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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.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 RSI13 and change in RSI50%; and complete response=post-treatment RSI13 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.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 (P0.01). 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 (P0.01), Brief Symptom Inventory-18 (P0.01), and Negative Affect Scale (P0.01).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.

Distal oesophageal spasm is a rare and under-investigated motility abnormality. Recent studies indicate effective bolus transit in varying percentages of distal oesophageal spasm patients.Explore functional aspects including contraction onset velocity and contraction amplitude cut-off values for simultaneous contractions to predict complete bolus transit.We re-examined data from 107 impedance-manometry recordings with a diagnosis of distal oesophageal spasm. Receiver operating characteristic analysis was conducted, regarding effects of onset velocity on bolus transit taking into account distal oesophageal amplitude and correcting for intra-individual repeated measures.Mean area under the receiver operating characteristic curve for saline and viscous swallows were 0.84±0.05 and 0.84±0.04, respectively. Velocity criteria of30 cm/s when distal oesophageal amplitude100 mmHg and 8 cm/s when distal oesophageal amplitude100 mmHg for saline and 32cm/s when distal oesophageal amplitude100 mmHg and7 cm/s when distal oesophageal amplitude100 mmHg for viscous had a sensitivity of 75% and specificity of 80% to identify complete bolus transit. Using these criteria, final diagnosis changed in 44.9% of patients. Abnormal bolus transit was observed in 50.9% of newly diagnosed distal oesophageal spasm patients versus 7.5% of patients classified as normal. Distal oesophageal spasm patients with distal oesophageal amplitude100 mmHg suffered twice as often from chest pain than those with distal oesophageal amplitude100 mmHg.The proposed velocity cut-offs for diagnosing distal oesophageal spasm improve the ability to identify patients with spasm and abnormal bolus transit.

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.

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.

Background Postpartum depression is highly prevalent in low-income women and has significant health and mental health effects on mother and child. Home visiting (HV) programs provide services to large numbers of perinatal women in the United States and are a logical setting for delivering mental health services. Although there are interventions that reduce the risk of developing postpartum depression among low-income women, none have used nonhealth or nonmental health professionals as interventionists. Objective This study aimed to outline the protocol of a cluster randomized trial funded by the Patient-Centered Outcomes Research Institute that evaluates whether the Mothers and Babies (MB) group intervention, when led by paraprofessional home visitors, is more efficacious than usual care. It will also examine if MB, when led by home visitors, is not inferior to MB delivered by mental health professionals (MHPs). MB has previously demonstrated efficacy when delivered by MHPs, and pilot work indicated promising results using home visitors to deliver the intervention. Methods A cluster randomized trial is being conducted with 38 HV programs. Sixteen HV programs will deliver MB using MHPs, 16 will deliver MB using paraprofessional home visitors, and 6 will deliver usual HV services. The study employs a modified covariate-constrained randomization design at the site level. We anticipate recruiting 933 women aged ≥16 years enrolled in HV programs, who are 33 or more weeks' gestation and speak either English or Spanish. Women in the 2 intervention arms will receive the 6-session MB group intervention. Baseline, postintervention, 12-week postpartum, and 24-week postpartum assessments will be conducted to assess client outcomes. The primary outcome will be the change in Quick Inventory of Depressive Symptomatology Self-Report 16 scores from baseline to 24-week follow-up. Secondary outcomes associated with core MB content will also be examined. Semistructured interviews will be conducted with home visitors and MHPs who are group facilitators and 90 study participants to gain data on intervention successes and challenges. Analyses will proceed at the participant level. Primary analyses for depressive symptoms score at 24 weeks postpartum will involve a linear mixed model, controlling for baseline symptoms and other covariates, and random effects to account for clustering. Results We have recruited 838 women through the end of August 2018. Recruitment will be completed at the end of September 2018. Conclusions There is considerable potential to disseminate MB to HV programs throughout the United States. Should our results demonstrate home visitor efficacy when compared with usual care and/ noninferiority between home visitors and MHPs in improving mental health outcomes, no additional financial resources would be required for the existing HV staff to implement MB. Should this study determine that home visitors are less effective than MHPs, we will generate more wide-scale evidence on MB effectiveness when led by MHPs. Trial registration ClinicalTrials.gov NCT02979444; https://clinicaltrials.gov/ct2/show/NCT02979444 (Archived by Webcite at http://www.webcitation.org/archive.php). International registered report identifier (irrid) PRR1-10.2196/11624.

