Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing.

BACKGROUND: The role of serologic testing for SARS-CoV-2 has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA. OBJECTIVE: To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. METHODS: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. RESULTS: The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first two weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for IgG, IgG/IgM, or total antibodies to nucleocapsid protein three to five weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, we suggest against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence.) The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. CONCLUSIONS: The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing (December 2023).

Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19) and for identifying asymptomatic carriage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of available SARS-CoV-2 nucleic acid detection tests continues to increase as does the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) developed an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients, and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss nuances of test result interpretation in a variety of practice settings, and highlight important unmet research needs related to COVID-19 diagnostic testing. IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel agreed on 12 diagnostic recommendations. Access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention, and the public health response to COVID-19 infection. Information on the clinical performance of available tests continues to grow, but the quality of evidence of the current literature to support this updated molecular diagnostic guideline remains moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is suggested for asymptomatic individuals with known or suspected contact with a COVID-19 case when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions. Evidence in support of rapid testing and testing of upper respiratory specimens other than nasopharyngeal swabs, which offer logistical advantages, is sufficient to warrant conditional recommendations in favor of these approaches.

Use of the Pfizer Pentavalent Meningococcal Vaccine Among Persons Aged ≥10 Years: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023.

Meningococcal disease is a life-threatening invasive infection caused by Neisseria meningitidis. Two quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccines (MenACWY) (MenACWY-CRM [Menveo, GSK] and MenACWY-TT [MenQuadfi, Sanofi Pasteur]) and two serogroup B meningococcal vaccines (MenB) (MenB-4C [Bexsero, GSK] and MenB-FHbp [Trumenba, Pfizer Inc.]), are licensed and available in the United States and have been recommended by CDC's Advisory Committee on Immunization Practices (ACIP). On October 20, 2023, the Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer Inc.]) for prevention of invasive disease caused by N. meningitidis serogroups A, B, C, W, and Y among persons aged 10-25 years. On October 25, 2023, ACIP recommended that MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for the following groups: 1) healthy persons aged 16-23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccine, and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia). Different manufacturers' serogroup B-containing vaccines are not interchangeable; therefore, when MenACWY-TT/MenB-FHbp is used, subsequent doses of MenB should be from the same manufacturer (Pfizer Inc.). This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of MenACWY-TT/MenB-FHbp.

The role of influenza Hemagglutination-Inhibition antibody as a vaccine mediator in children.

BACKGROUND: Influenza vaccination may protect through the humoral immune response, cellular immune response, or possibly both. Immunity after vaccination can be mediated through antibodies that may be detected by the rise of serum hemagglutination inhibition (HAI) titers. Our objective was to investigate the proportion of protection against influenza mediated through antibodies by measuring the rise of HAI titer (indirect effect) compared to that induced through other immune mechanisms (direct effect) for influenza A and B. METHODS: We analysed data from a cluster randomized trial conducted during the 2008-2009 season in which Canadian Hutterite children were vaccinated against influenza. We used inverse probability weighting to calculate the indirect and direct effect of vaccination against influenza A/H3N2 and influenza B/Brisbane using HAI titres and overall vaccine efficacy. RESULTS: We included data on 617 children from 46 Hutterite colonies, aged between 3 and 15 years who were vaccinated with either inactivated trivalent influenza vaccine or hepatitis A vaccine. Vaccine efficacy was 63 % for influenza A (H3N2) and 28 % for influenza B. The hazard ratio for protection against influenza A/H3N2 due to an indirect effect of vaccination was 0.96 (95 % confidence interval (CI) of 0.00 to 2.89) while for the direct effect it was 0.38 (95 % CI of 0.00 to 5.47). The hazard ratio for influenza B indirect effect was 0.75 (95 % CI of 0.07 to 1) and for the direct effect 0.96 (95 % CI of 0.00 to 12.02). In contrast, repeating the analysis using microneutralization in a subgroup of 488 children revealed that the protective effect for vaccination for A/H3N2 was entirely mediated by antibodies but only for 13 % for influenza B. CONCLUSIONS: Although vaccination provided higher protective effectiveness against influenza A than B, most of the influenza A vaccine efficacy likely occurred through antibodies other than what could be detected by HAI titres. In contrast, for influenza B, while the HAI titres appeared to mediate most of the vaccine effectiveness, this was not confirmed by microneutralization analysis.

