Medical Data Center Claims Database Research Articles

Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan

Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear. To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment. This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023. Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy. The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively. The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone. Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.

Trends of HbA1c and BMI in People with Type 2 Diabetes: A Japanese Claims-Based Study.

Obesity prevalence has increased in Japan in recent years. Given the strong association of obesity with poor glycemic control, and increased risk of type 2 diabetes (T2D) with central obesity, this study describes the current trends and relationships between glycated hemoglobin (HbA1c), body mass index (BMI), and waist circumference in the Japanese people with T2D. This was a retrospective, cross-sectional study of people with T2D who had at least one recorded HbA1c and BMI (or waist circumference) value in the Japan Medical Data Center Claims database. Five annual cohorts of the study population were formed between January 2017 and December 2021. Annual trends of HbA1c across BMI categories (obesity class I [≥ 25 ~ < 30kg/m2]-IV [≥ 40kg/m2]) and in people with central obesity (waist circumference: ≥ 85cm in men; ≥ 90cm in women) were described by sex and age groups. Overall, 106,089 people with T2D (HbA1c and BMI data: 106,079; HbA1c and waist circumference data: 105,424) were included, with the majority of people belonging to obesity class I (range: 39.7-40.6%) and obesity class II (range: 16.2-17.7%) categories across all annual cohorts. People in higher BMI categories had higher mean HbA1c, with > 50% of people with T2D in obesity class I-IV (54.8-56.5%) having HbA1c ≥ 7%. Between 2017 and 2021, BMI and waist circumference increased in the age group 18-44years. More than 50% of people with T2D and central obesity in both sexes and people of age group 18-44years across obesity class I-IV or with central obesity had HbA1c ≥ 7%. More than half of the people with T2D belonging to obesity class I-IV or central obesity had poor glycemic control (HbA1c ≥ 7%), especially in the 18-44 age group. This highlights the need for body weight management for better glycemic control in relatively young Japanese people with T2D and obesity.

Association between oral corticosteroid starting dose and the incidence of pneumonia in Japanese patients with ulcerative colitis: a nation-wide claims database study.

A previous study demonstrated that half of patients started oral corticosteroids (OCS) for ulcerative colitis (UC) exacerbations at lower doses than recommended by Japanese treatment guidelines (initial OCS prednisolone equivalent dose, 30-40 mg). This may relate to physician's concern about infection, especially pneumonia including Pneumocystis jirovecii pneumonia (PJP), from high OCS doses. We assessed whether pneumonia incidence is increased with guideline-recommended OCS initial doses. This retrospective cohort study used the Japan Medical Data Center claims database (2012-2021). The whole cohort consisted of all UC patients who started OCS during the study period meeting the inclusion and exclusion criteria. The matched cohort was created by propensity score matching; the lower (initial OCS dose < 30 mg), guideline-recommended (30-40 mg), and higher groups ( > 40 mg) in a 2:2:1 ratio. Pneumonia incidence in the primary analysis was evaluated in the matched cohort. A Poisson regression model determined pneumonia-related risk factors in the whole cohort. After screening, 3,349 patients comprised the whole cohort; 1,775 patients comprised the matched cohort (lower dose, n = 710; guideline-recommended dose, n = 710; higher dose, n = 355). The incidence of any pneumonia was low; no differences were observed in incidence rates across these dose subgroups. In total, 3 PJP cases were found in the whole cohort, but not detected in the matched cohort. Several risk factors for any pneumonia were identified, including age, higher comorbidities index, treatment in large facility and hospitalization. The incidence of pneumonia, including PJP, in UC patients was low across initial OCS dose treatment subgroups.

Characterizing Fit-for-Purpose Real-World Data: An Assessment of a Mother-Infant Linkage in the Japan Medical Data Center Claims Database.

