Private sector delivery of health services in developing countries: a mixed-methods study on quality assurance in social franchises

BACKGROUND: Across the developing world health care services are most often delivered in the private sector and social franchising has emerged, over the past decade, as an increasingly popular method of private sector health care delivery. Social franchising aims to strengthen business practices through economies of scale: branding clinics and purchasing drugs in bulk at wholesale prices. While quality is one of the established goals of social franchising, there is no published documentation of how quality levels might be set in the context of franchised private providers, nor what quality assurance measures can or should exist within social franchises. The aim of this study was to better understand the quality assurance systems currently utilized in social franchises, and to determine if there are shared standards for practice or quality outcomes that exist across programs. METHODS: The study included three data sources and levels of investigation: 1) Self-reported program data; 2) Scoping telephone interviews; and 3) In-depth field interviews and clinic visits. RESULTS: Social Franchises conceive of quality assurance not as an independent activity, but rather as a goal that is incorporated into all areas of franchise operations, including recruitment, training, monitoring of provider performance, monitoring of client experience and the provision of feedback. CONCLUSIONS: These findings are the first evidence to support the 2002 conceptual model of social franchising which proposed that the assurance of quality was one of the three core goals of all social franchises. However, while quality is important to franchise programs, quality assurance systems overall are not reflective of the evidence to-date on quality measurement or quality improvement best practices. Future research in this area is needed to better understand the details of quality assurance systems as applied in social franchise programs, the process by which quality assurance becomes a part of the organizational culture, and the components of a quality assurance system that are most correlated with improved quality of clinical care for patients

Activation of targetable inflammatory immune signaling is seen in myelodysplastic syndromes with SF3B1 mutations

Background: Mutations in the SF3B1 splicing factor are commonly seen in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), yet the specific oncogenic pathways activated by mis-splicing have not been fully elucidated. Inflammatory immune pathways have been shown to play roles in the pathogenesis of MDS, though the exact mechanisms of their activation in splicing mutant cases are not well understood. Methods: RNA-seq data from SF3B1 mutant samples was analyzed and functional roles of interleukin-1 receptor-associated kinase 4 (IRAK4) isoforms were determined. Efficacy of IRAK4 inhibition was evaluated in preclinical models of MDS/AML. Results:: RNA-seq splicing analysis of SF3B1 mutant MDS samples revealed retention of full-length exon 6 of IRAK4, a critical downstream mediator that links the Myddosome to inflammatory NF-kB activation. Exon 6 retention leads to a longer isoform, encoding a protein (IRAK4-long) that contains the entire death domain and kinase domain, leading to maximal activation of NF-kB. Cells with wild-type SF3B1 contain smaller IRAK4 isoforms that are targeted for proteasomal degradation. Expression of IRAK4-long in SF3B1 mutant cells induces TRAF6 activation leading to K63-linked ubiquitination of CDK2, associated with a block in hematopoietic differentiation. Inhibition of IRAK4 with CA-4948, leads to reduction in NF-kB activation, inflammatory cytokine production, enhanced myeloid differentiation in vitro and reduced leukemic growth in xenograft models. Conclusions: SF3B1 mutation leads to expression of a therapeutically targetable, longer, oncogenic IRAK4 isoform in AML/MDS models.</p