Inventory of real-world data sources in Japan: Annual survey conducted by the Japanese Society for Pharmacoepidemiology Task Force.

PURPOSE: The Database Task Force of the Japan Society for Pharmacoepidemiology began its annual surveys of databases available for clinico and pharmacoepidemiological studies in 2010. In this report, we summarize the characteristics of the databases available in Japan based on the results of our 2021 survey to illustrate the recent developments in the infrastructure for database research in Japan. METHODS: We included 20 major databases from the academia, government, or industry that were accessible to third parties. We used a web-based questionnaire to ask the database providers about their characteristics, such as their organization, data source(s), numbers of individuals enrolled, age distribution, code(s) used, and average follow-up periods. RESULTS: We received responses from all 20 databases approached: eight hospital-based databases, six insurer-based databases, four pharmacy-based databases, and two in the "other" category. Among them, 17 contained information from medical claims, pharmacy claims, and/or Diagnosis Procedure Combination data. Most insurer databases contained health check-up data that could be attached to the claims component. Some hospital-based databases had data from electronic medical records. Most insurer-based databases collected data from the insurers of working-age employees and therefore had limited coverage of older people. Most databases coded their medication data using the Japanese reimbursement codes, and many provided Anatomical Therapeutic Chemical Classification codes. CONCLUSIONS: The number of databases available for clinico and pharmacoepidemiological research and the proportion of the population they cover are increasing in Japan. The differences in their characteristics mean that the appropriate database must be selected for a particular study purpose.

Comparison of the Effectiveness of Vedolizumab and Ustekinumab in Crohn's Disease Patients Who Failed Anti-tumor Necrosis Factor-α Treatment in Japan: An Observational Study Utilizing Claims Database.

This study aimed to investigate whether the approved sequence of vedolizumab and ustekinumab impacts the results of previous observational studies conducted in the European Union (EU), comparing the effectiveness of these drugs in Crohn's disease (CD) patients who failed anti-tumor necrosis factor-α (TNFα) treatment. We conducted this study in Japan, where the approved sequence of drugs is different from that of the EU. We extracted 256 patients diagnosed with CD, who had a history of anti-TNFα treatment and were prescribed either vedolizumab or ustekinumab, from JMDC claims database. The patients' backgrounds were adjusted by inverse probability of treatment weighting using propensity score. The primary outcome was treatment persistence. Secondary outcomes were a steroid-free period, time to hospitalization, and time to CD-related surgery. The hazard ratios (HR) for survival times were estimated using the Cox proportional hazard model. The treatment persistence (primary endpoint) was significantly longer for ustekinumab than vedolizumab (HR, 0.32; 95% confidence interval (CI), 0.15-0.72). The results of the secondary endpoints were as follows: steroid-free period (HR, 0.38; 95% CI, 0.10-1.48), time to hospitalization (HR, 1.07; 95% CI, 0.60-1.91), or time to CD-related surgery (HR, 0.33; 95% CI, 0.11-0.97). There were no outcomes indicating the superiority of vedolizumab. Our findings suggest that ustekinumab is a more effective treatment option than vedolizumab for CD patients who failed to anti-TNFα treatment, and this finding remains consistent across both Japan and the EU.

Relationship Between Severe Respiratory Depression and Codeine-Containing Antitussives in Children: A Nested Case-Control Study.

