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The aim of the study was to assess factors leading to revision surgery and implant position of primary orbital fracture reconstructions. A retrospective cohort included patients who underwent orbital floor and/or medial wall fracture reconstruction for recent trauma. Demographics, fracture type, surgery and implant-related variables, and postoperative implant position were analyzed. The overall revision surgery rate was 6.5% (15 of 232 surgeries). The rate was highest in combined midfacial fractures with rim involvement (14.0%), lower in zygomatico-orbital fractures (8.7%), and lowest in isolated blowout fractures (3.8%). Fracture type, orbital rim fixation and implant malposition predicted revision. The best positioning was achieved with patient-specific milled titanium implants (mtPSI) and resorbable materials, whereas the poorest with preformed three-dimensional titanium plates. Combined midfacial fractures with rim involvement in particular have a high risk for orbital revision surgery. Within the limitations of the present study, mtPSIs should be preferred in the reconstruction of primary orbital fractures if possible. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery.

Aims: To estimate change in young people's alcohol consumption during COVID-19 restrictions in Australia in early-mid 2020, and test whether those changes were consistent by gender and level of consumption prior to the pandemic. Design: Prospective longitudinal cohort. Setting: Secondary schools in New South Wales, Tasmania and Western Australia. Participants: Subsample of a cohort (n = 443) recruited in the first year of secondary school in 2010-11. Analysis data included three waves collected in September 2017-July 2018, September 2018-May 2019 and August 2019-January 2020), and in May-June 2020. Measurements: The primary predictors were time, gender and level of consumption prior to the pandemic. Outcome variables, analysed by mixed-effects models, included frequency and typical quantity of alcohol consumption, binge drinking, peak consumption, alcohol-related harm and drinking contexts. Findings: Overall consumption (frequency × quantity) during the restrictions declined by 17% [incidence rate ratio (IRR) = 0.83; 95% confidence interval (CI) = 0.73, 0.95] compared to February 2020, and there was a 35% decline in the rate of alcohol-related harms in the same period (IRR = 0.66; 95% CI = 0.54, 0.79). Changes in alcohol consumption were largely consistent by gender. Conclusions: From a survey of secondary school students in Australia, there is evidence for a reduction in overall consumption and related harms during the COVID-19 restrictions.

BackgroundYoung people may have elevated risk for poorer mental health during the coronavirus disease 2019 (COVID-19) pandemic, yet longitudinal studies documenting this impact are lacking. This study assessed changes in mental health and help-seeking since COVID-19 restrictions in young Australians, including gender differences.MethodsData were drawn from a recent subsample (n = 443; 60% female; Mage = 22.0) of a prospective cohort originally recruited in secondary school to complete annual surveys. The subsample completed an additional COVID-19 survey during COVID-19 restrictions (May–June 2020), which was compared to responses from their latest annual survey (August 2019–March 2020). Mixed effect models with time and gender as the primary predictors were conducted for: (i) scores on the Patient Health Questionnaire Depression 9-item (PHQ-9) and Generalised Anxiety Disorder 7-item (GAD-7) modules assessed before and during COVID-19 restrictions, and (ii) self-reported help-seeking from a health professional in February 2020, and the month preceding May–June 2020.ResultsMean symptom scores increased from before to during COVID-19 restrictions on the PHQ-9 (coefficient: 1.29; 95% CI 0.72–1.86) and GAD-7 (0.78; 95% CI 0.26–1.31), but there was no increase in help-seeking over time (odds ratio 0.50; 95% CI 0.19–1.32). There was no evidence of differential changes by gender.ConclusionsThis study found increases in depression and anxiety symptoms but not greater help-seeking among young Australian adults during the first wave of the pandemic. Increasing availability and awareness of accessible treatment options and psychoeducation is critical, as well as further research into risk and protective factors to help target treatment to this vulnerable age group.

Ruiping Wang,1,* Qiong Yang,2,* Ting Sun,3,* Yan Qiang,1,* Xiaopan Li,4 Huan Li,3 Yue Tang,3 Liang Yang,5 Jie Sun,5 Bin Li1 1Clinical Research & Innovation Transformation Center, Shanghai Skin Diseases Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 2Office of Public Health, Songjiang Fang Song Community Health Service Center, Shanghai, People’s Republic of China; 3Obstetrics and Gynecology Department, Songjiang Maternal and Child Health-Care Hospital, Shanghai, People’s Republic of China; 4Department of Non-Communicable Disease Control and Prevention, Pudong District Center for Diseases Control and Prevention, Shanghai, People’s Republic of China; 5Department of Women Health, Jing’an Institute of Maternal and Child Health-Care, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruiping WangClinical Research & Innovation Transformation Center, Shanghai Skin Diseases Hospital Affiliated to Tongji University, 1278 Baode Road, Jing’an District, Shanghai, 200443, People’s Republic of ChinaFax +86-21-3680 3000Email w19830901@126.comBin LiClinical Research & Innovation Transformation Center, Shanghai Skin Diseases Hospital Affiliated to Tongji University, 1278 Baode Road, Jing’an District, Shanghai, 200443, People’s Republic of ChinaEmail l8930568129@126.comObjective: Physical exercise during pregnancy is beneficial to women with gestational diabetes mellitus (GDM), but evidence on the association between physical exercise and glycemic control among women with GDM is limited in China. We conducted this study to understand the total exercise times, the percentage of abnormal plasma glucose (PG), and to explore if longer physical exercise is positively associated with a lower percentage of abnormal PG among GDM women.Methods: During 2019 and 2020, we established a prospective cohort with 1,050 GDM women recruited. GDM was confirmed by a diagnostic 75g OGTT, and plasma glucose in over 10 hours overnight fasting and 2-hour after breakfast was implemented during a routine antenatal checkup. Information for demographic features and physical exercises among GDM women were collected by questionnaire interviews, and abnormal PG percentage was calculated as abnormal PG times divided by total PG test times.Results: Among 1,050 GDM women, the percentage of exercise times < 150 minutes/week, < 30 minutes/day and < 60 minutes/day was 17.33%, 26.57%, and 54.10%, respectively. The median percentage of abnormal PG was 40% (IQR=20– 70%). GDM women with less exercise had a higher abnormal PG percentage (y=0.0049x2-1.20x+88.96), ORs for women with exercise < 150 minutes/week were 3.78 (95% CI=1.33– 8.25), 6.97 (3.45– 14.07), and 6.39 (3.61– 11.33) compared with ≥ 150 minutes/week, and ORs for women with exercise < 60 minutes/day were 4.62 (2.71– 8.14), 3.58 (2.60– 4.93), and 7.28 (4.31– 12.30) compared with ≥ 60 minutes/day in groups divided by quartiles of P25, P50 and P75, respectively.Conclusion: This study indicated high physical exercise times and abnormal PG percentage among women with GDM in Shanghai, China. GDM women with more exercise times had a lower percentage of abnormal PG, especially when exercise times were ≥ 60 minutes/day, and supplementary treatments should be provided for women with over 70% abnormal plasma glucose.Keywords: physical exercise, gestational diabetes mellitus, prospective cohort, association, glycemic control, abnormal plasma glucose

Background The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer risk prediction models are commonly used in clinical practice and have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative prospective validation of these models after incorporating the recently developed 313-variant PRS. Methods Calibration and discrimination of 5-year absolute risk was assessed in a nested case-control sample of 1337 women of European ancestry (619 incident breast cancer cases) aged 23–75 years from the Generations Study. Results The extended BOADICEA model with reproductive/lifestyle factors and PRS was well calibrated across risk deciles; expected-to-observed ratio (E/O) at the highest risk decile :0.97 (95 % CI 0.51 − 1.86) for women younger than 50 years and 1.09 (0.66 − 1.80) for women 50 years or older. Adding reproductive/lifestyle factors and PRS to the BOADICEA model improved discrimination modestly in younger women (area under the curve (AUC) 69.7 % vs. 69.1%) and substantially in older women (AUC 64.6 % vs. 56.8%). The Tyrer-Cuzick model with PRS showed evidence of overestimation at the highest risk decile: E/O = 1.54(0.81 − 2.92) for younger and 1.73 (1.03 − 2.90) for older women. Conclusion The extended BOADICEA model identified women in a European-ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. With the increasing availability of PRS, these analyses can inform choice of risk models incorporating PRS for risk stratified breast cancer prevention among women of European ancestry.

