Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States.

Contemporary information on the fraction of cancers that potentially could be prevented is useful for priority setting in cancer prevention and control. Herein, the authors estimate the proportion and number of invasive cancer cases and deaths, overall (excluding nonmelanoma skin cancers) and for 26 cancer types, in adults aged 30 years and older in the United States in 2014, that were attributable to major, potentially modifiable exposures (cigarette smoking; secondhand smoke; excess body weight; alcohol intake; consumption of red and processed meat; low consumption of fruits/vegetables, dietary fiber, and dietary calcium; physical inactivity; ultraviolet radiation; and 6 cancer-associated infections). The numbers of cancer cases were obtained from the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute; the numbers of deaths were obtained from the CDC; risk factor prevalence estimates were obtained from nationally representative surveys; and associated relative risks of cancer were obtained from published, large-scale pooled analyses or meta-analyses. In the United States in 2014, an estimated 42.0% of all incident cancers (659,640 of 1570,975 cancers, excluding nonmelanoma skin cancers) and 45.1% of cancer deaths (265,150 of 587,521 deaths) were attributable to evaluated risk factors. Cigarette smoking accounted for the highest proportion of cancer cases (19.0%; 298,970 cases) and deaths (28.8%; 169,180 deaths), followed by excess body weight (7.8% and 6.5%, respectively) and alcohol intake (5.6% and 4.0%, respectively). Lung cancer had the highest number of cancers (184,970 cases) and deaths (132,960 deaths) attributable to evaluated risk factors, followed by colorectal cancer (76,910 cases and 28,290 deaths). These results, however, may underestimate the overall proportion of cancers attributable to modifiable factors, because the impact of all established risk factors could not be quantified, and many likely modifiable risk factors are not yet firmly established as causal. Nevertheless, these findings underscore the vast potential for reducing cancer morbidity and mortality through broad and equitable implementation of known preventive measures. CA Cancer J Clin 2018;68:31-54. © 2017 American Cancer Society.

Length of overnight fasting and six-year weight change in the Cancer Prevention Study-3.

BACKGROUND: Longer overnight fasting (ONF) is a potential strategy for weight control. While promising, the evidence from large population-based studies is limited. OBJECTIVE: To examine the association of self-reported ONF duration with three- and six-year weight change in the American Cancer Society's Cancer Prevention Study-3 (CPS-3) prospective cohort. METHODS: U.S. adult CPS-3 participants completed a 24-hour validated meal and snack timing and frequency grid (weekday and weekend) in 2015, from which weighted ONF hours were calculated. Participants reported body weight in 2015, 2018 and 2021. Three- and six-year weight change (kg, and % body weight) were assessed. RESULTS: Among 104,420 mostly female (78.5%) participants aged 52.7 +/- 9.5 (SD) years followed for six years, a one hour increase in ONF length was associated with a small but statistically significant reduction in weight gain over three- and six-year periods (multivariable-adjusted mean difference in % body weight= -0.02, 95% CI -0.05-0.00, p=0.03 and -0.04, 95 % CI, -0.07 to -0.01, p=0.007, respectively). The mean difference of 6-year % reduction in weight gain was slightly greater among individuals with overweight (-0.05, 95% CI, -0.10 to 0.00, p=0.05) and obesity (-0.06, 95% CI, -0.12 to 0.01, p=0.08) compared to those with healthy BMI (-0.03, 95% CI -0.07 to 0.01, p=0.13) or underweight (0.16, 95% CI, -0.04 to 0.36, p=0.13, pinteraction<0.0001). Stronger associations were observed among those ≤55 y than 56+ (pinteraction=0.01), and those with higher waist circumference (pinteraction<0.0001) but not by sex or earlier/later fasting period. CONCLUSIONS: Longer ONF was associated with slightly lower body weight in adult men and women over six years that was stronger among those with overweight or obesity, higher waist circumference, and those ≤age 55. The magnitude of weight change, though in the hypothesized direction, suggests that prolonged ONF may have modest impact on weight control over time.

Negative-Control Exposures: Adjusting for Unmeasured and Measured Confounders With Bounds for Remaining Bias.

