Mediterranean diet for cardiovascular disease: an evidence mapping study.

OBJECTIVE: This study aimed to evaluate the methodological quality of existing meta-analyses (MA) and the quality of evidence for outcome indicators to provide an updated overview of the evidence concerning the therapeutic efficacy of the Mediterranean diet (MD) for various types of CVD. DESIGN: We conducted comprehensive searches of PubMed, Cochrane Library, and Embase databases. The quality of the MA was assessed using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence evaluation system was employed to evaluate the quality of evidence for significant outcomes. SETTING: The CVD remains a significant contributor to global mortality. Multiple MA have consistently demonstrated the efficacy of medical interventions in managing CVD. However, due to variations in the scope, quality and outcomes of these reviews, definitive conclusions are yet to be established. PARTICIPANTS: This study included five randomized trials and twelve non-randomized studies, with a combined participant population of 716 318. RESULTS: The AMSTAR 2 checklist revealed that 54·55 % of the studies demonstrated high quality, while 9·09 % exhibited low quality, and 36·36 % were deemed critically low quality. Additionally, there was moderate evidence supporting a positive correlation between MD and CHD/acute myocardial infarction, stroke, heart failure, cardiovascular events, coronary events and major adverse cardiovascular events. CONCLUSIONS: This study indicates that although recognizing the potential efficacy of MD in managing CVD, the quality of the methodology and the evidence for the outcome indicators remain unsatisfactory.

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.

Similar Outcomes of Web-Based and Face-to-Face Training of the GRADE Approach for the Certainty of Evidence: Randomized Controlled Trial.

BACKGROUND: The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach is a system for transparent evaluation of the certainty of evidence used in clinical practice guidelines and systematic reviews. GRADE is a key part of evidence-based medicine (EBM) training of health care professionals. OBJECTIVE: This study aimed to compare web-based and face-to-face methods of teaching the GRADE approach for evidence assessment. METHODS: A randomized controlled trial was conducted on 2 delivery modes of GRADE education integrated into a course on research methodology and EBM with third-year medical students. Education was based on the Cochrane Interactive Learning "Interpreting the findings" module, which had a duration of 90 minutes. The web-based group received the web-based asynchronous training, whereas the face-to-face group had an in-person seminar with a lecturer. The main outcome measure was the score on a 5-question test that assessed confidence interval interpretation and overall certainty of evidence, among others. Secondary outcomes included writing a recommendation for practice and course satisfaction. RESULTS: In all, 50 participants received the web-based intervention, and 47 participants received the face-to-face intervention. The groups did not differ in the overall scores for the Cochrane Interactive Learning test, with a median of 2 (95% CI 1.0-2.0) correct answers for the web-based group and 2 (95% CI 1.3-3.0) correct answers for the face-to-face group. Both groups gave the most correct answers to the question about rating a body of evidence (35/50, 70% and 24/47, 51% for the web-based and face-to-face group, respectively). The face-to-face group better answered the question about the overall certainty of evidence question. The understanding of the Summary of Findings table did not differ significantly between the groups, with a median of 3 correct answers to 4 questions for both groups (P=.352). The writing style for the recommendations for practice also did not differ between the 2 groups. Students' recommendations mostly reflected the strengths of the recommendations and focused on the target population, but they used passive words and rarely mentioned the setting for the recommendation. The language of the recommendations was mostly patient centered. Course satisfaction was high in both groups. CONCLUSIONS: Training in the GRADE approach could be equally effective when delivered asynchronously on the web or face-to-face. TRIAL REGISTRATION: Open Science Framework akpq7; https://osf.io/akpq7/.

Society for Maternal-Fetal Medicine Special Statement: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) update.

The Society for Maternal-Fetal Medicine Publications Committee first adopted the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system in 2013. This document provides an update on the Society for Maternal-Fetal Medicine Publications Committee process for creating evidence-based practice recommendations and describes the GRADE process as it is currently implemented in the SMFM Consult and Guidelines series.

Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence.

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.

[The German Standing Committee on Vaccination: organization and mode of functioning]. / Ständige Impfkommission: Organisation und Arbeitsweise.

By law the Standing Committee on Vaccination (STIKO) has the mandate to develop recommendations for carrying out vaccinations and other measures of specific prophylaxis of communicable diseases. Currently, the committee has 18 members who meet 3 times per year to discuss and vote on recommendations. The secretariat of STIKO is located at the Immunization Unit of the Robert Koch Institute (RKI). In 2011 the STIKO adopted a new standard operating procedure (SOP) for the development of evidence-based vaccination recommendations. Using methods of evidence-based medicine, the respective STIKO working group, comprised of STIKO members, RKI staff and external experts, develops a draft recommendation on which the commission votes. After conclusion of the external consultation procedure the vaccination recommendation is considered by the Federal Joint Committee and in the case of a positive vote, is incorporated into the guidelines for protective vaccination and therefore becomes a mandatory service of the statutory health insurance. This article provides an overview on the organization and modes of functioning of the STIKO.

[Medical imaging clinical appropriateness:rational examination according to evidence-based medical imaging].

The rational clinical examination is important. The authors raised the concept of "medical imaging clinical appropriateness (MICA) " to meet the medical need in clinic (for diagnosis or assessment of a kind of disease or syndrome), which means radiologists and clinicians work together to carefully evaluate the necessity and rationality of an examination according to evidence of evidence-based medicine, expertise, experience, and patient's willing.The necessity is prerequisite, the rationality is the core, the evaluation of evidence is the basis, the application of evidence-based medicine is the important method. This work will provide us a series of criteria in the format of guidelines, providing evidence of rational examination for clinicians. Based on hard working and cooperation between radiologists and clinicians, we will establish the system of MICA in China, standardizing medical process, promoting rationalization, optimizing medical resources allocation and usage.

Efficacy and safety of allergen immunotherapy in patients with allergy to molds: A systematic review.

BACKGROUND: Allergen immunotherapy (AIT) with mould extracts has been performed for many years but the final demonstration of its clinical efficacy is still missing, due to the small number of studies and their inconsistent results. OBJECTIVE: To systematically review efficacy and safety of AIT for the treatment of respiratory allergies to moulds. DESIGN: The primary outcomes were safety and reduction of symptoms (Symptom Score, SS) and medication use (Medication Score, MS) in patients treated with AIT compared to controls. The strength of the evidence was graded based on the risk of bias, consistency and magnitude of effect, according to the GRADE Working Group's guide. DATA SOURCES: Medline, Web of Science and the Cochrane Library (through September 2017) supplemented with manual searches of reference lists. ELIGIBILITY CRITERIA: Randomized studies of intervention comparing AIT to placebo/pharmacotherapy. Studies not reporting on our outcome of interest or without a control population were excluded. RESULTS: Nine studies (168 children, 99 adults; median sample size, 27) met the inclusion criteria. The risk of bias was moderate-to-high in all but one study. Low strength evidence supports the assumption that AIT is effective in reducing symptoms and medication use, with only four of nine studies reporting higher benefit of AIT vs. comparators. The highest benefit of AIT compared to pharmacotherapy/placebo was reported in studies with a longer follow-up (SMD for MS from -3.96 to -3.97 in favour of AIT) and low risk of bias (VAS for SS: 66.3 ± 13 in AIT group; 186.6 ± 39 in comparators; P < 0.05). No difference was reported with respect to study sample size, route of administration, age of participants. Generalised adverse reactions were reported in 12.5% of participants treated with sublingual immunotherapy, and 37.2% of participants treated with subcutaneous immunotherapy. CONCLUSIONS: Low strength evidence suggests that mould AIT is efficacious for the treatment of respiratory allergies. High-quality studies with an adequate sample size are needed.

Recommendations from the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis.

