Diagnosis and Therapy of Community-Acquired Pneumonia in the Emergency Department: A Retrospective Observational Study and Medical Audit.

BACKGROUND: Despite advances in therapy, community-acquired pneumonia (CAP) is still associated with significant morbidity and mortality. Several studies conducted in different countries have reported suboptimal adherence to the guidelines. However, there are currently no available data on adherence to CAP guidelines specifically in Switzerland. OBJECTIVES: The aim of this study was to audit the quality of diagnosis and therapy of CAP at a Swiss general hospital. METHODS: A retrospective, observational, single-center cohort study was conducted, including patients older than 18 years diagnosed with CAP and admitted to a medical ward throughout 2019 without prior antibiotic therapy prescribed by their general practitioner (GP). The baseline characteristics of the patients were analyzed, and the diagnostic workup and treatment were compared to the Swiss guidelines for CAP. RESULTS: A total of 254 patients diagnosed with CAP were included in this study (median age 78 years, 51.6% males). Atypical pneumonia was diagnosed in 4% of patients, while an organism was identified in 33% of cases, with Streptococcus pneumoniae being the most frequently detected pathogen (57%). A chest image was taken in almost all patients. Documentation of respiratory rate was missing in 23% of cases. Procalcitonin was measured in 23.2% of cases. Pneumococcal and legionella urinary antigen testing was performed on approximately 90% of all patients and blood cultures were drawn in approximately 80% of patients. In 39% of cases, arterial blood gas analysis was performed. Guideline adherence for the administration of empiric antibiotics was documented/recorded in 75% of cases. Twelve different antibiotic regimens were administered, and they were mostly amoxicillin/clavulanate with or without macrolides, as suggested by the guidelines. In particular, the use of ceftriaxone was higher (19.7%) compared to the Swiss guidelines. The average length of antibiotic therapy was longer (8.2 days) compared to the guidelines (5-7 days). Oral steroid therapy was administered to 29.1% of patients, including to 75% of those diagnosed with COPD. CONCLUSION: Overall, guideline adherence was moderately low, especially with regards to the assessment of respiratory rate, performance of arterial blood gas analysis, and sputum collection. Regarding antibiotic therapy, the use of ceftriaxone and the length of antibiotic therapy should be reduced. Further research is needed to identify the reasons for guideline non-adherence, and to find effective measures for the improvement of guideline adherence.

Clinical characteristics governing treatment adjustment in COPD patients: results from the Swiss COPD cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a widespread chronic disease characterised by irreversible airway obstruction [1]. Features of clinical practice and healthcare systems for COPD patients can vary widely, even within similar healthcare structures. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy is considered the most reliable guidance for the management of COPD and aims to provide treating physicians with appropriate insight into the disease. COPD treatment adaptation typically mirrors the suggestions within the GOLD guidelines, depending on how the patient has been categorised. However, the present study posits that the reasons for adjusting COPD-related treatment are hugely varied. OBJECTIVES: The objective of this study was to assess the clinical symptoms that govern both pharmacological and non-pharmacological treatment changes in COPD patients. Using this insight, the study offers suggestions for optimising COPD management through the implementation of GOLD guidelines. METHODS: In this observational cohort study, 24 general practitioners screened 260 COPD patients for eligibility from 2015-2019. General practitioners were asked to collect general information from patients using a standardised questionnaire to document symptoms. During a follow-up visit, the patient's symptoms and changes in therapy were assessed and entered into a central electronic database. Sixty-five patients were removed from the analysis due to exclusion criteria, and 195 patients with at least one additional visit within one year of the baseline visit were included in the analysis. A change in therapy was defined as a change in either medication or non-medical treatment, such as pulmonary rehabilitation. Multivariable mixed models were used to identify associations between given symptoms and a step up in therapy, a step down, or a step up and a step down at the same time. RESULTS: For the 195 patients included in analyses, a treatment adjustment was made during 28% of visits. In 49% of these adjustments, the change in therapy was a step up, in 33% a step down and in 18% a step up (an increase) of certain treatment factors and a step down (a reduction) of other prescribed treatments at the same time. In the multivariable analysis, we found that the severity of disease was linked to the probability of therapy adjustment: patients in GOLD Group C were more likely to experience an increase in therapy compared to patients in GOLD Group A (odds ratio [OR] 3.43 [95% confidence interval {CI}: 1.02-11.55; p = 0.135]). In addition, compared to patients with mild obstruction, patients with severe (OR 4.24 [95% CI: 1.88-9.56]) to very severe (OR 5.48 [95% CI: 1.31-22.96]) obstruction were more likely to experience a therapy increase (p <0.0001). Patients with comorbidities were less likely to experience a treatment increase than those without (OR 0.42 [95% CI: 0.24-0.73; p = 0.002]). A therapy decrease was associated with both a unit increase in COPD Assessment Test (CAT) score (OR 1.07 [95% CI: 1.01-1.14; p = 0.014]) and having experienced an exacerbation (OR 2.66 [95% CI: 1.01-6.97; p = 0.047]). The combination of steps up as well as steps down in therapy was predicted by exacerbation (OR 8.93 [95% CI: 1.16-68.28; p = 0.035]) and very severe obstruction (OR 589 [95% CI: 2.72 - >999; p = 0.109]). CONCLUSIONS: This cohort study provides insight into the management of patients with COPD in a primary care setting. COPD Group C and airflow limitation GOLD 3-4 were both associated with an increase in COPD treatment. In patients with comorbidities, there were often no treatment changes. Exacerbations did not make therapy increases more probable. The presence of neither cough/sputum nor high CAT scores was associated with a step up in treatment.

