The mediating effect of health literacy on COVID-19 vaccine confidence among a diverse sample of urban adults in Boston and Chicago

Background A high rate of COVID-19 vaccination is critical to reduce morbidity and mortality related to infection and to control the COVID-19 pandemic. Understanding the factors that influence vaccine confidence can inform policies and programs aimed at vaccine promotion. We examined the impact of health literacy on COVID-19 vaccine confidence among a diverse sample of adults living in two major metropolitan areas. Methods Questionnaire data from adults participating in an observational study conducted in Boston and Chicago from September 2018 through March 2021 were examined using path analyses to determine whether health literacy mediates the relationship between demographic variables and vaccine confidence, as measured by an adapted Vaccine Confidence Index (aVCI). Results Participants (N = 273) were on average 49 years old, 63% female, 4% non-Hispanic Asian, 25% Hispanic, 30% non-Hispanic white, and 40% non-Hispanic Black. Using non-Hispanic white and other race as the reference category, Black race and Hispanic ethnicity were associated with lower aVCI (-0.76, 95% CI -1.00 to -0.50;-0.52, 95% CI -0.80 to -0.27, total effects from a model excluding other covariates). Lower education was also associated with lower aVCI (using college or more as the reference, -0.73 for 12th grade or less, 95% CI -0.93 to -0.47;-0.73 for some college/associate's/technical degree, 95% CI -1.05 to -0.39). Health literacy partially mediated these effects for Black and Hispanic participants and those with lower education (indirect effects -0.19 and -0.19 for Black race and Hispanic ethnicity;0.27 for 12th grade or less;-0.15 for some college/associate's/technical degree). Conclusions Lower levels of education, Black race, and Hispanic ethnicity were associated with lower scores on health literacy, which in turn were associated with lower vaccine confidence. Our findings suggest that efforts to improve health literacy may improve vaccine confidence, which in turn may improve vaccination rates and vaccine equity. Clinical Trials Number: NCT03584490

The mediating effect of health literacy on COVID-19 vaccine confidence among a diverse sample of urban adults in Boston and Chicago.

BACKGROUND: A high rate of COVID-19 vaccination is critical to reduce morbidity and mortality related to infection and to control the COVID-19 pandemic. Understanding the factors that influence vaccine confidence can inform policies and programs aimed at vaccine promotion. We examined the impact of health literacy on COVID-19 vaccine confidence among a diverse sample of adults living in two major metropolitan areas. METHODS: Questionnaire data from adults participating in an observational study conducted in Boston and Chicago from September 2018 through March 2021 were examined using path analyses to determine whether health literacy mediates the relationship between demographic variables and vaccine confidence, as measured by an adapted Vaccine Confidence Index (aVCI). RESULTS: Participants (N = 273) were on average 49 years old, 63 % female, 4 % non-Hispanic Asian, 25 % Hispanic, 30 % non-Hispanic white, and 40 % non-Hispanic Black. Using non-Hispanic white and other race as the reference category, Black race and Hispanic ethnicity were associated with lower aVCI (-0.76, 95 % CI -1.00 to -0.50; -0.52, 95 % CI -0.80 to -0.27, total effects from a model excluding other covariates). Lower education was also associated with lower aVCI (using college or more as the reference, -0.73 for 12th grade or less, 95 % CI -0.93 to -0.47; -0.73 for some college/associate's/technical degree, 95 % CI -1.05 to -0.39). Health literacy partially mediated these effects for Black and Hispanic participants and those with lower education (indirect effects -0.19 and -0.19 for Black race and Hispanic ethnicity; 0.27 for 12th grade or less; -0.15 for some college/associate's/technical degree). CONCLUSIONS: Lower levels of education, Black race, and Hispanic ethnicity were associated with lower scores on health literacy, which in turn were associated with lower vaccine confidence. Our findings suggest that efforts to improve health literacy may improve vaccine confidence, which in turn may improve vaccination rates and vaccine equity. CLINICAL TRIALS NUMBER: NCT03584490.

Using time-weighted average change from baseline of SARS-CoV-2 viral load to assess impact of hydroxychloroquine as postexposure prophylaxis and early treatment for COVID-19.

Two randomized controlled trials demonstrated no clinical benefit of hydroxychloroquine (HCQ) for either postexposure prophylaxis or early treatment of SARS-CoV-2 infection. Using data from these studies, we calculated the time-weighted average change from baseline SARS-CoV-2 viral load and demonstrated that HCQ did not affect viral clearance.

