Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial.

OBJECTIVE: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19. DESIGN: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory). RESULTS: Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days (95% CI: 7 to 9.8 days) for famotidine and 11.4 days (95% CI: 10.3 to 12.6 days) for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms. CONCLUSIONS: Famotidine was safe and well tolerated in outpatients with mild to moderate COVID-19. Famotidine led to earlier resolution of symptoms and inflammation without reducing anti-SARS-CoV-2 immunity. Additional randomised trials are required.

Effect of Technology-Assisted Brief Abstinence Game on Long-term Smoking Cessation in Individuals Not Yet Ready to Quit: A Randomized Clinical Trial.

IMPORTANCE: Most trials of behavioral or pharmaceutical interventions for people who smoke are limited to individuals reporting they are ready to quit smoking. Engaging individuals who initially report they are not yet ready to quit in brief, precessation, skills-building interventions (eg, practice quit attempts or nicotine replacement therapy [NRT] sampling) is challenging. OBJECTIVE: To test an integrated behavioral plus NRT-sampling intervention using a gamification approach supported by mobile health. DESIGN, SETTING, AND PARTICIPANTS: A multisite randomized clinical trial with site-level 1-to-1 allocation into 2 conditions was conducted in 4 US health care systems. A total of 433 individuals who were currently smoking and reported at enrollment that they were not ready to quit smoking were enrolled. The study was conducted from November 7, 2016, to July 31, 2020. INTERVENTIONS: Take a Break (TAB) was a 3-week game experience and included 5 behavioral components (motivational messaging, challenge quizzes, brief abstinence goal setting, mobile health apps for cravings management, and reward points for participation) integrated with NRT sampling. TAB draws on social cognitive theory and game mechanics concepts to engage participants in health behavior change. The comparison included NRT sampling only. MAIN OUTCOMES AND MEASURES: Time to first quit attempt (duration from TAB experience to primary outcome) and carbon monoxide level-verified smoking cessation at 6-month follow-up. All analyses used an intention-to-treat approach. RESULTS: Of the 433 individuals included in the trial, 223 were women (52%); mean (SD) age was 54 (13) years. More than half (53% [112 of 213]) of the TAB participants completed 100% of the daily challenge quizzes in the first week, 73% (145 of 199) of participants who completed the goal-setting call set a brief abstinence goal (most frequently 1-2 days of abstinence from cigarettes), and 75% (159 of 213) of participants used the mobile health apps to manage nicotine cravings. Time to the first quit attempt was lower for the TAB vs comparison group (hazard ratio, 1.68; 95% CI, 1.09-2.60; P = .02). At the 6-month follow-up, 18% (28 of 160) of TAB participants and 10% (17 of 171) of the comparison (χ2 test, P = .045) participants obtained carbon monoxide level-verified smoking cessation (accounting for clustering of outcomes by site; odds ratio, 1.92; 95% CI, 1.01-3.68; P = .048). CONCLUSIONS AND RELEVANCE: The findings of this randomized clinical trial demonstrate that individuals not yet ready to quit smoking could be engaged in a brief abstinence game. Six months later, the TAB group had nearly double the rate of smoking cessation vs the NRT sampling comparison group. Integrating a skills-building game experience with brief NRT sampling can enhance long-term cessation among those not yet ready to quit smoking. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02973425.

Examination of social determinants of health among patients with limited English proficiency.

OBJECTIVES: The purpose of this study is to examine the prevalence of social needs by English proficiency using data from Northwell Health's social determinants of health screening program. The screening program evaluates 12 domains of social needs: material need, employment, medical-legal assistance, health insurance, public benefits, health literacy, transportation, medical care, utilities, housing quality, food security, and housing insecurity. We have identified patients to have limited English proficiency if they have selected a language other than English as their primary language. RESULTS: The study population includes 92,958 individuals; of these, 83,445 (89.8%) patients are English proficient, and 9513 (10.2%) patients have limited English proficiency. A higher percentage of patients with limited English proficiency has social needs, including material need, employment, medical-legal assistance, health insurance, public benefit, health literacy, medical care, utility bill, poor housing quality, and food insecurity (all p-values < 0.05). In multivariable logistic regression models adjusting for sociodemographic information, LEP status (odds ratio = 1.36 [1.25-1.49]) has been associated with having social needs. These findings suggest that system-wide SDH screening and referral programs should identify ways to ensure capturing social needs among patients with limited English proficiency.

Racial and ethnic minority patient participation in N-of-1 trials: perspectives of healthcare providers and patients.

Aim: Patients from racial and ethnic minority backgrounds in the USA have historically been under-represented in research trials. Understanding their viewpoints regarding participation in N-of-1 trials is imperative as we design and implement these studies. Materials & methods: We conducted six focus groups of racial and ethnic minority patients (n = 25) and providers (n = 9). We used content analysis to identify themes. Results: Our results noted the importance of considering family members in N-of-1 trial recruitment and participation, patients' desire for education as a design feature, for 'lifestyle' changes as a treatment option and for use of nonevidence-based treatments in the design of future N-of-1 trials. Conclusion: Personalized trials have the potential to change the way we deliver primary care and improve disparities for minorities.

Lay abstract Commonly, research studies seek to enroll large groups of individuals to test a new product or medication. However, the personalized trial/N-of-1 trial has a different goal. This is to focus on a single person and study their response to different treatments. Our focus group-based study of medical providers and racial and ethnic minority patients, sought to learn how personalized trials can be designed to include the life experiences and cultural considerations of members of minority populations. Participants noted factors such as the role of family, including educational programming or lifestyle changes in the trial, and the use of natural remedies (not prescribed by a physician) as specific cultural considerations. N-of-1 trials have the potential to change the way we deliver primary care and improve disparities, but we must design them to address the concerns of importance to minority populations.

Examination of resident characteristics associated with interest in primary care and identification of barriers to cross-cultural care.

BACKGROUND: There is an increasing shortage of primary care physicians in the U.S. The difficult task of addressing patients' sociocultural needs is one reason residents do not pursue primary care. However, associations between residents' perceived barriers to cross-cultural care provision and career interest in primary care have not been investigated. OBJECTIVE: We examined residents' career interest in primary care and associations with resident characteristics and their perceived barriers in providing cross-cultural care. METHODS: We conducted a cross-sectional analysis of a resident survey from the 2018-2019 academic year. We first described residents' sociodemographic characteristics based on their career interest in primary care (Chi-square test). Our primary outcome was high career interest in primary care. We further examined associations between residents' characteristics and perceived barriers to cross-cultural care. RESULTS: The study included 155 family medicine, pediatrics, and internal medicine residents (response rate 68.2%), with 17 expressing high career interest in primary care. There were significant differences in high career interest by race/ethnicity, as Non-White race was associated with high career interest in primary care (p < 0.01). Resident characteristics associated with identifying multiple barriers to cross-cultural care included disadvantaged background, multilingualism, and foreign-born parents (all p-values< 0.05). There were no significant associations between high career interest in primary care and barriers to cross-cultural care. CONCLUSION: Residents from diverse racial/ethnic and socioeconomic backgrounds demonstrated higher career interest in primary care and perceived more barriers to cross-cultural care, underscoring the importance of increasing physician workforce diversity to address the primary care shortage and to improve cross-cultural care.

"I Felt I Was Reaching a Point with My Health": Understanding Reasons for Engagement and Acceptability of Treatment Services for Unhealthy Alcohol Use in Primary Care.

INTRODUCTION/OBJECTIVES: Despite increasing need, there are large gaps in provision of care for unhealthy alcohol use. Primary care practices have become increasingly important in providing services for unhealthy alcohol use, yet little is known about the reasons patients engage in these services and their views on acceptability of such programs. The purpose of this study was to examine primary care patients' reasons for engagement, experiences with, and acceptability of a primary care practice-based program for treating unhealthy alcohol use. METHODS: This qualitative study was conducted in a primary care practice that was developing a collaborative care model for treating unhealthy alcohol use in primary care. Semi-structured interviews were conducted with 24 primary care patients. Data were analyzed using conventional qualitative content analysis. RESULTS: Findings suggest that patients engaged for both internal (concerns about drinking and health) and external reasons (family or provider concern). Patient experiences in the program were shaped by their affective responses (enjoyable, enlightening), as well as therapeutic benefits (gaining new insights about drinking; staff/provider support). Acceptability was driven by core program elements (medication, therapy, integration) as well as positive impacts on drinking cognition and behavior and flexible, patient-centered approaches. CONCLUSIONS: Offering flexible and comprehensive programs with mutiple elements and both abstinence and moderation goals could also improve patient engagement and views on acceptability. Primary care practices will need to be thoughtful about the resources needed to implement these programs in terms of staffing, training, and program support.