The Correct Indication to Induce Labour in a Swiss Cantonal Hospital.

BACKGROUND: Induction of labour (IOL) is a way to stimulate the onset of labour using mechanical and pharmacological methods. IOL is one of the most frequently performed obstetric procedures worldwide. We aimed to determine compliance with guidelines and to investigate factors associated with the success of labour. METHODS: In this retrospective, observational study, we analysed all induced deliveries in a Swiss hospital between January 2020 and December 2022. RESULTS: Out of 1705 deliveries, 349 women underwent IOL, and 278 were included in this study, with an average age of 32 years (range 19-44 years). Most of the women were induced for missed deadlines (20.1%), the premature rupture of membranes (16.5%), and gestational diabetes mellitus (9.3%), and there was a good adherence to the guideline, especially with the indication and IOL monitoring (100%). However, an improvement needs to be made in measuring and documenting the Bishop score (41%). The success of labour was associated with multiparity (81.8% vs. 62.4% p = 0.001) and maternal non-obesity (73.4 vs. 54.1% p = 0.026). CONCLUSIONS: An improvement is needed in the measurement and documentation of the Bishop score. Further research is needed to confirm the found associations between parity, obesity, and the success of IOL.

Adherence to the GOLD Guidelines in Primary Care: Data from the Swiss COPD Cohort.

(1) Introduction: Chronic obstructive pulmonary disease (COPD) and its associated morbidity and mortality are a global burden on both affected patients and healthcare systems. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) issues guidelines with the aim of improving COPD management. Previous studies reported significant variability in adherence to these recommendations. The objective of this study was to evaluate Swiss primary practitioners' adherence to the GOLD guidelines for the pharmacological treatment of stable COPD. (2) Methods: We studied patients who were included in the Swiss COPD cohort study, an ongoing prospective study in a primary care setting, between 2015 and 2022. The key inclusion criteria are age ≥ 40 years, FEV1/FVC ratio < 70%, and a smoking history of at least 20 pack-years. Adherence to the GOLD guidelines was assessed per visit and over time. (3) Results: The data of 225 COPD patients (mean age 67 ± 9 years, 64% male) and their respective 1163 visits were analyzed. In 65% of visits (726/1121), treatment was prescribed according to the GOLD guidelines. Non-adherence was most common in GOLD groups A and B (64% and 33%) and mainly consisted of over-treatment (two long-acting bronchodilators in group A (98/195, 50%) and ICS in groups A (21/195, 11%) and B (198/808, 25%)). In group D, the prescriptions conformed with the guidelines in 99% of cases (109/108). Guideline adherence was associated with high symptom load (COPD Assessment Test) (OR 1.04, p = 0.002), high number of exacerbations (OR = 2.07, p < 0.001), asthma overlap (OR 3.36, p = 0.049), and diabetes mellitus (OR 2.82, p = 0.045). (4) Conclusion: These results confirm a conflict between the GOLD recommendations and primary practice, mainly concerning over-treatment in GOLD groups A and B. Patients with high symptom load, high exacerbation risk, asthma overlap, and diabetes mellitus are more likely to be treated in conformity with the guidelines. Further research is needed to uncover the reasons for the discrepancies and to design strategies for improvement.

