Commissioning and co-production in health and care services in the United Kingdom and Ireland: An exploratory literature review.

INTRODUCTION: This exploratory literature review seeks to examine the literature around commissioning processes in the co-production of health and care services, focusing on two questions: How do health and care commissioning processes facilitate and/or pose barriers to co-production in service design and delivery? What are the contextual factors that influence these processes? METHOD: A systematic search of three databases (Medline, Public Health and Social Policy and Practice) and a search platform (Web of Science) was conducted for the period 2008-2023. A total of 2675 records were retrieved. After deduplication, 1925 were screened at title and abstract level. Forty-seven reports from 42 United Kingdom and Ireland studies were included in the review. A thematic synthesis of included studies was conducted in relation to the research questions. RESULTS: The review identified one overarching theme across the synthesised literature: the complexity of the commissioning landscape. Three interconnected subthemes illuminate the contextual factors that influence this landscape: commissioners as leaders of co-production; navigating relationships and the collective voice. CONCLUSION: Commissioning processes were commonly a barrier to the co-production of health and care services. Though co-production was an aspiration for many commissioners, the political and economic environment and service pressures meant that it was often not fully realised. More flexible funding models, longer-term pilot projects, an increased emphasis in social value across the health and care system and building capacity for strong leadership in commissioning is needed. PATIENT AND PUBLIC CONTRIBUTION: Patients and the public did not contribute to this review as it was a small piece of work following on from a completed project, with no budget for public involvement.

Household water use and greywater management in Khulna city, Bangladesh.

While substantial progress has been made in improving water and sanitation services in low- and middle-income countries, aligned basic services such as greywater, stormwater, and solid waste management have progressed little in recent decades. Data was collected in Khulna city, Bangladesh via a household survey (n = 192) of low-income areas exploring domestic water use and greywater volumes, characteristics, and disposal practices. Most households (71%) use a piped water supply for domestic purposes, supplemented by seasonal rainwater harvesting (26%) and greywater use (13%). Of the total water used by households (mean: 594 L/household/day and equivalent to 116 L/person/day), approximately 58% becomes greywater through bathing, dishwashing, religious practices, handwashing, laundry, and mopping. Greywater produced ranges from 61-1274 L/household/day, with a mean of 345 L/household/day and equivalent to 78.4 L/person/day. Greywater characteristics vary depending on the activity, individual behaviours and any products used during cooking, bathing, or cleaning. After generation, households dispose greywater to open drains (67%), nearby waterbodies (17%) directly to the ground (9%), or decentralised wastewater treatment system (7%). Without services for greywater management, greywater disposal may have considerable public and environmental health implications, necessitating careful attention and oversight from service-providers and stakeholders beyond the household-level.

UCHL1-dependent control of hypoxia-inducible factor transcriptional activity during liver fibrosis.

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver disease. At the cellular level, liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) which transdifferentiate into a myofibroblast-like phenotype that is contractile, proliferative and profibrogenic. HSC transdifferentiation induces genome-wide changes in gene expression that enable the cell to adopt its profibrogenic functions. We have previously identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation; however, the cellular targets of its deubiquitinating activity are poorly defined. Here, we describe a role for UCHL1 in regulating the levels and activity of hypoxia-inducible factor 1 (HIF1), an oxygen-sensitive transcription factor, during HSC activation and liver fibrosis. HIF1 is elevated during HSC activation and promotes the expression of profibrotic mediator HIF target genes. Increased HIF1α expression correlated with induction of UCHL1 mRNA and protein with HSC activation. Genetic deletion or chemical inhibition of UCHL1 impaired HIF activity through reduction of HIF1α levels. Furthermore, our mechanistic studies have shown that UCHL1 elevates HIF activity through specific cleavage of degradative ubiquitin chains, elevates levels of pro-fibrotic gene expression and increases proliferation rates. As we also show that UCHL1 inhibition blunts fibrogenesis in a pre-clinical 3D human liver slice model of fibrosis, these results demonstrate how small molecule inhibitors of DUBs can exert therapeutic effects through modulation of HIF transcription factors in liver disease. Furthermore, inhibition of HIF activity using UCHL1 inhibitors may represent a therapeutic opportunity with other HIF-related pathologies.