Hereditary multiple exostoses (HME), the most frequent of all skeletal dysplasias, is an autosomal dominant disorder characterized by the presence of multiple exostoses localized mainly at the end of long bones. HME is genetically heterogeneous, with at least three loci, on 8q24.1 (EXT1), 11p11-p13 (EXT2), and 19p (EXT3). Both the EXT1 and EXT2 genes have been cloned recently and define a new family of potential tumor suppressor genes. This is the first study in which mutation screening has been performed for both the EXT1 and EXT2 genes prior to any linkage analysis. We have screened 17 probands with the HME phenotype, for alterations in all translated exons and flanking intronic sequences, in the EXT1 and EXT2 genes, by conformation-sensitive gel electrophoresis. We found the disease-causing mutation in 12 families (70%), 7 (41%) of which have EXT1 mutations and 5 (29%) EXT2 mutations. Together with the previously described 1-bp deletion in exon 6, which is present in 2 of our families, we report five new mutations in EXT1. Two are missense mutations in exon 2 (G339D and R340C), and the other three alterations (a nonsense mutation, a frameshift, and a splicing mutation) are likely to result in truncated nonfunctional proteins. Four new mutations are described in EXT2. A missense mutation (D227N) was found in 2 different families; the other three alterations (two nonsense mutations and one frameshift mutation) lead directly or indirectly to premature stop codons. The missense mutations in EXT1 and EXT2 may pinpoint crucial domains in both proteins and therefore give clues for the understanding of the pathophysiology of this skeletal disorder.
BackgroundSurgical procedures are now very common, with estimates ranging from 4% of the general population having an operation per annum in economically-developing countries; this rising to 8% in economically-developed countries. Whilst these surgical procedures typically result in considerable improvements to health outcomes, it is increasingly appreciated that surgery is a high risk industry. Tools developed in the aviation industry are beginning to be used to minimise the risk of errors in surgery. One such tool is the World Health Organization's (WHO) surgery checklist. The National Patient Safety Agency (NPSA) manages the largest database of patient safety incidents (PSIs) in the world, already having received over three million reports of episodes of care that could or did result in iatrogenic harm. The aim of this study was to estimate how many incidents of wrong site surgery in orthopaedics that have been reported to the NPSA could have been prevented by the WHO surgical checklist.MethodsThe National Reporting and Learning Service (NRLS) database was searched between 1st January 2008- 31st December 2008 to identify all incidents classified as wrong site surgery in orthopaedics. These incidents were broken down into the different types of wrong site surgery. A Likert-scale from 1-5 was used to assess the preventability of these cases if the checklist was used.Results133/316 (42%) incidents satisfied the inclusion criteria. A large proportion of cases, 183/316 were misclassified. Furthermore, there were fewer cases of actual harm [9% (12/133)] versus 'near-misses' [121/133 (91%)]. Subsequent analysis revealed a smaller proportion of 'near-misses' being prevented by the checklist than the proportion of incidents that resulted in actual harm; 18/121 [14.9% (95% CI 8.5 - 21.2%)] versus 10/12 [83.3% (95%CI 62.2 - 104.4%)] respectively. Summatively, the checklist could have been prevented 28/133 [21.1% (95%CI 14.1 - 28.0%)] patient safety incidents.DiscussionOrthopaedic surgery is a high volume specialty with major technical complexity in terms of equipment demands and staff training and familiarity. There is therefore an increased propensity for errors to occur. Wrong-site surgery still occurs in this specialty and is a potentially devastating situation for both the patient and surgeon. Despite the limitations of inclusion and reporting bias, our study highlights the need to match technical precision with patient safety. Tools such as the WHO surgical checklist can help us to achieve this.
Objective. Symptomatic knee osteoarthritis (OA) is present in 1 in 8 patients age >60 years and is associated with significant activity limitation. Several tools have been devised to assess knee problems. The goal of this study was to evaluate the Oxford Knee Scale (OKS) against strict modern psychometric standards through application of the Rasch measurement model. Methods. A total of 224 OKS assessments were included from patients with a clinical diagnosis of knee OA. Data from the OKS were fitted to the Rasch measurement model. We examined the validity of the item scoring functions, the presence of item bias or differential item functioning, the fit of data to model expectations, and whether or not the item set formed a unidimensional scale, thus giving a valid summed score. Results. The mean age of the 224 patients was 61 years (range 26 -90) and 61.5% were women. After rescoring some items, the scale showed good fit to the Rasch model, with a chi-square interaction statistic of 42.663 (36 df, P ؍ 0.206). Overall targeting of the scale (to the patients) was good, with high reliability. Conclusion. Data from the OKS were consistent with the expectations of the unrestricted (partial credit) derivation of the Rasch model. The targeting of the instrument shows good coverage of thresholds across the whole construct and has good reliability (internal consistency) with a high patient separation. Consequently, this scale can be used in confidence with the knowledge that it is a unidimensional scale largely free of bias.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.