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Taisuke Jo,1,2 Nobuaki Michihata,1 Hayato Yamana,1 Yusuke Sasabuchi,3 Hiroki Matsui,4 Hirokazu Urushiyama,2 Akihisa Mitani,2 Yasuhiro Yamauchi,2 Kiyohide Fushimi,5 Takahide Nagase,2 Hideo Yasunaga4 1Department of Health Services Research, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 2Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 3Data Science Center, Jichi Medical University, Tochigi, Japan; 4Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan; 5Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan Purpose: Patients with symptomatic COPD are recommended to use inhaled bronchodilators containing long-acting muscarinic receptor antagonists (LAMAs). However, bronchodilators may cause gastrointestinal adverse effects due to anticholinergic reactions, especially in advanced-age patients with COPD. Dai-kenchu-to (TU-100, Da Jian Zhong Tang in Chinese) is the most frequently prescribed Japanese herbal Kampo medicine and is often prescribed to control abdominal bloating and constipation. The purpose of this study was to evaluate the role of Dai-kenchu-to as a supportive therapy in advanced-age patients with COPD. Patients and methods: We used the Japanese Diagnosis Procedure Combination inpatient database and identified patients aged ≥75 years who were hospitalized for COPD exacerbation. We then compared the risk of re-hospitalization for COPD exacerbation or death between patients with and without Dai-kenchu-to using 1-to-4 propensity score matching. A Cox proportional hazards model was used to compare the two groups. We performed subgroup analyses for patients with and without LAMA therapy. Results: Patients treated with Dai-kenchu-to had a significantly lower risk of re-hospitalization or death after discharge; the HR was 0.82 (95% CI, 0.67–0.99) in 1-to-4 propensity score matching. Subgroup analysis of LAMA users showed a significant difference in re-hospitalization or death, while subgroup analysis of LAMA non-users showed no significant difference. Conclusion: Our findings indicate that Dai-kenchu-to may have improved the tolerability of LAMA in advanced-age patients with COPD and, therefore, reduced the risk of re-hospitalization or death from COPD exacerbation. Dai-kenchu-to may be recommended as a useful supportive therapy for advanced-age patients with COPD. Keywords: TU-100, herbal medicine, muscarinic receptor antagonists, propensity score, survival analysis

Abstract Background Calcium channel blockers and angiotensin II receptor blockers are commonly prescribed to treat hypertension. Massive overdoses can cause both distributive and cardiogenic shock because of their effects on vascular smooth muscles and severe myocardial depression. Case Presentation We present the case of a 46‐year‐old man who was brought to our emergency department after ingesting 1210 mg amlodipine and 936 mg candesartan. The patient's hemodynamic status deteriorated despite treatment with vasopressors, calcium gluconate, and hyperinsulinemia‐euglycemia therapy with mechanical ventilation. Venoarterial extracorporeal membrane oxygenation was initiated for refractory shock. The patient was weaned off extracorporeal membrane oxygenation on day 5 and discharged on day 18 of hospitalization. Conclusion When medical therapies are ineffective, aggressive venoarterial extracorporeal membrane oxygenation should be considered for the management of refractory shock in the setting of calcium channel blocker with angiotensin II receptor blocker overdose.