Gastrointestinal manifestations in pediatric and adult patients with Rett syndrome: an analysis of US claims and physician survey data.

Aim: Patients with Rett syndrome (RTT) experience gastrointestinal (GI) manifestations. This study aimed to describe the prevalence of GI manifestations and the associated medical costs in patients with RTT in the USA. Patients & Methods: The study combined an insurance claims database analysis with a survey of 100 physicians experienced in RTT management. Results: GI manifestations affected 43.0% of 5940 patients, with increased prevalence in pediatric patients (45.6%) relative to adult patients (40.2%). Annualized mean medical cost of managing GI manifestations was $4473. Only 5.9-8.2% of neurologists and pediatricians ranked GI symptom management among the five most important treatment goals. Conclusion: Patients with RTT experience a high burden of GI manifestations, which translate to considerable medical costs. Importantly, the prevalence of GI manifestations was likely underestimated in this study, as only those symptoms which resulted in a healthcare encounter were captured.

Economic Burden of Delayed Diagnosis in Patients with Pulmonary Arterial Hypertension (PAH).

BACKGROUND: The aim of this study was to assess health care resource utilization (HRU) and costs associated with delayed pulmonary arterial hypertension (PAH) diagnosis in the United States. METHODS: Eligible adults with newly diagnosed PAH from Optum's de-identified Clinformatics® Data Mart Database (2016-2021) were assigned to mutually exclusive cohorts based on time between first PAH-related symptom and first PAH diagnosis (i.e., ≤12 months' delay, >12 to ≤24 months' delay, >24 months' delay). All-cause HRU and health care costs per patient per month (PPPM) were assessed during the first year following diagnosis and compared across cohorts using regression analysis adjusted for baseline covariates. Sensitivity analyses were conducted to assess outcomes during all available follow-up post-diagnosis. RESULTS: Among 538 patients (mean age: 65.6 years; 60.6% female), 60.8% had ≤12 months' delay, 23.4% had a delay of >12 to ≤24 months, and 15.8% had >24 months' delay. Compared with ≤12 months, delays of >12 to ≤24 months and >24 months were associated with increased hospitalizations (incidence rate ratio [95% confidence interval]: 1.40 [1.11-1.71] vs 1.71 [1.29-2.12]) and outpatient visits (1.17 [1.06-1.30] vs 1.26 [1.08-1.41]). Longer delays were also associated with more intensive care unit (ICU) stays and 30-day readmissions. Diagnosis delays translated into excess costs PPPM of US$3986 [1439-6436] for >12 to ≤24 months and US$5366 [2107-8524] for >24 months compared with ≤12 months' delay; increased hospitalization costs (US$3248 [1108-5135] and US$4048 [1401-6342], respectively) being the driver. Sensitivity analyses yielded similar trends. CONCLUSIONS: Delayed PAH diagnosis is associated with significant incremental economic burden post-diagnosis, driven by hospitalizations including ICU stays and 30-day readmissions, highlighting the need for increased awareness and a potential benefit of earlier screening.

Real-world clinical management of individuals with Rett syndrome: a physician survey.

BACKGROUND: Rett syndrome (RTT) is a severe neurodevelopmental disorder. Management strategies are heterogeneous with no clear definition of success. This study describes physician decision-making regarding diagnosis, therapeutic goals, and management strategies to better understand RTT clinical management in the US. METHODS: This study was conducted among practicing physicians, specifically neurologists and pediatricians in the US with experience treating ≥2 individuals with RTT, including ≥1 individuals within the past two years. In-depth interviews with five physicians informed survey development. A cross-sectional survey was then conducted among 100 physicians. RESULTS: Neurologists had treated more individuals with RTT (median: 12 vs. 5, p < 0.001) than pediatricians throughout their career and were more likely to report being "very comfortable" managing RTT (31 vs. 4%, p < 0.001). Among physicians with experience diagnosing RTT (93%), most evaluated symptoms (91%) or used genetic testing (86%) for RTT diagnoses; neurologists used the 2010 consensus diagnostic criteria more than pediatricians (54 vs. 29%; p = 0.012). Improving the quality of life (QOL) of individuals with RTT was the most important therapeutic goal among physicians, followed by improving caregivers' QOL. Most physicians used clinical practice guidelines to monitor the progress of individuals with RTT, although neurologists relied more on clinical scales than pediatricians. Among all physicians, the most commonly treated symptoms included behavioral issues, epilepsy/seizures, and feeding issues. Management strategies varied by symptom, with referral to appropriate specialists being common across symptoms. A large proportion of physicians (37%) identified the lack of novel therapies and reliance on symptom-specific management as an unmet need. CONCLUSION: Although most physicians had experience and were comfortable diagnosing and treating individuals with RTT, better education and support among pediatricians is warranted. Additionally, novel treatments that target multiple symptoms associated with RTT could reduce the burden and improve the QOL of individuals with RTT and their caregivers.

