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The authors assessed the utility and cost-effectiveness of using a World Wide Web-based questionnaire in a large prospective cohort study, the Black Women's Health Study (BWHS). In 1995, 59,000 African-American women were recruited into the BWHS through a paper questionnaire. Follow-up paper questionnaires have been mailed every 2 years since then. During the 2003, 2005, and 2007 questionnaire cycles, participants were given the option of completing a Web-based questionnaire. The cost of developing and processing a returned paper questionnaire was 4 times that of a returned Web questionnaire, primarily because of return postage costs and greater processing time for paper questionnaires. The proportion of respondents who completed a Web questionnaire doubled from 2003 to 2007, from 10.1% to 19.9%, but the characteristics of those completing the Web questionnaire remained the same. Web response was greatest at younger ages (20.9% of those aged <30 years) and declined with age to 3.6% among women aged 60 years or more. Web questionnaires were filled out more completely than paper questionnaires, regardless of the sensitivity of a question. The use of a Web questionnaire in the BWHS resulted in cost savings and more complete responses. Although there are advantages to using a Web questionnaire, the use of multiple means of soliciting questionnaire responses is still needed. [ABSTRACT FROM PUBLISHER]

Epidemiologists commonly use an adjusted hazard ratio or incidence density ratio, or a standardized mortality ratio, to measure a difference in all-cause mortality rates. They seldom translate it into an age-, time-, or probability-based measure that would be easier to communicate and to relate to. Several articles have shown how to translate from a standardized mortality ratio or hazard ratio to a longevity difference, a difference in actuarial ages, or a probability of being outlived. In this paper, we describe the settings where these translations are and are not appropriate and provide some of the heuristics behind the formulae. The tools that yield differences in "effective age" and in longevity are applicable when both 1) the mortality rate ratio (hazard ratio) is constant over age and 2) the rates themselves are log-linear in age. The "probability/odds of being outlived" metric is applicable whenever the first condition holds, and thus it provides no direct information on the magnitude of the effective age/longevity difference. [ABSTRACT FROM AUTHOR]

In a 1989 paper, Marchbanks et al. (Am J Epidemiol. 1989; 130(2):259-267) noted inconsistent definitions of infertility across research and clinical practice and examined differences in prevalence estimates across definitions. Since their study, there have been substantial changes in society, technology, and clinical practice related to female reproductive health. In response, we revisited the original paper using data from a recent study among reproductive-aged women. Internal comparisons across various definitions of infertility were made by assessing how many and which women were classified as infertile, their age at infertility, and the probability of spontaneous pregnancy after infertility. Results were also compared with Marchbanks et al. Black women were more likely to be classified as infertile than white women based on the definition "12 months of unprotected intercourse" (40.1% vs. 33.7%) but less likely by "12 months of attempting pregnancy" (14.3% vs. 21.8%) and "visiting a doctor for help getting pregnant" (8.4% vs. 19.7%). After unprotected intercourse for 12 months, 36.1% of women who were attempting pregnancy spontaneously conceived by 6 months compared with 13.5%of women who were not attempting pregnancy. While our results for most infertility definitions were similar to those of Marchbanks et al., prevalence estimates continued to differ across demographic groups by definition. [ABSTRACT FROM AUTHOR]

The majority of people living with Alzheimer disease (AD) and related dementias are women. Longer life expectancy is one factor thought to contribute to this observation, but possible sex-specific biological mechanisms have received considerable attention from the research community. In the current issue of the Journal , Buckley et al. (Am J Epidemiol. 2019;188(7):1213–1223) use death certificate information on all deaths occurring among adults aged ≥60 years in Australia between 2006 and 2014 to evaluate sex/gender differences in rates of death with dementia (all types), AD dementia, and vascular dementia listed on the death certificate. The paper by Buckley et al. highlights several important methodological challenges for research examining sex/gender differences in risk of AD and related dementias, including challenges in measurement, survival bias and competing risks, and selection bias arising from sample selection. The current evidence on possible sex-specific biological risk factors for AD is intriguing, but there are numerous alternative explanations for differences in AD dementia and AD biomarkers between women and men. Triangulation of evidence from study designs with different strengths and weaknesses and transdisciplinary collaboration will be vital to generating conclusive evidence about sex/gender differences in risk of AD and related dementias. [ABSTRACT FROM AUTHOR]

Cohort or period components of trends can provide a rationale for new research or point to clues on the effectiveness of control strategies. Graphical display of trends guides models that quantify the experience of a population. In this paper, a method for smoothing rates by single year of age and year is developed and displayed to show the contributions of period and cohort to trends. The magnitude of the contribution of period and/or cohort in a model for trends may be assessed by the percentage of deviance explained and the relative contributions of cohort (C) and period (P) individually, known as the C-P score. The method is illustrated using Surveillance, Epidemiology, and End Results data (1975–2014) on lung and bronchial cancer mortality in females and prostate and colorectal cancer incidence in males. Smoothed age-period and age-cohort rates provide a useful first step in studies of etiology and the impact of disease control without imposing a restrictive model. We found that, in this data set, cohort predominates for female lung and bronchial cancer and period predominates for male prostate cancer. However, the effects change with age for male colorectal cancer incidence, indicating an age shift in relevant exposures. These methods are applied on an interactive website for both incidence and mortality at over 20 cancer sites in the United States. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on themes including gaps in surveillance/measurement issues; the need to enrich understanding of cultural factors that influence risk; and the mental health of humanitarian relief workers.

Increasingly often in epidemiologic research, associations between survival time and predictors of interest are measured by differences between distribution functions rather than hazard functions. For example, differences in percentiles of survival time, expressed in absolute time units (e.g., weeks), may complement the popular risk ratios, which are unitless measures. When analyzing time to an event of interest (e.g., death) in prospective cohort studies, the time scale can be set to start at birth or at study entry. The advantages of one time origin over the other have been thoroughly explored for the estimation of risks but not for the estimation of survival percentiles. In this paper, we analyze the use of different time scales in the estimation of survival percentiles with Laplace regression. Using this regression method, investigators can estimate percentiles of survival time over levels of an exposure of interest while adjusting for potential confounders. Our findings may help to improve modeling strategies and ease interpretation in the estimation of survival percentiles in prospective cohort studies. [ABSTRACT FROM AUTHOR]

