Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Interdisciplinary Team Meetings in Practice: an Observational Study of IDTs, Sensemaking Around Care Transitions, and Readmission Rates.

BACKGROUND: Interdisciplinary teams (IDTs) have been implemented to improve collaboration in hospital care, but their impact on patient outcomes, including readmissions, has been mixed. These mixed results might be rooted in differences in organization of IDT meetings between hospitals, as well as variation in IDT characteristics and function. We hypothesize that relationships between IDT members are an important team characteristic, influencing IDT function in terms of how members make sense of what is happening with patients, a process called sensemaking OBJECTIVE: (1) To describe how IDT meetings are organized in practice, (2) assess differences in IDT member relationships and sensemaking during patient discussions, and (3) explore their potential association with risk-stratified readmission rates (RSRRs). DESIGN: Observational, explanatory convergent mixed-methods case-comparison study of IDT meetings in 10 Veterans Affairs hospitals. PARTICIPANTS: Clinicians participating in IDTs and facility leadership. APPROACH: Three-person teams observed and recorded IDT meetings during week-long visits. We used observational data to characterize relationships and sensemaking during IDT patient discussions. To assess sensemaking, we used 2 frameworks that reflected sensemaking around each patient's situation generally, and around care transitions specifically. We examined the association between IDT relationships and sensemaking, and RSRRs. KEY RESULTS: We observed variability in IDT organization, characteristics, and function across 10 hospitals. This variability was greater between hospitals than between teams at the same hospital. Relationship characteristics and both types of sensemaking were all significantly, positively correlated. General sensemaking regarding each patient was significantly negatively associated with RSRR (- 0.65, p = 0.044). CONCLUSIONS: IDTs vary not only in how they are organized, but also in team relationships and sensemaking. Though our design does not allow for inferences of causation, these differences may be associated with hospital readmission rates.

Development of a multisystem point of care ultrasound skills assessment checklist.

BACKGROUND: Many institutions are training clinicians in point-of-care ultrasound (POCUS), but few POCUS skills checklists have been developed and validated. We developed a consensus-based multispecialty POCUS skills checklist with anchoring references for basic cardiac, lung, abdominal, and vascular ultrasound, and peripheral intravenous line (PIV) insertion. METHODS: A POCUS expert panel of 14 physicians specializing in emergency, critical care, and internal/hospital medicine participated in a modified-Delphi approach to develop a basic POCUS skills checklist by group consensus. Three rounds of voting were conducted, and consensus was defined by ≥ 80% agreement. Items achieving < 80% consensus were discussed and considered for up to two additional rounds of voting. RESULTS: Thirteen POCUS experts (93%) completed all three rounds of voting. Cardiac, lung, abdominal, and vascular ultrasound checklists included probe location and control, basic machine setup, image quality and optimization, and identification of anatomical structures. PIV insertion included additional items for needle tip tracking. During the first round of voting, 136 (82%) items achieved consensus, and after revision and revoting, an additional 21 items achieved consensus. A total of 153 (92%) items were included in the final checklist. CONCLUSIONS: We have developed a consensus-based, multispecialty POCUS checklist to evaluate skills in image acquisition and anatomy identification for basic cardiac, lung, abdominal, and vascular ultrasound, and PIV insertion.

Addressing chronic pain with Focused Acceptance and Commitment Therapy in integrated primary care: findings from a mixed methods pilot randomized controlled trial.

