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.

[Polymedication and oral antitumour therapies - which drug interactions should be considered?]

INTRODUCTION: Oral anticancer therapies offer various advantages but also entail risks due to their toxicity and narrow therapeutic ranges. Since these drugs are increasingly prescribed in patients with existing polypharmacy, identifying and assessing potential drug interactions is of great importance for safe and effective therapy. This article provides an overview of the most common pharmacokinetic and pharmacodynamic drug-drug interactions of targeted anticancer therapies, with focus on protein kinase inhibitors.

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.

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.

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.

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.

Gastrointestinal bleeding during anticoagulation with direct oral anticoagulants compared to vitamin K antagonists.

Aim: Patients receiving oral anticoagulants with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) have an increased risk of gastrointestinal bleeding (GIB). We compared cases of GIB associated with VKAs and DOACs in terms of risk factors, scores, timing, location, severity, and outcome. Methods: Data from patients treated at a university hospital in Switzerland for GIB under VKA and DOACs between 2012 and 2018 were analyzed in this investigator-driven, retrospective, single-center study. Results: A total of 248 patients (110 males; median age, 80 years; 134 VKA, 114 DOAC) were included. No significant differences in age, weight or sex were observed. The propensity of the VKA group for risk factors such as comorbidities, interacting medications, or a high risk for bleeding (HAS-BLED score) was higher than that of the DOAC group. 56% of the VKA-treated patients had a supratherapeutic INR, and 25% in the DOAC group received an unlicensed dose. Significantly more patients in the DOAC group were not formally overdosed with OAC whilst receiving amiodarone compared to the VKA group (57% vs. 18%, respectively, p = 0.03). Latency between the documented start of oral anticoagulation and GIB was shorter in the DOAC group (median 3 months) than in the VKA group (median 23.5 months, p¡0.001). There were no differences in terms of location and severity of the GIB, length of hospitalization, or mortality. Conclusion: Patients taking VKAs displayed more risk factors for GIB than those taking DOACs. Treatment with DOACs was associated with early GIB and calls for increased vigilance during the first months after commencement. Co-medication with amiodarone appeared to be a risk factor for GIB in patients taking DOACs.

Immune thrombocytopenia associated with COVID-19 mRNA vaccine tozinameran - a clinical case and global pharmacovigilance data.

We report the occurrence of immune thrombocytopenia (ITP) in a 77-year-old man a few days after receiving the first dose of the COVID-19 mRNA vaccine tozinameran (Comirnaty®). The patient was treated with systemic corticosteroids, intravenous immunoglobulins and eltrombopag. He elected to proceed with the second dose of tozinameran 14 weeks after the first and his platelet count remained stable under a tapered eltrombopag dose. To our knowledge, this is the first case in which a second tozinameran dose has been administered to a patient who developed presumed secondary ITP after the first vaccination. We also report global pharmacovigilance data for the occurrence of ITP after vaccination with tozinameran.

Myocarditis and pericarditis in association with COVID-19 mRNA-vaccination: cases from a regional pharmacovigilance centre.

In this article we summarize suspected adverse events following immunization (AEFI) of pericarditis, myocarditis and perimyocarditis that were reported by our regional pharmacovigilance centre after COVID-19 mRNA-vaccination and discuss their association with these vaccines. Seventeen cases were reported between March and July 2021. Of these, nine had perimyocarditis, five myocarditis and three pericarditis. Twelve patients were male (71%). The median age was 38 years (range 17-88). The most commonly observed presenting symptom was acute chest pain (65%). While 47% of the patients were previously healthy, 53% had at least one pre-existing comorbidity, with hypertension being the most prevalent (24%). The European Society of Cardiology diagnostic criteria for the reported AEFIs were fulfilled in twelve cases (71%). The AEFIs occurred after the first vaccine dose in six cases (35%), after the second vaccine dose in ten cases (59%) and after both doses in one case (6%). The median latency of all AEFIs taken together was 14 days (range 1-28) after the first vaccination and 3 days (range 1-17) after the second one. All patients except one were hospitalized (94%) with a median length of stay of 7.5 days (range 3-13). The majority of patients (n = 11, 65%) did not experience any complications, and 13 (77%) of the patients had recovered or were recovering at the time of discharge. In 16 of the 17 cases (94%), the association between the AEFI and mRNA-vaccination was considered possible by the pharmacovigilance centre.

Comparative Effects of Metamizole (Dipyrone) and Naproxen on Renal Function and Prostacyclin Synthesis in Salt-Depleted Healthy Subjects - A Randomized Controlled Parallel Group Study.

