obesity and diabetes are rising pandemics, few low-cost and effective prevention and management strategies exist, especially in the Middle East. Nearly 20% of adults in Jordan suffer from diabetes, and over 75% are overweight or obese. Social network-based programs have shown promise as a viable public health intervention strategy to address these growing crises. We evaluated the effectiveness of the Microclinic Program (MCP) via a 6-month multi-community randomized trial in Jordan, with follow-up at 2 years. The MCP leverages existing social relationships to propagate positive health behaviors and information. We recruited participants from 3 community health centers in Amman, Jordan. Participants were eligible for the study if they had diabetes, pre-diabetes, or possessed ≥1 metabolic risk factor along with a family history of diabetes. We randomized participants into three trial arms: (A Group) received the Full MCP with curriculum-activated social network interactions; (B Group) received Basic MCP educational sessions with organic social network interactions; or (C Group-Control) received standard care coupled with active monitoring and parallel screenings. Groups of individuals were randomized as units in a 3:1:1 ratio, with resulting group sizes of n = 540, 186, and 188 in arms A, B, and C, respectively. We assessed the overall changes in body weight, fasting glucose, hemoglobin A1c (HbA1c) and mean arterial blood pressure between study arms in multiple evaluations across 2 years (including at 6-months and 2-years follow-up). We investigated the effectiveness of Full and Basic MCP social network interventions using multilevel models for longitudinal data with hierarchical nesting of individuals within MCP classrooms, within community centers, and within temporal cohorts. We observed significant overall 2-year differences between all 3 groups for changes in body weight (P = 0.0003), fasting blood glucose (P = 0.0015), and HbA1c (P = 0.0004), but not in mean arterial blood pressure (P = 0.45). However, significant changes in mean arterial pressure were observed for Full MCP versus controls (P = 0.002). Weight loss in the Full MCP exceeded (-0.97 kg (P<0.001)) the Basic MCP during the intervention. Furthermore, both Full and Basic MCP yielded greater weight loss compared to the control group at 2 years. The Full MCP also sustained a superior fasting glucose change over 2 years (overall P<0.0001) versus the control group. For HbA1c, the Full MCP similarly led to greater 6-month reduction in HbA1c versus the control group (P<0.001), with attenuation at 2 years. For mean arterial blood pressure, the Full MCP yielded a greater drop in blood pressure versus control at 6 months; with attenuation at 2 years. These results suggest that activated social networks of classroom interactions can be harnessed to improve health behaviors related to obesity and diabetes. Future studies should investigate how public health policies and initiatives can further leverage social network programs for greater community propagation. Trial registration. ClinicalTrials.gov Identifier: NCT01818674.

Social Induction via a Social Behavioral Intervention on Changes in Metabolic Risk Factors: A Randomized Controlled Trial in Rural Appalachia, United States.

OBJECTIVE: To conduct a randomized controlled trial examining the effects of a social network intervention on health. PARTICIPANTS AND METHODS: The Microclinic Social Network Program randomized controlled trial (implemented from June 1, 2011, through December 31, 2014) delivered weekly social-health classroom interventions for 9 to 10 months vs standard of care. Longitudinal multilevel analyses examined end-of-trial and 6-month post-intervention outcomes. Social network effects were estimated via a novel social induction ratio. RESULTS: We randomized 494 participants, comprising 27 classroom clusters from five neighborhood cohorts. Compared with controls, the intervention showed decreased body weight -6.32 pounds (95% CI, -8.65 to -3.98; overall P<.001), waist circumference -1.21 inches (95% CI, -1.84 to -0.58; overall P<.001), hemoglobin A1c % change -1.60 (95% CI, -1.88 to -1.33; overall P<.001), mean arterial blood pressure -1.83 mm Hg (95% CI, -3.79 to 0.32; overall P<.01), borderline-increased high-density lipoprotein cholesterol 1.09 (95% CI, 0.01-2.17; P=.05; overall P=.01). At 6 months post-intervention, net improvements were: weight change 97% sustained (P<.001), waist circumference change 92% sustained (P<.001), hemoglobin A1c change 82.5% sustained (P<.001), high-density lipoprotein change 79% sustained (overall P=.01), and mean arterial blood pressure change greater than 100% sustained improvement of -4.21 mm Hg (P<.001). Mediation analysis found that diet and exercise did not substantially explain improvements. In the intent-to-treat analysis of social causal induction, the weight-change social induction ratio (SIR) was 1.80 for social-network weight change-meaning that social networks explained the greater weight loss in the intervention than controls. Furthermore, we observed an even stronger weight-loss SIR of 2.83 at 6 months post-intervention. CONCLUSION: Results show intervention effectiveness for improving health in resource-limited communities, with SIR demonstrating that social-network effects helped induce such improvements. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01651065.

