Systematic Review and Meta-analysis of Fenestrated and Chimney/Snorkel Techniques for Endovascular Repair of Juxtarenal Aortic Aneurysms.

OBJECTIVES: Comparative effectiveness of fenestrated endovascular aneurysm repair (FEVAR) and chimney graft endovascular aneurysm repair (ChEVAR) for juxtarenal aortic aneurysms (JAAs) remains unclear. Our objective was to identify and analyze the current body of evidence comparing the effectiveness of both techniques for JAA. METHODS: We performed a systematic review and meta-analysis comparing the effectiveness of FEVAR and ChEVAR for JAA repair. We searched MEDLINE, EMBASE, and Cochrane Register for Controlled Trials from January 1, 1990, for randomized and non-randomized studies assessing outcomes of FEVAR and ChEVAR for JAA repair. Screening, data extraction, risk of bias assessment, and GRADE (Grading of Recommendations, Assessments, Development, and Evaluations) certainty of evidence were performed in duplicate. Data were pooled statistically where possible. RESULTS: Nine retrospective cohort studies comparing the use of FEVAR and ChEVAR for juxtarenal aneurysm were included for meta-analysis. The FEVAR and ChEVAR arms of the meta-analysis consisted of 726 participants and 518 participants, respectively. There were 598 (86.8%) and 332 (81.6%) men in each arm. The mean diameter was larger in the ChEVAR arm (59 mm vs 52.5 mm). Both techniques had similar rates of postoperative 30-day mortality, 3.38% (8/237) versus 3.52% (8/227), acute kidney injury, 16.76% (31/185) versus 17.31% (18/104), and major adverse cardiac events, 7.30% (46/630) versus 6.60% (22/333). The meta-analysis supported the use of FEVAR for most outcomes, with significant advantage for technical success (odds ratio [OR]: 3.24, 95% CI: 1.24-8.42) and avoidance of type 1 endoleak (OR: 5.76, 95% CI: 1.94-17.08), but a disadvantage for spinal cord ischemia (OR: 10.21, 95% CI: 1.21-86.11), which had a very low number of events. The quality of evidence was "moderate" for most outcomes. CONCLUSION: Both endovascular techniques had good safety profiles. The evidence does not support superiority of either FEVAR or ChEVAR for JAA. CLINICAL IMPACT: While lack of equipoise has hampered the design of randomised trials of open versus endovascular repair of juxtarenal aortic aneurysms, concern about the durability of endovascular repair highlights the need for stronger evidence of the comparative efficacy of endovascular techniques. This review performed meta-analysis and evidence appraisal of recent data from large observational studies comparing fenestrated and chimney techniques, using a comprehensive outcome set. Superiority of either intervention could not be established due to differences in participants' baseline risk in each study arm. However, data suggests that both techniques are safe and suitable for use when indicated.

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.

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.

Approaches of integrating the development of guidelines and quality indicators: a systematic review.

BACKGROUND: Guidelines and quality indicators (for example as part of a quality assurance scheme) aim to improve health care delivery and health outcomes. Ideally, the development of quality indicators should be grounded in evidence-based, trustworthy guideline recommendations. However, anecdotally, guidelines and quality assurance schemes are developed independently, by different groups of experts who employ different methodologies. We conducted an extension and update of a previous systematic review to identify, describe and evaluate approaches to the integrated development of guidelines and related quality indicators. METHODS: On May 24th, 2019 we searched in Medline, Embase and CINAHL and included studies if they reported a methodological approach to guideline-based quality indicator development and were published in English, French, or German. RESULTS: Out of 16,034 identified records, we included 17 articles that described a method to integrate guideline recommendations development and quality indicator development. Added to the 13 method articles from original systematic review we included a total 30 method articles. We did not find any evaluation studies. In most approaches, guidelines were a source of evidence to inform the quality indicator development. The criteria to select recommendations (e.g. level of evidence or strength of the recommendation) and to generate, select and assess quality indicators varied widely. We found methodological approaches that linked guidelines and quality indicator development explicitly, however none of the articles reported a conceptual framework that fully integrated quality indicator development into the guideline process or where quality indicator development was part of the question formulation for developing the guideline recommendations. CONCLUSIONS: In our systematic review we found approaches which explicitly linked guidelines with quality indicator development, nevertheless none of the articles reported a comprehensive and well-defined conceptual framework which integrated quality indicator development fully into the guideline development process.

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.

Improving grading of recommendations assessment, development, and evaluation evidence tables part 4: a three-arm noninferiority randomized trial demonstrates improved understanding of content in summary of findings tables with a new format.

OBJECTIVES: To evaluate alternative formats of summary of findings (SoF) tables for single comparison with multiple outcomes. STUDY DESIGN AND SETTING: We conducted a three-arm randomized controlled noninferiority trial (RCT) in the following systematic review (SR) users: researchers, clinical practice guideline developers, health care providers, policymakers, and knowledge transfer organizations to measure understanding, accessibility, satisfaction, and preference across the current grading of recommendations assessment, development, and evaluation (GRADE) SoF, an alternative GRADE SoF, or an adapted evidence-based practice center (EPC) program SoF table. RESULTS: One Hundred Seventy-Nine participants were randomized, and 129 participants completed the RCT (n = 47 current GRADE, n = 41 alternative GRADE, n = 41 adapted EPC). Understanding the certainty of evidence and treatment effect was comparable across groups. The adapted EPC SoF table was inferior for quantifying risk and RD compared to the alternatives (<35% correct vs. >85% correct). Participants reported increased satisfaction when SoF tables presented number needed to treat (NNT), anticipated absolute effect differences, and narrative syntheses for evidence that could not be meta-analyzed. Participants reported accessibility to information as significantly better in both GRADE SoF tables, when compared with the adapted EPC SoF table. Participants preferred the alternative GRADE SoF table format. CONCLUSION: The alternative GRADE SoF table is a promising format for SR users preferring a comprehensive presentation of SR results for single comparisons.

Standardized wording to improve efficiency and clarity of GRADE EtD frameworks in health guidelines.

BACKGROUND: Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence-to-Decision (EtDs) frameworks are increasingly applied by health guideline developers to improve the use of evidence and transparency of health recommendations. Typically, EtDs include 12 criteria but these are flexible and EtDs have been adapted to different types of health decisions. However, developers of health recommendations struggle with the content that they should include in the EtD. The goal of this work was to provide a standardized template that facilitate the development of GRADE EtDs in health guidelines and examples for practical training. METHODS: We began by establishing the need for standardized wording templates in 10 American Society of Hematology guidelines with over 250 recommendations. We drafted template wording, and examples, and sought iterative feedback from methodologists and guideline panels in this guideline and two additional guidelines. RESULTS: We generated templates for all EtD criteria describing the type of research evidence considered, ideally based on systematic reviews, using standardized reporting of effect size, integrating the certainty of evidence and additional considerations. We also produced templates to inform the completion of the EtD conclusions section that includes recommendations, justification, implementation considerations, monitoring and evaluation and research priorities. CONCLUSION: We developed a pragmatic and useful tool to support clarity, transparency, and efficiency of the guideline EtD process.

GRADE guidance 35: update on rating imprecision for assessing contextualized certainty of evidence and making decisions.

OBJECTIVES: Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to rate the certainty domain of imprecision is presently not fully operationalized for rating down by two levels and when different baseline risk or uncertainty in these risks are considered. In addition, there are scenarios in which lowering the certainty of evidence by three levels for imprecision is more appropriate than lowering it by two levels. In this article, we conceptualize and operationalize rating down for imprecision by one, two and three levels for imprecision using the contextualized GRADE approaches and making decisions. METHODS: Through iterative discussions and refinement in online meetings and through email communication, we developed draft guidance to rating the certainty of evidence down by up to three levels based on examples. The lead authors revised the approach according to the feedback and the comments received during these meetings and developed GRADE guidance for how to apply it. We presented a summary of the results to all attendees of the GRADE Working Group meeting for feedback in October 2021 (approximately 80 people) where the approach was formally approved. RESULTS: This guidance provides GRADE's novel approach for the considerations about rating down for imprecision by one, two and three levels based on serious, very serious and extremely serious concerns. The approach includes identifying or defining thresholds for health outcomes that correspond to trivial or none, small, moderate or large effects and using them to rate imprecision. It facilitates the use of evidence to decision frameworks and also provides guidance for how to address imprecision about implausible large effects and trivial or no effects using the concept of the 'review information size' and for varying baseline risks. The approach is illustrated using practical examples, an online calculator and graphical displays and can be applied to dichotomous and continuous outcomes. CONCLUSION: In this GRADE guidance article, we provide updated guidance for how to rate imprecision using the partially and fully contextualized GRADE approaches for making recommendations or decisions, considering alternate baseline risks and for both dichotomous and continuous outcomes.

An International Survey on the Use of Thromboprophylaxis in Urological Surgery.

BACKGROUND: The use of perioperative thromboprophylaxis in urological surgery is common but not standardized. OBJECTIVE: To characterize international practice variation in thromboprophylaxis use in urological surgery. DESIGN, SETTING, AND PARTICIPANTS: We conducted a scenario-based survey addressing the use of mechanical and pharmacological thromboprophylaxis in urological cancer procedures (radical cystectomy [RC], radical prostatectomy [RP], and radical nephrectomy [RN]) among practicing urologists in Canada, Finland, and Japan. The survey presented patient profiles reflecting a spectrum of risk for venous thromboembolism; the respondents described their clinical practice. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The proportion of respondents who routinely used (1) mechanical, (2) pharmacological, and (3) extended pharmacological prophylaxis was stratified by procedure. A logistic regression identified characteristics associated with thromboprophylaxis use. RESULTS AND LIMITATIONS: Of 1051 urologists contacted, 570 (54%) participated in the survey. Japanese urologists were less likely to prescribe pharmacological prophylaxis than Canadian or Finnish urologists (p < 0.001 for all procedures). Canadian and Finnish urologists exhibited large variation for extended pharmacological prophylaxis for RP and RN. Finnish urologists were most likely to prescribe extended prophylaxis versus Canadian and Japanese urologists (RC 98%, 84%, and 26%; Open RP 25%, 8%, and 3%; robotic RP 11%, 9%, and 0%; and RN 43%, 7%, and 1%, respectively; p < 0.001 for each procedure). Less variation was found regarding the prescription of mechanical prophylaxis, which was most commonly used until ambulation or discharge. The length of hospital stay was longer in Japan and may bias estimates of extended prophylaxis in Japan. CONCLUSIONS: We found large variation in clinical practice regarding pharmacological thromboprophylaxis within and between countries. Knowledge translation of evidence-based guidelines may reduce problematic international variation in practice. PATIENT SUMMARY: Use of medications to decrease blood clots after urological cancer surgery differs within and between countries. Closer adherence to urology guidelines addressing the prevention of blood clots may decrease this variation and improve patient outcomes.

Consideration of antimicrobial resistance and contextual factors in infectious disease guidelines: a systematic survey.

OBJECTIVES: Guidelines that include antimicrobial recommendations should explicitly consider contextual factors that influence antimicrobial resistance and their downstream effects on resistance selection. The objectives were to analyse (1) how, and to what extent, tuberculosis, gonorrhoea and respiratory tract infection guidelines are considering antimicrobial resistance; (2) are of acceptable quality and (3) if they can be easily contextualised to fit the needs of specific populations and health systems. METHODS: We conducted a systematic review and searched Ovid MEDLINE and Embase from 1 January 2007 to 7 June 2019 for tuberculosis, gonorrhoea and respiratory tract infection guidelines published in English. We also searched guideline databases, key websites and reference lists. We identified guidelines and recommendations that considered contextual factors including antimicrobial resistance, values, resource use, equity, acceptability and feasibility. We assessed quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool focusing on the domains scope and purpose, rigour of development, and editorial independence. RESULTS: We screened 10 365 records, of which 74 guidelines met inclusion criteria. Of these guidelines, 39% (n=29/74) met acceptable quality scores. Approximately two-thirds of recommendations considered antimicrobial resistance at the population and/or outcome level. Five of the 29 guidelines reported all factors required for recommendation contextualisation. Equity was the least considered across guidelines. DISCUSSION: Relatively few guidelines for highly prevalent infectious diseases are considering resistance at a local level, and many do not consider contextual factors necessary for appropriate antimicrobial use. Improving the quality of guidelines targeting specific regional areas is required. PROSPERO REGISTRATION NUMBER: CRD42020145235.

Supporting effective participation in health guideline development groups: The Guideline Participant Tool.

OBJECTIVES: Health guidelines are a key knowledge translation tool produced and used by numerous stakeholders worldwide. Effective participation in guideline development groups or development groups is crucial for guideline success, yet little guidance exists for members of these groups. In this study, we present the Guideline Participant Tool (GPT) to support effective participation in guideline groups, in particular those using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. STUDY DESIGN AND SETTING: We used a mixed methods and iterative approach to develop a tool to support guideline participation. We used the findings of a published systematic review to develop an initial list of items for considerations for guideline participants. Then, we refined this list through key informant interviews with guideline chairs, sponsors, and participants. Finally, we validated the GPT in three guideline groups with 26 guideline group members. RESULTS: The initial list of items based on 37 articles from the existing systematic review included 15 themes and 61 items for a draft tool. Ten key informant interviews helped us refine the list to include the following themes: selection of participants, guideline group process, and tool format. 26 respondents completed the validation survey from three guideline groups. Refinement of the tool ultimately generated a GPT with 33 items for participant consideration before, during, and in follow-up to guideline group meetings. CONCLUSION: The GPT contains helpful guidance for all guideline participants, particularly those without previous guideline experience. Future research should further explore the need for additional tools to support guideline participants and identify and develop strategies for improving guideline members' participation in guideline groups. This work will be incorporated into INGUIDE.org guideline training and credentialing efforts by the Guidelines International Network and McMaster University.

Controversy and Debate Series on Core Outcome Sets. Paper 3: Debate on Paper 1 from the perspective of GRADE [Grading of Recommendations Assessment, Development and Evaluation].

BACKGROUND AND OBJECTIVES: Outcome measures can be defined as the quality and cost targets health care organizations are trying to improve. Health-related outcomes are used to assess the effect, both positive and negative, of an intervention or treatment. To be meaningful and relevant, outcomes should ideally focus on what matters to the population to whom an intervention is applied and who may experience the outcomes. In this commentary, with a GRADE perspective in mind, we will introduce a conceptual model to address the many health care stakeholders, for example, in health technology assessment (HTA), quality assurance, systematic reviews, guidelines, and coverage decisions, who are involved in making different types of health decisions based on the same health outcomes. We will also propose and describe a method of defining core outcomes that will support reconciliation as well as harmonization across these different fields. STUDY DESIGN AND SETTING: The main focus here is on outcomes that matter most to people including patients, family members, and caregivers. We describe the hub and spokes model for core outcome sets that allows for communication and integration across different disciplines and decision makers. Ideally, the core outcomes, also called main outcomes, would be identical across these fields, including, for instance, a systematic review, an HTA, and a clinical or public health guideline. We illustrate this challenge using examples. RESULTS: We present the hub and spokes model for direct core outcome sets and describe the challenge and solution in what we call the Standardized Outcomes Linking Across StakeholdeRs (SOLAR) system approach. Judgments will have to be made regarding how directly the outcome of interest for decision makers corresponds to the intended outcome and GRADE offers it through its indirectness domain. Health outcome descriptors (HODs) provide a solution to this. CONCLUSION: Relevant stakeholders should strive to harmonize outcome assessment for the different decision-making contexts and describe how the outcomes they use, optimally informed by systematic reviews of the importance of outcomes, relate to harmonized HODs. In the ideal world, decision makers would use the same harmonized HODs and transparently rate the degree of indirectness of the actual outcomes addressed.

More pilot trials could plan to use qualitative data: a meta-epidemiological study.

BACKGROUND: Pilot trials often use quantitative data such as recruitment rate and retention rate to inform the design and feasibility of a larger trial. However, qualitative data such as patient, healthcare provider, and research staff perceptions of an intervention may also provide insights for a larger trial. METHODS: As part of a larger study investigating the reporting of progression criteria in pilot studies, we sought to determine how often pilot studies planned to use qualitative data to inform the design and feasibility of a larger trial and the factors associated with plans to use qualitative data. We searched for protocols of pilot studies of randomized trials in PubMed between 2013 and 2017. RESULTS: We included 227 articles. Only 92 (40.5%; 95% confidence interval [CI] 34.1-47.2) reported plans to collect qualitative data. The factors associated with collecting qualitative data were large studies (defined as sample size ≥ 60; adjusted odds ratio [aOR] 2.77; 95% CI 1.47-5.23; p = 0.002) and studies from Europe (aOR 3.86; 95% CI 1.68-8.88; p = 0.001) compared to North America and the rest of the world. Pilot trials with pharmacological interventions were less likely to plan to collect qualitative data (aOR 0.20; 95% CI 0.07-0.58; p = 0.003). CONCLUSIONS: Qualitative data is not used enough in pilot trials. Large pilot trials, pilot trials from Europe, and pilot trials of non-pharmacological interventions are more likely to plan for qualitative data.

Over half of the WHO guidelines published from 2014 to 2019 explicitly considered health equity issues: a cross-sectional survey.

OBJECTIVE: To evaluate how and to what extent health equity considerations are assessed in World Health Organization (WHO) guidelines. STUDY DESIGN AND SETTING: We evaluated WHO guidelines published between January 2014 and May 2019. Health equity considerations were assessed in relation to differences in baseline risk, importance of outcomes for socially disadvantaged populations, inclusion of health inequity as an outcome, equity-related subgroup analysis, and indirectness in each recommendation. RESULTS: We identified 111 WHO guidelines, and 54% (60 of 111) of these used the Evidence to Decision (EtD) framework. For the 60 guidelines using an EtD framework, the likely impact on health equity was supported by research evidence in 28% of the recommendations (94 of 332). Research evidence was mostly provided as differences in baseline risk (23%, 78/332). Research evidence less frequently addressed the importance of outcomes for socially disadvantaged populations (11%, 36/332), considered indirectness of the evidence for socially disadvantaged populations (2%, 5/332), considered health inequities as an outcome (2%, 5/332) and considered differences in the magnitude of effect in relative terms between disadvantaged and more advantaged populations (1%, 3/332). CONCLUSION: The provision of research evidence to support equity judgements in WHO guidelines is still suboptimal, suggesting the need for better guidance and more training.

Patient values and preferences regarding VTE disease: a systematic review to inform American Society of Hematology guidelines.

Values and preferences relate to the importance that patients place on health outcomes (eg, bleeding, having a deep venous thrombosis) and are essential when weighing benefits and harms in guideline recommendations. To inform the American Society of Hematology guidelines for management of venous thromboembolism (VTE) disease, we conducted a systematic review of patients' values and preferences related to VTE. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature from inception to April of 2018 (PROSPERO-CRD42018094003). We included quantitative and qualitative studies. We followed Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance for rating the certainty and presenting findings for quantitative research about the relative importance of health outcomes and a grounded theory approach for qualitative thematic synthesis. We identified 14 quantitative studies (2465 participants) describing the relative importance of VTE-related health states in a widely diverse population of patients, showing overall small to important impact on patients' lives (certainty of the evidence from low to moderate). Additionally, evidence from 34 quantitative studies (6424 participants) and 15 qualitative studies (570 participants) revealed that patients put higher value on VTE risk reduction than on the potential harms of the treatment (certainty of evidence from low to moderate). Studies also suggested a clear preference for oral medication over subcutaneous medication (moderate certainty). The observed variability in health state values may be a result of differences in the approaches used to elicit them and the diversity of included populations rather than true variability in values. This finding highlights the necessity to explore the variability induced by different approaches to ascertain values.

Evaluating prophylactic heparin in ambulatory patients with solid tumours: a systematic review and individual participant data meta-analysis.

BACKGROUND: Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type. METHODS: In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526. FINDINGS: We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta-analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0·99 (95% CI 0·93-1·06) and a hazard ratio of 1·01 (95% CI 0·96-1·07). The number of patients with venous thromboembolic events was 158 (4·0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7·1%) of 3957 in the control group. Major bleeding events occurred in 71 (1·7%) of 4139 patients in the control population and 88 (2·1%) in the low-molecular-weight heparin group, and minor bleeding events in 478 (12·1%) of 3945 patients with available data in the control group and 652 (16·6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0·58 (95% CI 0·47-0·71) for venous thromboembolism, 1·27 (0·92-1·74) for major bleeding, and 1·34 (1·19-1·51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0·59 [95% CI 0·42-0·81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high. INTERPRETATION: Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival. FUNDING: Canadian Institutes of Health Research.

The Khorana score for prediction of venous thromboembolism in cancer patients: An individual patient data meta-analysis.

BACKGROUND: Oncology guidelines suggest using the Khorana score to select ambulatory cancer patients receiving chemotherapy for primary venous thromboembolism (VTE) prevention, but its performance in different cancers remains uncertain. OBJECTIVE: To examine the performance of the Khorana score in assessing 6-month VTE risk, and the efficacy and safety of low-molecular-weight heparin (LMWH) among high-risk Khorana score patients. METHODS: This individual patient data meta-analysis evaluated (ultra)-LMWH in patients with solid cancer using data from seven randomized controlled trials. RESULTS: A total of 3293 patients from the control groups with an available Khorana score had lung (n = 1913; 58%), colorectal (n = 452; 14%), pancreatic (n = 264; 8%), gastric (n = 201; 6%), ovarian (n = 184; 56%), breast (n = 164; 5%), brain (n = 84; 3%), or bladder cancer (n = 31; 1%). The 6-month VTE incidence was 9.8% among high-risk Khorana score patients and 6.4% among low-to-intermediate-risk patients (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The dichotomous Khorana score performed differently in lung cancer patients (OR 1.1; 95% CI, 0.72-1.7) than in the group with other cancer types (OR 3.2; 95% CI, 1.8-5.6; Pinteraction  = .002). Among high-risk patients, LMWH decreased the risk of VTE by 64% compared with controls (OR 0.36; 95% CI, 0.22-0.58), without increasing the risk of major bleeding (OR 1.1; 95% CI, 0.59-2.1). CONCLUSION: The Khorana score was unable to stratify patients with lung cancer based on their VTE risk. Among those with other cancer types, a high-risk score was associated with a three-fold increased risk of VTE compared with a low-to-intermediate risk score. Thromboprophylaxis was effective and safe in patients with a high-risk Khorana score.

American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients.

BACKGROUND: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality. OBJECTIVE: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery. METHODS: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2). CONCLUSIONS: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.

Evaluation of non-adherence to anti-retroviral therapy, the associated factors and infant outcomes among HIV-positive pregnant women: a prospective cohort study in Lesotho.

INTRODUCTION: Success in addressing prevention of mother-to-child transmission of HIV depends largely on good adherence to anti-retroviral therapy (ART) by pregnant women. Knowledge of the levels of ART adherence among pregnant women is essential to inform strategies to prevent or reduce HIV transmission rates, particularly in African settings. Aim: the primary objective of this study was to measure adherence to anti-retroviral therapy (ART) among pregnant women living with human immunodeficiency virus (HIV). The secondary objectives were to determine: i) the rate of new infections among children at Mabote Filter Clinic in Maseru, Lesotho whose mothers were enrolled in PMTCT, and ii) the factors associated with non-adherence to ART among pregnant women. METHODS: In this prospective cohort study, HIV-positive pregnant women receiving antiretroviral therapy (ART) for prevention of mother to child transmission (PMTCT) were followed up to delivery and their children were tested for HIV. We collected socio-demographic information, knowledge of PMTCT and adherence to ART (three-day recall and pill count) including reasons for non-adherence. We also used logistic regression to explore factors associated with non-adherence. RESULTS: One hundred and seven women were included. The mean (standard deviation) age of the participants was 28.2 (5.7) years. Most, 81.3% (87/107), were married, only 9.3% (10/107) had a postsecondary education. Two-thirds (63.6%: 68/107) of the participants started ART because of PMTCT. Only 78.5% (84/107) of the participants had adequate knowledge of the importance of PMTCT. The three-day self-reported non-adherence rate at the first visit was 7.5% (95% confidence interval (CI): 3.7, 13.1), but up to 43.4% (95% CI: 35.2, 51.9) using pill count. The most frequently reported reasons for not adhering were: running out of pills (7.5%), nausea (5.6%) and to avoid side-effects (3.7%). Women who were employed (odds ratio (OR) 4.35; 95% CI: 1.38,14.29; p = 0.012) and at a higher gestational age (OR = 1.43; 95% CI: 1.11, 1.85; p = 0.006) were more likely to be non-adherent. Only 1 of the 77 exposed infants was found to be positive for HIV at 6 weeks after birth. CONCLUSION: We found a higher non-adherence rate for participants with pill count compared to a three-day adherence self-report. However, mother to child HIV transmission was relatively low. Lack of employment and relatively high gestational age were found to be predictive factors of non-adherence.