Faculty Bibliography

BACKGROUND: Randomized clinical trials provide gold-standard evidence for the efficacy of interventions, but have limitations, including highly selected populations that make inference on effectiveness difficult and a lack of ability to adapt and change midstream. METHODS: We propose two innovations for pragmatic trial design. RESULTS: Evidence-based evolutionary testing, a framework that allows adaptation of interventions and rapid-cycle innovation, preserves the power of randomization while acknowledging the need for adaptation and learning. An opt-out consent framework increases the fraction of the target population who participate in trials, but may lead to dampening of effect sizes. CONCLUSION: Pragmatic trials offer numerous advantages in the evaluation of behavioral interventions in health. Statistical innovations, including evidence-based evolutionary testing and opt-out framing of consent and enrollment processes, can enhance the power of pragmatic trials and lead to more rapid progress.

BACKGROUND:Congestive heart failure is a major cause of morbidity, mortality, and cost. Disease management programs have shown promise but lack firm evidence of effectiveness and scalability. We describe the motivation, design, and planned analyses of EMPOWER (Electronic Monitoring of Patients Offers Ways to Enhance Recovery), a randomized clinical trial of an innovative intervention incorporating behavioral economic principles with remote monitoring technology embedded within a healthcare system. METHODS AND RESULTS/RESULTS:EMPOWER is an ongoing, pragmatic, randomized clinical trial comparing usual care to an automated hovering intervention that includes patient-level incentives for daily weight monitoring and diuretic adherence combined with automated feedback into the clinical care pathway, enabling real-time response to concerning clinical symptoms. Identification of eligible patients began in May 2016, and implementation of the intervention is feasible. Trial processes are embedded into existing clinical pathways. The primary outcome is time to readmission for any cause. Cost-effectiveness analyses are planned to evaluate the healthcare costs and health outcomes of the approach. CONCLUSIONS:The EMPOWER trial incorporates leading-edge approaches in human motivation, derived from behavioral economics, with contemporary technology to provide scale and exception handling at low cost. The trial is also implemented within the naturalized environment of a health system, as much as possible taking advantage of the existing journeys of patients and workflows of clinicians. A goal of this pragmatic design is to limit resource utilization and also to test an intervention that would need minimal modification to be translated from research into a new way of practice. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: https://www.clinicaltrials.gov . Unique identifier: NCT02708654.

Many health issues require adherence to recommended daily activities, such as taking medication to manage a chronic condition, walking a certain distance to promote weight loss, or measuring weights to assess fluid balance in heart failure. The cost of nonadherence can be high, with respect to both individual health outcomes and the healthcare system. Incentivizing adherence to daily activities can promote better health in patients and populations and potentially provide long-term cost savings. Multiple incentive structures are possible. We focus here on a daily lottery incentive in which payment occurs when both the participant's lottery number matches the number drawn and the participant adheres to the targeted daily behavior. Our objective is to model the lottery's effect on participants' probability to complete the targeted task, particularly over the short term. We combine two procedures for analyzing such binary time series: a parameter-driven regression model with an autocorrelated latent process and a comparative interrupted time series. We use the output of the regression model as the control generator for the comparative time series in order to create a quasi-experimental design.

OBJECTIVE:To compare the pre-post intervention findings of dentists remotely trained to use shared decision-making (SDM) and motivational interviewing (MI) techniques. METHODS:In partnership with the New York Simulation Center for the Health Sciences and a Motivational Interviewing Network of Trainers consultant, three scenarios regarding interprofessional care were developed toward fostering the essential skills to build nonjudgmental dentist-patient partnerships: (1) screening and referral for the social determinants of health with an older adult dental patient; (2) parental consideration of the human papillomavirus vaccine for a 9-year-old dental patient; and (3) engagement with an obese adolescent dental patient to decrease their sugary drink intake. A Welch t-test was used to compare the importance and confidence ruler poll ratings pre-post intervention. RESULTS:In Fall 2024, four remote objective structured clinical exercise training sessions were conducted where standardized participants previously trained as patients rotated between three different breakout rooms so that dentist learners were able to participate in all three scenarios. The subset of dentist learners who responded to both the pre- and post-intervention surveys (37%) reported both greater use and usefulness of MI when discussing oral health recommendations with their patients/parents after the training. Poll results with 16 dentist learners were that they were more likely to feel confident in using SDM and MI techniques with parents/patients post- versus pre-intervention: mean difference [95% confidence interval] = 1.12 [-0.16, 2.41]. CONCLUSIONS:Respectful, participatory training strategies can shift the focus from healthcare providers as the authorities to patients as the agents of their behavior change.

Millions of Americans affected by Long COVID (LC) report difficulty accessing care and support. One barrier is obtaining a diagnosis. In response, US federal agencies commissioned a National Academies of Sciences, Engineering, and Medicine (NASEM) committee to re-examine the existing federal definitions for LC. The Committee concluded that LC is "an infection-associated chronic condition (IACC) occurring after SARS-CoV-2 infection that is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that can present as singular or multiple symptoms and/or diagnosable conditions." The full report was released in June 2024. We briefly highlight features and aspects of the definition that may help clinicians identify those who remain undiagnosed and improve care for all LC patients.

BACKGROUND:While fatal food-induced anaphylaxis is rare, adolescence is the period of highest risk. However, we lack strong estimates of the incidence of food allergic reactions among adolescents. OBJECTIVE:To estimate the incidence of food allergic reactions and anaphylactic reactions among adolescents with food allergy who have a prescription for epinephrine. METHODS:As part of a cohort study that was embedded in a randomized trial to promote safe food allergy management, we followed adolescents ages 15-19 years with food allergy and a current prescription for epinephrine for a period of 15 months in 2019-2020. At monthly intervals, participants were asked, via text message check-in, whether they had experienced a food allergic reaction due to accidental exposure to food allergens in the past month. RESULTS:Among the cohort of 131 adolescents, 112 answered at least one of the 15 monthly check-ins. Together, these respondents contributed 742 person-months of follow-up data out of a total possible 1,680 person-months. Over the 15-month study period, the incidence of food allergic reactions among adolescents with food allergy was 34.0 events per 100 person-years (95% CI: 21.0, 51.9). The incidence of food allergic reactions meeting the criteria for anaphylaxis was 16.2 events per 100 person-years (95% CI: 7.8, 29.7). CONCLUSION/CONCLUSIONS:Data on the incidence of food allergic reactions can help set expectations for safe food allergy management for adolescents and their families and can help inform discussions between patients, families, and physicians regarding different treatment options available and their associated risks and benefits.

BACKGROUND:Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores. METHODS:BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase. RESULTS:Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection). CONCLUSIONS:The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.

IMPORTANCE/UNASSIGNED:Among older adults with ischemic heart disease, participation in traditional ambulatory cardiac rehabilitation (CR) remains low. While mobile health CR (mHealth-CR) provides a novel opportunity to deliver care, age-specific impairments to technology use may limit uptake, and efficacy data are currently lacking. OBJECTIVE/UNASSIGNED:To test whether mHealth-CR improves functional capacity in older adults. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The RESILIENT phase 2, multicenter, randomized clinical trial recruited patients aged 65 years or older with ischemic heart disease (defined as a hospital visit for myocardial infarction or coronary revascularization) from 5 academic hospitals in New York, Connecticut, and Massachusetts between January 9, 2020, and April 22, 2024. INTERVENTION/UNASSIGNED:Participants were randomized 3:1 to mHealth-CR or usual care. mHealth-CR consisted of commercially available software delivered on a tablet computer, coupled with remote monitoring and weekly exercise therapist telephone calls, delivered over a 3-month duration. As RESILIENT was a trial conducted in a routine care setting to inform decision-making, participants in both arms were also allowed to receive traditional CR at their cardiologist's discretion. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was change from baseline to 3 months in functional capacity, measured by 6-minute walk distance (6MWD). Secondary outcomes were health status (12-Item Short Form Health Survey [SF-12]), residual angina, and impairment in activities of daily living. RESULTS/UNASSIGNED:A total of 400 participants (median age, 71.0 years [range, 65.0-91.0 years]; 291 [72.8%] male) were randomized to mHealth-CR (n = 298) or usual care (n = 102) and included in the intention-to-treat analysis. Of those, 356 participants (89.0%) returned in person for 6MWD assessment at 3 months. For the primary outcome, there was no adjusted difference in 6MWD between participants receiving mHealth-CR vs usual care (15.6 m; 95% CI, -0.3 to 31.5 m; P = .06). Among subgroups, there was an improvement in 6MWD among women (36.6 m; 95% CI, 8.7-64.4 m). There were no differences in any secondary outcomes between groups (eg, adjusted difference in SF-12 physical component scores at 3 months: -1.9 points; 95% CI, -3.9 to 0.2 points). Based on inverse propensity score weighting, there was no effect of mHealth-CR on 6MWD among those who did not attend traditional CR (25.7 m; 95% CI, -8.7 to 60.2 m). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial of mHealth-CR vs usual care, mHealth-CR did not significantly increase 6MWD or result in improvements in secondary outcomes. The findings suggest the older adult population may require more age-tailored mHealth strategies to effectively improve outcomes. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03978130.

BACKGROUND:In cohort studies with time-to-event outcomes, covariates of interest often have values that change over time. The classical Cox regression model can handle time-dependent covariates but assumes linear effects on the log hazard function, which can be limiting in practice. Furthermore, when multiple correlated covariates are studied, it is of great interest to model their joint effects by allowing a flexible functional form and to delineate their relative contributions to survival risk. METHODS:Motivated by the World Trade Center (WTC)-exposed Fire Department of New York cohort study, we proposed a partial-linear single-index Cox (PLSI-Cox) model to investigate the effects of repeatedly measured metabolic syndrome indicators on the risk of developing WTC lung injury associated with particulate matter exposure. The PLSI-Cox model reduces the dimensionality of covariates while providing interpretable estimates of their effects. The model's flexible link function accommodates nonlinear effects on the log hazard function. We developed an iterative estimation algorithm using spline techniques to model the nonparametric single-index component for potential nonlinear effects, followed by maximum partial likelihood estimation of the parameters. RESULTS:Extensive simulations showed that the proposed PLSI-Cox model outperformed the classical time-dependent Cox regression model when the true relationship was nonlinear. When the relationship was linear, both the PLSI-Cox model and classical time-dependent Cox regression model performed similarly. In the data application, we found a possible nonlinear joint effect of metabolic syndrome indicators on survival risk. Among the different indicators, BMI had the largest positive effect on the risk of developing lung injury, followed by triglycerides. CONCLUSION/CONCLUSIONS:The PLSI-Cox models allow for the evaluation of nonlinear effects of covariates and offer insights into their relative importance and direction. These methods provide a powerful set of tools for analyzing data with multiple time-dependent covariates and survival outcomes, potentially offering valuable insights for both current and future studies.

BACKGROUND:The optimal management of patients with intermediate-risk pulmonary embolism (PE), who have right heart dysfunction (determined by a combination of imaging and cardiac biomarkers) but a normal blood pressure, is uncertain. These patients suffer from reduced functional capacity and a lower quality of life over the long-term, despite use of anticoagulant therapy. Catheter-directed therapy (CDT) is a promising treatment for acute PE that rapidly removes thrombus and potentially improves cardiac dysfunction. However, CDT has risk and is costly, and it is not known whether it improves long-term cardiorespiratory fitness and/or quality of life compared with anticoagulation alone. METHODS:) with cardiopulmonary exercise testing at 3 months and reduce New York Heart Association (NYHA) Class at 12 months compared with No-CDT. These 2 primary efficacy outcomes will be analyzed sequentially using a "gatekeeping" procedure; for NYHA class to be compared, peak oxygen consumption must first be shown to be significantly increased by CDT. Safety and cost-effectiveness will also be assessed. CONCLUSION/CONCLUSIONS:When completed, PE-TRACT will provide important evidence regarding the benefits and risks of CDT to treat intermediate-risk PE compared with anticoagulation alone. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov: NCT05591118.