Jody D. Ciolino

Gender differences in the effect of early life trauma on hypothalamic–pituitary–adrenal axis functioning†

Background: The objective of this study was to examine the modifying effect of gender on the association between early life trauma and the hypothalamic–pituitary–adrenal (HPA) axis response to a pharmacologic challenge and a social stress task in men and women. Participants (16 men, 23 women) were the control sample of a larger study examining HPA axis function. Individuals with major depressive disorder, posttraumatic stress disorder, bipolar disorder, or psychotic or eating disorders were excluded. Methods: In two test sessions, subjects received 1 µg/kg of corticotropin‐releasing hormone (CRH) intravenously and participated in the Trier Social Stress Test (TSST). Primary outcomes included plasma cortisol and corticotropin levels measured at baseline and more than five time points following the challenges. Predictors included gender and early life trauma, as measured by the Early Trauma Index. Using factor analysis, the domains general trauma, severe trauma, and the effects of trauma were established. Using regression, these constructs were used to predict differential HPA reactivity in men and women following the challenges. Results: The three factors accounted for the majority of the variance in the ETI. Following the CRH challenge, women had higher overall corticotropin response as dictated by the area under the curve analysis. There were no significant associations between trauma and neuroendocrine response to the TSST. Conclusions: CRH challenge results indicate that gender differences in the impact of early trauma may help explain the differential gender susceptibility to psychopathology following adverse childhood events. This may help explain gender differences in some stress‐sensitive psychiatric disorders. Depression and Anxiety, 2011.

Diagnosis of esophageal motility disorders: Esophageal pressure topography vs. conventional line tracing

OBJECTIVES:Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT.METHODS:Forty previously completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder.RESULTS:The total group agreement was moderate (κ=0.57; 95% CI: 0.56–0.59) for EPT and fair (κ=0.32; 0.30–0.33) for CLT. Inter-rater agreement between attendings was good (κ=0.68; 0.65–0.71) for EPT and moderate (κ=0.46; 0.43–0.50) for CLT. Inter-rater agreement between fellows was moderate (κ=0.48; 0.45–0.50) for EPT and poor to fair (κ=0.20; 0.17–0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR: 3.3; 95% CI: 2.4–4.5; P<0.0001), and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than with EPT (OR: 3.4; 2.4–5.0; P<0.0001).CONCLUSIONS:Superior inter-rater agreement and diagnostic accuracy of esophageal motility diagnoses were demonstrated with analysis using EPT over CLT among our selected raters. On the basis of these findings, EPT may be the preferred assessment modality of esophageal motility.

High-resolution impedance manometry measurement of bolus flow time in achalasia and its correlation with dysphagia

We assessed whether a high‐resolution impedance manometry (HRIM) metric, bolus flow time (BFT) across the esophagogastric junction (EGJ), was abnormal in achalasia patients subtyped by the Chicago Classification and compared BFT to other HRM metrics.

Patient-reported pain and impaired sleep quality in adult patients with cystic fibrosis ☆

BACKGROUND Sleep impairment has been described in patients with cystic fibrosis (CF). Pain is a known cause of sleep disturbance and as pain is commonly reported in patients with CF, we sought to find an association between impaired sleep quality and pain. METHODS Fifty adult CF patients completed surveys of pain and sleep quality. The results were analyzed with additional clinical data including age, sex, nutritional status, and lung function. RESULTS Thirty-two patients (64%) reported recent pain and 33 patients (66%) reported abnormal sleep quality. The patients with pain report worse sleep quality than those without pain (p=0.006). There was a strong correlation between impaired sleep quality and pain (p<0.0001). CONCLUSIONS We found that pain and poor sleep quality are reported in a majority of adult CF patients and there is a strong correlation between the two. This will have important clinical implications in the evaluation and treatment of adult patients.

Physician Report Cards and Implementing Standards of Practice Are Both Significantly Associated With Improved Screening Colonoscopy Quality

OBJECTIVES:Adenoma-detection rates (ADRs) are associated with decreased interval colorectal cancer (CRC) rates and CRC mortality; quality improvement strategies focus on improving physician ADRs. The objective of this study was to examine the sequential effect of physician report cards and implementing institutional standards of practice (SOP) on ADRs.METHODS:Colonoscopy metrics were prospectively evaluated at a single academic medical center over a 23-month period (November 2012 to October 2014). ADRs were evaluated over three time periods—Period 1: Before initial report card distribution or SOP (November 2012 to March 2013); Period 2: After individualized report card distribution detailing physician and institutional ADRs (April 2013 to March 2014); Period 3: After second report card and SOP implementation (April 2014 to October 2014). The SOP required physicians to have a minimum 5-min withdrawal time in normal colonoscopies (WT) and an ADR minimum of 20%; those who did not meet benchmarks would require further training or endoscopy block time alterations. Only endoscopists averaging >15 colonoscopies/month were included in this analysis.RESULTS:Twenty endoscopists met the inclusion criteria, performing 12,894 screening colonoscopies over the 23-month period. Following report card distribution, physician ADRs increased by 3% (P<0.001). SOP implementation resulted in a further significant increase in mean physician ADR of 8% (P<0.0001). Overall, mean ADR increased by 11% from Period 1 to Period 3 (P<0.0001). All physicians met the minimum 20% ADR benchmark during Period 3. Although ADRs significantly correlated with WT overall (r=0.45; 95% CI 0.01, 0.75; P=0.04), mean WT did not significantly increase from Period 1 to Period 3.CONCLUSIONS:Our data suggest that distributing colonoscopy quality report cards resulted in a significant ADR improvement. Further, we report evidence that implementing SOP significantly improved ADRs beyond report card distribution and resulted in all endoscopists meeting minimum benchmarks. This suggests that report cards and SOPs may have an additive effect in improving colonoscopy quality, and their implementation in endoscopy labs should be encouraged.

Pulmonary nocardiosis: Computed tomography features at diagnosis

Purpose To review the computed tomography (CT) imaging features of pulmonary nocardiosis (PN) at the time of initial presentation. Materials and Methods All patients from 1991 to 2008 with PN were identified (n=105). Patients without CT scan available at initial presentation were excluded (n=52). For the remaining 53 patients, standardized radiographic features were recorded. The patients were grouped by predisposing condition. Analysis includes descriptive summary statistics as well as associations among radiographic findings, associated findings, and host characteristics. Parametric and nonparametric statistical methods were used. Results Median age of the patients was 52 years (range, 6 to 82 y). Some form of immunosuppression was present in 83% of the cases. Preexisting structural abnormalities of the lung were uncommon (bronchiectasis, 7; chronic obstructive pulmonary disease, 3). Twenty (38%) patients had interstitial opacities. Airspace disease was seen in 34 (64%) cases. Thirty (57%) cases revealed discrete nodules, 25 patients had 1 to 6 nodules (mean, 2), and 5 patients had fewer than 6 nodules, with the mean size of the largest nodule being 1.67 cm. Masses were seen in 11 patients (21%), 9 of whom had concomitant nodules. Cavitary lesions, including nodules, masses, or airspace disease, occurred in 40% of the cohort. Mediastinal lymphadenopathy was present in 8 (15%) patients. Fifteen patients (28%) had pleural effusions; the effusions were unilateral in 10 patients. Analysis of radiographic associations with patient groups found discrete nodules to be more often associated with immunosuppression compared with the nonimmunosuppressed group (66% vs. 11%; P=0.0067). Conclusion The CT presentation of PN is heterogeneous. Airspace disease appeared most frequently (in 64% of the cases), and nodules were present in 57% of the cases. Nocardiosis should be considered in the differential diagnosis of immunosuppressed patients with new nodules or masses.

Severity of endoscopically identified esophageal rings correlates with reduced esophageal distensibility in eosinophilic esophagitis.

BACKGROUND/AIMS A grading system for the endoscopic features of eosinophilic esophagitis (EoE) has recently been validated. The EoE Endoscopic Reference Score (EREFS) incorporates both inflammatory and remodeling features of EoE. High resolution impedance planimetry using the functional luminal imaging probe (FLIP) is a technique for quantification of esophageal remodeling. The aim of this study was to evaluate the association between endoscopic severity with EREFS and esophageal distensibility as measured with the FLIP. METHODS Upper gastrointestinal endoscopy with biopsies and FLIP were performed in 72 adults with EoE. Endoscopic features of edema, rings, exudates, furrows, and stricture were evaluated using the EREFS system. Esophageal distensibility metrics obtained by FLIP, including the distensibility slope and distensibility plateau, were compared with EREFS parameters. Bivariate associations between EREFS parameters and histologic eosinophil density were assessed. RESULTS Higher ring scores were associated with a lower distensibility plateau (rs = -0.46; P < 0.0001). An association was found between severity of exudates and eosinophil density (rs = 0.27; P = 0.02), as well as between furrows and eosinophil density (rs = 0.49; P < 0.0001). Severity of exudates and furrows, and degree of eosinophilia were not associated with the distensibility parameters. CONCLUSIONS Endoscopic assessment of ring severity can serve as a marker for esophageal remodeling and may be useful for food impaction risk stratification in EoE. Eosinophil count was not significantly associated with esophageal distensibility, consistent with previous reports of dissociation between inflammatory activity and fibrostenosis in EoE. Endoscopic inflammatory features show a weak correlation with histopathology but should not replace histologic indices of inflammation.

