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The higher prevalence of attention-deficit/hyperactivity disorder (ADHD) in males raises the question of whether testosterone is implicated in ADHD risk. However, cross-sectional studies did not identify an association between ADHD and testosterone levels. Mendelian randomization (MR) studies can overcome limitations inherent to association studies, especially of reverse causation and residual confounding. In the current study, sex-combined and sex-specific two-sample MR analyses were conducted to address whether testosterone has a causal influence on ADHD risk. Sex-combined as well as sex-specific target-genetic variants for bioavailable testosterone were derived from a large genome-wide association study (GWAS) on up to 382,988 adult white European UK Biobank study participants. In our sex-specific analyses for ADHD, including data from 14,154 males and 4,945 females with ADHD (17,948 and 16,246 controls respectively), no association between bioavailable testosterone and ADHD risk was found, neither in males (inverse-variance weighted (IVW): beta = 0.09, 95%-CI [-0.10, 0.27]) nor in females (IVW: beta=-0.01, 95%-CI [-0.20, 0.19]). However, in the sex-combined analysis, including 38,691 cases and 186,843 controls, genetically predicted bioavailable testosterone was associated with ADHD risk (IVW: beta = 0.24, 95%-CI [0.09, 0.39]). The inclusion of birth weight and/or SHBG as additional variables in multivariable MR analyses did not alter this result. However, when correcting for potential BMI-driven pleiotropy by a multivariable MR study, all effect estimates for testosterone showed non-significant results. Taken together, no robust evidence for a causal effect of bioavailable testosterone on the risk for ADHD was found. [ABSTRACT FROM AUTHOR]

Background: Within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aimed to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations. Methods: White adults with normal spirometry, BMI ≤30 kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5–11–19 Hz, Resmon PRO FULL, RESTECH Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5–19), and within-breath changes of X (ΔX) were submitted to lambda-mu-sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied. Results: A total of 144 subjects (age 20.8–86.3 years; height 146–193 cm; BMI 17.42–29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality. Conclusions: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults. [ABSTRACT FROM AUTHOR]

• Women with type 2 diabetes and ethnic minorities remain underrepresented across multiple GLP-1RA cardiovascular outcome trials. • GLP-1 receptor agonists significantly reduced MACE in both males and females with type 2 diabetes, among Asians and Whites, and in Asia and Europe. • There was no statistical difference in the reduction of MACE by GLP-1RAs among Blacks and Hispanics. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been pivotal in the management of type 2 diabetes mellitus (T2DM) and in the reduction of major adverse cardiovascular events (MACE). Notably, large cardiovascular outcomes trials (CVOTs) demonstrate significant disparities in inclusion, based on sex, race, ethnicity, and geographical regions. We examined the impact of GLP-1RA on MACE in patients with or without T2DM, based on sex, race, ethnicity, and geography. A literature search for placebo controlled randomized controlled trials on GLP-1RA treatment was conducted. Thorough data extraction and quality assessment were carried out, focusing on key outcome, and ensuring a robust statistical analysis using a random effects model to calculate log odds ratio (OR) with 95% confidence intervals (CIs). A total of 8 CVOTs comprising 71,616 patients were included. Compared with placebo, GLP-1RAs significantly reduced MACE in both sexes (females: logOR -0.19, (95% CI, -0.28 to -0.10), p < 0.01) versus (males: logOR -0.17, (95% CI, -0.23 to -0.10), p < 0.01), (p interaction NS), and among Asians (logOR -34 (95% CI, -0.53 to -0.15), p < 0.01), and Whites (logOR -17 (95% CI, -0.25 to -0.09), p < 0.01), with no difference in MACE among Blacks and Hispanics. Odds of MACE were also reduced in Asia (logOR -31 (95% CI, -0.50 to -0.11), p < 0.01), and Europe (logOR -27 (95% CI, -0.40 to -0.13), p < 0.01), but there was no statistical difference in MACE in North America and Latin America. Significant reductions in MACE with GLP-1RA treatment were demonstrated between both sexes and across certain ethnicities and certain geographical regions. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is known to be associated with the race and ethnicity of patients regarding the tumor characteristics and patient survival. However, in worldwide clinical trials, the participation of Black and Hispanic patients is lower than expected based on the frequency of breast cancer in these populations. This article aims to assess race reporting and representation trends in European trials. Ninety-seven such trials conducted exclusively in Europe between 2010 and 2022 were identified in the PubMed and ClinicalTrials.gov databases. Race was reported in 10.31% of these, and mostly in trials carried out across multiple European countries. They featured a White-predominant population, with 1.08% Asian and 0.88% Black patients included. Race reporting trends in European trials are much lower than in worldwide or American-based trials on the same subject. Systematic race reporting among other patient demographics and adequate minority inclusion will ameliorate the quality of European clinical trials and promote equality in healthcare access. Breast cancer is the most prevalent female cancer worldwide with known correlations between the race and tumor characteristics of the patients and prognosis. International and US-based studies, however, have reported a disproportionate representation of Black and Hispanic patients in clinical trials. This is the first study assessing race and ethnicity reporting trends and inclusion in European breast cancer trials. The PubMed and ClinicalTrials.gov databases were systematically searched for trials on breast cancer treatment conducted exclusively in Europe between 2010 and 2022. Of the 97 identified trials, race was reported in 10.31%. Multinational participation, but not the study size or trial phase, was significantly associated with higher race reporting trends. These 10 trials featured a White-predominant population, with 1.08% Asian and 0.88% Black patients included. The acquisition of the race and ethnicity data of patients in European trials is lower compared to the U.S. or worldwide studies and does not permit extensive analysis of minority participation. In a limited analysis, the low rates of minority participation are concerning, based on population-based data on minorities in select European countries. These observations should encourage race reporting practices in European breast cancer trials and adequate minority participation to support the generalizability of the results of the studies and promote healthcare equity. [ABSTRACT FROM AUTHOR]

Background: Hospital-based biobanks are being increasingly considered as a resource for translating polygenic risk scores (PRS) into clinical practice. However, since these biobanks originate from patient populations, there is a possibility of bias in polygenic risk estimation due to overrepresentation of patients with higher frequency of healthcare interactions. Methods: PRS for schizophrenia, bipolar disorder, and depression were calculated using summary statistics from the largest available genomic studies for a sample of 24 153 European ancestry participants in the Mass General Brigham (MGB) Biobank. To correct for selection bias, we fitted logistic regression models with inverse probability (IP) weights, which were estimated using 1839 sociodemographic, clinical, and healthcare utilization features extracted from electronic health records of 1 546 440 non-Hispanic White patients eligible to participate in the Biobank study at their first visit to the MGB-affiliated hospitals. Results: Case prevalence of bipolar disorder among participants in the top decile of bipolar disorder PRS was 10.0% (95% CI 8.8–11.2%) in the unweighted analysis but only 6.2% (5.0–7.5%) when selection bias was accounted for using IP weights. Similarly, case prevalence of depression among those in the top decile of depression PRS was reduced from 33.5% (31.7–35.4%) to 28.9% (25.8–31.9%) after IP weighting. Conclusions: Non-random selection of participants into volunteer biobanks may induce clinically relevant selection bias that could impact implementation of PRS in research and clinical settings. As efforts to integrate PRS in medical practice expand, recognition and mitigation of these biases should be considered and may need to be optimized in a context-specific manner. [ABSTRACT FROM AUTHOR]

