The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect.

Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Rosa26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in patients with OI type V. Surprisingly, expression of mutant Ifitm5 in mature osteoblasts caused no obvious skeletal abnormalities. In contrast, earlier expression in osteo-chondroprogenitors was associated with an increase in the skeletal progenitor cell population within the periosteum. Lineage tracing showed that chondrogenic cells expressing the mutant Ifitm5 had decreased differentiation into osteoblastic cells in diaphyseal bone. Moreover, mutant IFITM5 disrupted early skeletal homeostasis in part by activating ERK signaling and downstream SOX9 protein, and inhibition of these pathways partially rescued the phenotype in mutant animals. These data identify the contribution of a signaling defect altering osteo-chondroprogenitor differentiation as a driver in the pathogenesis of OI type V.

Dominant negative variants in KIF5B cause osteogenesis imperfecta via down regulation of mTOR signaling.

BACKGROUND: Kinesin motor proteins transport intracellular cargo, including mRNA, proteins, and organelles. Pathogenic variants in kinesin-related genes have been implicated in neurodevelopmental disorders and skeletal dysplasias. We identified de novo, heterozygous variants in KIF5B, encoding a kinesin-1 subunit, in four individuals with osteogenesis imperfecta. The variants cluster within the highly conserved kinesin motor domain and are predicted to interfere with nucleotide binding, although the mechanistic consequences on cell signaling and function are unknown. METHODS: To understand the in vivo genetic mechanism of KIF5B variants, we modeled the p.Thr87Ile variant that was found in two patients in the C. elegans ortholog, unc-116, at the corresponding position (Thr90Ile) by CRISPR/Cas9 editing and performed functional analysis. Next, we studied the cellular and molecular consequences of the recurrent p.Thr87Ile variant by microscopy, RNA and protein analysis in NIH3T3 cells, primary human fibroblasts and bone biopsy. RESULTS: C. elegans heterozygous for the unc-116 Thr90Ile variant displayed abnormal body length and motility phenotypes that were suppressed by additional copies of the wild type allele, consistent with a dominant negative mechanism. Time-lapse imaging of GFP-tagged mitochondria showed defective mitochondria transport in unc-116 Thr90Ile neurons providing strong evidence for disrupted kinesin motor function. Microscopy studies in human cells showed dilated endoplasmic reticulum, multiple intracellular vacuoles, and abnormal distribution of the Golgi complex, supporting an intracellular trafficking defect. RNA sequencing, proteomic analysis, and bone immunohistochemistry demonstrated down regulation of the mTOR signaling pathway that was partially rescued with leucine supplementation in patient cells. CONCLUSION: We report dominant negative variants in the KIF5B kinesin motor domain in individuals with osteogenesis imperfecta. This study expands the spectrum of kinesin-related disorders and identifies dysregulated signaling targets for KIF5B in skeletal development.

Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma that frequently becomes chemoresistant over time. The distinct mechanisms of ibrutinib and lenalidomide provided a judicious rationale to explore the combination with anti-CD20 immunotherapy. In this phase 1b study (NCT02446236), patients (n = 25) with relapsed/refractory MCL received rituximab with escalating doses of lenalidomide (days 1-21) and ibrutinib 560 mg (days 1-28) of 28-day cycles. The MTD for lenalidomide was 20 mg; most common grade ≥3 adverse events were skin rashes (32%) and neutropenic fever (24%). The best ORR was 88%, CR rate was 83%, and median duration of response (DOR) was 36.92 months (95% CI 33.77, 51.37). Responses were seen even in refractory patients or with high-risk features (e.g. blastoid variant, TP53 mutation, Ki-67 > 30%). R2I was safe and tolerable in patients with R/R MCL.

A bioinformatics screen reveals hox and chromatin remodeling factors at the Drosophila histone locus.

BACKGROUND: Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. RESULTS: To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets of 27 unique factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B), suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other factors that target the histone gene array: JIL-1, hormone-like receptor 78 (Hr78), the long isoform of female sterile homeotic (1) (fs(1)h) as well as the general transcription factors TBP associated factor 1 (TAF-1), Transcription Factor IIB (TFIIB), and Transcription Factor IIF (TFIIF). CONCLUSIONS: Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.

A bioinformatics screen reveals Hox and chromatin remodeling factors at the Drosophila histone locus.