Background Previous studies have shown that hyponatremia is associated with greater mortality in hemodialysis (HD) patients. However, there have been few reports regarding the importance of the change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions. To investigate the relationships of pre-dialysis hyponatremia and ΔSNa during a dialysis session with mortality, we analyzed data from a national registry of Japanese patients with end-stage kidney disease. Methods We identified 178,114 patients in the database who were undergoing HD 3 times weekly. The study outcome was 2-year all-cause mortality, and the baseline SNa concentrations were categorized into quintiles. We evaluated the relationships of SNa concentration and ΔSNa with mortality using Cox proportional hazards models. Results During a 2-year follow-up period, 25,928 patients died. Each 1-mEq/l reduction in pre-HD SNa concentration was associated with a cumulatively greater risk of all-cause mortality (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.05–1.06). In contrast, a larger ΔSNa was associated with higher all-cause mortality (HR for a 1-mEq/l increase in ΔSNa, 1.02; 95% CI 1.01–1.02). The combination of low pre-HD SNa concentration and large ΔSNa was also associated with higher mortality (HR 1.09; 95% CI 1.05–1.13). Participants with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137–140 mEq/L) and the lowest ΔSNa (≤2 mEq/L). Conclusions Lower pre-HD SNa concentration and higher ΔSNa are associated with a greater risk of mortality in patients undergoing HD., Graphical abstract

Little is known on the association between clinical factors and coronavirus disease 2019 (COVID‐19) more than 15 days after diagnosis. We conducted a multicentric prospective cohort of COVID‐19 hospitalized patients to describe clinical, biological, and virological characteristics at hospital admission and over time, according to mortality up to Day 60 after admission. For the analysis of risk factors of survival, analyses assessing associations between mortality and demographic characteristics or comorbidities were performed using a Cox regression model. Between January 24 and March 15, 2020, 246 patients with reverse‐transcriptase polymerase chain reactions virologically confirmed COVID‐19 were enrolled. In multivariate analysis, mortality at Day 60 (n = 42 patients, 17.1% [95% confidence interval, 12.6–22.4]) was associated with older age (adjusted hazard ratio [aHR] for age ≥ 65 years: 5.22 [2.56–10.63, p, Highlights Older age, male gender, chronic pulmonary disease (not asthma), obesity, and diabetes were associated with mortality in COVID‐19 hospitalized patients. Viral load at admission decreased with the time since symptom onset, with an association with mortality adjusted on clinical risk factors.

While the association between fruit consumption and bladder cancer risk has been extensively reported, studies have had inadequate statistical power to investigate associations between types of fruit and bladder cancer risk satisfactorily. Fruit consumption in relation to bladder cancer risk was investigated by pooling individual data from 13 cohort studies. Cox regression models with attained age as time scale were used to estimate hazard ratios (HRs) for intakes of total fruit and citrus fruits, soft fruits, stone fruits, tropical fruits, pome fruits and fruit products. Analyses were stratified by sex, smoking status and bladder cancer subtype. During on average 11.2 years of follow-up, 2836 individuals developed incident bladder cancer. Increasing fruit consumption (by 100 g/day) was inversely associated with the risk of bladder cancer in women (HR = 0.92; 95% CI 0.85-0.99). Although in women the association with fruit consumption was most evident for higher-risk nonmuscle invasive bladder cancer (NMIBC; HR = 0.72; 95% CI 0.56-0.92), the test for heterogeneity by bladder cancer subtype was nonsignificant (P-heterogeneity = .14). Increasing fruit consumption (by 100 g/day) was not associated with bladder cancer risk in men (HR = 0.99; 95% CI 0.94-1.03), never smokers (HR = 0.96; 95% CI 0.88-1.05), former smokers (HR = 0.98; 95% CI 0.92-1.05) or current smokers (HR = 0.95; 95% CI 0.89-1.01). The consumption of any type of fruit was not found to be associated with bladder cancer risk (P values > .05). Our study supports no evidence that the consumption of specific types of fruit reduces the risk of bladder cancer. However, increasing total fruit consumption may reduce bladder cancer risk in women.

Background The association of nuts with cardiovascular disease and deaths has been investigated mostly in Europe, the USA, and East Asia, with few data available from other regions of the world or from low- and middle-income countries. Objective To assess the association of nuts with mortality and cardiovascular disease (CVD). Methods The Prospective Urban Rural Epidemiology study is a large multinational prospective cohort study of adults aged 35–70 y from 16 low-, middle-, and high-income countries on 5 continents. Nut intake (tree nuts and ground nuts) was measured at the baseline visit, using country-specific validated FFQs. The primary outcome was a composite of mortality or major cardiovascular event [nonfatal myocardial infarction (MI), stroke, or heart failure]. Results We followed 124,329 participants (age = 50.7 y, SD = 10.2; 41.5% male) for a median of 9.5 y. We recorded 10,928 composite events [deaths (n = 8,662) or major cardiovascular events (n = 5,979)]. Higher nut intake (>120 g per wk compared with

BACKGROUND Mounting evidence, yet with varying levels of proof, suggests that dietary fibers (DFs) may exert a protective role against various chronic diseases, but this might depend on the DF type and source. OBJECTIVES Our objectives were to assess the associations between the intake of DFs of different types [total (TDF), soluble (SF), insoluble (IF)] and from different sources (fruits, vegetables, whole grains, legumes, potatoes and tubers) and the risk of cardiovascular diseases (CVDs), cancer, type 2 diabetes (T2D), and mortality in the large-scale NutriNet-Sante prospective cohort (2009-2019). METHODS Overall, 107,377 participants were included. Usual DF intake was estimated from validated repeated 24-h dietary records over the first 2 y following inclusion in the cohort. Associations between sex-specific quintiles of DF intake and the risk of chronic diseases and mortality were assessed using multiadjusted Cox proportional hazards models. RESULTS T2D risk was inversely associated with TDFs [HR for quintile 5 compared with quintile 1: 0.59 (95% CI: 0.42, 0.82), P-trend

Introduction Walking is free, does not require special training, and can be done almost everywhere. Therefore, walking is a feasible behavior on which to tailor public health messages. This study assesses the prospective association and dose-response relationship between daily steps and all-cause mortality. Materials and methods Daily steps were measured by waist-mounted accelerometers in 2183 individuals (53% women) for seven consecutive days at baseline (2008-09). Participants were followed for a median period of 9.1 years and associations between steps and all-cause mortality determined by registry linkage were assessed using Cox proportional hazard regression with adjustment for relevant covariates. Results Mean age was 57.0 (SD 10.9) years at baseline. Median (IQR) daily steps across ascending quartiles were 4651 (3495-5325), 6862 (6388-7350), 8670 (8215-9186), and 11 467 (10 556-13 110), respectively. During follow-up, 119 individuals died (68% men). Higher number of daily steps was associated with a lower risk of all-cause mortality with hazard ratios of 1.00 (referent), 0.52 (0.29-0.93), 0.50 (0.27-0.94), and 0.43 (0.21-0.88) across ascending quartiles of daily steps in the multivariable-adjusted model with follow-up commencing 2 years after baseline. Risk differences per 1000 individuals for ascending quartiles were 6.8 (2.9-9.3), 7.1 (0.8-11.1), and 8.0 (1.7-12.1), respectively. Conclusions Daily steps were associated with lower mortality risk in a non-linear dose-response pattern. The risk is almost halved when comparing the least active referent against the second quartile equivalent to a difference of about 2200 daily steps. Encouraging those least active to increase their daily steps may have substantial public health implications.

Purpose We evaluated the performance of the recently extended Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA version 5) in a Dutch prospective cohort, using a polygenic risk score (PRS) based on 313 breast cancer (BC)-associated variants (PRS313) and other, nongenetic risk factors. Methods Since 1989, 6522 women without BC aged 45 or older of European descent have been included in the Rotterdam Study. The PRS(313)was calculated per 1 SD in controls from the Breast Cancer Association Consortium (BCAC). Cox regression analysis was performed to estimate the association between the PRS(313)and incident BC risk. Cumulative 10-year risks were calculated with BOADICEA including different sets of variables (age, risk factors and PRS313). C-statistics were used to evaluate discriminative ability. Results In total, 320 women developed BC. The PRS(313)was significantly associated with BC (hazard ratio [HR] per SD of 1.56, 95% confidence interval [CI] [1.40-1.73]). Using 10-year risk estimates including age and the PRS313, other risk factors improved the discriminatory ability of the BOADICEA model marginally, from a C-statistic of 0.636 to 0.653. Conclusions The effect size of the PRS(313)is highly reproducible in the Dutch population. Our results validate the BOADICEA v5 model for BC risk assessment in the Dutch general population.

Rapid physical growth and the onset of menstruation during adolescence can increase the risk of iron deficiency (ID) and related adverse effects. However, little is known about the risk of anemia and ID among adolescent girls in Ethiopia. Therefore, we aimed to determine the prevalence of ID, low iron stores, and anemia and characterize selected risk factors in Huruta, Arsi Zone, Oromia Region, Ethiopia. A cross-sectional study was conducted among non-pregnant adolescent girls (15–19 years of age; n = 257). Data on household socio-demographic characteristics, anthropometric measurements, and women’s dietary diversity score (WDDS) were collected. Hemoglobin (Hb) and serum ferritin (SF), C-reactive protein (CRP), and α−1-acid-glycoprotein (AGP) concentrations were measured. Diets were predominantly plant-based, with a low consumption of animal source foods, fruits, and dark-green leafy vegetables. Only 4% of the adolescent girls had adequate dietary diversity (WDDS ≥5), and 35% were underweight. The prevalence of anemia (Hb

South Asians (i.e., people who originate from India, Pakistan, Sri Lanka, Nepal, and Bangladesh) have higher cardiovascular disease rates than other populations, and these differences persist in their offspring. Nutrition is a critical lifestyle-related factor that influences fetal development, and infant and child health in early life. In high-income countries such as Canada, nutrition-related health risks arise primarily from overnutrition, most strikingly for obesity and associated non-communicable diseases. Evidence for developmental programming during fetal life underscores the critical influence of maternal diet on fetal growth and development, backed by several birth cohort studies including the Pune Maternal Nutrition Study, the South Asian Birth Cohort Study, and the Born in Bradford Study. Gestational diabetes mellitus is a strong risk factor for type 2 diabetes, future atherosclerosis and cardiovascular disease in the mother and increases the risk of type 2 diabetes in her offspring. Non-pharmacological trials to prevent gestational diabetes are few, often not randomized, and are heterogeneous with respect to design, and outcomes have not converged upon a single optimal prevention strategy. The aim of this review is to provide an understanding of the current knowledge around perinatal nutrition and gestational diabetes among the high-risk South Asian population as well as summarize our research activities investigating the role of culturally-tailored nutrition advice to South Asian women living in high-income settings such as Canada. In this paper, we describe these qualitative and quantitative studies, both completed and underway. We conclude with a description of the design of a randomized trial of a culturally tailored personalized nutrition intervention to reduce gestational glycaemia in South Asian women living in Canada and its implications.

