Seasonal exacerbation of rheumatoid arthritis detected by big claims data analysis: A retrospective population study.

OBJECTIVES: The objective of the study was to determine the seasonal changes in the initiation of biological disease-modifying antirheumatic drugs (bDMARDs) and methotrexate (MTX) using big claims data. METHODS: We counted the monthly number of initial administrations of each bDMARD and MTX in patients with rheumatoid arthritis (RA) between April 2010 and March 2017. Data were collected from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. This database covers more than 95% of Japanese citizens. Seasonal changes in the number of initiations were determined. Patient claims were also classified according to drugs, districts, gender, and ages. RESULTS: The initiation of bDMARDs and MTX administration varied according to the season in a sine curve shape, with the highest numbers in May to July and the lowest numbers in November to January. The same changing pattern was observed among each bDMARD, district, gender, and age groups particularly when the number was on the higher side. CONCLUSION: We noted an apparent seasonal change in the number of bDMARDs initiated, with a peak during spring, suggesting an exacerbation of RA in the spring in Japan. These changes are overlooked in daily practice and are only visible using big data.

Incidence of opportunistic infections in patients with rheumatoid arthritis treated with different molecular-targeted drugs: A population-based retrospective cohort study.

OBJECTIVES: We compared the incidences of four opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with molecular-targeted drugs from big claims data. MATERIALS AND METHODS: We identified 205,906 patients with RA who were prescribed molecular-targeted drugs in 2010-17 from the National Database of Japan and calculated the incidence of four OIs (Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster). RESULTS: The total number of Pneumocystis pneumonia, tuberculosis, nontuberculous mycobacterial infection, and herpes zoster patients with biological disease-modifying antirheumatic drugs or tofacitinib treatment history in RA was 765, 1158, 834, and 18,336, respectively. The incidence rates of each OI for all biological disease-modifying antirheumatic drugs were 0.14, 0.14, 0.09, and 2.40 per 100 person-years, respectively, while for tofacitinib they were 0.22, 0.22, 0.07, and 7.00 per 100 person-years. No big difference was observed among biological disease-modifying antirheumatic drugs. All OIs showed higher incidence in those >65 years, but Pneumocystis pneumonia, nontuberculous mycobacterial infection, and herpes zoster showed no difference between those 65-74 years old and those >75 years old. The median of occurrence was the third, seventh, ninth, and thirteenth month after treatment, respectively. CONCLUSIONS: We counted real incidence rates of OIs for the whole nation from big claims data.

Trend in prescription and treatment retention of molecular-targeted drugs in 121,131 Japanese patients with rheumatoid arthritis: A population-based real-world study.

OBJECTIVES: To describe the real-world prescription and treatment retention of molecular-targeted drugs for rheumatoid arthritis (RA) in Japan. METHODS: A total of 204,416 patients with RA were prescribed at least one of the eight molecular-targeted drugs in 7 years from the National Database of Health Insurance Claims and Specific Health Checkups of Japan covering 98.3% of the Japanese population. The retention rates of each drug as well as head-to-head comparisons were estimated by Kaplan-Meier method. RESULTS: A total of 121,131 RA patients were prescribed any molecular-targeted drug for the first time, while 36,633 uses of molecular-targeted drug were switched from another (switch use). The overall retention rates of molecular-targeted drugs at 12, 36, and 60 months were 0.64, 0.42, and 0.32 for the naïve use and 0.59, 0.40, and 0.31 for the switch use, respectively. Non-tumour necrosis factor (TNF)-inhibitor molecular-targeted drugs, particularly tocilizumab and tofacitinib, had higher retention rates than TNF inhibitors for both naïve and switch uses regardless of the previous drug and showed higher retention rates in head-to-head comparisons between eight molecular-targeted drugs. CONCLUSIONS: Our data reveal that the real-world drug retention is overall lower than previously reported and higher with non-TNF inhibitors than with TNF inhibitors.

Comparing the effectiveness of biological disease-modifying antirheumatic drugs using real-world data.