BACKGROUND: In collaboration with United European Gastroenterology, the working group on 'Harmonizing diagnosis and treatment of chronic pancreatitis across Europe' (HaPanEU) developed European guidelines for the management of chronic pancreatitis using an evidence-based approach. METHODS: Recommendations of multidisciplinary review groups based on systematic literature reviews to answer predefined clinical questions are summarised. Recommendations are graded using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Recommendations covered topics related to the clinical management of chronic pancreatitis: aetiology, diagnosis of chronic pancreatitis with imaging, diagnosis of pancreatic exocrine insufficiency, surgical therapy, medical therapy, endoscopic therapy, treatment of pancreatic pseudocysts, pancreatic pain, nutrition and malnutrition, diabetes mellitus and the natural course of the disease and quality of life. CONCLUSIONS: The HaPanEU/United European Gastroenterology guidelines provide evidence-based recommendations concerning key aspects of the medical and surgical management of chronic pancreatitis based on current available evidence. These recommendations should serve as a reference standard for existing management of the disease and as a guide for future clinical research. This article summarises the HaPanEU recommendations and statements.

A Comparative Analysis of Pulmonary and Critical Care Medicine Guideline Development Methodologies.

RATIONALE: The Institute of Medicine (IOM) standards for guideline development have had unintended negative consequences. A more efficient approach is desirable. OBJECTIVES: To determine whether a modified Delphi process early during guideline development discriminates recommendations that should be informed by a systematic review from those that can be based upon expert consensus. METHODS: The same questions addressed by IOM-compliant pulmonary or critical care guidelines were addressed by expert panels using a modified Delphi process, termed the Convergence of Opinion on Recommendations and Evidence (CORE) process. The resulting recommendations were compared. Concordance of the course of action, strength of recommendation, and quality of evidence, as well as the duration of recommendation development, were measured. MEASUREMENTS AND MAIN RESULTS: When 50% agreement was required to make a recommendation, all questions yielded recommendations, and the recommended courses of action were 89.6% concordant. When 70% agreement was required, 17.9% of questions did not yield recommendations, but for those that did, the recommended courses of action were 98.2% concordant. The time to completion was shorter for the CORE process (median, 19.3 vs. 1,309.0 d; P = 0.0002). CONCLUSIONS: We propose the CORE process as an early step in guideline creation. Questions for which 70% agreement on a recommendation cannot be achieved should go through an IOM-compliant process; however, questions for which 70% agreement on a recommendation can be achieved can be accepted, avoiding a lengthy systematic review.

No 369 - Prise en charge de la grossesse aprés une mortinaissance.

OBJECTIF: L'objectif principal de la présente déclaration de consensus est d'élaborer des énoncés de consensus qui guideront la pratique clinique et des recommandations pour les soins prénataux et les soins intrapartum, et les considérations psychosociales dont il faut tenir compte pour prendre soin des femmes enceintes ayant des antécédents de mortinaissance. UTILISATEURS CIBLES: Les cliniciens participant à la prise en charge obstétrique des femmes ayant des antécédents de mortinaissance ou d'autres formes de décès périnatal. POPULATION CIBLE: Les femmes et les familles recevant des soins après une grossesse s'étant soldée par une mortinaissance ou une autre forme de décès périnatal. ÉVIDENCE: La présente directive clinique résume la littérature publiée et énonce un consensus général sur la prise en charge des grossesses suivant une mortinaissance ou un décès périnatal. Nous avons interrogé les bases de données MEDLINE, Embase et Cochrane au moyen des mots-clés : « previous stillbirth ¼, « perinatal loss ¼ et « subsequent pregnancy ¼. Nous avons ensuite étudié les résultats et lu les articles pertinents. Nous avons également consulté les références des articles retenus et les documents citant des études pertinentes. Les données ont ensuite été présentées pendant une réunion de consensus, et les énoncés ont été formulés. En raison du manque de données probantes, nous avons également consulté les cheminements de soins de cliniques spécialisées. VALIDATION: Le contenu et les lignes directrices ont été élaborés par les auteurs principaux en consultation avec les participants à la rencontre. Le Conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version finale avant publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) [tableau 1]. L'interprétation des recommandations solides et conditionnelles est décrite dans le tableau 2. Le résumé des conclusions peut être fourni sur demande. AVANTAGES, INCONVéNIENTS, COûTS: Nous avons exploré une approche multidisciplinaire de prestation des soins prénataux et intrapartum aux femmes et aux familles ayant des antécédents de mortinaissance ou de décès périnatal. Bien qu'il manque de données probantes dans ce domaine, certains membres du groupe de travail fournissent ces soins à des femmes et à des familles dans plusieurs pays et nous ont fait part de leurs connaissances et de leurs expériences dans le but de guider les soins. MIS-à-JOUR: Une revue des données probantes sera menée cinq ans après la publication de la présente directive clinique afin d'évaluer si une mise à jour complète ou partielle s'impose. Cependant, si de nouvelles données probantes importantes sont publiées avant la fin du cycle de cinq ans, le processus pourrait être accéléré afin que certaines recommandations soient mises à jour rapidement. COMMANDITAIRES: La présente directive clinique a été élaborée à l'aide de ressources financées par la Société des obstétriciens et gynécologues du Canada et le Programme pour les femmes et les bébés du Centre Sunnybrook des sciences et la santé tableau 1,2. DéCLARATIONS SOMMAIRES ET RECOMMANDATIONS.

Systematic review and meta-analysis of the technique of subtotal resection and stereotactic radiosurgery for large vestibular schwannomas: a "nerve-centered" approach.

OBJECTIVE During the last decade, the primary objective for large vestibular schwannoma (VS) management has progressively shifted, from tumor excision to nerve preservation by using a combined microsurgical and radiosurgical approach. The aim of this study was to provide a systematic review and meta-analysis of the available literature regarding the combined strategy of subtotal resection (STR) followed by stereotactic radiosurgery (SRS) for large VSs. METHODS The authors performed a systematic review and meta-analysis in compliance with the PRISMA guidelines for article identification and inclusion using the PubMed, Embase, and Cochrane databases. Established inclusion criteria were used to screen all identified relevant articles published before September 2017 without backward date limit. RESULTS The authors included 9 studies (248 patients). With a weighted mean follow-up of 46 months (range 28-68.8 months), the pooled rate of overall tumor control was 93.9% (95% CI 91.0%-96.8%). Salvage treatment (second STR and/or SRS) was necessary in only 13 (5.24%) of 18 patients who experienced initial treatment failure. According to the House-Brackmann (HB) grading scale, functional facial nerve preservation (HB grade I-II) was achieved in 96.1% of patients (95% CI 93.7%-98.5%). Serviceable hearing after the combined approach was preserved in 59.9% (95% CI 36.5%-83.2%). CONCLUSIONS A combined approach of STR followed by SRS was shown to have excellent clinical and functional outcomes while still achieving a tumor control rate comparable to that obtained with a total resection. Longer-term follow-up and larger patient cohorts are necessary to fully evaluate the rate of tumor control achieved with this approach.

European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology.

BACKGROUND AND PURPOSE: Current guidelines on cerebral venous thrombosis (CVT) diagnosis and management were issued by the European Federation of Neurological Societies in 2010. We aimed to update the previous European Federation of Neurological Societies guidelines using a clearer and evidence-based methodology. METHOD: We followed the Grading of Recommendations, Assessment, Development and Evaluation system, formulating relevant diagnostic and treatment questions, performing systematic reviews and writing recommendations based on the quality of available scientific evidence. RESULTS: We suggest using magnetic resonance or computed tomographic angiography for confirming the diagnosis of CVT and not routinely screening patients with CVT for thrombophilia or cancer. We recommend parenteral anticoagulation in acute CVT and decompressive surgery to prevent death due to brain herniation. We suggest preferentially using low-molecular-weight heparin in the acute phase and not direct oral anticoagulants. We suggest not using steroids and acetazolamide to reduce death or dependency. We suggest using antiepileptics in patients with an early seizure and supratentorial lesions to prevent further early seizures. We could not make recommendations concerning duration of anticoagulation after the acute phase, thrombolysis and/or thrombectomy, therapeutic lumbar puncture, and prevention of remote seizures with antiepileptic drugs. We suggest that, in women who have suffered a previous CVT, contraceptives containing oestrogens should be avoided. We suggest that subsequent pregnancies are safe, but use of prophylactic low-molecular-weight heparin should be considered throughout pregnancy and puerperium. CONCLUSIONS: Multicentre observational and experimental studies are needed to increase the level of evidence supporting recommendations on the diagnosis and management of CVT.

A systematic review and meta-analysis of nut consumption and incident risk of CVD and all-cause mortality.

Dietary patterns containing nuts are associated with a lower risk of CVD mortality, and increased nut consumption has been shown to have beneficial effects on CVD risk factors including serum lipid levels. Recent studies have reported on the relationship between nut intake and CVD outcomes and mortality. Our objective was to systematically review the literature and quantify associations between nut consumption and CVD outcomes and all-cause mortality. Five electronic databases (through July 2015), previous reviews and bibliographies of qualifying articles were searched. In the twenty included prospective cohort studies (n 467 389), nut consumption was significantly associated with a lower risk of all-cause mortality (ten studies; risk ratio (RR) 0·81; 95 % CI 0·77, 0·85 for highest v. lowest quantile of intake, P het=0·04, I 2=43 %), CVD mortality (five studies; RR 0·73; 95 % CI 0·68, 0·78; P het=0·31, I 2=16 %), all CHD (three studies; RR 0·66; 95 % CI 0·48, 0·91; P het=0·0002, I 2=88 %) and CHD mortality (seven studies; RR 0·70; 95 % CI 0·64, 0·76; P het=0·65, I 2=0 %), as well as a statistically non-significant reduction in the risk of non-fatal CHD (three studies; RR 0·71; 95 % CI 0·49, 1·03; P het=0·03, I 2=72 %) and stroke mortality (three studies; RR 0·83; 95 % CI 0·69, 1·00; P het=0·54, I 2=0 %). No evidence of association was found for total stroke (two studies; RR 1·05; 95 % CI 0·69, 1·61; P het=0·04, I 2=77 %). Data on total CVD and sudden cardiac death were available from one cohort study, and they were significantly inversely associated with nut consumption. In conclusion, we found that higher nut consumption is associated with a lower risk of all-cause mortality, total CVD, CVD mortality, total CHD, CHD mortality and sudden cardiac death.

EFNS-ENS/EAN Guideline on concomitant use of cholinesterase inhibitors and memantine in moderate to severe Alzheimer's disease.

BACKGROUND AND PURPOSE: Previous studies have indicated clinical benefits of a combination of cholinesterase inhibitors (ChEI) and memantine over ChEI monotherapy in Alzheimer's disease (AD). Our objective was the development of guidelines on the question of whether combined ChEI/memantine treatment rather than ChEI alone should be used in patients with moderate to severe AD to improve global clinical impression (GCI), cognition, behaviour and activities of daily living (ADL). METHODS: A systematic review and meta-analysis of randomized controlled trials based on a literature search in ALOIS, the register of the Cochrane Dementia and Cognitive Improvement Group, was carried out with subsequent guideline development according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Pooled data from four trials including 1549 AD patients in the moderate to severe disease stage demonstrated significant beneficial effects of combination therapy compared to ChEI monotherapy for GCI [standardized mean difference (SMD) -0.20; 95% confidence interval (CI) -0.31; -0.09], cognitive functioning (SMD -0.27, 95% CI -0.37; -0.17) and behaviour (SMD -0.19; 95% CI -0.31; -0.07). The quality of evidence was high for behaviour, moderate for cognitive function and GCI and low for ADL. Agreement of panellists was reached after the second round of the consensus finding procedure. The desirable effects of combined ChEI and memantine treatment were considered to outweigh undesirable effects. The evidence was weak for cognition, GCI and ADL so that the general recommendation for using combination therapy was weak. CONCLUSIONS: We suggest the use of a combination of ChEI plus memantine rather than ChEI alone in patients with moderate to severe AD. The strength of this recommendation is weak.

Evidence quality in clinical guidelines: a comparison of two methods.

INTRODUCTION: Guidelines report the quality of the evidence used when formulating recommendations to ensure transparency and allow end-users to assess the estimates of effect that underlie the recommendation. The aim of this study was to investigate the differences in grading of evidence quality between the Scottish Intercollegiate Guideline Network (SIGN) model and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. MATERIALS AND METHODS: The GRADE system was used to create evidence profiles for recommendations from a guideline that used the SIGN method to assess the quality of evidence. Scores were allocated to the quality assessment in its GRADE and SIGN forms, so that the difference between the two methods could be quantified. RESULTS: The SIGN grading system led to quality ratings of the evidence of high and moderate but using the GRADE system, the majority of ratings were graded as low or very low. All of the recommendations were graded as higher quality by SIGN than by GRADE. The points' difference ranged from one to three points (maximum difference possible was four points). The most common reasons for downgrading evidence were "study limitations", "imprecision"' and "publication bias". "Indirectness" and "inconsistency" were rarely selected as reasons to downgrade the evidence. CONCLUSIONS: The GRADE and SIGN methods produce varying estimates of the quality of evidence.

Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review.

BACKGROUND: Many patients with moderate-to-severe atopic dermatitis (AD) require systemic immunomodulating treatment to achieve adequate disease control. OBJECTIVE: We sought to systematically evaluate the efficacy and safety of systemic treatments for moderate-to-severe AD. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, and CENTRAL (until June 2012). Randomized controlled trials (RCTs) evaluating systemic immunomodulating treatments for moderate-to-severe AD were included. Selection, data extraction, quality assessment, and generation of treatment recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were performed independently by 2 reviewers. Efficacy outcomes were clinical signs, symptoms, quality of life, and the course of AD. Safety data were compared by calculating the weekly incidence rates (as percentages) for adverse events. RESULTS: Thirty-four RCTs with 12 different systemic treatments and totaling 1653 patients were included. Fourteen trials consistently indicate that cyclosporin A efficaciously improves clinical signs of AD. Cyclosporin A is recommended as first-line treatment for short-term use. A second-line treatment option is azathioprine, but efficacy is lower, and evidence is weaker. Methotrexate can be considered a third-line treatment option. Recommendations are impossible for mycophenolate, montelukast, intravenous immunoglobulins, and systemic glucocorticosteroids because of limited evidence. A meta-analysis was not performed because of a lack of standardization in outcome measures. CONCLUSION: Although 12 different interventions for moderate-to-severe AD have been studied in 34 RCTs, strong recommendations are only possible for the short-term use of cyclosporin A. Methodological limitations in the majority of trials prevent evidence-based conclusions. Large head-to-head trials evaluating long-term treatments are required.

Economic evaluation of adult rehabilitation: a systematic review and meta-analysis of randomized controlled trials in a variety of settings.

OBJECTIVES: To report if there is a difference in costs from a societal perspective between adults receiving rehabilitation in an inpatient rehabilitation setting versus an alternative setting. If there are cost differences, to report whether opting for the least expensive program setting adversely affects patient outcomes. DATA SOURCES: Electronic databases from the earliest possible date until May 2011. All languages were included. STUDY SELECTION: Multiple reviewers identified randomized controlled trials with a full economic evaluation that compared adult inpatient rehabilitation with an alternative. There were 29 included trials with 6746 participants. DATA EXTRACTION: Multiple observers extracted data independently. Trial appraisal included a risk of bias assessment and a checklist to report the strength of the economic evaluation. DATA SYNTHESIS: Results were synthesized using standardized mean differences (SMDs) and meta-analyses for the primary outcome of cost. The Grading of Recommendations Assessment, Development, and Evaluation was applied to assess for risk of bias across studies for meta-analyses. There was high-quality evidence that cost was significantly reduced for rehabilitation in the home versus inpatient rehabilitation in a meta-analysis of 732 patients poststroke (pooled SMD [δ]=-.28; 95% confidence interval [CI], -.47 to -.09), without compromise to patient outcomes. Results of individual trials in other patient groups (orthopedic, rheumatoid arthritis, and geriatric) receiving rehabilitation in the home or community were generally consistent with the meta-analysis. There was moderate quality evidence that cost was significantly reduced for inpatient rehabilitation (stroke unit) versus general acute care in a meta-analysis of 463 patients poststroke (δ=.31; 95% CI, .15-.48), with improvement to patient outcomes. These results were not replicated in 2 individual trials with a geriatric and a mixed cohort, where costs did not differ between general acute care and inpatient rehabilitation. Three of the 4 individual trials, inclusive of a stroke or orthopedic population, reported less cost for an intensive inpatient rehabilitation program compared with usual inpatient rehabilitation. Sensitivity analysis included a health service perspective and varied inflation rates with no change to the significant findings of the meta-analyses. CONCLUSIONS: Based on this systematic review and meta-analyses, a single rehabilitation service may not provide health economic benefits for all patient groups and situations. For some patients, inpatient rehabilitation may be the most cost-effective method of providing rehabilitation; yet, for other patients, rehabilitation in the home or community may be the most cost-effective model of care. To achieve cost-effective outcomes, the ideal combination of rehabilitation services and patient inclusion criteria, as well as further data for nonstroke populations, warrants further research.

The effect of oral appliances that advanced the mandible forward and limited mouth opening in patients with obstructive sleep apnea: a systematic review and meta-analysis of randomised controlled trials.

Oral appliances (OAs) have demonstrated efficacy in treating obstructive sleep apnea (OSA), but many different OA devices are available. The Japanese Academy of Dental Sleep Medicine supported the use of OAs that advanced the mandible forward and limited mouth opening and suggested an evaluation of their effects in comparison with untreated or CPAP. A systematic search was undertaken in 16 April 2012. The outcome measures of interest were as follows: Apnea Hypopnea Index (AHI), lowest SpO2 , arousal index, Epworth Sleepiness Scale (ESS), the SF-36 Health Survey. We performed this meta-analysis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Five studies remained eligible after applying the exclusion criteria. Comparing OA and control appliance, OA significantly reduced the weighted mean difference (WMD) in both AHI and the arousal index (favouring OA, AHI: -7.05 events h(-1) ; 95% CI, -12.07 to -2.03; P = 0.006, arousal index: -6.95 events h(-1) ; 95% CI, -11.75 to -2.15; P = 0.005). OAs were significantly less effective at reducing the WMD in AHI and improving lowest SpO2 and SF-36 than CPAP, (favouring OA, AHI: 6.11 events h(-1) ; 95% CI, 3.24 to 8.98; P = 0.0001, lowest SpO2 : -2.52%; 95% CI, -4.81 to -0.23; P = 0.03, SF-36: -1.80; 95% CI, -3.17 to -042; P = 0.01). Apnea Hypopnea Index and arousal index were significantly improved by OA relative to the untreated disease. Apnea Hypopnea Index, lowest SpO2 and SF-36 were significantly better with CPAP than with OA. The results of this study suggested that OAs improve OSA compared with untreated. CPAP appears to be more effective in improving OSA than OAs.