Effectiveness of sublingual immunotherapy in pediatric cedar pollinosis: A real-world database study.

BACKGROUND: Pediatric allergic rhinitis (AR), including cedar pollinosis (CP), is increasing in Japan. We investigated the effects of sublingual immunotherapy (SLIT), which has limited studies of its effectiveness in real-world settings, on children with CP. METHODS: This retrospective cohort study used a claim database in 2018-2021. Children aged ≤15 years with CP records in 2019 were eligible and were followed up through 2021. We included 2962 CP children undergoing SLIT and 547 who were not. The medication score was used to evaluate SLIT effectiveness in the cedar pollen dispersal season each year. Adverse events and the occurrence of allergic diseases were also evaluated. RESULTS: Medication score was higher in the SLIT group during the index period but lower in 2021 compared to the non-SLIT group (mean ± standard deviation: 5.17 ± 2.39 and 4.74 ± 2.38 in 2019, 3.13 ± 2.30 and 3.55 ± 2.48 in 2021, respectively). The adjusted mean difference between groups from 2019 to 2021 was -0.62 (95% confidence interval: -0.86 to -0.39, p < .0001), and the medication score was reduced in the SLIT group (risk ratio: 1.2: 1.1 to 1.3). The occurrence of adverse events involving abdominal disorders (adjusted odds ratio [aOR]: 0.64: 0.51 to 0.81), asthma exacerbation (aOR: 0.37: 0.24 to 0.57), and allergic diseases involving hay fever unrelated to CP (aOR: 0.60: 0.45 to 0.80) or asthma (aOR: 0.71: 0.58 to 0.86) was lower in the SLIT group. CONCLUSION: In children with CP, SLIT is effective, well tolerated, and could decrease the occurrence of other allergic diseases.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors in improvement of fatty liver index in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: A retrospective nationwide claims database study in Japan.

AIM: To date, there are limited clinical studies and real-world evidence investigating whether sodium-glucose cotransporter-2 inhibitors (SGLT2i) are associated with improved hepatic steatosis. This study aimed to evaluate the effectiveness of SGLT2i compared with that of dipeptidyl peptidase-4 inhibitors (DPP4i) in improving the fatty liver index (FLI) in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: This retrospective cohort study included new users of SGLT2i or DPP4i with T2DM and MASLD from a large claims database (JMDC Claims Database). The primary outcome was the incidence of improvement of the FLI. Cox proportional hazard models, weighted using propensity scores for predicting the initiation of treatment, were fitted to estimate hazard ratios with 95% confidence intervals (CIs). Time-course changes in the FLI values were also assessed. RESULTS: This study included 9127 SGLT2i and 12 286 DPP4i initiators. SGLT2i showed a higher incidence of improvement in the FLI (≥30%, ≥40% and ≥50% reduction from baseline FLI) compared with DPP4i, and the weighted hazard ratios were 1.27 (95% CI 1.18-1.38), 1.24 (95% CI 1.13-1.37) and 1.19 (95% CI 1.05-1.33), respectively. SGLT2i indicated a greater decreased in FLI values compared with DPP4i at up to 3 years of the follow-up period. CONCLUSION: SGLT2is use appeared to be associated with a greater improvement of the FLI than DPP4i use in patients with T2DM and MASLD. In the absence of direct head-to-head comparisons from clinical studies, our study, using real-world data, may support physicians' decision-making in clinical practice.

Clinical Characteristics and Outcomes of Patients With Venous Thromboembolism Receiving Edoxaban in the Real World.

BACKGROUND: The effectiveness and safety of edoxaban for venous thromboembolism (VTE) in unselected real-world patients have not been fully evaluated.Methods and Results: In the Japanese nationwide administrative database, we identified 6,262 VTE patients in whom edoxaban was initiated; these patients were divided into 3 groups based on their index doses: 15 mg/day (n=235), 30 mg/day (n=4,532), and 60 mg/day (n=1,495). We evaluated patient characteristics, recurrent VTEs, and a composite endpoint of intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding. Patient characteristics among the 15-, 30-, and 60-mg edoxaban groups varied widely regarding several aspects, including age (mean 81.0, 76.2, and 65.0 years, respectively) and body weight (mean 49.5, 51.8, and 70.3 kg, respectively). At 180 days, the cumulative incidence of recurrent VTEs in the 15-, 30-, and 60-mg edoxaban groups was 4.4%, 2.6%, and 1.8%, respectively, whereas that of ICH or GI bleeding was 7.3%, 5.4%, and 3.3%, respectively. Subgroup analyses showed that the cumulative incidence of ICH or GI bleeding in patients in the 15-mg edoxaban group was 3.6% for patients aged ≥80 years, 8.4% for those with a body weight <60 kg, and 31.3% for those with renal dysfunction. CONCLUSIONS: Only a minority of patients with VTEs received a super low dose (15 mg) of edoxaban, and these patients may be at higher risk of bleeding as well as VTE recurrence.

