A rare case of histiocytic proliferative disease in a cat.

A 7-year-old intact female domestic medium hair cat was examined at a veterinary clinic for a scabbed nodule over the right shoulder. Multiple nodules recurred at the same site after the first surgical excision, and a second surgical excision was performed. Histopathology demonstrated high-mitotic-rate neoplastic cells and therefore a histiocytic proliferative disease was initially suspected. The condition progressed rapidly within a 5-month period and the cat was euthanized due to sudden onset of severe dyspnea. Necropsy showed diffuse metastatic nodules in the lungs, confirming a histiocytic proliferative disease, with histiocytic sarcoma being the most likely differential diagnosis.

Un cas rare de maladie histiocytaire proliférative chez un chat. Une chatte domestique á poil moyen intacte de 7 ans a été examinée dans une clinique vétérinaire pour un nodule croûteux sur l'épaule droite. Plusieurs nodules sont réapparus au même site après la première excision chirurgicale, et une deuxième excision chirurgicale a été réalisée. L'histopathologie a mis en évidence des cellules néoplasiques á taux mitotique élevé et, par conséquent, une maladie proliférative histiocytaire a été initialement suspectée. L'état a progressé rapidement en l'espace de 5 mois et le chat a été euthanasié en raison de l'apparition soudaine d'une dyspnée sévère. L'autopsie a montré des nodules métastatiques diffus dans les poumons, confirmant une maladie proliférative histiocytaire, le sarcome histiocytaire étant le diagnostic différentiel le plus probable.(Traduit par Dr Serge Messier).

Reliability and Convergent Construct Validity of Quantitative Ultrasound for Synovitis, Meniscal Extrusion, and Osteophyte in Knee Osteoarthritis With MRI.

AIMS: To determine: 1) inter-rater reliability of quantitative measurements of ultrasound-detected synovitis, meniscal extrusion, and osteophytes; and 2) construct (convergent) validity via correlations and absolute agreements between ultrasound- and gold-standard magnetic resonance imaging (MRI)-outcomes in knee osteoarthritis. METHODS: Dynamic ultrasound images for supra-patellar synovitis, meniscal extrusion, and osteophytes were acquired and quantified by a physician operator, musculoskeletal ultrasonographer, and medical student independently. On the same day, 3T MRI images were acquired. Effusion-synovitis, meniscal extrusion, and osteophytes were quantified on sagittal or coronal proton-density-weighted fat-suppressed noncontrast TSE sequences, respectively. Intra-class correlation coefficients (ICCs), Pearson's correlations (r), and Bland-Altman plots were used to analyze inter-rater reliability, and correlations, and agreements between the two imaging modalities. RESULTS: Eighty-nine participants [48 females (53.9%)] with mean (standard deviation) age of 61.5 ± 6.9 years were included. The inter-rater reliability was excellent for osteophytes (ICC range = 0.90-0.96), meniscal extrusion (ICC range = 0.90-0.93), and synovitis (ICC range = 0.86-0.88). The correlations between ultrasound pathologies and their MRI counterparts were very strong (ICC range = 0.85-0.98) except for lateral meniscal extrusion [0.66 (95% CI, 0.52-0.76)]. Bland-Altman plots showed 0.01, 0.05, 0.10, 0.53, and 0.60 mm larger size in ultrasound medial tibial and medial femoral osteophytes, medial meniscal extrusions, synovitis, and lateral meniscal extrusions with 95% limits of agreements [±0.39, ±0.44, ±0.85, ±0.70, and ±0.90 (SDs)] than MRI measures, respectively. The lines of equality were within 95% CI of the mean differences (bias) only for medial osteophytes and medial meniscal extrusion. CONCLUSION: The quantitative assessment of synovitis, meniscal extrusion, and osteophytes generally showed excellent inter-rater reliability and strong correlations with MRI-based measurements. Absolute agreement was strong for medial tibiofemoral pathologies.

Single-Cell Transcriptomic Profiling in Inherited Retinal Degeneration Reveals Distinct Metabolic Pathways in Rod and Cone Photoreceptors.

The cellular mechanisms underlying hereditary photoreceptor degeneration are still poorly understood. The aim of this study was to systematically map the transcriptional changes that occur in the degenerating mouse retina at the single cell level. To this end, we employed single-cell RNA-sequencing (scRNA-seq) and retinal degeneration-1 (rd1) mice to profile the impact of the disease mutation on the diverse retinal cell types during early post-natal development. The transcriptome data allowed to annotate 43,979 individual cells grouped into 20 distinct clusters. We further characterized cluster-specific metabolic and biological changes in individual cell types. Our results highlight Ca2+-signaling as relevant to hereditary photoreceptor degeneration. Although metabolic reprogramming in retina, known as the 'Warburg effect', has been documented, further metabolic changes were noticed in rd1 mice. Such metabolic changes in rd1 mutation was likely regulated through mitogen-activated protein kinase (MAPK) pathway. By combining single-cell transcriptomes and immunofluorescence staining, our study revealed cell type-specific changes in gene expression, as well as interplay between Ca2+-induced cell death and metabolic pathways.

Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial.

Importance: Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing. Objective: To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA. Design, Setting, and Participants: This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020. Interventions: Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants). Main Outcomes and Measures: The 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up. Results: Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of -2.1 vs -1.8 points, respectively (difference, -0.4 [95% CI, -0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was -1.4% vs -1.2%, respectively (difference, -0.2% [95% CI, -1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences. Conclusions and Relevance: Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617000853347.

Current status and future prospects for disease modification in osteoarthritis.

OA is a chronic, progressive and disabling joint disease, leading to a poor quality of life and an enormous social and economic burden. Current therapies for OA patients remain limited, which creates an area of huge unmet medical need. For some time, researchers have been looking for approaches that can inhibit the structural progression of OA. A variety of potential disease-modifying OA drugs have been developed, targeting cartilage, inflammatory pathways or subchondral bone. In addition, non-pharmacological therapies, including joint distraction and weight loss, draw increasing attention, with some showing disease-modifying potential. Thus we performed a comprehensive review to discuss the current status of disease-modifying therapies in OA and appraise the potentials of emerging novel agents.

Disease-modifying drugs in osteoarthritis: current understanding and future therapeutics.

INTRODUCTION: Osteoarthritis (OA) is a leading cause of pain and disability among adults with a current prevalence of around 15% and a predicted prevalence of 35% in 2030 for symptomatic OA. It is increasingly recognized as a heterogeneous multi-faceted joint disease with multi-tissue involvement of varying severity. Current therapeutic regimens for OA are only partially effective and often have significant associated toxicities. There are no disease-modifying drugs approved by the regulatory bodies. Areas covered: We reviewed the opportunities within key OA pathogenetic mechanism: cartilage catabolism/anabolism, pathological remodeling of subchondral bone and synovial inflammation to identify targeted disease-modifying osteoarthritis drugs, based on compounds currently in Phase II and III stages of clinical development in which x-ray and/or MRI was used as the structural outcome with/without symptomatic outcomes according to regulatory requirements. Expert opinion: Given the heterogeneity of the OA disease process and complex overlapping among these phenotypes, a 'one size fits all' approach used in most clinical trials would unlikely be practical and equally effective in all patients, as well as in all anatomical OA sites. On the other hand, it is a challenge to develop a targeted drug with high activity, specificity, potency, and bioavailability in the absence of toxicity for long-term use in this chronic disease of predominantly older adults. Further research and insight into evaluation methods for drug-targeted identification of early OA and specific characterization of phenotypes, improvement of methodological designs, and development/refinement of sensitive imaging and biomarkers will help pave the way to the successful discovery of disease-modifying drugs and the optimal administration strategies in clinical practice.

Efficacy of intra-articular injections of platelet-rich plasma as a symptom- and disease-modifying treatment for knee osteoarthritis - the RESTORE trial protocol.

BACKGROUND: Knee osteoarthritis (OA) causes substantial pain, physical dysfunction and impaired quality of life. There is no cure for knee OA, and for some people, the disease may involve progressive symptomatic and structural deterioration over time. Platelet-rich plasma (PRP) is a therapeutic agent that aims to address underlying biological processes responsible for OA pathogenesis. As such, it has the potential to improve both symptoms and joint structure. The aim of this clinical trial is to determine whether a series of injections of PRP into the knee joint will lead to a significantly greater reduction in knee pain, and less loss of medial tibial cartilage volume over 12 months when compared to a series of placebo saline injections in people with knee OA. METHODS: This will be a two-group, superiority, randomised, participant-, interventionist- and assessor-blinded, placebo-controlled trial. Two hundred and eighty-eight participants aged over 50 years with painful knee OA and mild to moderate structural change on x-ray (Kellgren and Lawrence grade 2 and 3) will be randomly allocated to receive either three PRP injections or three normal saline injections into the knee joint at weekly intervals. The primary outcomes will be 12-month change in average overall knee pain severity (numeric rating scale) and medial tibial cartilage volume (magnetic resonance imaging (MRI)). Secondary outcomes include additional measures of knee pain and other symptoms, function in daily living and sport and recreation, quality of life, participant-perceived global ratings of change, and other MRI structural outcomes including meniscal and cartilage morphology, synovitis, effusion, bone marrow lesions and cartilage defects. A range of additional measures will be recorded, and a separate health economic evaluation will be performed. DISCUSSION: The findings from this study will help determine whether PRP improves both clinical and structural knee OA outcomes over 12 months when compared to a series of placebo saline injections. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry reference: ACTRN12617000853347 . Prospectively registered 9th of June 2017.

Mouse model of human RPE65 P25L hypomorph resembles wild type under normal light rearing but is fully resistant to acute light damage.

Human RPE65 mutations cause a spectrum of blinding retinal dystrophies from severe early-onset disease to milder manifestations. The RPE65 P25L missense mutation, though having <10% of wild-type (WT) activity, causes relatively mild retinal degeneration. To better understand these mild forms of RPE65-related retinal degeneration, and their effect on cone photoreceptor survival, we generated an Rpe65/P25L knock-in (KI/KI) mouse model. We found that, when subject to the low-light regime (∼100 lux) of regular mouse housing, homozygous Rpe65/P25L KI/KI mice are morphologically and functionally very similar to WT siblings. While mutant protein expression is decreased by over 80%, KI/KI mice retinae retain comparable 11-cis-retinal levels with WT. Consistently, the scotopic and photopic electroretinographic (ERG) responses to single-flash stimuli also show no difference between KI/KI and WT mice. However, the recovery of a-wave response following moderate visual pigment bleach is delayed in KI/KI mice. Importantly, KI/KI mice show significantly increased resistance to high-intensity (20 000 lux for 30 min) light-induced retinal damage (LIRD) as compared with WT, indicating impaired rhodopsin regeneration in KI/KI. Taken together, the Rpe65/P25L mutant produces sufficient chromophore under normal conditions to keep opsins replete and thus manifests a minimal phenotype. Only when exposed to intensive light is this hypomorphic mutation manifested physiologically, as its reduced expression and catalytic activity protects against the successive cycles of opsin regeneration underlying LIRD. These data also help define minimal requirements of chromophore for photoreceptor survival in vivo and may be useful in assessing a beneficial therapeutic dose for RPE65 gene therapy in humans.

Emerging drugs for the treatment of knee osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is the most prevailing form of joint disease, with symptoms affecting 10 - 12% of the adult population with a projection of a 50% increase in prevalence in the next two decades. The disease characteristics are defined by articular cartilage damage, low-grade synovial inflammation and hypertrophic bone changes, leading to pain and functional deterioration. To date, available pain treatments are limited in their efficacy and have associated toxicities. No structural disease modification agents have been approved by regulatory agencies for this indication. AREAS COVERED: We reviewed drugs in Phase II - III for OA pain and joint structure modification. Different aspects of structure modification are divided into targets of inflammatory pathway, cartilage catabolism and anabolism, and subchondral bone remodeling. EXPERT OPINION: Further insight into the pathophysiology of the disease will allow for development of novel target classes focusing on the link between symptomatology and structural changes. Given the complexity of OA, one single therapy is unlikely to be universally and uniformly effective. Promising therapies are under development, but there are obstacles in the translation of treatment from preclinical models and trial designs need to be cognizant of the complex reasons for previous trial failures.

Managing osteoarthritis.

Management of osteoarthritis should be based on a combination of non-drug and drug treatments targeted towards prevention, modifying risk and disease progression. Obesity is the most important modifiable risk factor, so losing weight in addition to land- and water-based exercise and strength training is important. While paracetamol can be tried, guidelines recommend non-steroidal anti-inflammatory drugs as first-line treatment for osteoarthritis. If there are concerns about the adverse effects of oral treatment, particularly in older patients or those with comorbidities, topical non-steroidal anti-inflammatory drugs can be used. Glucosamine does not appear to be any better than placebo for pain. Its effect on the structural progression of disease when taken alone or in combination with chondroitin is uncertain. Fish oil has not been found to reduce the structural progression of knee arthritis. Surgical interventions should be avoided in the first instance, with arthroscopic procedures not showing benefit over sham procedures or optimised physical and medical therapy. Joint replacement surgery should be considered for severe osteoarthritis.

Retinal metabolism displays evidence for uncoupling of glycolysis and oxidative phosphorylation via Cori-, Cahill-, and mini-Krebs-cycle.

The retina consumes massive amounts of energy, yet its metabolism and substrate exploitation remain poorly understood. Here, we used a murine explant model to manipulate retinal energy metabolism under entirely controlled conditions and utilised 1H-NMR spectroscopy-based metabolomics, in situ enzyme detection, and cell viability readouts to uncover the pathways of retinal energy production. Our experimental manipulations resulted in varying degrees of photoreceptor degeneration, while the inner retina and retinal pigment epithelium were essentially unaffected. This selective vulnerability of photoreceptors suggested very specific adaptations in their energy metabolism. Rod photoreceptors were found to rely strongly on oxidative phosphorylation, but only mildly on glycolysis. Conversely, cone photoreceptors were dependent on glycolysis but insensitive to electron transport chain decoupling. Importantly, photoreceptors appeared to uncouple glycolytic and Krebs-cycle metabolism via three different pathways: (1) the mini-Krebs-cycle, fuelled by glutamine and branched chain amino acids, generating N-acetylaspartate; (2) the alanine-generating Cahill-cycle; (3) the lactate-releasing Cori-cycle. Moreover, the metabolomics data indicated a shuttling of taurine and hypotaurine between the retinal pigment epithelium and photoreceptors, likely resulting in an additional net transfer of reducing power to photoreceptors. These findings expand our understanding of retinal physiology and pathology and shed new light on neuronal energy homeostasis and the pathogenesis of neurodegenerative diseases.

Predictors of Placebo Response to Local (Intra-Articular) Therapy In Osteoarthritis: An Individual Participant Data Meta-Analysis.

OBJECTIVE: We undertook this study to evaluate potential predictors of placebo response with intra-articular (IA) injections for knee/hip osteoarthritis (OA) using individual participant data (IPD) from existing trials. METHODS: Randomized placebo-controlled trials evaluating IA glucocorticoid or hyaluronic acid published to September 2018 were selected. IPD for disease characteristics and outcome measures were acquired. Potential predictors of placebo response included participant characteristics, pain severity, intervention, and trial design. Placebo response was defined as at least a 20% reduction in baseline pain. Logistic regression models and odds ratios were computed as effect measures to evaluate patient and pain mechanisms and then pooled using a random effects model. Generalized mixed-effect models were applied to intervention and trial characteristics. RESULTS: Of 56 eligible trials, 6 shared data, and these were combined with the existing 4 OA Trial Bank studies, yielding 10 studies with IPD of 621 placebo participants for analysis. In the total placebo population, at short-term follow-up, the use of local anesthetic and ultrasound guidance were associated with reduced odds of placebo response. At midterm follow-up, mid- to long-term trial duration was associated with increased odds of placebo response, and worse baseline function scores were associated with reduced odds of a placebo response. CONCLUSION: The administration of local anesthetics or ultrasound guidance may reduce IA placebo response at short-term follow-up. At midterm follow-up, participants with worse baseline function scores may be less likely to respond to IA placebo, and mid- to long-term trial duration may enhance the placebo response. Further studies are required to corroborate these potential predictors of IA placebo response.

Association of biochemical markers with bone marrow lesion changes on imaging-data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium.

BACKGROUND: To assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI. METHODS: Data from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed. BMLs were measured according to the MRI Osteoarthritis Knee Score (MOAKS) system (0-3), in 15 knee subregions. Serum and urinary biochemical markers assessed were as follows: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), serum crosslinked N-telopeptide of type I collagen (NTX-I), urinary CTX-Iα and CTX-Iß, urinary NTX-I, urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum matrix metalloproteinase (MMP)-degraded type I, II, and III collagen (C1M, C2M, C3M), serum high sensitivity propeptide of type IIb collagen (hsPRO-C2), and matrix metalloproteinase-generated neoepitope of C-reactive protein (CRPM). The association between change in biochemical markers over 12 months and BMLs over 24 months was examined using regression models adjusted for covariates. The relationship between C1M, C2M, C3M, hsPRO-C2, and CRPM and BMLs at baseline and over 24 months was examined. RESULTS: Increases in serum CTX-I and urinary CTX-Iß over 12 months were associated with increased odds of changes in the number of subregions affected by any BML at 24 months. Increase in hsPRO-C2 was associated with decreased odds of worsening in the number of subregions affected by any BML over 24 months. C1M and C3M were associated with BMLs affected at baseline. CONCLUSIONS: Short-term changes in serum CTX-I, hsPRO-C2, and urinary CTX-Iß hold the potential to be prognostic of BML progression on MRI. The association of C1M and C3M with baseline BMLs on MRI warrants further investigation.

Inflammatory ultrasound features as prognostic factors of pain and functional outcomes following intra-articular platelet-rich plasma in knee osteoarthritis.

AIM: To explore inflammatory ultrasound predictors of improvements in pain and function over 2, 6, and 12 months following administration of intra-articular platelet-rich plasma (PRP) in knee osteoarthritis (OA). METHOD: Patients with painful mild-moderate radiographic knee OA from a subset of the RESTORE RCT underwent ultrasound assessment according to the standardized OMERACT scanning protocol to detect inflammatory features such as synovitis, synovial hypertrophy, and effusion with power Doppler. The study knee was treated with 3 once-weekly PRP injections obtained after centrifugation at 1500 g for 5 min. Numerical Rating Score (NRS), Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) function sub-score were used to measure pain and functional severity. Separate linear regression models were performed to determine whether baseline ultrasound-detected features of inflammation predicted the improvement in pain and function following PRP injection in both unadjusted and adjusted models for confounders. RESULTS: Forty-four participants were included, with 25 (56.8%) being female. In an unadjusted model, higher OMERACT scores for inflammatory features such as global synovitis and/or effusion were significantly associated with greater improvement in all outcomes measured at 2 months but not at 6 and 12 months for pain measures. Only global synovitis showed significant association with functional improvement at 2 and 12 months. Similar findings were observed in the adjusted model. CONCLUSION: Ultrasound indices of knee inflammation predicted short-term improvements in pain severity and both short- and longer-term improvements in function following intra-articular PRP injection.

The OA Trial Bank: Update of individual patient data meta-analysis of intra-articular glucocorticoids in persons with knee and hip osteoarthritis.

Objective: To evaluate the efficacy of intra--articular (IA) glucocorticoid for knee or hip osteoarthritis (OA) in specific subgroups of patients according to the baseline severity of pain and inflammatory signs using individual patient data (IPD) from existing trials. Furthermore, this study aims to assess if a baseline pain cut-off was associated with clinically important effectiveness of IA glucocorticoid. This is an update of an IA glucocorticoid IPD meta-analysis by the OA Trial Bank. Method: Randomized trials evaluating one or more IA glucocorticoid preparations in hip and knee OA, published to May 2018 were selected. IPD of patient and disease characteristics and outcome measures were acquired. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). Potential interaction effect of severe pain (≥70 points, 0-100 scale) and signs of inflammation at baseline were studied using a two-stage approach with general liner model followed by random effects model. Analysis of trend was conducted, assessing if a baseline pain cut-off was associated with the threshold for clinically important treatment effect of IA glucocorticoid compared to placebo. Results: Four out of 16 eligible randomized clinical trials (n â€‹= â€‹641) were combined with the existing OA Trial Bank studies (n â€‹= â€‹620), yielding 1261 participants from eleven studies. Participants with severe baseline pain compared to those with less severe pain had greater pain reduction at mid-term (around 12 weeks) (mean reduction: -6.90 (95%CI -10.91; -2.90)), but not at short- and long-term. No interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo at all follow-up time-points. Analysis of trend demonstrated treatment response to IA glucocorticoid from baseline pain levels >50 (0-100 scale) and above. Conclusion: This updated IPD meta-analysis demonstrated that participants with severe pain compared to those with less severe pain at baseline experienced significantly more pain relief with IA glucocorticoid compared with placebo at mid-term.

Self-regulation of time: The importance of time estimation accuracy.

Time management is one central aspect of students' self-regulated learning. In addition, biased time estimation seems to be central to students' self-regulation of their time. In this study, we explored college students' time estimation bias. In addition, we were interested in whether the activation of task beliefs influenced students' time estimation bias and how specific beliefs about task difficulty influence time estimation bias. Findings suggested that students tended to demonstrate bias in their estimations of the time their academic tasks would take. Additionally, the activation of task beliefs did not influence students' time estimation accuracy. Finally, both prior task difficulty and anticipated difficulty influenced students' time estimation bias. These findings highlight the complexity of students' time estimation bias and point to the opportunities for future directions.

Corrigendum: Self-regulation of time: The importance of time estimation accuracy.

[This corrects the article DOI: 10.3389/fpsyg.2022.925812.].

Responsiveness of an activity tracker as a measurement tool in a knee osteoarthritis clinical trial (ACTIVe-OA study).

BACKGROUND: In osteoarthritis (OA) clinical trials, reliable and responsive outcome measures to document physical and functional improvements are limited. OBJECTIVE: This study aimed to assess whether the use of an activity tracker in an OA clinical trial is a responsive measurement tool. Secondary objectives assessed feasibility and validity. METHODS: We recruited 65 participants in a prospective cohort study nested in a placebo-controlled clinical trial of platelet-rich plasma injection in knee OA. Participants wore an activity tracker (Fitbit Flex 2), and a smartphone was preloaded with a mobile application (OApp) designed to monitor load rates as a surrogate of knee loading. Participants used the systems for 7 days at baseline and for 7 days before the 2-month follow-up assessment. Effect size (ES) and standardised response mean (SRM) were calculated for change in step count and knee loading rate and regularly used knee OA outcome measures. Correlation coefficients (r) were calculated to examine the strength of the association between outcome measures. RESULTS: . Step count showed a trivial ES and SRM and mean knee loading rate measurements a moderate ES and SRM. We found a weak but significant correlation between change in mean steps per day and global improvement overall (r= 0.28) and Western Ontario and McMaster Universities Osteoarthritis Index function (r = -0.28). Compliance was high with the activity trackers. CONCLUSIONS: Despite good feasibility, this study did not show significant responsiveness or validity of the activity trackers as compared with currently recommended outcome measures in OA clinical trials. The main challenge is the lack of a gold standard outcome measure to validate against, and because of the complex interplay between pain and measured function, a lack of correlation does not necessarily represent a failed validation in this context. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12617000853347. This trial is a substudy of the "Platelet-rich plasma as a symptom-and disease-modifying treatment for knee osteoarthritis - the RESTORE trial".

Effects of Knowledge and Value on Quality of Supportive Peer Feedback.

BACKGROUND: Motivational barriers and lack of knowledge about peer review inhibit creation of supportive peer feedback between nursing students. PURPOSE: The purpose of this study was to examine the effects of knowledge of peer-review practices and value for the process of creating supportive peer feedback on the quality of feedback nursing students create for their peers. METHOD: Data from 155 graduate nursing students were analyzed in this quasi-experimental, repeated-measures design, using analysis of covariance and conditional process analysis. RESULTS: Students who had high levels of knowledge and a strong sense of value for providing feedback to peers produced higher-quality supportive peer feedback. CONCLUSION: Even when a student has sufficient knowledge and skills to produce supportive peer feedback, their ability may not transfer to real peer-review contexts if they do not also have a strong sense of value for providing high-quality feedback to peers.