Faculty Bibliography

AIM/OBJECTIVE:To explore the resources supporting current nurse practice in the post-emergency country of Liberia, using the nursing intellectual capital framework, as nurses work to meet the targets set by Government of Liberia's Essential Package of Health Services. DESIGN/METHODS:Case study. METHODS:Data were collected in Liberia February-June 2019. Direct observation, semi-structured interviews and photographs were used to investigate how nurse practice is supported. Field notes, transcripts and photographs were coded using both directed and conventional content analysis. Reports were then generated by code to triangulate the data. RESULTS:Thirty-seven nurses at 12 health facilities participated. The intellectual capital supporting inpatient and outpatient nurse practice differs in important ways. Inpatient nurse practice is more likely to be supported by facility-based protocols and trainings, whereas outpatient nurse practice is more likely to be supported by external protocols and trainings, often developed by the Liberian government or non-governmental organizations. This can lead to uneven provision of inpatient protocols and trainings, often favouring private facilities. Similarly, inpatient nurses rely primarily on other nurses at their facilities for clinical support while outpatient nurses often have external professional relationships that provided them with clinical guidance. CONCLUSION/CONCLUSIONS:Much has been accomplished to enable outpatient nurses to provide the primary- and secondary-care target services in the Essential Package of Health Services. However, as the Liberian government and its partners continue to work towards providing certain tertiary care services, developing analogous protocols, trainings and clinical mentorship networks for inpatient nurses will likely be fruitful, and will decrease the burden on individual facilities. IMPACT/CONCLUSIONS:Nurses are often expected to meet new service provision targets in post-emergency states. Further research into how best to support nurses as they work to meet those targets has the potential to strengthen health systems.

 /UNASSIGNED:Fibromyalgia (FM) is a chronic pain disorder characterized by chronic widespread musculoskeletal pain (CWP), resting pain, movement-evoked pain (MEP), and other somatic symptoms that interfere with daily functioning and quality of life. In clinical studies, this symptomology is assessed, while preclinical models of CWP are limited to nociceptive assays. The aim of the study was to investigate the human-to-model translatability of clinical behavioral assessments for spontaneous (or resting) pain and MEP in a preclinical model of CWP. For preclinical measures, the acidic saline model of FM was used to induce widespread muscle pain in adult female mice. Two intramuscular injections of acidic or neutral pH saline were administered following baseline measures, five days apart. An array of adapted evoked and spontaneous pain measures and functional assays were assessed for three weeks. A novel paradigm for MEP assessment showed increased spontaneous pain following activity. For clinical measures, resting and movement-evoked pain and function were assessed in adult women with FM. Moreover, we assessed correlations between the preclinical model of CWP and in women with fibromyalgia to examine whether similar relationships between pain assays that comprise resting and MEP existed in both settings. For both preclinical and clinical outcomes, MEP was significantly associated with mechanical pain sensitivity. Preclinically, it is imperative to expand how the field assesses spontaneous pain and MEP when studying multi-symptom disorders like FM. Targeted pain assessments to match those performed clinically is an important aspect of improving preclinical to clinical translatability of animal models. SUMMARY/CONCLUSIONS:Preclinical assessments of chronic musculoskeletal pain recapitulate several outcome measures for clinical assessment of patients with FM, particularly prolonged spontaneous (resting) pain, and MEP.

The engineering of patient T-cells for adoptive cell therapies has revolutionized the treatment of several cancer types. However, further improvements are needed to increase durability and response rate. While CRISPR-based loss-of-function screens have shown promise for high-throughput identification of genes that modulate T-cell response, these methods have been limited thus far to negative regulators of T-cell functions, and raise safety concerns due to the permanent nature of genome modification. Here we identify positive T-cell regulators via overexpression of ~12,000 barcoded human open reading frames (ORFs). Using this genome-scale ORF screen, we find modulator genes that may not normally be expressed by T-cells. The top-ranked genes increased primary human T-cell proliferation, activation, and secretion of key cytokines. In addition, we developed a single-cell genomics method for high-throughput quantification of the transcriptome and surface proteome in ORF-engineered T-cells. The top-ranked ORF, lymphotoxin beta receptor (LTBR), is typically expressed by myeloid cells but absent in lymphocytes. When expressed in T-cells, LTBR induced profound transcriptional and epigenomic remodeling, resulting in an increase in T-cell stemness and effector functions, as well as resistance to apoptosis and exhaustion in chronic stimulation settings. Using mutagenesis and epistasis approaches, we demonstrated that LTBR constitutive activates the canonical NFkB pathway via ligand shortcircuiting and tonic signaling. Expression of several top-ranked genes, including LTBR, improved antigen-specific chimeric antigen receptor (CAR) T-cell responses in healthy donors and diffuse large B-cell lymphoma patients. Finally, the top-ranked genes discovered in alphabeta T-cells also improved antigen-specific responses of gammadelta T-cells, highlighting the potential for cancer-agnostic therapies. Our results provide several strategies for improving next generation T-cell therapies via induction of new synthetic cell programs