Negative-control exposures can be used to detect and even adjust for confounding that remains after control of measured confounders. A newly described method allows the analyst to reduce residual confounding by unmeasured confounders U by using negative-control exposures to define and select a subcohort wherein the U-distribution among the exposed is similar to that among the unexposed. Here, we show that conventional methods can be used to control for measured confounders in conjunction with the new method to control for unmeasured ones. We also derive an expression for bias that remains after applying this approach. We express remaining bias in terms of a "balancing" parameter and show that this parameter is bounded by a summary variational distance between the U-distribution in the exposed and the unexposed. These measures describe and bound the extent of remaining confounding after using negative controls to adjust for unmeasured confounders with conventional control of measured confounders.

Ambient Air Quality and Fatal Asthma Exacerbations among Children in North Carolina.

BACKGROUND: Little is known about the role of air quality in fatal asthma exacerbations among children. METHODS: We collected information about 80 deaths that occurred in North Carolina from 2001 through 2016, among children aged 5-17 years, with asthma identified as the primary cause of death. We linked information about each death with county-level estimates of particulate matter ≤2.5 µm (PM2.5) and ozone (O3). Using the linked data, we conducted a case-crossover analysis of associations between PM2.5 and O3 lagged by 3-5 days with the odds of fatal asthma exacerbations. RESULTS: In the highest tertile of PM2.5 lag(3-5), the odds of a fatal exacerbation of asthma were more than twice the odds in the lowest tertile (odds ratio = 2.2; 95% confidence interval = 1.1, 4.6). CONCLUSION: These findings from North Carolina provide evidence to support the hypothesis that ambient air pollution increases the risk of fatal exacerbations of asthma among children.

Self-Reported Eating-Occasion Frequency and Timing are Reproducible and Relatively Valid in the American Cancer Society Cancer Prevention Study-3 Diet Assessment Substudy.

BACKGROUND: Accurate assessment of eating-occasion behaviors, such as timing, frequency, and consumption intervals, is important for evaluating associations with obesity and other chronic diseases. OBJECTIVES: The main objective of this study was to assess the relative validity of a 24-hour grid approach to assess eating-occasion timing and frequency in comparison to data derived from repeated 24-hour dietary recalls (DRs). A second objective was to assess the 1-year test-retest reproducibility of the 24-hour grid. METHODS: Between 2015 and 2016, 626 participants in the Cancer Prevention Study-3 (CPS-3) Diet Assessment Substudy (mean age, 52 years; age range, 31-70 years; 64% female; 64% non-Hispanic white, 22% non-Hispanic black, 14% Hispanic) completed 2 grids and up to 6 unannounced, telephone, interviewer-administered DRs over 1 year. Spearman correlations (ρ; 95% CIs) were calculated to assess reproducibility between the repeated eating-occasion grid-derived variables (e.g., numbers of snacks and meals per day, timing of eating occasions) and to assess relative validity by comparing the meal grid and DR-derived summary data separately for weekdays and weekend days. RESULTS: Reproducibility correlations for eating-occasion variables derived from the eating-occasion grids completed 1 year apart were ≥0.5 for the majority of variables analyzed for both weekdays and weekend days, including numbers of snacks and meals per day and timing of the first and last eating occasions of the day. Relative validity was highest among weekday variables and was ≥0.5 for the majority of variables, with correlations ranging from ρ values of 0.32 (number of meals per day) to 0.68 (hour of the first eating occasion). CONCLUSIONS: These findings suggest the eating-occasion grid used in CPS-3 has good reproducibility over 1 year and yields estimates comparable to those from a more detailed method of assessment of eating timing and frequency.

Associations of dietary and lifestyle inflammation scores with mortality due to CVD, cancer, and all causes among Black and White American men and women.

