Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of microscopic polyangiitis and granulomatosis with polyangiitis: The 2023 update - secondary publication.

OBJECTIVE: To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field. METHODS: Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added. RESULTS: We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy. CONCLUSIONS: The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost.

Systematic review and meta-analysis for 2017 clinical practice guidelines of the Japan research committee of the ministry of health, labour, and welfare for intractable vasculitis for the management of ANCA-associated vasculitis.

OBJECTIVES: To provide evidence for the revision of clinical practice guideline (CPG) for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by the Japan Research Committee for Intractable Vasculitis. METHODS: PubMed, CENTRAL, and the Japan Medical Abstracts Society were searched for articles published between January 1994 and January 2015 to conduct systematic review (SR), and the quality of evidence was assessed with GRADE approach. RESULTS: Nine randomized controlled trials (RCTs) and two non-RCTs were adopted for remission induction therapy, three RCTs and two non-RCTs for plasma exchange, and five RCTs and one non-RCT for remission maintenance therapy. A significant difference was found in efficacy and safety for the following comparisons. In the non-RCT adopted for remission induction therapy, glucocorticoid (GC) + cyclophosphamide (CY) was significantly superior to GC monotherapy regarding remission. GC + intravenous CY for remission induction therapy was superior to GC + oral CY regarding death at one year, serious adverse events, and serious infection. Concomitant use of plasma exchange for remission induction therapy of AAV with severe renal dysfunction reduced risk of end-stage renal disease versus non-users at month 3. CONCLUSION: This SR provided necessary evidence for developing CPG for the management of ANCA-associated vasculitis.

2017 Clinical practice guidelines of the Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis for the management of ANCA-associated vasculitis.

OBJECTIVE: The Japan Research Committee for Intractable Vasculitis has fully revised the clinical practice guidelines (CPG) for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) to improve and standardize the medical treatment of the disease in Japan. METHODS: The previous CPG was published in a classical review style in Japanese in 2011 and 2014. We adopted the Grading of Recommendations Assessment, Development and Evaluation system for this revision, and various stakeholders, including patients, participated in it. The expected users of this CPG are AAV patients in Japan and their families and healthcare professionals, including both AAV specialists and non-specialists. We set clinical questions concerning the three important clinical topics of remission induction therapy, plasma exchange, remission maintenance therapy, and developed eight recommendation statements. RESULTS: For remission induction therapy for newly developed AAV, we weakly recommend glucocorticoid (GC) plus intravenous cyclophosphamide pulse (IVCY) or oral cyclophosphamide (POCY) rather than GC alone, and IVCY rather than POCY. We also weakly recommend CY rather than rituximab. In the case of AAV with severe renal impairment, we weakly recommend plasma exchange as a conjunction therapy. We weakly recommend azathioprine for remission maintenance therapy. CONCLUSION: The revised CPG has demonstrated evidence-based treatment recommendations for AAV.

Fluoride supplementation (with tablets, drops, lozenges or chewing gum) in pregnant women for preventing dental caries in the primary teeth of their children.

BACKGROUND: Dental caries (tooth decay) is one of the most common chronic childhood diseases. Caries prevalence in most industrialised countries has declined among children over the past few decades. The probable reasons for the decline are the widespread use of fluoride toothpaste, followed by artificial water fluoridation, oral health education and a slight decrease in sugar consumption overall. However, in regions without water fluoridation, fluoride supplementation for pregnant women may be an effective way to increase fluoride intake during pregnancy. If fluoride supplements taken by pregnant women improve neonatal outcomes, pregnant women with no access to a fluoridated drinking water supply can obtain the benefits of systemic fluoridation. OBJECTIVES: To evaluate the effects of women taking fluoride supplements (tablets, drops, lozenges or chewing gum) compared with no fluoride supplementation during pregnancy to prevent caries in the primary teeth of their children. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 25 January 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 11) in the Cochrane Library (searched 25 January 2017); MEDLINE Ovid (1946 to 25 January 2017); Embase Ovid (1980 to 25 January 2017); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 25 January 2017); and CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 25 January 2017). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials to 25 January 2017. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) of fluoride supplements (tablets, drops, lozenges or chewing gum) administered to women during pregnancy with the aim of preventing caries in the primary teeth of their children. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts (when available) of all reports identified through electronic searches. Two review authors independently extracted data and assessed risk of bias, as well as evaluating overall quality of the evidence utilising the GRADE approach. We could not conduct data synthesis as only one study was included in the analysis. MAIN RESULTS: Only one RCT met the inclusion criteria for this review. This RCT showed no statistical difference on decayed or filled primary tooth surfaces (dfs) and the percentage of children with caries at 3 years (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.75 to 2.85; participants = 938, very low quality of evidence) and 5 years old (RR 0.84, 95% CI 0.53 to 1.33; participants = 798, very low quality of evidence). The incidence of fluorosis at 5 years was similar between the group taking fluoride supplements (tablets) during the last 6 months of pregnancy and the placebo group. AUTHORS' CONCLUSIONS: There is no evidence that fluoride supplements taken by women during pregnancy are effective in preventing dental caries in their offspring.

Effects of non-invasive ventilation in patients with acute respiratory failure excluding post-extubation respiratory failure, cardiogenic pulmonary edema and exacerbation of COPD: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis compared the effects of non-invasive ventilation (NIV) with invasive mechanical ventilation (InMV) and standard oxygen (O2) therapy on mortality and rate of tracheal intubation in patients presenting acute respiratory failure (ARF). METHODS: We searched the MEDLINE, EMBASE and Cochrane Central Register of clinical trials databases between 1949 and May 2015 to identify randomized trials of NIV for ARF. We excluded the ARF caused by extubation, cardiogenic pulmonary edema, and COPD. RESULTS: The meta-analysis included 21 studies and 1691 patients, of whom 846 were assigned to NIV and 845 to control (InMV or standard O2 therapy). One hundred ninety-one patients (22.6%) in the NIV group and 261 patients (30.9%) in the control group died before discharge from hospital. The pooled odds ratio (OR) for short-term mortality (in-hospital mortality) was 0.56 (95% CI 0.40-0.78). When comparing NIV with standard O2 therapy, the short-term mortality was 155 (27.4%) versus 204 (36.0%), respectively. For this comparison, the pooled OR of short-term mortality was 0.56 (95% CI 0.36-0.85). When comparing NIV with InMV, the short-term mortality was 36 (12.9%) versus 57 (20.5%) patients, respectively. For this comparison, the pooled OR of short-term mortality was 0.56 (95% CI 0.34-0.90). Tracheal intubation was performed in 106 patients (22.7%) in the NIV and in 183 patients (39.4%) in the standard O2 group, representing a pooled OR of 0.37 (95% CI 0.25-0.55). There were publication biases and the quality of the evidence was graded as low. CONCLUSION: Compared with standard O2 therapy or InMV, NIV lowered both the short-term mortality and the rate of tracheal intubation in patients presenting with ARF.

[How to Use Presentations and Leaflets from Pharmaceutical Companies].

Presentations and leaflets from pharmaceutical companies are still a major source of information for physicians in Japan. Most physicians trust them and base their clinical practice on them. Such products from pharmaceutical companies are just advertising, because they are profit-making enterprises. Gifts from pharmaceutical companies to health care providers introduce bias when prescribing medicine. Thus, it is important that health care providers who receive this information from pharmaceutical companies, interpret it correctly. There are several methods for information supplements used by pharmaceutical companies. The range of the vertical axis on a survival curve may not be the full range, and differences between treatment groups are expanded in graphs. Sometimes the shape of the survival curve is artificial. The treatment effects should be interpreted based on various indicators such as raw incidence, relative risk or the number needed to treat. A composite endpoint is often used in mega-studies because each individual outcome which comprises the composite endpoint has a small event rate that is not enough to reach statistical significance, whether outcomes are important for patients or not. Evidence-based medicine is a formulated method of clinical reasoning from evidence used to make decisions. We should consider not only the evidence, but also a patient's clinical state and circumstances, a patient's preferences and actions, and the clinical expertise of the health care providers. Although pharmaceutical companies seduce health care providers, they have to recognize the true magnitude of the effects of their products and recommend their use for patients carefully.

ARDS clinical practice guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

ARDS Clinical Practice Guideline 2021.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

Variation of treatment decision-making for laryngeal cancer in Japan a retrospective observational study using a claim- and electronic medical record-based database.

BACKGROUND: Primary curative treatment of resectable laryngeal cancer includes surgery and chemoradiotherapy. Other treatment options include radiotherapy, chemoradiotherapy, partial laryngectomy, and total laryngectomy. Larynx-preserving treatments (partial laryngectomy, radiotherapy, and chemoradiotherapy) are recommended in early stage cases, although total laryngectomy is needed in advanced cases. Here, we evaluated trends in treatment strategies and identified the factors that are important in decision making. METHODS: We performed a retrospective analysis of data acquired from electronic medical records in Japan. Hospitalized laryngeal cancer patients admitted between January 2014 and December 2018 were included in our analyses. The primary outcome was the initial treatment. RESULTS: A total of 363 patients (mean age 71.8 ± 9.5, male/female = 333/30) met the inclusion criteria. Of these, 10.1% of the patients were treated with total laryngectomy, while 17.9% underwent partial resection, 65.8% received radiotherapy (chemoradiotherapy), and 6.1% had no treatment. Larynx-preserving treatment was used in most T1-2 cases (96.9%), and 40% of the patients with T3 cancer underwent total laryngectomy (adjusted odds ratio 26.7 [95% CI, 9.29-91.6]). Of the T3 cancers that were treated, total laryngectomy was performed in only 26.7% of patients aged ≤65 years, but in more than 50% of those aged >65 years. CONCLUSIONS: This retrospective study showed that larynx-preserving treatments were used in most T1-2 cases, and suggested that T stage is the most important factor affecting decision making in the treatment of laryngeal cancer. Older patients with T3 disease tended to undergo total laryngectomy, and age is an important factor in the decision-making process for cases of T3 laryngeal cancer.

Optimal Upper Limits of Plateau Pressure for Patients With Acute Respiratory Distress Syndrome During the First Seven Days: A Meta-Regression Analysis.

BACKGROUND: The effects of plateau pressure during the initial days of mechanical ventilation on outcomes for patients with acute respiratory distress syndrome have not been fully examined. We conducted meta-regression analysis of plateau pressure during the first 7 days using randomized control trials to investigate the optimal upper limits of plateau pressure on different days of mechanical ventilation. METHODS: Randomized controlled trials comparing two mechanical ventilation strategies with lower and higher plateau pressures in patients with acute respiratory distress syndrome were included. Meta-regression analysis was performed to determine the association of plateau pressure with mortality on days 1, 3, and 7 of mechanical ventilation. RESULTS: After evaluation of 2,975 citations from a comprehensive search across electronic databases, 14 studies were included in the final qualitative analysis. A total of 4,984 patients were included in the quantitative analysis. As a result of the pairwise comparison, overall short-term mortality was significantly higher for patients with plateau pressures over 32 cm H2O during the first 3 days after intensive care unit (ICU) admission (day 1: relative risk (RR), 0.77; 95% confidence interval (CI), 0.66 - 0.89; I2 = 0%; day 3: RR, 0.76; 95% CI, 0.64 - 0.90; I2 = 0%), but not on day 7 (RR, 0.82; 95% CI, 0.65 - 1.04; I2 = 16%). Plateau pressures below 27 cm H2O and 30 cm H2O were not associated with an absolute risk reduction of short-term mortality. According to univariable meta-regression analysis, mortality was significantly associated with plateau pressure on day 1 (ß = 0.01 (95% CI, 0.002 - 0.024), P = 0.02). On days 3 and 7, however, no significant difference was detected. When the cutoffs were set at 27, 30 and 32 cm H2O on day 1, which showed a significant difference, plateau pressure tended to be associated with increased mortality at pressures above the cut-off values, and there were no significant differences at pressures below the cut-off values, regardless of the cutoff used. CONCLUSIONS: This study suggests that the optimal cut-off value for plateau pressure may be 27 cm H2O especially during the initial period of mechanical ventilation, although this association may not continue during the latter period of mechanical ventilation.

Quality of clinical practice guidelines in Japan remains low: A cross-sectional meta-epidemiological study.

OBJECTIVES: We aimed to evaluate the characteristics, quality, and related factors of the Japanese Clinical Practice Guidelines (CPGs) published in recent years. STUDY DESIGN AND SETTING: In this cross-sectional, meta-epidemiological study, we conducted a Google search for CPGs published by 30 Japanese medical societies that are the basis for training specialties between 2018 and 2019. We used the Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool and the Reporting Items for practice Guidelines in HealThcare (RIGHT) statement to evaluate the quality. RESULTS: We included 53 systematic review-based CPGs. The median score was 0.54 (IQR, 0.38-0.62) for Stakeholder involvement, 0.57 (IQR, 0.51-0.66) in Rigor of development, 0.33 (IQR 0.21-0.46) in Applicability, and 0.63 (IQR 0.46-0.73) in Editorial independence. The number of guideline developers/clinical question ratio (odds ratio [OR]: 4.14, 95% confidence interval [CI]: 1.97, 8.70) and the adopted guideline development methods (OR: 3.69, 95% CI: 1.14, 12.0) were significantly related to the Rigor of development. CONCLUSION: The quality of Japanese CPGs published in recent years remains low. Our study suggests that increasing contributors and adopting the latest guideline development methods at the beginning of the project may improve the quality of the Japanese CPGs.

Problem-based learning in a multidisciplinary group enhances clinical decision making by medical students: a randomized controlled trial.

BACKGROUND: The effect of multidisciplinary education on clinical decision making by medical students is not well known. METHODS: Twenty of fourth, fifth or sixth year medical students were randomly assigned to multidisciplinary groups (MultiG, n = 7) with two medical, pharmacy and nursing students or medical student groups (MedG, n = 10) with six medical students only and given a two-day PBL program using evidence-based medicine (EBM) methodology. The main outcome measure is clinical decision making by medical students for the case, measured by a 100 mm visual analog scale (VAS). Additional patient information requested and self-evaluation of the PBL program were also measured. RESULTS: Correct answers to assess clinical epidemiology knowledge increased significantly in both groups (4.1 to 9.9 points in MultiG, p < 0.001: 3.6 to 9.7 points in MedG, p = 0.002), while scores at baseline and post-program were not significantly different. The number of additional patient information cards requested was not significantly different (p = 0.10). After the program, the VAS for clinical decision making was significantly different (54 mm and 89 mm, p = 0.013), although preprogram values for both groups were similar. CONCLUSION: Pharmacy and nursing students may have potential to change the clinical decision making by medical students.

Optimal duration of prone positioning in patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-regression analysis.

INTRODUCTION: Several systematic reviews and meta-analyses have demonstrated that prolonged (≥16 hours) prone positioning can reduce the mortality associated with acute respiratory distress syndrome (ARDS). However, the effectiveness and optimal duration of prone positioning was not fully evaluated. To fill these gaps, we will first investigate the effectiveness of prone positioning compared with the conventional management of patients with ARDS, regarding outcomes using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Second, if statistical heterogeneity in effectiveness with regard to short-term mortality (intensive care unit death or ≤30-day mortality) is shown, we will conduct a meta-regression analysis to explore the association between duration and effectiveness, and determine the optimal duration of prone positioning. METHOD AND ANALYSIS: Relevant studies are collected using PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials and the WHO International Clinical Trials Platform Search Portal. Randomised controlled trials comparing prone and supine positioning in adults with ARDS will be included in the meta-analysis. Two independent investigators will screen trials obtained by search eligibility and extract data from selected studies to standardised data recording forms. For each selected trial, the risk of bias and quality of evidence will be evaluated using the GRADE system. Meta-regression analyses will be performed to identify the most important factors associated with short-term mortality, and subgroup analysis will be used to analyse the following: duration of mechanical ventilation in the prone position per day, patient severity, tidal volume and cause of ARDS. If heterogeneity or inconsistency among the studies is detected, subgroup analysis will be conducted on factors that may cause heterogeneity. ETHICS AND DISSEMINATION: This study requires no ethical approval. The results obtained from this systematic review and meta-analysis will be disseminated through international conference presentations and publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017078340.

The clinical practice guideline for the management of ARDS in Japan.

BACKGROUND: The Japanese Society of Respiratory Care Medicine and the Japanese Society of Intensive Care Medicine provide here a clinical practice guideline for the management of adult patients with ARDS in the ICU. METHOD: The guideline was developed applying the GRADE system for performing robust systematic reviews with plausible recommendations. The guideline consists of 13 clinical questions mainly regarding ventilator settings and drug therapies (the last question includes 11 medications that are not approved for clinical use in Japan). RESULTS: The recommendations for adult patients with ARDS include: we suggest against early tracheostomy (GRADE 2C), we suggest using NPPV for early respiratory management (GRADE 2C), we recommend the use of low tidal volumes at 6-8 mL/kg (GRADE 1B), we suggest setting the plateau pressure at 30cmH20 or less (GRADE2B), we suggest using PEEP within the range of plateau pressures less than or equal to 30cmH2O, without compromising hemodynamics (Grade 2B), and using higher PEEP levels in patients with moderate to severe ARDS (Grade 2B), we suggest using protocolized methods for liberation from mechanical ventilation (Grade 2D), we suggest prone positioning especially in patients with moderate to severe respiratory dysfunction (GRADE 2C), we suggest against the use of high frequency oscillation (GRADE 2C), we suggest the use of neuromuscular blocking agents in patients requiring mechanical ventilation under certain circumstances (GRADE 2B), we suggest fluid restriction in the management of ARDS (GRADE 2A), we do not suggest the use of neutrophil elastase inhibitors (GRADE 2D), we suggest the administration of steroids, equivalent to methylprednisolone 1-2mg/kg/ day (GRADE 2A), and we do not recommend other medications for the treatment of adult patients with ARDS (GRADE1B; inhaled/intravenous ß2 stimulants, prostaglandin E1, activated protein C, ketoconazole, and lisofylline, GRADE 1C; inhaled nitric oxide, GRADE 1D; surfactant, GRADE 2B; granulocyte macrophage colony-stimulating factor, N-acetylcysteine, GRADE 2C; Statin.). CONCLUSIONS: This article was translated from the Japanese version originally published as the ARDS clinical practice guidelines 2016 by the committee of ARDS clinical practice guideline (Tokyo, 2016, 293p, available from http://www.jsicm.org/ARDSGL/ARDSGL2016.pdf). The original article, written for Japanese healthcare providers, provides points of view that are different from those in other countries.

Optimal plateau pressure for patients with acute respiratory distress syndrome: a protocol for a systematic review and meta-analysis with meta-regression.

INTRODUCTION: Lower tidal volume ventilation in patients with acute respiratory distress syndrome (ARDS) is a strategy to reduce the plateau pressure and driving pressure to limit ventilator-induced lung injury (VILI). Several randomised controlled trials (RCTs) and meta-analyses showed that limiting both the plateau pressure and the tidal volume decreased mortality, but the optimal plateau pressure to demonstrate a benefit is uncertain. The aim of this systematic review is to investigate the optimal upper limit of plateau pressure in patients with ARDS to prevent VILI and improve clinical outcomes using meta-analysis with and without meta-regression. METHODS AND ANALYSIS: RCTs comparing two mechanical ventilation strategies will be included, with lower plateau pressure and with higher plateau pressure, among patients with ARDS and acute lung injury. Data sources include MEDLINE via the NCBI Entrez system, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Ichushi, a database of papers in Japanese. Two of three physicians will independently screen trials obtained by search for eligibility, and extract data from included studies onto standardised data recording forms. For each included trial, the risk of bias and the quality of evidence will be evaluated using the Grading of Recommendation Assessment Development and Evaluation system. ETHICS AND DISSEMINATION: This study does not require ethical approval. The results of this systematic review and meta-analysis with and without meta-regression will be disseminated through conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42016041924.