Background: Studies investigating biomechanical risk factors for knee injuries in sport-specific tasks are needed. Purpose: To investigate the association between change of direction (COD) biomechanics in a 180-degree pivot turn and knee injury risk among youth team sport players. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 258 female and male basketball and floorball players (age range, 12-21 years) participated in the baseline COD test and follow-up. Complete data were obtained from 489 player-legs. Injuries, practice, and game exposure were registered for 12 months. The COD test consisted of a quick ball pass before and after a high-speed 180-degree pivot turn on the force plates. The following variables were analyzed: peak vertical ground-reaction force (N/kg); peak trunk lateral flexion angle (degree); peak knee flexion angle (degree); peak knee valgus angle (degree); peak knee flexion moment (N·m/kg); peak knee abduction moment (N·m/kg); and peak knee internal and external rotation moments (N·m/kg). Legs were analyzed separately and the mean of 3 trials was used in the analysis. Main outcome measure was a new acute noncontact knee injury. Results: A total of 18 new noncontact knee injuries were registered (0.3 injuries/1000 hours of exposure). Female players sustained 14 knee injuries and male players 4. A higher rate of knee injuries was observed in female players compared with male players (incidence rate ratio, 6.2; 95% CI, 2.1-21.7). Of all knee injuries, 8 were anterior cruciate ligament (ACL) injuries, all in female players. Female players displayed significantly larger peak knee valgus angles compared with male players (mean for female and male players, respectively: 13.9°± 9.4° and 2.0°± 8.5°). No significant associations between biomechanical variables and knee injury risk were found. Conclusion: Female players were at increased risk of knee and ACL injury compared with male players. Female players performed the 180-degree pivot turn with significantly larger knee valgus compared with male players. However, none of the investigated variables was associated with knee injury risk in youth basketball and floorball players.

Background Parent-to-child maltreatment is considered one of the risk factors for Generalized Anxiety Disorder (GAD) symptoms, but this hypothesis has not been adequately tested in Pakistani settings. Aim This study aimed to examine the association between parent-to-child maltreatment and the risk of developing GAD symptoms among adolescents. Methods The association of none to rare, occasionally, and frequently parent-to-child maltreatment with the incidence of GAD symptoms was investigated in a sample of 800 adolescents aged 11–17 years who were followed for two years. Parent-to-child maltreatment was assessed using ICAST-C (International child abuse screening tool). GAD Symptoms were determined by SCARED (Screen for children anxiety-related disorders). Cox Proportional Algorithm was used to estimate risk ratios. Results Among children with both uneducated parents, frequently maltreatment was associated with 7.31 (2.20–24.04) times the risk of GAD symptoms compared to none to rare maltreatment. In contrast, the risk of GAD symptoms in frequently maltreated children was 5.58 times (1.40–21.97) than negligibly maltreated children with either educated parent. Conclusion The frequency of parent-to-child maltreatment is significantly associated with an increased risk of developing GAD symptoms in which parental education plays a crucial role. Parents should be imparted with the awareness of the consequences of child maltreatment. In Pakistani settings the need to have this awareness is even more necessary due to the culturally acceptable disciplinary measures used by parents.

An important group of breast cancers is those associated with inherited susceptibility. In women, several predisposing mutations in genes involved in DNA repair have been discovered. Women with a germline pathogenic variant in BRCA1 have a lifetime cancer risk of 70%. As part of a larger prospective study on heavy metals, our aim was to investigate if blood arsenic levels are associated with breast cancer risk among women with inherited BRCA1 mutations. A total of 1084 participants with pathogenic variants in BRCA1 were enrolled in this study. Subjects were followed from 2011 to 2020 (mean follow-up time: 3.75 years). During that time, 90 cancers were diagnosed, including 67 breast and 10 ovarian cancers. The group was stratified into two categories (lower and higher blood As levels), divided at the median (&lt, 0.85 µg/L and ≥0.85 µg/L) As level among all unaffected participants. Cox proportional hazards models were used to model the association between As levels and cancer incidence. A high blood As level (≥0.85 µg/L) was associated with a significantly increased risk of developing breast cancer (HR = 2.05, 95%CI: 1.18–3.56, p = 0.01) and of any cancer (HR = 1.73, 95%CI: 1.09–2.74, p = 0.02). These findings suggest a possible role of environmental arsenic in the development of cancers among women with germline pathogenic variants in BRCA1.

Background: Coffee is a highly popular beverage worldwide, containing caffeine which is a central nervous system stimulant. Objectives: We examined whether habitual coffee consumption is associated with differences in brain volumes or the odds of dementia or stroke. Methods: We conducted prospective analyses of habitual coffee consumption on 398,646 UK Biobank participants (age 37–73 years), including 17,702 participants with MRI information. We examined the associations with brain volume using covariate adjusted linear regression, and with odds of dementia (4,333 incident cases) and stroke (6,181 incident cases) using logistic regression. Results: There were inverse linear associations between habitual coffee consumption and total brain (fully adjusted β per cup −1.42, 95% CI −1.89, −0.94), grey matter (β −0.91, 95% CI −1.20, −0.62), white matter (β −0.51, 95% CI −0.83, −0.19) and hippocampal volumes (β −0.01, 95% CI −0.02, −0.003), but no evidence to support an association with white matter hyperintensity (WMH) volume (β −0.01, 95% CI −0.07, 0.05). The association between coffee consumption and dementia was non-linear (P non-linearity= 0.0001), with evidence for higher odds for non-coffee and decaffeinated coffee drinkers and those drinking >6 cups/day, compared to light coffee drinkers. After full covariate adjustment, consumption of >6 cups/day was associated with 53% higher odds of dementia compared to consumption of 1–2 cups/day (fully adjusted OR 1.53, 95% CI 1.28, 1.83), with less evidence for an association with stroke (OR 1.17, 95% CI 1.00, 1.37, p = 0.055). Conclusion: High coffee consumption was associated with smaller total brain volumes and increased odds of dementia. Refereed/Peer-reviewed

Aims There is conflicting evidence whether heart failure (HF) is a risk factor for incident cancer. Despite population-based cohorts demonstrating this association, an analysis of the Physician's Health Study found no association in a cohort of mostly healthy males. We investigated the association of HF with incident cancer among a large cohort of post-menopausal women. Methods and results A prospective cohort study of 146,817 post-menopausal women age 50 to 79 years enrolled in the Women's Health Initiative from 1993-1998, and followed through 2015. The primary exposure was adjudicated incident HF diagnosis, including preserved and reduced ejection fraction in a subcohort. The primary outcome was adjudicated incident total and site-specific cancers. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazard regression models. Over a median follow-up of 8.4 years, 3,272 and 17,474 women developed HF and cancer, respectively. HF developed in 235 women prior to cancer. HF was associated with subsequent incident cancer (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.11-1.48). Associations were observed for obesity-related cancers (HR 1.24 [95% CI, 1.02-1.51]), as well as lung and colorectal cancers (HR 1.58 [95% CI, 1.31-2.30], 1.52 [95% CI, 1.02-2.27], respectively). HF with preserved ejection fraction (HFpEF) (HR 1.34 [95% CI, 1.06-1.67]), but not HF reduced ejection fraction (HFrEF) (HR 0.99 [95% CI 0.74-1.34]), was associated with total cancer. Conclusion HF was associated with an increase in cancer diagnoses in post-menopausal women. This association was strongest for lung cancer. Further research is needed to appreciate the underlying mechanisms responsible for this association. This article is protected by copyright. All rights reserved.

