Cost-Effectiveness Analysis of Maternal Respiratory Syncytial Virus Vaccine in Protecting Infants from RSV Infection in Japan.

INTRODUCTION: Respiratory syncytial virus (RSV) is one of the major causes of respiratory tract infections among children. Until recently, the monoclonal antibody palivizumab was the only RSV prophylaxis available in Japan. In 2024, the bivalent RSV prefusion F protein-based (RSVpreF) vaccine was approved for the prevention of RSV infection in infants by active immunization of pregnant women. In this study, we assessed the cost-effectiveness of a combined strategy of RSVpreF vaccine and palivizumab in Japanese setting. METHODS: Using a Markov model, we evaluated prevented cases and deaths of medically attended RSV infections from birth to age 11 months for each of the three healthcare settings: inpatient (hospitalization), emergency department visits, and outpatient visits. Incremental cost-effectiveness ratios (ICERs) were calculated from economic outcomes (intervention costs, medication costs, and productivity losses) and quality-adjusted life years (QALYs). Further, we calculated the maximum price of RSVpreF vaccine within which the program would be cost-effective. RESULTS: In comparison with the current prophylaxis (palivizumab alone), a combined prophylaxis of year-round RSVpreF vaccination of pregnant women and palivizumab prescription for premature infants born in < 32 weeks gestational age (wGA) and all infants with high risk prevented 14,382 medically attended cases of RSV (hospitalization, 7490 cases; emergency department, 2239 cases; outpatient, 4653 cases) and 7 deaths, respectively. From a healthcare payer perspective, when the price of RSVpreF vaccine was equal to or less than ¥23,948 (US $182), a combination prophylaxis was cost-effective under the ICER threshold of ¥5 million per QALY. The other combination prophylaxis of year-round RSVpreF vaccination and palivizumab prescription of premature born in < 32 wGA regardless of risk in infants was a dominant strategy (more effective and less costly). CONCLUSION: A combined prophylaxis of year-round RSVpreF vaccine and palivizumab could be a cost-effective strategy to protect neonates throughout the infant stage (< 1 years old) in Japan.

Neurological prognosis prediction upon arrival at the hospital after out-of-hospital cardiac arrest: R-EDByUS score.

AIM: To develop a new scoring model for patients with cardiogenic out-of-hospital cardiac arrest (OHCA) to facilitate neurological prognosis prediction upon hospital arrival by using prehospital resuscitation features alone. METHODS: Between 2005 and 2019, we enrolled 942,891 adult patients with OHCA of presumed cardiac aetiology from the All-Japan Utstein Registry. Scoring models applied prehospital resuscitation features a priori from the variables the American College of Cardiology algorithm including age, duration to return of spontaneous circulation (ROSC) or hospital arrival, no bystander cardiopulmonary resuscitation (CPR), unwitnessed arrest, and nonshockable rhythm (R-EDByUS score) to predict unfavorable neurological outcomes defined as Cerebral Performance Category 3, 4, or 5 at 1 month. We created nomograms as a "Regression-based model," and created a "Simplified model" in which points were assigned by category for predicting unfavorable neurological outcomes for both the prehospital ROSC cohort (67,064 patients) and the ongoing CPR cohort (875,827 patients). For internal validation, bootstrap optimism-corrected estimates of predictive performance were calculated. RESULTS: A total of 46,971 (70.0%) and 870,991 (99.4%) patients in the prehospital ROSC and ongoing CPR cohorts, respectively, had unfavorable neurological outcomes. In the prehospital ROSC cohort, the C-statistics of the Regression-based and Simplified models were 0.851 and 0.842, and the bootstrap-validated C-statistics were 0.852 and 0.841, respectively. In the ongoing CPR cohort, the C-statistics of the Regression-based and Simplified models were 0.872 and 0.865, and the bootstrap-validated C-statistics were 0.852 and 0.841, respectively. CONCLUSIONS: The R-EDByUS score accurately predicted the neurological prognosis of cardiogenic OHCA upon hospital arrival.

