Generic antiepileptic drugs achieve blood concentrations similar to those of innovator drugs in healthy volunteers, but their comparative effectiveness has not been well evaluated. Thus, we assessed ...the efficacy, tolerability, and safety of innovator versus generic antiepileptic drugs. We searched the MEDLINE database, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science for studies that evaluated innovator and generic antiepileptic drugs in patients with epilepsy and reported data on prespecified outcomes. We extracted data on study design, interventions, quality criteria, study population, baseline characteristics, and outcomes. Compared with initiation of innovator antiepileptic drugs, initiation of generic antiepileptic drugs did not significantly alter seizure occurrence (relative risk RR 0.87, 95% confidence interval CI 0.64–1.18; strength of evidence: low) or frequency (standardized mean difference 0.03, 95% CI −0.08–0.14; strength of evidence: low), withdrawals due to lack of efficacy (RR 1.02, 95% CI 0.41–2.54; strength of evidence: low) or adverse events (RR 0.79, 95% CI 0.28–2.20; strength of evidence: low), pharmacokinetic concentrations (maximum, minimum, or area under the curve strength of evidence: low), or a myriad of adverse events (strength of evidence: low or insufficient) in clinical trials. In qualitatively evaluated observational studies, switching between forms of antiepileptic drug (innovator to generic, generic to generic) may increase the risk of hospitalization (strength of evidence: low), hospital stay duration (strength of evidence: low), and a composite end point of medical service utilization (strength of evidence: insufficient) but may not increase outpatient service utilization (strength of evidence: low). Data are limited predominantly to carbamazepine, phenytoin, and valproic acid. Clinical trials are limited by small sample size, short‐term nature, and lack of specification of A‐rated generic products (generics that the United States Food and Drug Administration has deemed bioequivalent to the innovator drug). Observational trials lack full accounting for confounders and have inherent limitations. With a low strength of evidence, it appears that initiating an innovator or generic antiepileptic drug will provide similar efficacy, tolerability, and safety but that switching from one form to the other may be associated with more hospitalizations and longer hospital stays.
An exact solution of visco-capillary flow in an inclined channel is presented. Assuming that the flow is steady and unidirectional, the surface shape and the velocity profile are obtained as exact ...solutions of the Navier Stokes equations valid for arbitrary Reynolds numbers. The contributions of the determining parameters of the problem to the surface shape and to the velocity profile are discussed. A structural change in the velocity profile, the 'velocity overshoot', is found for cases with meniscus elevation higher than the apex height of the flow. The theoretical findings are compared to experimental results. (Author)
Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear.
To review ...the effectiveness of rhGH in the treatment of patients with CF.
Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high.
Ten unique controlled trials (n = 312) and 8 observational studies (n = 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, health-related quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control.
rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.
To compare patient-reported limitations, concerns, and burdens in those receiving and not receiving warfarin for thromboprophylaxis in atrial fibrillation (AF).
We conducted a cross-sectional survey ...study of patients with AF receiving thromboprophylaxis for stroke prevention. Patients were administered the validated Anti-Clot Treatment Scale (ACTS). Mean scores of patients receiving and not receiving warfarin were compared for each ACTS item, and for the Burden and Benefit subscales.
From July 2010 to August 2011, 80 patients with AF were administered the survey, with 65 patients receiving a regimen containing warfarin and 15 patients not receiving a regimen containing warfarin. Six of the 17 individual questions depicting patient- perceived limitations in physical activity due to bleeding, limitations on diet, feelings of inconvenience of occasional aspects of thromboprophylaxis therapy, and frustration, and burden had less favorable scores in the warfarin-managed patients compared with the patients not receiving warfarin (P < 0.05 for all). Mean ACTS Burden scores were more favorable in the no-warfarin group (44.5 ± 6.4) compared with the warfarin group (39.8 ± 8.0; P = 0.003). No difference was seen between the 2 groups on the ACTS Benefits score (11.1 ± 3.4 vs 10.4 ± 3.7; P = 0.38).
Patients with AF receiving warfarin may have less favorable feelings regarding thromboprophylaxis versus those receiving non-warfarin thromboprophylaxis. Patients report having more limitations and having greater feelings of burden on warfarin.
In this paper a comparative study is conducted to analyze the accuracy of a magnetic field-based positioning system, for the position estimation of a vehicle relative to a charging device. The effect ...on position estimation accuracy of metallic structures on both the vehicle side and charging device's side after the addition of steel floor reinforcements is studied. The best suited modelling tool is found to be Method of Moments after experimentally verifying the tool and comparing it on computational effort and accuracy to the Finite Element Method. It is found that a configuration with a metallic bottom plate including raised edges is the least influenced on the position estimation accuracy due to the steel floor reinforcements, independent on the transmitter location. Moreover, for the researched configurations a system with the transmitter located in the vehicle achieves a higher position estimation accuracy compared to a system with the transmitter in the charging device.
Computational methods in continuum mechanics, especially those encompassing fluid dynamics, have emerged as an essential investigative tool in nearly every field of technology. Despite being ...underpinned by a well-developed mathematical theory and the existence of readily available commercial software codes, computing solutions to the governing equations of fluid motion remains challenging: in essence due to the non-linearity involved. Additionally, in the case of free surface film flows the dynamic boundary condition at the free surface complicates the mathematical treatment notably. Recently, by introduction of an auxiliary potential field, a first integral of the two-dimensional Navier-Stokes equations has been constructed leading to a set of equations, the differential order of which is lower than that of the original Navier-Stokes equations. In this paper a physical interpretation is provided for the new potential, making use of the close relationship between plane Stokes flow and plane linear elasticity. Moreover, it is shown that by application of this alternative approach to free surface flows the dynamic boundary condition is reduced to a standard Dirichlet-Neumann form, which allows for an elegant numerical treatment. A least squares finite element method is applied to the problem of gravity driven film flow over corrugated substrates in order to demonstrate the capabilities of the new approach. Encapsulating non-Newtonian behaviour and extension to three-dimensional problems is discussed briefly.
The biosynthesis of CoA from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. The CoA biosynthetic genes in bacteria have all recently been identified, ...but their counterparts in humans and other eukaryotes remained mostly unknown. Using comparative genomics, we have identified human genes encoding the last four enzymatic steps in CoA biosynthesis: phosphopantothenoylcysteine synthetase (EC ), phosphopantothenoylcysteine decarboxylase (EC ), phosphopantetheine adenylyltransferase (EC ), and dephospho-CoA kinase (EC ). Biological functions of these human genes were verified using a complementation system in Escherichia coli based on transposon mutagenesis. The individual human enzymes were overexpressed in E. coli and purified, and the corresponding activities were experimentally verified. In addition, the entire pathway from phosphopantothenate to CoA was successfully reconstituted in vitro using a mixture of purified recombinant enzymes. Human recombinant bifunctional phosphopantetheine adenylyltransferase/dephospho-CoA kinase was kinetically characterized. This enzyme was previously suggested as a point of CoA biosynthesis regulation, and we have observed significant differences in mRNA levels of the corresponding human gene in normal and tumor cells by Northern blot analysis.
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