Findings from a Peer-Facilitated, Social Isolation Intervention in the Veterans Health Administration Healthcare System: A Mixed-Methods, Pilot Feasibility Study.

BACKGROUND: Social isolation is a global public health threat. Veterans are particularly at risk for social isolation due to high rates of comorbid physical and mental health problems. Yet, effective interventions are limited. OBJECTIVES: Our primary objective was to assess the feasibility and acceptability of CONNECTED, a novel, transdiagnostic intervention to reduce social isolation that includes individual and group components and is delivered by peers via telehealth. Secondary objectives were to identify appropriate outcome measures and explore preliminary intervention effects. METHODS: This was a two-phase study. In Phase 1, to evaluate study feasibility, we surveyed 200 veterans to assess prevalence of social isolation and their interest in social connectedness interventions. In Phase 2, we employed a mixed-methods, pre-post study design in which we piloted CONNECTED with 19 veterans through 2 successive cohorts to further assess feasibility, to evaluate acceptability, and to explore preliminary effectiveness. Quantitative analyses involved descriptive and bivariate analyses as well as multivariate modeling. Qualitative interviews were analyzed using thematic analysis. RESULTS: For Phase 1, 39% of veterans surveyed were socially isolated. Participants who were ≤ 55 years old, caregivers, and those who experienced unmet social needs were more likely to report social isolation. Over 61% expressed interest in VA programs to reduce social isolation. For Phase 2, the pilot intervention, recruitment rate was 88% and the enrollment rate was 86%. Retention rates for the two cohorts were 80% and 50%, respectively, and satisfaction rates among intervention completers were 100%. Results also showed statistically significant improvements in social isolation (+ 5.91, SD = 4.99; p = .0028), social support (+ 0.74, SD = 1.09; p = .03), anxiety (-3.92, SD = 3.73; p = .003), and depression (-3.83, SD = 3.13; p = .001). Results for the other measures were not statistically significant. CONCLUSION: CONNECTED is a feasible and acceptable intervention and is likely to be an effective tool to intervene on social isolation among veterans.

Proactive, Recovery-Oriented Treatment Navigation to Engage Racially Diverse Veterans in Mental Healthcare (PARTNER-MH), a Peer-Led Patient Navigation Intervention for Racially and Ethnically Minoritized Veterans in Veterans Health Administration Mental Health Services: Protocol for a Mixed Methods Randomized Controlled Feasibility Study.

BACKGROUND: Mental health care disparities are persistent and have increased in recent years. Compared with their White counterparts, members of racially and ethnically minoritized groups have less access to mental health care. Minoritized groups also have lower engagement in mental health treatment and are more likely to experience ineffective patient-provider communication, which contribute to negative mental health care experiences and poor mental health outcomes. Interventions that embrace recovery-oriented practices to support patient engagement and empower patients to participate in their mental health care and treatment decisions may help reduce mental health care disparities. Designed to achieve this goal, the Proactive, Recovery-Oriented Treatment Navigation to Engage Racially Diverse Veterans in Mental Healthcare (PARTNER-MH) is a peer-led patient navigation intervention that aims to engage minoritized patients in mental health treatment, support them to play a greater role in their care, and facilitate their participation in shared treatment decision-making. OBJECTIVE: The primary aim of this study is to assess the feasibility and acceptability of PARTNER-MH delivered to patients over 6 months. The second aim is to evaluate the preliminary effects of PARTNER-MH on patient activation, patient engagement, and shared decision-making. The third aim is to examine patient-perceived barriers to and facilitators of engagement in PARTNER-MH as well as contextual factors that may inhibit or promote the integration, sustainability, and scalability of PARTNER-MH using the Consolidated Framework for Implementation Research. METHODS: This pilot study evaluates the feasibility and acceptability of PARTNER-MH in a Veterans Health Administration (VHA) mental health setting using a mixed methods, randomized controlled trial study design. PARTNER-MH is tested under real-world conditions using certified VHA peer specialists (peers) selected through usual VHA hiring practices and assigned to the mental health service line. Peers provide PARTNER-MH and usual peer support services. The study compares the impact of PARTNER-MH versus a wait-list control group on patient activation, patient engagement, and shared decision-making as well as other patient-level outcomes. PARTNER-MH also examines organizational factors that could impact its future implementation in VHA settings. RESULTS: Participants (N=50) were Veterans who were mostly male (n=31, 62%) and self-identified as non-Hispanic (n=44, 88%) and Black (n=35, 70%) with a median age of 45 to 54 years. Most had at least some college education, and 32% (16/50) had completed ≥4 years of college. Randomization produced comparable groups in terms of characteristics and outcome measures at baseline, except for sex. CONCLUSIONS: Rather than simply documenting health disparities among vulnerable populations, PARTNER-MH offers opportunities to evaluate a tailored, culturally sensitive, system-based intervention to improve patient engagement and patient-provider communication in mental health care for racially and ethnically minoritized individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT04515771; https://clinicaltrials.gov/ct2/show/NCT04515771. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37712.

