Understanding the physical literacy development of 8- to 12-year-old children living with chronic medical conditions: A comprehensive, mixed methods inquiry.

BACKGROUND: Physical literacy is a concept used to describe the combined physical, affective and cognitive capacities facilitating an active lifestyle. Physical activity participation is essential for children living with chronic medical conditions, but knowledge of physical literacy among this group is scarce. METHODS: An explanatory, sequential mixed methods design was used to comprehensively describe the physical literacies of children with chronic medical conditions (CMCs). Participants were recruited from paediatric cardiology, respirology/cystic fibrosis, neurology, haematology and endocrinology outpatient clinics. All participants completed the Canadian Assessment of Physical Literacy (2nd Edition), and those with higher and lower scores were invited to a semi-structured interview. A deductive-inductive thematic analysis was applied using Margaret Whitehead's conceptualization of physical literacy. RESULTS: Using normative strata, 80.0% of the 99 children assessed (mean age = 9.97 ± 1.3 years, 48% girls) were considered beginning or progressing in their overall physical literacy (mean score = 56.5 ± 13.8/100). Meanwhile, physical literacy informed participants' approach to new, active experiences and may have contributed to a strong sense of self. There was a significant difference between endocrinology and haematology patients on total physical literacy score (p = 0.03) but not domain scores. Participants scored high on motivation/confidence (mean = 22.9 ± 5.0/30) but obtained low physical competence (mean = 11.8 ± 5.6/30) and daily behaviour scores (n = 72, mean = 15.5 ± 7.1/30). Main themes represent salient experiences of children with CMCs within the domains of physical literacy, including their need to evaluate active contexts, self-regulate activity intensity and manage physical limitations. CONCLUSIONS: Children with CMCs can achieve recommended levels of physical literacy without meeting normative standards for physical competence. Participants would benefit from a physical literacy intervention that targets the development of bodily self-regulation skills and risk evaluation in active settings.

What's in a name: defining pediatric refractory ITP.

There are no agreed upon terminology to define "refractory" pediatric Immune Thrombocytopenia (ITP). Guidelines are therefore limited to arbitrary and outdated definitions. The Pediatric ITP Consortium of North America held a meeting in 2023 to define this entity. With 100% agreement, the faculty established that pediatric ITP that is refractory to emergent therapy could be defined as no platelet response after treatment with all eligible emergent pharmacotherapies. With 100% agreement, the working group established that pediatric patients with ITP that continue to demonstrate high disease burden and/or no platelet response despite treatment with multiple classes of disease modifying therapies represent a challenging subset of ITP. These patients are at higher risk of ongoing disease burden and merit additional investigation as well as consideration for clinical trials or novel therapies. Future efforts to define disease burden and disease response will be completed in collaboration with the ITP International Working Group.

Quality of life in childhood immune thrombocytopenia: Revision of the Kids' ITP Tools (KIT).

The Kids ITP Tools (KIT) is a health-related quality of life (HRQoL) questionnaire that evaluates quality of life in children with immune thrombocytopenia (ITP). There are three formats: Child Self-Report, Parent Proxy-Report and Parent Impact-Report. This study aimed to develop a domain structure by grouping-related questions from the questionnaire into domains that independently reflect various aspects of HRQoL. The study was conducted in two phases. Phase 1 involved an online survey distributed to experts to identify conceptual domains for the KIT. Phase 2 utilized a statistical approach to analyse responses from patients with ITP and their families. A revised KIT 2.0 was ultimately developed to aid in treatment decision-making and monitoring of ITP.

Childhood autoimmune hemolytic anemia: A scoping review.

BACKGROUND AND OBJECTIVE: Autoimmune hemolytic anemia (AIHA) is a rare but important cause of morbidity in pediatric hematology patients. Given its rarity, there is little high-quality evidence on which to base the investigation and management of pediatric AIHA. This scoping review aims to summarize the current evidence and highlight key gaps to inform future studies. METHODS: This review searched MEDLINE and the Cochrane CENTRAL Trials Register from 2000 to November 03, 2023. Experimental and observational studies reporting AIHA diagnostic criteria, laboratory workup, or treatment/management in populations with at least 20% of patients ≤18 years were included. RESULTS: Forty-three studies were included, with no randomized controlled trials identified. AIHA diagnostic criteria, diagnostic tests, and treatments were highly variable. First-line treatment approaches include corticosteroids, intravenous immunoglobulin, or both. Approaches to AIHA resistance to first-line therapy were widely variable between studies, but most commonly included rituximab and/or cyclosporine. CONCLUSIONS: We identify a heterogenous group of observational studies into this complex, immune-mediated disorder. Standardized definitions and classifications are needed to guide collaborative efforts needed to study this rare disease. The work done by the CEREVANCE group provides an important paradigm for future studies.

