Treatment for patients with autosomal dominant polycystic kidney disease in the chronic kidney disease without kidney replacement therapy in real-world clinical practice: a descriptive retrospective cohort study.

BACKGROUND: In real-world clinical practice, treatments selected for patients with autosomal dominant polycystic kidney disease (ADPKD) in the chronic kidney disease (CKD) without kidney replacement therapy (KRT) have not been reported. This study investigated the oral treatments used in these patients and the changes in their use in recent years. Additionally, we studied the factors affecting tolvaptan dose reduction or discontinuation. METHODS: This retrospective cohort study was conducted using the medical records of 160 hospitals in Japan. Patients with ADPKD or polycystic kidney disease registered on the database between January 2014 and December 2020 were selected. Changes in prescription proportions over time were assessed using the Cochran-Armitage test. We focused on patients prescribed with >15 mg of tolvaptan daily to identify the factors related to its dose reduction or discontinuation and used Multivariate Cox regression analysis to evaluate them. RESULTS: Tolvaptan use in patients with ADPKD in the CKD without KRT stage has increased. As of 2020, 25% of patients were treated with tolvaptan. Overall, 3639 patients with ADPKD were enrolled in the database, of whom 156 were treated with tolvaptan. Of these, 64 patients (41%) reduced or discontinued tolvaptan during the observation period. The presence of an estimated glomerular filtration rate <60 mL/min/1.73 m2 at the beginning of the treatment was associated with a higher risk of tolvaptan dose reduction or discontinuation. CONCLUSION: The proportion of patients with ADPKD treated with high-dose tolvaptan is increasing. However, patients with late-stage CKD tended to reduce or discontinue tolvaptan.

The Association Between Children's Autism Spectrum Disorders and Central Nervous System Infections: Using a Nationwide Claims Database.

Several studies have reported an association of autism spectrum disorder (ASD) with central nervous system (CNS) infections and intrauterine infections; however, the results remain unclear. This study aimed to examine this issue using an extensive national database. Utilizing JMDC medical claims database, we conducted a retrospective cohort study of children with at least three years of follow-up from birth, ensuring the mother's information was available. The focus was on the relationship between ASD incidence and exposures like viral meningitis/encephalitis, bacterial meningitis, and intrauterine infections. Cox proportional hazards was used to calculate hazard ratios (HRs) with covariates such as presence of maternal history of mental illness, preterm, low birth weight, respiratory and cardiac disorder, epilepsy, and cranial malformations. Sensitivity analysis was performed on sibling and multiple birth cohorts to adjust for genetic factors. Out of 276,195 mother-child pairs, bacterial meningitis was observed in 1326 (0.5%), viral meningitis/encephalitis in 6066 (2.2%), intrauterine infection in 3722 (1.3%), and ASD in 14,229 (5.2%) children. The adjusted HRs (95% confidence interval, p value) for ASD were 1.40 (1.25-1.57, p < 0.001), 1.14 (1.02-1.26, p = 0.013), and 1.06 (0.87-1.30, p = 0.539) for viral meningitis/encephalitis, intrauterine infection, and bacterial meningitis, respectively. After sensitivity analysis, the HRs for viral meningitis/encephalitis and ASD remained significantly high. Viral meningitis/encephalitis may be an independent risk factor for ASD. Awareness of this risk among healthcare professionals can lead to early intervention and potentially improved outcomes for affected children.

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.

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.

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

Potent CTLs can be induced against tumor cells in an environment of lower levels of systemic MFG-E8.

