Effects of vedolizumab, adalimumab and infliximab on biliary inflammation in individuals with primary sclerosing cholangitis and inflammatory bowel disease.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure. AIM: To evaluate the effect of biological therapies on PSC progression in IBD patients. METHODS: We performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017. Hepatic biochemistries were compared using the paired t-test (patients served as their own controls) ≤3 months before and 6-8 and 12-14 months after biological initiation. Radiographic information of biliary stenosis and liver fibrosis were obtained via abdominal ultrasound, abdominal magnetic resonance imaging and magnetic resonance elastography. RESULTS: Use of adalimumab was associated with a significant decrease in alkaline phosphatase (ALP) after 6-8 months (P = 0.03; mean change -70 U/L, standard deviation [SD] 88 U/L) compared to vedolizumab (mean change +50 U/L, SD 142 U/L) or infliximab (mean change +37 U/L, SD 183 U/L) but the change was not significant after 12-14 months (P = 0.24). No significant decreases were observed with AST, ALT, total or direct bilirubin, elastography score or radiographic imaging of biliary tree dilation/strictures with any biological therapy after 6-8 or 12-14 months. CONCLUSIONS: Current evidence suggests that biological therapies used for the treatment of IBD are not effective treatments for PSC. Further study is needed to elucidate any potential beneficial effect of adalimumab on PSC.

Postoperative outcomes in vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.

BACKGROUND: Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. AIM: We sought to compare 30-day postoperative infectious complication rate among vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. METHODS: A retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. RESULTS: One hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). CONCLUSIONS: Twenty-six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable analysis. While vedolizumab-treated Crohn's disease patients may be a sicker cohort of patients, it is important to consider these findings with regard to preoperative counselling, operative timing and primary closure of wounds.

The utility of a non-verbal prospective memory measure as a sensitive marker for early-stage Alzheimer's disease in Hong Kong.

ABSTRACT Background: With the proportion of older adults in Hong Kong projected to double in size in the next 30 years, it is important to develop measures for detecting individuals in the earliest stage of Alzheimer's disease (AD, 0.5 in Clinical Dementia Rating, CDR). We tested the utility of a non-verbal prospective memory task (PM, ability to remember what one has to do when a specific event occurs in the future) as an early marker for AD in Hong Kong Chinese. Methods: A large community dwelling sample of older adults who are healthy controls (CDR 0, N = 125), in the earliest stage of AD (CDR 0.5, N = 125), or with mild AD (CDR 1, N = 30) participated in this study. Their reaction time/accuracy data were analyzed by mixed-factor analyses of variance to compare the performance of the three CDR groups. Logistic regression analyses were performed to test the discriminative power of these measures for CDR 0 versus 0.5 participants. Results: Prospective memory performance declined as a function of AD severity: CDR 0 > CDR 0.5 > CDR 1, suggesting the effects of early-stage AD and AD progression on PM. After partialling out the variance explained by psychometric measures (e.g., ADAS-Cog), reaction time/accuracy measures that reflected the PM still significantly discriminated between CDR 0 versus 0.5 participants in most of the cases. Conclusion: The effectiveness of PM measures in discriminating individuals in the earliest stage of AD from healthy older adults suggests that these measures should be further developed as tools for early-stage AD discrimination.

Effects of education on very mild dementia among Chinese people in Hong Kong: potential mediators in the Cantonese Mini-Mental State Examination tasks.

