Safety of pyrazinamide in elderly patients with tuberculosis in Japan: A nationwide cohort study.

BACKGROUND AND OBJECTIVE: Pyrazinamide (PZA) is the standard first-line treatment for tuberculosis (TB); however, its safety in elderly patients has not been thoroughly investigated. METHODS: This retrospective study used data from the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for TB between July 2010 and March 2022. Patients were categorized into HRE (isoniazid, rifampicin and ethambutol) and HREZ (isoniazid, rifampicin, ethambutol and PZA) groups. Primary outcomes included in-hospital mortality and overall adverse events (characterized by a composite of hepatotoxicity, gout attack, allergic reactions and gastrointestinal intolerance). Secondary outcomes included the length of hospital stay, 90-day readmission and use of drugs related to the primary outcome adverse events. Data were analysed using propensity score matching; we also conducted a subgroup analysis for those aged ≥75 years. RESULTS: Among 19,930 eligible patients, 8924 received HRE and 11,006 received HREZ. Propensity score matching created 3578 matched pairs with a mean age of approximately 80 years. Compared with the HRE group, the HREZ group demonstrated a higher proportion of overall adverse events (3.1% vs. 4.7%; p < 0.001), allergic reactions (1.4% vs. 2.5%; p < 0.001) and antihistamine use (21.9% vs. 27.6%; p < 0.001). No significant differences were observed regarding in-hospital mortality, hepatotoxicity or length of hospital stay between the groups. Subgroup analysis for those aged ≥75 years showed consistent results. CONCLUSION: Medical practitioners may consider adding PZA to an initial treatment regimen even in elderly patients with TB.

Neuromuscular blocking agents during targeted temperature management for out-of-hospital cardiac arrest patients.

BACKGROUND: Neuromuscular blocking agents (NMBAs) can control shivering during targeted temperature management (TTM) of patients with cardiac arrest. However, the effectiveness of NMBA use during TTM on neurologic outcomes remains unclear. We aimed to evaluate the association between NMBA use during TTM and favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: A multicenter, prospective, observational cohort study from 2019 to 2021. It included OHCA patients who received TTM after hospitalization. We conducted overlap weight propensity-score analyses after multiple imputation to evaluate the effect of NMBAs during TTM. The primary outcome was a favorable neurological outcome, defined as a cerebral performance category of 1 or 2 at discharge. Subgroup analyses were conducted based on initial monitored rhythm and brain computed tomography findings. RESULTS: Of the 516 eligible patients, 337 received NMBAs during TTM. In crude analysis, the proportion of patients with favorable neurological outcome was significantly higher in the NMBA group (38.3% vs. 16.8%; risk difference (RD): 21.5%; 95% confidence interval (CI): 14.0% to 29.1%). In weighted analysis, a significantly higher proportion of patients in the NMBA group had a favorable neurological outcome compared to the non-NMBA group (32.7% vs. 20.9%; RD: 11.8%; 95% CI: 1.2% to 22.3%). In the subgroup with an initial shockable rhythm and no hypoxic encephalopathy, the NMBA group showed significantly higher proportions of favorable neurological outcomes. CONCLUSIONS: The use of NMBAs during TTM was significantly associated with favorable neurologic outcomes at discharge for OHCA patients. NMBAs may have benefits in selected patients with initial shockable rhythm and without poor prognostic computed tomography findings.

