Physicians found an interactive tool displaying structured evidence summaries for multiple comparisons understandable and useful: a qualitative user testing study.

OBJECTIVES: To evaluate and improve "Making Alternative Treatment Choices Intuitive and Trustworthy" (MATCH-IT)-a digital, interactive decision support tool displaying structured evidence summaries for multiple comparisons-to help physicians interpret and apply evidence from network meta-analysis (NMA) for their clinical decision-making. STUDY DESIGN AND SETTING: We conducted a qualitative user testing study, applying principles from user-centered design in an iterative development process. We recruited a convenience sample of practicing physicians in Norway, Belgium, and Canada, and asked them to interpret structured evidence summaries for multiple comparisons-linked to clinical guideline recommendations-displayed in MATCH-IT. User testing included (a) introduction of a clinical scenario, (b) a think-aloud session with participant-tool interaction, and (c) a semistructured interview. We video recorded, transcribed, and analyzed user tests using directed content analysis. The results informed new updates in MATCH-IT. RESULTS: Distributed across 5 development cycles we tested MATCH-IT with 26 physicians. Of these, 24 (94%) reported either no or sparse prior experience with interpretation of NMA. Physicians perceived MATCH-IT as easy to interpret and navigate, and appreciated its ability to provide an overview of the evidence. Visualization of effects in pictograms and inclusion of information on burden of treatment ("practical issues") were highlighted as potentially useful features in interacting with patients. We also identified problems, including undiscovered functionalities (drag and drop), suboptimal tutorial, and cumbersome navigation of the tool. In addition, physicians wanted definition/explanation of key terms (eg, outcomes and "certainty"), and there were concerns that overwhelming evidence from a large NMA would complicate applicability to clinical practice. This led to several updates with development of a new start page, tutorial, updated user interface for more efficient maneuvering, solutions to display definition of key terms and a "frequently asked questions" section. To facilitate interpretation of large networks, we improved categorization of results using color coding and added filtering functionality. These modifications allowed physicians to focus on interventions of interest and reduce information overload. CONCLUSION: This study provides proof of concept that physicians can use MATCH-IT to understand NMA evidence. Key features of MATCH-IT in a clinical context include providing an overview of the evidence, visualization of effects, and the display of information on burden of treatments. However, unfamiliarity with the Grading of Recommendations Assessment, Development and Evaluation concepts, time constraints, and accessibility at the point of care may be challenges for use. To what extent our results are transferable to real-world clinical contexts remains to be explored.

A systematic review of shared decision making training programs for general practitioners.

BACKGROUND: Shared decision making (SDM) has been presented as the preferred approach for decisions where there is more than one acceptable option and has been identified a priority feature of high-quality patient-centered care. Considering the foundation of trust between general practitioners (GPs) and patients and the variety of diseases in primary care, the primary care context can be viewed as roots of SDM. GPs are requesting training programs to improve their SDM skills leading to a more patient-centered care approach. Because of the high number of training programs available, it is important to overview these training interventions specifically for primary care and to explore how these training programs are evaluated. METHODS: This review was reported in accordance with the PRISMA guideline. Eight different databases were used in December 2022 and updated in September 2023. Risk of bias was assessed using ICROMS. Training effectiveness was analyzed using the Kirkpatrick evaluation model and categorized according to training format (online, live or blended learning). RESULTS: We identified 29 different SDM training programs for GPs. SDM training has a moderate impact on patient (SMD 0.53 95% CI 0.15-0.90) and observer reported SDM skills (SMD 0.59 95%CI 0.21-0.97). For blended training programs, we found a high impact for quality of life (SMD 1.20 95% CI -0.38-2.78) and patient reported SDM skills (SMD 2.89 95%CI -0.55-6.32). CONCLUSION: SDM training improves patient and observer reported SDM skills in GPs. Blended learning as learning format for SDM appears to show better effects on learning outcomes than online or live learning formats. This suggests that teaching facilities designing SDM training may want to prioritize blended learning formats. More homogeneity in SDM measurement scales and evaluation approaches and direct comparisons of different types of educational formats are needed to develop the most appropriate and effective SDM training format. TRIAL REGISTRATION: PROSPERO: A systematic review of shared-decision making training programs in a primary care setting. PROSPERO 2023 CRD42023393385 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023393385 .

Establishing the Reportable Interval for Routine Clinical Laboratory Tests: A Data-Driven Strategy Leveraging Retrospective Electronic Medical Record Data.

BACKGROUND: This paper presents a data-driven strategy for establishing the reportable interval in clinical laboratory testing. The reportable interval defines the range of laboratory result values beyond which reporting should be withheld. The lack of clear guidelines and methodology for determining the reportable interval has led to potential errors in reporting and patient risk. METHODS: To address this gap, the study developed an integrated strategy that combines statistical analysis, expert review, and hypothetical outlier calculations. A large data set from an accredited clinical laboratory was utilized, analyzing over 124 million laboratory test records from 916 distinct tests. The Dixon test was applied to identify outliers and establish the highest and lowest non-outlier result values for each test, which were validated by clinical pathology experts. The methodology also included matching the reportable intervals with relevant Logical Observation Identifiers Names and Codes (LOINC) and Unified Code for Units of Measure (UCUM)-valid units for broader applicability. RESULTS: Upon establishing the reportable interval for 135 routine laboratory tests (493 LOINC codes), we applied these to a primary care laboratory data set of 23 million records, demonstrating their efficacy with over 1% of result records identified as implausible. CONCLUSIONS: We developed and tested a data-driven strategy for establishing reportable intervals utilizing large electronic medical record (EMR) data sets. Implementing the established interval in clinical laboratory settings can improve autoverification systems, enhance data reliability, and reduce errors in patient care. Ongoing refinement and reporting of cases exceeding the reportable limits will contribute to continuous improvement in laboratory result management and patient safety.

Monitoring COVID-19 in Belgian general practice: A tool for syndromic surveillance based on electronic health records.

BACKGROUND: COVID-19 may initially manifest as flu-like symptoms. As such, general practitioners (GPs) will likely to play an important role in monitoring the pandemic through syndromic surveillance. OBJECTIVES: To present a COVID-19 syndromic surveillance tool in Belgian general practices. METHODS: We performed a nationwide observational prospective study in Belgian general practices. The surveillance tool extracted the daily entries of diagnostic codes for COVID-19 and associated conditions (suspected or confirmed COVID-19, acute respiratory infection and influenza-like illness) from electronic medical records. We calculated the 7-day rolling average for these diagnoses and compared them with data from two other Belgian population-based sources (laboratory-confirmed new COVID-19 cases and hospital admissions for COVID-19), using time series analysis. We also collected data from users and stakeholders about the syndromic surveillance tool and performed a thematic analysis. RESULTS: 4773 out of 11,935 practising GPs in Belgium participated in the study. The curve of contacts for suspected COVID-19 followed a similar trend compared with the curves of the official data sources: laboratory-confirmed COVID-19 cases and hospital admissions but with a 10-day delay for the latter. Data were quickly available and useful for decision making, but some technical and methodological components can be improved, such as a greater standardisation between EMR software developers. CONCLUSION: The syndromic surveillance tool for COVID-19 in primary care provides rapidly available data useful in all phases of the COVID-19 pandemic to support data-driven decision-making. Potential enhancements were identified for a prospective surveillance tool.

Data extracted daily from electronic medical records can be used to monitor the COVID-19 pandemic in general practice.The Barometer provided rapidly available data to support data-driven decision-making.Improvements such as a greater standardisation were identified for a potential future tool using the same technology.

The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice.

BACKGROUND: The DAWN antivirals trial was a multicentric, randomised placebo-controlled trial evaluating antiviral medication for COVID-19 in general practice. The trial was prematurely terminated because of insufficient recruitment. AIM: To explore which factors contributed to the premature termination. DESIGN & SETTING: General practice in Belgium. METHOD: Patients were randomised to camostat or placebo (patients and physicians blinded) between June 2021 and July 2022; a third arm evaluating molnupiravir (open label) was opened in March 2022. The outcome assessor was blinded for all comparisons except for the patient reported outcomes in case of molnupiravir. The authors analysed available trial data and evaluated trial context, implementation, and mechanisms of impact based on semi-structured interviews with trial stakeholders. RESULTS: The trial recruited 44 participants; 19 were allocated to camostat (median age 55 years), 8 to molnupiravir (median age 60 years), and 17 to placebo (median age 56 years). There were no serious adverse events in either group. Most difficulties were related to the pandemic context: disruption to routine clinical services; multiple changes to the service model for COVID-19 patients; overwhelmed clinical staff; delays of trial medication; and staff shortages in the sponsor and clinical team. In addition, regulatory approval processes were lengthy and led to additional study procedures. It was felt that the trial started too late, when vaccinations had already begun. CONCLUSION: The DAWN antivirals trial was stopped prematurely. Although many barriers were related to the pandemic itself, hurdles such as a small and inexperienced sponsor and clinical teams, delays in regulatory processes, and research capacity in routine settings could be overcome by established research infrastructure and standardisation of processes.

Infographic summaries for clinical practice guidelines: results from user testing of the BMJ Rapid Recommendations in primary care.

OBJECTIVES: Infographics have the potential to enhance knowledge translation and implementation of clinical practice guidelines at the point of care. They can provide a synoptic view of recommendations, their rationale and supporting evidence. They should be understandable and easy to use. Little evaluation of these infographics regarding user experience has taken place. We explored general practitioners' experiences with five selected BMJ Rapid Recommendation infographics suited for primary care. METHODS: An iterative, qualitative user testing design was applied on two consecutive groups of 10 general practitioners for five selected infographics. The physicians used the infographics before clinical encounters and we performed hybrid think-aloud interviews afterwards. 20 interviews were analysed using the Qualitative Analysis Guide of Leuven. RESULTS: Many clinicians reported that the infographics were simple and rewarding to use, time-efficient and easy to understand. They were perceived as innovative and their knowledge basis as trustworthy and supportive for decision-making. The interactive, expandable format was preferred over a static version as general practitioners focused mainly on the core message. Rapid access through the electronic health record was highly desirable. The main issues were about the use of complex scales and terminology. Understanding terminology related to evidence appraisal as well as the interpretation of statistics and unfamiliar scales remained difficult, despite the infographics. CONCLUSIONS: General practitioners perceive infographics as useful tools for guideline translation and implementation in primary care. They offer information in an enjoyable and user friendly format and are used mainly for rapid, tailored and just in time information retrieval. We recommend future infographic producers to provide information as concise as possible, carefully define the core message and explore ways to enhance the understandability of statistics and difficult concepts related to evidence appraisal. TRIAL REGISTRATION NUMBER: MP011977.

Digital encounter decision aids linked to clinical practice guidelines: results from user testing SHARE-IT decision aids in primary care.

BACKGROUND: Encounter decision aids (EDAs) are tools that can support shared decision making (SDM), up to the clinical encounter. However, adoption of these tools has been limited, as they are hard to produce, to keep up-to-date, and are not available for many decisions. The MAGIC Evidence Ecosystem Foundation has created a new generation of decision aids that are generically produced along digitally structured guidelines and evidence summaries, in an electronic authoring and publication platform (MAGICapp). We explored general practitioners' (GPs) and patients' experiences with five selected decision aids linked to BMJ Rapid Recommendations in primary care. METHODS: We applied a qualitative user testing design to evaluate user experiences for both GPs and patients. We translated five EDAs relevant to primary care, and observed the clinical encounters of 11 GPs when they used the EDA with their patients. We conducted a semi-structured interview with each patient after the consultation and a think-aloud interview with each GPs after multiple consultations. We used the Qualitative Analysis Guide (QUAGOL) for data analysis. RESULTS: Direct observations and user testing analysis of 31 clinical encounters showed an overall positive experience. The EDAs created better involvement in decision making and resulted in meaningful insights for patients and clinicians. The design and its interactive, multilayered structure made the tool enjoyable and well-organized. Difficult terminology, scales and numbers hindered understanding of certain information, which was sometimes perceived as too specialized or even intimidating. GPs thought the EDA was not suitable for every patient. They perceived a learning curve was required and the need for time investment was a concern. The EDAs were considered trustworthy as they were provided by a credible source. CONCLUSIONS: This study showed that EDAs can be useful tools in primary care by supporting actual shared decision making and enhancing patient involvement. The graphical approach and clear representation help patients better understand their options. To overcome barriers such as health literacy and GPs attitudes, effort is still needed to make the EDAs as accessible, intuitive and inclusive as possible through use of plain language, uniform design, rapid access and training. TRIAL REGISTRATION: The study protocol was approved by the The Research Ethics Committee UZ/KU Leuven (Belgium) on 31-10-2019 with reference number MP011977.

The Impact of the COVID-19 Pandemic on the Registration and Care Provision of Mental Health Problems in General Practice: Registry-Based Study.

BACKGROUND: The impact of the COVID-19 pandemic on mental health in general practice remains uncertain. Several studies showed an increase in terms of mental health problems during the pandemic. In Belgium, especially during the first waves of the pandemic, access to general practice was limited. Specifically, it is unclear how this impacted not only the registration of mental health problems itself but also the care for patients with an existing mental health problem. OBJECTIVE: This study aimed to know the impact of the COVID-19 pandemic on (1) the incidence of newly registered mental health problems and (2) the provision of care for patients with mental health problems in general practice, both using a pre-COVID-19 baseline. METHODS: The prepandemic volume of provided care (care provision) for patients with mental health problems was compared to that from 2020-2021 by using INTEGO, a Belgian general practice morbidity registry. Care provision was defined as the total number of new registrations in a patient's electronic medical record. Regression models evaluated the association of demographic factors and care provision in patients with mental health problems, both before and during the pandemic. RESULTS: During the COVID-19 pandemic as compared to before the COVID-19 pandemic, the incidence of registered mental health problems showed a fluctuating course, with a sharp drop in registrations during the first wave. Registrations for depression and anxiety increased, whereas the incidence of registered eating disorders, substance abuse, and personality problems decreased. During the 5 COVID-19 waves, the overall incidence of registered mental health problems dropped during the wave and rose again when measures were relaxed. A relative rise of 8.7% and 40% in volume of provided care, specifically for patients with mental health problems, was seen during the first and second years of the COVID-19 pandemic, respectively. Care provision for patients with mental health problems was higher in older patients, male patients, patients living in center cities (centrumsteden), patients with lower socioeconomic status (SES), native Belgian patients, and patients with acute rather than chronic mental health problems. Compared to prepandemic care provision, a reduction of 10% was observed in people with a low SES. CONCLUSIONS: This study showed (1) a relative overall increase in the registrations of mental health problems in general practice and (2) an increase in care provision for patients with mental health problems in the first 2 years of the COVID-19 pandemic. Low SES remained a determining factor for more care provision, but care provision dropped significantly in people with mental health problems with a low SES. Our findings suggest that the pandemic in Belgium was also largely a "syndemic," affecting different layers of the population disproportionately.

The impact of the Covid-19 pandemic on the incidence of diseases and the provision of primary care: A registry-based study.

INTRODUCTION: The Covid-19 pandemic had a tremendous impact on healthcare but uncertainty remains about the extent to which primary care provision was affected. Therefore, this paper aims to assess the impact on primary care provision and the evolution of the incidence of disease during the first year of the Covid-19 pandemic in Flanders (Belgium). METHODS: Care provision was defined as the number of new entries added to a patient's medical history. Pre-pandemic care provision (February 1, 2018-January 31, 2020) was compared with care provision during the pandemic (February 1, 2020-January 31, 2021). A large morbidity registry (Intego) was used. Regression models compared the effect of demographic characteristics on care provision and on acute and chronic diagnoses incidence both prior and during the pandemic. RESULTS: During the first year of the Covid-19 pandemic, overall care provision increased with 9.1% (95%CI 8.5%;9.6%). There was an increase in acute diagnoses of 5.1% (95%CI 4.2%;6.0%) and a decrease in the selected chronic diagnoses of 12.8% (95% CI 7.0%;18.4%). Obesity was an exception with an overall incidence increase. The pandemic led to strong fluctuations in care provision that were not the same for all types of care and all demographic groups in Flanders. Relative to other groups in the population, the pandemic caused a reduction in care provision for children aged 0-17 year and patients from a lower socio-economic situation. CONCLUSION: This paper strengthened the claim that Covid-19 should be considered as a syndemic instead of a pandemic. During the first Covid-19 year, overall care provision and the incidence of acute diagnoses increased, whereas chronic diseases' incidence decreased, except for obesity diagnoses which increased. More granular, care provision and chronic diseases' incidence decreased during the lockdowns, especially for people with a lower socio-economic status. After the lockdowns they both returned to baseline.

Incidence rates and trends of childhood urinary tract infections and antibiotic prescribing: registry-based study in general practices (2000 to 2020).

BACKGROUND: To improve the management of childhood urinary tract infections, it is essential to understand the incidence rates, testing and treatment strategy. METHODS: A retrospective study using data from 45 to 104 general practices (2000 to 2020) in Flanders (Belgium). We calculated the incidence rates (per 1000 person-years) of cystitis, pyelonephritis, and lab-based urine tests per age (< 2, 2-4, 5-9 and 10-18 years)) and gender in children and performed an autoregressive time-series analysis and seasonality analysis. In children with UTI, we calculated the number of lab-based urine tests and antibiotic prescriptions per person-year and performed an autoregressive time-series analysis. RESULTS: There was a statistically significant increase in the number of UTI episodes from 2000 to 2020 in each age group (p < 0.05), except in boys 2-4 years. Overall, the change in incidence rate was low. In 2020, the incidence rates of cystitis were highest in girls 2-4 years old (40.3 /1000 person-years 95%CI 34.5-46.7) and lowest in boys 10-18 (2.6 /1000 person-years 95%CI 1.8-3.6) The incidence rates of pyelonephritis were highest in girls 2-4 years (5.5, 95%CI 3.5-8.1 /1000 person-years) and children < 2 years of age (boys: 5.4, 95%CI 3.1-8.8 and girls: 4.9, 95%CI 2.7-8.8 /1000 person-years). In children 2-10 years, there was an increase in number of lab-based urine tests per cystitis episode per year and a decrease in total number of electronic antibiotic prescriptions per cystitis episode per year, from 2000 to 2020. In children with cystitis < 10 years in 2020, 51% (95%CI 47-56%) received an electronic antibiotic prescription, of which the majority were broad-spectrum agents. CONCLUSIONS: Over the last 21 years, there was a slight increase in the number of UTI episodes diagnosed in children in Flemish general practices, although the overall change was low. More targeted antibiotic therapy for cystitis in accordance with clinical guidelines is necessary to reduce the use of broad-spectrum agents in children below 10 years.

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis.

OBJECTIVE: To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN: Network meta-analysis. DATA SOURCES: Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES: We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS: We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS: Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk.

PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations.

CLINICAL QUESTION: In adults with low density lipoprotein (LDL) cholesterol levels >1.8 mmol/L (>70 mg/dL) who are already taking the maximum dose of statins or are intolerant to statins, should another lipid-lowering drug be added, either a proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor or ezetimibe, to reduce the risk of major cardiovascular events? If so, which drug is preferred? Having decided to use one, should we add the other lipid-lowering drug? CURRENT PRACTICE: Most guidelines emphasise LDL cholesterol targets in their recommendations for prescribing PCSK9 inhibitors and/or ezetimibe in adults at high risk of experiencing a major adverse cardiovascular event. However, to achieve these goals in very high risk patients with statins alone is almost impossible, so physicians are increasingly considering other lipid-lowering drugs solely for achieving LDL cholesterol treatment goals rather than for achieving important absolute cardiovascular risk reduction. Most guidelines do not systematically assess the cardiovascular benefits of adding PCSK9 inhibitors and/or ezetimibe for all risk groups across primary and secondary prevention, nor do they report, in accordance with explicit judgments of assumed patients' values and preferences, absolute benefits and harms and potential treatment burdens. RECOMMENDATIONS: The guideline panel provided mostly weak recommendations, which means we rely on shared decision making when applying these recommendations. For adults already using statins, the panel suggests adding a second lipid-lowering drug in people at very high and high cardiovascular risk but recommends against adding it in people at low cardiovascular risk. For adults who are intolerant to statins, the panel recommends using a lipid-lowering drug in people at very high and high cardiovascular risk but against adding it in those at low cardiovascular risk. When choosing to add another lipid-lowering drug, the panel suggests ezetimibe in preference to PCSK9 inhibitors. The panel suggests further adding a PCSK9 inhibitor to ezetimibe for adults already taking statins at very high risk and those at very high and high risk who are intolerant to statins. HOW THIS GUIDELINE WAS CREATED: An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified four risk groups of patients (low, moderate, high, and very high cardiovascular risk) and primarily applied an individual patient perspective in moving from evidence to recommendations, though societal issues were a secondary consideration. The panel considered the balance of benefits and harms and burdens of starting a PCSK9 inhibitor and/or ezetimibe, making assumptions of adults' average values and preferences. Interactive evidence summaries and decision aids accompany multi-layered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that also allows re-use and adaptation. THE EVIDENCE: A linked systematic review and network meta-analysis (14 trials including 83 660 participants) of benefits found that PCSK9 inhibitors or ezetimibe probably reduce myocardial infarctions and stroke in patients with very high and high cardiovascular risk, with no impact on mortality (moderate to high certainty evidence), but not in those with moderate and low cardiovascular risk. PCSK9 inhibitors may have similar effects to ezetimibe on reducing non-fatal myocardial infarction or stroke (low certainty evidence). These relative benefits were consistent, but their absolute magnitude varied based on cardiovascular risk in individual patients (for example, for 1000 people treated with PCSK9 inhibitors in addition to statins over five years, benefits ranged from 2 fewer strokes in the lowest risk to 21 fewer in the highest risk). Two systematic reviews on harms found no important adverse events for these drugs (moderate to high certainty evidence). PCSK9 inhibitors require injections that sometimes result in injection site reactions (best estimate 15 more per 1000 in a 5 year timeframe), representing a burden and harm that may matter to patients. The MATCH-IT decision support tool allows you to interact with the evidence and your patients across the alternative options: https://magicevidence.org/match-it/220504dist-lipid-lowering-drugs/. UNDERSTANDING THE RECOMMENDATIONS: The stratification into four cardiovascular risk groups means that, to use the recommendations, physicians need to identify their patient's risk first. We therefore suggest, specific to various geographical regions, using some reliable risk calculators that estimate patients' cardiovascular risk based on a mix of known risk factors. The largely weak recommendations concerning the addition of ezetimibe or PCSK9 inhibitors reflect what the panel considered to be a close balance between small reductions in stroke and myocardial infarctions weighed against the burdens and limited harms.Because of the anticipated large variability of patients' values and preferences, well informed choices warrant shared decision making. Interactive evidence summaries and decision aids linked to the recommendations can facilitate such shared decisions. The strong recommendations against adding another drug in people at low cardiovascular risk reflect what the panel considered to be a burden without important benefits. The strong recommendation for adding either ezetimibe or PCSK9 inhibitors in people at high and very high cardiovascular risk reflect a clear benefit.The panel recognised the key uncertainty in the evidence concerning patient values and preferences, namely that what most people consider important reductions in cardiovascular risks, weighed against burdens and harms, remains unclear. Finally, availability and costs will influence decisions when healthcare systems, clinicians, or people consider adding ezetimibe or PCSK9 inhibitors.

Safety of proprotein convertase subtilisin/kexin 9 inhibitors: a systematic review and meta-analysis.

OBJECTIVE: To determine the harms of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in people who need lipid-lowering therapy. METHODS: This systematic review included randomised controlled trials that compared PCSK9 inhibitors with placebo, standard care or active lipid-lowering comparators in people who need lipid-lowering therapy with the follow-up duration of at least 24 weeks. We summarised the relative effects for potential harms from PCSK9 inhibitors using random-effect pairwise meta-analyses and assessed the certainty of evidence using GRADE (Grading of Recommendation Assessment, Development and Evaluation) for each outcome. RESULTS: We included 32 trials with 65 861 participants (with the median follow-up duration of 40 weeks, ranging from 24 to 146 weeks). The meta-analysis showed an incidence of injection-site reaction leading to discontinuation (absolute incidence of 15 events (95% CI 11 to 20) per 1000 persons in a 5-year time frame, high certainty evidence). PCSK9 inhibitors do not increase the risk of new-onset diabetes mellitus, neurocognitive events, cataracts or gastrointestinal haemorrhage with high certainty evidence. PCSK9 inhibitors probably do not increase the risks of myalgia or muscular pain leading to discontinuation or any adverse events leading to discontinuation with moderate evidence certainty. Given very limited evidence, PCSK9 inhibitors might not increase influenza-like symptoms leading to discontinuation (risk ratio 1.5; 95% CI 0.06 to 36.58). We did not identify credible subgroup analyses results, including shorter versus longer follow-up duration of trials. CONCLUSIONS: PCSK9 inhibitors slightly increase the risk of severe injection-site reaction but not cataracts, gastrointestinal haemorrhage, neurocognitive events, new-onset diabetes or severe myalgia or muscular pain.

Downstream activities after laboratory testing in primary care: an exploratory outcome of the ELMO cluster randomised trial (Electronic Laboratory Medicine Ordering with evidence-based order sets in primary care).

OBJECTIVE: To estimate the rate and type of downstream activities (DAs) after laboratory testing in primary care, with a specific focus on check-up laboratory panels, and to explore the effect of a clinical decision support system (CDSS) for laboratory ordering on these DAs. DESIGN: Cluster randomised clinical trial. SETTING: 72 primary care practices in Belgium, with 272 general practitioners (GPs), randomly assigned to the intervention arm or the control arm. PARTICIPANTS: The study included 10 270 lab panels from 9683 primary care patients (women 55.1%, mean age 56.5). All adult patients who consulted one of the participating GPs during the trial period and needed a laboratory exam were eligible for participation. INTERVENTIONS: GPs in the intervention group used a CDSS integrated into their online laboratory ordering system, while GPs in the control arm used their lab ordering system as usual. The trial duration was 6 months, with another 6 months follow-up. MAIN OUTCOME MEASURES: This publication reports on the exploratory outcome of DAs after an initial laboratory exam and the effect of the CDSS on these DAs. RESULTS: 19.7% of all laboratory panels resulted in further diagnostic procedures (95% CI 18.9% to 20.5%) and 19% (95% CI 18.2% to 19.7%) in treatment changes. Check-up laboratory exams showed similar rates of DAs, with 17.5% (95% CI 13.8% to 21.2%) diagnostic DAs and 18.9% (95% CI 13.9% to 23.9%) treatment changes. Using the CDSS resulted in a significant reduction in downstream referrals (-2.4%; 95% CI -4.2% to -0.6%; p=0008), imaging and endoscopies (-0.9%; 95% CI -1.6% to -0.1%; p=0026) and treatment changes (-5.4%; 95% CI -9.5% to -1.2%; p=0.01). CONCLUSION: This is the largest study so far to examine DAs after laboratory testing. It shows that almost one in three laboratory exams leads to further DAs, even in check-up panels. Using a CDSS for laboratory orders may reduce the rate of some DAs. TRIAL REGISTRATION NUMBER: NCT02950142.

Safety of ezetimibe in lipid-lowering treatment: systematic review and meta-analysis of randomised controlled trials and cohort studies.

Objective: To determine the harms of ezetimibe in people who need lipid-lowering treatment. Design: Systematic review and meta-analysis. Data sources: Randomised controlled trials and cohort studies. Eligibility criteria for selecting studies: Studies comparing ezetimibe with placebo, standard care, or other lipid-lowering agents in people who need lipid-lowering treatment with a follow-up duration of at least six months (or 24 weeks). The relative effects for potential harms of ezetimibe were pooled by use of random effect pairwise meta-analyses for randomised controlled trials and the evidence from observational studies was narratively summarised. The certainty of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation. Results: 48 randomised controlled trials with 28 444 participants (median follow-up 34 weeks, range 24-312 weeks) and four observational studies with 1667 participants (median follow-up 282 weeks, range 72-400 weeks) were included. The meta-analyses of randomised trials showed moderate to high certainty that ezetimibe was not associated with cancer (relative risk 1.01; 95% confidence interval 0.92 to 1.11), fractures (0.90; 0.74 to 1.10), discontinuation due to any adverse event (0.87; 0.74 to 1.03), gastrointestinal adverse events leading to discontinuation (1.34; 0.58 to 3.08), myalgia or muscular pain leading to discontinuation (0.82; 0.51 to 1.33), neurocognitive events (1.48; 0.58 to 3.81), or new-onset diabetes (0.88; 0.61 to 1.28). The narrative analysis of observational studies provided consistent findings. No credible subgroup effects were identified for the harm outcomes, including shorter versus longer follow-up duration of trials. Conclusions: Ezetimibe results in little to no difference in adverse events or other undesirable effects compared with placebo, usual care or other lipid-lowering agents. Review registration: PROSPERO CRD42020187437.

A Tool to Assess the Trustworthiness of Evidence-Based Point-of-Care Information for Health Care Professionals (CAPOCI): Design and Validation Study.

BACKGROUND: User-friendly information at the point of care for health care professionals should be well structured, rapidly accessible, comprehensive, and trustworthy. The reliability of information and the associated methodological process must be clear. There is no standard tool to evaluate the trustworthiness of such point-of-care (POC) information. OBJECTIVE: We aim to develop and validate a new tool for assessment of trustworthiness of evidence-based POC resources to enhance the quality of POC resources and facilitate evidence-based practice. METHODS: We designed the Critical Appraisal of Point-of-Care Information (CAPOCI) tool based on the criteria important for assessment of trustworthiness of POC information, reported in a previously published review. A group of health care professionals and methodologists (the authors of this paper) defined criteria for the CAPOCI tool in an iterative process of discussion and pilot testing until consensus was reached. In the next step, all criteria were subject to content validation with a Delphi study. We invited an international panel of 10 experts to rate their agreement with the relevance and wording of the criteria and to give feedback. Consensus was reached when 70% of the experts agreed. When no consensus was reached, we reformulated the criteria based on the experts' comments for a next round of the Delphi study. This process was repeated until consensus was reached for each criterion. In a last step, the interrater reliability of the CAPOCI tool was calculated with a 2-tailed Kendall tau correlation coefficient to quantify the agreement between 2 users who piloted the CAPOCI tool on 5 POC resources. Two scoring systems were tested: a 3-point ordinal scale and a 7-point Likert scale. RESULTS: After validation, the CAPOCI tool was designed with 11 criteria that focused on methodological quality and author-related information. The criteria assess authorship, literature search, use of preappraised evidence, critical appraisal of evidence, expert opinions, peer review, timeliness and updating, conflict of interest, and commercial support. Interrater agreement showed substantial agreement between 2 users for scoring with the 3-point ordinal scale (τ=.621, P<.01) and scoring with the 7-point Likert scale (τ=.677, P<.01). CONCLUSIONS: The CAPOCI tool may support validation teams in the assessment of trustworthiness of POC resources. It may also provide guidance for producers of POC resources.

BET 1: Do homemade or cloth face masks work as a preventive measure for respiratory virus transmission?

A short-cut review of the available medical literature was carried out to establish whether homemade or cloth face masks can prevent respiratory virus transmission or clinical illness. After abstract review, twelve papers were found to answer this clinical question using the detailed search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that there is currently no direct evidence to support the use of homemade or cloth masks by the general public for protection against viral infections.

Closing schools for SARS-CoV-2: a pragmatic rapid recommendation.

Background: In Belgium, schools closed during the first lockdown in March 2020, with a partial reopening in May. They fully reopened in September. During the summer, infections started to increase in the general population, speeding up in September. Some measures were taken to limit social contacts but those were insufficient to mitigate the exponential rise of infections in October. Children were still receiving all lessons at school at that time and it was questioned whether this position was tenable. We systematically compared the benefits and harms of closing primary and secondary schools and developed a recommendation. Methods: A multidisciplinary panel, including school pupils and teachers, educational experts, clinicians and researchers, produced this recommendation in compliance with the standards for trustworthy rapid guidelines. The recommendation is based on data collected through national surveillance or studies from Belgium, and supported by a rapid literature review. Results: Closing schools during the first lockdown probably resulted in a large learning delay and possibly led to more cases of child abuse. We are uncertain about the effect on the infection rate, hospitalisations, transmission rates, mental health of children, teachers and parents. The panel concluded that the balance of benefits and harms of closing schools clearly shifts against closing schools. Detrimental effects are even worse for vulnerable children. This recommendation is affected by the local virus circulation. Conclusion: The guideline panel issues a strong recommendation against closing schools when the virus circulation is low to moderate, and a weak recommendation against closing schools when the virus circulation is high. It does not apply when the school system cannot function due to lack of teachers, too many children who are at home or a shortage of support services. As the results of international studies are consistent with Belgian study results, this recommendation may also be relevant internationally.

Clinical decision support improves the appropriateness of laboratory test ordering in primary care without increasing diagnostic error: the ELMO cluster randomized trial.

BACKGROUND: Inappropriate laboratory test ordering poses an important burden for healthcare. Clinical decision support systems (CDSS) have been cited as promising tools to improve laboratory test ordering behavior. The objectives of this study were to evaluate the effects of an intervention that integrated a clinical decision support service into a computerized physician order entry (CPOE) on the appropriateness and volume of laboratory test ordering, and on diagnostic error in primary care. METHODS: This study was a pragmatic, cluster randomized, open-label, controlled clinical trial. SETTING: Two hundred eighty general practitioners (GPs) from 72 primary care practices in Belgium. PATIENTS: Patients aged ≥ 18 years with a laboratory test order for at least one of 17 indications: cardiovascular disease management, hypertension, check-up, chronic kidney disease (CKD), thyroid disease, type 2 diabetes mellitus, fatigue, anemia, liver disease, gout, suspicion of acute coronary syndrome (ACS), suspicion of lung embolism, rheumatoid arthritis, sexually transmitted infections (STI), acute diarrhea, chronic diarrhea, and follow-up of medication. INTERVENTIONS: The CDSS was integrated into a computerized physician order entry (CPOE) in the form of evidence-based order sets that suggested appropriate tests based on the indication provided by the general physician. MEASUREMENTS: The primary outcome of the ELMO study was the proportion of appropriate tests over the total number of ordered tests and inappropriately not-requested tests. Secondary outcomes of the ELMO study included diagnostic error, test volume, and cascade activities. RESULTS: CDSS increased the proportion of appropriate tests by 0.21 (95% CI 0.16-0.26, p < 0.0001) for all tests included in the study. GPs in the CDSS arm ordered 7 (7.15 (95% CI 3.37-10.93, p = 0.0002)) tests fewer per panel. CDSS did not increase diagnostic error. The absolute difference in proportions was a decrease of 0.66% (95% CI 1.4% decrease-0.05% increase) in possible diagnostic error. CONCLUSIONS: A CDSS in the form of order sets, integrated within the CPOE improved appropriateness and decreased volume of laboratory test ordering without increasing diagnostic error. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02950142 , registered on October 25, 2016.

Coding Systems for Clinical Decision Support: Theoretical and Real-World Comparative Analysis.

BACKGROUND: Effective clinical decision support systems require accurate translation of practice recommendations into machine-readable artifacts; developing code sets that represent clinical concepts are an important step in this process. Many clinical coding systems are currently used in electronic health records, and it is unclear whether all of these systems are capable of efficiently representing the clinical concepts required in executing clinical decision support systems. OBJECTIVE: The aim of this study was to evaluate which clinical coding systems are capable of efficiently representing clinical concepts that are necessary for translating artifacts into executable code for clinical decision support systems. METHODS: Two methods were used to evaluate a set of clinical coding systems. In a theoretical approach, we extracted all the clinical concepts from 3 preventive care recommendations and constructed a series of code sets containing codes from a single clinical coding system. In a practical approach using data from a real-world setting, we studied the content of 1890 code sets used in an internationally available clinical decision support system and compared the usage of various clinical coding systems. RESULTS: SNOMED CT and ICD-10 (International Classification of Diseases, Tenth Revision) proved to be the most accurate clinical coding systems for most concepts in our theoretical evaluation. In our practical evaluation, we found that International Classification of Diseases (Tenth Revision) was most often used to construct code sets. Some coding systems were very accurate in representing specific types of clinical concepts, for example, LOINC (Logical Observation Identifiers Names and Codes) for investigation results and ATC (Anatomical Therapeutic Chemical Classification) for drugs. CONCLUSIONS: No single coding system seems to fulfill all the needs for representing clinical concepts for clinical decision support systems. Comprehensiveness of the coding systems seems to be offset by complexity and forms a barrier to usability for code set construction. Clinical vocabularies mapped to multiple clinical coding systems could facilitate clinical code set construction.