A comparison of psychiatric inpatient admissions in youth before and during the COVID-19 pandemic.

Background: The current understanding of the effect of COVID-19 on child and youth admissions to psychiatric inpatient units over time is limited, with conflicting findings and many studies focusing on the initial wave of the pandemic. Objectives: This study identified changes in psychiatric inpatient admissions, and reasons for admission, including suicidality and self-harm, before and during the COVID-19 pandemic. Method: This time series study analyzed 3,723 admissions of youth (ages 0-18.88 years) admitted to four major psychiatry inpatient units in a large Canadian city between January 1st, 2016 and December 31st, 2021. Pre-pandemic (before March 11, 2020) and during-pandemic (after March 11, 2020) trends of admissions were explored using a Bayesian structural time series model (BSTS). Results: The model revealed that overall admissions during the pandemic period exceeded what would have been predicted in the absence of a pandemic, a relative increase of 29%. Additionally, a rise in the total number of admissions due to self-harm and suicidality (29% increase), externalizing/behavioral issues (69% increase), and internalizing/emotional issues (28% increase) provided strong evidence of increased admissions compared to what might have been expected from pre-pandemic numbers. Conclusions: There was strong evidence of increases in psychiatric inpatient admissions during the COVID-19 pandemic compared to expected trends based on pre-pandemic data. To ensure accessible and continuous mental health supports and services for youth and their families during future pandemics, these findings highlight the need for rapid expanse of inpatient mental health services, similar to what occurred in many intensive care units across Canada.

Contexte: La compréhension actuelle de l'effet de la COVID-19 sur les enfants et jeunes patients admis aux unités d'hospitalisation psychiatrique avec le temps est limitée, avec des conclusions contradictoires et des études portant sur la vague initiale de la pandémie. Objectifs: La présente étude a identifié les changements dans les admissions de patients hospitalisés en psychiatrie, et les raisons de l'admission, notamment la suicidabilité et l'automutilation, avant et durant la pandémie de la COVID-19. Méthode: Cette étude de séries chronologiques a analysé 3 723 admissions de jeunes (de 0 à 18,88 ans) admis à quatre grandes unités d'hospitalisation en psychiatrie dans une grande ville canadienne entre le 1er janvier 2016 et le 31 décembre 2021. Les tendances des admissions pré-pandémiques (avant le 11 mars 2020) et pendant la pandémie (après le 11 mars 2020) ont été explorées à l'aide d'un Modèle bayésien de séries chronologiques structurelles (BSTS). Résultats: Le modèle a révélé que globalement, les admissions durant la période pandémique excédaient ce qui aurait été prédit en l'absence d'une pandémie, une hausse relative de 29%. En outre, une hausse du nombre total d'admissions attribuables à l'automutilation et à la suicidabilité (hausse de 29%), à des problèmes de comportement/d'externalisation (hausse de 69%), et à des problèmes d'internalisation/émotionnels (hausse de 28%) a fourni des preuves solides des admissions accrues comparé à ce qu'on aurait pu attendre des chiffres pré-pandémiques. Conclusions: Il y avait des preuves solides des augmentations des admissions de patients hospitalisés en psychiatrie durant la pandémie de la COVID19 comparé aux tendances prévues selon les données pré-pandémiques. Afin d'assurer des soutiens et des services de santé mentale accessibles et continus pour les jeunes et leur famille durant les futures pandémies, ces résultats soulignent la nécessité d'une expansion rapide des services de santé mentale pour patients hospitalisés, pareillement à ce qui s'est produit dans de nombreuses unités de soins intensifs du Canada.

Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19: A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States.

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country-level estimates of 90-day absolute risk (with 95% confidence intervals) of ATE and VTE. Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID-19 vaccines were available (through November 2020). The 90-day absolute risk of ATE during this period ranged from 0.11% (0.09-0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90-day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90-day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90-day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99-1.04%) in the US. Conclusion: There was heterogeneity by country in 90-day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability.

