Longitudinal Validity and Minimal Important Change for the Modified Lower Extremity Functional Scale (LEFS) in Orthopedic Foot and Ankle Patients

The lower extremity functional scale (LEFS) is a patient-reported outcome measure for lower extremity disorders. Aim of this study was to assess the longitudinal validity including responsiveness and test-retest reliability of the revised 15-item version, and to define the minimal important change (MIC) of the modified LEFS in a generic sample of orthopedic foot and ankle patients who underwent surgery. Responsiveness, effect size, and standardized response mean were measured by determining the score change between the baseline and 6 months administration of the LEFS from 156 patients. There was no significant difference between preoperative (median 78, interquartile range [IQR] 64.2-90.3) and postoperative (median 75.0, IQR 61.7-95.0) scores. Both effect size and standardized response mean were low (0.06 and 0.06, respectively). Test-retest reliability of the LEFS was satisfactory. Intraclass correlation coefficient was 0.85 (95% confidence interval 0.81-0.88). MIC value could not be estimated due to the lack of significant score change. The modified LEFS presented with relatively low longitudinal validity in a cohort of generic orthopedic foot and ankle patients. The findings of this study indicate that the modified LEFS might not be the optimal instrument in assessing the clinical change over time for these patients. (c) 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Peer reviewe

Structural and Construct Validity of the Foot and Ankle Ability Measure (FAAM) With an Emphasis on Pain and Functionality After Foot Surgery : A Multicenter Study

The Foot and Ankle Ability Measure (FAAM) is a patient-reported outcome measure that is available in several languages. We aim to assess the structural and construct validity of the FAAM with an emphasis on pain and functionality after foot surgery. The activities of daily living (ADL) and Sports subscales of the Finnish version of the FAAM were completed by 182 patients who underwent operative treatment for disorders of the foot. Convergent validity was assessed by principal component analysis using Spearman's correlation coefficient between the FAAM subscales and the principal components (Function-PC and Pain-PC) derived from validated patient-reported outcome measures. Subscales were studied for floor and ceiling effects, internal consistency and unidimensionality. Internal consistency was examined with Cronbach's alpha and the subscale structure with exploratory factor analysis. FAAM-ADL had high correlation with the Function-PC (r = 0.87, 95% confidence interval [CI] 0.81-0.91) and the Pain-PC (r = 0.75, 95% CI 0.65-0.83). FAAM-Sports had moderate correlation (r = 0.64, 95% CI 0.50-0.74) with the Function-PC and high correlation (r = 0.74, 95% CI 0.64-0.82) with the Pain-PC. No floor or ceiling effects were observed. Cronbach's alpha was 0.97 (95% CI 0.96-0.98) for the ADL and 0.93 (95% CI 0.91-0.95) for the Sports subscales. The results supported the unidimensionality of the FAAM-Sports. Within the ADL subscale, 3 factors were identified, suggesting a 3-factor model for the FAAM overall. Results highlighted the inter-relationship of pain and physical function. Further research on longitudinal validity is needed. (C) 2021 The Author(s).Peer reviewe

Treatment of hallux rigidus (HARD trial) : study protocol of a prospective, randomised, controlled trial of arthrodesis versus watchful waiting in the treatment of a painful osteoarthritic first metatarsophalangeal joint

Introduction Hallux rigidus is a common problem of pain and stiffness of the first metatarsophalangeal joint (MTPJ) caused mainly by degenerative osteoarthritis. Several operative techniques have been introduced for the treatment of this condition without high-quality evidence comparing surgical to non-surgical care. In this trial, the most common surgical procedure, arthrodesis, will be compared with watchful waiting in the management of hallux rigidus. Methods and analysis Ninety patients (40 years or older) with symptomatic first MTPJ osteoarthritis will be randomised to arthrodesis or watchful waiting in a ratio of 1:1. The primary outcome will be pain during walking, assessed using the 0-10 Numerical Rating Scale (NRS) at 1 year after randomisation. The secondary outcomes will be pain at rest (NRS), physical function (Manchester-Oxford Foot Questionnaire), patient satisfaction in terms of the patient-acceptable symptom state, health-related quality of life (EQ-5D-5L), activity level (The Foot and Ankle Ability Measure Sports subscale), use of analgesics or orthoses and the rate of complications. Our null hypothesis is that there will be no difference equal to or greater than the minimal important difference of the primary outcome measure between arthrodesis and watchful waiting. Our primary analysis follows an intention-to-treat principle. Ethics and dissemination The study protocol has been approved by the Ethics Committee of Helsinki and Uusimaa Hospital District, Finland. Written informed consent will be obtained from all the participants. We will disseminate the findings of this study through peer-reviewed publications and conference presentations. Protocol version 21 June 2021 V.2.0.Peer reviewe

