Background

The inability to achieve high COVID-19 vaccination rates can continue to have serious harm to our communities. Vaccine hesitancy is a major barrier towards high vaccination rates. We evaluated the relationship between COVID-19 vaccine uptake and vaccine hesitancy, and then examined whether community factors were associated with COVID-19 vaccine uptake and hesitancy.

Methods

We constructed and evaluated a cross-sectional, county-level dataset that included the levels of vaccination uptake and vaccine hesitancy, and population characteristics based on those included in the CDC's Social Vulnerability Index.

Results

Across 3142 US counties, vaccine hesitancy was significantly and negatively correlated with vaccine uptake rates (r = -0.06, P value <.01). The 2 predictors associated with a low vaccination level within highly hesitant communities were: no high school education (OR:0.70, P value <.001), and concern on vaccine availability and distribution (CVAC) (OR:0.00, P value <.001). The most common reason driving vaccine hesitancy was lack of trust in COVID-19 vaccines (55%), followed by concerns around side effects of the vaccine (48%), and lack of trust in government (46%).

Conclusions

COVID-19 vaccine hesitancy is a public health threat. Our findings suggest that low education levels are a major contributor to vaccine hesitancy and ultimately vaccination levels. Since education levels are not easily modifiable, our results suggest that policymakers would be best served by closing knowledge gaps to overcome negative perceptions of the vaccine through tailored interventions.

Background

Previous efforts to preserve β cell function in individuals with type 1 diabetes (T1D) have focused largely on the use of single immunomodulatory agents administered within 100 days of diagnosis. Based on human and preclinical studies, we hypothesized that a combination of low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte CSF (G-CSF) would preserve β cell function in patients with established T1D (duration of T1D >4 months and <2 years).

Methods

A randomized, single-blinded, placebo-controlled trial was performed on 25 subjects: 17 subjects received ATG (2.5 mg/kg intravenously) followed by pegylated G-CSF (6 mg subcutaneously every 2 weeks for 6 doses) and 8 subjects received placebo. The primary outcome was the 1-year change in AUC C-peptide following a 2-hour mixed-meal tolerance test (MMTT). At baseline, the age (mean ± SD) was 24.6 ± 10 years; mean BMI was 25.4 ± 5.2 kg/m²; mean A1c was 6.5% ± 1.1%; insulin use was 0.31 ± 0.22 units/kg/d; and length of diagnosis was 1 ± 0.5 years.

Results

Combination ATG/G-CSF treatment tended to preserve β cell function in patients with established T1D. The mean difference in MMTT-stimulated AUC C-peptide between treated and placebo subjects was 0.28 nmol/l/min (95% CI 0.001-0.552, P = 0.050). A1c was lower in ATG/G-CSF-treated subjects at the 6-month study visit. ATG/G-CSF therapy was associated with relative preservation of Tregs.

Conclusions

Patients with established T1D may benefit from combination immunotherapy approaches to preserve β cell function. Further studies are needed to determine whether such approaches may prevent or delay the onset of the disease.

Trial registration

Clinicaltrials.gov NCT01106157.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust and Sanofi.

Low-dose antithymocyte globulin (ATG) plus pegylated granulocyte colony-stimulating factor (G-CSF) preserves β-cell function for at least 12 months in type 1 diabetes. Herein, we describe metabolic and immunological parameters 24 months following treatment. Patients with established type 1 diabetes (duration 4-24 months) were randomized to ATG and pegylated G-CSF (ATG+G-CSF) (N = 17) or placebo (N = 8). Primary outcomes included C-peptide area under the curve (AUC) following a mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "super responders" (24-month C-peptide ≥ baseline), and "nonresponders" (12-month C-peptide < baseline) were evaluated for biomarkers of outcome. At 24 months, MMTT-stimulated AUC C-peptide was not significantly different in ATG+G-CSF (0.49 nmol/L/min) versus placebo (0.29 nmol/L/min). Subjects treated with ATG+G-CSF demonstrated reduced CD4⁺ T cells and CD4⁺/CD8⁺ T-cell ratio and increased CD16⁺CD56^hi natural killer cells (NK), CD4⁺ effector memory T cells (Tem), CD4⁺PD-1⁺ central memory T cells (Tcm), Tcm PD-1 expression, and neutrophils. FOXP3⁺Helios⁺ regulatory T cells (Treg) were elevated in ATG+G-CSF subjects at 6, 12, and 18 but not 24 months. Immunophenotyping identified differential HLA-DR expression on monocytes and NK and altered CXCR3 and PD-1 expression on T-cell subsets. As such, a group of metabolic and immunological responders was identified. A phase II study of ATG+G-CSF in patients with new-onset type 1 diabetes is ongoing and may support ATG+G-CSF as a prevention strategy in high-risk subjects.

Background and aims  Rectal lesions traditionally represent the first lesions approached during endoscopic submucosal dissection (ESD) training in the West. We evaluated the safety and efficacy of rectal ESD in North America. Methods  This is a multicenter retrospective analysis of rectal ESD between January 2010 and September 2018 in 15 centers. End points included: rates of en bloc resection, R0 resection, adverse events, comparison of pre- and post-ESD histology, and factors associated with failed resection. Results  In total, 171 patients (median age 63 years; 56 % men) underwent rectal ESD (median size 43 mm). En bloc resection was achieved in 141 cases (82.5 %; 95 %CI 76.8-88.2), including 24 of 27 (88.9 %) with prior failed endoscopic mucosal resection (EMR). R0 resection rate was 74.9 % (95 %CI 68.4-81.4). Post-ESD bleeding and perforation occurred in 4 (2.3 %) and 7 (4.1 %), respectively. Covert submucosal invasive cancer (SMIC) was identified in 8.6 % of post-ESD specimens. There was one case (1/120; 0.8 %) of recurrence at a median follow-up of 31 weeks; IQR: 19-76 weeks). Older age and higher body mass index (BMI) were predictors of failed R0 resection, whereas submucosal fibrosis was associated with a higher likelihood of both failed en bloc and R0 resection. Conclusion  Rectal ESD in North America is safe and is associated with high en bloc and R0 resection rates. The presence of submucosal fibrosis was the main predictor of failed en bloc and R0 resection. ESD can be considered for select rectal lesions, and serves not only to establish a definitive tissue diagnosis but also to provide curative resection for lesions with covert advanced disease.