The Financial Cost of Interprofessional Ambulatory Training: What's the Bottom Line?

BACKGROUND: Team-based care is recommended as a building block of high-performing primary care but has not been widely adapted in training sites. Cost may be one barrier to a team-based approach. OBJECTIVE: We quantified incremental annual faculty and staff costs as well as potential cost savings associated with an interprofessional (IP) ambulatory training program compared to a traditional residency clinic at the same site. METHODS: Cost calculations for the 2017-2018 academic year were made using US Department of Labor median salaries by profession and divided by the number of residents trained per year. Cost implications of lower no-show rates were calculated by multiplying the difference in no-show rate by the number of scheduled appointments, and then by the weighted average of the reimbursement rate. RESULTS: A total of 1572 arrived appointments were seen by the 10 residents in the IP program compared with 8689 arrived appointments seen by 57 residents in the traditional clinic. The no-show rate was 11.5% (265 of 2311) in the IP program and 19.2% (2532 of 13 154) in the traditional clinic (P < .001). Total cost to the health system through higher staffing needs was $113,897, or $11,390 per trained resident. CONCLUSIONS: Total costs of the IP model due to higher faculty and staff to resident ratios totaled $11,390 per resident per year. Understanding the faculty and staff costs and potential cost-saving opportunities associated with transformation to an IP model may assist in sustainability.

Examination of patient characteristics and hydroxychloroquine use based on the US Food and Drug Administration's recommendation: a cross-sectional analysis in New York.

OBJECTIVE: To describe the pattern of hydroxychloroquine use and examine the association between hydroxychloroquine use and clinical outcomes arising from changes in the US Food and Drug Administration (FDA)'s recommendation during the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: A retrospective cross-sectional analysis. SETTING AND PARTICIPANTS: We included hospitalised adult patients at Northwell Health hospitals with confirmed COVID-19 infections between 1 March 2020 and 11 May 2020. We categorised changes in the FDA's recommendation as pre-FDA approval (1 March 2020-27 March 2020), FDA approval (28 March 2020-23 April 2020), and FDA warning (24 April 2020-11 May 2020). The hydroxychloroquine-treated group received at least one dose within 48 hours of hospital admission. PRIMARY OUTCOME: A composite of intubation and inpatient death. RESULTS: The percentages of patients who were treated with hydroxychloroquine were 192/2202 (8.7%) pre-FDA approval, 2902/6741 (43.0%) FDA approval, and 176/1066 (16.5%) FDA warning period (p<0.001). Using propensity score matching, there was a higher rate of the composite outcome among patients treated with hydroxychloroquine (49/192, 25.5%) compared with no hydroxychloroquine (66/384, 17.2%) in the pre-FDA approval period (p=0.03) but not in the FDA approval period (25.5% vs 22.6%, p=0.08) or the FDA warning (21.0% vs 15.1%, p=0.11) periods. Coincidently, there was an increase in number of patients with COVID-19 and disease severity during the FDA approval period (24.1% during FDA approval vs 21.4% during pre-FDA approval period had the composite outcome). Hydroxychloroquine use was associated with increased odds of the composite outcome during the pre-FDA approval period (OR=1.65 (95% CI 1.09 to 2.51)) but not during the FDA approval (OR=1.17 (95% CI 0.99 to 1.39)) and FDA warning (OR=1.50 (95% CI 0.94 to 2.39)) periods. CONCLUSIONS: Hydroxychloroquine use was associated with adverse clinical outcomes only during the pre-FDA approval period but not during the FDA approval and warning periods, even after adjusting for concurrent changes in the percentage of patients with COVID-19 treated with hydroxychloroquine and the number (and disease severity) of hospitalised patients with COVID-19 infections.

Examination of Post-discharge Follow-up Appointment Status and 30-Day Readmission.

BACKGROUND: Post-hospital discharge follow-up appointments are intended to evaluate patients' recovery following a hospitalization, but it is unclear how appointment statuses are associated with readmissions. OBJECTIVE: To examine the association between post-discharge ambulatory follow-up status, (1) having a scheduled appointment and (2) arriving to said appointment, and 30-day readmission. DESIGN AND SETTING: A retrospective cohort study of patients hospitalized at 12 hospitals in an Integrated Delivery Network and their ambulatory appointments in that same network. PATIENTS AND MAIN MEASURES: We included 50,772 patients who had an ambulatory appointment within 18 months of an inpatient admission in 2018. Primary outcome was readmission within 30 days post-discharge. KEY RESULTS: There were 32,108 (63.2%) patients with scheduled follow-up appointments and 18,664 (36.8%) patients with no follow-up; 28,313 (88.2%) patients arrived, 3149 (9.8%) missed, and 646 (2.0%) were readmitted prior to their scheduled appointments. Overall 30-day readmission rate was 7.3%; 6.0% [5.75-6.31] for those who arrived, 8.8% [8.44-9.25] for those without follow-up, and 10.3% [9.28-11.40] for those who missed a scheduled appointment (p < 0.001). After adjusting for covariates, patients who arrived at their appointment in the first week following discharge were significantly less likely to be readmitted than those not having any follow-up scheduled (medical adjusted hazard ratio (aHR) 0.57 [0.47-0.69], p < 0.001; surgical aHR 0.58 [0.44-0.75], p < 0.001) There was an increased risk at weeks 3 and 4 for medical patients who arrived at a follow-up compared to those with no follow-up scheduled (week 3 aHR 1.29 [1.10-1.51], p = 0.001; week 4 aHR 1.46 [1.26-1.70], p < 0.001). CONCLUSIONS: The benefit of patients arriving to their post-discharge appointments compared with patients who missed their follow-up visits or had no follow-up scheduled, is only significant during first week post-discharge, suggesting that coordination within 1 week of discharge is critical in reducing 30-day readmissions.

Prevalence and risk characteristics of COVID-19 in outpatients: A cross-sectional study of New York-area clinics.

Outpatients can be at heightened risk of COVID-19 due to interaction between existing non-communicable diseases in outpatients and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study measured the magnitude of COVID-19 prevalence and explored related risk characteristics among adult outpatients visiting medicine clinics within a New York state-based tertiary hospital system. Data were compiled from 63,476 adult patients visiting outpatient medicine clinics within a New York-area hospital system between March 1, 2020, and August 28, 2020. The outcome was a clinical diagnosis of COVID-19. Crude and adjusted prevalence ratios (PR) of a COVID-19 were analyzed using univariable and multivariable Poisson regression with robust standard errors. The prevalence of COVID-19 was higher among these outpatients (3.0%) than in the total population in New York State (2.2%) as of August 28, 2020. Multivariable analysis revealed adjusted prevalence ratios significantly greater than one for male sex (PR=1.10), age 40 to 64 compared to <40 (PR=1.19), and racial/ethnic minorities in comparison to White patients (Hispanic: PR=2.76; Black: PR=1.89; and Asian/others: PR=1.56). Nonetheless, factors including the advanced age of ≥65 compared to <40 (PR=0.69) and current smoking compared to non-smoking (PR=0.60) were related to significantly lower prevalence. Therefore, the prevalence of COVID-19 in outpatients was higher than that of the general population. The findings also enabled hypothesis generation that routine clinical measures comprising sex, age, race/ethnicity, and smoking were candidate risk characteristics of COVID-19 in outpatients to be further verified by designs capable of assessing temporal association.

A novel longitudinal interprofessional ambulatory training practice: the improving patient access care and cost through training (IMPACcT) clinic.

