Mary J. Kwasny

Colonic microbiome is altered in alcoholism

Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus we interrogated the mucosa-associated colonic microbiome in 48 alcoholics with and without ALD as well as 18 healthy subjects. Colonic biopsy samples from subjects were analyzed for microbiota composition using length heterogeneity PCR fingerprinting and multitag pyrosequencing. A subgroup of alcoholics have an altered colonic microbiome (dysbiosis). The alcoholics with dysbiosis had lower median abundances of Bacteroidetes and higher ones of Proteobacteria. The observed alterations appear to correlate with high levels of serum endotoxin in a subset of the samples. Network topology analysis indicated that alcohol use is correlated with decreased connectivity of the microbial network, and this alteration is seen even after an extended period of sobriety. We show that the colonic mucosa-associated bacterial microbiome is altered in a subset of alcoholics. The altered microbiota composition is persistent and correlates with endotoxemia in a subgroup of alcoholics.

Esophageal Distensibility as a Measure of Disease Severity in Patients With Eosinophilic Esophagitis

BACKGROUND & AIMS The aim of this study was to assess whether measurements of esophageal distensibility, made by high-resolution impedance planimetry, correlated with important clinical outcomes in patients with eosinophilic esophagitis. METHODS Seventy patients with eosinophilic esophagitis (50 men; age, 18-68 y) underwent endoscopy with esophageal biopsy collection and high-resolution impedance planimetry using the functional lumen-imaging probe. The patients were followed up prospectively for an average of 9.2 months (range, 3-14 mo), and the risk of food impaction, requirement for dilation, and symptom severity during the follow-up period was determined from medical records. Esophageal distensibility metrics and the severity of mucosal eosinophilia at baseline were compared between patients presenting with and without food impaction and those requiring or not requiring esophageal dilation. Logistic regression and stratification assessments were used to assess the predictive value of esophageal distensibility metrics in assessing risk of food impaction, the need for dilation, and continued symptoms. RESULTS Patients with prior food impactions had significantly lower distensibility plateau (DP) values than those with solid food dysphagia alone. In addition, patients sustaining food impaction and requiring esophageal dilation during the follow-up period had significantly lower DP values than those who did not. The severity of mucosal eosinophilia did not correlate with risk for food impaction, the requirement for dilation during follow-up evaluation, or DP values. CONCLUSIONS Reduced esophageal distensibility predicts risk for food impaction and the requirement for esophageal dilation in patients with eosinophilic esophagitis. The severity of mucosal eosinophilia was not predictive of these outcomes and had a poor correlation with esophageal distensibility.

Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial.

We evaluated the impact of diabetes mellitus (DM) and diabetic therapy on outcomes in patients with reduced ejection fraction (EF) after hospitalization for heart failure (HF). DM is prevalent in patients hospitalized with HF, yet inconclusive data exist on the post‐discharge outcomes of this patient population.

Clinical course and predictive value of liver function tests in patients hospitalized for worsening heart failure with reduced ejection fraction: an analysis of the EVEREST trial

Abnormal liver function tests (LFTs) are common in ambulatory heart failure (HF). The aim of this study was to characterize abnormal LFTs during index hospitalization.

Cutaneous γδ T-cell lymphomas: a spectrum of presentations with overlap with other cytotoxic lymphomas.