Association between institutional volume of out-of-hospital cardiac arrest cases and short term outcomes.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a serious condition. The volume-outcome relationship and various post-cardiac arrest care elements are believed to be associated with improved neurological outcomes. Although previous studies have investigated the volume-outcome relationship, adjusting for post-cardiac arrest care, intra-class correlation for each institution, and other covariates may have been insufficient. OBJECTIVE: To investigate the volume-outcome relationships and favorable neurological outcomes among OHCA cases in each institution. METHODS: We conducted a prospective observational study of adult patients with non-traumatic OHCA using the OHCA registry in Japan. The primary outcome was 30-day favorable neurological outcomes, and the secondary outcome was 30-day survival. We set the cutoff values to trisect the number of patients as equally as possible and classified institutions into high-, middle-, and low-volume. Generalized estimating equations (GEE) were performed to adjust for covariates and within-hospital clustering. RESULTS: Among the 9909 registry patients, 7857 were included. These patients were transported to either low- (2679), middle- (2657), or high- (2521) volume institutions. The median number of eligible patients per institution in 19 months of study periods was 82 (range, 1-207), 252 (range, 210-353), and 463 (range, 390-701), respectively. After multivariable GEE using the low-volume institution as a reference, no significant difference in odds ratios and 95% confidence intervals were noted for 30-day favorable neurological outcomes for middle volume [1.22 (0.69-2.17)] and high volume [0.80 (0.47-1.37)] institutions. Moreover, there was no significant difference for 30-day survival for middle volume [1.02 (0.51-2.02)] and high volume [1.09 (0.53-2.23)] institutions. CONCLUSION: The patient volume of each institution was not associated with 30-day favorable neurological outcomes. Although this result needs to be evaluated more comprehensively, there may be no need to set strict requirements for the type of institution when selecting a destination for OHCA cases.

Impact of the COVID-19 pandemic on prehospital and in-hospital treatment and outcomes of patients after out-of-hospital cardiac arrest: a Japanese multicenter cohort study.

BACKGROUND: In the chain of survival for Out-of-hospital cardiac arrest (OHCA), each component of care contributes to improve the prognosis of the patient with OHCA. The SARS-CoV-2 (COVID-19) pandemic potentially affected each part of care in the chain of survival. The aim of this study was to compare prehospital care, in-hospital treatment, and outcomes among OHCA patients before and after the COVID-19 pandemic. METHODS: We analyzed data from a multicenter prospective study in Kanto area, Japan, named SOS-KANTO 2017. We enrolled patients who registered during the pre-pandemic period (September 2019 to December 2019) and the post-pandemic period (June 2020 to March 2021). The main outcome measures were 30-day mortality and the proportion of favorable outcomes at 1 month, and secondary outcome measures were changes in prehospital and in-hospital treatments between the pre- and post-pandemic periods. RESULTS: There were 2015 patients in the pre-pandemic group, and 5023 in the post-pandemic group. The proportion of advanced airway management by emergency medical service (EMS) increased (p < 0.01), and EMS call-to-hospital time was prolonged (p < 0.01) in the post- versus pre-pandemic group. There were no differences between the groups in defibrillation, extracorporeal membrane oxygenation, or temperature control therapy (p = 0.43, p = 0.14, and p = 0.16, respectively). Survival rate at 1 month and favorable outcome rate at 1 month were lower (p = 0.01 and p < 0.01, respectively) in the post- versus pre-pandemic group. CONCLUSION: Survival rate and favorable outcome rate 1 month after return of spontaneous circulation of OHCA worsened, EMS response time was prolonged, and advanced airway management by EMS increased in the post- versus pre-pandemic group; however, most prehospital and in-hospital management did not change between pre- and post-COVID-19 pandemic.

Comparison of prophylactic antibiotics for endonasal transsphenoidal surgery using a national inpatient database in Japan.

BACKGROUND: The choice of prophylactic antibiotics for use in endonasal transsphenoidal surgery (ETSS) lacks universal standards. This study aimed to investigate the effectiveness of cefazolin, ampicillin and third-generation cephalosporins for preventing postoperative meningitis and secondary outcomes (in-hospital death and the combination of pneumonia and urinary tract infection) in patients who have undergone ETSS. METHODS: The study used data from the Diagnosis Procedure Combination database in Japan. Data from 10 688 patients who underwent ETSS between April 2016 and March 2021 were included. Matching weight analysis based on propensity scores was conducted to compare the outcomes of patients receiving cefazolin, ampicillin or third-generation cephalosporins as prophylactic antibiotics. RESULTS: Of the 10 688 patients, 9013, 102 and 1573 received cefazolin, ampicillin and third-generation cephalosporins, respectively. The incidence of postoperative meningitis did not significantly differ between the cefazolin group and the ampicillin group (OR, 1.02; 95% CI, 0.14-7.43) or third-generation cephalosporins group (OR, 0.81; 95% CI, 0.10-6.44). Similarly, in-hospital death and the composite incidence of pneumonia and urinary tract infection did not differ between the cefazolin group and the ampicillin or third-generation cephalosporins group. CONCLUSIONS: Cefazolin, ampicillin and third-generation cephalosporins as perioperative prophylactic antibiotics for ETSS do not differ significantly in terms of preventing meningitis.