Ozone is associated with adverse health; however, less is known about vulnerable/sensitive populations, which we refer to as sensitive populations. We systematically reviewed epidemiologic evidence (1988-2013) regarding sensitivity to mortality or hospital admission from short-term ozone exposure. We performed meta-analysis for overall associations by age and sex; assessed publication bias; and qualitatively assessed sensitivity to socioeconomic indicators, race/ethnicity, and air conditioning. The search identified 2,091 unique papers, with 167 meeting inclusion criteria (73 on mortality and 96 on hospitalizations and emergency department visits, including 2 examining both mortality and hospitalizations). The strongest evidence for ozone sensitivity was forage. Per 10-parts per billion increase in daily 8-hour ozone concentration, mortality risk for younger persons, at 0.60% (95% confidence interval (Cl): 0.40, 0.80), was statistically lower than that for older persons, at 1.27% (95% Cl: 0.76,1.78). Findings adjusted for publication bias were similar. Limited/suggestive evidence was found for higher associations among women; mortality risks were 0.39% (95% Cl: -0.22,1.00) higher than those for men. We identified strong evidence for higher associations with unemployment or lower occupational status and weak evidence of sensitivity for racial/ethnic minorities and persons with low education, in poverty, or without central air conditioning. Findings show that some populations, especially the elderly, are particularly sensitive to short-term ozone exposure. [ABSTRACT FROM AUTHOR]

Mumps is a potentially severe viral infection. The incidence of mumps has declined dramatically in high-income countries since the introduction of mumps antigen-containing vaccines. However, recent large outbreaks of mumps in highly vaccinated populations suggest waning of vaccine-induced immunity and primary vaccine failure. In this paper we present a simple method for identifying geographic regions with high outbreak potential, demonstrated using 2006 mumps seroprevalence data from Belgium and Belgian vaccination coverage data. Predictions of the outbreak potential in terms of the effective reproduction number in future years signal an increased risk of new mumps outbreaks. Literature reviews on serological information for both primary vaccine failure and waning immunity provide essential information for our predictions. Tailor-made additional vaccination campaigns would be valuable for decreasing local pockets of susceptibility, thereby reducing the risk of future large-scale mumps outbreaks. [ABSTRACT FROM PUBLISHER]

Although there is strong evidence that short-term exposure to particulate matter is associated with health risks, less is known about whether some subpopulations face higher risks. We identified 108 papers published after 1995 and summarized the scientific evidence regarding effect modification of associations between short-term exposure to particulate matter and the risk of death or hospitalization. We performed a meta-analysis of estimated mortality associations by age and sex. We found strong, consistent evidence that the elderly experience higher risk of particular matter-associated hospitalization and death, weak evidence that women have higher risks of hospitalization and death, and suggestive evidence that those with lower education, income, or employment status have higher risk of death. Meta-analysis showed a statistically higher risk of death of 0.64% (95% confidence interval (Cl): 0.50, 0.78) for older populations compared with 0.34% (95% Cl: 0.25, 0.42) for younger populations per 10 ng/m³ increase of particulate matter with aerodynamic diameter ≤10 µm. Women had a slightly higher risk of death of 0.55% (95% Cl: 0.41,0.70) compared with 0.50% (95% Cl: 0.34, 0.54) for men, but these 2 risks were not statistically different. Our synthesis on modifiers for risks associated with particulate matter can aid the design of air quality policies and suggest directions for future research. Studies of biological mechanisms could be informed by evidence of differential risks by population, such as by sex and preexisting conditions. [ABSTRACT FROM AUTHOR]

In this paper, we propose new methods for investigating the extent of heterogeneity in effective contact rates relevant to the transmission of infections. These methods exploit the correlations between ages at infection for different infections within individuals. The methods are developed for serological surveys, which provide accessible individual data on several infections, and are applied to a wide range of infections. We find that childhood infections are often highly correlated within individuals in early childhood, with the correlations persisting into adulthood only for infections sharing a transmission route. We discuss 2 applications of the methods: 1) to making inferences about routes of transmission when these are unknown or uncertain and 2) to estimating epidemiologic parameters such as the basic reproduction number and the critical immunization threshold. Two examples of such applications are presented: elucidating the transmission route of polyomaviruses BK and JC and estimating the basic reproduction number and critical immunization coverage of varicella-zoster infection in Belgium, Italy, Poland, and England and Wales. We speculate that childhood correlations stem from confounding of different transmission routes and represent heterogeneity in childhood circumstances, notably nursery-school attendance. In contrast, it is suggested that correlations in adulthood are route-specific. [ABSTRACT FROM PUBLISHER]

There are several measures that summarize the mortality experience of a population. Of these measures, life expectancies are generally preferred based on their simpler interpretation and direct age standardization, which makes them directly comparable between different populations. However, traditional life expectancy estimations are highly inaccurate for smaller populations and consequently are seldom used in small-area applications. In this paper, the authors compare the relative performance of traditional life expectancy estimation with a Bayesian random-effects approach that uses correlations (i.e., borrows strength) between different age groups, geographic areas, and sexes to improve the small-area life expectancy estimations. In the presented Monte Carlo simulations, the Bayesian random-effects approach outperforms the traditional approach in terms of bias, root mean square error, and coverage of the 95% confidence intervals. Moreover, the Bayesian random-effects approach is found to be usable for populations as small as 2,000 person-years at risk, which is considerably smaller than the minimum of 5,000 person-years at risk recommended for the traditional approach. As such, the proposed Bayesian random-effects approach is well-suited for estimation of life expectancies in small areas. [ABSTRACT FROM AUTHOR]

The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program provides a rich source of data stratified according to tumor biomarkers that play an important role in cancer surveillance research. These data are useful for analyzing trends in cancer incidence and survival. These tumor markers, however, are often prone to missing observations. To address the problem of missing data, the authors employed sequential regression multivariate imputation for breast cancer variables, with a particular focus on estrogen receptor status, using data from 13 SEER registries covering the period 1992–2007. In this paper, they present an approach to accounting for missing information through the creation of imputed data sets that can be analyzed using existing software (e.g., SEER*Stat) developed for analyzing cancer registry data. Bias in age-adjusted trends in female breast cancer incidence is shown graphically before and after imputation of estrogen receptor status, stratified by age and race. The imputed data set will be made available in SEER*Stat (http://seer.cancer.gov/analysis/index.html) to facilitate accurate estimation of breast cancer incidence trends. To ensure that the imputed data set is used correctly, the authors provide detailed, step-by-step instructions for conducting analyses. This is the first time that a nationally representative, population-based cancer registry data set has been imputed and made available to researchers for conducting a variety of analyses of breast cancer incidence trends. [ABSTRACT FROM PUBLISHER]

The authors conducted a meta-analysis of the association between smoking before a first pregnancy, when undifferentiated breast tissue may be vulnerable to tobacco carcinogens, and the risk of breast cancer. A search of the published literature through August 2010 identified 23 papers reporting on associations between smoking before a first pregnancy and breast cancer. Odds ratios or hazard ratios and 95% confidence intervals, adjusted for known or suspected breast cancer risk factors, were abstracted from each study. Data were pooled using both fixed- and random-effects models. The fixed-effect summary risk ratio for breast cancer among the women who smoked before their first pregnancy versus women who had never smoked was 1.10 (95% confidence interval: 1.07, 1.14); the random-effects estimate was similar. The separate fixed-effect risk ratios for smoking only before the first pregnancy (5 studies) or only after the first pregnancy (16 studies) were both 1.07, providing no evidence that breast tissue is more susceptible to malignant transformation from smoking before the first pregnancy. While these small summary risk ratios may represent causal effects, residual confounding could readily produce estimates of this size in the absence of any causal effect. [ABSTRACT FROM AUTHOR]

