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Long-term sequelae of COVID-19 can affect health-related quality of life (HRQOL). We examined the long-term impact of COVID-19 on HRQOL and elucidated factors associated with low HRQOL. Discharged COVID-19 patients were assessed at 3 and 6 months after disease onset. The patients completed a medical examination and SF-36 questionnaire at the two time points and underwent pulmonary function testing at 6 months. All had undergone computed tomography (CT) imaging upon hospital admission. Of the 74 included patients, 38% reported respiratory symptoms at 3 months and 26% at 6 months. The aggregated SF-36 scores declined in the role/social component summary (RCS), a category related to social activity. Patients with respiratory sequelae or impaired pulmonary function had lower RCS scores. There was a negative linear relation between the RCS score and the CT score, which reflected the extent of COVID-19 pneumonia (3 months, P = 0.0024; 6 months, P = 0.0464). A high CT score (≥ 10 points) predicted a low RCS score at 6 months (P = 0.026). This study highlights the long-term impairment of RCS and its associations with respiratory sequelae. The study also emphasizes the importance of radiological findings in predicting long-term HRQOL outcomes after COVID-19.

Dental trauma may occur in school settings and it can impact patients' quality of life. Analysis of the occurrences of dental trauma is essential in identifying preventive methods. There are numerous reports of such accidents but most are quantitative analyses with limited data. The aim of this study was to extract information on the mechanisms of injuries that leads to prevention by performing a qualitative analysis of the occurrence of dental trauma.After screening 7684 cases of dental injuries that occured in schools and were reported to the Japan Sports Council between 2005 and 2020, 533 detailed descriptions of injuries that occurred during sports were included. Quantitative text analysis was performed on the target data by performing statistical analysis, extracting frequently used words, and creating a co-occurrence network. Injury mechanisms were evaluated based on appearance of words.Dental injuries occurred frequently in five sports included in the survey. They were in order of decreasing frequency: baseball, basketball, soccer, volleyball, and rugby. Males were injured more often in all sports other than volleyball. The number of accidents increased in all sports among high school students. The frequent word list and co-occurrence network were different for each sport. This allowed typical accident occurrence mechanisms to be extracted for these five sports.Typical accident occurrence mechanisms were extracted from quantitative text analysis targeting free texts on the occurrence of accidents for five sports. Quantitative text analysis is useful for the evaluation of accident cases, which may aid in accident prevention.

Although ablation energy (AE) and force-time integral (FTI) are well-known active predictors of lesion characteristics, these parameters do not reflect passive tissue reactions during ablation, which may instead be represented by drops in local impedance (LI). This study aimed to investigate if additional LI data improves predicting lesion characteristics and steam pops. RF applications at a range of powers (30 W, 40 W, and 50 W), contact forces (8 g, 15 g, 25 g, and 35 g), and durations (10–180 s) using perpendicular/parallel catheter orientations were performed in excised porcine hearts (N = 30). The correlation between AE, FTI, and lesion characteristics was examined, and the impact of LI (%LI drop (%LID) defined by the ΔLI divided by the initial LI) was additionally assessed. Three hundred seventy-five lesions without steam pops were examined. Ablation energy (W × s) and FTI (g × s) showed a positive correlation with lesion depth (ρ = 0.824:P < 0.0001 and ρ = 0.708:P < 0.0001), surface area (ρ = 0.507:P < 0.0001 and ρ = 0.562:P < 0.0001), and volume (ρ = 0.807:P < 0.0001 and ρ = 0.685:P < 0.0001). %LID also showed a positive correlation individually with lesion depth (ρ = 0.643:P < 0.0001), surface area (ρ = 0.547:P < 0.0001), and volume (ρ = 0.733:P < 0.0001). However, the combined indices of AE × %LID (AE multiplied by %LID) and FTI × %LID (FTI multiplied by %LID) provided significantly stronger correlation with lesion depth (ρ = 0.834:P < 0.0001 and ρ = 0.809:P < 0.0001), surface area (ρ = 0.529:P < 0.0001 and ρ = 0.656:P < 0.0001), and volume (ρ = 0.864:P < 0.0001 and ρ = 0.838:P < 0.0001). This tendency was observed regardless of the catheter placement (parallel/perpendicular). AE (P = 0.02) and %LID (P = 0.002) independently remained as significant predictors to predict steam pops (N = 27). However, the AE × %LID did not increase the predictive power of steam pops compared to the AE alone. LI, when combined with conventional parameters (AE and FTI), may provide stronger correlation with lesion characteristics.

