Citations

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

Introduction Acute stroke patients presenting with large vessel occlusion secondary to intracranial atherosclerosis (ICAS‐LVO) may require rescue therapy (RT) in addition to mechanical thrombectomy (MT) to achieve and maintain successful recanalization. We performed a systematic review and meta‐analysis of comparative studies that reported outcomes of RT in ICAS‐LVO patients 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 to outcomes of ICAS‐LVO patients who did not undergo RT or to those presenting with embolic LVO patients (non‐ICAS LVO). Meta‐analysis using the random effects model was used to combine estimates reporting odds ratios (OR) and 95% confidence intervals (CI). Results Total of 9 nonrandomized studies were included: 5 studies in ICAS‐LVO RT vs. ICAS‐LVO non‐RT analysis and 5 ICAS‐LVO RT vs. non‐ICAS LVO analysis. Rescue treatments included intra‐arterial antiplatelets, angioplasty, stenting or combination of treatments. Compared to non‐RT ICAS LVO, RT was associated with increased favorable 90‐day outcome (OR 3.19, 95% CI 1.91‐5.32, I2 14%) and decreased 90‐day mortality (OR 0.35, 95% CI 0.16‐0.76, I2 21%) (Figure 1). In the analysis of ICAS LVO vs embolic LVO, the incidence of favorable 90‐day outcome and 90‐day mortality did not differ between the ICAS‐LVO RT and non‐ICAS LVO (OR 0.97, 95% CI 0.58‐1.64, I2 50%) and (OR 1.22, 95% CI 0.90‐1.66, I2 0%), respectively. Conclusions Rescue treatment is associated with better outcomes in ICAS‐LVO patients. The outcomes of ICAS‐LVO patients who receive RT may be comparable to embolic LVO patients (non‐ICAS LVO).

Abstract Background Optimizing therapy and monitoring response are integral aspects of inflammatory bowel disease treatment. We conducted a systematic review and meta-analysis to determine whether serum ustekinumab trough concentrations during maintenance therapy were associated with ustekinumab treatment response in patients with inflammatory bowel disease. Methods A systematic review was performed to March 21, 2022, to identify studies using MEDLINE, EMBASE, and the Cochrane library. We included studies that reported the association between serum ustekinumab trough concentrations with clinical or endoscopic remission. Outcome measures were combined across studies using the random-effects model with an odds ratio (OR) for binary outcomes of endoscopic and clinical remission. Results We identified 14 observational studies that were included in the analysis for clinical remission (919 patients, 63% with Crohn’s disease) or endoscopic remission (290 patients, all with Crohn’s disease). Median ustekinumab trough concentrations were higher amongst individuals achieving clinical remission compared with those not achieving remission (mean difference, 1.6 ug/mL; 95% confidence interval [CI], 0.21-3.01 ug/mL). Furthermore, individuals with median serum trough concentration in the fourth quartile were significantly more likely to achieve clinical (OR, 3.61; 95% CI, 2.11-6.20) but not endoscopic remission (OR, 4.67; 95% CI, 0.86-25.19) compared with those with first quartile median trough concentrations. Conclusion Based on the results of this meta-analysis primarily relating to patients with Crohn’s disease on maintenance ustekinumab treatment, it appears that there is an association between higher ustekinumab trough concentration and clinical outcomes. Prospective studies are required to determine whether proactive dose adjustments of ustekinumab therapy provides additional clinical benefit.

INTRODUCTION: Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network meta-analysis comparing early symptomatic remission with approved therapies. METHODS: Through a systematic literature review to December 31, 2022, we identified randomized trials in adult outpatients with moderate-severe UC treated with approved therapies (tumor necrosis factor α antagonists, vedolizumab, ustekinumab, janus kinase inhibitors, or ozanimod), compared with each other or placebo, reporting rates of symptomatic remission (based on partial Mayo score, with resolution of rectal bleeding and near-normalization of stool frequency) at weeks 2, 4, and/or 6. We performed random-effects network meta-analysis using a frequentist approach and estimated relative risk (RR) and 95% confidence interval values. RESULTS: On network meta-analysis, upadacitinib was more effective than all agents in achieving symptomatic remission at weeks 2 (range of RR, 2.85–6.27), 4 (range of RR, 1.78–2.37), and 6 (range of RR, 1.84–2.79). Tumor necrosis factor α antagonists and filgotinib, but not ustekinumab and vedolizumab, were more effective than ozanimod in achieving symptomatic remission at week 2, but not at weeks 4 and 6. With approximately 10% placebo-treated patients achieving symptomatic remission at 2 weeks, we estimated 68%, 22%, 23.7%, 23.9%, 22.2%, 18.4%, 15.7%, and 10.9% of upadacitinib-, filgotinib-, infliximab-, adalimumab-, golimumab-, ustekinumab-, vedolizumab-, and ozanimod-treated patients would achieve early symptomatic remission, ustekinumab and vedolizumab achieving rapid remission only in biologic-naïve patients. DISCUSSION: In a systematic review and network meta-analysis, upadacitinib was most effective in achieving early symptomatic remission, whereas ozanimod was relatively slower acting.