Frailty and Neurologic Outcomes of Patients Resuscitated From Nontraumatic Out-of-Hospital Cardiac Arrest: A Prospective Observational Study.

STUDY OBJECTIVE: To elucidate the clinical utility of the Clinical Frailty Scale score for predicting poor neurologic functions in patients resuscitated from out-of-hospital cardiac arrest (OHCA). METHODS: This was a prospective, multicenter, observational study conducted between 2019 and 2021. The study included adults with nontraumatic OHCA admitted to the intensive care unit after return of spontaneous circulation (ROSC). Pre-arrest high Clinical Frailty Scale score was defined as 5 or more. Favorable neurologic outcomes defined as a Cerebral Performance Category score of 2 or less at 30 days after admission were compared between patients with and without high Clinical Frailty Scale scores. Multivariable logistic regression analyses fitted with generalized estimating equations were performed to adjust for patient characteristics, out-of-hospital information, and resuscitation content and account for within-institution clustering. RESULTS: Of 9,909 patients with OHCA during the study period, 1,216 were included, and 317 had a pre-arrest high Clinical Frailty Scale score. Favorable neurologic outcomes were fewer among patients with high Clinical Frailty Scale scores. The high Clinical Frailty Scale score group showed a lower percentage of favorable neurologic outcomes after OHCA than the low Clinical Frailty Scale score group (6.1% vs 24.4%; adjusted odds ratio, 0.45 [95% confidence interval 0.22 to 0.93]). This relationship remained in subgroups with cardiogenic OHCA, with ROSC after hospital arrival, and without a high risk of dying (Clinical Frailty Scale score of 7 or less), whereas the neurologic outcomes were comparable regardless of pre-arrest frailty in those with noncardiogenic OHCA and with ROSC before hospital arrival. CONCLUSIONS: Pre-arrest high Clinical Frailty Scale score was associated with unfavorable neurologic functions among patients resuscitated from OHCA. The Clinical Frailty Scale score would help predict clinical consequences following intensive care after ROSC.

Effectiveness of vaccination on influenza-related critical illnesses in the elderly population.

OBJECTIVES: The prevention of serious influenza-related severe conditions due to influenza is important, particularly in elderly patients, age is a risk factor for death resulting from influenza-related respiratory diseases. The aim of the present study was to investigate the association of influenza vaccination with severe condition requiring critical care and death in elderly people, using vaccine records and healthcare administrative claims data in a Japanese city. RESULTS: Among 5608 patients aged ≥65 years diagnosed with influenza, we identified 96 patients who had received invasive mechanical ventilation or died. Thereafter, we matched 384 controls with the cases. The cases were less vaccinated than the controls (37.5% vs. 56.0%, P < 0.01). In the multivariate analysis, influenza vaccination was associated with a lower proportion of the composite outcome (odds ratio, 0.35; 95% confidence interval, 0.21-0.60). In patients aged ≥80 years old and those with cardiovascular disease, influenza vaccination was associated with low composite outcomes. CONCLUSIONS: Influenza vaccination was associated with reduced proportions of receiving invasive mechanical ventilation or influenza-related mortality, particularly in those aged ≥80 years old.

Comparison of bleeding complications after pediatric kidney biopsy between intravenous sedation and general anesthesia: a nationwide cohort study.