Observational postapproval safety studies are needed to inform medication safety during pregnancy. Real-world databases can be valuable for supporting such research, but fitness for regulatory purpose must first be vetted. Here, we demonstrate a fit-for-purpose assessment of the Japan Medical Data Center (JMDC) claims database for pregnancy safety regulatory decision-making. The Duke-Margolis framework considers a database's fitness for regulatory purpose based on relevancy (capacity to answer the research question based on variable availability and a sufficiently sized, representative population) and quality (ability to validly answer the research question based on data completeness and accuracy). To assess these considerations, we examined descriptive characteristics of infants and pregnancies among females ages 12-55 years in the JMDC between January 2005 and March 2022. For relevancy, we determined that critical data fields (maternal medications, infant major congenital malformations, covariates) are available. Family identification codes permitted linkage of 385,295 total mother-infant pairs, 57% of which were continuously enrolled during pregnancy. The prevalence of specific congenital malformation subcategories and maternal medical conditions were representative of the general population, but preterm births were below expectations (3.6% versus 5.6%) in this population. For quality, our methods are expected to accurately identify the complete set of mothers and infants with a shared health insurance plan. However, validity of gestational age information was limited given the high proportion (60%) of missing live birth delivery codes coupled with suppression of infant birth dates and inaccessibility of disease codes with gestational week information. The JMDC may be well suited for descriptive studies of pregnant people in Japan (eg, comorbidities, medication usage). More work is needed to identify a method to assign pregnancy onset and delivery dates so that in utero medication exposure windows can be defined more precisely as needed for many regulatory postapproval pregnancy safety studies.

Trends in Influenza and Related Health Resource Use During 2005-2021 Among Children in Japan.

To determine the epidemiological trends in pediatric influenza and changes in healthcare resource use from 2005 to 2021 using nationally representative outpatient database in Japan. We conducted a retrospective cohort study consisting of 3.5 million children with 177 million person-months during 2005-2021 using Japan Medical Data Center claims database in Japan. We investigated trends in incidence rates of influenza and changes in healthcare resource use (eg, use of antivirals) over 17 years. Generalized estimation equations were used to investigate the impact of the 2009 influenza pandemic and the coronaviral disease 2019 (COVID-19) pandemic on incidence rates of influenza and related healthcare utilization. Annual incidence rates of influenza were estimated at 55 cases per 1000 person-years with a 93% relative increase [95% confidence interval (CI): 80%-107%] during the 2009 influenza pandemic and a 99.4% relative reduction (95% CI: 99.3%-99.4%) during the COVID-19 pandemic. Similar patterns were observed for health resource use, total healthcare costs, admission rates and antiviral agent use. Approximately 80% of children with influenza received prescriptions for antivirals. The most prescribed antivirals were oseltamivir, but we observed a temporal increase in zanamivir use during 2007-2009, an increasing trend in laminamivir use during 2010-2017, a temporal increase in baloxavir use in 2018. Symptomatic medications with serious side effects (codeine, salicylate, sedative antihistamine) showed decreasing trends over the study period. Influenza incidence and healthcare resource use were largely affected by the 2009 influenza pandemic and the COVID-19 pandemic. Our study indicates improvement of quality in healthcare delivered to children.

Advanced or metastatic biliary tract cancer in Japan: a study using the Japan Medical Data Center payer claims database.

Aim: Biliary tract cancers are aggressive, with poor prognosis. This study describes clinical characteristics, treatment patternsand healthcare resource utilization in patients with metastatic biliary tract cancer in Japan. Materials & methods: This cohort-based study collected data from the Japan Medical Data Center claims database (2014-2018). Results: A total of325 patients were included; 65.2% were maleand the mean age was 59.2years. A47.6% had an Elixhauser Comorbidity Index score ≥5. Most frequent regimens were gemcitabine+cisplatin (52.9%) for first-line therapy and tegafur+gimeracil+oteracil for second-line therapy (48.6%) and third-line therapy (27.2%). Approximately 77% of patients had ≥1 hospital admission, with a median length of 57days. Conclusion: This study provides insights on the characteristics and burden of metastatic biliary tract cancer in Japan, highlighting high disease burden in a younger population.

