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Background Diagnostic error (DE) is a common problem in clinical practice, particularly in the emergency department (ED) setting. Among ED patients presenting with cardiovascular or cerebrovascular/neurological symptoms, a delay in diagnosis or failure to hospitalise may be most impactful in terms of adverse outcomes. Minorities and other vulnerable populations may be at higher risk of DE. We aimed to systematically review studies reporting the frequency and causes of DE in under-resourced patients presenting to the ED with cardiovascular or cerebrovascular/neurological symptoms. Methods We searched EBM Reviews, Embase, Medline, Scopus and Web of Science from 2000 through 14 August 2022. Data were abstracted by two independent reviewers using a standardised form. The risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results Of the 7342 studies screened, we included 20 studies evaluating 7436,737 patients. Most studies were conducted in the USA, and one study was multicountry. 11 studies evaluated DE in patients with cerebrovascular/neurological symptoms, 8 studies with cardiovascular symptoms and 1 study examined both types of symptoms. 13 studies investigated missed diagnoses and 7 studies explored delayed diagnoses. There was significant clinical and methodological variability, including heterogeneity of DE definitions and predictor variable definitions as well as methods of DE assessment, study design and reporting. Among the studies evaluating cardiovascular symptoms, black race was significantly associated with higher odds of DE in 4/6 studies evaluating missed acute myocardial infarction (AMI)/acute coronary syndrome (ACS) diagnosis compared with white race (OR from 1.18 (1.12–1.24) to 4.5 (1.8–11.8)). The association between other analysed factors (ethnicity, insurance and limited English proficiency) and DE in this domain varied from study to study and was inconclusive. Among the studies evaluating DE in patients with cerebrovascular/neurological symptoms, no consistent association was found indicating higher or lower odds of DE. Although some studies showed significant differences, these were not consistently in the same direction. The overall ROB was low for most included studies; however, the certainty of evidence was very low, mostly due to serious inconsistency in definitions and measurement approaches across studies. Conclusions This systematic review demonstrated consistent increased odds of missed AMI/ACS diagnosis among black patients presenting to the ED compared with white patients in most studies. No consistent associations between demographic groups and DE related to cerebrovascular/neurological diagnoses were identified. More standardised approaches to study design, measurement of DE and outcomes assessment are needed to understand this problem among vulnerable populations. Trial registration number The study protocol was registered in the International Prospective Register of Systematic Reviews PROSPERO 2020 CRD42020178885 and is available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020178885.

Importance The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown. Objective To assess the comparative effectiveness of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups. Data Sources For this systematic review and meta-analysis, Ovid MEDLINE and Embase were searched from each database’s inception (MEDLINE, 1946; Embase, 1974) through June 16, 2021. Subsequently, a “living” auto search was created with weekly updates to identify new evidence as it became available. Study Selection Phase 3 randomized clinical trials (RCTs) assessing first-line treatment options for mCSPC. Data Extraction and Synthesis Two independent reviewers extracted data from eligible RCTs. The comparative effectiveness of different treatment options was assessed with a fixed-effect network meta-analysis. Data were analyzed on July 10, 2022. Main Outcomes and Measures Outcomes of interest included overall survival (OS), progression-free survival (PFS), grade 3 or higher adverse events, and health-related quality of life. Results This report included 10 RCTs with 11 043 patients and 9 unique treatment groups. Median ages of the included population ranged from 63 to 70 years. Current evidence for the overall population suggests that the darolutamide (DARO) triplet (DARO + docetaxel [D] + androgen deprivation therapy [ADT]; hazard ratio [HR], 0.68; 95% CI, 0.57-0.81), as well as the abiraterone (AAP) triplet (AAP + D + ADT; HR, 0.75; 95% CI, 0.59-0.95), are associated with improved OS compared with D doublet (D + ADT) but not compared with API doublets. Among patients with high-volume disease, AAP + D + ADT may improve OS compared with D + ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP + ADT, enzalutamide (E) + ADT, and apalutamide (APA) + ADT. For patients with low-volume disease, AAP + D + ADT may not improve OS compared with APA + ADT, AAP + ADT, E + ADT, and D + ADT. Conclusions and Relevance The potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.