OBJECTIVES This study aimed to evaluate the outcomes of the patients who underwent restrictive annuloplasty (RA) plus papillary muscle relocation anteriorly (PMR-A) with the risk factors in mitral valve repair for functional mitral regurgitation (FMR). METHODS Eighty-six patients underwent mitral valve repair with RA for FMR. Thirty-five of them received additional bilateral papillary muscle relocation for severe leaflet tethering. The papillary muscles were relocated posteriorly (PMR-P) early in the study. Then, in the later period, the technique was modified to PMR-A, in which the papillary muscles were relocated anteriorly for 24 cases. The survival of the patients undergoing RA + PMR-A was examined retrospectively, adjusting for differences in patient background. RESULTS Twenty-three deaths were observed during the follow-up period out of the 86 cases. Independent preoperative risk factors for survival were left ventricular ejection fraction, patient age and B-type natriuretic peptide (BNP) level. Among the patients with BNP CONCLUSIONS Long-term survival for patients who underwent RA plus bilateral PMR-A was promising. Patients with significantly higher BNP had lower survival after valve repair for FMR.

Background The prediction of COVID-19 disease behavior in the early phase of infection is challenging but urgently needed. MuLBSTA score is a scoring system that predicts the mortality of viral pneumonia induced by a variety of viruses, including coronavirus, but the scoring system has not been verified in novel coronavirus pneumonia. The aim of this study was to validate this scoring system for estimating the risk of disease worsening in patients with COVID-19. Methods This study included the patients who were treated between April 1 st and March 13 th , 2020. The patients were classified into mild, moderate, and severe groups according to the extent of respiratory failure. MuLBSTA score was applied to estimate the risk of disease worsening in each severity group and we validated the utility of the scoring system. Results A total of 72 patients were analyzed. Among the 46 patients with mild disease, 17 showed disease progression to moderate or severe disease after admission. The model showed a sensitivity of 100% and a specificity of only 34.5% with a cut-off value of 5 points. Among the 55 patients with mild or moderate disease, 6 deteriorated to severe disease, and the model showed a sensitivity of 83.3% and a specificity of 71.4% with a cut-off value of 11 points. Conclusions This study showed that MuLBSTA score is a potentially useful tool for predicting COVID-19 disease behavior. This scoring system may be used as one of the criteria to identify high-risk patients worsening to life-threatening status.

The size of the distal electrode and the method of measuring local impedance (LI) are different between the IntellaNav MiFi-OI™ (MiFi-OI) and IntellaNav STABLE POINT™ (SP) catheters. We investigated the impact of these differences on LI, efficacy, and safety of radiofrequency (RF) applications.RF applications at a range of powers (30 W, 40 W, and 50 W), contact forces (10 g and 20 g), and durations (10-120 s) were performed in excised porcine hearts (N = 48). LI variation was defined by δLI-drop (= initial LI - post-RF LI) and %LI-drop (= δLI-drop/initial LI) × 100, and the relationship between lesion characteristics and LI variation was compared.A total of 576 lesions were examined. Although absolute δLI-drop during RF applications was significantly larger for the SP than MiFi-OI catheter (47[31-65]ohm for SP vs 37[24-51]ohm for MiFi-OI, p 0.0001), %LI-drop was similar (23.3 [15.5-30.6]% in SP vs 24.9[17.3-32.5]% in MiFi-OI, p = 0.10). Although lesions produced by both catheters were similarly correlated with LI variation, the SP catheter produced generally larger lesions (depth; 5.0 [3.7-6.1]mm vs 4.7 [3.3-6.0]mm, p = 0.06; surface areas, 46.9 [36.8-58.8]mmAlthough no difference in safety profile is observed between MiFi-OI and SP catheters, the SP catheter produces larger lesions. %LI-drop is superior to δLI-drop in correlation to lesion size and in predicting steam pops as well as in normalizing the difference between catheters.

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., 「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.

During the COVID-19 pandemic in Japan, various measures have been implemented to prevent the spread of infection, including restrictions on human mobility. A dynamic fluctuation in the number of suicides has been observed during this period. The question is whether the increase/decrease in suicides during the pandemic is related to changes in human mobility. To answer the same, we estimated incidence rate ratios (IRR) of suicide for changes in human mobility using the relative number of suicides by month from March 2020 to September 2021, based on the same months in 2019 as reference. The IRR of suicide during the pandemic were significantly lower in the months when mobility decreased-in both the previous and current month-than in the months when mobility was stable; the IRR of suicide were statistically higher in the months with increased mobility compared with the stable months. The burden from a decrease in one's mobility, which might lead to an increase in suicide, may not occur immediately, as seen in the delayed effects of unemployment. It may be important to investigate people's mental health and stress levels after pandemic restrictions were relaxed. The findings may help practitioners and families consider the timing of intervention.

