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.

Associations of multimorbidity with breast, cervical, and colorectal cancer screening delivery: a cross-sectional study of a nationally representative Japanese sample.

BACKGROUND: Multimorbidity is associated with a high mortality rate and low health-related quality of life. Previous studies have indicated that multimorbidity tends to be associated with not receiving cancer screening, although this association remains unclear. This study aimed to investigate the associations between multimorbidity and the delivery of breast, cervical, and colorectal cancer screening in Japan, and to identify subgroups that did not receive cancer screening. METHODS: This study used cross-sectional data from the 2016 Comprehensive Survey of Living Conditions, which used a stratified random sample of the general Japanese population. Multivariable logistic regression models were used to evaluate the associations between the number of chronic conditions and each cancer's screening proportion. The relevant covariates included age, marital status, education level, occupation, and household income. RESULTS: Relative to subjects with no chronic conditions, subjects with two chronic conditions received more screening for breast, cervical, and colorectal cancers (breast cancer, adjusted odds ratio [aOR]: 5.42, 95% confidence interval [CI]: 2.80-10.5; cervical cancer, aOR: 4.59, 95% CI: 2.03-10.4; male colorectal cancer, aOR: 3.26, 95% CI: 1.29-8.24; female colorectal cancer, aOR: 1.05, 95% CI: 0.39-2.81). Low socioeconomic status was associated with not receiving any type of cancer screening consistently. CONCLUSION: Multimorbidity and high socioeconomic status were associated with higher proportions of screening for breast, cervical, and colorectal cancers in the Japanese population. More aggressive strategies may be needed to promote screening among Japanese individuals with no chronic conditions and individuals with low socioeconomic status.

Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells.

OBJECTIVE: Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), likely prevent cardiovascular disease, however their mechanisms remain unclear. Recently, the role of DNA damage in atherogenesis has been receiving considerable attention. Here, we investigated the effects of EPA and DHA on DNA damage in vascular endothelial cells to clarify their antiatherogenic mechanisms. METHODS AND RESULTS: We determined the effect of EPA and DHA on H2O2-induced DNA damage response in human aortic endothelial cells. Immunofluorescence staining showed that γ-H2AX foci formation, a prominent marker of DNA damage, was significantly reduced in the cells treated with EPA and DHA (by 47% and 48%, respectively). H2O2-induced activation of ATM, a major kinase orchestrating DNA damage response, was significantly reduced with EPA and DHA treatment (by 31% and 33%, respectively). These results indicated EPA and DHA attenuated DNA damage independently of the DNA damage response. Thus the effects of EPA and DHA on a source of DNA damage were examined. EPA and DHA significantly reduced intracellular reactive oxygen species under both basal condition and H2O2 stimulation. In addition, the mRNA levels of antioxidant molecules, such as heme oxygenase-1, thioredoxin reductase 1, ferritin light chain, ferritin heavy chain and manganese superoxide dismutase, were significantly increased with EPA and DHA. Silencing nuclear factor erythroid 2-related factor 2 (NRF2) remarkably abrogated the increases in mRNA levels of antioxidant molecules and the decrease in intracellular reactive oxygen species. Furthermore, EPA and DHA significantly reduced H2O2-induced senescence-associated ß-galactosidase activity in the cells (by 31% and 22%, respectively), which was revoked by NRF2 silencing. CONCLUSIONS: Our results suggested that EPA and DHA attenuate oxidative stress-induced DNA damage in vascular endothelial cells through upregulation of NRF2-mediated antioxidant response. Therefore omega-3 fatty acids likely help prevent cardiovascular disease, at least in part, by their genome protective properties.