Burden of Medically Attended Diarrhea and Outpatient Clostridioides difficile Infection Among Persons in 2 Large Integrated Healthcare Settings, 2016-2021.

Background: Identification of Clostridioides difficile infection (CDI) in the community setting is increasing. We describe testing for CDI among patients with medically attended diarrhea (MAD) in the outpatient setting, and the incidence of outpatient CDI. Methods: This was a retrospective cohort study among members ≥18 years of age from Kaiser Permanente Southern California and Kaiser Permanente Northwest from 1 January 2016 through 31 December 2021. MAD was identified by outpatient diarrheal International Classification of Diseases, Tenth Revision diagnosis codes, and CDI through positive laboratory results. Outpatient CDI was defined by no hospitalization ≤7 days after specimen collection. Incidence rates (IRs) of outpatient CDI were stratified by select demographic and clinical variables. Outpatient CDI burden 12 months following index date was measured by CDI-associated healthcare visits, and CDI testing and treatment. Results: We identified 777 533 MAD episodes; 12.1% (93 964/777 533) were tested for CDI. Of those tested, 10.8% (10 110/93 964) were positive. Outpatient CDI IR was 51.0 (95% confidence interval [CI], 49.8-52.2) per 100 000 person-years, decreasing from 58.2 (95% CI, 55.7-60.7) in 2016 to 45.7 (95% CI, 43.7-47.8) in 2021. Approximately 44% (n = 4200) received an antibiotic 30 days prior to index date and 84.1% (n = 8006) CDIs were "community-associated" (no hospitalizations 12 weeks prior to index date). Of outpatient CDIs, 6.7% (n = 526) had a CDI-associated hospitalization ≤12 months. Conclusions: There was a high incidence of outpatient CDI despite infrequent CDI testing among patients with MAD. The majority of those with outpatient CDI had no recent antibiotic use and no recent hospitalization. Further studies are needed to understand the source and management of medically attended outpatient CDI.

Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

COVID-19 and Neurodevelopmental Disabilities: Examining the Impact of the First 2 Years of the Pandemic on the Demand for Pediatric Inpatient Care.

The COVID-19 pandemic has strained the resources of the world's healthcare systems. Most individuals with neurodevelopmental disabilities (NDDs) experience significant mental health issues and face substantial barriers in accessing appropriate supports which have been exacerbated during the pandemic. It is unknown the extent to which COVID-19 impacted the demand for and effectiveness of inpatient care for those with NDDs. The impact of COVID-19 on the number of admissions of youth with NDDs to pediatric inpatient psychiatry units, as well as their functioning and length of stay during the first two years of the pandemic was analyzed using Bayesian structural time series models. Admission data of youth with NDDs from four pediatric inpatient units in Alberta, Canada (n = 2144) was examined. Inpatient admissions of youth with NDDs significantly increased following the onset of the pandemic. Compared to the period prior to the pandemic, patients with NDDs had significantly worse overall functioning and received fewer days of treatment. These findings highlight the need for increased resources to support the mental health needs of this vulnerable population and are consistent with other studies in the general population examining the utilization of inpatient psychiatric units during the pandemic.

CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

Risk of admission to hospital with arterial or venous thromboembolism among patients diagnosed in the ambulatory setting with covid-19 compared with influenza: retrospective cohort study.