One potential mechanism by which diet and lifestyle may affect chronic disease risk and subsequent mortality is through chronic systemic inflammation. In this study, we investigated whether the inflammatory potentials of diet and lifestyle, separately and combined, were associated with all-cause, all-CVD and all-cancer mortality risk. We analysed data on 18 484 (of whom 4103 died during follow-up) Black and White men and women aged ≥45 years from the prospective REasons for Geographic and Racial Differences in Stroke study. Using baseline (2003-2007) Block 98 FFQ and lifestyle questionnaire data, we constructed the previously validated inflammation biomarker panel-weighted, 19-component dietary inflammation score (DIS) and 4-component lifestyle inflammation score (LIS) to reflect the overall inflammatory potential of diet and lifestyle. From multivariable Cox proportional hazards models, the hazards ratios (HR) and their 95 % CI for the DIS-all-cause mortality and LIS-all-cause mortality risk associations were 1·32 (95 % CI (1·18, 1·47); Pfor trend < 0·01) and 1·25 (95 % CI (1·12, 1·38); Pfor trend < 0·01), respectively, among those in the highest relative to the lowest quintiles. The findings were similar by sex and race and for all-cancer mortality, but weaker for all-CVD mortality. The joint HR for all-cause mortality among those in the highest relative to the lowest quintiles of both the DIS and LIS was 1·91 (95 % CI 1·57, 2·33) (Pfor interaction < 0·01). Diet and lifestyle, via their contributions to systemic inflammation, separately, but perhaps especially jointly, may be associated with higher mortality risk among men and women.

Changes in asthma emergency department visits in the United States during the COVID-19 pandemic.

OBJECTIVE: A better understanding of the impacts of the Coronavirus disease 2019 (COVID-19) pandemic on emergency department (ED) visits for asthma is needed to improve asthma control. METHODS: Using data from the National Syndromic Surveillance Program (NSSP), we assessed changes in average weekly asthma ED visits in the United States in 3 surveillance periods: 1) March 15, 2020-January 2, 2021; 2) January 3, 2021-January 1, 2022; and 3) January 2-March 5, 2022, relative to pre-pandemic comparison periods between December 30, 2018 and December 28, 2019. For each surveillance period, we assessed changes in asthma ED visits by age group and sex. RESULTS: For the surveillance period beginning March 15, 2020, average weekly asthma ED visits declined 31% relative to what was observed during the comparison period - that is, from 45,276 visits/week in 2019 to 31,374 visits/week in 2020. Declines of over 19% and 26% were observed for 2021 and 2022, respectively, relative to the comparison periods. In all surveillance periods, the largest declines occurred among children, especially those ages 0-4 (74%) and 5-11 (66%) years. CONCLUSIONS: The COVID-19 pandemic impacted asthma ED visits in the United States. The impact was greater among children than adults, as ED visits among children were notably lower during all three pandemic surveillance periods than during the corresponding pre-pandemic periods. Additional information about the roles of behaviors of patients with asthma and changes in asthma care might improve our understanding of the reasons underlying these observed changes.

Using Randomized Controlled Trials to Estimate the Effect of Community Interventions for Childhood Asthma.

INTRODUCTION: The Centers for Disease Control and Prevention's Controlling Childhood Asthma and Reducing Emergencies initiative aims to prevent 500,000 emergency department (ED) visits and hospitalizations within 5 years among children with asthma through implementation of evidence-based interventions and policies. Methods are needed for calculating the anticipated effects of planned asthma programs and the estimated effects of existing asthma programs. We describe and illustrate a method of using results from randomized control trials (RCTs) to estimate changes in rates of adverse asthma events (AAEs) that result from expanding access to asthma interventions. METHODS: We use counterfactual arguments to justify a formula for the expected number of AAEs prevented by a given intervention. This formula employs a current rate of AAEs, a measure of the increase in access to the intervention, and the rate ratio estimated in an RCT. RESULTS: We justified a formula for estimating the effect of expanding access to asthma interventions. For example, if 20% of patients with asthma in a community with 20,540 annual asthma-related ED visits were offered asthma self-management education, ED visits would decrease by an estimated 1,643; and annual hospitalizations would decrease from 2,639 to 617. CONCLUSION: Our method draws on the best available evidence from RCTs to estimate effects on rates of AAEs in the community of interest that result from expanding access to asthma interventions.

Gestational Weight Gain and Birth Outcome: A Comparison of Methods of Accounting for Gestational Age.

