Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19.

BACKGROUND: The effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed coronavirus disease 2019 (Covid-19). Nonhospitalized adults 30 years of age or older who had at least two symptoms of acute infection that had been present for no more than 7 days before enrollment were randomly assigned to receive inhaled fluticasone furoate at a dose of 200 µg once daily for 14 days or placebo. The primary outcome was the time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Key secondary outcomes included hospitalization or death by day 28 and a composite outcome of the need for an urgent-care or emergency department visit or hospitalization or death through day 28. RESULTS: Of the 1407 enrolled participants who underwent randomization, 715 were assigned to receive inhaled fluticasone furoate and 692 to receive placebo, and 656 and 621, respectively, were included in the analysis. There was no evidence that the use of fluticasone furoate resulted in a shorter time to recovery than placebo (hazard ratio, 1.01; 95% credible interval, 0.91 to 1.12; posterior probability of benefit [defined as a hazard ratio >1], 0.56). A total of 24 participants (3.7%) in the fluticasone furoate group had urgent-care or emergency department visits or were hospitalized, as compared with 13 participants (2.1%) in the placebo group (hazard ratio, 1.9; 95% credible interval, 0.8 to 3.5). Three participants in each group were hospitalized, and no deaths occurred. Adverse events were uncommon in both groups. CONCLUSIONS: Treatment with inhaled fluticasone furoate for 14 days did not result in a shorter time to recovery than placebo among outpatients with Covid-19 in the United States. (Funded by the National Center for Advancing Translational Sciences and others; ACTIV-6 ClinicalTrials.gov number, NCT04885530.).

A point-of-care pilot randomized intervention to connect patients with cancer-induced financial toxicity to telehealth financial counseling.

PURPOSE: Elevated costs of cancer treatment can result in economic and psychological "financial toxicity" distress. This pilot study assessed the feasibility of a point-of-care intervention to connect adult patients with cancer-induced financial toxicity to telehealth-delivered financial counseling. METHODS: We conducted a three-armed parallel randomized pilot study, allocating newly referred patients with cancer and financial toxicity to individual, group accredited telehealth financial counseling, or usual care with educational material (1:1:1). We assessed the feasibility of recruitment, randomization, retention, baseline and post-intervention COmprehensive Score for Financial Toxicity (COST), and Telehealth Usability Questionnaire (TUQ) scores. RESULTS: Of 382 patients screened, 121 were eligible and enrolled. 58 (48%) completed the intervention (9 individual, 9 group counseling, 40 educational booklet). 29 completed follow-up surveys: 45% female, 17% African American, 79% white, 7% Hispanic, 55% 45-64 years old, 31% over 64, 34% lived in rural areas, 24% had cancer stage I, 21% II, 7% III, 31% IV. Baseline characteristics were balanced across arms, retention status, surveys completion. Mean (SD) COST was 12.4 (6.1) at baseline and 16.0 (8.4) post-intervention. Mean (SD) COST score differences were 6.3 (11.6) after individual counseling, 5.8 (8.5) after group counseling, and 2.5 (6.4) after usual care. Mean TUQ score among nine counseling participants was 5.5 (0.9) over 7.0. Non-parametric comparisons were not statistically meaningful. CONCLUSION: Recruitment and randomization were feasible, while study retention presented challenges. Nine participants reported good usability and satisfaction with telehealth counseling. Larger-scale trials focused on improving participation, retention, and impact of financial counseling among patients with cancer are justified.

Developing an automated algorithm for identification of children and adolescents with diabetes using electronic health records from the OneFlorida+ clinical research network.

AIM: To develop an automated computable phenotype (CP) algorithm for identifying diabetes cases in children and adolescents using electronic health records (EHRs) from the UF Health System. MATERIALS AND METHODS: The CP algorithm was iteratively derived based on structured data from EHRs (UF Health System 2012-2020). We randomly selected 536 presumed cases among individuals aged <18 years who had (1) glycated haemoglobin levels ≥ 6.5%; or (2) fasting glucose levels ≥126 mg/dL; or (3) random plasma glucose levels ≥200 mg/dL; or (4) a diabetes-related diagnosis code from an inpatient or outpatient encounter; or (5) prescribed, administered, or dispensed diabetes-related medication. Four reviewers independently reviewed the patient charts to determine diabetes status and type. RESULTS: Presumed cases without type 1 (T1D) or type 2 diabetes (T2D) diagnosis codes were categorized as non-diabetes/other types of diabetes. The rest were categorized as T1D if the most recent diagnosis was T1D, or otherwise categorized as T2D if the most recent diagnosis was T2D. Next, we applied a list of diagnoses and procedures that can determine diabetes type (e.g., steroid use suggests induced diabetes) to correct misclassifications from Step 1. Among the 536 reviewed cases, 159 and 64 had T1D and T2D, respectively. The sensitivity, specificity, and positive predictive values of the CP algorithm were 94%, 98% and 96%, respectively, for T1D and 95%, 95% and 73% for T2D. CONCLUSION: We developed a highly accurate EHR-based CP for diabetes in youth based on EHR data from UF Health. Consistent with prior studies, T2D was more difficult to identify using these methods.

Using Power Analysis to Choose the Unit of Randomization, Outcome, and Approach for Subgroup Analysis for a Multilevel Randomized Controlled Clinical Trial to Reduce Disparities in Cardiovascular Health.

We give examples of three features in the design of randomized controlled clinical trials which can increase power and thus decrease sample size and costs. We consider an example multilevel trial with several levels of clustering. For a fixed number of independent sampling units, we show that power can vary widely with the choice of the level of randomization. We demonstrate that power and interpretability can improve by testing a multivariate outcome rather than an unweighted composite outcome. Finally, we show that using a pooled analytic approach, which analyzes data for all subgroups in a single model, improves power for testing the intervention effect compared to a stratified analysis, which analyzes data for each subgroup in a separate model. The power results are computed for a proposed prevention research study. The trial plans to randomize adults to either telehealth (intervention) or in-person treatment (control) to reduce cardiovascular risk factors. The trial outcomes will be measures of the Essential Eight, a set of scores for cardiovascular health developed by the American Heart Association which can be combined into a single composite score. The proposed trial is a multilevel study, with outcomes measured on participants, participants treated by the same provider, providers nested within clinics, and clinics nested within hospitals. Investigators suspect that the intervention effect will be greater in rural participants, who live farther from clinics than urban participants. The results use published, exact analytic methods for power calculations with continuous outcomes. We provide example code for power analyses using validated software.

Telehealth Implementation Response to COVID-19 in the OneFlorida+ Clinical Research Network: Perspectives of Clinicians and Health Systems Leaders.

Introduction: The COVID-19 pandemic forced health systems worldwide to make rapid adjustments to patient care. Nationwide stay-at-home mandates and public health concerns increased demand for telehealth to maintain patients' continuity of care. These circumstances permitted observation of telehealth implementation in real-world settings at a large scale. This study aimed to understand clinician and health system leader (HSL) experiences in expanding, implementing, and sustaining telehealth during COVID-19 in the OneFlorida+ clinical research network. Methods: We conducted semistructured videoconference interviews with 5 primary care providers, 7 specialist providers, and 12 HSLs across 7 OneFlorida+ health systems and settings. Interviews were audiorecorded, transcribed, and summarized using deductive team-based template coding. We then used matrix analysis to organize the qualitative data and identify inductive themes. Results: Rapid telehealth implementation occurred even among sites with low readiness, facilitated by responsive planning, shifts in resource allocation, and training. Common hurdles in routine telehealth use, including technical and reimbursement issues, were also barriers to telehealth implementation. Acceptability of telehealth was influenced by benefits such as the providers' ability to view a patient's home environment and the availability of tools to enhance patient education. Lower acceptability stemmed from the inability to conduct physical examinations during the shutdown. Conclusions: This study identified a broad range of barriers, facilitators, and strategies for implementing telehealth within large clinical research networks. The findings can contribute to optimizing the effectiveness of telehealth implementation in similar settings, and point toward promising directions for telehealth provider training to improve acceptability and promote sustainability.

Avenues for Strengthening PCORnet's Capacity to Advance Patient-Centered Economic Outcomes in Patient-Centered Outcomes Research (PCOR).

PCORnet, the National Patient-Centered Clinical Research Network, provides the ability to conduct prospective and observational pragmatic research by leveraging standardized, curated electronic health records data together with patient and stakeholder engagement. PCORnet is funded by the Patient-Centered Outcomes Research Institute (PCORI) and is composed of 8 Clinical Research Networks that incorporate at total of 79 health system "sites." As the network developed, linkage to commercial health plans, federal insurance claims, disease registries, and other data resources demonstrated the value in extending the networks infrastructure to provide a more complete representation of patient's health and lived experiences. Initially, PCORnet studies avoided direct economic comparative effectiveness as a topic. However, PCORI's authorizing law was amended in 2019 to allow studies to incorporate patient-centered economic outcomes in primary research aims. With PCORI's expanded scope and PCORnet's phase 3 beginning in January 2022, there are opportunities to strengthen the network's ability to support economic patient-centered outcomes research. This commentary will discuss approaches that have been incorporated to date by the network and point to opportunities for the network to incorporate economic variables for analysis, informed by patient and stakeholder perspectives. Topics addressed include: (1) data linkage infrastructure; (2) commercial health plan partnerships; (3) Medicare and Medicaid linkage; (4) health system billing-based benchmarking; (5) area-level measures; (6) individual-level measures; (7) pharmacy benefits and retail pharmacy data; and (8) the importance of transparency and engagement while addressing the biases inherent in linking real-world data sources.

Stratified split sampling of electronic health records.

Although superficially similar to data from clinical research, data extracted from electronic health records may require fundamentally different approaches for model building and analysis. Because electronic health record data is designed for clinical, rather than scientific use, researchers must first provide clear definitions of outcome and predictor variables. Yet an iterative process of defining outcomes and predictors, assessing association, and then repeating the process may increase Type I error rates, and thus decrease the chance of replicability, defined by the National Academy of Sciences as the chance of "obtaining consistent results across studies aimed at answering the same scientific question, each of which has obtained its own data."[1] In addition, failure to account for subgroups may mask heterogeneous associations between predictor and outcome by subgroups, and decrease the generalizability of the findings. To increase chances of replicability and generalizability, we recommend using a stratified split sample approach for studies using electronic health records. A split sample approach divides the data randomly into an exploratory set for iterative variable definition, iterative analyses of association, and consideration of subgroups. The confirmatory set is used only to replicate results found in the first set. The addition of the word 'stratified' indicates that rare subgroups are oversampled randomly by including them in the exploratory sample at higher rates than appear in the population. The stratified sampling provides a sufficient sample size for assessing heterogeneity of association by testing for effect modification by group membership. An electronic health record study of the associations between socio-demographic factors and uptake of hepatic cancer screening, and potential heterogeneity of association in subgroups defined by gender, self-identified race and ethnicity, census-tract level poverty and insurance type illustrates the recommended approach.

Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear. Objective: To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US. Interventions: Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28. Results: Among 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether ivermectin, with a maximum targeted dose of 600 µg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19. Objective: To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1206 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022. Interventions: Participants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 µg/kg (n = 602) daily, or placebo (n = 604) for 6 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. Results: Among 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Early prediction of Alzheimer's disease and related dementias using real-world electronic health records.

INTRODUCTION: This study aims to explore machine learning (ML) methods for early prediction of Alzheimer's disease (AD) and related dementias (ADRD) using the real-world electronic health records (EHRs). METHODS: A total of 23,835 ADRD and 1,038,643 control patients were identified from the OneFlorida+ Research Consortium. Two ML methods were used to develop the prediction models. Both knowledge-driven and data-driven approaches were explored. Four computable phenotyping algorithms were tested. RESULTS: The gradient boosting tree (GBT) models trained with the data-driven approach achieved the best area under the curve (AUC) scores of 0.939, 0.906, 0.884, and 0.854 for early prediction of ADRD 0, 1, 3, or 5 years before diagnosis, respectively. A number of important clinical and sociodemographic factors were identified. DISCUSSION: We tested various settings and showed the predictive ability of using ML approaches for early prediction of ADRD with EHRs. The models can help identify high-risk individuals for early informed preventive or prognostic clinical decisions.

Clinicians' perceptions of barriers to cervical cancer screening for women living with behavioral health conditions: a focus group study.

BACKGROUND: Women with behavioral health (BH) conditions (e.g., mental illness and substance abuse) receive fewer cervical cancer (CC) screenings, are diagnosed at more advanced cancer stages, and are less likely to receive specialized treatments. The aim of this study was to identify barriers that healthcare providers face in providing CC screening to women with BH conditions. METHODS: Guided by the Consolidated Framework for Implementation Research, we conducted four focus groups in North Florida with 26 primary care and BH clinicians and staff to examine perceived barriers to CC screening among their patients with BH conditions to guide the future development of a tailored cervical cancer screening and follow-up intervention. Thematic analysis was used to analyze verbatim transcripts from audiotaped focus groups. RESULTS: Three main themes of barriers emerged from the data: 1) BH conditions related barriers included a history of trauma, stigma and discrimination, and uncontrolled comorbid conditions, 2) System level barriers related to lack of integration between BH and primary care, and 3) Similar barriers to the general population including lack of health insurance, insufficient processes to send out reminders, and challenges with communicating with patients. CONCLUSIONS: Tailored CC screening interventions that address the unique needs of women with BH conditions are needed. Strategies that address improving trust between patients and healthcare providers, identifying avenues to improve receipt of screening during time-limited clinical visits, connecting BH and primary care providers, and addressing the social determinants of health have potential to improve CC screening rates for women with BH conditions.

Hepatitis C virus (HCV) seroprevalence, RNA detection, and genotype distribution across Florida, 2015-2018.

Chronic hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma (HCC) in the U.S. Due to high rates of HCV among baby boomers (born 1945-1965), it was recommended they receive universal screening. This was expanded to all U.S. adults in 2020 due to evidence of increasing rates of chronic HCV in younger adults. An assessment of HCV burden across demographics is crucial to understand the future burden of HCC and target under-screened adults for HCV. Using the OneFlorida Clinical Research Consortium, of more than one million individuals in Florida, all HCV antibody and viral RNA tests completed from 2015 to 2018 were identified. HCV seroprevalence, HCV viral load (active infection), and HCV genotype distribution by risk groups were assessed. Overall, HCV seroprevalence and active infection were highest among White non-Hispanic individuals, males, and baby boomers. However, odds of a positive HCV antibody test were higher among Black non-Hispanic individuals born before 1945 (aOR: 2.74; 95% CI: 1.98-3.78) or 1945-1965 (aOR: 1.46; 95% CI: 1.36-1.56) compared to White non-Hispanic individuals. In contrast, among individuals born after 1965, Black non-Hispanics were less likely than White non-Hispanics to test HCV antibody positive (aOR of 0.5-0.28). A similar age/race pattern was observed for active HCV infection. There was a higher prevalence of genotype 1A and 3 and lower prevalence of 1B in younger adults. Patterns of HCV seroprevalence and active HCV infection identified in our study support the recent shift from age and risk-based screening guidelines to universal adult screening.

Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 µg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 µg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Cost evaluation of tobacco control interventions in clinical settings: A systematic review.

Elucidating the cost implications of tobacco control interventions is a prerequisite to their adoption in clinical settings. This review fills a knowledge gap in characterizing the extent to which cost is measured in tobacco control studies. A search of English literature was conducted in the following electronic databases: MEDLINE, EconLit, PsychINFO, and CINAHL using MeSH terms from 2009 to 2018. Studies were reviewed by two independent reviewers and included if they were conducted in U.S. inpatient or outpatient facilities and reported costs associated with a tobacco control intervention. They were categorized according to evaluation type, clinical setting, target population, cost measures, and stakeholder perspective. Bias risk was evaluated for RCTs. Seventeen publications were included, representing counseling interventions (n = 8) and combination (i.e., counseling and pharmacotherapy) interventions (n = 9). Studies were categorized by evaluation type: cost-effectiveness analysis (n = 10), cost utility analysis (n = 3) and cost identification (n = 4). The selected studies targeted the following populations: general adults (n = 6), hospitalized/inpatient (n = 4), military/veterans (n = 4), individuals with low socioeconomic status (n = 4), mental health or medical comorbidities (n = 2), and pregnant women (n = 2). Intervention costs included personnel, medication, education material, technology, and overhead costs. Stakeholder perspectives included: healthcare organization (n = 10), payer (n = 8), patient (n = 2), and societal (n = 1). Few studies have reported the cost of tobacco control interventions in clinical settings. Cost is a critical outcome that should be consistently measured in evaluations of tobacco control interventions to promote their uptake in clinical settings.

HCV testing: Order and completion rates among baby boomers obtaining care from seven health systems in Florida, 2015-2017.

Many U.S. residents infected with hepatitis C virus (HCV) are baby boomers (born 1945-1965), who remain undiagnosed. Past CDC and USPSTF guidelines recommended one-time HCV testing for all baby boomers, with newer guidelines recommending universal screening for all adults. This retrospective cohort study examined electronic medical records for patient visits from 2015 to 2017 within the OneFlorida Data Trust and University of South Florida Health system. We assessed percentages of HCV tests ordered and completed across four age groups (those born before 1945, 1945-1965, 1966-1985, and after 1985). In 2019, we used logistic regression to examine factors associated with HCV test ordering and completion among baby boomers, including age, race, sex, number of primary care visits, HIV status, hepatitis diagnosis, and liver cancer history. All age groups had low rates of HCV test orders. 4.4% of baby boomers had a test ordered in 2015, and 6.7% in 2016. Of those, 94.5% and 89.7% completed testing, respectively. All other races/ethnicities had lower likelihood of testing completion than Whites (Blacks (aOR 0.82, 95%, CI 0.75-0.91); Asians (0.69, 0.52-0.92); Hispanics (0.29, 0.26-0.32)), although test orders were higher for Asians (1.48, 1.37-1.61) and Blacks (1.78, 1.73-1.82). Tests ordered (11.42, 10.94-11.92) and completed (2.25, 1.94-2.60) were more likely among those with hepatitis history. Test orders were more likely for HIV-positive patients (3.68, 3.45-3.93), but completion was less likely (0.67, 0.57-0.78). Interventions are needed to increase testing rates so that HCV infections are treated early, mitigating HCV-related morbidity and mortality, especially related to liver cancer.

Cost-Effectiveness of the Wellness Incentives and Navigation (WIN) Program.

OBJECTIVES: Promoting patient involvement in managing co-occurring physical and mental health conditions is increasingly recognized as critical to improving outcomes and controlling costs in this growing chronically ill population. The main objective of this study was to conduct an economic evaluation of the Wellness Incentives and Navigation (WIN) intervention as part of a longitudinal randomized pragmatic clinical trial for chronically ill Texas Medicaid enrollees with co-occurring physical and mental health conditions. METHODS: The WIN intervention used a personal navigator, motivational interviewing, and a flexible wellness expense account to increase patient activation, that is, the patient's knowledge, skills, and confidence in managing their self-care and co-occurring physical and mental health conditions. Regression models were fit to both participant-level quality-adjusted life years (QALYs) and total costs of care (including the intervention) controlling for demographics, health status, poverty, Medicaid managed care plan, intervention group, and baseline health utility and costs. Incremental costs and QALYs were calculated based on the difference in predicted costs and QALYs under intervention versus usual care and were used to calculate the incremental cost-effectiveness ratios (ICERs). Confidence intervals were calculated using Fieller's method, and sensitivity analyses were performed. RESULTS: The mean ICER for the intervention compared with usual care was $12 511 (95% CI $8971-$16 842), with a sizable majority of participants (70%) having ICERs below $40 000. The WIN intervention also produced higher QALY increases for participants who were sicker at baseline compared to those who were healthier at baseline. CONCLUSION: The WIN intervention shows considerable promise as a cost-effective intervention in this challenging chronically ill population.

Perspectives of pregnant and breastfeeding women on longitudinal clinical studies that require non-invasive biospecimen collection - a qualitative study.

BACKGROUND: Investigation of the microbiome during early life has stimulated an increasing number of cohort studies in pregnant and breastfeeding women that require non-invasive biospecimen collection. The objective of this study was to explore pregnant and breastfeeding women's perspectives on longitudinal clinical studies that require non-invasive biospecimen collection and how they relate to study logistics and research participation. METHODS: We completed in-depth semi-structured interviews with 40 women who were either pregnant (n = 20) or breastfeeding (n = 20) to identify their understanding of longitudinal clinical research, the motivations and barriers to their participation in such research, and their preferences for providing non-invasive biospecimen samples. RESULTS: Perspectives on research participation were focused on breastfeeding and perinatal education. Participants cited direct benefits of research participation that included flexible childcare, lactation support, and incentives and compensation. Healthcare providers, physician offices, and social media were cited as credible sources and channels for recruitment. Participants viewed lengthy study visits and child protection as the primary barriers to research participation. The barriers to biospecimen collection were centered on stool sampling, inadequate instructions, and drop-off convenience. CONCLUSION: Women in this study were interested in participating in clinical studies that require non-invasive biospecimen collection, and motivations to participate center on breastfeeding and the potential to make a scientific contribution that helps others. Effectively recruiting pregnant or breastfeeding participants for longitudinal microbiome studies requires protocols that account for participant interests and consideration for their time.

A feasibility trial of parent HPV vaccine reminders and phone-based motivational interviewing.

BACKGROUND: We assessed the feasibility and acceptability of a sequential approach of parent-targeted HPV vaccine reminders and phone-based Motivation Interviewing (MI). METHODS: In 2016, we selected all 11- to 12-year-old boys and girls seen in one clinic whose vaccine records did not include the HPV vaccine (n=286). By gender, we individually randomized parents of adolescents to an interactive text message (74 girls and 45 boys), postcard reminder (46 boys and no girls because of previously demonstrated efficacy), or standard care group (75 girls and 46 boys). Reminders were sent with medical director permission and a HIPAA waiver. Two months after reminders, among the adolescents whose vaccine records still did not include the HPV vaccine, we selected a gender-stratified random sample of 20 parents for phone-based MI. We assessed the percentage of deliverable messages, the percentage of parents' responding to the interactive text message, parent acceptability of receiving a text message, and MI parent responsiveness and interviewer competence (MI Treatment Integrity Coding system). RESULTS: Nearly all messages were deliverable (98% of postcards and 74% of text messages). Six of the 88 parents (7%) receiving text messages scheduled an appointment through our interactive system. The acceptability survey response rate was 37% (38/102). Respondents were favorable toward vaccine reminders for all parents (82%). Among 20 sampled parents, 17 were reached by phone of whom 7 completed MI, 4 had or were getting the HPV vaccine for their child, and 5 expressed disinterest. Across the 7 MI calls, the interviewer was rated 100% MI adherent and scored an average 4.19 rating for Global Spirit. CONCLUSION: Without providing explicit consent to receive vaccine-related messages, parents nonetheless found postcards and interactive text messages acceptable. Centralizing MI to phone calls with trained staff was acceptable to parents and resulted in highly MI-adherent interviews.

Specific adverse childhood experiences and their association with other adverse childhood experiences, asthma and emotional, developmental and behavioral problems in childhood.

BACKGROUND: Adverse childhood experiences (ACEs) have lifelong health consequences, yet screening remains challenging. Particularly in clinical settings, brief screeners that could lead to comprehensive assessments may be more feasible. We explore how two ACEs (economic hardship, parental/caregiver divorce/separation) are associated with other ACEs, asthma, and emotional, developmental, or behavioral (EDB) problems. METHODS: Using the 2016 National Survey of Children's Health, we assessed the associations between ACEs and asthma and EDB problems and calculated sensitivities, specificities and predictive values. RESULTS: Parents frequently reported 1+ ACEs for their child (50.3%). Individual ACE frequency ranged from 4.2 to 29.6%; all were significantly associated with EDB problems (adjusted odds ratios (aORs): 2.2-5.1) and more ACEs confirmed higher odds. Two ACES (economic hardship, parental/caregiver divorce/separation) co-occurred frequently with other ACEs, having either predicted EDB problems similarly to other ACEs (aORs 1.8; 95% CI 1.4, 2.3) and having both greatly increased odds (aOR 3.8; 95% CI 2.8, 5.2). The negative predictive value of EDB problems associated with citing neither ACE was high (95.7%). Similar trends with asthma were observed. CONCLUSIONS: Economic hardship and caregiver separation are strongly associated with other ACEs, EDB problems and asthma. A brief screener including these ACEs may reduce clinical barriers to broader ACEs screening.