BACKGROUND: An increasing number of studies are evaluating the safety of intravenous sedation compared with that of general anesthesia; however, data on bleeding complications after pediatric percutaneous renal biopsy performed under intravenous sedation or general anesthesia are lacking. We aimed to examine differences in bleeding complications between intravenous sedation and general anesthesia in pediatric patients. METHODS: Data of pediatric patients aged ≤ 15 years undergoing percutaneous kidney biopsy for kidney disease between July 2007 and March 2019 were retrieved from a national inpatient database in Japan. We examined differences in bleeding complications after renal biopsy performed under intravenous sedation, defined by the absence of the record of general anesthesia with intubation but by the presence of intravenous sedation during biopsy, and general anesthesia, defined by the presence of the record of general anesthesia with intubation during biopsy, among pediatric patients admitted for percutaneous renal biopsy. We performed binomial regression using overlap weights based on propensity scores for patients receiving intravenous sedation. Analyses stratified by age or sex, a sensitivity analysis using generalized estimating equations considering cluster effects by hospital among a propensity score-matched cohort, and another sensitivity analysis using the instrumental variable method were performed to confirm the robustness of the results. RESULTS: We identified 6,560 biopsies performed in 5,999 children aged 1-15 years from 328 hospitals and 178 events. Only three severe complications and no death were observed. No significant difference in the proportion of bleeding complications was observed between procedures performed under intravenous sedation and those performed under general anesthesia (unadjusted proportions, 2.8% and 2.3%; adjusted proportions, 2.5% and 2.2%), with an unadjusted relative risk of 1.21 (95% confidence interval, 0.80-1.81) and adjusted relative risk of 1.13 (95% confidence interval, 0.74-1.73). Both age- and sex-stratified analyses yielded similar results. The analysis using generalized estimating equation and the instrumental variable method showed relative risks of 0.95 (95% confidence interval, 0.48-1.88) and 1.18 (95% confidence interval, 0.74-1.89), respectively. CONCLUSION: This retrospective cohort study using a national database revealed that the risk of biopsy-related bleeding was comparable between intravenous sedation and general anesthesia during pediatric percutaneous kidney biopsy, suggesting that intravenous sedation alone and general anesthesia may have a similar bleeding risk in pediatric percutaneous kidney biopsies.

Outcomes After Endoscopic Evacuation Versus Evacuation Using Craniotomy or Stereotactic Aspiration for Spontaneous Intracerebral Hemorrhage: Analysis Using a Japanese Nationwide Database.

BACKGROUND: Various surgical methods are available for managing large intracerebral hemorrhage. This study compared the prognosis of patients with spontaneous intracerebral hemorrhage who underwent endoscopic evacuation, stereotactic aspiration, and craniotomy by using a nationwide inpatient database in Japan. METHODS: Using the Diagnosis Procedure Combination database, we identified patients who underwent surgery for spontaneous intracerebral hemorrhage within 48 h after admission between April 2014 and March 2018. Eligible patients were classified into three groups according to the type of surgery (endoscopic surgery, stereotactic surgery, and craniotomy). Propensity score matching weight analysis was conducted to compare poor modified Rankin Scale score at discharge (severe disability or death) and hospitalization cost among the groups. RESULTS: Among 17,860 eligible patients, craniotomy, stereotactic surgery, and endoscopic surgery were performed in 14,354, 474, and 3,032 patients, respectively. In the matching weight analysis, all covariates were well balanced. Compared with the endoscopic surgery group, the proportion of poor prognosis (modified Rankin Scale score at discharge of 5 or 6) was significantly higher in craniotomy groups (odds ratio 2.51, 95% confidence interval 1.11-5.68; p = 0.028). Subgroup analysis based on hemorrhage location and consciousness level at the time of admission showed no significant difference between the surgical procedures. Hospitalization costs were significantly higher in the craniotomy group than in the endoscopic surgery group (difference US $9,724, 95% confidence interval 2,169-17,259; p = 0.011). CONCLUSIONS: Endoscopic surgery for spontaneous intracerebral hemorrhage was associated with improved prognosis compared with craniotomy at the hospital discharge. Future large-scale clinical trials are needed to evaluate the optimal surgical techniques for intracerebral hemorrhage.

Endoscopic surgery versus craniotomy for spontaneous intracerebral hemorrhage in the late elderly patients.

