Evaluation of Clinical Practice Guidelines for Rare Diseases in Japan.

Introduction: The insufficient quantity and quality of clinical epidemiological evidence in the field of rare diseases have posed methodological challenges to develop clinical practice guidelines (CPGs). Guideline development groups struggle to provide patients and their families with beneficial guidance, such as that for medical care and in complex circumstances. Motivated by the challenges, we focused on information on resources for supporting the daily and social life to improve the CPGs for users. We aimed to assess the methodological quality of CPGs for rare diseases in Japan and to evaluate information on resources to support the daily and social life in the CPGs. Methods: We conducted a systematic search using PubMed, three electronic Japanese databases, and two hand-searched sources in Japan. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument with six domains was used to assess the methodological quality of the CPGs. A content analysis of the CPG text was conducted using five keywords as information on non-medical resources, e.g., "Intractable Disease Consultation Support Center," "Japan Intractable Disease Information Center," and "Patient Association." Results: A total of 55 CPGs met the inclusion criteria. Among four domains of AGREE II with low scores (Stakeholder Involvement, Rigor of Development, Applicability, and Editorial Independence), Rigor of Development had the lowest median score. As for information on non-medical resources, 41 CPGs included at least 1 of the 5 keywords, while 14 CPGs included none. Conclusions: At the Rigor of Development domain, methodological challenges may have resulted in an insufficient description of items regarding the translation evidence to recommendations. As the sufficiency of five keywords as information on non-medical resources could be improved, the information will be advocative as clues to provide pragmatic guidance, particularly for rare diseases with limited medical evidence.

Prevalence of type 2 diabetes by age, sex and geographical area among two million public assistance recipients in Japan: a cross-sectional study using a nationally representative claims database.

BACKGROUND: Recognising the importance of the social determinants of health, the Japanese government introduced a health management support programme targeted at type 2 diabetes (T2D) for public assistance recipients (PAR) in 2018. However, evidence of the T2D prevalence among PAR is lacking. We aimed to estimate T2D prevalence by age and sex among PAR, compared with the prevalence among health insurance enrollees (HIE). Additionally, regional differences in T2D prevalence among PAR were examined. METHODS: This was a cross-sectional study using 1-month health insurance claims of both PAR and HIE. The Fact-finding Survey data on Medical Assistance and the National Database of Health Insurance Claims data were used. T2D prevalence among PAR and HIE were assessed by age and sex, respectively. Moreover, to examine regional differences in T2D prevalence of inpatients and outpatients among PAR, T2D crude prevalence and age-standardised prevalence were calculated by prefecture. Multilevel logistic regression analysis was also conducted at the city level. RESULTS: T2D crude prevalence was 7.7% in PAR (inpatients and outpatients). Among outpatients, the prevalence was 7.5% in PAR and 4.1% in HIE, respectively. The mean crude prevalence and age-standardised prevalence of T2D (inpatients and outpatients) among 47 prefectures were 7.8% and 3.9%, respectively. In the city-level analysis, the OR for the prevalence of T2D by region ranged from 0.31 to 1.51. CONCLUSION: The prevalence of T2D among PAR was higher than HIE and there were regional differences in the prevalence of PAR. Measures to prevent the progression of diabetes among PAR by region are needed.

Evaluation of rapid drug safety communication materials for patients in Japan.

Since 2011, pharmaceutical companies in Japan have been required to issue two types of documents regarding severe adverse drug reactions reported post-marketing, namely the Rapid Safety Communication Materials for Patients and the Related Materials. However, the adequacy of these documents has not yet been systematically assessed. The aim of this study was to evaluate the adequacy of these two types of materials. The Rapid Safety Communications for Patients were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website. The Related Materials were obtained from pharmaceutical companies or the PMDA website. Three assessors independently scored the Rapid Safety Communication for Patients and the Related Materials using the Centers for Disease Control and Prevention Clear Communication Index (CCI). In addition, the contents and descriptions of the materials were analyzed. In total, 13 materials for seven drugs were assessed. Almost all materials contained the "main message" and "call to action". However, the average CCI scores for the Rapid Safety Communication for Patients and Related Materials for Patients were 68.8 and 74.3 (out of 100), respectively. Further, none of the evaluated materials were scored above the CCI threshold score (i.e., ≥ 90%). Descriptions regarding "language", "state of science", and "risk" were not adequate. In particular, the terminology used in materials seemed difficult for patients to understand. In conclusion, the Japanese Rapid Communication Materials for Patients require improvement. Furthermore, a system for evaluating these materials prior to publication should be established.

