Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

Preference for and impact of telehealth vs in-person asthma visits among Black and Latinx adults.

BACKGROUND: Black and Latinx adults experience disproportionate asthma-related morbidity and limited specialty care access. The severe acute respiratory syndrome coronavirus 2 pandemic expanded telehealth use. OBJECTIVE: To evaluate visit type (telehealth [TH] vs in-person [IP]) preferences and the impact of visit type on asthma outcomes among Black and Latinx adults with moderate-to-severe asthma. METHODS: For this PREPARE trial ancillary study, visit type preference was surveyed by e-mail or telephone post-trial. Emergency medical record data on visit types and asthma outcomes were available for a subset (March 2020 to April 2021). Characteristics associated with visit type preferences, and relationships between visit type and asthma outcomes (control [Asthma Control Test] and asthma-related quality of life [Asthma Symptom Utility Index]), were tested using multivariable regression. RESULTS: A total of 866 participants consented to be surveyed, with 847 respondents. Among the participants with asthma care experience with both visit types, 42.0% preferred TH for regular checkups, which associated with employment (odds ratio [OR] = 1.61; 95% confidence interval [CI], 1.09-2.39; P = .02), lower asthma medication adherence (OR = 1.06; 95% CI, 1.01-1.11; P = .03), and having more historical emergency department and urgent care asthma visits (OR = 1.10 for each additional visit; 95% CI, 1.02-1.18; P = .02), after adjustment. Emergency medical record data were available for 98 participants (62 TH, 36 IP). Those with TH visits were more likely Latinx, from the Southwest, employed, using inhaled corticosteroid-only controller therapy, with lower body mass index, and lower self-reported asthma medication adherence vs those with IP visits only. Both groups had comparable Asthma Control Test (18.4 vs 18.9, P = .52) and Asthma Symptom Utility Index (0.79 vs 0.84, P = .16) scores after adjustment. CONCLUSION: TH may be similarly efficacious as and often preferred over IP among Black and Latinx adults with moderate-to-severe asthma, especially for regular checkups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02995733.

Socioeconomic status associates with worse asthma morbidity among Black and Latinx adults.

BACKGROUND: Asthma disproportionately affects African American/Black (AA/B) and Hispanic/Latinx (H/L) patients and individuals with low socioeconomic status (SES), but the relationship between SES and asthma morbidity within these racial/ethnic groups is inadequately understood. OBJECTIVE: To determine the relationship between SES and asthma morbidity among AA/B and H/L adults with moderate to severe asthma using multidomain SES frameworks and mediation analyses. METHODS: We analyzed enrollment data from the PeRson EmPowered Asthma RElief randomized trial, evaluating inhaled corticosteroid supplementation to rescue therapy. We tested for direct and indirect relationships between SES and asthma morbidity using structural equation models. For SES, we used a latent variable defined by poverty, education, and unemployment. For asthma morbidity, we used self-reported asthma exacerbations in the year before enrollment (corticosteroid bursts, emergency room/urgent care visits, or hospitalizations), and Asthma Control Test scores. We tested for mediation via health literacy, perceived stress, and self-reported discrimination. All models adjusted for age, sex, body mass index, ethnicity, and comorbidities. RESULTS: Among 990 AA/B and H/L adults, low SES (latent variable) was directly associated with hospitalizations (ß = 0.24) and worse Asthma Control Test scores (ß = 0.20). Stress partially mediated the relationship between SES and increased emergency room/urgent care visits and worse asthma control (ß = 0.03 and = 0.05, respectively). Individual SES domains were directly associated with asthma morbidity. Stress mediated indirect associations between low educational attainment and unemployment with worse asthma control (ß = 0.05 and = 0.06, respectively). CONCLUSIONS: Lower SES is directly, and indirectly through stress, associated with asthma morbidity among AA/B and H/L adults. Identification of stressors and relevant management strategies may lessen asthma-related morbidity among these populations.

Caribbean Latinx with moderate-severe asthma bear greater asthma morbidity than other Latinx.

BACKGROUND: Hispanic/Latinx (HL) ethnicity encompasses racially and culturally diverse subgroups. Studies suggest that Puerto Ricans (PR) may bear greater asthma-related morbidity than Mexicans, but these were conducted in children or had limited clinical characterization. OBJECTIVES: This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups. METHODS: Adults with moderate-severe asthma were recruited from US clinics, including from Puerto Rico, for the Person Empowered Asthma Relief (PREPARE) trial. Considering the shared heritage between PR and other Caribbean HL (Cubans and Dominicans [C&D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and C&D: n = 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n = 141), and between CHL subgroups (C&D [n = 56] and PR [n = 401]). This study compared asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids, emergency department/urgent care (ED/UC) visits, hospitalizations, health care utilization) through negative binomial regression. RESULTS: CHL compared to OHL were similar in age, body mass index, poverty status, blood eosinophils, and fractional exhaled nitric oxide but were prescribed more asthma controller therapies. Relative to OHL, CHL had significantly increased odds of asthma exacerbations (odds ratio [OR]: 1.84; 95% CI: 1.4-2.4), ED/UC visits (OR: 1.88; 95% CI: 1.4-2.5), hospitalization (OR: 1.98; 95% CI: 1.06-3.7), and health care utilization (OR: 1.91; 95% CI: 1.44-2.53). Of the CHL subgroups, PR had significantly increased odds of asthma exacerbations, ED/UC visits, hospitalizations, and health care utilization compared to OHL, whereas C&D only had increased odds of exacerbations compared to OHL. PR compared to C&D had greater odds of ED/UC and health care utilization. CONCLUSIONS: CHL adults, compared with OHL, adults reported nearly twice the asthma morbidity; these differences are primarily driven by PR. Novel interventions are needed to reduce morbidity in this highly impacted population.

Continuous glucose monitoring for primary care patients with diabetes: Barriers, facilitators, & resources to support access.

Context: Continuous glucose monitoring (CGM) for patients with type 1 and type 2 diabetes is associated with improved patient health outcomes including reduced glycated hemoglobin (A1c) and hypoglycemia and is part of ADA Standards of Medical Care. CGM prescription often takes place in endocrinology practices. With limited access to endocrinologists, many patients could benefit from receiving CGM through primary care. Objective: The overall study aims to understand primary care clinicians' CGM prescribing experience and likelihood to prescribe, and identify resources needed to support prescribing CGM. This qualitative phase examines barriers and facilitators to prescribing, and resources to support prescribing. Study Design: Qualitative phase of an explanatory sequential mixed-methods study following a cross-sectional online survey. Respondents were invited to participate in phone/virtual interviews to understand CGM prescribing attitudes and behaviors. Participants were stratified based on factors related to distance to an endocrinologist and prescribing behavior. Rapid qualitative analysis was used to understand relationships and trends, and identify resources to support CGM prescription in primary care. Setting: Two primary care research networks. Population studied: Primary care physicians and advanced practice providers in the U.S. Outcome Measures: Resources needed, barriers, and facilitators to prescribing CGM. Results: 55 interviews were conducted. The following themes emerged in the analysis: Insurance and cost-related barriers were most commonly cited, as well as distance to endocrinology when > 40 miles away. Facilitators included training and experience with CGM and staff to support patient education and insurance navigation. Resources (e.g., webinars, online guides, conferences) to increase knowledge about CGM use and clinical outcomes and guidance with insurance processes/coverage could support CGM prescription in primary care. Conclusions: Increased understanding among primary care clinicians of the use and benefits of CGM can help with confidence in prescribing. CGM management in primary care could benefit patients with diabetes, especially those with access barriers to endocrinologists. Addressing cost and insurance barriers at a policy level can make CGM more attainable to underserved populations and reduce disparities in diabetes control.

Adherence to adding inhaled corticosteroids to rescue therapy in a pragmatic trial with adults with asthma: A pilot study.

BACKGROUND: Underuse of guideline-recommended inhaled corticosteroids (ICS) controller therapy is a risk factor for greater asthma burden. ICS concomitantly used with rescue inhalers (Patient-Activated Reliever-Triggered ICS ['PARTICS']) reduced asthma exacerbations in efficacy trials, but whether PARTICS is effective in pragmatic trials is unknown. OBJECTIVE: We conducted this pilot to determine the feasibility of executing a large-scale pragmatic PARTICS trial and to improve study protocols. METHODS: Four sites recruited 33 Hispanic or black adults with persistent asthma, randomized them approximately 3:1 to intervention or usual care, and followed them for 12 weeks. All participants received asthma guideline-based educational videos; intervention participants received video-based instructions on implementing PARTICS plus usual medications. The study involved 1 randomization visit and monthly questionnaires. Timely questionnaire responses (±2 weeks) were monitored. Participants underwent qualitative phone interviews to assess self-reported adherence to PARTICS and understand barriers to completing study procedures. RESULTS: Timely questionnaire response rates were 61%, 64%, and 70% at 4, 8, and 12 weeks, respectively. Self-reported adherence to PARTICS was 76% (95% confidence interval [CI], 58%-94% [n = 21]), 88% (95%CI, 72%-100% [n = 16]), and 62% (95%CI, 36%-88% [n = 13]) at weeks 1, 6, and 12, respectively. Barriers to completing study procedures included difficulties with questionnaire access, remembering to use ICS and rescue inhalers together, and obtaining refills. Only 22% of participants recognized their short-acting bronchodilator as "reliever" or "rescue." CONCLUSION: Recruitment was feasible within the allocated period. Adherence to PARTICS was incomplete, questionnaire completion was suboptimal, and common rescue inhaler nomenclature usage was limited. We have modified the full study protocol to attempt to improve adherence to PARTICS and minimize barriers to study procedures. CLINICAL TRIALS REGISTRATION: pilot study for 'PeRson EmPowered Asthma Relief' (PREPARE, NCT02995733).

The asthma Symptom Free Days Questionnaire: how reliable are patient responses?

Objective: Symptom free days are a widely used patient-reported outcome (PRO) in asthma clinical trials. We assessed the internal consistency of one instrument for this PRO, the Symptom Free Days Questionnaire (SFDQ), in a population of Black adults with asthma enrolled in the Blacks and Exacerbations on Long-acting beta agonists and Tiotropium (BELT) trial. Methods: We assessed responses to the SFDQ collected at baseline, 6 and 12 months as part of the BELT trial. The internal consistency of responses, specifically number of patient-reported days with symptoms in 14 days were compared to the number of patient-reported days with no symptoms in the same 14 days. Lin concordance correlation coefficients (Lin ccc) were calculated over time to assess "learning" and by age, sex, geographic location, and annual family income. Results: The internal consistency of the responses of the 1070 enrolled patients was consistently low over the 12 months of the study; varying from 43.8% at baseline to 52.1% at 12 months. This corresponded to Lin cccs of 0.33-0.32 over the study period. Internal consistency and the Lin ccc did not vary by age group, sex, geographic location or percent poverty. Concordance was slightly but not significantly higher at all time points in those with family annual income of ≥$50,000 compared to those with lower annual incomes. Conclusions: The SFDQ did not work well in the BELT population of Black adults with asthma. Further validation is required before the SFDQ is used in other large clinical trials with any population.

A Systematic Review and Meta-analysis of Thrombotic Events Following Endovenous Thermal Ablation of the Great Saphenous Vein.

OBJECTIVES: A systematic review and meta-analysis was performed to determine the incidence of thrombotic events following great saphenous vein (GSV) endovenous thermal ablation (EVTA). METHODS: MEDLINE, Embase and conference abstracts were searched. Eligible studies were randomised controlled trials and case series that included at least 100 patients who underwent GSV EVTA (laser ablation or radiofrequency ablation [RFA]) with duplex ultrasound (DUS) within 30 days. The systematic review focused on the complications of endovenous heat induced thrombosis (EHIT), deep venous thrombosis (DVT), and pulmonary embolism (PE). The primary outcome for the meta-analysis was deep venous thrombotic events which were defined as DVT or EHIT Type 2, 3, or 4. Secondary outcomes for the meta-analysis were EHIT Type 2, 3, or 4, DVT and PE. Subgroup analyses were performed for both the RFA and EVLA groups. Pooled proportions were calculated using random effects modelling. RESULTS: Fifty-two studies (16,398 patients) were included. Thrombotic complications occurred infrequently. Deep venous thrombotic events occurred in 1.7% of cases (95% CI 0.9-2.7%) (25 studies; 10,012 patients; 274 events). EHIT Type 2, 3, or 4 occurred in 1.4% of cases (95% CI 0.8-2.3%) (26 studies; 10,225 patients; 249 events). DVT occurred in 0.3% of cases (95% CI = 0.2%-0.5%) (49 studies; 15,676 patients; 48 events). PE occurred in 0.1% of cases (95% CI = 0.1-0.2%) (29 studies; 8223 patients; 3 events). Similar results were found when the RFA and EVLA groups were analysed separately. CONCLUSION: Thrombotic events occur infrequently following GSV EVTA. Given the large numbers of procedures worldwide and the potential for serious consequences, further research is needed on the burden of these complications and their management.

Low-Dose Carotid Computed Tomography Angiography Using Pure Iterative Reconstruction.

UNLABELLED: The aim of this study was to assess if a low-dose carotid computed tomography angiography (CTA) performed with pure iterative reconstruction (IR) is comparable to a conventional dose CTA protocol. METHODS: Twenty patients were included. Radiation dose was divided into a low-dose acquisition reconstructed with pure IR and a conventional dose acquisition reconstructed with 40% hybrid IR. Dose, image noise, contrast resolution, spatial resolution, and carotid artery stenosis were measured. RESULTS: Mean effective dose was significantly lower for low-dose than conventional dose studies (1.84 versus 3.71 mSv; P < 0.001). Subjective image noise, contrast resolution, and spatial resolution were significantly higher for the low-dose studies. There was excellent agreement for stenosis grading accuracy between low- and conventional dose studies (Cohen κ = 0.806). CONCLUSIONS: A low-dose carotid CTA protocol reconstructed with pure IR is comparable to a conventional dose CTA protocol in terms of image quality and diagnostic accuracy while enabling a dose reduction of 49.6%.

Exploiting highly ordered subnanoliter volume microcapillaries as microtools for the analysis of antibody producing cells.

The interrogation of highly diverse repertoires of heterogeneous cell populations on a single cell basis increases the likelihood that a cell with unique characteristics will be identified. We have developed a new single cell analysis system comprising millions of bundled subnanoliter volume bioincubation chambers for the identification and recovery of target specific antibody secreting cells (ASCs). This platform integrates dual surface screening with dedicated user driven data analysis and automated cell recovery enabling multiple biophysical parameters to be tracked for millions of antibody leads in parallel. This direct clone analysis and selection technology is a clear deviation from current microfabricated well-based approaches and offers drastically enhanced screening throughput, simultaneous dual surface analysis, and rapid automated single cell recovery. The technology is also applicable to screening both bacterial and mammalian antibody secreting cells. We demonstrate the implementation and feasibility of this platform in identifying target specific antibodies from bacterial, hybridoma, and B cell libraries.

Clinician suspicion of an alcohol problem: an observational study from the AAFP National Research Network.

PURPOSE: In clinical practice, detection of alcohol problems often relies on clinician suspicion instead of using a screening instrument. We assessed the sensitivity, specificity, and predictive values of clinician suspicion compared with screening-detected alcohol problems in patients. METHODS: We undertook a cross-sectional study of 94 primary care clinicians' office visits. Brief questionnaires were completed separately after a visit by both clinicians and eligible patients. The patient's anonymous exit questionnaire screened for hazardous drinking based on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and for harmful drinking (alcohol abuse or dependence) based on 2 questions from the Diagnostic and Statistical Manual of Mental Disorders. After the visit, clinicians responded to the question, "Does this patient have problems with alcohol?" with answer options including "yes, hazardous drinking" and "yes, alcohol abuse or dependence." Analyses assessed the associations between patients' responses to screening questions and clinician's suspicions. RESULTS: Of 2,518 patients with an office visit, 2,173 were eligible, and 1,699 (78%) completed the exit questionnaire. One hundred seventy-one (10.1%) patients had a positive screening test for hazardous drinking (an AUDIT-C score of 5 or greater) and 64 (3.8%) for harmful drinking. Clinicians suspected alcohol problems in 81 patients (hazardous drinking in 37, harmful drinking in 40, and both in 4). The sensitivity of clinician suspicion of either hazardous or harmful drinking was 27% and the specificity was 98%. Positive and negative predictive values were 62% and 92%, respectively. CONCLUSION: Clinician suspicion of alcohol problems had poor sensitivity but high specificity for identifying patients who had a positive screening test for alcohol problems. These data support the routine use of a screening tool to supplement clinicians' suspicions, which already provide reasonable positive predictive value.

Effectiveness of 2 methods of promoting physical activity, healthy eating, and emotional well-being with the americans in motion--healthy interventions approach.

PURPOSE: An increasing number of Americans are putting their health at risk from being overweight. We undertook a study to compare patient-level outcomes of 2 methods of implementing the Americans In Motion-Healthy Interventions (AIM-HI) approach to promoting physical activity, healthy eating, and emotional well-being. METHODS: We conducted a randomized trial in which 24 family medicine practices were randomized to (1) an enhanced practice approach in which clinicians and office staff used AIM-HI tools to make personal changes and created a healthy environment, or (2) a traditional practice approach in which physicians and staff were trained and asked to use the tools with patients. Of the 610 patients enrolled, 331 were in healthy practices, and 279 were in traditional practices. At 0, 4, and 10 months we assessed blood pressure, body mass index, fasting blood glucose and insulin levels, nuclear magnetic resonance lipoprotein profiles, fitness, dietary intake, physical activity, and emotional well-being. Outcome data were analyzed using linear, mixed-effects multivariate models, adjusting for practices as a random effect. RESULTS: Regardless of patient group, 16.2% of patients who completed a 10-month visit (n = 378 patients, 62% of enrollees) and 10% of all patients enrolled lost 5% or more of their body weight; 16.7% of patients who completed a 10-month visit (10.3% of all enrollees) had a 2-point or greater increase in their fitness level; and 29.2% of 10-month completers (18.0% of all enrollees) lost 5% or more of their body weight and/or increased their fitness level by 2 or more points. There were no significant differences in these outcomes between groups. CONCLUSIONS: There was no difference between the 2 groups in the primary and most secondary outcomes. Both patient groups were able to show significant before-after improvements in selected patient-level outcomes.

Identification of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor.

The discovery of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor is described. The characterization and redressing of the issues associated with these compounds is detailed. An efficient three-step synthesis and a binding assay were relied upon as the primary means of rapidly improving potency and ADMET properties for this class of inverse agonist compounds. Compound 10 n bearing distributed polarity in the form of an imidazo-thiazole acetamide and a phenyl triazole is a unit lower in logP and has significantly improved binding affinity compared to the hit molecule 10a, providing support for further optimization of this series of compounds.

A computationally efficient discrete pseudomodulation algorithm for real-time magnetic resonance measurements.

Rapid-scan electron paramagnetic resonance (RSEPR) results in a significant improvement in signal-to-noise over magnetic field modulated continuous wave EPR (CWEPR). However, the RSEPR raw absorption spectra can make the real-time comparison of CWEPR spectra difficult, especially in systems where the total number of paramagnetic spins is low. In this paper, we illustrate a method of applying pseudomodulation within RSEPR data collection software in real-time. Pseudomodulation is generally carried out in post-processing to increase signal-to-noise and simulate the effects of modulation on the spectra observed in traditional magnetic field modulated CWEPR. By applying the pseudomodulation method on a discrete computational basis, the technique can be utilized in parallel with data collection due to the significantly reduced computational power of the discretized pseudomodulation calculation. This allows for the live alteration of modulation parameters, such as the modulation amplitude and modulation harmonic. This real-time simulation allows for the comparison of the accumulated non-adiabatic rapid-sweep EPR spectra with the known CWEPR spectra available in the literature and has the ability to view smaller and less sensitive resonance features for various harmonics during high-frequency experiments while retaining all signal-to-noise improvements.

Socioeconomic impact of COVID-19 and willingness to be vaccinated in African American/Black and Hispanic/Latinx adults.

PURPOSE: To describe the socioeconomic and healthcare-related effects of the COVID-19 pandemic, and willingness to receive a free COVID-19 vaccine, among African American/Black (AA/B) and Hispanic/Latinx (H/L) adults with asthma currently enrolled in a large trial. METHODS: The present analysis is a sub-study of the PeRson EmPowered Asthma RElief (PREPARE) study, a pragmatic study of 1201 AA/B and H/L adults with asthma. A monthly questionnaire was completed by a subset of PREPARE participants (n = 325) during May-August, 2020. The 5-item questionnaire assessed self-reported impact of COVID-19 on respondents' ability to obtain asthma medications, medical care quality, employment, income and ability to pay bills; and willingness to get a free COVID-19 vaccine. Bivariate analysis and multivariate logistic regression were performed to investigate factors associated with vaccine hesitancy. RESULTS: Of 325 survey respondents (25% AA/B, 75% H/L), the majority reported no impact of COVID-19 on medical care or ability to get asthma medications. Approximately half of employed respondents experienced a lower level of employment or job loss, and approximately half reported having difficulty paying bills during the pandemic. Thirty-five percent of respondents reported unwillingness and 31% reported being somewhat likely to receive a free COVID-19 vaccine. AA/B race/ethnicity and poorer reported physical health were associated with a higher likelihood of COVID-19 vaccine hesitancy. CONCLUSION: AA/B and H/L adults with asthma may experience changes in the quality of their asthma care and increased socioeconomic stressors as a result of the COVID-19 pandemic and may be hesitant or unwilling to receive a COVID-19 vaccine.