Few graduating health professionals choose primary care. Trainees satisfied with continuity ambulatory experiences are more likely to pursue primary care. The authors developed a longitudinal interprofessional ambulatory training program to improve team-based care and encourage primary care careers. The Improving Patient Access Care and cost through Training (IMPACcT) clinic, launched in 2016, includes physician, physician assistant, pharmacy, and psychology trainees. Residents, faculty, and interprofessional trainees complete "on-service" weeks together. Co-located administrative team members coordinate care and lead team "huddles." Interprofessional signout facilitates patient follow-up. The initial evaluation included process and quality indicators compared to the traditional resident practice. Learners reported increased perceived competence in interprofessional communication and teamwork after completing their training. Clinical quality outcomes suggested improved provider continuity and arrival rate compared to traditional resident practice (56.5% vs. 32.9%; 66.3% vs. 62.2%, p < .01). Patient satisfaction was higher in the IMPACcT clinic in the areas of coordinated care and team functioning. Ten of eighteen physician graduates in the program chose further training in primary care compared to 20 of 150 graduates not in the program (55.6% vs. 13.3%, p < .01). Implementing a longitudinal team-based ambulatory interprofessional training practice was associated with improved continuity of care and improved patient satisfaction indicators.

A Faculty Development Graduate Medical Education Retreat to Teach and Address Social Determinants of Health.

BACKGROUND: Social determinants of health (SDH) account for a large percentage of health outcomes. Therefore, ensuring providers can address SDH is paramount yet curricula in this area is limited. AIM: The authors aimed to raise awareness, identify learning opportunities, foster positive attitudes, and equip educators to implement SDH curriculum. SETTING AND PARTICIPANTS: This retreat occurred at a large academic institution and had over 130 participants who represented 56 distinct training programs and over 20 disciplines. PROGRAM DESCRIPTION: The retreat was titled "Social Determinants of Health: Walking in Your Patients' Shoes." The retreat was holistic and used a multidimensional approach that included traditional learning, team-based learning, reflective practice, and prompted action. PROGRAM EVALUATION: The evaluation of this retreat included electronic surveys and both qualitative and quantitative data. The retreat's quality and effectiveness at improving participants' knowledge and skill in addressing SDH was highly rated and resulted in numerous programs, including surgical and subspecialty programs reporting adopting SDH curricular and clinical workflow changes. DISCUSSION: The retreat was successful and reached a wide and diverse set of faculty educators and can serve as an education model to the graduate medical education community on how to start to develop "physician-citizens."

Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series.

OBJECTIVE: Treatment options for non-hospitalised patients with coronavirus disease 2019 (COVID-19) to reduce morbidity, mortality and spread of the disease are an urgent global need. The over-the-counter histamine-2 receptor antagonist famotidine is a putative therapy for COVID-19. We quantitively assessed longitudinal changes in patient reported outcome measures in non-hospitalised patients with COVID-19 who self-administered high-dose famotidine orally. DESIGN: Patients were enrolled consecutively after signing written informed consent. Data on demographics, COVID-19 diagnosis, famotidine use, drug-related side effects, temperature measurements, oxygen saturations and symptom scores were obtained using questionnaires and telephone interviews. Based on a National Institute of Health (NIH)-endorsed Protocol to research Patient Experience of COVID-19, we collected longitudinal severity scores of five symptoms (cough, shortness of breath, fatigue, headaches and anosmia) and general unwellness on a four-point ordinal scale modelled on performance status scoring. All data are reported at the patient level. Longitudinal combined normalised symptom scores were statistically compared. RESULTS: Ten consecutive patients with COVID-19 who self-administered high-dose oral famotidine were identified. The most frequently used famotidine regimen was 80 mg three times daily (n=6) for a median of 11 days (range: 5-21 days). Famotidine was well tolerated. All patients reported marked improvements of disease related symptoms after starting famotidine. The combined symptom score improved significantly within 24 hours of starting famotidine and peripheral oxygen saturation (n=2) and device recorded activity (n=1) increased. CONCLUSIONS: The results of this case series suggest that high-dose oral famotidine is well tolerated and associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19.