Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration: ClinicalTrials.gov: NCT04332991.

Barriers and facilitators associated with establishment of emergency department-initiated buprenorphine for opioid use disorder in rural Maine.

PURPOSE: The opioid epidemic in the United States continues to grow, particularly impacting rural communities served by critical access hospitals (CAHs) in Maine. Buprenorphine is an effective medication for the treatment of opioid use disorder (OUD) that can be successfully initiated in the emergency department (ED). However, many EDs have not implemented programs to initiate buprenorphine. This study sought to identify barriers and facilitators to successful implementation of buprenorphine programs inCAH EDs. METHODS: Semistructured interviews were conducted with ED directors of Maine CAHs regarding barriers and facilitators to developing programs for ED-initiated buprenorphine. Seventeen Maine CAH EDs exist and 11 of their directors agreed to participate and completed interviews, which were audio-recorded, transcribed, and analyzed using a thematic approach. RESULTS: Four themes and 11 subthemes were identified, including (1) compelled to act-directors' personal experiences with patients facilitated the development of buprenorphine programs in their EDs; (2) leadership and mentorship-peer mentorship from other CAH ED directors facilitated, and senior hospital administrators facilitated, or created a barrier in some cases; (3) stigma-fear that EDs would be overcrowded by drug-seeking patients was a common barrier; and (4) follow-up-finding appropriate outpatient follow-up for OUD patients created the greatest logistical barrier. DISCUSSION: ED directors' clinical experience with OUD patients, supportive hospital leadership, and peer mentorship facilitated ED-initiated buprenorphine programs in rural Maine CAH EDs. Overcoming stigma, developing community outreach, and appropriate follow-up were the greatest barriers. Future research should focus on enhancing peer mentorship, administrative support, community outreach, and staff education.

Psychological Evaluation of Patients With Cancer Presenting to the Emergency Department With Pain: Independent Predictors of Worse Pain Severity, Interference, and Higher Hourly Opioid Administration.

PURPOSE: Pain is a common complaint in patients with cancer presenting to the emergency department (ED). This prospective study evaluated whether biopsychosocial factors could help predict cancer patients with risk of higher pain severity, pain interference, and opioid consumption. METHODS: Patients with cancer presenting to the ED with a complaint of moderate-severe pain (≥ 4/10-numeric rating scale) completed validated self-report measures assessing sociodemographics, cancer-related treatments, pain severity and interference, medication use, and psychological symptoms (depression, anxiety, pain catastrophizing, and sleep disturbance). Opioids administered and subsequent hospitalization were abstracted. Univariable and multivariable regression analyses assessed factors associated with pain-related outcomes. RESULTS: Participants (n = 175) presented with a variety of cancer types, with 76% having metastatic disease and 42% reporting current outpatient opioid use. Higher pain catastrophizing, lower depressive symptoms, lower income, outpatient opioid use, and historical chronic pain were independently associated with worse pain (P ≤ .05). Higher pain catastrophizing, anxiety, sleep disturbance, outpatient opioid use, and education were independently associated with worse pain interference (P ≤ .05). The sole independent predictor of ED opioid administration was outpatient opioid use. Patients taking outpatient opioids were younger, had lower health literacy, worse pain catastrophizing, sleep disturbance, depression/anxiety, and greater rates of metastatic cancer and cancer-related surgery (P ≤ .05). CONCLUSION: Biopsychosocial factors, particularly pain catastrophizing, remained significantly associated with worse pain outcomes for patients with cancer in the ED even after controlling for demographic and clinical variables. Patient outpatient opioid use was independently associated with worse pain, interference, and greater opioid administration, identifying this as a marker for who may benefit most from adjuvant pharmacologic and behavioral interventions.

Heal the Healers: A pilot study evaluating the feasibility, acceptability, and exploratory efficacy of a Transcendental Meditation intervention for emergency clinicians during the coronavirus disease 2019 pandemic.

OBJECTIVE: Emergency clinicians face elevated rates of burnout that result in poor outcomes for clinicians, patients, and health systems. The objective of this single-arm pilot study was to evaluate the feasibility of a Transcendental Meditation (TM) intervention for emergency clinicians during the coronavirus disease 2019 (COVID-19) pandemic and to explore the potential effectiveness in improving burnout, sleep, and psychological health. METHODS: Emergency clinicians (physicians, nurses, and physician-assistants) from 2 urban hospitals were recruited to participate in TM instruction (8 individual or group in-person and remote sessions) for 3 months. Session attendance was the primary feasibility outcome (prespecified as attending 6/8 sessions), and burnout was the primary clinical outcome. Participant-reported measures of feasibility and validated measures of burnout, depression, anxiety, sleep disturbance, and stress were collected at baseline and the 1-month and 3-month follow-ups. Descriptive statistics and linear mixed-effects models were used. RESULTS: Of the 14 physicians (46%), 7 nurses (22%), and 10 physician-assistants (32%) who participated, 61% were female (n = 19/32). TM training and at-home meditation practice was feasible for clinicians as 90.6% (n = 29/32) attended 6/8 training sessions and 80.6% self-reported meditating at least once a day on average. Participants demonstrated significant reductions in burnout (P < .05; effect sizes, Cohen's d = 0.43-0.45) and in symptoms of depression, anxiety, stress, and sleep disturbance (P values < .001; Cohen's d = 0.70-0.87). CONCLUSION: TM training was feasible for emergency clinicians during the COVID-19 pandemic and led to significant reductions in burnout and psychological symptoms. TM is a safe and effective meditation tool to improve clinicians' well-being.