Association Between Arterial Pulse Waveform Analysis and Mortality in Patients With Septic Shock: A Retrospective Cohort Study Using Japanese Diagnosis Procedure Combination Data.

Purpose: Specialized pressure transducers for arterial pulse waveform analysis (S-APWA) devices are dedicated kits connected to an arterial pressure catheter that monitors hemodynamic parameters, such as cardiac output, pulse pressure variation, and stroke volume variation, less invasively. While the association between the use of S-APWA devices and clinical outcomes in perioperative patients has been previously evaluated, its assessment in patients with septic shock remains inadequate. Materials and Methods: This retrospective cohort study utilized a nationwide Diagnosis Procedure Combination database in Japan. Adult patients with septic shock admitted to the intensive care unit (ICU) with arterial pressure catheter placement on the admission day from August 2012 to February 2021 were included. Hospitalizations meeting the eligibility criteria were categorized into groups based on S-APWA device usage. The primary outcome, evaluated using Cox regression analysis, was 30-day all-cause mortality in the propensity score overlap-weighted population. Secondary outcomes included in-hospital mortality, ICU duration, and overall hospital stay. Results: Among 5130 eligible hospitalizations, 643 were in the S-APWA group and 4487 were in the conventional pressure transducer group. Cox regression analysis within the propensity score overlap-weighted population showed no significant difference in 30-day mortality (adjusted hazard ratio: 0.94; 95% confidence interval: 0.9-1.38; P = .58). Logistic regression analysis indicated no significant differences in the in-hospital mortality. While the S-APWA group had prolonged ICU stays, no significant difference in the overall hospital stay was observed according to linear regression analyses. Conclusions: Our study found no significant association between S-APWA use and 30-day mortality in patients with septic shock. These findings offer insights into optimizing monitoring systems in ICUs.

Validity of Using Japanese Administrative Data to Identify Inpatients With Acute Pulmonary Embolism: Referencing the COMMAND VTE Registry.

BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening in-hospital complication. Recently, several studies have reported the clinical characteristics of PE among Japanese patients using the diagnostic procedure combination (DPC)/per diem payment system database. However, the validity of PE identification algorithms for Japanese administrative data is not yet clear. The purpose of this study was to evaluate the validity of using DPC data to identify acute PE inpatients. METHODS: The reference standard was symptomatic/asymptomatic PE patients included in the COntemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) registry, which is a cohort study of acute symptomatic venous thromboembolism (VTE) patients in Japan. The validation cohort included all patients discharged from the six hospitals included in both the registry and DPC database. The identification algorithms comprised diagnosis, anticoagulation therapy, thrombolysis therapy, and inferior vena cava filter placement. Each algorithm's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated. RESULTS: A total of 43.4% of the validation cohort was female, with a mean age of 67.3 years. The diagnosis-based algorithm showed a sensitivity of 90.2% (222/246; 95% confidence interval [CI], 85.8-93.6%), a specificity of 99.8% (228,485/229,027; 95% CI, 99.7-99.8%), a PPV of 29.1% (222/764; 95% CI, 25.9-32.4%) and an NPV of 99.9% (228,485/229,509; 95% CI, 99.9-99.9%) for identifying symptomatic/asymptomatic PE. Additionally, 94.6% (159/168; 95% CI, 90.1-97.5%) of symptomatic PE patients were identified using the diagnosis-based algorithm. CONCLUSION: The diagnosis-based algorithm may be a relatively sensitive method for identifying acute PE inpatients in the Japanese DPC database.

Safety of advanced laparoscopic hepatectomy for elderly patients: a Japanese nationwide analysis.

BACKGROUND: Although basic laparoscopic hepatectomy (LH) has become the standard procedure for hepatectomy, the safety of advanced LH remains to be clarified, especially in elderly patients. We investigated the safety of advanced LH in elderly Japanese patients. METHODS: Elderly patients (≥ 65 years) who underwent advanced LH between 2016 and 2021 were analyzed using a nationwide claims database in Japan. The perioperative outcomes of patients who underwent open hepatectomy (OH group) or LH (LH group) were compared using propensity score matching (PSM). The primary outcome was in-hospital mortality. The E-value method was performed to assess the strength of the outcome point estimates against possible unmeasured confounding factors. RESULTS: Among 5,021 patients, eligible patients were classified into the OH (n = 4,152) and LH (n = 527) groups. The median patient age was 74 years in both groups. Hepatocellular carcinoma and metastatic liver tumors were the major indications for hepatectomy (OH: 52.5% versus 30.6%; LH: 60.7% versus 26.4%). After PSM, in-hospital mortality rates for OH and LH were 1.7 and 0.76%, respectively. The risk ratio was 0.45 (95% confidence interval, 0.16-1.25; E-value = 3.87). Compared with OH, LH was associated with a longer anesthesia time (411 versus 432 min), lower rate of blood product use (red blood concentrate: 33.5% versus 20.3%; fresh frozen plasma: 29.2% versus 17.1%), and shorter hospital stay (13 versus 12 days). CONCLUSIONS: In elderly patients, the safety of advanced LH was similar to that of advanced OH, or might be better in Japan under the current policy of hospital accreditation.