Publisher Correction: Inadequate Folic Acid Intake Among Women Taking Antiepileptic Drugs During Pregnancy in Japan: A Cross-Sectional Study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Inadequate Folic Acid Intake Among Women Taking Antiepileptic Drugs During Pregnancy in Japan: A Cross-Sectional Study.

This study aimed to assess characteristics of pregnant women taking antiepileptic drugs with inadequate folic acid intake. This cross-sectional study examined pregnant women taking antiepileptic drugs who were registered in the Japanese Drug Information Institute in Pregnancy (JDIIP) database between October 2005 and December 2016. Participants were classified into two groups according to when they started folic acid supplementation (before pregnancy: 'adequate', after pregnancy or never: 'inadequate'). Logistic regression analysis was performed to investigate factors associated with inadequate folic acid intake. Of 12,794 registrants, 468 pregnant women were taking antiepileptics during the first trimester. Of these, we analysed data from 456 women who had no missing data. As a result, inadequate folic acid intake was noted among 83.3% of them, suggesting that the current level of folic acid intake is insufficient overall. Younger age, smoking, alcohol drinking, multiparity, unplanned pregnancy, and being prescribed AEDs by paediatric or psychiatric departments were independent factors associated with inadequate folic acid intake. As planned pregnancy was the strongest factor, healthcare professionals should ensure that childbearing women taking antiepileptics are informed of the importance of planned pregnancy. In addition, healthcare professionals must gain a better understanding of folic acid intake, as the prevalence of adequate intake differed according to which departments prescribed antiepileptic drugs.

Diagnostic accuracy of FDG-PET cancer screening in asymptomatic individuals: use of record linkage from the Osaka Cancer Registry.

BACKGROUND: Whole-body cancer screening with multimodalities including [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) detects a wide range of tumors. This program has been recognized as an option for opportunistic screening, particularly in Japan. However, reports on diagnostic accuracy have been limited. We aimed to evaluate the detectability and related properties of this screening program among asymptomatic individuals in a community setting. METHODS: The study participants were 1,762 residents of Osaka Prefecture, Japan, who underwent opportunistic cancer screening at Higashitemma Clinic for the first time between November 2004 and December 2005. FDG-PET cancer screening was performed with several imaging modalities (e.g., FDG-PET, computed tomography, magnetic resonance imaging and ultrasonography) and fecal occult blood test. Screening records were linked to the Osaka cancer registry within 1 year after the screening to determine sensitivity, specificity and positive predictive values. RESULTS: After excluding 12 participants with cancer detected before the screening, 33 were identified by the cancer registry to have primary cancers. Of these, the present screening program found that 28 were positive (6 prostate, 5 lung, 5 colorectal, 5 thyroid, 3 liver and 4 others). Sensitivity, specificity and positive predictive values were 84.8 % (28/33, 95 % confidence interval 69.1-93.3), 86.8 % (1,491/1,718, 85.1-88.3) and 10.1 % (28/277, 6.4-12.9), respectively. CONCLUSIONS: FDG-PET cancer screening with multimodalities reasonably and accurately detects existing asymptomatic cancer. However, the numbers of false negatives and false positives were not insignificant. Facilities that provide the screening should inform participants of relevant information, including the limitations of this program.

Usefulness of fully automated constant ROI analysis software for the brain: 3DSRT and FineSRT.

The positioning or selection of a region of interest (ROI) is an essential step for the quantification of brain images. However, so long as the ROIs were manually selected, results obtained fluctuated considerably with subtle changes in their positioning. To perform an ROI analysis of the brain with improved objectivity and excellent reproducibility, we recently established fully automated ROI-based analysis software for the brain, the so-called 3DSRT and the FineSRT. 3DSRT performed by consecutive analyzing process as follows: (1) anatomical standardization using the SPM99 algorithm; (2) analysis using constant 318 ROIs divided into 12 groups (segments) on each hemisphere; (3) calculation of the area-weighted average for each of the respective 24 segments; (4) display of the results followed by the saving of respective values of the 636 ROIs (both hemispheres). The processes of the FineSRT were fundamentally similar to that of 3DSRT, but on FineSRT more precise constant 1394 ROIs (both hemispheres) corresponding to the respective cerebral convolutions were used. Our programs have been useful for objective estimation of cerebrovascular reserve, especially for follow-up studies of an infant with moyamoya disease, because we could compare the results without consideration of the patient's growth during the follow-up period.