[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.

Antiseizure drugs and risk of developing smoking-related chronic obstructive pulmonary disease or lung cancer: A population-based case-control study.

AIMS: To determine whether enzyme-inducing antiseizure drugs (ASDs) affect the risk of developing chronic obstructive pulmonary disease (COPD) or lung cancer in smokers. METHODS: Cases of COPD and lung cancer and matched controls without these conditions were identified from a population of smokers with ≥1 prescription for any type of ASD in the Clinical Practice Research Datalink UK database of patients managed in primary care (1995-2016). A matched case-control study was performed utilising multivariate logistic regression analyses of exposure to enzyme-inducing ASDs compared to non-enzyme-inducing ASDs. The duration of ASD exposure and level of tobacco exposure were also assessed. RESULTS: We identified 5952 incident COPD and 1373 incident lung cancer cases, and 59 328 and 13 681 matched controls, respectively. Compared with never use, ever use of enzyme-inducing ASDs was associated with slightly decreased risk estimates of COPD (adjusted odds ratio: 0.85, 95% confidence interval: 0.81-0.89) and lung cancer (adjusted odds ratio: 0.82, 95% confidence interval: 0.73-0.92). These risk estimates were attenuated in heavy smokers. CONCLUSION: We found slightly decreased risk estimates of COPD and lung cancer among smokers taking enzyme-inducing ASDs and hypothesise that this may be related to induction of detoxification of tobacco-specific lung toxins.

High Incidence of New-Onset Joint Pain in Patients on Fluoroquinolones as Antituberculous Treatment.

BACKGROUND: Joint pain is frequently observed in patients on antituberculous treatment, and pyrazinamide is known to be associated with joint pain in patients receiving antituberculous treatment. Fluoroquinolone-associated joint pain and tendon injury have been reported in long-term corticosteroid and transplant recipients, but data are lacking in patients with tuberculosis. OBJECTIVES: The objective of this study was to examine the incidence of joint pain manifested during administration of antituberculous therapy and their association with fluoroquinolones. METHODS: Patients diagnosed with tuberculosis attending the outpatient clinic over a period of 1 year were reviewed and divided into 3 groups: group A receiving pyrazinamide, group B receiving a fluoroquinolone, and group C receiving both pyrazinamide and a fluoroquinolone. Latency to onset of joint pain was noted in all 3 groups. Joint pain was initially managed with analgesics, and associated hyperuricemia was treated with allopurinol/febuxostat. Causative drugs were stopped in case of intolerable joint pain. RESULTS: 260 patients (47% females, aged 38 ± 18 years; mean ± SD) were included [group A (n = 140), group B (n = 81), and group C (n = 39)]. Overall, 76/260 (29%) patients developed joint pain: group A - 24/140 patients (17%), group B - 32/81 patients (40%), and group C - 20/39 patients (51%). The median latency to the onset of joint pain was 83 days (interquartile range, IQR 40-167): 55 days (IQR 32-66) in group A, 138 days (IQR 74-278) in group B, and 88 days (IQR 34-183) in group C. Hyperuricemia was present in 12/24 (50%) patients in group A and 11/20 (55%) patients in group C. Pyrazinamide was stopped in 7/140 (5%) patients in group A, fluoroquinolones in 6/81 (7%) patients in group B, and both pyrazinamide and fluoroquinolones were stopped in 5/39 (13%) patients in group C because of intolerable joint pain. Major joints affected were knees and ankles. CONCLUSION: There is a high incidence of joint pain in patients receiving antituberculous treatment, which is higher when fluoroquinolones or the pyrazinamide-fluoroquinolone combination are administered as compared to pyrazinamide alone.

Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy.

Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.).

C-Reactive Protein and Procalcitonin in Case Reports of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome.

BACKGROUND: The spectrum of inflammatory marker response in DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome has not been systematically characterized. METHODS: An epidemiological biomarker study of C-reactive protein (CRP) and procalcitonin (PCT) values in patients with DRESS syndrome reported at 2 regional pharmacovigilance centers in Switzerland or published in the medical literature 2008-2016 was performed. RESULTS: Ninety-four DRESS cases were studied. All cases showed a CRP value > 10 mg/L (the upper limit of normal). The mean CRP value was 109.2 ± 79.4 mg/L. CRP values were significantly higher in 22 cases where a cause of inflammation besides DRESS could not be excluded (mean 162.1 vs. 92.9 mg/L; p = 0.003). Receiver operator characteristics curve analysis showed a moderate performance with a CRP cut-off value of 99.4 mg/L (AUC 0.717) to distinguish between patients with and without a possible additional cause of inflammation. The mean and median PCT values were 2.44 ± 5.94 and 0.69 ng/mL, respectively (n = 25 patients). Patients in whom an additional cause of inflammation besides DRESS could not be excluded showed a median PCT of 1.37 ng/mL (n = 9) versus 0.67 ng/mL (n = 16) in patients with DRESS only. PCT values were above the normal cut-off of 0.1 ng/mL, suggestive of bacterial infection in all but 1 case. Furthermore, there was a correlation between PCT values and hepatic enzyme measurements. CONCLUSIONS: Evaluating CRP and PCT values might be of use in helping physicians to distinguish between cases of DRESS syndrome with and without concurrent infection or other causes of inflammation. Further prospective investigation is required to define the use of these inflammatory markers in the management of DRESS.

Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity.

ADVERSE EVENT: A drug interaction leading to severe skin and mucosal toxicity. DRUGS IMPLICATED: Paclitaxel, docetaxel and amiodarone. THE PATIENT: A 77-year-old woman with a history of hypertension, hyperlipidemia, and palpitations, managed with amiodarone, was treated for HER2-positive invasive ductal breast cancer with paclitaxel and trastuzumab as an adjunct to surgery. EVIDENCE THAT LINKS THE DRUG TO THE EVENT: There was a strong temporal relationship between the taxane therapy and the development of severe skin and mucosal toxicity due to an unexpected reduction in taxane clearance. MANAGEMENT: Initially, conversion of paclitaxel to docetaxel, then cessation of docetaxel, symptomatic treatment, rehydration and placement of a nasogastric tube. MECHANISM: Increased exposure to paclitaxel and subsequently docetaxel due to interaction with amiodarone was suspected and confirmed on pharmacokinetic sampling. Analysis of two blood samples taken 9 and 10 days after docetaxel revealed plasma levels of 4.73 and 4.09 ng ml-1 , respectively, leading to a 79% decreased individual (Bayesian maximum a posteriori) clearance estimate of 9.15 l h-1 , corresponding to an estimated fivefold increase in AUC. Paclitaxel was also present in these samples (20 and 21 days after the last administration). IMPLICATIONS FOR THERAPY: Amiodarone inhibits cytochrome P450 (CYP) isoforms 2C8 and 3A4 as well as P-glycoprotein (P-gp) for which taxanes are substrates. However, interactions with amiodarone are not specified in the prescribing information. Clinicians should be aware of this interaction, particularly in an ageing population, where more patients requiring taxanes may already be receiving amiodarone for a comorbid cardiac condition.

[Drug-induced sexual dysfunction]. / Sexuelle Klagen im Zusammenhang mit Medikamenten.

Drugs can affect sexual function through their effects on the central nervous system, the peripheral (autonomic) nervous system or through hormonal effects. As most patients do not spontaneously talk about their sex life, it is important to assess patients with critical medication for possible sexual dysfunction. Critical medication in relation to sexual function include sedative drugs, drugs that affect the central serotonin, dopamine and/ or prolactin signaling pathways as well as certain antihypertensives. It is important to note, however, that the indications for these therapies, such as schizophrenia, depression and the metabolic syndrome are themselves associated with sexual dysfunction. if a disturbing sexual dysfunction arises, treatment with the suspected drug should be discontinued and possibly changed to one with fewer adverse effects. The use of phosphodiesterase 5 inhibitors, which are largely efficacious and safe for both patients with psychiatric conditions and patients with hypertension, can be considered

[ Preventing adverse drug events using clinical decision support systems]. / Verhindern von unerwünschten Arzneimittelereignissen mit Hilfe von elektronischen Entscheidungsunterstützungssystemen.

Adverse drug events pose a great risk to patients, are an everyday clinical problem and can have potential/ega/ consequences. Computerized physician order entry or computerized provider order entry (CPOE} in combination with clinical decision support systems {CDSS) are popular and aim to reduce prescribing errors as well as identifying potentially harmful drug drug interactions. The quantifiable benejit these systems bring to patients, has however, yet to be definitively proven. This article focusses on the current standpoint of CPOE-/CDSS, their risks and benefits, the potential for improvement and their perspectives for the future.

An open-label study examining the effect of pharmacological treatment on mannitol- and exercise-induced airway hyperresponsiveness in asthmatic children and adolescents with exercise-induced bronchoconstriction.

