Remote Blood Pressure Monitoring With Social Support for Patients With Hypertension: A Randomized Clinical Trial.

Importance: Hypertension management has traditionally been based on office visits. Integrating remote monitoring into routine clinical practices and leveraging social support might improve blood pressure (BP) control. Objective: To evaluate the effectiveness of a bidirectional text monitoring program focused on BP control and medication adherence with and without social support in adults with hypertension. Design, Setting, and Participants: This randomized clinical trial included adults aged 18 to 75 treated at an academic family medicine practice in Philadelphia in 2018 and 2019. Patients had been seen at least twice in the prior 24 months and had at least 2 elevated BP measurements (>150/90 mm Hg or >140/90 mm Hg for patients aged 18-59 years or with diabetes or chronic kidney disease) during visits. All participants had a cell phone with text messaging, offered at least 1 support partner, and were taking maintenance medications to treat hypertension. Patients were randomized 2:2:1 to remote monitoring of BP and medication adherence (RM), remote monitoring of BP and medication adherence with feedback provided to a social support partner (SS), or usual care (UC). Data were analyzed on an intention-to-treat basis between October 14, 2019, and May 30, 2020, and were revisited from May 23 through June 2, 2023. Interventions: The RM and SS groups received an automatic home BP monitor, 3 weekly texts requesting BP measurements, 1 weekly text inquiring about medication adherence, and a weekly text with feedback. In the SS arm, support partners received a weekly progress report. The UC group received UC through their primary care practice. Clinicians caring for the patients in the intervention groups received nudges via electronic health records to adjust medications when 3 of 10 reported BP measurements were elevated. Patients were followed up for 4 months. Main Outcomes and Measures: The primary outcome was systolic BP at 4 months measured during the final follow-up visit. Secondary outcomes included achievement of normotension and diastolic BP. Results: In all, 246 patients (mean [SD] age, 50.9 [11.4] years; 175 females [71.1%]; 223 Black individuals [90.7%] and 13 White individuals [5.3%]) were included in the intention-to-treat analysis: 100 patients in the RM arm, 97 in the SS arm, and 49 in the UC arm. Compared with the UC arm, there was no significant difference in systolic or diastolic BP at the 4-month follow-up visit in the RM arm (systolic BP adjusted mean difference, -5.25 [95% CI, -10.65 to 0.15] mm Hg; diastolic BP adjusted mean difference, -1.94 [95% CI, -5.14 to 1.27] mm Hg) or the SS arm (systolic BP adjusted mean difference, -0.91 [95% CI, -6.37 to 4.55] mm Hg; diastolic BP adjusted mean difference, -0.63 [95% CI, -3.77 to 2.51] mm Hg). Of the 206 patients with a final BP measurement at 4 months, BP was controlled in 49% (41 of 84) of patients in the RM arm, 31% (27 of 87) of patients in the SS arm, and 40% (14 of 35) of patients in the UC arm; these rates did not differ significantly between the intervention arms and the UC group. Conclusions and Relevance: In this randomized clinical trial, neither remote BP monitoring nor remote BP monitoring with social support improved BP control compared with UC in adults with hypertension. Additional efforts are needed to examine whether interventions directed at helping patients remember to take their BP medications can lead to improved BP control. Trial Registration: ClinicalTrials.gov Identifier: NCT03416283.

Partial-linear single-index transformation models with censored data.

In studies with time-to-event outcomes, multiple, inter-correlated, and time-varying covariates are commonly observed. 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. A class of semiparametric transformation (ST) models offers flexible specifications of the intensity function and can be a general framework to accommodate nonlinear covariate effects. In this paper, we propose a partial-linear single-index (PLSI) transformation model that reduces the dimensionality of multiple covariates into a single index and provides interpretable estimates of the covariate effects. We develop an iterative algorithm using the regression spline technique to model the nonparametric single-index function for possibly nonlinear joint effects, followed by nonparametric maximum likelihood estimation. We also propose a nonparametric testing procedure to formally examine the linearity of covariate effects. We conduct Monte Carlo simulation studies to compare the PLSI transformation model with the standard ST model and apply it to NYU Langone Health de-identified electronic health record data on COVID-19 hospitalized patients' mortality and a Veteran's Administration lung cancer trial.

A Phase 1/2 multicenter trial of DKN-01 as monotherapy or in combination with docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

BACKGROUND: Dickkopf-related protein 1 (DKK1) is a Wingless-related integrate site (Wnt) signaling modulator that is upregulated in prostate cancers (PCa) with low androgen receptor expression. DKN-01, an IgG4 that neutralizes DKK1, delays PCa growth in pre-clinical DKK1-expressing models. These data provided the rationale for a clinical trial testing DKN-01 in patients with metastatic castration-resistant PCa (mCRPC). METHODS: This was an investigator-initiated parallel-arm phase 1/2 clinical trial testing DKN-01 alone (monotherapy) or in combination with docetaxel 75 mg/m2 (combination) for men with mCRPC who progressed on ≥1 AR signaling inhibitors. DKK1 status was determined by RNA in-situ expression. The primary endpoint of the phase 1 dose escalation cohorts was the determination of the recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 expansion cohorts was objective response rate by iRECIST criteria in patients treated with the combination. RESULTS: 18 pts were enrolled into the study-10 patients in the monotherapy cohorts and 8 patients in the combination cohorts. No DLTs were observed and DKN-01 600 mg was determined as the RP2D. A best overall response of stable disease occurred in two out of seven (29%) evaluable patients in the monotherapy cohort. In the combination cohort, five out of seven (71%) evaluable patients had a partial response (PR). A median rPFS of 5.7 months was observed in the combination cohort. In the combination cohort, the median tumoral DKK1 expression H-score was 0.75 and the rPFS observed was similar between patients with DKK1 H-score ≥1 versus H-score = 0. CONCLUSION: DKN-01 600 mg was well tolerated. DKK1 blockade has modest anti-tumor activity as a monotherapy for mCRPC. Anti-tumor activity was observed in the combination cohorts, but the response duration was limited. DKK1 expression in the majority of mCRPC is low and did not clearly correlate with anti-tumor activity of DKN-01 plus docetaxel.

The Registry-Based Randomized Trial - A Pragmatic Study Design.

Randomized controlled trials are the gold standard of clinical research for comparing therapies in well-defined groups of participants.1 Randomization avoids confounding due to unmeasured variables or to treatment selection and enables a causal interpretation of the estimated treatment effect. It has long been recognized, however, that standard explanatory clinical trials are slow, costly, and subject to participant selection. To preserve the strengths of randomized trials while mitigating their weaknesses, pragmatic randomized clinical trials emerged; these trials aim to facilitate decision-making rather than explicate a mechanism of action and enroll a diverse set of participants using existing structures and data sources.2.

Baseline Participant Characteristics at Enrollment in the Zoster Eye Disease Study.

PURPOSE: The Zoster Eye Disease Study (ZEDS) is the first randomized clinical trial to study the efficacy of long-term (1 year) suppressive valacyclovir treatment on herpes zoster ophthalmicus (HZO) outcomes. This article details the baseline characteristics of participants. SETTING: The study was set at 95 participating clinical centers in 33 states, Canada, and New Zealand. STUDY POPULATION: Immunocompetent adults with a history of a characteristic HZO unilateral rash and documentation of an episode of active dendriform epithelial keratitis, stromal keratitis, endothelial keratitis, or iritis within the preceding year, enrolled in ZEDS from November 2017 to January 2023. INTERVENTION: Participants were randomized to double-masked oral valacyclovir 1 gm daily versus placebo for 1 year of treatment and followed for 18 months. RESULTS: Five hundred twenty-seven participants were enrolled across 4 strata according to age at HZO onset (younger or older than 60 years) and duration of HZO at enrollment (less or greater than 6 months), with an even distribution of men and women and a median age of 60 years. More participants with recent (57%, 300/527) than chronic HZO and younger than 60 years at HZO onset (54%, 286/527) were enrolled. Most participants were treated acutely with a recommended antiviral regimen (91%, 480/527) and had not been vaccinated against zoster (79%, 418/527). CONCLUSIONS: The broad ZEDS study population enhances the likelihood that ZEDS will provide generalizable high-quality evidence regarding the efficacy and safety of suppressive valacyclovir for HZO immunocompetent adults and whether it should become standard of care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03134196.

Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design.

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository. METHODS: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes. DISCUSSION: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.

Up-to-Date Colonoscopy Use in Asian and Hispanic Subgroups in New York City, 2003-2016.

BACKGROUND: Colorectal cancer screening uptake in the United States overall has increased, but racial/ethnic disparities persist and data on colonoscopy uptake by racial/ethnic subgroups are lacking. We sought to better characterize these trends and to identify predictors of colonoscopy uptake, particularly among Asian and Hispanic subgroups. STUDY: We used data from the New York City Community Health Survey to generate estimates of up-to-date colonoscopy use in Asian and Hispanic subgroups across 6 time periods spanning 2003-2016. For each subgroup, we calculated the percent change in colonoscopy uptake over the study period and the difference in uptake compared to non-Hispanic Whites in 2015-2016. We also used multivariable logistic regression to identify predictors of colonoscopy uptake. RESULTS: All racial and ethnic subgroups with reliable estimates saw a net increase in colonoscopy uptake between 2003 and 2016. In 2015-2016, compared with non-Hispanic Whites, Puerto Ricans, Dominicans, and Central/South Americans had higher colonoscopy uptake, whereas Chinese, Asian Indians, and Mexicans had lower uptake. On multivariable analysis, age, marital status, insurance status, primary care provider, receipt of flu vaccine, frequency of exercise, and smoking status were the most consistent predictors of colonoscopy uptake (≥4 time periods). CONCLUSIONS: We found significant variation in colonoscopy uptake among Asian and Hispanic subgroups. We also identified numerous demographic, socioeconomic, and health-related predictors of colonoscopy uptake. These findings highlight the importance of examining health disparities through the lens of disaggregated racial/ethnic subgroups and have the potential to inform future public health interventions.

Evaluation of the SSTR2-targeted Radiopharmaceutical 177Lu-DOTATATE and SSTR2-specific 68Ga-DOTATATE PET as Imaging Biomarker in Patients with Intracranial Meningioma.

PURPOSE: There are no effective medical therapies for patients with meningioma who progress beyond surgical and radiotherapeutic interventions. Somatostatin receptor type 2 (SSTR2) represents a promising treatment target in meningiomas. In this multicenter, single-arm phase II clinical study (NCT03971461), the SSTR2-targeting radiopharmaceutical 177Lu-DOTATATE is evaluated for its feasibility, safety, and therapeutic efficacy in these patients. PATIENTS AND METHODS: Adult patients with progressive intracranial meningiomas received 177Lu-DOTATATE at a dose of 7.4 GBq (200 mCi) every eight weeks for four cycles. 68Ga-DOTATATE PET-MRI was performed before and six months after the start of the treatment. The primary endpoint was progression-free survival (PFS) at 6 months (PFS-6). Secondary endpoints were safety and tolerability, overall survival (OS) at 12 months (OS-12), median PFS, and median OS. RESULTS: Fourteen patients (female = 11, male = 3) with progressive meningiomas (WHO 1 = 3, 2 = 10, 3 = 1) were enrolled. Median age was 63.1 (range 49.7-78) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated. Seven patients (50%) achieved PFS-6. Best radiographic response by modified Macdonald criteria was stable disease (SD) in all seven patients. A >25% reduction in 68Ga-DOTATATE uptake (PET) was observed in five meningiomas and two patients. In one lesion, this corresponded to >50% reduction in bidirectional tumor measurements (MRI). CONCLUSIONS: Treatment with 177Lu-DOTATATE was well tolerated. The predefined PFS-6 threshold was met in this interim analysis, thereby allowing this multicenter clinical trial to continue enrollment. 68Ga-DOTATATE PET may be a useful imaging biomarker to assess therapeutic outcome in patients with meningioma.

Sample Size Calculations for Stepped Wedge Designs with Treatment Effects that May Change with the Duration of Time under Intervention.

The stepped wedge design is often used to evaluate interventions as they are rolled out across schools, health clinics, communities, or other clusters. Most models used in the design and analysis of stepped wedge trials assume that the intervention effect is immediate and constant over time following implementation of the intervention (the "exposure time"). This is known as the IT (immediate treatment effect) assumption. However, recent research has shown that using methods based on the IT assumption when the treatment effect varies over exposure time can give extremely misleading results. In this manuscript, we discuss the need to carefully specify an appropriate measure of the treatment effect when the IT assumption is violated and we show how a stepped wedge trial can be powered when it is anticipated that the treatment effect will vary as a function of the exposure time. Specifically, we describe how to power a trial when the exposure time indicator (ETI) model of Kenny et al. (Statistics in Medicine, 41, 4311-4339, 2022) is used and the estimand of interest is a weighted average of the time-varying treatment effects. We apply these methods to the ADDRESS-BP trial, a type 3 hybrid implementation study designed to address racial disparities in health care by evaluating a practice-based implementation strategy to reduce hypertension in African American communities.

Qualitative analysis of a remote monitoring intervention for managing heart failure.

BACKGROUND: Heart failure (HF) is one of the most common reasons for hospital admission and is a major cause of morbidity, mortality, and increasing health care costs. The EMPOWER study was a randomized trial that used remote monitoring technology to track patients' weight and diuretic adherence and a state-of-the-art approach derived from behavioral economics to motivate adherence to the reverse monitoring technology. OBJECTIVE: The goal was to explore patient and clinician perceptions of the program and its impact on perceived health outcomes and better understand why some patients or clinicians did better or worse than others in response to the intervention. APPROACH: This was a retrospective qualitative study utilizing semi-structured interviews with 43 patients and 16 clinicians to understand the trial's processes, reflecting on successes and areas for improvement for future iterations of behavioral economic interventions. KEY RESULTS: Many patients felt supported, and they appreciated the intervention. Many also appreciated the lottery intervention, and while it was not an incentive for enrolling for many respondents, it may have increased adherence during the study. Clinicians felt that the intervention integrated well into their workflow, but the number of alerts was burdensome. Additionally, responses to alerts varied considerably by provider, perhaps because there are no professional guidelines for alerts unaccompanied by severe symptoms. CONCLUSION: Our qualitative analysis indicates potential areas for additional exploration and consideration to design better behavioral economic interventions to improve cardiovascular health outcomes for patients with HF. Patients appreciated lottery incentives for adhering to program requirements; however, many were too far along in their disease progression to benefit from the intervention. Clinicians found the amount and frequency of electronic alerts burdensome and felt they did not improve patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02708654.

Predictors of Colonoscopy Use Among Asian Indians in New York City, 2003 to 2016.

BACKGROUND: Asian Americans have the lowest colorectal cancer screening uptake of any racial and ethnic group in the United States. Asian Indians are among the most under-screened Asian American subgroups, but there is limited data for this population. We sought to characterize predictors of colonoscopy use among Asian Indians in New York City. METHODS: Using 2003 to 2016 data from the New York City Community Health Survey, we identified all Asian Indian participants aged 50 years or older. We examined the association between sociodemographic and medical factors and up-to-date colonoscopy use (defined as colonoscopy within the last 10 y) using logistic regression over 4 time periods: 2003 to 2008, 2009 to 2012, 2013 to 2014, 2015 to 2016. RESULTS: On multivariable analysis, language, age, income, recent exercise, body mass index, and influenza vaccination were associated with colonoscopy uptake in 1 time period. Compared with participants who preferred English, those who preferred an Indian language were less likely to have been up-to-date in 2013 to 2014 (odds ratio 0.12, 95% CI 0.02-0.66). Individuals older than 65 years were more likely than those aged 50 to 64 years to have received a colonoscopy in 2009 to 2012 (odds ratio 3.91, 95% CI 1.49-10.24), although the risk estimates were also consistently positive in the other 3 time periods. CONCLUSIONS: Among Asian Indians living in New York City, several demographic, socioeconomic, and health-related characteristics predict colonoscopy use. These findings highlight the importance of examining determinants of colonoscopy uptake in this understudied population to inform future public health interventions.

A feasibility and acceptability study of screening the parents/guardians of pediatric dental patients for the social determinants of health.

BACKGROUND: The social determinants of health (SDOH) are the conditions in which people are born, grow, work, live, and age. Lack of SDOH training of dental providers on SDOH may result in suboptimal care provided to pediatric dental patients and their families. The purpose of this pilot study is to report the feasibility and acceptability of SDOH screening and referral by pediatric dentistry residents and faculty in the dental clinics of Family Health Centers at NYU Langone (FHC), a Federally Qualified Health Center (FQHC) network in Brooklyn, NY, USA. METHODS: Guided by the Implementation Outcomes Framework, 15 pediatric dentists and 40 pediatric dental patient-parent/guardian dyads who visited FHC in 2020-2021 for recall or treatment appointments participated in this study. The a priori feasibility and acceptability criteria for these outcomes were that after completing the Parent Adversity Scale (a validated SDOH screening tool), ≥ 80% of the participating parents/guardians would feel comfortable completing SDOH screening and referral at the dental clinic (acceptable), and ≥ 80% of the participating parents/guardians who endorsed SDOH needs would be successfully referred to an assigned counselor at the Family Support Center (feasible). RESULTS: The most prevalent SDOH needs endorsed were worried within the past year that food would run out before had money to buy more (45.0%) and would like classes to learn English, read better, or obtain a high school degree (45.0%). Post-intervention, 83.9% of the participating parents/guardians who expressed an SDOH need were successfully referred to an assigned counselor at the Family Support Center for follow-up, and 95.0% of the participating parents/guardians felt comfortable completing the questionnaire at the dental clinic, surpassing the a priori feasibility and acceptability criteria, respectively. Furthermore, while most (80.0%) of the participating dental providers reported being trained in SDOH, only one-third (33.3%) usually or always assess SDOH for their pediatric dental patients, and most (53.8%) felt minimally comfortable discussing challenges faced by pediatric dental patient families and referring patients to resources in the community. CONCLUSIONS: This study provides novel evidence of the feasibility and acceptability of SDOH screening and referral by dentists in the pediatric dental clinics of an FQHC network.

The effects of exercise and diet on oxidative stress and telomere length in breast cancer survivors.

PURPOSE: Cancer and its treatments accelerate biological aging. This analysis tested the hypothesis that exercise and diet reduce oxidative stress and prevent telomere shortening in breast cancer survivors. METHODS: In a 2 × 2 factorial design, 342 breast cancer survivors who were insufficiently physically active and had overweight or obesity at enrollment were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. The endpoints of this analysis were the change from baseline to week 52 in 8-iso-prostaglandin F2α (8-iso-PGF2α) and lymphocyte telomere length. RESULTS: Baseline telomere length was shorter than age-adjusted normative values (median difference: - 1.8 kilobases; 95% CI - 2.4, - 1.1); equivalent to 21 years (95% CI 17, 25) of accelerated chronological aging. Compared to control, exercise alone did not change 8-iso-PGF2α [9.9%; 95% confidence interval (CI) - 1.0, 20.8] or telomere length (13.8%; 95% CI - 15.6, 43.3). Compared to control, diet alone was associated with reduced 8-iso-PGF2α (- 10.5%; 95% CI - 19.5, - 1.5) but did not change telomere length (12.1%; 95% CI - 17.2, 41.3). Compared to control, exercise plus diet was associated with reduced 8-iso-PGF2α (- 9.8%; 95% CI - 18.7, - 0.9) but did not change telomere length (- 8.5%; 95% CI - 32.1, 15.2). Change in 8-iso-PGF2α did not correlate with change in telomere length (r = 0.07; 95% CI - 0.07, 0.20). CONCLUSION: In breast cancer survivors, diet alone or exercise plus diet were associated with reduced oxidative stress but did not change telomere length. This analysis may inform future trials that aim to optimize healthy aging in cancer survivors.

Effect of Financial Incentives and Default Options on Food Choices of Adults With Low Income in Online Retail Settings: A Randomized Clinical Trial.

Importance: Despite recent growth in online redemption of Supplemental Nutrition Assistance Program (SNAP) benefits, no previous work has tested the impact of economic and behavioral economic strategies on food purchasing behaviors in an online grocery retail setting among adults with low income. Objective: To examine the extent to which financial incentives and default shopping cart options influence fruit and vegetable purchases. Design, Setting, and Participants: This randomized clinical trial used an experimental online grocery store for adults who currently or have ever received SNAP benefits. From October 7 to December 2, 2021, participants were instructed to shop for a week's worth of groceries for their household, with a budget tailored to household size; no payment was taken. Interventions: Random assignment to 1 of 4 conditions: no intervention, 50% discount on eligible fruits and vegetables, prefilled shopping carts with tailored fruit and vegetable items (ie, default options), or a combination of the discount and default options. Main Outcomes and Measures: The primary outcome was the percentage of nondiscounted dollars spent on eligible fruit and vegetables per basket. Results: Of 2744 participants, mean (SD) age was 46.7 (16.0) years, and 1447 (52.7%) identified as women. A total of 1842 participants (67.1%) reported currently receiving SNAP benefits and 1492 (54.4%) reported shopping online for groceries in the previous 12 months. Participants spent a mean (SD) 20.5% (23.5%) of total dollars on eligible fruits and vegetables. Compared with no intervention, those in the discount condition spent 4.7% (98.3% CI, 1.7%-7.7%) of more total dollars on eligible fruits and vegetables; those in the default condition, 7.8% (98.3% CI, 4.8%-10.7%) more; and those in the combination condition, 13.0% (98.3% CI, 10.0%-16.0%) more (P < .001 for all). There was no difference between the discount and the default conditions (P = .06), but the effect in the combination condition was significantly larger than both discount and default conditions (P < .001). Default shopping cart items were purchased by 679 participants (93.4%) in the default condition and 655 (95.5%) in the combination condition, whereas 297 (45.8%) in the control and 361 (52.9%) in the discount conditions purchased those items (P < .001). No variation was observed by age, sex, or race and ethnicity, and results were similar when those who reported never shopping online for groceries were excluded. Conclusions and Relevance: In this randomized clinical trial, financial incentives for fruits and vegetables and default options, especially in combination, led to meaningful increases in online fruit and vegetable purchases among adults with low income. Trial Registration: ClinicalTrials.gov Identifier: NCT04766034.

Mind-Body Intervention for Dysfunctional Breathing in Chronic Obstructive Pulmonary Disease: Feasibility Study and Lessons Learned.

Purpose: Dysfunctional breathing behaviors are prevalent in chronic obstructive pulmonary disease (COPD). Although these behaviors contribute to dyspnea, abnormal carbon dioxide (CO2) levels, and COPD exacerbations, they are modifiable. Current dyspnea treatments for COPD are suboptimal, because they do not adequately address dysfunctional breathing behaviors and anxiety together. We developed a complementary mind-body breathlessness therapy, called capnography-assisted respiratory therapy (CART), that uses real-time CO2 biofeedback at the end of exhalation (end-tidal CO2 or ETCO2), to target dysfunctional breathing habits and improve dyspnea treatment and pulmonary rehabilitation (PR) adherence in COPD. The study aim was to test the feasibility of integrating CART with a traditional, clinic-based PR program in an urban setting. Methods: We used a feasibility pre- and post-test design, with 2:1 randomization to CART+PR or control (PR-alone) groups, to test and refine CART. Multi-component CART consisted of six, 1-h weekly sessions of slow breathing and mindfulness exercises, ETCO2 biofeedback, motivational counseling, and a home program. All participants were offered twice weekly, 1-h sessions of PR over 10 weeks (up to 20 sessions). Results: Thirty-one participants with COPD were enrolled in the study. Approximately a third of participants had symptoms of psychological distress. Results showed that CART was feasible and acceptable based on 74% session completion and 91.7% homework exercise completion (n = 22). Within-group effect sizes for CART+PR were moderate to large (Cohen's d = 0.51-1.22) for reduction in resting Borg dyspnea (anticipatory anxiety) and respiratory rate, St. George's Respiratory Questionnaire (SGRQ) respiratory symptoms; and increase in Patient-Reported Outcomes Measurement Information System (PROMIS) physical function and physical activity; all p < 0.05. Conclusions: CART is a new mind-body breathing therapy that targets eucapnic breathing, interoceptive function, and self-regulated breathing to relieve dyspnea and anxiety symptoms in COPD. Study findings supported the feasibility of CART and showed preliminary signals that CART may improve exercise tolerance, reduce dyspnea, and enhance PR completion by targeting reduced dysfunctional breathing patterns (CTR No. NCT03457103).

Food Allergy Management for Adolescents Using Behavioral Incentives: A Randomized Trial.

OBJECTIVE: We sought to evaluate the use of behavioral economics approaches to promote the carrying of epinephrine auto-injectors (EAIs) among adolescents with food allergies. We hypothesized that adolescents who receive frequent text message nudges (Intervention 1) or frequent text message nudges plus modest financial incentives (Intervention 2) would be more likely to carry their epinephrine than members of the usual care control group. METHODS: We recruited 131 adolescents ages 15 to 19 with a food allergy and a current prescription for epinephrine to participate in a cohort multiple randomized controlled trial. Participants were randomly assigned to participate in Intervention 1, Intervention 2, or to receive usual care. The primary outcome was consistency of epinephrine-carrying, measured as the proportion of checkpoints at which a participant could successfully demonstrate they were carrying their EAI, with photo-documentation of the device. RESULTS: During Intervention 1, participants who received the intervention carried their EAI 28% of the time versus 38% for control group participants (P = .06). During Intervention 2, participations who received the intervention carried their EAI 45% of the time versus 23% for control group participants (P = .002). CONCLUSIONS: Text message nudges alone were unsuccessful at promoting EAI-carrying but text message nudges combined with modest financial incentives almost doubled EAI-carriage rates among those who received the intervention compared with the control group. However, even with the intervention, adolescents with food allergies carried their EAI <50% of the time. Alternative strategies for making EAIs accessible to adolescents at all times should be implemented.

Qualitative Analysis of a Remote Monitoring Intervention for Managing Heart Failure.

Background : Heart failure (HF) is one of the most common reasons for hospital admission and is a major cause of morbidity, mortality, and increasing health care costs. The EMPOWER study was a randomized trial that used remote monitoring technology to track patients' weight and diuretic adherence and a state-of-the-art approach derived from behavioral economics to motivate adherence to the reverse monitoring technology. Objective : The goal was to explore patient and clinician perceptions of the program and its impact on health outcomes and better understand why some patients/clinicians did better/worse than others in response to the intervention. Approach : This was a retrospective qualitative study to understand the trial's processes, reflecting on successes and areas for improvement for future iterations of behavioral economic interventions. Key Results: Many patients felt supported, and they appreciated the intervention. Many also appreciated the lottery intervention, and while it was not an incentive for enrolling for many respondents, it may have increased adherence during the study. Clinicians felt that the intervention integrated well into their workflow, but the number of alerts was burdensome. Additionally, responses to alerts varied considerably by provider, perhaps because there are no professional guidelines for alerts unaccompanied by severe symptoms. Conclusion : Those interviews offer insights into the potential reasons for the study's null result and opportunities for improvements in the future. Trial Registration: ClinicalTrials.gov Identifier: NCT02708654.