OBJECTIVES: The objective of this study is to compare the effectiveness of biological disease-modifying antirheumatic drugs (bDMARDs) by analyzing claims data of 13 Japanese national university hospitals. METHODS: We evaluated 4970 cases of rheumatoid arthritis treated with bDMARDs from the Clinical Information Statistical Analysis database, which has collected and integrated 13 Japanese national university hospitals' claims data for 10 years. We surveyed the medications and calculated the retention rates of bDMARDs using the Kaplan-Meier method and differentiated the effectiveness between the two bDMARDs by comparing the retention rates after switching from one drug to another. RESULTS: Of the 4970 cases, 1364 switched bDMARDs at least once. Tocilizumab (TCZ) reported the highest retention rate, whereas abatacept (ABT) revealed a similar rate compared with only naïve cases. The retention rate curves were higher in cases on TCZ that switched from the other bDMARDs than those in the reversed cases. Following TCZ, ABT and etanercept indicated better results than the other bDMARDs. CONCLUSION: We could compare the effectiveness among bDMARDs by differentiating the retention rates from big claims data. TCZ reported higher retention rates in both naïve and switched cases than other bDMARDs.

Estimation and Evaluation of Future Demand and Supply of Healthcare Services Based on a Patient Access Area Model.

Accessibility to healthcare service providers, the quantity, and the quality of them are important for national health. In this study, we focused on geographic accessibility to estimate and evaluate future demand and supply of healthcare services. We constructed a simulation model called the patient access area model (PAAM), which simulates patients' access time to healthcare service institutions using a geographic information system (GIS). Using this model, to evaluate the balance of future healthcare services demand and supply in small areas, we estimated the number of inpatients every five years in each area and compared it with the number of hospital beds within a one-hour drive from each area. In an experiment with the Tokyo metropolitan area as a target area, when we assumed hospital bed availability to be 80%, it was predicted that over 78,000 inpatients would not receive inpatient care in 2030. However, this number would decrease if we lowered the rate of inpatient care by 10% and the average length of the hospital stay. Using this model, recommendations can be made regarding what action should be undertaken and by when to prevent a dramatic increase in healthcare demand. This method can help plan the geographical resource allocation in healthcare services for healthcare policy.

Quality Requirements for Electronic Health Record Systems*. A Japanese-German Information Management Perspective.

BACKGROUND: For more than 30 years, there has been close cooperation between Japanese and German scientists with regard to information systems in health care. Collaboration has been formalized by an agreement between the respective scientific associations. Following this agreement, two joint workshops took place to explore the similarities and differences of electronic health record systems (EHRS) against the background of the two national healthcare systems that share many commonalities. OBJECTIVES: To establish a framework and requirements for the quality of EHRS that may also serve as a basis for comparing different EHRS. METHODS: Donabedian's three dimensions of quality of medical care were adapted to the outcome, process, and structural quality of EHRS and their management. These quality dimensions were proposed before the first workshop of EHRS experts and enriched during the discussions. RESULTS: The Quality Requirements Framework of EHRS (QRF-EHRS) was defined and complemented by requirements for high quality EHRS. The framework integrates three quality dimensions (outcome, process, and structural quality), three layers of information systems (processes and data, applications, and physical tools) and three dimensions of information management (strategic, tactical, and operational information management). CONCLUSIONS: Describing and comparing the quality of EHRS is in fact a multidimensional problem as given by the QRF-EHRS framework. This framework will be utilized to compare Japanese and German EHRS, notably those that were presented at the second workshop.

Overview of recent trans-institutional health network projects in Japan and Germany.

Worldwide populations are aging and countries have to prepare for the effects of demographic change in health care. Health information exchange (HIE), which is the process of moving patient information across health care providers electronically, can help overcome health data fragmentation and open opportunities to improve patient care in terms of quality, economy and efficiency. Since Japan and Germany are among the first countries strongly impacted by demographic changes of aging populations, we report on current developments about health information systems carrying out HIE based on case studies in both countries. Four projects that address the improvement of HIE within a defined region have been selected and investigated: the German project of the Lower Saxony Bank of Health and the Japanese projects Chiba ITnet, Nagasaki AjisaiNet and the National Disaster and Backup System of Japan. The project descriptions are based on relevant English publications, on-site visits and interviews with developers and users. The projects are introduced in terms of their basic architecture and implementation, their present status and future objectives. The projects' developments are still in progress and all have to cope with significant challenges before they will be able to provide a fully working trans-institutional health network solution.

