Goffdennis3081

The 21st Century Cures Act allows the US Food and Drug Administration (FDA) to utilize real-world data (RWD) to create real-world evidence (RWE) for new indications or post approval study requirements. We compared central adjudication with two insurance claims data sources to understand how endpoint accuracy differences impact RWE results.

We developed a decision analytic model to compare differences in efficacy (all-cause death, stroke and myocardial infarction) and safety (bleeding requiring transfusion) results for a simulated acute coronary syndrome antiplatelet therapy clinical trial. Endpoint accuracy metrics were derived from previous studies that compared centrally-adjudicated and insurance claims-based clinical trial endpoints.

Efficacy endpoint results per 100 patients were similar for the central adjudication model (intervention event rate, 11.3; control, 13.7; difference, 2.4) and the prospective claims data collection model (intervention event rate, 11.2; control 13.6; difference, 2.3). However, the retrospective claims linking model's efficacy results were larger (intervention event rate, 14.6; control, 18.0; difference, 3.4). True positive event rate results (intervention, control and difference) for both insurance claims-based models were less than the central adjudication model due to false negative events. Differences in false positive event rates were responsible for differences in efficacy results for the two insurance claims-based models.

Efficacy endpoint results differed by data source. Investigators need guidance to determine which data sources produce regulatory-grade RWE.

Efficacy endpoint results differed by data source. Investigators need guidance to determine which data sources produce regulatory-grade RWE.

Our 1-year pilot study aims to compare Behavioral and Psychological Symptoms of Dementia (BPSDs) number and frequency, globally an in sub-domains, and distress, of 20 residents with dementia, during periods with companion clown intervention and BPSDs during periods without companion clown intervention.

A duo of accompanying clowns intervened 24 times for a total of 72h (two interventions of 3h each per week for 4 weeks, 3 months of the year spaced 13 weeks apart) in the Special Care Unit. This unit was dedicated to residents with severe BPSDs. BPSDs were measured monthly by Health Care Professional using Neuro-Psychiatric Inventory (NPI).

Baseline NPI total score of the 20 residents (10 women, mean age 76.9years; standard deviation, SD 8.1, 70.6% with Alzheimer's disease) was 37.5 (SD =  ± 19.7). The total score of the NPI was not significantly different between the periods with the clowns (median total score at 63; 25p-75p = 57-67) and the periods without the clowns (59; 25p-75p = 43-76) (p = 0.08). Compared to the period without clowns, residents presented significantly fewer delusions, hallucinations, euphoria, aberrant motor behavior but significantly more depression, apathy, disinhibition and more appetite disorders (all p value < 0.05). No statistically significant difference was observed on the distress the symptoms caused on the HCP during periods with the clowns.

Accompanying clowns may not significantly reduce the overall BPSD of the residents, but may have beneficial effects in some behavioral issues.

Accompanying clowns may not significantly reduce the overall BPSD of the residents, but may have beneficial effects in some behavioral issues.

The aim of this study was to investigate the frequency of avascular necrosis (AVN) and its associations with clinical and laboratory parameters in patients with primary antiphospholipid antibody syndrome (pAPS).

This was a cross-sectional study of 66 patients with pAPS who fulfilled the Sidney criteria for APS. Epidemiological and clinical data, and data on antiphospholipid antibodies were collected. Diagnosis of AVN was based on studies of magnetic resonance (MRI) images of affected bones.

AVN was found in three of the 66 (4.5%) enrolled patients. Comparison of patients with pAPS with and without AVN showed that demographic data, comorbidities, and antiphospholipid antibodies profile were similar in both groups. Compared to patients without AVN, those with AVN had thrombocytopenia more frequently (66.7 vs. 7.9%) and used more glucocorticoids (100 vs. 35%).

AVN is rare in patients with pAPS and may be associated with thrombocytopenia and previous glucocorticoid use.

AVN is rare in patients with pAPS and may be associated with thrombocytopenia and previous glucocorticoid use.Steroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) - a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3+/- mice, hippocampus-dependent functions such as short-term memory and spatial memory were impaired. Biocytin We further demonstrated that the deficient learning and memory in Src3+/- mice was strongly associated with the impairment of long-term potentiation (LTP) at Schaffer Collateral-CA1 synapses. Mechanistic studies indicated that Src3+/- mutation altered the composition of N-methyl-D-aspartate receptor subunits in the postsynaptic densities of hippocampal neurons. Finally, we showed that SRC3 regulated synaptic plasticity and learning mainly dependent on its lysine acetyltransferase activity. Taken together, these results reveal previously unknown functions of SRC3 in the hippocampus and thus may provide insight into how steroid hormones regulate brain function.We assessed the intraspecific morphological variation in Erythrodiplax media Borror 1942 (Odonata, Libellulidae) among grassland physiognomies ("Coastal," "Highland," and "Steppic") in the South Brazilian Campos. We measured six morphological traits (total body length, thorax height, length, and width of the fore- and hindwings) from 90 specimens (60 males and 45 females). We tested the effect of the grassland type on the set of traits using one-way MANOVA and principal component analysis (PCA) (separately for each sex). Grassland physiognomy affected the morphology of males and females. In both sexes, the PCA mostly opposed the specimens of the Coastal from the Highland and Steppic grasslands. The first PCA axis separated specimens according to body lengths, thorax heights, and wing width, while the second PCA axis opposed specimens according to wing length and thorax height from specimens with broader wings and longer body lengths. Males from the Coastal had longer body lengths and shorter thorax heights than Highland and Steppic grasslands, while males from the Steppic had longer fore- and hindwings than specimens from the Coastal and Highland grasslands.