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Abstract Background Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS. Methods This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 μg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization. Discussion Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19. Trial registration ClinicalTrials.gov, NCT04536350 . Registered 02 September 2020.

Abstract Background The coronavirus disease 19 (COVID-19) pandemic has caused millions of deaths, and new treatments are urgently needed. Factors associated with a worse COVID-19 prognosis include old age (> 65 years), ethnicity, male sex, obesity, and people with comorbidities. Furthermore, vitamin D deficiency was reported as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. According to a recent clinical case series, vitamin D deficiency is a modifiable risk factor, which has the prospect of reducing hospital stay, intensive care, and fatal outcomes. Vitamin D has potent immunomodulatory properties, and its supplementation might improve important outcomes in critically ill and vitamin D-deficient COVID-19 patients. Despite the evidence that supports an association between vitamin D deficiency and COVID-19 severity, there is uncertainty about the direct link. Therefore, the aim of the trial is to assess if high-dose vitamin D supplementation has a therapeutic effect in vitamin D-deficient patients with COVID-19. Methods As the trial design, a randomized, placebo-controlled, double-blind, multi-center approach was chosen to compare a high single dose of vitamin D (140,000 IU) followed by treatment as usual (TAU) (VitD + TAU) with treatment as usual only (placebo + TAU) in patients with COVID-19 and vitamin D deficiency. Discussion Vitamin D substitution in patients with COVID-19 and vitamin D deficiency should be investigated for efficacy and safety. The study aim is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with high-dose vitamin D supplementation. Latest studies suggest that vitamin D supplementation in patients with COVID-19 is highly recommended to positively influence the course of the disease. With this randomized controlled trial, a contribution to new treatment guidelines shall be made. Trial registration ClinicalTrials.gov NCT04525820 and SNCTP 2020-01401

BackgroundPulmonary embolism (PE) is not only a life-threatening disease but also a public health issue with significant economic burden. The aim of the study was to identify factors—including the role of primary care—that predict length of hospital stay (LOHS), mortality and re-hospitalization within 6 months of patients admitted for PE.MethodA retrospective cohort study was conducted with patients presenting to a Swiss public hospital with PE diagnosed at the hospital between November 2018 and October 2020. Multivariable logistic and zero-truncated negative binomial regression analyses were performed to assess risk factors for mortality, re-hospitalization and LOHS. Primary care variables encompassed whether patients were sent by their general practitioner (GP) to the emergency department and whether a GP follow-up assessment after discharge was recommended. Further analyzed variables were pulmonary embolism severity index (PESI) score, laboratory values, comorbidities, and medical history.ResultsA total of 248 patients were analyzed (median 73 years and 51.6% females). On average patients were hospitalized for 5 days (IQR 3–8). Altogether, 5.6% of these patients died in hospital, and 1.6% died within 30 days (all-cause mortality), 21.8% were re-hospitalized within 6 months. In addition to high PESI scores, we detected that, patients with an elevated serum troponin, as well as with diabetes had a significantly longer hospital stay. Significant risk factors for mortality were elevated NT-proBNP and PESI scores. Further, high PESI score and LOHS were associated with re-hospitalization within 6 months. PE patients who were sent to the emergency department by their GPs did not show improved outcomes. Follow-up with GPs did not have a significant effect on re-hospitalization.ConclusionDefining the factors that are associated with LOHS in patients with PE has clinical implications and may help clinicians to allocate adequate resources in the management of these patients. Serum troponin and diabetes in addition to PESI score might be of prognostic use for LOHS. In this single-center cohort study, PESI score was not only a valid predictive tool for mortality but also for long-term outcomes such as re-hospitalization within 6 months.