The authors present a new centralized randomization method for multicenter emergency treatment clinical trials. With this step-forward method, treatment randomization for the next subject is performed immediately after the enrollment of the current subject. This design ensures the readiness of the treatment assignment for each subject at the point of study enrollment, and it simultaneously provides effective control on treatment assignments balance and distributions of covariates. The authors also discuss procedures of the step-forward randomization method along with its implementation for two National Institute of Neurological Disorders and Stroke–funded multicenter acute stroke trials, one double-blinded and one open-labeled. Advantages and limitations are presented based on experience gained in these two trials. ACADEMIC EMERGENCY MEDICINE 2010; 17:659–665 © 2010 by the Society for Academic Emergency Medicine

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 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.

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. 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. 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

Endoscopic resection (ER) is a safe and effective treatment for nonmalignant complex colorectal polyps (complex polyps). Surgical resection (SR) remains prevalent despite limited outcomes data. We aimed to evaluate SR outcomes for complex polyps and compare SR outcomes to those of ER.We performed a single-center, retrospective, cohort study of all patients undergoing SR (2003-2013) and ER (2011-2013) for complex polyps. We excluded patients with invasive carcinoma from the SR cohort. Primary outcomes were 12-month adverse event (AE) rate, length of stay (LOS), and costs. SR outcomes over a 3-year period (2011-2013) were compared with the overlapping ER cohort.Over the 11-year period, 359 patients (mean [± SD] age 64 ± 11 years) underwent SR (58% laparoscopic) for complex polyps. In total, 17% experienced an AE, and 3% required additional surgery; 12-month mortality was 1%. Including readmissions, median LOS was 5 days (IQR 4-7 days), and costs were $14,528. When an AE occurred, costs ($25,557 vs $14,029; P .0001) and LOS (11 vs 5 days; P .0001) significantly increased. From 2011 to 2013, 198 patients were referred for ER, and 73 underwent primary SR (70% laparoscopic). There was a lower AE rate for ER versus primary SR (10% vs 18%; P = .09). ER costs (including rescue SR, when required) were lower than those of primary SR ($2152 vs $15,264; P .0001).AEs occur in approximately one-sixth of patients after SR for complex polyps. ER-accounting for rescue SR caused by malignancy, AEs, or incomplete resection-is associated with markedly lower costs than SR. These data should be used when counseling patients about treatment options for complex polyps.

Background 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. Methods HRIM studies were performed in 60 achalasia patients (14 type I, 36 type II and 10 type III) and 15 healthy controls. Studies were analyzed with a MATLAB program to calculate BFT using a virtual HRIM sleeve. Integrated relaxation pressure (IRP) and basal end-expiratory EGJ pressure were also calculated. The relationship between BFT and dysphagia symptom scores was assessed using the impaction dysphagia questionnaire (IDQ). Key Results Median BFT was significantly lower in achalasia patients (0.5 s, range 0.0–3.5 s) compared to controls (3.5 s, range 2.0–5.0 s; p

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.

Adequate bowel preparation is essential to safe and effective inpatient colonoscopy. Predictors of poor inpatient colonoscopy preparation and the economic impacts of inadequate inpatient preparations are not defined. The aims of this study were to (1) determine risk factors for inadequate inpatient bowel preparations, and (2) examine the association between inadequate inpatient bowel preparation and hospital length of stay (LOS) and costs. We performed a retrospective cohort study of adult patients undergoing inpatient colonoscopy preparation over 12 months (1/1/2013–12/31/2013). Of 524 identified patients, 22.3 % had an inadequate preparation. A multiple logistic regression model identified the following potential predictors of inadequate bowel preparation: lower income (OR 1.11; 95 % CI 1.04, 1.22), opiate or tricyclic antidepressant (TCA) use (OR 1.55; 0.98, 2.46), and afternoon colonoscopy (OR 1.66; 1.07, 2.59); as well as American Society of Anesthesiologists (ASA) class ≥3 (OR 1.15; 1.05, 1.25) and symptoms of nausea/vomiting (OR 1.14; 1.04, 1.25) when a fair preparation was considered inadequate. Inadequate bowel preparation was associated with significantly increased hospital LOS (model relative mean estimate 1.25; 95 % CI 1.03, 1.51) and hospital costs (estimate 1.31; 1.03, 1.67) when compared to adequate preparations. The rate of inadequate inpatient bowel preparations is high and associated with a significant increase in hospital LOS and costs. We identified five potential predictors of inadequate inpatient preparation: lower socioeconomic class, opiate/TCA use, afternoon colonoscopies, ASA class ≥3, and pre-preparation nausea/vomiting; these data should guide future initiatives to improve the quality of inpatient bowel preparations.