CFP/Yit: An Inbred Mouse Strain with Slow Gastrointestinal Transit.

BACKGROUND: Gastrointestinal transit (GIT) is influenced by factors including diet, medications, genetics, and gut microbiota, with slow GIT potentially indicating a functional disorder linked to conditions, such as constipation. Although GIT studies have utilized various animal models, few effectively model spontaneous slow GIT. AIMS: We aimed to characterize the GIT phenotype of CFP/Yit (CFP), an inbred mouse strain with suggested slow GIT. METHODS: Female and male CFP mice were compared to Crl:CD1 (ICR) mice in GIT and assessed based on oral gavage of fluorescent-labeled 70-kDa dextran, feed intake, fecal amount, and fecal water content. Histopathological analysis of the colon and analysis of gut microbiota were conducted. RESULTS: CFP mice exhibited a shorter small intestine and a 1.4-fold longer colon compared to ICR mice. The median whole-GIT time was 6.0-fold longer in CFP mice than in ICR mice. CFP mice demonstrated slower gastric and cecal transits than ICR mice, with a median colonic transit time of 4.1 h (2.9-fold longer). CFP mice exhibited lower daily feed intakes and fecal amounts. Fecal water content was lower in CFP mice, apparently attributed to the longer colon. Histopathological analysis showed no changes in CFP mice, including tumors or inflammation. Moreover, CFP mice had a higher Firmicutes/Bacteroidota ratio and a relative abundance of Erysipelotrichaceae in cecal and fecal contents. CONCLUSIONS: This study indicates that CFP mice exhibit slow transit in the stomach, cecum, and colon. As a novel mouse model, CFP mice can contribute to the study of gastrointestinal physiology and disease.

Effect of multidisciplinary care on diabetic kidney disease: a retrospective cohort study.

BACKGROUND: Diabetic kidney disease (DKD) is the most common disease among patients requiring dialysis for the first time in Japan. Multidisciplinary care (MDC) may prevent the progression of kidney failure. However, the effectiveness and timing of MDC to preserve kidney function in patients with DKD is unclear. Therefore, the aim of this study was to investigate whether MDC for patients with DKD affects the preservation of kidney function as well as the timing of MDC in clinical practice. METHODS: In this retrospective cohort study, we identified patients with type 2 diabetes mellitus and DKD from April 2012 to January 2020 using a nationwide Japanese healthcare record database. The fee code for medical guidance to prevent dialysis in patients with diabetes was used to distinguish between the MDC and non-MDC groups. The primary outcome was a 40% decline in the estimated glomerular filtration rate, and secondary outcomes were death, hospitalization, permanent dialysis, kidney failure with replacement therapy, and emergency temporary catheterization. Propensity score matching was performed, and Kaplan-Meier and multivariable Cox regression analyses were performed. RESULTS: Overall, 9,804 eligible patients met the inclusion criteria, of whom 5,614 were matched for the main analysis: 1,039 in the MDC group, and 4,575 in the non-MDC group. The primary outcome did not differ between the groups (hazard ratio: 1.18, [95% confidence interval: 0.99-1.41], P = 0.07). The groups also did not differ in terms of the secondary outcomes. Most patients with DKD received their first MDC guidance within 1 month of diagnosis, but most received guidance only once per year. CONCLUSIONS: Although we could not demonstrate the effectiveness of MDC on kidney function in patients with DKD, we clarified the characteristics of such patients assigned the fee code for medical guidance to prevent dialysis related to diabetes.

Anesthesia practice for Cesarean delivery in Japan: a retrospective cohort study.

