Prediction of Acute COPD Exacerbation in the Swiss Multicenter COPD Cohort Study (TOPDOCS) by Clinical Parameters, Medication Use, and Immunological Biomarkers.

BACKGROUND AND OBJECTIVE: Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown. METHOD: We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from "The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland" cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD. RESULTS: Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV1% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (>1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV1 ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD. CONCLUSIONS: Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD.

Better response to low FODMAP diet in disorders of gut-brain interaction patients with pronounced hydrogen response to a nutrient challenge test.

BACKGROUND AND AIM: Previous studies have shown a reduction of gastrointestinal symptoms in irritable bowel syndrome (IBS) patients following a low FODMAP diet (LFD). It remains unknown which disorders of gut-brain interaction (DGBI) patients would benefit most from LFD. We aimed to analyze LFD response regarding a preceding nutrient challenge test (NCT). METHODS: Data of 110 consecutive DGBI patients undergoing NCT and LFD between August 2015 and August 2018 were analyzed retrospectively. LFD response was assessed by changes in IBS Symptom Severity Score (IBS-SSS). In mixed-effects linear regression models, the impact of hydrogen values and abdominal symptoms during NCT, performed with 30-g lactulose and 400-mL liquid test meal, on IBS-SSS changes were analyzed. RESULTS: Low FODMAP diet induced a significant IBS-SSS reduction of 78 points (95% confidence interval [CI] 50-96; P < 0.001). Patients with higher NCT-induced hydrogen increase during proximal intestinal transit had a significantly better LFD response (-66 IBS-SSS reduction per 10-ppm hydrogen increase, 95% CI -129 to -4, P = 0.045). Additionally, the higher the NCT-induced maximum hydrogen increase during mid-distal and distal intestinal transit, the better are the responses to LFD (-6 IBS-SSS per 10-ppm maximum delta hydrogen, 95% CI -11 to -1, P = 0.040). There was no association of LFD response with abdominal symptom generation during NCT. CONCLUSIONS: Our study is the first one analyzing and demonstrating significant associations between NCT results and LFD response. These findings are of high clinical importance, as they identify a subgroup of DGBI patients that may profit most from a restrictive LFD as first-line therapy.

The use of health care during the SARS-CoV-2 pandemic: repeated cross-sectional survey of the adult Swiss general population.

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.

The effect of COVID-19 on mental well-being in Switzerland: a cross-sectional survey of the adult Swiss general population.

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.

[Early recognition or screening of dementia in general practice]. / Früherkennung oder Screening von Demenzerkrankungen in der hausärztlichen Praxis.

Early recognition or screening of dementia in general practice Abstract. General practitioners play a key role in timely dementia diagnosis. In view that there are currently no drugs to prevent the progression of dementia or are effective in patients with mild cognitive impairment, a general screening of older people to recognize pre-symptomatic stages of dementia is not recommended. Crucial for a timely diagnosis is the GP's perception of warning signs, so-called "red flags". If the patients, family members, authorities or even the GP notice even discreet signs of a possible early dementia, a neuropsychological and medical evaluation should be initiated. Personal history, history by informant, a physical examination, supplemented by a GP's psychiatric evaluation and ideally the careful assessment with the MoCA form the basis of a preliminary clarification in general practice. If dementia is suspected, this clarification should be supplemented by an in-depth laboratory examination and, if applicable, neuroimaging before the patient is referred, depending on the findings, to a memory clinic or a consultant specialist to confirm the diagnosis and if appropriate initiate pharmacological and non-pharmacological therapies.

Does a tailored intervention to promote adherence in patients with chronic lung disease affect exacerbations? A randomized controlled trial.

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 < .001) and dry powder capsules (90 ± .10% vs. 80 ± 21%, P = .01). Timing adherence in participants using puff inhalers was higher in the intervention group (69 ± 25% vs. 51 ± 33%, P < .001). No significant differences in QoL were found between the two groups. CONCLUSION: Participants assigned to the intervention group had significantly better taking and timing adherence of inhaled medication resulting in a trend towards a decreased frequency of exacerbations. However, no effect on time to next exacerbation was observed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02386722, Registered 14 February 2014.

Differentiation of functional gastrointestinal disorders from healthy volunteers by lactulose hydrogen breath test and test meal.

BACKGROUND AND AIM: Functional dyspepsia (FD) is a common disorder of gut-brain interaction with incompletely understood pathophysiology. Consequently, heterogeneous expert opinions on diagnostic tests and assessment of treatment efficacies exist. So far, no consensus about the most relevant diagnostic and outcome tool has been reached. In this study, we aimed to analyze the significance of a combined lactulose hydrogen breath test (LHBT) and liquid meal, yet representing a standardized test in irritable bowel syndrome (IBS), in FD. METHODS: We analyzed data of 146 FD, 204 IBS patients, and 50 healthy volunteers (HV). All patients underwent LHBT with a meal-drink consisting of 30-g Lactulose and 400-mL Ensure®. Effect of abdominal symptom generation in FD/IBS compared with HV was assessed on a patient-reported Likert-scale. RESULTS: There was a significant difference between FD/IBS patients and HV in LHBT-induced abdominal pain (odds ratio [OR] 246.9, 95% confidence interval [CI] 26.6-2290.7; OR 161.2, 95% CI 16.9-1534.8), abdominal bloating (OR 384.8, 95% CI 92.9-2135.4; OR 524.1, 95% CI 114.7-3432.3), borborygmi (OR 9.9, 95% CI 2.2-46.9; OR 17.7, 95% CI 4.7-67.4), nausea only in FD (OR 174.4, 95% CI 15.5-5375.5), and diarrhea in IBS only (OR 25.8, 95% CI 2.0-7012.6). Hydrogen production was not significantly different in FD/IBS and HV. CONCLUSIONS: In this study, we demonstrated significant differences in postprandial symptom generation in FD and IBS compared with HV after LHBT. This does not only allow us to discriminate FD/IBS from HV but may also represent a diagnostic and monitoring tool for FD/IBS in the future, including monitoring of treatment effects.

General practitioners' attitudes towards early diagnosis of dementia: a cross-sectional survey.

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 (ß = - 0.05, 95% CI = - 0.09 - -0.02) or test fitness to drive (ß = - 0.05, 95% CI = - 0.09 - -0.02), and more often choose a watchful waiting strategy (ß = 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.

White matter correlates of the disorganized speech dimension in schizophrenia.

Disorganized speech is related to functional abnormalities in schizophrenia. To test the association between formal thought disorders (FTDs) and white matter microstructure, we applied a behavioral rating and diffusion tensor imaging in 61 patients with schizophrenia spectrum disorders. The Bern Psychopathology Scale was used to rate the dimension of language abnormalities ranging from negative FTDs, basically unaltered speech, to positive FTDs. Tract-based spatial statistics indicated increased fractional anisotropy in left hemispheric pathways of the language system in patients with negative FTDs. Thus, altered white matter properties in relevant fiber tracts may represent vulnerability to specific formal thought disorders.

A spontaneous deletion of α-synuclein is associated with an increase in CB1 mRNA transcript and receptor expression in the hippocampus and amygdala: effects on alcohol consumption.

α-Synuclein (α-syn) protein and endocannabinoid CB1 receptors are primarily located in presynaptic terminals. An association between α-syn and CB1 receptors has recently been established in Parkinson's disease, but it is completely unknown whether there is an association between these two proteins in alcohol addiction. Therefore, we aimed to examine the α-syn mRNA transcript and protein expression levels in the prefrontal cortex, striatum, amygdala and hippocampus. These brain regions are the most frequently implicated in alcohol and other drug addiction. In these studies, we used C57BL/6 mice carrying a spontaneous deletion of the α-syn gene (C57BL/6(Snca-/-) ) and their respective controls (C57BL/6(Snca) (+/) (+) ). These animals were monitored for spontaneous alcohol consumption (3-10%) and their response to a hypnotic-sedative dose of alcohol (3 g kg(-1) ) was also assessed. Compared with the C57BL/6(Snca+/+) mice, we found that the C57BL/6(Snca-/-) mice exhibited a higher expression level of the CB1 mRNA transcript and CB1 receptor in the hippocampus and amygdala. Furthermore, C57BL/6(Snca-/-) mice showed an increase in alcohol consumption when offered a 10% alcohol solution. There was no significant difference in sleep time after the injection of 3 g/kg alcohol. These results are the first to reveal an association between α-syn and the CB1 receptor in the brain regions that are most frequently implicated in alcohol and other drug addictions.