(1) Background: Near-miss incidents are the foundation of major injuries. They are warning signs that loss is imminent. Long working hours are a risk factor for near-misses along with sleep problems, job-related stress, and depressive symptoms. This study aimed to evaluate the indirect effects of long working hours via mediating variables on near-miss occurrences among Japanese healthcare professionals. (2) Methods: 1490 Japanese healthcare professionals’ reports from a web-based survey of workers in October 2018 were analyzed to evaluate total, direct, and indirect effects of long working hours on near-misses. We applied a generalized structural equation model with three mediating variables: sleep problems, job-related stress, and depressive symptoms. (3) Results: The total effect and direct effect of the categories of working hours longer than 41 h per week (h/w) for occurrence of near-misses were not significantly higher than that of 35–40 h/w. However, for indirect effects on occurrence of near-misses that first passed through job-related stress, there were higher reports for each category compared to 35–40 h/w, with odds ratios (OR) and 95% confidence intervals (95% CI) of OR = 1.12, 95% CI (1.07, 1.21) for 41–50 h/w, 1.25, (1.14, 1.41) for 51–60 h/w, and 1.31, (1.18, 1.51) for ≥ 61 h/w. 4) Conclusion: The results suggest that reducing working hours might improve job-related stress, which could reduce near-misses and prevent injuries.

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

Background Patients with COPD are less physically active. This post hoc analysis of a randomized, double-blind, active-controlled, crossover trial assessed the efficacy of once-daily tiotropium/olodaterol combination therapy versus tiotropium monotherapy in Japanese patients with COPD. Patients and methods Patients were provided with a three-axis accelerometer to measure sedentary and active behavior defined as 1.0-1.5 metabolic equivalents (METs), ≥2.0 METs, and ≥3.0 METs, respectively. Of the 182 patients enrolled, 131 satisfied the conditions for the present analysis and were randomized to tiotropium monotherapy (n=62) or tiotropium/olodaterol combination therapy (n=69). Results Tiotropium/olodaterol combination therapy significantly reduced the duration of 1.0-1.5 MET activity by 8.64 mins (p=0.040) and significantly increased the duration of ≥2.0 MET and ≥3.0 MET activity by 6.51 mins (p=0.017) and 2.60 mins (p=0.008), respectively, compared with tiotropium alone. Subgroup analyses showed that better lung function, milder dyspnea, and higher levels of physical activity at baseline were associated with reduced sedentary time and increased duration of physical activity. Conclusion Tiotropium/olodaterol combination therapy significantly reduced sedentary time and improved physical activity compared with tiotropium monotherapy. This trial was registered in ClinicalTrials.gov (NCT02629965).

Although ablation energy (AE) and force-time integral (FTI) are well-known active predictors of lesion characteristics, these parameters do not reflect passive tissue reactions during ablation, which may instead be represented by drops in local impedance (LI). This study aimed to investigate if additional LI data improves predicting lesion characteristics and steam pops.RF applications at a range of powers (30 W, 40 W, and 50 W), contact forces (8 g, 15 g, 25 g, and 35 g), and durations (10-180 s) using perpendicular/parallel catheter orientations were performed in excised porcine hearts (N = 30). The correlation between AE, FTI, and lesion characteristics was examined, and the impact of LI (%LI drop (%LID) defined by the ΔLI divided by the initial LI) was additionally assessed.Three hundred seventy-five lesions without steam pops were examined. Ablation energy (W × s) and FTI (g × s) showed a positive correlation with lesion depth (ρ = 0.824:P0.0001 and ρ = 0.708:P0.0001), surface area (ρ = 0.507:P0.0001 and ρ = 0.562:P0.0001), and volume (ρ = 0.807:P0.0001 and ρ = 0.685:P0.0001). %LID also showed a positive correlation individually with lesion depth (ρ = 0.643:P0.0001), surface area (ρ = 0.547:P0.0001), and volume (ρ = 0.733:P0.0001). However, the combined indices of AE × %LID (AE multiplied by %LID) and FTI × %LID (FTI multiplied by %LID) provided significantly stronger correlation with lesion depth (ρ = 0.834:P0.0001 and ρ = 0.809:P0.0001), surface area (ρ = 0.529:P0.0001 and ρ = 0.656:P0.0001), and volume (ρ = 0.864:P0.0001 and ρ = 0.838:P0.0001). This tendency was observed regardless of the catheter placement (parallel/perpendicular). AE (P = 0.02) and %LID (P = 0.002) independently remained as significant predictors to predict steam pops (N = 27). However, the AE × %LID did not increase the predictive power of steam pops compared to the AE alone.LI, when combined with conventional parameters (AE and FTI), may provide stronger correlation with lesion characteristics.