Cross-sectional studies of total gestational weight gain (GWG) and perinatal outcomes have used different approaches to operationalize GWG and adjust for duration of gestation. Using birth records from California (2007-2017), Nevada (2010-2017), and Oregon (2008-2017), we compared 3 commonly used approaches to estimate associations between GWG and cesarean delivery, small-for-gestational-age birth, and low birth weight (LBW): 1) the Institute of Medicine-recommended GWG ranges at a given gestational week, 2) total weight gain categories directly adjusting for gestational age as a covariate, and 3) weight-gain-for-gestational-age z scores derived from an external longitudinal reference population. Among 5,461,130 births, the 3 methods yielded similar conclusions for cesarean delivery and small-for-gestational-age birth. However, for LBW, some associations based on z scores were in the opposite direction of methods 1 and 2, paradoxically suggesting that higher GWG increases risk of LBW. This was due to a greater proportion of preterm births among those with high z scores, and controlling for gestational age in the z score model brought the results in line with the other methods. We conclude that the use of externally derived GWG z scores based on ongoing pregnancies can yield associations confounded by duration of pregnancy when the outcome is strongly associated with gestational age at delivery.

Have Paved Trails and Protected Bike Lanes Led to More Bicycling in Atlanta?: A Generalized Synthetic-Control Analysis.

BACKGROUND: Bicycling is an important form of physical activity in populations. Research assessing the effect of infrastructure on bicycling with high-resolution smartphone data is emerging in several places, but it remains limited in low-bicycling US settings, including the Southeastern US. The Atlanta area has been expanding its bicycle infrastructure, including off-street paved trails such as the Atlanta BeltLine and some protected bike lanes. METHODS: Using the generalized synthetic-control method, we estimated effects of five groups of off-street paved trails and protected bike lanes on bicycle ridership in their corresponding areas. To measure bicycling, we used 2 years (October 1, 2016 to September 30, 2018) of monthly Strava data in Atlanta's urban core along with data from 15 on-the-ground counters to adjust for spatiotemporal variation in app use. RESULTS: Considering all infrastructure as one joint intervention, an estimated 1.10 (95% confidence interval [CI]: 0.99, 1.18) times more bicycle-distance was ridden than would have been expected in the same areas had the infrastructure not been built, when defining treatment areas by the narrower of two definitions (defined in text). The Atlanta BeltLine Westside Trail and Proctor Creek Greenway had especially strong effect estimates, e.g., ratios of 1.45 (95% CI: 1.12, 1.86) and 1.55 (1.10, 2.14) under each treatment-area definition, respectively. We estimated that other infrastructure had weaker positive or no effects on bicycle-distance ridden. CONCLUSIONS: This study advances research on the topic because of its setting in the US Southeast, simultaneous assessment of several infrastructure groups, and data-driven approach to estimating effects. See video abstract at, http://links.lww.com/EDE/B936.

Negative Control Exposures: Causal Effect Identifiability and Use in Probabilistic-bias and Bayesian Analyses With Unmeasured Confounders.

BACKGROUND: Probabilistic bias and Bayesian analyses are important tools for bias correction, particularly when required parameters are nonidentifiable. Negative controls are another tool; they can be used to detect and correct for confounding. Our goals are to present conditions that assure identifiability of certain causal effects and to describe and illustrate a probabilistic bias analysis and related Bayesian analysis that use a negative control exposure. METHODS: Using potential-outcome models, we characterized assumptions needed for identification of causal effects using a dichotomous, negative control exposure when residual confounding exists. We defined bias parameters, characterized their relationships with the negative control and with specified causal effects, and described the corresponding probabilistic-bias and Bayesian analyses. We present analytic examples using data on hormone therapy and suicide attempts among transgender people. To address possible confounding by healthcare utilization, we used prior tetanus-diphtheria-pertussis (TdaP) vaccination as a negative control exposure. RESULTS: Hormone therapy was weakly associated with risk (risk ratio [RR] = 0.9). The negative control exposure was associated with risk (RR = 1.7), suggesting confounding. Based on an assumed prior distribution for the bias parameter, the 95% simulation interval for the distribution of confounding-adjusted RR was (0.17, 1.6), with median 0.5; the 95% credibility interval was similar. CONCLUSIONS: We used dichotomous negative control exposure to identify causal effects when a confounder was unmeasured under strong assumptions. It may be possible to relax assumptions and the negative control exposure could prove helpful for probabilistic bias analyses and Bayesian analyses.