PURPOSE Childhood cancer survivors report self-monitoring for and worrying about symptoms of disease recurrence and secondary cancers, although symptom-related worry is associated with poorer health-related quality of life. This survey captured pediatric oncologists’ beliefs and communication practices regarding symptom self-monitoring for childhood cancer survivors. METHODS Using a closed-loop snowball sampling technique, pediatric oncologists completed an online survey regarding the importance of symptom self-monitoring for off-therapy patients, the degree to which symptom self-monitoring was perceived to cause stress and worry, and communication practices. RESULTS 196 pediatric oncologists (White [78%]; female [64%]; Mage = 5 47 years) from every continent except Antarctica participated. Oncologists believed it is important for off-therapy patients to self-monitor for symptoms of cancer recurrence (90%) and treatment late effects (94%), although some noted that recurrence (30%) and late effects (55%) are typically detected by routine surveillance before symptoms appear. Oncologists varied in their beliefs that off-therapy patients do (31%) or do not (31%) worry unnecessarily about symptoms of recurrence. Two thirds (62%) of oncologists reported often/always discussing with off-therapy patients which symptoms could indicate cancer recurrence, whereas fewer than half (43%) often/always discussed which symptoms were unlikely to indicate recurrence. Oncologists identified a need for education regarding how to communicate around symptom self-monitoring and the potential utility of a screening tool to identify those who worry excessively. CONCLUSION Despite nearly universal belief that their off-therapy patients should self-monitor for symptoms of disease recurrence and late effects, a substantial proportion of pediatric oncologists do not counsel patients on symptom self-monitoring. Since nearly one-third believe that off-therapy patients worry unnecessarily about symptoms of recurrence, improving patient education regarding which symptoms are and are not medically concerning could decrease stress and improve health-related quality of life for pediatric cancer survivors. [ABSTRACT FROM AUTHOR]

Objectives: To estimate and compare the prevalence of cognitive limitations among Middle Eastern and North African (MENA) immigrants compared to US- and foreign-born non-Hispanic Whites from Europe (including Russia/former USSR) and examine differences after controlling for risk factors. Methods: Cross-sectional data using linked 2000-2017 National Health Interview Survey and 2001–2018 Medical Expenditure Panel Survey data (ages >=65 years, n = 24,827) were analyzed. Results: The prevalence of cognitive limitations was 17.3% among MENA immigrants compared to 9.6% and 13.6% among US- and foreign-born non-Hispanic Whites from Europe. MENA immigrants had higher odds (OR = 1.88; 95% CI = 1.06–3.34) of reporting a cognitive limitation than US-born non-Hispanic Whites after controlling for age, sex, education, hearing loss, hypertension, depression, social isolation, and diabetes. Discussion: To further examine cognitive health among the MENA aging population, policy changes are needed to identify this group that is often absent from research because of their federal classification as non-Hispanic Whites. [ABSTRACT FROM AUTHOR]

This qualitative study explored the experiences of transracial Korean adoptee returnees who were born in Korea, separated from their biological families, raised in the United States and three European countries by White families, and given an Anglicized or Germanic name at the time of their adoption. This study focused on participants' journeys of reclaiming their Korean birth names and the various influences that factored into this decision. Data were collected from in-depth, semi-structured interviews (in-person or via Skype) and coded using grounded-theory methods that integrated a constructivist-interpretivist and critical epistemological paradigm. Participants (N = 12) were transracial Korean adoptees with ages ranging from 22 to 42 years (M = 32.67 years) who were between 0 and 88 months (M = 22.33 months) at the time of adoption, all of whom had returned to Korea. Results from the interviews revealed 11 axial categories and 2 overarching selective categories related to the name reclamation process: (a) name reclamation was part of a larger identity development process; (b) factors that prevented or slowed the name reclamation process. Limitations and future areas of research are discussed. [ABSTRACT FROM AUTHOR]

Grounded by the ecological systems perspectives proposed by Bronfenbrenner (1977, 1979) and Fivush and Merrill (2016), the present study was conducted to examine whether autobiographical memory (AM) and self-construal differed in young adults raised in the same macrosystem, but with unique microsystems. European American (EA) participants were born in the United States to mothers who were born in the United States (n = 61) and Chinese American (CA) participants were born in the United States to mothers who were born in China (n = 47). Participants completed an online study in which they reported on and rated aspects of their earliest memory; they also completed measures of self-construal and acculturation. EA participants identified more with mainstream American culture relative to CA participants, who identified to a greater extent with their heritage culture. EA participants also talked and thought more about their earliest memories relative to CA participants; interactions between group and sex were found for social words. Group differences were not observed on measures of self-construal. These findings indicate that microsystem-level factors are associated with differences in AM in young adults even when individuals are born and raised in the same macro-level cultural environment. [ABSTRACT FROM AUTHOR]

African American (AA) and European American (EA) women often exhibit differences in hemoglobin (Hb) and 25-hydroxyvitamin D [25(OH)D], both of which can be altered by calorie restriction leading to weight loss. Given these known differences, it is of clinical interest to examine the potential for race-specific, adverse responses to weight loss. Sixty-four overweight (BMI 27-29.9 kg/²), premenopausal women consumed a standardized, very-low calorie diet to reduce BMI < 25 kg/². Ancestry informative markers provided estimates of African admixture, an objective mean of expressing race. Blood sampling and anthropometric measures were performed at baseline and upon meeting target BMI. At baseline, in the overweight state, Hb (g/dL) (AA, 11.7 ± 0.9 vs. EA, 12.5 ± 0.8; p < .01) and 25(OH)D (nmol/L) (AA, 35.7 ± 12.9 vs. EA, 57.0 ± 20.0; p < .01) were lower in AAs. After weight loss, Hb decreased (AA, -0.5 ± 0.7 vs. EA, -0.4 ± 0.6; p = .48) to a similar extent among races. Conversely, 25(OH)D increased (AA, 43.4 ± 14.0 vs. EA 68.2 ± 24.3; p < .01) though the magnitude of change (Δ) was not different (AA, +7.8 ± 13.5 vs. EA,+11.2 ± 16.7;p = .37) between races. Multiple linear regression revealed a positive association between ΔHb and Δ25(OH)D (r = .386; p < .01) adjusted for African admixture, Δtestosterone, and Δbody fat%. Path analyses revealed a significant indirect effect of Δbody fat% on ΔHb through Δ25(OH)D, β =-0.023, CI [-0.06, -0.004]. Following 15% weight loss, participants with the largest increase in serum 25(OH)D exhibited the smallest decrease in Hb. Future research should clarify the optimal degree of calorie restriction to stimulate weight loss while mitigating the potential risk of anemia associated with dieting efforts. [ABSTRACT FROM AUTHOR]

Background: Currently used pediatric kidney length normative values are based on small single-center studies, do not include kidney function assessment, and focus mostly on newborns and infants. We aimed to develop ultrasound-based kidney length normative values derived from a large group of European Caucasian children with normal kidney function. Methods: Out of 1,782 children aged 0–19 years, 1,758 individuals with no present or past kidney disease and normal estimated glomerular filtration rate had sonographic assessment of kidney length. The results were correlated with anthropometric parameters and estimated glomerular filtration rate. Kidney length was correlated with age, height, body surface area, and body mass index. Height-related kidney length curves and table were generated using the LMS method. Multivariate regression analysis with collinearity checks was used to evaluate kidney length predictors. Results: There was no significant difference in kidney size in relation to height between boys and girls. We found significant (p < 0.001), but clinically unimportant (Cohen's D effect size = 0.04 and 0.06) differences between prone vs. supine position (mean paired difference = 0.64 mm, 95% CI = 0.49–0.77) and left vs. right kidneys (mean paired difference = 1.03 mm, 95% CI = 0.83–1.21), respectively. For kidney length prediction, the highest coefficient correlation was observed with height (adjusted R2 = 0.87, p < 0.0001). Conclusions: We present height-related LMS-percentile curves and tables of kidney length which may serve as normative values for kidney length in children from birth to 19 years of age. The most significant predictor of kidney length was statural height. [ABSTRACT FROM AUTHOR]

This article discusses the settler colonial roots of family therapy, positing that much of what is considered the standard or ideal family form comes from colonialism. Utilising settler colonial theory as a guide, I identify how the colonial nations, built through the violent exclusion of Indigenous and exogenous peoples, utilised the family to further their goals. Rather than suggest settler colonialism was an historic event, I consider how it continues today, privileging white families of European descent. To move the conversation forward on how white therapists from majoritised cultures can engage with racialised clients, I describe the negotiated spaces as a meeting ground where therapists and clients navigate differing worldviews. In these negotiations, our clients trust us, and to be accountable to this trust, we can unsettle the influence of settler colonialism. To conclude this paper, I discuss four possible pathways to begin the complicated process of unsettling. Practitioner PointsSettler colonialism contributed to the standardisation of the nuclear family, informing the foundations of family therapy.Establishing a 'negotiated space' in therapy can encourage ethical engagement between therapist and client as they navigate differences in culture, knowledge and meaning.To ethically be in the negotiated spaces, therapists from majoritised cultures can 'unsettle' settler colonialism's influence.Learning personal and disciplinary relationships to settler colonialism, developing cultural humility and attending to power is the first step in unsettling. [ABSTRACT FROM AUTHOR]

