An Endoscopic Scoring System for Achalasia: The CARS score.

BACKGROUND AND AIMS: The diagnosis of achalasia is associated with an average delay of two years. Endoscopic features may prompt an earlier diagnosis. We aimed to develop and test a novel endoscopic CARS score for the prediction of achalasia. METHODS: Part 1: Twenty endoscopic videos were taken from patients undergoing endoscopy for dysphagia or reflux. A survey with videos and endoscopic criteria options was distributed to 6 esophagologists and 6 general gastroenterologists. Inter-rater reliability (IRR) was measured and logistic regression was used to evaluate predictive performance. Three rounds of review were conducted to select the final score of four components. PART 2: A retrospective review was conducted for consecutive patients who had comprehensive esophageal testing. Each patient had a CARS endoscopic score calculated based on findings reported at endoscopy. RESULTS: From a video review and analysis of score components, IRR ranged from 0.23 to 0.57 for score components. The final CARS score was selected based on the following four components: Contents, Anatomy, Resistance, and Stasis. In a mixed effects model, the mean score across raters was higher for achalasia compared to non-achalasia subjects (4.44 vs. 0.87, p = < 0.01). In part 2 of the study, achalasia patients had a higher mean CARS score compared to those with no / ineffective motility disorder (mean 4.1 vs 1.3, p = < 0.01). CONCLUSIONS: We developed a CARS score based on reliability performance in a video-based survey and tested the score in clinical setting. The CARS score performed well in predicting achalasia.

Performance of Tools and Measures to Predict Fluid Responsiveness in Pediatric Shock and Critical Illness: A Systematic Review and Meta-Analysis.

OBJECTIVES: In this systematic review and meta-analysis we asked: Do predictors of fluid responsiveness in children perform comparably: 1) in the PICU as in non-PICU settings? 2) in shock states compared with nonshock states? Additionally, 3) is there an association between preload responsiveness and clinical response? DATA SOURCES: Ovid Medline, PubMed, and Embase databases were searched from inception through May 2022. STUDY SELECTION: Included studies reported physiological response to IV fluid administration in humans less than 18 years. Only studies reporting an area under the receiver operating characteristic curve (AUROC) were included for descriptive analysis. Only studies for which a se could be estimated were included for meta-analysis. DATA EXTRACTION: Title, abstract, full text screening, and extraction were completed by two authors (S.B.W., J.M.W.). Variables extracted included predictors ("tools") and outcome measures ("reference tests") of fluid responsiveness, demographic, and clinical variables. DATA SYNTHESIS: We identified 62 articles containing 204 AUROCs for 55 tools, primarily describing mechanically ventilated children in an operating room or PICU. Meta-analysis across all tools showed poor predictive performance (AUROC, 0.66; 95% CI, 0.63-0.69), although individual performance varied greatly (range, 0.49-0.87). After controlling for PICU setting and shock state, PICU setting was associated with decreased predictive performance (coefficient, -0.56; p = 0.0007), while shock state was associated with increased performance (0.54; p = 0.0006). Effect of PICU setting and shock state on each tool was not statistically significant but analysis was limited by sample size. The association between preload responsiveness and clinical response was rarely studied but results did not suggest an association. Ultrasound measurements were prone to inherent test review and incorporation biases. CONCLUSIONS: We suggest three opportunities for further research in fluid responsiveness in children: 1) assessing predictive performance of tools during resuscitation in shock states; 2) separating predictive tool from reference test when using ultrasound techniques; and 3) targeting decreasing time in a shock state, rather than just increase in preload.

The Severity of Reduced Esophageal Distensibility Parallels Eosinophilic Esophagitis Disease Duration.

