Importance Health-related quality of life (HRQOL) is regarded as a key outcome for evaluating treatment efficacy. However, it is uncertain how HRQOL evolves after epilepsy surgery compared with medical therapy, such as whether it continues to improve over time, improves and then remains stable, or deteriorates after a period of time. Objective To assess trajectory of HRQOL over 2 years in children with drug-resistant epilepsy (DRE) treated with surgery compared with medical therapy. Design, Setting, and Participants Prospective cohort study assessing HRQOL longitudinally over 2 years. Participants were children recruited from 8 epilepsy centers in Canada from 2014 to 2019 with suspected DRE aged 4 to 18 years who were evaluated for surgery. Data were analyzed from May 2014 to December 2021. Exposures Epilepsy surgery or medical therapy. Main Outcomes and Measures HRQOL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55. HRQOL and seizure frequency were assessed at baseline, 6-month, 1-year, and 2-year follow-ups. Clinical, parent, and family characteristics were assessed at baseline. A linear mixed model was used to evaluate HRQOL over time, adjusting for baseline clinical, parent, and family characteristics. Results There were 111 surgical and 154 medical patients (mean [SD] age at baseline was 11.0 [4.1] years; 118 [45%] were female). At baseline, HRQOL was similar among surgical and medical patients. HRQOL of surgical patients was 3.0 (95% CI, −0.7 to 6.8) points higher at 6-month, 4.9 (95% CI, 0.7 to 9.1) points higher at 1-year, and 5.1 (95% CI, 0.7 to 9.5) points higher at 2-year follow-ups compared with medical patients. Surgical patients experienced greater improvements in social functioning relative to medical patients, but not for cognitive, emotional, and physical functioning. At 2-year follow-up, 72% of surgical patients were seizure-free, compared with 33% of medical patients. Seizure-free patients reported higher HRQOL than those who were not. Conclusions and Relevance This study provided evidence on the association between epilepsy surgery and children’s HRQOL, with improvement in HRQOL occurring within the first year and remaining stable 2 years after surgery. By demonstrating that surgery improved seizure freedom and HRQOL, which has downstream effects such as better educational attainment, reduced health care resource utilization, and health care cost, these findings suggest that the high costs of surgery are justified, and that improved access to epilepsy surgery is necessary.
The anticipation of financial distress has become increasingly important in the deregulated world of air transportation. Generic (non-industry specific) bankruptcy forecasting models have existed for years, and financial theorists have designed many industry specific models for various sectors of the economy. No one, however, has yet modeled the airline industry. This article attempts that task. Using a sample of 76 carriers, key predictive variables are identified. The variables employed are important financial ratios that measure liquidity, leverage, efficiency, and profitability. Both a univariate and a multivariate model are generated using these variables. The derived model, AIRSCORE, achieves significant accuracy in separating those carriers in a distressed profile from those which are stronger financially.
Hypophosphatasia (HPP) is the metabolic bone disease caused by loss-of-function mutation within the gene that encodes the "tissue nonspecific" isoenzyme of alkaline phosphatase (TNSALP). Perinatal HPP is usually fatal due to respiratory insufficiency, and infantile HPP often has a similar outcome although no formal study into the natural history of these severe forms of HPP has been undertaken. We reviewed our 80-year (1927-2007) cohort of 15 Canadian patients with perinatal HPP. All had Mennonite heritage. Family linkage studies indicated that nine were homozygous for a TNSALP disease allele, likely Gly334Asp. Three patients had parents who were carriers for the Gly334Asp allele by mutation analysis. One patient was confirmed by mutation analysis to be homozygous for the TNSALP Gly334Asp mutation. One patient who had only one Mennonite parent was a genetic compound for the Gly334Asp mutation and the Val382Ile mutation. This patient's sibling was also affected. All 15 patients had profound skeletal hypomineralization, severe rickets, and respiratory insufficiency. All died by 9 months of age, usually soon after birth, from pulmonary failure.
To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD).Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg-1·d-1, tadalafil 0.6 mg·kg-1·d-1, or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome.Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil (p = 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil (p = 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state.Tadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age.NCT01865084.This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy.
Objective: To assess the applicability of a smartphone-based electroencephalography (EEG), the Smartphone Brain Scanner-2 in a low-income country, including quality of results and usefulness of repeat testing. Background: People with epilepsy in Sub-Saharan Africa are often undiagnosed. We examine a low-cost, portable smartphone-based EEG technology in a heterogeneous epilepsy cohort in the West African Republic of Guinea. Design/Methods: The SBS2 system consists of an Android tablet wirelessly connected to a 14-electrode EasyCap headset. SBS2 was performed in people with suspected epilepsy in Guinea (2018–19), with a repeat EEG carried out at a variable time interval. Recordings were interpreted by U.S., Canadian, and U.K. experts in Clinical Neurophysiology. Results: We included 149 participants (41% female, median age 17.9 years). 66.6% ≤ 21 years; mean number of seizures per month 5.7 +/−15.5. The mean duration of EEG1 was 53 minutes +/−12.3 and EEG2 was 29.6 minutes +/−12.8. The mean quality score of EEG1 and EEG2 independently was 6.4 (range 1(low)-10(high), median 7.0). 29.5% of participants had epileptiform discharges (EDs) at EEG1 and 16.7% at EEG2. 41.6% had abnormal slowing and/or EDs at EEG1 and 28.8% at EEG2. 26.1% were recommended for neuro-imaging after EEG1 and 14.7% after EEG2. Of those without EDs at EEG1 (n=53, 55.8%), 7 (13.2%) had EDs at EEG2. Of those with detectable EDs on EEG1 (n = 23, 24.2%), 12 (52.1%) did not have EDs at EEG2. Patients for whom at least one EEG was not scored for EDs were excluded from the comparative ED analysis (n = 54, 36%). Conclusions: The SBS2 has a reproducible level of quality on repeat testing and is useful for the detection of EDs. One EEG of approximately 50 minutes was adequate to support diagnosis. The need for neuroimaging access in this patient population is evident. Disclosure: Dr. Ayub has nothing to disclose. Dr. Leung has nothing to disclose. Dr. Fantaneanu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB, Eisai, and Sunovion. Dr. Patel has nothing to disclose. Dr. Vyas has nothing to disclose. Dr. Milligan has nothing to disclose. Dr. Villamar has nothing to disclose. Dr. Hoch has nothing to disclose. Dr. Purves has nothing to disclose. Dr. Esmaeili has nothing to disclose. Dr. Tellez-Zenteno has nothing to disclose. Dr. Gonzalez-Giraldo has nothing to disclose. Dr. Tolokh has nothing to disclose. Dr. Heidarian has nothing to disclose. Dr. Worden has nothing to disclose. Dr. Jadeja has nothing to disclose. Dr. Fridinger has nothing to disclose. Dr. Lee has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Receive clinical trial funds from Novartis Canada, Roche Canada Serve on ad boards for Celgene, Novartis Canada, Roche Canada, Teva Neuroscience, Serono Canada, Genzyme Canada, Biogen Canada. Dr. Lee has received research support from Receive clinical trial funds from Novartis Canada, Roche Canada Serve on ad boards for Celgene, Novartis Canada, Roche Canada, Teva Neuroscience, Serono Canada, Genzyme Canada, Biogen Canada. Dr. Cisse has nothing to disclose. Dr. Mateen has received research support from IQVIA.
Purpose: There is uncertainty regarding the appropriate dose of Cannabidiol (CBD) for childhood epilepsy. We present the preliminary data of seven participants from the Cannabidiol in Children with Refractory Epileptic Encephalopathy (CARE-E) study. Methods: The study is an open-label, prospective, dose-escalation trial. Participants received escalating doses of a Cannabis Herbal Extract (CHE) preparation of 1:20 Δ9-tetrahydrocannabinol (THC): CBD up to 10-12 mg CBD/kg/day. Seizure frequency was monitored in daily logs, participants underwent regular electroencephalograms, and parents filled out modified Quality of Life in Childhood Epilepsy (QOLCE) and Side Effect rating scale questionnaires. Steady-state trough levels (Css, Min) of selected cannabinoids were quantified. Results: All seven participants tolerated the CHE up to 10-12 mg CBD/kg/day and had improvements in seizure frequency and QOLCE scores. CSS, Min plasma levels for CBD, THC, and cannabichromene (CBC) showed dose-independent pharmacokinetics in all but one participant. CSS, Min CBD levels associated with a >50% reduction in seizures and seizure freedom were lower than those reported previously with purified CBD. In most patients, CSS, Min levels of THC remained lower than what would be expected to cause intoxication. Conclusion: The preliminary data suggest an initial CBD target dose of 5-6 mg/kg/day when a 1:20 THC:CBD CHE is used. Possible non-linear pharmacokinetics of CBD and CBC needs investigation. The reduction in seizure frequency seen suggests improved seizure control when a whole plant CHE is used. Plasma THC levels suggest a low risk of THC intoxication when a 1:20 THC:CBD CHE is used in doses up to 12 mg/kg CBD/kg/day.
To compare the ability of a smartphone-based app, the Smartphone Brain Scanner-2(SBS2), and pre-placed EEG cap (Easycap), costing ~300USD, to detect abnormalities with that of standard EEG.
Objective: To assess the Smartphone Brain Scanner-2 (SBS2)'s ability to detect abnormal and epileptiform cortical discharges compared to standard electroencephalogram (EEG) among people with epilepsy (PWE) in Bhutan. Background: The SBS2 is a software application, utilizing a 14-lead headset connected wirelessly to an Android device. Portable, easily operated, and low-cost (<500USD per device), the SBS2 may aid in the diagnosis of epilepsy in resource-limited settings. Methods: PWE or suspected seizures in Bhutan underwent a SBS2 and a standard EEG (each ≥20 minutes duration). The SBS2 used circumference-matched EasyCaps with ring electrodes positioned at F3, C3, P3, O1, F4, C4, P4, O2, Fz, Cz, Pz, Fpz, A1, A2. The standard EEG (Xltek, Natus) used 10-20 system electrode placement and peripheral leads. Neurologists, blinded to clinical data, categorized recordings as normal or abnormal, and abnormalities as epileptiform or background. Each SBS2 recording was read once. Each standard EEG was independently assessed by ≥2 neurologists. A third neurologist or a group of neurologists resolved discrepancies. Results: 215 participants (53[percnt] female, mean age 25 years) completed both SBS2 and standard EEG with no safety or tolerability concerns. Epileptiform discharges were present on 25[percnt] and 15[percnt] of standard and SBS2 EEGs. For the detection of all abnormalities, the SBS2 had a sensitivity of 0.51, specificity of 0.84, and positive and negative predictive values of 0.65 and 0.74 versus standard EEG. For the detection of epileptiform discharges, the SBS2 had a sensitivity of 0.36, specificity of 0.94, and positive and negative predictive values of 0.68 and 0.84 versus standard EEG. Conclusions: The SBS2 EEG is specific but not sensitive for the detection of epileptiform discharges, and may have clinical relevance to help confirm a suspected epilepsy diagnosis in resource-limited settings. Sensitivity may be improved with hardware modifications including the addition of electrodes along the temporal chain.
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