Anne Gadomski

Purpose: To examine changes in health-related quality of life (HRQOL), this 2-year follow-up study reassessed the HRQOL of transgender and gender expansive (TG/GE) young people enrolled in a patient registry at the Gender Wellness Center (GWC) in upstate New York. Methods: Registry patients had to have a gender-affirming care follow-up visit at the GWC within a 2 year window (+6 months) of their baseline survey to complete follow-up. Youth 18 years of age completed the Short Form-36v2 (SF-36v2). We analyzed change from baseline to follow-up for 11 CHQ-CF87 subscales and 8 SF-36v2 subscales. We compared follow-up HRQOL results to U.S. population standards. We abstracted receipt of gender-affirming care from GWC electronic medical records. Results: Among the 173 patients who completed HRQOL assessments at baseline, 108 completed follow-up (62% response rate) from May 2019 to March 2022. The mean age for those completing the CHQ-CF87 was 14.6±2.2 years (range 10–17) and for the SF-36v2 was 19.7±2.3 years (range 18–24). CHQ-CF87 Behavior and Role/Social Physical Functioning subscale scores improved significantly among youth 8–17 years of age from baseline. Follow-up SF-36v2 scores for patients 18–24 years of age did not change significantly. Follow-up HRQOL mental health scores remained statistically significantly lower than U.S. population standards for both age groups. Conclusions: Two year follow-up HRQOL data from TG/GE youth receiving gender-affirming care improved in two domains, but did not change among young adults (>18 years of age). Mental health remains suboptimal compared to national standards.

Background: Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) have been hypothesized to benefit patients with COVID-19 via the inhibition of viral entry and other mechanisms. We conducted an individual participant data (IPD) meta-analysis assessing the effect of starting the ARB losartan in recently hospitalized COVID-19 patients. Methods: We searched ClinicalTrials.gov in January 2021 for U.S./Canada-based trials where an angiotensin-converting enzyme inhibitors/ARB was a treatment arm, targeted outcomes could be extrapolated, and data sharing was allowed. Our primary outcome was a 7-point COVID-19 ordinal score measured 13 to 16 days post-enrollment. We analyzed data by fitting multilevel Bayesian ordinal regression models and standardizing the resulting predictions. Results: 325 participants (156 losartan vs 169 control) from 4 studies contributed IPD. Three were randomized trials; one used non-randomized concurrent and historical controls. Baseline covariates were reasonably balanced for the randomized trials. All studies evaluated losartan. We found equivocal evidence of a difference in ordinal scores 13-16 days post-enrollment (model-standardized odds ratio [OR] 1.10, 95% credible interval [CrI] 0.76–1.71; adjusted OR 1.15, 95% CrI 0.15–3.59) and no compelling evidence of treatment effect heterogeneity among prespecified subgroups. Losartan had worse effects for those taking corticosteroids at baseline after adjusting for covariates (ratio of adjusted ORs 0.29, 95% CrI 0.08–0.99). Hypotension serious adverse event rates were numerically higher with losartan. Conclusions: In this IPD meta-analysis of hospitalized COVID-19 patients, we found no convincing evidence for the benefit of losartan versus control treatment, but a higher rate of hypotension adverse events with losartan.

Background: In our prior study of 643 children, ages 4–11 years, children with pet dogs had lower anxiety scores than children without pet dogs. This follow-up study examines whether exposure to pet dogs or cats during childhood reduces the risk of adolescent mental health (MH) disorders.Methods: Using a retrospective cohort study design, we merged our prior study database with electronic medical record (EMR) data to create an analytic database. Common MH diagnoses (anxiety, depression, ADHD) occurring from the time of prior study enrollment to 10/27/21 were identified using ICD-9 and ICD-10 codes. We used proportional hazards regression to compare time to MH diagnoses, between youths with and without pets. From 4/1/20 to 10/27/21, parents and youth in the prior study were interviewed about the amount of time the youth was exposed to a pet and how attached s/he was to the pet. Exposure included having a pet dog at baseline, cumulative exposure to a pet dog or cat during follow-up, and level of pet attachment. The main outcomes were anxiety diagnosis, any MH diagnosis, and MH diagnosis associated with a psychotropic prescription.Results: EMR review identified 571 youths with mean age of 14 years (range 11–19), 53% were male, 58% had a pet dog at baseline. During follow-up (mean of 7.8 years), 191 children received a MH diagnosis: 99 were diagnosed with anxiety (52%), 61 with ADHD (32%), 21 with depression (11%), 10 with combined MH diagnoses (5%). After adjusting for significant confounders, having a pet dog at baseline was associated with lower risk of any MH diagnosis (HR = 0.74, p = .04) but not for anxiety or MH diagnosis with a psychotropic prescription. Among the 241 (42%) youths contacted for follow-up, parent-reported cumulative exposure to pet dogs was borderline negatively associated with occurrence of any MH diagnosis (HR = 0.74, p = .06). Cumulative exposure to the most attached pet (dog or cat) was negatively associated with anxiety diagnosis (HR = 0.57, p = .006) and any MH diagnosis (HR = 0.64, p = .013).Conclusion: Cumulative exposure to a highly attached pet dog or cat is associated with reduced risk of adolescent MH disorders.