Objective: To measure the 90 day risk of arterial thromboembolism and venous thromboembolism among patients diagnosed with covid-19 in the ambulatory (ie, outpatient, emergency department, or institutional) setting during periods before and during covid-19 vaccine availability and compare results to patients with ambulatory diagnosed influenza. Design: Retrospective cohort study. Setting: Four integrated health systems and two national health insurers in the US Food and Drug Administration's Sentinel System. Participants: Patients with ambulatory diagnosed covid-19 when vaccines were unavailable in the US (period 1, 1 April-30 November 2020; n=272 065) and when vaccines were available in the US (period 2, 1 December 2020-31 May 2021; n=342 103), and patients with ambulatory diagnosed influenza (1 October 2018-30 April 2019; n=118 618). Main outcome measures: Arterial thromboembolism (hospital diagnosis of acute myocardial infarction or ischemic stroke) and venous thromboembolism (hospital diagnosis of acute deep venous thrombosis or pulmonary embolism) within 90 days after ambulatory covid-19 or influenza diagnosis. We developed propensity scores to account for differences between the cohorts and used weighted Cox regression to estimate adjusted hazard ratios of outcomes with 95% confidence intervals for covid-19 during periods 1 and 2 versus influenza. Results: 90 day absolute risk of arterial thromboembolism with covid-19 was 1.01% (95% confidence interval 0.97% to 1.05%) during period 1, 1.06% (1.03% to 1.10%) during period 2, and with influenza was 0.45% (0.41% to 0.49%). The risk of arterial thromboembolism was higher for patients with covid-19 during period 1 (adjusted hazard ratio 1.53 (95% confidence interval 1.38 to 1.69)) and period 2 (1.69 (1.53 to 1.86)) than for patients with influenza. 90 day absolute risk of venous thromboembolism with covid-19 was 0.73% (0.70% to 0.77%) during period 1, 0.88% (0.84 to 0.91%) during period 2, and with influenza was 0.18% (0.16% to 0.21%). Risk of venous thromboembolism was higher with covid-19 during period 1 (adjusted hazard ratio 2.86 (2.46 to 3.32)) and period 2 (3.56 (3.08 to 4.12)) than with influenza. Conclusions: Patients diagnosed with covid-19 in the ambulatory setting had a higher 90 day risk of admission to hospital with arterial thromboembolism and venous thromboembolism both before and after covid-19 vaccine availability compared with patients with influenza.

Association Between Diabetes Severity and Risks of COVID-19 Infection and Outcomes.

BACKGROUND: Little is known about whether diabetes increases the risk of COVID-19 infection and whether measures of diabetes severity are related to COVID-19 outcomes. OBJECTIVE: Investigate diabetes severity measures as potential risk factors for COVID-19 infection and COVID-19 outcomes. DESIGN, PARTICIPANTS, MEASURES: In integrated healthcare systems in Colorado, Oregon, and Washington, we identified a cohort of adults on February 29, 2020 (n = 1,086,918) and conducted follow-up through February 28, 2021. Electronic health data and death certificates were used to identify markers of diabetes severity, covariates, and outcomes. Outcomes were COVID-19 infection (positive nucleic acid antigen test, COVID-19 hospitalization, or COVID-19 death) and severe COVID-19 (invasive mechanical ventilation or COVID-19 death). Individuals with diabetes (n = 142,340) and categories of diabetes severity measures were compared with a referent group with no diabetes (n = 944,578), adjusting for demographic variables, neighborhood deprivation index, body mass index, and comorbidities. RESULTS: Of 30,935 patients with COVID-19 infection, 996 met the criteria for severe COVID-19. Type 1 (odds ratio [OR] 1.41, 95% CI 1.27-1.57) and type 2 diabetes (OR 1.27, 95% CI 1.23-1.31) were associated with increased risk of COVID-19 infection. Insulin treatment was associated with greater COVID-19 infection risk (OR 1.43, 95% CI 1.34-1.52) than treatment with non-insulin drugs (OR 1.26, 95% 1.20-1.33) or no treatment (OR 1.24; 1.18-1.29). The relationship between glycemic control and COVID-19 infection risk was dose-dependent: from an OR of 1.21 (95% CI 1.15-1.26) for hemoglobin A1c (HbA1c) < 7% to an OR of 1.62 (95% CI 1.51-1.75) for HbA1c ≥ 9%. Risk factors for severe COVID-19 were type 1 diabetes (OR 2.87; 95% CI 1.99-4.15), type 2 diabetes (OR 1.80; 95% CI 1.55-2.09), insulin treatment (OR 2.65; 95% CI 2.13-3.28), and HbA1c ≥ 9% (OR 2.61; 95% CI 1.94-3.52). CONCLUSIONS: Diabetes and greater diabetes severity were associated with increased risks of COVID-19 infection and worse COVID-19 outcomes.