OBJECTIVES: To compare the prognosis of late elderly patients with spontaneous intracerebral hemorrhage (ICH) treated by endoscopic evacuation and craniotomy MATERIALS AND METHODS: Using the Diagnosis Procedure Combination database, we identified patients aged ≥ 75 years who underwent surgery for spontaneous ICH within 48 hours after admission between April 2014 and March 2018. Eligible patients were classified into two groups according to the type of surgery (endoscopic surgery and craniotomy). Propensity-score matching weight analysis was conducted to compare the good neurological outcome modified Rankin Scale (mRS) score (0-4) at discharge as the primary endpoint between the two groups. Secondary endpoints were postoperative meningitis, tracheostomy, reoperation within 3 days and total hospitalization costs. RESULTS: Among the 5,396 eligible patients, endoscopic surgery and craniotomy were performed in 895 and 4,501 patients, respectively. In the propensity-score matching weight analysis, all covariates were well balanced. The proportions of patients with a good prognosis (mRS score at discharge: 0-4) did not significantly differ between the surgical procedures (42.1% vs. 42.8%, p = 0.828). The proportions of meningitis, tracheostomy and reoperation were not significantly different between the two groups. Hospitalization costs were significantly higher in the craniotomy group than in the endoscopic surgery group (25,536 vs. 29,603 US dollars, p = 0.012). CONCLUSIONS: Inhospital outcomes did not differ between endoscopic and open surgeries for spontaneous ICH in the late-stage elderly patients aged ≥75 years. Hospitalization costs were significantly higher in the craniotomy group, suggesting that endoscopic surgery may be more acceptable.

Trends in surgical procedures for spontaneous intracerebral hemorrhage in Japan.

OBJECTIVES: Minimally invasive surgery for spontaneous intracerebral hemorrhage (ICH) has become increasingly popular in recent years. However, there are no reports on the recent trends in surgical procedures for spontaneous ICH. To investigate current trends in surgical methods for spontaneous ICH using a nationwide inpatient database from Japan. MATERIALS AND METHODS: Patients who underwent surgery for spontaneous ICH between April 2014 and March 2018 were identified in a nationwide inpatient database from Japan. We examined patient characteristics, diagnoses, types of surgery, complications, and discharge status. RESULTS: We identified 21,129 inpatients who underwent surgery for spontaneous ICH. The procedures were as follows: 16,256 (76.9%) transcranial hemorrhage evacuations, 3722 (17.6%) endoscopic hemorrhage evacuations, and 1151 (5.4%) stereotactic aspirations of hemorrhage. Patients tended to receive transcranial hemorrhage evacuations in hospitals with fewer surgical cases. The proportions of endoscopic hemorrhage evacuations increased annually, whereas those of stereotactic surgery decreased. The proportions of transcranial surgery remained almost unchanged. Tracheostomy and hospitalization costs were lower in the stereotactic aspirations of hemorrhage group, and the proportions of reoperation were higher in the endoscopic hemorrhage evacuations group. CONCLUSIONS: The use of endoscopic surgery for spontaneous ICH has increased in Japan. This study can form the basis of future clinical investigations into spontaneous ICH surgery.

Dexmedetomidine and Mortality From Sepsis Requiring Mechanical Ventilation: A Japanese Nationwide Retrospective Cohort Study.

BACKGROUND: Dexmedetomidine has a mild sedative effect and may reduce mortality in mechanically ventilated critically ill patients. However, few studies have examined the effects of dexmedetomidine in patients with sepsis who require mechanical ventilation. The aim of this study was to investigate the association between dexmedetomidine and mortality in patients with sepsis requiring mechanical ventilation, using a nationwide inpatient database in Japan. METHODS: Using the Diagnosis Procedure Combination database from July 1, 2010, to March 31, 2016, we identified adult patients with sepsis who required mechanical ventilation for more than 2 days. Patients were divided into those who received dexmedetomidine and those who received midazolam or propofol within 1 day after admission. Logistic regression analysis, propensity score-matched analysis, and instrumental variable analysis were performed to compare all-cause 28-day mortality and duration of mechanical ventilation between the groups. RESULTS: In total, 50 671 were eligible patients, including dexmedetomidine group (n = 13 759) and propofol or midazolam group (n = 36 912). The dexmedetomidine group had significantly lower all-cause 28-day mortality compared with the group receiving midazolam or propofol, as shown by the logistic regression analysis (odds ratio [OR]: 0.78; 95% confidence interval [CI]: 0.73-0.84), the propensity score-matched analysis (OR: 0.85; 95% CI: 0.80-0.91), and the instrumental variable analysis (OR: 0.64; 95% CI: 0.57-0.73). The duration of mechanical ventilation in the dexmedetomidine group was significantly shorter than that in the midazolam or propofol group. CONCLUSIONS: Dexmedetomidine was associated with a reduction in all-cause 28-day mortality and duration of mechanical ventilation.

