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Background An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data. Setting Primary care data (country/database) from the UK/CPRD-GOLD (2007–20), Spain/SIDIAP (2010–20) and the Netherlands/IPCI (2008–20), standardised to a common data model. Methods Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)). Results We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI. In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891–32,862)) to 2010 (17,793 (17,083–18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021–25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199–52,855)) to 2020 (14,571 (14,109–15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967–29,031)) to 2020 (4763 (4176–5409)). Subjects aged ≥65–79 years and men (in the UK and the Netherlands) initiated more frequently an ADD. Conclusions Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed. [ABSTRACT FROM AUTHOR]

Summary: We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. Purpose: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. Methods: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. Results: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52–73% at 6 months to 29–53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50–66% at 6 months and decreased to 30–44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40–73% and decreased to 25–59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50–85% (6 month), 30–63% (12 month) and with teriparatide 40–75% (6 month) decreasing to 21–54% (12 month). Switching occurred most frequently in the alendronate group (2.8–5.8%) and in the teriparatide group (7.1–14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. Conclusion: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare. [ABSTRACT FROM AUTHOR]

Background: Studies revealed unidirectional associations between frailty and medication‐related problems (MRPs) among older adults. Less is known about the association between frailty and the risk of MRPs. We aimed to assess the bi‐directional association between frailty and the risk of MRPs in community‐dwelling older adults in five European countries. Methods: Participants were 1785 older adults in the population‐based Urban Health Centres Europe project. Repeated assessments were collected at baseline and one‐year follow‐up, including frailty, the risk of MRPs, and covariates. Linear regression analyses were conducted to examine the unidirectional associations. A cross‐lagged panel modeling was used to assess bi‐directional associations. Results: The unidirectional association between frailty at baseline and the risk of MRPs at follow‐up remained statistically significant after adjusting for covariates (β = 0.10, 95%CI:0.08, 0.13). The association between the risk of MRPs at baseline and frailty at follow‐up shows similar trends. The bi‐directional association was comparable with reported unidirectional associations, with a stronger effect from frailty at baseline to the risk of MRPs at follow‐up than reversed path (Wald test for comparing lagged effects: p < 0.05). Conclusion: This longitudinal study suggests that a cycle may exist where older adults with higher frailty levels are more likely to have a higher risk of MRPs, which in turn contributes to developing a higher level of frailty. Further research is needed to validate our findings and explore underlying pathways. [ABSTRACT FROM AUTHOR]

Dupilumab is prescribed in one dosage across adult atopic dermatitis patients. Differences in drug exposure may explain variation in treatment response. Investigating the clinical relevance of dupilumab serum concentration in atopic dermatitis in real-world practice. In two centers (Netherlands, UK), adults treated with dupilumab for atopic dermatitis were evaluated for effectiveness and safety pretreatment and at 2, 12, 24, and 48 weeks; trough serum samples were analyzed for dupilumab concentration at corresponding time points. In 149 patients, median dupilumab levels during follow-up ranged from 57.4 to 72.4 μg/mL. Levels showed high inter-patient and low intra-patient variability. No correlation was found between levels and ΔEASI. At 2 weeks, levels of ≥64.1 μg/mL predict EASI ≤7 at 24 weeks (specificity:100%, sensitivity:60%; p =.022). At 12 weeks, ≤32.7 μg/mL predicts EASI >7 at 24 weeks (sensitivity:95%, specificity:26%; p =.011). Inverse correlations were found between baseline EASI and levels at 2, 12, and 24 weeks (r = −0.25 to 0.36; p ≤.023). Low levels were particularly observed in patients with adverse events, treatment interval deviation, and discontinuation. At the on-label dosage, the measured range of dupilumab levels does not seem to yield differences in treatment effectiveness. However, disease activity does seem to influence dupilumab levels - higher baseline disease activity results in lower levels at follow-up. [ABSTRACT FROM AUTHOR]

Many researchers and practitioners consider ethnic segregation in neighbourhoods or schools detrimental to migrants' acculturation in host societies. Empirically, however, segregation is a 'mixed bag' and its effects depend crucially on the investigated acculturation domain (e.g., negative for language skills, positive for well‐being). As most prior studies have focused on a restricted spectrum of acculturation, a comprehensive assessment within one single study is needed to establish comparability across different acculturation domains. Among over 8000 immigrant‐background students from four countries, we investigated the association of classroom segregation, defined as opportunities for contact with natives and other migrants, with a broad spectrum of acculturation (academic, attitude‐related, identity‐related, social, health‐related, and psychological criteria). Some findings were consistent (e.g., academic acculturation), some were contrary to prior research (e.g., social acculturation). In sum, our results shed light on the 'mixed bag' of segregation and contribute to the understanding of a crucial social issue. [ABSTRACT FROM AUTHOR]

