Association of Receipt of Opioid Use Disorder-Related Telehealth Services and Medications for Opioid Use Disorder With Fatal Drug Overdoses Among Medicare Beneficiaries Before and During the COVID-19 Pandemic.

Importance: Federal emergency authorities were invoked during the COVID-19 pandemic to expand clinical telehealth for opioid use disorder (OUD). Objective: To examine the association of the receipt of telehealth services and medications for OUD (MOUD) with fatal drug overdoses before and during the pandemic. Design, Setting, and Participants: This cohort study used exploratory longitudinal data from 2 cohorts (prepandemic cohort: September 1, 2018, to February 29, 2020; pandemic cohort: September 1, 2019, to February 28, 2021) of Medicare Fee-for-Service beneficiaries aged 18 years or older initiating an episode of OUD-related care using Medicare Fee-for-Service data from the Centers for Medicare & Medicaid Services and National Death Index data from the Centers for Disease Control and Prevention. Data analysis was performed from September 19 to October 17, 2022. Exposures: Prepandemic vs pandemic cohort demographic, medical, substance use, and psychiatric characteristics. Main Outcomes and Measures: Receipt of OUD-related telehealth services, receipt of MOUD, and fatal drug overdose. Results: The prepandemic cohort comprised 105 162 beneficiaries (58.1% female; 67.6% aged 45-74 years). The pandemic cohort comprised 70 479 beneficiaries (57.1% female; 66.3% aged 45-74 years). The rate of all-cause mortality was higher in the pandemic cohort (99.9 per 1000 beneficiaries; 7041 deaths) than in the prepandemic cohort (76.8 per 1000; 8076 deaths) (P < .001). The rate of fatal drug overdoses was higher in the pandemic cohort (5.1 per 1000 beneficiaries; n = 358) than in the prepandemic cohort (3.7 per 1000; n = 391) (P < .001). The percentage of deaths due to a fatal drug overdose was similar in the prepandemic (4.8%) and pandemic (5.1%) cohorts (P = .49). In multivariable analysis of the pandemic cohort, receipt of OUD-related telehealth was associated with a significantly lower adjusted odds ratio (aOR) for fatal drug overdose (aOR, 0.67; 95% CI, 0.48-0.92) as was receipt of MOUD from opioid treatment programs (aOR, 0.41; 95% CI, 0.25-0.68) and receipt of buprenorphine in office-based settings (aOR, 0.62; 95% CI, 0.43-0.91) compared with those not receiving MOUD; receipt of extended-release naltrexone in office-based settings was not associated with lower odds for fatal drug overdose (aOR, 1.16; 95% CI, 0.41-3.26). Conclusions and Relevance: This cohort study found that, among Medicare beneficiaries initiating OUD-related care during the COVID-19 pandemic, receipt of OUD-related telehealth services was associated with reduced risk for fatal drug overdose, as was receipt of MOUD from opioid treatment programs and receipt of buprenorphine in office-based settings. Strategies to expand provision of MOUD, increase retention in care, and address co-occurring physical and behavioral health conditions are needed.

Risk of death in individuals hospitalized for COVID-19 with and without psychiatric disorders: an observational multicenter study in France.

BACKGROUND: Prior research suggests that psychiatric disorders could be linked to increased mortality among patients with COVID-19. However, whether all or specific psychiatric disorders are intrinsic risk factors of death in COVID-19, or whether these associations reflect the greater prevalence of medical risk factors in people with psychiatric disorders, has yet to be evaluated. METHODS: We performed an observational multicenter retrospective cohort study to examine the association between psychiatric disorders and mortality among patients hospitalized for laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals. RESULTS: Of 15,168 adult patients, 857 (5.7%) had an ICD-10 diagnosis of psychiatric disorder. Over a mean follow-up of 14.6 days (SD=17.9), death occurred in 326/857 (38.0%) patients with a diagnosis of psychiatric disorder versus 1,276/14,311 (8.9%) in patients without such a diagnosis (OR=6.27; 95%CI=5.40-7.28; p<0.01). When adjusting for age, sex, hospital, current smoking status, and medications according to compassionate use or as part of a clinical trial, this association remained significant (AOR=3.27; 95%CI=2.78-3.85; p<0.01). However, additional adjustments for obesity and number of medical conditions resulted in a non-significant association (AOR=1.02; 95%CI=0.84-1.23; p=0.86). Exploratory analyses following the same adjustments suggest that a diagnosis of mood disorders was significantly associated with reduced mortality, which might be explained by the use of antidepressants. CONCLUSIONS: These findings suggest that the increased risk of COVID-19-related mortality in individuals with psychiatric disorders hospitalized for COVID-19 might be explained by the greater number of medical conditions and the higher prevalence of obesity in this population, but not by the underlying psychiatric disease.