Risk Factors for Reinfection with SARS-CoV-2 Omicron Variant among Previously Infected Frontline Workers.

In a cohort of essential workers in the United States previously infected with SARS-CoV-2, risk factors for reinfection included being unvaccinated, infrequent mask use, time since first infection, and being non-Hispanic Black. Protecting workers from reinfection requires a multipronged approach including up-to-date vaccination, mask use as recommended, and reduction in underlying health disparities.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection History and Antibody Response to 3 Coronavirus Disease 2019 Messenger RNA Vaccine Doses.

BACKGROUND: Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. METHODS: Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. RESULTS: Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2-3.0) in group 2 and 2.9-fold (95% CI = 2.6-3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213-246] after dose 2) did not increase significantly after dose 3. CONCLUSIONS: A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster.

"I really had somebody in my corner." Patient experiences with a pharmacist-led opioid tapering program.

BACKGROUND: Opioid tapering has been identified as an effective strategy to prevent the dangers associated with long-term opioid therapy for patients with chronic pain. However, many patients are resistant to tapering, and conversations about tapering can be challenging for health care providers. Pharmacists can play a role in supporting both providers and patients with the process of opioid tapering. OBJECTIVE: Qualitatively describe patient experiences with a unique phone-based and pharmacy-led opioid tapering program implemented within an integrated health care system. METHODS: In-depth telephone interviews with patients who completed the program were recorded, transcribed, and analyzed. Themes were identified through a constant comparative approach. RESULTS: We completed 25 interviews; 80% of patients were women (20), with a mean age of 58 years, and 72% (18) had been using opioids for pain management for 10 or more years. Most (60%) described a positive and satisfying experience with the tapering program. Strengths of the program reported by patients included a patient-centered and compassionate taper approach, flexible taper pace, easy access to knowledgeable pharmacist advocates, and resultant improvements in quality of life (e.g., increased energy). Challenges reported included: unhelpful or difficult-to-access nonpharmacological pain management options, negative quality of life impacts (e.g., inability to exercise), and lack of choice in the taper process. At the end of tapering, most patients (72%) described their pain as reduced or manageable rather than worse and expressed willingness to use the program in the future if a need should arise. CONCLUSIONS: Patients in a pharmacist-led opioid tapering program appreciated the program's individualized approach to care and access to pharmacist' expertise. Most interviewed patients successfully reduced their opioid use and recommended that the program should continue as an offered service. To improve the program, patients suggested increased personalization of the taper process and additional support for withdrawal symptoms and nonpharmacological pain management.

Association of mRNA Vaccination With Clinical and Virologic Features of COVID-19 Among US Essential and Frontline Workers.

Importance: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance. Objective: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages. Design, Setting, and Participants: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported. Exposures: SARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status. Main Outcomes and Measures: Clinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase-polymerase chain reaction testing along with viral viability. Results: Among 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, -6.1 [95% CI, -11.8 to -0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log10 copies/µL; difference, -1.0 [95% CI, -1.7 to -0.2] for Delta and 2.8 vs 3.5 log10 copies/µL, difference, -1.0 [95% CI, -1.7 to -0.3] for Omicron). Conclusions and Relevance: In a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied.

Association of COVID-19 vs Influenza With Risk of Arterial and Venous Thrombotic Events Among Hospitalized Patients.

