Correction: Non-GABA sleep medications, suvorexant as risk factors for falls: Case-control and case-crossover study.

[This corrects the article DOI: 10.1371/journal.pone.0238723.].

Association of drugs with special caution in the guidelines with falls: A case-control and case-crossover study in Japan.

AIM: To determine the relationship between multiple medications and falls. METHODS: This case-control and case-crossover study was carried out at Kudanzaka Hospital in Chiyoda, Tokyo, Japan. A total of 325 patients who experienced their first falls when hospitalized between January 2016 and November 2018, and 1285 controls matched by sex, age and clinical departments were included in this study. Hospitalization duration and fall risk score were adjusted for in the analyses. RESULTS: In the case-control study, multivariable logistic regression showed that increasing the intake of oral medications was not significantly associated with the incidence of falls (odds ratio 1.02, 95% confidence interval 0.998-1.049). In contrast, drugs prescribed with special caution in accordance with the Elderly Oral Medication Guidelines were significantly associated with falls (odds ratio 1.17, 95% confidence interval 1.09-1.26). A similar pattern was observed in the case-crossover analysis. Among the drugs to be prescribed with special caution according to the guidelines, atypical antipsychotics, non-benzodiazepine hypnotics and magnesium oxide were significantly associated with the risk of falls. CONCLUSION: The drugs to be prescribed with special caution according to the guidelines were associated with an increased fall risk. The risk of falls in hospitalized older people due to multiple medications varies among medications. Geriatr Gerontol Int ••; ••: ••-•• Geriatr Gerontol Int 2021; ••: ••-••.

Non-GABA sleep medications, suvorexant as risk factors for falls: Case-control and case-crossover study.

The aim of this study was to examine the risk of falls associated with the use of non-gamma amino butyric acid (GABA) sleep medications, suvorexant and ramelteon. This case-control and case-crossover study was performed at the Kudanzaka Hospital, Chiyoda Ward, Tokyo. A total of 325 patients who had falls and 1295 controls matched by sex and age were included. The inclusion criteria for the case group were hospitalized patients who had their first fall and that for the control were patients who were hospitalized and did not have a fall, between January 2016 and November 2018. The internal sleep medications administered were classified as suvorexant, ramelteon, non-benzodiazepines, benzodiazepines, or kampo. In the case-control study, age, sex, clinical department, the fall down risk score, and hospitalized duration were adjusted in the logistic regression model. In the case-control study, multivariable logistic regression showed that the use of suvorexant (odds ratio [OR]: 2.61, 95% confidence interval [CI]: 1.29-5.28), nonbenzodiazepines (OR: 2.49, 95% CI: 1.73-3.59), and benzodiazepines (OR: 1.65, 95% CI: 1.16-2.34) was significantly associated with an increased OR of falls. However, the use of ramelteon (OR: 1.40, 95% CI: 0.60-3.16) and kampo (OR: 1.55, 95% CI: 0.75-3.19) was not significantly associated with an increased OR of falls. In the case-crossover study, the use of suvorexant (OR: 1.78, 95% CI: 1.05-3.00) and nonbenzodiazepines (OR: 1.63, 95% CI: 1.17-2.27) was significantly associated with an increased OR of falls. Similar patterns were observed in several sensitivity analyses. It was suggested that suvorexant increases the OR of falls. This result is robust in various analyses. This study showed that the risk of falls also exists for non-GABA sleep medication, suvorexant, and thus it is necessary to carefully prescribe hypnotic drugs under appropriate assessment.

Treatment of asthma in smokers: A questionnaire survey in Japanese clinical practice.

BACKGROUND: Cigarette smoking in patients with asthma leads to poor symptom control. As patients who are current smokers have been excluded from enrollment in many clinical trials on asthma, there are few reports on the treatment in current smokers with asthma. In this study, we aimed to assess how respiratory physicians manage asthma in current smokers in Japan. METHODS: Respiratory physicians in 16 Japanese hospitals answered a questionnaire on treatment for patients with asthma between December 2014 and February 2015. Medical records were reviewed for 1756 patients with asthma. RESULTS: The mean patient age was 61.1 years, and 62.9% of the patients were female. A total of 102 patients (5.8%) were current smokers, and 546 patients (31.1%) were former smokers. Long-acting muscarinic antagonists (LAMA) were prescribed more frequently for current smokers with asthma than for former smokers and never smokers with asthma (10.8% vs 4.6%, p = 0.01, 10.8% vs 3.8%, p < 0.01). In contrast, macrolides were prescribed more frequently for former smokers and never smokers with asthma than for current smokers with asthma (7.7% vs 1.0%, p = 0.01, 6.4% vs 1.0%, p = 0.03). Triple therapy, i.e., inhaled corticosteroids, long-acting beta agonists, and LAMA concomitantly, was prescribed for current smokers with asthma more frequently than for former smokers and never smokers with asthma (9.8% vs 4.0%, p = 0.01, 9.8% vs 3.3%, p < 0.01). CONCLUSIONS: According to this survey, current smokers with asthma received more intensive therapy, including LAMA, than did former smokers with asthma.