The direction and magnitude of immune responses are critically affected when dead cells are disposed of. Milk fat globule-epidermal growth factor-factor 8 (MFG-E8) promotes the engulfment of apoptotic normal and cancerous cells without inducing inflammation. We have previously reported that a certain proportion of the cancer cells express abundant MFG-E8, and that such expression is associated with the shorter survival of patients with esophageal cancer who had received chemotherapy before surgery. However, the influence of tumor-derived and systemically existing MFG-E8 on antitumor immune responses has not yet been fully investigated. Herein, we showed that CTL-dependent antitumor immune responses were observed in mice with no or decreased levels of systemic MFG-E8, and that such responses were enhanced further with the administration of anti-PD-1 antibody. In mice with decreased levels of systemic MFG-E8, the dominance of regulatory T cells in tumor-infiltrating lymphocytes was inverted to CD8+ T cell dominance. MFG-E8 expression by tumor cells appears to affect antitumor immune responses only when the level of systemic MFG-E8 is lower than the physiological status. We have also demonstrated in the clinical setting that lower levels of plasma MFG-E8, but not MFG-E8 expression in tumor cells, before the treatment was associated with objective responses to anti-PD-1 therapy in patients with non-small cell lung cancer. These results suggest that systemic MFG-E8 plays a critical role during the immunological initiation process of antigen-presenting cells to increase tumor-specific CTLs. Regulation of the systemic level of MFG-E8 might induce efficient antitumor immune responses and enhance the potency of anti-PD-1 therapy.

Prescribing Pattern and Efficacy of Oral Antibiotics for Pediatric Urinary Tract Infections in Japan: A Descriptive Study Using a Nationwide Claims Database.

BACKGROUND: Pediatric urinary tract infections are often treated with third-generation cephalosporins; however, the increasing prevalence of Escherichia coli resistant to cephalosporins has reduced their effectiveness. Although resistance is prevalent in Asia, the prescribing patterns and clinical effectiveness of antibiotics have mostly been reported in the United States. This study aimed to describe the prescription patterns and effectiveness of oral antibiotics for treating pediatric urinary tract infections in Japan. METHODS: This descriptive study used data from a nationwide Japanese claims database. We identified patients <6 years old with urinary tract infections who received oral antibiotics between January 2016 and December 2020. Descriptive analyses were performed to assess prescription patterns. Moreover, logistic regression analyses were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for treatment failure among the commonly prescribed antibiotics and patient characteristics. Treatment failure was defined as the prescription of different antibiotics within 7 days of the primary prescription. RESULTS: Of the 4,127 patients, 2,766 (67.0%) were prescribed third-generation cephalosporins, and 347 (8.4%) were prescribed amoxicillin. Trimethoprim-sulfamethoxazole and amoxicillin-clavulanate were prescribed to 63 (1.5%) and 50 (1.2%) patients, respectively. Treatment failure was observed in 118 (2.9%) patients and more often in amoxicillin-treated patients than in cefcapene pivoxil-treated patients [OR, 2.18 (95% CI: 1.04-4.58)]. CONCLUSIONS: Third-generation cephalosporins are the most commonly prescribed antibiotics for the initial therapy of pediatric urinary tract infections in Japan. Third-generation cephalosporins are still effective in Japan, despite the high prevalence of resistance against cephalosporins.

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.

Prediction models for in-hospital deaths of patients with COVID-19 using electronic healthcare data.

OBJECTIVE: Many models for predicting various disease prognoses have achieved high performance without laboratory test results. However, whether laboratory test results can improve performance remains unclear. This study aimed to investigate whether laboratory test results improve the model performance for coronavirus disease 2019 (COVID-19). METHODS: Prediction models were developed using data from the electronic healthcare record database in Japan. Patients aged ≥18 years hospitalized for COVID-19 after February 11, 2020, were included. Their age, sex, comorbidities, laboratory test results, and number of days from February 11, 2020, were collected. We developed a logistic regression, XGBOOST, random forest, and neural network analysis and compared the performance with and without laboratory test results. The performance of predicting in-hospital death was evaluated using the area under the curve (AUC). RESULTS: Data from 8,288 hospitalized patients (females, 46.5%) were analyzed. The median patient age was 71 years. A total of 6,630 patients were included in the training dataset, and 312 (4.7%) died. In the logistic regression model, the area under the curve was 0.88 (95% confidence interval [CI] = 0.83-0.93) and 0.75 (95% CI = 0.68-0.81) with and without laboratory test results, respectively. The performance was not fundamentally different between the model types, and the laboratory test results improved the performance in all cases. The variables useful for prediction were blood urea nitrogen, albumin, and lactate dehydrogenase. CONCLUSIONS: Laboratory test results, such as blood urea nitrogen, albumin, and lactate dehydrogenase levels, along with background information, helped estimate the prognosis of patients hospitalized for COVID-19.

