Publications

INTRODUCTION: Fear of cancer recurrence (FCR) is prevalent and distressing among survivors of cancer. Evidence-based mind-body and cognitive-behavioral skills lack integration and testing in scalable formats.

OBJECTIVE: This pilot randomized controlled trial (NCT04876599) tested a synchronous, virtual mind-body group resiliency intervention for FCR (IN FOCUS).

METHOD: Adults with elevated FCR (FCR Inventory severity ≥ 16; 16-21 = elevated, 22-36 = clinically elevated) after completing primary treatment for non-metastatic cancer were randomly assigned (1:1) to eight weekly sessions of IN FOCUS or usual care (UC; synchronous, virtual community group support referral). Feasibility metrics included ≥ 70% retention per arm (primary outcome), ≥ 75% attendance in ≥ 6 sessions, ≥ 75% adherence to relaxation skills practice ≥ 3 days per week and by delivery fidelity (% content covered in video-recorded sessions). Acceptability was assessed quantitatively via ratings of enjoyableness, convenience, helpfulness, odds of future use, and satisfaction (benchmark ≥ 80% of ratings ≥ 4 on 1-5 Likert scale) and qualitatively via individual exit interviews. Linear mixed models explicated slopes in FCR (secondary) and resiliency (exploratory; Current Experiences Scale) from baseline to 2 months (primary endpoint) and 5 months using intention-to-treat.

RESULTS: From July 2021 to March 2022, 64 survivors enrolled (25-73 years old, M = 7 years since diagnosis). IN FOCUS was feasible and acceptable (91% retention; attendance median = 7 sessions, 97% relaxation practice adherence, 95% content fully covered; 82% of acceptability ratings ≥ 4). Interviews (n = 59) revealed benefits in both arms. By 2 months, compared to UC, IN FOCUS reduced FCR to a medium-to-large effect (Mdiff = -2.4; 95% CI = -4.2, -0.7; d = 0.66). By 5 months, FCR effects had attenuated (Mdiff = -0.16, 95% CI -1.97, 1.65; d = -0.04), although levels of resiliency had increased with a medium-to-large effect (Mdiff = 10.0; 95% CI = 4.9, 15.1; d = 0.78).

CONCLUSIONS: For survivors of non-metastatic cancer, a synchronous, virtual mind-body resiliency program for FCR is feasible, acceptable, and seemingly beneficial compared to a community group referral.

BACKGROUND: Although the pathogenesis of delirium is poorly understood, increasing evidence supports a role for inflammation. Previously, individual inflammatory biomarkers have been associated with delirium. Aggregating biomarkers into an index may provide more information than individual biomarkers in predicting certain health outcomes (e.g., mortality); however, inflammatory indices have not yet been examined in delirium.

METHODS: Four inflammatory markers, C-reactive protein, Interleukin-6, Soluble Tumor Necrosis Factor Alpha Receptor-1, and Chitinase-3 Like Protein-1 (CHI3L1), were measured preoperatively (PREOP) and on postoperative day 2 (POD2) in 548 adults aged 70+ undergoing major noncardiac surgery (mean age 76.7 [standard deviation 5.2], 58% female, 24% delirium). From these markers, four inflammatory indices were considered: 1) quartile summary score, 2) weighted summary score (WSS), 3) principal component score, 4) a well-established inflammatory (LASSO-derived) index associated with mortality. Delirium was assessed using the Confusion Assessment Method (CAM), supplemented by chart review. Generalized linear models (GLM) with a log-link term were used to determine the association between each inflammatory index and delirium incidence.

RESULTS: Among the inflammatory indices, WSS demonstrated the strongest association with delirium: participants in WSS quartile (Q)4 had a higher risk of delirium vs. participants in Q1, after clinical variable adjustment (relative risk [RR], 95% confidence interval [CI] for PREOP: 3.07, 1.80-5.22; and POD2: 2.65, 1.63-4.30). WSS was more strongly associated with delirium than the strongest associated individual inflammatory marker (PREOP CHI3L1 [RR 2.45, 95% CI 1.53-3.92]; POD2 interleukin-6 [RR 2.39, 95% CI 1.50-3.82]).

CONCLUSIONS: A multi-protein inflammatory index using WSS provides a slight advantage over individual inflammatory markers in their association with delirium.

BACKGROUND: Delirium commonly occurs in older adults following surgery; although its pathophysiology is not fully understood, underlying neurodegeneration is a risk factor.

OBJECTIVE: Examine the association of preoperative levels of markers of neuronal damage, neurofilament light (NfL) and phosphorylated tau (p-tau)181, with postoperative delirium.

METHODS: Preoperative CSF and plasma were obtained from 158 patients undergoing hip fracture repair and enrolled in the clinical trial "A STrategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients" (STRIDE). Delirium diagnosis was adjudicated by a consensus panel. The association of plasma and CSF NfL and p-tau181 levels with delirium incidence and severity were examined for the overall cohort and for the subgroup (n=134) of patients without dementia.

RESULTS: Patients who developed delirium were older, had lower Mini-Mental State Exam (MMSE) score, higher Clinical Dementia Rating (CDR) and Geriatric Depression Scale (GDS) scores at baseline; the overall incidence of delirium was 37.6% and 31.1% for the subgroup without dementia. Plasma and CSF p-tau181 levels were not associated with delirium incidence or severity. CSF NfL levels were significantly associated with delirium severity, but not with incidence in the overall cohort. In the subgroup of patients without dementia, CSF NfL levels were significantly associated with increased odds of delirium incidence (OR 4.74, 95% CI 1.21-18.59, p=0.03) adjusted for age, sex, and CDR.

CONCLUSIONS: CSF NfL was significantly associated with delirium incidence and severity in patients without dementia undergoing hip fracture repair. Results confirm prior studies suggesting NfL as an important marker of delirium risk and supports an association between pre-existing axonal injury and delirium. These results highlight delirium vulnerability in older hip fracture patients, even when clinical dementia is not identified.

BACKGROUND: Concussions are common, particularly among young adults, and often are associated with persistent, debilitating, and hard-to-treat symptoms. Anxiety and concussion symptoms often amplify each other, and growing evidence indicates that anxiety plays a key role in symptoms persistence after concussion. Targeting anxiety early after concussion may be a promising means of helping prevent persistent concussion symptoms in this population. We developed the Toolkit for Optimal Recovery after Concussion (TOR-C), the first mind-body program tailored for young adults with a recent concussion and anxiety, aiming to prevent persistent concussion symptoms.

OBJECTIVE: This study aims to conduct an open pilot of TOR-C to test preliminary feasibility, signal of change in measures, and treatment perceptions.

METHODS: Five young adults (aged 18-24 years) attended 4 weekly one-on-one live video sessions with a clinician. Participants completed questionnaires measuring treatment targets (ie, pain catastrophizing, mindfulness, fear avoidance, limiting behaviors, and all-or-nothing behaviors) and outcomes (ie, postconcussive symptoms, physical function, anxiety, depression, and pain) at baseline, immediately following the intervention, and 3 months after intervention completion. At the conclusion of the program, participants attended a qualitative interview and provided feedback about the program to help optimize study content and procedures.

RESULTS: Feasibility markers were excellent for credibility and expectancy (5/5, 100% of participants scored above the credibility and expectancy scale midpoint), client satisfaction (4/5, 80% of participants scored above the Client Satisfaction Questionnaire midpoint), therapist adherence (97% adherence), acceptability of treatment (5/5, 100% of participants attended 3 or more sessions), adherence to homework (87% home practice completion), and feasibility of assessments (no measures fully missing). The feasibility of recruitment was good (5/7, 71% of eligible participants agreed to participate). There were preliminary signals of improvements from pre-post comparisons in treatment targets (d=0.72-2.20) and outcomes (d=0.41-1.38), which were sustained after 3 months (d=0.38-2.74 and d=0.71-1.63 respectively). Exit interviews indicated overall positive perceptions of skills and highlighted barriers (eg, busyness) and facilitators (eg, accountability) to engagement.

