Exploring how and why social prescribing evaluations work: a realist review.

OBJECTIVE: The evidence base for social prescribing is inconclusive, and evaluations have been criticised for lacking rigour. This realist review sought to understand how and why social prescribing evaluations work or do not work. Findings from this review will contribute to the development of an evidence-based evaluation framework and reporting standards for social prescribing. DESIGN: A realist review. DATA SOURCES: ASSIA, CINAHL, Embase, Medline, PsycINFO, PubMed, Scopus Online, Social Care Online, Web of Science and grey literature. ELIGIBILITY CRITERIA: Documents reporting on social prescribing evaluations using any methods, published between 1998 and 2020 were included. Documents not reporting findings or lacking detail on methods for data collection and outcomes were excluded. ANALYSIS: Included documents were segregated into subcases based on methodology. Data relating to context, mechanisms and outcomes and the programme theory were extracted and context-mechanism-outcome configurations were developed. Meta-inferences were drawn from all subcases to refine the programme theory. RESULTS: 83 documents contributed to analysis. Generally, studies lacked in-depth descriptions of the methods and evaluation processes employed. A cyclical process of social prescribing evaluation was identified, involving preparation, conducting the study and interpretation. The analysis found that coproduction, alignment, research agency, sequential mixed-methods design and integration of findings all contributed to the development of an acceptable, high-quality social prescribing evaluation design. Context-mechanism-outcome configurations relating to these themes are reported. CONCLUSIONS: To develop the social prescribing evidence base and address gaps in our knowledge about the impact of social prescribing and how it works, evaluations must be high quality and acceptable to stakeholders. Development of an evaluation framework and reporting standards drawing on the findings of this realist review will support this aim. PROSPERO REGISTRATION NUMBER: CRD42020183065.

COVID­19 and SARS­CoV­2 host cell entry mediators: Expression profiling of TMRSS4 in health and disease.

Severe acute respiratory syndrome (SARS) coronavirus­2 (SARS­CoV­2), the causative viral agent for the ongoing COVID­19 pandemic, enters its host cells primarily via the binding of the SARS­CoV­2 spike (S) proteins to the angiotensin­converting enzyme 2 (ACE2). A number of other cell entry mediators have also been identified, including neuropilin­1 (NRP1) and transmembrane protease serine 2 (TMPRSS2). More recently, it has been demonstrated that transmembrane protease serine 4 (TMPRSS4) along with TMPRSS2 activate the SARS­CoV­2 S proteins, and enhance the viral infection of human small intestinal enterocytes. To date, a systematic analysis of TMPRSS4 in health and disease is lacking. In the present study, using in silico tools, the gene expression and genetic alteration of TMPRSS4 were analysed across numerous tumours and compared to controls. The observations were also expanded to the level of the central nervous system (CNS). The findings revealed that TMPRSS4 was overexpressed in 11 types of cancer, including lung adenocarcinoma, lung squamous cell carcinoma, cervical squamous cell carcinoma, thyroid carcinoma, ovarian cancer, cancer of the rectum, pancreatic cancer, colon and stomach adenocarcinoma, uterine carcinosarcoma and uterine corpus endometrial carcinoma, whilst it was significantly downregulated in kidney carcinomas, acute myeloid leukaemia, skin cutaneous melanoma and testicular germ cell tumours. Finally, a high TMPRSS4 expression was documented in the olfactory tubercle, paraolfactory gyrus and frontal operculum, all brain regions which are associated with the sense of smell and taste. Collectively, these data suggest that TMPRSS4 may play a role in COVID­19 symptomatology as another SARS­CoV­2 host cell entry mediator responsible for the tropism of this coronavirus both in the periphery and the CNS.

Neuropilin­1 as a new potential SARS­CoV­2 infection mediator implicated in the neurologic features and central nervous system involvement of COVID­19.

Infection by the severe acute respiratory syndrome (SARS) coronavirus­2 (SARS­CoV­2) is the cause of the new viral infectious disease (coronavirus disease 2019; COVID­19). Emerging evidence indicates that COVID­19 may be associated with a wide spectrum of neurological symptoms and complications with central nervous system (CNS) involvement. It is now well­established that entry of SARS­CoV­2 into host cells is facilitated by its spike proteins mainly through binding to the angiotensin­converting enzyme 2 (ACE­2). Preclinical studies have suggested that neuropilin­1 (NRP1), which is a transmembrane receptor that lacks a cytosolic protein kinase domain and exhibits high expression in the respiratory and olfactory epithelium, may also be implicated in COVID­19 by enhancing the entry of SARS­CoV­2 into the brain through the olfactory epithelium. In the present study, we expand on these findings and demonstrate that the NRP1 is also expressed in the CNS, including olfactory­related regions such as the olfactory tubercles and paraolfactory gyri. This furthers supports the potential role of NRP1 as an additional SARS­CoV­2 infection mediator implicated in the neurologic manifestations of COVID­19. Accordingly, the neurotropism of SARS­CoV­2 via NRP1­expressing cells in the CNS merits further investigation.