BACKGROUND Personalized nutrition and protective diets and lifestyles represent a key cancer research priority. The association between consumption of specific dietary components and colorectal cancer (CRC) incidence has been evaluated by a number of population-based studies, which have identified certain food items as having protective potential, though the findings have been inconsistent. Herein we present a systematic review and meta-analysis on the potential protective role of five common phytochemically rich dietary components (nuts, cruciferous vegetables, citrus fruits, garlic and tomatoes) in reducing CRC risk. AIM To investigate the independent impact of increased intake of specific dietary constituents on CRC risk in the general population. METHODS Medline and Embase were systematically searched, from time of database inception to January 31, 2020, for observational studies reporting CRC incidence relative to intake of one or more of nuts, cruciferous vegetables, citrus fruits, garlic and/or tomatoes in the general population. Data were extracted by two independent reviewers and analyzed in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) reporting guidelines and according to predefined inclusion/exclusion criteria. Effect sizes of studies were pooled using a random-effects model. RESULTS Forty-six studies were identified. CRC risk was significantly reduced in patients with higher vs lower consumption of cruciferous vegetables [odds ratio (OR) = 0.90; 95% confidence interval (CI): 0.85-0.95; P < 0.005], citrus fruits (OR = 0.90; 95%CI: 0.84-0.96; P < 0.005), garlic (OR = 0.83; 95%CI: 0.76-0.91; P < 0.005) and tomatoes (OR = 0.89; 95%CI: 0.84-0.95; P < 0.005). Subgroup analysis showed that this association sustained when looking at case-control studies alone, for all of these four food items, but no significant difference was found in analysis of cohort studies alone. Nut consumption exhibited a similar trend, but overall results were not significant (OR = 0.72; 95%CI: 0.50-1.03; P < 0.07; I2 = 90.70%). Putative anticarcinogenic mechanisms are proposed using gene-set enrichment analysis of gene/protein perturbations caused by active compounds within each food item. CONCLUSION Increased cruciferous vegetable, garlic, citrus fruit and tomato consumption are all inversely associated with CRC risk. These findings highlight the potential for developing precision nutrition strategies for CRC prevention. Borgas P, Gonzalez G, Veselkov K, Mirnezami R. Phytochemically rich dietary components and the risk of colorectal cancer: A systematic review and meta-analysis of observational studies. World J Clin Oncol 2021; 12(6): 482-499 [PMID: 34189071 DOI: 10.5306/wjco.v12.i6.482]

Purpose Cardiovascular disease (CVD) is a leading cause of mortality globally and is strongly influenced by dietary risk factors. The aim was to assess the association between egg consumption and risk of CVD risk/mortality, including coronary heart disease (CHD), stroke, and heart failure. Methods MEDLINE, Embase, and Web of Science databases were searched through April 2020 for prospective studies. Two independent reviewers screened and extracted the data through standardized methods. Size effects were calculated as summary relative risks (SRRs) in a dose–response fashion through random-effects meta-analyses. Results Thirty-nine studies including nearly 2 million individuals and 85,053 CHD, 25,103 stroke, 7536 heart failure, and 147,124 CVD cases were included. The summary analysis including 17 datasets from 14 studies conducted on CVD (incidence and/or mortality) showed that intake of up to six eggs per week is inversely associated with CVD events, when compared to no consumption [for four eggs per week, SRR = 0.95 (95% CI: 0.90; 1.00)]; a decreased risk of CVD incidence was observed for consumption of up to one egg per day [SRR = 0.94 (95% CI: 0.89; 0.99)]. The summary analysis for CHD incidence/mortality including 24 datasets from 16 studies showed a decreased risk up to two eggs per week [(SRR = 0.96 (95% CI: 0.91; 1.00)]. No associations were retrieved with risk of stroke. The summary analysis for heart failure risk including six datasets from four studies showed that intake of one egg per day was associated with increased risk raising for higher intakes compared to no consumption [for 1 egg per day, SRR = 1.15 (95% CI:1.02; 1.30)]. After considering GRADE criteria for strength of the evidence, it was rated low for all outcomes but stroke, for which it was moderate (yet referring to no risk). Conclusion There is no conclusive evidence on the role of egg in CVD risk, despite the fact that higher quality studies are warranted to obtain stronger evidence for a possible protection of CVD associated with moderate weekly egg consumption compared to no intake; equally, future studies may strengthen the evidence for increased heart failure risk associated with high regular egg consumption.

ObjectiveTo assess the longitudinal associations of physical and psychosocial exposures with disability retirement due to a shoulder lesion.MethodsIn a nationwide register-based study, we followed 1 135 654 wage earners aged 30–59 years for the occurrence of disability retirement due to a shoulder lesion. The occupational exposures were assessed with job exposure matrices. We used a competing risk regression model to estimate HRs and their 95% CIs and to test for the association between the exposures and the outcome. We also calculated the attributable fraction of disability retirement due to occupational exposures.ResultsA total of 2472 persons had full disability retirement due to a shoulder lesion during the follow-up. Physically heavy work showed the strongest association with the outcome in both genders, in men with an HR of 2.90 (95% CI 2.37 to 3.55) and in women with an HR of 3.21 (95% CI 2.80 to 3.90). Of the specific physical exposures, working with hands above shoulder level was statistically significantly associated with disability retirement in men. When all physical exposures were taken into consideration, 46% and 41% of disability retirement due to a shoulder lesion were attributed to physical work load factors in men and women, respectively. In addition, 49% (men) and 35% (women) of disability retirement were attributed to psychosocial work-related factors.ConclusionsOur findings suggest that a considerable proportion of disability retirement due to a shoulder lesion could be prevented by reducing physical and psychosocial exposures at work to a low level.

Background Patent ductus arteriosus (PDA), the most commonly diagnosed cardiovascular condition in preterm infants, is associated with increased mortality and harmful long-term outcomes (chronic lung disease, neurodevelopmental delay). Although pharmacologic and/or interventional treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve outcomes. Most PDAs close spontaneously by 44-weeks postmenstrual age; treatment is increasingly controversial, varying markedly between institutions and providers. Because treatment detriments may outweigh benefits, especially in infants destined for early, spontaneous PDA closure, the relevant unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat (and when). Clinicians cannot currently predict in the first month which infants are at highest risk for persistent PDA, nor which combination of clinical risk factors, echocardiographic measurements, and biomarkers best predict PDA-associated harm. Methods Prospective cohort of untreated infants with PDA (n=450) will be used to predict spontaneous ductal closure timing. Clinical measures, serum (brain natriuretic peptide, N-terminal pro-brain natriuretic peptide) and urine (neutrophil gelatinase-associated lipocalin, heart-type fatty acid-binding protein) biomarkers, and echocardiographic variables collected during each of first 4 postnatal weeks will be analyzed to identify those associated with long-term impairment. Myocardial deformation imaging and tissue Doppler imaging, innovative echocardiographic techniques, will facilitate quantitative evaluation of myocardial performance. Aim1 will estimate probability of spontaneous PDA closure and predict timing of ductal closure using echocardiographic, biomarker, and clinical predictors. Aim2 will specify which echocardiographic predictors and biomarkers are associated with mortality and respiratory illness severity at 36-weeks postmenstrual age. Aim3 will identify which echocardiographic predictors and biomarkers are associated with 22 to 26-month neurodevelopmental delay. Models will be validated in a separate cohort of infants (n=225) enrolled subsequent to primary study cohort. Discussion The current study will make significant contributions to scientific knowledge and effective PDA management. Study results will reduce unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure and facilitate development of outcomes-focused trials to examine effectiveness of PDA closure in “high-risk” infants most likely to receive benefit. Trial registration ClinicalTrials.gov NCT03782610. Registered 20 December 2018.

PurposeThe association between dietary acrylamide intake and estrogen receptor-positive (ER+) breast cancer risk in epidemiological studies is inconsistent. By analyzing gene-acrylamide interactions for ER+breast cancer risk, we aimed to clarify the role of acrylamide intake in ER+breast cancer etiology.MethodsThe prospective Netherlands Cohort Study on diet and cancer includes 62,573 women, aged 55-69years. At baseline, a random subcohort of 2589 women was sampled from the total cohort for a case-cohort analysis approach. Dietary acrylamide intake of subcohort members (n=1449) and ER+breast cancer cases (n=844) was assessed with a food frequency questionnaire. We genotyped single nucleotide polymorphisms (SNPs) in genes in acrylamide metabolism, sex steroid systems, oxidative stress and DNA repair. Multiplicative interaction between acrylamide intake and SNPs was assessed with Cox proportional hazards analysis, based on 20.3years of follow-up.ResultsUnexpectedly, there was a statistically non-significant inverse association between acrylamide and ER+breast cancer risk among all women but with no clear dose-response relationship, and no association among never smokers. Among the results for 57 SNPs and 2 gene deletions, rs1056827 in CYP1B1, rs2959008 and rs7173655 in CYP11A1, the GSTT1 gene deletion, and rs1052133 in hOGG1 showed a statistically significant interaction with acrylamide intake for ER+breast cancer risk.ConclusionsThis study did not provide evidence for a positive association between acrylamide intake and ER+breast cancer risk. If anything, acrylamide was associated with a decreased ER+breast cancer risk. The interaction with SNPs in CYP1B1 and CYP11A1 suggests that acrylamide may influence ER+breast cancer risk through sex hormone pathways. This study was funded by the Dutch Cancer Society (KWF), Grant number: UM 2011-5123. Janneke Hogervorst is a postdoctoral research fellow from the Research Foundation-Flanders (FWO), no. 12J9516N. The authors thank the study participants, the Netherlands Cancer Registry, the Dutch Pathology Registry, and the Biobank of the Maastricht University Medical Center. We thank Dr. Sandra Bausch as initiator of the NLCS study, together with Prof. Piet van den Brandt. We also thank Sacha van de Crommert, Jolanda Nelissen, Conny de Zwart, Ellen Dutman, Henny Brants, and Annemie Pisters for their assistance with data entry or data management, Harry van Montfort for programming assistance, and Simone van Breda, Stijn Lumeij, Kristien Lemmens, Joy Goessens, and Leonie Jonkers for technical assistance with DNA isolation and genotyping.

