Publications

2024

Straus, Sabrina, Sai Divya Yadavalli, Sara Allievi, Andrew Sanders, Roger B Davis, Mahmoud B Malas, Grace J Wang, et al. (2024) 2024. “Seven Years of the Transcarotid Artery Revascularization Surveillance Project, Comparison to Transfemoral Stenting and Endarterectomy”. Journal of Vascular Surgery. https://doi.org/10.1016/j.jvs.2024.05.048.

OBJECTIVE: This study utilizes the latest data from the Vascular Quality Initiative (VQI), which now encompasses over 50,000 transcarotid artery revascularization (TCAR) procedures, to offer a sizeable dataset for comparing the effectiveness and safety of TCAR, transfemoral carotid artery stenting (tfCAS), and carotid endarterectomy (CEA). Given this substantial dataset, we are now able to compare outcomes overall and stratified by symptom status across revascularization techniques.

METHODS: Utilizing VQI data from September 2016 to August 2023, we conducted a risk-adjusted analysis by applying inverse probability of treatment weighting to compare in-hospital outcomes between TCAR vs tfCAS, CEA vs tfCAS, and TCAR vs CEA. Our primary outcome measure was in-hospital stroke/death. Secondary outcomes included myocardial infarction and cranial nerve injury.

RESULTS: A total of 50,068 patients underwent TCAR, 25,361 patients underwent tfCAS, and 122,737 patients underwent CEA. TCAR patients were older, more likely to have coronary artery disease, chronic kidney disease, and undergo coronary artery bypass grafting/percutaneous coronary intervention as well as prior contralateral CEA/CAS compared with both CEA and tfCAS. TfCAS had higher odds of stroke/death when compared with TCAR (2.9% vs 1.6%; adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.65-2.06; P < .001) and CEA (2.9% vs 1.3%; aOR, 2.21; 95% CI, 2.01-2.43; P < .001). CEA had slightly lower odds of stroke/death compared with TCAR (1.3% vs 1.6%; aOR, 0.83; 95% CI, 0.76-0.91; P < .001). TfCAS had lower odds of cranial nerve injury compared with TCAR (0.0% vs 0.3%; aOR, 0.00; 95% CI, 0.00-0.00; P < .001) and CEA (0.0% vs 2.3%; aOR, 0.00; 95% CI, 0.0-0.0; P < .001) as well as lower odds of myocardial infarction compared with CEA (0.4% vs 0.6%; aOR, 0.67; 95% CI, 0.54-0.84; P < .001). CEA compared with TCAR had higher odds of myocardial infarction (0.6% vs 0.5%; aOR, 1.31; 95% CI, 1.13-1.54; P < .001) and cranial nerve injury (2.3% vs 0.3%; aOR, 9.42; 95% CI, 7.78-11.4; P < .001).

CONCLUSIONS: Although tfCAS may be beneficial for select patients, the lower stroke/death rates associated with CEA and TCAR are preferred. When deciding between CEA and TCAR, it is important to weigh additional procedural factors and outcomes such as myocardial infarction and cranial nerve injury, particularly when stroke/death rates are similar. Additionally, evaluating subgroups that may benefit from one procedure over another is essential for informed decision-making and enhanced patient care in the treatment of carotid stenosis.

Duong, David B, Bethany Holt, Chris Munoz, and Todd M Pollack. (2024) 2024. “For and With People: Announcing the Lancet Global Health Commission on People-Centred Care for Universal Health Coverage and a Call for Commissioner Nominations”. The Lancet. Global Health 12 (7): e1089-e1090. https://doi.org/10.1016/S2214-109X(24)00216-X.
Haimovich, Adrian D, Ryan C Burke, Larry A Nathanson, David Rubins, Andrew Taylor, Erin K Kross, Kei Ouchi, Nathan I Shapiro, and Mara A Schonberg. (2024) 2024. “Geriatric End-of-Life Screening Tool Prediction of 6-Month Mortality in Older Patients”. JAMA Network Open 7 (5): e2414213. https://doi.org/10.1001/jamanetworkopen.2024.14213.

IMPORTANCE: Emergency department (ED) visits by older adults with life-limiting illnesses are a critical opportunity to establish patient care end-of-life preferences, but little is known about the optimal screening criteria for resource-constrained EDs.

OBJECTIVES: To externally validate the Geriatric End-of-Life Screening Tool (GEST) in an independent population and compare it with commonly used serious illness diagnostic criteria.

DESIGN, SETTING, AND PARTICIPANTS: This prognostic study assessed a cohort of patients aged 65 years and older who were treated in a tertiary care ED in Boston, Massachusetts, from 2017 to 2021. Patients arriving in cardiac arrest or who died within 1 day of ED arrival were excluded. Data analysis was performed from August 1, 2023, to March 27, 2024.

EXPOSURE: GEST, a logistic regression algorithm that uses commonly available electronic health record (EHR) datapoints and was developed and validated across 9 EDs, was compared with serious illness diagnoses as documented in the EHR. Serious illnesses included stroke/transient ischemic attack, liver disease, cancer, lung disease, and age greater than 80 years, among others.

MAIN OUTCOMES AND MEASURES: The primary outcome was 6-month mortality following an ED encounter. Statistical analyses included area under the receiver operating characteristic curve, calibration analyses, Kaplan-Meier survival curves, and decision curves.

RESULTS: This external validation included 82 371 ED encounters by 40 505 unique individuals (mean [SD] age, 76.8 [8.4] years; 54.3% women, 13.8% 6-month mortality rate). GEST had an external validation area under the receiver operating characteristic curve of 0.79 (95% CI, 0.78-0.79) that was stable across years and demographic subgroups. Of included encounters, 53.4% had a serious illness, with a sensitivity of 77.4% (95% CI, 76.6%-78.2%) and specificity of 50.5% (95% CI, 50.1%-50.8%). Varying GEST cutoffs from 5% to 30% increased specificity (5%: 49.1% [95% CI, 48.7%-49.5%]; 30%: 92.2% [95% CI, 92.0%-92.4%]) at the cost of sensitivity (5%: 89.3% [95% CI, 88.8-89.9]; 30%: 36.2% [95% CI, 35.3-37.1]). In a decision curve analysis, GEST outperformed serious illness criteria across all tested thresholds. When comparing patients referred to intervention by GEST with serious illness criteria, GEST reclassified 45.1% of patients with serious illness as having low risk of mortality with an observed mortality rate 8.1% and 2.6% of patients without serious illness as having high mortality risk with an observed mortality rate of 34.3% for a total reclassification rate of 25.3%.

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that both serious illness criteria and GEST identified older ED patients at risk for 6-month mortality, but GEST offered more useful screening characteristics. Future trials of serious illness interventions for high mortality risk in older adults may consider transitioning from diagnosis code criteria to GEST, an automatable EHR-based algorithm.

Juraschek, Stephen P. (2024) 2024. “Size Dimension Chart for Reference Cuff Validation and Limitations in Current Recommendations”. American Journal of Hypertension. https://doi.org/10.1093/ajh/hpae061.

BACKGROUND: International standards used for device validation protocols require that the reference cuff conform to a width and length that is 37 to 50% and 75 to 100% of the arm circumference, respectively. However, there is no published chart of appropriate width and length dimensions across the range of arm circumferences. Our objective was to create a chart that could be used to guide reference cuff selection and compare recommended dimensions with two common cuff systems.

METHODS: Arm circumferences, ranging from 22 to 52 cm were used to create a reference table for width and length requirements. Arm circumferences were grouped following the American Heart Association recommendation for cuff sizes. Cuff dimension data was extracted from the website of a cuff system commonly used for validations (the Baum Corporation) and compared both the American Heart Association recommendations and Baum sizes with the recommended reference dimensions.

RESULTS: There were discrepancies in size naming conventions between the Baum Corporation and the American Heart Association cuff systems. Moreover, there were gaps in both systems where the cuff would not be recommended for validation (31-32 cm for Baum and 30-31 cm for the American Heart Association). Neither system had cuffs that could be used for the largest arm circumferences.

CONCLUSIONS: Our chart highlights the need for more than one cuff system in validation studies and the critical need for cuffs that could be used for validation among larger arm circumferences.

Hamaya, Rikuta, Molin Wang, Stephen P Juraschek, Kenneth J Mukamal, JoAnn E Manson, Deirdre K Tobias, Qi Sun, et al. (2024) 2024. “Prediction of 24-Hour Urinary Sodium Excretion Using Machine-Learning Algorithms”. Journal of the American Heart Association 13 (10): e034310. https://doi.org/10.1161/JAHA.123.034310.

BACKGROUND: Accurate quantification of sodium intake based on self-reported dietary assessments has been a persistent challenge. We aimed to apply machine-learning (ML) algorithms to predict 24-hour urinary sodium excretion from self-reported questionnaire information.

METHODS AND RESULTS: We analyzed 3454 participants from the NHS (Nurses' Health Study), NHS-II (Nurses' Health Study II), and HPFS (Health Professionals Follow-Up Study), with repeated measures of 24-hour urinary sodium excretion over 1 year. We used an ensemble approach to predict averaged 24-hour urinary sodium excretion using 36 characteristics. The TOHP-I (Trial of Hypertension Prevention I) was used for the external validation. The final ML algorithms were applied to 167 920 nonhypertensive adults with 30-year follow-up to estimate confounder-adjusted hazard ratio (HR) of incident hypertension for predicted sodium. Averaged 24-hour urinary sodium excretion was better predicted and calibrated with ML compared with the food frequency questionnaire (Spearman correlation coefficient, 0.51 [95% CI, 0.49-0.54] with ML; 0.19 [95% CI, 0.16-0.23] with the food frequency questionnaire; 0.46 [95% CI, 0.42-0.50] in the TOHP-I). However, the prediction heavily depended on body size, and the prediction of energy-adjusted 24-hour sodium excretion was modestly better using ML. ML-predicted sodium was modestly more strongly associated than food frequency questionnaire-based sodium in the NHS-II (HR comparing Q5 versus Q1, 1.48 [95% CI, 1.40-1.56] with ML; 1.04 [95% CI, 0.99-1.08] with the food frequency questionnaire), but no material differences were observed in the NHS or HPFS.

CONCLUSIONS: The present ML algorithm improved prediction of participants' absolute 24-hour urinary sodium excretion. The present algorithms may be a generalizable approach for predicting absolute sodium intake but do not substantially reduce the bias stemming from measurement error in disease associations.

Minami, Christina A, Ginger Jin, Rachel A Freedman, Mara A Schonberg, Tari A King, and Elizabeth A Mittendorf. (2024) 2024. “Physician-Level Variation in Axillary Surgery in Older Adults With T1N0 Hormone Receptor-Positive Breast Cancer: A Retrospective Population-Based Cohort Study”. Journal of Geriatric Oncology 15 (5): 101795. https://doi.org/10.1016/j.jgo.2024.101795.

INTRODUCTION: We sought to determine how considerations specific to older adults impact between- and within-surgeon variation in axillary surgery use in women ≥70 years with T1N0 HR+ breast cancer.

MATERIALS AND METHODS: Females ≥70 years with T1N0 HR+/HER2-negative breast cancer diagnosed from 2013 to 2015 in SEER-Medicare were identified and linked to the American Medical Association Masterfile. The outcome of interest was axillary surgery. Key patient-level variables included the Charlson Comorbidity Index (CCI) score, frailty (based on a claims-based frailty index score), and age (≥75 vs <75). Multilevel mixed models with surgeon clusters were used to estimate the intracluster correlation coefficient (ICC) (between-surgeon variance), with 1-ICC representing within-surgeon variance.

RESULTS: Of the 4410 participants included, 6.1% had a CCI score of ≥3, 20.7% were frail, and 58.3% were ≥ 75 years; 86.1% underwent axillary surgery. No surgeon omitted axillary surgery in all patients, but 42.3% of surgeons performed axillary surgery in all patients. In the null model, 10.5% of the variance in the axillary evaluation was attributable to between-surgeon differences. After adjusting for CCI score, frailty, and age in mixed models, between-surgeon variance increased to 13.0%.

DISCUSSION: In this population, axillary surgery varies more within surgeons than between surgeons, suggesting that surgeons are not taking an "all-or-nothing" approach. Comorbidities, frailty, and age accounted for a small proportion of the variation, suggesting nuanced decision-making may include additional, unmeasured factors such as differences in surgeon-patient communication.

Yang, EunMee, Weidong Lu, Dennis Muñoz-Vergara, Esme Goldfinger, Ted J Kaptchuk, Vitaly Napadow, Andrew C Ahn, and Peter M Wayne. (2024) 2024. “Acupoint Sensitivity in Health and Disease: A Systematic Review”. Journal of Integrative and Complementary Medicine. https://doi.org/10.1089/jicm.2023.0204.

Introduction: The concept of acupoints is a key defining feature of acupuncture, yet the scientific basis of acupoints remains unclear. In recent years, there has been an emerging body of animal studies demonstrating an association between cutaneous sensitivity and visceral pathophysiology, through which acupoints over the skin are sensitized in pathologic conditions. Several studies with humans have also been conducted to assess whether the sensitivity of acupoints is distinct in healthy versus clinical populations. However, no systematic review has been conducted to collate and synthesize the status and quality of human studies on this topic. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Literature search was performed by combining variations of search terms related to acupoints and pain sensitivity in PubMed, EMBASE, and Alt HealthWatch (EBSCOHost). Screening of titles and abstracts and review of full-text articles for eligibility were performed by two independent investigators. Using a predefined template, information on subject characteristics, pathologic conditions, names of assessed acupoints, and relevant main findings were extracted from the included studies. The methodological quality of included studies was assessed using a modified Newcastle-Ottawa Scale (NOS) for case-control studies. A quality assessment checklist was also developed by the present authors to examine the quality of reporting of experimental variables that were considered important for evaluating acupoint sensitivity. Results: A total of 3453 studies were identified from the database search, of which 11 met the eligibility criteria to be included in this review. Six studies examined the mechanical sensitivity of body acupoints, and the remaining five studies examined the mechanical sensitivity of auricular points. Overall, findings suggest that the sensitivity of acupoints may be distinct in healthy versus clinical populations. However, there were various potential sources of bias and substantial heterogeneity across included studies in clinical conditions and acupoints. Conclusion: There is at present insufficient evidence to support or refute that acupoints in humans are sensitized in pathologic conditions. There were various methodological issues, including small sample size and poor reporting of experimental design and variables, which limit the ability to draw a definitive conclusion on this topic. It is also largely unclear whether it is the general body regions rather than specific acupoints that may be sensitized, as most studies did not include nonacupoint location(s) for comparison. Thus, further rigorous research is warranted.

Coylewright, Megan, Diana Otero, Brian R Lindman, Melissa M Levack, Aaron Horne, Long H Ngo, Melissa Beaudry, Hannah Col V, and Nananda F Col. (2024) 2024. “An Interactive, Online Decision Aid Assessing Patient Goals and Preferences for Treatment of Aortic Stenosis to Support Physician-Led Shared Decision-Making: Early Feasibility Pilot Study”. PloS One 19 (5): e0302378. https://doi.org/10.1371/journal.pone.0302378.

BACKGROUND: Guidelines recommend shared decision making when choosing treatment for severe aortic stenosis but implementation has lagged. We assessed the feasibility and impact of a novel decision aid for severe aortic stenosis at point-of-care.

METHODS: This prospective multi-site pilot cohort study included adults with severe aortic stenosis and their clinicians. Patients were referred by their heart team when scheduled to discuss treatment options. Outcomes included shared decision-making processes, communication quality, decision-making confidence, decisional conflict, knowledge, stage of decision making, decision quality, and perceptions of the tool. Patients were assessed at baseline (T0), after using the intervention (T1), and after the clinical encounter (T2); clinicians were assessed at T2. Before the encounter, patients reviewed the intervention, Aortic Valve Improved Treatment Approaches (AVITA), an interactive, online decision aid. AVITA presents options, frames decisions, clarifies patient goals and values, and generates a summary to use with clinicians during the encounter.

RESULTS: 30 patients (9 women [30.0%]; mean [SD] age 70.4 years [11.0]) and 14 clinicians (4 women [28.6%], 7 cardiothoracic surgeons [50%]) comprised 28 clinical encounters Most patients [85.7%] and clinicians [84.6%] endorsed AVITA. Patients reported AVITA easy to use [89.3%] and helped them choose treatment [95.5%]. Clinicians reported the AVITA summary helped them understand their patients' values [80.8%] and make values-aligned recommendations [61.5%]. Patient knowledge significantly improved at T1 and T2 (p = 0.004). Decisional conflict, decision-making stage, and decision quality improved at T2 (p = 0.0001, 0.0005, and 0.083, respectively). Most patients [60%] changed treatment preference between T0 and T2. Initial treatment preferences were associated with low knowledge, high decisional conflict, and poor decision quality; final preferences were associated with high knowledge, low conflict, and high quality.

CONCLUSIONS: AVITA was endorsed by patients and clinicians, easy to use, improved shared decision-making quality and helped patients and clinicians arrive at a treatment that reflected patients' values.

TRIAL REGISTRATION: Trial ID: NCT04755426, Clinicaltrials.gov/ct2/show/NCT04755426.

Moseholm, Kristine F, Jens W Horn, Annette L Fitzpatrick, Luc Djousse, W T Longstreth, Oscar L Lopez, Andrew N Hoofnagle, Majken K Jensen, Rozenn N Lemaitre, and Kenneth J Mukamal. (2024) 2024. “Circulating Sphingolipids and Subclinical Brain Pathology: The Cardiovascular Health Study”. Frontiers in Neurology 15: 1385623. https://doi.org/10.3389/fneur.2024.1385623.

BACKGROUND: Sphingolipids are implicated in neurodegeneration and neuroinflammation. We assessed the potential role of circulating ceramides and sphingomyelins in subclinical brain pathology by investigating their association with brain magnetic resonance imaging (MRI) measures and circulating biomarkers of brain injury, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the Cardiovascular Health Study (CHS), a large and intensively phenotyped cohort of older adults.

METHODS: Brain MRI was offered twice to CHS participants with a mean of 5 years between scans, and results were available from both time points in 2,116 participants (mean age 76 years; 40% male; and 25% APOE ε4 allele carriers). We measured 8 ceramide and sphingomyelin species in plasma samples and examined the associations with several MRI, including worsening grades of white matter hyperintensities and ventricular size, number of brain infarcts, and measures of brain atrophy in a subset with quantitative measures. We also investigated the sphingolipid associations with serum NfL and GFAP.

RESULTS: In the fully adjusted model, higher plasma levels of ceramides and sphingomyelins with a long (16-carbon) saturated fatty acid were associated with higher blood levels of NfL [β = 0.05, false-discovery rate corrected P (PFDR) = 0.004 and β = 0.06, PFDR = < 0.001, respectively]. In contrast, sphingomyelins with very long (20- and 22-carbon) saturated fatty acids tended to have an inverse association with levels of circulating NfL. In secondary analyses, we found an interaction between ceramide d18:1/20:0 and sex (P for interaction = <0.001), such that ceramide d18:1/20:0 associated with higher odds for infarcts in women [OR = 1.26 (95%CI: 1.07, 1.49), PFDR = 0.03]. We did not observe any associations with GFAP blood levels, white matter grade, ventricular grade, mean bilateral hippocampal volume, or total brain volume.

CONCLUSION: Overall, our comprehensive investigation supports the evidence that ceramides and sphingomyelins are associated with increased aging brain pathology and that the direction of association depends on the fatty acid attached to the sphingosine backbone.