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.

An endoscopic scoring system for achalasia: the CARS score.

BACKGROUND AND AIMS: The diagnosis of achalasia is associated with an average delay of 2 years. Endoscopic features may prompt an earlier diagnosis. We aimed to develop and test a novel endoscopic score, CARS, 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 4 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 4 components: Contents, Anatomy, Resistance, and Stasis. In a mixed-effects model, the mean score across raters was higher for achalasia compared with nonachalasia subjects (4.44 vs 0.87; P < .01). In part 2 of the study, achalasia patients had a higher mean CARS score compared with those with no or ineffective motility disorder (mean 4.1 vs 1.3; P < .01). CONCLUSIONS: We developed a CARS score based on reliability performance in a video-based survey and tested the score in a 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.

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.

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.

An Explainable Artificial Intelligence Software Tool for Weight Management Experts (PRIMO): Mixed Methods Study.

BACKGROUND: Predicting the likelihood of success of weight loss interventions using machine learning (ML) models may enhance intervention effectiveness by enabling timely and dynamic modification of intervention components for nonresponders to treatment. However, a lack of understanding and trust in these ML models impacts adoption among weight management experts. Recent advances in the field of explainable artificial intelligence enable the interpretation of ML models, yet it is unknown whether they enhance model understanding, trust, and adoption among weight management experts. OBJECTIVE: This study aimed to build and evaluate an ML model that can predict 6-month weight loss success (ie, ≥7% weight loss) from 5 engagement and diet-related features collected over the initial 2 weeks of an intervention, to assess whether providing ML-based explanations increases weight management experts' agreement with ML model predictions, and to inform factors that influence the understanding and trust of ML models to advance explainability in early prediction of weight loss among weight management experts. METHODS: We trained an ML model using the random forest (RF) algorithm and data from a 6-month weight loss intervention (N=419). We leveraged findings from existing explainability metrics to develop Prime Implicant Maintenance of Outcome (PRIMO), an interactive tool to understand predictions made by the RF model. We asked 14 weight management experts to predict hypothetical participants' weight loss success before and after using PRIMO. We compared PRIMO with 2 other explainability methods, one based on feature ranking and the other based on conditional probability. We used generalized linear mixed-effects models to evaluate participants' agreement with ML predictions and conducted likelihood ratio tests to examine the relationship between explainability methods and outcomes for nested models. We conducted guided interviews and thematic analysis to study the impact of our tool on experts' understanding and trust in the model. RESULTS: Our RF model had 81% accuracy in the early prediction of weight loss success. Weight management experts were significantly more likely to agree with the model when using PRIMO (χ2=7.9; P=.02) compared with the other 2 methods with odds ratios of 2.52 (95% CI 0.91-7.69) and 3.95 (95% CI 1.50-11.76). From our study, we inferred that our software not only influenced experts' understanding and trust but also impacted decision-making. Several themes were identified through interviews: preference for multiple explanation types, need to visualize uncertainty in explanations provided by PRIMO, and need for model performance metrics on similar participant test instances. CONCLUSIONS: Our results show the potential for weight management experts to agree with the ML-based early prediction of success in weight loss treatment programs, enabling timely and dynamic modification of intervention components to enhance intervention effectiveness. Our findings provide methods for advancing the understandability and trust of ML models among weight management experts.

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.

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.

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.

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.

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.

Early ß-hCG levels predict live birth after single embryo transfer.

PURPOSE: Specific serum beta human chorionic gonadotropin (ß-hCG) parameters that can predict live birth after an embryo transfer have yet to be defined. METHODS: We performed a retrospective cohort study of 1,028 patients with a detectable ß-hCG who underwent a single embryo transfer between 2002 and 2019 at a large academic center. Two ß-hCG parameters were examined in relation to live birth: 1) "doubling" defined as ß-hCG doubling over 48 h and 2) "reaching 100" defined as a ß-hCG ≥ 100 mIU/mL by 15 days after oocyte retrieval (AOR). RESULTS: One thousand three hundred forty cycles involving a single embryo were analyzed. Two thirds were frozen embryos and 86% were blastocyst transfers. Preimplantation genetic testing was performed in almost 30% of cycles. When ß-hCG levels "doubled," a live birth occurred in 80.7% of cycles and when ß-hCG levels "reached 100" by 15 days AOR, live birth occurred in 81.6% of cycles. When ß-hCG levels both doubled and reached 100 by 15 days, AOR 85.4% cycles resulted in live birth. A multiple logistic regression model to control for patient and cycle level factors revealed a live birth odds ratio (OR) of 8.0 (95% CI 5.7-11.1) when ß-hCG "doubled" and an OR of 21.2 (95% CI 14.3-31.5) when ß-hCG "reached 100." When both these latter parameters were met, the OR was 12.5 (95% CI 8.9-17.8). CONCLUSION: ß-hCG parameters of "doubling" and "reaching 100" by 15 days AOR are robust predictors of live birth and can aid in patient counseling regarding pregnancy outcomes soon after single embryo transfer.

Prediction of Esophageal Retention: A Study Comparing High-Resolution Manometry and Functional Luminal Imaging Probe Panometry.

INTRODUCTION: High-resolution manometry (HRM) is generally considered the primary method to evaluate esophageal motility; functional luminal imaging probe (FLIP) panometry represents a novel method to do so and is completed during sedated endoscopy. This study aimed to compare HRM and FLIP panometry in predicting esophageal retention on timed barium esophagram (TBE). METHODS: A total of 329 adult patients who completed FLIP, HRM, and TBE for primary esophageal motility evaluation were included. An abnormal TBE was defined by a 1-minute column height >5 cm or impaction of a 12.5-mm barium tablet. The integrated relaxation pressure (IRP) on HRM was assessed in the supine and upright patient positions. Esophagogastric junction (EGJ) opening was evaluated with 16-cm FLIP performed during sedated endoscopy through EGJ-distensibility index and maximum EGJ diameter. RESULTS: Receiver operating characteristic curves to identify an abnormal TBE demonstrated AUC (95% confidence interval) of 0.79 (0.75-0.84) for supine IRP, 0.79 (0.76-0.86) for upright IRP, 0.84 (0.79-0.88) for EGJ-distensibility index, and 0.88 (0.85-0.92) for maximum EGJ diameter. Logistic regression to predict abnormal TBE showed odds ratios (95% confidence interval) of 1.8 (0.84-3.7) for consistent IRP elevation and 39.7 (16.4-96.2) for reduced EGJ opening on FLIP panometry. Of 40 patients with HRM-FLIP panometry discordance, HRM-IRP was consistent with TBE in 23% while FLIP panometry was consistent with TBE in 78%. DISCUSSION: FLIP panometry provided superior detection of esophageal retention over IRP on HRM. However, application of a complementary evaluation involving FLIP panometry, HRM, and TBE may be necessary to accurately diagnose esophageal motility disorders.

The Impact of the COVID-19 Pandemic on Depression, Anxiety, and Stress among Black Women with Depressive Symptoms at a Federally Qualified Health Center.

While the COVID-19 pandemic disproportionately impacted Black American communities, there is a lack of empirical research examining mental health experiences during the COVID-19 pandemic among this population. This report examines the relationship between the COVID-19 pandemic and stress, depression, and anxiety among Black women. A cohort study with supplementary data was conducted among 45 Black American women with depressive symptoms participating in an ongoing randomized controlled trial of a mindfulness-based intervention (M-Body) at a Federally Qualified Health Center. Depressive symptoms, anxiety, and stress were measured at multiple time points before and during the COVID-19 pandemic. On average, anxiety [Pre-pandemic: 7.4 (0.5); Peri-pandemic: 7.0 (0.6); MD: -0.4 (0.5), p = 0.18] did not change substantially during the pandemic compared to pre-pandemic levels. However, depression [Pre-pandemic: 19.7 (1.4); Peri-pandemic: 24.4 (1.5); MD: 4.7 (1.0), p < 0.01] worsened while stress [Pre-pandemic: 21.7 (0.4); Peri-pandemic: 20.5 (0.5); MD: -1.2 (0.5), p = 0.01] slightly improved. Individuals caring for children exhibited modest but not statistically significant elevations in pre-pandemic stress than those who did not. These disparities more than doubled during the pandemic for stress [MD: 1.9 (0.9), p = 0.04] and depression [MD: 3.8 (2.6), p = 0.16] but increased only slightly for anxiety [MD: 1.8 (1.0), p = 0.08]. These data indicate that the COVID-19 pandemic impacted mental health among Black women with depressive symptoms, and those caring for children reported greater increases in depression, anxiety, and stress than those who did not during the pandemic. Trial Registration: ClinicalTrials.gov NCT03620721. Registered on 8 August 2018.