Previous studies have shown that survival outcomes for older patients with breast cancer vary substantially across Europe, with worse survival reported in the United Kingdom. It has been hypothesised that these differences in survival outcomes could be related to treatment variation. We aimed to compare patient and tumour characteristics, treatment selection and survival outcomes between two large prospective cohorts of older patients with operable breast cancer from the United Kingdom (UK) and The Netherlands. Women diagnosed with operable breast cancer aged ≥70 years were included. A baseline comprehensive geriatric assessment was performed in both cohorts, with data collected on age, comorbidities, cognition, nutritional and functional status. Baseline tumour characteristics and treatment type were collected. Univariable and multivariable Cox regression models were used to compare overall survival between the cohorts. 3262 patients from the UK Age Gap cohort and 618 patients from the Dutch Climb cohort were included, with median ages of 77.0 (IQR: 72.0–81.0) and 75.0 (IQR: 72.0–81.0) years, respectively. The cohorts were generally comparable, with slight differences in rates of comorbidity and frailty. Median follow-up for overall survival was 4.1 years (IQR 2.9–5.4) in Age Gap and 4.3 years (IQR 2.9–5.5) in Climb. In Age Gap, both the rates of primary endocrine therapy and adjuvant hormonal therapy after surgery were approximately twice those in Climb (16.6% versus 7.3%, p < 0.001 for primary endocrine therapy, and 62.2% versus 38.8%, p < 0.001 for adjuvant hormonal therapy). There was no evidence of a difference in overall survival between the cohorts (adjusted HR 0.94, 95% CI 0.74–1.17, p = 0.568). In contrast to previous studies, this comparison of two large national prospective longitudinal multi-centre cohort studies demonstrated comparable survival outcomes between older patients with breast cancer treated in the UK and The Netherlands, despite differences in treatment allocation. • No survival difference between UK and Netherlands for older breast cancer patients. • Similar patient and tumour characteristics seen in both cohorts. • Higher rates of mastectomy for older breast cancer patients in Netherlands. • Higher rates of adjuvant therapies for older breast cancer patients in UK. [ABSTRACT FROM AUTHOR]

Summary: Background: Anthropometry‐based equations are commonly used to estimate infant body composition. However, existing equations were designed for newborns or adolescents. We aimed to (a) derive new prediction equations in infancy against air‐displacement plethysmography (ADP‐PEA Pod) as the criterion, (b) validate the newly developed equations in an independent infant cohort and (c) compare them with published equations (Slaughter‐1988, Aris‐2013, Catalano‐1995). Methods: Cambridge Baby Growth Study (CBGS), UK, had anthropometry data at 6 weeks (N = 55) and 3 months (N = 64), including skinfold thicknesses (SFT) at four sites (triceps, subscapular, quadriceps and flank) and ADP‐derived total body fat mass (FM) and fat‐free mass (FFM). Prediction equations for FM and FFM were developed in CBGS using linear regression models and were validated in Sophia Pluto cohort, the Netherlands, (N = 571 and N = 447 aged 3 and 6 months, respectively) using Bland–Altman analyses to assess bias and 95% limits of agreement (LOA). Results: CBGS equations consisted of sex, age, weight, length and SFT from three sites and explained 65% of the variance in FM and 79% in FFM. In Sophia Pluto, these equations showed smaller mean bias than the three published equations in estimating FM: mean bias (LOA) 0.008 (−0.489, 0.505) kg at 3 months and 0.084 (−0.545, 0.713) kg at 6 months. Mean bias in estimating FFM was 0.099 (−0.394, 0.592) kg at 3 months and −0.021 (−0.663, 0.621) kg at 6 months. Conclusions: CBGS prediction equations for infant FM and FFM showed better validity in an independent cohort at ages 3 and 6 months than existing equations. [ABSTRACT FROM AUTHOR]

Objectives Chronic widespread musculoskeletal pain (CWP) is a characteristic symptom of fibromyalgia, which has been shown to be associated with an altered gut microbiome. Microbiome studies to date have not examined the milder CWP phenotype specifically nor have they explored the role of raised BMI. The aim of this study was to investigate whether the microbiome is abnormal in CWP. Methods CWP was assessed using a standardized screening questionnaire in female volunteers from the TwinsUK cohort including 113 CWP cases and 1623 controls. The stool microbiome was characterized using 16S rRNA amplicon sequencing and amplicon sequence variants, and associations with CWP examined using linear mixed-effects models adjusting for BMI, age, diet, family relatedness and technical factors. Results Alpha diversity was significantly lower in CWP cases than controls (Mann–Whitney test, P -values 2.3e-04 and 1.2e-02, for Shannon and Simpson indices respectively). The species Coprococcus comes was significantly depleted in CWP cases (P adj = 3.04e-03). A genome-wide association study (GWAS) performed for C. comes in TwinsUK followed by meta-analysis with three Dutch cohorts (total n  = 3521) resulted in nine suggestive regions, with the most convincing on chromosome 4 near the TRAM1L1 gene (rs76957229, P  = 7.4e-8). A Mendelian randomization study based on the results of the GWAS did not support a causal role for C. comes on the development of CWP. Conclusions We have demonstrated reduced diversity in the microbiome in CWP, indicating an involvement of the gut microbiota in CWP; prospectively the microbiome may offer therapeutic opportunities for this condition. [ABSTRACT FROM AUTHOR]