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.

Predictors of Length of Stay, Mortality and Rehospitalization in COPD Patients: A Retrospective Cohort Study.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic lung disease that has a significant impact on individuals and healthcare systems worldwide. This study aimed to identify factors that predict the length of a hospital stay (LOHS), one-year mortality, and rehospitalization within 6 months in patients admitted for acute exacerbation of COPD (AECOPD). A retrospective cohort study was conducted using data from 170 patients admitted to a district general hospital in Switzerland between January 2019 and February 2020. Sociodemographic and health-related variables measured at admission were analyzed as potential predictors. Multivariable zero-truncated negative binomial and logistic regression analyses were performed to assess the risk factors for LOHS (primary endpoint), mortality, and rehospitalization. The results show that an indication for oxygen supplementation was the only significant predictor of LOHS. In the logistic regression analysis, older age, COPD severity stages GOLD III and IV, active cancer and arrhythmias were associated with higher mortality, whereas rehabilitation after discharge was associated with lower mortality. There were no significant associations regarding rehospitalization. This study identified routinely available predictors for LOHS and mortality, which may further advance our understanding of AECOPD and thereby improve patient management, discharge planning, and hospital costs. The protective effect of rehabilitation after hospitalization regarding lower mortality warrants further confirmation and may improve the comprehensive management of patients with AECOPD.

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.

Diagnostic Workup and Outcome in Patients with Profound Hyponatremia.

Hyponatremia is the most common electrolyte disorder. A proper diagnosis is important for its successful management, especially in profound hyponatremia. The European hyponatremia guidelines point at sodium and osmolality measurement in plasma and urine, and the clinical evaluation of volume status as the minimum diagnostic workup for the diagnosis of hyponatremia. We aimed to determine compliance with guidelines and to investigate possible associations with patient outcomes. In this retrospective study, we analysed the management of 263 patients hospitalised with profound hyponatremia at a Swiss teaching hospital between October 2019 and March 2021. We compared patients with a complete minimum diagnostic workup (D-Group) to patients without (N-Group). A minimum diagnostic workup was performed in 65.5% of patients and 13.7% did not receive any treatment for hyponatremia or an underlying cause. The twelve-month survival did not show statistically significant differences between the groups (HR 1.1, 95%-CI: 0.58-2.12, p-value 0.680). The chance of receiving treatment for hyponatremia was higher in the D-group vs. N-Group (91.9% vs. 75.8%, p-value < 0.001). A multivariate analysis showed significantly better survival for treated patients compared to not treated (HR 0.37, 95%-CI: 0.17-0.78, p-value 0.009). More efforts should be made to ensure treatment of profound hyponatremia in hospitalised patients.

Pre-treatment comorbidities, C-reactive protein and eosinophil count, and immune-related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities.

BACKGROUND: The development of immune-related adverse events (irAEs) may be associated with clinical efficacy of checkpoint inhibitors (CPIs) in patients with cancer. We therefore investigated the effect of irAEs and pre-treatment parameters on outcome in a large, real-life patient cohort. METHODS: We performed a single-centre, retrospective, observational study including patients who received CPIs from 2011 to 2018 and followed until 2021. The primary outcome was overall survival, and the secondary outcome was the development of irAEs. RESULTS: In total, 229 patients with different tumour entities (41% non-small cell lung cancer [NSCLC], 29% melanoma) received a total of 282 CPI treatment courses (ipilimumab, nivolumab, pembrolizumab or atezolizumab). Thirty-four percent of patients developed irAEs (of these 17% had CTCAE Grade ≥3). Factors independently associated with mortality were pre-treatment CRP ≥10 mg/L (hazard ratio [HR] 2.064, p = 0.0003), comorbidity measured by Charlson comorbidity index (HR 1.149, p = 0.014) and irAEs (HR 0.644, p = 0.036) (age-adjusted, n = 216). Baseline eosinophil count ≤0.2 × 109 /L was a further independent predictor of mortality (age-, CRP-, CCI- and irAE-adjusted HR = 2.252, p = 0.002, n = 166). Anti-CTLA-4 use (p < 0.001), and pre-treatment CRP <10 mg/L were independently associated with irAE occurrence (p = 0.037). CONCLUSIONS: We found an independent association between irAE occurrence and improved overall survival in a real-life cohort spanning multiple tumour entities and treatment regimens. Pre-treatment comorbidities, CRP and eosinophil count represent potential markers for predicting treatment response.

