Faculty Bibliography

Persons living with advanced cancer have intensive symptoms and psychosocial needs that often result in visits to the Emergency Department (ED). We report on program engagement, advance care planning (ACP), and hospice use for a 6-month longitudinal nurse-led, telephonic palliative care intervention for patients with advanced cancer as part of a larger randomized trial. Patients 50 years and older with metastatic solid tumors were recruited from 18 EDs and randomized to receive nursing calls focused on ACP, symptom management, and care coordination or specialty outpatient palliative care (ClinicialTrials.gov: NCT03325985). One hundred and five (50%) graduated from the 6-month program, 54 (26%) died or enrolled in hospice, 40 (19%) were lost to follow-up, and 19 (9%) withdrew prior to program completion. In a Cox proportional hazard regression, withdrawn subjects were more likely to be white and have a low symptom burden compared to those who did not withdraw. Two hundred eighteen persons living with advanced cancer were enrolled in the nursing arm, and 182 of those (83%) completed some ACP. Of the subjects who died, 43/54 (80%) enrolled in hospice. Our program demonstrated high rates of engagement, ACP, and hospice enrollment. Enrolling subjects with a high symptom burden may result in even greater program engagement.

The American Society of Anesthesiologists Physical Status (ASA-PS) grade better risk stratifies geriatric trauma patients, but it is only reported in patients scheduled for surgery. The Charlson Comorbidity Index (CCI), however, is available for all patients. This study aims to create a crosswalk from the CCI to ASA-PS. Geriatric trauma cases, aged 55 years and older with both ASA-PS and CCI values (N = 4223), were used for the analysis. We assessed the relationship between CCI and ASA-PS, adjusting for age, sex, marital status, and body mass index. We reported the predicted probabilities and the receiver operating characteristics. A CCI of zero was highly predictive of ASA-PS grade 1 or 2, and a CCI of 1 or higher was highly predictive of ASA-PS grade 3 or 4. Additionally, while a CCI of 3 predicted ASA-PS grade 4, a CCI of 4 and higher exhibited greater accuracy in predicting ASA-PS grade 4. We created a formula that may accurately situate a geriatric trauma patient in the appropriate ASA-PS grade after adjusting for age, sex, marital status, and body mass index. In conclusion, ASA-PS grades can be predicted from CCI, and this may aid in generating more predictive trauma models.

This case study describes, for the time frame of June 2021 through August 2022, the U.S. Veterans Health Administration (VHA) organizational response to a manufacturer's recall of positive airway pressure devices used in the treatment of sleep disordered breathing. VHA estimated it could take over a year for Veterans to receive replacement devices. Veterans awaiting a replacement faced a dilemma. They could continue using the recalled devices and bear the product safety risks that led to the recall, or they could stop using them and bear the risks of untreated sleep disordered breathing. Using a program monitoring approach, we report on the processes VHA put in place to respond to the recall. Specifically, we report on the strategic, service, and operational plans associated with VHA's response to the recall for Veterans needing replacement devices. In program monitoring, the strategic plan reflects the internal process objectives for the program. The service plan articulates how the delivery of services will intersect the customer journey. The operational plan describes how the program's resources and actions must support the service delivery plan. VHA's strategic plan featured a clinician-led, as opposed to primarily legal or administrative response to the recall. The recall response team also engaged with VHA's medical ethics service to articulate an ethical framework guiding the allocation of replacement devices under conditions of scarcity. This framework proposed allocating scarce devices to Veterans according to their clinical need. The service plan invited Veterans to schedule visits with sleep providers who could assess their clinical need and counsel them accordingly. The operational plan distributed devices according to clinical need as they became available. Monitoring our program processes in real time helped VHA launch and adapt its response to a recall affecting more than 700,000 Veterans.

BACKGROUND:Epigenetic age acceleration (EAA) and epigenetic gestational age acceleration (EGAA) are biomarkers of physiological development and may be affected by the perinatal environment. The aim of this study was to evaluate performance of epigenetic clocks and to identify biological and sociodemographic correlates of EGAA and EAA at birth and in childhood. In the Project Viva pre-birth cohort, DNA methylation was measured in nucleated cells in cord blood (leukocytes and nucleated red blood cells, N = 485) and leukocytes in early (N = 120, median age = 3.2 years) and mid-childhood (N = 460, median age = 7.7 years). We calculated epigenetic gestational age (EGA; Bohlin and Knight clocks) and epigenetic age (EA; Horvath and skin & blood clocks), and respective measures of EGAA and EAA. We evaluated the performance of clocks relative to chronological age using correlations and median absolute error. We tested for associations of maternal-child characteristics with EGAA and EAA using mutually adjusted linear models controlling for estimated cell type proportions. We also tested associations of Horvath EA at birth with childhood EAA. RESULTS:Bohlin EGA was strongly correlated with chronological gestational age (Bohlin EGA r = 0.82, p < 0.001). Horvath and skin & blood EA were weakly correlated with gestational age, but moderately correlated with chronological age in childhood (r = 0.45-0.65). Maternal smoking during pregnancy was associated with higher skin & blood EAA at birth [B (95% CI) = 1.17 weeks (- 0.09, 2.42)] and in early childhood [0.34 years (0.03, 0.64)]. Female newborns and children had lower Bohlin EGAA [- 0.17 weeks (- 0.30, - 0.04)] and Horvath EAA at birth [B (95% CI) = - 2.88 weeks (- 4.41, - 1.35)] and in childhood [early childhood: - 0.3 years (- 0.60, 0.01); mid-childhood: - 0.48 years (- 0.77, - 0.18)] than males. When comparing self-reported Asian, Black, Hispanic, and more than one race or other racial/ethnic groups to White, we identified significant differences in EGAA and EAA at birth and in mid-childhood, but associations varied across clocks. Horvath EA at birth was positively associated with childhood Horvath and skin & blood EAA. CONCLUSIONS:Maternal smoking during pregnancy and child sex were associated with EGAA and EAA at multiple timepoints. Further research may provide insight into the relationship between perinatal factors, pediatric epigenetic aging, and health and development across the lifespan.

BACKGROUND:Only half of patients with hypertension have adequately controlled blood pressure. Clinical decision support (CDS) has the potential to overcome barriers to delivering guideline-recommended care and improve hypertension management. However, optimal strategies for scaling CDS have not been well established, particularly in small, independent primary care practices which often lack the resources to effectively change practice routines. Practice facilitation is an implementation strategy that has been shown to support process changes. Our objective is to evaluate whether practice facilitation provided with hypertension-focused CDS can lead to improvements in blood pressure control for patients seen in small primary care practices. METHODS/DESIGN/METHODS:We will conduct a cluster randomized control trial to compare the effect of hypertension-focused CDS plus practice facilitation on BP control, as compared to CDS alone. The practice facilitation intervention will include an initial training in the CDS and a review of current guidelines along with follow-up for coaching and integration support. We will randomize 46 small primary care practices in New York City who use the same electronic health record vendor to intervention or control. All patients with hypertension seen at these practices will be included in the evaluation. We will also assess implementation of CDS in all practices and practice facilitation in the intervention group. DISCUSSION/CONCLUSIONS:The results of this study will inform optimal implementation of CDS into small primary care practices, where much of care delivery occurs in the U.S. Additionally, our assessment of barriers and facilitators to implementation will support future scaling of the intervention. CLINICALTRIALS/RESULTS:gov Identifier: NCT05588466.

OBJECTIVE:To examine the percentage and correlates of giving and receiving cigarettes as gifts among adult non-smokers in China. METHODS:We analyzed non-smokers (N=1,813) aged ≥18 years using data from the International Tobacco Control China Wave 5 Survey. Descriptive statistics summarized the characteristics of those who gave and received cigarettes as gifts. Multivariable logistic regression models were used to identify factors associated with the two behaviors. RESULTS:Among non-smokers, 9.9% reported giving cigarettes as gifts to family or friends in the last 6 months. Higher level of knowledge about smoking harms was associated with lower adjusted odds of gifting cigarettes. Non-smokers aged 25-39, with middle income, positive attitude toward cigarette gifts, exposure to anti-smoking information and smoking promotion, and those who reported receiving cigarettes as gifts from family or friends were more likely to give cigarettes as gifts. 6.6% of non-smokers reported receiving cigarettes as gifts in the last 6 months. High education, neutral or positive attitude toward cigarette gifts, exposure to anti-smoking information, exposure to smoking promotion, and having smoking friends were associated with receiving cigarettes as gifts. CONCLUSIONS:It is concerning that Chinese cultural norms that support cigarette gifting have extended to giving non-smokers cigarettes as gifts. Effective anti-smoking messages are needed. Changing the norms around cigarette gifting and increasing knowledge about smoking harms should help reduce cigarette gifting among non-smokers. IMPLICATIONS/CONCLUSIONS:Easy access to cigarettes received as gifts, along with the wide acceptance of smoking in China, places Chinese non-smokers in a risky position. More educational campaigns targeting non-smokers to proactively prevent them from smoking are called for.The ineffectiveness of existing anti-smoking information highlights the need for more effective anti-smoking messages.That attitude toward cigarette gifts is the strongest predictor of giving cigarettes as gifts suggests a need for interventions to reverse the positive attitude about cigarette gifting in order to decrease the popularity of this activity.

Background The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for cardiovascular disease prevention. We aimed to identify protein biomarkers of the DASH diet using data from 2 randomized feeding studies and validate them in an observational study, the ARIC (Atherosclerosis Risk in Communities) study. Methods and Results Large-scale proteomic profiling was conducted in serum specimens (SomaLogic) collected at the end of 8-week and 4-week DASH diet interventions in multicenter, randomized controlled feeding studies of the DASH trial (N=215) and the DASH-Sodium trial (N=396), respectively. Multivariable linear regression models were used to compare the relative abundance of 7241 proteins between the DASH and control diet interventions. Estimates from the 2 trials were meta-analyzed using fixed-effects models. We validated significant proteins in the ARIC study (N=10 490) using the DASH diet score. At a false discovery rate <0.05, there were 71 proteins that were different between the DASH diet and control diet in the DASH and DASH-Sodium trials. Nineteen proteins were validated in the ARIC study. The 19 proteins collectively improved the prediction of the DASH diet intervention in the feeding studies (range of difference in C statistics, 0.267-0.313; P<0.001 for both tests) and the DASH diet score in the ARIC study (difference in C statistics, 0.017; P<0.001) beyond participant characteristics. Conclusions We identified 19 proteins robustly associated with the DASH diet in 3 studies, which may serve as biomarkers of the DASH diet. These results suggest potential pathways that are impacted by consumption of the DASH diet. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03403166, NCT00000608.

PURPOSE/UNASSIGNED:Lamina cribrosa (LC) deformation is hypothesized to play a major role in glaucoma pathogenesis. The purpose of this study was to determine in vivo how varying intraocular pressure (IOP) under fixed intracranial pressure (ICP), and vice versa, deforms the pore paths throughout the LC volume. METHODS/UNASSIGNED:Spectral-domain optical coherence tomography scans of the optic nerve head were acquired from healthy adult rhesus monkeys under different pressures. IOP and ICP were controlled with gravity-based perfusion systems into the anterior chamber and lateral ventricle, respectively. IOP and ICP were modulated from baseline to high (19-30 mmHg) and highest (35-50 mmHg) levels while maintaining a fixed ICP of 8 to 12 mmHg and IOP of 15 mmHg, respectively. After three-dimensional registration and segmentation, the paths of pores visible in all settings were tracked based on their geometric centroids. Pore path tortuosity was defined as the measured distance divided by the minimal distance between the most anterior and posterior centroids. RESULTS/UNASSIGNED:The median pore tortuosity at baseline varied among the eyes (range, 1.16-1.68). For the IOP effect under fixed ICP (six eyes, five animals), two eyes showed statistically significant increased tortuosity and one showed a decrease (P < 0.05, mixed-effects model). No significant change was detected in three eyes. When modulating ICP under fixed IOP (five eyes, four animals), a similar response pattern was detected. CONCLUSIONS/UNASSIGNED:Baseline pore tortuosity and the response to acute pressure increase vary substantially across eyes. TRANSLATIONAL RELEVANCE/UNASSIGNED:LC pore path tortuosity could be associated with glaucoma susceptibility.

BACKGROUND:The glucose management indicator (GMI) is an estimated measure of hemoglobin A1c (HbA1c) recommended for the management of persons with diabetes using continuous glucose monitoring (CGM). However, GMI was derived primarily in young adults with type 1 diabetes, and its performance in patients with type 2 diabetes is poorly characterized. METHODS:We conducted a prospective cohort study in 144 adults with obstructive sleep apnea and type 2 diabetes not using insulin (mean age: 59.4 years; 45.1% female). HbA1c was measured at the study screening visit. Participants simultaneously wore 2 CGM sensors (Dexcom G4 and Abbott Libre Pro) for up to 4 weeks (2 weeks at baseline and 2 weeks at the 3-month follow-up visit). GMI was calculated using all available CGM data for each sensor. RESULTS:Median wear time was 27 days (IQR: 23-29) for the Dexcom G4 and 28 days (IQR: 24-29) for the Libre Pro. The mean difference between HbA1c and GMI was small (0.12-0.14 percentage points) (approximately 2 mmol/mol). However, the 2 measures were only moderately correlated (r = 0.68-0.71), and there was substantial variability in GMI at any given value of HbA1c (root mean squared error: 0.66-0.69 percentage points [7 to 8 mmol/mol]). Between 36% and 43% of participants had an absolute difference between HbA1c and GMI ≥0.5 percentage points (≥5 mmol/mol), and 9% to 18% had an absolute difference >1 percentage points (>11 mmol/mol). Discordance was higher in the Libre Pro than the Dexcom G4. CONCLUSIONS:GMI may be an unreliable measure of glycemic control for patients with type 2 diabetes and should be interpreted cautiously in clinical practice.Clinicaltrials.gov Registration Number: NCT02454153.