[Randomized phase II study of carboplatin/paclitaxel followed by gemcitabine versus carboplatin/gemcitabine followed by docetaxel in patients with advanced nonsmall cell lung cancer].

PURPOSE: To evaluate the chemotherapeutic regimens suitable for the outpatient settings, we conducted a randomized phase II study of carboplatin/paclitaxel followed by gemcitabine versus carboplatin/gemcitabine followed by docetaxel. METHODS: Group CP(n=25): carboplatin AUC 6.0 day 1 and paclitaxel 70 mg/m2 day 1, 8, 15 every 4 weeks followed by gemcitabine 1.0 g/m2 day 1, 8, 15 every 4 weeks; group CG(n=26): carboplatin AUC 2.0 and gemcitabine 0.8 g/m2 day 1, 8 every 3 weeks followed by docetaxel 60 mg/m2 day 1, 8 every 3 weeks. RESULTS: The response rate of the first line therapy was 18.0% in group CP and 21.7% in group CG and that of the second line therapy was 10.0% and 14.3%, respectively. Time to progression of the first line therapy was 4.0 months in group CP and 4.3 months in group CG, that of the second line therapy was 2.1 months and 2.8 months, respectively. The median survival time was 10.9 months in group CP and 10.3 months in group CG. No statistically significant differences were documented in the response rate, time to progression, and overall survival between these two groups. Severe hematologic toxicity was rare in both groups and no symptomatic peripheral neuropathy was documented in carboplatin/paclitaxel therapy. CONCLUSION: Carboplatin /paclitaxel followed by gemcitabine and carboplatin/gemcitabine followed by docetaxel were well tolerated and equal in efficacy. Both regimens in this study seemed to be suitable for the outpatient settings because of their mild hematologic toxicity and peripheral neuropathy.

[A case of sarcoidosis presenting with high fever and rash progressing to acute respiratory failure].

A 66-year-old man who had been given a clinical diagnosis of vasculitis at another hospital after presenting with high fever and rash was admitted to our hospital for further examination following a relapse of fever during steroid reduction. The biopsy specimens of the leg with crusts showed the presence of epithelioid granuloma, and because of a negative tuberculin test, increased serum angiotensin converting enzyme (ACE) and lysozyme levels, and pulmonary Ga uptake, the patient was given a diagnosis of sarcoidosis. Although the patient had been treated on an outpatient basis following resolution of fever with NSAIDs and 5 mg prednisolone (PSL), he suffered acute respiratory failure during follow-up and required emergency admission. Chest CT revealed bilateral ground-glass opacity and pleural effusion, and serum ACE and soluble IL2R levels were significantly elevated. We diagnosed acute exacerbation of sarcoidosis and given high dose steroid therapy. The patient's symptoms, image findings, blood test results, and other findings promptly improved. Here we reported a highly unusual presentation of acute respiratory failure in sarcoidosis.

Suicide gene therapy using keratin 19 enhancer and promoter in malignant mesothelioma cells.

To achieve the specific expression of a transfected suicide gene in malignant mesothelioma cells, we applied the enhancer-promoter fusion sequence of the keratin 19 (K19) gene. Northern blot analysis of three mesothelioma cell lines demonstrated that K19 mRNA was expressed most abundantly in the H2052 mesothelioma cell line. Subsequently, in a luciferase reporting assay, K19 promoter (260 bp) exhibited higher promoter activity in H2052 cells than in the other two cell lines. In addition, ligation of a 3' enhancer (80 bp) of the K19 gene to upstream of the K19 promoter sufficiently enhanced the promoter activity. After transfecting an expression vector containing the K19 enhancer-promoter bound thymidine kinase gene (pK19-TK) into the H2052 cells, the pK19-TK transfected cells became more sensitive to GCV than non-transfected cells in vitro and in vivo. In a mouse peritoneal model of malignant mesothelioma, in vivo transfection of pK19-TK by cationic liposome and systemic administration of GCV inhibited the growth of peritoneal tumors. The K19 enhancer-promoter sequence seemed to be specific and efficient enough for the expression of the transfected suicide gene in malignant mesothelioma cells.

[Pulmonary empyema 48 years after Lucite-ball Plomb implantation for tuberculosis].

A 68-year-old woman was diagnosed as having empyema on the left side. She had a history of pulmonary tuberculosis and tuberculous pleurisy in 1949. She was treated with artificial pneumothorax and implantation of 7 Lucite-ball plombs in the left upper thorax. A chest radiograph taken 14 years after initial operation, revealed an increase in density inside some of the Lucite-ball plombs. She was again admitted after experiencing fever and dyspnea 48 years after initial operation. The chest radiograph then showed a large mass on the left side, which compressed the mediastinum to the right. Inside the mass, Lucite-ball plombs were detected. The fever and inflammatory findings were improved with antibiotic therapy, but the dyspnea was persistent. The Lucite-ball Plombs and coagulating tissue were removed successfully. The patient's symptoms and respiratory function improved after the second operation.