Sodium-containing versus sodium-trace preparations of IVIG for children with Kawasaki disease in the acute phase.

Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). There are two types of IVIG, sodium-containing (high-Na) and sodium-trace (low-Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low-Na IVIG preparations in KD children using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low-Na preparations of IVIG as an initial treatment. Outcomes included proportion of coronary artery abnormalities (CAA), IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. We identified 42,345 patients with KD. There were significant differences in proportions of CAA (2.8% vs. 3.2%; p = 0.031) and IVIG resistance (17% vs. 18%, p = 0.001) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analysis confirmed the same results as the propensity score analysis.Conclusion: The present study suggests that high-Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study. What is Known: • For treatments of Kawasaki Disease in acute phase, intravenous immunoglobulin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. There are two types of IVIG preparations, sodium-containing IVIG and sodium-trace IVIG. However, few studies have performed comparisons to determine which preparation of IVIG is superior. What is New: • The present findings suggest that high-Na IVIG is associated with reductions in the proportions of CAAs and IVIG resistance in KD patients.

Bacterial Contamination during Continuous Administration of Liquid Enteral Nutrition Formula in a Sterile Sealed Bag: A Prospective Interventional Study.

INTRODUCTION: In nutrition therapy for critically ill patients, it is recommended that enteral nutrition (EN) formula be changed every 8 h to avoid bacterial contamination. However, it remains unknown whether long-term administration of EN formula from a sterile sealed bag without changing the formula can cause bacterial contamination. This study investigates the association between bacterial contamination and administration of liquid EN formula from a sterile sealed bag without changing the formula for 24 h. METHODS: This single-center, prospective, interventional study included patients aged ≥20 years who were admitted to an intensive care unit and received 24-h continuous liquid EN formula from a sterile sealed bag. A 3-mL sample of the formula was collected from each bag every 4 h for bacterial culture. The primary outcome was the detection of bacterial colonies. RESULTS: A total of 630 specimens from 30 patients were cultured. No bacterial colonies were detected. CONCLUSION: There was no association between bacterial contamination and continuous administration of liquid EN formula from a sterile sealed bag for 24 h. Therefore, this study recommends continuous administration of EN from a sterile sealed bag for 24 h without changing the EN formula under those limited conditions.

Association Between IV Thiamine and Mortality in Patients With Septic Shock: A Nationwide Observational Study.

OBJECTIVES: To examine the effect of thiamine administration on mortality in patients with septic shock requiring norepinephrine. DESIGN: Retrospective observational cohort study from July 2010 to March 2017. SETTING: More than 1,000 acute care hospitals covering approximately 90% of all tertiary care emergency hospitals in Japan. PATIENTS: Patients with septic shock requiring norepinephrine within 2 days of admission were retrospectively reviewed. INTERVENTIONS: Patients who received greater than or equal to 100 mg of thiamine within 2 days of admission were included in the thiamine group and those who did not were included in the control group. MEASUREMENTS AND MAIN RESULTS: We identified a total of 68,571 eligible patients, including 18,780 and 49,791 patients in the thiamine and control groups, respectively. In the thiamine group, 100 and 200 mg of thiamine per day were administered to 10,143 (54.0%) and 7,679 (40.9%) patients, respectively. The 28-day mortality were 19.2% (3,609/18,780) and 17.8% (8,845/49,791) in the thiamine and control groups, respectively. After adjusting for confounders by inverse probability of treatment weighting, no significant differences were observed between the two groups (risk difference, 0.2%; 95% CI, -0.5% to 0.9%). There were also no significant differences between the 100-mg thiamine group and the control group (risk difference, 0.6%; 95% CI, -0.3% to 1.4%) or between the 200-mg thiamine group and the control group (risk difference, -0.3%; 95% CI, -1.3% to 0.8%). CONCLUSIONS: The findings of this nationwide database-based observational study did not support an association between thiamine administration early after admission and the 28-day mortality in patients with septic shock.

Pregabalin and injury: A nested case-control and case-crossover study.

