Contingency management with stepped care for unhealthy alcohol use among individuals with HIV: Protocol for a randomized controlled trial.

BACKGROUND: Although unhealthy alcohol use is associated with increased morbidity and mortality among people with HIV (PWH), many are ambivalent about engaging in treatment and experience variable responses to treatment. We describe the rationale, aims, and study design for the Financial Incentives, Randomization, with Stepped Treatment (FIRST) Trial, a multi-site randomized controlled efficacy trial. METHODS: PWH in care recruited from clinics across the United States who reported unhealthy alcohol use, had a phosphatidylethanol (PEth) >20 ng/mL, and were not engaged in formal alcohol treatment were randomized to integrated contingency management with stepped care versus treatment as usual. The intervention involved two steps; Step 1: Contingency management (n = 5 sessions) with potential rewards based on 1) short-term abstinence; 2) longer-term abstinence; and 3) completion of healthy activities to promote progress in addressing alcohol consumption or conditions potentially impacted by alcohol; Step 2: Addiction physician management (n = 6 sessions) plus motivational enhancement therapy (n = 4 sessions). Participants' treatment was stepped up at week 12 if they lacked evidence of longer-term abstinence. Primary outcome was abstinence at week 24. Secondary outcomes included alcohol consumption (assessed by TLFB and PEth) and the Veterans Aging Cohort Study (VACS) Index 2.0 scores; exploratory outcomes included progress in addressing medical conditions potentially impacted by alcohol. Protocol adaptations due to the COVID-19 pandemic are described. CONCLUSIONS: The FIRST Trial is anticipated to yield insights on the feasibility and preliminary efficacy of integrated contingency management with stepped care to address unhealthy alcohol use among PWH. CLINICALTRIALS: gov identifier: NCT03089320.

Evaluating clinical effectiveness of SARS-CoV-2 vaccine in solid organ transplant recipients: A propensity score matched analysis.

BACKGROUND: Solid organ transplant recipients (SOTRs) are at disproportionate risk for severe Coronavirus Disease 2019 (COVID-19). Vaccination is a key preventative strategy but is associated with decreased humoral responses among SOTR. Whether dampened immune responses correlate with reduced clinical effectiveness is unclear. Our study was designed to evaluate the clinical effectiveness of SARS-CoV-2 vaccination in the early vaccine era. METHODS: We conducted a retrospective cohort study comparing SARS-CoV-2 infection rates between SOTRs who received two doses of mRNA or one dose of Ad26.Cov2.S vaccine and those not fully vaccinated (partially vaccinated and unvaccinated). To evaluate clinical effectiveness of vaccine, cause-specific Cox regression model and modified Poisson regression model were built using the propensity score-matched cohort. Additionally, the clinical outcomes of COVID-19 of fully vaccinated and not fully vaccinated SOTR were compared. RESULTS: Of 2705 SOTRs, 1668 were included in our final matched analysis, which showed a 73% reduction of SARS-CoV-2 infection and 76% reduction of all-cause-mortality among fully vaccinated patients. Thirty-nine SOTRs developed SARS-CoV-2 infection, including nine fully vaccinated and 30 not fully vaccinated. Among fully vaccinated patients, 22% had severe/critical COVID-19 and 0% mortality versus not fully vaccinated SOTRs, of whom 37% had severe/critical COVID-19 and 6.67% COVID-19-related mortality. CONCLUSION: In SOTRs, completion of primary vaccine series in the early vaccine era was associated with a significant reduction of COVID-19 and was protective against severe/critical disease and death. Further studies are needed to evaluate the clinical effectiveness of current vaccine recommendations for SOTR against emerging new variants.

Safety and immunogenicity of SARS-CoV-2 vaccines in Chinese patients with cirrhosis: a prospective multicenter study.