Importance: The incidence of arterial thromboembolism and venous thromboembolism in persons with COVID-19 remains unclear. Objective: To measure the 90-day risk of arterial thromboembolism and venous thromboembolism in patients hospitalized with COVID-19 before or during COVID-19 vaccine availability vs patients hospitalized with influenza. Design, Setting, and Participants: Retrospective cohort study of 41 443 patients hospitalized with COVID-19 before vaccine availability (April-November 2020), 44 194 patients hospitalized with COVID-19 during vaccine availability (December 2020-May 2021), and 8269 patients hospitalized with influenza (October 2018-April 2019) in the US Food and Drug Administration Sentinel System (data from 2 national health insurers and 4 regional integrated health systems). Exposures: COVID-19 or influenza (identified by hospital diagnosis or nucleic acid test). Main Outcomes and Measures: Hospital diagnosis of arterial thromboembolism (acute myocardial infarction or ischemic stroke) and venous thromboembolism (deep vein thrombosis or pulmonary embolism) within 90 days. Outcomes were ascertained through July 2019 for patients with influenza and through August 2021 for patients with COVID-19. Propensity scores with fine stratification were developed to account for differences between the influenza and COVID-19 cohorts. Weighted Cox regression was used to estimate the adjusted hazard ratios (HRs) for outcomes during each COVID-19 vaccine availability period vs the influenza period. Results: A total of 85 637 patients with COVID-19 (mean age, 72 [SD, 13.0] years; 50.5% were male) and 8269 with influenza (mean age, 72 [SD, 13.3] years; 45.0% were male) were included. The 90-day absolute risk of arterial thromboembolism was 14.4% (95% CI, 13.6%-15.2%) in patients with influenza vs 15.8% (95% CI, 15.5%-16.2%) in patients with COVID-19 before vaccine availability (risk difference, 1.4% [95% CI, 1.0%-2.3%]) and 16.3% (95% CI, 16.0%-16.6%) in patients with COVID-19 during vaccine availability (risk difference, 1.9% [95% CI, 1.1%-2.7%]). Compared with patients with influenza, the risk of arterial thromboembolism was not significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.04 [95% CI, 0.97-1.11]) or during vaccine availability (adjusted HR, 1.07 [95% CI, 1.00-1.14]). The 90-day absolute risk of venous thromboembolism was 5.3% (95% CI, 4.9%-5.8%) in patients with influenza vs 9.5% (95% CI, 9.2%-9.7%) in patients with COVID-19 before vaccine availability (risk difference, 4.1% [95% CI, 3.6%-4.7%]) and 10.9% (95% CI, 10.6%-11.1%) in patients with COVID-19 during vaccine availability (risk difference, 5.5% [95% CI, 5.0%-6.1%]). Compared with patients with influenza, the risk of venous thromboembolism was significantly higher among patients with COVID-19 before vaccine availability (adjusted HR, 1.60 [95% CI, 1.43-1.79]) and during vaccine availability (adjusted HR, 1.89 [95% CI, 1.68-2.12]). Conclusions and Relevance: Based on data from a US public health surveillance system, hospitalization with COVID-19 before and during vaccine availability, vs hospitalization with influenza in 2018-2019, was significantly associated with a higher risk of venous thromboembolism within 90 days, but there was no significant difference in the risk of arterial thromboembolism within 90 days.

Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT): Protocol for a Multisite Longitudinal Cohort Study.

