A Cross-Sectional Study Based on Forty Systematic Reviews of Foods with Function Claims (FFC) in Japan: Quality Assessment Using AMSTAR 2.

BACKGROUND: The Foods with Function Claims (FFC) was introduced in Japan in April 2015 to make more products available that are labeled with health functions. The products' functionality of function claims must be explained by scientific evidence presented in systematic reviews (SRs), but the quality of recent SRs is unclear. This study assessed the quality of SRs in the FFC registered on the Consumer Affairs Agency (CAA) website in Japan. METHODS: We searched the database from 1 April to 31 October 2022. Confidence in the methodological quality of each SR was evaluated by the AMSTAR 2 checklist. RESULTS: Forty SRs were randomly extracted on the basis of the eligibility criteria and recruitment procedures. Overall confidence was rated as "high" (N = 0, 0%), "moderate" (N = 0, 0%), "low" (N = 2, 5%), or "critically low" (N = 38, 95%). The mean AMSTAR 2 score was 51.1% (SD 12.1%; range 19-73%). Among the 40 SRs, the number of critical domain deficiencies was 4 in 7.5% of SRs, 3 in 52.5% of SRs, 2 in 35% of SRs, and 1 in 5% of SRs. Registering the review's protocol and comprehensive search strategies were particularly common deficiencies. Additionally, the risk of bias (RoB) was insufficiently considered. CONCLUSION: Overall, the methodological quality of the SRs based on the FFC, introduced eight years earlier, was very poor. This was especially true in the interpretation and discussion of critical domains, which had many deficiencies in terms of protocol registration, a comprehensive literature search strategy, and accounting for the RoB.

Budget impact analysis of comprehensive genomic profiling for untreated advanced or recurrent solid cancers in Japan.

AIMS: In Japan, the use of comprehensive genomic profiling (CGP) is only available for cancer patients who have no standard of care (SoC), or those who have completed SoC. This may lead to missed treatment opportunities for patients with druggable alterations. In this study, we evaluated the potential impact of CGP testing before SoC on medical costs and clinical outcome in untreated patients with advanced or recurrent biliary tract cancer (BTC), non-squamous non-small cell lung cancer (NSQ-NSCLC), or colorectal cancer (CRC) in Japan between 2022 and 2026. MATERIALS AND METHODS: We constructed a decision-tree model reflecting the healthcare environment of Japan, to estimate the clinical outcome and medical costs impact of CGP testing by comparing two groups (with vs without CGP testing before SoC). The epidemiological parameters, detection rates of druggable alterations, and overall survival were collected from literature and claims databases in Japan. Treatment options selected based on druggable alterations were set in the model based on clinical experts' opinions. RESULTS: In 2026, the number of untreated patients with advanced or recurrent BTC, NSQ-NSCLC, and CRC was estimated to be 8600, 32,103, and 24,896, respectively. Compared with the group without CGP testing before SoC, CGP testing before SoC increased druggable alteration detection and treatment rate with matched therapies in all three cancer types. The medical costs per patient per month were estimated to increase with CGP testing before SoC in the three cancer types by 19,600, 2900, and 2200 JPY (145, 21, and 16 USD), respectively. LIMITATIONS: Only those druggable alterations with matched therapies were considered in the analysis model, while the potential impact of other genomic alterations provided by CGP testing was not considered. CONCLUSIONS: The present study suggested that CGP testing before SoC may improve patient outcomes in various cancer types with a limited and controllable increase in medical costs.

Revisiting the Term "Compassionate Use" and Leadership of the World Health Organization in Resolving Confusion in the Age of COVID-19 and Beyond.