OBJECTIVES To examine the longitudinal association between frequency of moderate physical activity (PA) and overall, physical, psychological, and social frailty among community‐dwelling older adults older than 70 years. Second, we assessed the association between a 12‐month change in frequency of moderate PA and frailty. DESIGN Longitudinal cohort study. SETTING Community settings in Spain, Greece, Croatia, the Netherlands, and the United Kingdom. PARTICIPANTS A total of 1735 participants (61.1% female; mean age = 79.6 years; SD = 5.5 years). MEASUREMENTS The frequency of self‐reported moderate PA was measured and classified into two categories: "regular frequency" and "low frequency." The 12‐month change in frequency of moderate PA between baseline and follow‐up was classified into four categories: "continued regular frequency," "decreased frequency," "continued low frequency," and "increased frequency." The 15‐item Tilburg Frailty Indicator assessed overall, physical, psychological, and social frailty. RESULTS: Participants who undertook moderate PA with a regular frequency at baseline were less frail at 12‐month follow‐up than participants with a low frequency. Participants who undertook moderate PA with a continued regular frequency were least frail at baseline and at 12‐month follow‐up. After controlling for baseline frailty and covariates, compared with participants with a continued regular frequency, participants with a decreased frequency were significantly more overall (B = 1.31; 95% confidence interval [CI] = 0.99‐1.63), physically (B = 0.80; 95% CI = 0.58‐1.03), psychologically (B = 0.43; 95% CI = 0.30‐0.56), and socially frail (B = 0.14; 95% CI = 0.04‐0.23) at 12‐month follow‐up; participants with a continued low frequency were significantly more overall (B = 1.16; 95% CI = 0.84‐1.49), physically (B = 0.73; 95% CI = 0.51‐0.96), psychologically (B = 0.42; 95% CI = 0.29‐0.55), and socially frail (B = 0.13; 95% CI = 0.04‐0.23) at 12‐month follow‐up; the 12‐month follow‐up frailty level of participants who undertook moderate PA with an increased frequency was similar to those with a continued regular frequency. CONCLUSION: Maintaining a regular frequency of PA as well as increasing to a regular frequency of PA are associated with maintaining or improving overall, physical, psychological, and social frailty among European community‐dwelling older adults older than 70 years. J Am Geriatr Soc 68:1484‐1493, 2020. [ABSTRACT FROM AUTHOR]

This paper analyses the presence of interest organizations in political news in the United Kingdom and the Netherlands between 1990 and 2017. Previous research on organized interests in the media revealed (1) a consistent overrepresentation of business interests across countries, but (2) also that this overrepresentation has decreased over time in a European context. However, these studies are snapshots of interest group patterns with either cross-country or longitudinal variation, and important players such as corporations have been largely excluded by European scholars. We argue that including corporations affects previous conclusions as it reveals substantial differences across countries and an increasing role of business interests in the news. We use a data set of Dutch and British news articles, in which we identified 34,657 interest organizations. This endeavor highlights that the distribution of organized interests in the media is skewed toward business interests and has not become more diverse. This suggests that the important insider role of business interests translates to outsider venues, which tells us something about how the news media maintain these patterns through the construction of news stories. These findings interfere with ideas of representativeness and flourishing democracies with a diverse public debate in which many different voices are expressed. [ABSTRACT FROM AUTHOR]

Purpose: As a component of thyroid hormones, adequate iodine intake is essential during pregnancy for fetal neurodevelopment. Across Europe, iodine deficiency is common in pregnancy, but data are lacking on the predictors of iodine status at this life stage. We, therefore, aimed to explore determinants of iodine status during pregnancy in three European populations of differing iodine status. Methods: Data were from 6566 pregnant women from three prospective population-based birth cohorts from the United Kingdom (ALSPAC, n = 2852), Spain (INMA, n = 1460), and The Netherlands (Generation R, n = 2254). Urinary iodine-to-creatinine ratio (UI/Creat, µg/g) was measured in spot-urine samples in pregnancy (≤ 18-weeks gestation). Maternal dietary intake, categorised by food groups (g/day), was estimated from food-frequency questionnaires (FFQs). Multivariable regression models used dietary variables (energy-adjusted) and maternal characteristics as predictors of iodine status. Results: Median UI/Creat in pregnant women of ALSPAC, INMA, and Generation R was 121, 151, and 210 µg/g, respectively. Maternal age was positively associated with UI/Creat in all cohorts (P < 0.001), while UI/Creat varied by ethnicity only in Generation R (P < 0.05). Of the dietary predictors, intake of milk and dairy products (per 100 g/day) was positively associated with UI/Creat in all cohorts [ALSPAC (B = 3.73, P < 0.0001); INMA (B = 6.92, P = 0.002); Generation R (B = 2.34, P = 0.001)]. Cohort-specific dietary determinants positively associated with UI/Creat included fish and shellfish in ALSPAC and INMA, and eggs and cereal/cereal products in Generation R. Conclusions: The cohort-specific dietary determinants probably reflect not only dietary habits but iodine-fortification policies; hence, public-health interventions to improve iodine intake in pregnancy need to be country-specific. [ABSTRACT FROM AUTHOR]