We reviewed our multicenter experience with gamma-delta (&ggr;&dgr;) T-cell lymphomas first presenting in the skin. Fifty-three subjects with a median age of 61 years (range, 25 to 91 y) were diagnosed with this disorder. The median duration of the skin lesions at presentation was 1.25 years (range, 1 mo to 20 y). The most common presentation was deep plaques (38 cases) often resembling a panniculitis, followed by patches resembling psoriasis or mycosis fungoides (10 cases). These lesions tended to ulcerate overtime (27 cases). Single lesions or localized areas of involvement resembling cellulitis or pyoderma were reported in 8 cases. The most common anatomic site of involvement was the legs (40 cases), followed by the torso (30 cases) and arms (28 cases). Constitutional symptoms were reported in 54% (25/46) of the patients, including some with limited skin involvement. Significant comorbidities included autoimmunity (12 cases), other lymphoproliferative disorders (5 cases), internal carcinomas (4 cases), and viral hepatitis (2 cases). Lymphadenopathy (3/42 cases) and bone marrow involvement (5/28 cases) were uncommon, but serum lactose dehydrogenase (LDH) was elevated in 55% (22/39) of the patients. Abnormal positron emission tomography and/or computed tomography scans in 20/37 subjects mostly highlighted soft tissue or lymph nodes. Disease progression was associated with extensive ulcerated lesions resulting in 27 deaths including complications of hemophagocytic syndrome (4) and cerebral nervous system involvement (3). Median survival time from diagnosis was 31 months. Skin biopsies varied from a pagetoid pattern to purely dermal or panniculitic infiltrates composed of intermediate-sized lymphocytes with tissue evidence of cytotoxicity. The most common immunophenotype was CD3+/CD4−/CD5−/CD8−/BF1−/&ggr;-M1+/TIA-1+/granzyme-B+/CD45RA−/CD7−, and 4 cases were Epstein-Barr virus positive. This is the largest study to date of cutaneous &ggr;&dgr; T-cell lymphomas and demonstrates a variety of clinical and pathologic presentations with a predictable poor outcome.

Trials of Intervention Principles: Evaluation Methods for Evolving Behavioral Intervention Technologies

In recent years, there has been increasing discussion of the limitations of traditional randomized controlled trial (RCT) methodologies for the evaluation of eHealth and mHealth interventions, and in particular, the requirement that these interventions be locked down during evaluation. Locking down these interventions locks in defects and eliminates the opportunities for quality improvement and adaptation to the changing technological environment, often leading to validation of tools that are outdated by the time that trial results are published. Furthermore, because behavioral intervention technologies change frequently during real-world deployment, even if a tested intervention were deployed in the real world, its shelf life would be limited. We argue that RCTs will have greater scientific and public health value if they focus on the evaluation of intervention principles (rather than a specific locked-down version of the intervention), allowing for ongoing quality improvement modifications to the behavioral intervention technology based on the core intervention principles, while continuously improving the functionality and maintaining technological currency. This paper is an initial proposal of a framework and methodology for the conduct of trials of intervention principles (TIPs) aimed at minimizing the risks of in-trial changes to intervention technologies and maximizing the potential for knowledge acquisition. The focus on evaluation of intervention principles using clinical and usage outcomes has the potential to provide more generalizable and durable information than trials focused on a single intervention technology.

A randomized controlled trial evaluating a manualized TeleCoaching protocol for improving adherence to a web-based intervention for the treatment of depression.

Background Web-based interventions for depression that are supported by coaching have generally produced larger effect-sizes, relative to standalone web-based interventions. This is likely due to the effect of coaching on adherence. We evaluated the efficacy of a manualized telephone coaching intervention (TeleCoach) aimed at improving adherence to a web-based intervention (moodManager), as well as the relationship between adherence and depressive symptom outcomes. Methods 101 patients with MDD, recruited from primary care, were randomized to 12 weeks moodManager+TeleCoach, 12 weeks of self-directed moodManager, or 6 weeks of a waitlist control (WLC). Depressive symptom severity was measured using the PHQ-9. Results TeleCoach+moodManager, compared to self-directed moodManager, resulted in significantly greater numbers of login days (p = 0.01), greater time until last use (p = 0.007), greater use of lessons (p = 0.03), greater variety of interactive tools used (p = 0.02), but total instances of tool use did not reach statistical significance. (p = 0.07). TeleCoach+moodManager produced significantly lower PHQ-9 scores relative to WLC at week 6 (p = 0.04), but there were no other significant differences in PHQ-9 scores at weeks 6 or 12 (ps>0.20) across treatment arms. Baseline PHQ-9 scores were no significantly related to adherence to moodManager. Conclusions TeleCoach produced significantly greater adherence to moodManager, relative to self-directed moodManager. TeleCoached moodManager produced greater reductions in depressive symptoms relative to WLC, however, there were no statistically significant differences relative to self-directed moodManager. While greater use was associated with better outcomes, most users in both TeleCoach and self-directed moodManager had dropped out of treatment by week 12. Even with telephone coaching, adherence to web-based interventions for depression remains a challenge. Methods of improving coaching models are discussed. Trial Registration Clinicaltrials.gov NCT00719979

High-resolution manometry correlates of ineffective esophageal motility.

