Sequential cellular and humoral responses after repetitive COVID-19 vaccination in patients treated with anti-CD20 antibodies.

Patients treated with anti-CD20 antibodies for haematological disorders have insufficient immune responses to mRNA COVID-19 vaccines; however, relevant sequential data are lacking. We sequentially evaluated the humoral and cellular immune responses in 22 patients who had received anti-CD20 antibodies within 12 months before the first vaccination, before and after the third and fourth vaccinations. Humoral responses improved gradually, along with the resolution of B-cell depletion. A steady increase was noted in cellular responses, regardless of the B-cell status. Our findings suggest the potential benefit of repeated vaccinations in these patients until B-cell recovery is confirmed while enhancing cellular responses.

Resurgence of Kawasaki Disease Following Relaxation of Coronavirus Disease 2019 Pandemic Restrictions in Japan.

OBJECTIVE: To compare the number and incidence of Kawasaki disease (KD) patients in years 2 through 4 of the coronavirus disease 2019 pandemic, and determine the impact of 3 years of implementation of infection control measures and their subsequent relaxation on the epidemiology of KD in Japan. STUDY DESIGN: We conducted a population-based, cohort study including consecutive KD patients in Kobe City between 2021 and 2023. We compared the incidence of KD cases, in relation to timing of infection control measures, as well as infectious disease cases based on a regional surveillance system. Data from a previous 2016 through 2020 study were used for comparison. RESULTS: A total of 566 children with KD were identified during the study period. During the infection control period in 2021 to 2022, the incidence of KD remained low compared with the prepandemic level (281.3 and 327.5/100 000 children aged 0-4 years in 2021 to 2022 and 2016 through 2019, respectively), but a recovery trend began in the 0-1-year age group. During the relaxation period in 2023, the incidence of KD increased across a wide-age range, reaching the highest recorded in Japan (426.7/100 000 children aged 0-4 years), and the median age of onset increased to age 30 months. The resurgence of KD coincided with the epidemic patterns for multiple infectious diseases in 2023. The seasonality of KD observed before the pandemic was altered. CONCLUSIONS: KD resurged in 2023 after relaxation of the prolonged coronavirus disease 2019 pandemic restrictions in Japan. This phenomenon coincided with the rise of multiple infectious diseases, and supports the pathogenesis of KD being triggered by infectious agents.

Degradation of Unsintered Hydroxyapatite and Poly-L-Lactide Composite Sheets In Vivo and In Vitro.

Bioabsorbable sheet-shaped implants made of forged composites of unsintered hydroxyapatite and poly-L-lactide (F-u-HA/PLLA) have been used for orbital fracture repair with good results. This is the first report using multiple specimens implanted in the human orbit to demonstrate the biodegradation and loss of strength of F-u-HA/PLLA sheets. Among the patients who underwent various facial fracture repairs with F-u-HA/PLLA sheets implanted in their orbits, those whose sheets were subsequently extracted were included in the study. Viscosity-average molecular weight, crystallinity, and bending strength of the extracted implants were measured. An in vitro degradation test was also performed for comparison. Among the 111 patients who underwent F-u-HA/PLLA sheet implantation, 13 subsequently underwent surgical extraction of implants; the majority were due to secondary correction of complex fractures. One patient developed an infection; none developed foreign body reactions. Overall, 11 specimens from 10 patients with consent were examined. The time from implantation to extraction ranged from 43 to 632 days (median: 210 d). Compared with the results of the in vitro degradation test, the viscosity-average molecular weight and bending strength had a slower decrease. The F-u-HA/PLLA sheets retained more than 50% of their initial bending strength after 12 months. Crystallinity varied widely. F-u-HA/PLLA sheets implanted in human orbits did not degrade faster than those of in vitro testing. Sheet-shaped implants made of forged composites of unsintered hydroxyapatite and poly-L-lactide can be considered appropriate reconstructive materials for orbital fractures as they retained sufficient strength to support the orbital contents at 12 months postoperatively, and no case of delayed foreign body reactions was observed.

