A comparison of social prescribing approaches across twelve high-income countries.

BACKGROUND: Social prescribing connects patients with community resources to improve their health and well-being. It is gaining momentum globally due to its potential for addressing non-medical causes of illness while building on existing resources and enhancing overall health at a relatively low cost. The COVID-19 pandemic further underscored the need for policy interventions to address health-related social issues such as loneliness and isolation. AIM: This paper presents evidence of the conceptualisation and implementation of social prescribing schemes in twelve countries: Australia, Austria, Canada, England, Finland, Germany, Portugal, the Slovak Republic, Slovenia, the Netherlands, the United States and Wales. METHODS: Twelve countries were identified through the Health Systems and Policy Monitor (HSPM) network and the EuroHealthNet Partnership. Information was collected through a twelve open-ended question survey based on a conceptual model inspired by the WHO's Health System Framework. RESULTS: We found that social prescribing can take different forms, and the scale of implementation also varies significantly. Robust evidence on impact is scarce and highly context-specific, with some indications of cost-effectiveness and positive impact on well-being. CONCLUSIONS: This paper provides insights into social prescribing in various contexts and may guide countries interested in holistically tackling health-related social factors and strengthening community-based care. Policies can support a more seamless integration of social prescribing into existing care, improve collaboration among sectors and training programs for health and social care professionals.

Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS.

PURPOSE: Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. METHODS: Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. RESULTS: We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. CONCLUSION: This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

Time trends in the regional distribution of physicians, nurses and midwives in Europe.

BACKGROUND: Country-level data suggest large differences in the supply of health professionals among European countries. However, little is know about the regional supply of health professionals taking a cross-country comparative perspective. The aim of the study was to analyse the regional distribution of physicians, nurses and midwives in the highest and lowest density regions in Europe and examine time trends. METHODS: We used Eurostat data and descriptive statistics to assess the density of physicians, nurses and midwives at national and regional levels (Nomenclature of Territorial Units for Statistics (NUTS) 2 regions) for 2017 and time trends (2005-2017). To ensure cross-country comparability we applied a set of criteria (working status, availability over time, geographic availability, source). This resulted in 14 European Union (EU) countries and Switzerland being available for the physician analysis and eight countries for the nurses and midwives analysis. Density rates per population were analysed at national and NUTS 2 level, of which regions with the highest and lowest density of physicians, nurses and midwives were identified. We examined changes over time in regional distributions, using percentage change and Compound Annual Growth Rate (CAGR). RESULTS: There was a 2.4-fold difference in the physician density between the highest and lowest density countries (Austria national average: 513, Poland 241.6 per 100,000) and a 3.5-fold difference among nurses (Denmark: 1702.5, Bulgaria: 483.0). Differences by regions across Europe were higher than cross-country variations and varied up to 5.5-fold for physicians and 4.4-fold for nurses/midwives and did not improve over time. Capitals and/or major cities in all countries showed a markedly higher supply of physicians than more sparsely populated regions while the density of nurses and midwives tended to be higher in more sparsely populated areas. Over time, physician rates increased faster than density levels of nurses and midwives. CONCLUSIONS: The study shows for the first time the large variation in health workforce supply at regional levels and time trends by professions across the European region. This highlights the importance for countries to routinely collect data in sub-national geographic areas to develop integrated health workforce policies for health professionals at regional levels.

Restless Legs Syndrome and Other Movement Disorders of Sleep-Treatment Update.

PURPOSE OF REVIEW: The purpose of this review article is to summarize and discuss the recent advances in the treatment of restless legs syndrome (RLS), as well as REM sleep behavior disorder (RBD), and periodic leg movement disorder (PLMD). RECENT FINDINGS: Traditionally, dopaminergic therapy has been considered the sole option for first-line treatment of RLS due to their impressive acute efficacy. Dopamine agonists such as oral pramipexole and ropinirole, as well as transdermal rotigotine are all effective treatment options. However, augmentation of the RLS symptoms is a major limitation of oral dopaminergic therapy. Recently, gabapentinoid agents such as gabapentin enacarbil and pregabalin have shown comparable short-term efficacy to dopaminergics with lower risk of augmentation of the RLS symptoms. Recent evidence on the efficacy of oxycodone-naloxone in treatment-resistant RLS provides an additional therapeutic avenue. The increasing understanding of the role of iron in RLS pathophysiology has led to new options in iron supplementation therapy in RLS, including treatment with ferric carboxymaltose. With emerging evidence of augmentation being a side effect specific to dopaminergic treatment, gabapentinoids are considered a safer option as initial treatment. In severe refractory RLS, oxycodone-naloxone can be used. If iron stores are low, IV iron formulations should be the initial treatment choice. New treatment options are needed to address issues with current therapies.