The Life Journeys of Young Women Project is the first population-based study to examine the role of economic uncertainty throughout early adulthood on age at first childbirth. A retrospective cross-sectional component was added to an existing cohort study that is based on a birth cohort of women born during 1973–1975 in Adelaide, South Australia (n ˜ 1,000). An event history calendar instrument was used to obtain data regarding a range of life domains including partnering, educational attainment, home ownership, higher education debt, employment, and pregnancies over a 20-year period (sometimes as detailed as at monthly intervals). Interviews were conducted between 2007 and 2009. An analysis framework applying time-varying and time-constant survival analysis techniques within a life-course framework was developed that will guide analyses to examine the role of duration and life-course timing of economic uncertainty on age at first childbirth. This paper discusses study objectives and design, fieldwork procedures, planned statistical analyses, and recruitment outcomes, focusing on novel features that would facilitate analogous epidemiologic research. [ABSTRACT FROM AUTHOR]

In this paper, the authors describe a simple method for making longitudinal comparisons of alternative markers of a subsequent event. The method is based on the aggregate prediction gain from knowing whether or not a marker has occurred at any particular age. An attractive feature of the method is the exact decomposition of the measure into 2 components: 1) discriminatory ability, which is the difference in the mean time to the subsequent event for individuals for whom the marker has and has not occurred, and 2) prevalence factor, which is related to the proportion of individuals who are positive for the marker at a particular age. Development of the method was motivated by a study that evaluated proposed markers of the menopausal transition, where the markers are measures based on successive menstrual cycles and the subsequent event is the final menstrual period. Here, results from application of the method to 4 alternative proposed markers of the menopausal transition are compared with previous findings. [ABSTRACT FROM PUBLISHER]

The article presents the authors' reply to a letter from D. Meyre regarding their systematic review and meta-analysis on the associations of variants of proprotein convertase subtilisine/kexin type I gene (PCSKI) with obesity. The reply addresses Meyre's criticisms of what he perceives as errors in the paper including an assertion that meta-analysis included 2 overlapping cohorts and suggestion that the analysis was underpowered to find significant association of rs632 with body mass index.

Colorectal cancer (CRC) incidence rates have decreased among adults aged 50 years or older while increasing in adults under age 50 years. Understanding these trends is challenging because of the multiple related time scales of age, diagnosis period, and birth cohort. We analyzed incidence rates of rectal, distal colon, and proximal colon cancer for individuals aged 20 years or more from the Surveillance, Epidemiology, and End Results Program for diagnosis years 1978–2017. We used a 2-stage generalized linear model to determine age, period, and cohort effects for CRC incidence. We first estimated birth cohort effects among people under age 45 years. We used these results to specify prior distributions for cohort effects in a Bayesian model to estimate period effects among people aged 45 years or more. There was no evidence of period effects for people under age 45 years. Risks of rectal and distal colon cancer increased for later birth cohorts. Compared with the 1943–1952 birth cohort, the 1983–1992 birth cohort had 2.2 times the risk of rectal cancer, 1.9 times the risk of distal colon cancer, and 1.3 times the risk of proximal colon cancer. For people aged ≥45 years, period effects showed declines in CRC risk that were attributable to screening. [ABSTRACT FROM AUTHOR]

Along with age and race, sex has historically been a core stratification and control variable in epidemiologic research. While in recent decades research guidelines and institutionalized requirements have incorporated an approach differentiating biological sex from social gender, neither sex nor gender is itself a unidimensional construct. The conflation of dimensions within and between sex and gender presents a validity issue wherein proxy measures are used for dimensions of interest, often without explicit acknowledgement or evaluation. Here, individual-level dimensions of sex and gender are outlined as a guide for epidemiologists, and 2 case studies are presented. The first case study demonstrates how unacknowledged use of a sex/gender proxy for a sexed dimension of interest (uterine status) resulted in decades of cancer research misestimating risks, racial disparities, and age trends. The second illustrates how a multidimensional sex and gender framework may be applied to strengthen research on coronavirus disease 2019 incidence, diagnosis, morbidity, and mortality. Considerations are outlined, including: 1) addressing the match between measures and theory, and explicitly acknowledging and evaluating proxy use; 2) improving measurement across dimensions and social ecological levels; 3) incorporating multidimensionality into research objectives; and 4) interpreting sex, gender, and their effects as biopsychosocial. [ABSTRACT FROM AUTHOR]

Investigations of age, period, and cohort effects are difficult because the 3 factors are linearly dependent. In a novel application, Kramer et al. (Am J Epidemiol. 2015; 182(4):302-312) have used graphical analysis and statistical models to estimate the impact that age, period, and cohort effects have had on trends in black-white inequalities in heart disease mortality. Using a constrained regression approach (with the first 2 periods' effects constrained to zero), Kramer et al. find evidence that age and cohort effects figure more prominently than do period effects in contributing to relative black-white mortality differences, and they argue that early-life exposures should be given greater consideration for mitigation of racial differences in heart disease. In this invited commentary, I argue that the utility of age-period-cohort models for understanding health inequalities depends on the plausibility of the assumptions used to break the link between the 3 factors. Based on the existing age-period-cohort literature, alternative assumptions seem likely to produce substantially different results. I also argue that interpretations of the impacts of age, period, and cohort effects on racial inequalities in heart disease mortality may depend on whether inequalities are assessed on the absolute scale or the relative scale. [ABSTRACT FROM AUTHOR]

Adolescent internalizing symptoms have increased since 2010, whereas adequate sleep has declined for several decades. It remains unclear how self-reported sleep attainment has affected internalizing-symptoms trends. Using 1991–2019 data from the Monitoring the Future Study (n  ~ 390,000), we estimated age-period-cohort effects in adolescent internalizing symptoms (e.g. loneliness, self-esteem, self-derogation, depressive affect) and the association with yearly prevalence of a survey-assessed, self-reported measure of attaining ≥7 hours of sleep most nights. We focused our main analysis on loneliness and used median odds ratios to measure variance in loneliness associated with period differences. We observed limited signals for cohort effects and modeled only period effects. The feeling of loneliness increased by 0.83% per year; adolescents in 2019 had 0.68 (95% CI: 0.49, 0.87) increased log odds of loneliness compared with the mean, which was consistent by race/ethnicity and parental education. Girls experienced steeper increases in loneliness than boys (P  < 0.0001). The period-effect median odds ratio for loneliness was 1.16 (variance = 0.09; 95% CI: 0.06, 0.17) before adjustment for self-reported frequency of getting ≥7 hours sleep versus 1.07 (variance = 0.02; 95% CI: 0.01, 0.03) after adjustment. Adolescents across cohorts are experiencing worsening internalizing symptoms. Self-reported frequency of <7 hours sleep partially explains increases in loneliness, indicating the need for feasibility trials to study the effect of increasing sleep attainment on internalizing symptoms. [ABSTRACT FROM AUTHOR]