Background There are few agents that have been proven effective for COVID-19. Predicting clinical improvement as well as mortality or severity is very important. Objectives This study aimed to investigate the factors associated with the clinical improvement of COVID-19. Methods Overall, 74 patients receiving treatment for COVID-19 at Tokyo Medical and Dental University Hospital from April 6th to May 15th, 2020 were included in this study. Clinical improvement was evaluated, which defined as the decline of two levels on a six-point ordinal scale of clinical status or discharge alive from the hospital within 28 days after admission. The clinical courses were particularly investigated and the factors related to time to clinical improvement were analyzed with the log-rank test and the Cox proportional hazard model. Results Forty-nine patients required oxygen support during hospitalization, 22 patients required invasive mechanical ventilation, and 5 patients required extracorporeal membrane oxygenation. A total of 83% of cases reached clinical improvement. Longer period of time from onset to admission (≥10 days) (HR, 1.057; 95% CI, 1.002–1.114), no hypertension (HR, 2.077; 95% CI, 1.006–4.287), and low D-dimer levels (

Clinical implication of local impedance (LI) for radiofrequency (RF) ablation has not been fully established. This study aimed to investigate this point using IntellaNav MiFi OITM catheter. LI and generator impedance drops (ΔLI and ΔGI) were evaluated in excised porcine hearts (N = 16) during RF applications at a range of powers (30 and 50 W), contact forces (5–40 g), and durations (10–180 s) using perpendicular or parallel catheter orientation. Additionally, temporal LI changes were assessed. Of the 240 lesions without steam pops (92.3%), ΔLI showed better correlations with lesion surface area (ρ = 0.55 vs 0.36, P = 0.004), maximum depth (ρ = 0.53 vs 0.14, P < 0.001), and lesion volume (ρ = 0.64 vs 0.23, P < 0.001) than ΔGI. Furthermore, %LI-drop (ΔLI/initial LI) demonstrated stronger correlations with lesion surface area (ρ = 0.60 vs 0.55, P < 0.001), maximum depth (ρ = 0.57 vs 0.53, P < 0.001), and volume (ρ = 0.69 vs 0.64, P < 0.001) than ΔLI. Parallel catheter orientation improved correlation of ΔLI with lesion surface area (ρ = 0.63 vs 0.40, P = 0.015) and depth (ρ = 0.68 vs 0.45, P = 0.008) and created a larger surface lesion (36.3[29.2–42.7] mm2 vs 28.8[21.6–34.2] mm2, P < 0.001) than the perpendicular. LI of the lesions significantly differed between baseline, immediately after RF, and 5 min after (P < 0.01). LI reaching plateau, larger initial LI, ΔLI, and %LI-drop, and larger RF power and longer duration were observed in pop lesions (P < 0.05). %LI-drop demonstrated a better correlation with lesion size than ΔLI. LI may be used as an additional parameter to predict lesion size and steam pops. Temporal variation and catheter orientation should be considered to interpret LI.

We evaluated the impact of event-free survival (EFS) status at 24 months (EFS24) and 60 months (EFS60) after hematopoietic stem cell transplantation (HSCT) using registry data. Patients who underwent their first autologous HSCT (auto-HSCT) or allogeneic HSCT (allo-HSCT) for lymphoma between 1981 and 2018 were included. Overall survival was compared with that of the age-, sex, and calendar period–matched general population. A total of 14 977 patients, including 10 964 and 4013 who underwent auto-HSCT and allo-HSCT, respectively, were analyzed. Although patients who achieved EFS24 and EFS60 had favorable outcomes, most had significantly poorer survival rates than the general population. The standardized mortality ratios (SMRs) of patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were significantly higher than that of the general population even after achieving EFS24 or EFS60. The SMRs of those after auto-HSCT were 2.5 to 3.5 and 2.7 to 3.7, respectively. The SMR was consistently highest in Hodgkin lymphoma (HL) patients after HSCT. By contrast, subsequent survival of patients with primary mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, or peripheral T-cell lymphoma, not otherwise specified, who achieved EFS60 after auto-HSCT, and those with extranodal natural killer/T-cell lymphoma who achieved EFS60 after allo-HSCT did not significantly differ from that of the general population, with SMRs of 1.6, 1.2, 1.8, and 1.3, respectively. Our results suggest that EFS24 and EFS60 were clinically useful end points after HSCT for lymphoma patients. Furthermore, patients with certain lymphoma subtypes who achieved EFS had a comparable prognosis with that of the general population and were potentially cured after HSCT.

Background: Fibrotic hypersensitivity pneumonitis (HP) is a chronic interstitial lung disease caused by allergic responses to repeated exposures to a causative antigen. Therapeutic evidence of corticosteroid for fibrotic HP remains lacking, although corticosteroid is recognized as a major treatment option. The purpose of this study was to evaluate the efficacy of corticosteroid for patients with fibrotic HP in a propensity score-matched cohort.Methods: Retrospective medical record review from 2005 to 2019 in a single center was conducted to identify 144 patients with fibrotic HP. Semiquantitative scores of lung abnormalities on HRCT were evaluated. Patients with corticosteroid treatment (PDN group) and without the treatment (non-PDN group) were matched using a propensity score method. Survival rates and serial changes in pulmonary function, and annual changes in HRCT scores werecompared between pair-matched patients. Results: In the matched analysis, 30 of the PDN group were matched with 30 of the non-PDN group, the majority of which comprised ILD without extensive fibrosis. The survival rate was significantly better in the PDN group (P = 0.032for the stratified Cox proportional hazards model; HR, 0.250). Absolute changes in %FVC at 6, 12, and 24 months from baseline were significantly better in the PDN group. Fewer cases experienced annual deterioration in HRCT scores in the non-PDN group for ground-glass attenuation, consolidation, reticulation, traction bronchiectasis and honeycombing. Conclusions: Fibrotic HP without extensive fibrosis may receive benefits from corticosteroid treatment in terms of improvements in survival rate and pulmonary function decline and inhibition of fibrotic progression. We propose that early initiation of corticosteroid be considered for fibrotic HP when worsening fibrosis is observed.

Background Fibrotic hypersensitivity pneumonitis (HP) is a chronic interstitial lung disease caused by allergic responses to repeated exposures to a causative antigen. Therapeutic evidence of the use of corticosteroids to treat fibrotic HP remains lacking, although corticosteroids are recognized as a major treatment option. The purpose of this study was to evaluate the efficacy of corticosteroid treatment in patients with fibrotic HP in a propensity score-matched cohort. Methods A retrospective review of the medical records from 2005 to 2019 in a single center was conducted, and 144 patients with fibrotic HP were identified. Semiquantitative scores for lung abnormalities on HRCT were evaluated. Patients who received (PDN group) and did not receive (non-PDN group) corticosteroid treatment were matched using a propensity score method. Survival rates, serial changes in pulmonary function and annual changes in HRCT scores were compared in the matched cohort. Results In the matched analysis, 30 individuals in the PDN group were matched with 30 individuals in the non-PDN group, the majority of whom had ILD without extensive fibrosis. The survival rate was significantly better in the PDN group (P = 0.032 for the stratified Cox proportional hazards model; HR, 0.250). The absolute changes in FVC at 6, 12, and 24 months from baseline were significantly better in the PDN group. Fewer patients in the PDN group experienced annual deterioration, as reflected in the HRCT score, due to ground-glass attenuation, consolidation, reticulation, traction bronchiectasis and honeycombing. Conclusion We demonstrated that corticosteroids improved survival and slowed fibrotic progression in a matched cohort, the majority of whom had ILD without extensive fibrosis. Fibrotic HP with less severe fibrosis may benefit from corticosteroid treatment. We propose that the early initiation of corticosteroids should be considered for fibrotic HP when worsening fibrosis is observed.

Background Little is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US). Methods We summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications. Results The proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for ‘general disorders and administration site conditions’ from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for ‘injury, poisoning, and procedural complications’ from the class of single psychiatric medication (OR = 2.8). Conclusions The main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results.

Objectives: We evaluated long-term control of rheumatoid arthritis (RA) in Japanese paid workers (PWs) and house workers (HWs) treated with subcutaneous tocilizumab (TCZ-SC) and explored factors affecting response to TCZ-SC regarding work productivity. Methods: This study collected data from patients with RA in the TCZ-SC +/− conventional synthetic disease-modifying antirheumatic drugs group. Factors affecting the response to tocilizumab regarding work productivity were explored using logistic regression. Differences in quality-adjusted life years (QALYs) between with/without response were analysed by a linear regression. Results: Data were analysed for 357/360 patients. Patients with a ≥ 75% improvement in activity impairment (AI) were considered responders. EuroQol-5 Dimension (EQ-5D), six-item Kessler psychological distress scale score (K6), Health Assessment Questionnaire Disability Index (HAQ-DI), and the patient’s disease global health by visual analogue scale were significant contributors to TCZ-SC response based on improvements in AI. Work Functioning Impairment Scale, presenteeism, EQ-5D, K6, and HAQ-DI significantly contributed to the improvement of overall work impairment in PWs. Shorter disease duration also was related to TCZ-SC response based on AI improvements. Responders had significantly larger mean QALYs than non-responders (difference = 0.2614; p Conclusions: These real-world clinical data support long-term work productivity control with TCZ-SC for biologic-naïve HWs and PWs with RA.