Microstructural white matter abnormalities in patients with COL6A3 mutations (DYT27 dystonia).

INTRODUCTION: Recently, mutations in the collagen gene COL6A3 have been reported in patients with autosomal-recessive, isolated dystonia (DYT27). Zebrafish models of COL6A3 mutations showed deficits in axonal targeting mechanisms. Therefore, COL6A3 mutations have been considered to contribute to irregular sensorimotor circuit formation. To test this hypothesis, we examined structural abnormalities in cerebral fiber tracts of dystonia patients with COL6A3 mutations using diffusion tensor imaging. METHODS: We performed a voxel-wise statistical analysis to compare fractional anisotropy within whole-brain white matter in four of the previously reported dystonia patients with COL6A3 mutations and 12 healthy controls. Region of interests-based probabilistic tractography was performed as a post-hoc-analysis. RESULTS: Dystonia patients with COL6A3 mutations showed significantly decreased fractional anisotropy bilaterally in midbrain, pons, cerebellar peduncles, thalamus, internal capsule and in frontal and parietal subcortical regions compared to healthy controls. Tractography revealed a decreased fractional anisotropy in patients with COL6A3-associated dystonia between bilateral dentate nucleus and thalamus. CONCLUSION: Diffusion tensor imaging demonstrates an altered white matter structure especially in various parts of the cerebello-thalamo-cortical network in dystonia patients with COL6A3 mutations. This suggests that COL6A3 mutations could contribute to abnormal circuit formation as potential basis of dystonia.

Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation.

A Task Force was established by the International Restless Legs Syndrome Study Group (IRLSSG) in conjunction with the European Restless Legs Syndrome Study Group (EURLSSG) and the RLS Foundation (RLS-F) to develop evidence-based and consensus-based recommendations for the prevention and treatment of long-term pharmacologic treatment of dopaminergic-induced augmentation in restless legs syndrome/Willis-Ekbom disease (RLS/WED). The Task Force made the following prevention and treatment recommendations: As a means to prevent augmentation, medications such as α2δ ligands may be considered for initial RLS/WED treatment; these drugs are effective and have little risk of augmentation. Alternatively, if dopaminergic drugs are elected as initial treatment, then the daily dose should be as low as possible and not exceed that recommended for RLS/WED treatment. However, the physician should be aware that even low dose dopaminergics can cause augmentation. Patients with low iron stores should be given appropriate iron supplementation. Daily treatment by either medication should start only when symptoms have a significant impact on quality of life in terms of frequency and severity; intermittent treatment might be considered in intermediate cases. Treatment of existing augmentation should be initiated, where possible, with the elimination/correction of extrinsic exacerbating factors (iron levels, antidepressants, antihistamines, etc.). In cases of mild augmentation, dopamine agonist therapy can be continued by dividing or advancing the dose, or increasing the dose if there are breakthrough night-time symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. For severe augmentation the patient can be switched either to an α2δ ligand or rotigotine, noting that rotigotine may also produce augmentation at higher doses with long-term use. In more severe cases of augmentation an opioid may be considered, bypassing α2δ ligands and rotigotine.

Narcolepsy is strongly associated with the T-cell receptor alpha locus.

Narcolepsy with cataplexy, characterized by sleepiness and rapid onset into REM sleep, affects 1 in 2,000 individuals. Narcolepsy was first shown to be tightly associated with HLA-DR2 (ref. 3) and later sublocalized to DQB1*0602 (ref. 4). Following studies in dogs and mice, a 95% loss of hypocretin-producing cells in postmortem hypothalami from narcoleptic individuals was reported. Using genome-wide association (GWA) in Caucasians with replication in three ethnic groups, we found association between narcolepsy and polymorphisms in the TRA@ (T-cell receptor alpha) locus, with highest significance at rs1154155 (average allelic odds ratio 1.69, genotypic odds ratios 1.94 and 2.55, P < 10(-21), 1,830 cases, 2,164 controls). This is the first documented genetic involvement of the TRA@ locus, encoding the major receptor for HLA-peptide presentation, in any disease. It is still unclear how specific HLA alleles confer susceptibility to over 100 HLA-associated disorders; thus, narcolepsy will provide new insights on how HLA-TCR interactions contribute to organ-specific autoimmune targeting and may serve as a model for over 100 other HLA-associated disorders.