BACKGROUND: Over 100 million Americans have chronic pain and most obtain their treatment in primary care clinics. However, evidence-based behavioral treatments targeting pain-related disability are not typically provided in these settings. Therefore, this study sought to: 1) evaluate implementation of a brief evidence-based treatment, Focused Acceptance and Commitment Therapy (FACT-CP), delivered by an integrated behavioral health consultant (BHC) in primary care; and 2) preliminarily explore primary (self-reported physical disability) and secondary treatment outcomes (chronic pain acceptance and engagement in valued activities). METHODS: This mixed-methods pilot randomized controlled trial included twenty-six participants with non-cancer chronic pain being treated in primary care (54% women; 46% Hispanic/Latino). Active participants completed a 30-min individual FACT-CP visit followed by 3 weekly 60-min group visits and a booster visit 2 months later. An enhanced treatment as usual (ETAU) control group received 4 handouts about pain management based in cognitive-behavioral science. Follow-up research visits occurred during and after treatment, at 12 weeks (booster visit), and at 6 months. Semi-structured interviews were conducted to collect qualitative data after the last research visit. General linear mixed regression models with repeated measures explored primary and secondary outcomes. RESULTS: The study design and FACT-CP intervention were feasible and acceptable. Quantitative analyses indicate at 6-month follow-up, self-reported physical disability significantly improved pre-post within the FACT-CP arm (d = 0.64); engagement in valued activities significantly improved within both the FACT-CP (d = 0.70) and ETAU arms (d = 0.51); and chronic pain acceptance was the only outcome significantly different between arms (d = 1.04), increased in the FACT-CP arm and decreased in the ETAU arm. Qualitative data analyses reflected that FACT-CP participants reported acquiring skills for learning to live with pain, consistent with increased chronic pain acceptance. CONCLUSION: Findings support that FACT-CP was acceptable for patients with chronic pain and feasible for delivery in a primary care setting by a BHC. Results provide preliminary evidence for improved physical functioning after FACT-CP treatment. A larger pragmatic trial is warranted, with a design based on data gathered in this pilot. TRIAL REGISTRATION: clinicaltrials.gov, NCT04978961 (27/07/2021).

Engaging Veterans, caregivers, and system stakeholders to improve VA home and community-based services.

OBJECTIVE: To understand Veterans', caregivers', and stakeholders' perceptions of home-based and caregiver support services and their suggestions for improvement to better align services with needs. DATA SOURCES: We identified Veterans and caregivers at four EDCoE sites using the VA high-need, high-risk list, representing Veterans who qualify for home-based primary care. We randomly selected Veterans and their caregivers, stratifying by age. We also identified leaders and clinicians involved in clinical service delivery. STUDY DESIGN: Between February and November 2019, we conducted in-person and telephone interviews and focus groups using semi-structured questions tailored to each group, analyzing them through a rapid qualitative analysis approach and providing real-time feedback to operational partners. DATA COLLECTION: Thirty-four Veterans, 24 caregivers, and 39 leaders and clinicians participated. PRINCIPAL FINDINGS: Respondents identified key categories of experience that could be monitored and improved, including navigating an increasingly complex system, coordinating and communicating across services, and unmet household and financial needs. Veterans and caregivers described quality in terms of reliability, timeliness, standardization, and accountability. Summaries were created to contextualize results and to highlight gaps and opportunities for new measures and policy development. CONCLUSIONS: Collaborating with Veterans, caregivers, and stakeholders enables us to understand their daily experiences and to develop meaningful approaches to evaluating services that incorporate their perspectives. Providing regular, actionable feedback to operational partners informs policy and operational initiatives, such as the scope of services and infrastructure for system navigation.

Large-scale provocation studies identify maladaptive responses to ubiquitous aeroallergens as a correlate of severe allergic rhinoconjunctivitis and asthma.

BACKGROUND: Allergic asthma (AA) and allergic rhinoconjunctivitis (ARC) are common comorbid environmentally triggered diseases. We hypothesized that severe AA/ARC reflects a maladaptive or unrestrained response to ubiquitous aeroallergens. METHODS: We performed provocation studies wherein six separate cohorts of persons (total n = 217) with ARC, with or without AA, were challenged once or more with fixed concentrations of seasonal or perennial aeroallergens in an aeroallergen challenge chamber (ACC). RESULTS: Aeroallergen challenges elicited fully or partially restrained vs. unrestrained evoked symptom responsiveness, corresponding to the resilient and adaptive vs. maladaptive AA/ARC phenotypes, respectively. The maladaptive phenotype was evoked more commonly during challenge with a non-endemic versus endemic seasonal aeroallergen. In an AA cohort, symptom responses evoked after house dust mite (HDM) challenges vs. recorded in the natural environment were more accurate and precise predictors of asthma severity and control, lung function (FEV1), and mechanistic correlates of maladaptation. Correlates included elevated levels of peripheral blood CD4+ and CD8+ T-cells, eosinophils, and T-cell activation, as well as gene expression proxies for ineffectual epithelial injury/repair responses. Evoked symptom severity after HDM challenge appeared to be more closely related to levels of CD4+ and CD8+ T-cells than eosinophils, neutrophils, or HDM-specific IgE. CONCLUSIONS: Provocation studies support the concept that resilience, adaptation, and maladaptation to environmental disease triggers calibrate AA/ARC severity. Despite the ubiquity of aeroallergens, in response to these disease triggers in controlled settings (ie, ACC), most atopic persons manifest the resilient or adaptive phenotype. Thus, ARC/AA disease progression may reflect the failure to preserve the resilient or adaptive phenotype. The triangulation of CD8+ T-cell activation, airway epithelial injury/repair processes and maladaptation in mediating AA disease severity needs more investigation.

Immunologic resilience and COVID-19 survival advantage.

BACKGROUND: The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). OBJECTIVE: We sought to examine whether deficits in IR that antedate or are induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection independently predict COVID-19 mortality. METHODS: IR levels were quantified with 2 novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n = 522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n = 13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to COVID-19 outcomes. RESULTS: IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection was associated with underrepresentation of IHG-I (21%) versus overrepresentation (77%) of IHG-II or IHG-IV, especially in males versus females (P < .01). Presentation with IHG-I was associated with 88% lower mortality, after controlling for age and sex; reduced risk of hospitalization and respiratory failure; lower plasma IL-6 levels; rapid clearance of nasopharyngeal SARS-CoV-2 burden; and gene expression signatures correlating with survival that signify immunocompetence and controlled inflammation. In non-COVID-19 cohorts, IR-preserving metrics were associated with resistance to progressive influenza or HIV infection, as well as lower 9-year mortality in the Framingham Heart Study, especially in females. CONCLUSIONS: Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19.

Comparison of in-person versus tele-ultrasound point-of-care ultrasound training during the COVID-19 pandemic.

BACKGROUND: Lack of training is currently the most common barrier to implementation of point-of-care ultrasound (POCUS) use in clinical practice, and in-person POCUS continuing medical education (CME) courses have been paramount in improving this training gap. Due to travel restrictions and physical distancing requirements during the COVID-19 pandemic, most in-person POCUS training courses were cancelled. Though tele-ultrasound technology has existed for several years, use of tele-ultrasound technology to deliver hands-on training during a POCUS CME course has not been previously described. METHODS: We conducted a retrospective observational study comparing educational outcomes, course evaluations, and learner and faculty feedback from in-person versus tele-ultrasound POCUS courses. The same POCUS educational curriculum was delivered to learners by the two course formats. Data from the most recent pre-pandemic in-person course were compared to tele-ultrasound courses during the COVID-19 pandemic. RESULTS: Pre- and post-course knowledge test scores of learners from the in-person (n = 88) and tele-ultrasound course (n = 52) were compared. Though mean pre-course knowledge test scores were higher among learners of the tele-ultrasound versus in-person course (78% vs. 71%; p = 0.001), there was no significant difference in the post-course test scores between learners of the two course formats (89% vs. 87%; p = 0.069). Both learners and faculty rated the tele-ultrasound course highly (4.6-5.0 on a 5-point scale) for effectiveness of virtual lectures, tele-ultrasound hands-on scanning sessions, and course administration. Faculty generally expressed less satisfaction with their ability to engage with learners, troubleshoot image acquisition, and provide feedback during the tele-ultrasound course but felt learners completed the tele-ultrasound course with a better basic POCUS skillset. CONCLUSIONS: Compared to a traditional in-person course, tele-ultrasound POCUS CME courses appeared to be as effective for improving POCUS knowledge post-course and fulfilling learning objectives. Our findings can serve as a roadmap for educators seeking guidance on development of a tele-ultrasound POCUS training course whose demand will likely persist beyond the COVID-19 pandemic.

Evidence based processes to prevent readmissions: more is better, a ten-site observational study.