We aimed to explore the causal effect of daytime napping on the risk of osteoporosis and the mediation role of testosterone in explaining this relationship. Summary data for Mendelian randomization (MR) analysis were obtained from the IEU OpenGWAS database. Univariable MR(UVMR) analysis and multiple sensitivity analyses were applied to explore the casual relationship between daytime napping and bone mineral density (BMD)/osteoporosis. We also conducted multivariable Mendelian randomization (MVMR) analysis to evaluate the correlation between testosterone-associated single-nucleotide variations and BMD/osteoporosis. Then, mediation analysis was performed to explore whether the association between daytime napping and BMD/osteoporosis was mediated via testosterone. Genetically predicted daytime napping was significantly associated with femoral neck BMD (β [95% CI]: 0.2573 [0.0487, 0.4660]; P = 0.0156), lumbar spine BMD (β [95% CI]: 0.2526 [0.0211, 0.4840]; P = 0.0324), and osteoporosis (OR [95% CI]: 0.5063 [0.2578, 0.9942]; P = 0.0481). β and 95%CIs indicate the standard deviation (SD) unit of BMD increase per category increase in daytime napping. OR and 95%CIs represent the change in the odds ratio of osteoporosis per category increase in daytime napping. We observed a potentially causal effect of more frequent daytime napping on higher BMD and a lower risk of osteoporosis. Daytime napping was causally associated with a higher level of bioavailable testosterone (β [95% CI]: 0.1397 [0.0619, 0.2175]; P = 0.0004). β and 95%CIs represent the change in the SD of testosterone per category increase in daytime napping. Furthermore, the causal effects of daytime napping on BMD/osteoporosis were partly mediated by bioavailable testosterone. Daytime napping can efficiently increase BMD and reduce the risk of osteoporosis, and testosterone plays a key mediating role in this process., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: We aimed to assess ethnic differences in inflammatory markers and their relationships with insulin sensitivity and regional adiposity between white European and black African men. Methods: A total of 53 white European and 53 black African men underwent assessment of inflammatory markers alongside Dixon‐magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue and intrahepatic lipid. A hyperinsulinaemic‐euglycaemic clamp was used to measure whole‐body and adipose tissue insulin sensitivity. To assess ethnic differences in relationships, the statistical significance of an interaction term between adipokines and ethnic group was tested in multivariable regression models. Results: The black African men exhibited significantly lower adiponectin and tumour necrosis factor‐α (TNF‐α) and greater interleukin‐10 (IL‐10) compared to white European men (all p < 0.05). There were no statistically significant ethnic differences in leptin, resistin, IL‐6, interferon‐γ, IL‐13, IL‐1β, IL‐8 and vascular endothelial growth factor. Several relationships differed significantly by ethnicity such that they were stronger in white European than black African men including IL‐6 with visceral adipose tissue; adiponectin with subcutaneous adipose tissue; leptin with intrahepatic lipid; adiponectin, IL‐6 and TNF‐α with whole‐body insulin sensitivity and TNF‐α with adipose tissue insulin sensitivity (all pinteraction <0.05). Leptin significantly predicted whole‐body insulin sensitivity in white European (R2 = 0.51) and black African (R2 = 0.29) men; however, adiponectin was a statistically significant predictor in only white European men (R2 = 0.22). Conclusions: While adiponectin is lower in black African men, its insulin sensitising effects may be greater in white men suggesting that the role of adipokines in the development of type 2 diabetes may differ by ethnicity. [ABSTRACT FROM AUTHOR]

Objective: Multiple sclerosis (MS) is a complex disorder in which environmental and genetic factors interact modifying disease risk and course. This multicentre, case-control study involving 18 Italian MS Centres investigated MS course by ethnicity and native-country economic status in foreign-born patients living in Italy., Methods: We identified 457 MS patients who migrated to Italy and 893 age- and sex-matched native-born Italian patients. In our population, 1225 (93.2%) subjects were White Europeans and White Northern Americans (WENA) and 89 (6.8%) patients were from other ethnical groups (OEG); 1109 (82.1%) patients were born in a high-income (HI) Country and 241 (17.9%) in a low-middle-income (LMI) Country. Medical records and patients interviews were used to collect demographic and disease data., Results: We included 1350 individuals (973 women and 377 men); mean (SD) age was 45.0 (11.7) years. At onset, 25.45% OEG patients vs 12.47% WENA (p = 0.039) had > 3 STIR spine lesions. At recruitment, the same group featured mean (SD) EDSS score of 2.85 (2.23) vs 2.64 (2.28) (p = 0.044) reached in 8.9 (9.0) vs 12.0 (9.0) years (p = 0.018) and underwent 1.10 (4.44) vs. 0.99 (0.40) annual MRI examinations (p = 0.035). At disease onset, patients from LMI countries had higher EDSS score than HI patients (2.40 (1.43) vs 1.99 (1.17); p = 0.032)., Discussion: Our results suggested that both ethnicity and socio-economic status of native country shape MS presentation and course and should be considered for an appropriate management of patients. To the best of our knowledge, this is the first study reporting on the impact of ethnicity in MS at an individual level and beyond an ecological population-perspective., (© 2024. The Author(s).)

