Using a priority setting exercise to identify priorities for guidelines on newborn and child health in South Africa, Malawi, and Nigeria.

BACKGROUND: Sub-Saharan Africa is the region with the highest under-five mortality rate globally. Child healthcare decisions should be based on rigorously developed evidence-informed guidelines. The Global Evidence, Local Adaptation (GELA) project is enhancing capacity to use global research to develop locally relevant guidelines for newborn and child health in South Africa (SA), Malawi, and Nigeria. The first step in this process was to identify national priorities for newborn and child health guideline development, and this paper describes our approach. METHODS: We followed a good practice method for priority setting, including stakeholder engagement, online priority setting surveys and consensus meetings, conducted separately in South Africa, Malawi and Nigeria. We established national Steering Groups (SG), comprising 10-13 members representing government, academia, and other stakeholders, identified through existing contacts and references, who helped prioritise initial topics identified by research teams and oversaw the process. Various stakeholders were consulted via online surveys to rate the importance of topics, with results informing consensus meetings with SGs where final priority topics were agreed. RESULTS: Based on survey results, nine, 10 and 11 topics were identified in SA, Malawi, and Nigeria respectively, which informed consensus meetings. Through voting and discussion within meetings, and further engagement after the meetings, the top three priority topics were identified in each country. In SA, the topics concerned anemia prevention in infants and young children and post-discharge support for caregivers of preterm and LBW babies. In Malawi, they focused on enteral nutrition in critically ill children, diagnosis of childhood cancers in the community, and caring for neonates. In Nigeria, the topics focused on identifying pre-eclampsia in the community, hand hygiene compliance to prevent infections, and enteral nutrition for LBW and preterm infants. CONCLUSIONS: Through dynamic and iterative stakeholder engagement, we identified three priority topics for guideline development on newborn and child health in SA, Malawi and Nigeria. Topics were specific to contexts, with no overlap, which highlights the importance of contextualised priority setting as well as of the relationships with key decisionmakers who help define the priorities.

Trustworthy guidelines - excellent; customized care tools - even better.

BACKGROUND: The ability to do online searches for health information has led to concerns that patients find the results confusing and that they often lead to expectations for treatments that have little supportive evidence. At the same time, the science of summarizing research evidence has advanced to the point where it is increasingly possible to quantify treatment tradeoffs and to describe the balance between harms and benefits for individual patients. DISCUSSION: Trustworthy clinical practice guidelines provide evidence-based recommendations to health care practitioners based on assessments of study-level averages. In an effort to customize the use of evidence and ensure that choices are consistent with their personal preferences, tools for patients have been developed. Gradually, there is recognition that the audience for high quality evidence is much wider than merely health care professionals - and that there is a case to be made for creating tools that translate existing evidence into tools to help patients and clinicians work together to decide next steps. We observe two processes occurring: first, is the recognition that decision making in healthcare requires collaboration and deliberation, and second, to achieve this, we need tools designed to customize care at the level of individuals.

Proceedings of the Guideline Workshop 2019: Strategies for the Optimization of Guideline Processes in Diabetes, Cardiovascular Diseases, and Kidney Diseases.

The Guideline Workshop 2019, held in October 2019 in Munich, Germany, had the purpose of facilitating discussion on strategies for optimization of guideline processes in diabetes among a group of representatives of renown national and international societies in the field of diabetes, cardiology, and nephrology. Results of this panel's discussions are presented in this article and comprise a variety of suggestions for improving the quality and usability of guidelines, as well as to accelerate the development and responsiveness of guidelines to newly published, relevant data from clinical trials such as cardiovascular outcome trials in diabetes mellitus. These include, but are not limited to, recommendations to optimize presentation of content in guidelines, use of the Grading of Recommendations Assessment, Development, and Evaluation approach to rating the quality of evidence to harmonize guidelines, and utilization of digital health technologies to accelerate, streamline, and optimize communication on relevant data and development of clinical guidelines and necessary updates, while reducing costs. Recognizing that achieving alignment in guideline development among various medical organizations will be a long-term process, representatives from cross-sectional medical organizations relevant to cardio/renal metabolic disease and experts in guideline methodology will work together in the future. Among other activities, it is planned to continue the activity and organize a Guideline Workshop in 2020.

Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: a systematic review and meta-analysis.

BACKGROUND: To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE). METHODS: Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence. RESULTS: We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence. CONCLUSIONS: This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke. TRIAL REGISTRATION: PROSPERO; CRD42017073904.

Development of a Tailored Intervention With Computerized Clinical Decision Support to Improve Quality of Care for Patients With Knee Osteoarthritis: Multi-Method Study.

BACKGROUND: Clinical practice patterns greatly diverge from evidence-based recommendations to manage knee osteoarthritis conservatively before resorting to surgery. OBJECTIVE: This study aimed to tailor a guideline-based computerized decision support (CDS) intervention that facilitates the conservative management of knee osteoarthritis. METHODS: Experts with backgrounds in clinical medicine, research, implementation, or health informatics suggested the most important recommendations for implementation, how to develop an implementation strategy, and how to form the CDS algorithms. In 6 focus group sessions, 8 general practitioners and 22 patients from Norway, Belgium, and Finland discussed the suggested CDS intervention and identified factors that would be most critical for the success of the intervention. The focus group moderators used the GUideline Implementation with DEcision Support checklist, which we developed to support consideration of CDS success factors. RESULTS: The experts prioritized 9 out of 22 recommendations for implementation. We formed the concept for 6 CDS algorithms to support implementation of these recommendations. The focus group suggested 59 unique factors that could affect the success of the presented CDS intervention. Five factors (out of the 59) were prioritized by focus group participants in every country, including the perceived potential to address the information needs of both patients and general practitioners; the credibility of CDS information; the timing of CDS for patients; and the need for personal dialogue about CDS between the general practitioner and the patient. CONCLUSIONS: The focus group participants supported the CDS intervention as a tool to improve the quality of care for patients with knee osteoarthritis through shared, evidence-based decision making. We aim to develop and implement the CDS based on these study results. Future research should address optimal ways to (1) provide patient-directed CDS, (2) enable more patient-specific CDS within the context of patient complexity, and (3) maintain user engagement with CDS over time.

Addition of Ezetimibe to statins for patients at high cardiovascular risk: Systematic review of patient-important outcomes.

Ezetimibe is widely used in combination with statins to reduce low-density lipoprotein. We sought to examine the impact of ezetimibe when added to statins on patient-important outcomes. Medline, EMBASE, CINAHL, and CENTRAL were searched through July, 2016. Randomized controlled trials (RCTs) of ezetimibe combined with statins versus statins alone that followed patients for at least 6 months and reported on at least one of all-cause mortality, cardiovascular deaths, non-fatal myocardial infarctions (MI), and non-fatal strokes were included. Pairs of reviewers extracted study data and assessed risk of bias independently and in duplicate. Quality of evidence was assessed using the GRADE approach. We conducted a narrative review with complementary subgroup and sensitivity analyses. IMPROVE-IT study enrolled 93% of all patients enrolled in the 8 included trials. Our analysis of the IMPROVE-IT study results showed that in patients at high risk of cardiovascular events, ezetimibe added to statins was associated with i) a likely reduction in non-fatal MI (17 fewer/1000 treated over 6 years, moderate certainty in evidence); ii) a possible reduction in non-fatal stroke (6 fewer/1000 treated over 6 years, low certainty); iii) no impact on myopathy (moderate certainty); iv) potentially no impact on all-cause mortality and cardiovascular death (both moderate certainty); and v) possibly no impact on cancer (low certainty). Addition of ezetimibe to moderate-dose statins is likely to result in 17 fewer MIs and possibly 6 fewer strokes/1000 treated over 6 years but is unlikely to reduce all-cause mortality or cardiovascular death. Patients who place a high value on a small absolute reduction in MI and are not adverse to use of an additional medication over a long duration may opt for ezetimibe in addition to statin therapy. Our analysis revealed no increased specific harms associated with addition of ezetimibe to statins.

Dual antiplatelet therapy with aspirin and clopidogrel for acute high risk transient ischaemic attack and minor ischaemic stroke: a clinical practice guideline.

WHAT IS THE ROLE OF DUAL ANTIPLATELET THERAPY AFTER HIGH RISK TRANSIENT ISCHAEMIC ATTACK OR MINOR STROKE? SPECIFICALLY, DOES DUAL ANTIPLATELET THERAPY WITH A COMBINATION OF ASPIRIN AND CLOPIDOGREL LEAD TO A GREATER REDUCTION IN RECURRENT STROKE AND DEATH OVER THE USE OF ASPIRIN ALONE WHEN GIVEN IN THE FIRST 24 HOURS AFTER A HIGH RISK TRANSIENT ISCHAEMIC ATTACK OR MINOR ISCHAEMIC STROKE? AN EXPERT PANEL PRODUCED A STRONG RECOMMENDATION FOR INITIATING DUAL ANTIPLATELET THERAPY WITHIN 24 HOURS OF THE ONSET OF SYMPTOMS, AND FOR CONTINUING IT FOR 10-21 DAYS CURRENT PRACTICE IS TYPICALLY TO USE A SINGLE DRUG.

Multilayered and digitally structured presentation formats of trustworthy recommendations: a combined survey and randomised trial.

OBJECTIVES: To investigate practicing physicians' preferences, perceived usefulness and understanding of a new multilayered guideline presentation format-compared to a standard format-as well as conceptual understanding of trustworthy guideline concepts. DESIGN: Participants attended a standardised lecture in which they were presented with a clinical scenario and randomised to view a guideline recommendation in a multilayered format or standard format after which they answered multiple-choice questions using clickers. Both groups were also presented and asked about guideline concepts. SETTING: Mandatory educational lectures in 7 non-academic and academic hospitals, and 2 settings involving primary care in Lebanon, Norway, Spain and the UK. PARTICIPANTS: 181 practicing physicians in internal medicine (156) and general practice (25). INTERVENTIONS: A new digitally structured, multilayered guideline presentation format and a standard narrative presentation format currently in widespread use. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary outcome was preference for presentation format. Understanding, perceived usefulness and perception of absolute effects were secondary outcomes. RESULTS: 72% (95% CI 65 to 79) of participants preferred the multilayered format and 16% (95% CI 10 to 22) preferred the standard format. A majority agreed that recommendations (multilayered 86% vs standard 91%, p value=0.31) and evidence summaries (79% vs 77%, p value=0.76) were useful in the context of the clinical scenario. 72% of participants randomised to the multilayered format vs 58% for standard formats reported correct understanding of the recommendations (p value=0.06). Most participants elected an appropriate clinical action after viewing the recommendations (98% vs 92%, p value=0.10). 82% of the participants considered absolute effect estimates in evidence summaries helpful or crucial. CONCLUSIONS: Clinicians clearly preferred a novel multilayered presentation format to the standard format. Whether the preferred format improves decision-making and has an impact on patient important outcomes merits further investigation.

Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials.

Objective To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat.Design Systematic review and meta-analysis of randomised control trials.Data sources Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews.Study selection Randomised controlled trials of the addition of corticosteroids to standard clinical care for patients aged 5 or older in emergency department and primary care settings with clinical signs of acute tonsillitis, pharyngitis, or the clinical syndrome of sore throat. Trials were included irrespective of language or publication status.Review methods Reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. Random effects model was used for meta-analyses. Quality of evidence was assessed with the GRADE approach.Results 10 eligible trials enrolled 1426 individuals. Patients who received single low dose corticosteroids (the most common intervention was oral dexamethasone with a maximum dose of 10 mg) were twice as likely to experience pain relief after 24 hours (relative risk 2.2, 95% confidence interval 1.2 to 4.3; risk difference 12.4%; moderate quality evidence) and 1.5 times more likely to have no pain at 48 hours (1.5, 1.3 to 1.8; risk difference 18.3%; high quality). The mean time to onset of pain relief in patients treated with corticosteroids was 4.8 hours earlier (95% confidence interval -1.9 to -7.8; moderate quality) and the mean time to complete resolution of pain was 11.1 hours earlier (-0.4 to -21.8; low quality) than in those treated with placebo. The absolute pain reduction at 24 hours (visual analogue scale 0-10) was greater in patients treated with corticosteroids (mean difference 1.3, 95% confidence interval 0.7 to 1.9; moderate quality). Nine of the 10 trials sought information regarding adverse events. Six studies reported no adverse effects, and three studies reported few adverse events, which were mostly complications related to disease, with a similar incidence in both groups.Conclusion Single low dose corticosteroids can provide pain relief in patients with sore throat, with no increase in serious adverse effects. Included trials did not assess the potential risks of larger cumulative doses in patients with recurrent episodes of acute sore throat.Systematic review registration PROSPERO CRD42017067808.

Values and preferences of women living with HIV who are pregnant, postpartum or considering pregnancy on choice of antiretroviral therapy during pregnancy.

OBJECTIVE: To investigate women's values and preferences regarding antiretroviral therapy (ART) during pregnancy to inform a BMJ Rapid Recommendation. SETTING: Primary studies reporting patient-reported outcomes relevant to decision-making regarding ART in any clinical and geographical setting. PARTICIPANTS: Women living with HIV who are pregnant, postpartum or considering pregnancy. OUTCOME MEASURES: Quantitative measurements and qualitative descriptions of values and preferences in relation to ART during pregnancy. We also included studies on women's reported barriers and facilitators to adherence. We excluded studies correlating objective measures (eg, CD4 count) with adherence, or reporting only outcomes which are not expected to differ between ART alternatives (eg, access to services, knowledge about ART). RESULTS: We included 15 qualitative studies reporting values and preferences about ART in the peripartum period; no study directly studied choice of ART therapy during pregnancy. Six themes emerged: a desire to reduce vertical transmission (nine studies), desire for child to be healthy (five studies), concern about side effects to the child (eight studies), desire for oneself to be healthy (five studies), distress about side effect to oneself (10 studies) and pill burden (two studies). None of the studies weighed the relative importance of these outcomes directly, but pill burden/medication complexity appears to be a lower priority for most women compared with other factors. Overall, the body of evidence was at low risk of bias, with minor limitations. CONCLUSIONS: Women who are or may become pregnant and who are considering ART appear to place a high value on both their own and their children's health. Evidence on the relative importance between these values when choosing between ART regimens is uncertain. There is variability in individual values and preferences among women. This highlights the importance of an individualised women-centred approach, such as shared decision-making when choosing between ART alternatives. TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews:CRD42017057157.

Compression Stockings for Preventing the Postthrombotic Syndrome in Patients with Deep Vein Thrombosis.

OBJECTIVE: We conducted a systematic review and meta-analysis to address benefits and harms of using elastic compression stockings after lower-extremity deep vein thrombosis. METHODS: We searched 7 electronic databases through January 15, 2015, including randomized controlled trials (RCTs)/quasi-randomized trials reporting on elastic compression stocking efficacy on postthrombotic syndrome incidence, recurrent venous thromboembolism, mortality, and acute pain after deep vein thrombosis. Two reviewers independently screened records, extracted data, assessed risk of bias, and assessed confidence in effect estimates using Grading of Recommendations Assessment, Development, and Evaluation methodology. We applied random-effects meta-analysis models. RESULTS: We included 5 RCTs (n = 1418) reporting on postthrombotic syndrome. The hazard ratio (HR) for postthrombotic syndrome with elastic compression stockings was 0.69 (95% confidence interval [CI], 0.47-1.02). We have very low confidence in this estimate due to heterogeneity and inclusion of unblinded studies at high risk of bias. Excluding high risk of bias studies, a single large RCT at low risk of bias provided moderate-quality evidence of no effect on postthrombotic syndrome (HR 1.00; 95% CI, 0.81-1.24). Moderate-quality evidence including all 5 studies suggests no effect of elastic compression stockings on recurrent venous thromboembolism (relative risk [RR] 0.88; 95% CI, 0.63-1.24) or mortality (RR 1.00; 95% CI, 0.73-1.37, 5 studies). Moderate-quality evidence from one large RCT does not suggest effect on acute pain after deep vein thrombosis. CONCLUSIONS: The highest-quality evidence available suggests no effect of elastic compression stockings on postthrombotic syndrome or pain relief, from a single large RCT. However, results for preventing postthrombotic syndrome differ substantially across studies, and future guideline updates should reflect uncertainty about treatment effects. Elastic compression stockings are unlikely to prevent death or recurrent venous thromboembolism.

Remdesivir for severe COVID-19: a clinical practice guideline

Clinical question: What is the role of remdesivir in the treatment of severe covid-19? This guideline was triggered by the ACTT-1 trial published in the New England Journal of Medicine on 22 May 2020.Remdesivir has received worldwide attention as a potentially effective treatment for severe covid-19. After rapid market approval in the US, remdesivir is already being used in clinical practice. The guideline panel makes a weak recommendation for the use of remdesivir in severe covid-19 while recommending continuation of active enrolment of patients into ongoing randomised controlled trials examining remdesivir.How this guideline was created: An international panel of patients, clinicians, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. The panel considered an individual patient perspective and allowed contextual factors (such as resources) to be taken into account for countries and healthcare systems.The evidence: The linked systematic review (published 31 Jul 2020) identified two randomised trials with 1300 participants, showing low certainty evidence that remdesivir may be effective in reducing time to clinical improvement and may decrease mortality in patients with severe covid-19. Remdesivir probably has no important effect on need for invasive mechanical ventilation. Remdesivir may have little or no effect on hospital length of stay.Understanding the recommendation: Most patients with severe covid-19 would likely choose treatment with remdesivir given the potential reduction in time to clinical improvement. However, given the low certainty evidence for critical outcomes and the fact that different perspectives, values, and preferences may alter decisions regarding remdesivir, the panel issued a weak recommendation with strong support for continued recruitment in randomised trials.

A living WHO guideline on drugs for COVID-19

What is the role of drug interventions in the treatment of patients with covid-19? The latest version of this WHO living guidance focuses on remdesivir, following the 15 October 2020 preprint publication of results from the WHO SOLIDARITY trial. It contains a weak or conditional recommendation against the use of remdesivir in hospitalised patients with covid-19 The first version on this living guidance focused on corticosteroids. The strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19 are unchanged.

Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a microsimulation modelling study

OBJECTIVE: To estimate benefits and harms of different colorectal cancer screening strategies, stratified by (baseline) 15-year colorectal cancer risk. DESIGN: Microsimulation modelling study using MIcrosimulation SCreening ANalysis-Colon (MISCAN-Colon).SETTING: A parallel guideline committee (BMJ Rapid Recommendations) defined the time frame and screening interventions, including selection of outcome measures.POPULATION: Norwegian men and women aged 50-79 years with varying 15-year colorectal cancer risk (1-7%).COMPARISONS: Four screening strategies were compared with no screening: biennial or annual faecal immunochemical test (FIT) or single sigmoidoscopy or colonoscopy at 100% adherence. MAIN OUTCOME MEASURES: Colorectal cancer mortality and incidence, burdens, and harms over 15 years of follow-up. The certainty of the evidence was assessed using the GRADE approach. RESULTS: Over 15 years of follow-up, screening individuals aged 50-79 at 3% risk of colorectal cancer with annual FIT or single colonoscopy reduced colorectal cancer mortality by 6 per 1000 individuals. Single sigmoidoscopy and biennial FIT reduced it by 5 per 1000 individuals. Colonoscopy, sigmoidoscopy, and annual FIT reduced colorectal cancer incidence by 10, 8, and 4 per 1000 individuals, respectively. The estimated incidence reduction for biennial FIT was 1 per 1000 individuals. Serious harms were estimated to be between 3 per 1000 (biennial FIT) and 5 per 1000 individuals (colonoscopy); harms increased with older age. The absolute benefits of screening increased with increasing colorectal cancer risk, while harms were less affected by baseline risk. Results were sensitive to the setting defined by the guideline panel. Because of uncertainty associated with modelling assumptions, we applied a GRADE rating of low certainty evidence to all estimates. CONCLUSIONS: Over a 15 year period, all screening strategies may reduce colorectal cancer mortality to a similar extent. Colonoscopy and sigmoidoscopy may also reduce colorectal cancer incidence, while FIT shows a smaller incidence reduction. Harms are rare and of similar magnitude for all screening strategies

Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline

Recent 15-year updates of sigmoidoscopy screening trials provide new evidence on the effectiveness of colorectal cancer screening. Prompted by the new evidence, we asked: "Does colorectal cancer screening make an important difference to health outcomes in individuals initiating screening at age 50 to 79? And which screening option is best?"

Patient values and preferences in decision making for antithrombotic therapy: a systematic review: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: Development of clinical practice guidelines involves making trade-offs between desirable and undesirable consequences of alternative management strategies. Although the relative value of health states to patients should provide the basis for these trade-offs, few guidelines have systematically summarized the relevant evidence. We conducted a systematic review relating to values and preferences of patients considering antithrombotic therapy. METHODS: We included studies examining patient preferences for alternative approaches to antithrombotic prophylaxis and studies that examined, in the context of antithrombotic prophylaxis or treatment, how patients value alternative health states and experiences with treatment. We conducted a systematic search and compiled structured summaries of the results. Steps in the process that involved judgment were conducted in duplicate. RESULTS: We identified 48 eligible studies. Sixteen dealt with atrial fibrillation, five with VTE, four with stroke or myocardial infarction prophylaxis, six with thrombolysis in acute stroke or myocardial infarction, and 17 with burden of antithrombotic treatment. CONCLUSION: Patient values and preferences regarding thromboprophylaxis treatment appear to be highly variable. Participant responses may depend on their prior experience with the treatments or health outcomes considered as well as on the methods used for preference elicitation. It should be standard for clinical practice guidelines to conduct systematic reviews of patient values and preferences in the specific content area.