A novel fatty acid profile index--the lipophilic index--and risk of myocardial infarction.

The lipophilic index (LI), a mean measure of fatty acid melting points, has been proposed to capture overall fatty acid profile and may play an important role in the etiology of coronary heart disease. We aimed to determine the association between LI in diet and in adipose tissue and metabolic risk factors for myocardial infarction (MI) and risk of MI. We used a population-based, matched case-control study of nonfatal first acute MI conducted in Costa Rica between 1994 and 2004, with 1,627 case-control pairs. The LI is defined as the mean of the melting points of specific fatty acids in diet or adipose tissue. LIs in diet and adipose tissue were significantly associated with higher plasma triglyceride concentrations, low-density lipoprotein cholesterol concentrations, and low-density:high-density lipoprotein cholesterol ratio. Comparing extreme quintiles for the LI in diet or adipose tissue, the odds ratios for MI were 1.57 (95% confidence interval: 1.22, 2.02; P for trend < 0.001) for dietary LI and 1.30 (95% confidence interval: 1.00, 1.69; P for trend = 0.02) for adipose tissue LI in the multivariable models. We hypothesize that a higher LI in diet and in adipose tissue represents decreased fatty acid fluidity and could play an important role in the etiology of coronary heart disease.

Isotemporal substitution analysis for physical activity, television watching, and risk of depression.

The isotemporal substitution model (ISM) was previously developed as a methodology to study the time-substitution effects of 1 type of activity for another in a data setting with continuous outcomes. To demonstrate the application of ISM with a dichotomous outcome, we prospectively examined the associations of different activities with various activity displacements with depression risk among 32,900 US women from the Nurses' Health Study who were free from depressive symptoms at baseline (in 1996). During a 10-year follow-up, 5,730 incident depression cases were documented. Results from the ISMs indicated that for each physical activity, differences in magnitude of effects of each activity type were observed, dependent on the activity being displaced/substituted. Notably, an isotemporal substitution gradient was found for television watching, in which its association with depression risk varied by its substitution for slow-, average-, or brisk-paced walking in a gradient toward high depression risk when television watching replaced a faster walking pace (relative risk = 1.18, 95% confidence interval: 1.05, 1.31). Conversely, no association with depression was found for replacement of television watching with 60 minutes/day of slow walking, whereas a lower depression risk (relative risk = 0.85, 95% confidence interval: 0.76, 0.95) was found when 60 minutes/day of brisk walking replaced 60 minutes/day of television watching. Thus, the ISM could offer a more meaningful alternative to the standard nonsubstitution models to support public health recommendations.

Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study.

BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal. METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol. FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)). INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction. FUNDING: US National Institutes of Health, The Wellcome Trust, European Union, British Heart Foundation, and the German Federal Ministry of Education and Research.

A novel fatty acid lipophilic index and risk of CHD in US men: the health professionals follow-up study.

Few epidemiological studies have examined the association between an overall fatty acid (FA) profile and CHD risk. The aim of the present study was to examine a novel index that summarises individual FA levels based on FA affinity and fluidity in relation to CHD risk in men. In a prospective nested case­control study, FA in plasma and erythrocytes were measured in 459 CHD cases and 879 matched controls. Lipophilic index (LI) was computed by summing the products between FA levels and melting point of each FA to reflect the overall FA lipophilicity. Among controls, higher plasma LI was significantly correlated with adverse profiles of blood lipids, inflammatory markers and adiponectin. After multivariate adjustment for age, smoking, BMI and other CHD risk factors, plasma LI was significantly associated with an increased risk of CHD: the relative risk was 1·61 (95% CI 1·03, 2·53; P for trend»0·04) comparing extreme quintiles. This association was attenuated to 1·21 (95% CI 0·48, 3·09; P for trend»0·77) after adjusting for plasma levels of total trans-FA, long-chain n-3 FA and polyunsaturated:saturated fat ratio. Erythrocyte LI was not significantly associated with CHD risk. The present data indicate that a novel LI is associated with an adverse profile of cardiovascular risk markers and increased risk of CHD in men; its usefulness as a complement of individual FA in assessing disease risk needs to be elucidated in future studies.

