Bile acid and immunosuppressive therapy in primary biliary cirrhosis

Primary Biliary Cirrhosis (PBC) is a chronic, cholestatic liver disease characterized by non-suppurative destruction of interlobular and septal bile ducts, with subsequent liver damage and eventually development of cirrhosis. The disease is relatively rare with an estimated annual incidence and point prevalence in Europe of about 14 and 114 per million population respectively.The course of the disease is variable and unpredictable, but potentially fa1tal

Oral naltrexone treatment for cholestatic pruritus: A double-blind, placebo-controlled study

Background and Aims: The efficacy of currently available therapeutic agents for cholestatic pruritus is often disappointing. The aim of this study was to assess the antipruritic effect of naltrexone, an oral opiate receptor antagonist. Methods: Sixteen patients with pruritus of chronic cholestasis were randomized to receive naltrexone (4-week course of 50 mg naltrexone daily) or placebo. Pruritus, quality of sleep, fatigue (using visual analogue scales), side effects, and liver function were assessed every 2 weeks. Serum naltrexone and 6β-naltrexol concentrations in all patients and 5 healthy controls were measured during the first day of naltrexone treatment. Results: Mean changes with respect to baseline were significantly different, in favor of the naltrexone group, for daytime itching (-54% vs. 8%; P = 0.001) and nighttime itching (-44% vs. 7%, P = 0.003). In 4 naltrexone-treated patients, side effects (transient in 3 cases) consistent with an opiate withdrawal syndrome were noted. No deterioration of the underlying disease was observed. Naltrexone and 6β-naltrexol levels did not differ between patients and controls, and there was no significant association with treatment response. Conclusions: For patients with cholestatic liver disease and itching, refractory to regular antipruritic therapy, oral naltrexone may be an effective and well-tolerated alternative

Long-term outcomes in patients newly diagnosed with iron deficiency anaemia in general practice: A retrospective cohort study

Objectives To describe all iron deficiency anaemia (IDA)-related causes during follow-up of patients newly diagnosed with IDA and to assess whether a delayed colorectal cancer (CRC) diagnosis influences survival. Design and setting Retrospective cohort study of patients from general practices in the Dordrecht area, the Netherlands. Participants Men and women aged ≥50 years with a new diagnosis of IDA (ie, no anaemia 2 years previously). Method From February 2007 to February 2018, all relevant data were collected from the files of the referral hospital. Early IDA-related cause was defined as established within 18 weeks after IDA diagnosis. Cox proportional-hazards regression was u

Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): Rationale and design of a multicenter randomized clinical trial

Background: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. Methods: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. Discussion: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. Trial registration:NCT02657044(Clinicaltrials.gov), registered January 8, 2016