Clinical outcomes among hospitalized US adults with asthma or chronic obstructive pulmonary disease, with or without COVID-19.

OBJECTIVE: This study assesses the risk of severe clinical outcomes during hospitalizations of adults with asthma and/or COPD plus COVID-19 and compares those risks with those during hospitalizations of adults with asthma and/or COPD without COVID-19. METHODS: We used data from 877 U.S. hospitals from the Premier Healthcare Database during March 2020-March 2021. Hospitalizations (n = 311,215) among patients aged ≥18 years with an ICD-10-CM diagnosis involving asthma or COPD were classified into three groups: adults with asthma (but not COPD), adults with COPD (but not asthma), and adults with both asthma and COPD. We used multivariable Poisson regression to assess associations of severe clinical outcomes [intensive care unit (ICU) admission, use of invasive mechanical ventilation (IMV), and death] and COVID-19 status. RESULTS: The percentage of hospitalizations among patients with asthma and COVID-19 resulting in ICU admission, IMV, and death were 46.9%, 14.0%, and 8.0%, respectively. These risks were higher than those among patients with asthma without COVID-19 (adjusted risk ratio [aRR], 1.17 [95% confidence interval (CI), 1.14-1.21], 1.61 [95% CI, 1.50-1.73], and 5.56 [95% CI, 4.89-6.32]), respectively. Risks of ICU admission, IMV, and death were also high among patients with COPD and COVID-19 and exceeded the corresponding risks among patients with COPD without COVID-19. CONCLUSION: Hospitalizations among patients with asthma and/or COPD with COVID-19 had a more severe clinical course than hospitalizations for asthma and/or COPD exacerbations without COVID-19.Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Joint associations of physical activity and body mass index with the risk of established excess body fatness-related cancers among postmenopausal women.

PURPOSE: Excess body fatness and physical activity independently influence the risk of several types of cancer. However, few studies have examined whether physical activity mitigates the excess risk associated with higher body mass index (BMI). METHODS: We examined the individual and joint associations between BMI (kg/m2) and leisure-time moderate-to-vigorous physical activity (MVPA, MET-hours/week) with the risk of three established excess body fatness-related cancers (breast, colon, and endometrial) among 43,795 postmenopausal women in the Cancer Prevention Study II (CPS-II) Nutrition Cohort (1992/1993-2015). Further exclusions for women without an intact uterus resulted in 31,805 women for endometrial cancer analyses. Multivariable Cox proportional hazards regression was used to calculate hazard ratio (HR) and 95% confidence intervals (CIs) with interaction terms to assess multiplicative interaction. The relative excess risk due to interaction (RERI) was calculated to assess additive interaction. RESULTS: BMI and MVPA were individually associated with breast and endometrial cancer risk, but only BMI was associated with colon cancer risk. In joint analyses, increasing levels of MVPA did not lower the risk of these cancers among obese women. For example, compared to the common referent (BMI 18.5- < 25 kg/m2, MVPA > 0- < 7.5 MET-hours/week), BMI ≥ 30 kg/m2 was associated with a higher risk of breast cancer among women with low MVPA (> 0-< 7.5 MET-hours/week: HR = 1.42, 95% CI: 1.22 - 1.67) and high MVPA (≥ 15 MET-hours/week: HR = 1.53, 95% CI: 1.25 - 1.87; RERI = 0.20, 95% CI: -0.14, 0.54, multiplicative Pinteraction = 0.64). CONCLUSION: Our results do not support the hypothesis that leisure-time physical activity mitigates the excess risk associated with higher BMI for risk of breast, endometrial, or colon cancer among postmenopausal women.

At-risk-measure Sampling in Case-Control Studies with Aggregated Data.

