Osimertinib is a standard second-line therapy for patients who develop EGFR Thr790Met resistance mutation after treatment with first-line epidermal growth factor receptor tyrosine kinase inhibitors. Although no other effective targeted treatment option exists for these patients, osimertinib might be permanently discontinued owing to the onset of severe drug-induced toxicities like hepatotoxicity. Herein, we report a case of successful oral desensitization with osimertinib after the patient developed osimertinib-induced fever and hepatotoxicity. In the present case report, a 62-year-old Japanese woman received osimertinib as the sixth-line therapy for non-small cell lung carcinoma harboring EGFR Thr790Met-mutation. After 15 days of treatment, she developed general malaise. Although we reduced the drug at a lower dose, she again presented with high fever and elevated serum AST/ALT levels three days after re-initiating treatment. We then attempted oral desensitization with osimertinib over a two-week period. Thereafter, the patient continued osimertinib treatment for 6 months without the recurrence of side effects. In conclusion, oral desensitization may be a useful method in treating hepatotoxicity and drug fever caused by osimertinib.
Background: The 4-m gait speed test is a simple functional performance measure for older adults or patients with chronic obstructive lung disease. However, limited data exist regarding these measures for patients with interstitial lung disease. We evaluated the correlation between the 4-m gait speed and 6-min walk distance tests for interstitial lung disease patients and examined their underlying physiological factors. Methods: The 4-m gait speed and 6-min walk tests were prospectively conducted for 51 patients with interstitial lung disease. Other measurements included health-related quality of life, modified Medical Research Council score, arterial blood gas levels, pulmonary function, muscle strength according to the skeletal muscle mass index and physical activity. Results: Thirty-five patients were male (68.6%). Thirty-four patients had idiopathic pulmonary fibrosis (66.7%). There were significant correlations between the 4-m gait speeds and 6-min walk distances (r=0.57; P<0.001). Multivariate analyses showed that both the 4-m gait speed and 6-min walk distance were correlated with the modified Medical Research Council score. In addition, the 6-min walk distance was correlated with age and the percentage of the predicted diffusion capacity of carbon monoxide. Conclusions: The 4-m gait speed test is a simple, easy to perform and reliable functional performance measure for interstitial lung disease patients.
Background Non-tuberculous mycobacteria cause chronic pulmonary infection, but pleuritis and pleural effusion are rarely associated with infection with non-tuberculous mycobacteria, especially rapid-growing mycobacteria. Case presentation A 68-year-old woman with rheumatoid arthritis who was using prednisone, azathioprine, and certolizumab pegol presented complaining of fever, dry cough, and night sweats for the past 2 weeks. Chest examination revealed bilateral opacity that was more pronounced on her right side. Bronchoalveolar lavage fluid and pleural effusion fluid were obtained, and revealed coinfection with Mycobacterium fortuitum and Mycobacterium mageritense . Imipenem/cilastatin, levofloxacin, and minocycline were prescribed for 6 months, and the patient was well and asymptomatic for the subsequent 6 months. Conclusions This is the first case report describing pleural effusion associated with coinfection with two different mycobacterial species. If the species cannot be identified, the possibility of mycobacterial coinfection should be considered.
Background: Pirfenidone is an anti-fibrotic agent used to treat patients with idiopathic pulmonary fibrosis (IPF). Managing adverse drug events and ensuring compliance with pirfenidone treatment for a prolonged period are important to reduce the rate of disease progression. To maximize the benefits of pirfenidone treatment, we established and evaluated an ambulatory care pharmacy practice, a model of pharmacist–physician collaborative management, for patients receiving pirfenidone.Methods: We conducted a retrospective chart review of 76 consecutive patients treated with pirfenidone in the Kobe City Medical Center General Hospital, Japan, between January 2012 and January 2019. The first group (61 patients) received pirfenidone treatment as conventional management, whereas the second group (15 patients) started pirfenidone based on collaborative pharmacist–physician management. The drug discontinuation rate and time to drug discontinuation were compared between the groups. To analyze factors associated with pirfenidone discontinuation, we used a multivariate Cox regression analysis to evaluate the baseline characteristics of patients, including those receiving the collaborative management. Clinical outcomes were compared using a propensity score matched analysis.Results: In the collaborative management group, pharmacists made 56 suggestions, including suggestions for supportive care (51 suggestions), to the physicians. Among these suggestions, 52 were accepted by the physicians. The discontinuation rates at 3 [6.7% (1/15) vs. 26.2% (16/61)] and 6 [9.1% (1/11) vs. 36.1% (22/61)] months were lower in the collaborative management group than in the conventional management group. Multivariate analysis revealed that collaborative management [hazard ratio (HR) 0.34, 95% CI 0.08–0.96, p = 0.041] and predicted baseline forced vital capacity <60% (HR 2.13, 95% CI 1.17–3.85, p = 0.015) were significantly associated with pirfenidone discontinuation. The time to drug discontinuation was also significantly longer in the collaborative management group than in the conventional management group (p = 0.034, log-rank test). Propensity score matched analysis confirmed a significant correlation between collaborative management and drug discontinuation time (HR 0.20, 95% CI 0.03–0.84, p = 0.027).Conclusions: We established an ambulatory care pharmacy practice for out-patients with IPF receiving pirfenidone. The results suggest that collaborative management may help prevent pirfenidone discontinuation compared with conventional management.
Background Barotrauma frequently occurs in coronavirus disease 2019. Previous studies have reported barotrauma to be a mortality-risk factor; however, its time-dependent nature and pathophysiology are not elucidated. To investigate the time-dependent characteristics and the etiology of coronavirus disease 2019-related-barotrauma. Methods and findings We retrospectively reviewed intubated patients with coronavirus disease 2019 from March 2020 to May 2021. We compared the 90-day survival between the barotrauma and non-barotrauma groups and performed landmark analyses on days 7, 14, 21, and 28. Barotrauma within seven days before the landmark was defined as the exposure. Additionally, we evaluated surgically treated cases of coronavirus disease 2019-related pneumothorax. We included 192 patients. Barotrauma developed in 44 patients (22.9%). The barotrauma group’s 90-day survival rate was significantly worse (47.7% vs. 82.4%, p < 0.001). In the 7-day landmark analysis, there was no significant difference (75.0% vs. 75.7%, p = 0.79). Contrastingly, in the 14-, 21-, and 28-day landmark analyses, the barotrauma group’s survival rates were significantly worse (14-day: 41.7% vs. 69.1%, p = 0.044; 21-day: 16.7% vs. 62.5%, p = 0.014; 28-day: 20.0% vs. 66.7%, p = 0.018). Pathological examination revealed a subpleural hematoma and pulmonary cyst with heterogenous lung inflammation. Conclusions Barotrauma was a poor prognostic factor for coronavirus disease 2019, especially in the late phase. Heterogenous inflammation may be a key finding in its mechanism. Barotrauma is a potentially important sign of lung destruction.
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