Cells orchestrate histone biogenesis with strict temporal and quantitative control. To efficiently regulate histone biogenesis, the repetitive Drosophila melanogaster replication-dependent histone genes are arrayed and clustered at a single locus. Regulatory factors concentrate in a nuclear body known as the histone locus body (HLB), which forms around the locus. Historically, HLB factors are largely discovered by chance, and few are known to interact directly with DNA. It is therefore unclear how the histone genes are specifically targeted for unique and coordinated regulation. To expand the list of known HLB factors, we performed a candidate-based screen by mapping 30 publicly available ChIP datasets and 27 factors to the Drosophila histone gene array. We identified novel transcription factor candidates, including the Drosophila Hox proteins Ultrabithorax, Abdominal-A and Abdominal-B, suggesting a new pathway for these factors in influencing body plan morphogenesis. Additionally, we identified six other transcription factors that target the histone gene array: JIL-1, Hr78, the long isoform of fs(1)h as well as the generalized transcription factors TAF-1, TFIIB, and TFIIF. Our foundational screen provides several candidates for future studies into factors that may influence histone biogenesis. Further, our study emphasizes the powerful reservoir of publicly available datasets, which can be mined as a primary screening technique.

Evaluating the Need for Preoperative MRI Before Primary Hip Arthroscopy in Patients 40 Years and Younger With Femoroacetabular Impingement Syndrome: A Multicenter Comparative Analysis.

Background: Routine hip magnetic resonance imaging (MRI) before arthroscopy for patients with femoroacetabular impingement syndrome (FAIS) offers questionable clinical benefit, delays surgery, and wastes resources. Purpose: To assess the clinical utility of preoperative hip MRI for patients aged ≤40 years who were undergoing primary hip arthroscopy and who had a history, physical examination findings, and radiographs concordant with FAIS. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 1391 patients (mean age, 25.8 years; 63% female; mean body mass index, 25.6) who underwent hip arthroscopy between August 2015 and December 2021 by 1 of 4 fellowship-trained hip surgeons from 4 referral centers. Inclusion criteria were FAIS, primary surgery, and age ≤40 years. Exclusion criteria were MRI contraindication, reattempt of nonoperative management, and concomitant periacetabular osteotomy. Patients were stratified into those who were evaluated with preoperative MRI versus those without MRI. Those without MRI received an MRI before surgery without deviation from the established surgical plan. All preoperative MRI scans were compared with the office evaluation and intraoperative findings to assess agreement. Time from office to arthroscopy and/or MRI was recorded. MRI costs were calculated. Results: Of the study patients, 322 were not evaluated with MRI and 1069 were. MRI did not alter surgical or interoperative plans. Both groups had MRI findings demonstrating anterosuperior labral tears treated intraoperatively (99.8% repair, 0.2% debridement, and 0% reconstruction). Compared with patients who were evaluated with MRI and waited 63.0 ± 34.6 days, patients who were not evaluated with MRI underwent surgery 6.5 ± 18.7 days after preoperative MRI. MRI delayed surgery by 24.0 ± 5.3 days and cost a mean $2262 per patient. Conclusion: Preoperative MRI did not alter indications for primary hip arthroscopy in patients aged ≤40 years with a history, physical examination findings, and radiographs concordant with FAIS. Rather, MRI delayed surgery and wasted resources. Routine hip MRI acquisition for the younger population with primary FAIS with a typical presentation should be challenged.

Preoperative Magnetic Resonance Imaging Offers Questionable Clinical Utility, Delays Time to Hip Arthroscopy, and Lacks Cost-Effectiveness in Patients Aged ≤40 Years With Femoroacetabular Impingement Syndrome: A Retrospective 5-Year Analysis.