BackgroundThe transition between hospital and home is a vulnerable period for acutely hospitalized older patients during which they are at increased risk for adverse health outcomes. Yet, studies describing experiences of a geriatric patient population postdischarge from a patient perspective are missing.ObjectiveTo characterize patient experiences with recovering at home after acute hospitalization.Design and MethodsQualitative semi-structured interviews, involving 20 recently discharged patients (age ≥ 70), were conducted. A thematic analysis of the content was performed.ResultsTen categories were identified as recurring topics, which were grouped into 3 major themes. The first theme describes the effect of hospitalization on daily life. Participants described that the problems they encountered were mostly caused by symptoms they experienced since discharge, which were grouped into 2 themes: (a) physical consequences of hospitalization and (b) motivational and psychological problems after hospitalization. Among most frequently presented symptoms were fatigue, apathy, unsteadiness while standing, and fear of falling.ImplicationsImpairment in mobility and instrumental activities of daily living was the dominant experience for interviewed patients. This disability was mainly attributed to four main symptoms: fatigue, apathy, unsteadiness while standing, and fear of falling. We propose a tentative model that summarizes the role of posthospital symptoms in the recovery process and the potential syndromes (frailty, posthospital syndrome, palliative symptoms, and sickness behavior) that could underlie these shared symptoms which may act as a conceptual framework for future research. Our study points at the relevance of symptom experiences in functional recovery postdischarge.

Background Evidence suggests that regular eating patterns (i.e., consistent day-to-day frequency and timing of consumption) may be favorable with respect to weight status, and breakfast may be a particularly important meal for weight maintenance. We examined the relationship between regular breakfast consumption habits and weight status among women. Materials and methods Modified Poisson regression models examined day-to-day regularity in breakfast consumption among 46,037 women in the prospective Sister Study cohort in relation to weight status. Cross-sectional outcomes included overweight (body mass index (BMI) ≥ 25.0 kg/m2) and obesity (BMI ≥ 30.0 kg/m2); waist circumference (WC) ≥ 88 cm; and waist-to-hip ratio (WHR) ≥ 0.85. Self-reported weight 5 years post-baseline was used to calculate 5 kg weight gain and incident overweight and obesity using BMI. Results Compared to women who reported eating breakfast 3 to 4 days/week (irregular breakfast eaters), women who ate breakfast 7 days/week were between 11% to 17% less likely to be obese as measured by WHR (prevalence ratio (PR): 0.89; 95%CI: 0.85, 0.94), WC (PR: 0.85; 95%CI: 0.82, 0.88), and BMI (PR: 0.83; 95%CI: 0.79, 0.87) after multivariable adjustment. Women who never ate breakfast were between 11% to 22% less likely to be obese as measured by WHR (PR: 0.89; 95%CI: 0.83, 0.96), WC (PR: 0.82; 95%CI: 0.78, 0.87), and BMI (PR: 0.78; 95%CI: 0.72, 0.84) compared to irregular breakfast eaters. Prospective analyses showed a 21% and 28% lower risk of 5-year incident obesity among participants who always (relative risk (RR): 0.79; 95%CI: 0.70, 0.90) or never (RR: 0.72; 95%CI: 0.59, 0.87) ate breakfast, respectively, compared to those who ate breakfast 3 to 4 days/week. No association was observed for incident 5 kg weight gain. Conclusions Results suggest that a regular breakfast consumption habit, comprising eating breakfast every day or never, may be important for maintaining a healthy weight.

Background Epidemiologic data suggest that parity increases risk of hormone receptor-negative breast cancer and that breastfeeding attenuates this association. Prospective data, particularly on the joint effects of higher parity and breastfeeding, are limited. Methods We investigated parity, breastfeeding, and breast cancer risk by hormone-receptor (estrogen (ER) and progesterone receptor (PR)) and molecular subtypes (luminal A, luminal B, HER2-enriched, and basal-like) in the Nurses’ Health Study (NHS; 1976–2012) and NHSII (1989–2013). A total of 12,452 (ER+ n = 8235; ER− n = 1978) breast cancers were diagnosed among 199,514 women. We used Cox proportional hazards models, adjusted for breast cancer risk factors, to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results Parous women had lower risk of ER+ breast cancer (vs. nulliparous, HR = 0.82 [0.77–0.88]); no association was observed for ER− disease (0.98 [0.84–1.13]; Phet = 0.03). Among parous women, breastfeeding was associated with lower risk of ER− (vs. never 0.82 [0.74–0.91]), but not ER+, disease (0.99 [0.94–1.05]; Phet

Although a possible role of reproductive factors in lymphomagenesis has been hypothesized, results of epidemiological studies have been inconsistent. Here, we investigated the association between reproductive factors and the risk of lymphoid neoplasm and its subgroups. We used data from a large-scale, population-based prospective study in a Japanese cohort with 42 691 eligible women aged 40-69 years from 1990 to 1994. During a mean follow up of 18.7 years, we identified 176 cases of lymphoid neoplasm and 90 of non-Hodgkin lymphoma (NHL). A multivariable-adjusted Cox proportional hazards regression model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risk of lymphoid neoplasms and its subgroups according to self-reported reproductive factors. Parous women had an increased risk of lymphoid neoplasm compared with nulliparous women (HR = 2.51, 95% CI, 1.03-6.13). An increased risk of lymphoid neoplasms was found in women with later onset of menarche (≤13 years old; reference: 14-15; HR = 1.75, 95% CI = 1.10-2.79: ≥16; HR = 1.93, 95% CI = 1.17-3.19: P-trend: 0.01) and a shorter menstrual cycle (28-29 days; reference: ≤27; HR = 1.60, 95% CI = 1.05-2.43, P-trend = 0.81). No association was observed between lymphoid neoplasms and other reproductive factors, including age at first birth, breastfeeding, type of menopause, or exogenous hormone use. Our study suggests that ever parity, late age at menarche and a short menstrual cycle length may be associated with the development of lymphoid neoplasms. The inconsistency seen in epidemiological research to date warrants further investigation.

Aims/hypothesis The study aimed to assess the associations of maternal early-pregnancy blood glucose levels with fetal growth throughout pregnancy and the risks of adverse birth outcomes. Methods In a population-based prospective cohort study among 6116 pregnant women, maternal non-fasting glucose levels were measured in blood plasma at a median 13.2 weeks of gestation (95% range 9.6–17.6). We measured fetal growth by ultrasound in each pregnancy period. We obtained information about birth outcomes from medical records and maternal sociodemographic and lifestyle factors from questionnaires. Results Higher maternal early-pregnancy non-fasting glucose levels were associated with altered fetal growth patterns, characterised by decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, resulting in an increased length and weight at birth (p ≤0.05 for all). A weaker association of maternal early-pregnancy non-fasting glucose levels with fetal head circumference growth rates was present. Higher maternal early-pregnancy non-fasting glucose levels were also associated with an increased risk of delivering a large-for-gestational-age infant, but decreased risk of delivering a small-for-gestational-age infant (OR 1.28 [95% CI 1.16, 1.41], OR 0.88 [95% CI 0.79, 0.98] per mmol/l increase in maternal early-pregnancy non-fasting glucose levels, respectively). These associations were not explained by maternal sociodemographic factors, lifestyle factors or BMI. Maternal early-pregnancy non-fasting glucose levels were not associated with preterm birth or delivery complications. Conclusions/interpretation Higher maternal early-pregnancy non-fasting glucose levels are associated with decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, and an increased risk of delivering a large-for-gestational-age infant. Future preventive strategies need to focus on screening for an impaired maternal glucose metabolism from preconception and early pregnancy onwards to improve birth outcomes. Electronic supplementary material The online version of this article (10.1007/s00125-019-4957-3) contains peer-reviewed but united supplementary material, which is available to authorised users.

Background:Surgical management of cam femoroacetabular impingement (FAI) aims to preserve the native hip and restore joint function, although it is unclear how the capsulotomy, cam deformity, and capsular repair influence joint mechanics to balance functional mobility.Purpose:To examine the contributions of the capsule and cam deformity to hip joint mechanics. Using in vitro, cadaveric methods, we examined the individual effects of the surgical capsulotomy, cam resection, and capsular repair on passive range of motion and resistance of applied torque.Study Design:Descriptive laboratory study.Methods:Twelve cadaveric hips with cam deformities were skeletonized to the capsule and mounted onto a robotic testing platform. The robot positioned each intact hip in multiple testing positions: (1) extension, (2) neutral 0°, (3) flexion 30°, (4) flexion 90°, (5) flexion-adduction and internal rotation (FADIR), and (6) flexion-abduction and external rotation. Then the robot performed applicable internal and external rotations, recording the neutral path of motion until a 5-N·m of torque was reached in each rotational direction. Each hip then underwent a series of surgical stages (T-capsulotomy, cam resection, capsular repair) and was retested to reach 5 N·m of internal and external torque again after each stage. During the capsulotomy and cam resection stages, the initial intact hip’s recorded path of motion was replayed to measure changes in resisted torque.Results:Regarding changes in motion, external rotation increased substantially after capsulotomies, but internal rotation only further increased at flexion 90° (change +32%, P = .001, d = 0.58) and FADIR (change +33%, P < .001, d = 0.51) after cam resections. Capsular repair provided marginal restraint for internal rotation but restrained the external rotation compared with the capsulotomy stage. Regarding changes in torque, both internal and external torque resistance decreased after capsulotomy. Compared with the capsulotomy stage, cam resection further reduced internal torque resistance during flexion 90° (change −45%, P < .001, d = 0.98) and FADIR (change −37%, P = .003, d = 1.0), where the cam deformity accounted for 21% of the intact hip’s torsional resistance in flexion 90° and 27% in FADIR.Conclusion:Although the capsule played a predominant role in joint constraint, the cam deformity provided 21% to 27% of the intact hip’s resistance to torsional load in flexion and internal rotation. Resecting the cam deformity would remove this loading on the chondrolabral junction.Clinical Relevance:These findings are the first to quantify the contribution of the cam deformity to resisting hip joint torsional loads and thus quantify the reduced loading on the chondrolabral complex that can be achieved after cam resection.

Background: Several documents and guidelines provide recommendations for effective management of COPD patients. However, there is often a significant imbalance between recommended treatment of COPD patients and the actual care provided both in primary care and specialty setting. This imbalance could result in a significant negative impact on patients’ health status and quality of life, leading to increased hospitalisations and health resource utilisation in COPD patients Methods: MISTRAL was an observational, longitudinal, prospective cohort study, designed to assess the overall pharmacological approach of COPD in routine clinical practice in Italy. Eligible patients were divided into two cohorts based on their exacerbation history in the year prior to the enrolment, frequent exacerbators (FEs; ≥2 exacerbations), and non-frequent exacerbators (NFEs; ≤1 exacerbation). The primary objective was to assess adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 treatment recommendations in FEs and NFEs at baseline and follow-up visits Results: Of the 1489 enrolled patients, 1468 (98.6%; FEs, 526; NFEs, 942) were considered evaluable for analyses. At baseline, 57.8% of patients were treated according to GOLD 2011 recommendations; a greater proportion of FEs were treated according to GOLD recommendations, compared with NFEs patients at baseline (77.1% versus 46.7%; P < 0.0001), and all study visits. At baseline, GOLD group D patients were the most adherent (81.2%) to treatment recommendations, while group A patients were the least adherent (30.3%) at baseline, attributed mainly to overuse of inhaled corticosteroids in less severe GOLD groups. Triple therapy with long-acting muscarinic antagonist (LAMA) + long-acting β2-agonist/inhaled corticosteroid (LABA/ICS) was the most frequent prescribed treatment at all study visits, irrespective of patient's exacerbation history. Changes in treatment were more frequent in FEs versus NFEs Conclusions: The Mistral study reports a scarce adherence to the GOLD 2011 treatment recommendations in routine clinical practice in Italy. The adherence was particularly low in less severe, non-frequent exacerbating patients mostly for ICS overuse, and was higher in high-risk, frequent exacerbating COPD patients

Adult-attained height is a marker for underlying mechanisms, such as cell growth, that may also influence postmenopausal breast cancer (BC) risk, perhaps specifically hormone-sensitive BC subtypes. Early life energy restriction may inhibit these mechanisms, resulting in shorter height and a reduced postmenopausal BC risk. Women (62,573) from the Netherlands Cohort Study completed a self-administered questionnaire in 1986 when 55-69 years old, and were followed-up for 20.3 years (case-cohort: N-subcohort = 2,438; N-cases = 3,354). Cox multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated for BC risk overall and by estrogen and progesterone receptor subtypes in relation to height and early life energy restriction during the Hunger Winter, War Years, and Economic Depression. Although energy restriction can only influence longitudinal growth in women exposed before and/or during the growth spurt, it may also influence BC risk when occurring after the growth spurt, possibly through different growth processes. Therefore, Cox analyses were additionally conducted according to timing of energy restriction in relation to the growth spurt. Height was associated with an increased BC risk (HRper 5cm = 1.07, 95%CI:1.01-1.13), particularly hormone receptor-positive BC. Energy restriction before and/or during the growth spurt was associated with a decreased hormone receptor-positive BC risk. Energy restriction during the Hunger Winter increased the estrogen receptor-negative BC risk regardless of the timing of energy restriction. In conclusion, height and energy restriction before and/or during the growth spurt were both associated with hormone receptor-positive BC risk, in the direction as expected, indicating critical exposure windows for hormonal growth-related mechanisms.

Background: Prevention of persistent pain after breast cancer surgery, via early identification of patients at high risk, is a clinical need. Psychological factors are among the most consistently proposed predictive parameters for the development of persistent pain. However, repeated use of long psychological questionnaires in this context may be exhaustive for a patient and inconvenient in everyday clinical practice. Methods: Supervised machine learning was used to create a short form of questionnaires that would provide the same predictive performance of pain persistence as the full questionnaires in a cohort of 1000 women followed up for 3 yr after breast cancer surgery. Machine-learned predictors were first trained with the full-item set of Beck's Depression Inventory (BDI), Spielberger's StateeTrait Anxiety Inventory (STAI), and the StateeTrait Anger Expression Inventory (STAXI-2). Subsequently, features were selected from the questionnaires to create predictors having a reduced set of items. Results: A combined seven-item set of 10% of the original psychological questions from STAI and BDI, provided the same predictive performance parameters as the full questionnaires for the development of persistent postsurgical pain. The seven-item version offers a shorter and at least as accurate identification of women in whom pain persistence is unlikely (almost 95% negative predictive value). Conclusions: Using a data-driven machine-learning approach, a short list of seven items from BDI and STAI is proposed as a basis for a predictive tool for the persistence of pain after breast cancer surgery.

We performed a prospective cohort study of 311 outpatients with non-severe COVID-19 (187 women, median age 39 years). Of the 214 (68.8%) who completed the 6-week follow-up questionnaire, 115 (53.7%) had recovered. Others mostly reported dyspnea (n = 86, 40.2%), weight loss (n = 83, 38.8%), sleep disorders (n = 68, 31.8%), and anxiety (n = 56, 26.2%). Of those who developed ageusia and anosmia, these symptoms were still present at week 6 in, respectively, 11/111 (9.9%) and 19/114 (16.7%). Chest CT scan and lung function tests found no explanation in the most disabled patients (n = 23). This study confirms the high prevalence of persistent symptoms after non-severe COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04261-y.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders, study eligibility and design, recruitment strategies, standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data, our cloud-based data management platform, and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

Purpose Our aim was to investigate prospective associations of consumption of total dairy and dairy types with incident prediabetes in a Dutch population-based study. Methods Two enrolment waves of the Hoorn Studies were harmonized, resulting in an analytic sample of 2262 participants without (pre-) diabetes at enrolment (mean age 56 ± 7.3 years; 50% male). Baseline dietary intake was assessed by validated food frequency questionnaires. Relative risks (RRs) were calculated between dairy, fermented dairy, milk, yogurt (all total/high/low fat), cream and ice cream and prediabetes. Additionally, substituting one serving/day of dairy types associated with prediabetes with alternative dairy types was analysed. Results During a mean 6.4 ± 0.7 years of follow-up, 810 participants (35.9%) developed prediabetes. High fat fermented dairy, cheese and high fat cheese were associated with a 17% (RR 0.83, 95% CI 0.69–0.99, ptrend = 0.04), 14% (RR 0.86, 95% CI 0.73–1.02, ptrend = 0.04) and 21% (RR 0.79, 95% CI 0.66–0.94, ptrend = 0.01) lower risk of incident prediabetes, respectively, in top compared to bottom quartiles, after adjustment for confounders. High fat cheese consumption was continuously associated with lower prediabetes risk (RRservings/day 0.94, 95% CI 0.88–1.00, p = 0.04). Total dairy and other dairy types were not associated with prediabetes risk in adjusted models, irrespective of fat content (RR ~ 1). Replacing high fat cheese with alternative dairy types was not associated with prediabetes risk. Conclusion The highest intake of high fat fermented dairy, cheese and high fat cheese were associated with a lower risk of prediabetes, whereas other dairy types were not associated. Cheese seems to be inversely associated with type 2 diabetes risk, despite high levels of saturated fatty acids and sodium.

Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank cohort, we investigate risk factors for COVID-19 mortality in comparison with non-COVID-19 mortality. We investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N = 473,550) in relation to 459 COVID-19 and 2626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Age (OR = 2.76 [2.18–3.49] per S.D. [8.1 years], p = 2.6 × 10–17), male sex (OR = 1.47 [1.26–1.73], p = 1.3 × 10–6) and Black versus White ethnicity (OR = 1.21 [1.12–1.29], p = 3.0 × 10–7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC = 0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin–angiotensin–aldosterone system inhibitors may be explained by the aforementioned factors.

Many healthcare workers in eldercare are pushed out of the labor market before the official retirement age due to poor health. Identification of early warnings signs is important to avoid complete loss of work ability. The aim of this study was to investigate to what degree sickness absence and presenteeism increase future risk for disability pension among eldercare workers. A total of 8952 Danish female eldercare workers responded to a survey about work environment and health. They were followed for 11 years in the Danish Register for Evaluation of Marginalization, with time-to-event analyses estimating the hazard ratios (HRs) for disability pension from sickness absence and presenteeism at baseline. Analyses were adjusted for age, education, body mass index, leisure-time physical activity, smoking, physical exertion at work, and psychosocial factors related to the work environment. During the 11-year follow-up, 11.9% participants received disability pension. For the whole cohort, the highest risk for disability pension was observed for the category of >30 days of combined sickness absence and presenteeism at baseline in the fully adjusted model (HR = 7.93 [95%CI 5.20–12.09]). Eldercare workers aged >45 years were at a higher risk for disability pension in all included categories. Sickness absence and presenteeism increased the risk of disability pension among female eldercare workers. These results suggest that organizations would benefit from identifying early warning signs among workers in the prevention of involuntary early retirement. © 2021 Elsevier Inc.

International audience; Introduction: Polychlorinated biphenyls (PCB) are persistent and bioaccumulative lipophilic substances, mostly used in the past by industry. Known to be cancerogenic, PCB are suspected to increase Non-Hodgkin's Lymphoma (NHL) risk in the general population mainly due to evidence from cases-controls studies. Since their interdiction in 1987, diet represents the main route of exposure for the general population, nevertheless no study has assessed the relationship between PCB dietary exposure and NHL risk. The aim of this study was to analyze the association between dietary exposures to dioxin like PCB (DL PCB) and non-dioxin like PCB (NDL PCB) and NHL risk in the E3N prospective cohort of French women. Materials and methods: Among 67,879 women included in this study, 457 cases of NHL were confirmed during 21 years of follow-up. Dietary exposure to PCB was estimated combining food consumption data collected in E3N and food contamination data provided by French Agency for Food, Environmental and Occupational Health & Safety (ANSES) in the second French total diet study. Cox regression models, adjusted for potential confounders, were used to estimate hazard ratio (HR) and 95% confidence intervals (CI). Results: Average age at diagnosis was 67 years. The median dietary exposure to DL PCB and NDL PCB was, 18.5 pg TEQ/d and 138,843.2 pg/d, respectively. While no association was found between dietary exposure to DL PCB or NDL PCB and overall NHL risk, analyses by NHL histological subgroups showed a positive association between dietary exposures to DL PCB and Diffuse Large B Cell Lymphoma (OR3vs1 1.90, 95%CI [1.03–3.51], ptrend 0.02). Nevertheless these findings were no longer statistically significant when the models were adjusted for fish and dairy products consumption. In addition, an inverse association was found between dietary exposure to NDL PCB and the risk of follicular lymphoma (OR3vs1 0.46, 95%CI [0.24–0.87], ptrend 0.01). Conclusion: This is the first study to evaluate the association between dietary exposure to DL and NDL PCB and the risk of NHL in a prospective cohort study. Overall, the findings suggest a lack of association between dietary exposure to DL or NDL PCB and NHL risk. Additional studies are needed to reproduce these findings.

Objective: To investigate the association between estimated whole-brain radiofrequency electromagnetic fields (RF-EMF) dose, using an improved integrated RF-EMF exposure model, and cognitive function in preadolescents and adolescents. Methods: Cross-sectional analysis in preadolescents aged 9-11 years and adolescents aged 17-18 years from the Dutch Amsterdam Born Children and their Development Study (n = 1664 preadolescents) and the Spanish INfancia y Medio Ambiente Project (n = 1288 preadolescents and n = 261 adolescents), two population-based birth cohort studies. Overall whole-brain RF-EMF doses (mJ/kg/day) were estimated for several RF-EMF sources together including mobile and Digital Enhanced Cordless Telecommunications phone calls (named phone calls), other mobile phone uses than calling, tablet use, laptop use (named screen activities), and far-field sources. We also estimated whole-brain RF-EMF doses in these three groups separately (i.e. phone calls, screen activities, and far-field) that lead to different patterns of RF-EMF exposure. We assessed non-verbal intelligence in the Dutch and Spanish preadolescents, information processing speed, attentional function, and cognitive flexibility in the Spanish preadolescents, and working memory and semantic fluency in the Spanish preadolescents and adolescents using validated neurocognitive tests. Results: Estimated overall whole-brain RF-EMF dose was 90.1 mJ/kg/day (interquartile range (IQR) 42.7; 164.0) in the Dutch and Spanish preadolescents and 105.1 mJ/kg/day (IQR 51.0; 295.7) in the Spanish adolescents. Higher overall estimated whole-brain RF-EMF doses from all RF-EMF sources together and from phone calls were associated with lower non-verbal intelligence score in the Dutch and Spanish preadolescents (-0.10 points, 95% CI-0.19; -0.02 per 100 mJ/kg/day increase in each exposure). However, none of the whole-brain RF-EMF doses was related to any other cognitive function outcome in the Spanish preadolescents or adolescents. Conclusions: Our results suggest that higher brain exposure to RF-EMF is related to lower non-verbal intelligence but not to other cognitive function outcomes. Given the cross-sectional nature of the study, the small effect sizes, and the unknown biological mechanisms, we cannot discard that our resultsare due to chance finding or reverse causality. Longitudinal studies on RF-EMF brain exposure and cognitive function are needed.

A baseline oral microbiome study of the Tohoku Medical Megabank Organization (TMM) was planned to characterize the profile of the oral microbiome in the Japanese population. The study also aimed to clarify risk factors for multifactorial diseases by integrated analysis of the oral microbiome and host genome/omics information. From 2013 to 2016, we collected three types of oral biospecimens, saliva, supragingival plaque, and tongue swab, from a total of 25,101 participants who had a dental examination in TMM. In this study, we used two independent cohorts; the Community-Based Cohort and Birth and Three-Generation Cohort as discovery and validation cohorts, respectively, and we selected participants examined by a single dentist. We found through the 16S ribosomal RNA gene sequencing analysis of 834 participants of the Community-Based Cohort Study that there are differences in the microbial composition and community structure between saliva and plaque. The species diversities in both saliva and plaque were increased in correlation with the severity of periodontal disease. These results were nicely reproduced in the analysis of 455 participants of the Birth and Three-Generation Cohort Study. In addition, strong positive and negative associations of microbial taxa in both plaque and saliva with periodontitis-associated biofilm formation were detected by co-occurrence network analysis. The classes Actinobacteria and Bacilli, including oral health-associated bacterial species, showed a positive correlation in saliva. These results revealed differences in microbial composition and community structure between saliva and plaque and a correlation between microbial species and the severity of periodontal disease. We expect that the large database of the oral microbiome in the TMM biobank will help in the discovery of novel targets for the treatment and prevention of oral diseases, as well as for the discovery of therapeutic and/or preventive targets of systemic diseases.

Background: The association between long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and prostate cancer (PC) remains unclear. Methods: We compared incident PC rates as a function of the Omega-3 Index [O3I, erythrocyte eicosapentaenoic and docosahexaenoic acids (EPA + DHA)] in 5607 men (40&ndash, 80 years of age) seen at the Cooper Clinic who were free of PC at baseline. The average follow-up was 5.1 &plusmn, 2.8 years until censoring or reporting a new PC diagnosis. Proportional hazards regression was used to model the linear association between baseline O3I and the age-adjusted time to diagnosis. A meta-analysis of n-3 PUFA biomarker-based studies and incident PC was updated with the present findings. Results: A total of 116 cases of incident PC were identified. When O3I was examined as a continuous variable, the age-adjusted hazard ratio (HR) (95% CI) was 0.98 (0.89, 1.07, p = 0.25) for each 1% increment in the O3I. The updated meta-analysis with 10 biomarker-based studies found no significant relationship between EPA or DHA levels and risk for PC. Conclusions: We find no evidence in this study nor in a meta-analysis of similar studies that consuming n-3 PUFA-rich fish or using fish oil supplements affects the risk of PC.

Background Harmful maternal and neonatal health outcomes result from malaria in pregnancy, the prevention of which primarily relies on intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP). The World Health Organization recommends IPTp-SP in sub-Saharan Africa, but implementation is highly heterogeneous and often suboptimal in terms of the number of doses and their timing. In this study, we assessed the impact of this heterogeneity on malaria in pregnancy, mainly with respect to submicroscopic Plasmodium falciparum infections. Methods We used data from 273 Beninese women followed throughout pregnancy. Screening for P. falciparum infections, using both microscopy-based and polymerase chain reaction (PCR)–based methods, was performed monthly, and information on IPTp-SP doses was collected. Gestational age was estimated by repeated ultrasound scans. Using a negative binomial model, we investigated the effect of IPTp-SP doses and timing after 17 weeks of gestation on the number of P. falciparum infections, focusing on submicroscopic infections detectable only by PCR. Results At least 2 IPTp-SP doses were taken by 77.3% of the women. The median gestational age at the first IPTp-SP dose was 22 weeks. A late first IPTp-SP dose (>21.2 weeks) was marginally associated with an increased number of P. falciparum infections (adjusted incidence rate ratio [aIRR] = 1.3; P = .098). The number of IPTp-SP doses was not associated with the number of submicroscopic infections (aIRR = 1.2, P = .543). Conclusions A late first IPTp-SP dose failed to provide optimal protection against P. falciparum, especially submicroscopic infections. This highlights the need for a new antimalarial drug for IPTp that could be taken early in pregnancy., In a cohort study, increased numbers of Plasmodium falciparum infections were found in pregnant women with suboptimal dose numbers and late first doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP). The timing of IPTp-SP primarily affects submicroscopic infections.