Association between defibrillation-to-adrenaline interval and short-term outcomes in patients with out-of-hospital cardiac arrest and an initial shockable rhythm.

Aim: The optimal timing of adrenaline administration after defibrillation in patients with out-of-hospital cardiac arrest (OHCA) and an initial shockable rhythm is unknown. We investigated the association between the defibrillation-to-adrenaline interval and clinical outcomes. Methods: Between 2011 and 2020, we enrolled 1,259,960 patients with OHCA into a nationwide prospective population-based registry in Japan. After applying exclusion criteria, 20,905 patients with an initial shockable rhythm documented at emergency medical services (EMS) arrival who received adrenaline after defibrillation were eligible for this study. Multivariable logistic regression analysis was used to predict favourable short-term outcomes: prehospital return of spontaneous circulation (ROSC), 30-day survival, or a favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. Patients were categorised into 2-minute defibrillation-to-adrenaline intervals up to 18 min, or more than 18 min. Results: At 30 days, 1,618 patients (8%) had a favourable neurological outcome. The defibrillation-to-adrenaline interval in these patients was significantly shorter than in patients with an unfavourable neurological outcome [8 (5-12) vs 11 (7-16) minutes; P < 0.001]. The proportion of patients with prehospital ROSC, 30-day survival, or a favourable neurological outcome at 30 days decreased as the defibrillation-to-adrenaline interval increased (P < 0.001 for trend). Multivariable analysis revealed that a defibrillation-to-adrenaline interval of > 6 min was an independent predictor of worse prehospital ROSC, 30-day survival, or neurological outcome at 30 days when compared with an interval of 4-6 min. Conclusion: A longer defibrillation-to-adrenaline interval was significantly associated with worse short-term outcomes in patients with OHCA and an initial shockable rhythm.

Cost-effectiveness analysis of adult pneumococcal conjugate vaccines for pneumococcal disease in Japan.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is used in the Japanese National Immunization Program for older adults and adults with increased risk for pneumococcal disease, however, disease incidence and associated burden remain high. We evaluated the cost-effectiveness of pneumococcal conjugate vaccines (PCVs) for adults aged 65 years and high-risk adults aged 60-64 years in Japan. RESEARCH DESIGN AND METHODS: Using a Markov model, we evaluated lifetime costs using societal and healthcare payer perspectives and estimated quality-adjusted life-years (QALYs), and number of prevented cases and deaths caused by invasive pneumococcal disease (IPD) and non-IPD. The base case analysis used a societal perspective. RESULTS: In comparison with PPSV23, the 20-valent PCV (PCV20) prevented 127 IPD cases 10,813 non-IPD cases (inpatients: 2,461, outpatients: 8,352) and 226 deaths, and gained more QALYs (+0.0015 per person) with less cost (-JPY22,513 per person). All sensitivity and scenario analyses including a payer perspective analysis indicated that the incremental cost-effectiveness ratios (ICERs) were below the cost-effectiveness threshold value in Japan (JPY5 million/QALY). CONCLUSIONS: PCV20 is both cost saving and more effective than PPSV23 for adults aged 65 years and high-risk adults aged 60-64 years in Japan.

Impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest outcomes in Japan.