Abstract Objectives We aimed to identify migraine treatment features preferred by patients and treatment outcomes most valued by patients. Background The values and preferences of people living with migraine are critical for both the choice of acute therapy and management approach of migraine. Methods We conducted a qualitative evidence synthesis. Two reviewers independently selected studies, appraised methodological quality, and undertook a framework synthesis. We developed summary of findings tables following the approach of Grading of Recommendations, Assessment, Development and Evaluations Confidence in the Evidence from Reviews of Qualitative Research to assess confidence in the findings. Results Of 1691 candidate references, we included 19 studies (21 publications) involving 459 patients. The studies mostly recruited White women from North America (11 studies) and Europe (8 studies). We identified eight themes encompassing features preferred by patients in a migraine treatment process. Themes described a treatment process that included shared decision‐making, a tailored approach, trust in health‐care professionals, sharing of knowledge and diversity of treatment options, a holistic approach that does not just address the headache, ease of communication especially for complex treatments, a non‐undermining approach, and reciprocity with mutual respect between patient and provider. In terms of the treatment itself, seven themes emerged including patients’ preferences for nonpharmacologic treatment, high effectiveness, rapidity of action, long‐lasting effect, lower cost and more accessibility, self‐management/self‐delivery option that increases autonomy, and a mixed preference for abortive versus prophylactic treatments. The treatment outcomes that have high value to patients included maintaining or improving function; avoiding side effects, potential for addiction to medications, and pain reoccurrence; and avoiding non‐headache symptoms such as nausea, vomiting, and sensitivity to light or sounds. Conclusion Patient values and preferences were individually constructed, varied widely, and could be at odds with conventional medical perspectives and evidence of treatment effects. Considering the availability of numerous treatments for acute migraine, it is necessary that decision‐making incorporates patient values and preferences identified in qualitative research. The findings of this qualitative synthesis can be used to facilitate an individually tailored approach, strengthen the patient–health‐care system relationship, and guide choices and decisions in the context of a clinical encounter or a clinical practice guideline.

AbstractBackgroundIntegrating 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).ObjectiveEvaluate patient and physician values, preferences, and attitudes to better inform CPGs to treat HCM in adults.MethodsWe 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.ResultsIn 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.ConclusionUsing 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.

Abstract Context Interventions targeting hypoglycemia in people with diabetes are important for improving quality of life and reducing morbidity and mortality. Objective To support development of the Endocrine Society Clinical Practice Guideline for management of individuals with diabetes at high risk for hypoglycemia. Methods We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. Results We included 149 studies reporting on 43 344 patients. Continuous glucose monitoring (CGM) reduced episodes of severe hypoglycemia in patients with type 1 diabetes (T1D) and reduced the proportion of patients with hypoglycemia (blood glucose [BG] levels <54 mg/dL). There were no data on use of real-time CGM with algorithm-driven insulin pumps vs multiple daily injections with BG testing in people with T1D. CGM in outpatients with type 2 diabetes taking insulin and/or sulfonylureas reduced time spent with BG levels under 70 mg/dL. Initiation of CGM in hospitalized patients at high risk for hypoglycemia reduced episodes of hypoglycemia with BG levels lower than 54 mg/dL and time spent under 54 mg/dL. The proportion of patients with hypoglycemia with BG levels lower than 70 mg/dL and lower than 54 mg/dL detected by CGM was significantly higher than point-of-care BG testing. We found no data evaluating continuation of personal CGM in the hospital. Use of an inpatient computerized glycemic management program utilizing electronic health record data was associated with fewer patients with and episodes of hypoglycemia with BG levels lower than 70 mg/dL and fewer patients with severe hypoglycemia compared with standard care. Long-acting basal insulin analogs were associated with less hypoglycemia. Rapid-acting insulin analogs were associated with reduced severe hypoglycemia, though there were more patients with mild to moderate hypoglycemia. Structured diabetes education programs reduced episodes of severe hypoglycemia and time below 54 mg/dL in outpatients taking insulin. Glucagon formulations not requiring reconstitution were associated with longer times to recovery from hypoglycemia, although the proportion of patients who recovered completely from hypoglycemia was not different between the 2 groups. Conclusion This systematic review summarized the best available evidence about several interventions addressing hypoglycemia in people with diabetes. This evidence base will facilitate development of clinical practice guidelines by the Endocrine Society.

