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Objective: Prescription trends and patterns of anti-COVID-19 drugs in hospitalized patients were examined based on real world data to understand the use of anti-COVID-19 drugs in clinical practice in Japan. Design: The longitudinal and cross-sectional study was conducted utilizing data from January 1, 2019 to December 31, 2021 of the MID-NET® medical information database, which stored the electronic medical records, administrative claim data, and diagnosis procedure combination data of patients in Japan. Participants: Hospitalized patients with a COVID-19-related diagnosis who received at least one anti-COVID-19 drug between April 1, 2020 and December 31, 2021. Exposures: The following 14 drugs were included in this study: remdesivir, baricitinib, combination product of casirivimab and imdevimab, favipiravir, dexamethasone, ivermectin, azithromycin, nafamostat mesylate, camostat mesylate, ciclesonide, tocilizumab, sarilumab, combination product of lopinavir and ritonavir, and hydroxychloroquine. Results: We identified 5,717 patients hospitalized with COVID-19 and prescribed at least one anti-COVID-19 drug. The entire cohort generally included patients over 41–50 years and more males. The most common prescription pattern was dexamethasone monotherapy (22.9%), followed by the concomitant use of remdesivir and dexamethasone (15.0%), azithromycin monotherapy (15.0%), remdesivir monotherapy (10.2%), and nafamostat mesylate monotherapy (8.5%). However, an often prescribed anti-COVID-19 drug differed depending on the period. Conclusions and relevance: This study revealed the real-world situation of anti-COVID-19 drug prescriptions in hospitalized COVID-19 patients in Japan. A prescribed drug would depend on the latest scientific evidence, such as efficacy, safety, and approval status, at the time of prescription. Understanding the prescription of anti-COVID-19 drugs will be important for providing the most up-to-date treatments to patients and evaluating the benefit and/or risk of anti-COVID-19 drugs based on the utilization of an electronic medical record database. [ABSTRACT FROM AUTHOR]

Previous systematic review and meta-analysis indicates that rehabilitation within a week of intensive care unit (ICU) admission benefits physical function in critically ill patients. This updated systematic review and meta-analysis aim to clarify effects of initiating rehabilitation within 72 h of ICU admission on long-term physical, cognitive, and mental health. We systematically searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for randomized controlled trials (RCTs) between April 2019 and November 2022 to add to the previous review. Two investigators independently selected and extracted data. Pooled effect estimates for muscle strength, cognitive function, mental health after discharge, and adverse events were calculated. Evidence certainty was assessed via Grading of Recommendations, Assessment, Development, and Evaluations. Eleven RCTs were included in the meta-analysis. Early rehabilitation may improve muscle strength (three trials; standard mean difference [SMD], 0.16; 95% confidence interval [CI], −0.04–0.36) and cognitive function (two trials; SMD, 0.54; 95% CI, −0.13–1.20). Contrastingly, early mobilization showed limited impact on mental health or adverse events. In summary, initiating rehabilitation for critically ill patients within 72 h may improve physical and cognitive function to prevent post-intensive care syndrome without increasing adverse events. The effect on mental function remains uncertain. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to investigate the association between urate‐lowering drugs and cardiovascular events, primarily focusing on the risk of febuxostat and topiroxostat when compared with allopurinol in Japan. We conducted an observational study with a cohort design using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, including new urate‐lowering drugs users between August 1, 2010, and March 31, 2018. Exposure and control groups were defined based on the first prescription of urate‐lowering drugs as follows: febuxostat or topiroxostat for exposure groups, allopurinol for the control group, and benzbromarone for the secondary control group. The primary outcome was cardiovascular events, defined as a composite of acute coronary syndrome, cerebral infarction, and cerebral hemorrhage. Hazard ratios were estimated using a Cox proportional hazards model. The number of patients in each exposure and control group was 1,357,671 in the febuxostat group, 83,683 in the topiroxostat group, 1,273,211 in the allopurinol group, and 258,786 in the benzbromarone group. The adjusted hazard ratios for the cardiovascular risk were 0.97 (95% confidence interval [CI]: 0.95–0.98) for febuxostat and 0.84 (95% CI: 0.78–0.90) for topiroxostat groups. The benzbromarone group exhibited similar results. No increased cardiovascular risk was observed with febuxostat or topiroxostat when compared with allopurinol in patients with hyperuricemia in Japan. These results provide real‐world evidence regarding the cardiovascular risk associated with urate‐lowering drugs, indicating that no additional safety‐related regulatory actions are warranted in Japan. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this trial was to investigate whether a digital device that provides real-time visualized brushing instructions would contribute to the removal of dental plaque over usual brushing instructions. Methods: We conducted a single-center, parallel-group, stratified permuted block randomized control trial with 1:1 allocation ratio. Eligibility criteria included people aged ≥ 18 years, and exclude people who met the following criteria: severely crowded teeth; using interdental cleaning implement; having external injury in the oral cavity, or stomatitis; having less than 20 teeth; using orthodontic apparatus; visited to a dental clinic; having the possibility of consulting a dental clinic; having a dental license; not owning a smartphone or tablet device; smoker; taken antibiotics; pregnant; an allergy to the staining fluid; and employee of Sunstar Inc. All participants received tooth brushing instructions using video materials and were randomly assigned to one of two groups for four weeks: (1) an intervention group who used the digital device, providing real-time visualized instructions by connection with a mobile application; and (2) a control group that used a digital device which only collected their brushing logs. The primary outcome was the change in 6-point method plaque control record (PCR) score of all teeth between baseline and week 4. The t-test was used to compare the two groups in accordance with intention-to-treat principles. Results: Among 118 enrolled individuals, 112 participants were eligible for our analyses. The mean of PCR score at week 4 was 45.05% in the intervention group and 49.65% in the control group, and the change of PCR score from baseline was −20.46% in the intervention group and −15.77% in the control group (p = 0.088, 95% confidence interval −0.70–10.07). Conclusions: A digital device providing real-time visualized brushing instructions may be effective for the removal of dental plaque. [ABSTRACT FROM AUTHOR]

Randomized controlled trials or observational studies showed that the use of public-access automated external defibrillator (AED) was effective for patients with out-of-hospital cardiac arrest (OHCA). However, it is unclear whether public-access AED use is effective for all patients with OHCA irrespective of first documented rhythm. We aimed to evaluate the effect of public-access AED use for OHCA patients considering first documented rhythm (shockable or non-shockable) in public locations. From the Utstein-style registry in Osaka City, Japan, we obtained information on adult patients with OHCA of medical origin in public locations before emergency-medical-service personnel arrival between 2011 and 2015. Primary outcome was 1-month survival with favorable neurological outcome. Multivariable logistic regression analysis was performed to assess the association between the public-access AED pad application and favorable neurological outcome after OHCA by using one-to-one propensity score matching analysis. Among 1743 eligible patients, a total of 336 (19.3%) patients received public-access AED pad application. The proportion of patients who survived 1-month with favorable neurological outcome was significantly higher in the pad application group than in the non-pad application group (29.8% vs. 9.7%; adjusted odds ratio [AOR], 2.85; 95% confidence interval [CI], 1.73–4.68, AOR after propensity score matching, 2.46; 95% CI, 1.29–4.68). In a subgroup analysis, the AORs of patients with shockable or non-shockable rhythms were 3.36 (95% CI, 1.78–6.35) and 2.38 (95% CI, 0.89–6.34), respectively. Public-access AED pad application was associated with better outcome among patients with OHCA of medical origin in public locations irrespective of first documented rhythm. • Public-access AED pad application was effective for OHCA in public locations regardless of first documented rhythm. • The result from propensity score matching method supported the robustness of this effect. • The AED pad application could improve neurological outcome after OHCA. • The combination of bystander CPR and AED pad application is important to improve the outcome after OHCA. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate whether intra-aortic balloon pump (IABP) use in nontraumatic out-of-hospital cardiac arrest (OHCA) patients who achieved return of spontaneous circulation (ROSC) is associated with favorable neurological outcome after OHCA.Background: The association between the IABP use in OHCA patients and favorable neurological outcome has not been extensively evaluated.Methods: The Comprehensive Registry of Intensive Cares for OHCA Survival (CRITICAL) study, a multicenter, prospective observational registry in Osaka, Japan, included consecutive nontraumatic OHCA patients aged ≥18 years who achieved ROSC from July 2012 to December 2016. The primary outcome was 1-month survival with favorable neurological outcome. Logistic regression analysis was used to evaluate the association between the IABP use or non-IABP use and favorable neurological outcome using one-to-one propensity score (PS) matching analysis.Results: Among the 2894 eligible patients, 10.4% used IABP, and 89.6% did not use IABP. In all patients, the proportion of 1-month survival with favorable neurological outcome was higher in the IABP use group than in the non-IABP use group (30.7% [92/300] vs. 13.2% [342/2594]). However, in PS-matched patients, the proportions of 1-month survival with favorable neurological outcome were almost consistent, and there were no significant differences between the IABP use group and the non-IABP use group (37.3% [59/158] vs. 41.1% [65/158]; adjusted odds ratio, 0.97; 95% confidence interval, 0.48-1.96).Conclusions: In this population, the current PS matching analysis did not reveal any association between the IABP use and 1-month survival with favorable neurological outcome among adult patients with ROSC after OHCA. [ABSTRACT FROM AUTHOR]