PURPOSE: To assess the clinical utility of preoperative magnetic resonance imaging (MRI) and quantify the delay in surgical care for patients aged ≤40 years undergoing primary hip arthroscopy with history, physical examination, and radiographs concordant with femoroacetabular impingement syndrome (FAIS). METHODS: From August 2015 to December 2020, 1,786 consecutive patients were reviewed from the practice of 1 fellowship-trained hip arthroscopist. Inclusion criteria were FAIS, primary surgery, and age ≤40 years. Exclusion criteria were MRI contraindication, reattempt of conservative management, or concomitant periacetabular osteotomy. After nonoperative treatment options were exhausted and a surgical plan was established, patients were stratified by those who presented with versus without MRI. Those without existing MRI received one, and any deviations from the surgical plan were noted. All preoperative MRIs were compared with office evaluation and intraoperative findings to assess agreement. Demographic data, Hip Disability and Osteoarthritis Outcome Score (HOOS)-Pain, and time from office to MRI or arthroscopy were recorded. RESULTS: Of the patients indicated by history, physical examination, and radiographs alone (70% female, body mass index 24.8 kg/m2, age 25.9 years), 198 patients presented without MRI and 934 with MRI. None of the 198 had surgical plans altered after MRI. Patients in both groups had MRI findings demonstrating anterosuperior labral tears that were visualized and repaired intraoperatively. Mean time from office to arthroscopy for patients without MRI versus those with was 107.0 ± 67 and 85.0 ± 53 days, respectively (P < .001). Time to MRI was 22.8 days. No difference between groups was observed among the 85% of patients who surpassed the HOOS-Pain minimal clinically important difference (MCID). CONCLUSION: Once indicated for surgery based on history, physical examination, and radiographs, preoperative MRI did not alter the surgical plan for patients aged ≤40 years with FAIS undergoing primary hip arthroscopy. Moreover, preoperative MRI delayed time to arthroscopy. The necessity of routine preoperative MRI in the young primary FAIS population should be challenged.

Visual inspection with acetic acid screening for cervical cancer among women receiving anti-retroviral therapy for human immunodeficiency virus infection in northern Tanzania.

AIM: To evaluate visual inspection with acetic acid (VIA) screening for cervical cancer among human immunodeficiency virus (HIV)-positive patients in an East African community. METHODS: During a July 2018 cervical cancer screen-and-treat in Mwanza, Tanzania, participants were offered free cervical VIA screening, cryotherapy when indicated, and HIV testing. Acetowhite lesions and/or abnormal vascularity were designated VIA positive in accordance with current guidelines. The association between VIA results and HIV status was compared using Chi-square and Fisher exact tests. RESULTS: Eight hundred and twenty-four of 921 consented participants underwent VIA screening and 25.0% (n = 206) were VIA positive. VIA-positive nonpregnant women (n = 147) received cryotherapy and 15 (1.8%) with cancerous-appearing lesions were referred to Bugando Hospital. Sixty-six women were HIV-positive and included 25 diagnosed with HIV at the cervical cancer VIA screening and 41 with a prior diagnosis of HIV who were receiving antiretroviral therapy (ART) at the time of cervical cancer VIA screening. Sixty-four of these 66 patients, were screened with VIA. HIV infection was not associated with VIA findings. Abnormal VIA positive screening was observed in 20.3% (n = 13) of HIV-positive patients and in 24.4% (n = 145) of HIV-negative patients (p = 0.508). A nonsignificant trend of higher VIA positive screens among newly diagnosed HIV patients of 26.1% (n = 6) versus patients with preexisting HIV on ART of 17.1% (n = 7) was observed (p = 0.580). CONCLUSION: The unexpected lack of correlation between HIV infection and VIA positivity in a community with access to ART warrants additional research regarding the previously described role of ART in attenuating HPV-mediated neoplasia.

Evaluation of retinal and optic nerve vasculature by optic coherence tomography angiography in Migraine with Aura.

PURPOSE: This study aimed to evaluate the retina by optic coherence tomography angiography (OCTA) in patients with migraine with aura (MA) in comparison with healthy controls. MATERIALS AND METHODS: A total of 60 patients with MA and 56 control subjects who applied to the Ophthalmology Clinic of Dicle University between January 2020 and February 2020 were included in this study. In all patients, the vascular density (VD) of the radial peripapillary capillaries (RPCs) and optic nerve head (ONH), the VD of deep and superficial macular vascular networks, and foveal avascular zone (FAZ) were measured. RESULTS: Patients with MA showed reduced VD measurements of the nasal and inferotemporal ONH, inferonasal RPCs, and deep macular plexus. No statistically significant difference was observed in the superficial macular VD values between the study groups. The majority of patients with MA showed hypertrophy in the deep FAZ. CONCLUSION: There was a decrease in VD measurements in the deep macular capillary plexus, ONH, and peripapillary capillaries and hypertrophy in the deep FAZ in patients with MA. According to these results, patients with MA may have an increased risk of developing ocular and systemic vascular complications. Therefore, OCTA can be used to evaluate systemic and ocular hypoperfusion in patients with MA.

Implementation of human papillomavirus video education for women participating in mass cervical cancer screening in Tanzania.