PURPOSE: General anesthesia for Cesarean delivery affects maternal and neonatal outcomes. We aimed to evaluate temporal trends in anesthesia management for Cesarean deliveries over 16 years and analyze interinstitutional variations in general anesthesia use in Japan. METHODS: In this retrospective cohort study, we obtained patient data from the nationwide health insurance claims database containing data for ten million individuals. We included patients who underwent Cesarean delivery between 1 January 2005 and 31 August 2021. The primary outcome was the use of general anesthesia. We evaluated institutional variations in general anesthesia use in medical facilities using two-level hierarchical logistic regression analyses with median odds ratios and intraclass correlation coefficients. RESULTS: The cohort included 86,793 patients who underwent 102,617 Cesarean deliveries at 2,496 institutions. General anesthesia was used in 3.7% (95% confidence interval [CI], 3.6 to 3.9) of all Cesarean deliveries. The temporal trend in the use of general anesthesia decreased gradually from 10.8% in 2005 to 2.9% in 2021 (P for trend < 0.001). The adjusted median odds ratio for medical facilities was 6.1 (95% CI, 5.9 to 6.7), and the intraclass correlation coefficient was 0.52 (95% CI, 0.51 to 0.55). CONCLUSION: Although the rate of general anesthesia use for Cesarean delivery in Japan decreased gradually from 2005 to 2021, general anesthesia was used in 3.7% of all Cesarean deliveries. The use of general anesthesia varied significantly across institutions, and 52% of the overall variations in general anesthesia practice can be explained by differences between facilities.

RéSUMé: OBJECTIF: L'anesthésie générale pour l'accouchement par césarienne affecte les issues maternelles et néonatales. Notre objectif était d'évaluer les tendances temporelles de la prise en charge anesthésique pour les accouchements par césarienne sur 16 ans et d'analyser les variations interinstitutionnelles dans l'utilisation de l'anesthésie générale au Japon. MéTHODE: Dans cette étude de cohorte rétrospective, nous avons obtenu des données sur les patient·es à partir de la base de données nationale des réclamations d'assurance maladie contenant des données pour dix millions de personnes. Nous avons inclus les personnes ayant bénéficié d'un accouchement par césarienne entre le 1er janvier 2005 et le 31 août 2021. Le critère d'évaluation principal était le taux d'utilisation de l'anesthésie générale. Nous avons évalué les variations institutionnelles dans l'utilisation de l'anesthésie générale dans les établissements médicaux à l'aide d'analyses de régression logistique hiérarchique à deux niveaux avec des rapports de cotes médians et des coefficients de corrélation intraclasse. RéSULTATS: La cohorte comprenait 86 793 patient·es ayant bénéficié de 102 617 accouchements par césarienne dans 2496 établissements. L'anesthésie générale a été utilisée dans 3,7 % (intervalle de confiance [IC] à 95 %, 3,6 à 3,9) de tous les accouchements par césarienne. La tendance temporelle de l'utilisation de l'anesthésie générale a diminué graduellement, passant de 10,8 % en 2005 à 2,9 % en 2021 (P pour la tendance < 0,001). Le rapport de cotes médian ajusté pour les établissements médicaux était de 6,1 (IC 95 %, 5,9 à 6,7), et le coefficient de corrélation intraclasse était de 0,52 (IC 95 %, 0,51 à 0,55).

Are Dental Procedures Associated With Pyogenic Vertebral Osteomyelitis?

BACKGROUND: Dental procedures can lead to bacteremia and have been considered a potential risk factor for pyogenic vertebral osteomyelitis (PVO). However, data on the association between dental procedures and PVO are limited. QUESTIONS/PURPOSES: (1) After controlling for relevant confounding variables, are dental procedures associated with an increased risk of PVO? (2) Does antibiotic prophylaxis before dental procedures effectively decrease the risk of PVO? METHODS: A case-crossover study was conducted to investigate the association between dental procedures and PVO using a Japanese claims database. The advantage of this study design is that confounding factors that do not vary over time are automatically adjusted for, because cases act as their own controls. From April 2014 to September 2021, the database included 8414 patients who were hospitalized for PVO. Of these, 50% (4182 of 8414) were excluded because they had not undergone any dental procedures before the index date, a further 0.1% (10 of 8414) were excluded because they were younger than 18 years at the index date, and a further 7% (623 of 8414) were excluded because they did not have at least 20 weeks of continuous enrollment before the index date, leaving 43% (3599 of 8414) eligible for analysis here. The mean age was 77 ± 11 years, and 55% (1985 of 3599) were men. Sixty-five percent (2356 of 3599) of patients had a diagnosis of diabetes mellitus, and 42% (1519 of 3599) of patients had a diagnosis of osteoporosis. We compared the frequency of dental procedures between a 4-week hazard period before the admission date for PVO and two control periods, 9 to 12 weeks and 17 to 20 weeks before the admission date for PVO, within individuals. We calculated odds ratios and 95% confidence intervals using conditional logistic regression analysis. RESULTS: Comparing the hazard and matched control periods within individuals demonstrated that dental procedures were not associated with an increased risk of PVO (OR 0.81 [95% CI 0.72 to 0.92]; p < 0.001). Additional analysis stratified by antibiotic prophylaxis use showed that antibiotic prophylaxis was not associated with a lower OR of developing PVO after dental procedures (with antibiotic prophylaxis: OR 1.11 [95% CI 0.93 to 1.32]; p < 0.26, without antibiotic prophylaxis: OR 0.72 [95% CI 0.63 to 0.83]; p < 0.001). Our sensitivity analyses, in which the exposure assessment interval was extended from 4 to 8 or 12 weeks and exposure was stratified by whether the dental procedure was invasive, demonstrated results that were consistent with our main analysis. CONCLUSION: Dental procedures were not associated with an increased risk of subsequent PVO in this case-crossover study. The effectiveness of antibiotic prophylaxis was not demonstrated in the additional analysis that categorized exposure according to the use of antibiotic prophylaxis. Our results suggest that the association between dental procedures and PVO may have been overestimated. Maintaining good oral hygiene may be important in preventing the development of PVO. The indications for antibiotic prophylaxis before dental procedures should be reconsidered in view of the potential risk of adverse drug reactions to antibiotic prophylaxis and the emergence of drug-resistant pathogens. Larger randomized controlled trials are needed to confirm these findings and assess the role of antibiotic prophylaxis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Correction: Electronic Health Record-Nested Reminders for Serum Lithium Level Monitoring in Patients With Mood Disorder: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/40595.].