Abstract Background In addition to the threat of the COVID-19 pandemic to physical health, mental health is challenged by the emotional response to the situation and the official measures taken to stop the pandemic. This study aimed to assess the prevalence of impaired mental well-being due to COVID-19 and explore associated factors. Methods The study was an observational, population-based, nationwide, cross-sectional online survey of a representative sample of the general Swiss population performed between March and April 2020. Participants reported on mental well-being, self-isolation/quarantine, their risk for developing severe COVID-19, and their work situation. Multivariable logistic regression analyses assessed risk factors for impaired mental well-being due to the pandemic. Results Data from 1022 individuals were analysed. The median age was 44 years (range 18 to 78) and 49% were women. A third of respondents reported that the COVID-19 pandemic impaired their mental well-being and almost half reported specific mental health concerns. Impaired mental well-being was associated with having health problems (OR = 1.88, 95% CI: 1.29–2.74, vs no problems), being or living with someone at risk for severe COVID-19 (OR = 1.38, 95% CI: 1–1.9,), smoking (OR = 1.8, 95% CI: 1.24–2.61), living in urban residential environments (OR = 1.62, 95% CI: 1.13–2.32, vs rural), not being able to work due to closed workplace (OR = 1.66, 95% CI: 1.04–2.67), aged between 18 and 29 years old (OR = 1.99, 95% CI: 1.32–3.01, vs 45 to 59 years old), and living in a single household (living with someone, OR = 0.65, 95% CI: 0.44–0.97,vs single household). Overall, the most significant covariates of impaired mental well-being were specific mental health concerns: feeling depressed (OR = 7.21, 95% CI: 4.5–11.55), feeling less pleasure in doing things than before (OR = 6.28, 95% CI: 4.1–9.62), feeling anxious (OR = 6.13, 95% CI: 3.91–9.59) and feeling lonely (OR = 4.08, 95% CI: 2.53–6.58). Conclusion Impaired mental well-being can carry long-term consequences. We encourage policymakers to implement strategies to promote mental health during this pandemic situation. Special attention should be addressed to the youngest, those at risk for severe COVID-19 and those with government-imposed work restrictions.

BackgroundIntermediate care is often defined as healthcare occurring somewhere between traditional primary (community) and secondary (hospital) care settings. High quality intermediate care is important in dementia, may prevent caregiver burnout and also lead to optimal care for people with dementia. However, very little is known about the point of intermediate care for persons with dementia in Europe.Research questionsWhat intermediate care services exist and how are they utilized in the care of people with dementia in Europe?ObjectiveThis study aims at describing the point of view of General Practitioners on intermediate care services for people with dementia across Europe.MethodsKey informant survey was sent to GPs via a self-developed questionnaire with space for open ended comments. 16 European countries participated to this cross-sectional mixed method study. Given the volunteer nature of the study, no minimum sample size requirements were applied to participation. Convenience sampling technique was used to address variations due to regional variations and regulations within the same country. Descriptive analyses of all intermediate care facilities groups by countries were performed. Qualitative analyses approach was used for the optional-free text to exemplify and/or complete the reasons contained in the closed response categories.ResultsThe questionnaire was sent to 16 European countries. 583 questionnaires were analyzed. The responding physicians were 48 (± 11) years old on average and they had been in practice for an average of 18 (+ /11) years. The types of intermediate care considered were integrated at-home services, respite and relief services, day care centers and nursing homes. Their availability was considered very inhomogeneous by the majority of respondents. The main benefits of intermediate care cited were better medical care for the patient (78%), better quality of life for the caregiver (67%), prevention of the caregiver burden (73%) and a break for the caregiver (59%). The reported difficulties were: accessing these facilities due to limited financial support (76%) and cumbersome administrative procedures (67%). Many other facets of our findings were captured in the qualitative themes that emerged.ConclusionIntermediate care in Europe is diverse and heterogeneous. Major concerns of GPs are about the cost issues and the cumbersome administrative procedures to access them.

Abstract Background The distribution of health care resources during a pandemic is challenging. The aim of the study was to describe the use of health care in a representative sample of the Swiss population during the SARS-CoV-2 pandemic in 2020, and to compare it to data from a survey conducted in 2018. Methods We conducted an observational, population-based, nationwide, repeated cross-sectional survey of the adult Swiss general population in 2018 and in March and April 2020 during the first wave of the SARS-CoV-2 pandemic. Recruitment and data acquisition was conducted by the Link Institute in Lucerne in representative samples of Swiss citizens in 2020 and in 2018. Variables of interest were estimates of health problems, health seeking behaviour, medication and health care use in the population. Results In total, we included data of 1980 individuals (in 2018 N = 958 and in 2020 N = 1022). Across both rounds of data collection the median age was 46 years (range = 18–79 years) and 50% were women. Per 1000 adults, half had at least one symptom and a quarter sought medical advice across both surveys. The most frequently consulted health providers in 2020 were general practitioners (GP) (180/1000), specialist physicians (41/1000), pharmacies (38/1000), the internet (26/1000) and accident and emergency units (25/1000). Compared to 2018, we noted a significant increase in the use of health providers during the pandemic, which was independent of demographic variables for the following health care providers: use of internet (OR = 9.8), pharmacy (OR = 2.64), accident and emergency units (OR = 2.54), and a significant decrease in the number of people who consulted specialist physicians (OR = 0.46). Overall, 76/1000 contacted their GP in relation to COVID-19. Conclusions Compared to 2018, GPs remained the most important source of medical advice for the population during the first wave of the COVID-19 pandemic in Switzerland. While the self-appraisal of health problems and of the need for medical advice remained constant, individuals seemed to change their provider choice during the pandemic, with an increased utilisation of accident and emergency units and pharmacies, which represent easily accessible and low-threshold medical services.

