Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments

In Vivo Electroporation Enhances the Immunogenicity of an HIV-1 DNA Vaccine Candidate in Healthy Volunteers

DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987

Impact of the COVID-19 Vaccination Program on case incidence, emergency department visits, and hospital admissions among children aged 5-17 Years during the Delta and Omicron Periods-United States, December 2020 to April 2022.

BackgroundIn the United States, national ecological studies suggest a positive impact of COVID-19 vaccination coverage on outcomes in adults. However, the national impact of the vaccination program on COVID-19 in children remains unknown. To determine the association of COVID-19 vaccination with U.S. case incidence, emergency department visits, and hospital admissions for pediatric populations during the Delta and Omicron periods.MethodsWe conducted an ecological analysis among children aged 5-17 and compared incidence rate ratios (RRs) of COVID-19 cases, emergency department visits, and hospital admissions by pediatric vaccine coverage, with jurisdictions in the highest vaccine coverage quartile as the reference.ResultsRRs comparing states with lowest pediatric vaccination coverage to the highest pediatric vaccination coverage were 2.00 and 0.64 for cases, 2.96 and 1.11 for emergency department visits, and 2.76 and 1.01 for hospital admissions among all children during the Delta and Omicron periods, respectively. During the 3-week peak period of the Omicron wave, only children aged 12-15 and 16-17 years in the states with the lowest versus highest coverage, had a significantly higher rate of emergency department visits (RR = 1.39 and RR = 1.34, respectively).ConclusionsCOVID-19 vaccines were associated with lower case incidence, emergency department visits and hospital admissions among children during the Delta period but the association was weaker during the Omicron period. Pediatric COVID-19 vaccination should be promoted as part of a program to decrease COVID-19 impact among children; however, vaccine effectiveness may be limited when available vaccines do not match circulating viral variants

Impact of the COVID-19 Vaccination Program on case incidence, emergency department visits, and hospital admissions among children aged 5–17 Years during the Delta and Omicron Periods—United States, December 2020 to April 2022

Background In the United States, national ecological studies suggest a positive impact of COVID-19 vaccination coverage on outcomes in adults. However, the national impact of the vaccination program on COVID-19 in children remains unknown. To determine the association of COVID-19 vaccination with U.S. case incidence, emergency department visits, and hospital admissions for pediatric populations during the Delta and Omicron periods. Methods We conducted an ecological analysis among children aged 5–17 and compared incidence rate ratios (RRs) of COVID-19 cases, emergency department visits, and hospital admissions by pediatric vaccine coverage, with jurisdictions in the highest vaccine coverage quartile as the reference. Results RRs comparing states with lowest pediatric vaccination coverage to the highest pediatric vaccination coverage were 2.00 and 0.64 for cases, 2.96 and 1.11 for emergency department visits, and 2.76 and 1.01 for hospital admissions among all children during the Delta and Omicron periods, respectively. During the 3-week peak period of the Omicron wave, only children aged 12–15 and 16–17 years in the states with the lowest versus highest coverage, had a significantly higher rate of emergency department visits (RR = 1.39 and RR = 1.34, respectively). Conclusions COVID-19 vaccines were associated with lower case incidence, emergency department visits and hospital admissions among children during the Delta period but the association was weaker during the Omicron period. Pediatric COVID-19 vaccination should be promoted as part of a program to decrease COVID-19 impact among children; however, vaccine effectiveness may be limited when available vaccines do not match circulating viral variants

COVID-19 Booster Dose Vaccination Coverage and Factors Associated with Booster Vaccination among Adults, United States, March 2022

The Centers for Disease Control and Prevention recommends a COVID-19 vaccine booster dose for all persons >18 years of age. We analyzed data from the National Immunization Survey–Adult COVID Module collected during February 27–March 26, 2022 to assess COVID-19 booster dose vaccination coverage among adults. We used multivariable logistic regression analysis to assess factors associated with vaccination. COVID-19 booster dose coverage among fully vaccinated adults increased from 25.7% in November 2021 to 63.4% in March 2022. Coverage was lower among non-Hispanic Black (52.7%), and Hispanic (55.5%) than non-Hispanic White adults (67.7%). Coverage was 67.4% among essential healthcare personnel, 62.2% among adults who had a disability, and 69.9% among adults who had medical conditions. Booster dose coverage was not optimal, and disparities by race/ethnicity and other factors are apparent in coverage uptake. Tailored strategies are needed to educate the public and reduce disparities in COVID-19 vaccination coverage

Weekly “fully vaccinated” pediatric vaccination coverage rates by age group among children aged 5–17 years, U.S., from December 13, 2020, through April 30, 2022.

Weekly “fully vaccinated” pediatric vaccination coverage rates by age group among children aged 5–17 years, U.S., from December 13, 2020, through April 30, 2022.</p

Weekly rate ratios among children aged 5–17 comparing lowest COVID-19 vaccination coverage quartile states to highest coverage quartile states by outcome: December 13, 2020–April 30, 2022.

Vaccine coverage estimates for children aged 5–17 years during the first and last week of the Delta and Omicron periods of predominance in the US: (Delta: 9.21% as of the week of June 20th, 2021, 22.57% the week of October 31, 2021); (Omicron: 29.19% the week of December 19, 2021, 40.03% the week of April 24, 2022). Full vaccination coverage ranges for bottom and top quartile states as of the week of April 24, 2022: Bottom quartile: 20.14%–28.46%, Top quartile: 47.24%–59.42%.</p

Rate ratios among children aged 5–17 years by outcome comparing COVID-19 pediatric vaccination coverage quartiles of states to states in the highest vaccination coverage quartile during Delta and Omicron predominant periods–by age group and overall.

Rate ratios among children aged 5–17 years by outcome comparing COVID-19 pediatric vaccination coverage quartiles of states to states in the highest vaccination coverage quartile during Delta and Omicron predominant periods–by age group and overall.</p

Number and rates of COVID-19 cases, emergency department (ED) visits, and hospital admissions in the United States during the Delta and Omicron periods, by age group and overall (5–17 years).

(DOCX)</p

Complete vaccination coverage ranges by state coverage quartile for midpoints^a of Delta and Omicron predominant time periods.

Complete vaccination coverage ranges by state coverage quartile for midpointsa of Delta and Omicron predominant time periods.</p