PURPOSE: This study was performed to investigate the association between the use of pregabalin and injury. METHODS: The study was based on a predefined cohort of patients aged ≥20 years who had been registered for ≥6 months and contributed to the Japan Medical Data Center claims database. All patients (cases) had been treated for injuries from January 2014 to December 2016. One-to-four case-control matching was performed for age, sex, calendar day of injury (index date), and follow-up duration. A conditional logistic regression analysis was performed to calculate the odds ratio (OR) for pregabalin use within 180 days prior to the index date between the matched cases and controls, with adjustment for comorbidities and relevant drug categories associated with a risk of injury. To minimize within-individual confounding, we also performed a case-crossover analysis to compare the odds of pregabalin use between a 30-day hazard period immediately before the injury and five consecutive 30-day control periods within individuals with injury. RESULTS: Among the 2 324 974 people in the nested cohort, we identified 18 084 cases with injury and 71 885 matched controls. The proportion of pregabalin use was 1.7% (304/18 084) and 1.1% (803/71 885), respectively. The adjusted OR for injury was 1.22 (95% confidence interval [CI], 1.06-1.40). In the case-crossover analysis (n = 304), pregabalin use was also significantly associated with an increased risk of injury (adjusted OR, 1.48; 95% CI, 1.10-2.00). CONCLUSION: This large database study using two different study designs consistently suggested that the use of pregabalin may be associated with an increased risk of injury.

Influence of the Fukushima Daiichi Nuclear Power Plant Accident on the Use of Computed Tomography in Children With Mild Head Injuries.

BACKGROUND: Computed tomography (CT) is commonly used in children with mild head injuries. People in Japan are concerned about radiation exposure and radiation-induced cancer because of the Fukushima Daiichi Nuclear Power Plant accident on March 11, 2011. This study investigated whether the accident influenced the use of CT in children with mild head injuries. METHODS: Using the Japan Medical Data Center database, we identified patients aged ≤15 years visiting hospitals because of mild head injuries from January 1, 2008, to December 31, 2013. We excluded patients who were admitted to the hospital or received other medical examinations. Regression discontinuity analysis was used to compare proportions of patients undergoing head CT and having clinically important traumatic brain injury (ciTBI) overlooked before versus after the accident, adjusting for patient characteristics, secular trends, and hospital effect. RESULTS: Eligible patients (n = 40,440) were classified as visiting the hospital before (n = 11,659) or after (n = 28,781) the accident. The regression discontinuity analysis showed that the accident was associated with a reduction in the proportion of patients undergoing head CT (odds ratio [OR] 0.73; 95% confidence interval [CI], 0.63-0.86), whereas the accident was not associated with an increase in cases where ciTBI was overlooked (OR 0.72; 95% CI, 0.13-4.00). CONCLUSIONS: The use of CT in children with mild head injuries declined after the Fukushima Daiichi Nuclear Power Plant accident. Improving awareness of radiation exposure risks among patients and physicians could reduce unnecessary CT.

Hyperbaric oxygen therapy and mortality from carbon monoxide poisoning: A nationwide observational study.

BACKGROUND: The effects of hyperbaric oxygen therapy (HBOT) on mortality or morbidity in patients with carbon monoxide (CO) poisoning remain unknown. We examined the effects of HBOT on CO poisoning and further strived to delineate its inherent effects on specific subgroups of patients using a nationwide inpatient database. METHODS: We identified adult patients with CO poisoning who were registered in the Japanese Diagnosis Procedure Combination inpatient database from 2010 to 2016. Propensity score-matching was performed to compare patients who received HBOT within 1 day of admission (HBOT group) with those who did not receive HBOT (control group). The primary outcome was in-hospital mortality. The secondary outcomes were a depressed mental status and reduced activities of daily living (ADL) at discharge. We also performed subgroup analyses divided according to severity of CO poisoning. RESULTS: Eligible patients were categorized into the HBOT group (n = 2034) or the control group (n = 4701). One-to-one propensity score-matching created 2034 pairs. In-hospital mortality was not significantly different between the HBOT and control groups (0.8% vs. 1.2%, risk difference: -0.4%, 95% confidence interval: -1.0 to 0.2). Patients in the HBOT group had significantly lower proportions of a depressed mental status and reduced ADL at discharge than did those in the control group. Similar associations were shown in the non-severe poisoning subgroup. CONCLUSIONS: Although HBOT was not significantly associated with reduced mortality, it was significantly associated with a favorable consciousness level and ADL in patients with CO poisoning. HBOT may be beneficial even for patients with non-severe CO poisoning.

