Effectiveness of residential versus outpatient therapy for smoking cessation: The START randomized clinical trial.

BACKGROUND AND AIMS: Tobacco smoking represents a major cause for preventable death and morbidity. Results from non-randomized studies suggest that smoking cessation therapy in a residential setting might be a new viable way to facilitate smoking abstinence. We aimed to test the effects of residential multicomponent group therapy for smoking cessation compared with outpatient group therapy. DESIGN: Prospective parallel-group open-label randomized superiority trial, with assessments at baseline, 6 and 12 months. SETTING: Recruitment throughout Germany via media advertisements. PARTICIPANTS: Adult smokers (≥10 cigarettes/day) randomly assigned to residential (n = 157) or outpatient (n = 158) therapy. 51.8% female; mean age 53.2 years; mean years of smoking 34.4. INTERVENTION AND COMPARATOR: Residential 9-day smoking cessation group therapy comprising six daily therapy sessions and supportive interventions for cessation and daily structure embedded in the routines of a somatic rehabilitation center, compared with weekly outpatient smoking cessation group therapy (3-7 weeks) provided in routine care courses close to the participants' places of residence, both including at least 9 h of behavioral therapy. MEASUREMENTS: Co-primary outcomes were self-reported continuous 6- and 12-month abstinence (hierarchically ordered). Primary analyses were conducted in the therapy-uptake population including participants who started therapy with sensitivity analyses in the intention-to-treat population of all randomized participants. FINDINGS: Intervention uptake rates were 87.3% (n = 137) in the residential and 60.1% (n = 95) in the outpatient group. In the therapy-uptake population, abstinence rates were 46.7% in the residential versus 26.3% in the outpatient group at 6 months (odds ratio [OR] = 2.46, 95% confidence interval [CI] = 1.39-4.33, P = 0.0019) and 39.4% versus 24.2% at 12 months (OR = 2.04, 95% CI = 1.14-3.64, P = 0.017). Biochemically validated abstinence rates at 12 months were 33.1% in the residential versus 17.4% in the outpatient group (OR = 2.35, 95% CI = 1.22-4.51, P = 0.011). In the intention-to-treat population, self-reported and biochemically validated abstinence rates at 12 months were 34.4% in the residential versus 14.6% in the outpatient group (OR = 3.08, 95% CI = 1.77-5.34, P < 0.0001) and 28.6% versus 10.3% (OR = 3.48, 95% CI = 1.85-6.52, P = 0.0001), respectively. CONCLUSIONS: Residential therapy exclusively for smoking cessation is feasible and effective and could be a beneficial new treatment for smokers.

Sleep-Related Predictors of Risk for Alcohol Use and Related Problems in Adolescents and Young Adults.

PURPOSE: Growing evidence supports sleep and circadian rhythms as influencing alcohol use and the course of alcohol use disorder (AUD). Studying sleep/circadian-alcohol associations during adolescence and young adulthood may be valuable for identifying sleep/circadian-related approaches to preventing and/or treating AUD. This paper reviews current evidence for prospective associations between sleep/circadian factors and alcohol involvement during adolescence and young adulthood with an emphasis on the effects of sleep/circadian factors on alcohol use. SEARCH METHODS: The authors conducted a literature search in PsycInfo, PubMed, and Web of Science using the search terms "sleep" and "alcohol" paired with "adolescent" or "adolescence" or "young adult" or "emerging adult," focusing on the title/abstract fields, and restricting to English-language articles. Next, the search was narrowed to articles with a prospective/longitudinal or experimental design, a sleep-related measure as a predictor, an alcohol-related measure as an outcome, and confirming a primarily adolescent and/or young adult sample. This step was completed by a joint review of candidate article abstracts by two of the authors. SEARCH RESULTS: The initial search resulted in 720 articles. After review of the abstracts, the list was narrowed to 27 articles reporting on observational longitudinal studies and three articles reporting on intervention trials. Noted for potential inclusion were 35 additional articles that reported on studies with alcohol-related predictors and sleep-related outcomes, and/or reported on candidate moderators or mediators of sleep-alcohol associations. Additional articles were identified via review of relevant article reference lists and prior exposure based on the authors' previous work in this area. DISCUSSION AND CONCLUSIONS: Overall, the review supports a range of sleep/circadian characteristics during adolescence and young adulthood predicting the development of alcohol use and/or alcohol-related problems. Although sleep treatment studies in adolescents and young adults engaging in regular and/or heavy drinking show that sleep can be improved in those individuals, as well as potentially reducing alcohol craving and alcohol-related consequences, no studies in any age group have yet demonstrated that improving sleep reduces drinking behavior. Notable limitations include relatively few longitudinal studies and only two experimental studies, insufficient consideration of different assessment timescales (e.g., day-to-day vs. years), insufficient consideration of the multidimensional nature of sleep, a paucity of objective measures of sleep and circadian rhythms, and insufficient consideration of how demographic variables may influence sleep/circadian-alcohol associations. Examining such moderators, particularly those related to minoritized identities, as well as further investigation of putative mechanistic pathways linking sleep/circadian characteristics to alcohol outcomes, are important next steps.