Gait Speed and Cardiovascular Disease by Glycemic Status

The aim of this study was to clarify whether the association of gait speed with the incidence of cardiovascular disease depends on baseline glycemic status. This retrospective observational cohort study used the Japan Medical Data Center Claims Database between 2005 and 2021 and analyzed 3,090,048 participants without a cardiovascular disease history. The median (IQR) age was 44 (37-53) years, and 1,755,205 of the participants (56.8%) were men. Information on gait speed was obtained from self-reported questionnaires in health checkups. Study participants were categorized according to HbA1c levels (<5.7%, 5.7-6.4%, and ≥6.5%). The primary endpoint was defined as a composite cardiovascular disease outcome that consists of heart failure, myocardial infarction, angina pectoris, and stroke. During the mean follow-up period of 1,120±857 days, 116,678 composite cardiovascular disease outcomes were documented. Self-reported fast gait speed was related to a lower risk of developing cardiovascular disease; this relationship was more pronounced with increasing HbA1c levels. Compared with slow gait speed, the hazard ratio (95% CI) of self-reported fast gait speed for cardiovascular disease was 0.935 (0.921-0.949) in participants with an HbA1c <5.7%, 0.911 (0.891-0.932) in participants with an HbA1c of 5.7-6.4%, and 0.846 (0.811-0.883) in participants with HbA1c ≥6.5% (p-value for interaction<0.001). The relationship of subjective gait speed with the risk of cardiovascular disease was amplified in individuals with prediabetes or diabetes mellitus, suggesting that maintaining exercise capacity could be more important in individuals with impaired glucose tolerance for preventing cardiovascular disease.

Real-world outcomes associated with vonoprazan-based versus proton pump inhibitor-based therapy for Helicobacter pylori infection in Japan.

Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori (H. pylori) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns. To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns. Retrospective matched cohort. We used data from the Japan Medical Data Center claims database (July 2014-January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period. Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori-related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p < 0.001]. Over 80% of patients received a post-treatment test for H. pylori. Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p < 0.001) between 31 days and 12 months after the index date. Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori-related HCRU, and lower healthcare costs than patients treated with PPI-based therapy.

Cost-consequence of abatacept as first-line therapy in Japanese rheumatoid arthritis patients using IORRA real-world data.

To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database. A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score). Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5. ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers.

Prevalence, comorbidities, and treatment patterns of Japanese patients with alopecia areata: A descriptive study using Japan medical data center claims database.

Real-world data on alopecia areata (AA) demographics, comorbidities, and treatment patterns are sparse, not only in Japan but worldwide. This cross-sectional study assessed the current prevalence of AA in Japan, including analysis of severe subsets, frequency of comorbidities, and unmet medical needs surrounding treatment. Patients registered in the Japan Medical Data Center claims database (January 2012 to December 2019) and diagnosed with AA were included. Prevalence was calculated yearly, with the most common comorbidities evaluated, and treatments described in the Japanese Dermatological Association AA management guidelines and approved in Japan were included in the analysis. In total, 61 899 patients were diagnosed with AA. Among them, 1497 were diagnosed with severe subtypes. AA prevalence in Japan has been gradually increasing (from 0.16% in 2012 to 0.27% in 2019). The most common comorbidities are allergic rhinitis, atopic dermatitis, and asthma. Depression and anxiety are frequent in these patients, as are autoimmune diseases, e.g., vitiligo, thyroid diseases, and rheumatoid arthritis. Intriguingly, the analysis found Down syndrome to be a comorbidity associated with severe AA in children. The principal treatments were topical corticosteroids, followed by carpronium chloride and cepharanthine. The use of systemic corticosteroids and antihistamines is increased in severe disease. The Japanese Dermatological Association guidelines do not support the use of oral corticosteroids in children; however, in the database, this has been prescribed in up to 2.5% and 9.8% of all pediatric and severe pediatric AA cases, respectively. Despite the limitations of using a claims database, the current study demonstrates that AA prevalence in Japan has gradually increased in recent years, with allergic diseases being the most common comorbidities. The data also imply that there is a need for effective and safe therapies, especially for severe and pediatric cases.

Amelioration of prevalence of threatened preterm labor during the COVID-19 pandemic: nationwide database analysis in Japan

We aimed to evaluate the changes in maternal and neonatal complications such as threatened preterm labor (TPL) and preterm birth before and during the coronavirus disease 2019 (COVID-19) pandemic using large-scale real-world data in Japan. We obtained data from the Japan Medical Data Center claims database and evaluated differences in maternal and neonatal complications, such as the prevalence of TPL and preterm birth before the COVID-19 pandemic (in the year 2018 or 2019) and during the COVID-19 pandemic (in 2020). We included 5533, 6257, and 5956 deliveries in the years 2018, 2019, and 2020, respectively. TPL prevalence and preterm birth had significantly decreased in 2020 (41.3%, 2.6%, respectively) compared with those reported in 2018 (45.3%, 3.9%, respectively) and 2019 (44.5%, 3.8%, respectively). Neonatal outcomes such as low-birth-weight infants and retinopathy of prematurity were also improved during the pandemic. There were no clear trends in the prevalence of maternal complications such as hypertensive disorders of pregnancy; hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome; and preeclampsia. Oral ritodrine hydrochloride usage in all participants had significantly decreased during the COVID-19 pandemic. In conclusion, our results suggest that the COVID-19 pandemic has ameliorated TPL and consequently reduced the number of preterm births.

Real-World Insurance Claims Analysis of Venous Thromboembolism in Japanese Patients with Inflammatory Bowel Disease

BackgroundInflammatory bowel disease (IBD), which encompasses both ulcerative colitis (UC) and Crohn’s disease (CD), is a risk factor for venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE).AimTo investigate the incidence of, and risk factors for, VTE in patients with IBD in Japan.MethodsThis was a retrospective, non-interventional study in patients with IBD from the Japan Medical Data Center claims database. Incidence rates (IRs; unique patients with events per 100 patient‐years) were calculated for VTE, DVT, and PE among the IBD, UC, and CD cohorts. Odds ratios of potential risk factors were calculated by univariate and multivariate analyses in a nested case–control design.ResultsOverall, 16 273 patients with IBD were included: 13 585 with UC and 3443 with CD. VTE events occurred in 1.3%, 1.2%, and 1.9% of patients with IBD, UC, and CD, respectively. In patients with IBD, UC, and CD, IRs of VTE were 0.45, 0.40, and 0.64, respectively, IRs of DVT were 0.42, 0.38, and 0.61, respectively, and IRs of PE were 0.07, 0.07, and 0.11, respectively. In patients with IBD, treatment history (immunomodulators), cardiovascular risk (hypertension, high-density lipoprotein or diabetes mellitus, and history of coronary artery disease or heart failure), malignancy, and undergoing major surgery were identified as potential risk factors for VTE in the multivariate analysis, with similar risk factors reported for patients with UC and CD.ConclusionsThis large study provides insight into the incidence and risk factors for VTE in patients with IBD from Japan.

Factors Associated with Surgical Treatment in Postpartum Women with Mastitis or Breast Abscess: A Retrospective Cohort Study.

Objective: The aim of this study was to identify factors associated with requiring surgical treatment for mastitis or breast abscess in postpartum mothers. Materials and Methods: This was a retrospective cohort study using the Japan Medical Data Center Claims Database. Information on pairs of infants born between April 2012 and December 2016 and their mothers were extracted. Data regarding the baseline characteristics, medical history, medical practice, and prescription drugs of mothers and their infants were collected. Multivariable logistic regression analysis was used to examine factors associated with undergoing surgical treatment. Results: The data of 69,363 eligible mothers were analyzed. The proportion of mothers who were diagnosed with mastitis or breast abscess within 1 year after childbirth was 10.8% (7,516/69,363). There were 114 mothers who underwent surgical treatment within 1 year after childbirth. This was 0.2% of all mothers and 1.5% of those diagnosed with mastitis or breast abscess. Surgical treatment was significantly associated with mothers having their first child (adjusted odds ratio [AOR], 2.58; 95% confidence interval [CI], 1.63-4.07) compared to those with a second or later child; it was also significantly associated with the diagnosis of breast abscess (AOR, 10.38; 95% CI, 5.28-20.40). Conclusions: This was the first report of the prevalence of mastitis or breast abscess and the requirement for surgical treatment among postpartum mothers in Japan. A first diagnosis of breast abscess and having a first child were associated with requiring surgical treatment. Health care professionals providing postpartum care should be aware of these factors.

Association between adherence to warfarin and thrombotic events in patients with antiphospholipid syndrome in Japan: A claims‐based retrospective cohort study

We aimed to evaluate adherence and persistence to warfarin therapy among patients with antiphospholipid syndrome (APS) and investigate the association between adherence and thrombotic events in those patients. We conducted a retrospective cohort study using the Japan Medical Data Center claims database from 2005 to 2018. Patients with APS receiving warfarin treatment were included in this study. Adherence and persistence were evaluated using the proportion of days covered (PDS) and refill gap methods, respectively. Demographic characteristics of patients were obtained. Kaplan-Meier curves with log-rank tests and Cox regression models were used to examine the association between adherence or persistence and time to thrombotic events. A total of 186 patients (mean age: 46.5 ± 12.4 years, females 68.8%) were included in this study. No significant differences were observed in risk factors for thrombosis and cardiovascular diseases among groups. Most patients were adherent (91.4%) and persistent (88.2%) to warfarin treatment. Adherent and persistent patients had a significantly higher rate of thrombotic event-free survival than nonadherent and nonpersistent patients (p < 0.05). Multivariable Cox regression showed that the risk of thrombotic events was higher in nonadherent patients (with a hazard ratio of 3.23 [95% confidence interval CI: 1.15-9.11]) and in nonpersistent patients (with a hazard ratio of 3.45 [95% CI: 1.35-8.82]). In patients with APS, nonadherence and nonpersistence to warfarin treatment was associated with a higher risk of thrombotic events, suggesting the careful monitoring of those patients.