This study investigates the impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest (OHCA) outcomes in Japan, aiming to address a critical research gap. Analyzing data from the All-Japan Utstein registry covering pediatric OHCA cases from 2018 to 2021, the study observed no significant changes in one-month survival, neurological outcomes, or overall performance when comparing the pre-pandemic (2018-2019) and pandemic (2020-2021) periods among 6765 cases. However, a notable reduction in pre-hospital return of spontaneous circulation (ROSC) during the pandemic (15.1-13.1%, p = .020) was identified. Bystander-initiated chest compressions and rescue breaths declined (71.1-65.8%, 22.3-13.0%, respectively; both p < .001), while bystander-initiated automated external defibrillator (AED) use increased (3.7-4.9%, p = .029). Multivariate logistic regression analyses identified factors associated with reduced pre-hospital ROSC during the pandemic. Post-pandemic, there was no noticeable change in the one-month survival rate. The lack of significant change in survival may be attributed to the negative effects of reduced chest compressions and ventilation being offset by the positive impact of widespread AED availability in Japan. These findings underscore the importance of innovative tools and systems for safe bystander cardiopulmonary resuscitation during a pandemic, providing insights to optimize pediatric OHCA care.

Cost-effectiveness analysis of 20-valent pneumococcal conjugate vaccine for routine pediatric vaccination programs in Japan.

BACKGROUND: The Japanese National Immunization Program currently includes the pediatric 13 valent pneumococcal conjugate vaccine (PCV13) to prevent pneumococcal infections. We aimed to evaluate the cost-effectiveness of 20-valent PCV (PCV20) as a pediatric vaccine versus PCV13. METHODS: A decision-analytic Markov model was used to estimate expected costs, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by invasive pneumococcal disease, pneumonia, and acute otitis media over a ten-year time horizon from the societal and healthcare payer perspectives. RESULTS: PCV20 was dominant, i.e. less costly and more effective, over PCV13 (gained 294,599 QALYs and reduced Japanese yen [JPY] 352.6 billion [2.6 billion United States dollars, USD] from the societal perspective and JPY 178.9 billion [USD 1.4 billion] from the payer perspective). Sensitivity and scenario analyses validated the robustness of the base scenario results. When comparing PCV20 with PCV13, the threshold analysis revealed an incremental cost-effectiveness ratio that was within the threshold value (JPY 5 million/QALY) at a maximum acquisition cost of JPY 74,033 [USD 563] (societal perspective) and JPY 67,758 [USD 515] (payer perspective). CONCLUSIONS: As a pediatric vaccine, PCV20 was dominant over PCV13 regardless of the study perspective.

Burden of Antimicrobial Resistance in Japan: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Antimicrobial resistance (AMR) is one of the most serious public health challenges worldwide, including in Japan. However, there is limited evidence assessing the AMR burden in Japan. Thus, this systematic literature review (SLR) and meta-analysis (MA) were conducted to assess the clinical and economic burden of AMR in Japan. METHODS: Comprehensive literature searches were performed on EMBASE, MEDLINE, the Cochrane Library, and ICHUSHI between 2012 and 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MA estimated a pooled effect between the two comparative arms (AMR vs. non-AMR). The results were reported in measures of odds ratios (ORs) for in-hospital mortality and in standardized mean differences (SMDs) for length of stay (LOS) and direct medical costs. RESULTS: Literature searches identified 1256 de-duplicated records, of which 56 observational studies (English, n = 35; Japanese, n = 21) were included. Of note, twenty-two studies (39.3%) compared the AMR group with non-AMR group. In the SLR, in-hospital mortality, LOS, and direct medical costs were higher in the AMR group compared to the non-AMR group. Eight studies were selected for the MA. In the AMR group, the pooled estimate showed a statistically higher in-hospital mortality [random effect (RE)-OR 2.25, 95% CI 1.34-3.79; I2 = 89%; τ2 = 0.2257, p < 0.01], LOS (RE-SMD 0.37, 95% CI - 0.09-0.84; I2 = 99%; τ2 = 0.3600, p < 0.01), and direct medical cost (RE-SMD 0.53, 95% CI 0.43-0.62; I2 = 0.0%; τ2 = 0.0, p = 0.88) versus the non-AMR group. CONCLUSION: Our study presents an overview of the clinical and economic burden of AMR in Japan. Patients with AMR infections experience significantly higher in-hospital mortality, LOS, and direct medical costs compared with patients without AMR infections.