Tobacco, Alcohol, Cannabis, and Other Drug Use in the US Before and During the Early Phase of the COVID-19 Pandemic.

Importance: Information about national substance use trends among youths and adults after mid-March 2020 is limited due to constraints on surveillance during the COVID-19 pandemic. Objective: To evaluate whether substance use prevalence in the early part of the pandemic (2020) differed from the prepandemic periods of 2018 to 2019 and 2016 to 2018. Design, Setting, and Participants: This cross-sectional study was a repeated analysis of 2016 to 2020 data from a nationally representative sample of youths and adults in the Population Assessment of Tobacco and Health (PATH) Study. Participants were representative of the US civilian noninstitutionalized population. Household residents age 13 years or older were interviewed in person from 2016 to 2019 and via telephone in 2020. Exposures: Age, calendar year. Main Outcomes and Measures: Past 30-day self-reported use of any tobacco, any alcohol, binge drinking, cannabis, and any other illegal or misused prescription drugs. Results: The overall nationally representative 2020 sample included 7129 youths (ages 13-17 years), 3628 young adults (ages 18-20 years), and 8874 adults (ages ≥21 years). Comparing 2018 to 2019 with 2020 among youths, prevalence of all substances used declined (eg, cannabis use declined in those aged 16-17 years from 14.9% to 7.6%; absolute difference, -7.3 percentage points [95% CI -8.8 to -5.8 percentage points]). Among young adults, prevalence of all substances other than any alcohol decreased significantly (eg, tobacco use declined from 37.8% to 22.8%; absolute difference, -15.1 percentage points [95% CI -16.8 to -13.3 percentage points]). In adults ages 21 to 24 years, any tobacco use declined from 39.0% to 30.9% (absolute difference, -8.2 percentage points [95% CI, -10.6 to -5.7 percentage points]), and alcohol use increased from 60.2% to 65.2% (absolute difference, 5.0 percentage points [95% CI, 2.3 to 7.7 percentage points]). Among adults aged 25 years or older, any tobacco use declined from 39.0% to 30.9% (absolute difference, -8.2 percentage points [95% CI, -10.6 to -5.7 percentage points]), cannabis use increased from 11.3% to 12.4% (absolute difference, 1.2 percentage points [95% CI, 0.3 to 2.0 percentage points]), and other substance use declined from 5.8% to 3.7% (absolute difference, -2.1 percentage points [95% CI, -2.9 to -1.4 percentage points]). Conclusions and Relevance: In this cross-sectional study, substance use decreased between 2019 and 2020 among those aged 13 to 20 years; consistent declines were not seen in older persons other than tobacco use reductions, and cannabis use increased among adults ages 25 years and older. While social changes during the COVID-19 pandemic could have affected substance use, findings should be interpreted with caution due to differences in data collection methods in 2016 to 2019 and 2020.

Implications of Telepsychiatry for Cost, Quality, and Equity of Mental Health Care.

This Viewpoint discusses overlapping challenges to multiple stakeholders as telepsychiatry continues to expand.

Antidepressant Use and Its Association with 28-Day Mortality in Inpatients with SARS-CoV-2: Support for the FIASMA Model against COVID-19.