BACKGROUND: Guidelines recommend against all codeine use in children for its common indications of analgesia and cough suppression because of uncertain benefits and potential risk of death. However, because of its rarity, the occurrence of severe respiratory depression associated with codeine-containing antitussives has been poorly investigated. The objective of this study was to investigate the association between codeine-containing antitussives and severe respiratory depression in children. METHODS: We retrospectively identified Japanese children who were prescribed antitussives for respiratory diseases from a large Japanese administrative claims database (JMDC, Tokyo, Japan). We collected data on baseline characteristics including age, sex, and comorbidity. Each case was matched with four controls with the same sex and age in the same year from the same type of medical institution. We then examined the association between codeine-containing antitussives and subsequent severe respiratory depression using multivariable conditional logistic regression analysis. RESULTS: Of 164,047 children, 18,210 (11.1%) were prescribed codeine-containing antitussives. Of the children who took codeine-containing drugs, seven experienced severe respiratory depression. After adjusting for confounding factors, there was no significant difference in the proportion of severe respiratory depression between children with and without codeine-containing antitussives (odds ratio 1.15; 95% confidence interval, 0.48-2.78). CONCLUSION: Occurrence of respiratory depression was very rare, and the association of codeine with respiratory depression was insignificant, even in a large sample of children in Japan.

Association Between Routine Nephropathy Monitoring and Subsequent Change in Estimated Glomerular Filtration Rate in Patients With Diabetes Mellitus: A Japanese Non-Elderly Cohort Study.

BACKGROUNDS: Current guidelines recommend routine nephropathy monitoring, including microalbuminuria or proteinuria testing, for people with diabetes mellitus; however, its effect in terms of preserving renal function remains unclear. We conducted this study to examine the impact of routine nephropathy monitoring on subsequent changes in estimated glomerular filtration rate. METHODS: We retrospectively identified non-elderly individuals with diabetes mellitus based on the prescription of hypoglycemic agents from a large Japanese database (JMDC, Tokyo, Japan) of screening for lifestyle diseases linked with administrative claims data. We collected data on baseline characteristics including age, sex, comorbidity, and laboratory data. We then examined the association between routine nephropathy monitoring results and change in estimated glomerular filtration rate using a propensity-score inverse probability of treatment weighting method. RESULTS: Among 1,602 individuals who started taking hypoglycemic agents between 2005 and 2016, 102 (6.0%) underwent routine nephropathy monitoring during the first year of medication for diabetes mellitus. After adjusting for multiple confounding factors, there was no significant difference in subsequent estimated glomerular filtration rate changes between individuals with and without routine nephropathy monitoring (difference in percent change 0.11; 95% confidence interval -2.74 to 2.95). CONCLUSION: Routine nephropathy monitoring was not associated with preserved renal function. Current recommendations for the universal application of nephropathy monitoring may have limited value to prevent renal dysfunction in non-elderly individuals with diabetes mellitus.

Positive predictive value of ICD-10 codes for acute myocardial infarction in Japan: a validation study at a single center.

BACKGROUND: In Japan, several large healthcare databases have become available for research since the early 2000's. However, validation studies to examine the accuracy of these databases remain scarce. We conducted a validation study in order to estimate the positive predictive value (PPV) of local or ICD-10 codes for acute myocardial infarction (AMI) in Japanese claims. In particular, we examined whether the PPV differs between claims in the Diagnosis Procedure Combination case mix scheme (DPC claims) and in non-DPC claims. METHODS: We selected a random sample of 200 patients from all patients hospitalized at a large tertiary-care university hospital between January 1, 2009 and December 31, 2011 who had an inpatient claim assigned a local or ICD-10 code for AMI. We used a standardized data abstraction form to collect the relevant information from an electronic medical records system. Abstracted information was then categorized by a single cardiologist as being either definite or not having AMI. RESULTS: In a random sample of 200 patients, the average age was 67.7 years and the proportion of males was 78.0%. The PPV of the local or ICD-10 code for AMI was 82.5% in this sample of 200 patients. Further, of 178 patients who had an ICD-10 code for AMI based on any of the 7 types of condition codes in the DPC claims, the PPV was 89.3%, whereas of the 161 patients who had an ICD-10 code for AMI based on any of 3 major types of condition codes in the DPC claims, the PPV was 93.8%. CONCLUSION: The PPV of the local or ICD-10 code for AMI was high for inpatient claims in Japan. The PPV was even higher for the ICD-10 code for AMI for those patients who received AMI care through the DPC case mix scheme. The current study was conducted in a single center, suggesting that a multi-center study involving different types of hospitals is needed in the future. The accuracy of condition codes for DPC claims in Japan may also be worth examining for conditions other than AMI such as stroke.