Uncontrolled asthma: a retrospective cohort study in Japanese patients newly prescribed with medium-/high-dose ICS/LABA

Many asthma patients remain uncontrolled despite guideline-based therapies. We examined real-life asthma control in Japanese patients prescribed with inhaled corticosteroid/long-acting β2-agonist (ICS/LABA). Patients (≥12 years) with ≥2 asthma diagnoses, newly initiated on medium-/high-dose ICS/LABA (Japanese asthma guidelines), from 01 April 2009 to 31 March 2015 were included, using Japan Medical Data Center Claims Database. Primary objective: proportion of patients with uncontrolled asthma in the year following ICS/LABA initiation. Secondary objectives: predictors of uncontrolled asthma and healthcare resource utilization. In medium-dose (N = 24,937) and high-dose (N = 8661) ICS/LABA cohorts, 23% and 21% patients, respectively, were uncontrolled. Treatment step up and exacerbation were most common indicators of uncontrolled asthma. Predictors of uncontrolled asthma, analyzed by multivariable Cox model, included systemic corticosteroid use, exacerbation history, comorbidities, and being female. In both cohorts, healthcare resource utilization was higher in patients with uncontrolled asthma. Over 20% patients with persistent asthma who initiated medium- or high-dose ICS/LABA were uncontrolled, highlighting unmet need for novel therapies in these patients.

Decline incidence in upper gastrointestinal bleeding in several recent years: data of the Japan claims database of 13 million accumulated patients.

This study was to examine the recent trends in upper gastrointestinal bleeding in Japan using a large-scale real-world database. The incidence of upper gastrointestinal bleeding was evaluated in the Japan Medical Data Center claims database of 13,019,713 patients aged 20 to 74 years with traceability for 3 months from 2009 to 2014. The incidence was compared with peptic ulcers and gastroesophageal reflux disease. The prescription of medications was also evaluated. The incidence of bleeding was 0.137%, 0.121%, 0.113%, 0.106%, 0.099%, and 0.105% during 2009 to 2014 with a time-dependent decline (p<0.001). Peptic ulcers (>10 times higher than the incidence of bleeding) decreased with time (p<0.001), whereas gastroesophageal reflux disease increased (p = 0.006). Upper gastrointestinal bleeding was higher in male patients and older patients (60–74 years old) (p<0.001 respectively). The prescription rate of antithrombotic medications and proton pump inhibitors increased from 2009 to 2014 (p<0.001 respectively). The incidence of upper gastrointestinal bleeding decreased from 2009 to 2014 in this relatively large-scale real-world database in Japan, concomitant with the decrease in peptic ulcers. The decreased incidence might have been due to changes in the disease structure and therapeutic strategies over time.

Risk of Cancer in Association with Ranitidine and Nizatidine vs Other H2 Blockers: Analysis of the Japan Medical Data Center Claims Database 2005-2018.

