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.

Efficacy of topical treatments for mild-to-moderate acne: A systematic review and meta-analysis of randomized control trials.

Acne is a common skin condition, but little data exist on the comparative efficacy of topical acne therapies. We conducted a systematic review and network meta-analysis to evaluate the efficacy of topical therapies for mild-to-moderate acne. Searches in PubMed/MEDLINE, Cochrane CENTRAL via Ovid, Embase via Ovid and Web of Science were conducted on 29 November 2021. Randomized controlled trials examining ≥12 weeks of topical treatments for acne vulgaris in subjects aged 12 and older were included. Main outcomes were absolute or percent change in acne lesion count and treatment success on the Investigator's Global Assessment scale. Thirty-five randomized clinical trials with 33,472 participants comparing nine different topical agents were included. Adapalene-benzoyl peroxide (BPO), clindamycin-BPO and clindamycin-tretinoin demonstrated the greatest reduction in non-inflammatory (ratio of means [RoM] 1.76; 95% CI [1.46; 2.12], RoM 1.70; 95% CI [1.44; 2.02] and RoM 1.87; 95% CI [1.53; 2.30], respectively), inflammatory (RoM 1.56; 95% CI [1.44; 1.70], RoM 1.49; 95% CI [1.39; 1.60] and RoM 1.48; 95% CI [1.36; 1.61], respectively) and total lesion count (ROM 1.67; 95% CI [1.47; 1.90], RoM 1.59; 95% CI [1.42; 1.79] and RoM 1.64; 95% CI [1.42; 1.89], respectively) compared to placebo. All single agents outperformed placebo except tazarotene, which did not significantly outperform placebo for inflammatory and non-inflammatory lesion count reduction. Most combination agents significantly outperformed their individual components in lesion count reduction and global assessment scores, except for clindamycin-tretinoin and clindamycin-BPO, which did not significantly outperform tretinoin (RoM 1.13; 95% CI [0.94; 1.36]) and BPO (RoM = 1.15, 95% CI [0.98; 1.36]), respectively, for non-inflammatory lesion reduction. There was no significant difference amongst most single agents when evaluating lesion count reduction. Combination agents are generally most effective for mild-to-moderate acne; however for non-inflammatory acne, the addition of clindamycin in topical regimens is unnecessary and should be avoided.

Association between COVID-19 convalescent plasma antibody levels and COVID-19 outcomes stratified by clinical status at presentation.

BACKGROUND: There is a need to understand the relationship between COVID-19 Convalescent Plasma (CCP) anti-SARS-CoV-2 IgG levels and clinical outcomes to optimize CCP use. This study aims to evaluate the relationship between recipient baseline clinical status, clinical outcomes, and CCP antibody levels. METHODS: The study analyzed data from the COMPILE study, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) assessing the efficacy of CCP vs. control, in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. SARS-CoV-2 IgG levels, referred to as 'dose' of CCP treatment, were retrospectively measured in donor sera or the administered CCP, semi-quantitatively using the VITROS Anti-SARS-CoV-2 IgG chemiluminescent immunoassay (Ortho-Clinical Diagnostics) with a signal-to-cutoff ratio (S/Co). The association between CCP dose and outcomes was investigated, treating dose as either continuous or categorized (higher vs. lower vs. control), stratified by recipient oxygen supplementation status at presentation. RESULTS: A total of 1714 participants were included in the study, 1138 control- and 576 CCP-treated patients for whom donor CCP anti-SARS-CoV2 antibody levels were available from the COMPILE study. For participants not receiving oxygen supplementation at baseline, higher-dose CCP (/control) was associated with a reduced risk of ventilation or death at day 14 (OR = 0.19, 95% CrI: [0.02, 1.70], posterior probability Pr(OR < 1) = 0.93) and day 28 mortality (OR = 0.27 [0.02, 2.53], Pr(OR < 1) = 0.87), compared to lower-dose CCP (/control) (ventilation or death at day 14 OR = 0.79 [0.07, 6.87], Pr(OR < 1) = 0.58; and day 28 mortality OR = 1.11 [0.10, 10.49], Pr(OR < 1) = 0.46), exhibiting a consistently positive CCP dose effect on clinical outcomes. For participants receiving oxygen at baseline, the dose-outcome relationship was less clear, although a potential benefit for day 28 mortality was observed with higher-dose CCP (/control) (OR = 0.66 [0.36, 1.13], Pr(OR < 1) = 0.93) compared to lower-dose CCP (/control) (OR = 1.14 [0.73, 1.78], Pr(OR < 1) = 0.28). CONCLUSION: Higher-dose CCP is associated with its effectiveness in patients not initially receiving oxygen supplementation, however, further research is needed to understand the interplay between CCP anti-SARS-CoV-2 IgG levels and clinical outcome in COVID-19 patients initially receiving oxygen supplementation.

The National Institutes of Health COVID-19 Neuro Databank/Biobank: Creation and Evolution.

Introduction Diverse neurological conditions are reported associated with the SARS-CoV-2 virus; neurological symptoms are the most common conditions to persist after resolution of acute infection, affecting 20% of patients six months after acute illness. The COVID-19 Neuro Databank (NeuroCOVID) was created to overcome the limitations of siloed small local cohorts to collect detailed, curated, and harmonized de-identified data from a large diverse cohort of adults with new or worsened neurological conditions associated with COVID-19 illness, as a scientific resource. Methods A Steering Committee including U.S. and international experts meets quarterly to provide guidance. Initial study sites were recruited to include a wide U.S. geographic distribution, academic and non-academic sites, urban and non-urban locations, and patients of different ages, disease severity, and comorbidities seen by a variety of clinical specialists. The NeuroCOVID REDCap database was developed, incorporating input from professional guidelines, existing common data elements, and subject matter experts. A cohort of eligible adults is identified at each site; inclusion criteria are: a new or worsened neurological condition associated with a COVID-19 infection confirmed by testing. De-identified data are abstracted from patients' medical records, using standardized common data elements and five case report forms. The database was carefully enhanced in response to feedback from site investigators and evolving scientific interest in post-acute conditions and their timing. Additional U.S. and international sites were added, focusing on diversity and populations not already described in published literature. By early 2024, NeuroCOVID included over 2700 patient records, including data from 16 U.S. and 5 international sites. Data are being shared with the scientific community in compliance with NIH requirements. The program has been invited to share case report forms with the National Library of Medicine as an ongoing resource for the scientific community. Conclusion The NeuroCOVID database is a unique and valuable source of comprehensive de-identified data on a wide variety of neurological conditions associated with COVID-19 illness, including a diverse patient population. Initiated early in the pandemic, data collection has been responsive to evolving scientific interests. NeuroCOVID will continue to contribute to scientific efforts to characterize and treat this challenging illness and its consequences.

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.

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.

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.

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.

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.

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.

Survival After Invasive or Conservative Management of Stable Coronary Disease.

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. METHODS: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. RESULTS: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. CONCLUSIONS: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04894877.