Faculty Bibliography

AIMS/OBJECTIVE:Sacubitril/valsartan combines renin-angiotensin-aldosterone system inhibition with amplification of natriuretic peptides. In addition to well-described effects, natriuretic peptides exert direct effects on pulmonary vasculature. The effect of sacubitril/valsartan on pulmonary artery pressure (PAP) has not been fully defined. METHODS AND RESULTS/RESULTS:This was a retrospective case-series of PAP changes following transition from angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) to sacubitril/valsartan in patients with heart failure reduced ejection fraction and a previously implanted CardioMEMS™ sensor. Pre-sacubitril/valsartan and post-sacubitril/valsartan PAPs were compared for each patient by examining averaged consecutive daily pressure readings from 1 to 5 days before and after sacubitril/valsartan exposure. PAP changes were also compared between patients based on elevated trans-pulmonary gradients (trans-pulmonary gradient ≥ 12 mmHg) at time of CardioMEMS™ sensor implantation. The cohort included 18 patients, 72% male, mean age 60.1 ± 13.6 years. There was a significant decrease in PAPs associated with transition from ACEI/ARB to sacubitril/valsartan. The median (interquartile range) pre-treatment and post-treatment change in mean, systolic and diastolic PAPs were -3.6 (-9.8, -0.7) mmHg (P < 0.001), -6.5 (-15.0, -2.0) mmHg (P = 0.001), and -2.5 (-5.7, -0.7) (P = 0.001), respectively. The decrease in PAPs was independent of trans-pulmonary gradient (F(1,16) = 0.49, P = 0.49). CONCLUSIONS:In this retrospective case series, transition from ACEI/ARB to sacubitril/valsartan was associated with an early and significant decrease in PAPs.

Three cohorts including the Fire Department of the City of New York (FDNY), the World Trade Center Health Registry (WTCHR), and the General Responder Cohort (GRC), each funded by the World Trade Center Health Program have reported associations between WTC-exposures and cancer. Results have generally been consistent with effect estimates for excess incidence for all cancers ranging from 6 to 14% above background rates. Pooling would increase sample size and de-duplicate cases between the cohorts. However, pooling required time consuming steps: obtaining Institutional Review Board (IRB) approvals and legal agreements from entities involved; establishing an honest broker for managing the data; de-duplicating the pooled cohort files; applying to State Cancer Registries (SCRs) for matched cancer cases; and finalizing analysis data files. Obtaining SCR data use agreements ranged from 6.5 to 114.5 weeks with six states requiring >20 weeks. Records from FDNY (n = 16,221), WTCHR (n = 29,372), and GRC (n = 33,427) were combined de-duplicated resulting in 69,102 unique individuals. Overall, 7894 cancer tumors were matched to the pooled cohort, increasing the number cancers by as much as 58% compared to previous analyses. Pooling resulted in a coherent resource for future research for studies on rare cancers and mortality, with more representative of occupations and WTC- exposure.

Taxi and for-hire vehicle (FHV) drivers are a largely immigrant, low-income occupational group at increased cardiovascular disease (CVD) risk. Poor dental health is a CVD risk factor, and dental care access is an unexamined taxi/FHV driver CVD risk factor. A cross-sectional survey was administered to 422 taxi/FHV drivers (2016-2017) to identify predictors of access to dental health care among drivers. One-third (n = 128, 30.3%) reported needing dental care/tests/treatment within the past six months, and nearly one-half (n = 61, 48%) were delayed/unable to obtain care. Only 57.6% (n = 241) had past-year dental cleanings. Not having enough money to cover household expenses was a significant predictor of being delayed/unable to obtain needed dental care/tests/treatment in the prior six months (0.5 OR; 95% CI, 0.28-0.89; p < .05). Lack of dental insurance coverage (2.72 OR; 95% CI, 1.60-4.63; p < .001) or lack of primary care provider (2.72 OR; 95% CI, 1.60-4.63; p < .001) were associated with lack of past-year dental cleaning. Seventeen percent of drivers with Medicaid were unaware of their dental coverage, which was associated with both inability to access needed dental care/tests/treatment in the past 6 months (p = .026) and no past-year dental cleaning (p < .001). Limited understanding of dental coverage was associated with both an inability to access needed dental care/tests/treatment in the past 6 months (p = .028) and lack of past-year dental cleaning (p = .014). Our findings can inform targeted intervention development to increase taxi/FHV driver dental care access/uptake, potentially improving their CVD risk.

BACKGROUND:There is currently no clinical trial data regarding the efficacy of everolimus exemestane (EE) following prior treatment with CDK4/6 inhibitors (CDK4/6i). This study assesses the use and efficacy of everolimus exemestane in patients with metastatic HR+ HER2- breast cancer previously treated with endocrine therapy (ET) or endocrine therapy + CDK4/6i. METHODS:Retrospective analysis of electronic health record-derived data for HR+ HER2- metastatic breast cancer from 2012 to 2018. The proportion of patients receiving EE first-line, second-line, or third-line, and the median duration of EE prior to next line of treatment (TTNT) by line of therapy was calculated. OS for patients receiving EE first-line, second-line, or third-line, indexed to the date of first-line therapy initiation and stratified by prior treatment received, was calculated with Kaplan-Meier method with multivariable Cox proportional hazards regression analysis. RESULTS:Six hundred twenty-two patients received EE first-line (n = 104, 16.7%), second-line (n = 273, 43.9%) or third-line (n = 245, 39.4%). Median TTNT was 8.3 months, 5.5 months, and 4.8 months respectively. Median TTNT of EE second-line was longer following prior ET alone compared to prior ET + CDK4/6i (6.2 months (95% CI 5.2, 7.3) vs 4.3 months (95% CI 3.2, 5.7) respectively, p = 0.03). Similarly, EE third-line following ET alone vs ET + CDK4/6i in first- or second-line resulted in median TTNT 5.6 months (95% CI 4.4, 6.9) vs 4.1 months (95% CI 3.6, 6.1) respectively, although this was not statistically significant (p = 0.08). Median OS was longer for patients who received EE following prior ET + CDK4/6i. EE second-line following ET + CDK 4/6i vs ET alone resulted in median OS 37.7 months vs. 32.7 months (p = 0.449). EE third-line following ET + CDK4/6i vs prior ET alone resulted in median OS 59.2 months vs. 40.8 months (p < 0.010). This difference in OS was not statistically significant when indexed to the start of EE therapy. CONCLUSION/CONCLUSIONS:This study suggests that EE remains an effective treatment option after prior ET or ET + CDK4/6i use. Median TTNT of EE was longer for patients who received prior ET, whereas median OS was longer for patients who received prior ET + CDK4/6i. However, this improvement in OS was not statistically significant when indexed to the start of EE therapy suggesting that OS benefit is primarily driven by prior CDK4/6i use. EE remains an effective treatment option regardless of prior treatment option.

BACKGROUND:Daratumumab-based combination therapies have shown high rates of complete response (CR) and minimal residual disease negativity in patients with multiple myeloma. However, daratumumab, an IgGĶ monoclonal antibody, interferes with electrophoretic techniques making it difficult to reliably define residual disease versus CR, especially in patients with IgGĶ multiple myeloma. METHODS:Enrichment with polyclonal sheep antibody-coated magnetic microparticles combined with MALDI-TOF mass spectrometry (MALDI-TOF MS) analysis was used to detect M-proteins in serial samples from newly diagnosed multiple myeloma patients treated with daratumumab-based therapy. The performance of the MALDI-TOF MS assay was compared to that of a routine test panel (serum protein electrophoresis (SPEP), immunofixation (IFE) and serum free light chain (FLC)). RESULTS:Comparison of MALDI-TOF MS to SPEP/IFE/FLC showed a concordance of 84.9% (p<0.001). When MALDI-TOF MS and FLC results were combined, the M-protein detection rate was the same or better than the routine test panel. For the 9 patients who obtained CR during follow-up, MALDI-TOF MS detected an M-protein in 46% of subsequent samples. Daratumumab could be distinguished from the M-protein in 215/222 samples. CONCLUSION/CONCLUSIONS:MALDI-TOF MS is useful in assessing CR in patients treated with monoclonal antibody-based therapies.

BACKGROUND:Coronavirus Disease 2019 (COVID-19) has caused over 1 200 000 deaths worldwide as of November 2020. However, little is known about the clinical outcomes among hospitalized patients with active COVID-19 after in-hospital cardiac arrest (IHCA). AIM/OBJECTIVE:We aimed to characterize outcomes from IHCA in patients with COVID-19 and to identify patient- and hospital-level variables associated with 30-day survival. METHODS:We conducted a multicentre retrospective cohort study across 11 academic medical centres in the U.S. Adult patients who received cardiopulmonary resuscitation and/or defibrillation for IHCA between March 1, 2020 and May 31, 2020 who had a documented positive test for Severe Acute Respiratory Syndrome Coronavirus 2 were included. The primary outcome was 30-day survival after IHCA. RESULTS:There were 260 IHCAs among COVID-19 patients during the study period. The median age was 69 years (interquartile range 60-77), 71.5% were male, 49.6% were White, 16.9% were Black, and 16.2% were Hispanic. The most common presenting rhythms were pulseless electrical activity (45.0%) and asystole (44.6%). ROSC occurred in 58 patients (22.3%), 32 (12.3%) survived to 30 days, and 31 (11.9%) survived to discharge. Rates of ROSC and 30-day survival in the two hospitals with the highest volume of IHCA over the study period compared to the remaining hospitals were considerably lower (10.8% vs. 64.3% and 5.9% vs. 35.7% respectively, p < 0.001 for both). CONCLUSIONS:We found rates of ROSC and 30-day survival of 22.3% and 12.3% respectively. There were large variations in centre-level outcomes, which may explain the poor survival in prior studies.

OBJECTIVE:To establish the reliability and validity of a self-report measure designed to assess self-efficacy for hypertension treatment adherence. METHODS:This investigation was embedded within a six-month randomized clinical trial (RCT), which demonstrated that a tailored, stage-matched intervention was more effective at improving hypertension control than usual care among individuals (n = 533) with repeated uncontrolled hypertension. The instrument used to assess self-efficacy for hypertension treatment adherence (SE-HTA) comprised three subscales that assessed diet self-efficacy (DSE), exercise self-efficacy (ESE), and medication self-efficacy (MSE). To determine SE-HTA validity and reliability, we assessed internal consistency using Cronbach's α coefficients, conducted exploratory factor analysis, and evaluated convergent and discriminant validity, as well as test-retest reliability using Spearman's ρ correlation coefficients. RESULTS:Cronbach's α (internal consistency) values for DSE, ESE, and MSE were 0.81, 0.82 and 0.74. Factor analysis and the scree plot demonstrated three distinct factors, which correspond to the three subscales contained in the SE-HTA instrument. SE-HTA possessed good convergent and discriminant validity, and moderate test-retest reliability. CONCLUSION/CONCLUSIONS:The SE-HTA instrument containing diet, exercise, and medication adherence subscales is valid and reliable in adults with uncontrolled hypertension. PRACTICE IMPLICATIONS/CONCLUSIONS:This SE-HTA instrument measures self-efficacy and could help facilitate behavior change in hypertension.

PURPOSE/UNASSIGNED:Hospital at home (HaH) is a means of providing inpatient-level care at home. Selection of admissions potentially suitable for HaH in oncology is not well studied. We sought to create a predictive model for identifying admissions of patients with cancer, specifically solid-tumor malignancies, potentially suitable for HaH. METHODS/UNASSIGNED:In this observational study, we analyzed admissions of patients with solid-tumor malignancies and unplanned admissions (January 1, 2015, to June 12, 2019) at an academic, urban cancer hospital. Potential suitability for HaH was the primary outcome. Admissions were considered potentially suitable if they did not involve escalation of care, rapid response evaluation, in-hospital death, telemetry, surgical procedure, consultation to a procedural service, advanced imaging, transfusion, restraints, and nasogastric tube placement. Admission source, patient demographics, vital signs, laboratory test results, comorbidities, admission and active cancer diagnoses, and recent hospital utilization were included as candidate variables in a multivariable logistic regression model. RESULTS/UNASSIGNED:Of 3,322 admissions, 905 (27.2%) patients were potentially suitable for HaH. After variable selection in the derivation cohort (n = 1,097), thirteen factors predicted potential suitability: admission source; temperature and respiratory rate at presentation; hemoglobin; breast cancer, GI cancer, or malignancy of secondary or ill-defined origin; admission for genitourinary, musculoskeletal, or neurologic symptoms, intestinal obstruction or ileus, or evaluation of secondary malignancy; and emergency department visit in prior 90 days. Model c-statistics were 0.71 (95% CI, 0.68 to 0.75) and 0.63 (0.59 to 0.67) in the derivation and validation (n = 1,095) cohorts. CONCLUSION/UNASSIGNED:Hospital admissions of patients potentially suitable for HaH may be identifiable using data available at admission.