Pre-implementation Evaluation of PARTNER-MH: A Mental Healthcare Disparity Intervention for Minority Veterans in the VHA.

To design PARTNER-MH, a peer-led, patient navigation program for implementation in Veterans Health Administration (VHA) mental health care settings, we conducted a pre-implementation evaluation during intervention development to assess stakeholders' views of the intervention and to explore implementation factors critical to its future adoption. This is a convergent mixed-methods study that involved qualitative semi-structured interviews and survey data. Data collection was guided by the Consolidated Framework for Implementation Research (CFIR). We interviewed and administered the surveys to 23 peers and 10 supervisors from 12 midwestern VHA facilities. We used deductive and inductive approaches to analyze the qualitative data. We also conducted descriptive analysis and Fisher Exact Test to compare peers and supervisors' survey responses. We triangulated findings to refine the intervention. Overall, participants viewed PARTNER-MH favorably. However, they saw the intervention's focus on minority Veterans and social determinants of health framework as potential barriers, believing this could negatively affect the packaging of the intervention, complicate its delivery process, and impact its adoption. They also viewed clinic structures, available resources, and learning climate as potential barriers. Peers and supervisors' selections and discussions of CFIR items were similar. Our findings informed PARTNER-MH development and helped identify factors that could impact its implementation. This project is responsive to the increasing recognition of the need to incorporate implementation science in healthcare disparities research. Understanding the resistance to the intervention's focus on minority Veterans and the potential barriers presented by contextual factors positions us to adjust the intervention prior to testing, in an effort to maximize implementation success.

Blinded Comparative Review of Lubricants Commonly Used for Split-Thickness Skin Graft Harvest.

Lubricating agents facilitate effective harvesting of split-thickness skin grafts. Multiple agents, including water-based gel, mineral oil, glycerin, and poloxamer 188, have been utilized in this capacity. The agent selected is typically at the discretion of the provider and institution, as a single "ideal" lubricant remains to be objectively established. Furthermore, a recent discontinuation of Shur-Clens® Skin Wound Cleanser1 (a wound cleansing solution consisting of the surfactant poloxamer 188) has prompted the search for a suitable substitute for many providers. The purpose of this study is to directly compare five lubricants (including a novel surgical lubricant-based solution) to select a preferred agent. Four practitioners blindly tested five lubricants while harvesting a split-thickness skin graft on a porcine skin model (glycerin, mineral oil, saline, poloxamer 188, and a novel lubricant solution created with surgical lube and sterile water). The results were recorded on a Likert scale where 1 indicated poor performance and 5 indicated excellent performance. Data were pooled, and means were compared with analysis of variance and post hoc Tukey test. The cost of each lubricating solution was also reported. Mean scores for each of the solutions were as follows: dry control = 1.1 ± 0.1; glycerin = 2.62 ± 1.02, saline = 3.88 ± 0.81, mineral oil = 3.75 ± 1.00, novel water-based lubricant solution = 4.63 ± 0.71, and poloxamer 188 = 3.88 ± 0.81. All solutions were superior to dry control (P < .01). Glycerin was noted to have statistically lower scores than all of the other solutions (P < .01). The novel water-based surgical lubricant solution had significantly higher mean scores than both glycerin (P < .01) and mineral oil (P < .05). Each solution was compared according to dollars per 100cc with glycerin and Shur-Clens® representing the most expensive options at almost $3/100cc and saline the least expensive at less than $0.15/100cc. In a porcine skin model, the novel water-based surgical lubricant solution had the best performance. It was statistically superior to glycerin and mineral oil and was also found to be the most cost-effective option in terms of overall performance compared with relative cost. Glycerin had the worst performance with statistically lower scores than all other solutions. Glycerin was also found to be the least cost-effective due to a large discrepancy between high cost and low overall performance. Saline performed better than expected. These results may be skewed due to the inherently greasy nature of the butcher shop porcine skin, creating limitations and decreasing the fidelity of the model. In a search for the "ideal" lubricant, other models should be further studied.

Homogeneous BTK Occupancy Assay for Pharmacodynamic Assessment of Tirabrutinib (GS-4059/ONO-4059) Target Engagement.

Bruton's tyrosine kinase (BTK) is a clinically validated target for B-cell leukemias and lymphomas with FDA-approved small-molecule inhibitors ibrutinib and acalabrutinib. Tirabrutinib (GS-4059/ONO-4059, Gilead Sciences, Inc., Foster City, CA) is a second-generation, potent, selective, irreversible BTK inhibitor in clinical development for lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). An accurate pharmacodynamic assay to assess tirabrutinib target coverage in phase 1/2 clinical studies will inform dose and schedule selection for advanced clinical evaluation. We developed a novel duplex homogeneous BTK occupancy assay based on time-resolved fluorescence resonance energy transfer (TR-FRET) to measure free and total BTK levels in a multiplexed format. The dual-wavelength emission property of terbium-conjugated anti-BTK antibody served as the energy donor for two fluorescent energy acceptors with distinct excitation and emission spectra. The assay was characterized and qualified using full-length purified recombinant human BTK protein and peripheral blood mononuclear cells derived from healthy volunteers and patients with CLL. We demonstrated assay utility using cells derived from lymph node and bone marrow samples from patients with CLL and DLBCL. Our TR-FRET-based BTK occupancy assay provides accurate, quantitative assessment of BTK occupancy in the clinical trial program for tirabrutinib and is in use in ongoing clinical studies.

Early Assessment of Burn Depth with Far Infrared Time-Lapse Thermography.

BACKGROUND: Diagnosing the extremes of superficial burns and full-thickness burns is straightforward. It is in the middle ground of partial-thickness burns where the diagnostic difficulties emerge; it can take up to 3 to 5 days for signs of healing to appear. We hypothesize that cooling partial-thickness burns and tracking the rate of rewarming will immediately reflect the condition of the burn: shallow partial-thickness burns that retain cell health and blood flow will rewarm rapidly, and deeper burns with damaged microvessels will rewarm slowly. STUDY DESIGN: We enrolled 16 patients with isolated, partial-thickness burns on their extremities who were diagnosed as indeterminate by our burn surgeon. Within 24 hours after presentation, room-temperature saline was poured over the burn as a cooling challenge. An infrared camera that was sensitive to body temperature produced false-color images showing pixel-by-pixel temperatures. A time-lapse recording from the infrared camera images taken as the burn rewarmed produced a time-temperature curve that reflected the kinetics of rewarming. The outcomes variable was whether or not the patient received a skin graft, which was determined 72 hours after presentation. RESULTS: The method correctly predicted whether or not the patient required a skin graft. CONCLUSIONS: Here we report a new technique that permits determination of wound viability much earlier than clinical examination. Due to the simplicity of the method, non-experts can successfully perform the technique on the first day of the burn and make the correct diagnosis and decision to graft or not to graft.

Guideline on the requirements of external quality assessment programs in molecular pathology.

Molecular pathology is an integral part of daily diagnostic pathology and used for classification of tumors, for prediction of prognosis and response to therapy, and to support treatment decisions. For these reasons, analyses in molecular pathology must be highly reliable and hence external quality assessment (EQA) programs are called for. Several EQA programs exist to which laboratories can subscribe, but they vary in scope, number of subscribers, and execution. The guideline presented in this paper has been developed with the purpose to harmonize EQA in molecular pathology. It presents recommendations on how an EQA program should be organized, provides criteria for a reference laboratory, proposes requirements for EQA test samples, and defines the number of samples needed for an EQA program. Furthermore, a system for scoring of the results is proposed as well as measures to be taken for poorly performing laboratories. Proposals are made regarding the content requirements of an EQA report and how its results should be communicated. Finally, the need for an EQA database and a participant manual are elaborated. It is the intention of this guideline to improve EQA for molecular pathology in order to provide more reliable molecular analyses as well as optimal information regarding patient selection for treatment.

The value of banked samples for oncology drug discovery and development.

To gain insights into human biology and pathobiology, ready access to banked human tissue samples that encompass a representative cross section of the population is required. For optimal use, the banked human tissue needs to be appropriately consented, collected, annotated, and stored. If any of these elements are missing, the studies using these samples are compromised. These elements are critical whether the research is for academic or pharmaceutical industry purposes. An additional temporal element that adds enormous value to such banked samples is treatment and outcome information from the people who donated the tissue. To achieve these aims, many different groups have to work effectively together, not least of which are the individuals who donate their tissue with appropriate consent. Such research is unlikely to benefit the donors but others who succumb to the same disease. The development of a large accessible human tissue bank resource (National Cancer Institute's Cancer HUman Biobank [caHUB]) that provides an ongoing supply of human tissue for all working toward the common goal of understanding human health and disease has a number of advantages. These include, but are not limited to, access to a broad cross section of healthy and diseased populations beyond what individual collections may achieve for understanding disease pathobiology, therapeutic target discovery, as well as a source of material for diagnostic assay validation. Models will need to be developed to enable fair access to caHUB under terms that enable appropriate intellectual property protection and ultimate data sharing to ensure that the biobank successfully distributes samples to a broad range of researchers.

Translational biomarkers: from preclinical to clinical a report of 2009 AAPS/ACCP Biomarker Workshop.

There have been some successes in qualifying biomarkers and applying them to drug development and clinical treatment of various diseases. A recent success is illustrated by a collaborative effort among the US Food and Drug Administration, the European Medicines Agency, and the pharmaceutical industry to provide a set of seven preclinical kidney toxicity biomarkers for drug development. Other successes include, but are not limited to, clinical biomarkers for cancer treatment and clinical management of heart transplant patients. The value of fully qualified surrogate endpoints in facilitating successful drug development is undisputed, especially for diseases in which the traditional clinical outcome can only be assessed in large, multi-year trials. Emerging biomarkers, including chemical genomic or imaging biomarkers, and measurement of circulating tumor cells hold great promise for early diagnosis of disease and as prognostic tests for managing treatment of chronic diseases such as osteoarthritis, Alzheimer disease, cardiovascular disease, and cancer. To advance the success of treating and managing these diseases, efforts are needed to establish the temporal relationship between changes in inflammatory or imaging biomarkers with the progression of the chronic disease, and in the case of cancer, between the extent of circulating cancer cells and tumor progression or remission.

Learning from product labels and label changes: how to build pharmacogenomics into drug-development programs.

The 2010 US FDA-Drug Industry Association (DIA) Pharmacogenomics (PGx) Workshop follows a series that began in 2002 bringing together multidisciplinary experts spanning regulatory authorities, medical research, healthcare and industry. This report summarizes the 'Building PGx into Labels' sessions from the workshop, which discussed the critical elements in developing PGx outcomes leading to product labels that inform efficacy and/or safety. Examples were drawn from US prescribing information, which integrated PGx knowledge into medical decisions (e.g., panitumumab, warfarin and clopidogrel). Attendees indicated the need for broader dialog and for guidelines on evidentiary considerations for PGx to be included into product labels. Also discussed was the understanding of appropriate PGx placement on labels; how to encourage adoption by medical communities of label recommendations on PGx tests; and, given the global nature of drug development, worldwide considerations including European Summary of Product Characteristics.

Designing pharmacogenomic studies to be fit for purpose.

The 2010 US FDA-Drug Industry Association (DIA) Pharmacogenomics Workshop, the fifth in a series of meetings that begun in 2002, brought together multidisciplinary experts from regulatory authorities, medical research, healthcare and drug development. This article summarizes the 'Designing Pharmacogenomic Studies to be Fit for Purpose' track in which considerations regarding the use of retrospective and prospective studies were examined in relation to their ability to influence treatment decisions and labeling for drugs. The aim of the session, using real-world examples (KRAS/panitumumab and HLA-B*5701/abacavir), was to identify good scientific principles that would guide the design of studies to identify subgroups of responders during development programs (including marketed drugs), which could subsequently be used to guide treatment decisions.

Report from the Wellcome Trust/EBA "Perspectives in Clinical Proteomics" retreat--a strategy to implement next-generation proteomic analyses to the clinic for patient benefit: pathway to translation.

Proteomics has long been thought to hold the promise of producing results of clinical utility which will influence patient treatment and outcomes. A recent Wellcome Trust/EBI meeting and retreat--"Perspectives in Clinical Proteomics"--brought together experts from a broad range of stakeholder groups with an interest in ensuring proteomics achieves this aim. This viewpoint presents views derived from these forums, proposing a pathway for the development of next-generation proteomic analyses in the clinical setting from selection of candidates through to their validation and ultimate demonstration of utility through health technology assessments. Although not meant to be all encompassing, important elements for proteomics researchers to consider are presented.