Plant-Based Diet Index and Metabolic Risk in Men: Exploring the Role of the Gut Microbiome.

BACKGROUND: Healthy plant-based diet index (hPDI) is associated with a lower risk of cardiometabolic conditions, but its association as well as interactions with microbiome have not been elucidated. OBJECTIVES: We aimed to investigate the interrelations between hPDI, gut microbiome, and cardiometabolic risk markers. METHODS: hPDI was derived from dietary assessments by a validated FFQ and was examined in relation to metagenomic profiles of 911 fecal samples collected from 303 men aged 71 ± 4 y with an average BMI (in kg/m2) of 25.2 ± 3.6 in the Men's Lifestyle Validation Study. Principal coordinate (PCo) analysis based on Bray-Curtis dissimilarity was conducted, and interactions between hPDI and PCo were examined by using a metabolic risk score composed of blood lipids, BMI, and glycated hemoglobin. RESULTS: After multivariable adjustment, hPDI was significantly associated with the relative abundance of 7 species and 9 pathways. In particular, higher hPDI was significantly associated with a higher relative abundance of Bacteroides cellulosilyticus and Eubacterium eligens, amino acid biosynthesis pathways (l-isoleucine biosynthesis I and III and l-valine biosynthesis), and the pathway of pyruvate fermentation to isobutanol. A favorable association between hPDI and the metabolic risk score was more pronounced among men with a higher PCo characterized by higher abundance of Bacteroides uniformis and lower abundance of Prevotella copri. At the individual species level, a similar interaction was also observed between hPDI and P. copri, as well as with Clostridium clostridioforme or Blautia hydrogenotrophica (all P-interaction < 0.01). CONCLUSION: A greater adherence to a healthy plant-based diet by older men was associated with a microbial profile characterized by a higher abundance of multiple species, including B. cellulosilyticus and E. eligens, as well as pathways in amino acid metabolism and pyruvate fermentation. In addition, inverse associations between healthy plant-based diet and human metabolic risk may partially depend on microbial compositions.

Persistence to hypomethylating agents and clinical and economic outcomes among patients with myelodysplastic syndromes.

OBJECTIVES: To evaluate hypomethylating agent (HMA) persistence in patients with myelodysplastic syndromes (MDS), and examine its association with healthcare resource utilization (HRU) and progression to acute myeloid leukemia (AML). METHODS: A total of 2,400 adults diagnosed with MDS initiating HMAs were included from IBM MarketScan databases during 1/1/2011-3/31/2018. The index date was HMA initiation following MDS diagnosis. Patients were classified according to their persistence status by the end of a fixed 'landmark period' of 4 months post-index. RESULTS: Median persistence to HMAs was 5.6 months (95% CI: 5.2, 6.1); HMA non-persistence increased with time. Non-persistent patients had a significantly higher non-HMA-related HRU burden than persistent patients [adjusted incidence rate ratios, outpatient visits: 1.12 (95% CI: 1.10, 1.14); inpatient visits: 1.48 (95% CI: 1.30, 1.69); emergency department visits 1.30 (95% CI: 1.12, 1.50); all p-values < 0.001]. All-cause and HMA-related outpatient visits were lower among non-persistent patients, likely because of fewer HMA administration-related visits. The incidence rate of AML was numerically, although not significantly, higher in non-persistent patients, when starting follow-up at the end of the landmark period. When follow-up began at the index date, non-persistent patients had a significantly higher rate of AML [adjusted hazard ratio, 1.88 (95% CI: 1.53, 2.32); p-value < 0.001]. CONCLUSIONS: HMA non-persistence, which increased over time, was associated with significantly higher non-HMA-related HRU, and numerically higher AML progression in MDS patients initiating HMAs. Future studies should evaluate predictors of HMA non-persistence in this patient population.

Veterans Affairs Prostate Cancer Treatment Sequencing (VAPCaTS): A Real-World Evidence Study of Men with Metastatic Prostate Cancer.