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.

[Predictors for Early Unplanned Readmissions]. / Prädiktoren für frühe ungeplante Rehospitalisationen.

Predictors for Early Unplanned Readmissions Abstract. Unplanned rehospitalizations represent a major burden for patients, their relatives and the healthcare system. Since the introduction of the SwissDRG in 2012, financial incentives for hospitals have been promoted to forestall readmissions. Not every patient is at risk for rehospitalization. Affected patients can be identified by predictors from various areas in order to implement adequate interventions and avoid readmissions. Predictors can be directly related to patients as in the case of polypharmacy, multiple comorbidities or related to gender, but also provider-related and system-related. Early follow-up visits or a pre-discharge medication review are cited as effective interventions.

Predictors for Unplanned Readmissions within 18 Days after Hospital Discharge: a Retrospective Cohort Study.

Since the introduction of the reimbursement system based on diagnosis-related groups (DRG) in Swiss hospitals in 2012, most readmissions occurring within 18 days and appertaining to the same major diagnostic category (MDC) are merged and thus often reimbursed to a lesser extent. While readmissions reflect increased distress for patients and their relatives, the causes are mainly patient-related and difficult to influence. However, it may be possible to identify cases at higher risk for readmission. Therefore, the aim of this study was to find predictors for early readmissions in the same MDC, to identify high-risk index hospitalizations and possibly prevent unnecessary readmissions. The data of all patients admitted to the Clinic of Internal Medicine at the University Hospital of Basel, Switzerland, hospitalized for longer than 24 hours during the pre-DRG period between October 2009 and September 2010 were retrospectively collected. Data were examined for predictors of unplanned readmission within 18 days under the same MDC ('relevant readmission') by means of logistic regression. 7479 patients (median age 67.8 years, 56% male) were admitted to the Clinic of Internal Medicine, with 232 patients (3.1%) being readmitted at least once. Logistic regression revealed male sex (p =0.035) and a high number of prescribed drugs at discharge (p <0.005) as patient-related predictors. The MDCs respiratory system, cardiovascular system, and gastrointestinal/hepatobiliary system were identified as high-risk categories (each p <0.005). Age and length of index hospital stay added no significant explanatory value to the regression model. Unplanned readmissions under the same MDC within 18 days were infrequent and not related to patients' age or length of hospital stay. Overall, multimorbid patients, and hospitalizations regarding the cardiovascular, respiratory, or gastrointestinal system appear to be most at risk and should therefore be specifically targeted in the prevention of early readmissions.

Audit of Asthma Exacerbation Management in a Swiss General Hospital.

BACKGROUND: Adequate management is crucial to reduce symptoms, hospitalization, and relapses in patients with asthma. Hospitals often struggle to meet treatment guidelines, and no recent data for Switzerland are available. OBJECTIVES: The aim of the study was to audit the asthma exacerbation management in the Cantonal Hospital of Baselland in order to evaluate the level of compliance with guidelines in a narrative discussion. METHOD: The study design is a retrospective observational cohort study. We evaluated all adult patients presenting to the hospital with a physician-diagnosed asthma exacerbation in 2018 and 2019. The asthma management patients received was compared to the Swiss guidelines and the international GINA guidelines. RESULTS: 160 patients were included (mean age: 50 years old, 57.5% female). SpO2 and heart rate were assessed at presentation in nearly all patients. Peak expiratory flow (PEF) was measured in only 14%. Adequate management of asthma exacerbation with inhaled bronchodilator medication in a combination of short-acting beta-agonists and short-acting anticholinergics was administered to 96% of the patients. Patients with severe symptoms received systemic glucocorticosteroids within 6 h in 55%. At discharge, a reliever medication was prescribed for 64% of the patients and 55% received a new or increased controller therapy with inhaled glucocorticosteroid (ICS). 49% of the patients had no follow-up organized. CONCLUSION: To increase the guideline conformity and quality of asthma exacerbation management, the severity should be better assessed, especially by routinely performing PEF measurements. Treatment needs to be intensified; in particular, the ICS dose should be increased significantly and systemic glucocorticosteroids should be given with a lower threshold.