Quantifying the cost in power of ignoring continuous covariate imbalances in clinical trial randomization.

Motivated by potentially serious imbalances of continuous baseline covariates in clinical trials, we investigated the cost in statistical power of ignoring the balance of these covariates in treatment allocation design for a logistic regression model. Based on data from a clinical trial of acute ischemic stroke treatment, computer simulations were used to create scenarios varying from the best possible baseline covariate balance to the worst possible imbalance, with multiple balance levels between the two extremes. The likelihood of each scenario occurring under simple randomization was evaluated. The power of the main effect test for treatment was examined. Our simulation results show that the worst possible imbalance is highly unlikely, but it can still occur under simple random allocation. Also, power loss could be nontrivial if balancing distributions of important continuous covariates were ignored even if adjustment is made in the analysis for important covariates. This situation, although unlikely, is more serious for trials with a small sample size and for covariates with large influence on primary outcome. These results suggest that attempts should be made to balance known prognostic continuous covariates at the design phase of a clinical trial even when adjustment is planned for these covariates at the analysis.

The feasibility, acceptability, and preliminary effectiveness of a Promotora-Led Diabetes Prevention Program (PL-DPP) in Latinas: a pilot study.

Purpose The purpose of this pilot study is to test the feasibility, acceptability, and preliminary effectiveness of a Promotora-Led Diabetes Prevention Program (PL-DPP) in Hispanic women (Latinas). Methods Twenty Latina adults with prediabetes were enrolled in this single-arm pilot trial of PL-DPP. Participants underwent a year-long lifestyle intervention consisting of 24 sessions divided into 14 weekly core sessions and 10 post-core sessions offered either biweekly or monthly. Each session was led by a promotora in Spanish. The primary outcome was weight change over the 12-month study period. Results The study participants were socioeconomically challenged, middle-aged Latinas with limited access to health care. Eighteen participants (90%) completed at least 12 sessions, and 1 was lost to follow-up. Overall, participants reported high levels of satisfaction with PL-DPP. At 12 months, the participants achieved a mean weight loss of 10.8 pounds, which corresponded to 5.6% of initial body weight. Significant pre-post reductions in waist circumference, diastolic blood pressure, LDL cholesterol, and insulin levels were also observed. Modest reductions in A1C and fasting plasma glucose were not significant. Conclusions The PL-DPP demonstrated feasibility, acceptability, and preliminary effectiveness in a high-risk population of Latinas. Future research examining this intervention in a randomized clinical trial should explore factors impacting its effects using both qualitative and quantitative methods.

Oropharyngeal pH Testing Does Not Predict Response to Proton Pump Inhibitor Therapy in Patients with Laryngeal Symptoms

Objectives:Predicting response to proton pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms.Methods:We conducted a physician-blinded prospective cohort study at a single academic institution between January 2013 and October 2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-h oropharyngeal pH monitoring, followed by an 8- to 12-week trial of omeprazole 40 mg daily. Prior to and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on the post-treatment RSI score and % RSI response: non-response=RSI ≥13; partial response=post-treatment RSI <13 and change in RSI <50%; and complete response=post-treatment RSI <13 and change in RSI ≥50%. The primary analysis utilized a multinomial logistic regression controlling for the pre-treatment RSI score. A secondary analysis assessed the relationship between the change in RSI (post–pre) and oropharyngeal pH metrics via ordinary least square regression.Results:Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial response, and 35% complete response. Non-responders had a higher pre-treatment RSI (P<0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0, and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and a greater total percent time below pH of 5.0 (P=0.03), upright percent time below pH of 5.0 (P=0.07), and RYAN supine (corrected; P=0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P<0.01), Brief Symptom Inventory-18 (P<0.01), and Negative Affect Scale (P<0.01).Conclusions:Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.