To reduce Coronavirus Disease 2019 (COVID-19)-related mortality and morbidity, widely available oral COVID-19 treatments are urgently needed. Certain antidepressants, such as fluvoxamine or fluoxetine, may be beneficial against COVID-19. We included 388,945 adult inpatients who tested positive for SARS-CoV-2 at 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 2 November 2021. We compared the prevalence of antidepressant use at admission in a 1:1 ratio matched analytic sample with and without COVID-19 (N = 82,586), and assessed its association with 28-day all-cause mortality in a 1:1 ratio matched analytic sample of COVID-19 inpatients with and without antidepressant use at admission (N = 1482). Antidepressant use was significantly less prevalent in inpatients with COVID-19 than in a matched control group of inpatients without COVID-19 (1.9% versus 4.8%; Odds Ratio (OR) = 0.38; 95%CI = 0.35-0.41, p < 0.001). Antidepressant use was significantly associated with reduced 28-day mortality among COVID-19 inpatients (12.8% versus 21.2%; OR = 0.55; 95%CI = 0.41-0.72, p < 0.001), particularly at daily doses of at least 40 mg fluoxetine equivalents. Antidepressants with high FIASMA (Functional Inhibitors of Acid Sphingomyelinase) activity seem to drive both associations. These treatments may reduce SARS-CoV-2 infections and COVID-19-related mortality in inpatients, and may be appropriate for prophylaxis and/or COVID-19 therapy for outpatients or inpatients.

Receipt of Telehealth Services, Receipt and Retention of Medications for Opioid Use Disorder, and Medically Treated Overdose Among Medicare Beneficiaries Before and During the COVID-19 Pandemic.

Importance: Federal emergency authorities were invoked during the COVID-19 pandemic to expand use of telehealth for new and continued care, including provision of medications for opioid use disorder (MOUD). Objective: To examine receipt of telehealth services, MOUD (methadone, buprenorphine, and extended-release [ER] naltrexone) receipt and retention, and medically treated overdose before and during the COVID-19 pandemic. Design, Setting, and Participants: This exploratory longitudinal cohort study used data from the US Centers for Medicare & Medicaid Services from September 2018 to February 2021. Two cohorts (before COVID-19 pandemic from September 2018 to February 2020 and during COVID-19 pandemic from September 2019 to February 2021) of Medicare fee-for-service beneficiaries 18 years and older with an International Statistical Classification of Diseases, Tenth Revision, Clinical Modification OUD diagnosis. Exposures: Pre-COVID-19 pandemic vs COVID-19 pandemic cohort demographic characteristics, medical and substance use, and psychiatric comorbidities. Main Outcomes and Measures: Receipt and retention of MOUD, receipt of OUD and behavioral health-related telehealth services, and experiencing medically treated overdose. Results: The pre-COVID-19 pandemic cohort comprised 105 240 beneficiaries; of these, 61 152 (58.1%) were female, 71 152 (67.6%) were aged 45 to 74 years, and 82 822 (79.5%) non-Hispanic White. The COVID-19 pandemic cohort comprised 70 538 beneficiaries; of these, 40 257 (57.1%) were female, 46 793 (66.3%) were aged 45 to 74 years, and 55 510 (79.7%) were non-Hispanic White. During the study period, a larger percentage of beneficiaries in the pandemic cohort compared with the prepandemic cohort received OUD-related telehealth services (13 829 [19.6%] vs 593 [0.6%]; P < .001), behavioral health-related telehealth services (28 902 [41.0%] vs 1967 [1.9%]; P < .001), and MOUD (8854 [12.6%] vs 11 360 [10.8%]; P < .001). The percentage experiencing a medically treated overdose during the study period was similar (18.5% [19 491 of 105 240] in the prepandemic cohort vs 18.4% [13 004 of 70 538] in the pandemic cohort; P = .65). Receipt of OUD-related telehealth services in the pandemic cohort was associated with increased odds of MOUD retention (adjusted odds ratio [aOR], 1.27; 95% CI, 1.14-1.41) and lower odds of medically treated overdose (aOR, 0.67; 95% CI, 0.63-0.71). Among beneficiaries in the pandemic cohort, those receiving MOUD from opioid treatment programs only (aOR, 0.54; 95% CI, 0.47-0.63) and those receiving buprenorphine from pharmacies only (aOR, 0.91; 95% CI, 0.84-0.98) had lower odds of medically treated overdose compared with beneficiaries who did not receive MOUD. Conclusions and Relevance: Emergency authorities to expand use of telehealth and provide flexibilities for MOUD provision during the pandemic were used by Medicare beneficiaries initiating an episode of OUD-related care and were associated with improved retention in care and reduced odds of medically treated overdose. Strategies to expand provision of MOUD and increase retention in care are urgently needed.

Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study.

(1) Background: Based on its antiviral activity, anti-inflammatory properties, and functional inhibition effects on the acid sphingomyelinase/ceramide system (FIASMA), we sought to examine the potential usefulness of the H1 antihistamine hydroxyzine in patients hospitalized for COVID-19. (2) Methods: In a multicenter observational study, we included 15,103 adults hospitalized for COVID-19, of which 164 (1.1%) received hydroxyzine within the first 48 h of hospitalization, administered orally at a median daily dose of 25.0 mg (SD = 29.5). We compared mortality rates between patients who received hydroxyzine at hospital admission and those who did not, using a multivariable logistic regression model adjusting for patients' characteristics, medical conditions, and use of other medications. (3) Results: This analysis showed a significant association between hydroxyzine use and reduced mortality (AOR, 0.51; 95%CI, 0.29-0.88, p = 0.016). This association was similar in multiple sensitivity analyses. (4) Conclusions: In this retrospective observational multicenter study, the use of the FIASMA hydroxyzine was associated with reduced mortality in patients hospitalized for COVID-19. Double-blind placebo-controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results, as are studies to examine the potential usefulness of this medication for outpatients and as post-exposure prophylaxis for individuals at high risk for severe COVID-19.

Author Correction: A stochastic agent-based model of the SARS-CoV-2 epidemic in France.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Association Between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: An Observational Multicenter Study.

Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the ASM/ceramide system may be central to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe coronavirus disease 2019 (COVID-19) in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID-19, 277 (9.7%) were taking an FIASMA medication at the time of their hospital admission. The primary end point was a composite of intubation and/or death. We compared this end point between patients taking vs. not taking an FIASMA medication in time-to-event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow-up of 9.2 days (SD = 12.5), the primary end point occurred in 104 patients (37.5%) receiving an FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.58-0.87, P < 0.001) and primary IPW (HR = 0.58, 95%CI = 0.46-0.72, P < 0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID-19 and support the continuation of FIASMA medications in these patients. Double-blind controlled randomized clinical trials of these medications for COVID-19 are needed.

Research on substance use disorders during the COVID-19 pandemic.

The COVID-19 pandemic has triggered changes in the substance use disorder (SUD) treatment delivery system, in the availability of legal and illicit drugs, and in other social and economic factors. As such, these changes necessitate that the field re-evaluate research approaches to SUDs, including in epidemiology, clinical trials, health services, implementation and policy research, as well as basic and translational neuroscience. COVID-19 has reduced researchers' access to target populations and made it difficult for them to obtain timely data to monitor changes in patterns of drug use and overdoses. These changes have increased researchers' interest in virtual technologies to expand and accelerate access to populations; increased modifications in the design, conduct, and analysis of clinical trials; and increased emphasis on implementation. Similarly, as researchers better understand the biology of COVID-19, they will better understand potential effects of COVID-19 on neurotransmitter receptors and signaling pathways, mechanisms underlying COVID-19 associated neurological and psychiatric sequelae, and interactions between COVID-19 treatments and psychoactive substances. The pandemic has also revealed the need for research that addresses health disparities. Overall, the COVID-19 pandemic has challenged several aspects of current research on SUD. Responding to these challenges provides opportunities to develop robust research approaches that align with the goals of improving patient outcomes and public health and are resilient to the challenges of future crises.

Observational study of haloperidol in hospitalized patients with COVID-19.