INTRODUCTION: Limited real-world data are available on treatment sequences for patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy plus docetaxel or abiraterone who progress to castrate resistance. METHODS: Veterans Health Affairs electronic medical records were used to analyze 240 men treated for metastatic hormone-sensitive prostate cancer with androgen deprivation therapy plus either docetaxel ("docetaxel cohort," 208 patients, selected to be overrepresented, July 2014 to August 2018) or abiraterone ("abiraterone cohort," 32 patients, December 2016 to September 2018) who received at least 1 treatment after progressing to castrate resistance. RESULTS: For docetaxel and abiraterone cohorts, respectively, mean age at androgen deprivation therapy initiation was 65 and 72 years, and median followup was 2.2 and 1.4 years. Overall, the maximum number of metastatic castrate resistant prostate cancer treatment lines was 6; 106 patients (44%) had 1, 71 (30%) had 2, and 63 (26%) had 3 or more lines. Most patients received an androgen receptor targeted agent for initial metastatic castrate resistant prostate cancer treatment (94% vs 78% in docetaxel vs abiraterone cohort). Androgen receptor targeted agents were given consecutively to 62% of the docetaxel cohort receiving second line therapy, and to 78% of the abiraterone cohort. Across all metastatic castrate resistant prostate cancer treatment lines 72 (30%) received a taxane (47 docetaxel and 41 cabazitaxel). CONCLUSIONS: Most patients received androgen receptor targeted agents as first metastatic castrate resistant prostate cancer treatment regardless of initial metastatic hormone-sensitive treatment. Moreover, a large proportion were treated with consecutive androgen receptor targeted agents. Given recent evidence suggesting poorer outcomes with this treatment in some patients, longer followup is needed to assess the association between treatment sequence and optimal outcomes.

Red meat intake and risk of coronary heart disease among US men: prospective cohort study.

OBJECTIVES: To study total, processed, and unprocessed red meat in relation to risk of coronary heart disease (CHD) and to estimate the effects of substituting other protein sources for red meat with CHD risk. DESIGN: Prospective cohort study with repeated measures of diet and lifestyle factors. SETTING: Health Professionals Follow-Up Study cohort, United States, 1986-2016. PARTICIPANTS: 43 272 men without cardiovascular disease or cancer at baseline. MAIN OUTCOME MEASURES: The primary outcome was total CHD, comprised of acute non-fatal myocardial infarction or fatal CHD. Cox models were used to estimate hazard ratios and 95% confidence intervals across categories of red meat consumption. Substitution analyses were conducted by comparing coefficients for red meat and the alternative food in models, including red meat and alternative foods as continuous variables. RESULTS: During 1 023 872 person years of follow-up, 4456 incident CHD events were documented of which 1860 were fatal. After multivariate adjustment for dietary and non-dietary risk factors, total, unprocessed, and processed red meat intake were each associated with a modestly higher risk of CHD (hazard ratio for one serving per day increment: 1.12 (95% confidence interval 1.06 to 1.18) for total red meat, 1.11 (1.02 to 1.21) for unprocessed red meat, and 1.15 (1.06 to 1.25) for processed red meat). Compared with red meat, the intake of one serving per day of combined plant protein sources (nuts, legumes, and soy) was associated with a lower risk of CHD (0.86 (0.80 to 0.93) compared with total red meat, 0.87 (0.79 to 0.95) compared with unprocessed red meat, and 0.83 (0.76 to 0.91) compared with processed red meat). Substitutions of whole grains and dairy products for total red meat and eggs for processed red meat were also associated with lower CHD risk. CONCLUSIONS: Substituting high quality plant foods such as legumes, nuts, or soy for red meat might reduce the risk of CHD. Substituting whole grains and dairy products for total red meat, and eggs for processed red meat, might also reduce this risk.

Changes in Plant-Based Diet Quality and Total and Cause-Specific Mortality.