ImportanceProstate cancer (PCa) is marked by disparities in clinical outcomes by race, ethnicity, and age. Equitable enrollment in clinical trials is fundamental to promoting health equity.ObjectiveTo evaluate disparities in the inclusion of racial and ethnic minority groups and older adults across PCa clinical trials.Data SourcesMEDLINE, Embase, and ClinicalTrials.gov were searched to identify primary trial reports from each database's inception through February 2021. Global incidence in age subgroups and US population-based incidence in racial and ethnic subgroups were acquired from the Global Burden of Disease and Surveillance, Epidemiology, and End Results 21 incidence databases respectively.Study SelectionAll phase 2/3 randomized PCa clinical trials were eligible for age disparity analyses. Trials recruiting exclusively from the US were eligible for primary racial and ethnic disparity analyses.Data Extraction and SynthesisThis study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were pooled using a random-effects model.Main Outcomes and MeasuresEnrollment incidence ratios (EIRs), trial proportions (TPs) of participants 65 years or older or members of a racial and ethnic subgroup divided by global incidence in the corresponding age group, or US population–based incidence in the corresponding racial and ethnic subgroup, were calculated. Meta-regression was used to explore associations between trial characteristics and EIRs and trends in EIRs during the past 3 decades.ResultsOf 9552 participants among trials reporting race, 954 (10.8%) were African American/Black, 80 (1.5%) were Asian/Pacific Islander, and 8518 (78.5) were White. Of 65 US trials, 45 (69.2%) reported race and only 9 (13.8%) reported data on all 5 US racial categories. Of 286 global trials, 75 (26.2%) reported the enrollment proportion of older adults. Outcomes by race and age were reported in 2 (3.1%) and 41 (15.0%) trials, respectively. Black (EIR, 0.70; 95% CI, 0.59-0.83) and Hispanic (EIR, 0.70; 95% CI, 0.59-0.83) patients were significantly underrepresented in US trials. There was no disparity in older adult representation (TP, 21 143 [71.1%]; EIR, 1.00; 95% CI, 0.95-1.05). The representation of Black patients was lower in larger trials (meta-regression coefficient, −0.06; 95% CI, −0.10 to −0.02; P = .002).Conclusions and RelevanceThe results of this meta-analysis suggest that Black and Hispanic men are underrepresented in trials compared with their share of PCa incidence. The representation of Black patients has consistently remained low during the past 2 decades.

Background Patients with acute stroke presenting with large vessel occlusion secondary to intracranial atherosclerosis (ICAS‐LVO) may require rescue therapy (RT) in addition to mechanical thrombectomy to achieve and maintain successful recanalization. We performed a systematic review and meta‐analysis of comparative studies that reported outcomes of RT in patients with ICAS‐LVO to evaluate its safety and efficacy. Methods Databases searched include PubMed, CINAHL Complete, and Scopus from database date of inception through August 17, 2021. We included comparative studies that reported the outcomes of ICAS‐LVO RT compared with outcomes of patients with ICAS‐LVO who did not undergo RT or to those patients presenting with embolic large vessel occlusion (non–ICAS‐LVO). Meta‐analysis using the random‐effects model was used to combine estimates reporting odds ratios (ORs) and 95% CIs. Results A total of 9 nonrandomized studies were included: 5 studies in ICAS‐LVO RT versus ICAS‐LVO non‐RT analysis and 5 in ICAS‐LVO RT versus non‐ICAS LVO analysis. Rescue treatments included intra‐arterial antiplatelets, angioplasty, stenting, or a combination of treatments. Compared with non‐RT ICAS‐LVO, RT was associated with an increased favorable 90‐day outcome (OR, 3.19 [95% CI, 1.91–5.32]; I 2 = 14%) and decreased 90‐day mortality (OR, 0.35 [95% CI, 0.16–0.76]; I 2 = 21%). In the analysis of ICAS‐LVO RT versus embolic LV, the incidence of favorable 90‐day outcome and 90‐day mortality did not differ between ICAS‐LVO RT and non–ICAS‐LVO (OR, 0.97 [95% CI, 0.58–1.64; I 2 = 50%]; and OR, 1.22 [95% CI, 0.90–1.66; I 2 = 0%], respectively). Conclusions Rescue treatment is likely associated with better outcomes in patients with ICAS‐LVO. The outcomes of patients with ICAS‐LVO who receive RT may be comparable with patients with embolic large vessel occlusion (non–ICAS‐LVO).