Estimation of right atrial pressure on inferior vena cava ultrasound in Asian patients.

BACKGROUND: Right atrial pressure (RAP) is commonly estimated using inferior vena cava (IVC) diameter and its respirophasic variations. Although a guideline has been provided for estimation of RAP due to variation in IVC dimensions based on studies in Western subjects, echocardiographic values in Asian subjects are unknown. METHODS AND RESULTS: We studied 369 patients who underwent IVC ultrasound within 24h of right heart catheterization (RHC). The maximum and minimum IVC diameter during a respiratory cycle and the percent collapse after a sniff test were measured. These IVC parameters were compared with mean RAP measured on RHC. Receiver operating characteristic curves were generated for each IVC parameter to determine the optimal cut-off to detect RAP >10mmHg. The IVC maximum diameter cut-off for detecting RAP >10mmHg was 19mm (sensitivity, 75%; specificity, 78%) and the percent collapse cut-off was 30% (sensitivity, 75%; specificity, 83%). Both cut-offs were smaller than those previously reported in patients from Western countries. When the cut-off values from the existing guideline were applied to the present cohort, the sensitivity and specificity for normal RAP (0-5mmHg) were 38.6% and 74.2%, respectively, and 60.0% and 92.0% for elevated RAP (>10mmHg). CONCLUSIONS: The optimal IVC maximum diameter and percent collapse cut-offs to detect elevated RAP were smaller in Asian subjects than in a previously reported Western cohort.

Causality Assessment Between Drugs and Fatal Cerebral Haemorrhage Using Electronic Medical Records: Comparative Evaluation of Disease-Specific and Conventional Methods.

INTRODUCTION: A new algorithm for causality assessment of drugs and fatal cerebral haemorrhage (ACAD-FCH) was published in 2021. However, its use in clinical practice has not been verified. OBJECTIVES: This study aimed to explore the practical value of the ACAD-FCH when applying information available in clinical practice. METHODS: The medical records of patients who died at the University of Tokyo Hospital in 2020 were reviewed, and cases with intracranial haemorrhage were selected. Two evaluators independently assessed these cases using three methods (the ACAD-FCH, Naranjo algorithm, and WHO-UMC scale). The number of 'Yes', 'No', and 'No information/Do not know' responses to each question by both evaluators were summed and compared. Inter-rater reliability was evaluated for each method using agreement rates and kappa coefficients with 95% confidence intervals (CI). RESULTS: Among 316 deaths, 24 cases with intracranial haemorrhage were evaluated. The proportion of ?No information/Do not know' responses for each question was 35.6% (95% CI 31.4-40.6%) for the ACAD-FCH and 66.9% (95% CI 62.5-71.1%) for the Naranjo algorithm. The respective agreement rates and kappa coefficients were 0.917 (0.798-1.00) and 0.867 (0.675-1.00) for the ACAD-FCH, 0.708 (0.512-0.904) and 0.139 (-0.236 to 0.513) for the Naranjo algorithm, and 0.50 (0.284-0.716) and 0.326 (0.110-0.541) for the WHO-UMC scale, respectively. CONCLUSION: Our findings suggest the utility of the ACAD-FCH when assessing death cases with intracranial haemorrhage. However, larger studies including intra-rater assessments are warranted for further validation of this algorithm.

Patient concern regarding bleeding side effects from oral anticoagulation therapy for atrial fibrillation: An analysis from the multicenter KiCS-AF registry.

