Publications

OBJECTIVE

To improve our understanding of patients' treatment preferences for chronic hepatitis C (HCV).

METHODS

Subjects with HCV were recruited from 2 VA medical centers. Preferences were ascertained using conjoint analysis. We used segmentation analysis to examine whether there were groups of respondents with similar preferences that were systematically different from the preferences of others. We then measured the associations between treatment preference with subjects' characteristics and their gist principles related to living with HCV and the burden of therapy.

RESULTS

A total of 199 subjects participated in this study. The segmentation analysis demonstrated that subjects could be classified into 2 distinct groups. The larger group [group 1, n=118 (59%)] opted for current treatment and the other [group 2, n=81 (41%)] preferred to defer. Patients with cirrhosis were less likely to belong to group 2 (prefer to defer) compared with those without cirrhosis (40.5% vs. 21.3%), whereas subjects self-identifying as African American were more likely to belong to group 2 than white subjects (51.3% vs. 30.5%). Members of group 1 had a more positive overall gist principles related to HCV compared with members of group 2 [mean (SD) score=28.63 (3.06) vs. 26.46 (2.79), P<0.0001]. These gist principles mediated the relationship between race and treatment preference (Sobel test statistic=-2.68, 2-tailed P=0.007).

CONCLUSIONS

Our findings indicate that there are groups of HCV patients with similar preferences that are distinct from other groups' preferences. Patients' gist principles related to the significance of having a chronic viral infection and the burdens of therapy are strongly related to their current treatment decisions. These findings help inform how best to initiate and deliver treatment for patients with HCV.

INTRODUCTION

Colonoscopic surveillance guidelines for serrated polyps (SPs) are predicated upon the histologic characteristics of the index polyp. However, discrimination between SP subtypes [hyperplastic polyps vs. sessile serrated adenoma/polyps (SSA/P)] is often unreliable.

MATERIALS AND METHODS

We studied the impact of (1) a novel tissue orientation method, performed in the endoscopy laboratory, whereby polyps are flattened in a small paper envelope immediately after resection (modified protocol); and (2) 2012 consensus-modified criteria (CM-2012). These interventions were compared with conventional tissue-handling protocol (CP) and traditional 2008 World Health Organization criteria (WHO). Twenty blinded community pathologists from around the United States scored 100, independent, 0.5 to 2.0 cm, proximal colonic SPs randomly selected from a 2-site tissue section archive. We compared interobserver agreement and diagnostic grading.

RESULTS

Interobserver agreement was higher using CM-2012 than WHO criteria (absolute agreement: 13% vs. 4%, P<0.01; 75% agreement: 54% vs. 38%, P<0.01). Interobserver agreement was higher with the modified protocol than with CP (WHO absolute agreement: 6% vs. 2%, P>0.05; WHO 75% agreement: 46% vs. 30%, P>0.05, and CM-2012 absolute agreement: 20% vs. 6%, P=0.07; CM-2012 75% agreement: 66% vs. 42%, P=0.03). Compared with WHO, use of CM-2012 criteria resulted in fewer diagnoses of "indeterminate"; more diagnoses of SSA/P (P<0.01); and "upgraded" the diagnosis from hyperplastic polyps to SSA/P in approximately 7% of cases. These observations were independent of polyp size, patient gender, and study site.

CONCLUSIONS

Simple enhancements to postresection SP handling and diagnostic criteria markedly improve interobserver agreement of SP diagnosis among nongastrointestinal community pathologists. This finding, if confirmed, has important implications for SP colonoscopy surveillance guidelines.

OPINION STATEMENT

Patients with long-standing ulcerative colitis (UC) and extensive Crohn's disease (CD) colitis have a high risk of colorectal cancer (CRC) and are recommended to undergo surveillance with colonoscopy. Recent data highlights their increased risk of CRC compared to the general population despite colonoscopy surveillance. The proportion of IBD patients diagnosed with interval CRC within 6 to 36 months following a clearing colonoscopy was 15 %. Optimizing colonoscopy surveillance methods is important. Studies have demonstrated that the best endoscopic surveillance strategy to detect dysplasia is chromoendoscopy with surface application of dyes to enhance the mucosal visualization and that visible dysplasia should be endoscopically resected. In this chapter we will summarize the optimal surveillance and management techniques for colorectal dysplasia in IBD patients.

