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Smoking prevalence remains high in Europe and widening socioeconomic group differences are driving health inequalities. While plain packaging policies disrupt tobacco industry tactics that sustain smoking, evidence of their equity impact is sparse. This study evaluated the implementation of plain packaging in Ireland in 2018 on consumer responses, overall and by the socioeconomic group. Consecutive nationally representative cross-sectional surveys (2018, n  = 7701 and 2019, n  = 7382) measured changes in 13 consumer responses among respondents who smoked across three domains: product appeal, health warnings effectiveness, and perceived harmfulness of smoking. Multiple logistic regression-derived adjusted odds ratios with 95% confidence intervals to compare responses post- versus pre-implementation adjusting for age, gender, educational level, and heaviness of smoking. A stratified analysis examined changes by socioeconomic group indexed using educational level. There were statistically significant changes in consumer responses to plain packaging policy implementation across 7/13 outcomes studied. Five changes were aligned with expected policy impacts (2/6 product appeal outcomes and 3/4 health warning effectiveness outcomes). Two responses were also observed which were not expected policy impacts (1 appeal-related and 1 perceived harm-related outcome). There was no change in five outcomes. Differences in consumer responses between educational groups were generally small, mixed in nature, and indistinguishable when interval estimates of effect were compared. Implementation of plain packaging in Ireland had intended impacts on consumer responses. Including plain packaging requirements in revising the European Union's legislative frameworks for tobacco control will help build progress towards a Tobacco-Free Europe without exacerbating smoking inequalities. [ABSTRACT FROM AUTHOR]

Background Non-pharmaceutical interventions (NPIs) decrease COVID-19 transmission. Reliability and validity of adherence to NPIs in accordance with normalization process theory (NPT) in coherent and convenient social subgroups using reflective measurement model assessment has not been evaluated. Methods In February 2021, a sample of medical students and people with substance use disorders in treatment as coherent (based on continuous probability distribution) vs. convenient groups (based on convenience, not equal probability) composed of travellers and COVID-19 suspected persons from Split-Dalmatia County (SDC) (n  = 656) in the Mediterranean completed self-administered surveys. Partial least squares structural equation modelling (PLS-SEM) was used to measure reflective model assessment of adherence to NPIs according to NPT. Results PLS-SEM reflective model assessment provided two-group specific factors in inverse relationships which determined adherence to NPIs with excellent goodness-of-fit [ χ 2 = 1.292, df = 1; P  = 0.297, CFI = 1, TLI = 0.997, RMSEA = 0.011 (90% CI 0–0.105), RMSEA P  = 0.604, SRMR = 0.008, Hoelter CN (α = 0.05) = 2322.757]. Significant negative factors covariance estimate (−0.716) revealed an inverse relationship between first (adherence to NPIs and internal locus of control (LoC) (0.640)) and second factor; young adulthood age (≤25) and highest level of education (1362). As the first factor increased the second tended to decrease. LoC is expected potential mechanism by which sex (MLsex = −0.017, SE = 0.007, P  < 0.016) and belonging to coherent subgroups (MLgroup = −0.008, SE = 0.003, P  = 0.015) can produce indirect effect of adherence to NPIs. Conclusions Coherent subgroups had a more pronounced tendency toward integration of NPIs in everyday life. Group factors that facilitate the normalization were higher educated younger adults with a tendency toward external LoC. [ABSTRACT FROM AUTHOR]

Background Consumption of alcohol is a risk factor for non-communicable and infectious diseases, mental health problems, and can lead injuries and violence. The aim of this study was to evaluate the prevalence of alcohol-involved deaths among decedents who died of external causes and underwent autopsy in Lithuania. Methods Study includes age persons of any age (from 0 to 110 years) who died and were autopsied in Lithuania from 1 January 2017 to 31 December 2020. Data were obtained from the Lithuanian State Register of Deaths and Their Causes. Results Among external causes of death, the presence of alcohol was detected in 55.0% of cases. Male decedents had a significantly higher number of positive BAC level recorded, at 46.6%, compared with female decedents (32.1%; P  < 0.001). The highest incidence of deaths where the alcohol was detected in the deceased's blood was found when the decedent was listed as being in the victims of assault group (71.5%, 95% CI 65.4–77.2). However, the highest median BAC score was found for those in the accidents group (59.7%, 95% CI: 58.2–61.2, BAC 2.42 ‰, IQR 1.86). Conclusions The findings of this study suggest that alcohol use may be a contributing factor in a wide range of fatal incidents, including accidents, injuries, and cases of violent intent. Inequalities between males and females were identified, with a higher proportion of males with alcohol detected in blood at the time of death. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV) remains a significant cause of morbidity and mortality worldwide. The aim of this study was to describe the mortality rate and associated comorbidities in a nationwide population-based cohort of persons living with HIV (PLWHIV) and to compare it with mortality in an age and gender-matched cohort of non-HIV individuals in France. Methods Using data from the French national health data system, we identified and included 173 712 PLWHIV (66.5% men) and 173 712 non-HIV participants (66.5% men) matched for age and gender. PLHIV were identified based on ICD-10 HIV diagnoses, HIV-specific laboratory tests, and/or prescriptions for antiretroviral therapy specific to HIV. Hazard ratios (HRs) of mortality were assessed using multiple Cox regression models. Results During the 13 years of follow-up (2006–18), we observed 20 018 deaths among PLWHIV compared with 6262 deaths among non-HIV participants (11.52% vs. 3.60%, P  < 0.001). The over-mortality of PLWHIV was expressed by univariable HR = 2.135 (2.072–2.199), which remained significant after adjustment for region, Complementary Universal Health Insurance and AME, with multivariable HR = 2.182 (2.118–2.248). The results remained significant after adjusting for comorbidities, including infectious diseases [HR = 1.587 (1.538–1.638)]. Notably, PLWHIV were more importantly associated with mortality in women [HR = 2.966 (2.767–3.180)], compared in men [HR = 1.961 (1.898–2.027)]. Conclusion Although the life expectancy of PLWHIV has globally increased, the causes of death should be prioritized in prevention policies and care management. Gender-specific policies should be highlighted, as we observed a higher impact of HIV mortality in women. [ABSTRACT FROM AUTHOR]

Aims Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined. Methods and results Utilizing the UK Biobank cohort, we assessed biological age using the Klemera–Doubal and PhenoAge methods. BAA was quantified by residual analysis compared with chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analysis was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations. A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF [26% per standard deviation (SD) increase in KDM-BA acceleration, 95% confidence intervals (CI): 23–28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32–35%]. Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk. Conclusion In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions. [ABSTRACT FROM AUTHOR]

Aims The prevalence and difference in risk factors for having thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) in men compared with women in the general population is not well described. This study aimed to test the hypotheses that (i) cardiovascular risk factors for TAA and AAA differ and (ii) the prevalence of TAA and AAA is sex specific. Methods and results Aortic examination using computed tomography angiography was performed in 11 294 individuals (56% women), with a mean age of 62 (range 40–95) years participating in the Copenhagen General Population Study. TAAs were defined as an ascending aortic diameter ≥45 mm and a descending aortic diameter ≥35 mm, while AAAs were defined as an abdominal aortic diameter ≥30 mm. Demographic data were obtained from questionnaires. Overall prevalence of aortic aneurysms (AAs) in the study population included: total population 2.1%, men 4.0% and women 0.7% (P -value men vs. women P < 0.001). AAs were independently associated with male sex, increasing age, and body surface area (BSA). While TAAs were associated with hypertension, odds ratio (OR) = 2.0 [95% confidence interval (CI): 1.5–2.8], AAAs were associated with hypercholesterolaemia and smoking, OR = 2.4 (95% CI: 1.6–3.6) and 3.2 (95% CI: 1.9–5.4). Conclusion Subclinical AAs are four times more prevalent in men than in women. In both sexes, increasing age and BSA are risk factors for AAs of any anatomical location. Whereas arterial hypertension is a risk factor for TAAs, hypercholesterolaemia and smoking are risk factors for AAAs. [ABSTRACT FROM AUTHOR]

Background The Nordic countries represent a unique case study for the COVID-19 pandemic due to socioeconomic and cultural similarities, high-quality comparable administrative register data and notable differences in mitigation policies during the pandemic. We aimed to compare weekly excess mortality in the Nordic countries across the three full pandemic years 2020–2022. Methods Using data on weekly all-cause mortality from official administrative registers in Denmark, Finland, Norway and Sweden, we employed time series regression models to assess mortality developments within each pandemic year, with the period 2010–2019 used as reference period. We then compared excess mortality across the countries in 2020–2022, taking differences in population size and age- and sex-distribution into account. Results were age- and sex-standardized to the Danish population of 2020. Robustness was examined with a variety of sensitivity analyses. Results While Sweden experienced excess mortality in 2020 [75 excess deaths per 100 000 population (95% prediction interval 29–122)], Denmark, Finland and Norway experienced excess mortality in 2022 [52 (14–90), 130 (83–177) and 88 (48–128), respectively]. Weekly death data reveal how mortality started to increase in mid-2021 in Denmark, Finland and Norway, and continued above the expected level through 2022. Conclusion Although the Nordic countries experienced relatively low pandemic excess mortality, the impact and timing of excess mortality differed substantially. These estimates—arguably the most accurate available for any region in capturing pandemic-related excess deaths—may inform future research and policy regarding the complex mortality dynamics in times of a health crisis such as the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background Oesophageal cancer (OC) is a significant public health issue, despite the decreasing trends in OC mortality rates observed globally in the past decades. The objective of our study is to analyze the pattern of OC mortality in Montenegro between 1990 and 2018 and contribute to the development of a national long-term strategy for the prevention and control of this malignancy. Methods The data on OC death cases in Montenegro between 1990 and 2018 were collected. The mortality rates were standardized according to the World Standard Population. The Joinpoint, Linear and Poisson regressions were applied to analyze the OC mortality trend. Results Joinpoint regression analysis showed an increase in death rates for men and the overall level which were not statistically significant. However, the number of cases increases significantly with an average annual percentage change (AAPC) increase of 2.6% for the overall level [AAPC (95% CI)=2.6 (1.0–4.2); P  = 0.002] at the expense of the increase in men, which on average was 2.6% annually [AAPC (95%CI) = 2.6 (1.2–4.1); P  = 0.001]. The age groups 55–64 and 65–74 have the highest percentage of deaths cases from OC with 30.6% and 31.4%, respectively. Conclusion Montenegro has witnessed a recent increase in the number of deaths from OC, although the mortality rates remain stable. National strategies to further reduce mortality rates for OC are necessary. Individuals aged 55–64 and 65–74 need specific attention during the ongoing monitoring of this cancer. [ABSTRACT FROM AUTHOR]

Background Although the global chronic morbidity indicator (GCMI) of the Minimum European Health Module (MEHM) was not specifically designed to monitor chronic disease in the population, it is increasingly used for this purpose in Europe and elsewhere. However, its metrological characteristics have seldom been examined, with various sensitivity issues being raised. The present study investigated the metrological performances of the GCMI and analyzed its implications in terms of prevalence and demographic and socioeconomic gradients of chronic conditions in the population. Methods We used data from two large French nationwide representative surveys with cross-sectional and longitudinal data conducted between 2010 and 2021. The surveys used MEHM and collected data on numerous chronic conditions and socioeconomic indicators. Criterion and predictive validity of the GCMI regarding chronic conditions and the resultant socioeconomic gradients were compared with indicators based on reports of individual chronic conditions. Results GCMI sensitivity to capture chronic conditions varied from <20 to 80% depending on the chronic condition. Number of chronic conditions, gender, age and education were also associated with GCMI endorsement. However, the GCMI was predictive of mortality and activity limitations independently of individual conditions. Conclusion The varying lack of sensitivity depending on the chronic condition and the respondent's sociodemographic status may bias estimates of demographic and socioeconomic gradients compared with indicators based on reports of individual chronic conditions. Differences between GCMI and list-based approaches should be more cautiously considered when monitoring chronic conditions in the population. These approaches should be viewed as complementary rather than contradictory or interchangeable. [ABSTRACT FROM AUTHOR]

Background Insulin resistance has been reported to increase the risk of breast, prostate and colorectal cancer. However, the role of insulin resistance and its interaction with genetic risk in the development of lung cancer remains controversial. Therefore, we aimed to explore the association between a novel metabolic score for insulin resistance (METS-IR) and lung cancer risk. Methods A total of 395 304 participants without previous cancer at baseline were included. The Cox proportional hazards regression model was performed to investigate the association between METS-IR and lung cancer risk. In addition, a Mendelian randomization analysis was also performed to explore the causal relationship. The joint effects and additive interactions between METS-IR and polygenetic risk score (PRS) of lung cancer were also investigated. Results During a median follow-up of 11.03 years (Inter-quartile range (IQR): 10.30–11.73), a total of 3161 incident lung cancer cases were diagnosed in 395 304 participants. There was a significant association between METS-IR and lung cancer risk, with an HR of 1.28 (95% CI: 1.17–1.41). Based on the Mendelian randomization analysis, however, no causal associations were observed. We observed a joint effect but no interaction between METS-IR and genetic risk. The lung cancer incidence was estimated to be 100.42 (95% CI: 91.45–109.38) per 100 000 person-year for participants with a high METS-IR and PRS, while only 42.76 (95% CI: 36.94–48.59) with low METS-IR and PRS. Conclusions High METS-IR was significantly associated with an increased risk of lung cancer. Keeping a low level of METS-IR might help reduce the long-term incident risk of lung cancer. [ABSTRACT FROM AUTHOR]

Background Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits multi-organ damage with diverse complications, the correlation between age, gender, medical history and clinical manifestations of novel coronavirus disease 2019 (COVID-19) patients was investigated. Methods 1640 patients who were infected with SARS-CoV-2 and hospitalized at the First Affiliated Hospital of Ningbo University from 22 December 2022 to 1 March 2023 were categorized and analysed. Normal distribution test and variance homogeneity test were performed. Based on the test results, one-way analysis of variance, Pearson's chi-squared test and logistic regression analysis were conducted in the study. Results According to the ANOVA, there was a significant difference in the age distribution (P  = .001) between different clinical presentations, while gender did not (P  = .06). And regression analysis showed that age, hypertension, atherosclerosis and cancer were significant hazard factors for the development of predominant clinical manifestations in patients hospitalized with novel COVID-19. Additionally, infection with SARS-CoV-2 has the potential to exacerbate the burden on specific diseased or related organs. Conclusion The elderly who are infected with SARS-CoV-2 ought to be treated with emphasis not only on antiviral therapy but also on individualized treatment that takes their medical history and comorbidities into account. [ABSTRACT FROM AUTHOR]

Aims With an ageing population, the presence of asymptomatic valvular heart disease (VHD) in the community remains unknown. The aim of this study is to determine the prevalence and associated factors of asymptomatic VHD in individuals ≥60 years old and to evaluate the feasibility of echocardiographic screening for VHD in this population. Methods and results This was a prospective cohort study conducted between 2007 and 2016 in the UK. Asymptomatic patients with no prior indication for echocardiography were invited to participate and evaluated with a health questionnaire, clinical examination, and transthoracic echocardiography. A total of 10,000 individuals were invited through their general practices. A total of 5429 volunteered to participate, of whom 4237 were eligible for inclusion. VHD was diagnosed in more than a quarter of patients (28.2%). The most common types of VHD were regurgitation of the tricuspid (13.8%), mitral (12.8%), and aortic (8.3%) valves (trivial regurgitation was not included). The rate of prevalence of clinically significant VHD was 2.4% (2.2% moderate and 0.2% severe), with mitral and aortic regurgitation being the most common. The only parameter associated with significant VHD was age (odds ratio 1.07 per 1 year increment, 95% confidence interval 1.05–1.09, P < 0.001). The number needed to scan to diagnose one clinically significant case of VHD is 42 for individuals ≥60 and 15 for those ≥75 years old. Conclusion Asymptomatic VHD is present in a significant proportion of otherwise healthy individuals without known VHD over 60 years old. Age is strongly associated with an increased incidence of significant VHD. [ABSTRACT FROM AUTHOR]

Aims The atherosclerotic profile and advanced plaque subtype burden in symptomatic patients ≤45 years old have not been established. This study aimed to assess the prevalence and predictors of coronary artery calcium (CAC), plaque subtypes, and plaque burden by coronary computed tomography angiography (CCTA) in symptomatic young patients. Methods and results We included 907 symptomatic young patients (18–45 years) from Montefiore undergoing CCTA for chest pain evaluation. Prevalence and predictors of CAC, plaque subtypes, and burden were evaluated using semi-automated software. In the overall population (55% female and 44% Hispanic), 89% had CAC = 0. The likelihood of CAC or any plaque by CCTA increased with >3 risk factors {RFs, odds ratio [OR] 7.13 (2.14–23.7) and OR 10.26 (3.36–31.2), respectively}. Any plaque by CCTA was present in 137 (15%); the strongest independent predictors were age ≥35 years [OR 3.62 (2.05–6.41)] and family history of premature coronary artery disease (FHx) [OR 2.76 (1.67–4.58)]. Stenosis ≥50% was rare (1.8%), with 31% of those having CAC = 0. Significant non-calcified plaque (NCP, 37.2%) and low-attenuation plaque (LAP, 4.24%) burdens were seen, even in those with non-obstructive stenosis. Among patients with CAC = 0, 5% had plaque, and the only predictor of exclusively NCP was FHx [OR 2.29 (1.08–4.86)]. Conclusion In symptomatic young patients undergoing CCTA, the prevalence of CAC or any coronary atherosclerosis was not negligible, and the likelihood increased with RF burden. The presence of coronary stenosis ≥50% was rare and most often accompanied by CAC >0, but there was a significant burden of NCP and LAP even within the non-obstructive group. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular diseases manifest differently in males and females, potentially influenced by inherent sex- and age-related differences in myocardial tissue composition. Such inherent differences are not well-established in the literature. With this study using cardiac magnetic resonance (CMR) native T1 mapping, we aim to determine the effect of sex and age on myocardial tissue composition in healthy individuals. Methods and results CMR native T1 mapping was performed in 276 healthy individuals (55% male, age 8--–84 years) on a 1.5 Tesla scanner using a MOLLI 5(3)3 acquisition scheme. Additionally, 30 healthy participants (47% male, age 24–68 years) underwent a 1-year follow-up CMR to assess the longitudinal changes of native T1. Mean native T1 values were 1000 ± 22 ms in males and 1022 ± 23 ms in females [mean difference (MD) = 22 ms, 95% confidence interval (CI) (17, 27)]. Female sex was associated with higher native T1 in multivariable linear regression adjusting for age, heart rate, left ventricular mass index, and blood T1 [β=10 ms, 95% CI (3.4, 15.8)]. There was no significant interaction between sex and age (P = 0.27). Further, age was not associated with native T1 [β=0.1 ms, 95% CI (−0.02, 0.2)], and native T1 did not change during a 1-year period [MD −4 ms, 95% CI (−11, 3)]. Conclusion Female sex was associated with higher native T1; however, there was no association between age and native T1. Additionally, there was no evidence of an interaction between sex and age. Our findings indicate intrinsic sex-based disparities in myocardial tissue composition. [ABSTRACT FROM AUTHOR]

Aims Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. Methods and results A total of 82 healthy individuals (46 women) aged 45–78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. Conclusion MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP. [ABSTRACT FROM AUTHOR]

Aims Age-related changes in cardiac structure and function are well recognized and make the clinical determination of abnormal left ventricular (LV) diastolic dysfunction (LVDD) particularly challenging in the elderly. We investigated whether a deep neural network (DeepNN) model of LVDD, previously validated in a younger cohort, can be implemented in an older population to predict incident heart failure (HF). Methods and results A previously developed DeepNN was tested on 5596 older participants (66–90 years; 57% female; 20% Black) from the Atherosclerosis Risk in Communities Study. The association of DeepNN predictions with HF or all-cause death for the American College of Cardiology Foundation/American Heart Association Stage A/B (n = 4054) and Stage C/D (n = 1542) subgroups was assessed. The DeepNN-predicted high-risk compared with the low-risk phenogroup demonstrated an increased incidence of HF and death for both Stage A/B and Stage C/D (log-rank P < 0.0001 for all). In multi-variable analyses, the high-risk phenogroup remained an independent predictor of HF and death in both Stages A/B {adjusted hazard ratio [95% confidence interval (CI)] 6.52 [4.20–10.13] and 2.21 [1.68–2.91], both P < 0.0001} and Stage C/D [6.51 (4.06–10.44) and 1.03 (1.00–1.06), both P < 0.0001], respectively. In addition, DeepNN showed incremental value over the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) guidelines [net re-classification index, 0.5 (CI 0.4–0.6), P < 0.001; C -statistic improvement, DeepNN (0.76) vs. ASE/EACVI (0.70), P < 0.001] overall and maintained across stage groups. Conclusion Despite training with a younger cohort, a deep patient-similarity–based learning framework for assessing LVDD provides a robust prediction of all-cause death and incident HF for older patients. [ABSTRACT FROM AUTHOR]

Background The objective is to estimate the importance of the decrease of smoking habits in Sweden for the occurrence of lung cancer. Methods The change in smoking habits in the general population was retrieved from surveys and on taxation of sale of cigarettes. We used data from the Swedish Cancer Register on incidence of lung cancer between 1970 and 2021, stratified for sex, age and cell type, and compared the occurrence overtime in ages between 40 and 84 years. Results The sale of cigarettes peaked in 1980 to 1800 cigarettes per person and decreased to 600 per person in 2021. The change in incidence rates of squamous cell cancer and other cell types varied over time, sex, and age in a pattern that partly seems to be explained by change in the prevalence of daily smokers. The incidence of adenocarcinoma was similar in men and women 1970–2021 and increased, e.g. for women and men 75–79 years of age from around 20 cases in early 1970s to around 120 cases per 100 000 person-years in the 2020s. Conclusions Our data indicate that the risk of lung cancer several years after smoking cessation is less favourable than previously studies have indicated. There is a similar increase in the incidence of adenocarcinoma in men and women which is hard to explain only with changing smoking habits. The change from non-filter to filter cigarettes in the 1960s–1970s may be a contributing factor. [ABSTRACT FROM AUTHOR]

Background Complementary feeding has long-term effects on health but there is heterogeneity in recommendations across Europe. Recommendations include responsive feeding practices and nutritional needs but there is a debate in primary paediatricians as to which one should be the main criterion for complementary feeding. This pilot study investigated (i) the factors affecting the recommendations of paediatricians in Cyprus for starting complementary feeding, (ii) whether their main criterion is the developmental readiness or the nutritional needs of the infant and (iii) how this priority influences recommendations. Methods The 11-item questionnaire was completed by 73 Cypriot paediatricians. Results Approximately 66% of paediatricians recommended starting complementary feeding between 5 and 6 months, 29% between 4 and 5 and 3% between 6 and 7 months. Predefined schemes were recommended by ∼25% of paediatricians, baby-led weaning by 14% and 58% of paediatricians recommended either modality depending on the family circumstances whilst 4% involve the mother in the decision process. Approximately 64% of paediatricians recommended the introduction of parent's diet after the first year of life. Approximately 55% of paediatricians chose developmental readiness and 45% nutritional needs of the infant as their primary criterion for starting complementary feeding. Paediatricians who prioritized developmental readiness were more likely to be younger, less likely to advice on meat quantity and less likely to follow good nutritional practice. Conclusions The younger the paediatrician the more likely they are to prioritize developmental readiness over nutritional needs of the infant for complementary feeding. Paediatricians who prioritized developmental readiness were also less likely to provide nutritional advice. [ABSTRACT FROM AUTHOR]

Background During the coronavirus disease 2019 (COVID-19) pandemic, there were under-recognized and unaddressed psychosomatic health problems among medical staff. The purpose of this study was to investigate their psychosomatic status. Methods An online questionnaire was performed to the medical staff of major hospitals in Jinan in January 2023. In total, 1244 valid questionnaires were collected, and their psychosomatic status was assessed by the Psychosomatic Symptom Scale (PSSS) and Perceived Stress Scale-10 (PSS-10). Finally, we analyzed the influencing factors for their psychosomatic status. Results The psychological health of the medical staff was poor, and the level of stress perception was intense, accompanied by obvious psychosomatic symptoms. Regression analysis indicated that age, gender, frontline involvement, work experience, marriage, presence of disease history and COVID-19 infection history were risk factors for psychosomatic symptoms, while education, frontline involvement and presence of disease history were risk factors for stress feeling. Conclusion Medical staff often showed obvious psychosomatic symptoms and intense stress. Psychological health education and intervention should be given in order to improve their working quality. [ABSTRACT FROM AUTHOR]

Background Socioeconomic inequalities constitute an important focus area for public health, and it has long been established that higher educational level and longer lifespan are correlated. Little is known about decennial time trends in poor self-rated health and mental distress. Methods This study linked decennial cross-sectional survey data on self-rated health and mental distress from the Trøndelag Health Study (HUNT) from 1984 to 2019 with educational registry data using personal identification numbers. Survey participation ranged from 50 807 to 77 212. Slope index of inequality (SII) and relative index of inequality (RII) were calculated using generalized linear models in Stata. Analyses were stratified by sex and age, using the age categories of 30–59 years and 60–80 years. Results Absolute inequalities in self-rated health and mental distress between educational groups have stayed relatively stable throughout all rounds of HUNT. Relative inequalities in self-rated health and mental distress have generally increased, and both men and women with the lowest education level were more likely to experience poor self-rated health and mental distress relative to those with the highest education level. RII in self-rated health increased over time for both sexes and both age groups. RII for mental distress increased in both sexes and both age groups, except for men and women aged 60–80. Discussion This study shows that relative inequalities in self-rated and mental health in the Norwegian population are still persistent and have increased. Further knowledge about groups with a disadvantageous health situation should have implications for health care resource allocation. [ABSTRACT FROM AUTHOR]

Background Studying transmission within the home is essential to understand the transmission dynamics of numerous infectious diseases. For Coronavirus Disease-2019 (COVID-19), transmission within the home constitutes the majority exposure context. The risk of infection in this setting can be quantified by the household/intra-family secondary attack rate (SAR). In the literature, there are discrepancies in these values and little information about its social determinants. The aim of this study was to investigate transmission in the home by analyzing the influence of occupational social class, country of origin and gender/sex. Methods This was a retrospective cohort study of a population registry of cohabiting contacts with COVID-19 cases diagnosed from 15 June to 23 December 2020, in the Murcia Region. The household SAR was analyzed considering the characteristics of the primary case (sex, age, symptoms, occupational social class, country of origin and number of people in the household) and contact (age and sex) using a multilevel binary logistic regression model. Results Among the 37 727 contacts included, the intra-family SAR was 39.1%. The contacts of confirmed primary cases in the migrant population (Africa and Latin America) had higher attack rates, even after adjusting for the other variables. Older age and female sex were independent risk factors for contracting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within the home. Conclusion There was greater intra-domiciliary transmission among immigrants, likely related to the conditions of the home and situation of social vulnerability. Women were more likely to be infected by transmission from a cohabiting infected individual. [ABSTRACT FROM AUTHOR]

Background The poor prognosis of breast cancer in Sudan could be due to delayed treatment and diagnosis at an advanced stage. Our study aimed to assess the extent of delays from onset of symptoms to treatment in Sudanese women with breast cancer, as well as identify factors contributing to these delays. Materials and Methods We conducted a multi-center cross sectional study between March and April 2023. Data were collected from the medical records and interviews with women with breast cancer in the two main oncology centers in Sudan. Linear regression was used to identify the predictors of delayed presentation. Results We interviewed 601 women with breast cancer. The majority of women (50.1%) were diagnosed at locally advanced or metastatic disease. The median interval from the onset of symptoms to receiving oncologic treatment was 221 days (IQR = 92, 496). The longest delay was the presentation delay 61 (31 244) days. The median duration for diagnosis delay and treatment delay was 21 (10.57) days and 27 (10.64) days, respectively. Predictors of early presentation included, being young (β = −5.3; 95% CI = 0.06 to 10), married (β = −264; 95% CI = −427 to −101), divorced (β = −306; 95% CI = −549 to −63), or widowed (β = −320; 95% CI = −-543 to −97), urban residence (β = −107; 95% CI = −213 to −2.3), and seeking traditional healer (β = −204; 95% CI = −383 to −26). Conclusion Most Sudanese women with breast cancer experience significant patient delays, often presenting at advanced stages. Factors like being single, older, and living in rural areas contribute to these delays. Increasing breast cancer education, improving healthcare access and addressing sociodemographic barriers can potentially expedite diagnosis and improve outcomes. [ABSTRACT FROM AUTHOR]

Aims 3D echocardiographic (3DE) assessment of the left atrium (LA) is a new modality of potential clinical value. Age- and sex-based normative values are needed to benchmark these parameters for clinical use. Methods and results Of 4466 participants in the 5th Copenhagen City Heart Study, a prospective longitudinal cohort study on the general population, 2082 participants underwent 3DE of the LA. Healthy participants were included to establish normative values for LA strain, volume, and function by 3DE. The effects of age and sex were also evaluated. After excluding participants with comorbidities, 979 healthy participants (median age 44 years, 39.6% males) remained. The median and limits of normality (2.5th and 97.5th percentiles) for functional and volumetric measures were as follows: LA reservoir strain (LASr) 30.8% (18.4–44.2%), LA conduit strain (LAScd) 19.1% (6.8–32.0%), LA contractile strain 11.7% (4.3–22.2%), total LA emptying fraction (LAEF) 61.4% (47.8–71.0%), passive LAEF 37.7% (17.4–53.9%), active LAEF 37.4% (22.2–52.5%), LA minimum volume index (LAVimin) 10.2 (5.9–18.5) mL/m2, and LA maximum volume index (LAVimax) 26.8 (16.5–40.1) mL/m2. All parameters changed significantly with increasing age (P value for all <0.001). Significant sex-specific differences were observed for all parameters except active LAEF and LAVimax. Sex significantly modified the association between age and LASr (P for interaction < 0.001), LAScd (P for interaction < 0.001), LAVimin (P for interaction = 0.037), and total LAEF (P for interaction = 0.034) such that these parameters deteriorated faster with age in females than males. Conclusion We present age- and sex-specific reference material including limits of normality for LA strain, volume, and function by 3DE. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common cancer in younger adults. In patients undergoing liver resection with RAS -altered CRCs, there is evidence suggesting younger patients have worse outcomes than older patients. To explain this pattern, differences in associations between RAS status and other cancer-related biomarkers in tumors from younger versus older patients with CRC were evaluated in a cohort of 925 patients with CRC, 277 (30.0%) of whom were ≤50 years old, and 454 (49.1%) who had RAS -altered tumors. For 3 biomarkers, RNF43 , APC , and microsatellite instability (MSI), the association with RAS status was significantly modified by age after adjustment for multiple testing. Specifically, younger patients with RAS -altered tumors were more likely to be MSI-high, RNF43 mutated, and APC wild type. These differences might contribute to the observed pattern of diminished survival in younger versus older patients with CRC with RAS -mutated tumors undergoing liver metastasis resection. [ABSTRACT FROM AUTHOR]

Background: Work-family conflicts (WFC) have been associated with poor mental health, poor self-rated health and sickness absence. However, studies on short sickness absence are lacking and more information is needed also about long sickness absence regarding the direction of WFC, and potential explaining factors particularly among young and early middle-aged employees. Methods: The Helsinki Health Study baseline survey (2017) among 19- to 39-year-old municipal employees (N=3683, 80% women, response rate 51.5%) was linked to employer's sickness absence data. The associations of work-to-family conflicts (WTFC) and family-to-work conflicts (FTWC) with short (1-7 days) and long (over 7 days) sickness absence were analyzed using negative binomial regression analysis. Covariates were age, gender, family-related factors and work-related factors. Stratified analyses by occupational class were performed. The results are presented as rate ratios and their 95% confidence intervals. Results: High WTFC were associated with short (1.25, 1.12-1.40) and long (1.37, 1.11-1.70) sickness absence. High FTWC were also associated with short (1.12, 1.03-1.22) and long (1.24, 1.06-1.45) sickness absence. Adjustment for family-related factors strengthened the associations, whereas adjustment for work-related factors abolished the associations between WTFC and sickness absence. Associations between WFC and sickness absence were observed among two lowest occupational classes only. Conclusion: WFC are associated with both short and long sickness absence. Work-related factors including the quality of supervisory work and shift work play a role in the association. Intervention studies could determine if improvements in combining work and family life lead to a reduction in sickness absence. [ABSTRACT FROM AUTHOR]

Background: Cognitive development in pre-schoolers through healthy eating and socio-demographic support is crucial for their later lives. We investigated healthy eating encouragement, socio-demographic factors and their association with cognitive development in pre-schoolers. Methods: Quantitative data were collected using a multi-stage random sampling between February and April 2021. Pre-schoolers 36 and 71 months and their primary caregivers were recruited from three local government units of Rupandehi district. We compared healthy eating encouragement, socioeconomic and demographic factors with cognitive development using t-test, one-way analysis of variance and multiple linear regression analysis to identify the predictors of the cognitive development among pre-schoolers. Results: Cognitive development in pre-schoolers is significantly positively associated with age 36-48 months (β = 0.153; 95% CI: 0.12, 13.96), living in a nuclear family (β = 0.121; 95% CI: 0.59, 6.88) and following Buddhism (β = 0.148; 95% CI: 0.88, 14.32). Conversely, children from specific caste/ethnic backgrounds, such as Dalit (β = -0.126; 95% CI: -10.79, -0.68), Janajati (β = -0.237; 95% CI: -6.14, -2.09) and non-Dalit Tarai caste or ethnicity (β = -0.133; 95% CI: -3.46, -0.25) and mothers employed (β = -0.134; 95% CI: -10.62, -1.44) show significantly lower levels of cognitive development. Conclusions: The finding shows that socioeconomic factors have an influence on cognitive development and also stimulate the adoption of healthy eating encouragement practices. [ABSTRACT FROM AUTHOR]