Aim: The objective was to investigate the effect of metamizole on renal function in healthy, salt-depleted volunteers. In addition, the pharmacokinetics of the four major metamizole metabolites were assessed and correlated with the pharmacodynamic effect using urinary excretion of the prostacyclin metabolite 6-keto-prostaglandin F1α. Methods: Fifteen healthy male volunteers were studied in an open-label randomized controlled parallel group study. Eight subjects received oral metamizole 1,000 mg three times daily and seven subjects naproxen 500 mg twice daily for 7 days. All subjects were on a low sodium diet (50 mmol sodium/day) starting 1 week prior to dosing until the end of the study. Glomerular filtration rate was measured using inulin clearance. Urinary excretion of sodium, potassium, creatinine, 6-keto-prostaglandin F1α, and pharmacokinetic parameters of naproxen and metamizole metabolites were assessed after the first and after repeated dosing. Results: In moderately sodium-depleted healthy subjects, single or multiple dose metamizole or naproxen did not significantly affect inulin and creatinine clearance or sodium excretion. Both drugs reduced renal 6-keto-prostaglandin F1α excretion after single and repeated dosing. The effect started 2 h after intake, persisted for the entire dosing period and correlated with the concentration-profile of naproxen and the active metamizole metabolite 4-methylaminoantipyrine (4-MAA). PKPD modelling indicated less potent COX-inhibition by 4-MAA (EC50 0.69 ± 0.27 µM) compared with naproxen (EC50 0.034 ± 0.033 µM). Conclusions: Short term treatment with metamizole or naproxen has no significant effect on renal function in moderately sodium depleted healthy subjects. At clinically relevant doses, 4-MAA and naproxen both inhibit COX-mediated renal prostacyclin synthesis.

Switching COPD patients from the disposable to the new reusable Respimat soft mist inhaler: a real-world study from Switzerland.

OBJECTIVE: The aims of the survey were to assess first experiences of Swiss COPD patients switching from the disposable to the new reusable Respimat inhaler, and to evaluate physicians´ and patients´ views of the new training material. METHODS: Patients with a confirmed diagnosis of COPD using a disposable Respimat inhaler for at least three months were included. Patients´ demographics, COPD stage, current treatment, and comorbidities relevant for the handling of the device were assessed. Further, patients were trained on the reusable Respimat by placebo inhaler, patient brochure, video cards/demo films and SMS reminder service. After at least one cartridge change, patients gave comprehensive feedback on their satisfaction with the reusable Respimat and physicians evaluated the need for re-training. RESULTS: 235 patients participated in the survey. Of these, 37% suffered from comorbidities restricting the handling of the Respimat. 216 (92%) patients had a better overall satisfaction with the reusable than with the disposable Respimat. Dose counter (86%), monthly preparation (81%) and daily handling (77%) were also assessed as better by most of the patients. In 80% of cases, the user ability was stated as better than for the disposable Respimat. Less than 15% of the patients required further training. Placebo inhaler was the mostly preferred training material by both, physicians (in 86% of the patients) and patients (75%). In patients with comorbidities affecting inhaler handling, overall satisfaction was also better in 86% of the patients. CONCLUSION: The majority of patients were satisfied with the new reusable Respimat device and proper handling could be attained using the provided training material, even in patients with restricting comorbidities.

Cardiovascular adverse effects of lopinavir/ritonavir and hydroxychloroquine in COVID-19 patients: Cases from a single pharmacovigilance centre.

In this article we summarize the cardiovascular adverse events that were observed in three patients during their treatment for COVID-19 and discuss their association with lopinavir/ ritonavir (LPV/r) and hydroxychloroquine (HCQ). The cases were reported to our regional pharmacovigilance centre in April 2020. All three patients were above 75 years in age, male and multimorbid, and had been hospitalized for treatment of COVID-19. As part of their treatment, all of them received a very strictly monitored off-label therapy with LPV/r and HCQ, for which they had given their prior, written, informed consent. In one patient, erythromycin was also administered. All three patients developed a significant QTc time prolongation during or shortly after therapy with the above drugs. On account of this, the treatment had to be discontinued early in each case and QTc time recovered in all three patients.

A case of intoxication with tea made from Digitalis purpurea.

We present the case of a 34-year-old woman with recurrent depressive disorder who ingested purple foxglove with suicidal intent. She bought a foxglove plant (Digitalis purpurea) over the internet and used all of its leaves to make a tea that she then drank over a period of a few hours. Seventeen hours later, she developed abdominal pain, emesis and bradycardia and was admitted via the emergency department to the intensive care unit for further treatment and monitoring. The plasma digoxin concentration measured 3.53 nmol/l (therapeutic reference range 0.77-1.50 nmol/l) 21 hours after ingestion of the tea. She remained heamodynamically and neurologically stable, was treated with antiemetics and simple analgesia and did not require digoxin-specific antibodies. Despite normal renal function, her plasma digoxin half-life was prolonged (estimated 76 h), reflecting the long half-life of the parent compound digitoxin which is the main cardiac glycoside in Digitalis purpurea. She was transferred to psychiatric care 48 h after admission. In this report, we compare this case to other similar cases, which to date have only been rarely reported in the literature.