Quality of Life in Transfusion-Dependent Thalassemia Patients in Greece Before and During the COVID-19 Pandemic.

OBJECTIVES: The peak of the COVID-19 pandemic was a challenging situation for transfusion-dependent thalassemia (TDT) patients. The objectives of this study were to measure the quality of life (QoL) in TDT patients during the COVID-19 lockdown restriction measures, compare the results with the pre-COVID-19 era, and evaluate the influence of sociodemographic and clinical factors on QoL. METHODS: This was a cross-sectional study of 110 consecutively selected adult TDT patients, during the stringent lockdown restriction measures implemented in Greece. All participants completed a combination of 2 QoL questionnaires, the generic Short-Form Health Survey 36 version 2 and the disease-specific Transfusion-Quality of life (TranQol). We used the "1/2 SD method," a distribution-based approach to calculate minimal clinically important differences and clinically compare the QoL scores between the pre-COVID-19 and post-COVID-19 era. A backward stepwise linear regression was selected to explore the influence of potential predictors on TranQol scores. RESULTS: The Short-Form Health Survey 36 version 2 and TranQol scores remained low but not clinically different compared with the pre-COVID-19 era. Older, married, and higher educated TDT patients exhibited significantly lower TranQol summary scores. The patients who reported a negative effect of the COVID-19 pandemic had significantly lower TranQol scores in summary and all subdomains except for school and career. CONCLUSIONS: During the COVID-19 pandemic, the overall QoL of TDT patients was clinically similar to the status of the pre-COVID-19 era. Nevertheless, most of the significant QoL subdomains were negatively affected, and distinct groups of TDT patients were more vulnerable.

Shared decision-making related to treatment of haemophilia: A scoping review of influential factors and available support tools.

INTRODUCTION: Treatment selection in haemophilia is increasingly challenging given evolving therapeutic options and the need for individualization. Shared decision-making (SDM) approaches have recently gained interest, though a synthesis of available studies is lacking. AIM: A scoping review was conducted to summarize literature reporting on factors impacting treatment SDM in haemophilia and tools or models available to support such decisions. METHODS: PubMed, Embase, the Cochrane Library, Web of Science and grey literature were searched for studies published through August 2023. Original studies reporting on facilitators and barriers to haemophilia SDM and SDM tools were included and analyzed for themes, characteristics and gaps. RESULTS: A total of 625 records were identified and 14 unique studies were selected (factors influencing treatment SDM, n = 7; SDM tools, n = 7). The studies typically included input from persons with haemophilia, caregivers and healthcare practitioners (HCPs). Thematic organization of factors influencing SDM revealed three main categories: knowledge, patient characteristics and HCP-patient interactions. Availability of information was a commonly reported facilitator of SDM, while poor HCP-patient engagement was a commonly reported barrier. Tools varied in focus, with some facilitating general treatment SDM while others supported selection of certain therapy types. The studies underscored additional factors critical for SDM, such as alignment of HCP-patient perceptions, shared language and tailoring of tools to specific subpopulations. CONCLUSION: Few studies report on treatment SDM factors and tools in haemophilia; available tools vary considerably. It remains unclear whether published tools have been successfully implemented into clinical practice. Additional research is warranted.

A Cross-Sectional, Multicentric, Disease-Specific, Health-Related Quality of Life Study in Greek Transfusion Dependent Thalassemia Patients.

The assessment of health-related quality of life (HRQoL) in thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of transfusion-dependent thalassemia (TDT) patients in Greece. This was a multicentric, cross-sectional study conducted in 2017 involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in the univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower compared to the general population in Greece. The mean summary score of TranQol was relatively high (71 ± 14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment of a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

Face validity of the Kids' ITP Tools (KIT) in the era of thrombopoietin receptor agonists.

The Kids' ITP Tools (KIT) is a questionnaire to assess quality of life of children with immune thrombocytopenia (ITP). The aim of this study was to update this previously validated tool to align with changes in clinical practice, specifically, treatment with thrombopoietin receptor agonists (TPO-RAs). Children aged 1-18 with ITP and/or their families were recruited to participate in interviews to review the KIT. Twenty-six interviews were conducted. Based on interview data from children and families, current guidelines, and expert opinion, five changes were made to the KIT in order to improve its face validity.