Design and rationale of the mobile health intervention for rural atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a highly morbid condition which requires long-term adherence to oral anticoagulation and may be associated with adverse quality of life and health care utilization. We developed a relational agent-an interactive smartphone-based intervention accessible regardless of digital or health literacy-to assist individuals residing in rural, Western Pennsylvania, with AF with chronic disease self-management. METHODS: The "Mobile health intervention for rural atrial fibrillation" is a single center, parallel-arm randomized clinical trial for adults with AF funded by the National Institute of Health's National Heart, Lung, and Blood Institute to enroll 264 participants. All participants receive a smartphone with data plan: The intervention is a 4 month relational agent coupled with the AliveCor Kardia for heart rate and rhythm monitoring provided by smartphone, and the control a pre-installed, smartphone-based application for health-related information (WebMD). The study uses remote recruitment and engagement to enroll individuals who would otherwise be unlikely to participate in clinical research due to rurality. The primary outcome of the trial is adherence to oral anticoagulation, determined by proportion of days covered, as measured at 12 months. The secondary outcomes are quality of life, both AF-specific and general, and health care utilization. The study entails a baseline visit, a 4 month intervention phase, and 8 and 12 month follow-up visits. CONCLUSIONS: This mobile health trial tests the effectiveness of a smartphone-based relational agent to improve clinical and patient-reported outcomes in rural-dwelling individuals.

Implementation of a fully remote randomized clinical trial with cardiac monitoring.

Background: The coronavirus disease 2019 (COVID-19) pandemic has challenged researchers performing clinical trials to develop innovative approaches to mitigate infectious risk while maintaining rigorous safety monitoring. Methods: In this report we describe the implementation of a novel exclusively remote randomized clinical trial (ClinicalTrials.gov NCT04354428) of hydroxychloroquine and azithromycin for the treatment of the SARS-CoV-2-mediated COVID-19 disease which included cardiovascular safety monitoring. All study activities were conducted remotely. Self-collected vital signs (temperature, respiratory rate, heart rate, and oxygen saturation) and electrocardiographic (ECG) measurements were transmitted digitally to investigators while mid-nasal swabs for SARS-CoV-2 testing were shipped. ECG collection relied on a consumer device (KardiaMobile 6L, AliveCor Inc.) that recorded and transmitted six-lead ECGs via participants' internet-enabled devices to a central core laboratory, which measured and reported QTc intervals that were then used to monitor safety. Results: Two hundred and thirty-one participants uploaded 3245 ECGs. Mean daily adherence to the ECG protocol was 85.2% and was similar to the survey and mid-nasal swab elements of the study. Adherence rates did not differ by age or sex assigned at birth and were high across all reported race and ethnicities. QTc prolongation meeting criteria for an adverse event occurred in 28 (12.1%) participants, with 2 occurring in the placebo group, 19 in the hydroxychloroquine group, and 7 in the hydroxychloroquine + azithromycin group. Conclusions: Our report demonstrates that digital health technologies can be leveraged to conduct rigorous, safe, and entirely remote clinical trials.

Self-Assessed Severity as a Determinant of Coronavirus Disease 2019 Symptom Specificity: A Longitudinal Cohort Study.

Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%-66.7%) to 31.5% (95% CI, 25.7%- 38.0%) but increased specificity from 77.5% (95% CI, 75.3%-79.5%) to 93.8% (95% CI, 92.7%-94.8%).

Detection and Kinetics of Subgenomic Severe Acute Respiratory Syndrome Coronavirus 2 RNA Viral Load in Longitudinal Diagnostic RNA-Positive Samples.

While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness.

Association of an Advance Care Planning Video and Communication Intervention With Documentation of Advance Care Planning Among Older Adults: A Nonrandomized Controlled Trial.

Importance: COVID-19 has disproportionately killed older adults and racial and ethnic minority individuals, raising questions about the relevance of advance care planning (ACP) in this population. Video decision aids and communication skills training offer scalable delivery models. Objective: To assess whether ACP video decision aids and a clinician communication intervention improved the rate of ACP documentation during an evolving pandemic, with a focus on African American and Hispanic patients. Design, Setting, and Participants: The Advance Care Planning: Communicating With Outpatients for Vital Informed Decisions trial was a pre-post, open-cohort nonrandomized controlled trial that compared ACP documentation across the baseline pre-COVID-19 period (September 15, 2019, to March 14, 2020), the COVID-19 wave 1 period (March 15, 2020, to September 14, 2020), and an intervention period (December 15, 2020, to June 14, 2021) at a New York metropolitan area ambulatory network of 22 clinics. All patients 65 years or older who had at least 1 clinic or telehealth visit during any of the 3 study periods were included. Main Outcomes and Measures: The primary outcome was ACP documentation. Results: A total of 14 107 patients (mean [SD] age, 81.0 [8.4] years; 8856 [62.8%] female; and 2248 [15.9%] African American or Hispanic) interacted with clinicians during the pre-COVID-19 period; 12 806 (mean [SD] age, 81.2 [8.5] years; 8047 [62.8%] female; and 1992 [15.6%] African American or Hispanic), during wave 1; and 15 106 (mean [SD] 80.9 [8.3] years; 9543 [63.2%] female; and 2535 [16.8%] African American or Hispanic), during the intervention period. Clinicians documented ACP in 3587 patients (23.8%) during the intervention period compared with 2525 (17.9%) during the pre-COVID-19 period (rate difference [RD], 5.8%; 95% CI, 0.9%-7.9%; P = .01) and 1598 (12.5%) during wave 1 (RD, 11.3%; 95% CI, 6.3%-12.1%; P < .001). Advance care planning was documented in 447 African American patients (30.0%) during the intervention period compared with 233 (18.1%) during the pre-COVID-19 period (RD, 11.9%; 95% CI, 4.1%-15.9%; P < .001) and 130 (11.0%) during wave 1 (RD, 19.1%; 95% CI, 11.7%-21.2%; P < .001). Advance care planning was documented for 222 Hispanic patients (21.2%) during the intervention period compared with 127 (13.2%) during the pre-COVID-19 period (RD, 8.0%; 95% CI, 2.1%-10.9%; P = .004) and 82 (10.2%) during wave 1 (RD, 11.1%; 95% CI, 5.5%-14.5%; P < .001). Conclusions and Relevance: This intervention, implemented during the evolving COVID-19 pandemic, was associated with higher rates of ACP documentation, especially for African American and Hispanic patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04660422.

Comparison of Racial, Ethnic, and Geographic Location Diversity of Participants Enrolled in Clinic-Based vs 2 Remote COVID-19 Clinical Trials.

Importance: Racial and ethnic diversity among study participants is associated with improved generalizability of clinical trial results and may address inequities in evidence that informs public health strategies. Novel strategies are needed for equitable access and recruitment of diverse clinical trial populations. Objective: To investigate demographic and geographical location data for participants in 2 remote COVID-19 clinical trials with online recruitment and compare with those of a contemporaneous clinic-based COVID-19 study. Design, Setting, and Participants: This cohort study was conducted using data from 3 completed, prospective randomized clinical trials conducted at the same time: 2 remotely conducted studies (the Early Treatment Study and Hydroxychloroquine COVID-19 Postexposure Prophylaxis [PEP] Study) and 1 clinic-based study of convalescent plasma (the Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study). Data were collected from March to August 2020 with 1 to 28 days of participant follow-up. All studies had clinical sites in Seattle, Washington; the 2 remote trials also had collaborating sites in New York, New York; Syracuse, New York; Baltimore, Maryland; Boston, Massachusetts; Chicago, Illinois; New Orleans, Louisiana; and Los Angeles, California. Two remote trials with inclusive social media strategies enrolled 929 participants with recent SARS-CoV-2 exposure (Hydroxychloroquine COVID-19 PEP Trial) and 231 participants with COVID-19 infection (Early Treatment Study); the clinic-based Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19 study enrolled 250 participants with recent COVID-19 infection. Data were analyzed from April to August 2021. Interventions: Remote trials used inclusive social media strategies and clinician referral for recruitment and telehealth, courier deliveries, and self-collected nasal swabs for remotely conducted study visits. For the clinic-based study, participants were recruited via clinician referral and attended in-person visits. Main Outcomes and Measures: Google Analytics data were used to measure online participant engagement and recruitment. Participant demographics and geographical location data from remote trials were pooled and compared with those of the clinic-based study. Statistical comparison of demographic data was limited to participants with COVID infections (ie, those in the remotely conducted Early Treatment Study vs those in the clinic-based study) to improve accuracy of comparison given that the Hydroxychloroquine COVID-19 PEP Trial enrolled participants with COVID-19 exposures and thus had different enrollment criteria. Results: A total of 1410 participants were included. Among 1160 participants in remote trials and 250 participants in the clinic-based trial, the mean (range) age of participants was 39 (18-80) years vs 50 (19-79) years and 676 individuals (58.3%) vs 131 individuals (52.4%) reported female sex. The Early Treatment Study with inclusive social media strategies enrolled 231 participants in 41 US states with increased rates of racial, ethnic, and geographic diversity compared with participants in the clinic-based study. Among 228 participants in the remotely conducted Early Treatment Study with race data vs participants in the clinic-based study, 39 individuals (17.1%) vs 1 individual (0.4%) identified as Alaska Native or American Indian, 11 individuals (4.8%) vs 22 individuals (8.8%) identified as Asian, 26 individuals (11.4%) vs 4 individuals (1.6%) identified as Black, 3 individuals (1.3%) vs 1 individual identified as Native Hawaiian or Pacific Islander, 117 individuals (51.3%) vs 214 individuals (85.6%) identified as White, and 32 individuals (14.0%) vs 8 individuals (3.2%) identified as other race (P < .001). Among 230 individuals in the Early Treatment Study vs 236 individuals in the clinic-based trial with ethnicity data, 71 individuals (30.9%) vs 11 individuals (4.7%) identified as Hispanic or Latinx (P<.001). There were 29 individuals in the Early Treatment Study with nonurban residences (ie, rural, small town, or peri-urban; 12.6%) vs 6 of 248 individuals in the clinic-based trial with residence data (2.4%) (P < .001). In remote trial online recruitment, the highest engagement was with advertisements on social media platforms; among 125 147 unique users with age demographics who clicked on online recruitment advertisements, 84 188 individuals (67.3%) engaged via Facebook. Conclusions and Relevance: These findings suggest that remote clinical trials with online advertising may be considered as a strategy to improve diversity among clinical trial participants.

Trajectory of Viral RNA Load Among Persons With Incident SARS-CoV-2 G614 Infection (Wuhan Strain) in Association With COVID-19 Symptom Onset and Severity.

Importance: The SARS-CoV-2 viral trajectory has not been well characterized in incident infections. These data are needed to inform natural history, prevention practices, and therapeutic development. Objective: To characterize early SARS-CoV-2 viral RNA load (hereafter referred to as viral load) in individuals with incident infections in association with COVID-19 symptom onset and severity. Design, Setting, and Participants: This prospective cohort study was a secondary data analysis of a remotely conducted study that enrolled 829 asymptomatic community-based participants recently exposed (<96 hours) to persons with SARS-CoV-2 from 41 US states from March 31 to August 21, 2020. Two cohorts were studied: (1) participants who were SARS-CoV-2 negative at baseline and tested positive during study follow-up, and (2) participants who had 2 or more positive swabs during follow-up, regardless of the initial (baseline) swab result. Participants collected daily midturbinate swab samples for SARS-CoV-2 RNA detection and maintained symptom diaries for 14 days. Exposure: Laboratory-confirmed SARS-CoV-2 infection. Main Outcomes and Measures: The observed SARS-CoV-2 viral load among incident infections was summarized, and piecewise linear mixed-effects models were used to estimate the characteristics of viral trajectories in association with COVID-19 symptom onset and severity. Results: A total of 97 participants (55 women [57%]; median age, 37 years [IQR, 27-52 years]) developed incident infections during follow-up. Forty-two participants (43%) had viral shedding for 1 day (median peak viral load cycle threshold [Ct] value, 38.5 [95% CI, 38.3-39.0]), 18 (19%) for 2 to 6 days (median Ct value, 36.7 [95% CI, 30.2-38.1]), and 31 (32%) for 7 days or more (median Ct value, 18.3 [95% CI, 17.4-22.0]). The cycle threshold value has an inverse association with viral load. Six participants (6%) had 1 to 6 days of viral shedding with censored duration. The peak mean (SD) viral load was observed on day 3 of shedding (Ct value, 33.8 [95% CI, 31.9-35.6]). Based on the statistical models fitted to 129 participants (60 men [47%]; median age, 38 years [IQR, 25-54 years]) with 2 or more SARS-CoV-2-positive swab samples, persons reporting moderate or severe symptoms tended to have a higher peak mean viral load than those who were asymptomatic (Ct value, 23.3 [95% CI, 22.6-24.0] vs 30.7 [95% CI, 29.8-31.4]). Mild symptoms generally started within 1 day of peak viral load, and moderate or severe symptoms 2 days after peak viral load. All 535 sequenced samples detected the G614 variant (Wuhan strain). Conclusions and Relevance: This cohort study suggests that having incident SARS-CoV-2 G614 infection was associated with a rapid viral load peak followed by slower decay. COVID-19 symptom onset generally coincided with peak viral load, which correlated positively with symptom severity. This longitudinal evaluation of the SARS-CoV-2 G614 with frequent molecular testing serves as a reference for comparing emergent viral lineages to inform clinical trial designs and public health strategies to contain the spread of the virus.

The Deaf Community's Experiences Navigating COVID-19 Pandemic Information.

BACKGROUND: Users of American Sign Language (ASL) who are deaf often face barriers receiving health information, contributing to significant gaps in health knowledge and health literacy. To reduce the spread of coronavirus disease 2019 (COVID-19) and its risk to the public, the government and health care providers have encouraged social distancing, use of face masks, hand hygiene, and quarantines. Unfortunately, COVID-19 information has rarely been available in ASL, which puts the deaf community at a disadvantage for accessing reliable COVID-19 information. OBJECTIVE: This study's primary objective was to compare COVID-19-related information access between participants who are deaf and participants who are hearing. METHODS: The study included 104 adults who are deaf and 74 adults who are hearing who had participated in a prior health literacy study. Surveys were conducted between April and July 2020 via video conference, smartphone apps, or phone calls. COVID-19 data were linked with preexisting data on demographic and health literacy data as measured by the Newest Vital Sign (NVS) and the ASL-NVS. KEY RESULTS: Neither group of participants differed in their ability to identify COVID-19 symptoms. Adults who are deaf were 4.7 times more likely to report difficulty accessing COVID-19 information (p = .011), yet reported using more preventive strategies overall. Simultaneously, adults who are deaf had 60% lower odds of staying home and calling their doctor versus seeking health care immediately or doing something else compared with participants who are hearing if they suspected that they had COVID-19 (p = .020). CONCLUSIONS: Additional education on recommended COVID-19 management and guidance on accessible health care navigation strategies are needed for the deaf community and health care providers. Public health officials should ensure that public service announcements are accessible to all audiences and should connect with trusted agents within the deaf community to help disseminate health information online in ASL through their social media channels. [HLRP: Health Literacy Research and Practice. 2021;5(2):e162-e170.] Plain Language Summary: Compared to participants who are hearing, a higher portion of participants who are deaf reported challenges with accessing, understanding, and trusting COVID-19 information. Although respondents who are deaf had similar knowledge of symptoms compared to participants who are hearing, they used more prevention strategies and were more likely to plan immediate care for suspected symptoms. Improved guidance on COVID-19 management and health care navigation accessible to the deaf community is needed.

Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.

BACKGROUND: Effective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention. OBJECTIVE: To test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection. DESIGN: Household-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961). SETTING: National U.S. multicenter study. PARTICIPANTS: Close contacts recently exposed (<96 hours) to persons with diagnosed SARS-CoV-2 infection. INTERVENTION: Hydroxychloroquine (400 mg/d for 3 days followed by 200 mg/d for 11 days) or ascorbic acid (500 mg/d followed by 250 mg/d) as a placebo-equivalent control. MEASUREMENTS: Participants self-collected mid-turbinate swabs daily (days 1 to 14) for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome was PCR-confirmed incident SARS-CoV-2 infection among persons who were SARS-CoV-2 negative at enrollment. RESULTS: Between March and August 2020, 671 households were randomly assigned: 337 (407 participants) to the hydroxychloroquine group and 334 (422 participants) to the control group. Retention at day 14 was 91%, and 10 724 of 11 606 (92%) expected swabs were tested. Among the 689 (89%) participants who were SARS-CoV-2 negative at baseline, there was no difference between the hydroxychloroquine and control groups in SARS-CoV-2 acquisition by day 14 (53 versus 45 events; adjusted hazard ratio, 1.10 [95% CI, 0.73 to 1.66]; P > 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026). LIMITATION: The delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days. CONCLUSION: This rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.

Hydroxychloroquine with or without azithromycin for treatment of early SARS-CoV-2 infection among high-risk outpatient adults: A randomized clinical trial.

BACKGROUND: Treatment options for outpatients with COVID-19 could reduce morbidity and prevent SARS-CoV-2 transmission. METHODS: In this randomized, double-blind, three-arm (1:1:1) placebo-equivalent controlled trial conducted remotely throughout the United States, adult outpatients with laboratory-confirmed SARS-CoV-2 infection were recruited. Participants were randomly assigned to receive hydroxychloroquine (HCQ) (400 mg BID x1day, followed by 200 mg BID x9days) with or without azithromycin (AZ) (500 mg, then 250 mg daily x4days) or placebo-equivalent (ascorbic acid (HCQ) and folic acid (AZ)), stratified by risk for progression to severe COVID-19 (high-risk vs. low-risk). Self-collected nasal swabs for SARS-CoV-2 PCR, FLUPro symptom surveys, EKGs and vital signs were collected daily. Primary endpoints were: (a) 14-day progression to lower respiratory tract infection (LRTI), 28-day COVID-19 related hospitalization, or death; (b) 14-day time to viral clearance; secondary endpoints included time to symptom resolution (ClinicalTrials.gov: NCT04354428). Due to the low rate of clinical outcomes, the study was terminated for operational futility. FINDINGS: Between 15th April and 27th July 2020, 231 participants were enrolled and 219 initiated medication a median of 5.9 days after symptom onset. Among 129 high-risk participants, incident LRTI occurred in six (4.7%) participants (two control, four HCQ/AZ) and COVID-19 related hospitalization in seven (5.4%) (four control, one HCQ, two HCQ/AZ); no LRTI and two (2%) hospitalizations occurred in the 102 low-risk participants (one HCQ, one HCQ/AZ). There were no deaths. Among 152 participants with viral shedding at enrollment, median time to clearance was 5 days (95% CI=4-6) in HCQ, 6 days (95% CI=4-8) in HCQ/AZ, and 8 days (95% CI=6-10) in control. Viral clearance was faster in HCQ (HR=1.62, 95% CI=1.01-2.60, p = 0.047) but not HCQ/AZ (HR=1.25, p = 0.39) compared to control. Among 197 participants who met the COVID-19 definition at enrollment, time to symptom resolution did not differ by group (HCQ: HR=1.02, 95% CI-0.63-1.64, p = 0.95, HCQ/AZ: HR=0.91, 95% CI=0.57-1.45, p = 0.70). INTERPRETATION: Neither HCQ nor HCQ/AZ shortened the clinical course of outpatients with COVID-19, and HCQ, but not HCQ/AZ, had only a modest effect on SARS-CoV-2 viral shedding. HCQ and HCQ/AZ are not effective therapies for outpatient treatment of SARV-CoV-2 infection. FUNDING: The COVID-19 Early Treatment Study was funded by the Bill & Melinda Gates Foundation (INV-017062) through the COVID-19 Therapeutics Accelerator. University of Washington Institute of Translational Health Science (ITHS) grant support (UL1 TR002319), KL2 TR002317, and TL1 TR002318 from NCATS/NIH funded REDCap. The content is solely the responsibility of the authors and does not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. PAN and MJA were supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.Trial registration ClinicalTrials.gov number NCT04354428.

Clinical Outcomes of Patients Hospitalized with Coronavirus Disease 2019 (COVID-19) in Boston.

BACKGROUND: Outcomes of hospitalized patients with COVID-19 have been described in health systems overwhelmed with a surge of cases. However, studies examining outcomes of patients admitted to hospitals not in crisis are lacking. OBJECTIVE: To describe clinical characteristic and outcomes of all patients with COVID-19 who are admitted to hospitals not in crisis, and factors associated with mortality in this population. DESIGN: A retrospective analysis PARTICIPANTS: In total, 470 consecutive patients with COVID-19 requiring hospitalization in one health system in Boston from January 1, 2020 to April 15, 2020. MAIN MEASURES: We collected clinical outcomes during hospitalization including intensive care unit (ICU) admission, receipt of mechanical ventilation, and vasopressors. We utilized multivariable logistic regression models to examine factors associated with mortality. KEY RESULTS: A total of 470 patients (median age 66 [range 23-98], 54.0% male) were included. The most common comorbidities were diabetes (38.5%, 181/470) and obesity (41.3%, 194/470). On admission, 41.9% (197/470) of patients were febrile and 60.6% (285/470) required supplemental oxygen. During hospitalization, 37.9% (178/470) were admitted to the ICU, 33.6% (158/470) received mechanical ventilation, 29.4% (138/470) received vasopressors, 16.4% (77/470) reported limitations on their desire for life-sustaining therapies such as intubation and cardiopulmonary resuscitation, and 25.1% (118/470) died. Among those admitted to the ICU (N=178), the median number of days on the ventilator was 10 days (IQR 1-29), and 58.4% (104/178) were discharged alive. Older age (OR=1.04, P<0.001), male sex (OR=2.14, P=0.007), higher comorbidities (OR=1.20, P=0.001), higher lactate dehydrogenase on admission (2nd tertile: OR=4.07, P<0.001; 3rd tertile: OR=8.04, P<0.001), and the need for supplemental oxygen on admission (OR=2.17, P=0.014) were all associated with higher mortality. CONCLUSIONS: The majority of hospitalized patients with COVID-19 and those who received mechanical ventilation survived. These data highlight the need to examine public health and system factors that contribute to improved outcomes for this population.

Organizational Health Literacy: Opportunities for Patient-Centered Care in the Wake of COVID-19.

BACKGROUND AND OBJECTIVES: The coronavirus disease-2019 (COVID-19) pandemic is transforming the health care sector. As health care organizations move from crisis mobilization to a new landscape of health and social needs, organizational health literacy offers practical building blocks to provide high-quality, efficient, and meaningful care to patients and their families. Organizational health literacy is defined by the Institute of Medicine as "the degree to which an organization implements policies, practices, and systems that make it easier for people to navigate, understand, and use information and services to take care of their health." METHODS: This article synthesizes insights from organizational health literacy in the context of current major health care challenges and toward the goal of innovation in patient-centered care. We first provide a brief overview of the origins and outlines of organizational health literacy research and practice. Second, using an established patient-centered innovation framework, we show how the existing work on organizational health literacy can offer a menu of effective, patient-centered innovative options for care delivery systems to improve systems and outcomes. Finally, we consider the high value of management focusing on organizational health literacy efforts, specifically for patients in health care transitions and in the rapid transformation of care into myriad distance modalities. RESULTS: This article provides practical guidance for systems and informs decisions around resource allocation and organizational priorities to best meet the needs of patient populations even in the face of financial and workforce disruption. CONCLUSIONS: Organizational health literacy principles and guidelines provide a road map for promoting patient-centered care even in this time of crisis, change, and transformation. Health system leaders seeking innovative approaches can have access to well-established tool kits, guiding models, and materials toward many organizational health literacy goals across treatment, diagnosis, prevention, education, research, and outreach.

Advance Care Planning: Promoting Effective and Aligned Communication in the Elderly (ACP-PEACE): the study protocol for a pragmatic stepped-wedge trial of older patients with cancer.

INTRODUCTION: Advance care planning (ACP) is associated with improved health outcomes for patients with cancer, and its absence is associated with unfavourable outcomes for patients and their caregivers. However, older adults do not complete ACP at expected rates due to patient and clinician barriers. We present the original design, methods and rationale for a trial aimed at improving ACP for older patients with advanced cancer and the modified protocol in response to changes brought by the COVID-19 pandemic. METHODS AND ANALYSIS: The Advance Care Planning: Promoting Effective and Aligned Communication in the Elderly study is a pragmatic, stepped-wedge cluster randomised trial examining a Comprehensive ACP Program. The programme combines two complementary evidence-based interventions: clinician communication skills training (VitalTalk) and patient video decision aids (ACP Decisions). We will implement the programme at 36 oncology clinics across three unique US health systems. Our primary outcome is the proportion of eligible patients with ACP documentation completed in the electronic health record. Our secondary outcomes include resuscitation preferences, palliative care consultations, death, hospice use and final cancer-directed therapy. From a subset of our patient population, we will collect surveys and video-based declarations of goals and preferences. We estimate 11 000 patients from the three sites will be enrolled in the study. ETHICS AND DISSEMINATION: Regulatory and ethical aspects of this trial include Institutional Review Board (IRB) approval via single IRB of record mechanism at Dana-Farber Cancer Institute, Data Use Agreements among partners and a Data Safety and Monitoring Board. We plan to present findings at national meetings and publish the results. TRIAL REGISTRATION NUMBER: NCT03609177; Pre-results.