Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Electronic prescribing reduces drug prescription errors and therefore improves patient safety. • Whether electronic prescribing compared with prescribing on paper facilitates the implementation of clinical pharmacologists' recommendations in the care of patients hospitalized with medical problems is not known. WHAT THIS STUDY ADDS • The use of electronic prescriptions when compared with handwritten prescriptions increased the uptake of clinical pharmacologists' recommendations for improving drug safety in hospitalized patients. AIMS To determine whether electronic prescribing facilitates the uptake of clinical pharmacologists' recommendations for improving drug safety in medical inpatients. METHODS Electronic case records and prescription charts (either electronic or paper) of 502 patients hospitalized on medical wards in a large Swiss teaching hospital between January 2009 and January 2010 were studied by four junior and four senior clinical pharmacologists. Drug-related problems were identified and interventions proposed. The implementation and time delays of these proposed interventions were compared between the patients for whom paper drug charts were used and the patients for whom electronic drug charts were used. RESULTS One hundred and fifty-eight drug-related problems in 109 hospital admissions were identified and 145 recommendations were made, of which 51% were implemented. Admissions with an electronic prescription chart ( n= 90) were found to have 2.74 times higher odds for implementation of the change than those with a paper prescription chart ( n= 53) (95% confidence interval 1.2, 6.3, P= 0.018, adjusted for any dependency introduced by patient, ward or clinical team; follow-up for two cases missing). The time delay between recommendations being made and their implementation (if any) was minimal (median 1 day) and did not differ between the two groups. CONCLUSIONS Electronic prescribing in this hospital setting was associated with increased implementation of clinical pharmacologists' recommendations for improving drug safety when compared with handwritten prescribing on paper. [ABSTRACT FROM AUTHOR]

Objectives. The concentration of atrial natriuretic peptide (ANP) in the circulation is approximately 10- to 50- fold higher than B-type natriuretic peptide (BNP). We sought to compare the accuracy of midregional pro-atrial natriuretic peptide (MRproANP) measured with a novel sandwich immunoassay with N-terminal pro-B-type natriuretic peptide (NTproBNP) in the diagnosis of heart failure. Design. The diagnosis of heart failure was adjudicated by two independent cardiologists using all available clinical data (including BNP levels) in 287 consecutive patients presenting with dyspnoea to the emergency department (ED). MRproANP and NTproBNP levels were determined at presentation in a blinded fashion. Results. Heart failure was the adjudicated final diagnosis in 154 patients (54%). Median MRproANP was significantly higher in patients with heart failure as compared to patients with other causes of dyspnoea (400 vs. 92 pmol L−1, P < 0.001). The diagnostic accuracy of MRproANP was very high with an area under the receiver operating characteristic curve of 0.92 and was comparable with that of NTproBNP (0.92, P = 0.791). Moreover, MRproANP provided incremental diagnostic information to BNP and NTproBNP in patients presenting with BNP levels in the grey zone between 100 and 500 pg mL−1. Conclusion. Midregional pro-atrial natriuretic peptide is as accurate in the diagnosis of heart failure as NTproBNP. MRproANP seems to provide incremental information on top of BNP or NT-proBNP in some subgroups and should be further investigated in other studies. [ABSTRACT FROM AUTHOR]