Pituitary surgery's epidemiology using a national inpatient database in Japan.

BACKGROUND: Between 2010 and 2014, microscopic transsphenoidal surgery (mTSS) was performed more frequently than endoscopic TSS (eTSS) in the USA. However, few epidemiological studies on pituitary surgery are currently available. METHODS: We performed a retrospective study on patients who had undergone pituitary surgery between July 2010 and March 2016. To this end, a nationwide inpatient database in Japan was used. Patients' characteristics, diagnoses, types of surgery, complications, and discharge status were examined. RESULTS: A total of 16,253 inpatients who received pituitary surgery were identified. Patients were diagnosed with diseases for insurance claims described below: pituitary adenoma, hyperprolactinemia, other pituitary disorders (e.g., Rathke's cleft cyst), hyperpituitarism, craniopharyngioma, acromegaly, Cushing's disease, and pituitary cancer. Among them, pituitary adenomas, primarily the non-functioning ones, were the most frequent (66.9%). A total of 14,285 (88%) patients underwent TSS, while 1968 (12%) patients were treated using transcranial surgery. The number of patients undergoing TSS increased each year. The number of eTSS operations was 8140 (77%) and that of mTSS operations was 2419 (23%). Of note, eTSS increased each year. We found that high-volume hospitals more frequently selected eTSS. Compared with mTSS, eTSS was associated with a reduction of hyponatremia incidence (odds ratio, 0.69; p = 0.019). Additionally, it was not associated with other major complications. CONCLUSION: The present study showed that both TSS and eTSS increased on a yearly basis. We believe that the present study will be the basis of future epidemiological investigations of pituitary surgery.

Outcomes in Elderly Japanese Patients Treated for Aneurysmal Subarachnoid Hemorrhage: A Retrospective Nationwide Study.

OBJECTIVE: Japan has the largest elderly population in the world. As data on the clinical outcomes in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH), including those older than 80 years, are lacking, we analyzed the characteristics of 54,805 aSAH patients and recorded their treatments and clinical outcomes using a Japanese nationwide inpatient database. METHODS: Using the Japanese Diagnostic Procedure Combination database, we identified aSAH patients aged 18 years or older who were hospitalized between July 1, 2010 and March 31, 2016. They were categorized as less than or equal to 60-, 61-70-, 71-80-, 81-90-, and greater than or equal to 91 years of age. The primary outcome was the modified Rankin Scale (mRS) score at discharge. Multivariable logistic regression analysis was performed to examine factors affecting the mRS score at discharge. RESULTS: Of 54,805 patients, 37.5% were aged less than or equal to 60 years; 24.8% were 61-70-, 21.8% were 71-80-, 13.9% were 81-90-, and 2.0% were greater than or equal to 91 years old at the time of the insult. Among 46,107 patients younger than 81 years, 58.9% underwent surgical clipping (SC), 22.9% endovascular coiling (EC), and 18.2% were treated conservatively. There were 8,698 patients aged 81 years or older, 32.4% underwent SC, 23.2% EC, and 44.4% were treated conservatively. A poor mRS score (3-6) at discharge was recorded in 87.2% of patients older than 80 years. Multivariable logistic regression was used to compare their estimated odds ratio (OR) for a poor mRS score at discharge with that of patients aged less than or equal to 60 years. The OR increased by 87% in patients between 61 and 70 years of age (P < .001; OR, 1.87; 95% confidence interval (CI), 1.77-1.98), by 358% in patients aged from 71 to 80 years (P < .001; OR, 4.58; 95%CI, 4.29-4.89), by 1,035% in patients between 81 and 90 years (P < .001; OR, 11.35; 95%CI, 10.32-12.49), and by 1,710% in patients aged more than or equal to 91 years (P < .001; OR, 18.10; 95%CI, 13.96-23.46). CONCLUSIONS: As the treatment outcomes in elderly aSAH patients, especially those 80 years old or older, were poor, the appropriate therapy decisions must be made on a case-by-case basis.