BACKGROUND: Because the global disease burden of cervical cancer is greatest in Africa, the World Health Organization has endorsed visual inspection with acetic acid screening with cryotherapy triage for the screen-and-treat approach. With the lowest doctor-to-patient ratio worldwide (1:50,000), Tanzania has nearly 10,000 new cases of cervical cancer and 7000 deaths annually. OBJECTIVE: We report on the feasibility of visual inspection with acetic acid in the severely resource-limited Mwanza district and on the impact of intervening education on baseline human papillomavirus and cervical cancer knowledge. STUDY DESIGN: Two 5-day free visual inspection with acetic acid (VIA) clinics in urban Buzuruga and rural Sangabuye on the shores of Lake Victoria were approved by our university institutional review board and local Tanzanian health authorities. Participants completed a demographic survey and a 6-question (1 point per question) multiple choice test written in Kiswahili to assess baseline knowledge. A 15-minute educational video in Kiswahili (MedicalAidFilms: Understanding screening, treatment, and prevention of cervical cancer) was followed by repeated assessment using the same test, visual inspection with acetic acid screening, and optional HIV testing. Pre- and postvideo scores and change of score were analyzed via t test, analysis of variance, and multivariate regression. Significance was considered at P<.05. RESULTS: From July 2, 2018 to July 6, 2018, 825 women were screened, and 207 women (25.1%) were VIA positive (VIA+). One hundred forty-seven VIA+ nonpregnant women received same-day cryotherapy. Seven hundred sixty women participated in an educational intervention-61.6% of whom were from an urban site and 38.2% from a rural site. The mean age was 36.4 (standard deviation, 11.1). Primary languages were Kiswahili (62.2%) and Kisukuma (30.6%). Literacy was approximately 73%, and average education level was equivalent to the seventh grade (United States). Less than 20% of urban and rural women reported access to healthcare providers. Mean score of the participants before watching the video was 2.22 (standard deviation, 1.76) and was not different between VIA+ and VIA negative groups. Mean score of the participants after watching the video was 3.86 (standard deviation, 1.78). Postvideo scores significantly improved regardless of age group, clinic site, primary language, education level, literacy, or access to healthcare provider (P<.0001). Change of score after watching the video was significantly greater in participants from urban areas (1.99±2.07) than in those from rural areas (1.07±1.95) (P<.0001). Multivariate analysis identified urban site as an independent factor in change of score (P=.0211). CONCLUSION: Visual inspection with acetic acid screening for cervical cancer is feasible and accepted in northern Tanzania. Short video-based educational intervention improved baseline knowledge on the consequences of human papillomavirus infection in the studied populations. The impact was greater in the urban setting than in the rural setting.

E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum.

The multiplexed, point-of-care measurement of specific antibodies could improve the speed with which diseases are diagnosed and their treatment initiated. To this end, we are developing E-DNA scaffold sensors, which consist of a rigid, nucleic acid "scaffold" attached on one end to an electrode and presenting both a redox reporter and an epitope on the other. In the absence of antibody, the reporter efficiently transfers electrons when interrogated electrochemically. Binding-induced steric hindrance limits movement, reducing electron transfer in a manner that is both easily measured and quantitatively related to target concentration. Previously we have used monoclonal antibodies to explore the analytical performance of E-DNA sensors, showing that they support the rapid, single-step, quantitative detection of multiple antibodies in small volume samples. Here, in contrast, we employ authentic human samples to better explore the platform's clinical potential. Specifically, we developed E-DNA sensors targeting three HIV-specific antibodies and then compared the analytical and clinical performance of these against those of gold standard serological techniques. Doing so we find that, although the multistep amplification of an ELISA leads to a lower detection limits, the clinical sensitivity of ELISAs, E-DNA sensors and lateral-flow dipsticks are indistinguishable across our test set. It thus appears that, by merging the quantitation and multiplexing of ELISAs with the convenience and speed of dipsticks, E-DNA scaffold sensors could significantly improve on current serological practice.

A Review of Clinical Informatics Competencies in Nursing to Inform Best Practices in Education and Nurse Faculty Development.

AIM: The aim of this literature review was to determine the state of the science related to clinical informatics competencies of registered nurses and to determine best practices in educational strategies for both nursing students and faculty. BACKGROUND: Continued emphasis on the provision of evidence-based patient care has implications for requisite informatics-focused competencies to be threaded throughout all levels of nursing educational programs. METHOD: Whittemore and Knalf's five-step integrative review process guided this research. An extensive search yielded 69 publications for critical appraisal. RESULTS: Results suggest nursing educational programs do not adhere to standardized criteria for teaching nursing informatics competencies. Another identified literature gap was the scarcity of research related to informatics training requirements for nurse educators. CONCLUSION: Findings support the need for continued research to provide clear direction about the expected clinical informatics competencies of graduate nurses and what training faculty need to facilitate student learning.

