It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.
To evaluate how genetic diagnoses in ...patients with epilepsy are associated with clinical management and outcomes.
This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals.
Genetic test results.
Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms.
Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 21.7%), the initiation of medication (51 14.2%), the referral of a patient to a specialist (48 13.4%), vigilance for subclinical or extraneurological disease features (46 12.8%), and the cessation of a medication (42 11.7%). Among 167 patients with follow-up clinical information available (mean SD time, 584 365 days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 12.0%), increased seizure frequency (6 3.6%), and adverse medication effects (3 1.8%). No clinical management changes were reported for 178 patients (42.6%).
Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.
ABSTRACT IMPACT: Long-acting insulin containing protamine is more likely to be associated with skin depigmentation. OBJECTIVES/GOALS: An acquired disorder, skin depigmentation was found to be ...significantly correlated with diabetes. While a recent meta-analysis pointed at a possible similar pathogenesis, the possibility of vitiligo occurring as a drug-induced disease was never explored. This study aimed at elucidating whether utilization of specific insulins may play a role. METHODS/STUDY POPULATION: Records from the Medical Panels Expenditure Survey (MEPS) database made available by the Agency for Healthcare Research and Quality were used to identify all injectable insulin users (n=8867). ICD-9/10 codes were abstracted from the medical conditions files for all the subjects reporting any type of injectable insulin use (1996-2017). Skin depigmentation codes identified in our dataset were 709 and L81. Insulins were categorized based on duration of action, short-acting (SA), intermediate-acting (IA), and long-acting (LA), as well as based on formulation ingredients (zinc, protamine-zinc, other), and insulin combination (SA with or without IA/LA containing or not protamine-zinc). The association between skin depigmentation occurrence and insulin type and/or category was assessed by Fisher’s exact test. RESULTS/ANTICIPATED RESULTS: A total of 225 out of 8867 individuals were diagnosed with skin depigmentation. Incidence of skin depigmentation was 2.25% in SA users (n1=3606, p=0.355), 2.24% in LA users (n2=3910, p=0.337), and 2.39% in IA users (n3=4015, p=0.062). Occurrence of skin depigmentation was similar between users of insulin mono- or combo therapy (p=0.758). Interestingly, among IA insulins, insulin protamine-zinc insulin (n4=3992) distinguished as being mainly responsible for the association with the occurrence of skin depigmentation (p=0.062), whereas insulin zinc was not (n5=37, p=1.000). The highest skin depigmentation incidence was observed among Pacific Islanders (2.66%, p=0.110). Males distinguished by a skin depigmentation incidence of 2.34% vs. 1.91% in females (p=0.086). DISCUSSION/SIGNIFICANCE OF FINDINGS: We report that presence of protamine-zinc may play a role in the development of skin depigmentation. It is uncertain whether this risk may be shared equally by insulin users diagnosed with type 1 and type 2 diabetes. Of note, we observed a higher skin depigmentation incidence than that reported by community- (0.2%) or hospital-based (1.8%) studies.
Ketamine is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist. It induces effects in healthy individuals that mimic symptoms associated with schizophrenia. We sought to root ...these experiences in altered brain function, specifically aberrant resting state functional connectivity (rsfMRI). In the present study, we acquired rsfMRI data under ketamine and placebo in a between-subjects design and analyzed seed-based measures of rsfMRI using large-scale networks, dorsolateral prefrontal cortex (DLPFC) and sub-nuclei of the thalamus. We found ketamine-induced alterations in rsfMRI connectivity similar to those seen in patients with schizophrenia, some changes that may be more comparable to early stages of schizophrenia, and other connectivity signatures seen in patients that ketamine did not recreate. We do not find any circuits from our regions of interest that correlates with positive symptoms of schizophrenia in our sample, although we find that DLPFC connectivity with ACC does correlate with a mood measure. These results provide support for ketamine's use as a model of certain biomarkers of schizophrenia, particularly for early or at-risk patients.
Reply to the comment by D. W. Hedding Roberts, R. James; Lehong, Keabetswe D.; Botha, Andries E. J. ...
Mineralogy and petrology,
08/2020, Letnik:
114, Številka:
4
Journal Article
Background and Aims EUS-guided FNA or biopsy sampling is widely practiced. Optimal sonographic visualization of the needle is critical for image-guided interventions. Of the several commercially ...available needles, bench-top testing and direct comparison of these needles have not been done to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development. Methods Descriptive bench-top testing and comparison of 8 commonly used EUS-FNA needles (all size 22 gauge): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition (Cook Medical); ClearView (Conmed); EZ Shot 2 (Olympus); and BNX (Beacon Endoscopic), and 2 new prototype needles, SonoCoat (Medi-Globe), coated by echogenic polymers made by Encapson. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in GI US examination who were unfamiliar with EUS needle devices. Results There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, 1 prototype needle was rated as the best, ranking 10% to 40% higher than all other needles ( P < .01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%-75% worse, P < .001). Conclusions All FNA needles have their inherent and different echogenicities, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity.
Interstitial lung disease (ILD) in connective tissue diseases (CTD) have highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality and ...immunosuppression response.
Patients with CTD-ILD had high-resolution chest computed tomography (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern (usual interstitial pneumonia UIP; non-specific interstitial pneumonia NSIP; organizing pneumonia OP; fibrotic hypersensitivity pneumonitis fHP; and other). Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment.
Of 645 CTD-ILD patients, the frequent CTDs were systemic sclerosis (n = 215), rheumatoid arthritis (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with UIP, FVC decline was slower for NSIP (1.1%/year, 95%CI 0.2, 1.9) and OP (3.5%/year, 95%CI 2.0, 4.9), and mortality was lower for NSIP (HR 0.65, 95%CI 0.45, 0.93) and OP (HR 0.18, 95%CI 0.05, 0.57), but higher in fHP (HR 1.58, 95%CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95%CI 1.4, 2.8), with no change for UIP or fHP.
Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.
Clinopyroxene megacrysts (up to 5 cm) from a scoria cone on Marion Island, Antarctic Ocean are zoned, with compositionally distinct low (Al + Ti) and high (Al + Ti) patches arranged haphazardly ...throughout crystals. Inclusions of olivine, pyrrhotite, oxides, sulphides, and rounded inclusions with euhedral micro-crystals interpreted as former melt inclusions are observed. Olivine inclusions have variable compositions, ranging from primary Ti-poor crystals to Ti-rich crystals hosting secondary haematite crystals formed by hydrogenation. The crystals contain voids that are concentrated in the middle of each crystal indicating that the initial crystal growth was skeletal. Subsequent crystallisation filled in the skeletal framework creating the patchy zoning in the crystals. The Marion Island megacrysts are not homogenous, but the combination of crustal clinopyroxene compositions, primary and hydrogenated olivine, and the mode of eruption in scoria eruptions indicates that these crystals most likely formed in a shallow magma chamber. Primary olivines crystallised from a mafic magma and secondary altered olivines were incorporated into a rapidly growing megacryst in a super-saturated, fluid-rich environment, prior to being ejected onto surface in a scoria eruption.
Pressure-sensitive paint (PSP) is playing an important role in aerodynamic testing. Its use provides a number of advantages over discrete pressure taps traditionally used on conventional wind tunnel ...models: (i) obtaining continuous quantitative pressure distributions over a surface; (ii) visualizing dynamic flow processes that measure areas not possible with conventional pressure taps (e.g. thin trailing edges); and (iii) real time modeling. The result is better integration of experimental and computational fluid dynamics leading to significant reductions in time for prototyping of new designs. The use of PSP relies on accurate measurement of changes in the paint’s luminescent intensity as a function of pressure change, which in turn requires careful monitoring and placement of light sources and pre-calibration of the PSP covered surface in “wind-off” conditions. Paint in-homogeneity and inconsistent surface illumination require exact registration of the calibration ‘wind-off’ image with subsequent ‘wind-on’ images for intensity change calculations to be meaningful. Model motion between ‘wind-on’ and ‘wind-off’ images leads to systematic errors that are hard to quantify. A dual-luminophor paint containing both a sensor and a reference luminophor molecule should alleviate these technical problems. This paper introduces such a dual-luminophor PSP made from our newly developed oxygen-sensitive molecule platinum tetra(pentafluorophenyl)porpholactone (PtTFPL), which provides
I
sen, and magnesium tetra(pentafluorophenyl)porphine (MgTFPP), which provides
I
ref as the pressure-independent reference. The ratio
I
ref/
I
sen in the FIB polymer produced ideal PSP measurements with a temperature dependency of −0.1%/°C.
In 1996, an epidemic of 393 cases of laboratory-confirmed West Nile meningoencephalitis occurred in southeast Romania, with widespread subclinical human infection. Two case-control studies were ...performed to identify risk factors for acquiring infection and for developing clinical meningoencephalitis after infection. Mosquitoes in the home were associated with infection (reported by 37 97% of 38 asymptomatically seropositive persons compared with 36 72% of 50 seronegative controls, P <.01) and, among apartment dwellers, flooded basements were a risk factor (reported by 15 63% of 24 seropositive persons vs. 11 30% of 37 seronegative controls, P = .01). Meningoencephalitis was not associated with hypertension or other underlying medical conditions but was associated with spending more time outdoors (meningoencephalitis patients and asymptomatically seropositive persons spent 8.0 and 3.5 h medians outdoors daily, respectively, P <.01). Disease prevention efforts should focus on eliminating peridomestic mosquito breeding sites and reducing peridomestic mosquito exposure.
Results of a comparative investigation of deterministic and random pulsewidth modulation (PWM) techniques to be employed in a new ac drive for electric vehicles are presented. The study, employing ...the advanced simulation package SABER from Avant! Corporation, was focused on the reduction of electromagnetic interference (EMI) when a deterministic PWM strategy is replaced with an RPWM method. To assess the impact of the PWM technique on the drive performance, the drive efficiency, torque ripple, and dynamic response of the current control system were also investigated. Two RPWM techniques characterized by random variations of switching frequency of the inverter were considered: one with the sampling frequency of the modulator varying in step with the switching frequency, and one with a fixed sampling frequency equal to the average switching frequency. The study has demonstrated good EMI-mitigating potentials of RPWM techniques, whose use results in EMI reduction by 10 dB and more, while the drive performance is barely affected.
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