ABSTRACT
OBJECTIVE: The objective of this study was to compare clinical- and cost-effectiveness of type A botulinum toxin (BoNT-A) therapies for management of pediatric upper limb spasticity, including AbobotulinumtoxinA (aboBoNT-A) and Onabotulinumtoxin A (onaBoNT-A). METHODS: Systematic literature review and indirect treatment comparisons were conducted of randomized controlled trials reporting efficacy and safety outcomes. Efficacy was characterized by Modified Ashworth Scale (MAS) and Ashworth Scale (AS) up to 16-weeks post-injection. Results were used to inform a cost-effectiveness model with a 1-year time horizon, linking response rates with health-related quality-of-life (HRQoL) outcomes and costs from a UK perspective. Other data sources included in the cost-effectiveness model were drug unit costs, health care resource utilization based on UK physician survey, and HRQoL impacts of adverse events associated with oral anti-spasticity therapies. Results were characterized as cost per quality-adjusted life year and cost per responder. RESULTS: Six studies were included in evidence syntheses. There was a trend towards greater response rate for aboBoNT-A which resulted in improved HRQoL and lower annual costs compared with onaBoNT-A. Safety outcomes were similar across BoNT-A therapies. In cost-effectiveness analysis, aboBoNT-A was an economically dominant therapy with respect to cost per quality-adjusted life year. The cost per responder at 1 year was estimated to be £39,056 for aboBoNT-A vs. £54,831 for onaBoNT-A. LIMITATIONS AND CONCLUSIONS: Based on observed safety and efficacy data, aboBoNT-A is estimated to result in higher treatment response and consequently increased quality-of-life and reduced costs, vs. onaBoNT-A in children with upper limb spasticity. Limitations to the study include study heterogeneity limited details available for onaBoNT-A studies (e.g. use of physical therapy), and limited availability of responder data. Where assumptions were required, they were made to be conservative towards aboBoN-A.
Subject(s)
Botulinum Toxins, Type A , Botulinum Toxins, Type A/adverse effects , Child , Cost-Benefit Analysis , Humans , Muscle Spasticity/drug therapy , Upper ExtremityABSTRACT
[This corrects the article DOI: 10.1186/s40734-020-0083-0.].
ABSTRACT
BACKGROUND: Botulinum neurotoxins type A (BoNT-As) are commonly used treatments for cervical dystonia (CD). Clinical trials have demonstrated the benefits of them in these patients, but data from real-life clinical practice as well as comparative data on the cost and outcome of different BoNT-A formulations are limited. The aim of this study was to compare abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) on their clinical outcomes and drug costs in real-life clinical practice. METHODS: This analysis included 356 adult patients with idiopathic CD treated with aboBoNT-A (n = 253) or onaBoNT-A (n = 103) from 38 centres across Europe and Australia (NCT00833196). The clinical outcome measures were treatment responses, changes in TWSTRS scores and changes in health utility scores from baseline to study visit 2 and 3. Health utility score was mapped from the TWSTRS total scale, using a previous publication. Costs included drug cost for France. RESULTS: The aboBoNT-A treated group had 2.06 (95% CI: 1.15 to 3.69) times higher odds of achieving treatment response than the onaBoNT-A treated group. The adjusted mean change in TWSTRS total score from baseline to visit 3 were - 6.42 (95% CI: - 7.52 to - 5.33) for aboBoNT-A and - 3.94 (95% CI: - 5.68 to - 2.2) for onaBoNT-A, with a difference of - 2.48 (95% CI: - 4.57 to - 0.39). The corresponding difference in the adjusted mean change for health utility score was 0.008 (95% CI: 0.001 to 0.014). Mean treatment costs for aboBoNT-A and onaBoNT-A were 314.1 (95% CI: 299.1 to 329.0) and 346.6 (95% CI: 322.9 to 370.4) Euros, respectively. CONCLUSIONS: This comparative analysis indicated that treatment with aboBoNT-A may be less costly and lead to improved clinical outcomes when compared with onaBoNT-A, from a French healthcare system perspective. Additional comparative clinical data from larger patient cohorts, as well as more information about cost consequences of an improvement in clinical outcome would be of value to further confirm the findings.
ABSTRACT
BACKGROUND: Patients frequently require several lines of therapy for treatment of major depressive episodes. This economic analysis details the management of patients who responded inadequately due to lack of efficacy or intolerability to two previous antidepressants in the UK. METHODS: The model included a decision tree and a Markov component. Health states considered in the decision tree were remission, response, no response, withdrawal due to adverse events, relapse, recovery, and recurrence. The time horizon was 24 months. Patients were on third-line treatment for up to a 3-month acute phase and a 6-month maintenance phase. As third-line efficacy data were not available, inputs were calculated by adjusting original second-line data to third-line based on proportionate reductions observed in STAR*D. Equivalent efficacy was assumed for all comparators. Healthcare resource use and utilities were based on UK estimates. RESULTS: Vortioxetine was a cost-effective treatment option at a threshold of £20,000/QALY vs. escitalopram, citalopram, sertraline, and was associated with more health benefits, less costs (was dominant) versus relevant third-line comparators venlafaxine and duloxetine. Agomelatine was found not to be a cost-effective option. The 22-month maintenance phase treatment scenario results were similar to the 6-month base case. LIMITATIONS: Third-line efficacy data were not available. This highlights the need for studies in patients receiving third-line treatment. CONCLUSION: This model provides an overview for the management of patients receiving third-line treatment where limited evidence currently exists. Vortioxetine, with its novel mechanism of action, is expected to be a dominant treatment option versus relevant comparators in the UK.
Subject(s)
Antidepressive Agents/economics , Cost-Benefit Analysis , Depressive Disorder, Major/drug therapy , Depressive Disorder, Treatment-Resistant/drug therapy , Piperazines/economics , Sulfides/economics , Adult , Decision Trees , Depressive Disorder, Major/economics , Depressive Disorder, Treatment-Resistant/economics , Female , Humans , Treatment Outcome , United Kingdom , VortioxetineABSTRACT
The ratio of bile acids in the bile of rats with alloxan diabetes was investigated using the method of thin-layer chromatography. Changes of coefficients of conjugation and hydroxylation of bile acids were calculated and analyzed in half-hour samples of bile obtained during the 3-hour experiment. It has been found that the processes of conjugation of cholic acid with glycine and taurine are inhibited in alloxan diabetes. At the same time a significant increase of free threehydroxycholic and dixydroxycholic bile acids and conjugates of the latter ones with taurine has been registered. Coefficients of hydroxylation in alloxan diabetes show the domination of "acidic" pathway in bile acid biosynthesis that is tightly connected with the activity of mitochondrial enzymes.
Subject(s)
Bile Acids and Salts/chemistry , Bile/chemistry , Diabetes Mellitus, Experimental/metabolism , Glycine/chemistry , Taurine/chemistry , Alloxan , Animals , Animals, Outbred Strains , Bile/metabolism , Bile Acids and Salts/metabolism , Chromatography, Thin Layer , Diabetes Mellitus, Experimental/chemically induced , Glycine/metabolism , Hydroxylation , Rats , Taurine/metabolismABSTRACT
The mechanisms of support of the prooxidant-antioxidant balance in the liver tissues of geese in hypo- and hyperoxia during the transition from embryonic to postnatal development. It is proved that the formation of adaptive response to these conditions by running the neuro-humoral mechanisms that are, first, to stimulate the synthesis of antioxidants of protein nature, and secondly, to reduce the unsaturation of fatty acids in the lipids of the liver, which greatly increases their resistance to the active forms of oxygenation and thirdly, to increase the efficiency of the antioxidant defense system by improving the consistency of its components performance.
Subject(s)
Antioxidants/metabolism , Hyperoxia/metabolism , Hypoxia/metabolism , Liver/metabolism , Oxygen/metabolism , Animals , Catalase/metabolism , Embryo, Nonmammalian , Fatty Acids, Unsaturated/metabolism , Geese , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Hypoxia/embryology , Lipid Peroxidation , Oxidation-Reduction , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolismABSTRACT
The location of the Drosophila orena chromocenter in polytene chromosomes of pseudonurse cells of the D. melanogaster ovaries (the otu11 mutation) and salivary glands has been studied. Numerous sites of location of the D. orena chromocenter DNA have been found throughout the length of D. melanogaster chromosomes. The specific distribution of the binding sites for the DNA probe has made it possible to identify chromosomes and analyze their mutual positions in the three-dimensional space of the nuclei of pseudonurse cells. The mutual positions of chromosomes have been found to vary, the pericentromeric regions of different chromosomes differing from one another in associative ratios.
Subject(s)
Drosophila melanogaster/cytology , Drosophila melanogaster/genetics , Drosophila/genetics , Polytene Chromosomes/genetics , Animals , Cell Nucleus/genetics , Centromere/genetics , Chromosome Banding , Drosophila/cytology , Drosophila Proteins/genetics , Gene Library , Heterochromatin/genetics , In Situ Hybridization, Fluorescence , MutationABSTRACT
Systemic lupus erythematosus (SLE) is a disease of multifactorial etiology. Quantifying the burden of SLE across different countries can clarify the role of genetic, environmental and other causative factors in the natural history of the disease, and to understand its clinical and societal consequences. The aim of this study is to summarize data on SLE incidence and prevalence in the USA, Europe, Asia, and Australia. An extensive review of electronic resources (PubMed and MedLine) and medical journals was conducted to identify published studies on SLE incidence and prevalence over the period of 1950-early 2006. Researchers in the countries of interest provided additional information on the epidemiology of SLE. The incidence and prevalence of SLE varies considerably across the countries. The burden of the disease is considerably elevated among non-white racial groups. There is a trend towards higher incidence and prevalence of SLE in Europe and Australia compared to the U.S.A. In Europe, the highest prevalence was reported in Sweden, Iceland and Spain. There are marked disparities in SLE rates worldwide. This variability may reflect true differences across populations, or result from methodological differences of studies. The true geographic, racial, and temporal differences in SLE incidence and prevalence may yield important clues to the etiology of disease.