Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent

Primary sclerosing cholangitis (PSC) is a rare, progressive liver disease characterized by cholestasis and bile duct fibrosis that has no accepted therapy known to delay or arrest its progression. We report a 23-year-old female patient who at age 14 was diagnosed with moderate pancolonic ulcerative colitis (UC) and at age 15 with small-duct PSC unresponsive to conventional therapy. The patient began single drug therapy with the antibiotic oral vancomycin (OVT) and achieved normalization of liver enzymes and resolution of UC symptoms with colonic mucosal healing. These improvements have persisted over 8 years. There has been no colon dysplasia, liver fibrosis or failure, bile duct stricture, or cancer. Of note, the patient's response was dependent on the brand of oral vancomycin capsule, as well as dose. This raised the questions of possible differences in bioequivalence of different commercial versions of the drug and whether this factor might play into the variability of efficacy seen in published trials. Evidence suggests that oral vancomycin both alters the intestinal microbiome and has immunomodulatory effects. Its striking effectiveness in this and other patients supports further investigation in randomized trials, with careful attention to its bioavailability profile in the gut

Awareness of pharmacy researchers about the national research code of ethics: A study from Jordan

Objective: In Jordan, research ethics have been subject to increasingly formal regulations and structuring. Recently the Ministry of Higher Education and Research Published the National Research Code of Ethics. However, little is known about the awareness of pharmacology researchers of this code and the extent of its applicability to their research. Methods: Purposeful sampling through institutions’ websites was used to identify staff members with excellent profiles from 20 Faculties of Pharmacy in Jordan. After obtaining the required approvals, in-depth interviews were conducted, recorded, transcribed, and analyzed using NVivo 11 Software. The interviews followed a previously prepared and validated interview guide that covered various aspects of education, research, and training. Key findings: Eighteen members of staff agreed to take part in the study. Qualitative analysis revealed three main themes each concerning respondents’ awareness of the National Code of Research Ethics in Jordan. The emerging themes were: the lack of awareness regarding the code of ethics, the need for clear guidelines for pharmacology research in Jordan, and the need for further workshops and training courses for pharmacology researchers. Conclusion: This study highlights a lack of awareness regarding the presence of the National Research Ethics Code among pharmacology researchers in Jordan. This might have negative implications on medical research. It was thought that the code of ethics should be incorporated in postgraduate pharmacy education, training courses for pharmacy researchers, and workshops for pharmacy academic staff

Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis

Background Oral vancomycin (OV) in primary sclerosing cholangitis (PSC) has been evaluated as a potential therapeutic agent. We report the long-term biochemical course and outcomes of patients with PSC treated with OV. Methods Patients were enrolled in 2 open-label clinical trials (ClinicalTrials.gov Identifier: NCT01802073 and NCT01322386) and offered OV at 50 mg/kg/day in 3 divided doses if weight = 30kg. Patients with biliary strictures requiring stenting or awaiting liver transplant were excluded. Liver biochemistry, MRCP and histology were documented at baseline and while on OV. The primary outcome was a decrease in elevated gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and/or alanine aminotransferase (ALT) from baseline. Results 30 subjects were enrolled, and 29 additional subjects who learned of the clinical trial requested OV (totaln = 59; median age was 13.5 years [range, 1.5-44 years]; 64.4% were male; and 94.9% had inflammatory bowel disease [IBD]). The median treatment duration was 2.7 years (range, 0.2-14 years). Ninety-six percent (57/59), 81.3% (48/59), and 94.9% (56/59) experienced reduction of GGT, ALP, and ALT, respectively. Furthermore, 39% (23/59), 22% (13/59), and 55.9% (33/59) experienced normalization of GGT, ALP, and ALT, respectively, within the first 6 months of OV treatment. One patient underwent liver transplantation 8 years after beginning OV treatment, and one developed biliary strictures requiring endoscopic intervention. OV was well-tolerated by patients, and no patient developed treatment-related adverse events. Conclusion In PSC, OV was well-tolerated and was associated with improvement in liver chemistry. A randomized placebo-controlled clinical trial is warranted