Incidence, prevalence, and treatment of Moyamoya disease in Japan: A population-based descriptive study.

BACKGROUND: Moyamoya disease (MMD) is characterized by progressive stenosis or occlusion of the terminal portions of the bilateral internal carotid arteries. A Japanese survey in 2003 reported an incidence and prevalence of MMD of 0.54 and 6.03 per 100,000 people, respectively, showing an upward trend over previous surveys. An update to these estimates is therefore warranted. Additionally, evidence is lacking on trends in revascularization and antiplatelet therapy in MMD patients. METHODS: We conducted a population-based descriptive study using a Japanese claims database. From fiscal year (FY) 2015 to 2019, we standardized the incidence and prevalence estimates of MMD to the 2015 Japanese census population by age and sex. We also estimated the 1-year cumulative incidence of revascularization among incident MMD patients and the proportion of prevalent MMD patients receiving antiplatelet therapy in each FY. RESULTS: The age-standardized male-to-female ratio of both incident and prevalent MMD patients was approximately 1:2. Standardized incidence and prevalence of MMD per 100,000 population increased slightly from 1.8 to 2.4 and 14.7 to 17.6, respectively. The 1-year cumulative incidence of revascularization among incident MMD patients varied between 21.9 % and 28.9 %. Among prevalent MMD patients, 36.6 % to 39.0 % received antiplatelet therapy. CONCLUSIONS: The incidence and prevalence of MMD in Japan from FY 2015 to 2019 were higher than those estimated in 2003. The trends in revascularization and antiplatelet therapy identified in this study will be useful in further improving the quality of MMD clinical practice.

The association between intraoperative anesthesia methods used during gastric cancer surgery and long-term mortality: A retrospective observational study using a Japanese claims database.

PURPOSE: Various basic and clinical studies have investigated the association between the types of anesthetic agents and prognosis. However, the results have varied among studies and remain controversial. In the present study, we aimed to investigate whether the risk of all-cause mortality differs between inhaled or intravenous anesthetics in patients with gastric cancer undergoing gastrectomy. METHODS: Using a Japanese nationwide insurance claims database, we analyzed patients who underwent gastrectomy under general anesthesia for gastric cancer between January 2005 and September 2019. Postoperative outcomes were compared between two groups: those who received inhaled anesthetics (Sevoflurane, Isoflurane, or Desflurane) and those who received intravenous anesthetics (propofol), using a multivariable Cox proportional hazards model. The primary outcome was overall survival. RESULTS: Among 2671 eligible patients, 2105 were in the inhaled anesthetic group, and 566 were in the intravenous anesthetic group. The median (interquartile range) age was 58 (51-63) years, and 1979 (74.1%) were men. The median follow-up period was 795 days. We identified 56 (2.7%) and 16 (2.8%) deaths during the follow-up period in the inhaled and intravenous anesthetic use groups, respectively. There was no difference in postoperative overall survival between the two groups (hazard ratio, 0.97; 95% confidence interval, 0.56-1.70; P = 0.93). CONCLUSIONS: We found no significant difference in the postoperative risks of overall survival between inhaled and intravenous anesthesia in patients with gastric cancer undergoing gastrectomy.