Background: Transport injuries are a major cause of mortality among adolescents. Our aim was to evaluate the circumstances and trauma associated with fatal accidents involving adolescents and two-wheeled vehicles. Methods: We analyzed retrospective data from the Finnish Crash Data Institute from 2008 to 2019 involving 10- to 24-year-old victims of fatal traffic accidents who were injured while riding a bicycle, moped or motorcycle. We collected data on patient characteristics, accident circumstances and possible treatment. These fatalities were compared with national mortality rates among the respective age groups. Results: We identified 147 fatalities over the 12-year period involving 20 bicycle, 50 moped and 77 motorcycle riders. Most accidents involved males (n=121, 82%). Less than half of vehicles were in good condition (46%); motorized vehicles were often illegally tuned (37%) or had tire problems (31%). Most of the accidents were collisions with another vehicle (n=99, 67%) or other objects (n=35, 24%). In 94% of cases, the Injury Severity Score was >25. Head injury was the most common cause of death (62%). Among 15-year-olds, every fifth death was due to accidents on two-wheeled vehicles. Conclusions: Fatal transport accidents among adolescents comprise several elements that should be incorporated into driver's education and in case of minors, also communicated to parents. These include the condition of the vehicle, proper helmet use and effects of speed on both control of the vehicle and the consequences of a possible collision. [ABSTRACT FROM AUTHOR]

Aims Mammography, commonly used for breast cancer screening in women, can also predict cardiovascular disease. We developed mammography-based deep learning models for predicting coronary artery calcium (CAC) scores, an established predictor of coronary events. Methods and results We evaluated a subset of Korean adults who underwent image mammography and CAC computed tomography and randomly selected approximately 80% of the participants as the training dataset, used to develop a convolutional neural network (CNN) to predict detectable CAC. The sensitivity, specificity, area under the receiver operating characteristic curve (AUROC), and overall accuracy of the model's performance were evaluated. The training and validation datasets included 5235 and 1208 women, respectively [mean age, 52.6 (±10.2) years], including non-zero cases (46.8%). The CNN-based deep learning prediction model based on the Resnet18 model showed the best performance. The model was further improved using contrastive learning strategies based on positive and negative samples: sensitivity, 0.764 (95% CI, 0.667–0.830); specificity, 0.652 (95% CI, 0.614–0.710); AUROC, 0.761 (95% CI, 0.742–0.780); and accuracy, 70.8% (95% CI, 68.8–72.4). Moreover, including age and menopausal status in the model further improved its performance (AUROC, 0.776; 95% CI, 0.762–0.790). The Framingham risk score yielded an AUROC of 0.736 (95% CI, 0.712–0.761). Conclusion Mammography-based deep learning models showed promising results for predicting CAC, performing comparably to conventional risk models. This indicates mammography's potential for dual-risk assessment in breast cancer and cardiovascular disease. Further research is necessary to validate these findings in diverse populations, with a particular focus on representation from national breast screening programmes. [ABSTRACT FROM AUTHOR]

Background Primary therapy of localized myxofibrosarcoma (MFS) remains controversial. Primary resection is complicated by a high rate of local recurrence, and the refractoriness to non-surgical treatment results in a higher risk of metastasis. The aim of the present study was to contribute the findings of a single sarcoma-specialized center and encourage investigating new treatment options. Patients and Methods We analyzed 134 patients treated with localized MFS in our center regarding prognostic factors defining overall survival, local recurrence, and metastasis. We focused on multimodal treatment of localized MFS: surgery, radiation, chemotherapy, hyperthermia, and isolated limb perfusion. Results The 5-year OS was 74.9%. From a total of 134 patients: 74 (55.2%) stayed disease free, 48 (35.8%) had a local recurrence (LR), and 23 (17.2%) developed a distant metastasis (DM). The 5-year LR-free survival (LRFS) and DM-free survival (DMFS) were 66.1% and 80.8%, respectively. Older age, tumor size (cT) cT ≥ 2, non-extremity localization, and distant metastasis were adverse predictive factors for OS. Performing an incision biopsy, surgery in a sarcoma-center, wide local excision or compartment-oriented excision, negative margins, and radiotherapy were positive predictive factors for LR. Tumor size cT ≥ 3 was a negative predictive factor for DM. Grading was a negative predictive factor for LR (G ≥ 2) and for DM (G3) in the multivariable analysis. Conclusion Adjuvant radiation had a positive impact on LRFS in all localized tumor stages, even in cT1 tumors. Chemotherapy did not have a significant impact on DMFS, regardless of tumor stage. Our findings indicate that myxofibrosarcoma may be a chemotherapy-resistant entity and a much closer monitoring is required, in case of neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular magnetic resonance parametric mapping enables non-invasive quantitative myocardial tissue characterization. Human myocardium has normal ranges of T1 and T2 values, deviation from which may indicate disease or change in physiology. Normal myocardial T1 and T2 values are affected by biological sex. Consequently, normal ranges created with insufficient numbers of each sex may result in sampling biases, misclassification of healthy values vs. disease, and even misdiagnoses. In this study, we investigated the impact of using male normal ranges for classifying female cases as normal or abnormal (and vice versa). Methods and results One hundred and forty-two healthy volunteers (male and female) were scanned on two Siemens 3T MR systems, providing averaged global myocardial T1 and T2 values on a per-subject basis. The Monte Carlo method was used to generate simulated normal ranges from these values to estimate the statistical accuracy of classifying healthy female or male cases correctly as 'normal' when using sex-specific vs. mixed-sex normal ranges. The normal male and female T1- and T2-mapping values were significantly different by sex, after adjusting for age and heart rate. Conclusion Using 15 healthy volunteers who are not sex specific to establish a normal range resulted in a typical misclassification of up to 36% of healthy females and 37% of healthy males as having abnormal T1 values and up to 16% of healthy females and 12% of healthy males as having abnormal T2 values. This paper highlights the potential adverse impact on diagnostic accuracy that can occur when local normal ranges contain insufficient numbers of both sexes. Sex-specific reference ranges should thus be routinely adopted in clinical practice. [ABSTRACT FROM AUTHOR]

The N 6-methyladenosine (m6A) modification is a highly conserved RNA modification found in eukaryotic messenger RNAs (mRNAs). It plays a vital role in regulating various biological processes. Dysregulation of m6A modifications has been linked to a range of complex genetic diseases in humans. However, there has been a lack of comprehensive characterization and comparison of m6A modifications at the transcriptome-wide level within families. To address this gap, we profiled transcriptome-wide m6A methylation in 18 individuals across 6 Yoruba trio families. The m6A methylomes of these 18 individuals revealed that m6A modifications in children showed greater similarity to each other than to their parents. This suggests that m6A modifications are influenced by multiple factors rather than solely determined by genetic factors. Additionally, we found that mRNAs exhibiting m6A modifications specific to children were enriched in cell cycle control processes, while those with m6A modifications specific to parents were associated with chromatin modifications. Furthermore, our analysis on the interactions between differentially expressed m6A-related regulatory genes and age-related genes suggested that age might be one of the factors influencing m6A modifications. In summary, our study provided a valuable dataset that highlighted the differences and functional diversity of m6A modifications within and between trio families. [ABSTRACT FROM AUTHOR]

Background Diagnostic testing is essential for disease surveillance and test–trace–isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates. Methods We included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 June 2020 to 9 February 2022. Using Poisson regression analyses, we investigated if postal code area Care Need Index (CNI; median 1.0, IQR 0.8–1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with COVID-19 daily testing rates after adjustments for community transmission. We assessed if the distance to testing station influenced testing, and performed a difference-in-difference-analysis of a new testing station targeting a disadvantaged neighbourhood. Results We observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants 5–69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5–14 years) ranging from 0.56 (95% CI 0.47–0.67) to 0.87 (95% CI 0.80–0.93) across three pandemic waves. Longer distance to the nearest testing station was linked to lower testing rates, e.g. every additional 10 km was associated with a 10–18% decrease in inhabitants 15–29 years in Uppsala County. The opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70–105, supporting an intervention effect. Conclusions Ensuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing. [ABSTRACT FROM AUTHOR]