The sustained psychological impact of coronavirus disease 2019 pandemic on hospital workers 2 years after the outbreak: a repeated cross-sectional study in Kobe.

BACKGROUND: Healthcare workers who are exposed to coronavirus disease 2019 are psychologically distressed. This study aimed to evaluate the mental health outcomes of hospital workers 2 years after the outbreak of coronavirus disease 2019 and to identify changes in the stress of hospital workers and predicted risk factors. METHODS: This survey was conducted 2 years after the initial evaluation performed under the first emergency declaration of the coronavirus disease 2019 pandemic among hospital workers at the same hospital in an ordinance-designated city in Japan from June to July 2022. Sociodemographic data, 19 stress-related question responses, the Impact of Event Scale-Revised, and the Maslach burnout inventory-general survey were collected. Multiple regression models were used to identify factors associated with each of the mental health outcomes 2 years after the coronavirus disease 2019 outbreak. RESULTS: We received 719 valid responses. Between 2020 and 2022, hospital workers' anxiety about infection decreased, whereas their exhaustion and workload increased. Multiple regression analysis revealed that 2 years after the coronavirus disease 2019 outbreak, nurses and young people were at a higher risk of experiencing stress and burnout due to emotional exhaustion, respectively. CONCLUSIONS: This is the first study to examine the long-term stress of hospital workers measured in Japan. Exhaustion and workload were worsened 2 years into the pandemic. Therefore, health and medical institutions should continuously monitor the physical and psychological health of staff members.

Detection of outlier prefectures on the mortality due to COVID-19 in Japan.

Japan has suffered from COVID-19 with significant mortality, but its prefectural differences are not well investigated. Since the mortality due to COVID-19 was likely to be associated with the number of infected cases, the population density, and the proportion of the elderly population, we tried to detect the outlier prefectures by multiple linear regression analyses. With the use of the Hampel identifier, we found that Hokkaido and Hyogo were the outlier prefectures with higher mortality after adjusting the variables above. Further studies should delineate the causes of these differences.

Humoral response and safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines in allogeneic hematopoietic stem cell transplant recipients: An observational study.

BACKGROUND: The effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients. METHOD: This prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared the geometric mean titers (GMT) of anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination. RESULTS: A humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The GMT of anti-S1 titers in patients and healthy controls were 277 (95% confidence interval [CI]: 120-643) BAU/mL and 532 (95% CI 400-708) BAU/mL, respectively. (p = 0.603). A short time interval between transplantation and vaccination (≤6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded. CONCLUSION: Messenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely.

Incidence and causative agent distribution of viral-induced paediatric asthma exacerbations under strict infection control measures: a single-centre retrospective study in Japan.

BACKGROUND: The prevalence of respiratory viruses in children changed under strict infection control measures during the coronavirus disease 2019 (COVID-19) outbreak. In this study, we investigated the frequency of viral detection in the nasopharynx of paediatric patients with asthma exacerbations requiring hospitalization during the COVID-19 pandemic, as well as the distribution of causative viruses. METHODS: We included paediatric patients admitted for asthma exacerbations between November 2020 and December 2022 at a single centre in Kobe, Japan. Demographic, clinical, and laboratory data were collected from their medical records and using additional questionnaires. All patients enrolled in this study met the diagnostic criteria for asthma exacerbations outlined in the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2020. Statistical differences were calculated using univariate analyses (chi-square or Mann‒Whitney U test). RESULTS: We enrolled 203 children hospitalized for asthma attacks and collected nasopharyngeal samples from 189 patients. The median patient age was 3.0 years. Asthma severity was classified as mild (4.0%), moderate (82.3%), or severe (13.8%). The proportion of viral respiratory infections was 95.2% (180/189). The rate of patients with multiple viral infections was 20.6% (39/189). The most frequently detected pathogens were rhinovirus and enterovirus (RV/EV) at 69.3% (131/189), allowing for duplicate detection, followed by respiratory syncytial virus (RSV) at 28.6% (54/189). We also detected RV/EV almost every month compared to RSV and other viruses. In addition, RV/EV-positive patients were significantly older (p = 0.033), exhibited higher WBC counts (p < 0.001) and higher Eos counts (p < 0.001), had elevated total IgE levels (p < 0.001) and house dust mite-specific IgE levels (p = 0.019), had a shorter duration of hospitalization (p < 0.001), and had a shorter duration of oxygen therapy (p < 0.001). In patients positive for RV/EV, the use of ICSs significantly reduced the severity of the condition (p < 0.001). CONCLUSION: Even under strict infection control measures, respiratory viruses were detected in the nasopharynx of almost all paediatric patients who had asthma exacerbations requiring hospitalization.