Summary: We identified demographic, health and lifestyle factors associated with falls in adults aged 50–64 years from Australia, The Netherlands, Great Britain and Ireland. Nearly all factors were associated with falls, but there were differences between countries and between men and women. Existing falls prevention programs may also benefit middle-aged adults. Introduction: Between ages 40–44 and 60–64 years, the annual prevalence of falls triples suggesting that middle age may be a critical life stage for preventive interventions. We aimed to identify demographic, health and lifestyle factors associated with falls in adults aged 50–64 years. Methods: Harmonised data were used from four population-based cohort studies based in Australia (Australian Longitudinal Study on Women's Health, n = 10,641, 51–58 years in 2004), Ireland (The Irish Longitudinal Study on Ageing, n = 4663, 40–64 years in 2010), the Netherlands (Longitudinal Ageing Study Amsterdam, n = 862, 55–64 years in 2012–13) and Great Britain (MRC National Survey of Health and Development, n = 2987, 53 years in 1999). Cross-sectional and prospective associations of 42 potential risk factors with self-reported falls in the past year were examined separately by cohort and gender using logistic regression. In the absence of differences between cohorts, estimates were pooled using meta-analysis. Results: In cross-sectional models, nearly all risk factors were associated with fall risk in at least one cohort. Poor mobility (pooled OR = 1.71, CI = 1.34–2.07) and urinary incontinence (OR range = 1.53–2.09) were consistently associated with falls in all cohorts. Findings from prospective models were consistent. Statistically significant interactions with cohort and sex were found for some of the risk factors. Conclusion: Risk factors known to be associated with falls in older adults were also associated with falls in middle age. Compared with findings from previous studies of older adults, there is a suggestion that specific risk factors, for example musculoskeletal conditions, may be more important in middle age. These findings suggest that available preventive interventions for falls in older adults may also benefit middle-aged adults, but tailoring by age, sex and country is required. [ABSTRACT FROM AUTHOR]

Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child’s age (ages 3 through 16 years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic and measures have placed various burdens on societies and individuals. Emerging evidence suggests that people in drug addiction recovery were negatively affected. This study investigates whether risk and protective factors associated with return to problematic substance use differed between the periods before and during the pandemic for those in recovery. A convenience sample of persons in drug addiction recovery for at least three months completed an assessment at baseline before the pandemic (T0, N = 367) and at two consecutive follow-ups 12 months apart (T1, N = 311; T2, N = 246). The final follow-up took place during the pandemic (2020−2021). We analyzed rates and predictors of problematic substance use in both periods, and whether relations between predictors and problematic use differed between the periods. Rates of problematic use did not differ significantly before and during the pandemic for those who were followed-up. However, the relationship between problematic use and commitment to sobriety differed between both periods (OR = 3.24, P = 0.010), as higher commitment was only associated with lower odds of problematic use during (OR = 0.27, P < 0.001), but not before, the pandemic (OR = 0.93, P = 0.762). In both periods, persons who were engaged in psychosocial support had lower odds of problematic use. The COVID-19 pandemic was not followed by significant return to problematic substance use in a cohort of people who were already in drug addiction recovery for some time before the pandemic. However, with restricted access to environmental resources, they may have been more dependent on internal motivations. Targeting personal recovery resources with interventions could therefore reduce the chances of return to problematic substance use during a pandemic. • The COVID-19 pandemic was not followed by an increase in problematic substance use in a drug addiction recovery cohort. • Different variables predicted problematic substance use in recovery in the period before and during the COVID-19 pandemic. • During the pandemic participants seem to have been more dependent on commitment from themselves to prevent problematic use. • Building up internal recovery resources may reduce vulnerability for return to problematic substance use during a pandemic. [ABSTRACT FROM AUTHOR]

The health and well-being consequences of social isolation and loneliness in old age are increasingly being recognised. The purpose of this scoping review was to take stock of the available evidence and to highlight gaps and areas for future research. We searched nine databases for empirical papers investigating the impact of social isolation and/or loneliness on a range of health outcomes in old age. Our search, conducted between July and September 2013 yielded 11,736 articles, of which 128 items from 15 countries were included in the scoping review. Papers were reviewed, with a focus on the definitions and measurements of the two concepts, associations and causal mechanisms, differences across population groups and interventions. The evidence is largely US-focused, and loneliness is more researched than social isolation. A recent trend is the investigation of the comparative effects of social isolation and loneliness. Depression and cardiovascular health are the most often researched outcomes, followed by well-being. Almost all (but two) studies found a detrimental effect of isolation or loneliness on health. However, causal links and mechanisms are difficult to demonstrate, and further investigation is warranted. We found a paucity of research focusing on at-risk sub-groups and in the area of interventions. Future research should aim to better link the evidence on the risk factors for loneliness and social isolation and the evidence on their impact on health. [ABSTRACT FROM AUTHOR]

Objectives:To identify caregiver profiles of persons with mild to moderate dementia and to investigate differences between identified caregiver profiles, using baseline data of the international prospective cohort study Actifcare. Methods:A latent class analysis was used to discover different caregiver profiles based on disease related characteristics of 453 persons with dementia and their 453 informal caregivers. These profiles were compared with regard to quality of life (CarerQoL score), depressive symptoms (HADS-D score) and perseverance time. Results:A 5-class model was identified, with the best Bayesian Information Criterion value, significant likelihood ratio test (p< 0.001), high entropy score (0.88) and substantive interpretability. The classes could be differentiated on two axes: (i) caregivers' age, relationship with persons with dementia, severity of dementia, and (ii) tendency towards stress and difficulty adapting to stress. Classes showed significant differences with all dependent variables, and were labelled ‘older low strain’, ‘older intermediate strain’, ‘older high strain’, ‘younger low strain’ and ‘younger high strain’. Conclusion:Differences exist between types of caregivers that explain variability in quality of life, depressive symptoms and perseverance time. Our findings may give direction for tailored interventions for caregivers of persons with dementia, which may improve social health and reduce health care costs. [ABSTRACT FROM PUBLISHER]