Background Well-established associations exist between the risk of small for gestational age (SGA) and unidimensional sociodemographic factors. We investigated social inequalities in SGA risk and adopted an intersectional approach that simultaneously considers different social categories. By doing so, we could assess heterogeneities in SGA risk within unidimensional sociodemographic categories. Methods We included all live 679 694 singleton births in Sweden between 2010 and 2016. The outcome was SGA, and the exposures were age, maternal educational level, dichotomous migration status and civil status. Thirty-six possible combinations of these factors constituted the exposure in an intersectional model. We present odds ratios (ORs) with 95% confidence intervals (95% CIs) and the area under the receiver operating characteristic curve (AUC)—a measurement of discriminatory accuracy (i.e. the ability to discriminate the babies born SGA from those who are not). Results Women with low education and women born outside Sweden had ORs of 1.46 (95% CI 1.38–1.54) and 1.50 (95% CI 1.43–1.56) in unidimensional analyses, respectively. Among women aged under 25 with low education who were born outside Sweden and unmarried, the highest OR was 3.06 (2.59–3.63). The discriminatory accuracy was low for both the unidimensional model that included all sociodemographic factors (AUC 0. 563) and the intersectional model (AUC 0.571). Conclusions The intersectional approach revealed a complex sociodemographic pattern of SGA risk. Sociodemographic factors have a low accuracy in identifying SGA at the individual level, even when quantifying their multi-dimensional intersections. This cautions against interventions targeted to individuals belonging to socially defined groups to reduce social inequalities in SGA risk. [ABSTRACT FROM AUTHOR]

Background Fatigue is common in patients undergoing radiotherapy (RT) and can significantly impact quality of life. Melatonin, a safe inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The purpose of this randomized double-blind placebo-controlled phase III trial was to assess the effects of melatonin for preventing fatigue and other symptoms in patients with breast cancer undergoing RT. Methods Female early stage or Ductal carcinoma in situ patients with breast cancer ≥18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status <3, hemoglobin ≥9 g/dL, planned for outpatient RT treatment with curative intent, were randomized 1:1 to melatonin 20 mg or placebo, orally, starting the night before RT initiation until 2 weeks post-RT. Randomization was stratified according to treatment duration (<3 weeks, ≥3 weeks) and prior chemotherapy. The primary endpoint was the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue scale), and secondary endpoints were FACIT-F subscales, Edmonton Symptom Assessment Scale (ESAS), and Patient-Reported Outcomes Measurement Information System (PROMIS) scores obtained at baseline, and 2 and 8 weeks post-RT. A 2-sided ANOVA F -test at a 4.5% significance level for the primary endpoint was used. Secondary analyses were reported using an F -test at a 5% significance level. The goal was to recruit approximately 140 patients with interim analysis planned mid-recruitment. Results Eighty-five patients were screened for eligibility; 79 patients were randomized: 40 to melatonin and 39 to placebo; 78 patients were treated and included in the interim analysis at the mid-recruitment point. Baseline patient characteristics of age, race, and ECOG performance status were similar in both arms. The treatment effect was studied using a longitudinal mixed effects model with the effect of treatment over time (treatment × time) as the primary outcome parameter. The treatment × time for FACIT-Fatigue did not demonstrate statistical significance (P -value.83) in the melatonin group compared to placebo. In addition, secondary analyses of FACIT physical, social, emotional, and functional well-being scores did not demonstrate statistical significance (P -values of.35,.06,.62, and.71, respectively). Total PROMIS scores, collected as secondary outcome reported by patients, did not demonstrate statistically significant change over time either (P -value is.34). The other secondary scale, ESAS, was analyzed for each individual item and found to be nonsignificant, anxiety (P  = .56), well-being (.82), drowsiness (.83), lack of appetite (.35), nausea (.79), pain (.50), shortness of breath (.77), sleep (.45), and tiredness (.56). Depression was the only item demonstrating statistical significance with a decrease of 0.01 unit in the placebo group, a change not considered clinically significant. Melatonin was well-tolerated with no grade 3 or 4 adverse events reported. The most common side effects were headache, somnolence, and abdominal pain. No patients died while participating in this study. Two patients died within a year of study completion from breast cancer recurrence. Sixteen patients withdrew prior to study completion for various reasons including adverse events, hospitalizations unrelated to study drug, RT discontinuation, and COVID-19 precautions. Conclusions In this double-blind placebo-controlled phase III trial, melatonin did not prevent or significantly improve fatigue and other symptoms in patients with early stage breast cancer undergoing RT. The analysis, showing little evidence of an effect, at mid-recruitment, assured early termination of the trial. [ABSTRACT FROM AUTHOR]

Aims Anterior mitral valve leaflet (AMVL) elongation is detectable in overt and subclinical hypertrophic cardiomyopathy (HCM). We sought to investigate the dynamic motion of the aorto-mitral apparatus to understand the behaviour of the AMVL and the mechanisms of left ventricular outflow tract obstruction (LVOTO) predisposition in HCM. Methods and results Cardiovascular magnetic resonance imaging using a 1.5 Tesla scanner was performed on 36 HCM sarcomere gene mutation carriers without left ventricular hypertrophy (G+LVH−), 31 HCM patients with preserved ejection fraction carrying a pathogenic sarcomere gene mutation (G+LVH+), and 53 age-, sex-, and body surface area–matched healthy volunteers. Dynamic excursion of the aorto-mitral apparatus was assessed semi-automatically on breath-held three-chamber cine steady-state free precession images. Four pre-defined regions of interest (ROIs) were tracked: ROIPMVL: hinge point of the posterior mitral valve leaflet; ROITRIG: intertrigonal mitral annulus; ROIAMVL: AMVL tip; and ROIAAO: anterior aortic annulus. Compared with controls, normalized two-dimensional displacement-vs.-time plots in G+LVH− revealed subtle but significant systolic anterior motion (SAM) of the AMVL (P < 0.0001) and reduced longitudinal excursion of ROIAAO (P = 0.014) and ROIPMVL (P = 0.048). In overt and subclinical HCM, excursion of the ROITRIG/AMVL/PMVL was positively associated with the burden of left ventricular fibrosis (P < 0.028). As expected, SAM was observed in G+LVH+ together with reduced longitudinal excursion of ROITRIG (P = 0.049) and ROIAAO (P = 0.008). Conclusion Dyskinesia of the aorto-mitral apparatus, including SAM of the elongated AMVL, is detectable in subclinical HCM before the development of LVH or left atrial enlargement. These data have the potential to improve our understanding of early phenotype development and LVOTO predisposition in HCM. [ABSTRACT FROM AUTHOR]

Background To improve research and care for patients with post - COVID-19 condition more insight into different subtypes of post - COVID-19 condition and their risk factors is urgently needed. We aimed to identify risk factors of post - COVID-19 condition in general and for specific symptom profiles. Methods This study is based on data collected within the Lifelines Coronavirus disease 2019 (COVID-19) cohort (N  = 76 503). Mean pre- and post-SARS-CoV-2 infection symptom scores were compared to classify post - COVID-19 condition. Latent Profile Analysis was used to identify symptom profiles. Logistic and multinomial regression analyses were used to examine the association between demographic, lifestyle and health-related risk factors and post - COVID-19 condition, and symptom profiles, respectively. Results Of the 3465 participants having had COVID-19, 18.5% (n  = 642) classified for post - COVID-19 condition. Four symptom profiles were identified: muscle pain, fatigue, cardiorespiratory and ageusia/anosmia. Female sex was a risk factor for the muscle pain and fatigue profiles. Being overweight or obese increased risk for all profiles, except the fatigue profile. Having a chronic disease increased the risk for all profiles except the ageusia/anosmia profile, with the cardiorespiratory profile being only significant in case of multimorbidity. Being unvaccinated increased risk of the ageusia/anosmia profile. Conclusions Findings from this study suggest that Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger different pathophysiological mechanisms that may result in different subtypes of post - COVID-19 condition. These subtypes have shared and unique risk factors. Further characterization of symptom profiles and quantification of the individual and societal impact of specific symptom profiles are pressing challenges for future research. [ABSTRACT FROM AUTHOR]

Background Missed opportunities constitute a main driver of suboptimal seasonal influenza vaccination (SIV) coverage in older adults. Vaccine co-administration is a way to reduce these missed opportunities. In this study, we quantified missed opportunities for SIV, identified some of their socio-structural correlates and documented SIV co-administration patterns. Methods In this registry-based retrospective cohort study, we verified the SIV status of all subjects aged ≥65 years who received at least one dose of coronavirus disease 2019 (COVID-19), pneumococcal or herpes zoster vaccines during the 2022/23 influenza season. The frequency of concomitant same-day administration of SIV with other target vaccines was also assessed. Results Among 41 112, 5482 and 3432 older adults who received ≥1 dose of COVID-19, pneumococcal and herpes zoster vaccines, missed opportunities for SIV accounted for 23.3%, 5.0% and 13.2%, respectively. Younger, male and foreign-born individuals were generally more prone to missing SIV. The co-administration of SIV with other recommended vaccines was relatively low, being 11.0%, 53.1% and 17.1% in COVID-19, pneumococcal and herpes zoster cohorts, respectively. Conclusions A sizeable proportion of older adults who received other recommended vaccines during the last influenza season did not receive SIV. This share of missed opportunities, which are subject to some social inequalities, may be addressed by increasing vaccine co-administration rates and implementing tailored health promotion interventions. [ABSTRACT FROM AUTHOR]

Background Male excess mortality is mostly related to non-biological factors, and is thus of high social- and health-policy concern. Previous research has mainly focused on national patterns, while subnational disparities have been less in the focus. This study takes a spatial perspective on subnational patterns, covering seven European countries at the crossroad between Eastern and Western Europe. Methods We analyze a newly gathered spatially detailed data resource comprising 228 regions with well-established demographic methods to assess the contribution of specific causes of death to the evolution of sex mortality differentials (SMDs) since the mid-1990s. Results Our results show that declines in SMDs were mostly driven by a reduction of male excess mortality from cardiovascular diseases and neoplasms (about 50–60% and 20–30%, respectively). In Western Europe, trends in deaths from neoplasms contributed more to the reduction of SMDs, while among regions located in Eastern-Central Europe narrowing SMDs were mostly driven by changes in cardiovascular disease-related deaths. Moreover, men show up to three times higher mortality levels from external causes as compared to women in several analyzed regions. But in absolute terms, external deaths play only a minor role in explaining SMDs due to their small contribution to overall mortality. Conclusions We conclude that examining the regional development of SMDs is useful for introducing targeted social and health policies in order to reduce and prevent mortality inequalities between women and men. [ABSTRACT FROM AUTHOR]

Background: Cancer remains a leading cause of mortality worldwide. While the main focus of palliative care (PC) is quality of life, the elements that comprise the quality of death are often overlooked. Dying at home, with home-hospice-care (HHC) support, rather than in-hospital, may increase patient satisfaction and decrease the use of invasive measures. We examined clinical and demographic characteristics associated with out-of-hospital death among patients with cancer, which serves as a proxy measure for HHC deaths. Methods: Using death certification data from the Israel Central Bureau of Statistics, we analyzed 209,158 cancer deaths between 1998 and 2018 in Israel including demographic information, cause of death, and place of death (POD). A multiple logistic regression model was constructed to identify factors associated with out-of-hospital cancer deaths. Results: Between 1998 and 2018, 69.1% of cancer deaths occurred in-hospital, and 30.8% out-of-hospital. Out-of-hospital deaths increased by 1% annually during the study period. Older patients and those dying of solid malignancies were more likely to die out-of-hospital (OR = 2.65, OR = 1.93, respectively). Likelihood of dying out-of-hospital varied with area of residency; patients living in the Southern district were more likely than those in the Jerusalem district to die out-of-hospital (OR = 2.37). Conclusion: The proportion of cancer deaths occurring out-of-hospital increased during the study period. We identified clinical and demographic factors associated with POD. Differences between geographical areas probably stem from disparity in the distribution of PC services and highlight the need for increasing access to primary EOL care. However, differences in age and tumor type probably reflect cultural changes and suggest focusing on educating patients, families, and physicians on the benefits of PC. Spending the last days of life at home has been shown to be associated with less invasive measures and better quality of life at such a critical time. This study identified factors associated with increased likelihood of home death among cancer patients. [ABSTRACT FROM AUTHOR]

Age-period-cohort analysis involves 3 temporal factors: age (the length of time from birth to diagnosis), period (the calendar time of diagnosis), and cohort (the calendar time of birth). The application of age-period-cohort analysis in disease forecasting can help researchers and health authorities anticipate future disease burden. In this study, a synthesized age-period-cohort prediction method was proposed based on 4 assumptions: 1) no single model can dominate as the most accurate prediction model in all forecasting scenarios; 2) historical trends will not continue indefinitely; 3) a model with the most accurate forecast for the training data will also be appropriate for forecasting future data; and 4) a model dominated by the stochastic temporal change will be the best-selected model with the robust forecasting. An ensemble of age-period-cohort prediction models was constructed, and Monte Carlo cross-validation was performed to evaluate forecasting accuracy of these models. Data on lung cancer mortality from 1996 to 2015 in Taiwan were used and projected to the year 2035 to illustrate the method. The actual lung cancer mortality rates from 2016 to 2020 were then used to verify the forecasting accuracy. [ABSTRACT FROM AUTHOR]

Background Internationally, screening programmes and clinical practice guidelines recommend when older adults should stop cancer screening using upper age limits, but it is unknown how older adults view these recommendations. Objective To examine older adults' views and experiences about continuing or stopping cancer screening beyond the recommended upper age limit for breast, cervical, prostate and bowel cancer. Design Qualitative, semi-structured interviews. Setting Australia, telephone. Subjects A total of 29 community-dwelling older adults (≥70-years); recruited from organisation newsletters, mailing lists and Facebook advertisements. Methods Interviews were audio-recorded, transcribed and analysed thematically using Framework Analysis. Results Firstly, older adults were on a spectrum between trusting recommendations and actively deciding about cancer screening, with some who were uncertain. Secondly, participants reported limited in-depth discussions with health professionals about cancer screening. In primary care, discussions were focused on checking they were up to date with screening or going over results. Discussions mostly only occurred if older adults initiated themselves. Finally, participants had a socially- and self-constructed understanding of screening recommendations and potential outcomes. Perceived reasons for upper age limits were cost, reduced cancer risk or ageism. Risks of screening were understood in relation to their own social experiences (e.g. shared stories about friends with adverse outcomes of cancer treatment or conversations with friends/family about controversy around prostate screening). Conclusions Direct-to-patient information and clinician support may help improve communication about the changing benefit to harm ratio of cancer screening with increasing age and increase understanding about the rationale for an upper age limit for cancer screening programmes. [ABSTRACT FROM AUTHOR]

Background Frailty is a dynamic process associated with adverse health outcomes. However, little is known about the long-term trajectories of frailty in older cancer survivors. Objectives To describe the trajectories of frailty phenotype over time amongst older cancer survivors and examine the socio-demographic and health-related predictors of different trajectories. Design Population-based longitudinal cohort study. Setting Community-dwelling older adults in the United States. Subjects 1,763 older adults who were diagnosed with cancer from the National Health and Ageing Trends Study. Methods Frailty was assessed by the Fried Frailty Phenotype. The group-based trajectory model was used to identify the trajectories of frailty. Multinomial logistic regression analyses were used to examine the socio-demographic and health-related predictors of different trajectories. Results Three frailty trajectories were identified; 52.8% of older cancer survivors had a sustained low risk of frailty over time, 25.0% had a low frailty risk at baseline but the risk increased steadily, and 22.3% had a high frailty risk with a slight change in the observed period. Older cancer survivors were at a high-risk frailty trajectory if they were older, female, African American, had lower education status, had lower annual income, were underweight or obese, self-rated poorer health, had more chronic conditions and difficulties with activities of daily living (ADL), and had worse cognitive functions (P  < 0.05). Conclusions Long-term frailty trajectories in older cancer survivors are heterogeneous. This study helps identify patients at high risk of sustained or deteriorating frailty and has the potential to inform targeted frailty management strategies addressing modifiable factors identified (e.g. body mass index, ADL). [ABSTRACT FROM AUTHOR]

Background Higher incidence of acute coronary syndrome (ACS), among those with lower income, has been recognized in the most recent decades. Still, there is a paucity of data on temporal changes. This study aims to investigate 20-year time trends in income-related disparity in the incidence of ACS in Denmark. Methods This Population‐based repeated cross-sectional study included all patients with first-time ACS, aged ≥20 years, registered in the Danish National Patient Registry 1998–2017. Aggregated sociodemographic data for the Danish population was accessed from Statistics Denmark. Yearly incidence rates (IR) and incidence rate ratios (IRR), with the highest-income quartile as a reference, were standardized using cell-specific personal equivalent income according to year, sex and age group with 95% confidence intervals. Interaction analysis was executed for differences in IR of ACS between the lowest- and highest-income quartile over time. Results A total of 220 070 patients hospitalized with ACS from 1998 to 2017 were identified. The yearly standardized ACS IRs decreased in all income quartiles. However, the IR remained higher in the lowest-income quartile compared to the highest for both men [1998: IRR 1.45 (95% confidence interval, CI 1.39–1.52) and 2017: 1.47 (1.40–1.54)] and women [1998: IRR 1.73 (1.64–1.82) and 2017: 1.76 (1.65–1.88)]. Interaction analysis showed that over the period the difference in IR between the lower- and the highest-income quartile decreased with 1–5 ACS cases per 100 000 person-year. Conclusion Income-related disparity in the incidence of ACS was present in Denmark between 1998 and 2017. Despite a marked overall decrease in the yearly ACS incidence, the extent of income-related disparity remained unchanged. [ABSTRACT FROM AUTHOR]

Background Estimating excess mortality and years of life lost (YLL) attributed to coronavirus disease 19 (COVID-19) infection provides a comprehensive picture of the mortality burden on society. We aimed to estimate the impact of the COVID-19 pandemic on age- and sex-specific excess mortality and YLL in Sweden during the first 17 months of the pandemic. Methods In this population-based observational study, we calculated age- and sex-specific excess all-cause mortality and excess YLL during 2020 and the first 5 months of 2021 and cause-specific death [deaths from cardiovascular disease (CVD), cancer, other causes and deaths excluding COVID-19] in 2020 compared with an average baseline for 2017–19 in the whole Swedish population. Results COVID-19 deaths contributed 9.9% of total deaths (98 441 deaths, 960 305 YLL) in 2020, accounting for 75 151 YLL (7.7 YLL/death). There were 2672 (5.7%) and 1408 (3.0%) excess deaths, and 19 141 (3.8%) and 3596 (0.8%) excess YLL in men and women, respectively. Men aged 65–110 years and women aged 75–110 years were the greatest contributors. Fewer deaths and YLL from CVD, cancer and other causes were observed in 2020 compared with the baseline adjusted to the population size in 2020. Conclusions Compared with the baseline, excess mortality and YLL from all causes were experienced in Sweden during 2020, with a higher excess observed in men than in women, indicating that more men died at a younger age while more women died at older ages than expected. A notable reduction in deaths and YLL due to CVD suggests a displacement effect from CVD to COVID-19. [ABSTRACT FROM AUTHOR]

Background Although adjuvant cancer treatments increase cure rates, they may induce clonal selection and tumor resistance. Information still lacks as whether (neo)adjuvant anti-HER2 treatments impact the patterns of recurrence and outcomes of HER2-positive (HER2+) metastatic breast cancer (MBC). We aimed to assess this in the large multicenter ESME real-world database. Patients and Methods We examined the characteristics and outcomes (overall survival (OS) and progression-free survival under first-line treatment (PFS1)) of HER2+ patients with MBC from the French ESME program with recurrent disease, as a function of the previous receipt of adjuvant trastuzumab. Multivariable analyses used Cox models adjusted for baseline demographic, prognostic factors, adjuvant treatment received, and disease-free interval. Results Two thousand one hundred and forty-three patients who entered the ESME cohort between 2008 and 2017 had a recurrent HER2+ MBC. Among them, 56% had received (neo)adjuvant trastuzumab and 2.5% another anti-HER2 in this setting. Patients pre-exposed to trastuzumab were younger, had a lower disease-free interval, more HR-negative disease and more metastatic sites. While the crude median OS appeared inferior in patients exposed to adjuvant trastuzumab, as compared to those who did not (37.2 (95%CI 34.4-40.3) versus 53.5 months (95% CI: 47.6-60.1)), this difference disappeared in the multivariable model (HR = 1.05, 95%CI 0.91-1.22). The same figures were observed for PFS1. Conclusions Among patients with relapsed HER2+ MBC, the receipt of adjuvant trastuzumab did not independently predict for worse outcomes when adjusted to other prognostic factors. [ABSTRACT FROM AUTHOR]

Objectives Genetics plays an important role in SLE risk, as well as osteonecrosis (ON), a significant and often debilitating complication of SLE. We aimed to identify genetic risk loci for ON in people with childhood-onset (cSLE) and adult-onset (aSLE) SLE. Methods We enrolled participants from two tertiary care centres who met classification criteria for SLE. Participants had prospectively collected clinical data and were genotyped on a multiethnic array. Un-genotyped single nucleotide polymorphisms (SNPs) were imputed, and ancestry was inferred using principal components (PCs). Our outcome was symptomatic ON confirmed by imaging. We completed time-to-ON and logistic regression of ON genome-wide association studies (GWASs) with covariates for sex, age of SLE diagnosis, five PCs for ancestry, corticosteroid use and selected SLE manifestations. We conducted separate analyses for cSLE and aSLE and meta-analysed results using inverse-variance weighting. Genome-wide significance was P  < 5 × 10−8. Results The study included 940 participants with SLE, 87% female and 56% with cSLE. ON was present in 7.6% (n  = 71). Median age of SLE diagnosis was 16.9 years (interquartile range [IQR]: 13.5, 29.3), with median follow-up of 8.0 years (IQR: 4.2, 15.7). Meta-GWAS of cSLE and aSLE time-to-ON of 4 431 911 SNPs identified a significant Chr.2 SNP, rs34118383 (minor allele frequency = 0.18), intronic to WIPF1 (hazard ratio = 3.2 [95% CI: 2.2, 4.8]; P  = 1.0 × 10−8). Conclusion We identified an intronic WIPF1 variant associated with a 3.2 times increased hazard for ON (95% CI: 2.2, 4.8; P   =  1.0 × 10−8) during SLE follow-up, independent of corticosteroid exposure. The effect of the SNP on time-to-ON was similar in cSLE and aSLE. This novel discovery represents a potential ON risk locus. Our results warrant replication. [ABSTRACT FROM AUTHOR]

Objective Optimization of maternal vitamin D (VD) status has beneficial effects on pregnancies, but little is known about it of twin pregnancies (TP). Our aim was to promote the current understanding of VD status and its associated factors in TP. Methods We performed liquid chromatography-tandem mass spectrometry to quantify 25-hydroxyvitamin D [25(OH)D] and used the enzyme-linked immunosorbent assay method to detect vitamin D binding protein (VDBP) in 218 singleton pregnancies (SP) and 236 TP. Results Levels of 25(OH)D and VDBP were higher in TP than SP. The 25(OH)D, free 25(OH)D, C-3 epimer of 25-hydroxyvitamin D [epi-25(OH)D], and VDBP all increased with gestational progress. Age, body 
mass index, and hemoglobin level were associated with VD deficiency (VDD). Analysis of covariance demonstrated that the 25(OH)D and VDBP of TP and SP still showed differences after adjusting for the above associated factors. Conclusion Differences in VD status were found in SP and TP, suggesting that the assessment of VD status in TP should be treated with caution. High VDD prevalence is observed among pregnant Chinese women, and it is recommended to promote evaluation for VDD. [ABSTRACT FROM AUTHOR]

Background Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP. Methods We included patients with FEP aged 18–64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP. Findings Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20–2.54, P =.004 and 1.62, 95% CI 1.25–2.09, P <.001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31–4.78] for recent use and 7.61% [95% CI 3.68–10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries. Interpretation Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries. [ABSTRACT FROM AUTHOR]

Introduction Family support plays a vital role in the outcome of individuals with tuberculosis (TB). Objectives To determine the family and social support among individuals with pulmonary TB during treatment. Methods A cross-sectional survey was conducted among 237 pulmonary TB patients currently in the continuous phase of treatment. Bivariate and multivariate analyses were conducted to determine the association and predictors for family and social support. P -value < 0.05 was considered statistically significant. Results The mean age of the respondents was 31.97 ± 12.51 years, and a majority (58.2%) of the respondents with TB disease were 18 to 38 years old, and 59.9% were males. Around 49.7% of the pulmonary TB patients received a high level of family support, whereas 73% received a high level of social support. The determinants like age, average monthly income, the educational level of the head of the family and the occupational level of both the patients and the head of the family are associated with family support. Conclusion This study recommends a coordinated strategy to treat TB that involves not only professional services but also the vital social support network of family and community that is required throughout therapy. [ABSTRACT FROM AUTHOR]

Background Forced displacement and war trauma cause high rates of post-traumatic stress, anxiety disorders and depression in refugee populations. We investigated the impact of forced displacement on mental health status, gender, presentation of type 2 diabetes (T2D) and associated inflammatory markers among Syrian refugees in Lebanon. Methods Mental health status was assessed using the Harvard Trauma Questionnaire (HTQ) and the Hopkins Symptom Checklist-25 (HSCL-25). Additional metabolic and inflammatory markers were analyzed. Results Although symptomatic stress scores were observed in both men and women, women consistently displayed higher symptomatic anxiety/depression scores with the HSCL-25 (2.13 ± 0.58 versus 1.95 ± 0.63). With the HTQ, however, only women aged 35–55 years displayed symptomatic post-traumatic stress disorder (PTSD) scores (2.18 ± 0.43). Furthermore, a significantly higher prevalence of obesity, prediabetes and undiagnosed T2D were observed in women participants (23.43, 14.91 and 15.18%, respectively). Significantly high levels of the inflammatory marker serum amyloid A were observed in women (11.90 ± 11.27 versus 9.28 ± 6.93, P  = 0.036). Conclusions Symptomatic PTSD, anxiety/depression coupled with higher levels of inflammatory marker and T2D were found in refugee women aged between 35 and 55 years favoring the strong need for psychosocial therapeutic interventions in moderating stress-related immune dysfunction and development of diabetes in this subset of female Syrian refugees. [ABSTRACT FROM AUTHOR]