AIMS: The purpose of this study is to utilize PROs to determine the percentage of patients concerned about mild to moderate bleeding side effects of anticoagulants. METHODS AND RESULTS: We consecutively enrolled 3,312 newly diagnosed or referred patients for atrial fibrillation (AF) management from 11 sites within the Keio interhospital Cardiovascular Studies-Atrial Fibrillation Registry between September 2012 and May 2018. Of these patients, 2,636 (79.5%) were taking oral anticoagulants at enrollment. Using the Atrial Fibrillation Effect on Quality-of-life questionnaire (AFEQT), the patients who responded "1: not at all bothered" or "2: hardly bothered" on the seven-point scale regarding bleeding side effects were classified as the "no OAC concern" group while those responding "3: a little bothered" to "7: extremely bothered" were classified as the "OAC concern" group. On baseline analysis, 29.3% (n = 772) were "concerned" about bleeding side effects. The proportion of women and patients with AF-related symptoms was higher in the OAC concern vs. no OAC concern group (36.9% vs. 29.8%, p < 0.0004 and 66.2% vs. 56.7%, p < 0.0001, respectively). The CHADS2 scores ≥ 2 were comparable between groups. Of the 430 patients in the 1-year follow-up analysis, the proportion of the continued OAC concern group (1 year from enrollment) was 41.6%.The dabigatran, rivaroxaban, and apixaban usage rates were comparable between the two groups in baseline and 1-year follow-up analysis. CONCLUSION: Approximately one-third of all patients with AF on anticoagulant therapy were concerned regarding bleeding from short-and long-term anticoagulant use.

Validation Study of Algorithms to Identify Malignant Tumors and Serious Infections in a Japanese Administrative Healthcare Database.

BACKGROUND: This retrospective observational study validated case-finding algorithms for malignant tumors and serious infections in a Japanese administrative healthcare database. METHODS: Random samples of possible cases of each disease (January 2015-January 2018) from two hospitals participating in the Medical Data Vision Co., Ltd. (MDV) database were identified using combinations of ICD-10 diagnostic codes and other procedural/billing codes. For each disease, two physicians identified true cases among the random samples of possible cases by medical record review; a third physician made the final decision in cases where the two physicians disagreed. The accuracy of case-finding algorithms was assessed using positive predictive value (PPV) and sensitivity. RESULTS: There were 2,940 possible cases of malignant tumor; 180 were randomly selected and 108 were identified as true cases after medical record review. One case-finding algorithm gave a high PPV (64.1%) without substantial loss in sensitivity (90.7%) and included ICD-10 codes for malignancy and photographing/imaging. There were 3,559 possible cases of serious infection; 200 were randomly selected and 167 were identified as true cases after medical record review. Two case-finding algorithms gave a high PPV (85.6%) with no loss in sensitivity (100%). Both case-finding algorithms included the relevant diagnostic code and immunological infection test/other related test and, of these, one also included pathological diagnosis within 1 month of hospitalization. CONCLUSIONS: The case-finding algorithms in this study showed good PPV and sensitivity for identification of cases of malignant tumors and serious infections from an administrative healthcare database in Japan.

Use of Clinical Data Interchange Standards Consortium (CDISC) Standards for Real-world Data: Expert Perspectives From a Qualitative Delphi Survey.