The rapid rise in childhood allergies (atopy) in Westernized nations has implicated associated environmental exposures and lifestyles as primary drivers of disease development. Culture-based microbiological studies indicate that atopy has demonstrable ties to altered gut microbial colonization in very early life. Infants who exhibit more severe multisensitization to food- or aero-allergens have a significantly higher risk of subsequently developing asthma in childhood. Hence an emerging hypothesis posits that environment- or lifestyle-driven aberrancies in the early-life gut microbiome composition and by extension, microbial function, represent a key mediator of childhood allergic asthma. Animal studies support this hypothesis. Environmental microbial exposures epidemiologically associated with allergy protection in humans confer protection against airway allergy in mice. In addition, gut microbiome-derived short-chain fatty acids produced from a high-fiber diet have been shown to protect against allergy via modulation of both local and remote mucosal immunity as well as hematopoietic antigen-presenting cell populations. Here we review key data supporting the concept of a gut-airway axis and its critical role in childhood atopy.

Carbapenemases are enzymes that are capable of inactivating all or almost all beta-lactam antimicrobial agents. These enzymes are frequently coexpressed with other resistance mechanisms to non-beta-lactams, leading to extremely drug-resistant pathogens. Once a curiosity, these enzymes have spread into organisms that are among the most common causes of infection, such as Klebsiella pneumoniae and Escherichia coli. Identification of these organisms has proved challenging for clinical microbiology laboratories, leading to revisions in susceptibility standards for carbapenems. Although currently a rare cause of infection in children, these carbapenem-resistant Enterobacteriaceae (CRE) are becoming endemic in a variety of healthcare settings. Management of infections due to CRE is complicated by a lack of effective treatment options and clinical data on their effectiveness. Treatment of CRE infections in children is particularly challenging because therapeutic options for CRE lack adequate data on dosing and safety in children. Use of unconventional combination treatment regimens, including agents to which the organism is resistant in vitro, may provide some benefit in the treatment of severe CRE infection. Fortunately, several agents with the potential for treatment of CRE infections have been recently approved or are in late clinical development, although few data will be available in the short term to inform use in children.

AIMS

Recommendations for metformin use are dependent on eGFR category: eGFR >45 ml/min/1.73 m - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR<30 - "do not use". Misclassification of metformin eligibility by creatinine-based MDRD GFR estimates (eGFRcr) may contribute to its misuse. We investigated the impact of cystatin c estimates of GFR (eGFRcys) on metformin eligibility.

METHODS

In a consecutive cohort of 550 Veterans with diabetes, metformin use and eligibility were assessed by eGFR category, using eGFRcr and eGFRcys. Discrepancy in eligibility was defined as cases where eGFRcr and eGFRcys categories (<30, 30-44, 45-60, and >60 ml/min/1.73 m) differed with an absolute difference in eGFR of >5 ml/min/1.73 m. We modeled predictors of metformin use and eGFR category discrepancy with multivariable relative risk regression and multinomial logistic regression.

RESULTS

Subjects were 95% male, median age 68, and racially diverse (45% White, 22% Black, 11% Asian, 22% unknown). Metformin use decreased with severity of eGFRcr category, from 63% in eGFRcr >60 to 3% in eGFRcr <30. eGFRcys reclassified 20% of Veterans into different eGFR categories. Factors associated with a more severe eGFRcys category compared to eGFRcr were older age (aOR = 2.21 per decade, 1.44-1.82), higher BMI (aOR = 1.04 per kg/m, 1.01-1.08) and albuminuria >30 mg/g (aOR = 1.81, 1.20-2.73).

CONCLUSIONS

Metformin use is low among Veterans with CKD. eGFRcys may serve as a confirmatory estimate of kidney function to allow safe use of metformin among patients with CKD, particularly among older individuals and those with albuminuria.