Background & Aims Quality esophageal high-resolution manometry (HRM) studies require competent interpretation of data. However, there is little understanding of learning curves, training requirements, or measures of competency for HRM. We aimed to develop and use a competency assessment system to examine learning curves for interpretation of HRM data. Methods We conducted a prospective multicenter study of 20 gastroenterology trainees with no experience in HRM, from 8 centers, over an 8-month period (May through December 2015). We designed a web-based HRM training and competency assessment system. After reviewing the training module, participants interpreted 50 HRM studies and received answer keys at the fifth and then at every second interpretation. A cumulative sum procedure produced individual learning curves with preset acceptable failure rates of 10%; we classified competency status as competency not achieved, competency achieved, or competency likely achieved. Results Five (25%) participants achieved competence, 4 (20%) likely achieved competence, and 11 (55%) failed to achieve competence. A minimum case volume to achieve competency was not identified. There was no significant agreement between diagnostic accuracy and accuracy for individual HRM skills. Conclusions We developed a competency assessment system for HRM interpretation; using this system, we found significant variation in learning curves for HRM diagnosis and individual skills. Our system effectively distinguished trainee competency levels for HRM interpretation and contrary to current recommendations, found that competency for HRM is not case-volume specific.

The question of when to adjust for important prognostic covariates often arises in the design of clinical trials, and there remain various opinions on whether to adjust during both randomization and analysis, at randomization alone, or at analysis alone. Furthermore, little is known about the impact of covariate adjustment in the context of noninferiority (NI) designs. The current simulation-based research explores this issue in the NI setting, as compared with the typical superiority setting, by assessing the differential impact on power, type I error, and bias in the treatment estimate as well as its standard error, in the context of logistic regression under both simple and covariate adjusted permuted block randomization algorithms. In both the superiority and NI settings, failure to adjust for covariates that influence outcome in the analysis phase, regardless of prior adjustment at randomization, results in treatment estimates that are biased toward zero, with standard errors that are deflated. However, as no treatment difference is approached under the null hypothesis in superiority and under the alternative in NI, this results in decreased power and nominal or conservative (deflated) type I error in the context of superiority but inflated power and type I error under NI. Results from the simulation study suggest that, regardless of the use of the covariate in randomization, it is appropriate to adjust for important prognostic covariates in analysis, as this yields nearly unbiased estimates of treatment as well as nominal type I error.

In logistic regression analysis for binary clinical trial data, adjusted treatment effect estimates are often not equivalent to unadjusted estimates in the presence of influential covariates. This paper uses simulation to quantify the benefit of covariate adjustment in logistic regression. However, International Conference on Harmonization guidelines suggest that covariate adjustment be pre-specified. Unplanned adjusted analyses should be considered secondary. Results suggest that that if adjustment is not possible or unplanned in a logistic setting, balance in continuous covariates can alleviate some (but never all) of the shortcomings of unadjusted analyses. The case of log binomial regression is also explored.

This paper presents and compares several methods of measuring continuous baseline covariate imbalance in clinical trial data. Simulations illustrate that though the t-test is an inappropriate method of assessing continuous baseline covariate imbalance, the test statistic itself is a robust measure in capturing imbalance in continuous covariate distributions. Guidelines to assess effects of imbalance on bias, type I error rate and power for hypothesis test for treatment effect on continuous outcomes are presented, and the benefit of covariate-adjusted analysis (ANCOVA) is also illustrated.

This editorial refers to ‘ Applying novel methods to assess clinical outcomes: insights from the TRILOGY ACS trial’[†][1], by J. A. Bakal et al. , on page 385 Though a seemingly simple notion, defining a clear research question or hypothesis at the conception of a clinical study can be a daunting task for investigators. Through the TRILOGY ACS study,1 Bakal and colleagues2 illustrate that subtle changes in the primary outcome definition for a clinical trial may result in substantial changes in the analytical methods, altering the overall interpretation of the study's result. Perhaps as an unintended consequence, their article also emphasizes a pitfall of post-hoc analyses. This editorial is intended to provide some insight into the statistical considerations in their article. In doing so, it aggregates their ideas to provide recommendations for appropriate analytical techniques driven by specific research questions. Most disease progressions are associated with the realization of multiple complications. Cardiovascular disease, for example, may have elevated blood pressure, atherosclerosis, altered perfusion, ischaemia, changes in activities of daily living, etc. From a clinical perspective, a myocardial infarction resulting in death may be more important than reduced cardiopulmonary function that only limits a patient's activities of daily living. That said, these extreme examples are intrinsically linked in a common disease process and represent different aspects of disease progression. These inter-relationships, when simultaneously modelled, often introduce the need for more sophisticated statistical analyses. These analyses can sometimes obfuscate … [1]: #fn-2

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. © 2011 Wiley-Liss, Inc.