Socioeconomic inequalities in childhood Body Mass Index (BMI) are becoming increasingly more pronounced across the world. Although countries differ in the direction and strength of these inequalities, cross-national comparative research on this topic is rare. This paper draws on harmonized longitudinal cohort data from four wealthy countries—Germany, the Netherlands, the United Kingdom (UK), and the United States (US)—to 1) map cross-country differences in the magnitude of socioeconomic inequalities in childhood BMI, and 2) to examine cross-country differences in the role of three energy-balance-related behaviors—physical activity, screen time, and breakfast consumption—in explaining these inequalities. Children were aged 5–7 at our first timepoint and were followed up at age 8–11. We used data from the German National Educational Panel Study, the Dutch Generation R study, the UK Millennium Cohort Study and the US Early Childhood Longitudinal-Kindergarten Study. All countries revealed significant inequalities in childhood BMI. The US stood out in having the largest inequalities. Overall, inequalities between children with low versus medium educated parents were smaller than those between children with high versus medium educated parents. The role of energy-balance-related behaviors in explaining inequalities in BMI was surprisingly consistent. Across countries, physical activity did not, while screen time and breakfast consumption did play a role. The only exception was that breakfast consumption did not play a role in the US. Cross-country differences emerged in the relative contribution of each behavior in explaining inequalities in BMI: Breakfast consumption was most important in the UK, screen time explained most in Germany and the US, and breakfast consumption and screen time were equally important in the Netherlands. Our findings suggest that what constitutes the most effective policy intervention differs across countries and that these should target both children from medium as well as low educated families. • All countries showed substantial socioeconomic inequalities in childhood BMI. • In all countries, inequalities in BMI steepen over course of primary school. • Protective factors among the most advantaged seem to mainly drive inequalities. • Across most countries, underlying mechanisms for inequalities in BMI are similar. • The relative contribution of each mechanism to BMI inequalities differs per country. [ABSTRACT FROM AUTHOR]

Objective: Cognitive behaviour therapy (CBT) reduces fatigue and disability in chronic fatigue syndrome (CFS). However, outcomes vary between studies, possibly because of differences in patient characteristics, treatment protocols, diagnostic criteria and outcome measures. The objective was to compare outcomes after CBT in tertiary treatment centres in the Netherlands (NL) and the United Kingdom (UK), using different treatment protocols but identical outcome measures, while controlling for differences in patient characteristics and diagnostic criteria.Methods: Consecutively referred CFS patients who received CBT were included (NL: n=293, UK: n=163). Uncontrolled effect sizes for improvement in fatigue (Chalder Fatigue Questionnaire), physical functioning (SF-36 physical functioning subscale) and social functioning (Work and Social Adjustment Scale) were compared. Multiple regression analysis was used to examine whether patient differences explained outcome differences between centres.Results: Effect sizes differed between centres for fatigue (Cohen's D NL=1.74, 95% CI=1.52-1.95; UK=0.99, CI=0.73-1.25), physical functioning (NL=0.99, CI=0.81-1.18; UK=0.33, CI=0.08-0.58) and social functioning (NL=1.47, CI=1.26-1.69; UK=0.61, CI=0.35-0.86). Patients in the UK had worse physical functioning at baseline and there were minor demographic differences. These could not explain differences in centre outcome.Conclusion: Effectiveness of CBT differed between treatment centres. Differences in treatment protocols may explain this and should be investigated to help further improve outcomes. [ABSTRACT FROM AUTHOR]

Aims To estimate associations between smoking initiation, smoking persistence and smoking heaviness and caffeine consumption in two population-based samples from the Netherlands and the United Kingdom. Design Observational study employing data on self-reported smoking behaviour and caffeine consumption. Setting Adults from the general population in the Netherlands and the United Kingdom. Participants Participants from the Netherlands Twin Register [NTR: n = 21 939, mean age 40.8, standard deviation (SD) = 16.9, 62.6% female] and the Avon Longitudinal Study of Parents and Children (ALSPAC: n = 9086, mean age 33.2, SD = 4.7, 100% female). Measurements Smoking initiation (ever versus never smoking), smoking persistence (current versus former smoking), smoking heaviness (number of cigarettes smoked) and caffeine consumption in mg per day through coffee, tea, cola and energy drinks. Findings After correction for age, gender (NTR), education and social class (ALSPAC), smoking initiation was associated with consuming on average 52.8 [95% confidence interval (CI) = 45.6-60.0; NTR] and 59.5 (95% CI = 51.8-67.2; ALSPAC) mg more caffeine per day. Smoking persistence was also associated with consuming more caffeine [+57.9 (95% CI = 45.2-70.5) and +83.2 (95% CI = 70.2-96.3) mg, respectively]. Each additional cigarette smoked per day was associated with 3.7 (95% CI = 1.9-5.5; NTR) and 8.4 (95% CI = 6.9-10.0; ALSPAC) mg higher daily caffeine consumption in current smokers. Smoking was associated positively with coffee consumption and less strongly with cola and energy drinks. For tea, associations were positive in ALSPAC and negative in NTR. Conclusions There appears to be a positive association between smoking and caffeine consumption in the Netherlands and the United Kingdom. [ABSTRACT FROM AUTHOR]

Objective: Studies have provided evidence of heterogeneity within chronic fatigue syndrome (CFS), but few have used data from large cohorts of CFS patients or replication samples.Methods: 29 UK secondary-care CFS services recorded the presence/absence of 12 CFS-related symptoms; 8 of these symptoms were recorded by a Dutch tertiary service. Latent Class Analysis (LCA) was used to assign symptom profiles (phenotypes). Regression models were fitted with phenotype as outcome (in relation to age, sex, BMI, duration of illness) and exposure (in relation to comorbidities and patient-reported measures).Results: Data were available for 7041 UK and 1392 Dutch patients. Almost all patients in both cohorts presented with post-exertional malaise, cognitive dysfunction and disturbed/unrefreshing sleep, and these 3 symptoms were excluded from LCA. In UK patients, six phenotypes emerged: 'full' polysymptomatic (median 8, IQR 7-9 symptoms) 32.8%; 'pain-only' (muscle/joint) 20.3%; 'sore throat/painful lymph node' 4.5%; and 'oligosymptomatic' (median 1, IQR 0-2 symptoms) 4.7%. Two 'partial' polysymptomatic phenotypes were similar to the 'full' phenotype, bar absence of dizziness/nausea/palpitations (21.4%) or sore throat/painful lymph nodes (16.3%). Women and patients with longer duration of illness were more likely to be polysymptomatic. Polysymptomatic patients had more severe illness and more comorbidities. LCA restricted to 5 symptoms recorded in both cohorts indicated 3 classes (polysymptomatic, oligosymptomatic, pain-only), which were replicated in Dutch data.Conclusions: Adults with CFS may have one of 6 symptom-based phenotypes associated with sex, duration and severity of illness, and comorbidity. Future research needs to determine whether phenotypes predict treatment outcomes, and require different treatments. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most common cause of disability in the elderly. Clinical frailty is associated with high mortality, but few studies have explored the relationship between OA and frailty. The objective of this study was to consider the association between OA and frailty/pre-frailty in an elderly population comprised of six European cohorts participating in the EPOSA project.Methods: Longitudinal study using baseline data and first follow-up waves, from EPOSA; 2,455 individuals aged 65-85 years were recruited from pre-existing population-based cohorts in Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom. Data were collected on clinical OA at any site (hand, knee or hip), based on the clinical classification criteria developed by the American College of Rheumatology (ACR). Frailty was defined according to Fried's criteria. The covariates considered were age, gender, educational level, obesity and country. We used multinomial logistic regression to analyse the associations between OA, frailty/pre-frailty and other covariates.Results: The overall prevalence of clinical OA at any site was 30.4 % (95 % CI:28.6-32.2); frailty was present in 10.2 % (95 % CI:9.0-11.4) and pre-frailty in 51.0 % (95 % CI:49.0-53.0). The odds of frailty was 2.96 (95 % CI:2.11-4.16) and pre-frailty 1.54 (95 % CI:1.24-1.91) as high among OA individuals than those without OA. The association remained when Knee OA, hip OA or hand OA were considered separately, and was stronger in those with increasing number of joints.Conclusions: Clinical OA is associated with frailty and pre-frailty in older adults in European countries. This association might be considered when designing appropriate intervention strategies for OA management. [ABSTRACT FROM AUTHOR]

Objective: Patients with repaired tetralogy of Fallot (TOF) are followed serially by cardiac magnetic resonance (CMR) for surveillance of RV dilation and dysfunction. We sought to define the prevalence of progressive RV disease and the optimal time interval between CMR evaluations.Methods: Candidates were selected from a multicentre TOF registry and were included if ≥2 CMR studies performed ≥6 months apart were available without interval cardiovascular interventions. Patients with 'disease progression' (defined as increase in RV end-diastolic volume index (RVEDVi) ≥30 mL/m(2), decrease in RVEF ≥10% or decrease in LVEF ≥10%) were compared with those with 'disease non-progression' (defined as RVEDVi increase ≤5 mL/m(2), RVEF decrease ≤3% and LVEF decrease ≤3%).Results: A total of 849 CMR studies in 339 patients (median age at first CMR 23.6 years) were analysed. Over a median interval of 2.2 years between CMR pairs, RVEDVi increased 4±18 mL/m(2) (p<0.001), RV end-systolic volume index increased 3±13 mL/m(2) (p<0.001), RVEF decreased 1%±6% (p=0.02) and LVEF decreased 1%±6% (p=0.001). Disease progression was observed in 15% (n=76) and non-progression in 26% (n=133). There were no significant differences between those with and without progression in baseline demographic, anatomic, ECG, exercise or baseline CMR characteristics. The optimal time interval between CMR studies for detection of progression was a 3-year interval (63% sensitivity, 65% specificity, area under the receiver operating characteristic curve 0.65).Conclusions: Although progressive RV dilation and decline in biventricular systolic function occur at a slow pace in the majority of adults with repaired TOF, 15% of patients experience rapid disease progression. The results of this study support the practice of serial CMR examinations to identify progressive disease at a time interval of up to 3 years. [ABSTRACT FROM AUTHOR]

Objective: To describe influences on decision-making and prognostic variables in the prenatal management of fetal lower urinary tract obstruction (LUTO).Methods: This was a prospective registry study of pregnant women with a male fetus with LUTO from centers within the British Isles and The Netherlands. Women and/or their clinicians were given the treatment option of either conservative management or vesicoamniotic shunting (VAS). Baseline characteristics of women in the registry, reasons for entry to the registry and pregnancy outcomes were assessed. The main study outcomes were survival to 28 days after delivery, further survival to 2 years and renal function. Logistic regression analysis was used to examine prognostic variables that affected outcome. Results were compared with those of women in a randomized controlled trial (RCT) who were allocated randomly to a treatment option.Results: Forty-five women were registered, of whom 78% (35/45) underwent conservative management. Twenty-seven women entered the registry owing to their clinician's preference for management and 18 because of their own preference. Compared to the conservative-management group of the RCT, a higher proportion of women in the registry opting for conservative management had a normal amniotic fluid volume at diagnosis (P = 0.05) and a diagnosis of LUTO ≥ 24 weeks' gestation (P = 0.003). On multivariable logistic regression analysis, these variables showed a significant association with perinatal survival (P < 0.001). Survival to 28 days after delivery was higher in the conservative-management group, at 69% (24/35), compared to 40% (4/10) in the VAS group (P = 0.02) but this difference had limited statistical significance owing to small study size (relative risk, 0.58 (95% CI, 0.26-1.29); P = 0.14).Conclusion: In our prospective registry, the majority of fetuses with LUTO received conservative management, which was associated with better short- and long-term outcomes. A significant proportion of these pregnancies had normal amniotic fluid volume and a gestational age at diagnosis of ≥ 24 weeks, characteristics shown to be associated with improved survival. [ABSTRACT FROM AUTHOR]

Aims To report a systematic review of the psychometric properties of self-report instruments to identify the symptoms of anxiety in pregnancy to help clinicians and researchers select the most suitable instrument. Background Excessive anxiety in pregnancy is associated with adverse birth outcomes, developmental and behavioural problems in infants and postnatal depression. Despite recommendations for routine psychological assessment in pregnancy, the optimal methods to identify anxiety in pregnancy have not been confirmed. Design Psychometric systematic review. Data sources A systematic literature search of the multiple databases (1990-September 2014). Review methods Identification of self-report instruments to measure anxiety in pregnancy using COSMIN guidelines to assess studies reporting a psychometric evaluation of validity and reliability. Results Thirty-two studies were included. Studies took place in the UK, Australia, Belgium, Canada, Germany, Italy, Scandinavia, Spain and the Netherlands. Seventeen different instruments were identified. Measures of validity were reported in 19 papers and reliability in 16. The overall quality of the papers was rated as fair to excellent using the COSMIN checklist. Only one paper scored excellent in more than one category. Conclusion Many instruments have been adapted for use in different populations to those for which they were designed. The State Trait Anxiety Inventory, Edinburgh Postnatal Depression Scale and the Hospital Anxiety and Depression Scale have been tested more frequently than other instruments, yet require further assessment to confirm their value for use in pregnancy. [ABSTRACT FROM AUTHOR]

BackgroundDo DSM-IV diagnostic criteria for major depression (MD) in Chinese and Western women perform in a similar manner?MethodThe CONVERGE study included interview-based assessments of women of Han Chinese descent with treated recurrent MD. Using Mplus software, we investigated the overall degree of between-sample measurement invariance (MI) for DSM-IV diagnostic criteria for MD in the CONVERGE sample and samples selected from four major Western studies from the USA and Europe matched to the inclusion criteria of CONVERGE. These analyses were performed one pair at a time. We then compared the results from CONVERGE paired with Western samples to those obtained when examining levels of MI between pairs of the Western samples.ResultsAssuming a single factor model for the nine diagnostic criteria for MD, the level of MI based on global fit indexes observed between the CONVERGE and the four Western samples was very similar to that seen between the Western samples. Comparable results were obtained when using a two-factor structure for MI testing when applied to the 14 diagnostic criteria for MD disaggregated for weight, appetite, sleep, and psychomotor changes.ConclusionsDespite differences in language, ethnicity and culture, DSM criteria for MD perform similarly in Chinese women with recurrent MD and comparable subjects from the USA and Europe. The DSM criteria for MD may assess depressive symptoms that are relatively insensitive to cultural and ethnic differences. These results support efforts to compare findings from depressed patients in China and Western countries. [ABSTRACT FROM AUTHOR]

Aim To investigate how work-related characteristics and work ability influence nursing staff decisions to change employer or leave the profession. Background Previous cross-sectional studies have indicated that decreased work ability and unfavourable work-related characteristics are important determinants for the intention to leave the profession among nursing staff. Methods A 1-year longitudinal study, using data from the European Nurses' Early Exit Study. The study population consisted of 9927 (66%) members of the eligible nursing staff of which 345 left their current employer. Work-related characteristics, work ability and employment status were assessed by questionnaires. Results Nursing staff with a low work ability were more likely to either change employer or leave the profession. Among nursing staff with a low work ability the risk of changing employer increased significantly with unfavourable work-related characteristics. However, among nursing staff with a good work ability the risk of changing employer barely changed with unfavourable work-related characteristics. Conclusion The negative effects of decreased work ability on changing employer and leaving the profession are partly counterbalanced by favourable psychological and physical work-related characteristics. Implications for nursing management Managers should implement strategies that focus on promoting the work ability of nursing staff in combination with improving work-related characteristics in order to prevent unnecessary changes of employment. [ABSTRACT FROM AUTHOR]

To explore, from a philosophy of knowledge perspective, the contribution of the guideline development process to reducing epistemic uncertainty in clinical decision-making – defined as the challenge of applying evidence to patients, dealing with conflicting information and determining the level of confidence in a medical conclusion. Longitudinal ethnographic study of national guideline development panels. Fieldnotes were collected from 19 panel meetings in UK, Netherlands and Norway (~120 h of observation) between September 2016 and February 2019. Draft guidelines, review protocols and background material were collated (~200 documents). Data were analyzed thematically to gain familiarity and then theorized using concepts of knowledge development and use and clinical decision-making. Guideline development panels in all three countries wrestled with epistemic tensions – notably between the desire to "purify" an assumed external truth (for example by limiting included evidence to high-quality randomized controlled trials) and a more pragmatic and pluralist approach that drew on a wider range of evidence including qualitative research, real-world data, clinical experience and patient testimony. Detailed analysis of the process by which particular guideline recommendations were constructed allowed us to draw out the implications of these tensions for guideline users in clinical practice. Guideline development panels apply multiple – often conflicting – understandings of knowledge, inference and truth in an attempt to reduce epistemic uncertainty. Guidelines makers, clinicians, scientists and students should engage critically and reflexively with the philosophical assumptions that underpin guideline development and inductive inference to build capability to deal with clinical complexity. • Ethnographic study of guideline development panels. • Informed by philosophical notions of the nature of knowledge, inference and truth. • Panel discussions included clinical experience and a broad range of knowledge. • Panels wrestled with tensions between purist and pluralist approaches of EBM. • Our findings question the philosophical assumptions of guideline development panels. [ABSTRACT FROM AUTHOR]

Facing rapidly ageing populations, many Western countries aim to stimulate informal care provision as a way to meet the growing long-term care (LTC) demand. While various studies report the impact of providing informal care on the health of caregivers, it is less clear whether and to what extent this impact differs across countries. Using propensity score matching we match caregivers to similar non-caregiving individuals using four waves of the Dutch Study on Transitions in Employment, Ability and Motivation and the UK Household Longitudinal Study. The samples consist of 8129 Dutch and 7186 UK respondents, among which respectively 1711 and 1713 individuals are identified as caregivers. We explore whether the health impact of providing informal care differs by country once similar caregivers, in terms of the intensity of provided care, are compared. In both countries we find negative mental health effects of providing informal care. While these effects slightly differ by country, the main differences arise between subgroups of caregivers. Individuals that provide more than 20 hours of informal care per week, and those who face a double burden of care and full-time employment experience the most severe negative mental health effects. These results indicate that health effects of providing informal care are mediated by the specific caregiving context, allowing policymakers to use information on this context to provide targeted aid. In addition, it suggests that previously reported differences of caregiving effects across countries could be driven by differences in the population of informal caregivers which are shaped by countries' LTC policies. • We estimate the caregiving effect on health in the Netherlands and the UK. • Providing informal care leads to lower mental health in both countries. • Impact of informal care provision on health is largest for high-intensity carers. • Irrespective of LTC system, a similar caregiving context leads to similar health effects. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE, including deep vein thrombosis [DVT] and pulmonary embolism [PE]) has an annual incidence rate of 104–183 per 100,000 person-years. After a VTE episode, the two-year recurrence rate is about 17%. Consequently, effective and safe anticoagulation is paramount. Edoxaban is a direct oral anticoagulant (DOAC) approved VTE treatment. Current safety and efficacy data are derived from clinical trials, and information about treatment durations beyond 12 months are not available. Methods: ETNA-VTE-Europe is an 18-month prospective, single-arm, non-interventional, multinational post-authorisation safety study. Approximately 310 sites across eight European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Switzerland and the United Kingdom) will participate in the study, with the intention to represent the regional distributions of centres, healthcare settings and specialties. An estimated cohort of 2700 patients will be recruited, the only enrolment criteria being acute symptomatic VTE, no participation in an interventional study, and treating physician decision to prescribe edoxaban independently from the registry. Data from patient medical records and/or telephone interviews will be collected at baseline, 1, 3, 6, 12 and 18 months. The primary objective is to evaluate the 18-month rate of symptomatic VTE recurrence in patients with VTE treated with edoxaban outside a clinical trial. The co-primary objective is to evaluate the real-world rates of bleeding and adverse drug reactions. Secondary outcomes include rates of other patient-relevant safety events, adherence to and discontinuation of edoxaban. Furthermore, 12-month ETNA-VTE-Europe data will be considered in the context of those for patients receiving different anticoagulants in the PREFER in VTE registry and Hokusai-VTE clinical trial. Conclusions: ETNA-VTE-Europe will allow the safety and effectiveness of edoxaban to be evaluated over an extended period in acute symptomatic VTE patients encountered in routine clinical practice. Findings will be informative for European practitioners prescribing edoxaban as part of real-world VTE treatment/prevention. Trial registration: ClinicalTrials.gov Identifier: NCT02943993. [ABSTRACT FROM AUTHOR]