Cervical cancer in Tanzania: A systematic review of current challenges in six domains.

Cervical cancer is the most common cancer in Tanzania. After excluding human immunodeficiency virus, lower respiratory infections, malaria, diarrheal diseases, and tuberculosis, cervical cancer kills more women than any other form of illness in the country. Unfortunately, Tanzania has a low doctor-to-patient ratio (1:50,000) and nearly 7000 women die each year from this disease. The clinical problem is further magnified by the country's lack of resources and prevailing poverty, sporadic cervical cancer screening, prevalence of high-risk oncogenic human papillomavirus subtypes, and relatively high rates of human immunodeficiency virus co-infection. In recent years, addressing the cervical cancer problem has become a priority for the Tanzanian government. In this systematic review of 39 peer-reviewed publications that appeared in the PubMed/MEDLINE (NCBI) database from 2013 to 2018, we synthesize the growing body of literature to capture current trends in Tanzania's evolving cervical cancer landscape. Six domains were identified, including risk factors, primary prevention, barriers to screening, treatment, healthcare worker education, and sustainability. In addition to traditional risk factors associated with sexual behavior, acetowhite changes observed during visual inspection of the cervix with acetic acid, lower education, rural setting, and HIV positivity also have a noteworthy clinical impact.

Does Time-in-Range Matter? Perspectives From People With Diabetes on the Success of Current Therapies and the Drivers of Improved Outcomes.

IN BRIEF After assessing patient perspectives on the success of current diabetes therapies and the factors that have the greatest impact on daily life, we show that time-in-range is a crucial outcome for people with diabetes and that current therapies are falling short on this metric. We also show that patients feel significant stress and worry, and they believe they are falling short in diet, exercise, and weight maintenance. In addition, they believe diet and exercise and in-range blood glucose are the biggest drivers of improved diabetes management and mindset. Together, these findings support the need for therapies that improve outcomes including and beyond A1C.

A Random Forest Model for Predicting Allosteric and Functional Sites on Proteins.

We created a computational method to identify allosteric sites using a machine learning method trained and tested on protein structures containing bound ligand molecules. The Random Forest machine learning approach was adopted to build our three-way predictive model. Based on descriptors collated for each ligand and binding site, the classification model allows us to assign protein cavities as allosteric, regular or orthosteric, and hence to identify allosteric sites. 43 structural descriptors per complex were derived and were used to characterize individual protein-ligand binding sites belonging to the three classes, allosteric, regular and orthosteric. We carried out a separate validation on a further unseen set of protein structures containing the ligand 2-(N-cyclohexylamino) ethane sulfonic acid (CHES).

Combining somatic mutations present in different in vivo affinity-matured antibodies isolated from immunized Lama glama yields ultra-potent antibody therapeutics.

Highly potent human antibodies are required to therapeutically neutralize cytokines such as interleukin-6 (IL-6) that is involved in many inflammatory diseases and malignancies. Although a number of mutagenesis approaches exist to perform antibody affinity maturation, these may cause antibody instability and production issues. Thus, a robust and easy antibody affinity maturation strategy to increase antibody potency remains highly desirable. By immunizing llama, cloning the 'immune' antibody repertoire and using phage display, we selected a diverse set of IL-6 antagonistic Fabs. Heavy chain shuffling was performed on the Fab with lowest off-rate, resulting in a panel of variants with even lower off-rate. Structural analysis of the Fab:IL-6 complex suggests that the increased affinity was partly due to a serine to tyrosine switch in HCDR2. This translated into neutralizing capacity in an in vivo model of IL-6 induced SAA production. Finally, a novel Fab library was designed, encoding all variations found in the natural repertoire of VH genes identified after heavy chain shuffling. High stringency selections resulted in identification of a Fab with 250-fold increased potency when re-formatted into IgG1. Compared with a heavily engineered anti-IL-6 monoclonal antibody currently in clinical development, this IgG was at least equally potent, showing the engineering process to have had led to a highly potent anti-IL-6 antibody.

5-Fluorouracil "Chemowraps" in the Treatment of Multiple Actinic Keratoses: A Norwich Experience.