Background: We recently implemented the Age-Friendly Health System's 4Ms (What Matters, Medication, Mentation, and Mobility) framework in New York City Health + Hospitals/Bellevue Hospital Center's Geriatrics clinic to improve care of older adults.
Method(s): We examined the impact of 4Ms assessment on patient care and changes in care processes through specific interventions triggered after assessment. We conducted chart reviews of patient visits during March 2021, the first month of 4Ms implementation and identified interventions made during these visits. To assess "What Matters" providers asked "What Matters the most to you;" potentially inappropriate Medications (PIM) were identified using the Beers list; Mentation was evaluated using the Mini-Cog; and Mobility was determined using timed up and go (TUG) test. We used descriptive statistics to characterize findings.
Result(s): Among the 121 patients who had 4Ms assessment in March 2021, 85% (n=103) were asked "What Matters;" providers reviewed Medications for almost all (n=118; 98%) and conducted a Mini-Cog for 64% (n=78). Most not cognitively assessed were either previously screened (n=11; 9%) or had dementia (n=12; 10%). Providers used the TUG test for 87% (n=105). What Mattered to patients most commonly was "getting better" (n=24; 23%). There were 39 (33%) patients with potentially inappropriate Medications (including proton pump inhibitors, gabapentinoids, and NSAIDS) of which 10 (26%) Medications were either discontinued or reduced. Other interventions included further cognitive evaluation (n=2) and home care referrals (n=2) among 14 (18%) with an abnormal Mini- Cog. Among the 51 (42%) patients with an abnormal TUG, providers intervened for 19 (37%) with devices, referrals or home services.
Conclusion(s): The adoption of 4Ms assessment during routine visits identified issues with Medications, Mentation and Mobility, triggering several interventions for common geriatric conditions. 4Ms assessment is a helpful strategy to organize geriatric care, routinely assess patients for common geriatric syndromes, and improve care. Future directions include prioritizing interventions integrated with "What Matters" to maintain patient-centered care

BACKGROUND:Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS:In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS/RESULTS:Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION/CONCLUSIONS:In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING/BACKGROUND:National Institute of Allergy and Infectious Diseases.

BACKGROUND/UNASSIGNED:Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE/UNASSIGNED:The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS/UNASSIGNED:This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS/UNASSIGNED:= 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS/UNASSIGNED:In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.

BACKGROUND:The American Board of Internal Medicine Foundation's Choosing Wisely campaign has resulted in a vast number of recommendations to reduce low-value care. Implementation of these recommendations, in conjunction with patient input, remains challenging. OBJECTIVE:To create updated Society of Hospital Medicine Adult Hospitalist Choosing Wisely recommendations that incorporate patient input from inception. DESIGN AND PARTICIPANTS/METHODS:This was a multi-phase study conducted by the Society of Hospital Medicine's High Value Care Committee from July 2017 to January 2020 involving clinicians and patient advocates. APPROACH/METHODS:Phase 1 involved gathering low-value care recommendations from patients and clinicians across the USA. Recommendations were reviewed by the committee in phase 2. Phase 3 involved a modified Delphi scoring in which 7 committee members and 7 patient advocates voted on recommendations based on strength of evidence, potential for patient harm, and relevance to either hospital medicine or patients. A patient-friendly script was developed to allow advocates to better understand the clinical recommendations. KEY RESULTS/RESULTS:A total of 1265 recommendations were submitted by clinicians and patients. After accounting for similar suggestions, 283 recommendations were categorized. Recommendations with more than 10 mentions were advanced to phase 3, leaving 22 recommendations for the committee and patient advocates to vote upon. Utilizing a 1-5 Likert scale, the top combined recommendations were reducing use of opioids (4.57), improving sleep (4.52), minimizing overuse of oxygen (4.52), reducing CK-MB use (4.50), appropriate venous thromboembolism prophylaxis (4.43), and decreasing daily chest x-rays (4.43). CONCLUSIONS:Specific voting categories, along with the use of patient-friendly language, allowed for the successful co-creation of recommendations.