Quick, Effective Screening Tasks Identify Children With Medical Conditions or Disabilities Needing Physical Literacy Support.

PURPOSE: This study evaluated screening tasks able to identify children with medical conditions or disabilities who may benefit from physical literacy. METHOD: Children completed ≤20 screening tasks during their clinic visit and then the Canadian Assessment of Physical Literacy (2nd edition) at a separate visit. Total Canadian Assessment of Physical Literacy scores <30th percentile were categorized as potentially needing physical literacy support. Receiver operator characteristic curves identified assessment cut points with 80% sensitivity and 40% specificity relative to total physical literacy scores. RESULTS: 223 children (97 girls; 10.1 [2.6] y) participated. Physical activity adequacy, predilection, and physical competence achieved ≥80% sensitivity and ≥40% specificity in both data sets. Adequacy ≤ 6.5 had 86% to 100% sensitivity and 48% to 49% specificity. Daily screen time >4.9 hours combined with Adequacy ≤6.15 had 88% to 10% sensitivity and 53% to 56% specificity. CONCLUSIONS: Activity adequacy, alone or with screen time, most effectively identified children likely to benefit from physical literacy support. Adequacy and screen time questionnaires are suitable for clinical use. Similar results regardless of diagnosis suggest physical competence deficits are not primary determinants of active lifestyles. Research to enhance screening specificity is required.

Psychometric validation of the Pyruvate Kinase Deficiency Diary and Pyruvate Kinase Deficiency Impact Assessment in adults in the phase 3 ACTIVATE trial.

BACKGROUND: Pyruvate kinase (PK) deficiency is a rare hereditary disorder characterized by chronic hemolytic anemia and serious sequalae which negatively affect patient quality of life. This study aimed to psychometrically validate the first disease-specific patient-reported outcome (PRO) instruments: the 7-item PK Deficiency Diary (PKDD) and 12-item PK Deficiency Impact Assessment (PKDIA), designed to assess signs, symptoms, and impacts of PK deficiency in patients enrolled in the ACTIVATE global phase 3 study of mitapivat versus placebo (NCT03548220). METHODS: All validation analyses for the PKDD and PKDIA were performed on blinded data, with analyses on item integrity, scoring, reliability, and validity conducted on data from screening and baseline. Completion rates and baseline response distributions were characterized using descriptive statistics. Item response modelling was used to inform a weighted scoring system. Reliability was assessed by internal consistency and test-retest reliability; and validity by convergent and known-groups analyses. RESULTS: Of the 80 adults enrolled, baseline data were available for 77 (96.3%) and 78 (97.5%) patients for the PKDD and PKDIA, respectively. Item responses skewed right, indicating that mean values exceeded median values, especially for items utilizing a 0-10 numeric scale, which were subsequently recoded to a 0-4 scale; 4 items were removed from the PKDIA due to redundancy or low relevance to the trial population. Both the PKDD and PKDIA demonstrated high internal consistency (McDonald's coefficient ω = 0.86 and 0.90, respectively), test-retest reliability (intra-class coefficients of 0.94 and 0.87, respectively), and convergent validity with other PROs (linear correlation coefficients [|r|] between 0.30-0.73 and 0.50-0.82, respectively). CONCLUSIONS: The findings provide evidence of validity and reliability for the PKDD and PKDIA, the first disease-specific PRO measures for PK deficiency, and can therefore increase understanding of, and more accurately capture, the wider impact of PK deficiency on health-related quality of life. Trial registration ClinicalTrials.gov, NCT03548220. Registered June 07, 2018; https://www. CLINICALTRIALS: gov/ct2/show/NCT03548220 .

Pyruvate kinase (PK) deficiency is a rare genetic blood disorder with a wide range of signs and symptoms that may have a negative impact on patients' quality of life. Patient-reported outcome (PRO) instruments are tools that assess how a disease affects a patient from the patient's perspective. These instruments must go through a validation process to make sure they truly capture the patient's experience with their condition or its treatment. This study aimed to validate two new PRO instruments in adult patients enrolled in the ACTIVATE clinical trial (NCT03548220), where patients with PK deficiency received the drug mitapivat or a placebo. These two new PRO instruments are the first to be developed specifically for PK deficiency: the PK Deficiency Diary (PKDD), a daily diary that asks 7 questions to measure the core signs and symptoms of PK deficiency, and the PK Deficiency Impact Assessment (PKDIA), a weekly questionnaire with 12 questions to assess the impact of PK deficiency on a patient's life. The results of this study showed that the PKDD and PKDIA properly and reliably measured the signs, symptoms, and impacts of PK deficiency that they aimed to capture. These findings indicate that the PKDD and PKDIA are the first validated PROs specifically for PK deficiency and can help improve the understanding of the impact of PK deficiency on patients' quality of life.

Pediatric refractory immune thrombocytopenia: A systematic review.

Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included suboptimal response to medical management, while some outlined specific platelet thresholds to define this suboptimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies.

Integration of Patient-reported Outcome Measures in Pediatric Hematology: A Qualitative Methods Study.

Patient-reported outcome measures (PROMs) are self-reported questionnaires that allow patients and families to evaluate health-related experiences without influence or oversight from health care professionals. This study aimed to rate the relevance of existing PROMs for pediatric hematology patients, as identified by a recent systematic review, as well as to evaluate the receptivity of electronic PROM integration into clinical practice. Focus groups and interviews were conducted with children (10) and parents (19) impacted by nonmalignant hematological disorders, as well as with health care professionals (6). We observed strong support for the TranQol in thalassemia (100% for both parents [P] and children [C]); the Canadian Haemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) (100% P, 75% C) and Haemophilia Quality of Life questionnaire (Haemo-QoL) (100% P and C) in hemophilia; the Pediatric Quality of Life Inventory (PedsQL) Sickle Cell Module (75% P, 100% C); and the Kids ITP Tool in immune thrombocytopenia (100% P, 66.7% C). Generic tools such as the PedsQL Generic were met with mixed support. Electronic PROM integration received universal support. We obtained strong support for the integration of a web-based platform into clinical practice and a preference for disease-specific PROMs over generic PROMs. Future projects may explore the development of a child-friendly Canadian web-based platform to standardize quality-of-life evaluation within the clinical encounter.

Evaluating the impact of thrombopoietin receptor agonist medications on patient outcomes and quality of life in paediatric immune thrombocytopenia through semi-structured interviews.

Over the last decade, treatment of immune thrombocytopenia (ITP) in children has advanced to include thrombopoietin receptor agonist (TPO-RA) medications. Concurrently, there has been an increased emphasis on patient-reported outcomes-especially quality of life-to guide treatment. Assessing the impact of TPO-RAs on quality of life in paediatric ITP is therefore a priority. In this single-centre integrative mixed-methods study, a cohort of children with ITP prescribed a TPO-RA was identified. These children and/or their caregivers were invited to participate in semi-structured interviews focussed on quality-of-life measures. Independently, a retrospective chart review collected ITP-related data (platelet count, bleeding events) and TPO-RA data (dosing, side effects). Among the 23 eligible patients, 20 were represented in interviews. On chart review, 11/20 patients responded to TPO-RA by meeting platelet count criteria of ≥50 × 109 /L for six or more weeks in the absence of rescue therapy. In interviews with these children and/or their parents, 19/20 expressed the TPO-RA had 'worked', with 11/20 reporting benefit to mood and 11/20 reporting increased participation in activities/sports. Concerns were raised in interviews about TPO-RA medication cost (17/20), medication administration (10/20) and potential side effects (10/20). In conclusion, this study suggests that TPO-RA use in children with ITP improves quality of life.

Patient-Reported Outcomes Measurement in Radiation Oncology: Interpretation of Individual Scores and Change over Time in Clinical Practice.

Tools for measuring patients' perceived health and quality of life, such as patient-reported outcome measures (PROMs), inform clinical decisions for patients requiring radiation therapy. However, there may be inconsistencies in how patients interpret and respond to PROMs due to cultural, environmental, personal, or experiential factors. Differential item functioning (DIF) and response shift (RS) refer to differences in the meaning of PROMs between patients or over time (respectively). DIF and RS can threaten the accurate interpretation and use of PROMs, potentially resulting in erroneous conclusions about effectiveness, and flawed individual-level clinical decision-making. Given the empirical evidence of DIF and RS, we aim to review clinical implications and solutions for addressing DIF and RS by providing vignettes from collaborative examinations with workshop participants, as well as the literature. By making these methodological concepts accessible and relevant, for practice, clinicians may feel more confident to ask clarifying questions of patients when PROM scores and the contextual patient information do not align. PROM scores need to be interpreted via dialogue with the patient to avoid misinterpretation due to DIF and RS, which could diminish patient-clinician communication and impede shared decision-making. This work is part of an interdisciplinary knowledge translation initiative focused on the interpretation of PROM scores by clinically-oriented audiences.

Novel cysteine substitution p.(Cys1084Tyr) causes variable expressivity of qualitative and quantitative VWF defects.

von Willebrand factor (VWF) is an extremely cysteine-rich multimeric protein that is essential for maintaining normal hemostasis. The cysteine residues of VWF monomers form intra- and intermolecular disulfide bonds that regulate its structural conformation, multimer distribution, and ultimately its hemostatic activity. In this study, we investigated and characterized the molecular and pathogenic mechanisms through which a novel cysteine variant p.(Cys1084Tyr) causes an unusual, mixed phenotype form of von Willebrand disease (VWD). Phenotypic data including bleeding scores, laboratory values, VWF multimer distribution, and desmopressin response kinetics were investigated in 5 members (2 parents and 3 daughters) of a consanguineous family. VWF synthesis and secretion were also assessed in a heterologous expression system and in a transient transgenic mouse model. Heterozygosity for p.(Cys1084Tyr) was associated with variable expressivity of qualitative VWF defects. Heterozygous individuals had reduced VWF:GPIbM (<0.40 IU/mL) and VWF:CB (<0.35 IU/mL), as well as relative reductions in high-molecular-weight multimers, consistent with type 2A VWD. In addition to these qualitative defects, homozygous individuals also displayed reduced factor VIII (FVIII):C/VWF:Ag, leading to very low FVIII levels (0.03-0.1 IU/mL) and reduced VWF:Ag (<0.40 IU/mL) and VWF:GPIbM (<0.30 IU/mL). Accelerated VWF clearance and impaired VWF secretion contributed to the fully expressed homozygous phenotype with impaired secretion arising because of disordered disulfide connectivity.

Poor outcome after hematopoietic stem cell transplantation of patients with unclassified inherited bone marrow failure syndromes.

Classification of inherited bone marrow failure syndromes (IBMFSs) according to clinical and genetic diagnoses enables proper adjustment of treatment. Unfortunately, 30% of patients enrolled in the Canadian Inherited Marrow Failure Registry (CIMFR) with features suggesting hereditability could not be classified with a specific syndromic diagnosis. We analyzed the outcome of hematopoietic stem cell transplantation (HSCT) in unclassified IBMFSs (uIBMFSs) and the factors associated with outcome. Twenty-two patients with uIBMFSs and 70 patients with classified IBMFSs underwent HSCT. Five-year overall survival of uIBMFS patients after HSCT was inferior to that of patients with classified IBMFSs (56% vs 76.5%). The outcome of patients with uIBMFS who received cord blood was significantly lower than that of patients who received other stem cell sources (14.8% vs 90.9%). Engraftment failure was higher among patients with uIBMFS who received cord blood than those who received bone marrow. None of the following factors were significantly associated with poor survival: transfusion load, transplant indication, the intensity of conditioning regimen, human leukocyte antigen-identical sibling/alternative donor. We suggest that identifying the genetic diagnosis is essential to modulate the transplant procedure including conditioning agents and stem cell sources for better outcome and the standard cord blood transplantation (CBT) should be avoided in uIBMFS.

Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency.

Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we used validated measures to assess the impact of disease on HRQoL (EuroQol 5-Dimension Questionnaire, Pediatric Quality of Life Inventory Generic Core Scale version 4.0, and Functional Assessment of Cancer Therapy-Anemia) and fatigue (Patient Reported Outcomes Measurement Information System Fatigue and Pediatric Functional Assessment of Chronic Illness Therapy-Fatigue). Significant variability in HRQoL and fatigue was reported for adults and children, although individual scores were stable over a 2-year interval. Although adults who were regularly transfused reported worse HRQoL and fatigue compared with those who were not (EuroQol-visual analog scale, 58 vs 80; P = .01), this difference was not seen in children. Regularly transfused adults reported lower physical, emotional, and functional well-being and more anemia symptoms. HRQoL and fatigue significantly differed in children by genotype, with the worst scores in those with 2 severe PKLR mutations; this difference was not seen in adults. However, iron chelation was associated with significantly worse HRQoL scores in children and adults. Pulmonary hypertension was also associated with significantly worse HRQoL. Additionally, 59% of adults and 35% of children reported that their jaundice upset them, identifying this as an important symptom for consideration. Although current treatments for PKD are limited to supportive care, new therapies are in clinical trials. Understanding the impact of PKD on HRQoL is important to assess the utility of these treatments. This trial was registered at www.clinicaltrials.gov as #NCT02053480.

Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study.

BACKGROUND: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. METHODS: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. RESULTS: The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8-16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08-2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92-11.57) and 5.25 (95% CI, 2.05-13.40) of later osteochondral changes on MRI. DISCUSSION: MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes.