Primary Care Engagement Among Individuals with Experiences of Homelessness and Serious Mental Illness: an Evidence Map.

BACKGROUND: Experiences of homelessness and serious mental illness (SMI) negatively impact health and receipt of healthcare. Interventions that promote the use of primary care services for people with both SMI and homelessness may improve health outcomes, but this literature has not been evaluated systematically. This evidence map examines the breadth of literature to describe what intervention strategies have been studied for this population, elements of primary care integration with other services used, and the level of intervention complexity to highlight gaps for future intervention research and program development. METHODS: We followed an a priori protocol developed in collaboration with clinical stakeholders. We systematically searched the published literature to identify interventions for adults with homelessness who also had SMI. We excluded case reports, editorials, letters, and conference abstracts. Data abstraction methods followed standard practice. Data were categorized into intervention strategies and primary care integration strategies. Then we applied the Complexity Assessment Tool for Systematic Reviews (iCAT_SR) to characterize intervention complexity. RESULTS: Twenty-two articles met our inclusion criteria evaluating 15 unique interventions to promote engagement in primary care for adults with experiences of homelessness and SMI. Study designs varied widely from randomized controlled trials and cohort studies to single-site program evaluations. Intervention strategies varied across studies but primarily targeted patients directly (e.g., health education, evidence-based interactions such as motivational interviewing) with fewer strategies employed at the clinic (e.g., employee training, multidisciplinary teams) or system levels (e.g., data sharing). We identified elements of primary care integration, including referral strategies, co-location, and interdisciplinary care planning. Interventions displayed notable complexity around the number of intervention components, interaction between intervention components, and extent to which interventions were tailored to specific patient populations. DISCUSSION: We identified and categorized elements used in various combinations to address the primary care needs of individuals with experiences of homeless and SMI.

Patients' Experiences With Staphylococcus aureus and Gram-Negative Bacterial Bloodstream Infections: Results From Cognitive Interviews to Inform Assessment of Health-Related Quality of Life.

BACKGROUND: We previously conducted a concept elicitation study on the impact of Staphylococcus aureus and gram-negative bacterial bloodstream infections (SAB/GNB) on health-related quality of life (HRQoL) from the patient's perspective and found significant impacts on HRQoL, particularly in the physical and functional domains. Using this information and following guidance on the development of patient-reported outcome (PRO) measures, we determined which combination of measures and items (ie, specific questions) would be most appropriate in a survey assessing HRQoL in bloodstream infections. METHODS: We selected a variety of measures/items from the Patient-Reported Outcomes Measurement Information System (PROMIS) representing different domains. We purposefully sampled patients ~6-12 weeks post-SAB/GNB and conducted 2 rounds of cognitive interviews to refine the survey by exploring patients' understanding of items and answer selection as well as relevance for capturing HRQoL. RESULTS: We interviewed 17 SAB/GNB patients. Based on the first round of cognitive interviews (n = 10), we revised the survey. After round 2 of cognitive interviewing (n = 7), we finalized the survey to include 10 different PROMIS short forms/measures of the most salient HRQoL domains and 2 adapted questions (41 items total) that were found to adequately capture HRQoL. CONCLUSIONS: We developed a survey from well-established PRO measures that captures what matters most to SAB/GNB patients as they recover. This survey, uniquely tailored to bloodstream infections, can be used to assess these meaningful, important HRQoL outcomes in clinical trials and in patient care. Engaging patients is crucial to developing treatments for bloodstream infections.

2-(2-Br-phenyl)-8-methoxy-benzoxazinone (HPW-RX2), a direct thrombin inhibitor with a suppressive effect on thromboxane formation in platelets.

2-(2-Br-phenyl)-8-methoxy-benzoxazinone (HPW-RX2), a newly synthetic benzoxazinone derivative, has previously been shown to inhibit rabbit platelet aggregation caused by thrombin and arachidonic acid. In the present study, the mechanism for the antiplatelet effect of HPW-RX2 was further investigated. In human platelets, HPW-RX2 concentration-dependently inhibited platelet aggregation, ATP release, P-selectin expression, and intracellular calcium mobilization caused by thrombin. In contrast, HPW-RX2 had no significant effect on either SFLLRN- or GYPGKF-induced platelet aggregation, indicating that HPW-RX2 did not interfere with platelet thrombin receptors. Moreover, HPW-RX2 inhibited the amidolytic activity of thrombin and prolonged the fibrinogen clotting time. These results suggest that the inhibitory effect of HPW-RX2 on thrombin-induced platelet aggregation is via direct inhibition of thrombin proteolytic activity. Besides the inhibition on thrombin, HPW-RX2 also prevented platelet aggregation, ATP release, and increase in [Ca2+]i caused by arachidonic acid and low concentration collagen. In a parallel manner, both arachidonic acid-induced thromboxane B2 and prostaglandin D2 formations were decreased in platelets treated with HPW-RX2. This indicates that HPW-RX2 is able to inhibit the arachidonic acid cascade at the cyclooxygenase level. This is the first report of a benzoxazinone derivative possessing both thrombin and cyclooxygenase inhibitory properties. The dual effect of HPW-RX2 might provide extra therapeutic benefits for treatment of arterial thrombosis.

The evaluation of 2,8-disubstituted benzoxazinone derivatives as anti-inflammatory and anti-platelet aggregation agents.

A series of 2,8-disubstituted benzoxazinones were synthesized and subjected to anti-platelet aggregation, inhibition of superoxide anion generation, and inhibition of neutrophil elastase release assays. Among them, 2-(2'-substituted-phenyl)-benzoxazinones exhibited significant inhibitory effect to target assays. Additionally, all of them were more potent than aspirin on AA-induced platelet aggregation, and these suggested that 2-(2'-substituted-phenyl)-benzoxazinones also possess aspirin-like activity. On the other hand, the compounds 6 and 16 showed inhibitory effects on neutrophil elastase release and superoxide generation.