Impact of Updating the Cardiopulmonary Resuscitation Guidelines on Out-of-Hospital Shockable Cardiac Arrest: A Population-Based Cohort Study in Japan.

BACKGROUND: International consensus on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care science and treatment recommendations (CoSTR) have reported updates on CPR maneuvers every 5 years since 2000. However, few national population-based studies have investigated the comprehensive effectiveness of those updates for out-of-hospital cardiac arrest due to shockable rhythms. The primary objective of the present study was to determine whether CPR based on CoSTR 2005 or 2010 was associated with improved outcomes in Japan, as compared with CPR based on Guidelines 2000. METHODS AND RESULTS: From the All-Japan Utstein Registry between 2005 and 2015, we included 73 578 adults who had shockable out-of-hospital cardiac arrest witnessed by bystanders or emergency medical service responders. The study outcomes over an 11-year period were compared between 2005 of the Guidelines 2000 era, from 2006 to 2010 of the CoSTR 2005 era, and from 2011 to 2015 of the CoSTR 2010 era. In the bystander-witnessed group, the adjusted odds ratios for favorable neurological outcomes at 30 days after out-of-hospital cardiac arrest by enrollment year increased year by year (1.19 in 2006, and 3.01 in 2015). Similar results were seen in the emergency medical service responder-witnessed group and several subgroups. CONCLUSIONS: Compared with CPR maneuvers for shockable out-of-hospital cardiac arrest recommended in the Guidelines 2000, CPR maneuver updates in CoSTR 2005 and 2010 were associated with improved neurologically intact survival year by year in Japan. Increased public awareness and greater dissemination of basic life support may be responsible for the observed improvement in outcomes. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: 000009918.

Cost-effectiveness analysis of COVID-19 booster vaccination with BNT162b2 in Japan.

BACKGROUND: The aim of this study was to evaluate the public health and economic impact of the COVID-19 booster vaccination with BNT162b2 in Japan during an Omicron-dominant period from early 2022. RESEARCH DESIGN AND METHODS: A combined cohort Markov decision tree model estimated the cost-effectiveness of annual or biannual booster vaccination strategies compared to no booster vaccination for those aged 65 years and above, and those aged 60-64 years at high risk as the base case. The societal perspective was primarily considered. We also examined other target populations with different age and risk groups. Sensitivity and scenario analyses with alternative inputs were performed. RESULTS: Annual and biannual vaccination strategies were dominant from the societal perspective in the base case. Incremental Cost Effectiveness Ratios (ICERs) from the payer perspective were JPY 1,752,499/Quality Adjusted Life Year (QALY) for annual vaccination and JPY 2,831,878/QALY for biannual vaccination, both less than the threshold value in Japan (JPY 5 million/QALY). The results were consistent even when examining other target age and risk groups. All sensitivity and scenario analyses indicated that ICERs were below JPY 5 million/QALY. CONCLUSIONS: Booster vaccination with the COVID-19 vaccine BNT162b2 is a dominant strategy and beneficial to public health in Japan.

Treatment patterns and characteristics of patients with migraine: results from a retrospective database study in Japan.

BACKGROUND: Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options. METHODS: Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort. RESULTS: In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities. CONCLUSIONS: This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described.

Impact of a national initiative to provide civilian cardiopulmonary resuscitation training courses on the rates of bystander intervention by citizens and survival after out-of-hospital cardiac arrest.