BACKGROUND: Plant-based diets have been associated with lower risk of type 2 diabetes mellitus and cardiovascular disease (CVD) and are recommended for both health and environmental benefits. However, the association between changes in plant-based diet quality and mortality remains unclear. METHODS: We investigated the associations between 12-year changes (from 1986 to 1998) in plant-based diet quality assessed by 3 plant-based diet indices (score range, 18-90)-an overall plant-based diet index (PDI), a healthful PDI, and an unhealthful PDI-and subsequent total and cause-specific mortality (1998-2014). Participants were 49 407 women in the Nurses' Health Study (NHS) and 25 907 men in the Health Professionals Follow-Up Study (HPFS) who were free from CVD and cancer in 1998. Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: We documented 10 686 deaths including 2046 CVD deaths and 3091 cancer deaths in the NHS over 725 316 person-years of follow-up and 6490 deaths including 1872 CVD deaths and 1772 cancer deaths in the HPFS over 371 322 person-years of follow-up. Compared with participants whose indices remained stable, among those with the greatest increases in diet scores (highest quintile), the pooled multivariable-adjusted HRs for total mortality were 0.95 (95% CI, 0.90-1.00) for PDI, 0.90 (95% CI, 0.85-0.95) for healthful PDI, and 1.12 (95% CI, 1.07-1.18) for unhealthful PDI. Among participants with the greatest decrease (lowest quintile), the multivariable-adjusted HRs were 1.09 (95% CI, 1.04-1.15) for PDI, 1.10 (95% CI, 1.05-1.15) for healthful PDI, and 0.93 (95% CI, 0.88-0.98) for unhealthful PDI. For CVD mortality, the risk associated with a 10-point increase in each PDI was 7% lower (95% CI, 1-12%) for PDI, 9% lower (95% CI, 4-14%) for healthful PDI, and 8% higher (95% CI, 2-14%) for unhealthful PDI. There were no consistent associations between changes in plant-based diet indices and cancer mortality. CONCLUSIONS: Improving plant-based diet quality over a 12-year period was associated with a lower risk of total and CVD mortality, whereas increased consumption of an unhealthful plant-based diet was associated with a higher risk of total and CVD mortality.

Association of changes in red meat consumption with total and cause specific mortality among US women and men: two prospective cohort studies.

OBJECTIVE: To evaluate the association of changes in red meat consumption with total and cause specific mortality in women and men. DESIGN: Two prospective cohort studies with repeated measures of diet and lifestyle factors. SETTING: Nurses' Health Study and the Health Professionals Follow-up Study, United States. PARTICIPANTS: 53 553 women and 27 916 men without cardiovascular disease or cancer at baseline. MAIN OUTCOME MEASURE: Death confirmed by state vital statistics records, the national death index, or reported by families and the postal system. RESULTS: 14 019 deaths occurred during 1.2 million person years of follow-up. Increases in red meat consumption over eight years were associated with a higher mortality risk in the subsequent eight years among women and men (both P for trend<0.05, P for heterogeneity=0.97). An increase in total red meat consumption of at least half a serving per day was associated with a 10% higher mortality risk (pooled hazard ratio 1.10, 95% confidence interval 1.04 to 1.17). For processed and unprocessed red meat consumption, an increase of at least half a serving per day was associated with a 13% higher mortality risk (1.13, 1.04 to 1.23) and a 9% higher mortality risk (1.09, 1.02 to 1.17), respectively. A decrease in consumption of processed or unprocessed red meat of at least half a serving per day was not associated with mortality risk. The association between increased red meat consumption and mortality risk was consistent across subgroups defined by age, physical activity, dietary quality, smoking status, or alcohol consumption. CONCLUSION: Increases in red meat consumption, especially processed meat, were associated with higher overall mortality rates.

Changes in intake of plant-based diets and weight change: results from 3 prospective cohort studies.

BACKGROUND: Studies have found beneficial effects of plant-based diets on weight. However, not all plant foods are necessarily beneficial. OBJECTIVES: The aim of this study was to examine associations of changes in intake of 3 variations of plant-based diet indices (overall, healthful, and unhealthful) with weight change over 4-y intervals spanning >20 y. METHODS: Data from 3 ongoing prospective observational cohort studies in the United States were used, namely the Nurses' Health Study (NHS), NHS2, and the Health Professionals Follow-up Study (HPFS), with 126,982 adult men and women. Self-reported diet data were collected every 4 y, and self-reported weight data were used to compute weight change every 4 y over >20 y of follow-up. RESULTS: On average, participants gained a mean of 0.90 kg (HPFS) to 1.98 kg (NHS2) over 4-y intervals. Different types of plant-based diet indices were associated with different amounts of weight gain. After adjusting for several potential confounders, including concomitant changes in other lifestyle factors, a 1-SD increase in intake of an overall plant-based diet index was associated with 0.04 kg less weight gain over 4-y periods (95% CI: 0.05, 0.02 kg; P < 0.001). A 1-SD increase in intake of a healthful version of a plant-based diet index (emphasizing whole grains, fruits/vegetables, nuts/legumes, vegetable oils, tea/coffee) was associated with 0.68 kg less weight gain over 4-y periods (95% CI: 0.69, 0.66 kg; P < 0.001). Conversely, a 1-SD increase in an unhealthful version of a plant-based diet index (emphasizing refined grains, potato/fries, sweets, sweetened drinks/juices) was associated with 0.36 kg more weight gain (95% CI: 0.34, 0.37 kg, P < 0.001). CONCLUSION: Plant-based diets, especially when rich in healthier plant foods, are associated with less weight gain over 4-y intervals. This supports current recommendations to increase intake of healthy plant foods, and reducing intake of less-healthy plant foods and animal foods, for improved health outcomes.

