Background
Frailty is often cited as a factor influencing oral anticoagulation (OAC) prescription in patients with non-valvular atrial fibrillation (NVAF). We sought to determine the prevalence of ...frailty and its association with OAC prescription in older veterans with NVAF.
Methods
We used ICD-9 codes in Veterans Affairs (VA) records and Medicare claims data to identify patients with NVAF and CHA
2
DS
2
VASC ≥2 receiving care between February 2010 and September 2015. We examined rates of OAC prescription, further stratified by direct oral anticoagulant (DOAC) or vitamin K antagonist (VKA). Participants were characterized into 3 categories: non-frail, pre-frail, and frail based on a validated 30-item EHR-derived frailty index. We examined relations between frailty and OAC receipt; and frailty and type of OAC prescribed in regression models adjusted for factors related to OAC prescription.
Results
Of 308,664 veterans with NVAF and a CHA
2
DS
2
VASC score ≥2, 121,839 (39%) were prescribed OAC (73% VKA). The mean age was 77.7 (9.6) years; CHA
2
DS
2
VASC and ATRIA scores were 4.6 (1.6) and 5.0 (2.9) respectively. Approximately a third (38%) were frail, another third (32%) were pre-frail, and the remainder were not frail. Veterans prescribed OAC were younger, had higher bleeding risk, and were less likely to be frail than participants not receiving OAC (all
p
’s<0.001). After adjustment for factors associated with OAC use, pre-frail (OR: 0.89, 95% CI: 0.87–0.91) and frail (OR: 0.66, 95% CI: 0.64–0.68) veterans were significantly less likely to be prescribed OAC than non-frail veterans. Of those prescribed OAC, pre-frail (OR:1.27, 95% CI: 1.22–1.31) and frail (OR: 1.75, 95% CI: 1.67–1.83) veterans were significantly more likely than non-frail veterans to be prescribed a DOAC than a VKA.
Conclusions
There are high rates of frailty among older veterans with NVAF. Frailty using an EHR-derived index is associated with decreased OAC prescription.
Neonatal intensive care unit (NICU) provider point-of-care ultrasound (POCUS) procedural competency for umbilical line placement confirmation has not been defined, and the necessary training to ...achieve competency has not been previously studied. This study's objective was to test the hypothesis that a simulation-enhanced curriculum will improve NICU providers' POCUS competency to confirm umbilical line placement.
Neonatal intensive care unit providers without prior ultrasound experience were randomized to a curriculum with or without simulation-based training. Competency for catheter detection, tip localization, and scan interpretation on patients was determined using learning curve-cumulative summation, a specific statistical tool designed to indicate when a predefined level of performance is reached. Differences in success rates were analyzed by χ2 test.
Two thirds (22/33) of participants completed 10 scans. Three (simulation) and 1 (control) attained catheter detection competency (P = 0.28). The simulation group was more successful for catheter detection (81% vs. 69%, P = 0.04) and scan interpretation (61% vs. 48%, P = 0.04). Success did not differ by umbilical vessel location, provider role, or duration of NICU experience.
A simulation-enhanced POCUS curriculum improved catheter detection rate and scan interpretation, but there was no difference in procedural competency between groups on ultrasound scans performed on patients with umbilical catheters. We speculate that more than 10 scans may be needed for NICU providers to obtain POCUS competency.
Background
While hydroxyurea is the mainstay of treatment for many of the comorbidities associated with sickle cell disease, its effect on obstructive sleep apnea has not been fully investigated. The ...purpose of this project is to help characterize the effects of hydroxyurea on obstructive sleep apnea in children with sickle cell disease and determine its therapeutic role in the condition.
Methods
Chart review was conducted on two pediatric patients with sickle cell disease who experienced resolution of obstructive sleep apnea following hydroxyurea administration.
Results
After undergoing approximately 11 months of hydroxyurea therapy, sleep apnea symptoms improved and obstructive sleep apnea resolution was confirmed by repeat polysomnography in both cases. This resolution was largely secondary to a reduction in the obstructive component of the apnea hypopnea index, highlighting a previously unreported association.
Conclusions
As adenotonsillectomy is associated with significant risks in patients with sickle cell disease, it appears reasonable to consider a period of observation for improvement of obstructive sleep apnea following hydroxyurea administration rather than directly proceeding with surgery.
Biomaterial-based approaches for bone regeneration seek to explore alternative strategies to repair non-healing fractures and critical-sized bone defects. Fracture non-union occurs due to a number of ...factors resulting in the formation of bone defects. Rigorous evaluation of the biomaterials in relevant models and assessment of their potential to translate towards clinical use is vital. Large animal experimentation can be used to model fracture non-union while scaling-up materials for clinical use. Growth factors modulate cell phenotype, behaviour and initiate signalling pathways leading to changes in matrix deposition and tissue formation. Bone morphogenetic protein-2 (BMP-2) is a potent osteogenic growth factor, with a rapid clearance time in vivo necessitating clinical use at a high dose, with potential deleterious side-effects. The current studies have examined the potential for Laponite® nanoclay coated poly(caprolactone) trimethacrylate (PCL-TMA900) scaffolds to bind BMP-2 for enhanced osteoinduction in a large animal critical-sized bone defect. An ovine femoral condyle defect model confirmed PCL-TMA900 scaffolds coated with Laponite®/BMP-2 produced significant bone formation compared to the uncoated PCL-TMA 900 scaffold in vivo, assessed by micro-computed tomography (μCT) and histology. This indicated the ability of Laponite® to deliver the bioactive BMP-2 on the PCL-TMA900 scaffold. Bone formed around the Laponite®/BMP-2 coated PCL-TMA900 scaffold, with no erroneous bone formation observed away from the scaffold material confirming localisation of BMP-2 delivery. The current studies demonstrate the ability of a nanoclay to localise and deliver bioactive BMP-2 within a tailored octet-truss scaffold for efficacious bone defect repair in a large animal model with significant implications for translation to the clinic.
•Acellular, bioactive scaffolds for bone tissue repair•Octet-truss design scaffolds are robust.•PCL-trimethacrylate is a 3D-printable, biocompatible polymer.•Bone formed on Laponite®/bone morphogenetic protein-2 coated scaffolds•Sheep are a valid model for large bone tissue defects.
Biodegradable polymer scaffolds have great potential for regenerative medicine applications such as the repair of musculoskeletal tissues. Here, we describe the development of scaffolds that blend ...hydrogel components with thermoplastic materials, combining the unique properties of both components to create mouldable formulations. This study focuses on the structural and mechanical properties of the composite scaffolds, produced by combining temperature-sensitive poly(DL-lactic acid-co-glycolic acid) (PLGA)/poly(ethylene glycol) (PEG) particles with a hydrogel component Pluronic F127, fibrin or hyaluronic acid (HyA). The composite formulations solidified over time at 37°C, with a significant increase (p ≤ 0.05) in compressive strength observed from 15 min to 2 h at this temperature. The maximum compressive strength was 1.2 MPa for PLGA/PEG-Pluronic F127 scaffolds, 2.4 MPa for PLGA/PEG-HyA scaffolds and 0.6 MPa for PLGA/PEG-fibrin scaffolds. Porosity for each of the PLGA/PEG-hydrogel formulations tested was between 50 and 51%. This study illustrates the ability to combine this thermoplastic PLGA/PEG system with hydrogels to fabricate composite scaffolds, and demonstrates that altering the particle to hydrogel ratio produces scaffolds with varying mechanical properties.
In an attempt to induce early spat settlement and improve mussel seed production, this study aims to determine the influence of water management, photoperiod, and aeration, on the growth, survival ...and settlement of green mussel (
Perna viridis
). Water in the pediveliger rearing tanks was changed every day, every 3 days and every 5 days for the water-management experiment. Pediveligers were exposed in 24L:0D h (light: dark), 12L:12D h and 0L:24D h conditions for the photoperiod experiment. Three aeration intensities were also tested—mild (10 L h
−1
), moderate (20 L h
−1
), and strong (30 L h
−1
). This study demonstrated that changing water every 3 days was effective in maintaining the rearing water quality and improving the growth and survival of
P. viridis
larvae. Highest growth and survival rates were observed in
P. viridis
spats grown in 0L:24D h photoperiod. There was no significant difference in the settlement rate of larvae exposed to different photoperiods. Mild aeration has shown to improve the growth of
P. viridis
larvae, but higher survival and settlement rates were attained in the strongly-aerated conditions. Therefore, when the larvae start to settle, it is recommended to expose them to darkness, change the water every 3 days and provide a strong aeration to be able to attain high survival and settlement rates, and bigger spats.
To dissect the individual effects of the four non-MHC, autosomal loci (Bxs1 to Bxs4) that contribute to SLE susceptibility in BXSB mice, we generated congenic lines from chromosome 1 on a ...C57BL/10.Y(BXSB) (B10.Yaa) background for the intervals (values in megabases (Mb)) Bxs1 (46.3-89.2 Mb), Bxs1/4 (20.0-65.9 Mb), Bxs1/2 (64.4-159.0 Mb), and Bxs2/3 (105.4-189.0 Mb). Glomerulonephritis, qualitatively similar to that seen in the parental BXSB strain, developed in three of these congenic strains. Early onset, severe disease was observed in B10.Yaa.BXSB-Bxs2/3 congenic mice and caused 50% mortality by 12 mo. In B10.Yaa.BXSB-Bxs1/4 mice disease progressed more slowly, resulting in 13% mortality at 12 mo. The progression of renal disease in both of these strains was correlated with the level of anti-dsDNA Abs. B10.Yaa.BXSB-Bxs1 mice, despite their genetic similarity to B10.Yaa.BXSB-Bxs1/4 mice, developed a low-grade glomerulonephritis in the absence of anti-dsDNA Abs. Thus, Bxs4 directed an increase in titer and spectrum of autoantibodies, whereas Bxs1 promoted the development of nephritis. The Bxs2 interval was linked to the production of anti-dsDNA Abs without concomitant glomerulonephritis. In contrast, the Bxs3 interval was sufficient to generate classic lupus nephritis in a nonautoimmune-prone strain. Immune phenotype differed between controls and congenics with a significant increase in B220(+) cells in BXSB and B10.Yaa.BXSB-Bxs2/3, and an increase in CD4 to CD8 ratio in both BXSB and B10.Yaa.BXSB-Bxs1/4. Disease in the Bxs3 mice was delayed in comparison to the BXSB parental strain, emphasizing the necessity for multiple interactions in the production of the full BXSB phenotype.
High levels of the retroviral envelope protein gp70 and gp70 immune complexes have been linked to a single locus on chromosome 13 (Bxs6) in the BXSB model, to which linkage of nephritis was also ...seen. Congenic lines containing the BXSB Bxs6 interval on a non-autoimmune C57BL/10 background were bred in the presence or absence of the BXSB Y chromosome autoimmune accelerator gene (Yaa), which accelerates disease in male mice. In these mice, we have shown that Bxs6 is sufficient to cause high-level expression of gp70 and the production of gp70 autoantibodies, independently of Yaa, with gp70 immune complex levels enhanced by Yaa. In the presence of Yaa, Bxs6 also causes mild nephritis, and interestingly the sporadic production of high levels of anti-DNA Abs in some mice. Fine mapping using rare recombinant mice suggested that Bxs6 lies between 59.7 and 74.8 megabases (Mb), although the interval of 0.6 Mb between 73.6 and 78.6 Mb on chromosome 13 cannot be excluded in this study.
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