INTRODUCTION: Topical 5-fluorouracil (5-FU) has been used to treat actinic keratosis for decades. It has been an important and effective treatment which the patient can self-administer, but is limited by the surface area of skin to be treated (according to the manufacturer's guidelines) of 500 cm(2). Other topical treatments can be painful, or require hospital/health care professional input. The use of 5-FU under occlusion (chemowraps) for large areas of sun-damaged skin on the arms or legs has been described and is a potentially useful treatment option. We describe our experiences with this technique in the Norfolk and Norwich University Hospital Dermatology Department (Norwich, UK). METHODS: Five patients were recruited into this pilot study. Topical 5-FU was applied to sun-damaged limbs under occlusion, and reviewed weekly for response, and local or systemic side effects. Treatment duration was 12-14 weeks. Clinical photography was undertaken prior to, during, and after treatment to document response. RESULTS: We show that there was substantial clinical improvement in the treated skin in our patients. Experienced dermatologists reviewed all the patients, and documented the changes photographically, and by counting lesions. All patients were satisfied with their treatment regimen, and also with the end result; although two did not complete the treatment regimen due to complications not directly attributable to the treatment. CONCLUSION: Topical 5-FU under occlusion (chemowraps) may be a valid treatment option for large areas of sun-damaged skin with field cancerization changes, due to low systemic and local toxicity, and acceptability to patients.

Indoor and Outdoor Mobility following Total Knee Arthroplasty.

PURPOSE: To determine the relationship between indoor and outdoor mobility capacity in older adults with unilateral total knee arthroplasty (TKA) and, secondarily, to determine walking intensity in the same population and to compare all outcomes to a control group of older adults without knee pathology. METHOD: In this cross-sectional study, participants (TKA=16, mean 22.9 (SD 9.7) mo post TKA; control=22) completed indoor walking tests and a 580 m outdoor course that included varying terrain (e.g., curbs, grass, sidewalk) and frequent changes in direction. Walking capacity was assessed using stopwatches, global positioning system watches and accelerometers. RESULTS: Outdoor walking time was moderately correlated (p<0.05) with the timed up-and-go (TUG) test (r=0.65), stair-climb test (SCT) (r=0.67 ascending, r=0.79 descending), 10 m walk test (10 mWT) (r=0.73), and 6-minute walk test (6 MWT) (r=-0.75). Based on activity counts, walking intensity levels for participants in both groups were moderate (outdoor walk and 6 MWT). There was no significant difference in walking capacity between groups (TUG, SCT, 10 mWT, 6 MWT, outdoor walk). CONCLUSIONS: Common clinical walking tests are moderately correlated with outdoor mobility. Mobility capacity of individuals post TKA was similar to controls in both indoor and outdoor environments, and participants in both groups achieved moderate physical activity levels with walking.

Objectifs : En premier lieu, établir la relation entre la capacité de mobilité à l'intérieur et à l'extérieur chez les aînés qui ont subi une arthroplastie unilatérale totale du genou (TKA); en second lieu, évaluer l'intensité de la marche chez les mêmes individus et comparer tous les résultats à l'aide d'un groupe de contrôle composé d'aînés n'ayant aucune pathologie du genou. Méthodologie : Dans le cadre d'une étude transversale, les participants (TKA=16, moyenne de 22,9 [écart-type 9,7] mois après TKA; groupe de contrôle=22) ont effectué des tests de marche à l'intérieur et ont marché sur un parcours extérieur de 580 m sur divers types de surfaces (p. ex. bordure de chaussée, gazon, trottoir), avec changements de direction fréquents. La capacité de marche a été évaluée à l'aide de montres chronomètres, de GPS et d'accéléromètres. Résultats : Le temps de marche à l'extérieur était modérément corrélé (p<0,05) avec un test TUG (timed up-and-go); (r=0,65), un test de l'escalier (stair-climb test, SCT) (r=0,67 en montée, r=0,79 en descente), un test de marche de 10 mètres (10 mWT); (r=0,73), et un test de marche de 6 minutes (6 MWT); (r=−0,75). En fonction du décompte des activités, les niveaux d'intensité pendant la marche pour les participants des deux groupes étaient modérés (marche à l'extérieur et 6 MWT). Il n'y a pas eu de différence significative dans la capacité de marche entre les deux groupes (pour le TUG, le SCT, le 10 mWT, le 6 MWT, et la marche à l'extérieur). Conclusions : Les tests de marche cliniques habituellement utilisés sont corrélés de façon modérée avec la mobilité à l'extérieur. La capacité de mobilité chez les personnes post-TKA était similaire aux participants du groupe de contrôle à l'intérieur comme à l'extérieur, et les participants des deux groupes sont parvenus à un niveau d'activité physique modérée grâce à la marche.