BACKGROUND: Assessing the real-world effectiveness of COVID-19 vaccines and understanding the incidence and severity of SARS-CoV-2 illness in children are essential to inform policy and guide health care professionals in advising parents and caregivers of children who test positive for SARS-CoV-2. OBJECTIVE: This report describes the objectives and methods for conducting the Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT) study. PROTECT is a longitudinal prospective pediatric cohort study designed to estimate SARS-CoV-2 incidence and COVID-19 vaccine effectiveness (VE) against infection among children aged 6 months to 17 years, as well as differences in SARS-CoV-2 infection and vaccine response between children and adolescents. METHODS: The PROTECT multisite network was initiated in July 2021, which aims to enroll approximately 2305 children across four US locations and collect data over a 2-year surveillance period. The enrollment target was based on prospective power calculations and accounts for expected attrition and nonresponse. Study sites recruit parents and legal guardians of age-eligible children participating in the existing Arizona Healthcare, Emergency Response, and Other Essential Workers Surveillance (HEROES)-Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) network as well as from surrounding communities. Child demographics, medical history, COVID-19 exposure, vaccination history, and parents/legal guardians' knowledge and attitudes about COVID-19 are collected at baseline and throughout the study. Mid-turbinate nasal specimens are self-collected or collected by parents/legal guardians weekly, regardless of symptoms, for SARS-CoV-2 and influenza testing via reverse transcription-polymerase chain reaction (RT-PCR) assay, and the presence of COVID-like illness (CLI) is reported. Children who test positive for SARS-CoV-2 or influenza, or report CLI are monitored weekly by online surveys to report exposure and medical utilization until no longer ill. Children, with permission of their parents/legal guardians, may elect to contribute blood at enrollment, following SARS-CoV-2 infection, following COVID-19 vaccination, and at the end of the study period. PROTECT uses electronic medical record (EMR) linkages where available, and verifies COVID-19 and influenza vaccinations through EMR or state vaccine registries. RESULTS: Data collection began in July 2021 and is expected to continue through the spring of 2023. As of April 13, 2022, 2371 children are enrolled in PROTECT. Enrollment is ongoing at all study sites. CONCLUSIONS: As COVID-19 vaccine products are authorized for use in pediatric populations, PROTECT study data will provide real-world estimates of VE in preventing infection. In addition, this prospective cohort provides a unique opportunity to further understand SARS-CoV-2 incidence, clinical course, and key knowledge gaps that may inform public health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/37929.

Incidence of SARS-CoV-2 infection among COVID-19 vaccinated and unvaccinated healthcare personnel, first responders, and other essential and frontline workers: Eight US locations, January-September 2021.

BACKGROUND: We sought to evaluate the impact of changes in estimates of COVID-19 vaccine effectiveness on the incidence of laboratory-confirmed infection among frontline workers at high risk for SARS-CoV-2. METHODS: We analyzed data from a prospective frontline worker cohort to estimate the incidence of COVID-19 by month as well as the association of COVID-19 vaccination, occupation, demographics, physical distancing, and mask use with infection risk. Participants completed baseline and quarterly surveys, and each week self-collected mid-turbinate nasal swabs and reported symptoms. RESULTS: Among 1018 unvaccinated and 3531 fully vaccinated workers, the monthly incidence of laboratory-confirmed SARS-CoV-2 infection in January 2021 was 13.9 (95% confidence interval [CI]: 10.4-17.4), declining to 0.5 (95% CI -0.4-1.4) per 1000 person-weeks in June. By September 2021, when the Delta variant predominated, incidence had once again risen to 13.6 (95% CI 7.8-19.4) per 1000 person-weeks. In contrast, there was no reportable incidence among fully vaccinated participants at the end of January 2021, and incidence remained low until September 2021 when it rose modestly to 4.1 (95% CI 1.9-3.8) per 1000. Below average facemask use was associated with a higher risk of infection for unvaccinated participants during exposure to persons who may have COVID-19 and vaccinated participants during hours in the community. CONCLUSIONS: COVID-19 vaccination was significantly associated with a lower risk of SARS-CoV-2 infection despite Delta variant predominance. Our data demonstrate the added protective benefit of facemask use among both unvaccinated and vaccinated frontline workers.

Neutralizing Antibody Response to Pseudotype Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Differs Between mRNA-1273 and BNT162b2 Coronavirus Disease 2019 (COVID-19) Vaccines and by History of SARS-CoV-2 Infection.