CONCLUSIONS: TOR-C shows preliminary feasibility, is associated with a signal of improvement in treatment targets and outcomes, and has the potential to support recovery from concussion. The quantitative findings along with the qualitative feedback obtained from the exit interviews will help optimize TOR-C in preparation for an upcoming randomized controlled trial of TOR-C versus an active control condition of health education for concussion recovery.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/25746.

OBJECTIVES: To assess the feasibility of the Toolkit for Optimal Recovery after Concussion (TOR-C), the first mind-body program aiming to prevent persistent concussion symptoms among young adults with anxiety, and an active control (Health Enhancement after Concussion; HE-C). We also tested preliminary improvements in outcome measures and putative mechanistic targets.

DESIGN: Single-blind, 2-arm, randomized controlled trial.

SETTING: Academic medical center in the US Northeast.

PARTICIPANTS: Fifty young adults (ages 18-35) with a recent concussion (3-10 weeks prior) and anxiety (≥5 on the GAD7 questionnaire).

INTERVENTIONS: Both interventions consisted of four 45-minute 1:1 sessions with a clinician over Zoom. TOR-C (n=25) taught mind-body, cognitive-behavioral, and return-to-activity skills. HE-C (n=25) taught health education (e.g., sleep, nutrition) without skills.

MAIN OUTCOME MEASURES: Primary: feasibility outcomes (e.g., recruitment, credibility, expectancy, acceptability, safety, feasibility of assessments, fidelity, satisfaction, TOR-C homework adherence) with a-priori-set benchmarks. Secondary: intervention outcomes were concussion symptoms (PCSS), physical function (WHODAS), anxiety (GAD7/HAD-A), depression (HADS-D) and pain (NRS). TOR-C mechanistic targets were pain catastrophizing (PCS), mindfulness (CAMS-R), fear avoidance (FAB-TBI), limiting behavior and all-or-nothing behavior (BRIQ).

RESULTS: Both interventions met all feasibility benchmarks and were associated with significant improvements in outcomes (concussion symptoms, physical function, anxiety, depression and pain; d=0.44-1.21) and TOR-C mechanistic targets (pain catastrophizing, mindfulness, fear-avoidance, and limiting behavior; Cohen's d=0.41-1.24). Improvements in all-or-nothing behavior were only significant in TOR-C (d=0.52). Improvements in all mechanistic targets except all-or-nothing behavior following TOR-C were significantly associated with improvements in at least one outcome.

CONCLUSION: Findings provide strong support for the feasibility of TOR-C and HE-C, and preliminary evidence for improvements in mechanistic targets and outcomes. Findings inform a future fully-powered RCT testing efficacy of TOR-C vs. HE-C.

BACKGROUND: Evidence is lacking on the relative contributions of specific lifestyle factors and their overall contribution to prevention of hypertension, in particular early-onset hypertension.

METHODS: This prospective cohort study included participants of the Nurses' Health Study (NHS, N = 52,780 women, aged 40-67 in 1986), the NHS II (N = 83,871 women, aged 27-46 in 1991), and the Health Professionals Follow-up Study (HPFS, N = 31,269 men, aged 40-75 in 1986), who were free from hypertension, cardiovascular disease and cancer at baseline. Four modifiable lifestyles were evaluated based on hypertension guidelines: BMI, moderate-to-vigorous physical activity, Dietary Approaches to Stop Hypertension (DASH) score, and alcohol intake. Primary outcome was incident self-reported diagnosis of hypertension with 27-31 years of follow-up.

RESULTS: Each lifestyle factor was associated with incident hypertension in dose-dependent manners across the cohorts, with BMI having the strongest associations. On average, adhering to BMI <25 kg/m2 was associated with 20.3 [18.5, 22.0], 25.0 [23.2, 26.8], and 18.6 [16.7, 20.7] months longer periods free from hypertension during 25-year follow-up in each cohort respectively. BMI accounted for approximately 20 % of incident hypertension in NHS and HPFS, and 35 % of early-onset hypertension (age < 55 y). Moderate-to-vigorous physical activity and diet accounted for 10-15 % of incident hypertension in women, and the contributions were greater for early-onset hypertension.

CONCLUSION: Healthy weight during adulthood was most substantially associated with incident hypertension among lifestyle factors, but diet, physical activity, and alcohol intake were also related to the risk across all ages, and hypertension-free periods, with stronger associations in early-onset hypertension.

IMPORTANCE: Social determinant of health (SDOH) data are essential to individualized care and reducing health disparities. However, there is little standardization in the way that SDOH data are collected, and barriers to increasing the collection of such data exist at both the patient and clinician levels.

OBJECTIVE: To evaluate clinician, patient, and care partner perspectives on the barriers to and facilitators of patients sharing SDOH information with their clinicians.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study included clinicians, patients, and care partners across the United States. Focus groups were conducted between September 2022 and February 2023 to understand the experience of collecting, documenting, and exchanging SDOH data.

MAIN OUTCOMES AND MEASURES: Rapid assessment procedures were used to analyze focus group transcripts, creating summaries, codes, and themes mapped directly to the project research questions.

RESULTS: A total of 235 individuals participated, including 109 (46.4%) clinicians (60 [55.0%] male; 25 [22.9%] Asian, 2 [1.8%] Black, and 74 [67.9%] White) and 126 (53.6%) patients and care partners (45 [35.7%] male; 1 [0.8%] Asian, 48 [38.1%] Black, and 64 [50.8%] White). Clinicians and patients agreed that SDOH data are important for clinicians to know. Both clinicians and patients wanted a structured, standardized way to collect SDOH data in the future, accompanied by time for more in-depth discussion during the visit. However, they highlighted numerous issues that impact collecting these data, including beliefs about how the information will be used, the clinician-patient relationship, having enough of the right staff, time needed to collect SDOH information, and technology used to collect the data (eg, usability, standardization).

CONCLUSIONS AND RELEVANCE: This qualitative study of the experience of collecting, documenting, and exchanging SDOH data underscores the ongoing barriers to widespread adoption of uniform approaches to SDOH data documentation as well as factors that may help lower those barriers, such as trusting patient-clinician relationships, greater transparency in how the data will be used, and targeted resources. A multifaceted approach to addressing the concerns raised by clinicians, patients, and care partners is required to ensure that such data can be captured in a way that improves care and allows for progress toward an equitable health care system.

IMPORTANCE: Despite guidelines recommending avoidance of benzodiazepine administration to older patients, many of them now receive benzodiazepines as a part of anesthesia care. The effectiveness of clinician- and patient-facing interventions to discourage such use remains insufficiently characterized.

OBJECTIVE: To evaluate the effect of clinician peer comparison, patient informational mail, or a combination of these interventions compared with usual care on the rate of perioperative benzodiazepine administration to older patients.

DESIGN, SETTING, AND PARTICIPANTS: This 2 × 2 factorial, stepped-wedge, cluster randomized clinical trial of a corporate quality improvement initiative was conducted between August 8, 2022, and May 28, 2023, across 415 hospitals, surgery centers, and physician offices in 8 US states served by anesthesia clinicians from a national anesthesia practice. Participants were adults aged 65 years or older who underwent an elective surgical or endoscopic procedure with general anesthesia. Data analyses followed the intention-to-treat principle.

INTERVENTION: Patients were randomly assigned to 1 of 4 groups-clinician peer comparison (wherein clinicians received feedback regarding their performance compared with other clinicians in the practice), patient informational mail (wherein patients received an informational letter encouraging them to have a discussion regarding medication selection with their clinician on the day of surgery), both interventions, or usual care (no intervention).

MAIN OUTCOMES AND MEASURES: Rate of benzodiazepine administration during anesthesia care and patient satisfaction with anesthesia care (measured by the Anesthesia Patient Satisfaction Questionnaire, version 2).

RESULTS: Among the 509 269 enrolled participants (255 871 females [50.2%]; mean [SD] age, 74 [7] years), 81 363 (16.0%) were assigned to clinician peer comparison, 98 520 (19.3%) to patient informational mail, 169 712 (33.3%) to both interventions, and 159 674 (31.4%) to usual care. Among patients who received benzodiazepine during anesthesia care, 24.5% were in the usual care group compared with 19.7% in the clinician peer comparison group, 20.0% in the patient informational mail group, and 19.7% in the combination group. After adjustment for time, none of the study interventions were associated with lower odds of benzodiazepine administration compared with usual care (odds ratio [OR], 1.02 [95% CI, 0.98-1.07]; P = .35 for clinician peer comparison; OR, 1.01 [95% CI, 0.96-1.05]; P = .81 for patient informational mail; and OR, 1.11 [95% CI, 1.05-1.16]; P < .001 for combined interventions). Satisfaction scores were high in all groups and did not vary by treatment assignment.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that clinician peer comparison, patient informational mail, or a combination of both interventions did not reduce benzodiazepine administration to older patients compared with usual care; patient satisfaction remained high throughout the study. Overall, the findings suggest a need to explore other patient-targeted interventions to improve anesthesia care.

TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT05436392.

BACKGROUND: Increased intraoperative electroencephalographic (EEG) burst suppression is associated with postoperative delirium. Cerebral desaturation is considered as one of the factors associated with burst suppression. Our study investigates the association between cerebral desaturation and burst suppression by analyzing their concurrence. Additionally, we aim to examine their association with cardiac surgical phases to identify potential for targeted interventions.

METHODS: We retrospectively analyzed intraoperative 1-minute interval observations in 51 patients undergoing cardiac surgery. Processed EEG and cerebral oximetry were collected, with the anesthesiologists blinded to the information. The associations between cerebral desaturation (defined as a 10% decrease from baseline) and burst suppression, as well as with phase of cardiac surgery, were analyzed using the Generalized Logistic Mixed Effect Model. The results were presented as odds ratio and 95% confidence intervals (CIs). A value of P < .05 was considered statistically significant.

RESULTS: The odds of burst suppression increased 1.5 times with cerebral desaturation (odds ratio [OR], 1.52, 95% CI, 1.11-2.07; P = .009). Compared to precardiopulmonary bypass (pre-CPB), the odds of cerebral desaturation were notably higher during CPB (OR, 22.1, 95% CI, 12.4-39.2; P < .001) and post-CPB (OR, 18.2, 95% CI, 12.2-27.3; P < .001). However, the odds of burst suppression were lower during post-CPB (OR, 0.69, 95% CI, 0.59-0.81; P < .001) compared to pre-CPB. Compared to pre-CPB, the odds of concurrent cerebral desaturation and burst suppression were notably higher during CPB (OR, 52.3, 95% CI, 19.5-140; P < .001) and post-CPB (OR, 12.7, 95% CI, 6.39-25.2; P < .001). During CPB, the odds of cerebral desaturation (OR, 6.59, 95% CI, 3.62-12; P < .001) and concurrent cerebral desaturation and burst suppression (OR, 10, 95% CI, 4.01-25.1; P < .001) were higher in the period between removal of aortic cross-clamp and end of CPB. During the entire surgery, the odds of burst suppression increased 8 times with higher inhalational anesthesia concentration (OR, 7.81, 95% CI, 6.26-9.74; P < .001 per 0.1% increase).

CONCLUSIONS: Cerebral desaturation is associated with intraoperative burst suppression during cardiac surgery, most significantly during CPB, especially during the period between the removal of the aortic cross-clamp and end of CPB. Further exploration with simultaneous cerebral oximetry and EEG monitoring is required to determine the causes of burst suppression. Targeted interventions to address cerebral desaturation may assist in mitigating burst suppression and consequently enhance postoperative cognitive function.