Meta-Analysis of Randomized Controlled Trials of Red Meat Consumption in Comparison With Various Comparison Diets on Cardiovascular Risk Factors.

BACKGROUND: Findings among randomized controlled trials evaluating the effect of red meat on cardiovascular disease risk factors are inconsistent. We provide an updated meta-analysis of randomized controlled trials on red meat and cardiovascular risk factors and determine whether the relationship depends on the composition of the comparison diet, hypothesizing that plant sources would be relatively beneficial. METHODS: We conducted a systematic PubMed search of randomized controlled trials published up until July 2017 comparing diets with red meat with diets that replaced red meat with a variety of foods. We stratified comparison diets into high-quality plant protein sources (legumes, soy, nuts); chicken/poultry/fish; fish only; poultry only; mixed animal protein sources (including dairy); carbohydrates (low-quality refined grains and simple sugars, such as white bread, pasta, rice, cookies/biscuits); or usual diet. We performed random-effects meta-analyses comparing differences in changes of blood lipids, apolipoproteins, and blood pressure for all studies combined and stratified by specific comparison diets. RESULTS: Thirty-six studies totaling 1803 participants were included. There were no significant differences between red meat and all comparison diets combined for changes in blood concentrations of total, low-density lipoprotein, or high-density lipoprotein cholesterol, apolipoproteins A1 and B, or blood pressure. Relative to the comparison diets combined, red meat resulted in lesser decreases in triglycerides (weighted mean difference [WMD], 0.065 mmol/L; 95% CI, 0.000-0.129; P for heterogeneity <0.01). When analyzed by specific comparison diets, relative to high-quality plant protein sources, red meat yielded lesser decreases in total cholesterol (WMD, 0.264 mmol/L; 95% CI, 0.144-0.383; P<0.001) and low-density lipoprotein (WMD, 0.198 mmol/L; 95% CI, 0.065-0.330; P=0.003). In comparison with fish, red meat yielded greater decreases in low-density lipoprotein (WMD, -0.173 mmol/L; 95% CI, -0.260 to -0.086; P<0.001) and high-density lipoprotein (WMD, -0.065 mmol/L; 95% CI, -0.109 to -0.020; P=0.004). In comparison with carbohydrates, red meat yielded greater decreases in triglycerides (WMD, -0.181 mmol/L; 95% CI, -0.349 to -0.013). CONCLUSIONS: Inconsistencies regarding the effects of red meat on cardiovascular disease risk factors are attributable, in part, to the composition of the comparison diet. Substituting red meat with high-quality plant protein sources, but not with fish or low-quality carbohydrates, leads to more favorable changes in blood lipids and lipoproteins.

Long-Term Change in both Dietary Insulinemic and Inflammatory Potential Is Associated with Weight Gain in Adult Women and Men.

BACKGROUND: The influence of long-term dietary patterns on weight gain and the underlying potential biological mechanisms are not fully understood. OBJECTIVE: We prospectively examined the association of changes in 2 empirical hypothesis-oriented dietary patterns (insulinemic and inflammatory) and weight gain over 24 y at 4-y intervals. METHODS: We followed 54,397 women in the Nurses' Health Study and 33,043 men in the Health Professionals Follow-Up Study (1986-2010), and computed the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores from food frequency questionnaires administered every 4 y. Both scores are weighted sums of 18 food groups, which characterize dietary insulinemic or inflammatory potential based on plasma levels of insulin response or inflammatory biomarkers. We used multivariable-adjusted linear regression to examine 4-y changes in the dietary scores and weight change within the same period. RESULTS: The mean baseline body mass index (BMI, in kg/m2) was 25.4. Compared with participants who made minimal dietary changes (quintile 3) over 6 4-y periods; participants who changed their diets toward lower insulinemic or inflammatory potential (quintile 1) gained significantly less weight (in kilograms per 4 y) independent of total energy intake, BMI, physical activity, and smoking status: EDIH: -0.65 (95% CI: -0.73, -0.57), EDIP: -0.29 (-0.37, -0.21) among women; and EDIH: -0.60 (-0.71, -0.49), EDIP: -0.19 (-0.27, -0.07) among men. In contrast, those who changed their diets toward higher insulinemic or inflammatory potential (quintile 5) gained significantly more weight: EDIH: 0.43 (0.36, 0.51), EDIP: 0.15 (0.07, 0.23) among women; and EDIH: 0.49 (0.38, 0.59), EDIP: 0.22 (0.11, 0.33) among men (P-trend < 0.0001 for all comparisons). Associations were stronger among individuals who were overweight or obese, younger, less physically active, and had never smoked. CONCLUSIONS: High dietary insulinemic and inflammatory potential is associated with substantial long-term weight gain in adult men and women independent of total energy intake. Dietary patterns with low insulinemic and inflammatory potential may aid in weight gain prevention.

Change in Plant-Based Diet Quality Is Associated with Changes in Plasma Adiposity-Associated Biomarker Concentrations in Women.

BACKGROUND: A healthful plant-based diet is associated with lower risk of cardiometabolic diseases. However, it is still unclear whether such benefits are due to its favorable effects on adiposity-associated biomarkers. OBJECTIVE: We investigated the associations between biomarkers and 3 plant-based diet indices: an overall plant-based diet index (PDI); a healthful plant-based diet index (hPDI); and an unhealthful plant-based diet index (uPDI). METHODS: In the Nurses' Health Study II, 831 women [baseline mean age: 45 y; body mass index (BMI, kg/m2): 24.6] were randomly selected from those who provided 2 blood samples in 1996-1999 and 2010-2011 to measure plasma concentrations of adiponectin, leptin, soluble leptin receptor (sOB-R), insulin, retinol-binding protein-4, high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6). Plant-based diet indices were derived from semiquantitative food frequency questionnaires assessed at each blood collection. Linear mixed models were used to evaluate cross-sectional associations, and general linear models were used to evaluate longitudinal associations. RESULTS: In cross-sectional analyses with multivariable adjustment including BMI, higher hPDI was associated with lower concentrations of leptin, insulin, and hsCRP, and higher adiponectin and sOB-R concentrations (biomarker differences per 10-point higher hPDI: -7.2%, -10.0%, -13.6%, 3.0%, and 1.9%, respectively; P ≤ 0.025). A higher uPDI was associated with higher concentrations of leptin and insulin (4.4% and 4.8%, respectively; P ≤ 0.048). In longitudinal analyses with multivariable adjustment including weight change, an increase in hPDI (improved plant-based diet quality) was inversely associated with changes in leptin and hsCRP (biomarker changes per 10-point hPDI increase: -7.7% and -17.8%, respectively; P ≤ 0.005), whereas an increase in uPDI (worsened plant-based diet quality) was positively associated with changes in leptin, hsCRP, and IL-6 (10.1%, 13.5%, and 12.4%, respectively; P ≤ 0.021). CONCLUSIONS: Adherence to a healthful plant-based diet is associated with favorable long-term changes in adiposity-associated biomarker concentrations in women.

Physical Activity Among Adolescents in India: A Qualitative Study of Barriers and Enablers.

Inadequate physical activity (PA) levels are reported in Indian youth, with lowest levels among adolescents, particularly girls. We aimed to identify barriers to and enablers of PA among school children in New Delhi and examine potential differences by gender and school type (government vs. private). A total of 174 students (private school students = 88, 47% girls; government school students = 86, 48% girls) aged 12 to 16 years from two Delhi schools participated in 16 focus group discussions (FGDs) conducted by bilingual moderators. We conducted FGDs separately for girls and boys, for students in Grades VIII and IX, and for private and government schools. We conducted FGDs among government school students in Hindi and translated the transcriptions to English for analysis. We coded transcriptions using a combination of inductive and deductive approaches, guided by the "youth physical activity promotion model." We identified various personal, social, and environmental barriers and enablers. Personal barriers: Private school girls cited body image-related negative consequences of PA participation. Social barriers: Girls from both schools faced more social censure for participating in PA. Environmental barriers: Reduced opportunity for PA in schools was commonly reported across all participants. Personal enablers: All participants reported perceived health benefits of PA. Social enablers: Several participants mentioned active parents and sports role models as motivators for increasing PA. Few environmental enablers were identified. This study highlights the need for further investment in physical activity within schools and for gender-sensitive policies for encouraging PA participation among adolescents in India.

Perspective: Are Large, Simple Trials the Solution for Nutrition Research?

Nutritional research and policies have been criticized for relying on observational evidence, using self-report diet assessment methods, and supposedly being unable to present a consensus on what constitutes a healthy diet. In particular, it is often asserted that for progress to occur in nutrition science, large, simple trials, which have worked well in evaluating the efficacy of drugs, need to replace most observational research and small trials in nutrition. However, this idea is infeasible, and is unlikely to advance nutritional sciences or improve policies. This article addresses some commonly held and unfounded "myths" surrounding dietary assessments, effect sizes, and confounding, demonstrating how carefully conducted observational studies can provide reliable and reproducible evidence on diet and health. Also, there is a strong consensus among nutritional researchers and practitioners about the basic elements of a healthy diet. To move forward, we should continue to improve study design and diet assessment methodologies, reduce measurement errors, and leverage new technologies. Advances in the field lie in coalescing evidence from multiple study designs, methodologies, and technologies, and translating what we already know into policy and practice, so we can improve diet quality and enhance health in an equitable and sustainable manner across the world.

Plant-based diets and cardiovascular health.

Plant-based diets, defined in terms of low frequency of animal food consumption, have been increasingly recommended for their health benefits. Numerous studies have found plant-based diets, especially when rich in high quality plant foods such as whole grains, fruits, vegetables, and nuts, to be associated with lower risk of cardiovascular outcomes and intermediate risk factors. This review summarizes the current evidence base examining the associations of plant-based diets with cardiovascular endpoints, and discusses the potential biological mechanisms underlying their health effects, practical recommendations and applications of this research, and directions for future research. Healthful plant-based diets should be recommended as an environmentally sustainable dietary option for improved cardiovascular health.

Association between empirically derived dietary patterns with blood lipids, fasting blood glucose and blood pressure in adults - the India migration study.

BACKGROUND: Dietary patterns (DPs) in India are heterogenous. To date, data on association of indigenous DPs in India with risk factors of nutrition-related noncommunicable diseases (cardiovascular disease and diabetes), leading causes of premature death and disability, are limited. We aimed to evaluate the associations of empirically-derived DPs with blood lipids, fasting glucose and blood pressure levels in an adult Indian population recruited across four geographical regions of India. METHODS: We used cross-sectional data from the Indian Migration Study (2005-2007). Study participants included urban migrants, their rural siblings and urban residents and their urban siblings from Lucknow, Nagpur, Hyderabad and Bangalore (n = 7067, mean age 40.8 yrs). Information on diet (validated interviewer-administered, 184-item semi-quantitative food frequency questionnaire), tobacco consumption, alcohol intake, physical activity, medical history, as well as anthropometric measurements were collected. Fasting-blood samples were collected for estimation of blood lipids and glucose. Principal component analysis (PCA) was used to identify major DPs based on eigenvalue> 1 and component interpretability. Robust standard error multivariable linear regression models were used to investigate the association of DPs (tertiles) with total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides, fasting-blood glucose (FBG), systolic and diastolic blood pressure (SBP and DBP) levels. RESULTS: Three major DPs were identified: 'cereal-savoury' (cooked grains, rice/rice-based dishes, snacks, condiments, soups, nuts), 'fruit-vegetable-sweets-snacks' (Western cereals, vegetables, fruit, fruit juices, cooked milk products, snacks, sugars, sweets) and 'animal food' (red meat, poultry, fish/seafood, eggs) patterns. High intake of the 'animal food' pattern was positively associated with levels of TC (ß = 0.10 mmol/L; 95% CI: 0.02, 0.17 mmol/L; p-trend = 0.013); LDL-C (ß = 0.07 mmol/L; 95% CI: 0.004, 0.14 mmol/L; p-trend = 0.041); HDL-C (ß = 0.02 mmol/L; 95% CI: 0.004, 0.04 mmol/L; p-trend = 0.016), FBG: (ß = 0.09 mmol/L; 95% CI: 0.01, 0.16 mmol/L; p-trend = 0.021) SBP (ß = 1.2 mm/Hg; 95% CI: 0.1, 2.3 mm/Hg; p-trend = 0.032); DBP: (ß = 0.9 mm/Hg; 95% CI: 0.2, 1.5 mm/Hg; p-trend = 0.013). The 'cereal-savoury' and 'fruit-vegetable-sweets-snacks' patterns showed no association with any parameter except for a positive association with diastolic blood pressure for high intake of 'fruits-vegetables-sweets-snacks' pattern. CONCLUSION: Our results indicate positive associations of the 'animal food' pattern with cardio-metabolic risk factors in India. Further longitudinal assessments of dietary patterns in India are required to validate the findings.

Healthful and Unhealthful Plant-Based Diets and the Risk of Coronary Heart Disease in U.S. Adults.

BACKGROUND: Plant-based diets are recommended for coronary heart disease (CHD) prevention. However, not all plant foods are necessarily beneficial for health. OBJECTIVES: This study sought to examine associations between plant-based diet indices and CHD incidence. METHODS: We included 73,710 women in NHS (Nurses' Health Study) (1984 to 2012), 92,329 women in NHS2 (1991 to 2013), and 43,259 men in Health Professionals Follow-up Study (1986 to 2012), free of chronic diseases at baseline. We created an overall plant-based diet index (PDI) from repeated semiquantitative food-frequency questionnaire data, by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful plant-based diet index (hPDI) where healthy plant foods (whole grains, fruits/vegetables, nuts/legumes, oils, tea/coffee) received positive scores, whereas less-healthy plant foods (juices/sweetened beverages, refined grains, potatoes/fries, sweets) and animal foods received reverse scores. To create an unhealthful PDI (uPDI), we gave positive scores to less-healthy plant foods and reverse scores to animal and healthy plant foods. RESULTS: Over 4,833,042 person-years of follow-up, we documented 8,631 incident CHD cases. In pooled multivariable analysis, higher adherence to PDI was independently inversely associated with CHD (hazard ratio [HR] comparing extreme deciles: 0.92; 95% confidence interval [CI]: 0.83 to 1.01; p trend = 0.003). This inverse association was stronger for hDPI (HR: 0.75; 95% CI: 0.68 to 0.83; p trend <0.001). Conversely, uPDI was positively associated with CHD (HR: 1.32; 95% CI: 1.20 to 1.46; p trend <0.001). CONCLUSIONS: Higher intake of a plant-based diet index rich in healthier plant foods is associated with substantially lower CHD risk, whereas a plant-based diet index that emphasizes less-healthy plant foods is associated with higher CHD risk.

Weight History and All-Cause and Cause-Specific Mortality in Three Prospective Cohort Studies.

BACKGROUND: The relationship between body mass index (BMI) and mortality is controversial. OBJECTIVE: To investigate the relationship between maximum BMI over 16 years and subsequent mortality. DESIGN: 3 prospective cohort studies. SETTING: Nurses' Health Study I and II and Health Professionals Follow-Up Study. PARTICIPANTS: 225 072 men and women with 32 571 deaths observed over a mean of 12.3 years of follow-up. MEASUREMENTS: Maximum BMI over 16 years of weight history and all-cause and cause-specific mortality. RESULTS: Maximum BMIs in the overweight (25.0 to 29.9 kg/m2) (multivariate hazard ratio [HR], 1.06 [95% CI, 1.03 to 1.08]), obese I (30.0 to 34.9 kg/m2) (HR, 1.24 [CI, 1.20 to 1.29]), and obese II (≥35.0 kg/m2) (HR, 1.73 [CI, 1.66 to 1.80]) categories were associated with increases in risk for all-cause death. The pattern of excess risk with a maximum BMI above normal weight was maintained across strata defined by smoking status, sex, and age, but the excess was greatest among those younger than 70 years and never-smokers. In contrast, a significant inverse association between overweight and mortality (HR, 0.96 [CI, 0.94 to 0.99]) was observed when BMI was defined using a single baseline measurement. Maximum overweight was also associated with increased cause-specific mortality, including death from cardiovascular disease and coronary heart disease. LIMITATION: Residual confounding and misclassification. CONCLUSION: The paradoxical association between overweight and mortality is reversed in analyses incorporating weight history. Maximum BMI may be a useful metric to minimize reverse causation bias associated with a single baseline BMI assessment. PRIMARY FUNDING SOURCE: National Institutes of Health.