Transient exposures are difficult to measure in epidemiologic studies, especially when both the status of being at risk for an outcome and the exposure change over time and space, as when measuring built-environment risk on transportation injury. Contemporary "big data" generated by mobile sensors can improve measurement of transient exposures. Exposure information generated by these devices typically only samples the experience of the target cohort, so a case-control framework may be useful. However, for anonymity, the data may not be available by individual, precluding a case-crossover approach. We present a method called at-risk-measure sampling. Its goal is to estimate the denominator of an incidence rate ratio (exposed to unexposed measure of the at-risk experience) given an aggregated summary of the at-risk measure from a cohort. Rather than sampling individuals or locations, the method samples the measure of the at-risk experience. Specifically, the method as presented samples person-distance and person-events summarized by location. It is illustrated with data from a mobile app used to record bicycling. The method extends an established case-control sampling principle: sample the at-risk experience of a cohort study such that the sampled exposure distribution approximates that of the cohort. It is distinct from density sampling in that the sample remains in the form of the at-risk measure, which may be continuous, such as person-time or person-distance. This aspect may be both logistically and statistically efficient if such a sample is already available, for example from big-data sources like aggregated mobile-sensor data.

Prenatal Exposure to Mixtures of Persistent Endocrine-disrupting Chemicals and Birth Size in a Population-based Cohort of British Girls.

BACKGROUND: Previous studies of endocrine-disrupting chemicals have examined one of these chemicals at a time in association with an outcome; studying mixtures better approximates human experience. We investigated the association of prenatal exposure to mixtures of persistent endocrine disruptors (perfluoroalkyl and polyfluoroalkyl substances [PFAS], polychlorinated biphenyls [PCBs], and organochlorine pesticides) with birth size among female offspring in the Avon Longitudinal Study of Parents and Children (ALSPAC), based in the United Kingdom in 1991-1992. METHODS: We quantified concentrations of 52 endocrine-disrupting chemicals in maternal serum collected during pregnancy at median 15-week gestation. Birth weight, crown-to-heel length, and head circumference were measured at birth; ponderal index and small for gestational age were calculated from these. We used repeated holdout Weighted Quantile Sum (WQS) regression and Bayesian kernel machine regression to examine mixtures in 313 mothers. RESULTS: Using WQS regression, all mixtures (each chemical class separately and all three together) were inversely associated with birth weight. A one-unit increase in WQS index (a one-decile increase in chemical concentrations) for all three classes combined was associated with 55 g (ß = -55 g, 95% confidence interval [CI] = -89, -22 g) lower birth weight. Associations were weaker but still inverse using Bayesian kernel machine regression. Under both methods, PFAS were the most important contributors to the association with birth weight. We also observed inverse associations for crown-to-heel length. CONCLUSIONS: These results are consistent with the hypothesis that prenatal exposure to mixtures of persistent endocrine-disrupting chemicals affects birth size.

The Cancer Prevention Study-3 FFQ Is a Reliable and Valid Measure of Nutrient Intakes among Racial/Ethnic Subgroups, Compared with 24-Hour Recalls and Biomarkers.

BACKGROUND: Valid assessment of dietary intake in diverse populations is important for studies of chronic disease risk in the United States. OBJECTIVES: We evaluated the reproducibility and validity of a food frequency questionnaire (FFQ) modified for the American Cancer Society's Cancer Prevention Study-3 (CPS-3) prospective cohort, among a racially/ethnically diverse subgroup. METHODS: The Diet Assessment Substudy included 677 CPS-3 participants (64% women; 61% non-Hispanic white, 24% non-Hispanic black, 15% Hispanic), aged 31-70 y, who completed 2 FFQs 1 y apart (FFQ1, FFQ2), 4-6 telephone-administered 24-h dietary recalls (24HRs), and 2 fasting blood samples and 24-h urine collections ∼6 mo apart in the interim. Spearman rank correlation coefficients (ρ) were used to evaluate FFQ reproducibility and validity compared with 24HRs for 67 nutrient exposures. For 18 of these nutrients, we used the method of triads to calculate validity coefficients (VCs, ρ) from pairwise correlations of FFQ2, 24HRs, and biomarkers. Analyses were stratified by sex, race/ethnicity, education, and BMI. RESULTS: Mean (range) FFQ reproducibility correlations were ρ = 0.65 (0.50-0.91) for men and ρ = 0.63 (0.37-0.89) for women; mean (range) energy-adjusted, deattenuated correlations of FFQ2 with 24HRs were ρ = 0.60 (0.33-0.84) for men and ρ = 0.55 (0.21-0.79) for women. FFQ2 VCs (ρ) among men ranged from 0.42 for ß-cryptoxanthin to 0.91 for omega-3 (n-3) fatty acids and, among women, from 0.41 for sodium to 0.79 for total vitamin D. Mean FFQ reproducibility and validity were highest among whites (ρ = 0.68, ρ = 0.58, respectively) and slightly lower among blacks (ρ = 0.57, ρ = 0.49, respectively) and Hispanics (ρ = 0.59, 0.55, respectively). FFQ reproducibility and validity were slightly lower among those with less than a 4-y college degree, and those with a BMI ≥30 kg/m2. CONCLUSIONS: Reproducibility and validity of the CPS-3 FFQ were comparable with similar studies for most nutrients, among all subgroups. These findings support future dietary analyses in the contemporary CPS-3 cohort and other similar cohorts.

Estimated Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1 and C9orf72 Genetic Variants.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare neurological disorder characterized by progressive deterioration of motor neurons. Assessment of the size/geographic distribution of the ALS population, including ALS with genetic origin, is needed to understand the burden of the disease and the need for clinical intervention and therapy. OBJECTIVES: The main objective of this study was to estimate the number of prevalent and incident ALS cases overall and superoxide dismutase 1 (SOD1) and chromosome 9 open reading frame 72 (C9orf72) ALS in 22 countries across Europe (Belgium, France, Germany, Ireland, Italy, Netherlands, Norway, Russia, Spain, Sweden, and UK), North America (USA and Canada), Latin America (Argentina, Brazil, Colombia, Mexico, and Uruguay), and Asia (China, Japan, South Korea, and Taiwan). METHODS: A comprehensive literature search was conducted to identify population-based studies reporting ALS prevalence and/or incidence rates. Pooled prevalence and incidence rates were obtained using a meta-analysis approach at the country and regional geographic level. A country-level pooled estimate was used when ≥2 studies were available per country and geographic regional pooled estimates were used otherwise. The proportion of cases with a SOD1 or C9orf72 mutation among sporadic (sALS) and familial (fALS) cases were obtained from a previous systematic review and meta-analysis. RESULTS: Pooled prevalence rates (per 100,000 persons) and incidence rates (per 100,000 person-years) were 6.22 and 2.31 for Europe, 5.20 and 2.35 for North America, 3.41 and 1.25 for Latin America, 3.01 and 0.93 for Asian countries excluding Japan, and 7.96 and 1.76 for Japan, respectively. Significant heterogeneity in reported incidence and prevalence was observed within and between countries/geographic regions. The estimated number of 2020 ALS cases across the 22 countries is 121,028 prevalent and 41,128 incident cases. The total estimated number of prevalent SOD1 cases is 2,876 cases, of which, 1,342 (47%) were fALS and 1,534 (53%) were sALS, and the number of incident SOD1 cases is 946 (434 [46%] fALS and 512 [54%] sALS). The total estimated number of prevalent C9orf72 cases is 4,545 (1,198 [26%] fALS, 3,347 [74%] sALS), and the number of incident C9orf72 cases is 1,706 (450 [26%] fALS and 1,256 [74%] sALS). DISCUSSION: The estimated number of patients with SOD1 and C9orf72 ALS suggests that although the proportions of SOD1 and C9orf72 are higher among those with fALS, the majority of SOD1 and C9orf72 ALS cases may be found among those with sALS (about 53 and 74%, respectively). These results suggest that classification of fALS based on reported family history does not capture the full picture of ALS of genetic origin.

A novel evolutionary-concordance lifestyle score is inversely associated with all-cause, all-cancer, and all-cardiovascular disease mortality risk.

PURPOSE: Evolutionary discordance may contribute to the high burden of chronic disease-related mortality in modern industrialized nations. We aimed to investigate the associations of a 7-component, equal-weight, evolutionary-concordance lifestyle (ECL) score with all-cause and cause-specific mortality. METHODS: Baseline data were collected in 2003-2007 from 17,465 United States participants in the prospective REasons for Geographic and Racial Differences in Stroke (REGARDS) study. The ECL score's components were: a previously reported evolutionary-concordance diet score, alcohol intake, physical activity, sedentary behavior, waist circumference, smoking history, and social network size. Diet was assessed using a Block 98 food frequency questionnaire and anthropometrics by trained personnel; other information was self-reported. Higher scores indicated higher evolutionary concordance. We used multivariable Cox proportional hazards regression models to estimate ECL score-mortality associations. RESULTS: Over a median follow-up of 10.3 years, 3771 deaths occurred (1177 from cardiovascular disease [CVD], 1002 from cancer). The multivariable-adjusted hazard ratios (HR) (95% confidence intervals [CI]) for those in the highest relative to the lowest ECL score quintiles for all-cause, all-CVD, and all-cancer mortality were, respectively, 0.45 (0.40, 0.50), 0.47 (0.39, 0.58), and 0.42 (0.34, 0.52) (all P trend < 0.01). Removing smoking and diet from the ECL score attenuated the estimated ECL score-all-cause mortality association the most, yielding fifth quintile HRs (95% CIs) of 0.56 (0.50, 0.62) and 0.50 (0.46, 0.55), respectively. CONCLUSIONS: Our findings suggest that a more evolutionary-concordant lifestyle may be inversely associated with all-cause, all-CVD, and all-cancer mortality. Smoking and diet appeared to have the greatest impact on the ECL-mortality associations.

Changes in Size and Demographic Composition of Transgender and Gender Non-Binary Population Receiving Care at Integrated Health Systems.

OBJECTIVE: To examine temporal changes in the number and demographic composition of transgender/gender non-binary (TGNB) population using data from integrated health care systems. METHODS: Electronic health records from Kaiser Permanente health plans in Georgia and Northern and Southern California were used to identify TGNB individuals, who sought care from January 2006 to December 2014, and the data were analyzed by year, site, age, and sex assigned at birth. RESULTS: In 2006, the number of TGNB people (and corresponding 95% CI) per 100 000 population were 3.5 (1.9, 6.3) in Georgia, 5.5 (4.8, 6.4) in Southern California, and 17 (16, 19) in Northern California. In 2014, these frequencies increased to 38 (32, 45), 44 (42, 46), and 75 (72, 78) per 100 000 population, respectively. When analyzed by age, the most rapid increase was observed among persons 18 to 25 years old, and this increase accelerated after 2010. The ratio of transmasculine to transfeminine persons also changed from 1:1.7 in 2006 to 1:1 in 2014 overall and from 1:1 in 2006 to 1.8:1 in 2014 among persons <18 years of age. CONCLUSION: This analysis confirms previous observations that the proportion of TGNB people is growing, especially among young adults. The composition of the TGNB population is also changing from predominantly transfeminine to roughly 1:1 overall and to predominantly transmasculine in children and adolescents.

Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D-binding protein isoforms.

Lower prediagnostic circulating 25-hydroxyvitamin D (25[OH]D)-considered the best marker of total vitamin D exposure-is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D-binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D-mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study-II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [<30], insufficient [30 - <50], sufficient [≥50 nmol/L]). In the pooled analysis, multivariable-adjusted hazard ratios (HRs) for CRC-specific mortality associated with deficient relative to sufficient 25(OH)D concentrations were 2.24 (95% CI 1.44-3.49) among cases with the Gc2 isoform, and 0.94 (95% CI 0.68-1.22) among cases without Gc2 (Pinteraction = .0002). The corresponding HRs for all-cause mortality were 1.80 (95% CI 1.24-2.60) among those with Gc2, and 1.12 (95% CI 0.84-1.51) among those without Gc2 (Pinteraction = .004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis.