Burnout among public health workers in Canada: a cross-sectional study.

BACKGROUND: This study presents the prevalence of burnout among the Canadian public health workforce after three years of the COVID-19 pandemic and its association with work-related factors. METHODS: Data were collected using an online survey distributed through Canadian public health associations and professional networks between November 2022 and January 2023. Burnout was measured using a modified version of the Oldenburg Burnout Inventory (OLBI). Logistic regressions were used to model the relationship between burnout and work-related factors including years of work experience, redeployment to pandemic response, workplace safety and supports, and harassment. Burnout and the intention to leave or retire as a result of the COVID-19 pandemic was explored using multinomial logistic regressions. RESULTS: In 2,079 participants who completed the OLBI, the prevalence of burnout was 78.7%. Additionally, 49.1% of participants reported being harassed because of their work during the pandemic. Burnout was positively associated with years of work experience, redeployment to the pandemic response, being harassed during the pandemic, feeling unsafe in the workplace and not being offered workplace supports. Furthermore, burnout was associated with greater odds of intending to leave public health or retire earlier than anticipated. CONCLUSION: The high levels of burnout among our large sample of Canadian public health workers and its association with work-related factors suggest that public health organizations should consider interventions that mitigate burnout and promote recovery.

User-experience testing of an evidence-to-decision framework for selecting essential medicines.

Essential medicine lists (EMLs) are important medicine prioritization tools used by the World Health Organization (WHO) EML and over 130 countries. The criteria used by WHO's Expert Committee on the Selection and Use of Essential Medicines has parallels to the GRADE Evidence-to-Decision (EtD) frameworks. In this study, we explored the EtD frameworks and a visual abstract as adjunctive tools to strengthen the integrate evidence and improve the transparency of decisions of EML applications. We conducted user-experience testing interviews of key EML stakeholders using Morville's honeycomb model. Interviews explored multifaceted dimensions (e.g., usability) on two EML applications for the 2021 WHO EML-long-acting insulin analogues for diabetes and immune checkpoint inhibitors for lung cancer. Using a pre-determined coding framework and thematic analysis we iteratively improved both the EtD framework and the visual abstract. We coded the transcripts of 17 interviews with 13 respondents in 103 locations of the interview texts across all dimensions of the user-experience honeycomb. Respondents felt the EtD framework and visual abstract presented complementary useful and findable adjuncts to the traditional EML application. They felt this would increase transparency and efficiency in evidence assessed by EML committees. As EtD frameworks are also used in health practice guidelines, including those by the WHO, respondents articulated that the adoption of the EtD by EML applications represents a tangible mechanism to align EMLs and guidelines, decrease duplication of work and improve coordination. Improvements were made to clarify instructions for the EtD and visual abstract, and to refine the design and content included. 'Availability' was added as an additional criterion for EML applications to highlight this criterion in alignment with WHO EML criteria. EtD frameworks and visual abstracts present additional important tools to communicate evidence and support decision-criteria in EML applications, which have global health impact. Access to essential medicines is important for achieving universal health coverage, and the development of essential medicine lists should be as evidence-based and trustworthy as possible.

Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.

BACKGROUND: Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear. This is an update of a Cochrane review published in 2015. OBJECTIVES: To compare the efficacy and safety, through network meta-analysis, of interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1-a and beta 1-b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS. SEARCH METHODS: CENTRAL, MEDLINE, Embase, and two trials registers were searched on 21 September 2021 together with reference checking, citation searching and contact with study authors to identify additional studies. A top-up search was conducted on 8 August 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) that studied one or more of the available immunomodulators and immunosuppressants as monotherapy in comparison to placebo or to another active agent, in adults with RRMS. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and extracted data. We considered both direct and indirect evidence and performed data synthesis by pairwise and network meta-analysis. Certainty of the evidence was assessed by the GRADE approach. MAIN RESULTS: We included 50 studies involving 36,541 participants (68.6% female and 31.4% male). Median treatment duration was 24 months, and 25 (50%) studies were placebo-controlled. Considering the risk of bias, the most frequent concern was related to the role of the sponsor in the authorship of the study report or in data management and analysis, for which we judged 68% of the studies were at high risk of other bias. The other frequent concerns were performance bias (34% judged as having high risk) and attrition bias (32% judged as having high risk). Placebo was used as the common comparator for network analysis. Relapses over 12 months: data were provided in 18 studies (9310 participants). Natalizumab results in a large reduction of people with relapses at 12 months (RR 0.52, 95% CI 0.43 to 0.63; high-certainty evidence). Fingolimod (RR 0.48, 95% CI 0.39 to 0.57; moderate-certainty evidence), daclizumab (RR 0.55, 95% CI 0.42 to 0.73; moderate-certainty evidence), and immunoglobulins (RR 0.60, 95% CI 0.47 to 0.79; moderate-certainty evidence) probably result in a large reduction of people with relapses at 12 months. Relapses over 24 months: data were reported in 28 studies (19,869 participants). Cladribine (RR 0.53, 95% CI 0.44 to 0.64; high-certainty evidence), alemtuzumab (RR 0.57, 95% CI 0.47 to 0.68; high-certainty evidence) and natalizumab (RR 0.56, 95% CI 0.48 to 0.65; high-certainty evidence) result in a large decrease of people with relapses at 24 months. Fingolimod (RR 0.54, 95% CI 0.48 to 0.60; moderate-certainty evidence), dimethyl fumarate (RR 0.62, 95% CI 0.55 to 0.70; moderate-certainty evidence), and ponesimod (RR 0.58, 95% CI 0.48 to 0.70; moderate-certainty evidence) probably result in a large decrease of people with relapses at 24 months. Glatiramer acetate (RR 0.84, 95%, CI 0.76 to 0.93; moderate-certainty evidence) and interferon beta-1a (Avonex, Rebif) (RR 0.84, 95% CI 0.78 to 0.91; moderate-certainty evidence) probably moderately decrease people with relapses at 24 months. Relapses over 36 months findings were available from five studies (3087 participants). None of the treatments assessed showed moderate- or high-certainty evidence compared to placebo. Disability worsening over 24 months was assessed in 31 studies (24,303 participants). Natalizumab probably results in a large reduction of disability worsening (RR 0.59, 95% CI 0.46 to 0.75; moderate-certainty evidence) at 24 months. Disability worsening over 36 months was assessed in three studies (2684 participants) but none of the studies used placebo as the comparator. Treatment discontinuation due to adverse events data were available from 43 studies (35,410 participants). Alemtuzumab probably results in a slight reduction of treatment discontinuation due to adverse events (OR 0.39, 95% CI 0.19 to 0.79; moderate-certainty evidence). Daclizumab (OR 2.55, 95% CI 1.40 to 4.63; moderate-certainty evidence), fingolimod (OR 1.84, 95% CI 1.31 to 2.57; moderate-certainty evidence), teriflunomide (OR 1.82, 95% CI 1.19 to 2.79; moderate-certainty evidence), interferon beta-1a (OR 1.48, 95% CI 0.99 to 2.20; moderate-certainty evidence), laquinimod (OR 1.49, 95 % CI 1.00 to 2.15; moderate-certainty evidence), natalizumab (OR 1.57, 95% CI 0.81 to 3.05), and glatiramer acetate (OR 1.48, 95% CI 1.01 to 2.14; moderate-certainty evidence) probably result in a slight increase in the number of people who discontinue treatment due to adverse events. Serious adverse events (SAEs) were reported in 35 studies (33,998 participants). There was probably a trivial reduction in SAEs amongst people with RRMS treated with interferon beta-1b as compared to placebo (OR 0.92, 95% CI 0.55 to 1.54; moderate-certainty evidence). AUTHORS' CONCLUSIONS: We are highly confident that, compared to placebo, two-year treatment with natalizumab, cladribine, or alemtuzumab decreases relapses more than with other DMTs. We are moderately confident that a two-year treatment with natalizumab may slow disability progression. Compared to those on placebo, people with RRMS treated with most of the assessed DMTs showed a higher frequency of treatment discontinuation due to AEs: we are moderately confident that this could happen with fingolimod, teriflunomide, interferon beta-1a, laquinimod, natalizumab and daclizumab, while our certainty with other DMTs is lower. We are also moderately certain that treatment with alemtuzumab is associated with fewer discontinuations due to adverse events than placebo, and moderately certain that interferon beta-1b probably results in a slight reduction in people who experience serious adverse events, but our certainty with regard to other DMTs is lower. Insufficient evidence is available to evaluate the efficacy and safety of DMTs in a longer term than two years, and this is a relevant issue for a chronic condition like MS that develops over decades. More than half of the included studies were sponsored by pharmaceutical companies and this may have influenced their results. Further studies should focus on direct comparison between active agents, with follow-up of at least three years, and assess other patient-relevant outcomes, such as quality of life and cognitive status, with particular focus on the impact of sex/gender on treatment effects.

GRADE Concept 7: Issues and Insights Linking Guideline Recommendations to Trustworthy Essential Medicine Lists.

OBJECTIVES: Guidelines and essential medicine lists (EMLs) bear similarities and differences in the process that lead to decisions. Access to essential medicines is central to achieve universal health coverage. The World Health Organization (WHO) EML has guided prioritization of essential medicines globally for nearly 50 years, and national EMLs (NEMLs) exist in over 130 countries. Guideline and EML decisions, at WHO or national levels, are not always coordinated and aligned. We sought to explore challenges, and potential solutions, for decision-making to support trustworthy medicine selection for EMLs from a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group perspective. We primarily focus on the WHO EML; however, our findings may be applicable to NEML decisions as well. STUDY DESIGN AND SETTING: We identified key challenges in connecting the EML to health guidelines by involving a broad group of stakeholders and assessing case studies including real applications to the WHO EML, South Africa NEML, and a multiple sclerosis guideline connected to a WHO EML application for multiple sclerosis treatments. To address challenges, we utilized the results of a survey and feedback from the stakeholders, and iteratively met as a project group. We drafted a conceptual framework of challenges and potential solutions. We presented a summary of the results for feedback to all attendees of the GRADE Working Group meetings in November 2022 (approximately 120 people) and in May 2023 (approximately 100 people) before finalizing the framework. RESULTS: We prioritized issues and insights/solutions that addressed the connections between the EML and health guidelines. Our suggested solutions include early planning alignment of guideline groups and EMLs, considering shared participation to strengthen linkage, further clarity on price/cost considerations, and using explicit shared criteria to make guideline and EML decisions. We also provide recommendations to strengthen the connection between WHO EML and NEMLs including through contextualization methods. CONCLUSION: This GRADE concept article, jointly developed by key stakeholders from the guidelines and EMLs field, identified key conceptual issues and potential solutions to support the continued advancement of trustworthy EMLs. Adopting structured decision criteria that can be linked to guideline recommendations bears the potential to advance health equity and gaps in availability of essential medicines within and between countries.

Wastewater surveillance for earlier detection of seniors congregate living COVID-19 outbreaks in Peterborough, Ontario.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected seniors living in congregate living settings. The evolving surveillance context has led to novel use of wastewater surveillance to monitor levels of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in these settings. This study presents a pilot of upstream congregate living wastewater surveillance of SARS-CoV-2 for the detection of COVID-19 outbreaks and the effects of early public health interventions. We monitored localized wastewater SARS-CoV-2 levels from four congregate living settings March 15, 2021 to October 1, 2022 and correlated these levels with suspected and confirmed COVID-19 outbreaks determined by other methods. We identified five wastewater signals that correlated with confirmed outbreaks and three wastewater signals that did not correlate with subsequent outbreaks. In the five confirmed outbreaks, the wastewater signal was detected 2-10 days (median, five days) prior to confirmation of the outbreak by case testing. This pilot demonstrates upstream sampling for SARS-CoV-2 in wastewater may effectively detect outbreaks prior to their detection through symptomatic case testing and could support a balanced approach to outbreak response in congregate living settings, leading to increased wellbeing of these residents.

Utility of the Peterborough Public Health COVID-19 rapid antigen test self-report tool: Implications for COVID-19 surveillance.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has necessitated novel testing strategies, including the use of rapid antigen tests (RATs). The widespread distribution of RATs to the public prompted Peterborough Public Health to launch a pilot RAT self-report tool to assess its utility in COVID-19 surveillance. The objective of this study is to investigate the utility of RAT using correlations between RAT self-report results and other indicators of COVID-19. Methods: We investigated the association between RAT results, PCR test results and wastewater levels of nmN1N2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes (to infer COVID-19 levels) using Pearson's correlation coefficient. Percent positivity and count of positive tests for RATs and polymerase chain reaction (PCR) tests were analyzed. Results: The PCR percent positivity and wastewater were weakly correlated (r=0.33, p=0.022), as were RAT percent positivity and wastewater nmN1N2 levels (r=0.33, p=0.002). The RAT percent positivity and PCR percent positivity were not significantly correlated (r=-0.035, p=0.75). Count of positive RATs and count of positive PCR tests were moderately correlated (r=0.59, p<0.001). Wastewater nmN1N2 levels were not significantly correlated with either count of positive RATs (r=0.019, p=0.864) or count of positive PCR tests (r=0.004, p=0.971). Conclusion: Our results support the use of RAT self-reporting as a low-cost simple adjunctive COVID-19 surveillance tool, and suggest that its utility is greatest when considering an absolute count of positive RATs rather than percent positivity due to reporting bias towards positive tests. These results can help inform COVID-19 surveillance strategies of local public health units and encourage the use of a RAT self-report tool.

Protocol for a living evidence synthesis on variants of concern and COVID-19 vaccine effectiveness.

BACKGROUND: It is evident that COVID-19 will remain a public health concern in the coming years, largely driven by variants of concern (VOC). It is critical to continuously monitor vaccine effectiveness as new variants emerge and new vaccines and/or boosters are developed. Systematic surveillance of the scientific evidence base is necessary to inform public health action and identify key uncertainties. Evidence syntheses may also be used to populate models to fill in research gaps and help to prepare for future public health crises. This protocol outlines the rationale and methods for a living evidence synthesis of the effectiveness of COVID-19 vaccines in reducing the morbidity and mortality associated with, and transmission of, VOC of SARS-CoV-2. METHODS: Living evidence syntheses of vaccine effectiveness will be carried out over one year for (1) a range of potential outcomes in the index individual associated with VOC (pathogenesis); and (2) transmission of VOC. The literature search will be conducted up to May 2023. Observational and database-linkage primary studies will be included, as well as RCTs. Information sources include electronic databases (MEDLINE; Embase; Cochrane, L*OVE; the CNKI and Wangfang platforms), pre-print servers (medRxiv, BiorXiv), and online repositories of grey literature. Title and abstract and full-text screening will be performed by two reviewers using a liberal accelerated method. Data extraction and risk of bias assessment will be completed by one reviewer with verification of the assessment by a second reviewer. Results from included studies will be pooled via random effects meta-analysis when appropriate, or otherwise summarized narratively. DISCUSSION: Evidence generated from our living evidence synthesis will be used to inform policy making, modelling, and prioritization of future research on the effectiveness of COVID-19 vaccines against VOC.

Defining Misinformation and Related Terms in Health-Related Literature: Scoping Review.

BACKGROUND: Misinformation poses a serious challenge to clinical and policy decision-making in the health field. The COVID-19 pandemic amplified interest in misinformation and related terms and witnessed a proliferation of definitions. OBJECTIVE: We aim to assess the definitions of misinformation and related terms used in health-related literature. METHODS: We conducted a scoping review of systematic reviews by searching Ovid MEDLINE, Embase, Cochrane, and Epistemonikos databases for articles published within the last 5 years up till March 2023. Eligible studies were systematic reviews that stated misinformation or related terms as part of their objectives, conducted a systematic search of at least one database, and reported at least 1 definition for misinformation or related terms. We extracted definitions for the terms misinformation, disinformation, fake news, infodemic, and malinformation. Within each definition, we identified concepts and mapped them across misinformation-related terms. RESULTS: We included 41 eligible systematic reviews, out of which 32 (78%) reviews addressed the topic of public health emergencies (including the COVID-19 pandemic) and contained 75 definitions for misinformation and related terms. The definitions consisted of 20 for misinformation, 19 for disinformation, 10 for fake news, 24 for infodemic, and 2 for malinformation. "False/inaccurate/incorrect" was mentioned in 15 of 20 definitions of misinformation, 13 of 19 definitions of disinformation, 5 of 10 definitions of fake news, 6 of 24 definitions of infodemic, and 0 of 2 definitions of malinformation. Infodemic had 19 of 24 definitions addressing "information overload" and malinformation had 2 of 2 definitions with "accurate" and 1 definition "used in the wrong context." Out of all the definitions, 56 (75%) were referenced from other sources. CONCLUSIONS: While the definitions of misinformation and related terms in the health field had inconstancies and variability, they were largely consistent. Inconstancies related to the intentionality in misinformation definitions (7 definitions mention "unintentional," while 5 definitions have "intentional"). They also related to the content of infodemic (9 definitions mention "valid and invalid info," while 6 definitions have "false/inaccurate/incorrect"). The inclusion of concepts such as "intentional" may be difficult to operationalize as it is difficult to ascertain one's intentions. This scoping review has the strength of using a systematic method for retrieving articles but does not cover all definitions in the extant literature outside the field of health. This scoping review of the health literature identified several definitions for misinformation and related terms, which showed variability and included concepts that are difficult to operationalize. Health practitioners need to exert caution before labeling a piece of information as misinformation or any other related term and only do so after ascertaining accurateness and sometimes intentionality. Additional efforts are needed to allow future consensus around clear and operational definitions.

Equity issues rarely addressed in the development of COVID-19 formal recommendations and good practice statements: a cross-sectional study.

BACKGROUND AND OBJECTIVE: To identify COVID-19 actionable statements (e.g., recommendations) focused on specific disadvantaged populations in the living map of COVID-19 recommendations (eCOVIDRecMap) and describe how health equity was assessed in the development of the formal recommendations. METHODS: We employed the place of residence, race or ethnicity or culture, occupation, gender or sex, religion, education, socio-economic status, and social capital-Plus framework to identify statements focused on specific disadvantaged populations. We assessed health equity considerations in the evidence to decision frameworks (EtD) of formal recommendations for certainty of evidence and impact on health equity criteria according to the Grading of Recommendations, Assessment, Development, and Evaluations criteria. RESULTS: We identified 16% (124/758) formal recommendations and 24% (186/819) good practice statements (GPS) that were focused on specific disadvantaged populations. Formal recommendations (40%, 50/124) and GPS (25%, 47/186) most frequently focused on children. Seventy-six percent (94/124) of the recommendations were accompanied with EtDs. Over half (55%, 52/94) of those considered indirectness of the evidence for disadvantaged populations. Considerations in impact on health equity criterion most frequently involved implementation of the recommendation for disadvantaged populations (17%, 16/94). CONCLUSION: Equity issues were rarely explicitly considered in the development COVID-19 formal recommendations focused on specific disadvantaged populations. Guidance is needed to support the consideration of health equity in guideline development during health emergencies.

Decision criteria for selecting essential medicines and their connection to guidelines: an interpretive descriptive qualitative interview study.

BACKGROUND AND OBJECTIVES: The World Health Organization Model List of Essential Medicines has led to at least 137 national lists. Essential medicines should be grounded in evidence-based guideline recommendations and explicit decision criteria. Essential medicines should be available, accessible, affordable, and the supporting evidence should be accompanied by a rating of the certainty one can place in it. Our objectives were to identify criteria and considerations that should be addressed in moving from a guideline recommendation regarding a medicine to the decision of whether to add, maintain, or remove a medicine from an essential medicines list. We also seek to explore opportunities to improve organizational processes to support evidence-based health decision-making more broadly. METHODS: We conducted a qualitative study with semistructured interviews of key informant stakeholders in the development and use of guidelines and essential medicine lists (EMLs). We used an interpretive descriptive analysis approach and thematic analysis of interview transcripts in NVIVO v12. RESULTS: We interviewed 16 key informants working at national and global levels across all WHO regions. We identified five themes: three descriptive/explanatory themes 1) EMLs and guidelines, the same, but different; 2) EMLs can drive price reductions and improve affordability and access; 3) Time lag and disconnect between guidelines and EMLs; and two prescriptive themes 4) An "evidence pipeline" could improve coordination between guidelines and EMLs; 5) Facilitating the link between the WHO Model List of Essential Medicines (WHO EML) and national EMLs could increase alignment. CONCLUSION: We found significant overlap and opportunities for alignment between guideline and essential medicine decision processes. This finding presents opportunities for guideline and EML developers to enhance strategies for collaboration. Future research should assess and evaluate these strategies in practice to support the shared goal of guidelines and EMLs: improvements in health.

Patient and Physician Decisional Factors Regarding Hypercalcemia of Malignancy Treatment: A Novel Mixed-Methods Study.

BACKGROUND: Integrating shared decision making between patients and physicians and incorporating their values and preferences in the development of clinical practice guidelines (CPGs) is of critical importance to optimize CPG implementation and treatment adherence. This applies to many debilitating diseases, including hypercalcemia of malignancy (HCM). OBJECTIVE: Evaluate patient and physician values, preferences, and attitudes to better inform CPGs to treat HCM in adults. METHODS: We followed a mixed-methods approach. We conducted a systematic review using 5 databases to identify studies reporting on patient and physician values, costs and resources, feasibility, acceptability, and equity regarding HCM treatment. We also gathered data from different countries on the cost of multiple treatment modalities. We collected data on outcome prioritization from the CPG Working Group. Similarly, we collected data from patients with HCM regarding outcome prioritization and administered a questionnaire to evaluate their attitudes and perceptions toward treatment as well as treatment acceptability and feasibility. RESULTS: In the systematic review, we included 2 cross-sectional surveys conducted on the same population of physicians who agreed that treating HCM alleviates symptoms and improves quality of life; however, harms and benefits should be thoroughly considered when deciding on the duration of treatment. We also included 2 studies on cost showing that intravenous (IV) bisphosphonate is more cost-effective than a combination of IV bisphosphonate and calcitonin and administration of IV zoledronic acid at home is more cost-effective than other IV bisphosphonates. The cost of zoledronic acid, denosumab, and cinacalcet varied widely among countries and types (brand vs generic). Both the CPG Working Group and patients with HCM agreed that the most important outcomes when deciding on treatment were survival and resolution of HCM, but there was some variability in the ratings for other outcomes. CONCLUSION: Using mixed methods, CPG developers can obtain meaningful information regarding evidence to decision criteria. In the case of HCM CPGs, this approach has provided the required contextual information and supported the development of evidence-based recommendations.

Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Hypercalcemia of malignancy (HCM) is the most common metabolic complication of malignancies, but its incidence may be declining due to potent chemotherapeutic agents. The high mortality associated with HCM has declined markedly due to the introduction of increasingly effective chemotherapeutic drugs. Despite the widespread availability of efficacious medications to treat HCM, evidence-based recommendations to manage this debilitating condition are lacking. OBJECTIVE: To develop guidelines for the treatment of adults with HCM. METHODS: A multidisciplinary panel of clinical experts, together with experts in systematic literature review, identified and prioritized 8 clinical questions related to the treatment of HCM in adult patients. The systematic reviews (SRs) queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. An independent SR was conducted in parallel to assess patients' and physicians' values and preferences, costs, resources needed, acceptability, feasibility, equity, and other domains relevant to the Evidence-to-Decision framework as well as to enable judgements and recommendations. RESULTS: The panel recommends (strong recommendation) in adults with HCM treatment with denosumab (Dmab) or an intravenous (IV) bisphosphonate (BP). The following recommendations were based on low certainty of the evidence. The panel suggests (conditional recommendation) (1) in adults with HCM, the use of Dmab rather than an IV BP; (2) in adults with severe HCM, a combination of calcitonin and an IV BP or Dmab therapy as initial treatment; and (3) in adults with refractory/recurrent HCM despite treatment with BP, the use of Dmab. The panel suggests (conditional recommendation) the addition of an IV BP or Dmab in adult patients with hypercalcemia due to tumors associated with high calcitriol levels who are already receiving glucocorticoid therapy but continue to have severe or symptomatic HCM. The panel suggests (conditional recommendation) in adult patients with hypercalcemia due to parathyroid carcinoma, treatment with either a calcimimetic or an antiresorptive (IV BP or Dmab). The panel judges the treatments as probably accessible and feasible for most recommendations but noted variability in costs, resources required, and their impact on equity. CONCLUSIONS: The panel's recommendations are based on currently available evidence considering the most important outcomes in HCM to patients and key stakeholders. Treatment of the primary malignancy is instrumental for controlling hypercalcemia and preventing its recurrence. The recommendations provide a framework for the medical management of adults with HCM and incorporate important decisional and contextual factors. The guidelines underscore current knowledge gaps that can be used to establish future research agendas.

Good or best practice statements: proposal for the operationalisation and implementation of GRADE guidance.

An evidence-based approach is considered the gold standard for health decision-making. Sometimes, a guideline panel might judge the certainty that the desirable effects of an intervention clearly outweigh its undesirable effects as high, but the body of supportive evidence is indirect. In such cases, the application of the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach for grading the strength of recommendations is inappropriate. Instead, the GRADE Working Group has recommended developing ungraded best or good practice statement (GPS) and developed guidance under which circumsances they would be appropriate.Through an evaluation of COVID-1- related recommendations on the eCOVID Recommendation Map (COVID-19.recmap.org), we found that recommendations qualifying a GPS were widespread. However, guideline developers failed to label them as GPS or transparently report justifications for their development. We identified ways to improve and facilitate the operationalisation and implementation of the GRADE guidance for GPS.Herein, we propose a structured process for the development of GPSs that includes applying a sequential order for the GRADE guidance for developing GPS. This operationalisation considers relevant evidence-to-decision criteria when assessing the net consequences of implementing the statement, and reporting information supporting judgments for each criterion. We also propose a standardised table to facilitate the identification of GPS and reporting of their development. This operationalised guidance, if endorsed by guideline developers, may palliate some of the shortcomings identified. Our proposal may also inform future updates of the GRADE guidance for GPS.

The GIN-McMaster guideline tool extension for the integration of quality improvement and quality assurance in guidelines: a description of the methods for its development.

BACKGROUND AND OBJECTIVES: Our objective was to develop an extension of the widely used GIN-McMaster Guideline Development Checklist and Tool for the integration of quality assurance and improvement (QAI) schemes with guideline development. METHODS: We used a mixed-methods approach incorporating evidence from a systematic review, an expert workshop and a survey of experts to iteratively create an extension of the checklist for QAI through three rounds of feedback. As a part of this process, we also refined criteria of a good guideline-based quality indicator. RESULTS: We developed a 40-item checklist extension addressing steps for the integration of QAI into guideline development across the existing 18 topics and created one new topic specific to QAI. The steps span from 'organization, budget, planning and training', to updating of QAI and guideline implementation. CONCLUSION: The tool supports integration of QAI schemes with guideline development initiatives and it will be used in the forthcoming integrated European Commission Initiative on Colorectal Cancer. Future work should evaluate this extension and QAI items requiring additional support for guideline developers and links to QAI schemes.

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.

Analytical frameworks in colorectal cancer guidelines: development of methods for systematic reviews, their application and practical guidance for their use.

OBJECTIVES: Analytical frameworks are graphical representation of the key questions answered by a systematic review and can support the development of guideline recommendations. Our objectives were to a) conduct a systematic review to identify, describe and compare all analytical frameworks published as part of a systematic and guideline development process related to colorectal cancer (CRC), and b) to use this case study to develop guidance on how to conduct systematic reviews of analytical frameworks. METHODS: We developed a search strategy to identify eligible studies in Medline and Embase from 1996 until December 2020. We also manually searched guideline databases and websites to identify all guidelines and systematic reviews in CRC that used an analytical framework. We assessed the quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool. The systematic review was registered in International Prospective Register of Systematic Reviews, registration CRD42020172117. RESULTS: We screened 34,505 records and identified 1,166 guidelines and 3,127 systematic reviews on CRC of which five met our inclusion criteria. These five publications included four analytical frameworks in colorectal cancer (one update). We also describe our methodological approach to systematic reviews for analytical frameworks and underlying concepts for developing analytical framework using a bottom-up or top-down approach. CONCLUSION: Few guidelines and systematic reviews are utilizing analytical frameworks in the development of recommendations. Development of analytical frameworks should begin with a systematic search for existing analytical frameworks and follow a structured conceptual approach for their development to support guideline recommendations. Our methods may be helpful in achieving these objectives.

Enhancing the Trustworthiness of the Endocrine Society's Clinical Practice Guidelines.

In an effort to enhance the trustworthiness of its clinical practice guidelines, the Endocrine Society has recently adopted new policies and more rigorous methodologies for its guideline program. In this Clinical Practice Guideline Communication, we describe these recent enhancements-many of which reflect greater adherence to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to guideline development-in addition to the rationale for such changes. Improvements to the Society's guideline development practices include, but are not limited to, enhanced inclusion of nonendocrinologist experts, including patient representatives, on guideline development panels; implementation of a more rigorous conflict/duality of interest policy; a requirement that all formal recommendations must be demonstrably underpinned by systematic evidence review; the explicit use of GRADE Evidence-to-Decision frameworks; greater use and explanation of standardized guideline language; and a more intentional approach to guideline updating. Lastly, we describe some of the experiential differences our guideline readers are most likely to notice.

In-Hospital Macro-, Meso-, and Micro-Drivers and Interventions for Antibiotic Use and Resistance: A Rapid Evidence Synthesis of Data from Canada and Other OECD Countries.

Hospitals continue to face challenges in reducing incorrect antibiotic use due to social and cultural factors at the level of the health system, the care facility, the provider, and the patient. The objective of this paper is to highlight the social and cultural drivers of antimicrobial use and resistance and targeted interventions for secondary and tertiary care settings in Canada and other OECD countries. This paper is an extension of the synthesis conducted for the Public Health Agency of Canada's 2019 Spotlight Report: Preserving Antibiotics Now and Into the Future. We conducted a systematic review with a few modifications to meet rapid timelines. We conducted a search in Ovid MEDLINE and McMaster University's evidence databases for systematic reviews and then for individual Canadian studies. To cast a wider net, we searched OECD organization websites and screened reference lists from systematic reviews. We synthesized the evidence narratively and categorized the evidence into macro-, meso-, and microlevel. A total of 70 studies were (a) from OCED countries and summarized evidence of potential sociocultural antimicrobial resistance and use barriers or facilitators and/or interventions addressing these challenges; (b) systematic reviews with 50% of included studies that are situated in secondary and tertiary settings; and (c) published in Canada's two official languages, English and French. We found that hospital structures and policies may influence antibiotic utilization and variations in antimicrobial management. Microlevel factors may sway inappropriate prescribing among clinicians. The amount and type of antibiotics used may affect resistance rates. Interventions were mainly comprised of antibiotic stewardship and training that modify clinician behavior and that educate patients and carers. This evidence synthesis illustrates the various drivers of, and interventions for, antimicrobial use and resistance at the macro-, meso-, and microlevel in secondary and tertiary settings. We demonstrate that upstream drivers may lead to downstream events that influence antimicrobial resistance.

The ecosystem of health decision making: from fragmentation to synergy.

Clinicians, patients, policy makers, funders, programme managers, regulators, and science communities invest considerable amounts of time and energy in influencing or making decisions at various levels, using systematic reviews, health technology assessments, guideline recommendations, coverage decisions, selection of essential medicines and diagnostics, quality assurance and improvement schemes, and policy and evidence briefs. The criteria and methods that these actors use in their work differ (eg, the role economic analysis has in decision making), but these methods frequently overlap and exist together. Under the aegis of WHO, we have brought together representatives of different areas to reconcile how the evidence that influences decisions is used across multiple health system decision levels. We describe the overlap and differences in decision-making criteria between different actors in the health sector to provide bridging opportunities through a unifying broad framework that we call theory of everything. Although decision-making activities respond to system needs, processes are often poorly coordinated, both globally and on a country level. A decision made in isolation from other decisions on the same topic could cause misleading, unnecessary, or conflicted inputs to the health system and, therefore, confusion and resource waste.