The Pharmaceuticals and Medical Devices Agency (PMDA) has conducted many pharmacoepidemiological studies for postmarketing drug safety assessments based on real-world data from medical information databases. One of these databases is the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), containing health insurance claims of almost all Japanese individuals (over 100 million) since April 2009. This article describes the PMDA's regulatory experiences in utilizing the NDB for postmarketing drug safety assessment, especially focusing on the recent cases of use of the NDB to examine the practical utilization and safety signal of a drug. The studies helped support regulatory decision-making for postmarketing drug safety, such as considering a revision of prescribing information of a drug, confirming the appropriateness of safety measures, and checking safety signals in real-world situations. Different characteristics between the NDB and the MID-NET ® (another database in Japan) were also discussed for appropriate selection of data source for drug safety assessment. Accumulated experiences of pharmacoepidemiological studies based on real-world data for postmarketing drug safety assessment will contribute to evolving regulatory decision-making based on real-world data in Japan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shida, Kajiyama, Sawada, Ishiguro, Kubo, Kimura, Hirano, Komiyama, Iguchi, Oniyama and Uyama.)

In the present study, we aimed to investigate the association between urate-lowering drugs and cardiovascular events, primarily focusing on the risk of febuxostat and topiroxostat when compared with allopurinol in Japan. We conducted an observational study with a cohort design using the National Database of Health Insurance Claims and Specific Health Checkups of Japan, including new urate-lowering drugs users between August 1, 2010, and March 31, 2018. Exposure and control groups were defined based on the first prescription of urate-lowering drugs as follows: febuxostat or topiroxostat for exposure groups, allopurinol for the control group, and benzbromarone for the secondary control group. The primary outcome was cardiovascular events, defined as a composite of acute coronary syndrome, cerebral infarction, and cerebral hemorrhage. Hazard ratios were estimated using a Cox proportional hazards model. The number of patients in each exposure and control group was 1,357,671 in the febuxostat group, 83,683 in the topiroxostat group, 1,273,211 in the allopurinol group, and 258,786 in the benzbromarone group. The adjusted hazard ratios for the cardiovascular risk were 0.97 (95% confidence interval [CI]: 0.95-0.98) for febuxostat and 0.84 (95% CI: 0.78-0.90) for topiroxostat groups. The benzbromarone group exhibited similar results. No increased cardiovascular risk was observed with febuxostat or topiroxostat when compared with allopurinol in patients with hyperuricemia in Japan. These results provide real-world evidence regarding the cardiovascular risk associated with urate-lowering drugs, indicating that no additional safety-related regulatory actions are warranted in Japan., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Although bystanders' performance is important to improve outcomes of patients after cardiac arrests, few studies have investigated the barriers of bystanders, including those who could not perform cardiopulmonary resuscitation or any other rescue actions in emergency situations. This study aimed to assess the relationship between the psychological barriers of laypersons who encountered emergency situations and their rescue actions.Methods and Results:A questionnaire survey was conducted and this included laypersons who had encountered emergency situations during the last 5 years. Six questions were about the psychological barriers and 8 questions were about the laypersons' rescue actions. The primary outcome was any rescue actions performed by laypersons in an actual emergency situation. Overall, 7,827 (92.8%) of 8,430 laypersons responded; of them, 1,361 (16.1%) had encountered emergency situations during the last 5 years, and 1,220 (14.5%) were eligible for inclusion in the analyses. Of the 6 psychological barriers, "fear of approaching a collapsed person" (adjusted odds ratio [AOR] 0.50; 95% confidence interval [95% CI] 0.32-0.79) and "difficulties in judging whether to perform any rescue action" (AOR 0.63; 95% CI 0.40-0.99) were significantly associated with performing any rescue actions., Conclusions: The fear of approaching a collapsed person and difficulties in judging whether to take any actions were identified as the psychological barriers in performing any rescue actions by laypersons who encountered emergency situations.

Background: Little is known about the association between serum potassium level on hospital arrival and neurological outcome after out-of-hospital cardiac arrest (OHCA). We investigated whether the serum potassium level on hospital arrival had prognostic indications for patients with OHCA., Methods: This prospective, multicenter observational study conducted in Osaka, Japan (CRITICAL study) enrolled consecutive patients with OHCA transported to 14 participating institutions from 2012 to 2016. We included adult patients aged ⩾18 years with OHCA of cardiac origin who achieved return of spontaneous circulation and whose serum potassium level on hospital arrival was available. Based on the serum potassium level, patients were divided into four quartiles: Q1 (K ⩽3.8 mEq/L), Q2 (3.8< K⩽4.5 mEq/L), Q3 (4.5< K⩽5.6 mEq/L) and Q4 (K >5.6 mEq/L). The primary outcome was one-month survival with favorable neurological outcome, defined as cerebral performance category scale 1 or 2., Results: A total of 9822 patients were registered, and 1516 of these were eligible for analyses. The highest proportion of favorable neurological outcome was 44.8% (189/422) in Q1 group, followed by 30.3% (103/340), 11.7% (44/375) and 4.5% (17/379) in the Q2, Q3 and Q4 groups, respectively ( p <0.001). In the multivariable analysis, the proportion of favorable neurological outcome decreased as the serum potassium level increased ( p <0.001)., Conclusions: High serum potassium level was significantly and dose-dependently associated with poor neurological outcome. Serum potassium on hospital arrival would be one of the effective prognostic indications for OHCA achieving return of spontaneous circulation.

Background: Little is known about the association between prehospital cardiopulmonary resuscitation duration for adults with out-of-hospital cardiac arrest and outcome by the location of arrests. This study aimed to investigate the association between prehospital cardiopulmonary resuscitation duration and one-month survival with favourable neurological outcome., Methods: We analysed 276,391 adults aged 18 years and older with out-of-hospital cardiac arrest of medical origin before emergency medical service arrival. Prehospital cardiopulmonary resuscitation duration was defined as the time from emergency medical service-initiated cardiopulmonary resuscitation to prehospital return of spontaneous circulation or to hospital arrival. The primary outcome was one-month survival with favourable neurological outcome (cerebral performance category 1 or 2). The association between prehospital cardiopulmonary resuscitation duration and favourable neurological outcome was assessed using univariable and multivariable logistic regression analyses., Results: The proportion of favourable neurological outcomes was 2.3% in total, 7.6% in public locations, 1.5% in residential locations and 0.7% in nursing homes ( P  < 0.001). In univariable and multivariable logistic regression analyses, longer prehospital cardiopulmonary resuscitation duration was associated with poor neurological outcome, regardless of arrest location ( P for trend < 0.001). Patients with shockable rhythm in both public and residential locations had better neurological outcome than those in nursing homes at any time point, and residential and public locations had a similar neurological outcome tendency among patients with shockable rhythm., Conclusions: Longer prehospital cardiopulmonary resuscitation duration was independently associated with a lower proportion of patients with favourable neurological outcomes. Moreover, the association between prehospital cardiopulmonary resuscitation duration and neurological outcome differed according to the location of arrest and the first documented rhythm.