BACKGROUND: Real-world data (RWD) and real-world evidence (RWE) are playing increasingly important roles in clinical research and health care decision-making. To leverage RWD and generate reliable RWE, data should be well defined and structured in a way that is semantically interoperable and consistent across stakeholders. The adoption of data standards is one of the cornerstones supporting high-quality evidence for the development of clinical medicine and therapeutics. Clinical Data Interchange Standards Consortium (CDISC) data standards are mature, globally recognized, and heavily used by the pharmaceutical industry for regulatory submissions. The CDISC RWD Connect Initiative aims to better understand the barriers to implementing CDISC standards for RWD and to identify the tools and guidance needed to more easily implement them. OBJECTIVE: The aim of this study is to understand the barriers to implementing CDISC standards for RWD and to identify the tools and guidance that may be needed to implement CDISC standards more easily for this purpose. METHODS: We conducted a qualitative Delphi survey involving an expert advisory board with multiple key stakeholders, with 3 rounds of input and review. RESULTS: Overall, 66 experts participated in round 1, 56 in round 2, and 49 in round 3 of the Delphi survey. Their inputs were collected and analyzed, culminating in group statements. It was widely agreed that the standardization of RWD is highly necessary, and the primary focus should be on its ability to improve data sharing and the quality of RWE. The priorities for RWD standardization included electronic health records, such as data shared using Health Level 7 Fast Health care Interoperability Resources (FHIR), and the data stemming from observational studies. With different standardization efforts already underway in these areas, a gap analysis should be performed to identify the areas where synergies and efficiencies are possible and then collaborate with stakeholders to create or extend existing mappings between CDISC and other standards, controlled terminologies, and models to represent data originating across different sources. CONCLUSIONS: There are many ongoing data standardization efforts around human health data-related activities, each with different definitions, levels of granularity, and purpose. Among these, CDISC has been successful in standardizing clinical trial-based data for regulation worldwide. However, the complexity of the CDISC standards and the fact that they were developed for different purposes, combined with the lack of awareness and incentives to use a new standard and insufficient training and implementation support, are significant barriers to setting up the use of CDISC standards for RWD. The collection and dissemination of use cases, development of tools and support systems for the RWD community, and collaboration with other standards development organizations are potential steps forward. Using CDISC will help link clinical trial data and RWD and promote innovation in health data science.

The use of anticoagulants in patients with non-valvular atrial fibrillation between 2005 and 2014: A drug utilization study using claims data in Japan.

BACKGROUND: Anticoagulant therapy is recommended in patients with atrial fibrillation (AF) but remains underused. The proper use of anticoagulants has been encouraged in guidelines frequently published over the past two decades. MATERIALS AND METHODS: In this study, we used insurance claims data collected from 2005 to 2014 to investigate the prevalence and incidence of non-valvular AF (NVAF) patients aged 20 to 74 years standardized to the Japanese population in 2012 and subdivided by stroke prevention drug type. We estimated the frequency of coagulation monitoring in patients with incident NVAF undergoing warfarin therapy in 2011 and later. RESULTS: From 2005 to 2014, the standardized prevalence of NVAF increased from 117/100,000 to 278/100,000 and the proportion of anticoagulant users increased from 38.4% to 58.0%, while that of antiplatelet monotherapy decreased from 32.3% to 12.0%. The standardized incidence of NVAF was stable at ~40/100,000 patient-years. The proportion of those patients who started anticoagulant soon after the initial diagnosis increased from 19.9% to 49.1% from 2006 to 2013. Among patients who started warfarin, switchers to DOAC had more frequent coagulation monitoring than non-switchers. CONCLUSION: The use of anticoagulant therapy has gradually increased in patients with NVAF in Japan during the study period from 2005 to 2014.

Evaluation of electronic health records from viewpoint of patients.

OBJECTIVE: To clarify the impacts of electronic health records (EHRs) on patients, especially patient's satisfaction by using questionnaire. DESIGN: Surveys were conducted at three hospitals. One of them was surveyed three times; three-months before (pre-EHR) and three-months after (post-3mo EHR) and nine-months after implementation of EHR (post-9mo EHR). The other two hospitals (metropolitan-stable EHR and suburban-stable EHR) spent more than three years after implementation. Thus there were five stages of EHR. MEASUREMENTS: Comparisons were made among these five stages. RESULTS: The longer EHR has been operating, the more patients answered waiting time shortened. The patients in pre-EHR (73%) expected the benefit of cooperation between hospitals and clinics using EHR more. The longer experience of EHR a hospital had, the more patients were explained by watching the screen. Although overall satisfaction was high, there was no difference among the stages except metropolitan-stable EHR. CONCLUSION: Main benefits of EHR are reducing patient's waiting time, and enhancing explanation to patients. However it does not have significant effects to improve patient's satisfaction.

Elevated Serum Uric Acid Levels Are Related to Cognitive Deterioration in an Elderly Japanese Population.

AIMS: The association between serum uric acid (UA) levels and cognitive function is controversial since UA can be a risk factor for cerebral ischemia as well as acting as a neuroprotective antioxidant. METHODS: We conducted a cross-sectional analysis of 228 elderly participants and examined neuropsychological test results, clinical data as well as brain magnetic resonance imaging data. PATIENTS: Overall, 64 participants were diagnosed with cognitive deterioration. To control for the effect of sex differences, 2 independent sets of single-variable and multivariate logistic regression analyses were performed with quartiles divided into non-sex-specific and sex-specific cutoff values for UA. RESULTS: In non-sex-specific quartiles, the participants in the highest quartiles of UA levels were found to be at a significantly higher risk of cognitive deterioration than those in the lowest quartiles. In sex-specific quartiles, the highest quartile showed an increased risk of cognitive deterioration, and a greater than fourfold increase in the risk in the highest quartiles was confirmed using multivariate regression models. However, no significant association was observed between serum UA levels and the presence of white matter lesions. CONCLUSIONS: Elevated serum UA levels were independently associated with cognitive deterioration. UA might have unknown adverse effects on cognitive function, other than causing vascular pathology.

Epidemiology of psoriasis and palmoplantar pustulosis: a nationwide study using the Japanese national claims database.

OBJECTIVE: The primary objective was to estimate the national prevalence of psoriasis and palmoplantar pustulosis (PPP) in Japan. Secondary objectives were to determine (1) whether psoriasis and PPP disease activity varies by season, and (2) whether disease severity is associated with concurrent diabetes mellitus, hyperlipidaemia and hypertension. SETTINGS: Patients with a psoriasis or PPP diagnosis code between April 2010 and March 2011 were identified using a Japanese national database. PARTICIPANTS: 565 903 patients with psoriasis or PPP were identified. No patient was excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: National prevalence was calculated using census data. We estimated the difference in the proportion of patients who used healthcare services, as a proxy for disease activity, between the hot and cold seasons and the difference in the standardised prevalence of comorbidities between severe and mild disease. The measures were estimated separately for the two broad disease categories of psoriasis and PPP but not in all patients as planned because the two disease categories had major differences. RESULTS: The national prevalence of psoriasis and PPP was 0.34% (95% CI 0.34% to 0.34%) and 0.12% (0.12% to 0.12%), respectively. The difference in the proportion of patients who used healthcare services in the hot compared to the cold season was -0.3% (-0.5% to -0.1%) for psoriasis and 10.0% (9.8% to 10.3%) for PPP. The difference in the standardised prevalence between severe and mild psoriasis was 3.1% (2.7% to 3.4%), 3.2% (2.8% to 3.6%) and 5.1% (4.7% to 5.6%) for concurrent diabetes mellitus, hyperlipidaemia and hypertension, respectively. No significant difference in the prevalence of comorbidity was observed for PPP. CONCLUSIONS: The national prevalence, seasonal variation in disease activity and prevalence of comorbidities in Japanese patients with psoriasis and PPP estimated in this descriptive study may be used as basic information for future studies.

Influence of municipality-level mean income on access to aortic valve surgery: a cross-sectional observational study under Japan's universal health-care coverage.

