Clinical practice guideline-inconsistent management of fever and neutropenia in pediatric oncology: A Children's Oncology Group study.

BACKGROUND: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described. METHODS: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015. Patients were randomly selected for chart review by participating sites from a COG-generated list. Care delivered in each episode was adjudicated (CPG-consistent or CPG-inconsistent) against each of five selected recommendations. RESULTS: A total of 107 patients from 22 sites, representing 157 FN episodes, were included. The most common CPG-inconsistent care delivered was omission of pulmonary computerized tomography in patients with persistent FN (60.3%). Of 74 episodes where assessment of four (episodes without persistent FN) or five (episodes with persistent FN) recommendations was possible, CPG-inconsistent care was delivered with respect to at least one recommendation in 63 (85%) episodes. Site size was not associated with CPG-inconsistent care delivery. No statistically significant association between CPG-inconsistent care and fever recurrence was observed. CONCLUSIONS: In this cohort of pediatric patients at high risk of poor FN outcomes, CPG-inconsistent care was common. Opportunities to optimize resource stewardship by boosting supportive care CPG implementation are highlighted.

Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update.

BACKGROUND: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. METHODS: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. RECOMMENDATIONS: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. INTERPRETATION: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

Association Between Inflammatory Bowel Diseases and Celiac Disease: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: There is controversy over the association between celiac disease (CeD) and inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis to assess evidence for an association between CeD and IBD. METHODS: We searched databases including MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, DARE, and SIGLE through June 25, 2019 for studies assessing the risk of CeD in patients with IBD, and IBD in patients with CeD, compared with controls of any type. We used the Newcastle-Ottawa Scale to evaluate the risk of bias and GRADE to assess the certainty of the evidence. RESULTS: We identified 9791 studies and included 65 studies in our analysis. Moderate certainty evidence found an increased risk of CeD in patients with IBD vs controls (risk ratio [RR] 3.96; 95% confidence interval [CI] 2.23-7.02) and increased risk of IBD in patients with CeD vs controls (RR 9.88; 95% CI 4.03-24.21). There was low-certainty evidence for the risk of anti-Saccharomyces antibodies, a serologic marker of IBD, in patients with CeD vs controls (RR 6.22; 95% CI 2.44-15.84). There was low-certainty evidence for no difference in risk of HLA-DQ2 or DQ8 in patients with IBD vs controls (RR 1.04; 95% CI 0.42-2.56), and very low-certainty evidence for an increased risk of anti-tissue transglutaminase in patients with IBD vs controls (RR 1.52; 95% CI 0.52-4.40). Patients with IBD had a slight decrease in risk of anti-endomysial antibodies vs controls (RR 0.70; 95% CI 0.18-2.74), but these results are uncertain. CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of IBD in patients with CeD and increased risk of CeD in patients with IBD, compared with other patient populations. High-quality prospective cohort studies are needed to assess the risk of CeD-specific and IBD-specific biomarkers in patients with IBD and CeD.

Effects of dance on cognitive function in older adults: a systematic review and meta-analysis.

BACKGROUND: dance is a mind-body activity that stimulates neuroplasticity. We explored the effect of dance on cognitive function in older adults. METHODS: we searched MEDLINE, EMBASE, CENTRAL and PsycInfo databases from inception to August 2020 (PROSPERO:CRD42017057138). Inclusion criteria were (i) randomised controlled trials (ii) older adults (aged ≥ 55 years), (iii) intervention-dance and (iv) outcome-cognitive function. Cognitive domains were classified with the Diagnostic and Statistical Manual of Mental Disorders-5 Neurocognitive Framework. Meta-analyses were performed in RevMan5.3 and certainty of evidence with GradePro. RESULTS: we reviewed 3,997 records and included 11 studies (N = 1,412 participants). Seven studies included only healthy older adults and four included those with mild cognitive impairment (MCI). Dance interventions varied in frequency (1-3×/week), time (35-60 minutes), duration (3-12 months) and type. We found a mean difference (MD) = 1.58 (95% confidence interval [CI) = 0.21-2.95) on the Mini Mental State Examination for global cognitive function (moderate-certainty evidence), and the Wechsler Memory Test for learning and memory had an MD = 3.02 (95% CI = 1.38-4.65; low-certainty evidence). On the Trail Making Test-A for complex attention, MD = 3.07 (95% CI = -0.81 to 6.95; high-certainty evidence) and on the Trail Making Test-B for executive function, MD = -4.12 (95% CI = -21.28 to 13.03; moderate-certainty evidence). Subgroup analyses did not suggest consistently greater effects in older adults with MCI. Evidence is uncertain for language, and no studies evaluated social cognition or perceptual-motor function. CONCLUSIONS: dance probably improves global cognitive function and executive function. However, there is little difference in complex attention, and evidence also suggests little effect on learning and memory. Future research is needed to determine the optimal dose and if dance results in greater cognitive benefits than other types of physical activity and exercise.

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence.

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).

Assessing the process and outcome of the development of practice guidelines and recommendations: PANELVIEW instrument development.

BACKGROUND: Guideline recommendations may be affected by flaws in the process, inappropriate panel member selection or conduct, conflicts of interest and other factors. To our knowledge, no validated tool exists to evaluate guideline development from the perspective of those directly involved in the process. Our objective was to develop and validate a universal tool, the PANELVIEW instrument, to assess guideline processes, methods and outcomes from the perspective of the participating guideline panellists and group members. METHODS: We performed a systematic literature search and surveys of guideline groups (identified through contacting international organizations and convenience sampling of working panels) to inform item generation. Subsequent groups of guideline methodologists and panellists reviewed items for face validity and missing items. We used surveys, interviews and expert review for item reduction and phrasing. For reliability assessment and feedback, we tested the PANELVIEW tool in 8 international guideline groups. RESULTS: We surveyed 62 members from 13 guideline panels, contacted 19 organizations and reviewed 20 source documents to generate items. Fifty-three additional key informants provided feedback about phrasing of the items and response options. We reduced the number of items from 95 to 34 across domains that included administration, training, conflict of interest, group dynamics, chairing, evidence synthesis, formulating recommendations and publication. The tool takes about 10 minutes to complete and showed acceptable measurement properties. INTERPRETATION: The PANELVIEW instrument fills a gap by enabling guideline organizations to involve clinicians, patients and other participants in evaluating their guideline processes. The tool can inform quality improvement of existing or new guideline programs, focusing on insight into and transparency of the guideline development process, methods and outcomes.

Dexamethasone dosing for prevention of acute chemotherapy-induced vomiting in pediatric patients: A systematic review.

A systematic review was undertaken to describe dexamethasone doses studied for chemotherapy-induced vomiting (CIV) prophylaxis in pediatric patients and their effects on achieving complete acute CIV control. No dose-finding studies were identified. However, 16 studies assessing pediatric patients who received dexamethasone were included and classified according to the emetogenicity of chemotherapy administered. Eight different total daily dexamethasone doses were administered to patients on day 1 of highly emetogenic chemotherapy: three in conjunction with aprepitant/fosaprepitant plus a 5HT3 antagonist and five in conjunction with a 5HT3 antagonist. Five different total daily dexamethasone doses were administered in conjunction with a 5HT3 antagonist to patients on day 1 of moderately emetogenic chemotherapy. Due to the heterogeneity of studies identified, meta-analysis was not possible. The optimal dexamethasone dose to control acute CIV and to minimize harms in pediatric patients remains uncertain. This is a key area for future research.

Development and use of health outcome descriptors: a guideline development case study.

BACKGROUND: During healthcare guideline development, panel members often have implicit, different definitions of health outcomes that can lead to misunderstandings about how important these outcomes are and how to balance benefits and harms. McMaster GRADE Centre researchers developed 'health outcome descriptors' for standardizing descriptions of health outcomes and overcoming these problems to support the European Commission Initiative on Breast Cancer (ECIBC) Guideline Development Group (GDG). We aimed to determine which aspects of the development, content, and use of health outcome descriptors were valuable to guideline developers. METHODS: We developed 24 health outcome descriptors related to breast cancer screening and diagnosis for the European Commission Breast Guideline Development Group (GDG). Eighteen GDG members provided feedback in written format or in interviews. We then evaluated the process and conducted two health utility rating surveys. RESULTS: Feedback from GDG members revealed that health outcome descriptors are probably useful for developing recommendations and improving transparency of guideline methods. Time commitment, methodology training, and need for multidisciplinary expertise throughout development were considered important determinants of the process. Comparison of the two health utility surveys showed a decrease in standard deviation in the second survey across 21 (88%) of the outcomes. CONCLUSIONS: Health outcome descriptors are feasible and should be developed prior to the outcome prioritization step in the guideline development process. Guideline developers should involve a subgroup of multidisciplinary experts in all stages of development and ensure all guideline panel members are trained in guideline methodology that includes understanding the importance of defining and understanding the outcomes of interest.

Identifying children exposed to maltreatment: a systematic review update.

BACKGROUND: Child maltreatment affects a significant number of children globally. Strategies have been developed to identify children suspected of having been exposed to maltreatment with the aim of reducing further maltreatment and impairment. This systematic review evaluates the accuracy of strategies for identifying children exposed to maltreatment. METHODS: We conducted a systematic search of seven databases: Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Cochrane Libraries, Sociological Abstracts and the Education Resources Information Center. We included studies published from 1961 to July 2, 2019 estimating the accuracy of instruments for identifying potential maltreatment of children, including neglect, physical abuse, emotional abuse, and sexual abuse. We extracted data about accuracy and narratively synthesised the evidence. For five studies-where the population and setting matched known prevalence estimates in an emergency department setting-we calculated false positives and negatives. We assessed risk of bias using QUADAS-2. RESULTS: We included 32 articles (representing 31 studies) that evaluated various identification strategies, including three screening tools (SPUTOVAMO checklist, Escape instrument, and a 6-item screening questionnaire for child sex trafficking). No studies evaluated the effects of identification strategies on important outcomes for children. All studies were rated as having serious risk of bias (often because of verification bias). The findings suggest that use of the SPUTOVAMO and Escape screening tools at the population level (per 100,000) would result in hundreds of children being missed and thousands of children being over identified. CONCLUSIONS: There is low to very low certainty evidence that the use of screening tools may result in high numbers of children being falsely suspected or missed. These harms may outweigh the potential benefits of using such tools in practice (PROSPERO 2016:CRD42016039659).

The safety and efficacy of ferumoxytol in the treatment of iron deficiency: a systematic review and meta-analysis.

INTRODUCTION: Ferumoxytol is an intravenous (IV) iron formulation for treatment of iron deficiency (ID) that faced post-marketing reports of serious adverse events (SAEs). OBJECTIVES: To determine the safety and efficacy of ferumoxytol compared to other iron formulations and placebo. METHODS: We searched the Cochrane Library, Medline, and EMBASE from inception until February 2018 as well as trial registries and reference lists of relevant articles for randomized or quasi-randomized controlled trials. RESULTS: The review included nine studies with 5691 participants. Studies were at low risk of bias. When comparing ferumoxytol to other IV iron formulations, there is moderate quality evidence (QE) of little to no difference in treatment emergent adverse events (TEAEs) (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.80-0.97), treatment related adverse events (TRAEs) (RR 0.73, 95% CI 0.61-0.88), SAEs (RR 1.13, 95% CI 0.77-1.67), hypotension or hypersensitivity reactions (RR 0.58, 95% CI 0.31-1.09), or composite cardiovascular outcomes (RR 0.56, 95% CI 0.24-1.29), low QE of little to no difference in related SAEs (RR 0.55, 95% CI 0.05-6.16), and high QE of little to no difference in the number of patients with an increase in hemoglobin by at least 1 g/dL (RR 1.04, 95% CI 0.96-1.12). Ferumoxytol had less TEAEs compared to oral iron (RR 0.78, 95% CI 0.61-0.98), but more compared to placebo (RR 1.62, 95% CI 1.01-2.61). DISCUSSION: Ferumoxytol is as efficacious and safe as alternative IV iron formulations with no clear safety concerns.

Strategies for eliciting and synthesizing evidence for guidelines in rare diseases.

BACKGROUND: Rare diseases are a global public health priority. Though each disease is rare, when taken together the thousands of known rare diseases cause significant morbidity and mortality, impact quality of life, and confer a social and economic burden on families and communities. These conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment. Clinical practice guidelines are necessary to support clinical and policy decisions. However, creating guidelines for rare diseases presents specific challenges, including a paucity of high certainty evidence to inform panel recommendations. METHODS: This paper draws from the authors' experience in the development of clinical practice guidelines for three rare diseases: hemophilia, sickle cell disease, and catastrophic antiphospholipid syndrome. RESULTS: We have summarized a number of strategies for eliciting and synthesizing evidence that are compatible with the rigorous, internationally accepted standards for guideline development set out by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. These strategies include: use of pre-existing and ad hoc qualitative research, use of systematic observation forms, use of registry data, and thoughtful use of indirect evidence. Their use in three real guideline development efforts, as well as their theoretical underpinnings, are discussed. Avenues for future research to improve clinical practice guideline creation for rare diseases - and any disease affected by a relative lack of evidence - are also identified. CONCLUSIONS: Rigorous clinical practice guidelines are needed to improve the care of the millions of people worldwide who suffer from rare diseases. Innovative evidence elicitation and synthesis methods will benefit not only the rare disease community, but also individuals with common diseases who have rare presentations, suffer rare complications, or require nascent therapies. Further refinement and improved uptake of these innovative methods should lead to higher quality clinical practice guidelines in rare diseases.

Actualisation 2023 des lignes directrices de pratique clinique pour la prise en charge de l'ostéoporose et la prévention des fractures au Canada.

CONTEXTE: Au Canada, plus de 2 millions de personnes vivent avec l'ostéoporose, une maladie qui accroît le risque de fracture, ce qui fait augmenter la morbidité et la mortalité, et entraîne une perte de qualité de vie et d'autonomie. La présente actualisation des lignes directrices vise à accompagner les professionnelles et professionnels de la santé au Canada dans la prestation de soins visant à optimiser la santé osseuse et à prévenir les fractures chez les femmes ménopausées et les hommes de 50 ans et plus. MÉTHODES: Le présent document fournit une actualisation des lignes directrices de pratique clinique de 2010 d'Ostéoporose Canada sur le diagnostic et la prise en charge de l'ostéoporose au pays. Nous avons utilisé l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) et effectué l'assurance de la qualité conformément aux normes de qualité et de présentation des rapports de la grille AGREE II (Appraisal of Guidelines for Research & Evaluation). Les médecins de premier recours et les patientes et patients partenaires ont été représentés à tous les niveaux des comités et des groupes ayant participé à l'élaboration des lignes directrices, et ont participé à toutes les étapes du processus pour garantir la pertinence des informations pour les futurs utilisateurs et utilisatrices. Le processus de gestion des intérêts concurrents a été entamé avant l'élaboration des lignes directrices et s'est poursuivi sur toute sa durée, selon les principes du Réseau international en matière de lignes directrices. Dans la formulation des recommandations, nous avons tenu compte des avantages et des risques, des valeurs et préférences de la patientèle, des ressources, de l'équité, de l'acceptabilité et de la faisabilité; la force de chacune des recommandations a été déterminée en fonction du cadre GRADE. RECOMMANDATIONS: Les 25 recommandations et les 10 énoncés de bonne pratique sont répartis en sections : activité physique, alimentation, évaluation du risque de fracture, instauration du traitement, interventions pharmacologiques, durée et séquence du traitement, et monitorage. La prise en charge de l'ostéoporose devrait se fonder sur le risque de fracture, établi au moyen d'une évaluation clinique réalisée avec un outil d'évaluation du risque de fracture validé. L'activité physique, l'alimentation et la pharmacothérapie sont des éléments essentiels à la stratégie de prévention des fractures, qui devraient être personnalisés. INTERPRÉTATION: Les présentes lignes directrices ont pour but d'outiller les professionnelles et professionnels de la santé et la patientèle afin qu'ensemble ils puissent parler de l'importance de la santé osseuse et du risque de fracture tout au long de la vie adulte avancée. La détection et la prise en charge efficace de la fragilité osseuse peuvent contribuer à réduire les fractures et à préserver la mobilité, l'autonomie et la qualité de vie.

Development of rapid guidelines: 2. A qualitative study with WHO guideline developers.

BACKGROUND: Situations such as public health emergencies and outbreaks necessitate the development and publication of high-quality recommendations within a condensed timeframe. For example, WHO has produced examples of and guidance for the development of rapid guidelines (RGs). However, more information is needed to understand the experiences and perceptions of guideline developers. This is the second of a series of three articles addressing methodological issues around RGs. This study describes the perceptions and experiences of guideline developers at WHO about RGs. METHODS: We conducted interviews consisting of open- and closed-ended questions with guideline developers at WHO. Our analysis described the definition and rationale of RGs, the differences from regular guidelines with regard to timelines from topic definition until publication, barriers to identifying the evidence and the lack of a standard methodology to develop RGs. RESULTS: We interviewed 10 participants, the majority of whom were comfortable with the current WHO definition of RGs. Most stated that the rationale for developing RGs should be in response to new evidence about efficacy, cost-effectiveness or safety. Respondents differed with regards to the amount of time RGs should take. While the majority of participants agreed that guidelines should be based on a systematic review, this step in the process was considered the most time and resource intensive. Challenges for developing RGs included limited personnel and financial resources as well as the lack of evidence. Facilitators, in turn, that may improve RG development include additional financial and personnel resources as well as the use of virtual meetings. CONCLUSIONS: While our study suggests a strong need and rationale for the development of RGs, standardisation of timelines and guidance on panel composition, peer-review process, conduct of meetings and sources of permissible evidence require further research.

Development of rapid guidelines: 1. Systematic survey of current practices and methods.

BACKGROUND: Guidelines in the healthcare field generally should contain evidence-based recommendations to inform healthcare decisions. Guidelines often require 2 years or more to develop, but certain circumstances necessitate the development of rapid guidelines (RGs) in a short period of time. Upholding methodological rigor while meeting the reduced development timeframe presents a challenge for developing RGs. Our objective was to review current practices and standards for the development of RGs. This is the first of a series of three articles addressing methodological issues around RGs. METHODS: We conducted a systematic survey of methods manuals and published RGs to identify reasons for the development of RGs. Data sources included existing guideline manuals, published RGs, Trip Medical Database, MEDLINE, EMBASE and communication with guideline developers until February 2018. RESULTS: We identified 46 guidelines that used a shortened timeframe for their development. Nomenclature describing RGs varied across organisations, wherein the United States Centers for Disease Control and Prevention produced 'Interim Guidelines', the National Institute for Health and Care Excellence in the United Kingdom developed 'Short Clinical Guidelines', and WHO provided 'Rapid Advice'. The rationale for RGs included response to emergencies, rapid increases in cases of a condition or disease severity, or new evidence regarding treatment. In general, the methods to assess the quality of evidence, the consensus process and the management of the conflict of interest were not always clear. While we identified another 11 RGs from other institutions, there was no reference to timeframe and reasons for conducting a RG. The three organisations mentioned above provide guidance for the development of RGs. CONCLUSIONS: There is a lack of standardised nomenclature and definitions regarding RGs and there is inconsistency in the methods described in manuals and in RG. It is therefore important that all RGs provide a detailed and transparent description of their methods in order for readers and end-users to be able to assess their quality and validate their findings.

Using patient values and preferences to inform the importance of health outcomes in practice guideline development following the GRADE approach.

BACKGROUND: There are diverse opinions and confusion about defining and including patient values and preferences (i.e. the importance people place on the health outcomes) in the guideline development processes. This article aims to provide an overview of a process for systematically incorporating values and preferences in guideline development. METHODS: In 2013 and 2014, we followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to adopt, adapt and develop 226 recommendations in 22 guidelines for the Ministry of Health of the Kingdom of Saudi Arabia. To collect context-specific values and preferences for each recommendation, we performed systematic reviews, asked clinical experts to provide feedback according to their clinical experience, and consulted patient representatives. RESULTS: We found several types of studies addressing the importance of outcomes, including those reporting utilities, non-utility measures of health states based on structured questionnaires or scales, and qualitative studies. Guideline panels used the relative importance of outcomes based on values and preferences to weigh the balance of desirable and undesirable consequences of alternative intervention options. However, we found few studies addressing local values and preferences. CONCLUSIONS: Currently there are different but no firmly established processes for integrating patient values and preferences in healthcare decision-making of practice guideline development. With GRADE Evidence-to-Decision (EtD) frameworks, we provide an empirical strategy to find and incorporate values and preferences in guidelines by performing systematic reviews and eliciting information from guideline panel members and patient representatives. However, more research and practical guidance are needed on how to search for relevant studies and grey literature, assess the certainty of this evidence, and best summarize and present the findings.

Cytology versus HPV testing for cervical cancer screening in the general population.

BACKGROUND: Cervical cancer screening has traditionally been based on cervical cytology. Given the aetiological relationship between human papillomavirus (HPV) infection and cervical carcinogenesis, HPV testing has been proposed as an alternative screening test. OBJECTIVES: To determine the diagnostic accuracy of HPV testing for detecting histologically confirmed cervical intraepithelial neoplasias (CIN) of grade 2 or worse (CIN 2+), including adenocarcinoma in situ, in women participating in primary cervical cancer screening; and how it compares to the accuracy of cytological testing (liquid-based and conventional) at various thresholds. SEARCH METHODS: We performed a systematic literature search of articles in MEDLINE and Embase (1992 to November 2015) containing quantitative data and handsearched the reference lists of retrieved articles. SELECTION CRITERIA: We included comparative test accuracy studies if all women received both HPV testing and cervical cytology followed by verification of the disease status with the reference standard, if positive for at least one screening test. The studies had to include women participating in a cervical cancer screening programme who were not being followed up for previous cytological abnormalities. DATA COLLECTION AND ANALYSIS: We completed a 2 x 2 table with the number of true positives (TP), false positives (FP), true negatives (TN), and false negatives for each screening test (HPV test and cytology) used in each study. We calculated the absolute and relative sensitivities and the specificities of the tests for the detection of CIN 2+ and CIN 3+ at various thresholds and computed sensitivity (TP/(TP + TN) and specificity (TN/ (TN + FP) for each test separately. Relative sensitivity and specificity of one test compared to another test were defined as sensitivity of test-1 over sensitivity of test-2 and specificity of test-1 over specificity of test-2, respectively. To assess bias in the studies, we used the Quality Assessment of Diagnostic test Accuracy Studies (QUADAS) tool. We used a bivariate random-effects model for computing pooled accuracy estimates. This model takes into account the within- and between-study variability and the intrinsic correlation between sensitivity and specificity. MAIN RESULTS: We included a total of 40 studies in the review, with more than 140,000 women aged between 20 and 70 years old. Many studies were at low risk of bias. There were a sufficient number of included studies with adequate methodology to perform the following test comparisons: hybrid capture 2 (HC2) (1 pg/mL threshold) versus conventional cytology (CC) (atypical squamous cells of undetermined significance (ASCUS)+ and low-grade squamous intraepithelial lesions (LSIL)+ thresholds) or liquid-based cytology (LBC) (ASCUS+ and LSIL+ thresholds), other high-risk HPV tests versus conventional cytology (ASCUS+ and LSIL+ thresholds) or LBC (ASCUS+ and LSIL+ thresholds). For CIN 2+, pooled sensitivity estimates for HC2, CC and LBC (ASCUS+) were 89.9%, 62.5% and 72.9%, respectively, and pooled specificity estimates were 89.9%, 96.6%, and 90.3%, respectively. The results did not differ by age of women (less than or greater than 30 years old), or in studies with verification bias. Accuracy of HC2 was, however, greater in European countries compared to other countries. The results for the sensitivity of the tests were heterogeneous ranging from 52% to 94% for LBC, and 61% to 100% for HC2. Overall, the quality of the evidence for the sensitivity of the tests was moderate, and high for the specificity.The relative sensitivity of HC2 versus CC for CIN 2+ was 1.52 (95% CI: 1.24 to 1.86) and the relative specificity 0.94 (95% CI: 0.92 to 0.96), and versus LBC for CIN 2+ was 1.18 (95% CI: 1.10 to 1.26) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). The relative sensitivity of HC2 versus CC for CIN 3+ was 1.46 (95% CI: 1.12 to 1.91) and the relative specificity 0.95 (95% CI: 0.93 to 0.97). The relative sensitivity of HC2 versus LBC for CIN 3+ was 1.17 (95% CI: 1.07 to 1.28) and the relative specificity 0.96 (95% CI: 0.95 to 0.97). AUTHORS' CONCLUSIONS: Whilst HPV tests are less likely to miss cases of CIN 2+ and CIN 3+, these tests do lead to more unnecessary referrals. However, a negative HPV test is more reassuring than a negative cytological test, as the cytological test has a greater chance of being falsely negative, which could lead to delays in receiving the appropriate treatment. Evidence from prospective longitudinal studies is needed to establish the relative clinical implications of these tests.

The effectiveness of physiologically based early warning or track and trigger systems after triage in adult patients presenting to emergency departments: a systematic review.

BACKGROUND: Changes to physiological parameters precede deterioration of ill patients. Early warning and track and trigger systems (TTS) use routine physiological measurements with pre-specified thresholds to identify deteriorating patients and trigger appropriate and timely escalation of care. Patients presenting to the emergency department (ED) are undiagnosed, undifferentiated and of varying acuity, yet the effectiveness and cost-effectiveness of using early warning systems and TTS in this setting is unclear. We aimed to systematically review the evidence on the use, development/validation, clinical effectiveness and cost-effectiveness of physiologically based early warning systems and TTS for the detection of deterioration in adult patients presenting to EDs. METHODS: We searched for any study design in scientific databases and grey literature resources up to March 2016. Two reviewers independently screened results and conducted quality assessment. One reviewer extracted data with independent verification of 50% by a second reviewer. Only information available in English was included. Due to the heterogeneity of reporting across studies, results were synthesised narratively and in evidence tables. RESULTS: We identified 6397 citations of which 47 studies and 1 clinical trial registration were included. Although early warning systems are increasingly used in EDs, compliance varies. One non-randomised controlled trial found that using an early warning system in the ED may lead to a change in patient management but may not reduce adverse events; however, this is uncertain, considering the very low quality of evidence. Twenty-eight different early warning systems were developed/validated in 36 studies. There is relatively good evidence on the predictive ability of certain early warning systems on mortality and ICU/hospital admission. No health economic data were identified. CONCLUSIONS: Early warning systems seem to predict adverse outcomes in adult patients of varying acuity presenting to the ED but there is a lack of high quality comparative studies to examine the effect of using early warning systems on patient outcomes. Such studies should include health economics assessments.

Rating the certainty in evidence in the absence of a single estimate of effect.

When studies measure or report outcomes differently, it may not be feasible to pool data across studies to generate a single effect estimate (ie, perform meta-analysis). Instead, only a narrative summary of the effect across different studies might be available. Regardless of whether a single pooled effect estimate is generated or whether data are summarised narratively, decision makers need to know the certainty in the evidence in order to make informed decisions. In this guide, we illustrate how to apply the constructs of the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach to assess the certainty in evidence when a meta-analysis has not been performed and data were summarised narratively.

What do patients and the public know about clinical practice guidelines and what do they want from them? A qualitative study.

BACKGROUND: Guideline producers are increasingly producing versions of guidelines for the public. The aim of this study was to explore what patients and the public understand about the purpose and production of clinical guidelines, and what they want from clinical guidelines to support their healthcare decisions. METHODS: Participants were purposively selected to represent a range of the likely users of patient versions of guidelines, including individuals with health conditions (diabetes and depression), general members of the public, health communication professionals and a group of young people. Participants were asked about their awareness and understanding of clinical guidelines and presented with scenario recommendations, or draft materials from patient guidelines to prompt discussion. Each discussion was facilitated by one or two researchers. All focus groups were recorded and transcribed prior to analysis. Data were analysed using framework analysis. RESULTS: We ran nine focus groups involving 62 individuals, supplemented by four interviews with people experiencing homelessness. Eight groups were held in Scotland, one in England. The four interviews were held in Scotland. The framework analysis yielded five themes: access and awareness; what patients want to know; properties of guidelines; presenting evidence; and format. Awareness of guidelines was low. Participants emphasised the need for information that enables them to choose between treatment options, including harms. They would like help with this from healthcare professionals, especially general practitioners. Participants differed in their support for the inclusion of numerical information and graphs. CONCLUSIONS: Members of the public want information to help them choose between treatments, including information on harms, particularly to support shared decisions with health professionals. Presenting numerical information is a challenge and layered approaches that present information in stages may be helpful. Ignoring the themes identified in this study is likely to lead to materials that fail to support public and patient healthcare decision making.

Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise.

BACKGROUND: Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline would address each item. METHODS: We searched data sources, including manuals of international guideline developers, literature on guidelines for guidelines (with a focus on methodology reports from international and national agencies, and professional societies) and recent articles providing systematic guidance. We reviewed these sources in duplicate, extracted items for the checklist using a sensitive approach and developed overarching topics relevant to guidelines. In an iterative process, we reviewed items for duplication and omissions and involved experts in guideline development for revisions and suggestions for items to be added. RESULTS: We developed a checklist with 18 topics and 146 items and a webpage to facilitate its use by guideline developers. The topics and included items cover all stages of the guideline enterprise, from the planning and formulation of guidelines, to their implementation and evaluation. The final checklist includes links to training materials as well as resources with suggested methodology for applying the items. INTERPRETATION: The checklist will serve as a resource for guideline developers. Consideration of items on the checklist will support the development, implementation and evaluation of guidelines. We will use crowdsourcing to revise the checklist and keep it up to date.