Background: Atogepant, an oral calcitonin gene-related peptide receptor antagonist, has been approved for the preventive treatment of migraine, but its efficacy and safety in people who have been failed by conventional oral preventive migraine treatments has not yet been evaluated in a dedicated clinical trial. The ELEVATE trial evaluated the safety, tolerability, and efficacy of atogepant for the preventive treatment of episodic migraine in participants for whom two to four classes of conventional oral preventive treatments have failed., Methods: ELEVATE was a randomised, double-blind, placebo-controlled, parallel-group, phase 3b trial done at 73 sites in Canada, the Czech Republic, Denmark, France, Germany, Hungary, Italy, the Netherlands, Poland, Russia, Spain, the UK, and the USA. Adults (18-80 years) with episodic migraine who had previously been failed by two to four classes of conventional oral treatments for migraine prevention were randomly assigned (1:1) using interactive web response technology to oral atogepant 60 mg once a day or placebo, stratified by baseline monthly migraine days, number of treatment classes participants have been failed by, and region. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period in the off-treatment hypothetical estimand (OTHE) population, which included participants in the safety population (all participants who received ≥1 dose of study intervention) who had evaluable data available for the baseline period and for one or more of the 4-week post-baseline periods (whether on treatment or off treatment). The primary endpoint was analysed using a mixed model for repeated measures and a fixed-sequence procedure was used to control for multiple comparisons. The trial is registered with ClinicalTrials.gov (NCT04740827) and EudraCT (2019-003448-58), and is completed., Findings: Between March 5, 2021, and Aug 4, 2022, 540 participants were screened, 315 were randomly assigned, and 313 participants (280 [89%] female, 33 [11%] male, and 300 [96%] White) received at least one dose of study intervention. In the OTHE population, which comprised 309 participants (155 assigned to placebo and 154 to atogepant), least squares mean changes from baseline in monthly migraine days across 12 weeks were -1·9 (SE 0·4) with placebo and -4·2 (0·4) with atogepant (least squares mean difference -2·4, 95% CI -3·2 to -1·5; adjusted p<0·0001). The most common treatment-emergent adverse event with atogepant was constipation in 16 (10%) of 156 participants (vs four [3%] of 157 for placebo). Serious adverse events occurred in four [3%] of 156 participants in the atogepant group vs none in the placebo group, and treatment-emergent adverse events resulting in treatment discontinuation occurred in three [2%] in the atogepant group vs two [1%] in the placebo group., Interpretation: Atogepant 60 mg once a day was safe, well tolerated, and showed significant and clinically relevant reductions in mean monthly migraine days compared with placebo across 12 weeks in patients with episodic migraine who had previously been failed by two to four classes of conventional oral preventive treatments. Atogepant might be an effective preventive treatment option for patients in this difficult-to-treat population., Funding: Allergan (now AbbVie)., Competing Interests: Declaration of interests JMT, KN, HG, RDAF, and GF are employees of AbbVie and may hold AbbVie stock. CT reports support from Abbvie and Novartis for investigator-initiated trials; consulting fees from Abbvie, Eli Lilly, Dompé, Teva, Lundbeck, Pfizer, and Medscape for participating in advisory boards; support from Abbvie, Eli Lilly, Dompé, Teva, Lundbeck, and Pfizer for attending meetings; and personal fees from Abbvie, Eli Lilly, Teva, Lundbeck, and Pfizer for lecturing at symposia. She is principal investigator of clinical trials sponsored by Abbvie, Eli Lilly, Lundbeck, Pfizer, and Teva. She has received research grants from the European Commission, the Italian Ministry of Health, and the Migraine Research Foundation. PP-R reports support for the present study from AbbVie and personal fees for consulting from AbbVie, Biohaven, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, Pfizer, and Teva. She has received personal fees for speaking from AbbVie, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, and Teva, and has had grants paid to her research group from AbbVie, AGAUR, EraNet Neuron, FEDER RIS3CAT, Instituto Investigación Carlos III, International Headache Society, Novartis, and Teva. She has participated in an advisory board for Lilly Foundation Spain. ML-M reports support for the present study from AbbVie and reports personal fees for speaker panels from Amicus, Eli Lilly, Lundbeck, Teva, UPSA, and Zambon. He has received consulting fees from AbbVie, Eli Lilly, Grunenthal, Lundbeck, Medtronic, Novartis, Orion, Pfizer, Reckitt Benkiser, Sun Pharmaceutical, Teva, UPSA, and Zambon. He has received grants for institutional support from Eli Lilly, Lundbeck, Medtronic, Novartis, Pfizer, and Teva. SS has received consulting fees from Impel Neuropharma, and personal payment as a speaker for AbbVie, Amgen, BDSI, Biohaven, Eli Lilly, Impel Neuropharma, and Teva. She has participated in advisory boards for AbbVie, Amgen, BDSI, Biohaven, Eli Lilly, Impel Neuropharma, and Teva and serves as Board of Directors for the Southern Headache Society and Carolina Headache Foundation. TN reports support for the present study from AbbVie and has received personal payments for consulting fees and speaking fees from Eli Lilly, Glenmark, Lundbeck, Novartis, Pfizer, St Jude Medical, Teva Pharmaceuticals, and UCB. He has received grants for institutional support from Eli Lilly, Glenmark, Lundbeck, Novartis, Pfizer, St Jude Medical, Teva Pharmaceuticals, and UCB. He also has served on advisory boards or as a principal investigator in clinical trials for AbbVie, Amgen, Eli Lilly, Lundbeck, Neurocrine, Novartis, Teva Pharmaceuticals, and UCB., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Patterns of—and correlates associated with—bullying perpetration and peer victimization have received widespread research attention. Somewhat less research has considered how protective factors in the parental domain help to buffer against both adverse behaviors. And perhaps more importantly, even less research has considered potential racial differences in the manner in which family-level variables relate to both bullying perpetration and peer victimization. Using a nationwide sample of adolescents, the present study examines (a) how parent/guardian support, mother's parental monitoring, father's parental monitoring, and family satisfaction buffer against bullying perpetration and peer victimization; and (b) whether these relationships vary across race. Data are derived from the 2009 to 2010 Health Behavior in School-Aged Children study in the United States. A total of 8,998 adolescents were included in the study sample, which consisted of 6,521 European Americans and 2,477 African Americans. Findings show that both European American and African American youth who received parental/guardian support were less likely to report being bullied. Among both African American and European American sub-samples, results showed that mother's parental monitoring was negatively associated with both bullying perpetration and peer victimization. Father's parental monitoring was negatively associated with peer victimization and bullying perpetration for European Americans only. Both European and African American youth who reported being satisfied with their family were less likely to report being bullied while European American youth who reported higher family satisfaction were less likely to engage in bullying. In sum, several family variables help to buffer against both bullying perpetration and peer victimization, but for the most part these relationships are race-invariant. [ABSTRACT FROM AUTHOR]

Background: Previous gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions.Methods: Analyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions.Results: Noteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth.Conclusions: Overall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors. [ABSTRACT FROM AUTHOR]

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries.Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group.Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China.Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol. [ABSTRACT FROM AUTHOR]

APOE is a well-studied gene with multiple effects on aging and longevity. The gene has three alleles: e2, e3, and e4, whose frequencies vary by ethnicity. While the e2 is associated with healthy cognitive aging, the e4 allele is associated with Alzheimer's disease and early mortality and therefore its prevalence among people with extreme longevity (EL) is low. Using the PopCluster algorithm, we identified several ethnically different clusters in which the effect of the e2 and e4 alleles on EL changed substantially. For example, PopCluster discovered a large group of 1,309 subjects enriched of Southern Italian genetic ancestry with weaker protective effect of e2 (odds ratio [OR] = 1.27, p = .14) and weaker damaging effect of e4 (OR = 0.82, p = .31) on the phenotype of EL compared to other European ethnicities. Further analysis of this cluster suggests that the odds for EL in carriers of the e4 allele with Southern Italian genetic ancestry differ depending on whether they live in the United States (OR = 0.29, p = .009) or Italy (OR = 1.21, p = .38). PopCluster also found clusters enriched of subjects with Danish ancestry with varying effect of e2 on EL. The country of residence (Denmark or United States) appears to change the odds for EL in the e2 carriers. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a common disorder that affects 6-10% of reproductive age women. In a previous study, we demonstrated that a polymorphism in let-7 microRNA-binding site in the 3' untranslated region of the KRAS gene was found in 31% of subjects with endometriosis resistant to medical therapy. This polymorphism was now tested in a large, case-control study.Methods: Peripheral blood or peritoneal biopsies from 2,077 European subjects with or without endometriosis and known infertility were tested for the presence of the variant allele using polymerase chain reaction.Results: Histologically proven endometriosis was found in 1,140 subjects, while 937 subjects were disease free. Variant allele carrier rates in subjects with and without endometriosis were 15.7 and 15.1%, respectively. No association between the variant KRAS allele and stage of the disease, age at surgery, body mass index, or type of infertility was identified.Conclusion: A germ-line single-nucleotide polymorphism in the let-7 microRNA-binding site of the KRAS gene was not associated with sporadic endometriosis in an infertile Caucasian population in this large case-control study. However, it remains possible that this gene variant may be a marker of treatment resistance. Further studies on the role of this polymorphism in endometriosis are needed. [ABSTRACT FROM AUTHOR]

Aims: To investigate the relationship between HbA1c and glucose in people with co‐existing liver disease and diabetes awaiting transplant, and in those with diabetes but no liver disease. Methods: HbA1c and random plasma glucose data were collected for 125 people with diabetes without liver disease and for 29 people awaiting liver transplant with diabetes and cirrhosis. Cirrhosis was caused by non‐alcoholic fatty liver disease, hepatitis C, alcoholic liver disease, hereditary haemochromatosis, polycystic liver/kidneys, cryptogenic/non‐cirrhotic portal hypertension and α‐1‐antitrypsin‐related disease. Results: The median (interquartile range) age of the diabetes with cirrhosis group was 55 (49–63) years compared to 60 (50–71) years (P=0.13) in the group without cirrhosis. In the diabetes with cirrhosis group there were 21 men (72%) compared with 86 men (69%) in the group with diabetes and no cirrhosis (P=0.82). Of the group with diabetes and cirrhosis, 27 people (93%) were of white European ethnicity, two (7%) were South Asian and none was of Afro‐Caribbean/other ethnicity compared with 94 (75%), 16 (13%), 10 (8%)/5 (4%), respectively, in the group with diabetes and no cirrhosis (P=0.20). Median (interquartile range) HbA1c was 41 (32–56) mmol/mol [5.9 (5.1–7.3)%] vs 61 (52–70) mmol/mol [7.7 (6.9–8.6)%] (P<0.001), respectively, in the diabetes with cirrhosis group vs the diabetes without cirrhosis group. The glucose concentrations were 8.4 (7.0–11.2) mmol/l vs 7.3 (5.2–11.5) mmol/l (P=0.17). HbA1c was depressed by 20 mmol/mol (1.8%; P<0.001) in 28 participants with cirrhosis but elevated by 28 mmol/mol (2.6%) in the participant with α‐1‐antitrypsin disorder. Those with cirrhosis and depressed HbA1c had fewer larger erythrocytes, and higher red cell distribution width and reticulocyte count. This was reflected in the positive association of glucose with mean cell volume (r=0.39) and haemoglobin level (r=0.49) and the negative association for HbA1c (r=–0.28 and r=–0.26, respectively) in the diabetes group with cirrhosis. Conclusion: HbA1c is not an appropriate test for blood glucose in people with cirrhosis and diabetes awaiting transplant as it reflects altered erythrocyte presentation. What's new?: HbA1c may not be an accurate reflection of blood glucose for the diagnosis/monitoring of diabetes in people with other illnesses or on certain drugs; people with diabetes and liver disease awaiting transplantation are one such group.HbA1c was found to be depressed relative to random plasma glucose by 20 mmol/mol in people with diabetes and cirrhosis (n = 28) compared to people with diabetes but no liver disease (n = 125); however, HbA1c was elevated in one person with cirrhosis attributable to α‐1‐antitrypsin disorder.Compromised HbA1c may be related to haematological differences associated with liver disease involving erythrocyte half‐life, with shorter/longer times giving less/more opportunity for glycation of haemoglobin. [ABSTRACT FROM AUTHOR]

Background: Alterations in glucose metabolism that lead to the development of metabolic and cardiovascular disease may begin already in childhood. Objective: This study aims to generate pediatric age and sex‐specific reference values for fasting concentrations of glucose, hemoglobin A1c (HbA1c), insulin, C‐peptide, and homeostasis model assessment: insulin resistance (HOMA‐IR) in Danish/North‐European white children and adolescents from a population‐based cohort and to compare values from children and adolescents with overweight/obesity with this reference. Methods: The population‐ and obesity clinic‐based cohorts consisted of 2451 and 1935 children and adolescents between 6 and 18 years of age. Anthropometric measurements and blood samples were obtained and percentile curves were calculated. Results: In the population‐based cohort, glucose, insulin, and HOMA‐IR values increased before the expected onset of puberty (P < .05). Thereafter, all variables decreased in girls (P < .05) and HbA1c decreased in boys (P < .05). Concentrations of all measured markers of glucose metabolism were higher in the obesity clinic‐based cohort than the population‐based cohort (both sexes P < .001). Specifically, insulin and HOMA‐IR continued to increase to 18 years in the clinic‐based cohort, particularly among boys. Conclusions: Fasting glucose, insulin, and HOMA‐IR change during childhood, making pediatric reference values essential for timely identification of derangements in glucose metabolism. Children and adolescents with obesity exhibit increased concentrations of these biomarkers. [ABSTRACT FROM AUTHOR]

Inequalities between native-born and foreign-born individuals in screening rates for a variety of conditions have been well-documented in literature on immigrant health. A preponderance of this research focuses on the Latin American case and on cancer-specific screening. This study seeks to expand knowledge of such preventative-health screening differences by analyzing screening rates for blood sugar, blood pressure, and serum cholesterol among nine groups overall and (for immigrants) at various stages of US residency. Using nationally representative data from the National Health Interview Survey, we find that immigrants from eight geographic regions receive preventative care at lower rates than US-born Whites and that preventative screening is generally higher after 15 years than during the first 4 years of residency in the United States. Importantly, our data also show that screening patterns and trends vary based on region of origin and outcome. These findings improve our understanding of immigrant health and health care use in the United States. [ABSTRACT FROM AUTHOR]

This article analyzes critically the most recent scientific bibliography on the causes of the growth of mortality and morbidity in the white working class of the United States. The methodology used in these studies, and also the insufficient conceptualization of the variables used (such as social class), limits the understanding of the increment of the "diseases of despair" in that sector of the population. This article emphasizes the need to analyze the evolution of the social classes in the United States, and the political determinants that have changed not only the character and composition of that class, but also the power differentials between this class and other classes in the United States. [ABSTRACT FROM AUTHOR]

Britain's vote to leave the European Union highlights the importance of White majority opposition to immigration. This article presents the results of a survey experiment examining whether priming an open form of ethno-nationalism based on immigrant assimilation reduces hostility to immigration and support for right-wing populism in Britain. Results show that drawing attention to the idea that assimilation leaves the ethnic majority unchanged significantly reduces hostility to immigration and support for Hard Brexit in the UK. Treatment effects are strongest among UK Independence Party, Brexit and White working-class voters. This is arguably the first example of an experimental treatment leading to more liberal immigration policy preferences. [ABSTRACT FROM AUTHOR]

Internalization of cultural standards of attractiveness and subscription to gender-based discourses are significant predictors of disordered eating attitudes in fully sighted women. Yet, whether these variables predict the disordered eating attitudes of women who are legally blind is underexplored. In the current study, we examined how internalization of White European cultural standards of attractiveness and subscription to gender-based discourses (body surveillance and self-silencing) and body shame predicted the disordered eating attitudes of 80, primarily White, heterosexual, Australian women who are legally blind. Participants completed an online survey comprising existing validated measures of all variables. A path analysis was performed using the Hayes PROCESS approach. As predicted, in women living with vision impairment, body surveillance, self-silencing, and shame fully mediated the relation between internalization of cultural standards of attractiveness and disordered eating attitudes. Results showed that in much the same way as sighted women, women living with vision impairment are susceptible to internalizing harmful messages related to socio-cultural standards of attractiveness. We provide further support for including subscription to gender-based discourses in research on women's body-image disturbances. Data will be available for other researchers from the author via email. Online slides for instructors who want to use this article for teaching are available on PWQ's website at http://journals.sagepub.com/page/pwq/suppl/index [ABSTRACT FROM AUTHOR]

Abstract: Aims: To clarify the frequency and severity of diabetic retinopathy in a group of people with Type 2 diabetes and chronic diabetic foot ulcers, and to compare visual acuity, levels of retinopathy and clinical significant macular oedema with a matched control group of people with Type 2 diabetes without a history of chronic diabetic foot ulcers. Methods: Visual acuity and fundus imaging were evaluated in 90 white people with at least 3 months’ duration of full‐thickness diabetic foot ulcers below the ankle and the results compared with those in 180 white people with Type 2 diabetes without a history of chronic diabetic foot ulcers (control group). Controls were matched for age, sex and duration of diabetes. Results: Despite similar age and diabetes duration, severe non‐proliferative or proliferative diabetic retinopathy was present in 41% of the people in the diabetic foot ulcer group as compared to 15% in the control group (P<0.001). Only 6% in the diabetic foot ulcer group was without any diabetic retinopathy as compared to 34% among controls. Proliferative diabetic retinopathy was more common in the diabetic foot ulcer group (31% vs 8%; P<0.001), but time‐to‐proliferative diabetic retinopathy did not differ between groups. Clinically significant macular oedema was more frequently present, and the diabetic foot ulcer group exhibited significantly worse results in best and worst eye visual acuity testing. Conclusions: In this northern European setting almost all people with Type 2 diabetes and chronic diabetic foot ulcers had diabetic retinopathy. Almost one‐third had proliferative diabetic retinopathy as compared to <10% in our matched control group. More advanced diabetic retinopathy was linked to worse visual acuity. [ABSTRACT FROM AUTHOR]