BACKGROUND & AIMS: Chronic inflammation of eosinophilic esophagitis (EoE) results in progressive, fibrostenotic remodeling of the esophageal wall. This study aimed to demonstrate objective changes in esophageal distensibility relative to duration of EoE disease using a functional lumen imaging probe (FLIP). METHODS: Adult patients with EoE who completed a 16-cm FLIP protocol during endoscopy were evaluated in a cross-sectional study. FLIP analysis focused on distensibility plateau (DP) of the esophageal body. The time from onset of symptoms to time of endoscopy with FLIP was assessed, as was time from symptom onset to EoE diagnosis (ie, diagnostic delay). RESULTS: A total of 171 patients (mean age 38 ± 12 years; 31% female) were included; the median symptom duration was 8 (interquartile range, 3-15) years and diagnostic delay was 4 (interquartile range, 1-12) years. At the time of endoscopy with FLIP, there were 54 patients (39%) in histologic remission (<15 eosinophils per high-power field [eos/hpf]). Symptom duration and diagnostic delay were negatively correlated with DP (rho = -0.326 and -0.309; P values < .001). Abnormal esophageal distensibility (DP ≤17 mm) was more prevalent with increased duration of symptoms (P < .004): 23% at <5 years to 64% at ≥25 years. When stratifying the cohort based on mucosal eosinophil density, patients with ≥15 eos/hpf had significantly lower DP with greater symptom duration (P = .004), while there was not a significant difference among patients with <15 eos/hpf (P = .060). CONCLUSIONS: Esophageal distensibility objectively measured with FLIP was reduced in EoE patients with greater symptom duration and diagnostic delay. This supports that EoE is a progressive, fibrostenotic disease and that FLIP may be a useful tool to monitor disease progression in EoE.

Promoting REproductive Planning And REadiness in Diabetes (PREPARED) Study protocol: a clinic-randomised controlled trial testing a technology-based strategy to promote preconception care for women with type 2 diabetes.

INTRODUCTION: Women with type 2 diabetes (T2DM) are more likely to experience adverse reproductive outcomes, yet preconception care can significantly reduce these risks. For women with T2DM, preconception care includes reproductive planning and patient education on: (1) the importance of achieving glycaemic control before pregnancy, (2) using effective contraception until pregnancy is desired, (3) discontinuing teratogenic medications if pregnancy could occur, (4) taking folic acid, and (5) managing cardiovascular and other risks. Despite its importance, few women with T2DM receive recommended preconception care. METHODS AND ANALYSIS: We are conducting a two-arm, clinic-randomised trial at 51 primary care practices in Chicago, Illinois to evaluate a technology-based strategy to 'hardwire' preconception care for women of reproductive age with T2DM (the PREPARED (Promoting REproductive Planning And REadiness in Diabetes) strategy) versus usual care. PREPARED leverages electronic health record (EHR) technology before and during primary care visits to: (1) promote medication safety, (2) prompt preconception counselling and reproductive planning, and (3) deliver patient-friendly educational tools to reinforce counselling. Post-visit, text messaging is used to: (4) encourage healthy lifestyle behaviours. English and Spanish-speaking women, aged 18-44 years, with T2DM will be enrolled (N=840; n=420 per arm) and will receive either PREPARED or usual care based on their clinic's assignment. Data will be collected from patient interviews and the EHR. Outcomes include haemoglobin A1c (primary), reproductive knowledge and self-management behaviours. We will use generalised linear mixed-effects models (GLMMs) to evaluate the impact of PREPARED on these outcomes. GLMMs will include a fixed effect for treatment assignment (PREPARED vs usual care) and random clinic effects. ETHICS AND DISSEMINATION: This study was approved by the Northwestern University Institutional Review Board (STU00214604). Study results will be published in journals with summaries shared online and with participants upon request. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04976881).

On the Accuracy of Replication Failure Rates.

A prominent approach to studying the replication crisis has been to conduct replications of several different scientific findings as part of the same research effort. The reported proportion of findings that these programs determined failed to replicate have become important statistics in the replication crisis. However, these "failure rates" are based on decisions about whether individual studies replicated, which are themselves subject to statistical uncertainty. In this article, we examine how that uncertainty impacts the accuracy of reported failure rates and find that the reported failure rates can be substantially biased and highly variable. Indeed, very high or very low failure rates could arise from chance alone.

Intrauterine Insemination After Human Chorionic Gonadotropin Trigger or Luteinizing Hormone Surge: A Meta-analysis.

OBJECTIVE: To assess the odds of pregnancy after intrauterine insemination (IUI) timed by ultrasound monitoring and human chorionic gonadotropin (hCG) administration compared with monitoring luteinizing hormone (LH) levels. DATA SOURCES: We searched PubMed (MEDLINE), EMBASE (Elsevier), Scopus (Elsevier), Web of Science (Clarivate Analytics), ClinicalTrials.gov (National Institutes of Health), and the Cochrane Library (Wiley) from the inception until October 1, 2022. No language limitations were applied. METHODS OF STUDY SELECTION: After deduplication, 3,607 unique citations were subjected to blinded independent review by three investigators. Thirteen studies (five retrospective cohort, four cross-sectional, two randomized controlled trials, and two randomized crossover studies) that enrolled women undergoing natural cycle, oral medication (clomid or letrozole), or both for IUI were included in the final random-effects model meta-analysis. Methodologic quality of included studies was assessed with the Downs and Black checklist. TABULATION, INTEGRATION, AND RESULTS: Data extraction was compiled by two authors, including publication information, hCG and LH monitoring guidelines, and pregnancy outcomes. No significant difference in odds of pregnancy between hCG administration and endogenous LH monitoring was observed (odds ratio [OR] 0.92, 95% CI 0.69-1.22, P =.53). Subgroup analysis of the five studies that included natural cycle IUI outcomes also showed no significant difference in odds of pregnancy between the two methods (OR 0.88, 95% CI 0.46-1.69, P =.61). Finally, a subgroup analysis of 10 studies that included women who underwent ovarian stimulation with oral medications (clomid or letrozole) did not demonstrate a difference in odds of pregnancy between ultrasonography with hCG trigger and LH-timed IUI (OR 0.88, 95% CI 0.66-1.16, P =.32). Statistically significant heterogeneity was noted between studies. CONCLUSION: This meta-analysis showed no difference between pregnancy outcomes between at-home LH monitoring and timed IUI. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021230520.

Interrater Reliability of Functional Lumen Imaging Probe Panometry and High-Resolution Manometry for the Assessment of Esophageal Motility Disorders.

INTRODUCTION: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations. METHODS: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard. RESULTS: Fifteen raters completed the HRM and FLIP studies. An excellent interrater agreement was seen in supine median integral relaxation pressure (ICC 0.96, 95% confidence interval 0.95-0.98), and a good agreement was seen with the assessment of esophagogastric junction (EGJ) outflow, peristalsis, and assignment of a Chicago Classification version 4.0 diagnosis using HRM (κ = 0.71, 0.75, and 0.70, respectively). An excellent interrater agreement for EGJ distensibility index and maximum diameter (0.91 [0.90-0.94], 0.92 [0.89-0.95]) was seen, and a moderate-to-good agreement was seen in the assignment of EGJ opening classification, contractile response pattern, and motility classification (κ = 0.68, 0.56, and 0.59, respectively) on FLIP. Rater accuracy for Chicago Classification version 4.0 diagnosis on HRM was 82% (95% confidence interval 78%-84%) and for motility diagnosis on FLIP Panometry was 78% (95% confidence interval 72%-81%). DISCUSSION: Our study demonstrates high levels of interrater agreement and accuracy in the interpretation of HRM and FLIP metrics and moderate-to-high levels for motility classification in FLIP, supporting the use of these approaches for primary or complementary evaluation of esophageal motility disorders.

The process of replication target selection in psychology: what to consider?

Increased execution of replication studies contributes to the effort to restore credibility of empirical research. However, a second generation of problems arises: the number of potential replication targets is at a serious mismatch with available resources. Given limited resources, replication target selection should be well-justified, systematic and transparently communicated. At present the discussion on what to consider when selecting a replication target is limited to theoretical discussion, self-reported justifications and a few formalized suggestions. In this Registered Report, we proposed a study involving the scientific community to create a list of considerations for consultation when selecting a replication target in psychology. We employed a modified Delphi approach. First, we constructed a preliminary list of considerations. Second, we surveyed psychologists who previously selected a replication target with regards to their considerations. Third, we incorporated the results into the preliminary list of considerations and sent the updated list to a group of individuals knowledgeable about concerns regarding replication target selection. Over the course of several rounds, we established consensus regarding what to consider when selecting a replication target. The resulting checklist can be used for transparently communicating the rationale for selecting studies for replication.

Comparative effectiveness of a mindfulness-based intervention (M-Body) on depressive symptoms: study protocol of a randomized controlled trial in a Federally Qualified Health Center (FQHC).

BACKGROUND: Mindfulness-based interventions have been shown to improve psychological outcomes including stress, anxiety, and depression in general population studies. However, effectiveness has not been sufficiently examined in racially and ethnically diverse community-based settings. We will evaluate the effectiveness and implementation of a mindfulness-based intervention on depressive symptoms among predominantly Black women at a Federally Qualified Health Center in a metropolitan city. METHODS: In this 2-armed, stratified, individually randomized group-treated controlled trial, 274 English-speaking participants with depressive symptoms ages 18-65 years old will be randomly assigned to (1) eight weekly, 90-min group sessions of a mindfulness-based intervention (M-Body), or (2) enhanced usual care. Exclusion criteria include suicidal ideation in 30 days prior to enrollment and regular (>4x/week) meditation practice. Study metrics will be assessed at baseline and 2, 4, and 6 months after baseline, through clinical interviews, self-report surveys, and stress biomarker data including blood pressure, heart rate, and stress related biomarkers. The primary study outcome is depressive symptom score after 6 months. DISCUSSION: If M-Body is found to be an effective intervention for adults with depressive symptoms, this accessible, scalable treatment will widely increase access to mental health treatment in underserved, racial/ethnic minority communities. TRIAL REGISTRATION: ClinicalTrials.gov NCT03620721. Registered on 8 August 2018.

Functional Lumen Imaging Probe Panometry Helps Identify Clinically Relevant Esophagogastric Junction Outflow Obstruction per Chicago Classification v4.0.

INTRODUCTION: Esophagogastric junction (EGJ) outflow obstruction (EGJOO) per Chicago Classification v4.0 (CCv4.0) represents a high-resolution manometry (HRM) diagnosis with uncertain clinical significance. This study aimed to evaluate functional lumen imaging probe (FLIP) panometry among patients with EGJOO on HRM/CCv4.0 to assess clinical/manometric associations and treatment outcomes. METHODS: An observational cohort study was performed on patients who completed FLIP during endoscopy and had an HRM/CCv4.0 diagnosis of EGJOO, i.e., HRM-EGJOO (inconclusive). Abnormal FLIP panometry motility classifications were applied to identify FLIP-confirmed conclusive EGJOO. Rapid drink challenge on HRM and timed barium esophagram were also assessed. Clinical management plan was determined by treating physicians and assessed through chart review. Clinical outcome was defined using the Eckardt score (ES) during follow-up evaluation: ES < 3 was considered a good outcome. RESULTS: Of 139 adult patients with manometric EGJOO (inconclusive per CCv4.0), a treatment outcome ES was obtained in 55 after achalasia-type treatment (i.e., pneumatic dilation, peroral endoscopic myotomy, laparoscopic Heller myotomy, or botulinum toxin injection) and 36 patients after other nonachalasia-type treatment. Among patients with conclusive EGJOO by HRM-FLIP complementary impression, 77% (33/43) had a good outcome after achalasia-type treatment, whereas 0% (0/12) of patients had a good outcome after nonachalasia-type treatment. Of patients with normal EGJ opening on FLIP, one-third of patients treated with achalasia-type treatment had a good outcome, while 9 of the 10 treated conservatively had a good outcome. DISCUSSION: FLIP panometry provides a useful complement to clarify the clinical significance of an HRM/CCv4.0 EGJOO diagnosis and help direct management decisions.

Estimating Probability for Esophageal Obstruction: A Diagnostic Decision Support Tool Applying Machine Learning to Functional Lumen Imaging Probe Panometry.

