Faculty Bibliography

Importance: Shift-to-shift transitions in care among house staff are associated with adverse events. However, the association between end-of-rotation transition (in which care of the patient is transferred) and adverse events is uncertain. Objective: To examine the association of end-of-rotation house staff transitions with mortality among hospitalized patients. Design, Setting, and Participants: Retrospective multicenter cohort study of patients admitted to internal medicine services (N = 230701) at 10 university-affiliated US Veterans Health Administration hospitals (2008-2014). Exposures: Transition patients (defined as those admitted prior to an end-of-rotation transition who died or were discharged within 7 days following transition) were stratified by type of transition (intern only, resident only, or intern + resident) and compared with all other discharges (control). An alternative analysis comparing admissions within 2 days before transition with admissions on the same 2 days 2 weeks later was also conducted. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included 30-day and 90-day mortality and readmission rates. A difference-in-difference analysis assessed whether outcomes changed after the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour regulations. Adjustments included age, sex, race/ethnicity, month, year, length of stay, comorbidities, and hospital. Results: Among 230701 patient discharges (mean age, 65.6 years; men, 95.8%; median length of stay, 3.0 days), 25938 intern-only, 26456 resident-only, and 11517 intern + resident end-of-rotation transitions occurred. Overall mortality was 2.18% in-hospital, 9.45% at 30 days, and 14.43% at 90 days. Adjusted hospital mortality was significantly greater in transition vs control patients for the intern-only group (3.5% vs 2.0%; odds ratio [OR], 1.12 [95% CI, 1.03-1.21]) and the intern + resident group (4.0% vs 2.1%; OR, 1.18 [95% CI, 1.06-1.33]), but not for the resident-only group (3.3% vs 2.0%; OR, 1.07 [95% CI, 0.99-1.16]). Adjusted 30-day and 90-day mortality rates were greater in all transition vs control comparisons (30-day mortality: intern-only group, 14.5% vs 8.8%, OR, 1.17 [95% CI, 1.13-1.22]; resident-only group, 13.8% vs 8.9%, OR, 1.11 [95% CI, 1.04-1.18]; intern + resident group, 15.5% vs 9.1%, OR, 1.21 [95% CI, 1.12-1.31]; 90-day mortality: intern-only group, 21.5% vs 13.5%, OR, 1.14 [95% CI, 1.10-1.19]; resident-only group, 20.9% vs 13.6%, OR, 1.10 [95% CI, 1.05-1.16]; intern + resident group, 22.8% vs 14.0%, OR, 1.17 [95% CI, 1.11-1.23]). Duty hour changes were associated with greater adjusted hospital mortality for transition patients in the intern-only group and intern + resident group than for controls (intern-only: OR, 1.11 [95% CI, 1.02-1.21]; intern + resident: OR, 1.17 [95% CI, 1.02-1.34]). The alternative analyses did not demonstrate any significant differences in mortality between transition and control groups. Conclusions and Relevance: Among patients admitted to internal medicine services in 10 Veterans Affairs hospitals, end-of-rotation transition in care was associated with significantly higher in-hospital mortality in an unrestricted analysis that included most patients, but not in an alternative restricted analysis. The association was stronger following institution of ACGME duty hour regulations.

Importance: The delivery of palliative care is not standard of care within most emergency departments (EDs). Objective: To compare quality of life, depression, health care utilization, and survival in ED patients with advanced cancer randomized to ED-initiated palliative care consultation vs care as usual. Design, Setting, and Participants: A single-blind, randomized clinical trial of ED-initiated palliative care consultation for patients with advanced cancer vs usual care took place from June 2011 to April 2014 at an urban, academic ED at a quaternary care referral center. Adult patients with advanced cancer who were able to pass a cognitive screen, had never been seen by palliative care, spoke English or Spanish, and presented to the ED met eligibility criteria; 136 of 298 eligible patients were approached and enrolled in the ED and randomized via balanced block randomization. Interventions: Intervention participants received a comprehensive palliative care consultation by the inpatient team, including an assessment of symptoms, spiritual and/or social needs, and goals of care. Main Outcomes and Measures: The primary outcome was quality of life as measured by the change in Functional Assessment of Cancer Therapy-General Measure (FACT-G) score at 12 weeks. Secondary outcomes included major depressive disorder as measured by the Patient Health Questionnaire-9, health care utilization at 180 days, and survival at 1 year. Results: A total of 136 participants were enrolled, and 69 allocated to palliative care (mean [SD], 55.1 [13.1] years) and 67 were randomized to usual care (mean [SD], 57.8 [14.7] years). Quality of life, as measured by a change in FACT-G score from enrollment to 12 weeks, was significantly higher in patients randomized to the intervention group, who demonstrated a mean (SD) increase of 5.91 (16.65) points compared with 1.08 (16.00) in controls (P = .03 using the nonparametric Wilcoxon test). Median estimates of survival were longer in the intervention group than the control group: 289 (95% CI, 128-453) days vs 132 (95% CI, 80-302) days, although this did not reach statistical significance (P = .20). There were no statistically significant differences in depression, admission to the intensive care unit, and discharge to hospice. Conclusions and Relevance: Emergency department-initiated palliative care consultation in advanced cancer improves quality of life in patients with advanced cancer and does not seem to shorten survival; the impact on health care utilization and depression is less clear and warrants further study. Trial Registration: clinicaltrials.gov Identifier: NCT01358110.

Recently many regularized estimators of large covariance matrices have been proposed, and the tuning parameters in these estimators are usually selected via cross-validation. However, there is a lack of consensus on the number of folds for conducting cross-validation. One round of cross-validation involves partitioning a sample of data into two complementary subsets, a training set and a validation set. In this manuscript, we demonstrate that if the estimation accuracy is measured in the Frobenius norm, the training set should consist of majority of the data; whereas if the estimation accuracy is measured in the operator norm, the validation set should consist of majority of the data. We also develop methods for selecting tuning parameters based on the bootstrap and compare them with their cross-validation counterparts. We demonstrate that the cross-validation methods with optimal' choices of folds are more appropriate than their bootstrap counterparts.

In this paper we develop a generalized partial linear model for longitudinal data. In the model, we allow the link and baseline functions to be unknown. We explicitly express the estimators of regression parameters and the baseline function; hence, the computation and programming of our estimators are simple. We show that the proposed estimators of regression parameters and the baseline function are asymptotically normal with a simple variance estimator for the baseline function. In simulation studies, we demonstrate that the proposed nonparametric method is robust with limited loss of efficiency.

Recently, Wang and Qin proposed various bias-corrected empirical likelihood confidence regions for any two of the three parameters, sensitivity, specificity, and cut-off value, with the remaining parameter fixed at a given value in the evaluation of a continuous-scale diagnostic test with verification bias. In order to apply those methods, quantiles of the limiting weighted chi-squared distributions of the empirical log-likelihood ratio statistics should be estimated. In order to facilitate application and reduce computation burden, in this paper, jackknife empirical likelihood-based methods are proposed for any pairs of sensitivity, specificity and cut-off value, and asymptotic results can be derived accordingly. The proposed methods can be easily implemented to construct confidence regions for the evaluation of continuous-scale diagnostic tests with verification bias. Simulation studies are conducted to evaluate the finite sample performance and robustness of the proposed jackknife empirical likelihood-based confidence regions in terms of coverage probabilities. Finally, a real case analysis is provided to illustrate the application of new methods.

BACKGROUND:Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25-60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. METHODS:Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. DISCUSSION/CONCLUSIONS:This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Patients with heart failure with preserved ejection fraction (HFpEF) often experience dyspnea, decreased exercise tolerance, and decreased quality of life (QOL). Exercise training is a promising non-pharmacological treatment, with some improvement in exercise tolerance and QOL in HFpEF patients in randomized controlled trials (RCTs). We conducted a systematic review and meta-analysis of RCTs examining the effect of exercise therapy on exercise tolerance, QOL, and echocardiographic parameters in patients with HFpEF. Article database search of PubMed, Embase, and Cochrane Central Register of Controlled Trials identified 15 publications representing 579 unique patients. Results are presented as weighted mean difference (WMD) with 95% confidence intervals (CI). Exercise training (compared to control) demonstrated a significant improvement in exercise tolerance as measured by peak absolute VO2 (WMD [95% CI] = 164.67 [65.54, 263.79] mL/min), peak relative VO2 (WMD [95% CI] = 1.85 [0.98, 2.73] mL/min/kg), workload (WMD [95% CI] = 12.92 [4.67, 21.17] W), exercise time (WMD [95% CI] = 2.05 [1.57, 2.53] min), anaerobic threshold (WMD [95% CI] = 170.31 [35.40, 305.22] mL/min/kg), and 6-min walk test distance (WMD [95% CI] = 32.77 [20.72, 44.83] m); in QOL as measured by Short Form (SF-36) physical functioning domain (WMD [95% CI] = 9.95 [2.85, 17.05]) and SF-36 vitality domain (WMD [95% CI] = 6.24 [0.15, 12.34]); and in the echocardiographic measure of LVESD (WMD [95% CI] =  - 0.16 [- 0.28, - 0.04] cm). In conclusion, we found after systematic review and meta-analysis of RCTs that exercise therapy improves exercise tolerance and physical-related quality of life measures.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To create a model of the anatomic distribution, recurrence, and growth patterns of recurrent respiratory papillomatosis (RRP). STUDY DESIGN/METHODS:Prospective, multi-institutional cohort study. METHODS:Adult patients with a diagnosis of RRP evaluated between August 1, 2018 and February 1, 2021 at six participating centers were invited to enroll. At each office or operating room encounter, laryngologists recorded the location and size of RRP lesions using a 22-region schematic. A generalized linear mixed effects model was used to compare region variations in lesion prevalence and recurrence. RESULTS:The cohort comprised 121 patients: 74% were male, 81% had been diagnosed with adult-onset RRP, and a plurality (34%) had undergone 0 to 3 RRP interventions prior to enrollment. Across the study period, the odds of a lesion occurring in the glottis was significantly higher (odds ratio [OR]: 26.51; 95% confidence interval [CI]: 11.76-59.75, P < .001) compared with all other areas of the larynx and trachea. Within the true vocal folds, the membranous vocal folds had significantly higher odds (OR: 6.16; 95% CI: 2.66-14.30, P < .001) of lesion occurrence compared to the cartilaginous vocal folds. Despite these strong trends in lesion distribution, there were no differences in the odds of lesion recurrence, growth, or in the time to recurrence, between anatomic subsites. CONCLUSIONS:RRP lesions are most likely to occur in the glottis, particularly the membranous vocal folds, compared with other regions of the larynx or trachea. However, all lesions demonstrate similar behavior with respect to recurrence, growth, and time to recurrence regardless of anatomic location. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2022.

BACKGROUND:Social determinants of health (SDOH) refer to the social, economic, and psychosocial conditions that influence health. Lower levels of SDOH factors including income, education, and employment are associated with a higher prevalence of diabetes, poorer glycemic control, and increased diabetes-related mortality. Few studies have conducted a comprehensive evaluation of multiple SDOH factors in a population with type 2 diabetes mellitus (T2DM). OBJECTIVE:This study aimed to identify the range of SDOH challenges-including diabetes-related distress-that impact patients with insulin-dependent diabetes at an urban safety-net clinic using the 5-domain SDOH framework developed by the Healthy People 2020 initiative. METHODS:The pilot study used a cross-sectional, mixed methods approach. Participants were recruited from 3 programs within a general internal medicine clinic that provides ambulatory care for patients with uncontrolled T2DM. We administered an investigator-developed SDOH survey based on the Healthy People 2020 framework and the validated Diabetes Distress Scale (DDS), which assesses 4 domains of diabetes-related distress. One-on-one interviews were conducted to gain in-depth information about challenges. RESULTS:level of 11.0% (SD 2.6%). Overall, 92% (52/57) of participants had a barrier in at least one SDOH domain. SDOH challenges were most commonly reported in the domain of Health and Health Care (84%, 48/57), followed by Economic Stability (54%, n=31), Neighborhood and Built Environment (53%, n=30), Education and Health Literacy (47%, n=27), and Social and Community context (37%, n=21). The mean overall DDS score was 2.09 (SD 0.84), where scores of ≥2 indicate distress. Further, 79% (45/57) of participants had at least moderate diabetes-related distress in one of the 4 DDS domains. General themes that emerged from participant interviews included job interference with healthy behaviors, concerns about burdening others, challenges communicating with providers, and difficulty getting appointments in a timely manner. CONCLUSIONS:We found high levels of SDOH barriers across all 5 domains of the Center for Disease Control and Prevention's Healthy People 2020 framework, including significant levels of diabetes-related distress. Future programs to address SDOH barriers in patients with uncontrolled insulin-dependent diabetes should consider screening for and focusing on a wide range of challenges.