Eishu Nango

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

Abstract 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.

The clinical practice guideline for the management of ARDS in Japan

BackgroundThe 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.MethodThe 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).ResultsThe 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 β2 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.)ConclusionsThis 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

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

Abstract 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.

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.

Letter by Iguchi and Nango Regarding Article, “Pioglitazone for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis”

We would like to commend Lee et al1 for their excellent article. Their systematic review and meta-analysis of pioglitazone for secondary stroke prevention is meaningful because the field of diabetes mellitus research recognizes the importance of analysis of significant clinical outcomes, including heart disease and mortality, rather than surrogate markers as the end point of diabetes mellitus drug analysis.2 A previous Cochrane Review showed that intensive glycemic control did not reduce stroke incidence in type 2 diabetes mellitus.3 However, we have a concern about their analysis and interpretation. As the authors pointed out, the data derived from PROactive …

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

BackgroundThis 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).MethodsWe 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.ResultsThe 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.ConclusionCompared with standard O2 therapy or InMV, NIV lowered both the short-term mortality and the rate of tracheal intubation in patients presenting with ARF.

Survival as a function of HbA1c in people with type 2 diabetes

Craig Currie and colleagues (Feb 6, p 481) report that the ideal glycosylated haemo globin (HbA1c) concentration for patients with type 2 diabetes is 7·5% and that revised recommendations should target such a value. In this retro spective study, increased mort ality was seen with high HbA1c, as expected, but also with low values, especially in patients on insulin. However, the inclusion period extended from November, 1986, to November, 2008, raising questions about the homogeneity of the populations and strategies studied. The guidelines for treatment of diabetes have changed strikingly since the 1980s. The demonstration of the benefi ts of intensive glycaemic control by the UK Prospective Diabetes Study (UKPDS) in 1998 and the introduction of new mol ecules, especially insulin analogues, possibly translated into better management of patients with type 2 diabetes. And basal insulin ana logues resulted in a lower incidence of hypoglycaemia than did neutral prot amine hagedorn insulin. This is an important issue since hypo glycaemia was suspected of being responsible for the higher mortality rates in patients achieving the lowest mean HbA1c, although this hypothesis was not supported by a subanalysis of the ACCORD study. Furthermore, the introduction and subsequent widespread use of other drugs, such as statins, in cardiovascular pre vention could have positively aff ected mortality. Thus we would be interested in the mortality rate of patients with HbA1c below 7% and treated in the post-UKPDS era. Is the same U-shaped relation between HbA1c and mortality seen in these more recently included patients? This issue should be addressed before considering any modifi cation of current guidelines. We declare that we have no confl icts of interest.

Survival as a function of HbA(1c) in people with type 2 diabetes.

Craig Currie and colleagues (Feb 6, p 481) report that the ideal glycosylated haemo globin (HbA1c) concentration for patients with type 2 diabetes is 7·5% and that revised recommendations should target such a value. In this retro spective study, increased mort ality was seen with high HbA1c, as expected, but also with low values, especially in patients on insulin. However, the inclusion period extended from November, 1986, to November, 2008, raising questions about the homogeneity of the populations and strategies studied. The guidelines for treatment of diabetes have changed strikingly since the 1980s. The demonstration of the benefi ts of intensive glycaemic control by the UK Prospective Diabetes Study (UKPDS) in 1998 and the introduction of new mol ecules, especially insulin analogues, possibly translated into better management of patients with type 2 diabetes. And basal insulin ana logues resulted in a lower incidence of hypoglycaemia than did neutral prot amine hagedorn insulin. This is an important issue since hypo glycaemia was suspected of being responsible for the higher mortality rates in patients achieving the lowest mean HbA1c, although this hypothesis was not supported by a subanalysis of the ACCORD study. Furthermore, the introduction and subsequent widespread use of other drugs, such as statins, in cardiovascular pre vention could have positively aff ected mortality. Thus we would be interested in the mortality rate of patients with HbA1c below 7% and treated in the post-UKPDS era. Is the same U-shaped relation between HbA1c and mortality seen in these more recently included patients? This issue should be addressed before considering any modifi cation of current guidelines. We declare that we have no confl icts of interest.

CorrespondenceSurvival as a function of HbA1c in people with type 2 diabetes

Craig Currie and colleagues (Feb 6, p 481) report that the ideal glycosylated haemo globin (HbA1c) concentration for patients with type 2 diabetes is 7·5% and that revised recommendations should target such a value. In this retro spective study, increased mort ality was seen with high HbA1c, as expected, but also with low values, especially in patients on insulin. However, the inclusion period extended from November, 1986, to November, 2008, raising questions about the homogeneity of the populations and strategies studied. The guidelines for treatment of diabetes have changed strikingly since the 1980s. The demonstration of the benefi ts of intensive glycaemic control by the UK Prospective Diabetes Study (UKPDS) in 1998 and the introduction of new mol ecules, especially insulin analogues, possibly translated into better management of patients with type 2 diabetes. And basal insulin ana logues resulted in a lower incidence of hypoglycaemia than did neutral prot amine hagedorn insulin. This is an important issue since hypo glycaemia was suspected of being responsible for the higher mortality rates in patients achieving the lowest mean HbA1c, although this hypothesis was not supported by a subanalysis of the ACCORD study. Furthermore, the introduction and subsequent widespread use of other drugs, such as statins, in cardiovascular pre vention could have positively aff ected mortality. Thus we would be interested in the mortality rate of patients with HbA1c below 7% and treated in the post-UKPDS era. Is the same U-shaped relation between HbA1c and mortality seen in these more recently included patients? This issue should be addressed before considering any modifi cation of current guidelines. We declare that we have no confl icts of interest.