For almost a century, epidemiologists have stratified age-specific disease rates by year of birth to better understand the distribution of a disease in a population and its evolution across time. In the present article, I review the contributions of John Brownlee, Kristian Feyer Andvord, and Wade Hampton Frost and, to accentuate the similarities of their approaches, redraw their original graphs of age-specific death rates of tuberculosis organized either by year of death or year of birth. In addition, this article reports on an apparently universally forgotten publication in the American Journal of Hygiene published in 1929, which both upsets the conventional history of the earliest reports of disease rates stratified by birth cohorts and challenges the theory that Frost discovered cohort analysis independently and gave it its name. [ABSTRACT FROM PUBLISHER]

Legg-Calvé-Perthes’ disease (Perthes’ disease) is a childhood osteonecrosis of the hip for which the disease determinants are poorly understood. In this review, the authors identify studies of Perthes’ disease incidence published up to December 2010 and make denominator populations comparable in order to allow meaningful between-study evaluation. Incidence rates and confidence intervals were determined, and, where appropriate, denominator populations were obtained from national statistical offices. Poisson regression was used to determine the influence of race and geography. The review included 21 studies that described 27 populations in 16 countries, with 124 million person-years of observation. The annual incidence among children under age 15 years ranged from 0.2 per 100,000 to 19.1 per 100,000. Race was a key determinant, with East Asians being least affected and whites most affected, though data were insufficient to consider incidence among blacks (for South Asians vs. East Asians, incidence rate ratio = 2.9, 95% confidence interval (CI): 2.4, 3.5; for whites vs. East Asians, incidence rate ratio = 8.8, 95% CI: 8.2, 9.6). Latitude was a strong predictor of disease, even after adjustment for race. Each 10° increase in latitude was associated with an incidence increase of 1.44 (95% CI: 1.30, 1.58) times. While much of the international variation appears to be a function of race, latitude demonstrates a strong association. This observation may offer new epidemiologic insights into the determinants of Perthes’ disease. [ABSTRACT FROM PUBLISHER]

This paper presents a mathematical model to show the conditions in which age standardization can be used to summarize age-specific rates for comparison purposes over calendar time. It shows that the conditions for valid comparison depend on the type of measure used for comparison, that is, difference, ratio, or percent change. If the measure for comparison is a difference of the standardized rates at two time points, then the age-specific rates need to maintain a constant rate difference over time for the comparison to be valid. If the measure for comparison is a ratio or percent change of the standardized rates at two time points, then the age-specific rates need to maintain a constant rate ratio over time for the comparison to be valid. Since in reality, as shown by our Canadian empirical data, age-specific rates do not always maintain a consistent pattern over time, it is recommended that one should always stratify the data to look at patterns of age-specific rates before applying age standardization. Am J Epidemiol 1999; 149:1087—96. [ABSTRACT FROM PUBLISHER]

The association between early-life greenness and child cognition is not well understood. Using prospective data from Project Viva (n  = 857) from 1999–2010, we examined associations of early-life greenness exposure with mid-childhood cognition. We estimated residential greenness at birth, early childhood (median age 3.1 years), and mid-childhood (7.8 years) using 30-m resolution Landsat satellite imagery (normalized difference vegetation index). In early childhood and mid-childhood, we administered standardized assessments of verbal and nonverbal intelligence, visual-motor abilities, and visual memory. We used natural splines to examine associations of early life-course greenness with mid-childhood cognition, adjusting for age, sex, race, income, neighborhood socioeconomic status, maternal intelligence, and parental education. At lower levels of greenness (greenness <0.6), greenness exposure at early childhood was associated with a 0.48% increase in nonverbal intelligence and 2.64% increase in visual memory in mid-childhood. The association between early-childhood greenness and mid-childhood visual memory was observed after further adjusting for early childhood cognition and across different methodologies, while the association with nonverbal intelligence was not. No other associations between early life-course greenness and mid-childhood cognition were found. Early childhood greenness was nonlinearly associated with higher mid-childhood visual memory. Our findings highlight the importance of nonlinear associations between greenness and cognition. [ABSTRACT FROM AUTHOR]

We compared 3 hypothetical trajectories of change in both general and coronavirus disease 2019 (COVID-19)-specific anxiety during the first wave of the spread in the state of Israel: panic (very high anxiety, either from the outset or rapidly increasing), complacency (stable and low anxiety), and threat-sensitive (a moderate, linear increase compatible with the increase in threat). A representative sample of 1,018 Jewish-Israeli adults was recruited online. A baseline assessment commenced 2 days prior to the identification of the first case, followed by 6 weekly assessments. Latent mixture modeling analyses revealed the presence of 3 trajectories: 1) "threat-sensitivity" (29% and 66%, for general and virus-specific anxiety, respectively), 2) panic (12% and 25%), and 3) complacency (29% and 9%). For general anxiety only, a fourth class representing a stable mid-level anxiety was identified ("balanced": 30%). For general anxiety, women and the initially anxious—both generally and specifically from the spread of the virus—were more likely to belong to the panic class. Men and older participants were more likely to belong to the complacency class. Findings indicate a marked heterogeneity in anxiety responses to the first wave of the spread of COVID-19, including a large group evincing a "balanced" response. [ABSTRACT FROM AUTHOR]

Longitudinal data are necessary to reveal changes within an individual as he or she ages. However, rarely will a single cohort study capture data throughout a person's entire life span. Here we describe in detail the steps needed to develop life-course trajectories from cohort studies that cover different and overlapping periods of life. Such independent studies are probably from heterogenous populations, which raises several challenges, including: 1) data harmonization (deriving new harmonized variables from differently measured variables by identifying common elements across all studies); 2) systematically missing data (variables not measured are missing for all participants in a cohort); and 3) model selection with differing age ranges and measurement schedules. We illustrate how to overcome these challenges using an example which examines the associations of parental education, sex, and race/ethnicity with children's weight trajectories. Data were obtained from 5 prospective cohort studies (carried out in Belarus and 4 regions of the United Kingdom) spanning data collected from birth to early adulthood during differing calendar periods (1936–1964, 1972–1979, 1990–2012, 1996–2016, and 2007–2015). Key strengths of our approach include modeling of trajectories over wide age ranges, sharing of information across studies, and direct comparison of the same parts of the life course in different geographical regions and time periods. We also introduce a novel approach of imputing individual-level covariates of a multilevel model with a nonlinear growth trajectory and interactions. [ABSTRACT FROM AUTHOR]