BACKGROUND: Universal health-care coverage has attracted the interest of policy makers as a way of achieving health equity. However, previous reports have shown that despite universal coverage, socioeconomic disparity persists in access to high-tech invasive care, such as cardiac treatment. In this study, we aimed to investigate the association between socioeconomic status and care of aortic stenosis in the context of Japan's health-care system, which is mainly publicly funded. METHODS: We chose aortic stenosis in older people as a target because such patients are likely to be affected by socioeconomic disparity. Using a large Japanese claim-based inpatient database, we identified 12,893 isolated aortic stenosis patients aged over 65 years who were hospitalized between July 2010 and March 2012. Municipality socioeconomic status was represented by the mean household income of the patients' residential municipality, categorized into quartiles. The likelihood of undergoing aortic valve surgery and in-hospital mortality was regressed against socioeconomic status level with adjustments for hospital volume, regional number of cardiac surgeons per 1 million population, and patients' clinical status. RESULTS: We found no significant differences between the highest and lowest quartile groups in surgical indication (odds ratio, 0.84; 95% confidence interval, 0.69-1.03) or in-hospital mortality (1.00; 0.68-1.48). Hospital volume was significantly associated with lower postoperative mortality (odds ratio of the highest volume tertile to the lowest, 0.49; 0.34-0.71). CONCLUSIONS: Under Japan's current universal health-care coverage, municipality socioeconomic status did not appear to have a systematic relationship with either treatment decision for surgical intervention or postoperative survival following aortic valve surgery among older patients. Our results imply that universal health-care coverage with high publicly funded coverage offers equal access to high-tech cardiovascular care.

Comparison of data mining methodologies using Japanese spontaneous reports.

PURPOSE: Five data mining methodologies for detecting a possible signal from spontaneous reports on adverse drug reactions (ADRs) were compared. METHODS: The five methodologies, the Bayesian method using the Gamma Poissson Shrinker (GPS), the method employed in the UK Medicines Control Agency (MCA), the Bayesian Confidence Propagation Neural Network (BCPNN), the method using the 95% confidence interval (CI) for the reporting odds ratio (RORCI) and that using the 95% CI of the proportional reporting ratio (PRRCI) were compared using Japanese data obtained between 1998 and 2000. RESULTS: There were all in all 38,731 drug-ADR combinations. The count of drug-ADR pairs was equal to 1 or 2 for 31,230 combinations and none of them were identified as a possible signal with the MCA or BCPNN. Similarly, the GPS detected a possible signal in none of the combinations where the count was equal to 1 but in 7.5% of the combinations where the count was equal to 2. The RORCI and PRRCI detected a possible signal in more than half of the combinations where the count was equal to 1 or 2. When the pairwise agreement on whether or not a drug-ADR combination satisfied the criteria for a possible signal was assessed for the 38,731 combinations, the concordance measure kappa was greater than 0.9 between the MCA and BCPNN and between the RORCI and PRRCI. Kappa was around 0.6 between the GPS and MCA and between the GPS and BCPNN. Otherwise, kappa was smaller than 0.2. CONCLUSIONS: The drug-ADR combinations detected as a possible signal vary between different methodologies.

Calcium channel blockers and myocardial infarction: a case--control study in a Japanese hospital.

PURPOSE: To examine the relationship of the use of calcium channel blockers (CCBs) in hypertensive patients to myocardial infarction in Japan, where CCBs are prescribed much more frequently than in Europe and America. DESIGN: We conducted a nested case-control study using a hospital information system in Japan. SUBJECTS: Cases were hypertensive patients who were repeat visitors to Tokyo University Hospital as of April 1996 and had an incidence of fatal or non-fatal myocardial infarction between 1996 and 1999. Controls were hypertensive patients individually matched to cases by sex, age and history of angina pectoris. RESULTS: The study consisted of 16 cases, who were matched to 80 controls. Of the 80 control patients, 54 (68%) received CCBs. On the other hand, all but one of 16 cases received CCBs and the crude odds ratio of myocardial infarction associated with the use of calcium channel blockers was as high as 7.0 (0.9-55.3). The odds ratio was reduced to 4.9 (0.6-42.4) when adjusted by diabetes and diastolic blood pressure. CONCLUSIONS: Although the crude odds ratio of myocardial infarction associated with CCBs was high, the ratio was reduced when adjusted by known confounding factors, suggesting a mechanism of confounding by indication. In addition, the results obtained in this study using records from a single hospital should not be generalized.