BACKGROUND: In Hong Kong, older Chinese adults generally have a low level of education. This study examined the effect of education on very mild Alzheimer's disease (AD), as quantified by Clinical Dementia Rating (CDR) scale (CDR 0.5 versus 0), in a Chinese community. The Cantonese version of the Mini-Mental State Examination (C-MMSE) was used to estimate cognitive abilities that were related to the level of education, and that in turn serve as protective factors for AD. METHODS: A total of 788 community-dwelling older adults (383 CDR 0 and 405 CDR 0.5) were recruited in this cross-sectional study, which was derived from a population-based prevalence project. The participants' number of years of education and C-MMSE scores were used to predict their CDR scores using logistic regression and the mediation effects of C-MMSE scores were analyzed. RESULTS: Consistent with previous studies, the chance of being rated as having very mild AD increased with age, but decreased with years of education, among the older adult community of Hong Kong. The effect of education on very mild dementia was weakened substantially when C-MMSE scores were included as mediating variables. CONCLUSIONS: The findings indicate that the protective effects of education on dementia were mediated by an enhancement of older adults' performance on some C-MMSE items, including attention and orientation to time and place.

Outcomes measurement across the continuum of care.

Outcomes management can only be truly achieved if it is conducted using data obtained from every possible care delivery site--the entire continuum of care. The author emphasizes that designing the most appropriate information infrastructure for an integrated health system requires a thorough understanding of the needs of the organization as reflected in its strategic business goals and objectives.

A model for developing longitudinal health records.

The future of population health management will focus on treatment of chronic diseases and avoidance of acute disorders for targeted populations. The key tools for managing population health must involve outcomes measurement and management, wellness/preventive programs, care management programs, and cost management. This can be achieved by the implementation of a computerized patient health record for longitudinal health information (lifetime) recording and management.

How to tie a drug therapy improvement program to physician credentialing.

The pharmacy staff and the management information system specialist at St. James Hospital and Health Centers, a 472-bed community medical center located in Chicago Heights, Illinois, developed a computer program for documenting the drug use patterns of physicians. This program was not only helpful in improving the appropriate use of medications within the institution, it was also tied to the prescriber credentialing process. How the program evolved as well as the cost savings/cost avoidance achieved as a result of the drug therapy improvement process is presented.

Phenytoin concentration elevation subsequent to ranitidine administration.

OBJECTIVE: To report elevated phenytoin (PHT) plasma concentrations in a patient receiving ranitidine. CASE SUMMARY: A patient treated with PHT and ranitidine experienced elevated PHT plasma concentrations that persisted several days after PHT was discontinued. The PHT plasma concentration declined rapidly after withdrawal of ranitidine. DISCUSSION: This is an unusual case report of elevated PHT plasma concentrations associated with concurrent ranitidine use. Ranitidine has been reported to interfere with the hepatic metabolism of other drugs. The proposed mechanism of this interaction is similar to that of other histamine 2-receptor antagonists--by binding to cytochrome P-450 hepatic mixed-function oxidase. We postulate that a small subset of patients may be susceptible to this effect of ranitidine. CONCLUSIONS: This case was complicated by several variables that may have affected the changes observed in total PHT concentrations. However, an interaction between ranitidine and PHT should be considered, especially in a subpopulation of patients that are more susceptible to this effect. Patients using ranitidine and phenytoin concurrently should be routinely monitored.

Inhibition of human endothelial cell proliferation in vitro in response to n-butyrate and propionate.

The study aimed to investigate the effects of n-butyrate and propionate on the proliferation and viability of human endothelial cells in culture. Proliferation was assessed by a 24-hour bromodeoxyuridine pulse labelling and immunoperoxidase method and viability was assessed by a colorimetric viability (MTT) assay. Endothelial cells were isolated from human umbilical vein by collagenase digestion. Experiments were performed on 96-well plates and cultures were exposed to different concentrations of n-butyrate and propionate for 2 days. n-butyrate and propionate caused significant reductions in the proliferation of endothelial cells at concentrations of 1.25 mM and 10 mM respectively (p less than 0.05); the reduction in proliferation was dose-dependent for both agents. n-butyrate was a more potent inhibitor of proliferation than propionate. However, there were no significant effects on the viability of the cells with both agents up to the highest concentrations tested (25 mM). The data indicate that n-butyrate and propionate inhibit endothelial cell proliferation which may contribute to the pathogenic effects of dental plaque in periodontal disease.