Introduction The superiority of tiotropium/olodaterol is demonstrated in improvement of lung function, dyspnea, lung hyperinflation, and quality of life compared with either monotherapy in patients with chronic obstructive pulmonary disease (COPD). Japanese Respiratory Society Guidelines for COPD management include improvement of exercise tolerance and daily physical activity as the treatment goals; however, there is limited evidence in Japanese patients with COPD. Methods A protocol is developed for the VESUTO® study that investigates the efficacy of tiotropium/olodaterol fixed-dose combination (FDC) compared with tiotropium alone on inspiratory capacity (IC, volume from functional residual capacity to total lung capacity), exercise capacity, and daily physical activity in Japanese patients with COPD. Results A total of 180 Japanese patients with COPD, aged ≥40 years will be enrolled into the double-blind, multicenter, active-controlled, crossover study (NCT02629965) and will be randomized to receive either tiotropium/olodaterol FDC or tiotropium for 6 weeks each [two puffs via RESPIMAT® (Boehringer Ingelheim, Ingelheim, Germany) inhaler in the morning]. The primary endpoint is IC at rest measured at 60 min post-dose after 6 weeks treatment. The secondary endpoints include the 6-min walk distance (6MWD) at 90 min post-dose and physical activity measured by the activity monitor in the last 2 weeks of the 6-week treatment periods. Lung function tests will also be assessed after 6 weeks treatment. A mixed-effects model repeated measures approach will be used for the primary and secondary endpoints. Conclusion The VESUTO® study is the first randomized interventional study to investigate exercise capacity (6MWD) and physical activity measured by a 3-axis accelerometer in Japanese patients with COPD. The study could provide additional evidence of long-acting muscarinic antagonist (LAMA) + long-acting β2-agonist (LABA) combination therapy on patients’ physical activities as well as lung function. Trial registration ClinicalTrials.gov: NCT02629965 (registered on December 1, 2015). Funding The VESUTO study was funded by Nippon Boehringer Ingelheim Co., Ltd., Tokyo, Japan. Electronic supplementary material The online version of this article (doi:10.1007/s12325-017-0554-3) contains supplementary material, which is available to authorized users.

Objective: Previous studies have not fully evaluated the measurement properties of the Work Functioning Impairment Scale (WFun) in clinical situations and there are no data from patients with rheumatoid arthritis (RA). This study aimed to investigate the convergent validity and responsiveness of the WFun in patients with RA.Methods: This substudy was a part of the multicenter, observational, prospective FIRST ACT-SC study. In total, 322 paid workers with RA received anti-rheumatic drugs at baseline. The WFun, Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Work Productivity and Activity Impairment Questionnaire (WPAI), and Japanese Health Assessment Questionnaire Disability Index (HAQ-DI) were administrated at baseline and weeks 12, 24, and 52. Multilevel regression analyses were performed.Results: High average WFun scores were associated with higher score categories of the DAS28-ESR, CDAI, SDAI, WPAI and HAQ-DI. Average WFun change scores linearly decreased with decreases on each instruments.Conclusion: The findings indicate that the WFun has reasonable measurement properties: the scale demonstrated validity and responsiveness with RA patients. The WFun could be useful in assessing presenteeism in patients with RA.