BACKGROUND: Haloperidol, a widely used antipsychotic, has been suggested as potentially useful for patients with COVID-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2, possibly through sigma-1 receptor antagonist effect. METHODS: We examined the associations of haloperidol use with intubation or death and time to discharge home among adult patients hospitalized for COVID-19 at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. In the primary analyses, we compared these two outcomes between patients receiving and not receiving haloperidol using univariate Cox regression models in matched analytic samples based on patient characteristics and other psychotropic medications. Sensitivity analyses included propensity score analyses with inverse probability weighting and multivariable Cox regression models. RESULTS: Of 15,121 adult inpatients with a positive COVID-19 PT-PCR test, 39 patients (0.03%) received haloperidol within the first 48 hours of admission. Over a mean follow-up of 13.8 days (SD = 17.9), 2,024 patients (13.4%) had a primary end-point event and 10,179 patients (77.6%) were discharged home at the time of study end on May 1st. The primary endpoint occurred in 9 patients (23.1%) who received haloperidol and 2,015 patients (13.4%) who did not. The secondary endpoint of discharge home occurred in 16 patients (61.5%) who received haloperidol and 9,907 patients (85.8%) who did not. There were no significant associations between haloperidol use and the primary (HR, 0.80; 95% CI, 0.39 to 1.62, p = 0.531) and secondary (HR, 1.30; 95% CI, 0.74 to 2.28, p = 0.355) endpoints. Results were similar in multiple sensitivity analyses. CONCLUSION: Findings from this multicenter observational study suggest that haloperidol use prescribed at a mean dose of 4.5 mg per day (SD = 5.2) for a mean duration of 8.4 days (SD = 7.2) may not be associated with risk of intubation or death, or with time to discharge home, among adult patients hospitalized for COVID-19.

Observational Study of Chlorpromazine in Hospitalized Patients with COVID-19.

INTRODUCTION: Chlorpromazine has been suggested as being potentially useful in patients with coronavirus disease 2019 (COVID-19) on the grounds of its potential antiviral and anti-inflammatory effects. OBJECTIVE: The aim of this study was to examine the association between chlorpromazine use and mortality among adult patients hospitalized for COVID-19. METHODS: We conducted an observational, multicenter, retrospective study at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of first prescription of chlorpromazine during hospitalization for COVID-19. The primary endpoint was death. Among patients who had not been hospitalized in intensive care units (ICUs), we compared this endpoint between those who received chlorpromazine and those who did not, in time-to-event analyses adjusted for patient characteristics, clinical markers of disease severity, and other psychotropic medications. The primary analysis used a Cox regression model with inverse probability weighting. Multiple sensitivity analyses were performed. RESULTS: Of the 14,340 adult inpatients hospitalized outside ICUs for COVID-19, 55 patients (0.4%) received chlorpromazine. Over a mean follow-up of 14.3 days (standard deviation [SD] 18.2), death occurred in 13 patients (23.6%) who received chlorpromazine and 1289 patients (9.0%) who did not. In the primary analysis, there was no significant association between chlorpromazine use and mortality (hazard ratio [HR] 2.01, 95% confidence interval [CI] 0.75-5.40; p = 0.163). Sensitivity analyses included a Cox regression in a 1:5 ratio matched analytic sample that showed a similar result (HR 1.67, 95% CI 0.91-3.06; p = 0.100) and a multivariable Cox regression that indicated a significant positive association (HR 3.10, 95% CI 1.31-7.34; p = 0.010). CONCLUSION: Our results suggest that chlorpromazine prescribed at a mean daily dose of 70.8 mg (SD 65.3) was not associated with reduced mortality.

A stochastic agent-based model of the SARS-CoV-2 epidemic in France.

Many European countries have responded to the COVID-19 pandemic by implementing nationwide protection measures and lockdowns1. However, the epidemic could rebound when such measures are relaxed, possibly leading to a requirement for a second or more, repeated lockdowns2. Here, we present results of a stochastic agent-based microsimulation model of the COVID-19 epidemic in France. We examined the potential impact of post-lockdown measures, including physical distancing, mask-wearing and shielding individuals who are the most vulnerable to severe COVID-19 infection, on cumulative disease incidence and mortality, and on intensive care unit (ICU)-bed occupancy. While lockdown is effective in containing the viral spread, once lifted, regardless of duration, it would be unlikely to prevent a rebound. Both physical distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing ICUs from becoming overwhelmed and a subsequent second lockdown. However, these measures coupled with the shielding of vulnerable people would be associated with better outcomes, including lower mortality and maintaining an adequate ICU capacity to prevent a second lockdown. Benefits would nonetheless be markedly reduced if most people do not adhere to these measures, or if they are not maintained for a sufficiently long period.