81 research outputs found
Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase
No full textCopyright © 2008 Elsevier Inc. All rights reserved.UnlabelledThe objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment.ResultsA significant reduction in urinary GAG (71-79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255+/-191 m (mean+/-SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183+/-26 m (mean+/- SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117+/-25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe.ConclusionrhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.Paul Harmatz, Roberto Giugliani, Ida Vanessa D. Schwartz, Nathalie Guffon, Elisa Leão Teles, M. Clara Sá Miranda, J. Edmond Wraith, Michael Beck, Laila Arash, Maurizio Scarpa, David Ketteridge, John J. Hopwood, Barbara Plecko, Robert Steiner, Chester B. Whitley, Paige Kaplan, Zi-Fan Yu, Stuart J. Swiedler, Celeste Decker and for the MPS VI Study Grouphttp://www.elsevier.com/wps/find/journaldescription.cws_home/622920/description#descriptio
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Cost-Effectiveness of PD-L1 Testing in Non-Small Cell Lung Cancer (NSCLC) Using In Vitro Diagnostic (IVD) Versus Laboratory-Developed Test (LDT)
No full textIntroduction: Accurate PD-L1 testing for non-small cell lung cancer (NSCLC) maximizes the benefits of immune checkpoint inhibitor (ICI) drugs like pembrolizumab. False negative test results deny ICI treatments to eligible patients, worsening clinical and economic outcomes, while false positives increase costs by using ICI treatments without their benefits. This study evaluates the cost-effectiveness of PD-L1 testing with an in vitro diagnostic (IVD) compared to a laboratory-developed test (LDT) for allocating patients with NSCLC to treatment with either pembrolizumab or chemotherapy using the German healthcare system as a model. Methods: We developed a decision analytical model to evaluate the cost-effectiveness of PD-L1 testing with a regulatory body approved IVD compared to an LDT from the national German healthcare payer (statutory health insurance system) perspective. Accuracy of PD-L1 testing was based on data from two independent proficiency testing programs. The 1-year model was based on outcomes data from the KEYNOTE-024 clinical trial and treatment patterns reflecting current German practices. Results: IVDs produced accurate PD-L1 testing results in 93% (752/811) of tested cases compared to 73% (492/672) with LDTs. Most misclassifications concerned false negatives, occurring in 21% of LDTs vs 7% of IVDs. Total costs of the IVD group (48,878 €) were 196 € higher than the LDT group (48,682 €). These costs incorporate testing, first- and second-line therapy, managing treatment-related grade 3+ adverse events (AEs), and end-of-life costs for those who died within the year. Total effectiveness (percentage of patients successfully diagnosed and prescribed the correct therapy per German treatment guidelines) was 19 percentage points higher for the IVD group (88%) compared to the LDT group (69%). These differences in costs and effects lead to an incremental cost-effectiveness ratio (ICER) of 1057 €. Conclusion: Compared to LDT technology, on-label IVD use for PD-L1 testing is only slightly more costly and substantially more effective for aligning patients with PD-L1-positive NSCLC with ICI therapy according to German practice guidelines. Given these findings, changes to testing and reimbursement policies may be considered to maximize patient outcomes in NSCLC. © 2022, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Palaeontological evidence reveals convergent evolution of intervertebral joint types in amniotes
No full text© 2020, The Author(s). The intervertebral disc (IVD) has long been considered unique to mammals. Palaeohistological sampling of 17 mostly extinct clades across the amniote tree revealed preservation of different intervertebral soft tissue types (cartilage, probable notochord) seen in extant reptiles. The distribution of the fossilised tissues allowed us to infer the soft part anatomy of the joint. Surprisingly, we also found evidence for an IVD in fossil reptiles, including non-avian dinosaurs, ichthyosaurs, plesiosaurs, and marine crocodiles. Based on the fossil dataset, we traced the evolution of the amniote intervertebral joint through ancestral character state reconstruction. The IVD evolved at least twice, in mammals and in extinct diapsid reptiles. From this reptilian IVD, extant reptile groups and some non-avian dinosaurs independently evolved a synovial ball-and-socket joint. The unique birds dorsal intervertebral joint evolved from this dinosaur joint. The tuatara and some geckos reverted to the ancestral persisting notochord
The Effect of Administering Platelet Rich Plasma in Cases of Intervertebral Disc Degeneration
No full textIntroduction: Intervertebral disc (IVD) degeneration is a significant contributor to persistent back pain, with the IVD serving a vital mechanical role in weight transfer, energy dissipation, and joint mobility. The nucleus pulposus and annulus fibrosus work together to distribute and transmit loads between vertebral bones. Platelet-rich plasma (PRP), containing various growth factors, has gained attention due to its potential in clinical settings for stimulating cell growth and proliferation. This study explores the potential of autologous PRP therapy for improving degenerating IVD.
Objectives: The objective of this study is to assess the effectiveness of autologous PRP therapy in improving degenerating IVD based on clinical and histological features.
Methods: The author conducted an evidence acquisition process by analyzing and synthesizing information from various references. We used "intervertebral disc degeneration" and "platelet-rich plasma" as keywords to search for relevant literature on PubMed, Google Scholar, ProQuest, and Clinical Key. The data for this study were extracted from a total of 10 articles, comprising 6 experimental studies and 4 clinical trial studies.
Results: The study findings reveal that autologous PRP therapy induces significant improvements in degenerating IVD based on both clinical and histological features.
Conclusions: This study suggests that autologous PRP therapy is an effective approach for enhancing degenerating IVD, as evidenced by improvements in clinical and histological features. This research underscores the potential of PRP as a valuable technique in the clinical setting for addressing IVD degeneration and its associated back pain
INTERVERTEBRAL SIZE MEASUREMENT WITH ANTHROPOMETRIC METHOD
No full textBackground. There is a positive correlation between the size of intervertebral disc (IVD) and the incidence of Low Back Pain (LBP). Columbini evaluated the size of IVD anthropometricaly but how this measurement correlates with radiologic measurements of IVD square size is steel unknown.Objective. The aim of the study was to search for non-invasive method and cheap and fast evaluation of IVD size with the modification of Columbini’s antropometric formula.Materials and methods. The measurements (anthropometrics, X-ray, CT with range of interest measurement [ROI]) were done on 40 bus-drivers. The realibility test was done on 65 bus-drivers.Results. CT measurement of the size of the intervertebral disc was done using ROI (Range of Interest). Using the statistical analysis based on linear regression, correlation, curve fitting and realibility the author made the modification of Columbini’s formula. The incidence of Low Back Pain was statistically significantly higher in people with smaller IVD, particularly in men.Conclusions. With the Columbini’s method of anthropometric measurement of the size of IVD modified by Turk it is possible to make the right measurement prognosis in 89% of cases. Consequently, there is no need to use invasive and costly diagnostic radiologic methods.</p
evidence of efficient transmission of HGV by the sexual route
No full textThe importance of sexual transmission in the epidemiology of hepatitis G
virus (HGV) and hepatitis C virus (HCV) was evaluated in two groups of HIV-1-positive
Lebanese patients. Members of one group (90 patients) were HIV-1-infected via sexual
route and denied intravenous drug (IVD) use, while members of the other group (28
patients) became HIV-1-infected parenterally and confessed frequent IVD use. The
overall prevalence of HGV infection was relatively high in both groups and with no
statistically significant difference between them (28% among IVD users vs 32% among
the non-IVD users) despite the fact that non-IVD users were significantly older (32.7+1.7
years) than the IVD users (24.0+1.4 years) (P50.01). Conversely, there was a clear
association between IVD use and HCV infection (25% for IVD users vs 7% for non-IVD
users) despite the significantly lower age of the IVD users. These results point to the
efficient transmission of HGV via the sexual route, while the transmission of HCV is
mainly via the parenteral route. CD4+ lymphocyte counts were known on only 82 HIV-
1-infected patients. Although the number of HGV-RNA-positive patients (three) was
small compared with anti-HGV-positive patients (24), a relationship was not found
between CD4+ lymphocyte counts and the presence of HGV-RNA in the HIV-1-positive
patients. The role of HGV in causing significant liver disease is still under disputePublishedN/
Acurracy assessment of four diagnostic tests for the detection of Giardia and Cryptosporidium in the absence of gold standard: a Bayesian approach
No full text2014 Fall.Includes bibliographical references.Giardia and Cryptosporidium are important parasites that cause gastrointestinal disease in numerous animal species including dogs and cats. The accurate diagnostic of this diseases is cucial for the aplication of preventive measures and precise treatment. Estimation of test accuraccy is not difficult when a reference test (gold standard) is available. However, when a gold standard test is not available the Bayesian Latent Class (BLC) Analysis is an effective analytical tool for the estimation of diagnostic accuracy. The aim of this study was to estimate the sensitivity (Se) and specificity (Sp) of four commercial diagnostic kits using BLC. The four diagnostic tests were (1) Merifluor®Direct Fluorecence Antigen (DFA; Giardia/Cryptosporidium; Meridian Diagnostics, Inc., Cincinnati, Ohio), (2) IVD®DFA (Giardia/Cryptosporidium; IDV Research Inc., Carlsbad, CA), (3) IVD Microwell ELISA® (Giardia ; IDV Research Inc., Carlsbad, CA), (4) and IDEXX SNAP® (Giardia ; IDEXX Laboratories Inc., Westbrook, ME). The results from 201 laboratory analysed samples, the prior distributions elicited from three experts, and the consistency of samples as splitting covariate were used as inputs for the BCL models. The estimated Se and Sp of the tests were 87.7% and 97.3% (Merifluor-Cryptosporidium), 68.0% and 99.1% (IVD-Cryptosporidium), 93.6% and 97.9% (Merifluor-Giardia), 96.1% and 97.9% (IVD-Giardia), 86.0% and 98.2% (ELISA-Giardia), and 84.8% and 98.0% (SNAP-Giardia) respectively. The prevalence for non-diarrheic versus diarrheic samples were 2.3% and 4.8% (Cryptosporidium), and 6.9% and 13.5% (Giardia) respectively. We were able to use BLC to assess the sensitivity and specificity of the four commercial diagnostic tests. We ran 36 models and used objective indicators of the performances of the models to choose the best model for estimation of parameters. The results of the study indicated that Merifluor, IVD, and ELISA are equally suitable as diagnostic tests for detection of Giardia. For detection of Cryptosporidium, Merifluor was more accurate than the IVD test
In-vitro models of disc degeneration - A review of methods and clinical relevance.
No full textThis is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThe intervertebral disc (IVD) provides flexibility, acts as a shock absorber, and transmits load. Degeneration of the IVD includes alterations in the biomechanics, extracellular matrix (ECM), and cellular activity. These changes are not always perceived, however, IVD degeneration can lead to severe health problems including long-term disability. To understand the pathogenesis of IVD degeneration and suitable testing methods for emerging treatments and therapies, this review documents in-vitro models of IVD degeneration including physical disruption, hyperphysiological loading, ECM degradation by enzyme digestion, or a combination of these methods. This paper reviews and critically analyses the models of degeneration published since the year 2000 in either in human or animal specimens. The results are categorised in terms of the IVD biomechanics, physical attributes, ECM composition, tissue damage and cellularity to evaluate the models with respect to natural human degeneration, and to provide recommendations for clinically relevant models for the various stages of degeneration. There is no one model that replicates the wide range of degenerative changes that occur as part of normal degeneration. However, cyclic overloading replicates many aspects of degeneration, with the advantage of a dose-response allowing the tuning of damage initiated. Models of severe degeneration are currently lacking, but there is potential that combining cyclic overloading and enzymatic digestion will provide model that closely resembles human IVD degeneration. This will provide an effective way to investigate the effects of severe degeneration, and the evaluation of treatments for the IVD, which would generally be indicated at this advanced stage of degeneration
Birth weight and birth rate of heavy calves conceived by transfer of in vitro or in vivo produced bovine embryos. Anim Reprod Sci 2000; 64:13–20
No full textAbstract The aim of this study was to evaluate the difference in birth weight and gestation length between Japanese Black calves obtained from transfer of bovine embryos produced in vitro (IVP) and those developed in vivo (IVD). An additional objective was to clarify the sire effect on birth weight and gestation length and to examine the birth rate of heavier calves. Two Japanese Black bulls breed at our experimental station were used as a semen source for production of IVP and IVD embryos. Thirty-eight Japanese Black heifers and cows of various genetic backgrounds were used as embryo donors for IVD embryos. Ovaries for IVP embryos were collected at random at a local slaughterhouse from Japanese Black cattle of various genetic backgrounds. IVP embryos were produced using co-culturing with cumulus cells in 5% CS + TCM 199. Both the IVD and IVP embryos were transferred non-surgically to Holstein recipients on day 7 ± 1 of estrous cycle. In this study, the birth weights and gestation lengths of half-sib single calves for bull A and B were analyzed. The numbers of single calves born by transfer of IVP and IVD embryos for bull A and B were 133 and 121, 243 and 465, respectively. The birth weight of the IVP calves was significantly higher (P < 0.01) than that of the IVD (bull A: 31.0 ± 0.4 kg versus 27.2 ± 0.4 kg and bull B: 29.9 ± 0.6 kg versus 26.6 ± 0.2 kg). Gestation length of the IVP calves for bull A was significantly longer (P < 0.01) than that of the IVD (291.9±0.9 days versus 283.6±0.5 days). However, for bull B, there were no differences in gestation length between the IVP and IVD calves (285.9 ± 0.7 days versus 286.2 ± 0.3 days). These results clearly indicated that IVP calves had heavier birth weights than IVD calves but that the average gestation length of IVP calves was not always longer than that of IVD calves. Furthermore, the birth rate of heavier calves and the incidence of stillbirth and * Corresponding author. Tel.: +81-229723101; fax: +81-229722326. E-mail address: [email protected] (T. Numabe). 0378-4320/00/$ -see front matter © 2000 Elsevier Science B.V. All rights reserved. PII: S 0 3 7 8 -4 3 2 0 ( 0 0 ) 0 0 1 9 0 -1 14 T. Numabe et al. / Animal Reproduction Science 64 (2000) [13][14][15][16][17][18][19][20] perinatal mortality up to 48 h post partum in IVP calves (bull A: 11.3%, bull B: 7.8%) were greater (P < 0.05) than those in IVD calves from both bulls (bull A: 4.1%, bull B: 3.7%)
The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain
No full textIn 2007, three times as many peer reviewed publications covering the biology and biotherapeutics of intervertebral disc (IVD) disease appeared in the literature than in 1997. This is testimony to the upsurge in interest in the IVD, mainly driven by the openings that modern molecular pathology has generated to investigate mechanisms of human disease and the potential offered by novel therapeutic technologies to use data coming from these studies to positively influence chronic discogenic back pain and sciatica. Molecular pathology has shown IVD degeneration, a major cause of low back pain, to be a complex, active disorder in which disturbed cytokine biology, cellular dysfunction and altered load responses play key roles. This has translated into a search for target molecules and disease processes that might be the focus of future, evidence-based therapies for back pain. It is not possible to describe the totality of advances that have been made in understanding the biology of the IVD in recent years, but in this review those areas of biology that are currently influencing, or could conceivably soon impinge on, clinical thinking or practice around IVD degeneration and discogenic back pain are described and discussed. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved
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