Objectives The Scleroderma Patient-centered Intervention Network (SPIN) Cohort is a web-based cohort designed to collect patient-reported outcomes at regular intervals as a framework for conducting trials of psychosocial, educational, self-management and rehabilitation interventions for patients with SSc. The aim of this study was to present baseline demographic, medical and patient-reported outcome data of the SPIN Cohort and to compare it with other large SSc cohorts. Methods Descriptive statistics were used to summarize SPIN Cohort characteristics; these were compared with published data of the European Scleroderma Trials and Research (EUSTAR) and Canadian Scleroderma Research Group (CSRG) cohorts. Results Demographic, organ involvement and antibody profile data for SPIN (N = 1125) were generally comparable with that of the EUSTAR (N = 7319) and CSRG (N = 1390) cohorts. There was a high proportion of women and White patients in all cohorts, though relative proportions differed. Scl70 antibody frequency was highest in EUSTAR, somewhat lower in SPIN, and lowest in CSRG, consistent with the higher proportion of interstitial lung disease among dcSSc patients in SPIN compared with in CSRG (48.5 vs 40.3%). RNA polymerase III antibody frequency was highest in SPIN and remarkably lower in EUSTAR (21.1 vs 2.4%), in line with the higher prevalence of SSc renal crisis (4.5 vs 2.1%) in SPIN. Conclusion Although there are some differences, the SPIN Cohort is broadly comparable with other large prevalent SSc cohorts, increasing confidence that insights gained from the SPIN Cohort should be generalizable, although it should be noted that all three cohorts include primarily White participants. [ABSTRACT FROM AUTHOR]

A considerable proportion of European adults report little or no interest in physical activity. Identifying individual-level and environmental-level characteristics of these individuals can help designing effective interventions and policies to promote physical activity. This cross-sectional study additionally explored associations between level of interest and physical activity, after controlling for other individual and environmental variables. Measures of objective and perceived features of the physical environment of residence, self-reported physical activity and other lifestyle behaviors, barriers towards physical activity, general health, and demographics were obtained from 5205 European adults participating in the 2014 online SPOTLIGHT survey. t-Tests, chi-square tests, and generalized estimating equations with negative binomial log-link function were conducted. Adults not interested in physical activity reported a higher BMI and a lower self-rated health, were less educated, and to a smaller extent female and less frequently employed. They were more prone to have less healthy eating habits, and to perceive more barriers towards physical activity. Only minor differences were observed in environmental attributes: the non-interested were slightly more likely to live in neighborhoods objectively characterized as less aesthetic and containing more destinations, and perceived as less functional, safe, and aesthetic. Even after controlling for other individual and environmental factors, interest in physical activity remained a significant correlate of physical activity, supporting the importance of this association. This study is among the first to describe characteristics of individuals with reduced interest in physical activity, suggesting that (lack of) interest is a robust correlate of physical activity in several personal and environmental conditions. [ABSTRACT FROM AUTHOR]

We conducted a cross-sectional study in 448 HIV positive patients attending five European outpatient clinics to determine prevalence of and factors associated with neurocognitive impairment (NCI) using computerized and pen-and-paper neuropsychological tests. NCI was defined as a normalized Z score ≤−1 in at least 2 out of 5 cognitive domains. Participants’ mean age was 45.8 years; 84% male; 87% white; 56% university educated; median CD4 count 550 cells/mm3; 89% on antiretroviral therapy. 156 (35%) participants had NCI, among whom 26 (17%; 5.8% overall) reported a decline in activities of daily living. Prevalence of NCI was lower in those always able to afford basic needs (adjusted prevalence ratio [aPR] 0.71, 95% confidence interval [CI] 0.54-0.94) or with a university education (aPR 0.72, 95% CI 0.54-0.97) and higher in those with severe depressive symptoms (aPR 1.53, 95% CI 1.09-2.14) or a significant comorbid condition (aPR 1.40, 95% CI 1.03-1.90). [ABSTRACT FROM AUTHOR]

Objective: To describe dietary patterns by applying cluster analysis and to describe the cluster memberships of European children over time and their association with body composition changes.Design: The analyses included k-means clustering based on the similarities between the relative frequencies of consumption of forty-three food items and regression models were fitted to assess the association between dietary patterns and body composition changes.Setting: Primary schools and pre-schools of selected regions in Italy, Estonia, Cyprus, Belgium, Sweden, Hungary, Germany and Spain.Subjects: Participants (n 8341) in the baseline (2-9 years old) and follow-up (4-11 years old) surveys of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) study.Results: Three persistent clusters were obtained at baseline and follow-up. Children consistently allocated to the 'processed' cluster presented increased BMI (β=0·050; 95 % CI 0·006, 0·093), increased waist circumference (β=0·071; 95 % CI 0·001, 0·141) and increased fat mass gain (β=0·052; 95 % CI 0·014, 0·090) over time v. children allocated to the 'healthy' cluster. Being in the 'processed'-'sweet' cluster combination was also linked to increased BMI (β=0·079; 95 % CI 0·015, 0·143), increased waist circumference (β=0·172; 95 % CI 0·069, 0·275) and increased fat mass gain (β=0·076; 95 % CI 0·019, 0·133) over time v. the 'healthy' cluster.Conclusions: Children consistently showing a processed dietary pattern or changing from a processed pattern to a sweet pattern presented the most unfavourable changes in fat mass and abdominal fat. These findings support the need to promote overall healthy dietary habits in obesity prevention and health promotion programmes targeting children. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases. [ABSTRACT FROM AUTHOR]

Conflicting evidence has led to uncertainty as to whether vitamin D2 and vitamin D3 are equally efficacious in improving vitamin D status, despite historically being considered equipotent. A systematic review and meta-analysis completed in 2012 indicated that D3 was more effective at raising vitamin D levels {using total 25-hydroxyvitamin D [25(OH)D] as a marker of status} but the meta-analysis identified high levels of heterogeneity between studies and a lack of statistically powered sample sizes to provide a conclusive answer. Thus, to meet the need for robust data, our research team conducted the largest (to date) randomised, controlled trial comparing the two forms of vitamin D. The D2-D3 Study was conducted in 335 healthy South Asian ( n = 90) and White European women ( n = 245). The study was designed to compare the respective efficacy of vitamin D2 with vitamin D3 at raising total 25(OH)D when added to a juice or a biscuit, at a relatively low dose of 15 μg/day for 12 weeks. Overall, the results showed that those who consumed vitamin D3 showed an average increase in vitamin D status of 74%-75%, whereas an average increase of 33%-34% in vitamin D status was found in those who consumed vitamin D2. Therefore, this study emphatically shows that vitamin D3 is more than twice as effective as vitamin D2 at raising total 25(OH)D concentrations, when given in a low dose that is both physiologically relevant and in line with public health guidance. [ABSTRACT FROM AUTHOR]

Objectives To examine the difference in the association between apolipoprotein ( APO)E allele and overall and cardiovascular mortality between African Americans ( AAs) and European Americans ( EAs). Design Longitudinal, cohort study of 18 years. Setting Biracial urban US population sample. Participants 4,917, 68% AA and 32% EA. Measurements APOE genotype and mortality based on National Death Index. Results A higher proportion of AAs than of EAs had an APOE ε2 allele ( ε2 ε2/ ε2 ε3/ ε2 ε4; 22% vs 13%) and an APOE ε4 allele ( ε3 ε4/ ε4 ε4; 33% vs 24%). After adjusting for known risk factors, the risk of mortality was 19% less with the APOE ε2 allele (hazard ratio ( HR) = 0.81, 95% confidence interval ( CI) = 0.76-0.87), and the risk of cardiovascular mortality was 35% less ( HR = 0.65, 95% CI = 0.58-0.76) than with the ε3 ε3 allele. The risk of mortality was 10% greater with the APOE ε4 allele ( HR = 1.10, 95% CI = 1.04-1.16), and the risk of cardiovascular mortality was 20% greater ( HR = 1.20, 95% CI = 1.07-1.29) than with the ε3 ε3 allele. No difference in the association between APOE allele and mortality was observed between AAs and EAs. Conclusion The APOE ε4 allele increased the risk of overall and cardiovascular mortality, whereas the APOE ε2 allele decreased the risk of overall and cardiovascular mortality. There was no racial difference in the association between these alleles and mortality. [ABSTRACT FROM AUTHOR]