Using geographic information systems to simulate patient access areas.

We constructed a simulation model with a geographic information system (GIS) to predict the future shortage of beds in the Tokyo Metropolitan Area. With a grid square method, we calculated patient numbers for every 500 square meters of the Tokyo Metropolitan Area until 2040 and estimated whether those in need could be admitted to hospitals within an hour's drive from their homes. The simulation demonstrates that after 2025 many patients may not be able to find hospitals within this time framework. The situation will be especially serious in the center of Tokyo and along the railway lines, where many senior citizens reside. We can now apply this innovative GIS method in many fields and especially for the precise estimation of future demands for and supply of medical assistance.

Assessing the prognoses on Health care in the information society 2013--thirteen years after.

Health care and information technology in health care is advancing at tremendous speed. We analysed whether the prognoses by Haux et al. - first presented in 2000 and published in 2002 - have been fulfilled in 2013 and which might be the reasons for match or mismatch. Twenty international experts in biomedical and health informatics met in May 2013 in a workshop to discuss match or mismatch of each of the 71 prognoses. After this meeting a web-based survey among workshop participants took place. Thirty-three prognoses were assessed matching; they reflect e.g. that there is good progress in storing patient data electronically in health care institutions. Twenty-three prognoses were assessed mismatching; they reflect e.g. that telemedicine and home monitoring as well as electronic exchange of patient data between institutions is not established as widespread as expected. Fifteen prognoses were assessed neither matching nor mismatching. ICT tools have considerably influenced health care in the last decade, but in many cases not as far as it was expected by Haux et al. in 2002. In most cases this is not a matter of the availability of technical solutions but of organizational and ethical issues. We need innovative and modern information system architectures which support multiple use of data for patient care as well as for research and reporting and which are able to integrate data from home monitoring into a patient centered health record. Since innovative technology is available the efficient and wide-spread use in health care has to be enabled by systematic information management.

Past and next 10 years of medical informatics.

More than 10 years ago Haux et al. tried to answer the question how health care provision will look like in the year 2013. A follow-up workshop was held in Braunschweig, Germany, for 2 days in May, 2013, with 20 invited international experts in biomedical and health informatics. Among other things it had the objectives to discuss the suggested goals and measures of 2002 and how priorities on MI research in this context should be set from the viewpoint of today. The goals from 2002 are now as up-to-date as they were then. The experts stated that the three goals: "patient-centred recording and use of medical data for cooperative care"; "process-integrated decision support through current medical knowledge" and "comprehensive use of patient data for research and health care reporting" have not been reached yet and are still relevant. A new goal for ICT in health care should be the support of patient centred personalized (individual) medicine. MI as an academic discipline carries out research concerning tools that support health care professionals in their work. This research should be carried out without the pressure that it should lead to systems that are immediately and directly accepted in practice.

Efficacy of anti-ribosomal P protein antibody testing for diagnosis of systemic lupus erythematosus.

OBJECTIVE: Anti-ribosomal P protein antibody (anti-P) is detected in a fraction of systemic lupus erythematosus (SLE) patients, especially with lupus psychosis, lupus nephritis, and lupus hepatitis. However, it has been unclear whether anti-P testing is specific for SLE. The current studies were designed to examine the efficacy of serum anti-P testing in diagnosis of SLE. METHOD: Multicenter retrospective study was performed with 102 SLE patients, 102 patients with non-SLE rheumatic diseases, and 100 normal healthy subjects, who gave informed consents. The diagnosis of SLE was confirmed according to the 1982 ACR revised criteria. Serum IgG anti-P was determined by ELISA using the C-terminal 22 amino-acids of ribosomal P protein conjugated to human serum albumin. The specificity and sensitivity of anti-P were compared with those of anti-DNA, anti-Sm, and anti-cardiolipin (CL) antibodies. RESULTS: Serum anti-P was positive in 38 of 102 SLE patients (37.3%), in 4 of 102 patients with non-SLE rheumatic diseases (3.9%), and in none of 100 normal subjects. Receiver operating characteristic (ROC) curve analysis revealed that anti-P provided higher AUC (area under the curve) than anti-Sm or anti-CL. Consistently, the sensitivity of anti-P (37.3%) was superior to that of anti-Sm (27.5%) and anti-CL (24.5%), but inferior to that of anti-DNA (51.0%), whereas the specificity of anti-P (96.1%) was superior to that of anti-CL (86.3%) and comparable to that of anti-DNA (96.1%) and anti-Sm (96.1%). CONCLUSION: These results indicate that serum anti-P testing might be an effective measure in diagnosing SLE, providing better diagnostic efficiency than anti-Sm and anti-CL.

Efficacy of abatacept for arthritis in patients with an overlap syndrome between rheumatoid arthritis and systemic lupus erythematosus.

INTRODUCTION: This study aimed to investigate the efficacy of abatacept for arthritis in patients with rhupus, an overlap syndrome between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Patients who fulfilled both the 2010 ACR/EULAR criteria for RA classification and the 1997 ACR revised criteria for classification of SLE and received abatacept treatment for arthritis were retrospectively studied. RESULTS: Six rhupus patients who fulfilled the inclusion criteria above were identified. All patients had active arthritis despite receiving antirheumatic drugs including methotrexate when abatacept was initiated. Clinical Disease Activity Index (CDAI) significantly decreased between baseline and 12 weeks (P = 0.028) and remained low through 24 weeks. All patients achieved either a good or moderate response according to the EULAR response criteria at 24 weeks. Health Assessment Questionnaire-Disability Index (HAQ-DI) also significantly decreased between baseline and 24 weeks (P = 0.043). In addition, the levels of immunoglobulin G and anti-DNA antibody significantly decreased between baseline and 24 weeks (P = 0.028 and P = 0.043, resp.). CONCLUSIONS: Treatment with abatacept is likely to be efficacious in patients with rhupus whose arthritis is refractory to methotrexate. In addition, abatacept may have a moderate effect on abnormal antibody production in rhupus patients.

Ultrasound can improve the accuracy of the 2010 American College of Rheumatology/European League against rheumatism classification criteria for rheumatoid arthritis to predict the requirement for methotrexate treatment.

OBJECTIVE: The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) refer to a possible use of ultrasound "for confirmation of the clinical findings." We undertook this study to determine the optimized definition of ultrasound-detected synovitis for the 2010 ACR/EULAR criteria and to assess the impact of its use on the accuracy of RA classification. METHODS: One hundred nine patients with musculoskeletal symptoms for ≤3 years were enrolled in the study. Patients underwent clinical, laboratory, radiographic, and comprehensive ultrasonographic assessments at baseline and received routine management from expert rheumatologists who were blinded to the ultrasound findings. RESULTS: Sensitivity and specificity of the 2010 ACR/EULAR criteria using different definitions of synovitis to identify patients who developed a disease requiring methotrexate (MTX) treatment within 1 year were 58.5% and 79.4%, respectively, for clinical synovitis (tenderness or swelling), 78.0% and 79.4%, respectively, for ultrasound-detected synovitis with a gray-scale (GS) imaging score≥1 (GS≥1 ultrasound synovitis), and 56.1% and 93.7%, respectively, for GS≥2 ultrasound synovitis or a synovial power Doppler (PD) signal score≥1 (GS≥2/PD≥1 ultrasound synovitis). Receiver operating characteristic curve analysis for the criteria scores revealed the largest area under the curve with GS≥2/PD≥1 ultrasound synovitis. CONCLUSION: Ultrasound assessment improves the accuracy of the 2010 ACR/EULAR criteria for identifying patients with a disease requiring MTX treatment. Our data provide preliminary but vital information for the methodology to confirm the presence of synovitis using ultrasound in the 2010 ACR/EULAR criteria.