In September 2019, ranitidine and nizatidine were suggested to contain N-nitrosodimethylamine, a carcinogenic substance. People have since been concerned about the potential impact of ranitidine/nizatidine use on the risk of cancer. The objective of this study was to investigate the risk of cancer among people receiving ranitidine or nizatidine compared with other histamine 2 receptor antagonists (H2 blockers) [cimetidine, famotidine, roxatidine, and lafutidine]. In the Japan Medical Data Center claims database (comprising people aged < 75years) from 2005 to 2018, we identified new adult users of H2 blockers and classified them into ranitidine/nizatidine users and other H2 blocker users. We estimated the incidence of cancer diagnosis in each group and conducted a multivariable Cox regression analysis. We identified 113,745 new users of ranitidine/nizatidine (median age 41.2years [interquartile range 31.7-51.1]; 49.1% men; median follow-up 2.4years [1.1-4.5]) and 503,982 new users of other H2 blockers (median age 40.9years [31.1-51.2]; 51.0% men; median follow-up 2.3years [0.9-4.2]). The incidence rate of cancer diagnosis was 6.39 (95% confidence interval 6.13-6.66) cases per 1000 person-years (top three sites: breast 14.8%; colorectal 14.6%; and stomach 11.5%) in the ranitidine/nizatidine group and 6.17 (6.05-6.30) cases per 1000 person-years (colorectal 14.7%; breast 13.5%; and stomach 11.2%) in the other H2 blockers group. The adjusted hazard ratio (ranitidine/nizatidine users vs other H2 blocker users) was 1.02 (0.98-1.07). The results were similar by follow-up length, by cancer site, and when ranitidine and nizatidine users were separately compared with the other H2 blockers group. By cumulative dose, the adjusted hazard ratio (95% confidence interval) was 1.03 (0.98-1.08) from 1 to 180 defined daily doses (DDDs), 1.00 (0.73-1.39) from 181 to 365 DDDs, 0.95 (0.61-1.48) from 366 to 730 DDDs, and 0.83 (0.45-1.55) at > 730 DDDs. We found no evidence that ranitidine/nizatidine is associated with an increased risk of cancer, although further studies with more accurate measurement of exposure, inclusion of older people, and longer follow-up may be needed.

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

This study was performed to investigate the association between the use of pregabalin and injury. 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. 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). 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.

Integrative analysis of clinical and bioinformatics databases to identify anticancer properties of digoxin

Cardiac glycosides, such as digoxin, inhibit Na+/K+-ATPases and cause secondary activation of Na+/Ca2+ exchangers. Preclinical investigations have suggested that digoxin may have anticancer properties. In order to clarify the functional mechanisms of digoxin in cancer, we performed an integrative analysis of clinical and bioinformatics databases. The US Food and Drug Administration Adverse Event Reporting System and the Japan Medical Data Center claims database were used as clinical databases to evaluate reporting odds ratios and adjusted sequence ratios, respectively. The BaseSpace Correlation Engine and Connectivity Map bioinformatics databases were used to investigate molecular pathways related to digoxin anticancer mechanisms. Clinical database analyses suggested an inverse association between digoxin and four cancers: gastric, colon, prostate and haematological malignancy. The bioinformatics database analysis suggested digoxin may exert an anticancer effect via peroxisome proliferator-activated receptor α and apoptotic caspase cascade pathways. Our integrative analysis revealed the possibility of digoxin as a drug repositioning candidate for cancers.

Impact of immunomodulator use on treatment persistence in patients with ulcerative colitis: A claims database analysis.

Background and AimIt is unclear how adding an anti‐tumor necrosis factor alpha agent to immunomodulator (IM) treatment, as a step‐up strategy, affects long‐term outcomes in ulcerative colitis. This retrospective study investigated persistence associated with biologic anti‐tumor necrosis factor alpha agents combined with IMs versus biologic monotherapy in patients with ulcerative colitis.MethodsThis was a longitudinal cohort study of patients in the Japan Medical Data Center claims database who had been newly prescribed infliximab or adalimumab as induction (completed) and maintenance (2010–2016). Biologic persistence (i.e. no switch/discontinuation during maintenance) was compared among patients prescribed biologic monotherapy (Bio) and those prescribed a biologic combined with an IM, as step‐up (Bio + prior IM) or simultaneously (Bio + IM).ResultsThree hundred and sixty‐nine eligible patients were analyzed (233, 78, and 58 in the Bio, Bio + prior IM, and Bio + IM subgroups, respectively). Multivariate analysis showed a lower probability of nonpersistence during maintenance for infliximab‐treated patients in the Bio + prior IM versus Bio subgroup (hazard ratio: 0.53; 95% confidence interval: 0.29–0.99; P = 0.045). No such effect was seen in adalimumab‐treated patients (P = 0.222) or in the overall population (P = 0.398). The probability of nonpersistence during maintenance in the Bio + IM subgroup was not significantly different from that in the Bio subgroup in either the biologic subpopulation or in the overall population.ConclusionsAdding infliximab to an existing IM results in a lower probability of nonpersistence compared with infliximab monotherapy in ulcerative colitis patients. This effect is not seen in adalimumab‐treated patients.