Aims The purpose of this study is to describe disease presentation, co-morbidities, diagnosis and initial therapeutic management of patients with peripartum cardiomyopathy (PPCM) living in countries belonging to the European Society of Cardiology (ESC) vs. non-ESC countries. Methods and results Out of 500 patients with PPCM entered by 31 March 2016, we report on data of the first 411 patients with completed case record forms (from 43 countries) entered into this ongoing registry. There were marked differences in socio-demographic parameters such as Human Development Index, GINI index on inequality, and Health Expenditure in PPCM patients from ESC vs. non-ESC countries (P < 0.001 each). Ethnicity was Caucasian (34%), Black African (25.8%), Asian (21.8%), and Middle Eastern backgrounds (16.4%). Despite the huge disparities in socio-demographic factors and ethnic backgrounds, baseline characteristics are remarkably similar. Drug therapy initiated post-partum included ACE inhibitors/ARBs and mineralocorticoid receptor antagonists with identical frequencies in ESC vs. non-ESC countries. However, in non-ESC countries, there was significantly less use of beta-blockers (70.3% vs. 91.9%) and ivabradine (1.4% vs. 17.1%), but more use of diuretics (91.3% vs. 68.8%), digoxin (37.0% vs. 18.0%), and bromocriptine (32.6% vs. 7.1%) (P < 0.001). More patients in non-ESC vs. ESC countries continued to have symptomatic heart failure after 1 month (92.3% vs. 81.3%, P < 0.001). Venous thrombo-embolic events, arterial embolizations, and cerebrovascular accidents were documented in 28 of 411 patients (6.8%). Neonatal death rate was 3.1%. Conclusion PPCM occurs in women from different ethnic backgrounds globally. Despite marked differences in socio-economic background, mode of presentation was largely similar. Embolic events and persistent heart failure were common within 1 month post-diagnosis and required intensive, multidisciplinary management. [ABSTRACT FROM AUTHOR]

Purpose: Previous research has not provided us with a comprehensive picture of the longitudinal course of psychotic disorders in Black people living in Europe. We sought to investigate clinical outcomes and pattern of care in Black African and Black Caribbean groups compared with White British patients during the first 5 years after first contact with mental health services for psychosis.Methods: 245 FEP cases aged 18-65 who presented to psychiatric services in 2005-2010 in South London (UK). Using the electronic psychiatric clinical notes in the South London and Maudsley NHS Foundation Trust (SLaM), extensive information was collected on three domains-clinical, social, and service use.Results: During the 5-year follow-up (mean = 5.1 years, s.d. = 2.4; 1251 person years) after first contact with mental health services, a higher proportion of Black African and Black Caribbean ethnicity had compulsory re-admissions (χ 2 = 17.34, p = 0.002) and instances of police involvement during an admission to a psychiatric unit (χ 2 = 22.82, p < 0.001) compared with White British ethnic group. Patients of Black African and Black Caribbean ethnicity did not differ from the ethnic group in overall functional disability and illness severity, or frequency of remission or recovery during the follow-up period. However, patients of Black ethnicity become increasing socially excluded as their illness progress.Conclusions: The longitudinal trajectory of psychosis in patients of Black ethnicity did not show greater clinical or functional deterioration than white patients. However, their course remains characterised by more compulsion, and longer periods of admission. [ABSTRACT FROM AUTHOR]

The present study aims to examine why parents engage in overprotective parenting in interaction with their emerging adults. Specifically, this study used an Actor-Partner Interdependence Model to examine associations between parental attachment representations (both maternal and paternal attachment anxiety and avoidance), parental separation anxiety, and parental overprotection. Additionally, we examined whether maternal attachment, separation anxiety, and overprotection predicted the emerging adult's actual living situation (at home / away from home) 1 year later, and maternal negative affect regarding emerging adults' home-leaving. The sample consisted of Caucasian participants and included 246 adolescents in their final year of secondary school (mean age Time 1 = 17.14) and their parents (242 mothers, 218 fathers). Results showed that both maternal and paternal attachment anxiety related to more maternal and paternal separation anxiety, respectively ( p's < .001). In turn, separation anxiety in mothers and fathers related to respectively maternal ( p < .001) and paternal overprotection ( p < .05), as perceived by the emerging adult. There was one significant partner-effect between maternal attachment anxiety and paternal separation anxiety ( p < .05). Further, higher scores on perceived maternal overprotection related to a higher likelihood that the emerging adult would still live at home 1 year later ( p < .01), as well as to more negative maternal affect related to the process of home-leaving ( p < .05). In sum, the current study revealed the importance of attachment and separation anxiety as significant parental factors related to parental overprotection. [ABSTRACT FROM AUTHOR]

Sleep restriction is a risk factor for weight gain and obesity. Few studies have formally investigated the mediating role of energy balance-related behaviours in the sleep - obesity association. The aim of this study was to explore the mediating role of physical activity, sedentary behaviours and dietary habits in the association of sleep duration with obesity in adults in five European urban regions. Data on self-reported sleep duration, energy balance-related behaviours, height and weight and other covariates were collected between February and September 2014 from participants to the SPOTLIGHT survey (N=5900, mean age 52years). Participants were recruited from 60 urban neighbourhoods in Belgium, France, Hungary, the Netherlands and the United Kingdom. Multilevel logistic regression analyses were used to assess the associations of sleep duration, energy balance-related behaviours and obesity and mediating effects were calculated using MacKinnon's product-of-coefficients method. Results indicated that a 1h increase in sleeping time was associated with a 14% lower likelihood of being obese (OR=0.86, 95%CI=0.80; 0.93). Only work-related sedentary behaviour was identified as a statistically significant mediator in the association between sleep duration and obesity for the total sample, and youngest and oldest age group. We did not find evidence for a mediating role of dietary habits and physical activities. [ABSTRACT FROM AUTHOR]

Aims: Vulvar cancer is a rare disease. In western European countries, the incidence is 1.2 cases per 100,000 women/year. The aim of this study was to analyze the management and disease-free survival (DFS) of vulvar cancer among European countries.Methods: An international multicenter retrospective study including patients diagnosed of squamous cell vulvar cancer was performed. Countries analyzed included Austria, Germany, Greece, Italy, Latvia, Lithuania, Poland, Portugal, Spain and Turkey. One hundred different centers were enrolled including 1,505 squamous cell tumors treated from January 2001 until December 2005.Results: The mean free surgical margin was 9.93 mm, which was different between countries (p = 0.076); it ranged from 5.79 mm (95% CI 4.44-7.13) in Germany to 33.39 mm (95% CI 22.21-44.58) in Lithuania. The global 5-year overall survival rate was 61.4%, and the global 5-year DFS rate was 32%. DFS times were different between countries as well as the treatments carried out. The country with the shortest DFS time had 15.9 ± 3.1 months compared to the one with the longest time with 66.0 ± 17.4 months.Conclusion: Wide differences in treatments and DFS times have been observed between countries. Homogeneous management for squamous cell vulvar cancer is needed to obtain the best survival rates for all patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate dietary sources of Ca and vitamin D (VitD) intakes, and the associated sociodemographic and lifestyle factors, among European adolescents.Design: Linear regression mixed models were used to examine sex-specific associations of Ca and VitD intakes with parental education, family affluence (FAS), physical activity and television (TV) watching while controlling for age, Tanner stage, energy intake and diet quality.Setting: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA)Cross-Sectional Study.Subjects: Adolescents aged 12·5-17·5 years (n 1804).Results: Milk and cheese were the main sources of Ca (23 and 19 % contribution to overall Ca intake, respectively). Fish products were the main VitD source (30 % contribution to overall VitD intake). Ca intake was positively associated with maternal education (β=56·41; 95 % CI 1·98, 110·82) and negatively associated with TV viewing in boys (β=-0·43; 95 % CI -0·79, -0·07); however, the significance of these associations disappeared when adjusting for diet quality. In girls, Ca intake was positively associated with mother's (β=73·08; 95 % CI 34·41, 111·74) and father's education (β=43·29; 95 % CI 5·44, 81·14) and FAS (β=37·45; 95 % CI 2·25, 72·65). This association between Ca intake and mother's education remained significant after further adjustment for diet quality (β=41·66; 95 % CI 0·94, 82·38). Girls with high-educated mothers had higher Ca intake.Conclusions: Low-educated families with poor diet quality may be targeted when strategizing health promotion programmes to enhance dietary Ca. [ABSTRACT FROM AUTHOR]

Objective Inclusion body myositis (IBM) is characterized by a combination of inflammatory and degenerative changes affecting muscle. While the primary cause of IBM is unknown, genetic factors may influence disease susceptibility. To determine genetic factors contributing to the etiology of IBM, we conducted the largest genetic association study of the disease to date, investigating immune-related genes using the Immunochip. Methods A total of 252 Caucasian patients with IBM were recruited from 11 countries through the Myositis Genetics Consortium and compared with 1,008 ethnically matched controls. Classic HLA alleles and amino acids were imputed using SNP2HLA. Results The HLA region was confirmed as the most strongly associated region in IBM ( P = 3.58 × 10−33). HLA imputation identified 3 independent associations (with HLA-DRB1*03:01, DRB1*01:01, and DRB1*13:01), although the strongest association was with amino acid positions 26 and 11 of the HLA-DRB1 molecule. No association with anti-cytosolic 5′-nucleotidase 1A-positive status was found independent of HLA-DRB1*03:01. There was no association of HLA genotypes with age at onset of IBM. Three non-HLA regions reached suggestive significance, including the chromosome 3 p21.31 region, an established risk locus for autoimmune disease, where a frameshift mutation in CCR5 is thought to be the causal variant. Conclusion This is the largest, most comprehensive genetic association study to date in IBM. The data confirm that HLA is the most strongly associated region and identifies novel amino acid associations that may explain the risk in this locus. These amino acid associations differentiate IBM from polymyositis and dermatomyositis and may determine properties of the peptide-binding groove, allowing it to preferentially bind autoantigenic peptides. A novel suggestive association within the chromosome 3 p21.31 region suggests a role for CCR5. [ABSTRACT FROM AUTHOR]

The association between ALOX5AP SG13S114 polymorphism and ischemic stroke (IS) susceptibility has extensively been investigated, especially in white populations; however, the results were inconclusive. Here, we perform a meta-analysis to clarify the effect of SG13S114 variant on the IS risk in Europeans. The Web of Science, PubMed, EMBASE, and Medline were searched up to August 1st, 2016. Data were extracted and the odd ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model. In total, 8 case control studies involved 8062 subjects were finally included in this meta-analysis. We observed a significantly decreased IS risk in persons carrying an A allele at the SG13S114 polymorphism compared with those with a T allele (A vs T, OR = 0.856, 95% CI = 0.797-0.919, p < 0.001). In addition, the results of sensitivity and cumulative meta-analysis indicated the robustness of our results. In addition, the publication bias was not detected using the funnel plot and Egger's tests. In summary, the present meta-analysis suggested that the A allele at the ALOX5AP SG13S114 polymorphism is a protective factor for the IS in the Europeans. In addition, further studies with large sample size are needed to validate the association, as well as in other ethnic groups. [ABSTRACT FROM AUTHOR]

This study uses data from the European Social Survey in order to test the Prinstein-Dodge hypothesis that posits that peer effects may be larger in collectivistic than in individualistic societies. When defining individualism and collectivism at the country level, our results show that peer effects on obesity are indeed larger in collectivistic than in individualistic societies. However, when defining individualism and collectivism with individual values based on the Shalom Schwartz universal values theory, we find little support for this hypothesis. [ABSTRACT FROM AUTHOR]

Aim We aimed to analyze computerized cardiotocographic (cCTG) parameters (including fetal heart rate baseline, short-term variability, Delta, long-term irregularity [LTI], interval index [II], low frequency [LF], movement frequency [MF], high frequency [HF], and approximate entropy [ApEn]) in physiological term pregnancies in order to correlate them with ethnic differences. The clinical meaning of numerical parameters may explain physiological or paraphysiological phenomena that occur in fetuses of different ethnic origins. Methods A total of 696 pregnant women, including 384 from Europe, 246 from sub-Saharan Africa, 45 from South-East Asia, and 21 from South America, were monitored from the 37th to the 41st week of gestation. Statistical analysis was performed with the analysis of variance test, Pearson correlation test and receiver-operator curves ( P < 0.05). Results Our results showed statistically significant differences ( P < 0.05) between white and black women for Delta, LTI, LF, MF, HF, and ApEn; between white and Asian women for Delta, LTI, MF, and the LF/(HF + MF) ratio; and between white and Latina women for Delta, LTI, and ApEn. In particular, Delta and LTI performed better in the white group than in the black, Asian, and Latina groups. Instead, LF, MF, HF, and ApEn performed better in the black than in the white group. Conclusion Our results confirmed the integrity and normal functionality of both central and autonomic nervous system components for all fetuses investigated. Therefore, CTG monitoring should include both linear and nonlinear components of fetal heart rate variability in order to avoid misinterpretations of the CTG trace among ethnic groups. [ABSTRACT FROM AUTHOR]

Fruit, vegetables, cereals, and olive oil are common elements of the Mediterranean diet (MD), but each country in the Mediterranean basin has its own gastronomic customs influenced by socio-cultural, religious, and economic factors. This study compared the dietary habits of three Mediterranean populations with different cultures and lifestyles, a total of 600 adults (61.9% females) between 25 and 70 yrs from Spain, Morocco, and Palestine. All participants completed a self administered questionnaire, including sociodemographic and anthropometric items, a validated semi-quantitative food frequency questionnaire adapted to the foods consumed in each country, and three 24-h recalls. MD adherence was estimated with the MD Serving Score (MDSS). All populations showed a moderate adherence to the Mediterranean dietary pattern. In comparison to the Palestine population, MDSS-assessed adherence to the MD was 6.36-fold higher in the Spanish population and 3.88-fold higher in the Moroccan population. Besides the country of origin, age was another predictive factor of MD adherence, which was greater (higher MDSS) in participants aged over 50 yrs than in those aged 30 yrs or younger. This preliminary study contributes initial data on dietary differences between European and non-European countries in the Mediterranean basin. The Spanish diet was shown to be closer to MD recommendations than the diet of Morocco or Palestine. Given the impact of good dietary habits on the prevention of chronic non-transmittable diseases, health policies should focus on adherence to a healthy diet, supporting traditional dietary patterns in an era of intense commercial pressures for change. [ABSTRACT FROM AUTHOR]

Sensory properties are reported as one of the main factors hindering an appropriate vegetable intake by the young. In the present work the sensory determinants of likings for vegetables were explored in adolescents of four European countries (Denmark, n = 88; France, n = 206; Italy, n = 110 and United Kingdom, n = 93). A questionnaire was designed to study cross country differences in stated liking for and familiarity with a list of vegetables popular among European markets (between-vegetable approach). A within-vegetable comparison approach with actual tasting was used to analyze differences and similarities in liking for canned pea and sweet corn samples across the countries. A close positive relationship between stated liking and familiarity was found. Irrespective of the country, one group of highly liked vegetables (carrots, tomatoes, green salad) was identified, characterized by innately liked tastes (sweet, umami), delicate flavour and bright appealing colour. A second group of highly disliked vegetables consists of cauliflowers and broccoli, characterized by disliked sensations such as bitter taste and objectionable flavour. Internal Preference Maps from actual liking scores indicate that the generally disliked tastes (bitter, sour), are clearly correlated with a negative hedonic response for both peas and sweet corn. The hedonic valence of a generally well accepted taste such as salty and texture descriptors depends on the type of vegetable. Internal preference maps from actual liking data indicate that flavour and appearance descriptors of the distinct sensory properties of each type of vegetable positively affect liking, while the intensity of unusual flavours is related to sample disliking. [ABSTRACT FROM AUTHOR]

Haemochromatosis is now known to be an iron-storage disease with genetic heterogeneity but with a final common metabolic pathway resulting in inappropriately low production of the hormone hepcidin. This leads to increase in intestinal absorption and deposition of excessive amounts of iron in parenchymal cells which in turn results in eventual tissue damage and organ failure. A clinical enigma has been the variable clinical expression with some patients presenting with hepatic cirrhosis at a young age and others almost asymptomatic for life. Research is unravelling this puzzle by identifying environmental factors-especially alcohol consumption-and associated modifying genes that modulate phenotypic expression. A high index of suspicion is required for early diagnosis but this can lead to presymptomatic therapy and a normal life expectancy. Venesection (phlebotomy) therapy remains the mainstay of therapy, but alternative therapies are the subject of current research. [ABSTRACT FROM AUTHOR]