Faculty Bibliography

BACKGROUND:Hepatitis C affects racial minorities disproportionately and is greatest among the black population. The incidence of hepatocellular carcinoma has increased with the largest increase observed in black and Hispanic populations, but limited data remain on whether hepatitis C hepatocellular carcinoma in racial-ethnic minorities have the same utilization of services compared with the white population. METHODS:We used the database of the National Inpatient Sample to identify hepatitis C-hepatocellular carcinoma patients (N = 200,163) who underwent liver transplantation (n = 11,491), liver resection (n = 4,896), or ablation of liver lesions (n = 6,933) from 2005 to 2015. We estimated utilization over time and assessed differences in utilization and inpatient mortality across patient characteristics. RESULTS:In multivariate analysis, factors associated with utilization of services included treatment year, sex, race, insurance status, hospital type, and comorbidity burden, with black and Hispanic patients having statistically significantly decreased utilization. Factors associated with inpatient mortality included treatment year, sex, race, insurance status, hospital type, hospital region, and comorbidity burden, with black patients having a statistically significantly greater risk of inpatient mortality. CONCLUSION/CONCLUSIONS:We identified racial and socioeconomic factors which were associated with utilization of services and inpatient mortality for patients with hepatitis C hepatocellular carcinoma. Blacks were especially disadvantaged in the receipt of care. Further work to abrogate these findings is imperative to ensure equitable provision of surgical therapies.

Objectives: Discharges against medical advice (AMA) occur when patients leave the hospital prior to a physician-recommended endpoint. It is unknown whether AMA discharges are associated with higher healthcare costs within 30 days of discharge. We examine healthcare costs following a hospital discharge in a commercially insured population.
Method(s): This retrospective cohort study examined individuals aged 18 to 64 with a hospitalization during 2007-2015 from a 10% random sample of enrollees in the IQVIA^TM Adjudicated Health Plan Claims Data. We included individuals with insurance coverage 6 months before and 30 days after their first hospitalization. Individuals with AMA and non-AMA discharges were matched on baseline covariates. Generalized linear models and cost ratios (CR) were used to quantify the association between AMA discharges and 30-day costs. We report CRs overall and by points of service (inpatient, emergency department (ED), physician office, non-physician outpatient encounter (NPOE) and prescription drug fill).
Result(s): Of the 467,746 individuals in the unmatched sample, 2,164 (0.46%) were discharged AMA. Mean (median) costs were 20% (5%) higher in the AMA group compared to the non-AMA group. In the matched sample and relative to those discharged routinely, individuals with an AMA discharge incurred 1.20 times (95% CI: 1.08, 1.34) higher costs. Similarly, individuals with an AMA discharge incurred higher inpatient (CR: 1.71, 95% CI: 1.45, 2.01) and ED (CR: 2.10, 95% CI: 1.84, 2.39) costs within 30 days post-discharge. Conversely, individuals with an AMA discharge incurred lower NPOE (CR: 0.84, 95% CI: 0.74, 0.95) and prescription drug fill (CR: 0.81; 95% CI: 0.73, 0.91) costs. There were no differences in physician office visit costs across the two groups.
Conclusion(s): An AMA discharge is associated with higher 30-day costs compared to those discharged routinely, particularly for acute care services. Future work should determine whether these findings extend to publicly-insured individuals.
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OBJECTIVES/OBJECTIVE:Peripherally-directed treatments (targeted exercise, surgery) can reduce, but not fully eliminate, pain for up to 40% of patients with Achilles tendinopathy. The objectives were to: 1) Identify indicators of altered central processing in participants with Achilles tendinopathy compared to controls; and 2) determine which indicators of altered central processing persisted after a local anesthetic injection in patients with Achilles tendinopathy. DESIGN/METHODS:Mechanistic clinical trial. METHODS:46 adults participated (23 with chronic Achilles tendinopathy, 23 matched-controls; NCT03316378). All participants repeated: 1) movement-evoked pain rating, 2) motor performance, 3) pain psychology questionnaires; 4) quantitative sensory testing. Participants with Achilles tendinopathy received a local anesthetic injection before repeat testing and controls did not. Mixed-effects ANOVAs examined group, time, and group*time effects. RESULTS:>0.05). CONCLUSION/CONCLUSIONS:.

Background/UNASSIGNED:The coronavirus disease 2019 pandemic has or threatens to overwhelm health care systems. Many institutions are developing ventilator triage policies. Objective/UNASSIGNED:To characterize the development of ventilator triage policies and compare policy content. Design/UNASSIGNED:Survey and mixed-methods content analysis. Setting/UNASSIGNED:North American hospitals associated with members of the Association of Bioethics Program Directors. Participants/UNASSIGNED:Program directors. Measurements/UNASSIGNED:Characteristics of institutions and policies, including triage criteria and triage committee membership. Results/UNASSIGNED:Sixty-seven program directors responded (response rate, 91.8%); 36 (53.7%) hospitals did not yet have a policy, and 7 (10.4%) hospitals' policies could not be shared. The 29 institutions providing policies were relatively evenly distributed among the 4 U.S. geographic regions (range, 5 to 9 policies per region). Among the 26 unique policies analyzed, 3 (11.3%) were produced by state health departments. The most frequently cited triage criteria were benefit (25 policies [96.2%]), need (14 [53.8%]), age (13 [50.0%]), conservation of resources (10 [38.5%]), and lottery (9 [34.6%]). Twenty-one (80.8%) policies use scoring systems, and 20 of these (95.2%) use a version of the Sequential Organ Failure Assessment score. Among the policies that specify the triage team's composition (23 [88.5%]), all require or recommend a physician member, 20 (87.0%) a nurse, 16 (69.6%) an ethicist, 8 (34.8%) a chaplain, and 8 (34.8%) a respiratory therapist. Thirteen (50.0% of all policies) require or recommend those making triage decisions not be involved in direct patient care, but only 2 (7.7%) require that their decisions be blinded to ethically irrelevant considerations. Limitation/UNASSIGNED:The results may not be generalizable to institutions without academic bioethics programs. Conclusion/UNASSIGNED:Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation.

BACKGROUND:The seminal Dietary Approaches to Stopping Hypertension (DASH) study demonstrated the effectiveness of diet to control hypertension; however, the effective implementation and dissemination of its principles have been limited. OBJECTIVE:This study aimed to determine the feasibility and effectiveness of a DASH mobile health intervention. We hypothesized that combining Bluetooth-enabled data collection, social networks, and a human coach with a smartphone DASH app (DASH Mobile) would be an effective medium for the delivery of the DASH program. METHODS:We conducted a single-arm pilot study from August 2015 through August 2016, using a pre-post evaluation design to evaluate the feasibility and preliminary effectiveness of a smartphone version of DASH that incorporated a human health coach. Participants were recruited both online and offline. RESULTS:A total of 17 patients participated in this study; they had a mean age of 59 years (SD 6) and 10 (60%) were women. Participants were engaged with the app; in the 120 days of the study, the mean number of logged blood pressure measurements was 63 (SD 46), the mean number of recorded weight measurements was 52 (SD 45), and participants recorded a mean of 55 step counts (SD 36). Coaching phone calls had a high completion rate (74/102, 73%). The mean number of servings documented per patient for the dietary assessment was 709 (SD 541), and patients set a mean number of 5 (SD 2) goals. Mean systolic and diastolic blood pressure, heart rate, weight, body mass index, and step count did not significantly change over time (P>.10 for all parameters). CONCLUSIONS:In this pilot study, we found that participants were engaged with an interactive mobile app that promoted healthy behaviors to treat hypertension. We did not find a difference in the physiological outcomes, but were underpowered to identify such changes.

Mycobacterium abscessus (Mab) is a highly drug-resistant nontuberculous mycobacteria (NTM). Efforts to discover new treatments for M. abscessus infections are accelerating with a focus on cell wall synthesis proteins (L, D-transpeptidases, Ldt_Mab1-5, and D,D-carboxypeptidase) that are targeted by β-lactam antibiotics. A challenge to this approach is the presence of chromosomally encoded β-lactamase, Bla_Mab Using a "mechanism based" approach, we show that a novel ceftaroline-imipenem combination effectively lowered the minimal inhibitory concentrations (MICs) of Mab isolates (MIC₅₀ ≤ 0.25, MIC₉₀ ≤ 0.5). Ceftaroline and imipenem combined with a β-lactamase inhibitor, relebactam or avibactam, demonstrated only a modest effect on susceptibility, compared to each of the beta-lactams alone. In steady state kinetic assays, Bla_Mab exhibited a lower K_{i app} (K_{i app} = 0.30 ± 0.03 μM, avibactam; 136 ± 14 μM, relebactam) and a faster acylation rate for avibactam (k₂/K = 3.4 ± 0.4 x 10⁵ M^-1s^-1, avibactam; 6 ± 0.6 x 10² M^-1s^-1, relebactam). The k_cat/K_m was nearly 10-fold lower for ceftaroline fosamil (0.007 ± 0.001 μM^-1s^-1) compared to imipenem (0.056 ± 0.006 μM^-1s^-1). Timed mass spectrometry captured complexes of avibactam and Bla_Mab, Ldt_{Mab1, 2, and 4}, and D,D-carboxypeptidase, whereas relebactam bound only Bla_Mab and Ldt_{Mab1 and 2} Interestingly, Ldt_{Mab1, 2, 4 and 5} and D, D-carboxypeptidase bound only to imipenem when incubated with imipenem and ceftaroline fosamil. We next determined the binding constants of imipenem and ceftaroline fosamil to Ldt_{Mab1, 2, 4 and 5} and showed that imipenem bound > 100 fold more avidly than ceftaroline fosamil for Ldt_Mab1 and Ldt_Mab2 (e.g. K_{i app} or K_m LdtMab1 = 0.01 ± 0.01 μM for imipenem vs 0.73 ± 0.08 μM for ceftaroline fosamil). Molecular modelling indicates that Ldt_Mab2 readily accommodates imipenem, but the active site must widen to ≥ 8Ã… for ceftaroline to enter. Our analysis demonstrates that ceftaroline and imipenem binding to multiple targets (L, D-transpeptidases and D, D-carboxypeptidase) provides mechanistic rationale for the effectiveness of this dual β-lactam combination in Mab infections.

Neurological complications of COVID-19 are not well described. We report two patients who were diagnosed with COVID-19 after presenting with diplopia and ophthalmoparesis.