BACKGROUND: Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with compensated (C-cirrhosis) and decompensated cirrhosis (D-cirrhosis) are limited. METHODS: In this prospective multicenter study, adult participants with C-cirrhosis and D-cirrhosis were enrolled and received two doses of inactivated whole-virion COVID-19 vaccines. Adverse events were recorded within 14 days after any dose of vaccination, and serum samples of enrolled patients were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. Risk factors for negative neutralizing antibody were analyzed. RESULTS: In total, 553 patients were enrolled from 15 centers in China, including 388 and 165 patients with C-cirrhosis and D-cirrhosis. The vaccines were well tolerated, most adverse reactions were mild and transient, and injection site pain (23/388 [5.9%] vs 9/165 [5.5%]) and fatigue (5/388 [1.3%] vs 3/165 [1.8%]) were the most frequently local and systemic adverse events in both the C-cirrhosis and D-cirrhosis groups. Overall, 4.4% (16/363) and 0.3% (1/363) of patients were reported Grades 2 and 3 alanine aminotransferase (ALT) elevations (defined as ALT > 2 upper limit of normal [ULN] but ≤ 5 ULN, and ALT > 5 ULN, respectively). The positive rates of COVID-19 neutralizing antibodies were 71.6% (278/388) and 66.1% (109/165) in C-cirrhosis and D-cirrhosis groups. Notably, Child-Pugh score of B and C levels was an independent risk factor of negative neutralizing antibody. CONCLUSIONS: Inactivated COVID-19 vaccinations are safe with acceptable immunogenicity in cirrhotic patients, and Child-Pugh score of B and C levels is associated with hyporesponsive to COVID-19 vaccination.

Association of renalase with clinical outcomes in hospitalized patients with COVID-19.

Renalase is a secreted flavoprotein with anti-inflammatory and pro-cell survival properties. COVID-19 is associated with disordered inflammation and apoptosis. We hypothesized that blood renalase levels would correspond to severe COVID-19 and survival. In this retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 subjects (March-June 2020) at a single institution tertiary hospital. Plasma renalase and cytokine levels were measured and clinical data abstracted from health records. Of 3,450 COVID-19 patients, 458 patients were enrolled. Patients were excluded if <18 years, or opted out of research. The primary composite outcome was intubation or death within 180 days. Secondary outcomes included mortality alone, intensive care unit admission, use of vasopressors, and CPR. Enrolled patients had mean age 64 years (SD±17), were 53% males, and 48% non-whites. Mean renalase levels was 14,108·4 ng/ml (SD±8,137 ng/ml). Compared to patients with high renalase, those with low renalase (< 8,922 ng/ml) were more likely to present with hypoxia, increased ICU admission (54% vs. 33%, p < 0.001), and cardiopulmonary resuscitation (10% vs. 4%, p = 0·023). In Cox proportional hazard model, every 1000 ng/ml increase in renalase decreased the risk of death or intubation by 5% (HR 0·95; 95% CI 0·91-0·98) and increased survival alone by 6% (HR 0·95; CI 0·90-0·98), after adjusting for socio-demographics, initial disease severity, comorbidities and inflammation. Patients with high renalase-low IL-6 levels had the best survival compared to other groups (p = 0·04). Renalase was independently associated with reduced intubation and mortality in hospitalized COVID-19 patients. Future studies should assess the pathophysiological relevance of renalase in COVID-19 disease.

Experiences with Telemedicine for HIV Care During the COVID-19 Pandemic: A Mixed-Methods Study.

To characterize perspectives and experiences with telemedicine during the COVID-19 pandemic, we conducted a mixed-methods study in two HIV clinics in the US Northeast. Among surveyed patients with HIV (PWH) who had a telemedicine appointment (n = 205), 42.4% perceived telemedicine visits as useful during the pandemic. PWH and clinical staff identified benefits of telemedicine: (1) ability to engage and re-engage patients in care; (2) perceived patient-centeredness and flexibility; (3) opportunity to engage family and multidisciplinary care team members; and (4) opportunity to enhance telemedicine use proficiency through practice and support. Identified barriers included: (1) technical challenges; (2) privacy concerns; (3) loss of routine clinical experiences and interactions; (4) limited objective patient remote monitoring; and (5) reimbursement concerns. Efforts to optimize telemedicine for HIV care should consider strategies to improve technology support for PWH, flexible options to access care, additional platforms to allow patient remote monitoring, and appropriate billing and reimbursement methods.

RESUMEN: Para caracterizar las perspectivas sobre y las experiencias con la telemedicina durante la pandemia de COVID-19, realizamos un estudio de métodos mixtos en dos clínicas de VIH en el noreste de los Estados Unidos. Entre los pacientes con VIH (PWH) encuestados que tuvieron una cita de telemedicina (n = 205), el 42.4% percibió las visitas de telemedicina como útiles durante la pandemia. Los PWH y el personal clínico identificaron como beneficios de la telemedicina: 1) la capacidad para involucrar y reinvolucrar a los pacientes en el cuidado; 2) el cuidado centrado en el paciente y flexibilidad percibidos; 3) la oportunidad de involucrar a la familia y miembros del equipo de cuidado multidisciplinario; y 4) la oportunidad de mejorar la capacidad para usar la telemedicina a través de la práctica y el apoyo. Las barreras identificadas incluyeron: 1) retos tecnológicos; 2) preocupaciones sobre la privacidad; 3) falta de experiencias e interacciones clínicas de rutina; 4) limitada monitorización remota objetiva del paciente; y 5) preocupaciones sobre los reembolsos. Los esfuerzos para optimizar la telemedicina para el cuidado del VIH deben considerar estrategias para mejorar el soporte tecnológico para los PWH, opciones flexibles para acceder a el cuidado, plataformas adicionales que permitan el monitoreo remoto del paciente, y métodos apropiados de facturación y reembolso.

The Trends of Psychological Status of People Entering from High-Risk Areas of COVID-19 Coronavirus During the Quarantine in Dedicated Hotels: A Longitudinal Survey Study from Guangzhou, China.

BACKGROUND: The quarantine in dedicated hotels has become an inevitable safety measure due to the frequent cross-border travel since the outbreak of COVID-19. The aim of the present study was to explore the trends in the psychological status of individuals entering from high-risk areas of COVID-19 coronavirus while quarantining in dedicated hotels. METHODS: A total of 591 individuals who isolated in dedicated hotels were recruited between March and June 2020. Participants self-reported mental symptoms [Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS)] every three days during the quarantine. A mixed-effects linear regression model was used to assess the trends. RESULTS: Participants reporting anxiety and depression symptoms at least one time during quarantine accounted for 4.5% and 18.4%, respectively. Their psychological status was alleviated during some first 9 days, and then it slightly deteriorated, which was suggested by SAS and SDS scores that were negatively correlated with the days of quarantine (T) (adjusted coefficient [ß] -0.81, 95% CI -1.00 to -0.62; and ß -0.75, 95% CI -0.97 to -0.53, respectively), and were positively correlated with the square of T (ß 0.04, 95% CI 0.02 to 0.06; and ß 0.04, 95% CI 0.02 to 0.06, respectively). The unemployed and 18~30-year-old participants were prone to greater levels of psychological distress. No significant difference in the trend of mental health was found among different subgroups. CONCLUSION: The mental health of the people entering Guangzhou from high-risk areas of COVID-19 coronavirus resulted positive during the early period of quarantine in dedicated hotels, after which it deteriorated. The psychological status of individuals should be closely monitored at the beginning and after more than 9 days of quarantine, especially for individuals who are unemployed and 18~30-year-old ones.

Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19.

BACKGROUND: Limited therapeutic options exist for coronavirus disease 2019 (COVID-19). COVID-19 convalescent plasma (CCP) is a potential therapeutic, but there is limited data for patients with moderate-to-severe disease. RESEARCH QUESTION: What are outcomes associated with administration of CCP in patients with moderate-to-severe COVID-19 infection? STUDY DESIGN AND METHODS: We conducted a propensity score-matched analysis of patients with moderate-to-severe COVID-19. The primary endpoints were in-hospital mortality. Secondary endpoints were number of days alive and ventilator-free at 30 days; length of hospital stay; and change in WHO scores from CCP administration (or index date) to discharge. Of 151 patients who received CCP, 132 had complete follow-up data. Patients were transfused after a median of 6 hospital days; thus, we investigated the effect of convalescent plasma before and after this timepoint with 77 early (within 6 days) and 55 late (after 6 days) recipients. Among 3,217 inpatients who did not receive CCP, 2,551 were available for matching. RESULTS: Early CCP recipients, of whom 31 (40%) were on mechanical ventilation, had lower 14-day (15% vs 23%) and 30-day (38% vs 49%) mortality compared to a matched unexposed cohort, with nearly 50% lower likelihood of in-hospital mortality (HR 0.52, [95% CI 0.28-0.96]; P = 0.036). Early plasma recipients had more days alive and ventilator-free at 30 days (+3.3 days, [95% CI 0.2 to 6.3 days]; P = 0.04) and improved WHO scores at 7 days (-0.8, [95% CI: -1.2 to -0.4]; P = 0.0003) and hospital discharge (-0.9, [95% CI: -1.5 to -0.3]; P = 0.004) compared to the matched unexposed cohort. No clinical differences were observed in late plasma recipients. INTERPRETATION: Early administration of CCP improves outcomes in patients with moderate-to-severe COVID-19, while improvement was not observed with late CCP administration. The importance of timing of administration should be addressed in specifically designed trials.

Significant Liver Injury During Hospitalization for COVID-19 Is Not Associated With Liver Insufficiency or Death.

BACKGROUND & AIMS: Coronavirus-19 disease (COVID-19) is associated with hepatocellular liver injury of uncertain significance. We aimed to determine whether development of significant liver injury during hospitalization is related to concomitant medications or processes common in COVID-19 (eg, ischemia, hyperinflammatory, or hypercoagulable states), and whether it can result in liver failure and death. METHODS: There were 834 consecutive patients hospitalized with COVID-19 who were included. Clinical, medication, and laboratory data were obtained at admission and throughout hospitalization using an identified database. Significant liver injury was defined as an aspartate aminotransferase (AST) level 5 or more times the upper limit of normal; ischemia was defined as vasopressor use for a minimum of 2 consecutive days; hyperinflammatory state was defined as high-sensitivity C-reactive protein value of 100 mg/L or more, and hypercoagulability was defined as D-dimer 5 mg/L or more at any time during hospitalization. RESULTS: A total of 105 (12.6%) patients developed significant liver injury. Compared with patients without significant liver injury, ischemia (odds ratio [OR], 4.3; range, 2.5-7.4; P < .0001) and tocilizumab use (OR, 3.6; range, 1.9-7.0; P = .0001) were independent predictors of significant liver injury. Although AST correlated closely with alanine aminotransferase (R = 0.89) throughout hospitalization, AST did not correlate with the international normalized ratio (R = 0.10) or with bilirubin level (R = 0.09). Death during hospitalization occurred in 136 (16.3%) patients. Multivariate logistic regression showed that significant liver injury was not associated with death (OR, 1.4; range, 0.8-2.6; P = .2), while ischemic (OR, 2.4; range, 1.4-4.0; P = .001), hypercoagulable (OR, 1.7; range, 1.1-2.6; P = .02), and hyperinflammatory (OR, 1.9; range, 1.2-3.1; P = .02) disease states were significant predictors of death. CONCLUSIONS: Liver test abnormalities known to be associated with COVID-19 are secondary to other insults, mostly ischemia or drug-induced liver injury, and do not lead to liver insufficiency or death.

A SMARTTT approach to Treating Tobacco use disorder in persons with HIV (SMARTTT): Rationale and design for a hybrid type 1 effectiveness-implementation study.

BACKGROUND: Tobacco use disorder is a leading threat to the health of persons with HIV (PWH) on antiretroviral treatment and identifying optimal treatment approaches to promote abstinence is critical. We describe the rationale, aims, and design for a new study, "A SMART Approach to Treating Tobacco Use Disorder in Persons with HIV (SMARTTT)," a sequential multiple assignment randomized trial. METHODS: In HIV clinics within three health systems in the northeastern United States, PWH with tobacco use disorder are randomized to nicotine replacement therapy (NRT) with or without contingency management (NRT vs. NRT + CM). Participants with response (defined as exhaled carbon monoxide (eCO)-confirmed smoking abstinence at week 12), continue the same treatment for another 12 weeks. Participants with non-response, are re-randomized to either switch medications from NRT to varenicline or intensify treatment to a higher CM reward schedule. Interventions are delivered by clinical pharmacists embedded in HIV clinics. The primary outcome is eCO-confirmed smoking abstinence; secondary outcomes include CD4 cell count, HIV viral load suppression, and the Veterans Aging Cohort Study (VACS) Index 2.0 score (a validated measure of morbidity and mortality based on laboratory data). Consistent with a hybrid type 1 effectiveness-implementation design and grounded in implementation science frameworks, we will conduct an implementation-focused process evaluation in parallel. Study protocol adaptations related to the COVID-19 pandemic have been made. CONCLUSIONS: SMARTTT is expected to generate novel findings regarding the impact, cost, and implementation of an adaptive clinical pharmacist-delivered intervention involving medications and CM to promote smoking abstinence among PWH. ClinicalTrials.govidentifier:NCT04490057.

Anxiety Status and Influencing Factors of Rural Residents in Hunan During the Coronavirus Disease 2019 Epidemic: A Web-Based Cross-Sectional Survey.

Objective: To explore the status quo of anxiety and its influencing factors among rural residents in Hunan Province during the coronavirus disease 2019 epidemic, and to provide an effective basis for prevention of and intervention for anxiety symptoms among rural residents. Methods: Convenience sampling was used. An online questionnaire was distributed to Hunan rural residents through the questionnaire star platform from February 26-29, 2020. The general data and anxiety of Hunan rural residents were investigated, and the data were analyzed using SPSS 18.0. Results: The mean Self-Rating Anxiety Scale score of 179 rural residents in Hunan was 40.93 ± 9.36. Based on the cutoff criteria, 32 residents had anxiety, including 26 with mild anxiety, five with moderate anxiety, and one with severe anxiety. The detection rate of anxiety was 17.88%. Self-rated health status, level of concern about the epidemic, and self-rated impact of the epidemic on one's life were the factors influencing the anxiety score of rural residents in Hunan (P < 0.05). Conclusion: During the coronavirus disease 2019 epidemic, the detection rate of anxiety in rural residents in Hunan was higher than that of the general population in China. The relevant departments should pay attention to the mental health of rural residents and implement targeted mental health prevention and intervention measures during the epidemic situation.

Abnormal Liver Tests in COVID-19: A Retrospective Observational Cohort Study of 1,827 Patients in a Major U.S. Hospital Network.

BACKGROUND AND AIMS: The coronavirus-19 disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 virus, is associated with significant morbidity and mortality attributable to pneumonia, acute respiratory distress syndrome, and multiorgan failure. Liver injury has been reported as a nonpulmonary manifestation of COVID-19, but characterization of liver test abnormalities and their association with clinical outcomes is incomplete. APPROACH AND RESULTS: We conducted a retrospective cohort study of 1,827 patients with confirmed COVID-19 who were hospitalized within the Yale-New Haven Health System between March 14, 2020 and April 23, 2020. Clinical characteristics, liver tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], total bilirubin [TBIL], and albumin) at three time points (preinfection baseline, admission, and peak hospitalization), and hospitalization outcomes (severe COVID-19, intensive care unit [ICU] admission, mechanical ventilation, and death) were analyzed. Abnormal liver tests were commonly observed in hospitalized patients with COVID-19, both at admission (AST 66.9%, ALT 41.6%, ALP 13.5%, and TBIL 4.3%) and peak hospitalization (AST 83.4%, ALT 61.6%, ALP 22.7%, and TBIL 16.1%). Most patients with abnormal liver tests at admission had minimal elevations 1-2× the upper limit of normal (ULN; AST 63.7%, ALT 63.5%, ALP 80.0%, and TBIL 75.7%). A significant proportion of these patients had abnormal liver tests prehospitalization (AST 25.9%, ALT 38.0%, ALP 56.8%, and TBIL 44.4%). Multivariate analysis revealed an association between abnormal liver tests and severe COVID-19, including ICU admission, mechanical ventilation, and death; associations with age, male sex, body mass index, and diabetes mellitus were also observed. Medications used in COVID-19 treatment (lopinavir/ritonavir, hydroxychloroquine, remdesivir, and tocilizumab) were associated with peak hospitalization liver transaminase elevations >5× ULN. CONCLUSIONS: Abnormal liver tests occur in most hospitalized patients with COVID-19 and may be associated with poorer clinical outcomes.