BACKGROUND: The impact of a national initiative to provide cardiopulmonary resuscitation (CPR) education to the public on the rates of citizen-initiated CPR and survival following out-of-hospital cardiac arrest (OHCA) remains uncertain. METHODS: We examined 358,025 cases of citizen-witnessed OHCA with presumed cardiac origin, recorded in the Japanese nationwide registry from 2005 to 2020. We assessed the relationship between the number of individuals certified in CPR courses, citizen interventions, and neurologically favorable survival at one month. RESULTS: The cumulative number of certified citizens has linearly increased from 9,930,327 in 2005 to 34,938,322 in 2020 (incidence rate ratio for annual number = 1.03, p < 0.001), encompassing 32.3% of the Japanese population aged 15 and above. Similarly, the prevalence of citizen-initiated CPR has consistently increased from 40.6% in 2005 to 56.8% in 2020 (P for trend < 0.001). Greater citizen CPR engagement was significantly associated with better outcome in initial shockable rhythm patients [chest compression only: odds ratio (OR) 1.24; 95% confidence interval (CI) 1.02-1.51; P = 0.029; chest compression with rescue breathing: OR 1.33; 95% CI 1.08-1.62; P = 0.006; defibrillation with chest compression: OR 2.27; 95% CI 1.83-2.83; P < 0.001; defibrillation with chest compression and rescue breathing: OR 2.15; 95% CI 1.70-2.73; P < 0.001 vs. no citizen CPR]. CONCLUSIONS: The incidence of citizen-initiated CPR across Japan has consistently and proportionately increased with the rising number of individuals certified in CPR courses. Greater citizen CPR involvement has been linked to neurologically favorable survival, particularly in cases with an initial shockable rhythm.

Impact of comprehensive quality improvement program on outcomes in very-low-birth-weight infants: A cluster-randomized controlled trial in Japan.

BACKGROUND: Differences in outcomes among neonatal intensive care units (NICUs) in Japan have been noted, prompting the need for quality improvement. AIM: To assess a comprehensive quality improvement program on outcomes in very-low-birth-weight (VLBW) infants. STUDY DESIGN: A cluster-randomized clinical trial. SUBJECTS: Forty hospitals and VLBW infants born in 2012-2014 and admitted to those hospitals were study subjects. OUTCOME MEASURES: The intervention group (IG) received a comprehensive quality improvement program involving clinical practice guidelines, educational outreach visits, workshops, opinion leader training, audits, and feedback. The control group (CG) was provided only with the guidelines. The primary outcome was survival without neurological impairment at three years of age. RESULTS: IG consisted of 19 hospitals and 1735 infants, while CG included 21 hospitals and 1700 infants. There were no significant differences in gestational weeks, 29.1(26.9-31.3) vs. 29.1(26.7-31.1) or birth weights (g), 1054(789-1298) vs. 1084(810-1309) between the two groups. Both groups showed survival rates without neurological impairment of 67.2 % (1166) and 66.9 % (1137), respectively, without a significant difference. There was no significant difference in mortalities at NICU discharge between the groups, with rates of 4.0 % (70) and 4.2 % (72) respectively. Several clinically relevant improvements were observed in IG, including reduced rates of sepsis, adrenal insufficiency, transfusion for anemia, and a shorter interval to achieve full enteral feeding. However, these did not lead to improvements in the primary outcome. CONCLUSION: The comprehensive quality improvement program to Japanese NICUs did not result in a significant improvement in survival without neurological impairment in VLBW infants.

Changes in health-related quality of life in patients admitted to emergency departments for attempted suicide: Findings from a large longitudinal study.

BACKGROUND: Studies of quality of life among suicide attempters are limited while it is considered important for preventing reattempt of suicide. We investigated health related quality of life (HRQoL) in suicide attempters immediately after the suicide attempt and in the long term. METHODS: This was longitudinal data from a randomized controlled multicenter trial. The Japanese version of the Short Form Health Survey-36 as HRQOL measured at 0, 6, and 12 months after randomization. RESULTS: 799 patients (356 men and 443 women) were analyzed. At baseline, the mean physical component summary (PCS) and the mental component summary (MCS) scores were 34.56 and 35.15, respectively, and they were significantly low compared with those of the general population. PCS scores significantly improved from baseline to 6 months (p = 0.003), from baseline to 12 months (p < 0.0001), and from baseline to 12 months (p = 0.002). MCS scores significantly improved from baseline to 6 months (p < 0.0001) and from baseline to 12 months (p < 0.0001). However, neither PCS nor MCS scores reached those of the general population norm at 12 months post-suicide attempt. LIMITATIONS: Patients younger than 20 years and patients who self-harmed but were not admitted to an emergency department were excluded. CONCLUSION: This study presents a trajectory of HRQoL scores in suicide attempters from immediately after the suicide attempt to 1 year later. Further studies on HRQoL in suicide attempters are needed to elucidate the effective care for the attempters.

