McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome.

Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

Evidence synthesis for health policy and systems: a methods guide

Over the last two decades, major gains have been made in global health: life expectancy has increased dramatically; polio eradication is tantalizingly within reach; six million more children survived until their fifth birthday; malaria deaths halved, while more than 20 million people living with HIV gained access to lifesaving treatment. These are all colossal achievements, which amount to millions of lives saved. Despite these successes, progress has often been uneven, both between and within countries. There remains a 31-year discrepancy between the countries with the shortest and longest life expectancies, while more than half of the world's population is unable to access health services without incurring financial hardship. The implications of this are profound. Lack of access to affordable, quality health care perpetuates a vicious cycle of poverty and ill health, and every year millions of people, mostly in the world's poorest countries, die from sicknesses that we know how to prevent and treat. Tackling these challenges will require modern health systems that ensure services reach the poorest, the most vulnerable and those who are most often left behind. These systems must be more dynamic and multisectoral; they must move beyond a focus on diseases and curative care, and place the needs of people and communities at their core. They must also empower people to take charge of their health, with a lifelong focus on preventing the major causes of disease and ill health. Realizing this vision calls for health system reforms and policies grounded in tangible evidence for 'what works' and how. This is a fundamental contribution of the research community - but it means providing research evidence that is synthesized, accessible and contextualized, to enhance its applicability in different health systems. That's what this guide is all about. Evidence Synthesis for Health Policy and Systems: A Methods Guide aims to support researchers and decision-makers, wherever they may live in the world, to generate and use high-quality evidence synthesis on health policy and systems. It outlines well-conducted, applied examples of relevant methods and techniques. I trust it will prove useful to researchers and decision-makers everywhere as they seek to play their part in promoting health, keeping the world safe, and serving the vulnerable.

McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome

Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

Impact of vitamin D replacement in adults and elderly in the Middle East and North Africa: a systematic review and meta-analysis of randomized controlled trials.

In the Middle East and North Africa (MENA), a vitamin D dose ≥2000 IU/day may be needed to allow to the majority of the population to reach the target 25-hydroxyvitamin D (25(OH)D) level ≥20 ng/ml. Data in the region on the effect of vitamin D supplementation on various skeletal and extra-skeletal effects are scarce. INTRODUCTION: Hypovitaminosis D is prevalent worldwide, more so in the Middle East and North Africa (MENA). This study aims to determine the effects of vitamin D replacement on the mean difference in 25-hydroxyvitamin D [25(OH)D] level reached and other outcomes, in the MENA. METHODS: This is a meta-analysis of randomized trials from the MENA, administering vitamin D supplementation for at least 3 months, without language or time restriction. We conducted a comprehensive search in seven databases until July 2015. We abstracted data from published reports, independently and in duplicate. We calculated the mean difference (MD) and 95 % CI of 25(OH)D level reached for eligible comparisons, and pooled data using RevMan version 5.3. RESULTS: We identified 2 studies in elderly and 17 in adults; for the latter, 11 were included in the meta-analysis. Comparing a high vitamin D dose (>2000 IU/day) to placebo (nine studies), the MD in 25(OH)D level achieved was 18.3 (CI 14.1; 22.5) ng/ml; p value < 0.001; I 2 = 92 %. Comparing an intermediate dose (800-2000 IU/day) to placebo (two studies), the MD in 25(OH)D level achieved was 14.7 (CI 4.6; 24.9) ng/ml; p value 0.004; I 2 = 91 %. Accordingly, 89 and 71 % of participants, in the high and intermediate dose groups, respectively, reached the desirable level of 20 ng/ml. The risk of bias in the included studies was unclear to high, except for three studies. CONCLUSION: In the MENA region, vitamin D doses ≥2000 IU/day may be needed to reach the target 25(OH)D level ≥20 ng/ml. The long-term safety and the efficacy of such doses on various outcomes are unknown.

Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment

BACKGROUND: It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR. METHODS: We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software. RESULTS: The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost (n = 5 [100%]), impact on health equities (n = 4 [80%]), the balance of benefits and harms (n = 1 [20%]) and acceptability (n = 1 [20%]). CONCLUSION: This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.(AU)

Guideline for opioid therapy and chronic noncancer pain

Guideline for opioid therapy and chronic noncancer pain: the objective is to inform the prescribing of opioids for adults with chronic noncancer pain.

The Saudi clinical practice guideline for the prophylaxis of venous thromboembolism in long-distance travelers

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable disease. Long distant travelers are prone to variable degree to develop VTE. However, the low risk of developing VTE among long-distance travelers and which travelers should receive VTE prophylaxis, and what prophylactic measures should be used led us to develop these guidelines. These clinical practice guidelines are the result of an initiative of the Ministry of Health of the Kingdom of Saudi Arabia involving an expert panel led by the Saudi Association for Venous Thrombo Embolism (a subsidiary of the Saudi Thoracic Society). The McMaster University Guideline working group provided the methodological support. The expert panel identified 5 common questions related to the thromboprophylaxis in long-distance travelers. The corresponding recommendations were made following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Using the Grade Approach to Support the Development of Recommendations for Public Health Interventions in Radiation Emergencies.

The World Health Organization (WHO) guideline development policy requires that WHO guidelines be developed in a manner that is transparent and based on all available evidences, which must be synthesised and formally assessed for quality. To fulfil this requirement, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach of rating quality of evidence and grading strength of recommendations was applied when developing the WHO recommendations on public health interventions in radiation emergencies. The guideline development group (GDG) formulated 10 PICO (P: population; I: intervention; C: comparator; O: outcomes) questions to guide the development of recommendations on response interventions during the early/intermediate and late emergency phases and on risk communications for mitigating psycho-social impact of radiation emergencies. For each PICO question, an extensive evidence search and systematic review was conducted. The GDG then formulated the recommendations using the evidence to recommendation (E-2-R) decision-making matrix and evaluated the strength of each recommendation.

Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis.

BACKGROUND: For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis. METHODS: A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non-perforated appendicitis. Key outcomes were analysed using random-effects meta-analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Five studies including 1116 patients reported major complications in 25 (4·9 per cent) of 510 patients in the antibiotic and 41 (8·4 per cent) of 489 in the appendicectomy group: risk difference -2·6 (95 per cent c.i. -6·3 to 1·1) per cent (low-quality evidence). Minor complications occurred in 11 (2·2 per cent) of 510 and 61 (12·5 per cent) of 489 patients respectively: risk difference -7·2 (-18·1 to 3·8) per cent (very low-quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8·2 (95 per cent c.i. 5·2 to 11·8) per cent (high-quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22·6 (15·6 to 30·4) per cent (high-quality evidence). For every 100 patients with non-perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year. CONCLUSION: The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value- and preference-dependent, suggesting a change in practice towards shared decision-making is necessary.

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015: recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.(AU)

2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis

OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

The Saudi clinical practice guideline for the prophylaxis of venous thromboembolism in medical and critically ill patients

Venous thromboembolism (VTE) acquired during hospitalization is common, yet preventable by the proper implementation of thromboprophylaxis which remains to be underutilized worldwide. As a result of an initiative by the Saudi Ministry of Health to improve medical practices in the country, an expert panel led by the Saudi Association for Venous Thrombo Embolism (SAVTE; a subsidiary of the Saudi Thoracic Society) with the methodological guidance of the McMaster University Guideline working group, produced this clinical practice guideline to assist healthcare providers in VTE prevention. The expert part panel issued ten recommendations addressing 10 prioritized questions in the following areas: thromboprophylaxis in acutely ill medical patients (Recommendations 1-5), thromboprophylaxis in critically ill medical patients (Recommendations 6-9), and thromboprophylaxis in chronically ill patients (Recommendation 10). The corresponding recommendations were generated following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach.

Prophylaxis and treatment of venous thromboembolism in patients with cancer: the Saudi clinical practice guideline

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) is commonly encountered in the daily clinical practice. Cancer is an important VTE risk factor. Proper thromboprophylaxis is key to prevent VTE in patients with cancer, and proper treatment is essential to reduce VTE complications and adverse events associated with the therapy. DESIGN AND SETTINGS: As a result of an initiative of the Ministry of Health of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University working group produced this clinical practice guideline to assist health care providers in evidence-based clinical decision-making for VTE prophylaxis and treatment in patients with cancer. METHODS: Six questions related to thromboprophylaxis and antithrombotic therapy were identified and the corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: Question 1. Should heparin versus no heparin be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation? RECOMMENDATION: For outpatients with cancer, the Saudi Expert Panel suggests against routine thromboprophylaxis with heparin (weak recommendation; moderate quality evidence).Question 2. Should oral anticoagulation versus no oral anticoagulation be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation? RECOMMENDATION: For outpatients with cancer, the Saudi Expert Panel recommends against thromboprophylaxis with oral anticoagulation (strong recommendation; moderate quality evidence).Question 3. Should parenteral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters? RECOMMENDATION: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests thromboprophylaxis with parenteral anticoagulation (weak recommendation; moderate quality evidence).Question 4. Should oral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters? RECOMMENDATION: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests against thromboprophylaxis with oral anticoagulation (weak recommendation; low quality evidence).Question 5. Should low-molecular-weight heparin versus unfractionated heparin be used in patients with cancer being initiated on treatment for venous thromboembolism? RECOMMENDATION: In patients with cancer being initiated on treatment for venous thromboembolism, the Saudi Expert Panel suggests low-molecular-weight heparin over intravenous unfractionated heparin (weak; very low quality evidence).Question 6. Should heparin versus oral anticoagulation be used in patients with cancer requiring long-term treatment of VTE? RECOMMENDATION: In patients with metastatic cancer requiring long-term treatment of VTE, the Saudi Expert Panel recommends low-molecular-weight heparin (LMWH) over vitamin K antagonists (VKAs) (strong recommendation; moderate quality evidence). In patients with non-metastatic cancer requiring long-term treatment of venous thromboembolism, the Saudi Expert Panel suggests LMWH over VKA (weak recommendation; moderate quality evidence).

The allure of the waterpipe: a narrative review of factors affecting the epidemic rise in waterpipe smoking among young persons globally.

OBJECTIVE: The objective of this narrative review is to highlight the determinants of the epidemic rise in waterpipe tobacco smoking (WTS) among youth globally. The Ecological Model of Health Promotion (EMHP) was the guiding framework for the review. DATA SOURCES: The following electronic databases were searched: Cochrane library, MEDLINE, EMBASE, PsycINFO, Web of Science and CINAHL Plus with Full Text. Search terms included waterpipe and its many variant terms. STUDY SELECTION: Articles were included if they were published between 1990 and 2014, were in English, were available in full text and included the age group 10-29 years. DATA EXTRACTION: Articles which analysed determinants of WTS at any of the levels of the EMHP were retained regardless of methodological rigour: 131 articles are included. Articles were coded in a standard template that abstracted methods as well as results. DATA SYNTHESIS: The review found that methodologies used to assess determinants of WTS among youth were often conventional and lacked rigor: 3/4 of the studies were cross-sectional surveys and most enrolled non-representative samples. Within the framework, the review identified determinants of WTS at the intrapersonal, interpersonal, organisational, community and policy levels. CONCLUSIONS: The review suggests potential interventions to control WTS among youth, with emphasis on creative utilisation of social media, and tobacco control policies that include the specificities of WTS. The review further suggests the need for rigorous qualitative work to better contextualise determinants, and prospective observational and experimental studies that track and manipulate them to assess their viability as intervention targets.

The Saudi Clinical Practice Guideline for the treatment of venous thromboembolism: outpatient versus inpatient management

Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is commonly encountered in daily clinical practice. After diagnosis, its management frequently carries significant challenges to the clinical practitioner. Treatment of VTE with the inappropriate modality and/or in the inappropriate setting may lead to serious complications and have life-threatening consequences. As a result of an initiative of the Ministry of Health of the Kingdom of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University Guideline working group, this clinical practice guideline was produced to assist health care providers in VTE management. Two questions were identified and were related to the inpatient versus outpatient treatment of acute DVT, and the early versus standard discharge from hospital for patients with acute PE. The corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.

A guide to GRADE guidelines for the readers of JTH.

More than 70 organizations worldwide have adopted the GRADE methodology for guideline development. The ninth iteration of the American Collage of Chest Physicians guidelines (AT9) adopted structural and policy changes that resulted in a greater adherence to GRADE guidance than previous iterations. The most important of these changes include minimizing the impact of financial and intellectual conflict of interest, increasing the rigor of evidence evaluation, acknowledging uncertainty in estimates of typical values and preferences, and awareness of the large variability in values and preferences. One of the consequences of the greater adherence to GRADE methodology is an increase in weak vs. strong recommendations in AT9. The result of the GRADE process highlights the desirability of higher-quality evidence both regarding the outcomes of alternative management strategies and regarding the distribution of values and preferences in patients considering those alternatives. It also encourages shared decision making in encounters between physicians and patients. Although some physicians might find the uncertainty underlying medical practice discouraging or unsettling, relative to denying or obscuring the uncertainty, acknowledging and addressing the uncertainty will lead to more credible, realistic, and useful recommendations.

Characteristics of physicians practising in Lebanon: a survey.

The last survey of the characteristics of the Lebanese physician workforce, in 1998, raised concerns about the oversupply of physicians and gaps in capacity building. This telephone survey in 2007 of a stratified random sample of physicians describes the demographic, educational and practice characteristics of 546 physicians practising in Lebanon. A majority of the physicians had graduated from an eastern European or a Lebanese medical school, in the1980s or 1990s, and had postgraduate training in a non-primary care specialty, in a western or eastern European country. The greatest numbers were practising solo, in a medical or surgical specialty, in a private hospital and in an urban setting. The average proportion of work time spent in teaching and research were 2.4% and 1.2% respectively. The findings suggest that less emphasis should be placed on training in specialty care compared with primary care/general practice and future policies should aim to attract physicians to rural areas.

Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Numerous randomised controlled trials (RCTs) published in first tier medical journals have evaluated the health effects of diets high in protein. We conducted a rigorous systematic review of RCTs comparing higher- and lower-protein diets. METHODS: We searched several electronic databases up to July 2011 for studies focusing on patient-important outcomes (for example, cardiovascular disease) and secondary outcomes such as risk factors for chronic disease (for example, adiposity). RESULTS: We identified 111 articles reporting on 74 trials. Pooled effect sizes using standardised mean differences (SMDs) were small to moderate and favoured higher-protein diets for weight loss (SMD -0.36, 95% confidence interval (CI) -0.56 to -0.17), body mass index (-0.37, CI -0.56 to 0.19), waist circumference (-0.43, CI -0.69 to -0.16), blood pressure (systolic: -0.21, CI -0.32 to -0.09 and diastolic: -0.18, CI -0.29 to -0.06), high-density lipoproteins (HDL 0.25, CI 0.07 to 0.44), fasting insulin (-0.20, CI -0.39 to -0.01) and triglycerides (-0.51, CI -0.78 to -0.24). Sensitivity analysis of studies with lower risk of bias abolished the effect on HDL and fasting insulin, and reduced the effect on triglycerides. We observed nonsignificant effects on total cholesterol, low-density lipoproteins, C-reactive protein, HbA1c, fasting blood glucose, and surrogates for bone and kidney health. Adverse gastrointestinal events were more common with high-protein diets. Multivariable meta-regression analysis showed no significant dose response with higher protein intake. CONCLUSIONS: Higher-protein diets probably improve adiposity, blood pressure and triglyceride levels, but these effects are small and need to be weighed against the potential for harms.

Introduction to the ninth edition: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines / Introdução à nona edição: terapia antitrombótica e prevenção de trombose, 9ª ed: Diretrizes de prática clínica baseada em evidências do Colégio Americano de Médicos Torácicos

The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines differs substantially from the prior versions both in process and in content. In this introduction, we describe some of the differences and the rationale for the changes.