Safety and tolerability of obeticholic acid in chronic liver disease: a pooled analysis of 1878 individuals.

BACKGROUND AND AIMS: Obeticholic acid (OCA) is a farnesoid X receptor agonist used in primary biliary cholangitis (PBC) treatment. Recent studies have expanded OCA use for NASH treatment and results from phase 3 clinical trial have shown beneficial reduction of ≥1 stage of fibrosis with no NASH worsening. However, safety concerns still preside, thus we systematically examine the safety profile of OCA in chronic liver disease. MATERIALS AND METHODS: A search was conducted in Medline and Embase databases for OCA randomized controlled trials in chronic liver disease. Binary events were pooled with Paule-Mandel random effects model and proportional events were examined in a generalized linear mixed model with Clopper-Pearson intervals. RESULTS: A total of 8 studies and 1878 patients were analyzed. There was a 75% [risk ratio (RR): 1.75, 95% CI: 1.43-2.15, p < 0.01] increased pruritis risk. OCA increased constipation incidence (RR: 1.88, 95% CI: 1.45-2.43, p < 0.01), decreased diarrhea (RR: 0.62, 95% CI: 0.50-0.77, p < 0.01), and increased development of hyperlipidemia (RR: 2.69, 95% CI: 1.85-3.92, p < 0.01) relative to placebo. Sensitivity analysis in NASH-only studies found a dose-dependent effect with pruritis which increases to RR: 3.07 (95% CI: 1.74-5.41) at 25 mg. However, up to 9.98% (95% CI: 5.01%-18.89%) of NAFLD patients with placebo similarly experience pruritis events. Overall, 16.55% (95% CI: 6.47%-36.24%) of patients with NAFLD on OCA experienced pruritis. There was no significant increase in cardiovascular events. CONCLUSIONS: OCA may represent the first pharmacological treatment approved for NASH. However, pruritis, constipation, diarrhea, and hyperlipidemia were major events with evident dose-dependent effect that affect tolerability in NASH. Future long-term studies for longitudinal safety events are required.

CARD14-associated papulosquamous eruption (CAPE) in a toddler responding to treatment with acitretin.

CARD14-associated papulosquamous eruption (CAPE) is a rare autosomal dominant dermatosis that presents classically in early childhood with clinical features of both psoriasis and pityriasis rubra pilaris (PRP). The disease is known to be refractory to topical and systemic therapies classically used for psoriasis, with the majority of reported cases requiring treatment with biologics, such as ustekinumab and secukinumab. We present a toddler with a clinical presentation consistent with CAPE and found to have a novel heterozygous variant of the CARD14 gene. She was refractory to treatment with topical emollients and topical corticosteroids, but responsive to oral acitretin.

Ethical Pricing: a Confucian Perspective.

Based on an analysis of a landmark case Lim Mey Lee Susan v Singapore Medical Council in Singapore where a doctor was professionally disciplined for over-charging a wealthy patient, a judgement upheld by the Singapore High Court, this paper will discuss the notion of an 'ethical price' (EP) and its determination with respect to the provision of healthcare services. It will first examine the limitations of a legal approach for setting an ethical limit to pricing. From there, it will argue that Confucian philosophy provides a useful ethical framework to explore EP, with focus on the context of Singapore. The following question is addressed: What is an ethical pricing standard for medical practice from a Confucian perspective? The strengths and limitations of a Confucian value base as regards the determination of an objective EP will be analysed through an examination of the shortcomings of the doctor's behaviour in the Susan Lim case as well as other case scenarios. The paper will conclude with some practical suggestions on how Confucian-based ideas can be applied to decision-making on pricing and the importance of this for medical professionalism and ethics teaching.