Prehospital predicting factors using a decision tree model for patients with witnessed out-of-hospital cardiac arrest and an initial shockable rhythm.

The effect of prehospital factors on favorable neurological outcomes remains unclear in patients with witnessed out-of-hospital cardiac arrest (OHCA) and a shockable rhythm. We developed a decision tree model for these patients by using prehospital factors. Using a nationwide OHCA registry database between 2005 and 2020, we retrospectively analyzed a cohort of 1,930,273 patients, of whom 86,495 with witnessed OHCA and an initial shockable rhythm were included. The primary endpoint was defined as favorable neurological survival (cerebral performance category score of 1 or 2 at 1 month). A decision tree model was developed from randomly selected 77,845 patients (development cohort) and validated in 8650 patients (validation cohort). In the development cohort, the presence of prehospital return of spontaneous circulation was the best predictor of favorable neurological survival, followed by the absence of adrenaline administration and age. The patients were categorized into 9 groups with probabilities of favorable neurological survival ranging from 5.7 to 70.8% (areas under the receiver operating characteristic curve of 0.851 and 0.844 in the development and validation cohorts, respectively). Our model is potentially helpful in stratifying the probability of favorable neurological survival in patients with witnessed OHCA and an initial shockable rhythm.

Sex- and Age-Based Disparities in Public Access Defibrillation, Bystander Cardiopulmonary Resuscitation, and Neurological Outcome in Cardiac Arrest.

Importance: Younger females with out-of-hospital cardiac arrest (OHCA) in public locations have less likelihood to receive public access defibrillation and bystander cardiopulmonary resuscitation (CPR). However, the association between age- and sex-based disparities and neurological outcomes remains underexamined. Objective: To investigate the association between sex and age and the rate of receiving bystander CPR, automated external defibrillator defibrillation, and neurological outcomes in patients with OHCA. Design, Setting, and Participants: This cohort study used the All-Japan Utstein Registry, a prospective, population-based, nationwide database in Japan containing data on 1 930 273 patients with OHCA between January 1, 2005, and December 31, 2020. The cohort comprised patients with OHCA of cardiac origin that was witnessed by citizens and treated by emergency medical service personnel. The data were analyzed from September 3, 2022, to May 5, 2023. Exposure: Sex and age. Main Outcomes and Measures: The primary outcome was favorable neurological outcome at 30 days after an OHCA. Favorable neurological outcome was defined as a Cerebral Performance Category score of 1 (indicating good cerebral performance) or 2 (indicating moderate cerebral disability). The secondary outcomes were the rates of receiving public access defibrillation and bystander CPR. Results: The 354 409 included patients who experienced bystander-witnessed OHCA of cardiac origin had a median (IQR) age of 78 (67-86) years and 136 520 were females (38.5%). The rate of receiving public access defibrillation was higher in males than females (3.2% vs 1.5%; P < .001). Stratified by age, age- and sex-based disparities in prehospital lifesaving interventions by bystanders and in neurological outcomes were observed. Although younger females had a lower rate of receiving public access defibrillation and bystander CPR than males, younger females had a higher favorable neurological outcome compared with males of the same age (odds ratio [OR], 1.19; 95% CI, 1.08-1.31). In younger females with OHCA that was witnessed by nonfamily bystanders, receiving public access defibrillation (OR, 3.51; 95% CI, 2.34-5.27) or bystander CPR (OR, 1.62; 95% CI, 1.20-2.22) was associated with a favorable neurological outcome. Conclusions and Relevance: Results of this study suggest a pattern of significant sex- and age-based differences in bystander CPR, public access defibrillation, and neurological outcomes in Japan. Improvement in neurological outcomes in patients with OHCA, especially younger females, was associated with increased use of public access defibrillation and bystander CPR.

Changes in neurological outcomes of out-of-hospital cardiac arrest during the COVID-19 pandemic in Japan: a population-based nationwide observational study.

Background: There is growing interest in the indirect negative effects of coronavirus disease 2019 (COVID-19) on mortality. We aimed to assess its indirect effect on out-of-hospital cardiac arrest (OHCA) outcomes. Methods: We analysed a prospective nationwide registry of 506,935 patients with OHCA between 2017 and 2020. The primary outcome was favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. The secondary outcomes were public access defibrillation (PAD) and bystander-initiated chest compression. We performed an interrupted time series (ITS) analysis to assess changes in the trends of these outcomes around the declaration of a state of emergency (April 7 - May 25, 2020). We also performed a subgroup analysis stratified by infection spread status. Findings: We identified 21,868 patients with OHCA witnessed by a bystander who had an initial shockable heart rhythm. ITS analysis showed a drastic decline in PAD use (relative risk [RR], 0.60; 95% confidence interval [CI], 0.49-0.72; p < 0.0001) and a reduction in favourable neurological outcomes (RR, 0.79; 95% CI, 0.68-0.91; p = 0.0032) all over Japan after the state of emergency was declared when compared with the equivalent time period in previous years. The decline in favourable neurological outcomes was more pronounced in areas with COVID-19 spread than in areas without spread (RR, 0.70; 95% CI, 0.58-0.86 vs. RR, 0.87; 95% CI, 0.72-1.03; p for effect modification = 0.019). Interpretation: COVID-19 is associated with worse neurological outcomes and less PAD use in patients with OHCA. Funding: None.

Real-world treatment patterns of novel drugs in relapsed or refractory acute lymphoblastic leukemia patients in Japan.

Aim: To evaluate treatment patterns of novel therapies (inotuzumab ozogamicin (inotuzumab), blinatumomab, and tisagenlecleucel) in patients with acute lymphoblastic leukemia (ALL) in a Japanese real-world setting. Patients & Methods: Patients with ALL diagnoses from a Japanese claims database were examined. Results: We included 194 patients (97 patients were prescribed inotuzumab; 97 patients were prescribed blinatumomab; and no patient was prescribed tisagenlecleucel); 81.4% in the inotuzumab group and 78.4% in the blinatumomab group were prescribed chemotherapy prior to the initiation of those drugs. Most patients were prescribed subsequent treatment (60.8 and 58.8%, respectively). A small number of patients were prescribed sequential treatment of inotuzumab-to-blinatumomab or blinatumomab-to-inotuzumab (20.3 and 10.5%, respectively). Conclusion: This study revealed inotuzumab and blinatumomab treatment features in Japan.

In acute lymphoblastic leukemia (ALL), the increase in leukemic cells prevents the production of normal blood cells. As a result, people with ALL become more susceptible to anemia, fatigue, infections, fever, bruising and bleeding easily. ALL progresses rapidly without treatment. In recent years, new therapeutic drugs, including inotuzumab and blinatumomab, have become available; however, it remains unclear how they have been used in clinical practice. In this report, we assess how they are used in clinical practice using a large database to collect the clinical data of ALL patients. To see the treatment pattern, we found that most of the patients (81.4% of patients who received inotuzumab and 78.4% of those who received blinatumomab) had received chemotherapy before starting treatment with inotuzumab or blinatumomab. After patients ended treatment with inotuzumab or blinatumomab, 60.8% of patients who received inotuzumab and 58.8% of those who received blinatumomab received the next therapies, including chemotherapy. However, a small number of patients had received inotuzumab-to-blinatumomab or blinatumomab-to-inotuzumab (20.3 and 10.5%, respectively). These findings show the real-world treatment patterns of inotuzumab and blinatumomab; that is, both inotuzumab and blinatumomab are more likely to be prescribed to patients who might not have enough efficacy from prior chemotherapy or might have had to stop chemotherapy early due to side effects. Overall, there is clinical meaningful information from our findings of how inotuzumab and blinatumomab have been used for treatment of ALL and this information could improve the clinical practice of ALL in Japan.