Abstract Aims To evaluate the association of basic life support with survival after sports-related sudden cardiac arrest (SR-SCA). Methods and results In this systematic review and meta-analysis, a search of several databases from each database inception to 31 July 2021 without language restrictions was conducted. Studies were considered eligible if they evaluated one of three scenarios in patients with SR-SCA: (i) bystander presence, (ii) bystander cardiopulmonary resuscitation (CPR), or (iii) bystander automated external defibrillator (AED) use and provided information on survival. Risk of bias was evaluated using Risk of Bias in Non-randomized Studies of Interventions. The primary outcome was survival at the longest follow up. The meta-analysis was conducted using the random-effects model. The Grading of Recommendations Assessment, Development, and Evaluations (GRADE) approach was used to rate certainty in the evidence. In total, 28 non-randomized studies were included. The meta-analysis showed significant benefit on survival in all three groups: bystander presence [odds ratio (OR) 2.55, 95% confidence interval (CI) 1.48–4.37; I2 = 25%; 9 studies—988 patients], bystander CPR (OR 3.84, 95% CI 2.36–6.25; I2 = 54%; 23 studies—2523 patients), and bystander AED use (OR 5.25, 95% CI 3.58–7.70; I2 = 16%; 19 studies—1227 patients). The GRADE certainty of evidence was judged to be moderate. Conclusion In patients with SR-SCA, bystander presence, bystander CPR, and bystander AED use were significantly associated with survival. These results highlight the importance of witness intervention and encourage countries to develop their first aid training policy and AED installation in sport settings.

Abstract Aims There are several risk scores designed to predict mortality in patients with heart failure (HF). This study aimed to assess performance of risk scores validated for mortality prediction in patients with acute HF (AHF) and chronic HF. Methods and results MEDLINE and Scopus were searched from January 2015 to January 2021 for studies which internally or externally validated risk models for predicting all-cause mortality in patients with AHF and chronic HF. Discrimination data were analysed using C-statistics, and pooled using generic inverse-variance random-effects model. Nineteen studies (n = 494 156 patients; AHF: 24 762; chronic HF mid-term mortality: 62 000; chronic HF long-term mortality: 452 097) and 11 risk scores were included. Overall, discrimination of risk scores was good across the three subgroups: AHF mortality [C-statistic: 0.76 (0.68–0.83)], chronic HF mid-term mortality [1 year; C-statistic: 0.74 (0.68–0.79)], and chronic HF long-term mortality [≥2 years; C-statistic: 0.71 (0.69–0.73)]. MEESSI-AHF [C-statistic: 0.81 (0.80–0.83)] and MARKER-HF [C-statistic: 0.85 (0.80–0.89)] had an excellent discrimination for AHF and chronic HF mid-term mortality, respectively, whereas MECKI had good discrimination [C-statistic: 0.78 (0.73–0.83)] for chronic HF long-term mortality relative to other models. Overall, risk scores predicting short-term mortality in patients with AHF did not have evidence of poor calibration (Hosmer–Lemeshow P > 0.05). However, risk models predicting mid-term and long-term mortality in patients with chronic HF varied in calibration performance. Conclusions The majority of recently validated risk scores showed good discrimination for mortality in patients with HF. MEESSI-AHF demonstrated excellent discrimination in patients with AHF, and MARKER-HF and MECKI displayed an excellent discrimination in patients with chronic HF. However, modest reporting of calibration and lack of head-to-head comparisons in same populations warrant future studies.

Abstract Introduction Indigenous North Americans have the highest cigarette smoking prevalence among all racial and ethnic groups in the United States. We seek to identify effective components of smoking cessation interventions in Indigenous people in the United States associated with favorable cessation outcomes. Methods A review of literature studying smoking cessation interventions in Indigenous North Americans (American Indians and Alaska Natives) from January 2010 through August 2021 was completed. The primary objective of this study was to identify components of interventions associated with positive smoking cessation outcomes in Indigenous people. The studies identified were synthesized in a meta-narrative approach. Results Ten studies out of 608 titles were included (6 randomized trials, 2 single-arm studies, 1 cohort study, and 1 prospective observational study). Five categories of smoking cessation interventions were identified; phone or web-based tools, culturally-tailored interventions, the inclusion of Indigenous study personnel, pharmaceutical cessation aids, and behavioral health interventions. Phone and web tools, cultural tailoring, and inclusion of Indigenous personnel conditions inconsistently influenced smoking cessation. Pharmaceutical aids were viewed favorably among participants. Individualized behavioral counseling sessions were effective at promoting smoking cessation, as was input from local communities in the planning and implementation phases of study. Conclusion A successful smoking cessation intervention in Indigenous North Americans includes Tribal or community input in intervention design and implementation; should provide individualized counseling sessions for participants, and offer access to validated smoking cessation tools including pharmacotherapy. Implications This study identifies a paucity of smoking interventions utilizing standard of care interventions in Indigenous North Americans. Standard of care interventions including individualized cessation counseling and pharmacotherapy were effective at promoting cessation. The use of novel culturally tailored cessation interventions was not more effective than existing evidence-based care with the exception of including Tribal and local community input in intervention implementation. Future smoking cessation interventions in Indigenous North Americans should prioritize the use of standard of care cessation interventions.