Background Rheumatoid arthritis (RA) is a major cause of work disability, sickness-related absence from work, presenteeism, and loss of productivity. The decrease in work productivity that results from persistent pain, impaired mobility and function, and reduced quality of life (QOL) has important personal, societal, and economic consequences[1]. The efficacy of tocilizumab (TCZ) as monotherapy and in combination with methotrexate for RA is well known. Thus, in this study, we expected TCZ treatment to improve work productivity on the basis of interim results of up to 52 weeks[2]. Objectives We aimed to evaluate the long-term (104 weeks) control of RA in Japanese paid workers and house workers treated with TCZ and identify factors affecting the response (responder/non-responder) to TCZ in terms of work productivity. Methods The FIRST ACT-SC Study (UMIN-CTR: UMIN000012306) was a cohort study that assessed the 2-year treatment outcome of TCZ-SC (administered alone or with disease modifying anti rheumatic drugs) in biologics-naive Japanese patients with RA. Logistic regression analysis was performed to determine the factors contributing to treatment response in terms of activity impairment (AI) in the WPAI questionnaire, which is an index for the evaluation of overall daily life performance. In addition, the associations of these responses to treatment withdrawal rate and QOL were also evaluated. Results Of the 377 enrolled participants, 357 who were treated with TCZ-SC were included in the analysis. AI was improved from 56.2% at baseline to 22.9% at 104 weeks in the patients who received TCZ. In the single regression analysis, the factors that were statistically significant in the logistic regression analysis were job type (p=0.045), K6 as a measure of psychological distress (p=0.030), Health Assessment Questionnaire-Disability Index (HAQ-DI; p=0.023), and EuroQol five-dimensional descriptive system (EQ-5D) score (p=0.006). In the multiple logistic regression analysis, disease duration, academic background, AI, EQ-5D score, ESR, and CRP level were identified as factors that affected response. The results showed a strong association between the results of the subjective assessments such as the utility value of EQ-5D. At 104 weeks, the mean difference in AI between the EQ-5D scores of Conclusion Starting TCZ-SC treatment at an early stage while taking into consideration the subjective self-assessments of the patients may contribute to improvements in labour productivity and QOL, and long-term treatment continuation. References [1] Best Pract Res Clin Rheumatol. 2015;29(3):495-511. [2] Arthritis Res Ther 2018;20:151. Disclosure of Interests Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics, Hideto Kameda Grant/research support from: AbbVie, Asahi Kasei Pharma, Astellas, Chugai, Eisai, GlaxoSmithKlein, Mitsubishi-Tanabe, Novartis, Consultant for: AbbVie, Eli Lilly, Novartis, Speakers bureau: AbbVie, Asahi Kasei Pharma, Bristol-Myers, Chugai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Novartis, Pfize, SAITO KAZUYOSHI: None declared, Yuko Kaneko Grant/research support from: AbbVie, Eisai, Daiichi Sankyo, Sanofi, Consultant for: Bristol-Myeres Squibb, Eli Lily, Janssen, Speakers bureau: AbbVie, Eisai, Astellas, Chugai Pharmaceutical, UCB, Pfizer, Bristol-Myeres Squibb, Janssen, Tanabe-Mitsubishi, Eiichi Tanaka Consultant for: Abbvie, Ayumi Pharmaceutical, Bristol Myers Squibb, Chugai Pharmaceutical, Eisai Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, and UCB Pharma., Shinsuke Yasuda Grant/research support from: Bristol Myers Squibb, MSD, Speakers bureau: Chugai Parmaceutical, Tanabe- Mitsubishi Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Naoto Tamura Grant/research support from: Astellas Pharma Inc., Asahi Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. LTD, Eisai Inc., :Takeda Pharmaceutical Company Ltd., Speakers bureau: Janssen Pharmaceutical K.K., Bristol-Myers Squibb K.K., :Mitsubishi Tanabe Pharma Co., Keishi Fujio Grant/research support from: Astellas, BMS, Daiichi-Sankyo, Mitsubishi Tanabe, Pfizer, Ayumi, Takeda, Chugai, Eisai, Taisho Toyama, UCB, Janssen, Eli Lilly, and NIPPON KAYAKU., Speakers bureau: Astellas, BMS, Daiichi-Sankyo, Mitsubishi Tanabe, Pfizer, Ayumi, Takeda, Chugai, Eisai, Taisho Toyama, UCB, Janssen, Eli Lilly, and NIPPON KAYAKU., Takao Fujii Grant/research support from: Chugai Pharmaceutical, Speakers bureau: Chugai Pharmaceutical, Toshihisa Kojima Grant/research support from: Chugai Pharmaceutical (Investigator Initiated Study), Novartis, Nippon Kayaku, Eli Lilly, Eisai, Speakers bureau: Chugai Pharmaceutical, Takeda Pharmaceutical, Pfizer, Eli Lilly Japan, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Astelas, UCB, Janssen Pharmaceutical, Tanabe Mitsubishi, Tatsuhiko Anzai Consultant for: Chugai Pharmaceutical, Yoshihisa Fujino: None declared, Shinya Matsuda: None declared, Hitoshi Kohsaka Consultant for: CSL Behring, Speakers bureau: Japan Blood Products Organization, Ayumi Pharmacutical. and Teijin Pharmaceutical.