Publication of pharmacy resident research projects: A systematic review and meta-analysis.

PURPOSE: Pharmacy residents often aspire to develop research skills through conducting a research project. Project publication rates among pharmacy residents are variable and at times low; however, previous studies have been limited to specific geographic regions and timeframes. This study sought to conduct a systematic review and meta-analysis to determine the proportion of pharmacy resident research projects published in the peer-reviewed literature. METHODS: A systematic review of PubMed MEDLINE, Embase, and the Web of Science Core Collection was performed from database inception to May 25, 2023. Articles were included if they were full-text, peer-reviewed manuscripts of original research presenting observational data regarding pharmacy resident research project publication rates. Data extraction and assessment of risk of bias were conducted by 2 independent reviewers. A proportional meta-analysis using a random effects model of the included studies was conducted to generate a pooled, overall proportion. RESULTS: The search yielded 5,225 records and 12 articles that met the inclusion criteria. All studies were retrospective and observational. Risk of selection and cohort identification biases was "high," whereas that of detection and timeframe biases was "low." The included studies represented 6,990 resident research projects, 777 of which were published in the peer-reviewed literature. Publication rates across individual studies ranged from 1.8% to 36.2%. The pooled proportion (scale of 0 to 1) of projects published was 0.13 (95% CI, 0.09-0.19). CONCLUSION: Pharmacy resident research project publication rates are low at 13%. Furthermore, studies reporting project publication rates over time suggest a neutral or negative trend in publication rates despite an exponential increase in the number of pharmacy residents.

A Systematic Review and Meta-Analysis of Noise Annoyance as a Determinant of Physiological Changes Linked to Disease Promotion.

This systematic review investigates the certainty of evidence (CoE) regarding noise annoyance as a determinant of biological changes known to contribute to disease development. We searched PubMed MEDLINE, EMBASE, Cochrane Central, and CINAHL for English-language comparative studies conducted on humans of any age from 1 January 1940, to 28 August 2023. Further, studies that provided quantitative data on the relationship between noise annoyance and biomarkers of interest were included. Where possible, random-effects meta-analyses were used to calculate the odds ratios of noise annoyance on biomarkers and biological conditions considered to be risk factors for developing health effects. The risk of bias of individual studies was assessed using the Risk of Bias of Non-randomized Studies of Exposures (ROBINS-E) instrument. The CoE for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The search identified 23 primary studies reporting on relevant biomarkers. Although some studies and pooled estimates suggest a possible association between noise annoyance and biological measures, the CoE overall is very low due to concerns with the risk of bias, inconsistency, and imprecision in the estimates of effects. In the context of environmental impact assessment, where guidelines aim to mitigate the prevalence of populations experiencing a high level of noise annoyance, our results suggest that such practices should be grounded in the understanding that annoyance is health-relevant because it reflects an undesirable reaction to noise, rather than a precursor to chronic physical health conditions.

Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.

BACKGROUND: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART. METHODS: We performed a PubMed search using the term "Dolutegravir", last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART. RESULTS: Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details. CONCLUSIONS: In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.

Towards a better understanding of real-world home-visiting programs: a large-scale effectiveness study of parenting mechanisms in Brazil.

