Summary
Objectives
To identify risk and risk factors for developing a subsequent febrile seizure (FS) in children with a first febrile status epilepticus (FSE) compared to a first simple febrile ...seizure (SFS). To identify home use of rescue medications for subsequent FS.
Methods
Cases included a first FS that was FSE drawn from FEBSTAT and Columbia cohorts. Controls were a first SFS. Cases and controls were classified according to established FEBSTAT protocols. Cumulative risk for subsequent FS over a 5‐year period was compared in FSE versus SFS, and Cox proportional hazards regression was conducted. Separate analysis examined subsequent FS within FSE. The use of rescue medications at home was assessed for subsequent FS.
Results
Risk for a subsequent FSE was significantly increased in FSE versus SFS. Any magnetic resonance imaging (MRI) abnormality increased the risk 3.4‐fold (p < 0.05), adjusting for age at first FS and FSE and in analyses restricted to children whose first FS was FSE (any MRI abnormality hazard ratio HR 2.9, p < 0.05). The risk for a second FS of any type or of subsequent FS lasting >10 min over the 5‐year follow‐up did not differ in FSE versus SFS. Rectal diazepam was administered at home to 5 (23.8%) of 21 children with subsequent FS lasting ≥10 min.
Significance
Compared to controls, FSE was associated with an increased risk for subsequent FSE, suggesting the propensity of children with an initial prolonged seizure to experience a prolonged recurrence. Any baseline MRI abnormality increased the recurrence risk when FSE was compared to SFS and when FSE was studied alone. A minority of children with a subsequent FS lasting 10 min or longer were treated with rectal diazepam at home, despite receiving prescriptions after the first FSE. This indicates the need to further improve the education of clinicians and parents in order to prevent subsequent FSE.
This study explores three unique approaches for closing valves and channels within microfluidic systems, specifically multilayer, centrifugally driven polymeric devices. Precise control over the ...cessation of liquid movement is achieved through either the introduction of expanding polyurethane foam, the application of direct contact heating, or the redeposition of xerographic toner via chloroform solvation and evaporation. Each of these techniques modifies the substrate of the microdevice in a different way. All three are effective at closing a previously open fluidic pathway after a desired unit operation has taken place, i.e., sample metering, chemical reaction, or analytical measurement. Closing previously open valves and channels imparts stringent fluidic control-preventing backflow, maintaining pressurized chambers within the microdevice, and facilitating sample fractionation without cross-contamination. As such, a variety of microfluidic bioanalytical systems would benefit from the integration of these valving approaches.
Total bilirubin (T-Bil) is an important clinical diagnostic marker that is measured frequently by physicians to assist in the diagnosis, treatment, and monitoring of multiple medical conditions. The ...work demonstrated here utilizes the 48-year-old mechanism of phototherapy that is commonly implemented in the treatment of infants with exaggerated physiologic and pathologic jaundice but adapts it to the microfluidic level for the ultimate purpose of total bilirubin quantitation. After acquisition of a small volume of blood (<10 μL) and through subsequent separation (plasma + red blood cells), a 3 μL plasma sample was imaged by a portable scanner and analyzed through a custom algorithm for color intensity. After blue light irradiation for 10 min at 470 nm, the sample was reimaged and analyzed. The resulting intensities obtained pre- and postimaging (clearly observed through a color change from yellow to clear) were then utilized to calculate the total bilirubin concentration. A total of 34 blood samples were analyzed with microfluidic photo treatment-image analysis (μPIA) and were found to have a Deming-regression slope of 0.97 (R 2 = 0.960) when compared to the total bilirubin values determined in the clinical laboratory. We demonstrate the implementation of a centrifugal microdevice fabricated through the Print, Cut, and Laminate (PCL) method that accepts eight whole blood samples and provides the capabilities to not only quantitate total bilirubin (Deming-regression slope of 0.95, R 2 = 0.990) but allow future integration with excess plasma sufficient for additional downstream clinical assays. This work will highlight the inexpensive nature of the analysis (absence of caustic, viscous, or additional reagents), the simplicity (does not require any chemical reactions), speed (sample-to-answer in <15 min), insusceptibility to biofouling (no protein matrix effects, hemoglobin interferences, and minimized turbidity), low volume plasma requirement (3 μL), and the ability for future downstream integration.
GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to ...examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions.
Nuclear magnetic resonance spectroscopy, specifically signal amplitudes originating from the N-acetyl methyl group protons of the N-acetylglucosamine residues on the glycan branches of glycoproteins, was used to quantify GlycA concentrations. GlycA was measured before and after completion of an exercise intervention in 1568 individuals across seven studies and 14 exercise interventions. Random effects inverse variance weighting models were used to pool effects across interventions.
Combined analysis of unadjusted data showed that regular exercise significantly (p = 2 × 10−6) reduced plasma GlycA (−8.26 ± 1.8 μmol/L). This reduction remained significant (−9.12 ± 1.9 μmol/L, p = 1.22 × 10−6) following adjustment for age, sex, race, baseline BMI, and baseline GlycA. Changes in GlycA were correlated with changes in traditional inflammatory markers, C-reactive protein, interleukin-6, and fibrinogen, however, these correlations were relatively weak (range r: 0.21–0.38, p < 0.0001).
Regular exercise significantly reduced plasma GlycA across 14 different exercise interventions despite differences in exercise programs and study populations. The current study provides a greater understanding of the use of exercise as a potential therapy for the reduction of systemic inflammation. Further research is needed to understand the mechanisms behind the exercise-related reductions in GlycA.
•Regular endurance exercise significantly reduces the inflammatory marker GlycA.•Regular endurance exercise does not reduce other traditional inflammatory markers.•Changes in GlycA are weakly correlated with changes in CRP, IL-6, and fibrinogen.
Initial screening of criminal evidence often involves serological testing of stains of unknown composition and/or origin discovered at a crime scene to determine the tissue of origin. This testing is ...presumptive but critical for contextualizing the scene. Here, we describe a microfluidic approach for body fluid profiling via fluorescent electrophoretic separation of a published mRNA panel that provides unparalleled specificity and sensitivity. This centrifugal microfluidic approach expedites and automates the electrophoresis process by allowing for simple, rotationally driven flow and polymer loading through a 5 cm separation channel; with each disc containing three identical domains, multi-sample analysis is possible with a single disc and multi-sample detection per disc. The centrifugal platform enables a series of sequential unit operations (metering, mixing, aliquoting, heating, storage) to execute automated electrophoretic separation. Results show on-disc fluorescent detection and sizing of amplicons to perform comparably with a commercial ‘gold standard’ benchtop instrument and permitted sensitive, empirical discrimination between five distinct body fluids in less than 10 min. Notably, our microfluidic platform represents a faster, simpler method for separation of a transcriptomic panel to be used for forensically relevant body fluid identification.
To compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United ...States.
Multicenter observational case-control study with a test negative design.
Hospitals in 18 US states.
4760 adults admitted to one of 21 hospitals with acute respiratory symptoms between 26 December 2021 and 30 June 2022, a period when the omicron variant was dominant. Participants included 2385 (50.1%) patients with laboratory confirmed covid-19 (cases) and 2375 (49.9%) patients who tested negative for SARS-CoV-2 (controls).
The main outcome was vaccine effectiveness against hospital admission with covid-19 for a primary series plus booster doses and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. Vaccine effectiveness analyses were stratified by immunosuppression status (immunocompetent, immunocompromised). The primary analysis evaluated all covid-19 vaccine types combined, and secondary analyses evaluated specific vaccine products.
Overall, median age of participants was 64 years (interquartile range 52-75 years), 994 (20.8%) were immunocompromised, 85 (1.8%) were vaccinated with a primary series plus two boosters, 1367 (28.7%) with a primary series plus one booster, and 1875 (39.3%) with a primary series alone, and 1433 (30.1%) were unvaccinated. Among immunocompetent participants, vaccine effectiveness for prevention of hospital admission with omicron related covid-19 for a primary series plus two boosters was 63% (95% confidence interval 37% to 78%), a primary series plus one booster was 65% (58% to 71%), and for a primary series alone was 37% (25% to 47%) (P<0.001 for the pooled boosted regimens compared with a primary series alone). Vaccine effectiveness was higher for a boosted regimen than for a primary series alone for both mRNA vaccines (BNT162b2 (Pfizer-BioNTech): 73% (44% to 87%) for primary series plus two boosters, 64% (55% to 72%) for primary series plus one booster, and 36% (21% to 48%) for primary series alone (P<0.001); mRNA-1273 (Moderna): 68% (17% to 88%) for primary series plus two boosters, 65% (55% to 73%) for primary series plus one booster, and 41% (25% to 54%) for primary series alone (P=0.001)). Among immunocompromised patients, vaccine effectiveness for a primary series plus one booster was 69% (31% to 86%) and for a primary series alone was 49% (30% to 63%) (P=0.04).
During the first six months of 2022 in the US, booster doses of a covid-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing hospital admissions with omicron related covid-19.
This article is a living test negative design study that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.
To date, most research regarding amino acid detection and quantification in fingermarks relies on spectrometric methods. Herein, the Sakaguchi colorimetric test was adapted to a rotationally-driven ...microfluidic platform and used to detect and quantify arginine in fingermarks deposited by male and female donors. A red color indicates the presence of arginine in a given sample following the reaction, and the intensity of this color is linearly proportional to the concentration. Objective detection and quantification of arginine were accomplished using image analysis software (freeware) based on this colorimetric result. The mean concentrations obtained in a blind study were 96.4 ± 5.1 µM for samples from female donors and 55.3 ± 5.3 µM for samples from males. These were not statistically different from the literature values of 94.8 µM ± 12.9 µM for females (
0.908) and 54.0 ± 12.6 µM for males (
0.914), respectively (± SEM in all cases). Conversely, the experimental means from males and female samples were statistically different from each other (
0.001). Objective differentiation between male and female fingermark deposits was achieved in a blind study with 93% accuracy. Additionally, the method was compatible both with samples lifted from common surfaces and with magnetically-powdered samples.
Variation in FOXC1 and PITX2 is associated with Axenfeld-Rieger syndrome, characterised by structural defects of the anterior chamber of the eye and a range of systemic features. Approximately half ...of all affected individuals will develop glaucoma, but the age at diagnosis and the phenotypic spectrum have not been well defined. As phenotypic heterogeneity is common, we aimed to delineate the age-related penetrance and the full phenotypic spectrum of glaucoma in FOXC1 or PITX2 carriers recruited through a national disease registry. All coding exons of FOXC1 and PITX2 were directly sequenced and multiplex ligation-dependent probe amplification was performed to detect copy number variation. The cohort included 53 individuals from 24 families with disease-associated FOXC1 or PITX2 variants, including one individual diagnosed with primary congenital glaucoma and five with primary open-angle glaucoma. The overall prevalence of glaucoma was 58.5% and was similar for both genes (53.3% for FOXC1 vs 60.9% for PITX2, P=0.59), however, the median age at glaucoma diagnosis was significantly lower in FOXC1 (6.0±13.0 years) compared with PITX2 carriers (18.0±10.6 years, P=0.04). The penetrance at 10 years old was significantly lower in PITX2 than FOXC1 carriers (13.0% vs 42.9%, P=0.03) but became comparable at 25 years old (71.4% vs 57.7%, P=0.38). These findings have important implications for the genetic counselling of families affected by Axenfeld-Rieger syndrome, and also suggest that FOXC1 and PITX2 contribute to the genetic architecture of primary glaucoma subtypes.
Purpose
The purpose of this study was to examine the relationship between psychological factors (depression, anxiety, and catastrophizing) and fear of falling avoidance behavior (FFAB) among ...individuals with Parkinson’s disease (PD).
Methods
A secondary analysis of cross-sectional data from 59 individuals with PD using hierarchical multiple regression.
Results
Disease severity (Movement Disorder Society - Unified PD Rating Scale) and catastrophizing (Consequences of Falling Questionnaire (CoF)) explained approximately 48.2% of the variance in the FFAB Questionnaire scores (P < .001). Catastrophizing was the only significant psychological variable (P < .001). The damage to identity subscale of the CoF was significant in the final model (P < .001).
Conclusions
Catastrophizing about the consequences of falls explained the largest portion of variability in FFAB after controlling for disease severity. Catastrophizing about the immediate consequences of falling may play a prominent role in FFAB and may be a potential treatment target for mitigating FFAB.
PDF