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.

The impact of primary peristalsis, contractile reserve, and secondary peristalsis on esophageal clearance measured by timed barium esophagogram.

BACKGROUND: Primary and secondary peristalsis facilitate esophageal bolus transport; however, their relative impact for bolus clearance remains unclear. We aimed to compare primary peristalsis and contractile reserve on high-resolution manometry (HRM) and secondary peristalsis on functional lumen imaging probe (FLIP) Panometry with emptying on timed barium esophagogram (TBE) and incorporate findings into a comprehensive model of esophageal function. METHODS: Adult patients who completed HRM with multiple rapid swallows (MRS), FLIP, and TBE for esophageal motility evaluation and without abnormal esophagogastric junction outflow/opening or spasm were included. An abnormal TBE was defined as a 1-min column height >5 cm. Primary peristalsis and contractile reserve after MRS were combined into an HRM-MRS model. Secondary peristalsis was combined with primary peristalsis assessment to describe a complementary neuromyogenic model. KEY RESULTS: Of 89 included patients, differences in rates of abnormal TBEs were observed with primary peristalsis classification (normal: 14.3%; ineffective esophageal motility: 20.0%; absent peristalsis: 54.5%; p = 0.009), contractile reserve (present: 12.5%; absent: 29.3%; p = 0.05), and secondary peristalsis (normal: 9.7%; borderline: 17.6%; impaired/disordered: 28.6%; absent contractile response: 50%; p = 0.039). Logistic regression analysis (akaike information criteria, area under the receiver operating curve) demonstrated that the neuromyogenic model (80.8, 0.83) had a stronger relationship predicting abnormal TBE compared to primary peristalsis (81.5, 0.82), contractile reserve (86.8, 0.75), or secondary peristalsis (89.0, 0.78). CONCLUSIONS AND INFERENCES: Primary peristalsis, contractile reserve, and secondary peristalsis were associated with abnormal esophageal retention as measured by TBE. Added benefit was observed when applying comprehensive models to incorporate primary and secondary peristalsis supporting their complementary application.

Assessing mechanical function of peristalsis with functional lumen imaging probe panometry: Contraction power and displaced volume.

BACKGROUND AND AIMS: The distal contractile integral (DCI) quantifies the contractile vigor of primary peristalsis on high-resolution manometry (HRM), whereas no such metric exists for secondary peristalsis on functional lumen imaging probe (FLIP) panometry. This study aimed to evaluate novel FLIP metrics of contraction power and displaced volume in asymptomatic controls and a patient cohort. METHODS: Thirty-five asymptomatic controls and adult patients (with normal esophagogastric junction outflow/opening and without spasm) who completed HRM and FLIP panometry were included. The patient group also completed timed barium esophagram (TBE). Contraction power (estimate of esophageal work over time) and displaced volume (estimate of contraction-associated fluid flow) were computed from FLIP. HRM was analyzed per Chicago Classification v4.0. KEY RESULTS: In controls, median (5th-95th percentile) contraction power was 27 mW (10-44) and displaced volume was 43 mL (17-66). 95 patients were included: 72% with normal motility on HRM, 17% with ineffective esophageal motility (IEM), and 12% with absent contractility. Among patients, DCI was significantly correlated with both contraction power (rho = 0.499) and displaced volume (rho = 0.342); p values < 0.001. Both contraction power and displaced volume were greater in patients with normal motility versus IEM or absent contractility, complete versus incomplete bolus transit, and normal versus abnormal retention on TBE; p values < 0.02. CONCLUSIONS: FLIP panometry metrics of contraction power and displaced volume appeared to effectively quantify peristaltic vigor. These novel metrics may enhance evaluation of esophageal motility with FLIP panometry and provide a reliable surrogate to DCI on HRM.

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).

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.

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.