BACKGROUND: The scale-up of parenting programmes to support early childhood development (ECD) is poorly understood. Little is known about how and when early interventions are most effective. Sustainability of ECD programming requires a better understanding of the mechanisms of real-world interventions. We examined the effects on caregiving practices of Primeira Infância Melhor (PIM), a state-wide home-visiting programme in Brazil. METHODS: This propensity score matched, longitudinal, quasiexperimental study uses data from the 2015 Pelotas Birth Cohort. We matched children who received PIM at any age with other cohort children on 25 key covariates. Sensitivity, guidance and responsiveness were assessed using video-recorded play tasks. Coerciveness and the parent-child relationship were assessed using the Parenting and Family Adjustment Scales. All parenting outcomes were examined at age 4 years. Separate moderation analyses were conducted for each effect modifier: family income, child age and duration of participation. RESULTS: Out of 4275 children in the cohort, 797 were enrolled in PIM up to age 4 years. 3018 children (70.6%) were included in the analytic sample, of whom 587 received PIM and 2431 were potential controls. We found a positive effect of PIM on responsiveness (ß=0.08, 95% CIs 0.002 to 0.16) and sensitivity (ß=0.10, 95% CIs 0.02 to 0.19). No effect was found for any secondary outcomes. Moderation analyses revealed a stronger positive effect on sensitivity for low-income parents (ß=0.18, 95% CIs 0.03 to 0.34). CONCLUSION: A state-wide, home-visiting programme in Brazil improved aspects of responsive caregiving. Effects were more pronounced for low-income families, suggesting benefits of purposeful targeting.

Considering planetary health in health guidelines and health technology assessments: a scoping review protocol.

BACKGROUND: This protocol outlines a scoping review with the objective of identifying and exploring planetary health considerations within existing health guidelines and health technology assessments (HTA). The insights gained from this review will serve as a basis for shaping future Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidance on planetary health. METHODS: We will adhere to the JBI methodology for scoping reviews. We will conduct a comprehensive search and screening of results in all languages across various databases including MEDLINE, EMBASE, CINAHL, Global Health, Health Systems Evidence, Greenfile, and Environmental Issues. Additionally, we will supplement this search with resources such as the GIN library, BIGG database, Epistemonikos, GRADE guidelines repository, GRADEpro Guideline Development Tool Database, MAGICapp, NICE website, WHO websites, and a manual exploration of unpublished relevant documents using Google incognito mode. Two independent reviewers will screen and assess the full texts of identified documents according to the eligibility criteria. The following information from each full text will be extracted: document title; first author's name; publication year; language; document type; document as a guideline or HTA; the topic/discipline; document purpose/study objective; developing/sponsoring organization; the country in which the study/guideline/HTA report was conducted; definition of planetary health or related concept provided; types of planetary health experts engaged; study methods; suggested methods to assess planetary health; use of secondary data on planetary health outcomes; description for use of life cycle assessment; description for assessing the quality of life cycle; population/intended audience; interventions; category; applicable planetary health boundaries; consideration of social justice/global equity; phase of intervention in life cycle related to planetary health addressed; the measure of planetary health impact; impact on biodiversity/land use; one health/animal welfare mention; funding; and conflict of interest. Data analysis will involve a combination of descriptive statistics and directed content analysis, with results presented in a narrative format and displayed in tables and graphs. DISCUSSION: The final review results will be submitted to open-access peer-reviewed journals for publication when they become available. The research findings will also be disseminated at relevant planetary health conferences and workshops. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://osf.io/3jmsa ).

A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E).

BACKGROUND: Observational epidemiologic studies provide critical data for the evaluation of the potential effects of environmental, occupational and behavioural exposures on human health. Systematic reviews of these studies play a key role in informing policy and practice. Systematic reviews should incorporate assessments of the risk of bias in results of the included studies. OBJECTIVE: To develop a new tool, Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) to assess risk of bias in estimates from cohort studies of the causal effect of an exposure on an outcome. METHODS AND RESULTS: ROBINS-E was developed by a large group of researchers from diverse research and public health disciplines through a series of working groups, in-person meetings and pilot testing phases. The tool aims to assess the risk of bias in a specific result (exposure effect estimate) from an individual observational study that examines the effect of an exposure on an outcome. A series of preliminary considerations informs the core ROBINS-E assessment, including details of the result being assessed and the causal effect being estimated. The assessment addresses bias within seven domains, through a series of 'signalling questions'. Domain-level judgements about risk of bias are derived from the answers to these questions, then combined to produce an overall risk of bias judgement for the result, together with judgements about the direction of bias. CONCLUSION: ROBINS-E provides a standardized framework for examining potential biases in results from cohort studies. Future work will produce variants of the tool for other epidemiologic study designs (e.g. case-control studies). We believe that ROBINS-E represents an important development in the integration of exposure assessment, evidence synthesis and causal inference.

GRADE Guidance 39: Using GRADE-ADOLOPMENT to adopt, adapt or create contextualized recommendations from source guidelines and evidence syntheses.

INTRODUCTION: The GRADE-ADOLOPMENT methodology has been widely used to adopt, adapt or de novo develop recommendations from existing or new guideline and evidence synthesis efforts. This guidance refines the operationalization for applying GRADE-ADOLOPMENT. METHODS: Through iterative discussions, online meetings and email communications, the GRADE-ADOLOPMENT Project Group drafted the updated guidance. We then conducted a review of handbooks of guideline-producing organizations, and a scoping review of published and planned Adolopment guideline projects. The lead authors refined the existing approach based on the scoping review findings and feedback from members of the GRADE Working Group. We presented the revised approach to the group in November 2022 (approximately 115 people), in May 2023 (approximately 100 people) and twice in September 2023 (approximately 60 and 90 people) for approval. RESULTS: This GRADE guidance shows how to effectively and efficiently contextualize recommendations using the GRADE-ADOLOPMENT approach by: (1) showcasing alternative pathways for starting an adolopment effort; (2) elaborating on the different essential steps of this approach, such as building on existing EtDs when available or developing new EtDs if necessary; and (3) providing examples from adolopment case studies to facilitate the application of the approach. We demonstrate how to use contextual evidence to make judgments about EtD criteria, and highlight the importance of making the resulting EtDs available to facilitate adolopment efforts by others. CONCLUSION: This updated GRADE guidance further operationalizes the application of GRADE-ADOLOPMENT based on over six years of experience. It serves to support uptake and application by end users interested in contextualizing recommendations to a local setting or specific reality in a short period of time or with limited resources.

Management of chronic pain secondary to temporomandibular disorders: a systematic review and network meta-analysis of randomised trials.

OBJECTIVE: We explored the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD). DESIGN: Systematic review and network meta-analysis of randomised clinical trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, CINAHL, CENTRAL, and SCOPUS were searched to May 2021, and again in January 2023. STUDY SELECTION: Interventional RCTs that enrolled patients presenting with chronic pain associated with TMD. DATA EXTRACTION AND SYNTHESIS: Pairs of reviewers independently identified eligible studies, extracted data, and assessed risk of bias. We captured all reported patient-important outcomes, including pain relief, physical functioning, emotional functioning, role functioning, social functioning, sleep quality, and adverse events. We conducted frequentist network meta-analyses to summarise the evidence and used the GRADE approach to rate the certainty of evidence and categorise interventions from most to least beneficial. RESULTS: 233 trials proved eligible for review, of which 153-enrolling 8713 participants and exploring 59 interventions or combinations of interventions-were included in network meta-analyses. All subsequent effects refer to comparisons with placebo or sham procedures. Effects on pain for eight interventions were supported by high to moderate certainty evidence. The three therapies probably most effective for pain relief were cognitive behavioural therapy (CBT) augmented with biofeedback or relaxation therapy (risk difference (RD) for achieving the minimally important difference (MID) in pain relief of 1 cm on a 10 cm visual analogue scale: 36% (95% CI 33 to 39)), therapist-assisted jaw mobilisation (RD 36% (95% CI 31 to 40)), and manual trigger point therapy (RD 32% (29 to 34)). Five interventions were less effective, yet more effective than placebo, showing RDs ranging between 23% and 30%: CBT, supervised postural exercise, supervised jaw exercise and stretching, supervised jaw exercise and stretching with manual trigger point therapy, and usual care (such as home exercises, self stretching, reassurance).Moderate certainty evidence showed four interventions probably improved physical functioning: supervised jaw exercise and stretching (RD for achieving the MID of 5 points on the short form-36 physical component summary score: 43% (95% CI 33 to 51)), manipulation (RD 43% (25 to 56)), acupuncture (RD 42% (33 to 50)), and supervised jaw exercise and mobilisation (RD 36% (19 to 51)). The evidence for pain relief or physical functioning among other interventions, and all evidence for adverse events, was low or very low certainty. CONCLUSION: When restricted to moderate or high certainty evidence, interventions that promote coping and encourage movement and activity were found to be most effective for reducing chronic TMD pain. REGISTRATION: PROSPERO (CRD42021258567).

SCAI Technical Review on Management of Patent Foramen Ovale.

Background: Patent foramen ovale (PFO) is a common anatomic variant associated with intermittent right-to-left shunting. Transcatheter PFO closure has been proposed to address multiple clinical conditions including stroke, transient ischemic attack, migraine, and decompression illness. Methods: A systematic review was conducted using the GRADE approach to address 5 questions formulated by the Society for Cardiovascular Angiography and Interventions (SCAI) Guideline Panel in patient, intervention, comparator, outcome (PICO) format. Medical literature from January 2015 through May 2021 was searched. Extracted data underwent review and risk-of-bias assessment by 2 independent researchers. Pooled effect estimates were calculated. Certainty of evidence was determined for each query. Results: Our search identified 2701 titles and abstracts, of which 30 met eligibility criteria and informed the technical review. Data were abstracted to address outcomes of PFO closure for patients with and without prior stroke, in comparison to antiplatelet therapy, in comparison to anticoagulation, and with various post-procedure antithrombotic regimens. Conclusion: In appropriately selected patients with prior stroke, transcatheter PFO closure reduces the risk of recurrent stroke more than antiplatelet therapy alone. Evidence to support PFO closure is weaker regarding older patients, anticoagulation, thrombophilia, transient ischemic attack, migraine, and decompression illness. Data from this technical review will inform the SCAI Guideline for Transcatheter Patent Foramen Ovale Closure.

SCAI Guidelines for the Management of Patent Foramen Ovale.

Background: Patent foramen ovale (PFO) is a vestigial congenital cardiovascular structure present in around 25% of adults. In most cases, PFO is entirely benign and requires no treatment. However, it may cause serious complications under certain circumstances. Objective: These evidence-based guidelines from the Society for Cardiovascular Angiography and Interventions (SCAI) aim to support patients, clinicians, and other stakeholders in decisions about management of PFO. Methods: SCAI convened a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The Evidence Foundation, a registered 501(c)(3) nonprofit organization, provided methodological support for the guideline-development process. Following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, the guideline panel formulated and prioritized clinical questions in population, intervention, comparison, outcome (PICO) format. A separate technical review team of clinical and methodological experts conducted systematic reviews of the evidence, synthesized data, and graded the certainty of the evidence across outcomes. The guideline panel then reconvened to formulate recommendations and supporting remarks informed by the results of the technical review and additional contextual factors described in the GRADE evidence-to-decision framework. Results: The panel agreed on 13 recommendations to address variations on 5 clinical scenarios. Conclusions: Key recommendations address patient selection for PFO closure in the prevention of recurrent PFO-associated stroke, including populations not commonly included in randomized studies, and scenarios where the PFO closure might serve a role in the prevention of other outcomes such as migraine headaches and decompression illness. The panel has also identified future research priorities to advance the field.