BACKGROUND: Data on the development of neutralizing antibodies (nAbs) against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with mRNA COVID-19 vaccines are limited. METHODS: From a prospective cohort of 3975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by reverse transcription-polymerase chain reaction assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t tests and linear mixed-effects models. RESULTS: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed nAbs with a GMT of 1003 (95% confidence interval, 766-1315). Among 139 previously uninfected participants, 138 (99%) developed nAbs after mRNA vaccine dose 2 with a GMT of 3257 (2596-4052). GMT was higher among those receiving mRNA-1273 vaccine (GMT, 4698; 3186-6926) compared with BNT162b2 vaccine (GMT, 2309; 1825-2919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21 655 (14 766-31 756) after mRNA vaccine dose 1, without further increase after dose 2. CONCLUSIONS: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAbs to SARS-CoV-2 than after 1 dose of vaccine or SARS-CoV-2 infection alone. nAb response also differed by mRNA vaccine product.

Experiences of Canadian mental health providers in identifying and responding to online and in-person sexual abuse and exploitation of their child and adolescent clients.

BACKGROUND: Sex offenders often use the internet to communicate with children to facilitate in-person sexual abuse or to create and distribute sexual images of children. Mental healthcare providers are a major source of referrals to child welfare authorities and are well-positioned to identify sexual exploitation. OBJECTIVE: This study investigated the perceived ability of mental healthcare workers to recognize and respond to concerns about online and in-person sexual exploitation of their pediatric clients. PARTICIPANTS AND SETTING: The authors administered a cross-sectional survey to 209 mental healthcare providers within the public health system of Alberta, Canada. METHODS: The survey contained four sections related to sexual exploitation: two of which can take place online or in-person (grooming and sexual abuse) and two of which require the internet or a digital device (luring and sexual image distribution). Each section asked whether the mental healthcare provider had experience working with clients affected by these concerns, what barriers they encounter, how confident they are in their abilities and whether they have formal training in a topic. RESULTS: The vast majority of participants (83%) worked with a client impacted by grooming, luring, sexual abuse or sexual image distribution in the last year. Participants reported more training, more confidence and fewer barriers when identifying and responding to sexual abuse as compared to grooming, luring or sexual image distribution. CONCLUSIONS: There is a need to improve mental health providers understanding of how technology is being utilized to exploit children, so that they can respond effectively to protect their clients.

Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER): Protocol for a Multisite Longitudinal Cohort Study.

BACKGROUND: Workers critical to emergency response and continuity of essential services during the COVID-19 pandemic are at a disproportionally high risk of SARS-CoV-2 infection. Prospective cohort studies are needed for enhancing the understanding of the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, identifying risk factors, assessing clinical outcomes, and determining the effectiveness of vaccination. OBJECTIVE: The Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) prospective cohort study was designed to estimate the incidence of symptomatic and asymptomatic SARS-CoV-2 infections, examine the risk factors for infection and clinical spectrum of illness, and assess the effectiveness of vaccination among essential workers. METHODS: The RECOVER multisite network was initiated in August 2020 and aims to enroll 3000 health care personnel (HCP), first responders, and other essential and frontline workers (EFWs) at 6 US locations. Data on participant demographics, medical history, and vaccination history are collected at baseline and throughout the study. Active surveillance for the symptoms of COVID-19-like illness (CLI), access of medical care, and symptom duration is performed by text messages, emails, and direct participant or medical record reports. Participants self-collect a mid-turbinate nasal swab weekly, regardless of symptoms, and 2 additional respiratory specimens at the onset of CLI. Blood is collected upon enrollment, every 3 months, approximately 28 days after a reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, and 14 to 28 days after a dose of any COVID-19 vaccine. From February 2021, household members of RT-PCR-confirmed participants are self-collecting mid-turbinate nasal swabs daily for 10 days. RESULTS: The study observation period began in August 2020 and is expected to continue through spring 2022. There are 2623 actively enrolled RECOVER participants, including 280 participants who have been found to be positive for SARS-CoV-2 by RT-PCR. Enrollment is ongoing at 3 of the 6 study sites. CONCLUSIONS: Data collected through the cohort are expected to provide important public health information for essential workers at high risk for occupational exposure to SARS-CoV-2 and allow early evaluation of COVID-19 vaccine effectiveness. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31574.

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

PURPOSE: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication. METHODS: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated. RESULTS: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82). CONCLUSIONS: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI.