A qualitative analysis of relatives', health professionals' and service users' views on the involvement in care of relatives in Bipolar Disorder

Background: Relatives of people with bipolar disorder report that services do not meet their own needs, despite clinical recommendations for the development of care plans for relatives, provision of information regarding their statutory entitlements, and formal involvement in decision making meetings. Further, there is now conclusive evidence highlighting the benefits of relatives' involvement in improving outcomes for service users, relatives, and the health system as a whole. This qualitative study explored the views of relatives of people with bipolar disorder, service users and healthcare professionals regarding the barriers and the facilitators to relatives' involvement in care. Methods: Thirty five people were interviewed (12 relatives, 11 service users and 12 healthcare professionals). Audio recordings were transcribed verbatim and common themes in participants' narratives emerged using framework analysis. Results: Participants' accounts confirmed the existence of opportunities for relatives to be involved. These, however, were limited and not always accessible. There were three factors identified that influenced accessibility namely: pre-existing worldviews, the quality of relationships and of communication between those involved, and specific structural impediments. Discussion: These themes are understood as intertwined and dependent on one another. People's thoughts, beliefs, attitudes, cultural identifications and worldviews often underlie the ways by which they communicate and the quality of their relationship. These, however, need to be conceptualised within operational frameworks and policy agendas in health settings that often limit bipolar relatives' accessibility to opportunities for being more formally involved. Conclusions: Involving relatives leads to clear benefits for relatives, service users, healthcare professionals, and the health system as a whole. Successful involvement of relatives, however, depends on a complex network of processes and interactions among all those involved and requires strategic planning from policy makers, operational plans and allocation of resources

Screening out irrelevant cell-based models of disease

The common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently used in drug discovery. An apparent reluctance to explore and adopt alternative cell-and tissue-based model systems, coupled with a detachment from clinical practice during assay validation, contributes to ineffective translational research. To help address these issues and stimulate debate, here we propose a set of principles to facilitate the definition and development of disease-relevant assays, and we discuss new opportunities for exploiting the latest advances in cell-based assay technologies in drug discovery, including induced pluripotent stem cells, three-dimensional (3D) co-culture and organ-on-a-chip systems, complemented by advances in single-cell imaging and gene editing technologies. Funding to support precompetitive, multidisciplinary collaborations to develop novel preclinical models and cell-based screening technologies could have a key role in improving their clinical relevance, and ultimately increase clinical success rates

Medical treatment of primary sclerosing cholangitis: A role for novel bile acids and other (post-)transcriptional modulators?

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of the liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease, and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic, making the development of targeted therapeutic strategies difficult. Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects. Ursodeoxycholic acid (UDCA) has consistently been shown to improve serum liver tests and might lower the risk of colon carcinoma and cholangiocarcinoma by yet unknown mechanisms. Whether "high dose" UDCA improves the long-term prognosis in PSC as suggested by small pilot trials remains to be demonstrated. The present overview discusses potential therapeutic options aside of targeted immunological therapies and UDCA. The C23 bile acid norUDCA has been shown to markedly improve biochemical and histological features in a mouse model of sclerosing cholangitis without any toxic effects. Studies in humans are eagerly being awaited. Nuclear receptors like the farnesoid-X receptor (FXR), pregnane-X receptor (PXR), vitamin D receptor (VDR), and peroxisome-proliferator-activator receptors (PPARs) have been shown to induce expression of diverse carriers and biotransformation enzymes of the intestinal and hepatic detoxification machinery and/or to modulate fibrogenesis. Pros and cons of respective receptor agonists for the future treatment of PSC are discussed in detail. In our view, the novel bile acid norUDCA and agonists of PPARs, VDR, and PXR appear particularly attractive for further studies in PSC