Risk factors for hospital outcomes in pulmonary embolism: A retrospective cohort study.

Background: Pulmonary 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. Method: A 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. Results: A 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. Conclusion: Defining 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.

Is Serum 25-Hydroxyvitamin D Level Associated with Severity of COVID-19? A Retrospective Study.

(1) Background: SARS-COV2 infection has a clinical spectrum ranging from asymptomatic infection to COVID-19 with acute respiratory distress syndrome (ARDS). Although vitamin D deficiency is often found in patients with ARDS, its role in COVID-19 is not clear. The aim of this study was to explore a possible association between serum 25-hydroxyvitamin D levels and the severity of COVID-19 in hospitalised patients. (2) Methods: In this retrospective observational study, we analysed data from 763 patients hospitalised for COVID-19 in 2020 and 2021. Patients were included in the study if serum 25-hydroxyvitamin D was assessed 30 days before or after hospital admission. Vitamin D deficiency was defined as <50 nmol/L (<20 ng/mL). The primary outcome was COVID-19 severity. (3) Results: The overall median serum 25-hydroxyvitamin D level was 54 nmol/L (IQR 35-76); 47% of the patients were vitamin D deficient. Most patients had mild to moderate COVID-19 and no differences were observed between vitamin D deficient and non-deficient patients (81% vs. 84% of patients, respectively p = 0.829). (4) Conclusion: No association was found between serum 25-hydroxyvitamin D levels and COVID-19 severity in this large observational study conducted over 2 years of the pandemic.

Predictors of Length of Stay, Rehospitalization and Mortality in Community-Acquired Pneumonia Patients: A Retrospective Cohort Study.

BACKGROUND: Community-acquired pneumonia (CAP) represents one of the leading causes of hospitalization and has a substantial impact on the financial burden of healthcare. The aim of this study was to identify factors associated with the length of hospital stay (LOHS), rehospitalization and mortality of patients admitted for CAP. METHODS: A retrospective cohort study was conducted with patients presenting to a Swiss public hospital between January 2019 and December 2019. Zero-truncated negative binomial and multivariable logistic regression analyses were performed to assess risk factors. RESULTS: A total of 300 patients were analyzed (median 78 years, IQR [67.56, 85.50] and 53% males) with an average LOHS of 7 days (IQR [5.00, 9.00]). Of the 300 patients, 31.6% (97/300) were re-hospitalized within 6 months, 2.7% (8/300) died within 30 days and 11.7% (35/300) died within 1 year. The results showed that sex (IRR = 0.877, 95% CI = 0.776-0.992, p-value = 0.036), age (IRR = 1.007, 95% CI = 1.002-1.012, p-value = 0.003), qSOFA score (IRR = 1.143, 95% CI = 1.049-1.246, p-value = 0.002) and atypical pneumonia (IRR = 1.357, 95% CI = 1.012-1.819, p-value = 0.04) were predictive of LOHS. Diabetes (OR = 2.149, 95% CI = 1.104-4.172, p-value = 0.024), a higher qSOFA score (OR = 1.958, 95% CI = 1.295-3.002, p-value = 0.002) and rehabilitation after discharge (OR = 2.222, 95% CI = 1.017-4.855, p-value = 0.044) were associated with a higher chance of being re-hospitalized within 6 months, whereas mortality within 30 days and within one year were both associated with older age (OR = 1.248, 95% CI = 1.056-1.562, p-value = 0.026 and OR = 1.073, 95% CI = 1.025-1.132, p-value = 0.005, respectively) and the presence of a cancer diagnosis (OR = 32.671, 95% CI = 4.787-369.1, p-value = 0.001 and OR = 4.408, 95% CI = 1.680-11.43, p-value = 0.002, respectively). CONCLUSION: This study identified routinely available predictors for LOHS, rehospitalization and mortality in patients with CAP, which may further advance our understanding of CAP and thereby improve patient management, discharge planning and hospital costs.

Effect of Single High Dose Vitamin D Substitution in Hospitalized COVID-19 Patients with Vitamin D Deficiency on Length of Hospital Stay.

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 (ß = 0.44; 95% CI: -2.17-2.22), and center (ß = 0.74; 95% CI: -1.25-2.73). The subgroup analysis in patients with severe 25(OH)D3-deficiency (<25 nmol/L) showed a non-significant reduction in the median length of hospital stay in the intervention group (5.5 vs. 9 days, 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.

Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. METHODS: COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire-based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. RESULTS: Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). CONCLUSION: Nomograms built from these models can assist clinicians in the decision-making process of COPD care.

Measuring workload of Swiss general practice: a five-yearly questionnaire-based survey on general practitioners' self-reported working activities (2005-2020).

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 <0.001, n = 1,780). The proportion of female GPs increased gradually from 16.5% in 2005 to 36.2% in 2020 (p <0.001). The GPs' workload significantly decreased over the last 15 years from 50.2 h/week to 43.4 h/week or from 90.9% FTE in 2005 to 78.9% FTE in 2020 (p <0.001). The decreased average workload across years was less pronounced in women (-4.4% FTE) than in men (-9.0% FTE, p = 0.015). Across all survey years, women worked on average 12.7 h/week or 23.2% FTE less than men (p <0.001). The time spent with patients gradually decreased, whereas the amount of time spent on clinical administrative work remained stable since 2005 (9 h/week). In 2020, GPs were working more frequently in group practices compared to 2005 (45.0% vs. 12.4%, p <0.001). CONCLUSION: This study demonstrates a decrease in GPs' overall workload from 2005 to 2020, indicating that the "new" generation of GPs prefers to work part-time. This decrease is at the expense of direct face-to-face encounters with patients. Over the last 15 years, a clear trend exists towards more women in the Swiss general practice, persisting over-ageing of GPs, replacement of single-handed practices by group practices, and increasing burden of administrative tasks, a risk factor for burnout and reduced job satisfaction. To maintain an efficient healthcare system in the future, substantial efforts are crucial to provide a positive and motivating insight into general practice to pre- and postgraduate students and improve the operational working conditions of GPs.

COVID-19 Symptoms and Testing in the Swiss General Population: A Cross-Sectional Survey.

We estimated the incidence of COVID-19-compatible symptoms, COVID-19 testing, and GP consultations during the first lockdown period in Switzerland (March-April 2020). A representative sample of the adult Swiss population completed an online survey. Of the 1022 respondents, 74 % reported at least one symptom, 5 % were tested for COVID-19, and 8 % contacted their GP regarding COVID-19. Testing was significantly associated with reduced sense of taste/smell, fever, cough with expectoration, and fatigue. Respondents at risk for severe COVID-19 were less likely to be tested but were five times more likely to contact their GP than those not at risk. We highlight the need to involve the appropriate health care setting to reach the vulnerable population when testing capacities are restricted (e.g. GPs).

High-dose vitamin D substitution in patients with COVID-19: study protocol for a randomized, double-blind, placebo-controlled, multi-center study-VitCov Trial.

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.

Intermediate care in caring for dementia, the point of view of general practitioners: A key informant survey across Europe.

Background: Intermediate 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 questions: What intermediate care services exist and how are they utilized in the care of people with dementia in Europe? Objective: This study aims at describing the point of view of General Practitioners on intermediate care services for people with dementia across Europe. Methods: Key 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. Results: The 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. Conclusion: Intermediate care in Europe is diverse and heterogeneous. Major concerns of GPs are about the cost issues and the cumbersome administrative procedures to access them.

Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial.

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.