A Systematic Review of the Economic and Health-Related Quality of Life Impact of Advanced Therapies Used to Treat Moderate-to-Severe Ulcerative Colitis.

INTRODUCTION: The clinical benefits of advanced therapies (i.e., biologics and small-molecule drugs) in the treatment of moderate-to-severe ulcerative colitis (UC) have been demonstrated; however, there is less clarity regarding the economic and health-related quality of life (HRQoL) impact of these treatments. We conducted a systematic literature review to synthesize data on cost, healthcare resource utilization (HCRU), and HRQoL for patients who received approved advanced therapies for moderate-to-severe UC in the United States and Europe. METHODS: Databases including MEDLINE, Embase, the Database of Abstracts of Reviews of Effects (DARE), the National Health Service Economic Evaluation Database (NHS EED), and EconLit were searched systematically to identify observational studies published between January 1, 2010 and October 14, 2021 that assessed the impact of advanced therapies on cost, HCRU, and/or HRQoL in adults with moderate-to-severe UC. Supplementary gray literature searches of conference proceedings from the past 4 years (January 2018 to October 2021) were also performed. RESULTS: 47 publications of 40 unique cost/HCRU studies and 13 publications of nine unique HRQoL studies were included. Findings demonstrated that biologics have a positive impact on indirect costs (i.e., productivity, presenteeism, and absenteeism) and HRQoL. High costs of biologics were not always fully offset by reductions in cost and HCRU associated with disease management. For many patients, treatment switching and dose escalations were required, thus increasing drug costs, particularly when switching across treatment classes. CONCLUSION: These findings highlight a high unmet need for therapies for moderate-to-severe UC that can reduce the healthcare burden and impact on society. Further research is warranted, as the reported evidence was limited by the small sample sizes of some treatment groups within a study.

Although advanced therapies, such as biologics and small-molecule drugs, have shown clinical benefit in treating moderate-to-severe ulcerative colitis, their economic impact and effect on patients' quality of life is less clear. This study comprehensively reviewed the cost and use of healthcare resources associated with starting treatment with advanced therapies for ulcerative colitis, as well as the impact of these treatments on quality of life. We found that while biologics have a benefit on work productivity, work attendance, work absence, and quality of life, the high costs of biologics were not always fully met by reductions in disease management costs and healthcare resources. Many patients needed to switch treatments or required dose increases, which were expensive. There is a high unmet need for therapies for moderate-to-severe ulcerative colitis that can reduce healthcare costs, use of healthcare resources, and effect on society.

Impact of pharmacy intervention on influenza vaccination acceptance: a systematic literature review and meta-analysis.

Background Vaccination plays an important role in the prevention of influenza. Channels that improve vaccination adherence can play a vital part in improving patient care. This study seeks to inform the design and implementation of pharmacy interventions at scale on improving influenza vaccination rates. Aim of the review The aim of this study was to identify key success factors for effective pharmacy intervention design and implementation to improve vaccination acceptance rates in influenza. Methods A systematic search of MEDLINE, Embase, and Cochrane CENTRAL was performed to find literature on influenza vaccinations delivered at pharmacies, pharmacist-delivered influenza vaccinations, or influenza vaccination campaigns originating in the pharmacy setting. A meta-analysis using a random effects model estimated the impact of pharmacy intervention on vaccination rates (assessed as relative risk [RR] and 95% confidence intervals [95% CI]). Results A total of 1221 studies were found that met the search criteria, of which 12 were selected for the literature review following eligibility screening. A meta-analysis of studies that contained binary total population and vaccination rate data was conducted on 6 studies, including 3182 participants, the vaccination rate was 24% higher in those who used the pharmacy-based intervention compared with those who used standard care [RR (95% CI) 1.24 (1.05, 1.47)]. Two separate sensitivity analyses were run for the vaccination rate. In participants aged ≥ 65 years, the vaccination rate was 3% higher in those who received the pharmacy-based intervention compared with those who received standard care; however, this change was not significant [RR (95% CI) 1.03 (0.86, 1.24)]. Additionally, a qualitative review showed that more successful pharmacy-based interventions were those with the more active involvement of pharmacists in routine care. This included regular checkup of vaccine status, proactive conversations and recommendations about vaccination, and pharmacy-based immunization programs, with specific vaccination days. In-pharmacy communication rather than passive information, such as through leaflets and posters was also more effective. Conclusion Pharmacists can play a significant role to improve patient treatment, adherence, and outcomes associated with influenza vaccines. Once pharmacy-based immunization is established, proactive involvement of is key to ensure successful program implementation and results. Expanding access for pharmacists and pharmacy intervention to provide vaccinations may increase vaccination acceptance and could be a valuable intervention in patient care. Additional studies should consider high-risk populations to inform optimal design and implementation strategies.

Transcellular neuroligin-2 interactions enhance insulin secretion and are integral to pancreatic ß cell function.

Normal glucose-stimulated insulin secretion is dependent on interactions between neighboring ß cells. Elucidation of the reasons why this cell-to-cell contact is essential will probably yield critical insights into ß cell maturation and function. In the central nervous system, transcellular protein interactions (i.e. interactions between proteins on the surfaces of different cells) involving neuroligins are key mediators of synaptic functional development. We previously demonstrated that ß cells express neuroligin-2 and that insulin secretion is affected by changes in neuroligin-2 expression. Here we show that the effect of neuroligin-2 on insulin secretion is mediated by transcellular interactions. Neuroligin-2 binds with nanomolar affinity to a partner on the ß cell surface and contributes to the increased insulin secretion brought about by ß cell-to-ß cell contact. It does so in a manner seemingly independent of interactions with neurexin, a known binding partner. As in the synapse, transcellular neuroligin-2 interactions enhance the functioning of the submembrane exocytic machinery. Also, as in the synapse, neuroligin-2 clustering is important. Neuroligin-2 in soluble form, rather than presented on a cell surface, decreases insulin secretion by rat islets and MIN-6 cells, most likely by interfering with endogenous neuroligin interactions. Prolonged contact with neuroligin-2-expressing cells increases INS-1 ß cell proliferation and insulin content. These results extend the known parallels between the synaptic and ß cell secretory machineries to extracellular interactions. Neuroligin-2 interactions are one of the few transcellular protein interactions thus far identified that directly enhance insulin secretion. Together, these results indicate a significant role for transcellular neuroligin-2 interactions in the establishment of ß cell function.

Neurexin-1α contributes to insulin-containing secretory granule docking.

Neurexins are a family of transmembrane, synaptic adhesion molecules. In neurons, neurexins bind to both sub-plasma membrane and synaptic vesicle-associated constituents of the secretory machinery, play a key role in the organization and stabilization of the presynaptic active zone, and help mediate docking of synaptic vesicles. We have previously shown that neurexins, like many other protein constituents of the neurotransmitter exocytotic machinery, are expressed in pancreatic ß cells. We hypothesized that the role of neurexins in ß cells parallels their role in neurons, with ß-cell neurexins helping to mediate insulin granule docking and secretion. Here we demonstrate that ß cells express a more restricted pattern of neurexin transcripts than neurons, with a clear predominance of neurexin-1α expressed in isolated islets. Using INS-1E ß cells, we found that neurexin-1α interacts with membrane-bound components of the secretory granule-docking machinery and with the granule-associated protein granuphilin. Decreased expression of neurexin-1α, like decreased expression of granuphilin, reduces granule docking at the ß-cell membrane and improves insulin secretion. Perifusion of neurexin-1α KO mouse islets revealed a significant increase in second-phase insulin secretion with a trend toward increased first-phase secretion. Upon glucose stimulation, neurexin-1α protein levels decrease. This glucose-induced down-regulation may enhance glucose-stimulated insulin secretion. We conclude that neurexin-1α is a component of the ß-cell secretory machinery and contributes to secretory granule docking, most likely through interactions with granuphilin. Neurexin-1α is the only transmembrane component of the docking machinery identified thus far. Our findings provide new insights into the mechanisms of insulin granule docking and exocytosis.

Expression of neurexin, neuroligin, and their cytoplasmic binding partners in the pancreatic beta-cells and the involvement of neuroligin in insulin secretion.

The composition of the beta-cell exocytic machinery is very similar to that of neuronal synapses, and the developmental pathway of beta-cells and neurons substantially overlap. beta-Cells secrete gamma-aminobutyric acid and express proteins that, in the brain, are specific markers of inhibitory synapses. Recently, neuronal coculture experiments have identified three families of synaptic cell-surface molecules (neurexins, neuroligins, and SynCAM) that drive synapse formation in vitro and that control the differentiation of nascent synapses into either excitatory or inhibitory fully mature nerve terminals. The inhibitory synapse-like character of the beta-cells led us to hypothesize that members of these families of synapse-inducing adhesion molecules would be expressed in beta-cells and that the pattern of expression would resemble that associated with neuronal inhibitory synaptogenesis. Here, we describe beta-cell expression of the neuroligins, neurexins, and SynCAM, and show that neuroligin expression affects insulin secretion in INS-1 beta-cells and rat islet cells. Our findings demonstrate that neuroligins and neurexins are expressed outside the central nervous system and help confer an inhibitory synaptic-like phenotype onto the beta-cell surface. Analogous to their role in synaptic neurotransmission, neurexin-neuroligin interactions may play a role in the formation of the submembrane insulin secretory apparatus.