External validation of two clinical prediction models for mortality in COVID-19 patients (4C and NEWS2), in three centers in Medellín, Colombia: Assessing the impact of vaccination over time.

OBJECTIVES: External validation of the 4C and NEWS2 scores for the prediction of in-hospital mortality in COVID-19 patients, and evaluation of its operational performance in two time periods: before and after the start of the vaccination program in Colombia. METHODS: Retrospective cohort in three high complexity hospitals in the city of Medellín, Colombia, between June 2020 and April 2022. RESULTS: The areas under the ROC curve (AUC) for the 4C mortality risk score and the NEWS2 were 0.75 (95% CI 0.73-0.78) and 0.68 (95% CI 0.66-0.71), respectively. For the 4C score, the AUC for the first and second periods was 0.77 (95% CI 0.74-0.80) and 0.75 (95% CI 0.71-0.78); whilst for the NEWS2 score, it was 0.68 (95% CI 0.65-0.71) and 0.69 (95% CI 0.64-0.73). The calibration for both scores was adequate, albeit with reduced performance during the second period. CONCLUSIONS: The 4C mortality risk score proved to be the more adequate predictor of in-hospital mortality in COVID-19 patients in this Latin American population. The operational performance during both time periods remained similar, which shows its utility notwithstanding major changes, including vaccination, as the pandemic evolved.

Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial.

INTRODUCTION: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers. METHODS: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing. RESULTS: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. DISCUSSION: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.

Baseline demographic, clinical, and cognitive characteristics of the Alzheimer's Prevention Initiative (API) Autosomal-Dominant Alzheimer's Disease Colombia Trial.

INTRODUCTION: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo. METHODS: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. RESULTS: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. DISCUSSION: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population.

Association of herd-level risk factors and incidence rate of clinical mastitis in 20 Brazilian dairy herds.

The objectives of this study were to characterize the pathogen frequency and severity of clinical mastitis (CM) in 20 dairy herds of southeastern Brazil; and to determine the incidence rate of clinical mastitis (IRCM; overall and based on specific-pathogen groups) based on quarter time at risk and its association with risk factors at the herd-level. Data were recorded in each herd for a period of 8 to 15 months. The association between herd-level risk factors and IRCM were determined by two groups of mixed regression models: one based on the overall IRCM, and five based on the following specific-pathogen groups: contagious, other Gram-positive, Gram-negative, other, and negative culture. The following herd-level risk factors were evaluated: herd size, housing system, average daily milk yield per cow, bulk milk somatic cell count (BMSCC), and bulk milk total bacterial count (BMTBC). A total of 5957 quarter-cases of CM were recorded from 2637 cows, but only 4212 cases had milk samples collected for culture. The most frequently isolated pathogens were Escherichia coli (6.6% of total cultures), Streptococcus uberis (6.1%), and Streptococcus agalactiae (5.9%). The majority of CM cases were mild (60.3%), while 34.1% were moderate and 5.6% severe. The frequency of severe CM cases was lower for those with a Gram-positive result (4.6%) compared to a Gram-negative result (11.4%). Overall, monthly mean IRCM was 9.7 cases per 10,000 quarter-days at risk (QDAR). Herds with a geometric mean BMSCC ≥ 601 × 103 cell/mL had higher overall IRCM (16/10,000 QDAR) than those with BMSCC ≤ 600 × 103 cell/mL (≤7.7/10,000 QDAR). When the specific-pathogen groups were evaluated, for contagious pathogens, variables housing (free-stalls or compost-bedded pack barns), BMSCC (≥601 × 103 cells/mL), and average daily milk yield per cow (21 and 25 Kg/d) presented the highest IRCM. Furthermore, in Gram-negative group, herds with BMTBC ≥ 31 × 103 cfu/mL had higher IRCM compared with herds with BMTBC ≤ 30 × 103 cfu/mL. Although environmental pathogens were the most common cause of CM in this study, contagious pathogens (e.g., Strep. agalactiae and Staph. aureus) are still a concern in dairy herds of Brazil. Additionally, as there were some herd-level risk factors associated with the IRCM, there may be opportunity for management strategies aiming to improve the control of CM in dairy herds.