Gordon H Guyatt

• Distinguished Professor at McMaster University

Supplementary Material for article: Current Practices in Monitoring Children and Adults with X-linked Hypophosphatemia: A Global Survey of Expert Experience Submitted to JCEM

Search strategy for the following Systematic Reviews: 1. Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Adult Patients with X-Linked Hypophosphatemia. 2. Systematic Review: Efficacy of Medical Therapy on Outcomes Important to Pediatric Patients with X-Linked Hypophosphatemia

GRADE Summary of Findings Tables (additional analysis)

Objective We explored the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD). Design Systematic review and network meta-analysis of randomised clinical trials (RCTs). Data Sources MEDLINE, EMBASE, CINAHL, CENTRAL, and SCOPUS were searched to May 2021, and again in January 2023....

Objective We explored the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD). Design Systematic review and network meta-analysis of randomised clinical trials (RCTs). Data sources MEDLINE, EMBASE, CINAHL, CENTRAL, and SCOPUS were searched to May 2021, and again in January 2023. Stu...

Objectives: This GRADE concept article offers systematic reviewers, guideline authors and other users of evidence assistance in addressing randomized trial situations in which interventions or comparators differ from those in the target people, interventions, comparators, outcomes (PICO). To clarify what GRADE considers under indirectness of inter...

Trustworthy clinical practice guidelines represent a fundamental tool to summarize relevant evidence regarding a set of clinical choices and provide guidance for making optimal clinical decisions. Clinicians must differentiate between guidelines that provide trustworthy evidence guidance and those that do not. We present six questions clinicians sh...

Background: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. Objective: To compare the effects of a hypotension-avoidance and...

Introduction Denosumab is an effective antiresorptive molecule and reduces the risk of fracture in postmenopausal osteoporosis. Cessation of denosumab therapy however is associated with rapid declines in bone mineral density (BMD), rises in bone remodeling, and an increased risk of fracture. We evaluated the effect of low dose denosumab (30 mg ever...

Background: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. Objective: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. Design: Rand...

Objective To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. Des...

Background and aims: Performance-based tests of mobility or physical function such as the Timed Up and Go (TUG), gait speed, chair-rise, and single-leg stance (SLS) are often administered using different protocols in aging populations, however, the reliability of their assessment protocols is not often considered. The purpose of this study was to...

Objective: To systematically survey Cochrane reviews' approaches to calculating, presenting and interpreting pooled estimates of patient reported outcome measures (PROMs). Study design and setting: We retrospectively selected 200 Cochrane reviews that met the eligibility criteria. Two researchers independently extracted the pooled effect measure...

Objective To determine the relative efficacy of structured named diet and health behaviour programmes (dietary programmes) for prevention of mortality and major cardiovascular events in patients at increased risk of cardiovascular disease. Design Systematic review and network meta-analysis of randomised controlled trials. Data sources AMED (Allie...

Background The health effects of dietary fats are a controversial issue on which experts and authoritative organizations have often disagreed. Care providers, guideline developers, policy-makers, and researchers use systematic reviews to advise patients and members of the public on optimal dietary habits, and to formulate public health recommendati...

Objectives: To gain insight into formal methods of integrating patient preferences and clinical evidence to inform treatment decisions, we explored patients' experience with a personalised decision analysis intervention, for prophylactic low-molecular-weight heparin (LMWH) in the antenatal period. Design: Mixed-methods explanatory sequential pil...

Objective: To extend the anchor-based minimal important differences (MIDs) credibility instrument by adding an item addressing construct proximity as the alternative to the correlation item. Study design and setting: The credibility instrument includes one core items addressing the correlation between the patient-reported outcome measure (PROM)...

Objectives: To update previous GRADE guidance addressing inconsistency and interpreting subgroup analyses. Study design and setting: Using an iterative process, we consulted with members of the GRADE working group through multiple rounds of written feedback and discussions at GRADE working group meetings. Results: The guidance complements prev...