Risk of pneumonitis in non-small cell lung cancer patients with preexisting interstitial lung diseases treated with immune checkpoint inhibitors: a nationwide retrospective cohort study.

BACKGROUND: Chemotherapy for non-small cell lung cancer (NSCLC) patients with preexisting interstitial lung diseases (ILDs) increases the risk of developing pneumonitis. However, the association between pneumonitis and immune checkpoint inhibitors (ICIs) and related factors remains unclear. METHODS: We conducted a retrospective cohort study using a nationwide inpatient database. We included patients (aged ≥ 20 years) newly diagnosed with ILD and NSCLC and who started chemotherapy (ICIs or conventional chemotherapy) between January 2016 and December 2019. The primary endpoint was the onset of pneumonitis. We estimated the cumulative incidence function of pneumonitis and compared it with patients taking ICIs and patients receiving conventional chemotherapy using Gray's test. We calculated the subdistribution hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pneumonitis using Fine and Gray's model to adjust for sex, age, smoking status, histology of NSCLC, surgical history, and medical histories, considering death as the competing risk. RESULTS: We identified 1177 patients (mean age 72 years, 13.8% female), of which 328 and 849 were in the ICI and conventional chemotherapy groups, respectively. There was no significant difference in the cumulative incidence function of pneumonitis between the two groups (p = 0.868). The adjusted subdistribution HR for the incidence of pneumonitis was 1.08 (95% CI: 0.74-1.57). Age (≥ 65 years) (HR: 1.86, 95% CI: 1.11-3.10) and smoking history (HR: 2.04, 95% CI: 1.02-4.11) were associated with developing pneumonitis. CONCLUSION: The risk of developing pneumonitis with ICIs for NSCLC patients with preexisting ILD was similar to that with conventional chemotherapy.

Appropriate dose of regorafenib based on body weight of colorectal cancer patients: a retrospective cohort study.

PURPOSE: Previous randomized studies have shown a survival benefit of using regorafenib but a high rate of adverse events in unresectable colorectal cancer patients. To reduce these adverse events and improve the tolerability, we examined the appropriate dose of regorafenib based on body weight. METHODS: We used a nationwide claims database in Japan and examined the efficacy and safety of regorafenib for patients with metastatic colorectal cancer between groups divided by body weight (60 kg) and median average dose (120 mg) between 2013 and 2018. We also assessed overall survival (OS) and adverse events between these groups. RESULTS: We identified 2530 Japanese patients (heavy weight/high dose: 513, light weight/low dose: 921, heavy weight/low dose: 452, and light weight/high dose: 644). There was no significant difference in the adverse events and OS after inverse probability treatment weighting (IPTW) adjustment between heavy weight/high dose group and light weight/low dose group (hazard ratio, HR=0.97). Among the light-weight patients, higher average dose was associated with shorter OS (IPTW adjusted HR=1.21, 95% CI 1.05 - 1.39, Table 3) while among the heavy-weight patients, there was no significant difference in OS between high and low dose groups (IPTW adjusted HR=1.14, 95% CI 0.95 - 1.37). CONCLUSION: The findings suggest that a low dose of regorafenib for light-weight patients may be as safe and effective as high doses for heavy-weight patients. Further studies should be conducted to identify an appropriate dose based on each patient's physique and condition.

Frequency and determinants of serum calcium monitoring during eldecalcitol therapy in patients with osteoporosis.

INTRODUCTION: Eldecalcitol (ELD) is an active vitamin D3 analog (AVD) commonly used to treat osteoporosis in Japan. Although routine monitoring of serum calcium levels during ELD therapy is recommended, little is known about the actual frequency and determinants of monitoring. MATERIALS AND METHODS: This was a descriptive cohort study using a Japanese electronic medical records database. We identified osteoporosis patients who initiated treatment with ELD or other AVDs (alfacalcidol and calcitriol) between April 1, 2011 and September 10, 2021. The index date for cohort entry was the first prescription date of ELD or other AVDs. The frequency of serum calcium monitoring was evaluated every 6 months. Determinants of serum calcium monitoring were identified using multivariable logistic regression models. We also calculated the incidence of hypercalcemia and the frequency of serum calcium monitoring within 6 months before hypercalcemia. RESULTS: We identified 12,671 ELD users and 7867 other AVD users. Within 6 months after cohort entry, 45.9% of ELD users and 58.7% of other AVD users underwent serum calcium monitoring. Female sex, no use of systemic corticosteroids, moderate-to-good renal function, treatment in smaller hospitals, and treatment in orthopedic surgery departments were associated with a lower likelihood of receiving serum calcium monitoring during ELD therapy. The incidence of hypercalcemia among ELD users was 6.36 per 100 person-years, with 20.6% of cases not receiving serum calcium monitoring before hypercalcemia. CONCLUSION: Our findings suggest that serum calcium monitoring is not given adequate attention during ELD therapy in routine clinical practice.

Efficacy of Daikenchuto in the prevention of bowel obstruction in patients with colorectal cancer undergoing laparoscopic surgery: An observational study using a Japanese administrative claims database.

PURPOSE: Daikenchuto is an herbal medicine widely used in Japan without clear evidence to prevent bowel obstruction after abdominal surgery. We evaluated the efficacy of Daikenchuto in laparoscopic surgery for colorectal cancer (CRC). METHODS: We included patients from the medical claims databases diagnosed with CRC between January 2012 and December 2019 and treated with laparoscopic surgery. We compared the Daikenchuto and control groups to evaluate early bowel obstruction (EBO) events for 1 year. The Daikenchuto group included patients prescribed Daikenchuto on postoperative day (POD) 0 or 1. An EBO event was defined as the use of a nasogastric tube, transnasal ileus tube, endoscopic balloon dilatation, or the requirement of reoperation for bowel obstruction from PODs 1 to 364. RESULTS: In total, 46,458 patients met the eligibility criteria; 2407 and 44,051 patients were included in the Daikenchuto and control groups, respectively. Some of the patient's characteristics were significantly different between the groups. The frequencies of EBO events in the Daikenchuto and control groups were 5.7% (95% confidence interval: 4.8-6.7) and 4.6% (4.4-4.8), respectively. The most frequent events were nasogastric tube (3.1%, 2.9%) and transnasal ileus tube insertions (1.4%, 0.8%) in the Daikenchuto and control groups, respectively. The hospital stay was significantly shorter in the Daikenchuto group than in the control; this trend was confirmed in the sensitivity analysis. CONCLUSIONS: Daikenchuto did not demonstrate efficacy for EBO. It might be adequate for shortening patient's hospital stay. Further studies are warranted.

Hypothetical intervention of targeted systolic blood pressure control of < 120 mmHg on renal prognosis for persons with stage 3-4 chronic kidney disease: an application of parametric g-formula using health checkup data in Japan.

BACKGROUND: The revised KDIGO guidelines recommend maintaining systolic blood pressure (sBP) < 120 mmHg in patients with chronic kidney disease (CKD), based on cardiovascular and survival benefits. However, the renal benefit of this strategy remains less clear. METHODS: We used data of routine health checkups in Japan. Persons whose estimated glomerular filtration rate (eGFR) was < 60 mL/min/1.73 m2 in 2015 without end-stage disease were followed until 2020. We estimated the 5-year benefit of hypothetical targeted sBP control using parametric g-formula modeling, accounting for both time-fixed and time-varying confounding variables. Four sensitivity analyses, including analysis using a marginal structural model (MSM) and positive control outcome analysis, were also done. RESULTS: We enrolled 28,972 persons with CKD (median age: 54 years, male: 69%, baseline eGFR [median]: 56 mL/min/1.73m2). As compared with the natural course without a targeted intervention, there was no renoprotective effect of targeted sBP control, with a 5-year difference in eGFR of 0.65 mL/min/1.73 m2 (95% confidence interval - 0.42 to 1.65 mL/min/1.73 m2). MSM analysis found a similar result. In contrast, the positive control analysis using the cardiovascular outcome showed that targeted sBP control would reduce the cardiovascular disease incidence by 6.0% over 5 years. CONCLUSIONS: A targeted sBP control strategy maintaining < 120 mmHg may not yield a renoprotective effect for patients with stage 3-4 CKD, although it was expected to offer a cardiovascular benefit. Future research may be warranted in higher-risk populations, such as elderly people or those with more advanced kidney disease.

Real-world practice of estrogen therapy after surgery for endometrial cancer: a descriptive study using a Japanese claims database.

BACKGROUND: Estrogen therapy (ET) plays a key role in maintaining the post-surgical quality of life of patients with endometrial cancer. This study investigated the reality of the use of ET after endometrial cancer surgery in Japan. METHODS: Using a healthcare database in Japan, patients who underwent surgery for endometrial cancer between the ages of 40 and 59 years from January 2006 to March 2021 were included. The cumulative prescriptions of ET after endometrial cancer surgeries in patients who had received chemotherapy or radiation therapy (adj-group) and those who did not (non-adj-group) was estimated using the Kaplan-Meier method. RESULTS: Of the 1475 patients, 115 received ET, among whom transdermal estradiol was initiated in 100 (87.0%) individuals. The cumulative proportions of ET prescription 24 months after surgery [95% confidence intervals (CIs)] were 0.088 [0.072, 0.11] in the non-adj-group and 0.058 [0.040, 0.084] in the adj-group. The cumulative proportion [95% CI] of women who received ET at 24 months after surgeries decreased with increasing age, ranging from 0.29 [0.21, 0.38] in the 40‒44 years old to 0.009 [0.002, 0.034] in the 55‒59 years old women in the non-adj-group and from 0.17 [0.094, 0.31] in the 40‒44 years old to 0 in the 55‒59 years old women in the adj-group. CONCLUSION: The present study shows that ET after endometrial cancer surgery may be underused, even in women who underwent surgery between 40 and 44 years of age and without adjuvant therapy.