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 Introduction: Deep learning (DL) has shown promising results for mammographic breast cancer diagnosis. However, the impact of artificial intelligence (AI) in the screening process have not yet been fully addressed in terms of workload reduction, which has potential to decrease healthcare disparities. Radiologists are tasked with overwhelming volumes of screening mammograms, particularly in medically underserved areas. Therefore, when applied to workflow improvement, AI might be a tool to reduce healthcare disparities. The purpose of this systematic review and meta-analysis was to assess if AI-based triaging of breast cancer screening mammograms could reduce the radiologist’s workload with non-inferior sensitivity. Methods: PubMed, EMBASE, Cochrane Central and Web of Science databases were systematically searched for studies that evaluated AI algorithms on computer-aided triage of breast cancer screening mammograms. We extracted data from homogenous studies and performed a proportion meta-analysis with random-effects model to verify the radiologist’s workload reduction and the software’s sensitivity. Results: A total of 14 studies were systematically selected. Three studies using the same commercially available DL algorithm were included in the meta-analysis, with 156852 examinations evaluated at the threshold of 8. The radiologist’s workload decreased by 68.3% (95%CI 0.655-0.711, I² = 98.76%, p < 0.001), with a sensitivity of 93.1% (95%CI 0.882-0.979, I² = 83.86%, p = 0.002). Conclusion: Our findings suggest that DL computer-aided triage of breast cancer screening mammograms significantly reduces the radiologist’s workload with high sensitivity. Although AI’s implementation remains complex and heterogeneous, it is a promising tool to optimize healthcare resources with a potential large impact in low resource settings that struggle with workforce shortage. Citation Format: Debora Xavier, Isabele A. Miyawaki, Carlos Alberto Campello Jorge, Matheus Jose Barbosa Moreira, Bruno M. Carvalho, Felipe Batalini. Artificial intelligence-based triaging of breast cancer screening mammograms and radiologist workload reduction: a systematic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-06.

Introduction: Self-directed learning has been recommended as a promising methodology for lifelong learning in medicine. However, the concept of self-directed learning continues to be elusive, with students and educators finding difficulty in defining it and agreeing on its worth. Methods: In this paper we review the literature of self-directed learning in health professions education and present a framework based on Malcolm Knowles’ key components of self-directed learning. Results: The key components of self-directed learning are: the educator as a facilitator, identification of learning needs, development of learning objectives, identification of appropriate resources, implementation of the process, commitment to a learning contract and evaluation of learning. Several but not all of these components are often described in the published literature. Conclusion: Although the presented framework provides some consistency for educators interested in applying SDL methods, future studies are needed to standardise self-directed learning curricula and to determine the effectiveness of these components on educational outcomes. Key words: Independent study, Medical education, Self-assessment, Self-directed learning, Selfeducation

Abstract Immunoassays designed to detect SARS-CoV-2 protein antigens (Ag) are commonly used to diagnose COVID-19. The most widely used tests are lateral flow assays that generate results in approximately 15 minutes for diagnosis at the point-of-care. Higher throughput, laboratory-based SARS-CoV-2 Ag assays have also been developed. The number of commercially available SARS-CoV-2 Ag detection tests has increased rapidly, as has the COVID-19 diagnostic literature. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the literature and develop best-practice guidance related to SARS-CoV-2 Ag testing. This guideline is an update to the third in a series of frequently updated COVID-19 diagnostic guidelines developed by the IDSA. IDSA's goal was to develop evidence-based recommendations or suggestions that assist clinicians, clinical laboratories, patients, public health authorities, administrators, and policymakers in decisions related to the optimal use of SARS-CoV-2 Ag tests in both medical and nonmedical settings. A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 Ag tests. A review of relevant, peer-reviewed published literature was conducted through 1 April 2022. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations. The panel made 10 diagnostic recommendations that address Ag testing in symptomatic and asymptomatic individuals and assess single versus repeat testing strategies. US Food and Drug Administration (FDA) SARS-CoV-2 Ag tests with Emergency Use Authorization (EUA) have high specificity and low to moderate sensitivity compared with nucleic acid amplification testing (NAAT). Ag test sensitivity is dependent on the presence or absence of symptoms and, in symptomatic patients, on timing of testing after symptom onset. In most cases, positive Ag results can be acted upon without confirmation. Results of point-of-care testing are comparable to those of laboratory-based testing, and observed or unobserved self-collection of specimens for testing yields similar results. Modeling suggests that repeat Ag testing increases sensitivity compared with testing once, but no empirical data were available to inform this question. Based on these observations, rapid RT-PCR or laboratory-based NAAT remain the testing methods of choice for diagnosing SARS-CoV-2 infection. However, when timely molecular testing is not readily available or is logistically infeasible, Ag testing helps identify individuals with SARS-CoV-2 infection. Data were insufficient to make a recommendation about the utility of Ag testing to guide release of patients with COVID-19 from isolation. The overall quality of available evidence supporting use of Ag testing was graded as very low to moderate.