Improving quality of life in patients with rare autoimmune liver diseases by structured peer-delivered support (Q.RARE.LI): study protocol for a transnational effectiveness-implementation hybrid trial.

BACKGROUND: Psychosocial support is a crucial component of adequate rare disease care, but to date psychosocial support needs of this patient population are insufficiently met. Within Q.RARE.LI, we strive to evaluate the effectiveness of a structured, transdiagnostic, and location-independent psychosocial support intervention in routine care of patients with rare autoimmune liver diseases in five countries and prepare its implementation. METHODS: Within an effectiveness-implementation hybrid trial, we aim to a) investigate the effectiveness of the intervention in routine care in five diverse healthcare systems and b) assess implementation outcomes, examine and prepare the implementation context, and develop country-specific implementation strategies. To assess effectiveness, we will include N = 240 patients with rare autoimmune liver diseases. Within a two-armed randomized controlled trial (allocation ratio 1:1), we will compare structured and peer-delivered psychosocial support in addition to care-as-usual (CAU) with CAU alone. Outcomes will be assessed via electronic database entry prior to intervention, directly after, and at a three-month follow-up. Our primary effectiveness outcome will be mental health-related quality of life at post-assessment. Secondary outcomes include depression and anxiety severity, perceived social support, helplessness, and disease acceptance. Implementation outcomes will be assessed within a mixed-methods process evaluation. In a quantitative cross-sectional survey, we will examine perceived acceptability and feasibility in patients, peer-counselors, and healthcare providers involved in delivery of the intervention. In qualitative focus groups, we will analyze the implementation context and determine barriers and facilitators for implementation with different stakeholders (patients and/or representatives, peer-counselors, healthcare providers, health insurers). Based on these results, we will derive country-specific implementation strategies and develop a concrete implementation plan for each country. DISCUSSION: The intervention is expected to help patients adjust to their disease and improve their mental quality of life. The transdiagnostic and location-independent program has the potential to reach patients for psychosocial support who are usually hard to reach. By preparing the implementation in five countries, the project can help to make low-threshold psychosocial support available to many patients with rare diseases and improve comprehensive healthcare for an often neglected group. TRIAL REGISTRATION: ISRCTN15030282.

Mucosal protection by phosphatidylcholine.

The colonic mucus serves a first barrier towards invasion of commensal bacteria in stools to prevent inflammation. One essential component of intestinal mucus is phosphatidylcholine (PC) which represents more than 90% of the phospholipids in mucus indicative for a selective transport of PC into this compartment. It is arranged in lamellar structures as surfactant-like particles which provide a hydrophobic surface on top of the hydrated mucus gel to prevent the invasion of bacteria from intestinal lumen. In ulcerative colitis (UC), the mucus PC content is reduced by 70%, irrespective of the state of inflammation. Thus, it could represent an intrinsic primary pathogenetic condition predisposing to bacterial invasion and the precipitation of inflammation. Since PC was shown to be mainly secreted by the ileal mucosa from where it is assumed to move distally to the colon, the PC content along the colonic wall towards the rectum gradually thins, with the least PC content in the rectum. This explains the start of the clinical manifestation of UC in the rectum and the expansion from there to the upper parts of the colon. In three clinical trials, when missing mucus PC in UC was supplemented by an oral, delayed release PC preparation, the inflammation improved and even resolved after a 3-month treatment course. The data indicate the essential role of the mucus PC content for protection against inflammation in colon.

Phosphatidylcholine (lecithin) and the mucus layer: Evidence of therapeutic efficacy in ulcerative colitis?

Colonic mucus protects against attacks from bacteria in stool. One component of mucus is phosphatidylcholine (PC) which is thought to be arranged as continuous lamellar layer in the apical mucus and to be responsible for establishing a protective hydrophobic surface. This 'intestinal surfactant' plays a key role in mucosal defense. Thus, a defective PC layer contributes to the development of inflammation. Analysis of rectoscopically acquired mucus aliquots revealed a 70% decrease in PC content in ulcerative colitis (UC) compared to Crohn's disease (CD) and healthy controls - independent of disease activity. Accordingly, we propose that lack of mucus PC is a key pathogenetic factor in UC. In clinical studies a delayed-release oral PC preparation (rPC) was found to substitute the lack of PC in rectal mucus. Indeed, in non-steroid-treated active UC, 53% of rPC patients reached remission [clinical activity index (CAI) ≤3] compared to 10% of placebo patients (p ≤ 0.001). Endoscopic and histologic findings improved concomitantly. A second trial with 60 chronic-active, steroid-dependent UC patients was conducted to test for steroid-sparing effects. Complete steroid withdrawal with a concomitant achievement of remission (CAI ≤3) or clinical response (≥50% CAI improvement) was reached in 15 PC-treated patients (50%) but only in 3 (10%) placebo patients (p = 0.002). In conclusion, intrinsic reduction of PC (lecithin) in colonic mucus may be a key pathogenetic feature of UC. Topical supplement of PC by a delayed-released oral PC preparation is effective in resolving inflammatory activity of UC and may develop to a first-choice therapy for this disease.