Importance There is a dearth of comparative immunologic durability data after COVID-19 vaccinations. Objective To compare antibody responses and vaccine effectiveness 8.4 months post-primary COVID-19 vaccination. Design Setting and Participants: In this cohort study of 903 healthcare workers who completed surveys about baseline characteristics and COVID-19 vaccine/infection history, 647 had antibody assays completed and were included herein. Exposure COVID-19 vaccination with mRNA-1273 (n=387); BNT162b2 (n=212); or Ad26.COV2.S (n=10); unvaccinated (n=10); or boosted (n=28). Main Outcomes and Measures The primary outcome was IgG anti-spike titer. Secondary/tertiary outcomes included IgG spike receptor-binding domain competitive antibody blocking ELISA pseudoneutralization against the USA-WA1/2020 strain, and vaccine effectiveness against COVID-19 infection. Antibody levels were compared using ANOVA and multiple linear regression. Results Mean age was 49.7, 75.3% were female, and mean comorbidities/patient was 0.7. Baseline variables were balanced (p>.05) except for immunosuppression (higher in boosted, p=.047), prior COVID-19 infections (higher with Ad26.COV2.S and unvaccinated, p<.001), and time since primary vaccination (higher with mRNA-1273 and BNT162b2 than Ad26.COV2.S, p<.001). Unadjusted median (IQR) IgG anti-spike titers (AU/mL) were 1539.5 (876.7-2626.7) for mRNA-1273, 751.2 (422.0-1381.5) for BNT162b2, 451.6 (103.0-2396.7) for Ad26.COV2.S, 113.4 (3.7-194.0) for unvaccinated, and 31898.8 (21347.1-45820.1) for boosted (mRNA-1273 vs. BNT162b2, p<.001; mRNA-1273, BNT162b2, or boosted vs. unvaccinated, p<.006; mRNA-1273, BNT162b2, Ad26.COV2.S, or unvaccinated vs. boosted, p<.001; all other comparisons, p>.05). Unadjusted median (IQR) pseudoneutralization percentages were 90.9% (80.1-95.0) for mRNA-1273, 77.2% (59.1-89.9) for BNT162b2, 57.9% (36.6-95.8) for Ad26.COV2.S, 40.1% (21.7-60.6) for unvaccinated, and 96.4% (96.1-96.6) for boosted (mRNA-1273 vs. BNT162b2, p<.001; mRNA-1273, BNT162b2, or boosted vs. unvaccinated, p<.028; mRNA-1273, BNT162b2, Ad26.COV2.S, or unvaccinated vs. boosted, p<.001; all other comparisons, p>.05). Adjusted anti-spike and pseudoneutralization comparisons of mRNA-1273 and BNT162b2 showed similar patterns (p<.001). Vaccine effectiveness was 87-89% for mRNA-1273, BNT162b2, and boosted, and 33% for Ad26.COV2.S; no group differences were statistically significant. Conclusions and Relevance Durability of antibody responses 8.4 months after COVID-19 primary vaccination was significantly higher with mRNA-1273 than with BNT162b2, however, vaccine effectiveness was equivalent. Antibody responses and vaccine effectiveness were lower but not significantly different for Ad26.COV2.S; given statistical uncertainty in the small Ad26.COV2.S group, clinically important effects cannot be excluded.

Background: ACEi/ARB medications have been hypothesized to have potential benefit in COVID-19. Despite concern for increased ACE-2 expression in some animal models, preclinical and observational-retrospective and uncontrolled trials suggested possible benefit. Two RCTs of the ARB losartan from University of Minnesota showed no benefit yet safety signals for losartan in outpatient and hospitalized COVID-19 patients. COVID MED, started early in the pandemic, also assessed losartan in a RCT in hospitalized patients with COVID-19. Methods: COVID MED was a double-blinded, placebo-controlled, multicenter, platform randomized clinical trial (RCT). Hospitalized COVID-19 patients were randomized to receive standard care and hydroxychloroquine, lopinavir/ritonavir, losartan, or placebo. Hydroxychloroquine and lopinavir/ritonavir arms were discontinued after RCTs showed no benefit. We report data from the losartan arm compared to combined (lopinavir-ritonavir and placebo) and prespecified placebo-only controls. The primary endpoint, the mean COVID-19 Ordinal Severity Score (COSS) slope of change, was compared with the Student’s t-test. Slow enrollment prompted early termination. Results: Of 448 screened patients, 15 (3.5%) were randomized/enrolled, 9 to receive losartan and 6 to receive control (lopinavir/ritonavir [N=2], placebo [N=4]); 1 patient who withdrew prior to study drug was excluded yielding 14 patients for analysis (losartan [N=9] vs. control [N=5] [lopinavir/ritonavir [N=2], placebo [N=3]]). Most baseline parameters were balanced. Treatment with losartan was not associated with a difference in mean COSS slope of change in comparison with combined control (p=0.4) or placebo-only control (p=0.05) (trend favoring placebo). 60-day mortality and overall AE and SAE rates were numerically but not significantly higher with losartan. Conclusions: In this small blinded RCT in hospitalized COVID-19 patients, losartan did not improve outcome vs. control comparisons and was associated with adverse safety signals.

Background: In the beginning of the COVID-19 pandemic, many hospitalized patients received empiric hydroxychloroquine/chloroquine (HC/CQ). Although some retrospective-observational trials suggested potential benefit, all subsequent randomized clinical trials (RCTs) failed to show benefit and use generally ceased. Herein, we summarize key studies that clinicians advising patients on HC/CQ’s efficacy:safety calculus in hospitalized COVID-19 patients would want to know about in a practical one-stop-shopping source. Methods: Pubmed and Google were searched on November 4, 2021. Search words included: COVID-19, hydroxychloroquine, chloroquine, in vitro , animal studies, clinical trials, and meta-analyses. Studies were assessed for import and included if considered impactful for benefit:risk assessment. Results: These searches led to inclusion of 12 in vitro and animal reports; 12 retrospective-observational trials, 19 interventional clinical trials (17 RCTs, 1 single-arm, 1 controlled but unblinded), and 51 meta-analyses in hospitalized patients. Inconsistent efficacy was seen in vitro and in animal studies for coronaviruses and nil in SARS-CoV-2 animal models specifically. Most retrospective-observational studies in hospitalized COVID-19 patients found no efficacy; QT prolongation and increased adverse events and mortality were reported in some. All RCTs and almost all meta-analyses provided robust data showing no benefit in overall populations and subgroups, yet concerning safety issues in many. Conclusions: HC/CQ have inconsistent anti-coronavirus efficacy in vitro and in animal models, and no convincing efficacy yet substantial safety issues in the overwhelming majority of retrospective-observational trials, RCTs, and meta-analyses in hospitalized COVID-19 patients. HC/CQ should not be prescribed for hospitalized COVID-19 patients outside of clinical trials. Key Summary Points: Preclinical hydroxychloroquine/chloroquine in vitro studies found inconsistent activity against coronaviruses including SARS-CoV-2. Preclinical hydroxychloroquine/chloroquine animals studies found inconsistent efficacy for coronaviruses in general and none for SARS-CoV-2. The overhwelming majority of RCTs and retrospective-observational trials found no benefit for hydroxychloroquine/chloroquine in hospitalized COVID-19 patients, and many found concerning safety signals. The majority of RCTs and retrospective-observational trials found no benefit for hydroxychloroquine/chloroquine in COVID-19 outpatients or for pre- or post-exposure prophylaxis, and some found concerning safety signals. The overwhelming majority of meta-analyses found no benefit for hydroxychloroquine/chloroquine in COVID-19 inpatients, outpatients, or for prophylaxis, and many found concerning safety signals.

Background: Our rural health system sought to (1) increase the number of primary care clinicians waivered to prescribe buprenorphine for treatment of opioid use disorder (OUD) and (2) consequently increase the number of our patients receiving this treatment. Methods: We used the Project for Extension for Community Health Outcomes (ECHO) tele-education model as an implementation strategy. We examined the number of clinicians newly waivered, the number of patients treated with buprenorphine, the relationship between clinician engagement with ECHO training and rates of buprenorphine prescribing, and treatment retention at 180 days. Results: The number of clinicians with a waiver and number of patients treated increased during and after ECHO training. There was a moderate correlation between the number of ECHO sessions attended by a clinician and number of their buprenorphine prescriptions (r = 0.50, p = 0.01). The 180-day retention rate was 80.7%. Conclusions: Project ECHO was highly effective for increasing access to this evidence-based treatment. The high retention rate in this rural context indicates that most patients are increasing their likelihood of favorable outcomes.

As part of our evaluation of the NIOSH-funded Northeast Center for Occupational Health and Safety: Agriculture, Forestry and Fishing (NEC), we present methodology, findings and the potential implications of a sequential social network analysis (SNA) conducted over ten years. Assessing the effectiveness of the center’s scientific projects was our overarching evaluation goal. The evaluation design employed SNA to (a) look at changes to the center’s network over time by visualizing relationships between center collaborators annually, (b) document collaborative ties and (c) identify particularly strong or weak areas of the network. Transdisciplinary social network criteria were applied to the SNA to examine the collaboration between center personnel, their partners and the industry groups they serve. SNA participants’ perspectives on the utility of the SNA were also summarized to assess their interest in ongoing SNA measures. Annual installments of the SNA (2011–2020) showed an expansion of the network with a 30% increase in membership from baseline, as well as an increase in total relational ties (any type of contact). SNA measures also indicated significant increases in co-publication, cross-sector and transdisciplinary ties. Overall, SNA is an effective tool in visualizing and sustaining an occupational safety and health research and outreach network. Its utility is limited by how ties are characterized, grant cycle timeframes and how SNA metrics relate to productivity.