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Abstract Background Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D. Methods Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers. Results In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25–75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356–568), 11.8% (10.1–13.4) and 0.50 µg/L (0.30–0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period. Conclusion The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change.

Background This study aims to assess the migraine-inducing effects of sildenafil in men with migraine without aura. While sildenafil has been shown to provoke migraine in women, its effect on men remains unknown. Methods The trial will enroll 12 men and 15 women, all diagnosed with migraine without aura. The men will participate in a randomized, placebo-controlled crossover trial and the women in an open-label study. Participants will be monitored for migraine attacks and associated symptoms for 12 h post-administration. The primary endpoints include the incidence of migraine attacks in sildenafil-treated men compared to placebo and between sildenafil-treated men and women. Secondary endpoints are headache incidence, heart rate, mean arterial pressure, and adverse events. Conclusion The findings will contribute to a better understanding of sex-related differences in migraine mechanisms, potentially leading to more tailored treatment approaches. Trial registration : The trial is registered in the Clinical Trial Information System (CTIS) of the European Union under the number 2024-512014-17-02.

Objective Suicidality is a major health problem. Decision-making deficits, including a lack of cognitive control (e.g., impulsivity and risk-taking behavior), have been associated with an increased risk of suicide.Method This study examined decision-making in a clinical group of 23 adult, suicidal acute psychiatric patients and compared their data to that of a control group of 17 healthy adults using the Cambridge Gambling Task (CGT) from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Group differences in outcomes on the six CGT subtests were compared using chi-square tests, t tests, and Mann–Whitney U tests where appropriate. Multiple regression analysis was used to explore whether background variables were associated with CGT outcomes.Results The main findings were significantly lower scores for risk-taking, quality of decision-making, and risk adjustment in the clinical group than in the control group. Within the clinical group, differences were observed in which suicide ideators scored worse in some measures than did suicide attempters. These findings suggest that suicidal acute psychiatric patients may struggle with making low-risk decisions that are considered reasonable.Conclusions These results support the potential for cognitive control training, specifically aimed at enhancing decision-making abilities, in suicide prevention efforts. The observed decision-making deficits in suicidal patients underscore the importance of further research on a larger population to solidify the foundation for targeted interventions, and we suggest adding to this knowledge by differentiate between depressed patients with and without severe suicidal ideation.

Poor mental health among youth in Greenland is a major challenge, childhood conditions are critical for mental health later in life. The study aimed to examine the clustering of childhood conditions by considering risk and protective factors for mental health among youth and young adults in Greenland and to explore the relationship between these clusters and mental health outcomes in youth. The study included 565 participants aged 15–34 living in Greenland. Seven indicators including childhood adversities (ACEs), childhood residence, language, and cultural indicators (protective factors) were used to define clusters via latent class analysis (LCA). The associations between clusters and mental health outcomes (satisfaction with life (Cantrill’s ladder), self-esteem, self-efficacy, loneliness, psychological distress (General Health Questionnaire) and mental illness (Kessler 6)) were assessed by logistic regression. Four clusters were identified through LCA. While most participants reported positive childhoods, 40% (in two clusters) experienced ACEs. The two clusters differed as more participants in one cluster had experienced protective factors than the other. ACEs were associated with increased odds of negative aspects of mental health in youth. However, participants who faced high levels of adversity and few protective factors also had reduced odds of positive aspects of mental health in youth.

Background Little is known about lung function in Inuit. The aim of this study was to describe lung function and the prevalence of obstructive and restrictive lung disease among Inuit in GreenlandMethods During the 2017–2019 Health Survey, spirometry, with forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio in liters (L), and percent of predicted value (pred%) were recorded according to Global Lung function Initiative standard reference values (GLI). Smoking history was obtained. Obstructive spirometry was defined as FEV1/FVC 90%.Results Based on validated spirometries, 795/2084 persons were included in this cross-sectional, descriptive study. Of those, 54.6% were current- and 27.7% former smokers. In Inuit, normal lung function was higher than predicted GLI (FEV1 107.2 pred%/FVC 113.5 pred%). In total, 106 (13.3%) were found to have an obstructive lung function measurement and 11 (1.4%) had a restrictive pattern. Among current smokers, the prevalence of obstructive lung function was 16.4%. An accelerated decline in lung function was observed > 50 years old (y.o), compared to

Since 1993, dietary assessment has been carried out in Greenland as part of recurrent population health surveys. In preparation for the next survey in 2024, 91 participants from the survey in 2018 were selected for a validation study of the Food Frequency Questionnaire (FFQ). The 91 participants were reinterviewed 38–50 months after the first FFQ and invited to complete a food diary. As part of the 2018 survey, blood was analysed for mercury. The food diary was completed by 65 participants. The agreement between the two FFQ interviews was very good for macronutrients and fatty acids (p > 0.20), whereas the calculated intake of mercury was 22% higher in the second FFQ (p = 0.04) due to a higher intake of whale meat and muktuk (whale skin). The agreement between the second FFQ and the food diary was good for local food, imported meat and cakes/sweets/snacks but fruit and vegetables, dairy products, beverages and added sugar were significantly underreported in the food diary. Food items not included in the FFQ were identified from the food diaries. The correlation between the intake of marine mammals and blood mercury was moderate (Spearman’s rho = 0.41–0.50; p

ABSTRACT Background Families with an infant in need of intensive care most often experience a harmful separation after birth. This is due to a division of medical specialties into neonatal care and maternal care. Therefore, a couplet care intervention is implemented for mother‐infant dyads in a neonatal intensive care unit. This study protocol provides a comprehensive evaluation of the intervention. The aim is to evaluate the effect and implementation of a complex couplet care intervention to promote zero separation between mother and infant. Methods The couplet care intervention is a family‐centered model of care, where treatment‐requiring mother‐infant dyads will be admitted together and receive couplet care by neonatal nurses. The study adheres to the framework of the Medical Research Council and will use a mixed methods embedded design comprising a quasi‐experimental trial and a qualitative process evaluation. Finally, a health economic evaluation will be conducted to assess the cost‐effectiveness of this complex couplet care intervention. Discussion Separation of mother‐infant dyads after birth has an adverse impact on family health and well‐being. This study protocol evaluates a complex couplet care intervention. With this study, a first step is taken to help bridge the gap between current practices and a new care model to prevent the separation of mothers and their infants

Arthrogenic Muscle Inhibition (AMI) is a phenomenon observed in individuals with joint injury or pathology, characterized by a reflexive inhibition of surrounding musculature, altered neuromuscular control, and compromised functional performance. After anterior cruciate ligament reconstruction (ACLR) one of the most obvious consequences of AMI is the lack of quadriceps activation and strength. Understanding the underlying mechanisms of AMI is crucial for developing effective therapeutic interventions. The surgical procedure needed to reconstruct the ACL has biochemical et physiological consequences such as inflammation, pain, and altered proprioception. These alterations contribute to the development of AMI. Therapeutic interventions aimed at addressing AMI encompass a multidimensional approach targeting pain reduction, inflammation management, proprioceptive training, and quadriceps activation. Early management focusing on pain modulation through modalities like ice, compression, and pharmacological agents help mitigate the inflammatory response and alleviate pain, thereby reducing the reflexive inhibition of quadriceps. Quadriceps activation techniques such as neuromuscular electrical stimulation (NMES) and biofeedback training aid in overcoming muscle inhibition and restoring muscle strength. NMES elicits muscle contractions through electrical stimulation, bypassing the inhibitory mechanisms associated with AMI, thus facilitating muscle activation and strength gains. Comprehensive rehabilitation programs tailored to individual needs and stage of recovery are essential for optimizing outcomes in AMI. The objective of this clinical viewpoint is to delineate the significance of adopting a multimodal approach for the effective management of AMI, emphasizing the integration of pain modulation, proprioceptive training, muscle activation techniques, and manual therapy interventions. Highlighting the critical role of early intervention and targeted rehabilitation programs, this article aims to underscore their importance in restoring optimal function and mitigating long-term complications associated with AMI.

Circular RNAs represent a class of endogenous RNAs that regulate gene expression and influence cell biological decisions with implications for the pathogenesis of several diseases. Here, we disclose a novel gene-regulatory role of circHIPK3 by combining analyses of large genomics datasets and mechanistic cell biological follow-up experiments. Using time-course depletion of circHIPK3 and specific candidate RNA-binding proteins, we identify several perturbed genes by RNA sequencing analyses. Expression-coupled motif analyses identify an 11-mer motif within circHIPK3, which also becomes enriched in genes that are downregulated upon circHIPK3 depletion. By mining eCLIP datasets and combined with RNA immunoprecipitation assays, we demonstrate that the 11-mer motif constitutes a strong binding site for IGF2BP2 in bladder cancer cell lines. Our results suggest that circHIPK3 can sequester IGF2BP2 as a competing endogenous RNA (ceRNA), leading to target mRNA stabilization. As an example of a circHIPK3-regulated gene, we focus on the STAT3 mRNA as a specific substrate of IGF2BP2 and validate that manipulation of circHIPK3 regulates IGF2BP2-STAT3 mRNA binding and, thereby, STAT3 mRNA levels. Surprisingly, absolute copy number quantifications demonstrate that IGF2BP2 outnumbers circHIPK3 by orders of magnitude, which is inconsistent with a simple 1:1 ceRNA hypothesis. Instead, we show that circHIPK3 can nucleate multiple copies of IGF2BP2, potentially via phase separation, to produce IGF2BP2 condensates. Our results support a model where a few cellular circHIPK3 molecules can induce IGF2BP2 condensation, thereby regulating key factors for cell proliferation.

Introduction Semaglutide is increasingly used for the treatment of type 2 diabetes mellitus, overweight and other conditions. It is well known that semaglutide lowers blood glucose levels and leads to significant weight loss. Still, a systematic review has yet to investigate the adverse effects with semaglutide for all patient groups.Methods and analysis We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medline, Embase, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index—Science) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in July 2024. Two review authors will independently extract data and perform risk-of-bias assessments. We will include randomised clinical trials comparing oral or subcutaneous semaglutide versus placebo. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be myocardial infarction, stroke, all-cause hospitalisation and non-serious adverse events. Data will be synthesised by meta-analyses and trial sequential analysis; risk of bias will be assessed with Cochrane Risk of Bias tool—version 2, an eight-step procedure will be used to assess if the thresholds for statistical and clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations.Ethics and dissemination This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.PROSPERO registration number CRD42024499511.

BackgroundFew cost-effective strategies to shift dietary habits of populations in a healthier direction have been identified. We examined if participating in a chatbot health education program transmitted by Short Messages Service ("SMS-program") could improve adolescent dietary behaviors and body weight trajectories. We also explored possible added effects of maternal or peer involvement.Methods and findingsWe conducted a randomized controlled trial (RCT) among adolescents from the Danish National Birth Cohort (DNBC). Eligible were adolescents who during 2015 to 2016 at age 14 years had completed a questionnaire assessing height, weight, and dietary habits. Two thirds were offered participation in an SMS-program, whereas 1/3 ("non-SMS group") received no offer. The SMS program aimed to improve 3 key dietary intake behaviors: sugar-sweetened beverages (SSBs), fruit and vegetables (FV), and fish. The offered programs had 3 factorially randomized schemes; the aims of these were to test effect of asking the mother or a friend to also participate in the health promotion program, and to test the effect of a 4-week individually tailored SMS program against the full 12-week SMS program targeting all 3 dietary factors. Height and weight and intakes of SSB, FV, and fish were assessed twice by a smartphone-based abbreviated dietary questionnaire completed at 6 months (m) and 18 m follow-up. Main outcome measures were (1) body mass index (BMI) z-score; and (2) an abbreviated Healthy Eating Index (mini-HEI, 1 m window, as mean of z-scores for SSB, FV, and fish). Among the 7,890 randomized adolescents, 5,260 were assigned to any SMS program; 63% (3,338) joined the offered program. Among the 7,890 randomized, 74% (5,853) and 68% (5,370) responded to follow-ups at 6 m and 18 m, respectively. Effects were estimated by intention-to-treat (ITT) analyses and inverse probability weighted per-protocol (IPW-PP) analyses excluding adolescents who did not join the program. Mean (standard deviation (SD)) mini-HEI at baseline, 6 m and 18 m was -0.01 (0.64), 0.01 (0.59), and -0.01 (0.59), respectively. In ITT-analyses, no effects were observed, at any time point, in those who had received any SMS program compared to the non-SMS group, on BMI z-score (6 m: -0.010 [95% confidence interval (CI) -0.035, 0.015]; p = 0.442, 18 m: 0.002 [95% CI -0.029, 0.033]; p = 0.901) or mini-HEI (6 m: 0.016 [95% CI -0.011, 0.043]; p = 0.253, 18m: -0.016 [95% CI -0.045, 0.013]; p = 0.286). In IPW-PP analyses, at 6 m, a small decrease in BMI z-score (-0.030 [95% CI -0.057, -0.003]; p = 0.032) was observed, whereas no significant effect was observed in mini-HEI (0.027 [95% CI -0.002, 0.056]; p = 0.072), among those who had received any SMS program compared to the non-SMS group. At 18 m, no associations were observed (BMI z-score: -0.006 [95% CI -0.039, 0.027]; p = 0.724, and mini-HEI: -0.005 [95% CI -0.036, 0.026]; p = 0.755). The main limitations of the study were that DNBC participants, though derived from the general population, tend to have higher socioeconomic status than average, and that outcome measures were self-reported.ConclusionsIn this study, a chatbot health education program delivered through an SMS program had no effect on dietary habits or weight trajectories in ITT analyses. However, IPW-PP-analyses, based on those 63% who had joined the offered SMS program, suggested modest improvements in weight development at 6 m, which had faded at 18 m. Future research should focus on developing gender-specific messaging programs including "booster" messages to obtain sustained engagement.Clinical trial registrationClinicalTrials.gov Identifier: NCT02809196 https://clinicaltrials.gov/study/NCT02809196.

Abstract A framework was developed to evaluate and compare cleaning systems and cleaning system delivery methods, collectively referred to as varnish removal methods, within art conservation practice. This framework was applied to two water-based cleaning systems, optimised for the removal of dammar varnish from an artificially aged brown earth oil paint, including the surfactant-containing microemulsion, Polar Coating B (from the Nanorestore Cleaning series) delivered via the chemical gel, Higher Water Retention (HWR) (from the Nanorestore Gel Dry series), and a surfactant-free microemulsion delivered via the microfiber cloth, Evolon. In addition, two water-based systems and one organic solvent were used to remove dammar varnish from an artificially aged lead white oil paint sample, including a xanthan gum-stabilised emulsion delivered via a synthetic brush, a surfactant-free microemulsion delivered via cotton swab rolling, and 2-propanol solvent delivered via cotton swab rolling. The evaluation framework was thus applied to two different oil paints, with different sensitivities to cleaning. Through this work, the comparative advantages and disadvantages of the varnish removal methods were demonstrated. Notably, cleaning system compatibility with multiple delivery methods afforded greater versatility, including for reducing unwanted interactions between the cleaning system and oil paint. In addition, a surfactant-free microemulsion proved to be a promising, clearance-free, inexpensive, and modifiable option within current offerings for largely water-based methods for varnish removal.

(1) Background: Shoulder pathologies are mostly found in overhead sports. Many risk factors have been identified, in particular a deficit in the kinetic chain. The aim of this review was to find out whether prevention by strengthening the kinetic chain can have an impact on the rate of shoulder injury in overhead pitching athletes. (2) Methods: A systematic review of the literature was carried out, including studies on the role of the kinetic chain in the prevention of overhead athletes. The studies used were works published over the last 10 years searched on PubMed, Cochrane Library, PEDro and Science Direct. They were also analyzed by methodological quality scales: the PEDro scale and the Newcastle–Ottawa scale. (3) Results: Eight studies met the inclusion criteria. The studies analyzed revealed a significant correlation between the use of the kinetic chain and the prevention of shoulder injuries, associating factors such as muscle strength, physical performance in tests (CMJ, FMS), static and dynamic balance and the ability to transfer energy from the lower to the upper body. (4) Conclusions: It is important to integrate core stability work and lower limb strengthening to minimize excessive stress on the shoulder complex, while optimizing force production and performance.

Small renal masses (SRMs) are often benign or early-stage cancers with low metastatic potential. The risk of overtreating SRMs is a particular concern in elderly or comorbid patients, for whom the risks associated with active surveillance (AS) are lower than the risks of surgical management. The aim is to systematically analyse a large cohort of AS patients to provide valuable insights into patient selection and outcomes concerning delayed intervention (DI) and AS termination. We retrospectively analysed data from 563 AS patients across three institutions from 2012 to 2023. Patients were classified into three groups: those currently in AS (n=283), those who underwent DI (n=75), and those who terminated AS (n=205). DI patients were younger, and had larger initial tumour size and higher growth rates (GRs) than AS patients. A significant number of patients terminated their AS, mainly due to comorbidities and death from non-kidney cancer causes, suggesting unsuitability for initial AS enrolment. AS appears to be a safe initial management strategy for SRMs, with an overall low GR and only one patient developing metastasis. The patient selection for AS appears inconsistent, highlighting the need for improved criteria to identify AS candidates, especially considering comorbidities and the possibility of subsequent active treatment in the event of progression.

Summary: Background: Anticipating the burden of intracerebral haemorrhage is crucial for proactive management and building resilience against future health challenges. Prior forecasts are based on population demography and to a lesser extent epidemiological trends. This study aims to utilise selected modifiable risk factors and socio-demographic indicators to forecast the incidence and mortality of intracerebral haemorrhage in Europe between 2019 and 2050. Methods: Three intracerebral haemorrhage risk factors identified in the Global Burden of Diseases, Injuries, and Risk Factors study (GBD 2019)—high systolic blood pressure, high fasting plasma glucose, and high body mass index—were utilised to predict the risk-attributable fractions between 2019 and 2050. Disease burden not attributable to these risk factors was then forecasted using time series models (autoregressive integrated moving average [ARIMA]), incorporating the Socio-demographic Index (SDI) as an external predictor. The optimal parameters of ARIMA models were selected for each age-sex-country group based on the Akaike Information Criterion (AIC). Different health scenarios were constructed by extending the past 85th and 15th percentiles of annualised rates of change in risk factors and SDI across all location-years, stratified by age and sex groups. A decomposition analysis was performed to assess the relative contributions of population size, age composition, and intracerebral haemorrhage risk on the projected changes. Findings: Compared with observed figures in 2019, our analysis predicts an increase in the burden of intracerebral haemorrhage in Europe in 2050, with a marginal rise of 0.6% (95% uncertainty interval [UI], −7.4% to 9.6%) in incident cases and an 8.9% (−2.8% to 23.6%) increase in mortality, reaching 141.2 (120.6–166.5) thousand and 144.2 (122.9–172.2) thousand respectively. These projections may fluctuate depending on trajectories of the risk factors and SDI; worsened trends could result in increases of 16.7% (8.7%–25.3%) in incidence and 31.2% (17.7%–48%) in mortality, while better trajectories may lead to a 10% (16.4%–2.3%) decrease in intracerebral haemorrhage cases with stabilised mortality. Individuals aged ≥80 years are expected to contribute significantly to the burden, comprising 62.7% of the cases in 2050, up from 40% in 2019, and 72.5% of deaths, up from 50.5%. Country-wide variations were noted in the projected changes, with decreases in the standardised rates across all nations but varying crude rates. The largest relative reductions in counts for both incidence and mortality are expected in Latvia, Bulgaria, and Hungary—ranging from −38.2% to −32.4% and −37.3% to −30.2% respectively. In contrast, the greatest increases for both measures were forecasted in Ireland (45.7% and 74.4%), Luxembourg (45% and 70.7%), and Cyprus (44.5% and 74.2%). The modelled increase in the burden of intracerebral haemorrhage could largely be attributed to population ageing. Interpretation: This study provides a comprehensive forecast of intracerebral haemorrhage in Europe until 2050, presenting different trajectories. The potential increase in the number of people experiencing and dying from intracerebral haemorrhage could have profound implications for both caregiving responsibilities and associated costs. However, forecasts were divergent between different scenarios and among EU countries, signalling the pivotal role of public health initiatives in steering the trajectories. Funding: The European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 754517. The National Institute for Health and Care Research (NIHR) under its Programme Grants for Applied Research (NIHR202339).

Background and purpose: Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH. Material and methods: Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2–3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time. Results: All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality. Interpretation: The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.

Objectives It has been hypothesised that functional somatic disorders (FSD) could be initiated by sympathetic predominance in the autonomic nervous system as measured by low heart rate variability (HRV). Earlier studies on the association between HRV and FSD are small case–control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study is to assess any associations between HRV and various FSDs and whether chronic stress confounds such an association.Design A cross-sectional general population-based study.Setting The Danish Study of Functional Somatic Disorders conducted 2013–2015 in 10 municipalities in the western part of Greater Copenhagen, Denmark.Participants A total of 6891 men and women aged 18–72 years were included in the analyses after exclusion of 602 persons with missing HRV data. Various delimitations of FSD (chronic fatigue, chronic widespread pain, irritable bowel and bodily distress syndrome) were identified by validated questionnaires and diagnostic interviews. HRV parameters in time and frequency domains were calculated from successive beat-to-beat heart rate (HR) data using the ‘E-motion’ HR monitor device during 7 min of supine rest. Chronic stress was assessed by Cohen’s self-perceived stress scale.Outcome measures Logistic regression analyses were used to calculate possible associations between the various delimitations of FSD and HRV adjusting for chronic stress.Results Persons with FSD had a slightly higher mean HR and lower HRV as measured by time domain parameters, whereas associations with frequency domain parameters were not consistent. Adjusting for chronic stress attenuated associations slightly.Conclusion The study supports a sympathetic predominance in persons with FSD, which could not be entirely explained by chronic stress. However, it is not possible to conclude whether the association is a causal factor to or a consequence of FSD.

BackgroundVocational school students exhibit significant risk behaviors in terms of poor diet, frequent use of nicotine products, inadequate fruit and vegetable intake, low levels of physical activity, and poor mental health. This makes vocational students vulnerable to the development of noncommunicable diseases. Therefore, effective health promotion programs targeting vocational students are required. ObjectiveThe Danish study “Data-driven and Systems Approach to Health Promotion Among Vocational Students” (Data Health) aims to develop, implement, and evaluate a systems approach to support vocational schools, municipalities, and local communities in implementing locally relevant health promotion actions among and for vocational students. This paper describes the Data Health program and how implementation and preliminary effectiveness will be evaluated. MethodsThe Data Health program offers an iterative 5-step process to develop changes in the systems that shape health behavior and well-being among vocational students. The program will be implemented and evaluated in 8 Danish vocational schools in 4 municipalities. The implementation of the process and actions will be explored using a systems-based evaluation design that assesses contextual differences and the mechanisms through which the program leads to changes in the systems. Preliminary effectiveness at the individual level (students’ self-reported health behavior and well-being) and organizational level (school organizational readiness reported by school staff) will be assessed using a quasi-experimental design, and cross-sectional data will be collected at all 8 schools simultaneously 4 times during the 2-year study period. ResultsThis study was launched in 2021, and data collection is expected to be completed in June 2024. The first results are expected to be submitted for publication in January 2024. ConclusionsWe expect that the Data Health study will make significant contributions to complex intervention research by contributing to the paucity of research studies that have used systems approaches in school settings. The study will also provide evidence of successful elements for systems change and effectiveness to determine whether a national scale-up can be recommended. Trial RegistrationClinicalTrials.gov NCT05308459; https://clinicaltrials.gov/study/NCT05308459 International Registered Report Identifier (IRRID)DERR1-10.2196/52571

Abstract Diverse representation in clinical trials is crucial to understand the efficacy and safety of drugs in minority groups. This review aims to (1) describe research participants' sex, racial, and ethnic diversity in clinical drug trials and (2) describe the sex distribution of researchers conducting the research. We reviewed all clinical drug trials published in the journals “Clinical Pharmacology and Therapeutics” and “Clinical and Translational Science” in 2000–2001 and 2020–2021 and analyzed the research participants' and researchers' demographics. We compared the race of the research participants with the concurrent race diversity of the reference population in the countries where the research was conducted. We identified 281 articles with 17,639 research participants. Approximately one‐third of the research participants were women in both 2000–2001 and 2020–2021. The representation from racial minorities of Black and Asian people increased from 2000–2001 to 2020–2021, but Asian and Native American people are still under‐represented in clinical drug trials today. The proportion of female authors increased, but female authors still made up less than 40% of the total number of authors in 2020–2021. In conclusion, men are still over‐represented in clinical pharmacology research, and some races are still vastly under‐represented. Furthermore, although the proportion of female authors increased with time, they are still under‐represented as first and last authors.

Abstract Polymorphism of the CYP2D6 gene leads to substantial interindividual variability in CYP2D6 enzyme activity. Despite improvements in prediction of CYP2D6 activity based on genotype information, large interindividual variability within CYP2D6 genotypes remains and ethnicity could be a contributing factor. The aim of this study was to investigate interethnic differences in CYP2D6 activity using clinical datasets of three CYP2D6 substrates: (i) brexpiprazole (N = 476), (ii) tedatioxetine (N = 500), and (iii) vortioxetine (N = 1073). The CYP2D6 activity of all individuals in the dataset was estimated through population pharmacokinetic analyses as previously reported. Individuals were assigned a CYP2D6 phenotype and CYP2D6 genotype group based on their CYP2D6 genotype and interethnic differences were investigated within each group. Among individuals categorized as CYP2D6 normal metabolizers, African Americans had a lower CYP2D6 activity compared to Asians (p

Abstract Background Sleep duration is associated with BMI and waist circumference. However, less is known about whether sleep duration affects different measurements of obesity differently. Objective To investigate the association between sleep duration and different measures of obesity. Methods In this cross‐sectional analysis 1309, Danish, older adults (55% men) completed at least 3 days of wearing a combined accelerometer and heart rate‐monitor for assessing sleep duration (hours/night) within self‐reported usual bedtime. Participants underwent anthropometry and ultrasonography to assess BMI, waist circumference, visceral fat, subcutaneous fat, and fat percentage. Linear regression analyses examined the associations between sleep duration and obesity‐related outcomes. Results Sleep duration was inversely associated with all obesity‐related outcomes, except visceral‐/subcutaneous‐fat‐ratio. After multivariate adjustment the magnitude of associations became stronger and statistically significant for all outcomes except visceral‐/subcutaneous‐fat‐ratio, and subcutaneous fat in women. The associations with BMI and waist circumference demonstrated the strongest associations, when comparing standardized regression coefficients. Conclusions Shorter sleep duration were associated with higher obesity across all outcomes except visceral‐/subcutaneous‐fat‐ratio. No specifically salient associations with local or central obesity were observed. Results suggest that poor sleep duration and obesity correlate, however, further research is needed to conclude on beneficial effects of sleep duration regarding health and weight loss.

ObjectivesEarlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population.DesignA cross-sectional general population-based study.SettingThe Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark.ParticipantsA total of 8,608 men and women aged 18-76 years were included in the analyses. Various delimitations of FSD such as chronic fatigue, chronic widespread pain, irritable bowel, and bodily distress syndrome were measured using validated self-administrated questionnaires. Lipid parameters were measured from fasting plasma samples using colorimetric slide methods with Vitros 4600/5600 Ortho Clinical Diagnostics.Outcome measuresLogistic regression analyses were used to calculate possible associations between plasma lipids and the various delimitations of FSD. Associations are presented by OR (95% CI) and shown in boxplots.ResultsWe found a positive association between bodily distress syndrome and triglycerides and non-HDL cholesterol and a negative association with HDL-cholesterol, but no consistent association with total cholesterol. A similar pattern was observed for persons with chronic fatigue, and to some degree for persons with chronic widespread pain, whereas persons with irritable bowel did not show a clear association with the lipid profiles.ConclusionThis is the first major study on plasma lipid profiles and FSD indicating an association between some delimitations of FSD and an unfavorable lipid profile. Due to the cross-sectional design, it cannot be determined whether the findings are consequences or determinants of FSD. Further studies-preferable prospective studies-are needed.

The present systematic review aims to identify, synthesize, and evaluate evidence of effects from interventions targeting youth not in education, employment, or training (NEET). We searched relevant multidisciplinary databases to identify randomized controlled trials (RCTs) and quasi-randomized re-engagement trials. Primary outcomes were participation in education and employment, and training status. Secondary outcomes included changes in financial status, quality of life and well-being, social functioning, and physical, psychological, and behavioral outcomes. The Joanna Briggs Institute methodology and PRISMA guidelines were applied. Eligible studies were screened, included, and extracted for data. Nine trials were included (eight RCTs and one quasi-experimental study), in which samples ranged from 96 to 7346 participants. Results on primary outcomes showed that five studies found an effect of interventions on employment outcomes, while three studies indicated an effect on education or training. Results on secondary outcomes included effects on mental health, subjective health complaints, drug use, self-esteem, and self-efficacy. Studies with other main outcomes than re-engagement showed an effect of interventions on pass rates for the driving test, independent housing, and increased job-seeking activities. Limitations and future directions are discussed, including the lack of rigorous studies, theoretical underpinnings, and standardized measures for re-engagement outcomes. Systematic review registration: registered in PROSPERO, CRD42023463837.

Malignant melanoma is a highly immunogenic tumour, and the immune profile significantly influences cancer development and response to immunotherapy. The peripheral immune profile may identify high risk patients. The current study showed reduced levels of CD4+ T cells and increased levels of CD8+ T cells in peripheral blood from malignant melanoma patients compared with controls. Percentages of peripheral CD56dimCD16+ NK cells were reduced and CD56brightCD16−KIR3+ NK cells were increased in malignant melanoma patients. Late stage malignant melanoma was correlated with low levels of CD4+ T cells and high levels of CD56brightCD16−KIR3+ NK cells. Finally, high levels of Tregs in peripheral blood were correlated with poor overall survival and disease-free survival. The results indicate that changes in specific immune cell subsets in peripheral blood samples from patients at the time of diagnosis may be potential biomarkers for prognosis and survival. Further studies will enable clarification of independent roles in tumour pathogenesis.

BackgroundThe early life factors of birthweight, child weight, height, body mass index (BMI) and pubertal timing are associated with risks of breast cancer. However, the predictive value of these factors in relation to breast cancer is largely unknown. Therefore, using a machine learning approach, we examined whether birthweight, childhood weights, heights, BMIs, and pubertal timing individually and in combination were predictive of breast cancer.MethodsWe used information on birthweight, childhood height and weight, and pubertal timing assessed by the onset of the growth spurt (OGS) from 164,216 girls born 1930-1996 from the Copenhagen School Health Records Register. Of these, 10,002 women were diagnosed with breast cancer during 1977-2019 according to a nationwide breast cancer database. We developed a feed-forward neural network, which was trained and tested on early life body size measures individually and in various combinations. Evaluation metrics were examined to identify the best performing model.ResultsThe highest area under the receiver operating curve (AUC) was achieved in a model that included birthweight, childhood heights, weights and age at OGS (AUC = 0.600). A model based on childhood heights and weights had a comparable AUC value (AUC = 0.598), whereas a model including only childhood heights had the lowest AUC value (AUC = 0.572). The sensitivity of the models ranged from 0.698 to 0.760 while the precision ranged from 0.071 to 0.076.ConclusionWe found that the best performing network was based on birthweight, childhood weights, heights and age at OGS as the input features. Nonetheless, this performance was only slightly better than the model including childhood heights and weights. Further, although the performance of our networks was relatively low, it was similar to those from previous studies including well-established risk factors. As such, our results suggest that childhood body size may add additional value to breast cancer prediction models.

ABSTRACTThe aim of this study was to examine the effect of diabetes and the diabetogenic TBC1D4 variant on kidney function in Greenland in a population-based setting. Health survey data and TBC1D4 genotypes from 5,336 Greenlanders were used to estimate odds ratios (ORs) of albuminuria (>30 mg/g creatinine) and chronic kidney disease (CKD, eGFR

ABSTRACTThe purpose was to analyse the association of muscular strength, muscle pain and reduced mobility in daily life with mental wellbeing among older Inuit men and women in Greenland. Data (N = 846) was collected as part of a countrywide cross-sectional health survey in 2018. Hand grip strength and 30-seconds chair stand test were measured according to established protocols. Mobility in daily life was assessed by five questions about the ability to perform specific activities of daily living. Mental wellbeing was assessed by questions about self-rated health, life satisfaction and Goldberg’s General Health Questionnaire. In binary multivariate logistic regression models adjusted for age and social position, muscular strength (OR 0.87–0.94) and muscle pain (OR 1.53–1.79) were associated with reduced mobility. In fully adjusted models, muscle pain (OR 0.68–0.83) and reduced mobility (OR 0.51–0.55) but were associated with mental wellbeing. Chair stand score was associated with life satisfaction (OR 1.05). With an increasingly sedentary lifestyle, increasing prevalence of obesity and increasing life expectancy the health consequences of musculoskeletal dysfunction are expected to grow. Prevention and clinical handling of poor mental health among older adults need to consider reduced muscle strength, muscle pain and reduced mobility as important determinants.

Abstract Background Between 1980 and 2018 Greenland has had one of the highest suicide rates in the world with an average rate of 96 suicides per 100,000 people annually. The aim of this study is to investigate suicide rates in Greenland according to age, birth cohort, period, sex, place of residence and suicide method from 1970 until 2018. Methods Suicide rates were examined using register and census data from 1970–2018 among Greenland Inuit. Rates were calculated by Poisson regression in Stata and by use of Excel. In analyses of the period trends, rates were standardized according to the World Standard Population 2000–2025. Results The suicide rate has been declining since a peak at 120 suicides per 100,000 people annually in the 1980s but remained high at a rate of 81.3 suicides per 100,000 people annually from 2015–2018. Descriptive analyses point to the decrease in male suicides as the primary factor for the overall decreasing rates while the rate among women has been increasing. Simultaneously, the proportion of women who used a violent suicide method increased from 60% in 1970–1979 to 90% in 2010–2018. The highest rates are seen among young people, especially young men aged 20–24 years and youth suicide rates increased with later birth cohorts. When the rates started to increase in the 1980s both the capital Nuuk and East Greenland had the highest rates. Since then, the rate in Nuuk has declined while the rate in East Greenland was three times the national rate from 2015–2018. Conclusions From 1970 to 1989 the suicide rate increased from 28.7 to 120.5 per 100,000 people mirroring a rapid societal transition in the post-colonial period. The rate has slowly declined from the peak in the 1980s but remains at a very high level. Young people in general are at risk, but the steady increase in the rate among women is worrying and there is a need to investigate underlying causes for this development.

Abstract Background Using XGBoost (XGB), this study demonstrates how flexible machine learning modelling can complement traditional statistical modelling (multinomial logistic regression) as a sensitivity analysis and predictive modelling tool in occupational health research. Design The study predicts welfare dependency for a cohort at 1, 3, and 5 years of follow-up using XGB and multinomial logistic regression (MLR). The models’ predictive ability is evaluated using tenfold cross-validation (internal validation) and geographical validation (semi-external validation). In addition, we calculate and graphically assess Shapley additive explanation (SHAP) values from the XGB model to examine deviation from linearity assumptions, including interactions. The study population consists of all 20–54 years old on long-term sickness absence leave due to self-reported common mental disorders (CMD) between April 26, 2010, and September 2012 in 21 (of 98) Danish municipalities that participated in the Danish Return to Work program. The total sample of 19.664 observations is split geospatially into a development set (n = 9.756) and a test set (n = 9.908). Results There were no practical differences in the XGB and MLR models’ predictive ability. Industry, job skills, citizenship, unemployment insurance, gender, and period had limited importance in predicting welfare dependency in both models. On the other hand, welfare dependency history and reason for sickness absence were strong predictors. Graphical SHAP-analysis of the XGB model did not indicate substantial deviations from linearity assumptions implied by the multinomial regression model. Conclusion Flexible machine learning models like XGB can supplement traditional statistical methods like multinomial logistic regression in occupational health research by providing a benchmark for predictive performance and traditional statistical models' ability to capture important associations for a given set of predictors as well as potential violations of linearity. Trial registration ISRCTN43004323.