Background/Aims: This study aimed to develop a diagnostic tool using machine learning to apply functional luminal imaging probe (FLIP) panometry data to determine the probability of esophagogastric junction (EGJ) obstruction as determined using the Chicago Classification version 4.0 (CCv4.0) and high-resolution manometry (HRM). Methods: Five hundred and fifty-seven adult patients that completed FLIP and HRM (with a conclusive CCv4.0 assessment of EGJ outflow) and 35 asymptomatic volunteers ("controls") were included. EGJ opening was evaluated with 16-cm FLIP performed during sedated endoscopy via EGJ-distensibility index and maximum EGJ diameter. HRM was classified according to the CCv4.0 as conclusive disorders of EGJ outflow or normal EGJ outflow (timed barium esophagram applied when required and available). The probability tool utilized Bayesian additive regression treesBART, which were evaluated using a leave-one-out approach and a holdout test set. Results: Per HRM and CCv4.0, 243 patients had a conclusive disorder of EGJ outflow while 314 patients (and all 35 controls) had normal EGJ outflow. The model accuracy to predict EGJ obstruction (based on leave-one-out/holdout test set, respectively) was 89%/90%, with 87%/85% sensitivity, 92%/97% specificity, and an area under the receiver operating characteristic curve of 0.95/0.97. A free, open-source tool to calculate probability for EGJ obstruction using FLIP metrics is available at https://www.wklytics.com/nmgi/prob_flip.html. Conclusions: Application of FLIP metrics utilizing a probabilistic approach incorporates the diagnostic confidence (or uncertainty) into the clinical interpretation of EGJ obstruction. This tool can provide clinical decision support during application of FLIP Panometry for evaluation of esophageal motility disorders.

Top Surgery and Chest Dysphoria Among Transmasculine and Nonbinary Adolescents and Young Adults.

Importance: Transgender and nonbinary (TGNB) adolescents and young adults (AYA) designated female at birth (DFAB) experience chest dysphoria, which is associated with depression and anxiety. Top surgery may be performed to treat chest dysphoria. Objective: To determine whether top surgery improves chest dysphoria, gender congruence, and body image in TGNB DFAB AYA. Design, Setting, and Participants: This is a nonrandomized prospective cohort study of patients who underwent top surgery between December 2019 and April 2021 and a matched control group who did not receive surgery. Patients completed outcomes measures preoperatively and 3 months postoperatively. This study took place across 3 institutions in a single, large metropolitan city. Patients aged 13 to 24 years who presented for gender-affirming top surgery were recruited into the treatment arm. Patients in the treatment arm were matched with individuals in the control arm based on age and duration of testosterone therapy. Exposures: Patients in the surgical cohort underwent gender-affirming mastectomy; surgical technique was at the discretion of the surgeon. Main Outcomes and Measures: Patient-reported outcomes were collected at enrollment and 3 months postoperatively or 3 months postbaseline for the control cohort. The primary outcome was the Chest Dysphoria Measure (CDM). Secondary outcomes included the Transgender Congruence Scale (TCS) and Body Image Scale (BIS). Baseline demographic and surgical variables were collected, and descriptive statistics were calculated. Inverse probability of treatment weighting (IPTW) was used to estimate the association of top surgery with outcomes. Probability of treatment was estimated using gradient-boosted machines with the following covariates: baseline outcome score, age, gender identity, race, ethnicity, insurance type, body mass index, testosterone use duration, chest binding, and parental support. Results: Overall, 81 patients were enrolled (mean [SD] age, 18.6 [2.7] years); 11 were lost to follow-up. Thirty-six surgical patients and 34 matched control patients completed the outcomes measures. Weighted absolute standardized mean differences were acceptable between groups with respect to body mass index, but were not comparable with respect to the remaining demographic variables baseline outcome measures. Surgical complications were minimal. IPTW analyses suggest an association between surgery and substantial improvements in CDM (-25.58 points; 95% CI, -29.18 to -21.98), TCS (7.78 points; 95% CI, 6.06-9.50), and BIS (-7.20 points; 95% CI, -11.68 to -2.72) scores. Conclusions and Relevance: Top surgery in TGNB DFAB AYA is associated with low complication rates. Top surgery is associated with improved chest dysphoria, gender congruence, and body image satisfaction in this age group.

Bilateral upper extremity motor priming (BUMP) plus task-specific training for severe, chronic upper limb hemiparesis: study protocol for a randomized clinical trial.

BACKGROUND: Various priming techniques to enhance neuroplasticity have been examined in stroke rehabilitation research. Most priming techniques are costly and approved only for research. Here, we describe a priming technique that is cost-effective and has potential to significantly change clinical practice. Bilateral motor priming uses the Exsurgo priming device (Exsurgo Rehabilitation, Auckland, NZ) so that the less affected limb drives the more affected limb in bilateral symmetrical wrist flexion and extension. The aim of this study is to determine the effects of a 5-week protocol of bilateral motor priming in combination with task-specific training on motor impairment of the affected limb, bimanual motor function, and interhemispheric inhibition in moderate to severely impaired people with stroke. METHODS: Seventy-six participants will be randomized to receive either 15, 2-h sessions, 3 times per week for 5 weeks (30 h of intervention) of bilateral motor priming and task-specific training (experimental group) or the same dose of control priming plus the task-specific training protocol. The experimental group performs bilateral symmetrical arm movements via the Exsurgo priming device which allows both wrists to move in rhythmic, symmetrical wrist flexion and extension for 15 min. The goal is one cycle (wrist flexion and wrist extension) per second. The control priming group receives transcutaneous electrical stimulation below sensory threshold for 15 min prior to the same 45 min of task-specific training. Outcome measures are collected at pre-intervention, post-intervention, and follow-up (8 weeks post-intervention). The primary outcome measure is the Fugl-Meyer Test of Upper Extremity Function. The secondary outcome is the Chedoke Arm and Hand Activity Index-Nine, an assessment of bimanual functional tasks. DISCUSSION: To date, there are only 6 studies documenting the efficacy of priming using bilateral movements, 4 of which are pilot or feasibility studies. This is the first large-scale clinical trial of bilateral priming plus task-specific training. We have previously completed a feasibility intervention study of bilateral motor priming plus task-specific training and have considerable experience using this protocol. TRIAL REGISTRATION: ClinicalTrials.gov NCT03517657 . Retrospectively registered on May 7, 2018.

Embedded emergency department physical therapy versus usual care for acute low back pain: a protocol for the NEED-PT randomised trial.

INTRODUCTION: Low back pain is a common problem and a substantial source of morbidity and disability worldwide. Patients frequently visit the emergency department (ED) for low back pain, but many experience persistent symptoms at 3 months despite frequent receipt of opioids. Although physical therapy interventions have been demonstrated to improve patient functioning in the outpatient setting, no randomised trial has yet to evaluate physical therapy in the ED setting. METHODS AND ANALYSIS: This is a single-centre cluster-randomised trial of an embedded ED physical therapy intervention for acute low back pain. We used a covariate-constrained approach to randomise individual physicians (clusters) at an urban academic ED in Chicago, Illinois, USA, to receive, or not receive, an embedded physical therapist on their primary treatment team to evaluate all patients with low back pain. We will then enrol individual ED patients with acute low back pain and allocate them to the embedded physical therapy or usual care study arms, depending on the randomisation assignment of their treating physician. We will follow patients to a primary endpoint of 3 months and compare a primary outcome of change in PROMIS-Pain Interference score and secondary outcomes of change in modified Oswestry Disability Index score and patient-reported opioid use. Our primary approach will be a modified intention-to-treat analysis, whereby all participants who complete at least one follow-up data time point will be included in analyses, regardless of their or their physicians' adherence to their assigned study arm. ETHICS AND DISSEMINATION: This trial is funded by the US Agency for Healthcare Research and Quality (R01HS027426) and was approved by the Northwestern University Institutional Review Board. All physician and patient participants will give written informed consent to study participation. Trial results will be submitted for presentation at scientific meetings and for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04921449).

Prognostic factors for polyp recurrence in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is frequently managed with endoscopic sinus surgery (ESS). Prior studies describe individual clinical variables and eosinophil density measures as prognostic for polyp recurrence (PR). However, the relative prognostic significance of these have not been extensively investigated. OBJECTIVES: We sought to evaluate the impact of PR on measures of disease severity post-ESS and quantify the prognostic value of various clinical variables and biomarkers. METHODS: Ninety-four patients with chronic rhinosinusitis with nasal polyps and prospectively biobanked polyp homogenates at the time of ESS were recruited 2 to 5 years post-ESS. Patients were evaluated with patient-reported outcome measures and endoscopic and radiographic scoring pre- and post-ESS. Biomarkers in polyp homogenates were measured with ELISA and Luminex. Relaxed least absolute shrinkage and selection operator regression optimized predictive clinical, biomarker, and combined models. Model performance was assessed using receiver-operating characteristic curve and random forest analysis. RESULTS: PR was found in 39.4% of patients, despite significant improvements in modified Lund-Mackay (MLM) radiographic and 22-item Sinonasal Outcomes Test scores (both P < .0001). PR was significantly associated with worse post-ESS MLM, modified Lund-Kennedy, and 22-item Sinonasal Outcomes Test scores. Relaxed least absolute shrinkage and selection operator identified 2 clinical predictors (area under the curve = 0.79) and 3 biomarkers (area under the curve = 0.78) that were prognostic for PR. When combined, the model incorporating these pre-ESS factors: MLM, asthma, eosinophil cationic protein, anti-double-stranded DNA IgG, and IL-5 improved PR predictive accuracy to area under the curve of 0.89. Random forest analysis identified and validated each of the 5 variables as the strongest predictors of PR. CONCLUSIONS: PR had strong associations with patient-reported outcome measures, endoscopic and radiographic severity. A combined model comprised of eosinophil cationic protein, IL-5, pre-ESS MLM, asthma, and anti-double-stranded DNA IgG could accurately predict PR.

On the bias of complete- and shifting-case meta-regressions with missing covariates.

Missing covariates is a common issue when fitting meta-regression models. Standard practice for handling missing covariates tends to involve one of two approaches. In a complete-case analysis, effect sizes for which relevant covariates are missing are omitted from model estimation. Alternatively, researchers have employed the so-called "shifting units of analysis" wherein complete-case analyses are conducted on only certain subsets of relevant covariates. In this article, we clarify conditions under which these approaches generate unbiased estimates of regression coefficients. We find that unbiased estimates are possible when the probability of observing a covariate is completely independent of effect sizes. When that does not hold, regression coefficient estimates may be biased. We study the potential magnitude of that bias assuming a log-linear model of missingness and find that the bias can be substantial, as large as Cohen's d = 0.4-0.8 depending on the missingness mechanism.

A multi-stage machine learning model for diagnosis of esophageal manometry.

High-resolution manometry (HRM) is the primary procedure used to diagnose esophageal motility disorders. Its manual interpretation and classification, including evaluation of swallow-level outcomes and then derivation of a study-level diagnosis based on Chicago Classification (CC), may be limited by inter-rater variability and inaccuracy of an individual interpreter. We hypothesized that an automatic diagnosis platform using machine learning and artificial intelligence approaches could be developed to accurately identify esophageal motility diagnoses. Further, a multi-stage modeling framework, akin to the step-wise approach of the CC, was utilized to leverage advantages of a combination of machine learning approaches including deep-learning models and feature-based models. Models were trained and tested using a dataset comprised of 1741 patients' HRM studies with CC diagnoses assigned by expert physician raters. In the swallow-level stage, three models based on convolutional neural networks (CNNs) were developed to predict swallow type and swallow pressurization (test accuracies of 0.88 and 0.93, respectively), and integrated relaxation pressure (IRP)(regression model with test error of 4.49 mmHg). At the study-level stage, model selection from families of the expert-knowledge-based rule models, xgboost models and artificial neural network(ANN) models were conducted. A simple model-agnostic strategy of model balancing motivated by Bayesian principles was utilized, which gave rise to model averaging weighted by precision scores. The averaged (blended) models and individual models were compared and evaluated, of which the best performance on test dataset is 0.81 in top-1 prediction, 0.92 in top-2 predictions. This is the first artificial-intelligence style model to automatically predict esophageal motility (CC) diagnoses from HRM studies using raw multi-swallow data and it achieved high accuracy. Thus, this proposed modeling framework could be broadly applied to assist with HRM interpretation in a clinical setting.

Exploratory Analyses for Missing Data in Meta-Analyses and Meta-Regression: A Tutorial.

OBJECTIVES: In this tutorial, we examine methods for exploring missingness in a dataset in ways that can help to identify the sources and extent of missingness, as well as clarify gaps in evidence. METHODS: Using raw data from a meta-analysis of substance abuse interventions, we demonstrate the use of exploratory missingness analysis (EMA) including techniques for numerical summaries and visual displays of missing data. RESULTS: These techniques examine the patterns of missing covariates in meta-analysis data and the relationships among variables with missing data and observed variables including the effect size. The case study shows complex relationships among missingness and other potential covariates in meta-regression, highlighting gaps in the evidence base. CONCLUSION: Meta-analysts could often benefit by employing some form of EMA as they encounter missing data.

Validation of Clinically Relevant Thresholds of Esophagogastric Junction Obstruction Using FLIP Panometry.

BACKGROUND & AIMS: This study aimed to assess the accuracy of functional luminal imaging probe (FLIP) panometry to detect esophagogastric junction (EGJ) obstruction assigned by high-resolution manometry (HRM) and the Chicago Classification version 4.0 (CCv4.0). METHODS: Six hundred eighty-seven adult patients who completed FLIP and HRM for primary esophageal motility evaluation and 35 asymptomatic volunteers (controls) were included. EGJ opening was evaluated with 16-cm FLIP during sedated endoscopy via EGJ-distensibility index (DI) and maximum EGJ diameter. HRM was classified according to CCv4.0 and focused on studies with a conclusive disorder of EGJ outflow (ie, achalasia subtypes I, II, or III; or EGJ outflow obstruction with abnormal timed barium esophagogram) or normal EGJ outflow. RESULTS: All 35 controls had EGJ-DI >3.0 mm2/mmHg and maximum EGJ diameter >16 mm. Per HRM and CCv4.0, 245 patients had a conclusive disorder of EGJ outflow, and 314 patients had normal EGJ outflow. Among the 241 patients with reduced EGJ opening (EGJ-DI <2.0 mm2/mmHg and maximum EGJ diameter <12 mm) on FLIP panometry, 86% had a conclusive disorder of EGJ outflow per CCv4.0. Among the 203 patients with normal EGJ opening (EGJ-DI ≥2.0 mm2/mmHg and maximum EGJ diameter ≥16 mm) on FLIP panometry, 99% had normal EGJ outflow per CCv4.0. CONCLUSIONS: FLIP panometry accurately identified clinically relevant conclusive EGJ obstruction as defined by CCv4.0 in patients evaluated for esophageal motor disorders. Thus, FLIP panometry is a valuable tool for both independent and complementary evaluation of esophageal motility.

Esophageal Dysmotility Is Associated With Disease Severity in Eosinophilic Esophagitis.

BACKGROUND & AIMS: An association of eosinophilic esophagitis (EoE) with esophageal dysmotility has been described, however, the related mechanism remains unclear. We aimed to evaluate clinical and physiologic characteristics, including esophageal distensibility, associated with secondary peristalsis in patients with EoE. METHODS: A total of 199 consecutive adult patients with EoE (age, 18-78 y; 32% female) who completed a 16-cm functional luminal imaging probe (FLIP) during endoscopy were evaluated in a cross-sectional study. FLIP panometry contractile response (CR) patterns were classified as normal CR or borderline CR if antegrade contractions were present, and abnormal CRs included impaired/disordered CR, absent CR, or spastic-reactive CR. The distensibility plateau of the esophageal body and esophagogastric junction distensibility was measured with FLIP. RESULTS: FLIP CR patterns included 68 (34%) normal CR, 65 (33%) borderline CR, 44 (22%) impaired/disordered CR, 16 (8%) absent CR, and 6 (3%) spastic-reactive CR. Compared with normal CRs, abnormal CRs more frequently had reduced esophageal distensibility (distensibility plateau <17 mm in 56% vs 32%), greater total EoE reference scores (median, 5; interquartile range [IQR], 3-6 vs median, 4; IQR, 3-5) with more severe ring scores, and a greater duration of symptoms (median, 10 y; IQR, 4-23 y vs median, 7 y; IQR, 3-15 y). Mucosal eosinophil density, however, was similar between abnormal CRs and normal CRs (median, 34 eosinophils/high-power field [hpf]; IQR, 14-60 eosinophils/hpf vs median, 25 eosinophils/hpf; IQR, 5-50 eosinophils/hpf). CONCLUSIONS: Although normal secondary peristalsis was observed frequently in this EoE cohort, abnormal esophageal CRs were related to EoE disease severity, especially features of fibrostenosis. This study evaluating secondary peristalsis in EoE suggests that esophageal wall remodeling, rather than eosinophilic inflammatory intensity, was associated with esophageal dysmotility in EoE.