Pneumonia hospitalization after introduction of pneumococcal conjugate vaccine in Japan: Descriptive study using a nationwide claims database.

BACKGROUND: The pneumococcal conjugate vaccine (PCV) was introduced to children in Japan in February 2010 for PCV7 and February 2013 for PCV13. This study aimed to investigate the changes in child pneumonia hospitalization in Japan, before and after the introduction of PCV. METHODS: We utilized the JMDC Claims Database, an insurance claims database in Japan, with a cumulative population of approximately 10.6 million as of 2022. We extracted data of approximately 3.16 million children below 15 years of age from January 2006 to December 2019, and evaluated the number of pneumonia hospitalizations per 1,000 persons per year. The primary analysis was a comparison of three categories according to PCVs: before PCV7, before PCV13, and after PCV13 (2006-2009, 2010-2012, and 2013-2019). The secondary analysis was an interrupted time series (ITS) analysis, assessing the slope change in pneumonia hospitalizations per month, with PCV introduction as an intervening factor. RESULTS: The cases of pneumonia hospitalizations during the study period was 19,920 (0.6 %); 25 % of these were 0-1 years, 48 % were 2-4 years, 18 % were 5-9 years, and 9 % were 10-14 years. Pneumonia hospitalizations per 1000 population was 6.10 before PCV7 and 4.03 after PCV13, representing a 34 % decrease (p < 0.001). The reduction by age group was -30.1 % in 0-1 years, -20.3 % in 2-4 years, -41.7 % in 5-9 years, and -52.9 % in 10-14 years, significant reduction in all groups. ITS analysis showed a further reduction of -0.17 % per month after the introduction of PCV13 than that before PCV7 (p = 0.006). CONCLUSION: Our study estimated 4-6 pneumonia hospitalizations per 1000 pediatric population in Japan, with a 34 % decrease after the introduction of PCV. This study examined the nationwide effectiveness of PCV, further studies are needed in all age groups.

Effectiveness of intraoperative nicorandil in patients with a history of ischemic heart disease undergoing high-risk noncardiac surgery: a retrospective cohort study.

PURPOSE: Nicorandil is occasionally administered to prevent myocardial ischemia during the perioperative period in patients with ischemic heart disease (IHD); however, its effectiveness has not been clarified. In this study, we examined the effectiveness of intraoperative nicorandil administration in noncardiac surgery. METHODS: We identified patients with a history of IHD who had undergone high-risk noncardiac surgery between April 2015 and March 2020 from a nationwide in-patient database in Japan. The patients were divided into those who received nicorandil (nicorandil group) and those who did not (control group). The primary outcome was the 30-day in-hospital mortality. The secondary outcome was major adverse cardiovascular events (MACE), defined as the composite outcome of the 30-day in-hospital mortality, acute myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. One-to-one propensity score matching was performed. The outcomes were analyzed using a Cox proportional hazards model. RESULTS: Of 8037 patients, 2886 received nicorandil during surgery. After propensity score matching, 2554 pairs were analyzed. There was no significant difference in the 30-day in-hospital mortality (26 [1.02%] vs. 36 [1.41%]; hazard ratio [HR] 1.36; 95% confidence interval [CI] 0.82-2.26; P = 0.229) or incidence of MACE (42 [1.64%] vs. 55 [2.15%]; HR 1.24; 95% CI 0.86-1.93; P = 0.216) between the control and nicorandil groups. CONCLUSION: The findings of this study suggest that intraoperative nicorandil administration is not associated with the 30-day in-hospital mortality in high-risk noncardiac surgery.

Longitudinal Association of Working From Home on Work Functioning Impairment in Desk Workers During COVID-19 Pandemic: A Nationwide Cohort Study.

OBJECTIVE: This study clarifies the longitudinal association between working from home and work functioning impairment among desk workers. METHODS: Nationwide surveys were conducted from 2020 to 2022, analyzing 3532 desk workers who never worked from home before the COVID-19 pandemic. RESULTS: The adjusted hazard ratio (95% confidence intervals) of working from home at least once a month or more with the composite result (incidence of work functioning or reduced work participation) was 1.22 (1.04-1.43). The cause-specific hazard ratios of work functioning impairment and reduced work participation were 1.30 (1.04-1.61) and 1.13 (0.86-1.47). CONCLUSIONS: Working from home could be longitudinally associated with work functioning impairment, especially for workers who are in higher positions. Workers and policy makers should be aware of the potential risk of working from home regarding presenteeism.

Association between combined spinal-epidural analgesia and neurodevelopment at 3 years old: The Japan Environment and Children's Study.

AIM: To investigate the association between maternal combined spinal-epidural analgesia during vaginal delivery and neurodevelopment in 3-year-old children. METHODS: Using data from the Japan Environment and Children's Study, a birth cohort study on pregnant women and their offspring, we described the background, perinatal outcomes, and neurodevelopmental outcomes of participants with a singleton pregnancy who received combined spinal-epidural analgesia during vaginal delivery and those who did not. The association between maternal combined spinal-epidural analgesia and abnormalities in five domains of the Ages and Stages Questionnaire, Third Edition, was analyzed using univariable and multivariable logistic regression analyses. Crude and adjusted odds ratios with 95% confidence intervals (95% CI) were calculated. RESULTS: Among 59 379 participants, 82 (0.1%) children (exposed group) were born to mothers who received combined spinal-epidural analgesia during vaginal delivery. In the exposed versus control groups, 1.2% versus 3.7% had communication abnormalities (adjusted odds ratio [95% CI]: 0.30 [0.04-2.19]), 6.1% versus 4.1% exhibited gross-motor abnormalities (1.36 [95% CI: 0.55-3.36]), 10.9% vs. 7.1% had fine-motor abnormalities (1.46 [95% CI: 0.72-2.96]), 6.1% vs. 6.9% showed difficulties with problem-solving (0.81 [95% CI: 0.33-2.01]), and 2.4% vs. 3.0% had personal-social problems (0.70 [95% CI: 0.17-2.85]). CONCLUSIONS: Exposure to combined spinal-epidural analgesia during vaginal delivery was not associated with the risk of neurodevelopmental abnormalities; however, the sample size of our study might not be appropriate for the study design.

Validity of using Japanese administrative data to identify inpatients with acute pulmonary embolism: Referencing the COMMAND VTE registry.

BackgroundAcute 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.MethodsThe 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 6 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.ResultsA 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% 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 by the diagnosis-based algorithm.ConclusionsThe diagnosis-based algorithm may be a relatively sensitive method for identifying acute PE inpatients in the Japanese DPC database.

Adherence to and persistence with lacosamide, perampanel, lamotrigine, and levetiracetam in adult patients with focal epilepsy in Japan: A descriptive cohort study using a claims database.

Objective: We evaluated adherence to and 1-year persistence of two third-generation anti-seizure medications (ASMs), lacosamide and perampanel, in adult patients with focal epilepsy, compared with lamotrigine and levetiracetam. Methods: A cohort study was conducted using a Japanese health insurance claims database (JMDC Inc.). We identified patients with adult-onset focal epilepsy who initiated any of the four ASMs between August 31, 2016, and October 31, 2019. Patients were further classified into ASM-naïve patients initiating any of the four ASMs as first-line treatment, and ASM-experienced patients initiating any of the four ASMs as second- or later-line treatment. Outcomes included adherence (proportion of days covered [PDC], defined as the total number of days covered by ASMs divided by the total number of days in the follow-up period) and 1-year persistence for the four ASMs. Results: We identified 141 lacosamide, 75 perampanel, 80 lamotrigine, and 530 levetiracetam initiators. Among these, the proportion of ASM-naïve patients was highest in the levetiracetam group (60.8%), followed by the lamotrigine (25.0%), lacosamide (20.6%), and perampanel groups (1.3%). Mean PDC (standard deviation) was similar across the four groups, at 0.95 (0.08) for lacosamide, 0.93 (0.12) for perampanel, 0.92 (0.10) for lamotrigine and 0.94 (0.11) for levetiracetam. The proportion of patients persisting with treatment for 1 year was highest in the lacosamide group (73.0%), followed by the levetiracetam (58.3%), lamotrigine (57.5%), and perampanel groups (54.7%). In ASM-naïve patients, adherence and 1-year persistence were almost identical in the lacosamide, lamotrigine, and levetiracetam groups. Results for ASM-experienced patients did not significantly differ from those of all patients. Significance: With regard to adherence and 1-year persistence, lacosamide may be equal to or better than lamotrigine and levetiracetam, especially in patients with experienced ASM, while perampanel may be comparable to lamotrigine and levetiracetam in patients with experienced ASM.