Masakazu Ichinose,1 Yoshiaki Minakata,2 Takashi Motegi,3 Jun Ueki,4 Yasuhiro Gon,5 Tetsuo Seki,6 Tatsuhiko Anzai,7 Shuhei Nakamura,6 Kazuto Hirata8 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, 2Department of Respiratory Medicine, National Hospital Organization Wakayama Hospital, Wakayama, 3Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, 4Clinical Research Unit of Respiratory Pathophysiology, Juntendo University Graduate School of Health Care and Nursing, Chiba, 5Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 6Medical Division, Nippon Boehringer Ingelheim Co., Ltd, 7Clinical Information Division Data Science Center, Statistics Analysis Department 1, EPS Corporation, Tokyo, 8Osaka City University, Osaka, Japan Purpose: This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD.Patients and methods: A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II–IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa. The primary endpoint was inspiratory capacity (IC) at peak post-dose.Results: Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p

Aim This study evaluates reports on neuroleptic malignant syndrome (NMS) as an adverse event associated with the use of atypical antipsychotic agents (AAA) in Japan. We examined NMS occurrence following monotherapy and combination therapy with AAA in real clinical practice using the Japanese Adverse Drug Event Report database. Methods Adverse drug reaction reports associated with the use of one or more AAA or haloperidol were analyzed. The odds ratios of NMS occurrence after monotherapy and combination therapy with AAA without typical antipsychotic agents (TAA) relative to those after haloperidol monotherapy were estimated using multiple logistic regression. Results Associated with the use of one or more AAA without TAA were 721 events of NMS in 11 071 cases. NMS occurrence after monotherapy with most AAA and their combinations had lower odds ratios than that after haloperidol use. However, the odds ratios after blonanserin monotherapy and combination therapies with quetiapine and zotepine, and risperidone and zotepine were estimated higher than 1. Conclusion Monotherapy or combination therapy with most AAA without TAA was not likely to cause NMS as an adverse reaction compared to haloperidol monotherapy. However, blonanserin monotherapy and combination therapies with quetiapine and zotepine, and risperidone and zotepine, possibly increase the report of NMS. Our results may provide useful information for medications such as AAA that are clinically used to treat mental disorders, though further research with more data are needed to clarify this.

Background Following the onset of rheumatoid arthritis (RA), patients experience a functional decline caused by various joint symptoms which affects their activities of daily living and can lead to reduced work productivity. We evaluated the effect of a 52-week treatment with tocilizumab by subcutaneous injection (TCZ-SC) among biologic-naive Japanese house workers (HWs) and paid workers (PWs) with RA in a real-world clinical practice. Methods This multicenter, observational, prospective study enrolled 377 and 347 RA patients into TCZ-SC and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)-alone groups, respectively. The primary endpoint was the change in percentage of overall work impairment (OWI) among PWs at week 52 assessed using the Work Productivity and Activity Impairment Questionnaire (WPAI). Inverse probability of treatment weighting analyses were used to compare treatments. The Work Functioning Impairment Scale, disease activity, quality of life (QOL) measures, and safety were also assessed. Results The weighted change in OWI from baseline for PWs was −18.9% (TCZ-SC group) and −19.0% (csDMARDs group) at week 52, without a significant between-group difference (adjusted treatment difference 0.1, 95% confidence interval (CI) −6.3 to 6.5; P = 0.978). Changes in WPAI activity impairment in the overall group (between-group difference −6.4, 95% CI −10.7 to −2.2; P = 0.003) and HWs (−9.5, 95% CI − 16.0 to −2.9; P = 0.005) were significantly better with TCZ-SC than with csDMARDs at week 52. TCZ-SC-treated HWs showed significant improvement in all QOL assessments (Frenchay Activities Index, EuroQol 5 Dimension (EQ-5D), Japanese Health Assessment Questionnaire Disability Index (HAQ-DI), and 6-item Kessler scale (K6)) at week 52; PWs did not show any between-group differences for these QOL measures. Disease activity (Disease Activity Score 28-erythrocyte sedimentation rate, Clinical Disease Activity Index, and Simplified Disease Activity Index) and QOL measures (EQ-5D, HAQ-DI, and K6) improved over time in the overall group. No new safety concerns were raised with TCZ-SC. Conclusions Despite the lack of differences in OWI between groups at week 52, the overall group (particularly HWs) receiving TCZ-SC in addition to csDMARDs showed significant improvements in activity impairment, disease activity, and QOL versus those receiving csDMARDs alone. This study may promote the evaluation of work productivity improvements in HWs and PWs by RA treatment. Electronic supplementary material The online version of this article (10.1186/s13075-018-1647-3) contains supplementary material, which is available to authorized users.