INTRODUCTION: General practitioners (GPs) play a key role in the delivery of health care in Switzerland. Assessing GPs’ workload over time is essential to meet the population’s health service demand and for future health care planning. METHODS: The study involved four questionnaire-based cross-sectional studies among a representative sample of Swiss GPs on a five-yearly basis since 2005. Data on GPs’ self-estimated workload and practice administration (face-to-face consultations, house calls, nursing home visits and clinical administrative work) were analysed in hours per week (h/week) or full-time equivalents (FTE; 100% = 55 h/week). RESULTS: The mean age of GPs (n = 2,037) in 2020 was 54.9 years, significantly higher than in 2005 (51.4 years, p

Vitamin D and its role in the coronavirus-19 disease (COVID-19) pandemic has been controversially discussed, with inconclusive evidence about vitamin D3 (cholecalciferol) supplementation in COVID-19 patients. Vitamin D metabolites play an important role in the initiation of the immune response and can be an easily modifiable risk factor in 25-hydroxyvitamin D3 (25(OH)D3)-deficient patients. This is a multicenter, randomized, placebo-controlled double-blind trial to compare the effect of a single high dose of vitamin D3 followed by treatment as usual (TAU) of daily vitamin D3 daily until discharge versus placebo plus TAU in hospitalized patients with COVID-19 and 25(OH)D3-deficiency on length hospital stay. We included 40 patients per group and did not observe a significant difference in the median length of hospital stay (6 days in both groups, p = 0.920). We adjusted the length of stay for COVID-19 risk factors (β = 0.44; 95% CI: −2.17–2.22), and center (β = 0.74; 95% CI: −1.25–2.73). The subgroup analysis in patients with severe 25(OH)D3-deficiency (p = 0.299). The competing risk model with death did not reveal significant differences between the group in the length of stay (HR = 0.96, 95% CI 0.62–1.48, p = 0.850). Serum 25(OH)D3 level increased significantly in the intervention group (mean change in nmol/L; intervention: +26.35 vs. control: –2.73, p < 0.001). The intervention with 140,000 IU vitamin D3 + TAU did not significantly shorten the length of hospital stay but was effective and safe for the elevation of serum 25(OH)D3 levels.

Abstract Background Poor medication-adherence is common in chronic lung patients, resulting in reduced health-outcomes and increased healthcare-costs. This study aimed to investigate the impact of an acoustic reminder and support calls on adherence to inhaled therapy in asthma and COPD patients and to determine their effect on exacerbations. Methods This single-blinded randomized controlled trial investigated asthma and COPD patients during 6 months in an ambulatory setting. The intervention consisted of daily alarm clock and support phone calls, whenever use of rescue medication doubled or inhaled medication was not taken as prescribed. Primary outcome was time to next exacerbation. Frequency of exacerbations, adherence to inhaled medication and quality of life scores were secondary outcomes. Cox and Poisson regression were used to determine intervention effect on time to exacerbation and frequency of exacerbations, respectively. Results Seventy-five participants were assigned to the intervention group and 74 to usual follow-up care. During a median follow-up of 6.2 months, 22 and 28% in the intervention and control groups respectively, experienced at least one exacerbation. Intervention had no effect on time to first exacerbation (HR 0.65, 95% CI 0.21 to 2.07, P = .24), but showed a trend toward a 39% decreased frequency of exacerbations (RR = 0.61, 95% CI 0.35 to 1.03, P = .070) for the adjusted models, respectively. The intervention group had significantly more days with 80–100% taking adherence regarding puff inhalers (82 ± 14% vs. 60 ± 30%, P

Abstract Background Dementia is often underdiagnosed in general practice, which may be based on general practitioners’ (GPs’) knowledge and emotional factors as well as external problems. This study aimed to describe GPs’ attitudes toward early diagnosis of dementia. Methods Cross-sectional postal survey in Switzerland in 2017. Members of the Swiss Association of General Practitioners (N = 4460) were asked to participate in the survey. The questionnaire assessed attitudes, enablers and barriers to early dementia diagnosis and post-diagnostic intervention strategies. Exploratory factor analysis and linear regression were used. Results The survey response rate was 21%. 85% of GPs agreed with enablers of early dementia recognition (e.g. “Plan for the future, organize support and care”, “Minimize the strain and insecurity of patients and their informal family caregivers”). On the other hand, 15% of respondents perceived barriers towards early dementia recognition (e.g. “Time constraints in carrying out the necessary procedures to diagnose dementia”). GPs who were more likely to agree with barriers would less often counsel family members (β = − 0.05, 95% CI = − 0.09 - -0.02) or test fitness to drive (β = − 0.05, 95% CI = − 0.09 - -0.02), and more often choose a watchful waiting strategy (β = 0.05, 95% CI = 0.02–0.09). Conclusions The attitude of the majority of GPs is not characterized by diagnostic and therapeutic nihilism. However, negative attitudes were associated with sub-optimal management after the diagnosis. Thus, health systems are required to critically examine the use of available resources allowing GPs to look after patients and their relatives in a holistic way.

IntroductionGeneral health check-up examinations in asymptomatic adults have not been shown to be beneficial. Instead, opportunistic prevention during regular primary care consultations is most cost-effective and recommended. The study aimed to elucidate the expectations about check-ups of the general Swiss population.MethodsA nationwide cross-sectional telephone survey was conducted in a representative sample of the population, stratified by sex, age, and language in November 2019.ResultsData of 1077 respondents were analysed. Mean age was 45 years (range 18 to 89), and 51% were female. Overall, 40% of respondents expected to have check-up examinations (yearly: 41.6%), and 42% expected opportunistic prevention. Most expected check-up interventions were sex-specific such as mammography (89% of women), Pap smear test (89% of women), and blood test of prostate-specific antigen (81% of men). The least favoured ones related to counselling (tobacco: 27%; alcohol abuse: 29%). Most significant predictors of positive check-up expectations were being male (OR = 1.45, CI: 1.02-2.05 P = 0.04)), age between 45 and 59 years old (OR = 2.03, CI: 1.27-3.23, P = 0.003 vs. 18 to 29 years), having a degree from professional (OR = 1.73, 95% CIs: 1.11-2.69, P 0.015) or, middle school (OR = 1.99, 95% CIs:1.04-3.78, P = 0.037) or university (OR = 1.66, 95% CIs: 1.06-2.61, P< 0.001, vs. secondary school) and the more importance attributed to regularly checking one's health (OR = 2.12, 95% CIs: 1.70-2.36, P < 0.001).ConclusionsAlmost half of the population expected to have mostly yearly check-up examinations in addition to regular care, which is in contradiction to recommendations. This behaviour impacts the rational use of health care resources and must be considered by physicians and given the active role of patients in the health care system.

BACKGROUND Recommendations for blood pressure goals have considerably changed across time, in particular for high-risk patients with diabetes mellitus and/or renal dysfunction. Before 2009, Swiss Society of Hypertension (SSH) guidelines recommended lowering blood pressure to

INTRODUCTION The allocation and equal distribution of healthcare resources is one of the major challenges of today. Therefore, a framework to analyse the prevalence of illness in the community and the use of various sources of healthcare is crucial. The aim of the study was to evaluate the health-seeking behaviour of 1025 individuals in Switzerland in a 2-month period in 2018. METHODS Population-based, cross-sectional health survey with a multistage, stratified cluster design. The LINK Institute interviewed a representative sample of the adult Swiss population (age ≥18 years, stratified by language region: German-, French- and Italian-speaking, 70, 25 and 5%, respectively) by telephone. There were two interview rounds to account for potential seasonal variations, in May (n = 506) and November 2018 (n = 516). The health-seeking behaviour of these individuals during the previous 2 months was analysed. RESULTS In total, data of 1025 individuals were analysed: 51% females, median age 52 years (range 18−85). During the preceding 2 months, per 1000 adults, 546 had at least one symptom, 184 reported several symptoms, 243 sought medical advice, 164 first contacted their general practitioner, 81 directly contacted a specialist in a private practice, 16 were self-admitted to an accident and emergency department, 17 firstly contacted a pharmacy and 6 contacted an alternative medicine healthcare provider. In total, 21 persons were admitted to a hospital, of whom 8 underwent surgical procedures, 18 were at first transferred to a regular ward and 3 required intensive care unit services. Because of their current health problem, 387 individuals took medication and 259 bought their medication themselves. The vast majority (95%) of subjects was registered with a general practitioner. CONCLUSIONS This study represented an attempt to map the healthcare utilisation of the Swiss population. These results may be useful for further delineation of healthcare policies and medical education to meet the demand and needs of people in Switzerland. They indicate that general practitioners are the most important healthcare resource in Switzerland. Compared with specialists, they provide twice as much health advice at less costs. To optimise the health care system in Switzerland, we suggest to allocate resources where they are most needed.

Background: Studies increasingly suggest that the efficacy of certain dual antiretroviral therapy (ART) combinations is equal to triple ART. Increasing concerns among HIV-positive patients and physicians in Switzerland include ART cost and long-term ART safety and toxicity, i.e. taking only as many ART agents as necessary. The aims of this retrospective analysis are to report on the de-escalation of our entire clinic population of eligible patients with well-controlled HIV-infection to dolutegravir-containing dual ART. Methods: Starting in March 2015, we systematically considered the de-escalation of eligible patients to either dolutegravir/emtricitabine or dolutegravir/lamivudine, by discontinuing tenofovir disoproxil fumarate or abacavir. We report on the virological efficacy, tolerability and patient satisfaction ≥ 48 weeks after de-escalation. Findings: Of 106 HIV-positive patients followed in our clinic, 70 patients were de-escalated. Three returned to triple ART (insomnia after dolutegravir start, n = 2; new wish for single tablet regimen, n = 1). All de-escalated patients and all who continued triple ART had suppressed HIV viremia at last follow-up and were satisfied with their ART regimen, except for one patient who had virological failure after ART discontinuation in the setting of major depression. The most common reasons to not de-escalate included hepatitis B co-infection (n = 6), physician's concern about ART adherence (n = 6), patient reluctance to switch from a single tablet to a 2-tablet regimen (n = 7), patient satisfied with current ART (n = 5) and others (n = 12). Interpretation: ART de-escalation to dolutegravir/FTC or dolutegravir/3TC is possible in the majority of patients virologically suppressed on triple ART, and may effectively address patient and physician concerns about long-term safety and cost of ART. Keywords: HIV infection, Dual antiretroviral therapy, Dolutegravir, De-escalation, Induction and maintenance treatment

INTRODUCTION In general practice, the diagnosis of dementia is often delayed. Therefore, the Swiss National Dementia Strategy 2014 concluded that action was needed to improve patient care. Little is known about GPs’ confidence in and approach to the diagnosis, disclosure and post-diagnostic management of individuals with dementia in Switzerland. The aim of this survey is to assess these elements of dementia care and GPs’ views on the adequacy of health care services regarding dementia. MATERIALS AND METHODS Cross-sectional postal survey in Switzerland in 2017 supported by all academic institutes of general practice in Swiss universities. Members of the Swiss Association of General Practitioners (n = 4460) were asked to participate in the survey. In addition to the GPs’ demographic characteristics, the survey addressed the following issues: GPs’ views on the adequacy of health care services, clinical approach and confidence in the management of dementia. RESULTS The survey response rate was 21%. The majority of GPs (64%) felt confident diagnosing dementia, but not in patients with a migration background (15%). For neuropsychological testing, three-quarters of GPs collaborated with memory clinics and were satisfied with the access to diagnostic services. At the time of first diagnosis, 62% of GPs diagnosed the majority of their patients with a mild stage of dementia, and 31% with a mild cognitive impairment. The most frequent actions taken by GPs after the diagnosis of mild dementia were giving advice to relatives (71%), testing fitness-to-drive (66%) and minimising cardiovascular risk factors (63%). While 65% of GPs felt confident taking care of patients with dementia, fewer (53%) felt confident in pharmacological treatment, coping with suicidal ideation (44%) or caring for patients with a migration background (16%). Half of GPs preferred to delegate the assessment of fitness-to-drive to an official authority. One in four GPs was not satisfied with the local provision of care and support facilities for patients with dementia. CONCLUSIONS Overall, GPs reported confidence in establishing a diagnosis of dementia and sufficient access to diagnostic services. Post-diagnostic management primarily focused on counselling and harm reduction rather than pharmacological treatment. Future educational support for GPs should be developed, concentrating on coping with their patients’ suicidal ideation and caring for patients with a migration background.

Diffusion tensor imaging (DTI) studies have provided evidence of widespread white matter (WM) abnormalities in schizophrenia. Although these abnormalities appear clinically significant, the relationship to specific clinical symptoms is limited and heterogeneous. This study examined the association between WM microstructure and the severity of the five main DSM-5 schizophrenia symptom dimensions. DTI was measured in forty patients with schizophrenia spectrum disorders. Using Tract-Based Spatial Statistics controlling for age, gender and antipsychotic dosage, our analyses revealed significant negative relationships between WM microstructure and two DSM-5 symptom dimensions: Whereas abnormal psychomotor behavior was particularly related to WM of motor tracts, negative symptoms were associated with WM microstructure of the prefrontal and right temporal lobes. However, we found no associations between WM microstructure and delusions, hallucinations or disorganized speech. These data highlight the relevance of characteristic WM disconnectivity patterns as markers for negative symptoms and abnormal psychomotor behavior in schizophrenia and provide evidence for relevant associations between brain structure and aberrant behavior.

BACKGROUND:Identifying essential competencies in end-of-life care, as well as general practitioners' (GPs) confidence in these competencies, is essential to guide training and quality improvement efforts in this domain. AIM:To determine which competencies in end-of-life care are considered important by GPs, to assess GPs' confidence in these competencies in a European context and their reasons to refer terminally ill patients to a specialist. DESIGN AND SETTING:Cross-sectional postal survey involving a stratified random sample of 2000 GPs in Switzerland in 2014. METHOD:Survey development was informed by a previous qualitative exploration of relevant end-of-life GP competencies. Main outcome measures were GPs' assessment of the importance of and confidence in 18 attributes of end-of-life care competencies, and reasons for transferring care of terminally-ill patients to a specialist. GP characteristics associated with main outcome measures were tested using multivariate regression models. RESULTS:The response rate was 31%. Ninety-nine percent of GPs considered the recognition and treatment of pain as important, 86% felt confident about it. Few GPs felt confident in cultural (16%), spiritual (38%) and legal end-of-life competencies such as responding to patients seeking assisted suicide (35%) although more than half of the respondents regarded these competencies as important. Most frequent reasons to refer terminally ill patients to a specialist were lack of time (30%), better training of specialists (23%) and end-of-life care being incompatible with other duties (19%). In multiple regression analyses, confidence in end-of-life care was positively associated with GPs' age, practice size, home visits and palliative training. CONCLUSIONS:GPs considered non-somatic competencies (such as spiritual, cultural, ethical and legal aspects) nearly as important as pain and symptom control. Yet, few GPs felt confident in these non-somatic competencies. These findings should inform training and quality improvement efforts in this domain, in particular for younger, less experienced GPs.

BACKGROUND:White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. METHODS:Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). RESULTS:CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. CONCLUSION:The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation.

Computational network analysis provides new methods to analyze the brain's structural organization based on diffusion imaging tractography data. Networks are characterized by global and local metrics that have recently given promising insights into diagnosis and the further understanding of psychiatric and neurologic disorders. Most of these metrics are based on the idea that information in a network flows along the shortest paths. In contrast to this notion, communicability is a broader measure of connectivity which assumes that information could flow along all possible paths between two nodes. In our work, the features of network metrics related to communicability were explored for the first time in the healthy structural brain network. In addition, the sensitivity of such metrics was analysed using simulated lesions to specific nodes and network connections. Results showed advantages of communicability over conventional metrics in detecting densely connected nodes as well as subsets of nodes vulnerable to lesions. In addition, communicability centrality was shown to be widely affected by the lesions and the changes were negatively correlated with the distance from lesion site. In summary, our analysis suggests that communicability metrics that may provide an insight into the integrative properties of the structural brain network and that these metrics may be useful for the analysis of brain networks in the presence of lesions. Nevertheless, the interpretation of communicability is not straightforward; hence these metrics should be used as a supplement to the more standard connectivity network metrics.

In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.