Reoperation Rates of Microendoscopic Discectomy Compared With Conventional Open Lumbar Discectomy: A Large-database Study.

BACKGROUND: Microendoscopic discectomy for lumbar disc herniation has been shown to be as effective as traditional microdiscectomy or open discectomy in terms of clinical outcomes such as pain relief, and it is less invasive. Nevertheless, the reoperation rate for microendoscopic discectomy compared with microdiscectomy or open discectomy remains unclear, possibly due to difficulties in conducting follow-up of sufficient duration and in obtaining information about reoperation in other facilities. QUESTIONS/PURPOSES: (1) What is the rate of reoperation after microendoscopic discectomy for primary lumbar disc herniation on a large scale at a median of 4 years postoperatively? (2) Is there any difference in revision rate at a median of 4 years and within 90 days postoperatively based on surgical method? METHODS: We conducted a retrospective, comparative study of adult patients who underwent microendoscopic discectomy or microdiscectomy or open discectomy for lumbar disc herniation from April 2008 to October 2017 and who were followed until October 2020 using a commercially available administrative claims database from JMDC Inc. This claims-based database provided information on individual patients collected across multiple hospitals, which improved the accuracy of postoperative reoperation rates. We included 3961 patients who received microendoscopic discectomy or microdiscectomy or open discectomy between April 2008 and October 2017 in the JMDC claims database. After applying exclusion criteria, 50% (1968 of 3961) of patients were eligible for this study. Propensity score-weighted analyses were conducted in 646 patients in the microendoscopic discectomy group and in 1322 in the microdiscectomy or open discectomy group, with a median (IQR) of 4 years (3 to 6) of follow-up in both groups. Mean patient age was 42 ± 12 years in the microendoscopic discectomy group and 43 ± 12 years in the microdiscectomy or open discectomy group. Males accounted for 78% (505 of 646) of patients in the microendoscopic discectomy group and 79% (1050 of 1322) of patients in microdiscectomy or open discectomy group. The proportion of patients with diabetes mellitus in the microendoscopic discectomy group (10% [64 of 646]) was less than in the microdiscectomy or open discectomy group (15% [195 of 1322]). The primary outcome was Kaplan-Meier survivorship free from any type of additional lumbar spine surgery at a median of 4 years after the index surgery. The secondary outcome was survival probability using the Kaplan-Meier method with endpoints of any type of reoperation within 90 days after the index surgery. To determine which procedure had the higher revision rate, we conducted propensity score overlap weighting analysis, which controlled for potential confounding variables such as age, sex, comorbidities, and type of hospital as well as Cox proportional hazard models to estimate HRs and 95% confidence intervals (CIs). RESULTS: The 5-year cumulative reoperation rate was 12% (95% CI 9% to 15%) in the microendoscopic discectomy group and 7% (95% CI 6% to 9%) in the microdiscectomy or open discectomy group. After controlling for potentially confounding variables like age, sex, and diabetes mellitus, the microendoscopic discectomy group had a higher reoperation risk than the microdiscectomy or open discectomy group (weighted HR 1.57 [95% CI 1.14 to 2.16]; p = 0.004). Within 90 days of the index surgery, after controlling for potentially confounding variables like age, sex, and diabetes mellitus, we found no difference between the microendoscopic discectomy group and microdiscectomy or open discectomy group in terms of risk of reoperation (weighted HR 1.38 [95% CI 0.68 to 2.79]; p = 0.38). CONCLUSION: Given the higher reoperation risk with microendoscopic discectomy compared with microdiscectomy or open discectomy at a median of 4 years of follow-up, surgeons should select microdiscectomy or open discectomy, despite the current popularity of microendoscopic discectomy. The revision risk of microendoscopic discectomy compared with microdiscectomy or open discectomy in the long term remains unclear. Future large, prospective, multicenter cohort studies with long-term follow-up are needed to confirm the association between microendoscopic discectomy and risk of reoperation. LEVEL OF EVIDENCE: Level Ⅲ, therapeutic study.