The state of US health, 1990-2010: burden of diseases, injuries, and risk factors.

IMPORTANCE: Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. OBJECTIVES: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. DESIGN: We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. RESULTS: US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. CONCLUSIONS AND RELEVANCE: From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.

Dairy intake and risk of hip fracture in prospective cohort studies: non-linear algorithmic dose-response analysis in 486 950 adults.

Previous studies on the relationship between dairy consumption and hip fracture risk have reported inconsistent findings. Therefore, we aimed to conduct an algorithmically driven non-linear dose-response meta-analysis of studies assessing dairy intake and risk of developing incident hip fracture. Meta-analysis from PubMed and Google Scholar searches for articles of prospective studies of dairy intake and risk of hip fracture, supplemented by additional detailed data provided by authors. Meta-regression derived dose-response relative risks, with comprehensive algorithm-driven dose assessment across the entire dairy consumption spectrum for non-linear associations. Review of studies published in English from 1946 through December 2021. A search yielded 13 studies, with 486 950 adults and 15 320 fractures. Non-linear dose models were found to be empirically superior to a linear explanation for the effects of milk. Milk consumption was associated with incrementally higher risk of hip fractures up to an intake of 400 g/d, with a 7 % higher risk of hip fracture per 200 g/d of milk (RR 1⋅07, 95 % CI 1⋅05, 1⋅10; P < 0⋅0001), peaking with 15 % higher risk (RR 1⋅15, 95 % CI 1⋅09, 1⋅21, P < 0⋅0001) at 400 g/d versus 0 g/d. Although there is a dose-risk attenuation above 400 g/d, milk consumption nevertheless continued to exhibit elevated risk of hip fracture, compared to zero intake, up to 750 g/d. Meanwhile, the analysis of five cohort studies of yoghurt intake per 250 g/d found a linear inverse association with fracture risk (RR 0⋅85, 95 % CI 0⋅82, 0⋅89), as did the five studies of cheese intake per 43 g/d (~1 serving/day) (RR 0⋅81, 95 % CI 0⋅72, 0⋅92); these studies did not control for socioeconomic status. However, no apparent association between total dairy intake and hip fracture (RR per 250 g/d of total dairy = 0⋅97, 95 % CI 0⋅93, 1⋅004; P = 0⋅079). There were both non-linear effects and overall elevated risk of hip fracture associated with greater milk intake, while lower risks of hip fracture were reported for higher yoghurt and cheese intakes.

Correction: Ramadan fasting and weight change trajectories: Time-varying association of weight during and after Ramadan in low-income and refugee populations.

[This corrects the article DOI: 10.1371/journal.pgph.0000371.].

Dose response between physical activity and risk of coronary heart disease: a meta-analysis.

BACKGROUND: No reviews have quantified the specific amounts of physical activity required for lower risks of coronary heart disease when assessing the dose-response relation. Instead, previous reviews have used qualitative estimates such as low, moderate, and high physical activity. METHODS AND RESULTS: We performed an aggregate data meta-analysis of epidemiological studies investigating physical activity and primary prevention of CHD. We included prospective cohort studies published in English since 1995. After reviewing 3194 abstracts, we included 33 studies. We used random-effects generalized least squares spline models for trend estimation to derive pooled dose-response estimates. Among the 33 studies, 9 allowed quantitative estimates of leisure-time physical activity. Individuals who engaged in the equivalent of 150 min/wk of moderate-intensity leisure-time physical activity (minimum amount, 2008 U.S. federal guidelines) had a 14% lower coronary heart disease risk (relative risk, 0.86; 95% confidence interval, 0.77 to 0.96) compared with those reporting no leisure-time physical activity. Those engaging in the equivalent of 300 min/wk of moderate-intensity leisure-time physical activity (2008 U.S. federal guidelines for additional benefits) had a 20% (relative risk, 0.80; 95% confidence interval, 0.74 to 0.88) lower risk. At higher levels of physical activity, relative risks were modestly lower. People who were physically active at levels lower than the minimum recommended amount also had significantly lower risk of coronary heart disease. There was a significant interaction by sex (P=0.03); the association was stronger among women than men. CONCLUSIONS: These findings provide quantitative data supporting US physical activity guidelines that stipulate that "some physical activity is better than none" and "additional benefits occur with more physical activity."