Normative Perceptions of Sexual Behavior and Alcohol Use among Bisexual Women.

Background: As compared to heterosexual and lesbian women, bisexual women report higher rates of alcohol, other substance use, and risky sexual behavior, and they experience more negative outcomes from these behaviors. Descriptive norms (i.e., perceptions of others' behavior) are an important predictor of risky behaviors, but scant research has examined whether bisexual women's perceptions of other bisexual women's alcohol use and sexual behavior are associated with their own alcohol or drug use during sex. Objectives: Consequently, the present study examined (1) whether perceived sex norms were related to engagement in sex and (2) the relative influence of drinking and sex norms on engaging in sex while drinking among bisexual women. Method: Data were collected from 225 self-identified bisexual women who completed an online survey about their typical weekly alcohol use, engagement in alcohol or drug use during sex in the past 30 days, and normative perceptions of drinking and sexual behavior. Results: Regression models demonstrated both sexual norms and drinking frequency norms were positively associated with alcohol or drug use during sex. In addition, only perceived norms of other bisexual women, compared to perceived norms of lesbian and heterosexual women, predicted engagement in sex. Conclusions: Bisexual women may be susceptible to normative perceptions, given their connectedness to a marginalized social group. Thus, alcohol prevention and intervention efforts aimed at reducing risky consequences among bisexual women should specifically consider drinking and sexual norms of other bisexual women.

Impulsivity, sex-related alcohol expectancies, alcohol use, and sexual risk-taking among bisexual women.

BACKGROUND AND OBJECTIVES: According to the acquired preparedness model, personality traits, such as impulsivity, may influence the learning process, contributing to heightened expectations surrounding risky behaviors (i.e., alcohol use, sexual risk-taking). As bisexual women demonstrate heightened risk for hazardous alcohol- and sex-related behaviors, the present study examined a sequential pathway, whereby the relation between impulsivity and sexual risk-taking is mediated through sex-related alcohol expectancies and alcohol use. METHODS: Data were collected from 225 self-identified cisgender, bisexual women between the ages of 18 and 30 years (M = 22.77, SD = 3.45), who participated in an online survey. Participants reported on impulsivity, sex-related alcohol expectancies, alcohol use, and experiences of sexual risk-taking. RESULTS: Results revealed that sex-related alcohol expectancies and alcohol use sequentially mediated the relation between impulsivity and sexual risk-taking. Thus, greater impulsivity was related to greater sexual risk-taking through heightened sex-related alcohol expectancies and elevated alcohol use. DISCUSSION AND CONCLUSIONS: Findings from this study highlight mechanisms associated with risky drinking and sexual behaviors among this at-risk population. Such information could aid the development of more efficacious prevention and intervention programs aimed at reducing consequences associated with alcohol use and sexual risk-taking among bisexual women. SCIENTIFIC SIGNIFICANCE: Bisexual women are at heightened risk for alcohol-related problems, including sexual risk-taking. Findings from the current study identify impulsivity and sex-related alcohol expectancies as independent and integrative predictors of such risky behaviors. Incorporation of these constructs may aid in the development of more efficacious clinical methods aimed at bettering health outcomes among bisexual women.

Using the theory of planned behavior to assess willingness and attitudes towards COVID-19 vaccination among a predominantly white U.S. college sample.

Objective: Through the lens of behavioral models such as the Theory of Planned Behavior (TPB) and the Health Belief Model, the present study (1) investigated U.S. university students' willingness to receive the COVID-19 vaccine and (2) examined predictors (e.g. demographics, past vaccine experience, TPB constructs) of vaccine willingness. Method: University students (n = 170) completed a survey assessing demographics, health behaviors, attitudes, perceived severity/susceptibility, norms, and vaccine intentions related to the COVID-19 pandemic. Data were collected from April 2020 through July 2020. Results: Overall, 56.5% of participants indicated that they would be willing to receive the COVID-19 vaccine once it is available, 39.4% were unsure of whether they would receive the vaccine, and 4.1% indicated they would not receive the vaccine. Multinomial logistic regression indicated that greater adherence to CDC guidelines (p = .030) and greater perceived pro-vaccine norms (p < .001) predicted greater vaccine willingness. Conclusions: Results from this study are consistent with previous literature on vaccine hesitancy, whereby normative beliefs and adherence to CDC guidelines were found to be determinants of vaccine willingness. To reduce transmission of the COVID-19 pandemic, interventions aimed at promoting positive attitudes towards vaccination should aim to incorporate these observed determinants.

Association between urinary iodine excretion, genetic disposition and fluid intelligence in children, adolescents and young adults: the DONALD study.

PURPOSE: Iodine deficiency increases the risk of cognitive impairment and delayed physical development in children. It is also associated with cognitive impairment in adults. Cognitive abilities are among the most inheritable behavioural traits. However, little is known about the consequences of insufficient postnatal iodine intake and whether the individual genetic disposition modifies the association between iodine intake and fluid intelligence in children and young adults. METHODS: The cultural fair intelligence test was used to assess fluid intelligence in the participants of the DONALD study (n = 238; mean age, 16.5 [SD = 7.7] years). Urinary iodine excretion, a surrogate iodine intake marker, was measured in 24-h urine. Individual genetic disposition (n = 162) was assessed using a polygenic score, associated with general cognitive function. Linear regression analyses were conducted to determine whether Urinary iodine excretion was associated with fluid intelligence and whether this association was modified by individual genetic disposition. RESULTS: Urinary iodine excretion above the age-specific estimated average requirement was associated with a five-point higher fluid intelligence score than that below the estimated average requirement (P = 0.02). The polygenic score was positively associated with the fluid intelligence score (ß = 2.3; P = 0.03). Participants with a higher polygenic score had a higher fluid intelligence score. CONCLUSION: Urinary iodine excretion above the estimated average requirement in childhood and adolescence is beneficial for fluid intelligence. In adults, fluid intelligence was positively associated with a polygenic score for general cognitive function. No evidence showed that the individual genetic disposition modifies the association between Urinary iodine excretion and fluid intelligence.

A daily examination of perceived stress and coping strategies used among college students during COVID-19.

This study examined inter- and intra-person level associations between stress and overwhelm and adaptive coping strategies used by college students during COVID-19. Participants were 55 college students (Mage = 23.31, SD = 4.49; 87% White, 85% Female), who completed a 21-day daily diary study. The common coping strategies endorsed were media use, relaxation techniques, and exercise. Variability among feelings of stress (ICC = .520) and overwhelm (ICC = .530) were similarly explained by between and within-person differences. Daily stress and overwhelm were positively associated with relaxation techniques, media, and total coping strategies. Further, daily stress was positively associated with connection with others to cope. At the between-person level, average stress was associated with avoidance strategies such as taking a break from news to cope. These findings may prove useful in the development of interventions to increase the practice of adaptive coping strategies to reduce stress and overwhelm.

A healthy lifestyle during adolescence was inversely associated with fatty liver indices in early adulthood: findings from the DONALD cohort study.

A healthy lifestyle during adolescence is associated with insulin sensitivity or liver enzyme levels and thus might contribute to the prevention of non-alcoholic fatty liver disease (NAFLD). Therefore, we examined the association between adherence to a hypothesis-based lifestyle score including dietary intake, physical activity, sedentary behaviour, sleep duration and BMI in adolescence and fatty liver indices in early adulthood. Overall, 240 participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed study completed repeated measurements of lifestyle score factors during adolescence (females: 8·5-15·5 years, males: 9·5-16·5 years). Multivariable linear regression models were used to investigate the association between adolescent lifestyle scores and NAFLD risk (hepatic steatosis index (HSI) and fatty liver index (FLI)) in early adulthood (18-30 years). Participants visited the study centre 4·9 times during adolescence and achieved on average 2·8 (min: 0·6, max: 5) out of five lifestyle score points. Inverse associations were observed between the lifestyle score and fatty liver indices (HSI: ß=-5·8 % (95 % CI -8·3, -3·1), P < 0·0001, FLI: ß=-32·4 % (95 % CI -42·9, -20·0), P < 0·0001) in the overall study population. Sex-stratified analysis confirmed these results in men, while inverse but non-significant associations were observed in women (P > 0·05). A higher lifestyle score was associated with lower HSI and FLI values, suggesting that a healthy lifestyle during adolescence might contribute to NAFLD prevention, predominantly in men. Our findings on repeatedly measured lifestyle scores in adolescents and their association with NAFLD risk in early adulthood warrant confirmation in larger study populations.

Analysis of associations between dietary patterns, genetic disposition, and cognitive function in data from UK Biobank.

PURPOSE: Research suggests that diet influences cognitive function and the risk for neurodegenerative disease. The present study aimed to determine whether a recently developed diet score, based on recommendations for dietary priorities for cardio metabolic health, was associated with fluid intelligence, and whether these associations were modified by individual genetic disposition. METHODS: This research has been conducted using the UK Biobank Resource. Analyses were performed using self-report data on diet and the results for the verbal-numerical reasoning test of fluid intelligence of 104,895 individuals (46% male: mean age at recruitment 57.1 years (range 40-70)). For each participant, a diet score and a polygenic score (PGS) were constructed, which evaluated predefined cut-offs for the intake of fruit, vegetables, fish, processed meat, unprocessed meat, whole grain, and refined grain, and ranged from 0 (unfavorable) to 7 (favorable). To investigate whether the diet score was associated with fluid intelligence, and whether the association was modified by PGS, linear regression analyses were performed. RESULTS: The average diet score was 3.9 (SD 1.4). After adjustment for selected confounders, a positive association was found between baseline fluid intelligence and PGS (P < 0.001). No association was found between baseline fluid intelligence and diet score (P = 0.601), even after stratification for PGS, or in participants with longitudinal data available (n = 9,482). CONCLUSION: In this middle-aged cohort, no evidence was found for an association between the investigated diet score and either baseline or longitudinal fluid intelligence. However, as in previous reports, fluid intelligence was strongly associated with a PGS for general cognitive function.

Dimensions of binegativity differentially predict drinking to cope motivations and alcohol use severity among bisexual women.

Research indicates that bisexual women experience greater stigmatization and discrimination compared to lesbian women. Such oppression is described as binegativity and is associated with alcohol use among bisexual women. Specifically, previous research has suggested that bisexual women may drink to cope in an effort to self-medicate from experiences of binegativity. Although substantial research has been conducted with regard to drinking behaviors among at-risk groups, research has yet to identify which specific types of binegativity may be most predictive of drinking outcomes among bisexual women. Consequently, the present study sought to examine the predictive utility of three dimensions of binegativity: (a) sexual orientation instability (e.g., the perception of bisexuality as an illegitimate sexual orientation), (b) sexual irresponsibility (e.g., the stereotype that bisexual persons are oversexualized or sexually promiscuous), and (c) interpersonal hostility (e.g., the alienation and uncomfortability with bisexual identification), on drinking to cope motivations and alcohol use severity. Participants were 225 self-identified bisexual women between the ages of 18 and 30 years (Mean = 22.77, SD = 3.45) who participated in a larger study about health behaviors among bisexual women. Multiple regressions revealed that, compared to other binegativity dimensions, sexual irresponsibility was the strongest predictor of typical alcohol use, drinking to cope motivations, and alcohol use severity. Thus, bisexual women who are stereotyped to be sexually promiscuous are at particular risk for problematic alcohol use. Prevention and intervention efforts should target stress associated with experiences of oversexualized stigmatizations, in an effort to reduce alcohol-related risk among bisexual women. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A lifestyle score in childhood and adolescence was positively associated with subsequently measured fluid intelligence in the DONALD cohort study.

PURPOSE: Lifestyle scores which combine single factors such as diet, activity, or sleep duration showed associations with cognitive decline in adults. However, the role of a favourable lifestyle in younger age and the build-up of cognitive reserve is less clear, which is why we investigated longitudinal associations between a lifestyle score in childhood and adolescence and fluid intelligence obtained on average 6 years later. METHODS: In the DONALD cohort, a lifestyle score of 0 to 4 points including healthy diet and duration of moderate-to-vigorous physical activity, sedentary behaviour and sleep was repeatedly assessed in participants aged 5 and 19 years. Data on fluid intelligence were assessed via a German version of the culture fair intelligence test (CFT), using CFT 1-R in children 8.5 years of age or younger (n = 62) or CFT 20-R in participants older than 8.5 years (n = 192). Multivariable linear regression models were used to investigate prospective associations between the lifestyle score and the fluid intelligence score. RESULTS: Mean lifestyle score of all participants was 2.2 (0.7-4) points. A one-point increase in the lifestyle score was associated with a higher fluid intelligence score (4.8 points [0.3-7.3], p = 0.0343) for participants completing the CFT 20-R. Furthermore, each additional hour of sedentary behaviour was associated with a lower fluid intelligence score (- 3.0 points [- 5.7 to - 0.3], p = 0.0313). For younger participants (CFT 1-R), no association was found in any analysis (p > 0.05). CONCLUSION: A healthy lifestyle was positively associated with fluid intelligence, whereby sedentary behaviour itself seemed to play a prominent role.

Associations of Adherence to a Dietary Index Based on the EAT-Lancet Reference Diet with Nutritional, Anthropometric, and Ecological Sustainability Parameters: Results from the German DONALD Cohort Study.

BACKGROUND: Validation of the EAT-Lancet reference diet (ELR-diet), recently proposed by the EAT-Lancet Commission, within the context of real-life studies is necessary to elucidate its feasibility, nutritional value, sustainability, and health effects. OBJECTIVES: We aimed to develop a dietary index (DI) score to measure adherence to the ELR-diet. We further aimed to study the association between the DI score and 1) nutritional characteristics, 2) indicators of ecological sustainability, and 3) anthropometric markers and biomarkers for cardiometabolic health. METHODS: A DI score was constructed by comparing the categories defined by the ELR-diet with the dietary data of 2-5 sets of 3-d weighed dietary records from DONALD (Dortmund Nutritional and Anthropometric Longitudinal Designed) study participants (n = 298; ≥15 y of age). Prospective associations between the DI score and risk markers (anthropometric and cardiometabolic) in young adulthood (≥18 y old) were investigated using multivariate linear regression. RESULTS: Adherence to the DI score components was considerable (majority > 50%), but varied within the population (2%-100%). The highest tertile of the DI score was inversely associated with the intake of protein (tertile 3 compared with tertile 1: 13.5 compared with 14.5 energy %), added sugars (10.5 compared with 12.4 energy %), and cholesterol (100 compared with 116 mg/1000 kcal), but positively associated with fiber intake (10.0 compared with 8.82 g/1000 kcal) (all P < 0.05). The DI score was inversely associated with greenhouse-gas emissions (tertile 1 compared with tertile 3: 6.48 compared with 5.85 kg of carbon dioxide equivalents/2500 kcal; P < 0.001) and land use (8.24 compared with 7.16 m2 × y/2500 kcal; P < 0.001). Inverse associations between the DI score and anthropometric markers during young adulthood were observed (e.g., BMI: tertile 1 compared with tertile 3: 22.9 compared with 21.9 kg/m2; P = 0.03) (all P < 0.05). No associations between the DI score and cardiometabolic risk markers were found (all P ≥ 0.05). CONCLUSIONS: Adherence to the ELR-diet was associated with favorable nutritional characteristics and reduced environmental impact. Adherence to the DI score in adolescence was also beneficial with respect to anthropometric markers in early adulthood, although not for further cardiometabolic risk markers.

Risk factors associated with alcohol and drug use among bisexual women: A literature review.

Bisexual women report elevated alcohol and drug use compared to other sexual minority women. This review summarized extant research on mechanisms (i.e., coping processes with minority stress and victimization, disclosure of sexual identity, connectedness to lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ +) community, religiosity, and normative perceptions) that may influence alcohol and other drug use among bisexual women. Specifically, bisexual women experience unique sexual discrimination (i.e., binegativity) and are at heightened risk for other forms of victimization and other stressful life events. Given this heightened experience with stress, bisexual women may use alcohol as a maladaptive coping mechanism. Further, disclosure of one's sexual identity may produce opportunities for connecting with the LGBTQ + community, but such openness may increase exposure to discrimination and stigmatization among bisexual women. Findings on religiosity have been mixed, but there is some support that bisexual women may use substances in response to internal conflict between their religious beliefs and sexual identity. Lastly, we found that normative perceptions of other bisexual women's drinking behaviors are strongly tied to their own levels of alcohol use. From a therapeutic perspective, we suggest that practitioners recognize the unique experience of minority stress and teach strategies that lessen internalized stigma and promote healthy psychosocial adjustment among their bisexual clients. Clinicians may also help their clients find sources of support, which may protect them against the use of alcohol and drugs to manage minority-induced stress. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A lifestyle pattern during adolescence is associated with cardiovascular risk markers in young adults: results from the DONALD cohort study.

Lifestyle score approaches combining individual lifestyle factors, e.g. favourable diet, physical activity or normal body weight, showed inverse associations with cardiovascular disease (CVD) risk. However, research mainly focussed on adult behaviour and is scarce for vulnerable time windows for adult health like adolescence. We investigated associations between an adolescent lifestyle score and CVD risk markers in young adulthood. Overall, we analysed 270 participants of the open DONALD cohort study with 1-6 complete measurements of five lifestyle factors (healthy diet, moderate-to-vigorous physical activity, sedentary behaviour, sleep duration and BMI standard deviation score) during adolescence (females: 8⋅5-15⋅5 years and males: 9⋅5-16⋅5 years). Multivariable linear regression models were used to investigate the prospective association between the adolescent lifestyle score (0-5 points) and CVD risk markers in young adulthood (18-30 years). On average, participants obtained a mean adolescent lifestyle score of 2⋅9 (0-5) points. Inverse associations between the adolescent lifestyle score and waist circumference, waist-to-height ratio and percentage of body fat were observed (4⋅1, 4⋅1 and 9⋅2 % decrease per 1 point increase in adolescent lifestyle score, respectively, P < 0⋅05). For the remaining CVD risk markers (glucose, blood lipids, blood pressure and a proinflammatory score), no associations were observed. A healthy adolescent lifestyle is particularly associated with CVD risk-related favourable anthropometric markers in adulthood. A more comprehensive understanding of lifestyle patterns in the life course might enable earlier, targeted preventive measures to assist vulnerable groups in prevention of chronic diseases.

Advances in dietary pattern analysis in nutritional epidemiology.

BACKGROUND AND PURPOSE: It used to be a common practice in the field of nutritional epidemiology to analyze separate nutrients, foods, or food groups. However, in reality, nutrients and foods are consumed in combination. The introduction of dietary patterns (DP) and their analysis has revolutionized this field, making it possible to take into account the synergistic effects of foods and to account for the complex interaction among nutrients and foods. Three approaches of DP analysis exist: (1) the hypothesis-based approach (based on prior knowledge regarding the current understanding of dietary components and their health relation), (2) the exploratory approach (solely relying on dietary intake data), and (3) the hybrid approach (a combination of both approaches). During the recent past, complementary approaches for DP analysis have emerged both conceptually and methodologically. METHOD: We have summarized the recent developments that include incorporating the Treelet transformation method as a complementary exploratory approach in a narrative review. RESULTS: Uses, peculiarities, strengths, limitations, and scope of recent developments in DP analysis are outlined. Next, the narrative review gives an overview of the literature that takes into account potential relevant dietary-related factors, specifically the metabolome and the gut microbiome in DP analysis. Then the review deals with the aspect of data processing that is needed prior to DP analysis, particularly when dietary data arise from assessment methods other than the long-established food frequency questionnaire. Lastly, potential opportunities for upcoming DP analysis are summarized in the outlook. CONCLUSION: Biological factors like the metabolome and the microbiome are crucial to understand diet-disease relationships. Therefore, the inclusion of these factors in DP analysis might provide deeper insights.

Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (ß = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (ß = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (ß = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.

Different domains of self-reported physical activity and risk of type 2 diabetes in a population-based Swedish cohort: the Malmö diet and Cancer study.

BACKGROUND: While a dose-response relationship between physical activity and risk of diabetes has been demonstrated, few studies have assessed the relative importance of different measures of physical activity on diabetes risk. The aim was to examine the association between different self-reported measures of physical activity and risk of type 2 diabetes in a prospective cohort study. METHODS: Out of 26,615 adults (45-74 years, 60% women) in the population-based Swedish Malmö Diet and Cancer Study cohort, 3791 type 2 diabetes cases were identified from registers during 17 years of follow-up. Leisure-time (17 activities), occupational and domestic physical activity were assessed through a questionnaire, and these and total physical activity were investigated in relation to type 2 diabetes risk. RESULTS: All physical activity measures showed weak to modest associations with type 2 diabetes risk. The strongest association was found in the lower end of leisure-time physical activity in dose-response analysis at levels approximately below 22 MET-hrs/week (300 min/week) representing around 40% of the population. Compared with the lowest quintile, the moderate leisure-time physical activity category had a 28% (95% CI: 0.71, 0.87) decreased risk of type 2 diabetes. Total physical activity showed a similar, but weaker, association with diabetes risk as to that of leisure-time physical activity. Domestic physical activity was positively and linearly related to diabetes risk, HR = 1.11 (95% CI: 0.99, 1.25) comparing highest to lowest quintile. There was no association between occupational physical activity and diabetes risk. CONCLUSION: A curvilinear association was observed between leisure-time physical activity and risk of diabetes. Beyond a threshold level of approximately 22 MET-hrs/week or 300 min/week, no additional risk reduction was observed with increase in physical activity.

Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years.

BACKGROUND: The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear. METHODS: At baseline (1991-1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malmö Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up. RESULTS: During a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 -1.36 versus quartile 4 -1.54 mL/min/1.73 m2; P < 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10-1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08-1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38-1.74) and OR 1.21 (95% CI 1.09-1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18-1.74)] during a mean follow-up time of 19.2 years. CONCLUSION: Our results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.

Genetic Predisposition for Renal Dysfunction and Incidence of CKD in the Malmö Diet and Cancer Study.

BACKGROUND: Genome-wide association studies (GWAS) have identified >50 single nucleotide polymorphisms (SNP) in association with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) but little is known about whether the combination of these SNPs may aid in prediction of future incidence of CKD in the population. METHODS: We included 2301 participants with baseline eGFR ≥60 mL/min per 1.73 m2 from the Malmö Diet and Cancer Study-Cardiovascular Cohort. The eGFR was estimated during baseline (1991-1996) and after a mean follow-up of 16.6 years using the CKD-Epidemiology Collaboration 2009 creatinine equation. We combined 53 SNPs into a genetic risk score weighted by the effect size (wGRSCKD), and examined its association with incidence of CKD stage 3A (eGFR ≤60 mL/min per 1.73 m2). RESULTS: At follow-up, 453 study participants were defined as having CKD stage 3A. We observed a strong association between wGRSCKD and eGFR at baseline (P = 6.5 × 10-8) and at the follow-up reexamination (P = 5.0 × 10-10). The odds ratio (OR) for incidence of CKD stage 3A was 1.25 per 1 SD increment in the wGRSCKD (95% confidence interval [CI]: 1.12-1.39) adjusting for potential confounders (sex, age, body mass index [BMI], baseline eGFR, fasting glucose, systolic blood pressure (SBP), antihypertensive treatment, smoking, follow-up time). Adding wGRSCKD on the top of traditional risk factors did not improve the C-statistics (P = 0.12), but the Net Reclassification-Improvement-Index was significantly improved (cNRI = 21.3%; 95% CI: 21.2-21.4; P < 0.0001). CONCLUSION: wGRSCKD was associated with a 25% increased incidence of CKD per 1 SD increment. Although the wGRSCKD did not improve the prediction model beyond clinical risk factors per se, the information of genetic predisposition may aid in reclassification of individuals into correct risk direction.

Quality of dietary fat and genetic risk of type 2 diabetes: individual participant data meta-analysis.

OBJECTIVE: To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes. DESIGN: Individual participant data meta-analysis. DATA SOURCES: Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators. REVIEW METHODS: Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score. RESULTS: Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I2=7.1%, τ2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I2=18.0%, τ2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, τ2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I2=25.9%, τ2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed. CONCLUSIONS: These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.