Influence of anti-coronavirus disease 2019 policies on 10 pediatric infectious diseases.

BACKGROUND: To combat the coronavirus disease 2019 pandemic, many countries, including Japan, implemented policies limiting social activities and encouraging preventive behaviors. This study examines the influence of such policies on the trends of 10 infectious pediatric diseases: pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; herpangina; respiratory syncytial virus; exanthem subitum; and mumps. METHODS: The research adopted a retrospective cohort study design. We collected data from Japan's National Epidemiological Surveillance Program detailing the incidences of the 10 diseases per pediatric sentinel site for a period beginning at 9 weeks before government-ordered school closures and ending at 9 weeks after the end of the state of emergency. We obtained corresponding data for the equivalent weeks in 2015-2019. We estimated the influence of the policies using a difference-in-differences regression model. RESULTS: For seven diseases (pharyngoconjunctival fever; group A streptococcal pharyngitis; infectious gastroenteritis; chickenpox; erythema infectiosum; hand, foot, and mouth disease; and herpangina), the incidence in 2020 decreased significantly during and after the school closures. Sensitivity analysis, in which the focus area was limited to the policy-implementation period or existing trend patterns, replicated these significant decreases for one of the above mentioned seven diseases - infectious gastroenteritis. CONCLUSIONS: Policies such as school closures and encouragement of preventive behaviors were associated with significant decreases in the incidences of most of the 10 diseases, which sensitivity analysis replicated in infectious gastroenteritis. To determine the long-term effects of these policies, prospective cohort studies are needed.

Outcomes of Pediatric Patients in Secondary Transport to Tertiary Hospital: A Retrospective Observational Study.

OBJECTIVES: Emergency medical service (EMS) providers play an important role in determining which hospital to choose. To date, there is no evidence-based guideline to support their decisions, except for major trauma cases. Secondary transport is considered when a patient needs further investigation or treatment after primary transport, but this can delay treatment and put patients at unnecessary risk. The objective of this study was to investigate the outcomes of pediatric secondary transport patients to tertiary hospitals. METHODS: This was a citywide population-based observational study conducted in Kobe, Japan. We reviewed the EMS registry to identify secondary transport patients younger than 19 years and investigated their clinical characteristics. We excluded cases of unknown hospital destinations, nontransported cases, and major trauma patients who followed a different protocol for a hospital destination. The primary endpoint was the hospital outcome 12 hours after transport. Because there was no link between the EMS patient transport data and the hospital medical records, a probabilistic linkage was performed to obtain the hospital outcomes. Patients who required secondary transport were compared with patients transported directly to tertiary hospitals. RESULTS: A total of 13,720 pediatric patients were transported from the field by Kobe EMS between January 2013 and December 2015. Among them, 81 pediatric patients (0.6%) required secondary transport to tertiary hospitals within 24 hours of the primary transport, whereas a total of 3673 patients (27%) were transported directly to tertiary hospitals. Despite no apparent difference in prehospital severity, secondary transport patients were associated with higher hospitalization rates and a need for critical care compared with those who had direct transport. Seizure was the most common reason for the use of secondary transport, and 89% of the seizure patients were hospitalized after undergoing secondary transport; minor trauma was the second most common reason for the use of secondary transport, and 53% of the patients were hospitalized. CONCLUSIONS: In this study, the characteristics of the secondary transport patients and hospital outcomes revealed a heterogeneity in pediatric prehospital transport. It is recommended that the development of pediatric EMS destination guidelines cover children's diverse conditions. Further studies are required, and linkages between prehospital and hospital data will help promote a better understanding of appropriate hospital destinations.

Relationship between serum calcium or phosphate levels and mortality stratified by parathyroid hormone level: an analysis from the MBD-5D study.

INTRODUCTION: There is limited evidence about the association between calcium and phosphate levels and mortality stratified by intact parathyroid hormone (iPTH) level. METHODS: We investigated whether differences in iPTH level affect the relationship between calcium and phosphate levels and all-cause mortality in hemodialysis patients with secondary hyperparathyroidism (SHPT). Calcium and phosphate levels were categorized as low (< 8.5 mg/dL, < 4.0 mg/dL), medium (≥ 8.5-< 9.5 mg/dL, ≥ 4.0-< 7.0 mg/dL), and high (≥ 9.5 mg/dL, ≥ 7.0 mg/dL), respectively. iPTH levels were grouped into < 300 or ≥ 300 pg/mL. Adjusted incidence rate ratios (aIRRs) were analyzed by weighted Poisson regression. RESULTS: For calcium, patients with higher iPTH (≥ 300 pg/mL) had significantly higher all-cause mortality rates in the high than in the medium category (aIRR 1.99, 95% confidence interval [CI] 1.16-3.42), and tended to have a higher mortality rate in the low category (aIRR 2.04, 95% CI 0.94-4.42). Patients with lower iPTH (< 300 pg/mL) had higher mortality rates in the high than in the medium category (aIRR 1.65, 95% CI 1.39-1.96). For phosphate, the mortality rate was significantly higher in the high than in the medium category in patients with higher and lower iPTH (aIRR 3.23, 95% CI 1.63-6.39 for iPTH ≥ 300 pg/mL; aIRR 1.58, 95% CI 1.06-2.36 for iPTH < 300 pg/mL). CONCLUSION: High calcium and phosphate levels were associated with increased risk of mortality irrespective of iPTH level.

Changes in 3-month mineral and bone disorder patterns were associated with all-cause mortality in prevalent hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: There is limited evidence on the association between short-term changes in mineral and bone disorder parameters and survival in maintenance hemodialysis patients. METHODS: We investigated the association between changing patterns of phosphorus, calcium and intact parathyroid hormone levels and all-cause mortality in hemodialysis patients with secondary hyperparathyroidism. Each parameter was divided into three categories (low [L], middle [M] and high [H]), and the changing patterns between two consecutive visits at 3-month intervals were categorized into nine groups (e.g., L-L and M-H). The middle category was defined as 4.0-7.0 mg/dL for phosphorous, 8.5-9.5 mg/dL for calcium and 200-500 pg/mL for intact parathyroid hormone. Adjusted incidence rates and rate ratios were analyzed by weighted Poisson regression models accounting for time-dependent exposures. RESULTS: For phosphorus, shifts from low/high to middle category (L-M/H-M) were associated with a lower mortality compared with the L-L and H-H groups, whereas shifts from middle to low/high category (M-L/M-H) were associated with a higher mortality compared with the M-M group. For calcium, shifts from low/middle to high category (L-H/M-H) were associated with a higher mortality compared with the L-L and M-M groups, whereas shifts from high to middle category (H-M) were associated with a lower mortality compared with the H-H group. For intact parathyroid hormone, shifts from low to middle category (L-M) were associated with a lower mortality compared with the L-L group. CONCLUSIONS: Changes in the 3-month patterns of phosphorus and calcium toward the middle category were associated with lower mortality. Our study also suggests the importance of avoiding hypercalcemia.

Heart Rate, Responsiveness to Intravenous Immunoglobulin, and Coronary Artery Aneurysms in Kawasaki Disease.

OBJECTIVE: To evaluate whether heart rate (HR) was associated with intravenous immunoglobulin (IVIG) responsiveness or development of coronary artery lesions (CALs) in patients with Kawasaki disease. STUDY DESIGN: We conducted a retrospective cohort study using data from in patients with Kawasaki disease who were hospitalized in our institution from 2006 to 2016. The patients were divided into 5 groups according to the age- and temperature-adjusted HR z score (HRZage/temp) just before IVIG administration. The ORs of outcomes were estimated by using logistic regression models, with the middle group set as the reference. RESULTS: Of the 322 patients, a total of 98 patients (30%) were refractory to initial IVIG treatment. The patients whose HRZage/temp belonged to the lowest group were at the highest risk of being refractory to the initial IVIG treatment (OR 2.10 [95% CI 1.01-4.37]). Multivariable analyses showed the same trend, though this was not statistically significant. The patients with the highest HRZage/temp were most likely to develop CALs (OR 2.61 [95%CI 0.86-7.92]). CONCLUSIONS: In patients with Kawasaki disease , HRs has a different relationship with IVIG responsiveness and CALs. Low HRZage/temp might be associated with high risk of being refractory to the initial IVIG treatment, while the risk of developing CALs increased among those whose HRs were high. Further studies are necessary to investigate the mechanisms regarding HR and these outcomes in Kawasaki disease.

Clinical features and risk factors of bile duct perforation associated with pediatric congenital biliary dilatation.

PURPOSE: This study aimed to investigate the clinical features and risk factors of bile duct perforation in pediatric congenital biliary dilatation (CBD) patients. METHODS: CBD patients, whose initial symptom was abdominal pain, were enrolled in this study and were divided into perforated and non-perforated groups. The clinical features of the perforated group were investigated. Moreover, the age at operation, sex, and morphologic features of the extrahepatic bile duct were compared between the groups. RESULTS: Fifteen cases of bile duct perforation (10.4%) were identified among the 144 CBD patients who had abdominal pain. Majority of bile duct perforation occurred in patients aged < 4 years. The median duration from onset of abdominal pain to bile duct perforation was 6 (4-14) days. Age at onset [< 4 years old; P = 0.02, OR 13.9, (1.663, 115.3)], shape of extrahepatic bile duct [non-cystic type; P = 0.009, OR 8.36, (1.683, 41.5)], and dilatation of the common channel [P = 0.02, OR 13.6, (1.651, 111.5)] were risk factors of bile duct perforation. CONCLUSIONS: Emergent bile duct drainage might be planned to prevent bile duct perforation if CBD patients have the abovementioned risk factors and experience persistent abdominal pain lasting for a few days from onset.

Predictive performance of the sequential organ failure assessment score for in-hospital mortality in patients with end-stage kidney disease in intensive care units: A multicenter registry in Japan.

INTRODUCTION: There is limited evidence regarding whether the performance of the Sequential Organ Failure Assessment (SOFA) score differs between patients with and without end-stage kidney disease (ESKD) in intensive care units (ICUs). METHODS: We used a multicenter registry (Japanese Intensive care Patient Database) to enroll adult ICU patients between April 2018 and March 2021. We recalibrated the SOFA score using a logistic regression model and evaluated its predictive ability in both ESKD and non-ESKD groups. The primary outcome was in-hospital mortality. RESULTS: 128 134 patients were enrolled. The AUROC of the SOFA score was lower in the ESKD group than in the non-ESKD group [0.789 (95% CI, 0.774-0.804) vs. 0.846 (95% CI, 0.841-0.850)]. The calibration plot revealed good performance in both groups. However, it overestimated in-hospital mortality in ESKD groups. CONCLUSION: The SOFA score demonstrated good predictive ability in patients with and without ESKD, but it overestimated the in-hospital mortality in ESKD patients.

Molecular Autopsy With Banked Cord Blood Reveals Brugada Syndrome in Past Sudden Death Case.

Molecular autopsy has recently been gaining attention as a means of postmortem diagnosis; however, it is usually performed using the victim's blood sample at the time of death. Here, we report the first case of a deceased infant with Brugada syndrome whose diagnosis was made with banked cord blood. A seemingly healthy 1-year-old male infant collapsed while having a fever; this collapse was witnessed by his mother. Despite cardiopulmonary resuscitation, he died of ventricular fibrillation. No abnormalities of cardiac structure were identified on autopsy. Genomic samples were not stored at the time because of a lack of suspicion for familial arrhythmia. Five years later, his sister showed Brugada electrocardiogram pattern while febrile from Kawasaki disease. Their father showed a spontaneous type 1 Brugada electrocardiogram pattern. A heterozygous SCN5A p.R893C variant was found by genetic testing in the proband's father and sister. Furthermore, the proband's genetic testing was performed using his banked cord blood, which identified the same variant. Family history of Brugada syndrome with an SCN5A-R893C variant and clinical evidence led to a postmortem diagnosis of Brugada syndrome in the proband. Identification of this variant in this case later contributed to verifying SCN5A-R893C as a pathogenic variant through data accumulation. Banked cord blood may prove useful for conducting molecular autopsies in previously undiagnosed cases of sudden death in which genomic samples were not stored.

Initial intravenous immunoglobulin therapy without aspirin for acute Kawasaki disease: a retrospective cohort study with a Bayesian inference.

OBJECTIVE: To clarify the necessity of acetylsalicylic acid (ASA) administration combined with intravenous immunoglobulin (IVIG) therapy in the treatment of acute Kawasaki disease. DESIGN: Retrospective cohort study. SETTING: Multicentre. PARTICIPANTS: This study included 735 patients with Kawasaki disease aged ≤10 years and hospitalised between 4 and 10 days of illness in eight Japanese hospitals from January 2016 to December 2020. EXPOSURES: High-dose (HD) ASA was administered with initial IVIG to 333 patients in 6 hospitals (HD group). ASA was not administered routinely to 402 patients in the other two hospitals, and low-dose ASA was only administered when patients developed coronary artery lesions or pericardial effusion (non-HD group). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the presence of coronary artery lesions, defined as a coronary artery diameter >+2.5 SD of body surface area within 1 month of onset. The secondary outcome was responsiveness to the initial IVIG therapy. Adjusted risk ratios for the outcomes were calculated using modified Poisson regression models. Bayesian analysis was conducted to estimate the posterior probability of the treatment effect of HD ASA under several prior distributions. RESULTS: The incidence of coronary artery lesions was not significantly higher in the HD group than in the non-HD group (12/333 (3.6%) vs 15/402 (4.0%)). The proportion of non-responders to initial IVIG was similar between the two groups (HD group: 78/333 (23%); non-HD group: 83/402 (22%)). In the Bayesian analysis, considering a difference of ≤2% to be of no clinical importance, there was only a 9.3% chance of reduced risk of coronary artery lesions in the HD group compared with the non-HD group even with a strongly enthusiastic prior for HD treatment. CONCLUSIONS: Compared with HD ASA treatment, treatment without ASA in the acute phase of Kawasaki disease was not associated with increased complications from Kawasaki disease.

Randomized Phase II Trial of Amrubicin Plus Irinotecan Versus Cisplatin Plus Irinotecan in Chemo-naïve Patients With Extensive-Disease Small-Cell Lung Cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08-01.

BACKGROUND: We conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: Chemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m2 on day 1 and irinotecan 50mg/m2 on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m2 on day 1 and irinotecan 60mg/m2 on days 1, 8 and 15 of a 28-day cycle). The primary endpoint was overall survival proportion at 1 year. RESULTS: A total of 100 patients were randomly assigned to AI (n = 50) or to PI (n = 50). The 1-year overall survival proportions were 68.0% (95% confidence interval (CI): 56.2-82.2%) for AI and 59.2% (46.9-74.7%) for PI (1-sided P = .18). Median survival time was 14.8 months for AI and 13.5 months for PI with a hazard ratio (HR) of 0.618 (0.398-0.961, stratified log-rank test P = .031). Median progression-free survival time was 4.8 months for AI and 5.4 months for PI (stratified log-rank test, P = .54). Objective response rate was 70.0% (55.4-82.1%) for AI and 55.1% (40.2-69.3%) for PI (Fisher exact test, P = .15). There was no significant difference in hematological toxicity, whereas rates of vomiting, loss of appetite, diarrhea, and elevated serum creatinine are more frequent in PI. Interstitial lung disease (Grade 2 or 3) developed in 5 patients in AI and in 1 patient in PI. There was no treatment-related death. CONCLUSION: Although the study did not meet its primary endpoint, AI showed promising efficacy and good tolerability in chemo-naïve patients with ED-SCLC.

Motivation and hesitation of healthcare workers to work during the H1N1 influenza and COVID-19 pandemics: An exploratory single-centered repeated cross-sectional study.

Aim: Pandemics of life-threatening viruses have detrimental impacts on the motivation of healthcare workers to work. However, no study has examined this impact during different pandemics with the same setting and design. This study aimed to reveal similarities and differences in factors associated with willingness and hesitation to work between two recent pandemics, H1N1 influenza and COVID-19, in the same hospital, using the same questionnaire. Methods: Healthcare workers in one hospital in Japan completed a questionnaire on basic characteristics and stress-related questions during the H1N1 influenza (n = 1061) and the COVID-19 (n = 1111) pandemics. Logistic regressions were performed to ascertain the effect of personal characteristics and stress-related questions on the likelihood that employees showed strong or weak motivation or hesitation to work. Results: The feeling of being protected by the hospital was the only factor that significantly decreased hesitation and increased motivation to work, and females felt significantly more hesitation to work than males did in both pandemics. Conclusions: Hospital managers and government officers should focus on increasing organizational support and caring for female workers to maintain healthcare workers' motivation to work during future pandemics.

α-Blocker Use in Hemodialysis: The Japan Dialysis Outcomes and Practice Patterns Study.

Rationale & Objective: Despite α-blockers' use for hypertension as add-on therapy in patients treated with hemodialysis, scant information is available on their association, particularly with safety, in these patients. Study Design: Prospective cohort study. Setting & Participants: patients treated with hemodialysis and receiving antihypertensive agents in the Japan Dialysis Outcomes and Practice Patterns Study, phases 4-6, were analyzed. Exposure: Primary exposure was the prescription of α-blocking antihypertensive agents at baseline. Outcomes: Incident fractures, falls, and all-cause mortality. Analytical Approach: Multivariable Cox and modified Poisson regression analysis. Results: Of 5,149 patients treated with hemodialysis (mean age, 65 years; 68% men) receiving antihypertensive drugs, 717 (14%) received α-blocking agents. During a mean follow-up period of 2.0 years, 247 fractures, 525 falls, and 498 deaths occurred. Multivariable analysis showed no significant association of α-blocker use and increased risk of fractures (hazard ratio [HR], 0.92 [95% confidence interval {CI}, 0.61-1.38]), falls (HR, 0.94 [95% CI, 0.74-1.20]), or all-cause deaths (HR, 0.87 [95% CI, 0.64-1.20]) compared with α-blocker nonuse. α-Blocker use was, however, significantly associated with a decreased risk of all-cause mortality in the subgroup analysis, for example, patients who were older (HR, 0.71 [95% CI, 0.51-0.99]), were women (HR, 0.68 [95% CI, 0.48-0.95]), or reported a history of cardiovascular disease (HR, 0.67 [95% CI, 0.48-0.95]) or a predialysis blood pressure of ≥140 mm Hg (HR, 0.69 [95% CI, 0.49-0.98]). Limitations: Selection bias cannot be ruled out given the prevalent user analysis. Conclusions: No significant association between α-blocker use and the risk of worse safety-related outcomes was seen, indicating that clinicians may safely prescribe α-blockers to patients receiving hemodialysis who require blood pressure lowering. Plain-Language Summary: α-Blockers have been generally reserved for use as add-on therapy for resistant or refractory hypertension. However, little is known about the safety of α-blockers in patients treated by hemodialysis. We analyzed 5,149 patients receiving hemodialysis in Japan who were receiving antihypertensive drugs from the Japan Dialysis Outcomes and Practice Patterns Study. The results showed no significant increase in the risk of fractures, falls, or deaths for patients using α-blockers compared with those who did not, suggesting that α-blockers may be safely prescribed for patients receiving hemodialysis who need to lower their blood pressure.