Background: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. Methods: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome co...

Importance: Improving methodological quality is a priority in the health research community. Finding appropriate methods guidance can be challenging due to heterogeneous terminology, poor indexing in medical databases, and variation in formats. The Library of Guidance for Health Scientists (LIGHTS) is a new searchable database for methods guidance...

Background: Although the time after surgery at which venous thromboembolism (VTE) occurs has major implications for the optimal duration of thromboprophylaxis, a comprehensive summary of the relevant research has been unavailable. We aimed to establish, using optimal meta-analytic techniques, the timing of postoperative VTE up to 4 weeks post-surge...

Importance Patient values and preferences can inform atopic dermatitis (AD) care. Systematic summaries of evidence addressing patient values and preferences have not previously been available. Objective To inform American Academy of Allergy, Asthma & Immunology (AAAAI)/American College of Allergy, Asthma and Immunology (ACAAI) Joint Task Force on...

Unlabelled: RATIONALE, AIMS AND OBJECTIVES: The development of clinical practice guidelines (CPG) suffers from the lack of an explicit and transparent framework for synthesising the key elements necessary to formulate practice recommendations. We matched deliberations of the American Society of Haematology (ASH) CPG panel for the management of pul...

Background: Myocardial injury after noncardiac surgery (MINS) is common and associated with short- and long-term major cardiovascular events. Diagnostic criteria for MINS using Abbott high-sensitivity cardiac troponin I (hs-cTnI) are unknown. Methods: We performed a prospective cohort study of adults who had in-patient noncardiac surgery and mea...

Background: The optimal isolation duration for COVID-19 patients remains unclear. To support an update of WHO Living Clinical management guidelines for COVID-19 (https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2022.2), this rapid systematic review and modelling study addresses the effects of different isolation periods for preventing...

Background: Health is not the only aspect people consider when choosing to consume meat; environmental concerns about the impact of meat (production and distribution) can influence people's meat choices. Methods: We conducted a mixed-methods systematic review, searched six databases from inception to June 2020, and synthesised our findings into...

Background Coronavirus disease 2019 (COVID-19) patients frequently suffer from long-term sequelae, often called “long COVID” or “post COVID-19 condition”. Remdesivir, given in early disease, decreases the risk of hospitalization and potentially mortality. No randomized trials have thus far published long-term follow-up data on any COVID-19 drug tre...

Background and objective The prognostic value of age and other non-hematological factors in predicting outcomes in older patients with newly diagnosed acute myeloid leukemia (AML) undergoing antileukemic therapy is not well understood. We performed a systematic review to determine the association between these factors and mortality and health-relat...

Background The non-causal and causal associations, possible age and sex differences between living alone and all-cause mortality among adults were unclear. We aimed to assess the association and causal relation between living alone and all-cause mortality among community-dwelling adults, addressing the certainty of evidence, possible age and sex di...

Introduction Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction (EGD). This systematic review and individual patient data (IPD) meta-analysis aims to evaluate: 1) mortality, 2) rates of major complications, 3) prognostic factors and 4) the effect of different VA-EC...

Rationale and Objective We sought to elicit patient preferences regarding the use of plasma exchange in ANCA associated vasculitis (AAV) and its tradeoffs of risk of kidney failure and risk of serious infection. Study Design Patient survey Setting & Participants The online survey was circulated to adults with AAV via kidney and vasculitis network...

Importance Racial disparities in treatment benchmarks have been documented among older patients with hip fractures. However, these studies were limited to patient-level evaluations. Objective To assess whether disparities in meeting fracture care time-to-surgery benchmarks exist at the patient level or at the hospital or institutional level using...

Purpose The use of computed tomography (CT) in fractures is time consuming, challenging and suffers from poor inter-surgeon reliability. Convolutional neural networks (CNNs), a subset of artificial intelligence (AI), may overcome shortcomings and reduce clinical burdens to detect and classify fractures. The aim of this review was to summarize liter...

Importance The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain. Objective To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care. Data Sourc...

Importance Chronic, non-cancer pain affects approximately 20–30% of the population in North America, Europe, and Australia, with surgery and trauma frequently cited as inciting events. Prospective studies of fracture patients have demonstrated an association between somatic pre-occupation, poor coping, and low recovery expectations following surger...

Introduction/Background Pharmacological thromboprophylaxis involves balancing lower risk of venous thromboembolism (VTE) against higher risk of bleeding, a trade-off that critically depends on VTE and bleeding risks in the absence of prophylaxis (baseline risk). Baseline risks likely vary between procedures, but their magnitude remains uncertain. A...

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At o...

Objective: Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management. Methods: We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥...

Rationale, aims and objectives: Critics have charged that evidence-based medicine (EBM) overemphasises algorithmic rules over unstructured clinical experience and intuition, but the role of structured decision support systems in improving health outcomes remains uncertain. We aim to assess if delivery of anticoagulant prophylaxis in hospitalised p...

Objective To assess the trustworthiness (ie, complete and consistent reporting of key methods and results between preprint and published trial reports) and impact (ie, effects of preprints on meta-analytic estimates and the certainty of evidence) of preprint trial reports during the covid-19 pandemic. Design Retrospective review. Data sources Wor...

Objectives Randomized controlled trials (RCTs) are the preferred source of evidence for the relative effect of healthcare interventions summarized in knowledge syntheses. Non-randomized studies of interventions (NRSI) may provide replacement, sequential, or complementary evidence to RCTs. The Grading of Recommendations, Assessment, Development and...

Objective To estimate the level of contamination in an encounter-randomized trial evaluating a shared decision-making (SDM) tool. Study design and setting We assessed contamination at three levels: (1) tool contamination (whether the tool was physically present in the usual care encounter), (2) functional contamination (whether components of the S...

Objective To establish whether items included in instruments published in the last decade assessing risk of bias of randomized controlled trials (RCTs) are indeed addressing risk of bias. Study Design and Setting We searched Medline, Embase, Web of Science, and Scopus from 2010 to October 2021 for instruments assessing risk of bias or methodologic...

Hypoparathyroidism is a rare disorder characterized by hypocalcemia in the presence of a low or inappropriately normal parathyroid hormone level. Hypoparathyroidism is most commonly seen after neck surgery, which accounts for approximately 75% of cases, whereas approximately 25% have HypoPT due to non‐surgical causes. In both groups of patients, co...

Aim Whether or not use of intravenous alteplase in combination with endovascular thrombectomy (EVT) improves outcomes versus EVT alone, for acute stroke patients with large vessel occlusion presenting directly to a comprehensive stroke center, is uncertain. Methods Six randomized trials exploring this issue were published, and we synthesized this...

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19...

Background Approximately 1 in 10 patients with a surgically treated open fracture will develop a surgical site infection. The Aqueous-PREP trial will investigate the effect of 10% povidone-iodine versus 4% chlorhexidine in aqueous antiseptic solutions in reducing infections after open fracture surgery. The study protocol was published in April 2020...

Approximately 20% of people infected with COVID-19 develop at least one persistent condition potentially attributable to their SARS-CoV-2 infection. We sought to determine the effectiveness of early COVID-19 treatment interventions on long COVID symptoms. We conducted a multi-arm multi-stage adaptive platform trial at 12 public health clinics in Br...

Chronic hypoparathyroidism (HypoPT) is associated with significant morbidity and impaired quality of life (QoL). The goals of management for chronic HypoPT include improvement in QoL as well as prevention of both hypo‐ and hypercalcemia symptoms and long‐term complications. Several groups have provided consensus statements and guidelines on the man...

Background Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli (eg. allergens, irritants, microbes). The role of environmental allergens (aeroallergens) in triggering AD remains unclear. Objective Systematically synthesize evidence regarding the benefits and harms of allerg...

Objective To identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas. Data source Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2...

Since the last international guidelines were published in 2014 on the evaluation and management of primary hyperparathyroidism (PHPT), new information has become available with regard to evaluation, diagnosis, epidemiology, genetics, classical and non‐classical manifestations, surgical and non‐surgical approaches, and natural history. In order to p...

To develop guidelines for hypoparathyroidism and primary hyperparathyroidism, the panel assembled a panel of experts in parathyroid disorders, general endocrinologists, representatives of the Hypoparathyroidism Association, and systematic review and guideline methodologists. The guideline panel referred to a formal process following Recommendations...

The efficacy and safety of parathyroid hormone (PTH) therapy for managing long‐term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta‐analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management o...

Background Trial recruitment of Black, indigenous, and people of color (BIPOC) is key for interventions that interact with socioeconomic factors and cultural norms, preferences, and values. We report on our experience enrolling BIPOC participants into a multicenter trial of a shared decision-making intervention about anticoagulation to prevent stro...

The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. 1) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of...

There are over 250,000 international treaties that aim to foster global cooperation. But are treaties actually helpful for addressing global challenges? This systematic field-wide evidence synthesis of 224 primary studies and meta-analysis of the higher-quality 82 studies finds treaties have mostly failed to produce their intended effects. The only...

This narrative report summarizes diagnostic criteria for hypoparathyroidism and describes the clinical presentation and underlying genetic causes of the non‐surgical forms. We conducted a comprehensive literature search from January 2000 to January 2021 and included landmark papers before 2000, presenting a comprehensive update of these topics and...

Objective To provide updated guidance on when GRADE users should consider rating down more than one level for imprecision using a minimally contextualized approach. Study design and setting Based on the first GRADE guidance addressing imprecision rating in 2011, a project group within the GRADE Working Group conducted iterative discussions and pre...

Introduction GRADE guidance to rate the certainty domain of imprecision is presently not fully operationalized for rating down by two levels and when different or uncertainty in baseline risks are considered. In addition, there are scenarios in which lowering the certainty of evidence by three levels for imprecision is more appropriate than lowerin...

Background At the initiation of the COVID-19 pandemic, restrictions forced researchers to decide whether to continue their ongoing clinical trials. The PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities) trial is a pragmatic cluster-randomized crossover trial in patients with open and closed...

The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, management, outcomes, presentations, new imaging modalities, target and other organ systems, pregnanc...

Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains regarding both medical and surgical therapy, this systematic review addresses the efficacy and safety of medical therapy in asymptomatic patients or symptomatic patients who decline...

This clinical practice guideline addresses the prevention, diagnosis and management of hypoparathyroidism (HypoPT) and provides evidence‐based recommendations. The HypoPT Task Forces included 4 teams with a total of 50 international experts including representatives from the sponsoring societies. A methodologist (GG) and his team supported the task...

Background: Many patients with end-stage kidney disease (ESKD) have valvular heart disease requiring surgery. The optimal prosthetic valve is not established in this population. We performed a systematic review and meta-analysis to assess outcomes of patients with dialysis-dependent ESKD who received mechanical or bioprosthetic valves. Methods:...

Background Specific treatments targeting Ebola virus are crucial in managing Ebola virus disease. To support the development of clinical practice guidelines on medications for Ebola virus disease, we aimed to evaluate the efficacy and safety of therapies for patients with Ebola virus disease. Methods In this systematic review and network meta-anal...

Background Most systematic reviews of opioids for chronic pain have pooled treatment effects across individual opioids under the assumption they provide similar benefits and harms. We examined the comparative effects of individual opioids for chronic non-cancer pain through a network meta-analysis of randomised controlled trials. Methods We search...

Single-subject trials have a rich history in the behavioral sciences, but a much more limited history in clinical medicine. This chapter deals with a particular single-subject design, the N-of-1 randomized control trial (RCT). N-of-1 RCTs are single-patient multiple crossover studies of an intervention and usually one comparator. Typically, patient...

Network meta-analysis (NMA) is an increasingly popular statistical method of synthesising evidence to assess the comparative benefits and harms of multiple treatments in a single analysis. Several automated software packages facilitate conducting NMA using either of two alternative approaches, Bayesian or frequentist frameworks. Researchers must ch...

Background Among patients who had an ischaemic stroke presenting directly to a stroke centre where endovascular thrombectomy (EVT) is immediately available, there is uncertainty regarding the role of intravenous thrombolysis agents before or concurrently with EVT. To support a rapid guideline, we conducted a systematic review and meta-analysis to e...

Objective: The Grades of Recommendations, Assessment, Development and Evaluation working group recently developed an innovative approach to interpreting results from network meta-analyses (NMA) through minimally and partially contextualised methods; however, the optimal method for presenting results for multiple outcomes using this approach remain...

Objective: We propose an operational definition of conflicts of interest (COI), a framework for categorizing interests, and an approach to assessing whether an interest qualifies as a COI. Study design and setting: We reviewed the literature and conducted methodological studies to inform the development of a draft framework for classifying inter...

Introduction Denosumab is an effective antiresorptive molecule and reduces the risk of fracture in postmenopausal osteoporosis. Cessation of denosumab therapy however is associated with rapid declines in bone mineral density (BMD), rises in bone remodelling and an increased risk of fracture. We evaluated the effect of low dose denosumab (30mg every...

Objective To provide a route map regarding systematic reviews (SRs) of acupuncture therapies that will meet two goals: (1) to identify areas in which more or better evidence is required and (2) to identify acupuncture applications that, although proven effective, remain underused in practice, and thus warrant more effective knowledge dissemination....

Introduction Community-acquired pneumonia (CAP), frequently encountered in both outpatient and inpatient settings, is the leading cause of infectious disease-related mortality. While equipoise regarding the optimal duration of antimicrobial therapy to treat CAP remains, recent studies suggest shorter durations of therapy may achieve optimal outcome...

Objective: To evaluate reporting of minimal important difference (MID) estimates using anchor-based methods for patient-reported outcome measures (PROMs), and the association with reporting deficiencies on their credibility. Study design and setting: Systematic survey of primary studies empirically estimating MIDs. We searched Medline, EMBASE, P...

Objective To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. Design Network meta-analysis. Data sources Medline, EMBASE, and Cochrane Library up to 31 December 2020. Eligibility criteri...

Objective To determine the harms of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in people who need lipid-lowering therapy. Methods This systematic review included randomised controlled trials that compared PCSK9 inhibitors with placebo, standard care or active lipid-lowering comparators in people who need lipid-lowering therapy wit...

Clinical question In adults with low density lipoprotein (LDL) cholesterol levels >1.8 mmol/L (>70 mg/dL) who are already taking the maximum dose of statins or are intolerant to statins, should another lipid-lowering drug be added, either a proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor or ezetimibe, to reduce the risk of major cardiova...

Objective To determine the harms of ezetimibe in people who need lipid-lowering treatment. Design Systematic review and meta-analysis. Data sources Randomised controlled trials and cohort studies. Eligibility criteria for selecting studies Studies comparing ezetimibe with placebo, standard care, or other lipid-lowering agents in people who need...

Background: Corneal abrasion is a common disorder frequently faced by ophthalmologists, emergency physicians, and primary care physicians. Ocular antibiotics are one of the management options for corneal abrasion. A comprehensive summary and synthesis of the evidence on antibiotic prophylaxis in traumatic corneal abrasion is thus far unavailable,...

Background: Randomized controlled trials established the cardiac protection of sodium-glucose cotransporter-2 (SGLT2) inhibitors among adults with type 2 diabetes. New evidence suggests that these results could extend to people without diabetes. Purpose: To evaluate the effect of SGLT2 inhibitors in patients with heart failure, regardless of the...