Validation of the Western Ontario and McMaster Universities Osteoarthritis Index in Patients Having Undergone Ankle Fracture Surgery

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a patient-reported outcome measure (PROM) that is widely used to evaluate the pain, stiffness, and physical function of patients with osteoarthritis of the hip and knee. Although the WOMAC has also been used for patients after foot and ankle surgery, it has not been validated for this purpose. A total of 130 patients with surgically treated ankle fractures completed the WOMAC, Visual Analogue Scale Foot and Ankle (VAS FA), Lower Extremity Functional Scale (LEFS), 15D Health-Related Quality-of-Life Questionnaire (15D), and Visual Analog Scale for General Health (VAS general health) after foot and ankle surgery. The structural validity of the WOMAC was assessed by using Cronbach's a, and convergent validity was tested between the WOMAC and reference outcome measures. Cronbach's a for the index score was 0.98 and 0.95, 0.86, and 0.98 for the Pain, Stiffness, and Physical Function subscales, respectively. The Spearman correlation coefficients were -0.84, -0.74, -0.58, and 0.55 for the VAS-FA, LEFS, 15D, and VAS general health, respectively. The relationships with the VAS-FA, LEFS, 15D, and VAS general health were strong. All relationships were statistically significant (p <.001). The WOMAC provides valid scores for assessing pain, stiffness, and physical function in patients having undergone ankle fracture surgery. (C) 2019 by the American College of Foot and Ankle Surgeons. All rights reserved.Peer reviewe

ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes

ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Biochemically validated analysis in human T-cells reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind one order of magnitude more promoters than previously thought. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the resolution of a more complete map of transcriptional targets reveals that MYC binds nearly all promoters bound by NOTCH1. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs

Structural validity of the foot and ankle outcome score for orthopaedic pathologies with Rasch Measurement Theory

Publisher Copyright: © 2021 The AuthorsA B S T R A C T Background: The Foot and Ankle Outcome Score (FAOS) is one of the most frequently used patient reported outcome measures for foot and ankle conditions. The aim is to test the structural validity of the Finnish version of the FAOS using Rasch Measurement Theory. Methods: FAOS scores were obtained from 218 consecutive patients who received operative treatment for foot and ankle conditions. The FAOS data were fitted into the Rasch model and person separation index (PSI) calculated. Results: All the five subscales provided good coverage and targeting. Three subscales presented unidimensional structure. Thirty-eight of the 42 items had ordered response category thresholds. Three of the 42 items had differential item functioning towards gender. All subscales showed sufficient fit to the Rasch model. PSI ranged from 0.73 to 0.94 for the subscales. Conclusions: The Finnish version of the FAOS shows acceptable structural validity for assessing complaints in orthopaedic foot and ankle patients. (c) 2021 The Authors. Published by Elsevier Ltd on behalf of European Foot and Ankle Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

An intuitionistic approach to scoring DNA sequences against transcription factor binding site motifs

Background: Transcription factors (TFs) control transcription by binding to specific regions of DNA called transcription factor binding sites (TFBSs). The identification of TFBSs is a crucial problem in computational biology and includes the subtask of predicting the location of known TFBS motifs in a given DNA sequence. It has previously been shown that, when scoring matches to known TFBS motifs, interdependencies between positions within a motif should be taken into account. However, this remains a challenging task owing to the fact that sequences similar to those of known TFBSs can occur by chance with a relatively high frequency. Here we present a new method for matching sequences to TFBS motifs based on intuitionistic fuzzy sets (IFS) theory, an approach that has been shown to be particularly appropriate for tackling problems that embody a high degree of uncertainty. Results: We propose SCintuit, a new scoring method for measuring sequence-motif affinity based on IFS theory. Unlike existing methods that consider dependencies between positions, SCintuit is designed to prevent overestimation of less conserved positions of TFBSs. For a given pair of bases, SCintuit is computed not only as a function of their combined probability of occurrence, but also taking into account the individual importance of each single base at its corresponding position. We used SCintuit to identify known TFBSs in DNA sequences. Our method provides excellent results when dealing with both synthetic and real data, outperforming the sensitivity and the specificity of two existing methods in all the experiments we performed. Conclusions: The results show that SCintuit improves the prediction quality for TFs of the existing approaches without compromising sensitivity. In addition, we show how SCintuit can be successfully applied to real research problems. In this study the reliability of the IFS theory for motif discovery tasks is proven

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

Lower extremity functional scale -mittarin suomenkielisen version 155 Rasch-osioanalyysin tulokset nilkka- ja jalkateräpotilailla

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