Impact of number of defibrillation attempts on neurologically favourable survival rate in patients with Out-of-Hospital cardiac arrest.

AIM OF THE STUDY: Defibrillation plays a crucial role in early return of spontaneous circulation (ROSC) and survival of patients with out-of-hospital cardiac arrest (OHCA) and shockable rhythm. Prehospital adrenaline administration increases the probability of prehospital ROSC. However, little is known about the relationship between number of prehospital defibrillation attempts and neurologically favourable survival in patients treated with and without adrenaline. METHODS: Using a nationwide Japanese OHCA registry database from 2006 to 2020, 1,802,084 patients with OHCA were retrospectively analysed, among whom 81,056 with witnessed OHCA and initial shockable rhythm were included. The relationship between the number of defibrillation attempts before hospital admission and neurologically favourable survival rate (cerebral performance category score of 1 or 2) at 1 month was evaluated with subgroup analysis for patients treated with and without adrenaline. RESULTS: At 1 month, 18,080 (22.3%) patients had a cerebral performance category score of 1 or 2. In the study population, the probability of prehospital ROSC and favourable neurological survival rate were inversely associated with number of defibrillation attempts. Similar trends were observed in patients treated without adrenaline, whereas a greater number of defibrillation attempts was counterintuitively associated with favourable neurological survival rate in patients treated with prehospital adrenaline. CONCLUSIONS: Overall, a greater number of prehospital defibrillation attempts was associated with lower neurologically favourable survival at 1 month in patients with OHCA and shockable rhythm. However, an increasing number of shocks (up to the 4th shock) was associated with better neurological outcomes when considering only patients treated with adrenaline.

Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials (CDM-J).

PURPOSE: Osteoporotic vertebral compression fracture (OVCF) is a common fragile fracture resulting from osteoporosis. We compared the efficacy and safety of romosozumab and commonly used osteoporosis drug treatments for the treatment of OVCF in postmenopausal women. METHODS: Through searching and screening five databases, we included randomized controlled trials (RCTs) published through June 18, 2021 comparing different treatments. Following the Preferred Reporting Items for Systematic Reviews statement, the main objective was to evaluate the mean difference and risk ratio of the treatment effect. The primary measures of romosozumab efficacy used in this study were vertebral, non-vertebral, and clinical fracture events, and secondary outcomes were bone mineral density (BMD) changes at the lumbar spine, total hip, and femoral neck and the incidence of adverse events (AEs), RESULTS: Nine RCTs including 12 796 participants were included in the analysis, and romosozumab was compared with placebo, alendronate, and teriparatide in the treatment of osteoporosis in postmenopausal women. The incidence of fractures, low BMD, and AEs was analyzed. Compared with the controls, three doses of romosozumab were linked to evident advantages in the treatment of low BMD and fractures but associated with increased hypersensitivity and injection site reaction risks. Furthermore, fewer AEs were observed in the romosozumab arms (210 mg: risk ratio = 0.96, 95% confidence interval = 0.93-0.99; 140 mg: risk ratio = 0.28, 95% confidence interval = 0.08-0.98) than in the alendronate and placebo arms. CONCLUSIONS: Our meta-analysis revealed the evident advantages of romosozumab in the treatment of osteoporosis and low BMD in postmenopausal women and increased risks of hypersensitivity and injection site reactions.