Risk of parkinsonism and related movement disorders with gabapentinoids or tramadol: A case-crossover study.

INTRODUCTION: A safety signal concerning parkinsonism and related movement disorders with gabapentinoids (gabapentin and pregabalin) or tramadol was detected by reviewing individual case reports and data mining in spontaneous report databases. Well-designed pharmacoepidemiological studies are needed to assess the signal. OBJECTIVE: This study aimed to investigate the association of exposure to gabapentinoids or tramadol with the risk of parkinsonism and related movement disorders. METHODS: We conducted a case-crossover study using a Japanese electronic medical records database. Patients with newly diagnosed parkinsonism or related movement disorders between January 1, 2007, and April 14, 2019, were identified. The diagnosis date of outcomes was defined as the index date. We assessed the exposure of each patient to gabapentinoids or tramadol during a 90-day hazard period ending 1 day before the index date and in three 90-day reference periods. Multivariable conditional logistic regression models were employed to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). To confirm the robustness of the primary findings, we also performed sensitivity analyses using a case-case-time-control design, a different time window for hazard and reference periods, a different definition of outcome, and different number of reference periods. RESULTS: A total of 28,972 eligible cases were included in the primary analysis. Exposure to gabapentinoids (aOR, 2.12; 95% CI, 1.73-2.61) and tramadol (aOR, 2.04; 95% CI, 1.57-2.64) was associated with increased risk. Results were consistent across sensitivity analyses. CONCLUSION: Our findings serve as a caution to physicians who prescribe gabapentinoids or tramadol in routine clinical practice.

Impact of Potentially Inappropriate Medications on Kidney Function in Chronic Kidney Disease: Retrospective Cohort Study.

INTRODUCTION: Chronic kidney disease (CKD) represents a major public health burden. Potential inappropriate medications (PIMs) are common in patients with CKD. However, its impact on kidney outcomes has not been adequately elucidated for middle-aged patients. This study aimed to clarify the prescription status of PIMs for middle-aged patients with CKD and its effect on kidney function decline. METHODS: Using an administrative claims database in Japan, a retrospective cohort study was conducted among Japanese patients with CKD (aged 20-74) who underwent annual health check-ups at least three times between April 2008 and December 2020. PIM exposure was defined as medications to be avoided in older adults as defined by the 2019 American Geriatrics Society Beers Criteria. The association between the number of prescribed PIMs and the decline in estimated glomerular filtration rate (eGFR) was examined using logistic regression models adjusted for clinical characteristics and laboratory variables. RESULTS: A total of 43,143 patients with CKD (mean age 57 years, median eGFR: 52 mL/min/1.73 m2) were analyzed, and approximately 40% of the patients were prescribed one or more PIMs. The most commonly prescribed PIMs were pain medications (18.5%), followed by gastrointestinal medications (9.8%), central nervous system medications (8.6%), and cardiovascular medications (8.6%). After adjustment, exposure to 2 or ≥3 PIMs was associated with an increased risk of 30% eGFR decline (adjusted odds ratio 1.71 [95% confidence interval, 1.24-2.37] and 1.65 [95% confidence interval, 1.08-2.52], respectively) as compared to the control group. CONCLUSION: This study showed that middle-aged patients with CKD who were prescribed ≥2 PIM had an increased risk of progression of CKD. Further studies are needed to analyze whether deprescribing steps contribute to reduce PIM prescriptions and prevent CKD progression.

Clinical epidemiology and pharmacoepidemiology studies with real-world databases.

Hospital-based registry data, including patients' information collected by academic societies or government based research groups, were previously used for clinical research in Japan. Now, real-world data routinely obtained in healthcare settings are being used in clinical epidemiology and pharmacoepidemiology. Real-world data include a database of claims originating from health insurance associations for reimbursement of medical fees, diagnosis procedure combinations databases for acute inpatient care in hospitals, a drug prescription database, and electronic medical records, including patients' medical information obtained by doctors, derived from electronic records of hospitals. In the past ten years, much evidence of clinical epidemiology and pharmacoepidemiology studies using real-world data has been accumulated. The purpose of this review was to introduce clinical epidemiology and pharmacoepidemiology approaches and studies using real-world data in Japan.

Incidence and Clinical Practice of Exudative Age-related Macular Degeneration: A Nationwide Population-Based Cohort Study.

Purpose: To elucidate the incidence and treatment pattern of active exudative age-related macular degeneration (AMD). Design: A population-based cohort study conducted using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), a national claims database managed by the Japanese Ministry of Health, Labour, and Welfare (MHLW). Participants: The entire Japanese population aged 40 years or older (76 million people). Methods: With the permission of the MHLW, we accessed the complete NDB dataset and identified patients with newly diagnosed active exudative AMD between 2011 and 2018. The incidence of active exudative AMD was categorized by age and sex per year between 2011 and 2018; moreover, details regarding first-line therapy and number of anti-vascular endothelial growth factor (VEGF) injections per elapsed year since initial treatment were obtained and changes in treatment pattern were investigated. Main Outcome Measures: Incidence rate of active exudative AMD. Results: During the specified 8-year period, 246 064 incident cases of active exudative AMD were identified; 61.4% of these patients were men. The overall incidence rate was 40.66 per 100 000 person-years (95% confidence interval [CI], 40.49-40.82) in the general population aged 40 years or older, 53.22 (95% CI, 52.95-53.49) in men, and 29.78 (95% CI, 29.60-29.98) in women. Mean age of onset was lower in men than in women (72.51 ± 10.50 years vs. 73.90 ± 10.46 years). Among patients with newly diagnosed active exudative AMD, 92.9% received anti-VEGF injections for initial treatments, whereas 1.8% underwent combination therapy with photodynamic therapy. The number of anti-VEGF injections in the first year (0-12 months), second year (13-24 months), and third year (25-36 months) after the initial injection was 3.66 ± 2.30, 1.39 ± 2.20, and 1.23 ± 2.19, respectively. Patients who received fewer injections in the first year received fewer injections in subsequent years and vice versa. Conclusions: This is a relatively large population-based study on the detailed epidemiology and actual treatment patterns of active exudative AMD in clinical practice. Our results can be a fundamental information source to ensure healthy eyes and promote well-being for all at all ages.

Association of prepregnancy physical activity with obesity in offspring: The Japan Environment and Children's Study.

OBJECTIVE: The aim of this study was to investigate the association between maternal prepregnancy physical activity (PA) and overweight/obesity in 3-year-old children. METHODS: Using data from the Japan Environment and Children's Study (a birth cohort study), maternal prepregnancy PA was categorized into low, moderate, and high with the International Physical Activity Questionnaire (IPAQ). The reference group was defined as children born to mothers with moderate PA. The association between prepregnancy PA and overweight/obesity or obesity in children was investigated using univariable and multivariable logistic regression analyses. RESULTS: Of the 65,245 participants, 48.7%, 32.7%, and 18.6% were born to mothers in the low, moderate, and high PA groups, respectively. Furthermore, 24.9%, 24.6%, and 25.9% of children with overweight/obesity and 9.4%, 9.2%, and 10.4% of children with obesity were born to mothers in the low, moderate, and high PA groups, respectively. The adjusted odds ratios for overweight/obesity in the low and high PA groups were 1.02 (95% CI: 0.98-1.06) and 1.04 (95% CI: 0.98-1.09), and those for obesity were 1.03 (95% CI: 0.97-1.09) and 1.08 (95% CI: 0.99-1.16), respectively. CONCLUSIONS: Maternal prepregnancy PA was not associated with overweight/obesity or obesity in 3-year-old children.