ObjectiveAs a standard therapy, tyrosine kinase inhibitors (TKIs) improved survival in patients with non-small cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutation. However, treatment-related cardiotoxicity, particularly arrhythmia, cannot be ignored. With the prevalence of EGFR mutations in Asian populations, the risk of arrhythmia among patients with NSCLC remains unclear.MethodsUsing data from the Taiwanese National Health Insurance Research Database and National Cancer Registry, we identified patients with NSCLC from 2001 to 2014. Using Cox proportional hazards models, we analyzed outcomes of death and arrhythmia, including ventricular arrhythmia (VA), sudden cardiac death (SCD), and atrial fibrillation (AF). The follow-up duration was three years.ResultsIn total, 3876 patients with NSCLC treated with TKIs were matched to 3876 patients treated with platinum analogues. After adjusting for age, sex, comorbidities, and anticancer and cardiovascular therapies, patients receiving TKIs had a significantly lower risk of death (adjusted HR: 0.767; CI: 0.729–0.807, p < 0.001) than those receiving platinum analogues. Given that approximately 80% of the studied population reached the endpoint of mortality, we also adjusted for mortality as a competing risk. Notably, we observed significantly increased risks of both VA (adjusted sHR: 2.328; CI: 1.592–3.404, p < 0.001) and SCD (adjusted sHR: 1.316; CI: 1.041–1.663, p = 0.022) among TKI users compared with platinum analogue users. Conversely, the risk of AF was similar between the two groups. In the subgroup analysis, the increasing risk of VA/SCD persisted regardless of sex and most cardiovascular comorbidities.ConclusionsCollectively, we highlighted a higher risk of VA/SCD in TKI users than in patients receiving platinum analogues. Further research is needed to validate these findings.

ImportanceTyrosine kinase inhibitors (TKIs) have been recognized as the standard treatment for patients with non–small cell lung cancers (NSCLCs) and epidermal growth factor receptor (EGFR) sequence variation. Although TKIs have been reported to cause cardiotoxicity, they are widely administered owing to the high prevalence of EGFR sequence variation in Taiwan.ObjectiveTo compare the outcomes of death and major adverse cardiac and cerebrovascular events among patients with NSCLC who use and do not use TKIs in a national cohort.Design, Setting, and ParticipantsUsing data from the Taiwanese National Health Insurance Research Database and National Cancer Registry, patients treated for NSCLC from 2011 to 2018 were identified, and their outcomes were analyzed, including death and major adverse cardiac and cerebrovascular events (MACCEs; such as heart failure, acute myocardial infarction, and ischemic stroke) after adjusting for age, sex, cancer stage, comorbidities, anticancer therapies, and cardiovascular drugs. The median follow-up duration was 1.45 years. The analyses were performed from September 2022 to March 2023.ExposuresTKIs.Main Outcomes and MeasuresCox proportional hazards models were used to estimate death and MACCEs in patients treated with and without TKIs. Given that death may reduce the incidence of cardiovascular events, the competing risk method was used to calculate the MACCE risk after adjustment for all potential confounders.ResultsOverall, 24 129 patients treated with TKIs were matched with 24 129 patients who did not receive TKIs (24 215 [50.18%] were female; and the mean [SD] age was 66.93 [12.37] years). Compared with those not receiving TKIs, the TKI group presented with a significantly lower hazard ratio (HR) of all-cause death (adjusted HR, 0.76; 95% CI, 0.75-0.78; P < .001), and the reason for death was primarily cancer. In contrast, the HR of MACCEs significantly increased (subdistribution HR, 1.22; 95% CI, 1.16-1.29; P < .001) in the TKI group. Furthermore, afatinib use was associated with a significantly reduced risk of death among patients receiving various TKIs (adjusted HR, 0.90; 95% CI, 0.85-0.94; P < .001) compared with those receiving erlotinib and gefitinib, although the outcomes of MACCEs were similar between the 2 groups.Conclusions and RelevanceIn this cohort study of patients with NSCLC, TKI use was associated with reduced HRs of cancer-related death but increased HRs of MACCEs. These findings suggest the importance of close monitoring of cardiovascular problems in individuals receiving TKIs.

Background Unplanned extubation (UE) occurs among 2%–16% of patients with mechanical ventilation (MV). Failed UE requiring reintubation could be associated with several adverse events. Aims The aim of this study was to investigate the outcomes and prognostic factors of patients with UE in intensive care units (ICUs). Methods We prospectively registered the patients who had UE and retrospectively reviewed the electronic medical records for 96‐bed ICUs between 1 January 2009, and 31 December 2020. Results A total of 392 patients had UE, and 234 patients (59.7%) were ≥65 years (older adult group). The median Acute Physiology and Chronic Health Evaluation (APACHE) II score were 17 and the median Glasgow Coma Scale score was 10. In total, 205 patients (52.3%) were reintubated within 48 h (due to failed UE) and 75 patients (19.1%) died during hospitalization. Multivariate analyses were performed to evaluate those factors predicting failed UE and mortality. These analyses demonstrated that higher positive end‐expiratory pressure (PEEP) and the admission APACHE II scores predicted failed UE. A higher fraction of inspiration O2 (FiO2) and minute ventilation; lower haemoglobin (Hb); and higher instances of liver cirrhosis, cancer, and failed UE were independently associated with hospital mortality. Conclusion We concluded that among patients who had UE, higher FiO2 or minute ventilation, or under MV or with lower Hb, liver cirrhosis, cancer, and failed UE tended to have higher mortality. Relevance to Clinical Practice Patients with high disease severity indices who have an increased risk of UE required special attention to techniques to prevent endotracheal tubes from accidental removal.

ObjectivesPatients with rheumatoid arthritis (RA) may have an increased risk for gastrointestinal perforation (GIP) caused by medications or chronic inflammation. However, the risk of GIP between patients with and without RA remains unclear. Therefore, we conducted this study to clarify it.MethodsUsing the Taiwan National Health Insurance Research Database, we identified patients with and without RA matched at 1:1 ratio by age, sex, and index date between 2000 and 2013 for this study. Comparison of the risk of GIP between the two cohorts was performed by following up until 2014 using Cox proportional hazard regression analyses.ResultsIn total, 11,666 patients with RA and an identical number of patients without RA were identified for this study. The mean age (±standard deviation) and female ratio were 55.3 (±15.2) years and 67.6% in both cohorts. Patients with RA had a trend of increased risk for GIP than patients without RA after adjusting for underlying comorbidities, medications, and monthly income [adjusted hazard ratio (AHR) 1.42; 95% confidence interval (CI) 0.99–2.04, p = 0.055]. Stratified analyses showed that the increased risk was significant in the female population (AHR 2.06; 95% CI 1.24–3.42, p = 0.005). Older age, malignancy, chronic obstructive pulmonary disease, and alcohol abuse were independent predictors of GIP; however, NSAIDs, systemic steroids, and DMARDs were not.ConclusionRA may increase the risk of GIP, particularly in female patients. More attention should be paid in female population and those with independent predictors above for prevention of GIP.