BACKGROUND: Mannitol- and exercise bronchial provocation tests are both used to diagnose exercise-induced bronchoconstriction. The study aim was to compare the short-term treatment response to budesonide and montelukast on airway hyperresponsiveness to mannitol challenge test and to exercise challenge test in children and adolescents with exercise-induced bronchoconstriction. METHODS: Patients were recruited from a paediatric asthma rehabilitation clinic located in the Swiss Alps. Individuals with exercise-induced bronchoconstriction and a positive result in the exercise challenge test underwent mannitol challenge test on day 0. All subjects then received a treatment with 400 µg budesonide and bronchodilators as needed for 7 days, after which exercise- and mannitol-challenge tests were repeated (day 7). Montelukast was then added to the previous treatment and both tests were repeated again after 7 days (day 14). RESULTS: Of 26 children and adolescents with exercise-induced bronchoconstriction, 14 had a positive exercise challenge test at baseline and were included in the intervention study. Seven of 14 (50%) also had a positive mannitol challenge test. There was a strong correlation between airway responsiveness to exercise and to mannitol at baseline (r = 0.560, p = 0.037). Treatment with budesonide and montelukast decreased airway hyperresponsiveness to exercise challenge test and to a lesser degree to mannitol challenge test. The fall in forced expiratory volume in one second during exercise challenge test was 21.7% on day 0 compared to 6.7% on day 14 (p = 0.001) and the mannitol challenge test dose response ratio was 0.036%/mg on day 0 compared to 0.013%/mg on day 14 (p = 0.067). CONCLUSION: Short-term treatment with an inhaled corticosteroid and an additional leukotriene receptor antagonist in children and adolescents with exercise-induced bronchoconstriction decreases airway hyperresponsiveness to exercise and to mannitol.

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.

Assessing potential risk factors for metamizole-induced leukopenia.

Background: Metamizole is a non-opioid analgesic agent that can rarely cause agranulocytosis, a severe form of leukopenia. Objectives: The aim of this study was to assess previously identified potential risk factors for the development of metamizole-induced leukopenia. Design: A retrospective, observational, matched case-control study was performed in a single-center setting. Methods: Patients who developed leukopenia in the setting of metamizole therapy were included as cases and matched 1:3 on the basis of age and sex to control patients who did not develop leukopenia when treated with metamizole. The data were obtained from the medical records of patients hospitalized at Cantonal Hospital Baselland between 2015 and 2020. Univariate and multivariate analyses were performed. Results: Eighty-six cases and 258 matched controls aged between 18 and 102 years were included. Fifty-seven percent were female. Previous leukopenic episodes (odds ratio (OR): 4.02, 95% CI: 1.95-8.28, p < 0.001) and a history of penicillin allergy (OR: 2.49, 95% CI: 1.03-6.03, p = 0.044) were found to be independent risk factors for metamizole-induced leukopenia. Conclusion: A history of previous leukopenic episodes and a history of penicillin allergy were confirmed as risk factors for metamizole-induced leukopenia. In our opinion, metamizole should be avoided in patients with these risk factors.

METHOD: We compared hospitalized patients treated with metamizole who developed leukopenia, with similar hospitalized patients who did not develop this side effect. RESULTS: It was observed that patients were more likely to develop leukopenia under metamizole therapy if they: - had previous episodes of leukopenia - were under cytostatic/immunosuppressive therapy (for example drugs used to treat cancer or autoimmune conditions) - had a history of penicillin allergy. CONCLUSION: These findings will help in identifying people who are at risk of developing this serious side effect, so that they can be given a medication for pain or fever that suits them better.

Assessing potential risk factors for metamizole-induced leukopenia Background: Metamizole is a medication used to treat pain and fever. It carries a risk of developing the side effect of a low white blood cell count (leukopenia). Researchers have identified certain risk factors which predispose some, but not all, people to develop this side effect. We undertook this study to examine these risk factors in more detail.

Effects of serial NT-proBNP measurements in patients with acute decompensated heart failure: Results of the POC-HF pilot trial.

INTRODUCTION: Serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements have proven to be useful for therapy monitoring in patients hospitalized for acute decompensated heart failure (ADHF). The POC-HF pilot study investigated whether serial NT-proBNP measurements influenced treatment decisions in these patients. METHODS: Patients hospitalized for ADHF were randomly assigned to an intervention group (serial NT-proBNP measurements made available to treating physicians) or a control group (care as usual). HF therapy was administered at the discretion of the treating physician. The primary endpoint was dose changes in HF therapy during hospitalization. Secondary endpoints included changes in NT-proBNP levels, recovery from HF symptoms, length of hospital stay, and quality of life. RESULTS: 52 patients (35% female; mean age 81.8 years) were included. The availability of serial NT-proBNP values was associated with higher dosages of ACE inhibitors (relative treatment effect (RTE) day 11:0.74, p = 0.007) and loop diuretics (RTE day 11:0.77, p = 0.005), and lower dosages of beta-blockers (RTE day 11:0.43, p  =  0.002). NT-proBNP levels decreased (-752 pg/ml, p = 0.162) and recovery rates from ADHF symptoms were more pronounced in the intervention group, but without statistical significance. No differences were found in terms of the length of hospital stay and quality of life. CONCLUSION: The results of this pilot trial indicate that serial NT-proBNP measurements are possibly associated with faster up-titration of HF medication, more pronounced NT-proBNP decrease, and faster recovery from symptoms than symptom-guided therapy in patients hospitalized for ADHF. These preliminary findings require further validation through larger studies. TRIAL REGISTRATION: http://www.swissethics.ch BASEC-ID 2017-01030, registered on 28 December 2017.

[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.

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.

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.

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.

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.

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.

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.