The Management of Acute Exacerbations in COPD: A Retrospective Observational Study and Clinical Audit.

(1) Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are not only associated with increased patient morbidity and mortality, but with extensive healthcare costs. Thus, adequate clinical management is crucial. The aim of this project was to evaluate the management of acute COPD exacerbations in a public teaching hospital in Switzerland. (2) Methods: We retrospectively analyzed clinical routine data of patients presenting with an acute exacerbation of COPD at the emergency department of a Swiss hospital between January 2019 and February 2020. Management was evaluated against recommendations from the GOLD 2019 report and previous audits. (3) Results: The data of 184 patients (mean age 73.5 years, range 41-95 years, 53% male) with 226 visits were included. While the documentation of GOLD stage (I-IV) and smoking status was consistent (81.0% and 91.6%), GOLD risk category (A-D) was only documented in 36% of the cases. Patients' respiratory rate upon presentation was measured in 73%, and blood gas analysis was performed in 70%. A total of 94% of the patients received a chest imaging; spirometry was performed in 10%. Initial symptomatic therapy with short acting bronchodilators was applied in 56%. Systemic steroid treatment was installed in 86%. Antibiotics were given in 56%, but in one fourth the indication was not clear. Non-invasive ventilation was applied in 25% of the indicated cases. Smoking cessation was recommended to 26% of the current smokers and referral to pulmonary rehabilitation was given in 16%. (4) Conclusion: GOLD recommendations were not comprehensively implemented, especially with regard to the assessment of severity, initial symptomatic therapy, and non-invasive ventilation. These results show the importance of the frequent revision of routine practice and may help to create awareness among practitioners and ultimately improve the quality of COPD management.

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.

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.

High-Intensity Interval Training for Heart Failure Patients With Preserved Ejection Fraction (HIT-HF)-Rational and Design of a Prospective, Randomized, Controlled Trial.

Background: The pathophysiology of HF with preserved ejection fraction (HFpEF) has not yet been fully understood and HFpEF is often misdiagnosed. Remodeling and fibrosis stimulated by inflammation appear to be main factors for the progression of HFpEF. In contrast to patients with HF with reduced ejection fraction, medical treatment in HFpEF is limited to relieving HF symptoms. Since mortality in HFpEF patients remains unacceptably high with a 5-year survival rate of only 30%, new treatment strategies are urgently needed. Exercise seems to be a valid option. However, the optimal training regime still has to be elucidated. Therefore, the aim of the study is to investigate the effects of a high-intensity interval (HIT) training vs. a moderate continuous training (MCT) on exercise capacity and disease-specific mechanisms in a cohort of patients with HFpEF. Methods: The proposed study will be a prospective, randomized controlled trial in a primary care setting including 86 patients with stable HFpEF. Patients will undergo measurements of exercise capacity, disease-specific blood biomarkers, cardiac and arterial vessel structure and function, total hemoglobin mass, metabolic requirements, habitual physical activity, and quality of life (QoL) at baseline and follow-up. After the baseline visit, patients will be randomized to the intervention or control group. The intervention group (n = 43) will attend a supervised 12-week HIT on a bicycle ergometer combined with strength training. The control group (n = 43) will receive an isocaloric supervised MCT combined with strength training. After 12 weeks, study measurements will be repeated in all patients to quantify the effects of the intervention. In addition, telephone interviews will be performed at 6 months, 1, 2, and 3 years after the last visit to assess clinical outcomes and QoL. Discussion: We anticipate clinically significant changes in exercise capacity, expressed as VO2peak, as well as in disease-specific mechanisms following HIT compared to MCT. Moreover, the study is expected to add important knowledge on the pathophysiology of HFpEF and the clinical benefits of a training intervention as a novel treatment strategy in HFpEF patients, which may help to improve both QoL and functional status in affected patients. Trial registration: ClinicalTrials.gov, identifier: NCT03184311, Registered 9 June 2017.

Point of care with serial NT-proBNP measurement in patients with acute decompensated heart failure as a therapy-monitoring during hospitalization (POC-HF): Study protocol of a prospective, unblinded, randomized, controlled pilot trial.

Despite important advances in diagnosis and medical therapy of heart failure (HF), disease monitoring and therapy guidance remains to be based on clinical signs and symptoms. NT-proBNP was repeatedly demonstrated to be a strong and independent predictor of morbidity and mortality in patients with HF. Only few - and conflicting - data are available on the efficacy of serial measurement of NT-proBNP as a tool for treatment monitoring in HF. These data are limited to the outpatient setting. Currently, no data are available on the effects of this approach in patients hospitalized for acute decompensated HF. The goal of this study is to explore whether the availability of serial NT-proBNP measurements may influence treatment decisions in patients with acute decompensated HF, and whether this leads to more rapid dose adjustments of prognostically beneficial medical therapies and earlier hospital discharge. In the intervention group, serial measurements of NT-proBNP every second business day are performed and made available to the treating physician, while no serial measurements are available in control group. HF therapy is left at the discretion of the treating physician. The primary endpoints are defined as the effects of monitoring NT-proBNP on medical HF therapy decisions, including type and dosing of medical therapies and the rapidity of adjustments, length of hospital stay, and evaluation of the changes in NT-proBNP values. Additional secondary endpoints include incidence of electrolyte imbalances and renal failure, changes in NYHA functional class, vital signs, body weight, quality of life, incidence of adverse events, transfer to Intensive Care Units, and mortality.

Reduction of corticosteroid use in outpatient treatment of exacerbated COPD - Study protocol for a randomized, double-blind, non-inferiority study, (The RECUT-trial).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately 4% to 7% of the Swiss population. According to current inpatient guidelines, systemic corticosteroids are important in the treatment of acute COPD exacerbations and should be given for 5 to 7 days. Several studies suggest that corticosteroids accelerate the recovery of FEV1 (forced expiratory volume in 1 second), enhance oxygenation, decrease the duration of hospitalization, and improve clinical outcomes. However, the additional therapeutic benefit regarding FEV1 recovery appears to be most apparent in the first 3 to 5 days. No data are available on the optimum duration of corticosteroid treatment in primary-care patients with acute COPD exacerbations. Given that many COPD patients are treated as outpatients, there is an urgent need to improve the evidence base on COPD management in this setting. The aim of this study is to investigate whether a 3-day treatment with orally administered corticosteroids is non-inferior to a 5-day treatment in acute exacerbations of COPD in a primary-care setting. METHODS/DESIGN: This study is a prospective double-blind randomized controlled trial conducted in a primary-care setting. It is anticipated that 470 patients with acutely exacerbated COPD will be recruited. Participants are randomized to receive systemic corticosteroid treatment of 40 mg prednisone daily for 5 days (conventional arm, n = 235) or for 3 days followed by 2 days of placebo (experimental arm, n = 235). Antibiotic treatment for 7 days is given to all patients with CRP ≥ 50 mg/l, those with a known diagnosis of bronchiectasis, or those presenting with Anthonisen type I exacerbation. Additional treatment after inclusion is left at the discretion of the treating general practitioner. Follow-up visits are performed on days 3 and 7, followed by telephone interviews on days 30, 90, and 180 after inclusion in the study. The primary endpoint is the time to next exacerbation during the 6-month follow-up period. DISCUSSION: The study is designed to assess whether a 3-day course of corticosteroid treatment is not inferior to the conventional 5-day treatment course in outpatients with exacerbated COPD regarding time to next exacerbation. Depending on the results, this trial may lead to a reduction in the cumulative corticosteroid dose in COPD patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02386735. Registered on 12 March 2015.