Morbidity and mortality have been increasing among middle-aged and young-old Americans since the turn of the century. We investigated whether these unfavorable trends extend to younger cohorts and their underlying physiological, psychological, and behavioral mechanisms. Applying generalized linear mixed-effects models to data from 62,833 adults from the National Health and Nutrition Examination Surveys (1988–2016) and 625,221 adults from the National Health Interview Surveys (1997–2018), we found that for all sex and racial groups, physiological dysregulation has increased continuously from Baby Boomers through late-Generation X and Generation Y. The magnitude of the increase was higher for White men than for other groups, while Black men had a steepest increase in low urinary albumin (a marker of chronic inflammation). In addition, Whites underwent distinctive increases in anxiety, depression, and heavy drinking, and they had a higher level than Blacks and Hispanics of smoking and drug use in recent cohorts. Smoking is not responsible for the increasing physiological dysregulation across cohorts. The obesity epidemic contributes to the increase in metabolic syndrome but not in low urinary albumin. The worsening physiological and mental health profiles among younger generations imply a challenging morbidity and mortality prospect for the United States, one that might be particularly inauspicious for Whites. [ABSTRACT FROM AUTHOR]

Within-individual variability of repeatedly measured exposures might predict later outcomes (e.g. blood pressure (BP) variability (BPV) is an independent cardiovascular risk factor above and beyond mean BP). Because 2-stage methods, known to introduce bias, are typically used to investigate such associations, we introduce a joint modeling approach, examining associations of mean BP and BPV across childhood with left ventricular mass (indexed to height; LVMI) in early adulthood with data (collected 1990–2011) from the UK Avon Longitudinal Study of Parents and Children cohort. Using multilevel models, we allowed BPV to vary between individuals (a "random effect") as well as to depend on covariates (allowing for heteroskedasticity). We further distinguished within-clinic variability ("measurement error") from visit-to-visit BPV. BPV was predicted to be greater at older ages, at higher body weights, and in female participants and was positively correlated with mean BP. BPV had a weak positive association with LVMI (10% increase in within-individual BP variance was predicted to increase LVMI by 0.21%, 95% credible interval: −0.23, 0.69), but this association became negative (−0.78%, 95% credible interval: −2.54, 0.22) once the effect of mean BP on LVMI was adjusted for. This joint modeling approach offers a flexible method of relating repeatedly measured exposures to later outcomes. [ABSTRACT FROM AUTHOR]

The elimination of cervical cancer rests on high efficacy of human papillomavirus (HPV) vaccines. The HPV type distribution among cases of invasive cervical cancer (ICC) is used to make predictions about the impact of eliminating different types of HPV, but accumulating evidence of differences in age-specific cancer incidence by HPV type exists. We used one of the largest population-based series of HPV genotyping of ICCs (n  = 2,850; Sweden, 2002–2011) to estimate age-specific ICC incidence by HPV type and obtain estimates of the cancer-protective impact of the removal of different HPV types. In the base case, the age-specific ICC incidence had 2 peaks, and the standardized lifetime risk (SLTR, the lifetime number of cases per birth cohort of 100,000 females) for HPV-positive ICC was 651 per 100,000 female births. In the absence of vaccine types HPV 16 and HPV 18, the SLTR for ICC was reduced to 157 per 100,000 female births (24% of HPV-positive SLTR). Elimination of all 9 types that can currently be vaccinated against reduced the remaining SLTR to 47 per 100,000 female births (7%), the remaining ICC incidence only slowly increasing with age. In conclusion, after elimination of vaccine-protected HPV types, very few cases of ICC will be left, especially among fertile, reproductive-age women. [ABSTRACT FROM AUTHOR]

In their accompanying article, Vänskä et al. (Am J Epidemiol. 2021;190(4):506–514) provide us with cohort lifetime risks of cervical cancer attributable to different types of human papillomavirus in Sweden. We argue that a standardized lifetime risk such as those calculated by Vänskä et al. might be a more appropriate public health target for cervical cancer elimination than age-standardized incidence rates. Age standardization to an arbitrary standard age distribution implies an implicit value choice regarding the weight of different age groups for which we find little moral justification. Conversely, a standardized lifetime risk uses standard life expectancy as a weight, corresponding to the likelihood that cervical cancer would impact a woman and prevent her from pursuing opportunities within a standard life span. Based on the data from Vänskä et al. a standardized lifetime risk of 129–250 cervical cancers per 100,000 women born could be an aspirational alternative public health target for cervical cancer elimination as a public health problem, complementary to the World Health Organization's arbitrary draft target of 4 cervical cancers per 100,000 age-standardized woman-years. [ABSTRACT FROM AUTHOR]

States adopt minimum wages to improve workers' economic circumstances and well-being. Many studies, but not all, find evidence of health benefits from higher minimum wages. This study used a rigorous "triple difference" strategy to identify the associations between state minimum wages and adult obesity, body mass index (weight (kg)/height (m)2), hypertension, diabetes, fair or poor health, and serious psychological distress. National Health Interview Survey data (United States, 2008–2015) on adults aged 25–64 years (n  = 131,430) were linked to state policies to estimate the prevalence odds ratio or mean difference in these outcomes associated with a $1 increase in current and 2-year lagged minimum wage among less-educated adults overall and by sex, race/ethnicity, and age. In contrast to prior studies, there was no association between current minimum wage and health; however, 2-year lagged minimum wage was positively associated with the likelihood of obesity (prevalence odds ratio = 1.08, 95% confidence interval: 1.00, 1.16) and with elevated body mass index (mean difference = 0.27, 95% confidence interval: 0.04, 0.49). In subgroup models, current and 2-year lagged minimum wage were associated with a higher likelihood of obesity among male and non-White or Hispanic adults. The associations with hypertension also varied by sex and the timing of the exposure. [ABSTRACT FROM AUTHOR]

The evidence that fetal life and early infancy are "critical" or "sensitive" ages for later development of cardiometabolic disease is based on flawed methods for comparing different age periods. Moreover, most previous studies have limited their focus to weight gain, rather than growth in length/height or body mass index (weight (kg)/height (m)2). We undertook a secondary analysis of data from the Promotion of Breastfeeding Intervention Trial (1996–2010), a birth cohort study nested within a large cluster-randomized trial in the Republic of Belarus, that had repeated measurements of weight and length/height taken from birth to 11.5 years of age. We used mixed-effects linear models to analyze associations of changes in standardized weight, length/height, and body mass index during 5 age periods (conception to birth, birth to age 3 months, ages 3–12 months, ages 12 months–6.5 years, and ages 6.5–11.5 years) with fasting glucose, insulin, insulin resistance, β-cell function, and adiponectin at age 11.5 years. We observed strong associations between the metabolic markers and all 3 growth measures, with the largest magnitudes being observed during the latest age period (ages 6.5–11.5 years) and negligible associations during gestation and the first year of life. Later age periods appear more "sensitive" than earlier periods to the adverse metabolic association with rapid growth in childhood. [ABSTRACT FROM AUTHOR]

To investigate the risk of lung cancer after exposure to welding fumes, hexavalent chromium (Cr(VI)), and nickel, we analyzed 3,418 lung cancer cases and 3,488 controls among men from 2 German case-control studies (1988–1996). We developed a welding-process exposure matrix from measurements of these agents, and this was linked with welding histories from a job-specific questionnaire to calculate cumulative exposure variables. Logistic regression models were fitted to estimate odds ratios with confidence intervals conditional on study, and they adjusted for age, smoking, and working in other at-risk occupations. Additionally, we mutually adjusted for the other exposure variables under study. Overall, 800 cases and 645 controls ever worked as regular or occasional welders. Odds ratios for lung cancer with high exposure were 1.55 (95% confidence interval (CI): 1.17, 2.05; median, 1.8 mg/m3 × years) for welding fumes, 1.85 (95% CI: 1.35, 2.54; median, 1.4 μg/m3 × years) for Cr(VI), and 1.60 (95% CI: 1.21, 2.12; median, 9 μg/m3 × years) for nickel. Risk estimates increased with increasing cumulative exposure to welding fumes and with increasing exposure duration for Cr(VI) and nickel. Our results showed that welding fumes, Cr(VI), and nickel might contribute independently to the excess lung cancer risk associated with welding. However, quantitative exposure assessment remains challenging. [ABSTRACT FROM AUTHOR]

National data on dengue notifications do not capture all dengue infections and do not reflect the true intensity of disease transmission. To assess the true dengue infection rate and disease control efforts in Singapore, we conducted age-stratified serosurveys among residents after a 2013 outbreak that was the largest dengue outbreak on record. The age-weighted prevalence of dengue immunoglobulin G among residents was 49.8% (95% confidence interval: 48.4, 51.1) in 2013 and 48.6% (95% confidence interval: 47.0, 50.0) in 2017; prevalence increased with age. Combining these data with those from previous serosurveys, the year-on-year estimates of the dengue force of infection from 1930 to 2017 revealed a significant decrease from the late 1960s to the mid-1990s, after which the force of infection remained stable at approximately 10 per 1,000 persons per year. The reproduction number (R 0) had also declined since the 1960s. The reduction in dengue transmission may be attributed to the sustained national vector program and partly to a change in the age structure of the population. The improved estimated ratio of notified cases to true infections, from 1:14 in 2005–2009 to 1:6 in 2014–2017, signifies that the national notification system, which relies on diagnosed cases, has improved over time. The data also suggest that the magnitudes of dengue epidemics cannot be fairly compared across calendar years and that the current disease control program remains applicable. [ABSTRACT FROM AUTHOR]

Adults with congenital heart disease are increasingly being exposed to low-dose ionizing radiation (LDIR) from cardiac procedures. In a recent study, Cohen et al. (Circulation. 2018;137(13):1334–1345) reported an association between increased LDIR exposure and cancer incidence but did not explore temporal relationships. Yet, the impact of past exposures probably accumulates over years, and its strength may depend on the amount of time elapsed since exposure. Furthermore, LDIR procedures performed shortly before a cancer diagnosis may have been ordered because of early symptoms of cancer, raising concerns about reversal causality bias. To address these challenges, we combined flexible modeling of cumulative exposures with competing-risks methodology to estimate separate associations of time-varying LDIR exposure with cancer incidence and all-cause mortality. Among 24,833 patients from the Quebec Congenital Heart Disease Database, 602 had incident cancer and 500 died during a follow-up period of up to 15 years (1995–2010). Initial results suggested a strong association of cancer incidence with very recent LDIR exposures, likely reflecting reverse causality bias. When exposure was lagged by 2 years, an increased cumulative LDIR dose from the previous 2–6 years was associated with increased cancer incidence, with a stronger association for women. These results illustrate the importance of accurate modeling of temporal relationships between time-varying exposures and health outcomes. [ABSTRACT FROM AUTHOR]

Studies have documented that age at immigration and generational status are important predictors of socioeconomic outcomes among children of immigrants. Whether these characteristics are related to long-term risk of death is unknown. Leveraging variation within sibships, we evaluated the association of age at immigration and generational status (i.e. first or second generation) with death among children of immigrant mothers to Sweden. Data included 272,429 individuals (126,701 sibships) aged 15 or more years from the total Swedish population followed between 1990 and 2009. Population-average and sibling fixed-effect regressions were estimated, with the latter controlling for unobserved factors shared by siblings. The foreign-born children of immigrants experienced a 17% higher risk of death than the Swedish-born children of immigrants. This excess risk was evident for external and nonexternal causes of death. In general, a graded association was not detected between age at immigration and death among the foreign-born individuals; however, those arriving during primary school ages appeared especially vulnerable. This study provides robust evidence that among children of immigrants, being foreign born was associated with a long-term death penalty compared with being born in the host country. [ABSTRACT FROM AUTHOR]

Understanding risk factors for Ebola transmission is key for effective prediction and design of interventions. We used data on 860 cases in 129 chains of transmission from the latter half of the 2013–2016 Ebola epidemic in Guinea. Using negative binomial regression, we determined characteristics associated with the number of secondary cases resulting from each infected individual. We found that attending an Ebola treatment unit was associated with a 38% decrease in secondary cases (incidence rate ratio (IRR) = 0.62, 95% confidence interval (CI): 0.38, 0.99) among individuals that did not survive. Unsafe burial was associated with a higher number of secondary cases (IRR = 1.82, 95% CI: 1.10, 3.02). The average number of secondary cases was higher for the first generation of a transmission chain (mean = 1.77) compared with subsequent generations (mean = 0.70). Children were least likely to transmit (IRR = 0.35, 95% CI: 0.21, 0.57) compared with adults, whereas older adults were associated with higher numbers of secondary cases. Men were less likely to transmit than women (IRR = 0.71, 95% CI: 0.55, 0.93). This detailed surveillance data set provided an invaluable insight into transmission routes and risks. Our analysis highlights the key role that age, receiving treatment, and safe burial played in the spread of EVD. [ABSTRACT FROM AUTHOR]

Few data exist on the incidence or duration of natural Plasmodium falciparum infections in high-transmission settings. School-aged children (SAC) carry a disproportionate burden of infections, suggesting either increased incidence or increased duration. We estimated the incidence and duration of unique infections according to age groups. The Mfera Cohort Study (2014–2017) in Malawi had 2 years of follow-up, with 120 participants tested monthly and during sick visits. Blood samples were collected to detect P. falciparum by microscopy and polymerase chain reaction. Positive samples underwent genotyping. Simulation was used to account for high rates of nondetection of infection among low-parasitemia infections, which increase in frequency with age. Adults had significantly fewer unique infections per person per year (median, 2.5) compared with SAC and children younger than 5 years of age (6.3 and 6.6, respectively). Over half of all genotypes were persistent. Infections lasted significantly longer in adults (median, 180 days) and SAC (median, 163 days) compared with children younger than 5 years of age (median, 97 days), after accounting for age-dependent nondetection of infection. SAC acquired new infections at the same rate as children younger than 5 years, but they maintained these infections for longer periods of time, similar to adults. This study provides new insights into P. falciparum infection dynamics that should be considered when designing malaria control strategies. [ABSTRACT FROM AUTHOR]

This study explored the association between exposure to acetaminophen during pregnancy and pubertal development using data from 15,822 boys and girls in the longitudinal Puberty Cohort, nested within the Danish National Birth Cohort. Use of acetaminophen was reported 3 times during pregnancy and 6 months postpartum. In total, 54% of mothers indicated use at least once during pregnancy. Between 2012 and 2017, sons and daughters provided information on a wide range of pubertal milestones—including Tanner stages, axillary hair growth, and age at menarche or voice break and first ejaculation—every 6 months from 11 years of age until full sexual maturation. Data were analyzed using a regression model for interval-censored data, providing adjusted mean monthly differences in age at attaining the pubertal milestones according to intrauterine cumulative (weeks) and trimester-specific acetaminophen exposure. Our results suggested a tendency towards slightly earlier attainment of almost all studied markers of female pubertal development with increasing number of weeks of exposure (i.e. about 1.5–3 months earlier age at pubic hair, axillary hair, and acne development comparing unexposed with those prenatally exposed for more than 12 weeks). Male pubertal development had no strong association with acetaminophen exposure. [ABSTRACT FROM AUTHOR]

A(H1N1) strains of Influenzavirus were responsible for 2 pandemics in the last 100 years. Because infections experienced early in life may have a long-lasting influence on future immune response against other influenza strains, we drew on previously collected seroincidence data from Singapore (n = 2,554; June–October 2009) to investigate whether the 1918 pandemic influenza virus and its early descendants produced an age-related signature in immune responses against the A/California/7/2009(H1N1)pdm09 virus of 2009. Hemagglutination inhibition assays revealed a J-shaped relationship; the oldest birth cohort (born in 1911–1926) had the highest titers, followed by the youngest (born in 1987–1992). Differential response by vaccination history was also observed, with seasonal influenza vaccine being associated with higher titers mainly in the oldest birth cohort. On the assumption that antibody titers are a correlate of protection, structural equation modeling predicted that a titer-mediated effect by the vaccine could, on its own, account for a negative association with seroconversion equivalent to a risk reduction of 23% (relative risk = 0.77, 95% confidence interval: 0.60, 0.99) in the oldest birth cohort. A subset of 503 samples tested against the A/Brisbane/59/2007(H1N1) and A/Puerto Rico/8/1934(H1N1) strains also revealed different age-related antibody profiles. The effectiveness of seasonal influenza vaccines against future pandemic strains could thus be age-dependent and related to early-life exposures. [ABSTRACT FROM AUTHOR]

In the present article, I aimed to test the hypothesis that possible fatal immunological reactions to the A/H1N1 virus of the 1918 "Spanish" influenza pandemic were the result of previous exposure to the A/H3N8 virus of the 1890–1892 "Russian" influenza pandemic. Using newspapers and official death records to reconstruct mortality peaks from influenza and excess pneumonia deaths in New Zealand before 1918 enabled comparisons with peaks of influenza mortality by age in 1918 from individual death records. For males, mortality peaks in the 1885, 1890–1892, 1894, and 1898 influenza outbreaks appeared to match those from the 1918 pandemic. For females, peaks of deaths in 1918 corresponded to those from the influenza outbreaks of 1887 and 1890–1892. The highest mortality rates for both sexes were among those 28–32 years of age. Although they lend strong support to the hypothesis of fatal immunological reactions derived from early exposure to a different influenza virus, the results from this study also raise more questions: Given that the A/H1N1 virus of 1918 was exceptionally virulent, why did so few children 5–15 years of age die from it? Influenza normally kills only the very young and the very old. In addition, why did twice as many European males as females die in the young-adult age groups, whereas Māori males and females died at almost identical rates? [ABSTRACT FROM AUTHOR]

Adequate dietary protein intake is important for the maintenance of fat-free mass (FFM) and muscle strength, but optimal requirements remain unknown. Our aim in the current study was to explore the associations of protein intake with FFM and grip strength. We used baseline data from the UK Biobank (a study of 146,816 participants aged 40–69 years with data collected across the United Kingdom in 2007–2010) to examine the associations of protein intake with FFM and grip strength. Protein intake was positively associated with FFM (men: 5.1% (95% confidence interval (CI): 5.0, 5.2); women: 7.7% (95% CI: 7.7, 7.8)) and grip strength (men: 0.076 kg/kg (95% CI: 0.074, 0.078); women: 0.074 kg/kg (95% CI: 0.073, 0.076)) per 0.5-g/kg/day (grams per kg of body mass per day) increment in protein intake. FFM and grip strength were higher with higher intakes across the full range of intakes (i.e. highest in persons who reported consuming ≥2.00 g/kg/day) independently of sociodemographic factors, other dietary measures, physical activity, and comorbidity. FFM and grip strength were lower with age, but this association did not differ by category of protein intake (P > 0.05). The current recommendation for all adults (ages 40–69 years) to maintain a protein intake of 0.8 g/kg/day may need to be increased to optimize FFM and grip strength. [ABSTRACT FROM AUTHOR]

Arsenic in drinking water is known to cause cancer and noncancer diseases, but little is known about its association with age at exposure. Here, we investigated age at arsenic exposure and mortality in Antofagasta, Chile, 30–40 years after a distinct period of very high water arsenic concentrations (1958–1970). We calculated standardized mortality ratios (SMRs) comparing Antofagasta with the rest of Chile for 2001–2010 by sex and age at potential first exposure. A remarkable relationship with age at first exposure was found for bronchiectasis, with increased risk in adults 30–40 years after exposure being confined to those who were in utero (SMR = 11.7, 95% confidence interval (CI): 4.3, 25.4) or aged 1–10 years (SMR = 5.4, 95% CI: 1.1, 15.8) during the high-exposure period. Increased SMRs for lung, bladder, and laryngeal cancer were evident for exposures starting at all ages, but the highest SMRs were for exposures beginning at birth (for bladder cancer, SMR = 16.0 (95% CI: 10.3, 23.8); for laryngeal cancer, SMR = 6.8 (95% CI: 2.2, 15.8); for lung cancer, SMR = 3.8 (95% CI: 2.9, 4.9)). These findings suggest that interventions targeting early-life arsenic exposure could have major impacts in reducing long-term mortality due to arsenic 30–40 years after exposure ends. [ABSTRACT FROM AUTHOR]

Madagascar reports few measles cases annually and high vaccination campaign coverage. However, the underlying age profile of immunity and risk of a measles outbreak is unknown. We conducted a nested serological survey, testing 1,005 serum samples (collected between November 2013 and December 2015 via Madagascar's febrile rash surveillance system) for measles immunoglobulin G antibody titers. We directly estimated the age profile of immunity and compared these estimates with indirect estimates based on a birth cohort model of vaccination coverage and natural infection. Combining these estimates of the age profile of immunity in the population with an age-structured model of transmission, we further predicted the risk of a measles outbreak and the impact of mitigation strategies designed around supplementary immunization activities. The direct and indirect estimates of age-specific seroprevalence show that current measles susceptibility is over 10%, and modeling suggests that Madagascar may be at risk of a major measles epidemic. [ABSTRACT FROM AUTHOR]

Circulating levels of vitamin D are generally lower in African Americans than in US whites, and 1 prior analysis carried out in a small number of African Americans suggested that, within this population, vitamin D levels may be related to the degree of genetic admixture. We assessed the association between percentage of European ancestry and serum vitamin D level (assessed in 2013-2015) among 2,183 African-American women from the Black Women's Health Study whose DNA had been genotyped for ancestry-informative markers. ADMIXMAP software was used to estimate the percentage of European ancestry versus African ancestry in each individual. In linear regression analyses with adjustment for genotype batch, age, body mass index, supplemental vitamin D use, ultraviolet B radiation flux in the participant's state of residence, and season of blood draw, each 10% increase in European ancestry was associated with a 0.67-ng/mL increase in serum vitamin D concentration (95% confidence interval: 0.17, 1.17). The association was statistically significant only among women who were not taking vitamin D supplements (for each 10% increase in European ancestry, β = 0.86, 95% confidence interval: 0.14, 1.57). Among African Americans, use of vitamin D supplements may help to reduce vitamin D deficiency associated with genetic ancestry. [ABSTRACT FROM AUTHOR]

Dietary protein may help prevent age-related declines in strength and functional capacity. This study examines the independent relationship between dietary protein and longitudinal changes in physical functioning among adults participating in the Framingham Offspring Study from examination 5 (1991-1995) to examination 8 (2005-2008). Protein intakes were derived from 3-day diet records during examinations 3 and 5; functional status was determined over 12 years using 7 items selected from standardized questionnaires. Multivariable models adjusted for age, sex, education, physical activity, smoking, height, and energy intake. Functional tasks that benefitted most from a higher-protein diet (≥1.2 g/kg/day vs. <0.8 g/kg/day) were doing heavy work at home, walking 1/2 mile (0.8 km), going up and down stairs, stooping/kneeling/crouching, and lifting heavy items. Those with higher protein intakes were 41% less likely (95% CI: 0.43, 0.82) to become dependent in 1 or more of the functional tasks over follow-up. Higher physical activity and lower body mass index were both independently associated with less functional decline. The greatest risk reductions were found among those with higher protein intakes combined with either higher physical activity, more skeletal muscle mass, or lower body mass index. This study demonstrates that dietary protein intakes above the current US Recommended Daily Allowance may slow functional decline in older adults. [ABSTRACT FROM AUTHOR]

The benefits of using electronic health records (EHRs) for disease risk screening and personalized health-care decisions are being increasingly recognized. Here we present a computationally feasible statistical approach with which to address the methodological challenges involved in utilizing historical repeat measures of multiple risk factors recorded in EHRs to systematically identify patients at high risk of future disease. The approach is principally based on a 2-stage dynamic landmark model. The first stage estimates current risk factor values from all available historical repeat risk factor measurements via landmark-age-specific multivariate linear mixed-effects models with correlated random intercepts, which account for sporadically recorded repeat measures, unobserved data, and measurement errors. The second stage predicts future disease risk from a sex-stratified Cox proportional hazards model, with estimated current risk factor values from the first stage. We exemplify these methods by developing and validating a dynamic 10-year cardiovascular disease risk prediction model using primary-care EHRs for age, diabetes status, hypertension treatment, smoking status, systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol in 41,373 persons from 10 primary-care practices in England and Wales contributing to The Health Improvement Network (1997-2016). Using cross-validation, the model was well-calibrated (Brier score = 0.041, 95% confidence interval: 0.039, 0.042) and had good discrimination (C-index = 0.768, 95% confidence interval: 0.759, 0.777). [ABSTRACT FROM AUTHOR]

Measures of biological age based on blood DNA methylation, referred to as age acceleration (AA), have been developed. We examined whether AA was associated with health risk factors and overall and cause-specific mortality. At baseline (1990-1994), blood samples were drawn from 2,818 participants in the Melbourne Collaborative Cohort Study (Melbourne, Victoria, Australia). DNA methylation was determined using the Infinium Human Methylation 450 BeadChip array (Illumina Inc., San Diego, California). Mixed-effects models were used to examine the association of AA with health risk factors. Cox models were used to assess the association of AA with mortality. A total of 831 deaths were observed during a median 10.7 years of follow-up. Associations of AA were observed with male sex, Greek nationality (country of birth), smoking, obesity, diabetes, lower education, and meat intake. AA measures were associated with increased mortality, and this was only partly accounted for by known determinants of health (hazard ratios were attenuated by 20%-40%). Weak evidence of heterogeneity in the association was observed by sex (P = 0.06) and cause of death (P = 0.07) but not by other factors. DNA-methylation-based AA measures are associated with several major health risk factors, but these do not fully explain the association between AA and mortality. Future research should investigate what genetic and environmental factors determine AA. [ABSTRACT FROM AUTHOR]

Although arrest rates among juveniles have substantially decreased since the 1990s, US national trends in conduct problems are unknown. Population variation in conduct problems would imply changes in the social environment, which would include emergent or receding risk factors. In the present study, we separated age, period, and cohort effects on conduct problems using nationally representative surveys of 375,879 US students conducted annually (1991-2015). The summed score of 7 items measuring the frequency of conduct problems was the outcome. Conduct problems have decreased during the past 25 years among boys; the total amount of the decrease was approximately 0.4 standard deviations (P < 0.01), and by item prevalence, the total amount of the decrease was 8%-11%. Declines are best explained by period effects beginning approximately in 2008, and a declining cohort effect beginning among those born after 1992, which suggests not only declines in population levels, but more rapid declines among younger cohorts of boys. Trends were also consistent with age-period-cohort effects on evenings spent out, which suggest a possible mechanism. Conduct problems among girls were lower than boys and did not demonstrate trends across time. These changes may reflect the changing nature of adolescence toward less unsupervised interaction. [ABSTRACT FROM AUTHOR]