BackgroundIncreasingly, strength-based approaches to health and wellbeing interventions with Aboriginal and Torres Strait Islander Australians are being explored. This is a welcome counter to deficit-based initiatives which can represent a non-Indigenous view of outcomes of interest. However, the evidence base is not well developed. This paper presents the protocol for evaluating a strengths-based initiative which provides life coaching services to Aboriginal and Torres Strait Islander community housing tenants. The study aims to evaluate the effect of life coaching on social and emotional wellbeing (SEWB) of tenants in three Victorian regions.MethodsThe More Than a Landlord (MTAL) study is a prospective cohort study of Aboriginal Housing Victoria tenants aged 16 years and over that embeds the evaluation of a life coaching program. All tenant holders in one metropolitan and two regional areas of Victoria are invited to participate in a survey of SEWB, containing items consistent with key categories of SEWB as understood and defined by Aboriginal and Torres Strait Islander peoples, and key demographics, administered by Aboriginal and Torres Strait Islander peer researchers at baseline, 6 and 18 months. Survey participants are then invited to participate in strengths based life coaching, using the GROW model, for a duration of up to 18 months. Indigenous life coaches provide tenants with structured support in identifying and making progress towards their goals and aspirations, rather than needs. The study aims to recruit a minimum of 200 survey participants of which it is anticipated that approximately 73% will agree to life coaching.DiscussionThe MTAL study is a response to Aboriginal and Torres Strait Islander community and organisational requests to build the evidence base for an initiative originally developed and piloted within an Aboriginal controlled organisation. The study design aligns with key principles for research in Indigenous communities in promoting control, decision making and capacity building. The MTAL study will provide essential evidence to evaluate the effectiveness of strengths-based initiatives in promoting SEWB in these communities and provide new evidence about the relationship between strengths, resilience, self-determination and wellbeing outcomes.Trial registrationThis trial was retrospectively registered with the ISRCTN Register on the 12/7/21 with the study ID:ISRCTN33665735.

Background: Socioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours. Methods: Using data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings. Findings: An increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12–1.16] and 1.09 [1.07–1.12] in men and women respectively), cancer (HR = 1.11 [1.09–1.14] and 1.07 [1.04–1.10]) and CVD (HR = 1.25 [1.20–1.31] and 1.21 [1.11–1.31]) mortality, CVD incidence (HR = 1.15 [1.13–1.16] and 1.17 [1.15–1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21–1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours. Interpretation: The BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death. © 2020 The Author(s)

Background Although research on the relationship between parent and child mental health is growing, the impact of early parenting stress on preschool-aged children’s mental health remains unclear. The objective was to evaluate the association between parenting stress during infancy and mental health problems in 3-year-old children. Methods A prospective cohort study of healthy preschool-aged children recruited from 9 primary care practices in Toronto, Canada was conducted through the TARGet Kids! primary care practice-based research network. Parenting stress was measured when children were between 0 to 16 months of age, using the Parent Stress Index Short Form, PSI-SF. Parent-reported child mental health problems were measured at 36 to 47 months using the preschool Strengths and Difficulties Questionnaire, total difficulties score (TDS). Hierarchical linear regression analysis was used to investigate the association between standardized PSI-SF and TDS, adjusted for child age, sex, temperament, sleep duration and household income. To strengthen clinical interpretation, analysis was repeated using adjusted multivariable logistic regression (TDS dichotomized at top 20%). Results A total of 148 children (mean ± SD age, 37.2 ± 1.7 months, 49% male) were included in the analysis. Parenting stress during infancy (11.4 ± 3.1 months of age) was significantly associated with mental health problems in 3-year-old children (β = 0.35; 95% CI = 0.20–0.49, p p Conclusion Healthy preschool-aged children with parents reporting parenting stress during infancy had a 2 times higher odds of mental health problems at 3 years.

Background: In patients with primary hyperparathyroidism (PHPT) locating hyperfunctioning glands (HPGs) is crucial when planning minimally invasive surgery. Dual-isotope subtraction scintigraphy with 99mTc-MIBI/123Iodide using SPECT/CT and planar pinhole imaging (Method A) has previously shown a sensitivity >93%. However, the method is costly and time consuming and entails a high radiation dose. 11C-Choline PET/CT (Method B) is an appealing candidate method unencumbered by these disadvantages. Methods: Sixty patients with newly diagnosed PHPT participated and were scanned using both methods prior to parathyroidectomy. We investigated whether sensitivities of Method A and Method B are similar in a method-to-method comparison when using surgical findings as the true location. Results: At the patient level, sensitivities were (A) 0.98 (95% CI: 0.90–1.00) and (B) 1.00 (95% CI: 0.93–1.00). At the gland level, sensitivities were (A) 0.88 (95% CI: 0.78–0.94) and (B) 0.87 (95% CI: 0.76–0.92). With a non-inferiority margin of ∆ = −0.1, we found a 1-sided p-value < 0.001. Conclusion: Our methods comparison study found that sensitivity of Method B was not inferior to Method A. We suggest that 11C-Choline PET/CT is a clinically relevant first-choice candidate for preoperative imaging of PHPT and that Method B can likely replace Method A in the near future.

To better understand the role of individual and lifestyle factors in human disease, an exposome‐wide association study was performed to investigate within a single‐study anthropometry measures and lifestyle factors previously associated with B‐cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed‐up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B‐cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL., What's new? The “exposome” includes all non‐genetic exposures (e.g. diet, viral, environmental, etc.), with the goal of understanding how those exposures may affect an individual's health. In this study, the authors used a technique called “EWAS” (exposome‐wide association study) to identify multiple factors that are associated with B‐cell lymphoma (BCL) risk. Their results confirm both previously reported risk factors and protective factors. In addition, they identify several previously unknown associations. These new insights, gained via the analysis of multiple exposures, suggest that traditional single‐factor approaches may be suboptimal compared with an EWAS approach.

Aims/hypothesis Our aim was to determine whether a range of prespecified retinal vessel traits were associated with incident diabetic retinopathy in adults with type 2 diabetes. Methods In the prospective observational cohort Edinburgh Type 2 Diabetes Study of 1066 adults with type 2 diabetes, aged 60–75 years at recruitment, 718 were free from diabetic retinopathy at baseline. Baseline retinal traits including vessel widths, tortuosity (curvature) and fractal dimensions (network complexity), were quantified using fundus camera images and semiautomated software, and analysed using logistic regression for their association with incident diabetic retinopathy over 10 years. Results The incidence of diabetic retinopathy was 11.4% (n = 82) over 10 years. After adjustment for a range of vascular and diabetes-related risk factors, both increased venular tortuosity (OR 1.51; 95% CI 1.15, 1.98; p = 0.003) and decreased fractal dimension (OR 0.75; 95% CI 0.58, 0.96; p = 0.025) were associated with incident retinopathy. There was no evidence of an association with arterial tortuosity, and associations between measurements of vessel widths and retinopathy lost statistical significance after adjustment for diabetes-related factors and vascular disease. Adding venular tortuosity to a model including established risk factors for diabetic retinopathy (HbA1c, BP and kidney function) improved the discriminative ability (C statistic increased from 0.624 to 0.640, p = 0.013), but no such benefit was found with fractal dimension. Conclusions/interpretation Increased retinal venular tortuosity and decreased fractal dimension are associated with incident diabetic retinopathy, independent of classical risk factors. There is some evidence that venular tortuosity may be a useful biomarker to improve the predictive ability of models based on established retinopathy risk factors, and its inclusion in further risk prediction modelling is warranted. Graphical abstract

Contains fulltext : 231582.pdf (Publisher’s version ) (Open Access) Background: Dropout in later years of the nursing degree programme involves lost investment and is a particular problem for both students and educators. Reasons for late dropout seem to be related to the work and learning environment of the clinical placement. Objectives: The aim of this study was to investigate associations between psychosocial work characteristics and distress and intention to leave nursing education among third-year nursing students. Design: A prospective cohort study. Setting A Bachelor of Nursing programme of a University of Applied Sciences in [name country]. Participants: 363 third-year nursing students. Methods: Baseline and one-year follow-up measurements were used from a prospective cohort study. Third-year nursing students were invited annually in May between 2016 and 2018. Psychosocial work characteristics were psychological demands, supervisor and co-worker support, and acts of offensive behaviour. Logistic regression analyses were used to build multivariate models. Results: Frequent exposure to violence (OR = 2.52, 95% CI: 1.29-4.92) was univariately associated with distress. In the multivariate model for distress, psychological demands (OR = 1.63, 95% CI: 1.05-2.52) and frequent exposure to violence (OR = 3.02, 95% CI: 1.48-6.19) were associated with distress. Supervisor support (OR = 0.54, 95% CI: 0.36-0.80) and co-worker support (OR = 0.41, 95% CI: 0.24-0.72) were negatively associated with intention to leave (i.e. were protective) in the univariate model. In the adjusted multivariate model, only co-worker support (OR = 0.50, 95% CI: 0.25-0.97) was a protective factor for an intention to leave. Conclusion: Psychological demands and frequent exposure to violence are risk factors for distress, and co-worker support is a protective factor reducing the intention to leave nursing education in the last stage of the programme. Improving the psychosocial working climate of nursing students may reduce the intention to leave at a late stage in nursing education, and hence actual late dropout. 8 p.