BACKGROUND: 30-day hospital readmissions are an indicator of quality of care; hospitals are financially penalized by Medicare for high rates. Numerous care transition processes reduce readmissions in clinical trials. The objective of this study was to examine the relationship between the number of evidence-based transitional care processes used and the risk standardized readmission rate (RSRR). METHODS: Design: Mixed method, multi-stepped observational study. Data collection occurred 2014-2018 with data analyses completed in 2021. SETTING: Ten VA hospitals, chosen for 5-year trend of improving or worsening RSRR prior to study start plus documented efforts to reduce readmissions. PARTICIPANTS: During five-day site visits, three observers conducted semi-structured interviews (n = 314) with staff responsible for care transition processes and observations of care transitions work (n = 105) in inpatient medicine, geriatrics, and primary care. EXPOSURE: Frequency of use of twenty recommended care transition processes, scored 0-3. Sites' individual process scores and cumulative total scores were tested for correlation with RSRR. OUTCOME: best fit predicted RSRR for quarter of site visit based on the 21 months surrounding the site visits. RESULTS: Total scores: Mean 38.3 (range 24-47). No site performed all 20 processes. Two processes (pre-discharge patient education, medication reconciliation prior to discharge) were performed at all facilities. Five processes were performed at most facilities but inconsistently and the other 13 processes were more varied across facilities. Total care transition process score was correlated with RSRR (R2 = 0..61, p < 0.007). CONCLUSIONS: Sites making use of more recommended care transition processes had lower RSRR. Given the variability in implementation and barriers noted by clinicians to consistently perform processes, further reduction of readmissions will likely require new strategies to facilitate implementation of these evidence-based processes, should include consideration of how to better incorporate activities into workflow, and may benefit from more consistent use of some of the more underutilized processes including patient inclusion in discharge planning and increased utilization of community supports. Although all facilities had inpatient social workers and/or dedicated case managers working on transitions, many had none or limited true bridging personnel (following the patient from inpatient to home and even providing home visits). More investment in these roles may also be needed.

Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.

BACKGROUND: Signifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation. OBJECTIVE: We sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers. METHODS: Adults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified. RESULTS: HDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8+ T cells, whereas airway inflammation associated with both CD8+ T cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased natural killer and CD8+ T cells, lower CD4+ mucosal-associated invariant T cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models. CONCLUSIONS: Repetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

Retention of Point-of-Care Ultrasound Skills Among Practicing Physicians: Findings of the VA National POCUS Training Program.

BACKGROUND: Point-of-care ultrasound (POCUS) use continues to increase in many specialties, but lack of POCUS training is a known barrier among practicing physicians. Many physicians are obtaining POCUS training through postgraduate courses, but the impact of these courses on skill retention and frequency of POCUS use post-course is unknown. The purpose of this study was to assess the change in POCUS knowledge, skills, and frequency of use after 6-9 months of participating in a brief training course. METHODS: Course participants' POCUS knowledge and hands-on technical skills were tested pre-course using an online, 30-question knowledge test and a directly observed skills test, respectively. The same knowledge and skills tests were repeated immediately post-course and after 6-9 months using remote tele-ultrasound software. Course participants completed a survey on their POCUS use pre-course and after 6-9 months post-course. RESULTS: There were 127 providers who completed the POCUS training course from October 2016 to November 2017. Knowledge test scores increased from a median of 60% to 90% immediately post-course followed by a slight decrease to 87% after 8 months post-course. Median skills test scores for 4 common POCUS applications (heart, lung, abdomen, vascular access) increased 36-74 points from pre-course to immediately post-course with a 2-7-point decrease after 8 months. Providers reported more frequent POCUS use post-course, which suggests application of their POCUS knowledge and skills in clinical practice. More frequent use of cardiac POCUS applications was associated with significantly greater retention of cardiac skills at 8 months. CONCLUSIONS: Practicing physicians can retain POCUS knowledge and hands-on skills 8 months after participating in a 2.5-day POCUS training course, regardless of frequency of POCUS use post-course.

Screening and Recognition of Chronic Kidney Disease in VA Health Care System Primary Care Clinics.

Background: The successful implementation of interventions targeted to improve kidney health requires early identification of CKD which involves screening at-risk populations as well as recognizing CKD. We aim to determine CKD screening and recognition rates, factors associated with these rates, and evaluate the effect of CKD awareness on delivery of care. Methods: A retrospective cohort study of veterans enrolled with Veterans Integrated Service Network 17 who had hypertension (HTN) and/or diabetes (DM) and were seen at least twice in primary care clinics within 18 months. The final cohort of 270,170 patients (52% HTN, 5% DM, and 44% both) was examined for serum creatinine/eGFR, urine protein/albumin, International Classification of Diseases (ICD) codes for CKD, and nephrology referral. CKD was defined as eGFR <60 ml/min per 1.73 m2 and/or urine albumin-creatinine ratio (uACR) >30 mg/g at least twice 90 days apart. Clinical covariates, HTN control, and prescription rates of renal prudent medications and nonsteroidal anti-inflammatory drugs (NSAIDs) were assessed. Results: Overall, 254,831 (94%) patients had either eGFR, urine protein/albumin, or both. However, screening for protein/albuminuria was low (56%), particularly in patients with isolated HTN (35%). Of 254,831 patients, 92,900 (36%) had laboratory evidence of CKD and, of these, 40,586 (44%) were recognized to have CKD by ICD code and/or nephrology referral. CKD due to presence of uACR criteria alone had the lowest recognition (19%) as compared with CKD due to eGFR criteria (44%) or both (67%). Frequency of emergency room visits, hospitalization, and cardiac and endovascular procedures requiring contrast had the highest odds and races other than white had the lower odds of screening. In contrast, CKD recognition was high in races other than white and increased with worsening eGFR and increasing uACR. In screened and recognized CKD, prescription was higher for angiotensin inhibitors, statins, and diuretics, and was lower for NSAIDs. Conclusions: Although overall CKD screening rate was high, screening of protein/albuminuria in isolated HTN and overall recognition of CKD was low in at-risk veterans. Increased recognition was associated with a favorable prescription rate for renal prudent medications.

Hospitalists as Triagists: Description of the Triagist Role across Academic Medical Centers.

From the hospitalist perspective, triaging involves the evaluation of a patient for potential admission to an inpatient service. Although traditionally done by residents, many academic hospitalist groups have assumed the responsibility for triaging. We conducted a cross-sectional survey of 235 adult hospitalists at 10 academic medical centers (AMCs) to describe the similarities and differences in the triagist role and assess the activities and skills associated with the role. Eight AMCs have a defined triagist role; at the others, hospitalists supervise residents/advanced practice providers. The triagist role is generally filled by a faculty physician and shared by all hospitalists.We found significant variability in verbal communication practices (P = .02) and electronic communication practices (P < .0001) between the triagist and the current provider (eg, emergency department, clinic provider), and in the percentage of patients evaluated in person (P < .0001). Communication skills, personal efficiency, and systems knowledge are dominant themes of attributes of an effective triagist.

Enhancing Access to Psychiatric Care for Posttraumatic Stress Disorder in Veterans with Mild Traumatic Brain Injury through Integrated Services.

(i) To describe an integrated model of psychiatric care for the treatment of posttraumatic stress disorder (PTSD) in veterans with mild traumatic brain injury (mTBI). (ii) To evaluate access to and engagement in psychiatric care among veterans with comorbid PTSD and mTBI after implementation of an Integrated Care (IC) model compared to the previous Usual Care (UC). 100 randomly selected charts, 50 from each of UC and IC were reviewed in this non-concurrent case- control study. Polytrauma Network Site (PNS), an outpatient rehabilitation clinic, for veterans who suffered from brain and other traumatic injuries at an urban VA Polytrauma Rehabilitation Center. Veterans receiving treatment for mTBI symptoms by the rehabilitation team were referred for medication management for PTSD to UC and IC. Co-located access to psychiatric care for medication management as part of the interdisciplinary team with the goal of expediting rehabilitation and functional recovery. Number of consults for psychiatric care for medication management scheduled and completed within 30 days, and number of veterans offered, initiating, and completing evidence-based psychotherapies for PTSD in UC compared to IC. After implementation of IC there were significant improvements in timely completion of consults and patient engagement with a psychiatrist. There also were improvements in number of referrals, initiation, and completion of evidence-based psychotherapies for the treatment of PTSD. IC within the PNS shows promise as an effective care model for increasing access and engagement in care for veterans with comorbid PTSD/mTBI. Future research is needed to examine the utility of this model in other sites.