[A new attempt to promote home medical care in Kashiwa city-usefulness of information and communication technology with seamless multidisciplinary cooperation].

Due to the rapidly increasing super-aging society, medical policy in Japan should be redefined. Therefore, the medical and nursing home care system should now be revised greatly. We need to change the current principle that is based on cure only. The patients should receive hospitable care closely connected with their life in their home-town(region)throughout their lifetime. This is termed as "home medical care system". Here, we promote patient-centered medical home care, which implements the chronic and/or End-Of-Life care models, in Kashiwa city, Chiba prefecture. This system is a promising framework for primary care transformation. There is a need for a multidisciplinary team-based care system using information and communication technology(ICT)with smooth and seamless cooperation. However, increased awareness among the workers engaged in home medical care is first required.

[Home medical care center project for an aging society].

We have to create a new paradigm for home medical care system towards a historical increase of elderly population in Japan. Tokyo University and Chiba University have been collaborating to erect a home medical care support center in Kashiwa, Chiba prefecture. We have been constructing a support center as well as a home care doctor system, and also created a teaching course for GPs to learn a home care doctor activity. We have also been constructing a regional network system called IT Net in Chiba, which connects all the entire medical and care staff. We will expand this model in many places and to instruct medical students and residents there in the near future.

Japanese EMRs and IT in Medicine: Expansion, Integration, and Reuse of Data.

OBJECTIVES: The prevalence of electronic medical record in Japan varies according to the size of the hospital which is 62.5% in major hospitals, 21.7% in medium, 9.1% in small size hospitals, and 16.5% in clinics. The complete paperless system is very limited, though some major hospitals are aiming at this system. Several regional network systems which connect different platforms of EMRs, have been developing in many districts, while the final picture of a regional network has not been clearly proposed. To develop a whole electronic health record or personal health records system from the regional network data, we have several obstacles to overcome such as standardization, a privacy act, unique national health number. METHODS: Some experimental trials have just been started. The reuse of the accumulated data has also just been initiated. We exploited text mining systems (term frequency-inverse document frequency method) to find similar cases and auto-audit Japanese diagnosis related group (DRG) coding by using discharge summaries. RESULTS: The same or even a more extreme phenomenon of huge data accumulation is occurring in genetic research and confluence of multi-disciplines of informatics is the next step, which has an enormous accumulation of data and discoveries of the relations beyond the dimension of each informatics. CONCLUSIONS: We need another approach to science apart from the conventional method, and data-driven approach with data mining techniques must be brought in for each field. Informaticians have new important roles as coordinators to link up numerous phenomena over dimensions.

Auto-selection of DRG codes from discharge summaries by text mining in several hospitals: analysis of difference of discharge summaries.

Recently, electronic medical record (EMR) systems have become popular in Japan, and number of discharge summaries is stored electronically, though they have not been reutilized yet. We performed text mining with Tf-idf method and morphological analysis in the discharge summaries from three Hospitals (Chiba University Hospital, St. Luke's International Hospital and Saga University Hospital). We showed differences in the styles of summaries, between hospitals, while the rate of properly classified DPC (Diagnosis Procedure Combination) codes were almost the same. Beyond different styles of the discharge summaries, text mining method could obtain proper extracts of proper DPC codes. Improvement was observed by using integrated model data between the hospitals. It seemed that huge database which contains the data of many hospitals can improve the precision of text mining.

[Recent investigations on the basis of pathogenesis of SLE and new therapeutic approaches].

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune, connective-tissue disorder with a broad range of clinical presentations. SLE predominantly affects women, especially from ethnic groups with African and Asian ancestry. This disorder is a chronic illness that can be life threatening when major organs are affected, but more commonly results in debilitating condition and affects employment and fertility. This article summarizes the recent advances in our understanding of the genetics, epidemiology and pathogenesis of SLE. In addition, progress in the assessment and management of serious complications such as lupus nephritis and CNS lupus is reviewed. New therapeutic approaches, such as low-dose cyclophosphamide regimens, mycophenolate mofetil and biological agents are also discussed.