We discuss the term "compassionate use" (CU) as an example of terminology having a huge impact on drug regulation. CU is used in many confusing situations, and its meaning varies significantly. We ethically affirm the necessity of CU. We insist that CU should be properly placed in exceptional status. The regulation of CUs is much more lenient than that of clinical trials because of the difference in the purpose. Whether consciously or unconsciously, abuse results in confusion and is never acceptable. The World Health Organization (WHO) proposed not to use the previous term CU but to replace it with another one. WHO also proposed the term MEURI (monitored emergency use of unregistered and experimental interventions). However, this was extremely incomplete, and WHO used the term CU subsequently. The main purpose of the proposal needs to be thoroughly implemented. In the context of the COVID-19 pandemic and beyond, expectations regarding WHO's role and leadership in global health issues are rising. We hope that WHO will play a major role in promoting research ethics preparedness while discontinuing the use of confusing terms such as CU and will develop alternative terms and their content. We discuss the evaluation of MEURI, the Japanese version of CU, and appropriate and inappropriate terminology related to the therapeutic use of unapproved drugs. We also discuss the expected appearance of CU including its name. It is appropriate to target group/cohort patients and unapproved drugs in the late stage of development. It is also important to solve the problem of incentives for CUs of pharmaceutical companies that are rushing to obtain marketing approval. The UK's Early Access to Medicine Scheme has provided many suggestions. We believe that our opinion can contribute to WHO's efforts to resolve the confusion and promote research ethics preparedness in health emergencies.

[Quality Control and Quality Assurance for the Intermediate Zone between Food and Drug: Rational Use of Such Products and the Need to Modify the Pharmacy Education].

General views on three aspects were discussed. The first aspect is regulatory categories, which can range from "soft to hard", an expression using the English and Japanese translation of the French term, "drogue douce" (soft drug). This categorization starts with "so-called health foods" and extends to Foods with Health Claims [Foods with Nutrient Functional Claims (FNFC); Foods with Functional Claims (FFC); Foods for Specified Health Uses (FOSHU)], OTC drugs, and ethical drugs. "The Basic Policy for New Drug Approval" (1967) made a distinction between OTC and prescription drugs. FOSHU (1991) originally included foods for "patients", such as low allergen rice with preventive "health claims". Foods for Medical Uses (FMU) later became an independent subcategory under Foods for Special Dietary Uses. On the other hand, manufacturers of FFC can make various "health claims" on the basis of randomized controlled trial or systematic review (2015). Products in the intermediate zone between food and drug have an annual market of over 2 trillion yen (US$ 20 billion). The second aspect is the five elements, i.e., quality, safety, efficacy, information, and cost, which are derived from WHO's "The rational use of drugs" (1985). The adoption of Sustainable Development Goals (SDGs) by the UN General Assembly (2015) led to the addition of "ecology" as the sixth element, which is applicable for herbal and animal raw materials. The third aspect is quality control and quality assurance. This initially began with manufactured products and was expanded to the service fields handled by various health workers including pharmacists.

Efficacy and safety of tacrolimus in patients with rheumatoid arthritis - A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of tacrolimus in adult patients with rheumatoid arthritis (RA) by using the GRADE approach. METHODS: We searched PubMed, Japana Centra Revuo Medicina Web (Ichu-shi web), and the Cochrane Database of Systematic Reviews. Articles fulfilling the predefined inclusion criteria were appraised and used for meta-analysis. The primary outcomes were American College of Rheumatology 20 (ACR20) and serum creatinine elevation. Other outcomes included ACR50, ACR70, changes in C-reactive protein, modified Health Assessment Questionnaire Disability Index, gastrointestinal disorders, metabolic and nutritional disorders, and infections and infestations. RESULTS: We identified five randomized controlled studies, four of which compared tacrolimus to placebo and were included in the meta-analysis. The risk ratio of ACR20 achievement was 1.71 (95% confidence interval [CI] 1.20-2.42) for 1-2 mg/day and 2.30 (95% CI 1.79-2.96) for 3 mg/day. The risk ratio of creatinine elevation was 1.95 (95% CI 1.18-3.23) for 1-2 mg/day and 3.81 (95% CI 2.43-5.99) for 3 mg/day. CONCLUSION: Tacrolimus is effective with acceptable safety in the management of RA.

Compliance of Clinical Trial Protocols for Foods with Function Claims (FFC) in Japan: Consistency between Clinical Trial Registrations and Published Reports.

BACKGROUND: A new type of foods with a health claims notification system, the Foods with Function Claims (FFC), was introduced in Japan in April 2015. This cross-sectional study sought to clarify compliance of clinical trial protocols reported as the scientific basis of efficacy in the FFC system. METHODS: All articles based on clinical trials published on the Consumer Affairs Agency website from 1 July 2018 to 30 June 2021 were reviewed. Items assessed included first author characteristics (for-profit or academia), journal name, year published, journal impact factor in 2020, article language, name of clinical trial registration (CTR), and seven compliance items (Title: T, Participant: P, Intervention: I, Comparison: C, Outcome: O, Study design: S, and Institutional Review Board, IRB). Among studies that conducted CTR, consistency with these seven compliance items was evaluated. RESULTS: Out of 136 studies that met all inclusion criteria, 103 (76%) performed CTR, and CTR was either not performed or not specified for 33 (24%). Compliance between the protocol and the text was high (≥96%) for items P and S, but considerably lower for items T, I, C, O, and IRB (52%, 15%, 13%, 69%, and 27%, respectively). Furthermore, 43% of protocols did not include functional ingredients or food names in items T or I. The total score was 3.7 ± 1.1 pts (out of 7). CONCLUSIONS: Some CTs had no protocol registration, and even registered protocols were suboptimal in transparency. In addition to selective reporting, a new problem identified was that the content of the intervention (test food) was intentionally concealed.

Clinical trial registration, and publication in acupuncture studies: A systematic review.

BACKGROUND: To research 1) how many acupuncture clinical trials are registered with the WHO International Clinical Trial Registry Platform (ICTRP) and what patterns they demonstrate, 2) publication of the articles of acupuncture clinical trials which were registered with ICTRP. METHODS: The search strategy using the ICTRP: Intervention: acupuncture; Recruitment status: All; Date of registration; from 1 Jan 1990 to 31 Dec 2018. We searched the indexed articles in PubMed using trial IDs on 25 Feb 2019. When the paper was published, we indicated the number of weeks from the date of registration with ICTRP to the date of publication in order to define time till the publication. We divided the whole period we analyzed into 6 periods of every 3 years and measured the proportion of publication and the time from the date of registration of each trial till its publication in each period by the Kaplan-Meier method. RESULTS: Forty-three countries/areas conducted at least one acupuncture clinical trial. The total number of registrations was 1758. China, the USA, and the Republic of Korea accounted for 61% of those registrations. The proportion of publication was 178/1758 10% for the fully published papers and 141/1758 8% for the protocol papers. CONCLUSIONS: The substantial increase of registrations by China, the Republic of Korea, Iran, Brazil, Japan was observed which may be attributed to improved awareness of the CONSORT statement. However, the fully published papers rate is low at 10%. The publication of results of acupuncture clinical trials should also be rigorously mandated.

Epidemiological characteristics of rheumatoid arthritis in Japan: Prevalence estimates using a nationwide population-based questionnaire survey.

Objectives: To elucidate the epidemiological characteristics of patients with rheumatoid arthritis (RA) in Japan using data from the Comprehensive Survey of Living Conditions, a nationwide questionnaire survey conducted in 2016.Methods: In total, 222,365 men and 245,251 women aged ≥16 years were included in the study. RA patients were defined as those who reported 'currently receiving treatment for RA at hospitals, clinics, or a facility for Japanese traditional massage, acupuncture, moxibustion, or judo-orthopedics.' The number of RA patients was estimated from the age-specific prevalence and total Japanese population in 2016. Further, the prevalence of individuals experiencing difficulties in activities of daily living due to health problems and those with mental distress as evaluated by K6 Scale was examined.Results: The estimated number and prevalence of RA in Japan with 95% confidence interval was 822 (768-880) thousand and 0.75% (0.70-0.80%). The population peaked in the late 60s, and the prevalence continued increasing until the early 80s, regardless of sex. Compared with non-RA participants, RA patients were more likely to experience difficulties in activities and to be distressed.Conclusion: High prevalence of RA in older age and mental and physical burden among RA patients were confirmed.

Quality of Systematic Reviews of the Foods with Function Claims in Japan: Comparative Before- and After-Evaluation of Verification Reports by the Consumer Affairs Agency.

Background: In Japan, a new type of foods with health claims, called Foods with Function Claims (FFC), was introduced in April 2015 in order to make more products available that are clearly labeled with certain health functions. Regarding substantiating product effectiveness, scientific evidence for the proposed function claims must be explained by systematic reviews (SRs), but the quality of SRs was not clear. The objectives of this review were to assess the quality of SRs based on the FFC registered on the Consumer Affairs Agency (CAA) website in Japan, and to determine whether the CAA's verification report in 2016 was associated with improvement in the quality of SRs. Methods: We evaluated the reporting quality of each SR by the AMSTAR checklist on methodological quality. We searched the database from 1 April to 31 October 2015 as the before-SR and from 1 July 2017 to 31 January 2018 as the after-SR. Results: Among the 104 SRs reviewed, 96 final products were included: 51 (53.1%) were supplements, 42 (43.8%) were processed foods without supplements, and 3 (3.1%) were fresh foods. Of the 104 SRs, 92 (88.5%) were qualitative reviews (i.e., without meta-analysis) and 12 (11.5%) performed a meta-analysis. The average quality score of before-SRs and after-SRs was 6.2 ± 1.8 and 5.0 ± 1.9, respectively, a statistically significant decrease (p < 0.001). Conclusion: Overall, the methodology and reporting quality of after-SRs based on the FFC were poorer than those of before-SRs. In particular, there were very poor descriptions and/or implementations of study selection and data extraction, search strategy, evaluation methods for risk of bias, assessment of publication bias, and formulating conclusions based on methodological rigor and scientific quality of the included studies.

The utilization of complementary and alternative medicine in Taiwan: An internet survey using an adapted version of the international questionnaire (I-CAM-Q).

BACKGROUND: In Taiwan, numerous studies have been conducted to investigate the use of complementary and alternative medicine (CAM). However, most of them focused on specific diseases or the use of particular methods. Therefore, the results of those studies were quite different and difficult to compare with those of studies from other countries. The International CAM Questionnaire (I-CAM-Q), meanwhile, is a unified tool that can provide comparable results for studies conducted worldwide. Thus, the aim of this study was to discover the proportions of people in Taiwan receiving CAM treatments from different types of health care providers by using an adapted version of I-CAM-Q (I-CAM-QT). METHODS: I-CAM-QT was developed by translating the Korean version of I-CAM-Q (I-CAM-QK) into traditional Chinese language because of the similarity of CAM usage and doctor licensing system. This study had two stages: the first was a pretest survey used to adjust the questionnaire, while the second was an internet-based survey used to collect data from the community. RESULTS: Of the 1200 survey respondents, 37% and 37.7% were prescribed or advised to use Chinese herbal medicine (CHM) by Western medicine (WM) physicians and traditional Chinese medicine (TCM) doctors, respectively. Other than CHM, dietary supplements and massage were the forms of CAM most commonly prescribed or recommended by WM physicians or TCM doctors. Overall, walking and relaxation techniques were the most commonly used self-help practices (used by 61.9% and 40.4% of the respondents, respectively). Additionally, 70.3% of the respondents had used at least one kind of dietary supplement in the past 12 months. CONCLUSION: Regarding the utilization of CAM in Taiwan, this internet-based survey revealed that CHM, dietary supplements, and massage were the types of CAM most commonly prescribed or recommended by WM physicians or TCM doctors.

Use of Complementary and Alternative Medicine in Japan: A Cross-sectional Internet Survey Using the Japanese Version of the International Complementary and Alternative Medicine Questionnaire.

INTRODUCTION: Although there have been several national survey studies on complementary and alternative medicine (CAM) use in Japan, previous studies have not been compared with investigations conducted in other countries. An international CAM questionnaire known as I-CAM-Q was developed through a two-day international workshop in 2006. The purpose of this study was to investigate the use of CAM by the general Japanese population using a modified version of the I-CAM-Q for the Japanese (I-CAM-QJ). METHODS: We developed the I-CAM-QJ to conduct an internet survey of 3,208 participants from the general population of Japan in February 2016. The respondents included 1,592 males (49.6%), 1,348 university graduates (38.8%), 1,105 individuals in good health (34.4%), and 1,028 individuals with long-term illness or disability (32.0%). RESULTS: Of the 3,208 respondents, 411 participants reported CAM use during the past 12 months (12.8%). The following therapies and products were used: Kampo medicines (over-the-counter Kampo medicines: 15.7%; prescribed Kampo medicines: 15.4%), dietary supplements 11.8%, massage services 3.9%, and physical therapy 3.5%. Regarding the use of self-care methods during the last 12 months, the following methods and products were used: bath salts 25.8% and walking 25.3%. CONCLUSIONS: An internet survey on CAM use by the general Japanese population with a modified I-CAM-Q (I-CAM-QJ) revealed that Kampo medicines and dietary supplements were the most commonly used CAMs in Japan.

Internet survey on the provision of complementary and alternative medicine in Japanese private clinics: a cross-sectional study.

OBJECTIVE: Although the use of complementary and alternative medicine (CAM) by the general population has been surveyed previously, the provision of CAM by Japanese physicians in private clinics has not been studied. Universal health insurance system was established in Japan in 1961, and most CAMs are not on the drug tariff. We aimed to clarify the current status of CAM provided by physicians at private clinics in Japan. METHODS: We conducted an internet survey on 400 directors/physicians of private clinics nationwide on the provision of CAM from February 6 to February 10, 2017. Survey items included attributes of subjects, presence/absence of sections or facilities for provision of CAM, proportions of health insurance coverage for medical practices, and source of information. Private clinic was defined as a clinic run by one physician, with less than 20 beds. RESULTS: Commonly provided CAMs were Kampo (traditional Japanese herbal) medicines (34.8%) and supplements/health foods (19.3%). CAMs on the drug tariff were provided in 46.5% of cases at the clinics, but only 16.5% of cases were provided CAMs which were not on the drug tariff, at different neighboring facilities. Among different specialties, Kampo medicines were prescribed at obstetrics/gynecology (54.0%), orthopedics (44.4%), and dermatology (43.0%). Clinics not providing any CAM accounted for 53.5%. With regard to health insurance coverage, 96.8% of the clinics provided only or mainly health services on the universal national health insurance tariff (29.8% and 67.0%, respectively). CONCLUSION: Kampo medicines represent the most commonly used CAM in private clinics in Japan, and universal national health insurance coverage is considered to be the reason for the high rate of their use.

An assessment of the use of complementary and alternative medicine by Korean people using an adapted version of the standardized international questionnaire (I-CAM-QK): a cross-sectional study of an internet survey.

BACKGROUND: In Korea, there are two types of medical doctors: one practises conventional medicine (hereafter called a physician), and the other practises traditional medicine (hereafter called a Korean medical doctor). This study aimed to compare the provision of complementary and alternative medicine (CAM) by these providers to CAM use per self-judgement in Korea. METHODS: We analysed 1668 Korean people via an internet survey with the Korean adopted version of the I-CAM-Q, namely, the International Questionnaire to measure use of CAM, to understand whether respondents used CAM based either on a prescription or advice from a physician or a Korean medical doctor or on self-judgement. RESULTS: In the previous 12 months, the proportions of respondents who were treated by a physician, who were treated by a Korean medical doctor and who were not treated by anyone were 67.9, 20.7 and 14.2%, respectively. Among the respondents who received CAM based on a prescription or advice from a physician, traditional Korean medicine practices and dietary supplements were commonly used; only a small percentage used other CAM therapies. Respondents who received CAM based on a prescription or advice from a Korean medical doctor showed similar results. Acupuncture and moxibustion, traditional Korean medicines (decoction), or cupping were more commonly used. Korean traditional medicines as over-the-counter (OTC) drugs were more commonly used by respondents who received CAM therapy based on a prescription or advice from a physician than by those who received CAM therapy based on a prescription or advice from a Korean medical doctor. A total of 74% of the responders used any CAM by self-judgement in the previous 12 months. CONCLUSIONS: For the use of CAM in Korea, in addition to the Korean traditional medical care provided by Korean medical doctors, general physicians advised people regarding Korean traditional medical care and dietary supplements.

Quality of systematic reviews of the Foods with Function Claims registered at the Consumer Affairs Agency Web site in Japan: a prospective systematic review.

The objective of this review was to assess the quality of systematic reviews (SRs) based on the Foods with Function Claims (FFC) registered at the Consumer Affairs Agency (CAA) Web site in Japan by AMSTAR checklist. Study design was a prospective SR of SRs based on the FFC registered at the CAA Web site in Japan. We searched the database from 1 April 2015 (starting date) through 27 October 2015 on the CAA Web site. A full quality appraisal of identified articles was made using the combined tool based on the AMSTAR checklist developed to assess the methodological quality of SRs. Each item was scored as "present" (yes), "absent" (no), "unclear or inadequately described" (cannot answer), or "not applicable" (N/A). Forty-nine SRs met inclusion criteria. The quality of the articles was in the poor description category (mean±SD; 6.2±1.8 points, range; 2-11 points). Especially, there were very poor descriptions and/or implementations regarding the registration (2%), evaluation of publication bias (12%), and appropriate conclusions based on scientific quality of the included studies (27%). As a whole, the quality of SRs based on the FFC was poor in methodology and reporting. To develop SRs of the FFC and healthy foods, it will be important for future research to introduce and use (1) the AMSTAR checklist (ie, a tool to assess the methodological quality of SRs), (2) the PRISMA (ie, a checklist in the general description of SRs) and PRISMA-NMA checklists (ie, a checklist in the specific description of SRs with meta-analysis), (3) many English databases, (4) development of the original checklist for the FFC and healthy foods, and (5) notification documents (including SR) of the FFC in English.

Standards of Reporting Kampo Products (STORK) in research articles.

There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials (CONSORT) checklist, we hereby propose the use of the Standards of Reporting Kampo Products (STORK) website, http://mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.

Integrating patients' perceptions into clinical practice guidelines for the management of rheumatoid arthritis in Japan.

OBJECTIVE: Patients' values and preferences are among the key factors that determine the strength of recommendations presented in clinical practice guidelines (CPG). The aim of this study was to summarize the integration process for patients' perceptions into the development of CPG for rheumatoid arthritis (RA) management in Japan. METHODS: We used a mixed-methods approach. Questionnaires that could be self-administered were mailed to 2222 RA patients randomly selected from the Japan Rheumatism Friendship Association (JRFA) membership list that was age- and prefecture-stratified. A focus group with five JRFA executive members was formed to verify the results of the questionnaire. RESULTS: A total of 1470 patients aged 20-79 years old returned the questionnaire. Analysis of the questionnaire data revealed that the topics selected by the CPG task force met the patients' needs. The focus group participants showed reluctance to use the term 'preference' because patients would not want to take any medications but would have to take them out of necessity. CONCLUSIONS: We confirmed that the new CPG successfully addressed clinical issues that were important to both rheumatologists and patients. Clinicians should understand patients' reluctance to take medications and explain the role of each medication well to increase adherence.

Cost-utility analysis of sofosbuvir for the treatment of genotype 2 chronic hepatitis C in Japan.

OBJECTIVE: Across Japan, around 2 million people are infected with hepatitis C virus (HCV) with long-term complications such as cirrhosis, hepatocellular carcinoma (HCC) and liver transplant (LT). Current treatment options have several limitations due to side effects, interferon intolerability and ineligibility, long treatment durations and low sustained virological responses (SVR) rates, especially for the most severe patients. Sofosbuvir (SOF) is the first nucleotide analog NS5B polymerase inhibitor with pan-genotypic activity. SOF, administered in combination with ribavirin (RBV) with or without pegylated interferon (PEGIFN) resulted in high SVR rates across genotype (GT) 1-6 patients. It is also the first available regimen for patients that are unsuitable for interferon. This analysis assessed the cost-utility ratio of sofosbuvir in GT2 patients in Japan. RESEARCH DESIGN AND METHODS: A Markov model followed a cohort of 10,000 GT2 patients until patients reached 100 years of age. Approximately 20% of patients initiated treatment at the cirrhotic stage. Comparators were based on the current recommendations in Japan, including PEGIFN with ribavirin (RBV), telaprevir (TVR) in combination with PEGIFN + RBV and no treatment. Costs and outcomes were discounted at 2%. RESULTS: Sofosbuvir was cost-effective across all the studied indications, especially in patients unsuitable for interferon, with incremental cost-effectiveness ratios (ICERs) lower than JPY 5,000,000. Compared to the other treatments included in the analysis, SOF + RBV resulted in improved clinical outcomes. Results were robust to sensitivity analyses. CONCLUSION: SOF combined with RBV was shown to be cost-effective in GT2 patients in Japan. Compared to PEGIFN + RBV, TVR + PEGIFN + RBV and no treatment SOF offers a more efficacious, shorter and better tolerated treatment option and extends treatment to reach HCV-infected patients who are ineligible for interferon-based regimens. Although adverse events were not included in the analyses, this would not make any changes to our conclusion.

Comparative Effectiveness of Oral Medications for Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head comparisons are difficult to conduct. Network meta-analysis (NMA) can be a useful alternative for direct comparison to estimate the relative effectiveness of multiple treatments. The objective of the present study was to conduct a systematic review and NMA to evaluate the relative effectiveness among oral PAH medications.Data collection was performed by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and Ichushi-Web. Randomized controlled trials (RCTs) assessing at least 1 of the following 3 outcome measurements; 6-minute walk distance test (6MWD), WHO functional class (WHOFC), and mean pulmonary artery pressure (mPAP) were included (PROSPERO registration number: CRD42015016557). Outcomes were evaluated by estimating the differences in the mean change from baseline or by estimating the odds ratios. Analyses were performed using WinBUGS 1.4.3.Seven double-blind RCTs were eligible. NMA results showed similar improvements in 6MWD for all medications assessed. Bosentan and sildenafil caused a statistically significant improvement in WHOFC compared to other medications.The relative effectiveness of oral PAH medications could be compared using NMA, which suggested the superiority of bosentan and sildenafil in the improvement of WHOFC.

Effectiveness of Pilates exercise: A quality evaluation and summary of systematic reviews based on randomized controlled trials.

OBJECTIVE: The objective of this review were to summarize evidence for the effectiveness of Pilates exercise (PE) and to assess the quality of systematic review (SRs) based on randomized controlled trials (RCTs). STUDY DESIGN: A systematic review of SRs based on RCTs. METHODS: Studies were eligible if they were RCTs. Studies included those with one treatment group in which PE was applied. We searched the following databases from 1995 up to August 20, 2014: MEDLINE via PubMed, CINAHL, Web of Science, Global Health Library, and Ichushi-Web. We also searched All Cochrane Database and Campbell Systematic Reviews up to August 20, 2014. Based on the International Classification of Diseases-10 (ICD-10), we identified a disease targeted for each article. RESULTS: Nine studies met all inclusion criteria. As a whole, the quality of the articles was good. Seven studies were about "Musculoskeletal system and connective tissue (M5456)". There were two studies in "Factors influencing health status and contact with health services (Z723)". The traits of participants were for females and the comparatively young- and middle-aged. Five SRs for chronic low back pain (CLBP) concluded that there was pain-relief and functional improvement of the intervention in the short term, but two SRs were inconclusive about the effectiveness of PE. There were no adverse events described in any of the studies. CONCLUSION: Although no SR reported any adverse effect or harm by PE, there was pain-relief and functional improvement attributed to PE in the short term in participants with CLBP. There was also evidence of improved flexibility and dynamic balance, and of enhanced muscular endurance in healthy people in the short term. In addition, there may have been an effect on body composition in the short term.

The process of collecting and evaluating evidences for the development of Guidelines for the management of rheumatoid arthritis, Japan College of Rheumatology 2014: Utilization of GRADE approach.

OBJECTIVES: To describe the process of collecting and evaluating evidence for treating rheumatoid arthritis (RA) for developing clinical practice guidelines (CPGs) for rheumatologists in Japan. METHODS: The task force comprised rheumatologists, epidemiologists, health economists, and patients. First, the critical outcomes were determined according to a three-round Delphi method, and eight topics with 88 clinical questions (CQs) were formulated. A systematic review of CQs was conducted using the Cochran Database of Systematic Reviews, MEDLINE, and Japana Centra Revvo Medicina (2003-2012). A questionnaire survey and focus group interview were performed to capture the patients' values and preferences. Data from the National Health Insurance drug price list and product information provided by pharmaceutical companies were collected to evaluate drug cost and safety. The GRADE approach was used to describe the evidence quality and determine the strength of recommendations. Recommendations were developed using a modified Delphi method by a multidisciplinary panel including patients. RESULTS: Eight meetings and frequent e-mail communications were conducted to draft a quality assessment of evidence and recommendations. For 88 CQs, recommendation statements were determined. CONCLUSIONS: Using the GRADE approach, new CPGs successfully addressed important clinical issues for treating RA patients. Timely updating of recommendations should be routinely considered.