OBJECTIVES:There are currently no criteria for ineffective esophageal motility (IEM) and ineffective swallow (IES) in esophageal pressure topography (EPT). Our aims were to use high-resolution manometry metrics to define IEM within the Chicago Classification and to determine the distal contractile integral (DCI) threshold for IES.METHODS:The EPT of 150 patients with either dysphagia or reflux symptoms were reviewed. Peristaltic function in EPT was defined by the Chicago Classification; the corresponding conventional line tracing (CLT) were reviewed separately. Generalized linear mixed models were used to find thresholds for DCI corresponding to traditionally determined IES and failed swallows. An external validation sample was used to confirm these thresholds.RESULTS:In terms of swallow subtypes, IES in CLT were a mixture of normal, weak, and failed peristalsis in EPT. A DCI of 450 mm Hg-s-cm was determined to be optimal in predicting IES. In the validation sample, the threshold of 450 mm Hg-s-cm showed strong agreement with CLT determination of IES (positive percent agreement 83%, negative percent agreement 90%). The patient diagnostic level agreement between CLT and EPT was good (78.6% positive percent agreement and 63.9% negative percent agreement), with negative agreement increasing to 92.0% if proximal breaks were excluded.CONCLUSIONS:The manometric correlate of IEM in EPT is a mixture of failed swallows and weak swallows with breaks in the middle/distal troughs. A DCI value <450 mm Hg-s-cm can be used to predict IES previously defined in CLT. IEM can be defined by >5 swallows with weak/failed peristalsis or with a DCI <450 mm Hg-s-cm.

Development and validation of a vitiligo-specific quality-of-life instrument (VitiQoL)

BACKGROUND Vitiligo significantly affects a persons health-related quality of life (HRQL). Although a small number of generic, and disease-specific, dermatologic HRQL measures exist, currently no vitiligo-specific instrument is available to capture disease-targeted concerns and issues. OBJECTIVE We sought to develop and validate a vitiligo-specific self-report instrument for HRQL. METHODS A pool of vitiligo-specific items was created based on in-depth interviews with patients with vitiligo (n = 16) and their responses to items in several previously validated HRQL measures. These items comprising our new instrument, VitiQoL, along with Skindex-16 and Dermatology Life Quality Index were administered to patients with vitiligo (n = 90) at two academic centers. This new instrument was validated using psychometric analysis. RESULTS The VitiQoL items showed high internal consistency (Cronbach alpha = 0.935). Exploratory factor analysis demonstrated 3 factors: participation limitation, stigma, and behavior. Concurrent validity was evidenced by large correlations between self-reported severity and VitiQoL scores (r = 0.51). Known groups validity was demonstrated for the VitiQoL behavior subscale between individuals with exposed and unexposed patches (P = .01). Convergent validity was shown by strong correlations between VitiQoL and outside dermatology scales measuring similar constructs (Skindex-16, r = 0.82; Dermatology Life Quality Index, r = 0.83). LIMITATIONS Potential selection bias was a limitation as most patients were recruited from academic centers. Reliability of the instrument was tested only with internal consistency and not reproducibility. Responsiveness of the instrument was not tested because of the prolonged time course necessary to observe clinically significant change in vitiligo. CONCLUSION VitiQoL is a reliable and valid HRQL instrument.

Can the American College of Surgeons Risk Calculator Predict 30-Day Complications After Knee and Hip Arthroplasty?

Accurate risk stratification of patients undergoing total hip (THA) and knee (TKA) arthroplasty is essential in the highly scrutinized world of pay-for-performance, value-driven healthcare. We assessed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculators ability to predict 30-day complications using 1066 publicly-reported Medicare patients undergoing primary THA or TKA. Risk estimates were significantly associated with complications in the categories of any complication (P = .005), cardiac complication (P < .001), pneumonia (P < .001) and discharge to skilled nursing facility (P < .001). However, predictability of complication occurrence was poor for all complications assessed. To facilitate the equitable provision and reimbursement of patient care, further research is needed to develop accurate risk stratification tools in TKA and THA surgery.