Fundamentals of osteoarthritis: outcome evaluation with patient-reported measures and functional tests.

Evaluating outcome in osteoarthritis (OA) clinical research and practice requires reliable, valid and responsive patient-reported outcome measures (PROMs) and functional tests that reflect important problems experienced by people with OA. The goal of this work is to provide information to start to guide the reader in selecting measures for people with OA. In this narrative review, we begin by providing an overview of measurement properties that can help clinicians and researchers in making decisions about whether a measure might be appropriate for use in their research or clinical context. We then report evidence supporting the use of measures of pain (e.g., Pain Visual Analogue (VAS), Numeric Pain Rating Scale (NPRS), Intermittent and Constant Osteoarthritis Pain, PROMIS Pain Interference, and, for screening in research, the painDETECT and the Self-report Leeds Assessment of Neuropathic Symptoms and Signs) and fatigue (e.g., PROMIS-Fatigue) at a group level in clinical research. Several multi-dimensional joint-specific measures (e.g., Western Ontario McMaster Universities' Osteoarthritis Outcomes Scale, Knee/Hip Injury and Osteoarthritis Outcome Score, Oxford Hip/Knee Scale) also have evidence for group-level use. Functional tests (e.g., timed walk tests, 30 Second Chair Stand, Timed Up and Go, etc.) have measurement properties supporting their use at the group level in clinical research and at the individual patient level as do the pain VAS and NPRS. Other generic and disease-specific PROMs have been used in or could be used in OA studies but their measurement properties require further evaluation in people with OA.

Development of an intervention to manage knee osteoarthritis risk and symptoms following anterior cruciate ligament injury.

INTRODUCTION: Anterior cruciate ligament (ACL) injury is a risk factor for developing knee osteoarthritis (OA). We developed an intervention to support people manage risk factors for OA. METHODS: We conducted one-on-one interviews with 20 individuals with OA symptoms 6-15 years post ACL injury and used a nominal group process during a workshop with 40 patients and healthcare professionals (HCPs) to elicit information on the intervention content and delivery characteristics (timing, HCPs, and methods). Interview data were analyzed using content analysis. Nominal group ideas with importance ratings ≥5 of 7 met criteria for inclusion. Results were integrated, considering similarities and differences. RESULTS: Eight content categories were identified: 1. understanding knee injury and expectations about recovery; 2. understanding OA risk; 3. understanding OA signs and symptoms; 4. managing OA risk; 5. managing knee OA symptoms; 6. information for influencers; 7. credible sources; and, 8. updates on new evidence and treatments. Delivery timing reflected a lifespan approach from time of injury through symptomatic knee OA management. Although multiple media for delivery were identified, introductory face-to-face discussions and opportunity for re-accessing HCPs were critical. All HCPs who treat people with ACL should be familiar with and able to deliver the intervention. CONCLUSIONS: This co-development approach identified that an intervention to support people with ACL injury to limit and manage knee OA requires content embedded within an easily accessible, multi-media delivery model with capacity for check-back with HCPs that is appealing to different age groups and personal preferences over the lifespan post injury.

Heating events in the nascent solar system recorded by rare earth element isotopic fractionation in refractory inclusions.

Equilibrium condensation of solar gas is often invoked to explain the abundance of refractory elements in planets and meteorites. This is partly motivated, by the observation that the depletions in both the least and most refractory rare earth elements (REEs) in meteoritic group II calcium-aluminum-rich inclusions (CAIs) can be reproduced by thermodynamic models of solar nebula condensation. We measured the isotopic compositions of Ce, Nd, Sm, Eu, Gd, Dy, Er, and Yb in eight CAIs to test this scenario. Contrary to expectation for equilibrium condensation, we find light isotope enrichment for the most refractory REEs and more subdued isotopic variations for the least refractory REEs. This suggests that group II CAIs formed by a two-stage process involving fast evaporation of preexisting materials, followed by near-equilibrium recondensation. The calculated time scales are consistent with heating in events akin to FU Orionis- or EX Lupi-type outbursts of eruptive pre-main-sequence stars.

Immediate outcomes following the GLA:D® program in Denmark, Canada and Australia. A longitudinal analysis including 28,370 patients with symptomatic knee or hip osteoarthritis.

OBJECTIVE: To report outcomes across three countries for patients with symptomatic knee or hip OA attending the evidence-based education and exercise therapy program Good Life with osteoArthritis from Denmark (GLA:D®). DESIGN: GLA:D® is a structured treatment program including 2-3 patient education sessions and 12 supervised exercise sessions delivered over 8 weeks by certified health care practitioners. The program was introduced in Denmark in 2013, in Canada 2015 and in Australia 2016. Absolute mean change in pain intensity, number of chair stands in 30 s, 40 m walk test time and Knee injury and Osteoarthritis Outcome Score (KOOS)/Hip dysfunction and Osteoarthritis Outcome Score (HOOS) QOL subscale scores from baseline to immediately after treatment were reported as means and 95 % CIs and proportion of responders for each country. RESULTS: Patients from the three countries improved 26-33% in mean pain intensity, 8-12% in walking speed, 18-30% in chair stand ability and 12-26% in joint-related quality of life from baseline to immediately after treatment, with no clinically relevant differences between patients with hip and knee OA. These improvements correspond with moderate to large within-group effect sizes and 43-47 % of the patients experienced clinically relevant pain reductions. CONCLUSION: About half or more of patients across the three countries were categorized as responders for pain and objective function following the implementation of GLA:D®. These findings indicate positive patient outcomes associated with GLA:D® participation across varying health care systems from implementation of guideline-based patient education and exercise therapy for knee and hip OA.

Weight status and associated comorbidities in children and adults with Down syndrome, autism spectrum disorder and intellectual and developmental disabilities.

BACKGROUND: Little is known about body weight status and the association between body weight and common comorbidities in children and adults with Down syndrome (DS), autism spectrum disorder (ASD) and other intellectual and developmental disabilities (IDDs). METHODS: Data were extracted from the University of Kansas Medical Center's Healthcare Enterprise Repository for Ontological Narration clinical integrated data repository. Measures included demographics (sex, age and race), disability diagnosis, comorbid health conditions, height, weight and body mass index percentiles (BMI%ile; <18 years of age) or BMI (≥18 years of age). RESULTS: Four hundred and sixty-eight individuals with DS (122 children and 346 adults), 1659 individuals with ASD (1073 children and 585 adults) and 604 individuals with other IDDs (152 children and 452 adults) were identified. A total of 47.0% (DS), 41.9% (ASD) and 33.5% (IDD) of children had overweight/obese (OW/OB), respectively. Children with DS were more likely to have OW/OB compared with children with IDD or ASD [odds ratio (OR) = 1.91, 95% confidence interval (CI): (1.49, 2.46); OR = 1.43, 95% CI: (1.19, 1.72)], respectively. A total of 81.1% (DS), 62.1% (ASD), and 62.4% (IDD) of adults were OW/OB, respectively. Adults with DS were more likely to have OW/OB compared with those with IDD [OR = 2.56, 95% CI: (2.16, 3.02)]. No significant differences were observed by race. In children with ASD, higher OW/OB was associated with significantly higher (compared with non-OW/OB) occurrence of sleep apnoea [OR = 2.94, 95% CI: (2.22, 3.89)], hypothyroidism [OR = 3.14, 95% CI: (2.17, 4.25)] and hypertension [OR = 4.11, 95% CI: (3.05, 5.54)]. In adults with DS, OW/OB was significantly associated with higher risk of sleep apnoea and type 2 diabetes [OR = 2.93, 95% CI: (2.10, 4.09); OR = 1.76, 95% CI: (1.11, 2.79) respectively]. Similarly, in adults with ASD and IDD, OW/OB was significantly associated with higher risk of sleep apnoea [OR = 3.39, 95% CI: (2.37, 4.85) and OR = 6.69, 95% CI: (4.43, 10.10)], type 2 diabetes [OR = 2.25, 95 % CI: (1.68, 3.01) and OR = 5.49, 95% CI: (3.96, 7.61)] and hypertension [OR = 3.55, 95% CI: (2.76, 4.57) and 3.97, 95% CI: (3.17, 4.97)]. CONCLUSION: Findings suggest higher rates of OW/OB in individuals with DS compared with ASD and IDD. Given the increased risk of comorbidities associated with the increased risk of OW/OB, identification of effective interventions for this special population of individuals is critical.

A systematic review of estimates of the minimal clinically important difference and patient acceptable symptom state of the Western Ontario and McMaster Universities Osteoarthritis Index in patients who underwent total hip and total knee replacement.

OBJECTIVE: To systematically review the minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) estimates in pain and function measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in patients who underwent primary total knee replacement (TKR) and primary total hip replacement (THR). DESIGN: The study was carried out following PRISMA recommendations. We searched five electronic databases. Two reviewers independently screened titles, abstracts and full-text papers using a priori inclusion/exclusion criteria. Data were extracted by two independent reviewers. Data were synthesized, with WOMAC values converted to 0-100 scores (0 = best, 100 = worst). RESULTS: Thirteen studies were included. Research methods used to calculate MCIDs and PASS varied across studies (e.g., using anchor-based or distribution methods, wording of anchor questions within anchor-based methods). Baseline WOMAC scores also varied across studies. Across studies and methods, MCIDs for the WOMAC in patients undergoing TKR ranged from 13.3 to 36.0 for pain and 1.8-33.0 for function; values for WOMAC in THR ranged from 8.3 to 41.0 for pain and from 9.7 to 34.0 for function. PASS cut-offs for TKR ranged from 25.0 to 28.6 for pain and 32.3-36.7 for function, and cut-offs for THR from 15.0 to 30.6 for pain and 28.0-42.0 for function. CONCLUSION: Although the WOMAC is a commonly used measure for a single condition, the variability in methods used to calculate MCID and PASS estimates results in a range of values across studies making it unclear whether values reported in the literature can be applied with confidence. Future research is needed to refine methods used to calculate MCIDs and PASS.

Microbiological changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in individuals with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection.

OBJECTIVES: Non-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, P aeruginosa and three or more PEx/year. We report microbiological results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in individuals with NCFBE with P aeruginosa and PEx history [Lancet Respir Med 2019;7:213-26]. METHODS: Respiratory secretions from 582 participants receiving up to six 28-day on/off treatment cycles were analysed for sputum P. aeruginosa, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Escherichia coli densities, P. aeruginosa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility and opportunist prevalence changes were studied. RESULTS: Sputum P. aeruginosa density reductions from baseline after ARD-3150 treatments ranged from 1.77 (95% CI 2.13-1.40) versus 0.54 (95% CI 0.89-0.19) log10 CFU/g for placebo (second period) to 2.07 (95% CI 2.45-1.69) versus 0.70 (95% CI 1.11-0.29) log10 CFU/g for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased P. aeruginosa ciprofloxacin MIC but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC50 increased from 0.5 to 1 mg/L, MIC90 increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected. CONCLUSION: Microbiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit.

Condensate refractory inclusions from the CO3.00 chondrite Dominion Range 08006: Petrography, mineral chemistry, and isotopic compositions.

We have found two refractory inclusions in the CO3.00 carbonaceous chondrite Dominion Range (DOM) 08006 that appear to be primary condensates from the early solar nebula. One, inclusion 56-1, contains the first four phases predicted to form by equilibrium gas-solid condensation: corundum; hibonite; grossite; and perovskite. The other, 31-2, contains nine predicted condensate phases: hibonite; grossite; perovskite; melilite; spinel; FeNi metal; diopside; forsterite; and enstatite. Except for melilite/spinel, the phases occur in the predicted sequence from core to rim of the inclusion, which has an irregular shape inconsistent with a molten stage. This inclusion preserves the most complete record of condensation in the early solar nebula that has yet been found. The physical evidence reported here supports equilibrium condensation calculations that predict the observed sequence as well as the assumptions upon which they are based, such as total pressure (~10-3 atm), bulk system composition (solar), and C-O-H proportions. All phases in both inclusions and the associated ferromagnesian silicates are 16O-rich, with ∆17O between -25 and -20‰, implying that this is the original composition of the vast majority of primary condensates and that 16O-poor compositions observed in many isotopically heterogeneous inclusions are largely due to subsequent isotopic exchange. While the nebula was well-mixed with respect to oxygen isotopic composition, clearly resolved anomalies in Ca and Ti isotopic compositions indicate that some isotopic heterogeneity existed early and was preserved during condensation. Inclusion 31-2 did not incorporate live 26Al and has nucleosynthetic anomalies in the heavy Ca and Ti isotopes (i.e., δ48Ca = 4.3 ± 1.9‰; δ50Ti = 8.8 ± 2.0‰). In contrast, inclusion 56-1 has radiogenic 26Mg excesses yielding a (26Al/27Al)0 ratio of (1.0 ± 0.1) × 10-5 and negative nucleosynthetic isotopic anomalies in Ca (δ48Ca = -10.3 ± 4.2‰) and Ti (δ50Ti = -4.3 ± 2.9‰). Thus, it represents a deviation from the mutual exclusivity relationship between 26Al incorporation and large nucleosynthetic anomalies. The reservoirs in which these inclusions formed had similar O-isotopic and different Al-, Ca- and Ti-isotopic compositions, suggesting that while the CAI-forming region was well-mixed with respect to oxygen isotopic composition, clearly resolved anomalies in Ca and Ti isotopic compositions indicate that some isotopic heterogeneity existed and was preserved during condensation.

Factors associated with the orthopaedic surgeon's decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1905 patients.

OBJECTIVE: To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA). DESIGN: Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0-4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country. RESULTS: In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69-4.97] and 3.30 [2.17-5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32-2.06] and 1.38 [1.15-1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA. CONCLUSION: Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR.

Depression and medication nonadherence in childhood-onset systemic lupus erythematosus.

Objectives Depression and medication nonadherence are important in managing chronic diseases, but little is known about these factors in childhood-onset systemic lupus erythematosus (cSLE). The objectives of this cross-sectional study were to estimate prevalence of depression and medication nonadherence, describe demographic and disease characteristics associated with depression and medication nonadherence, and evaluate the association between depression and medication nonadherence in cSLE patients. Methods Patients with cSLE ( n = 51) completed validated screening questionnaires to identify depression and medication nonadherence, Patient Health Questionnaire-9 and Medication Adherence Self-Report Inventory, respectively. Demographic and disease characteristics were obtained via chart abstraction, and compared between groups of depression or medication nonadherence status. A multivariable linear regression model adjusting for propensity scores was conducted to evaluate the association between depression and medication nonadherence. Results The prevalence of a positive depression screen was 58.8%, and seven patients reported suicidal ideation (13.7%). The prevalence of self-reported medication nonadherence was 19.7%. No statistically significant differences for demographic and disease characteristics were found between patients with a positive vs. negative depression screen. Patients reporting medication nonadherence were more likely to have longer disease duration (4.8 vs. 2.6 years, p = 0.035). As the severity of depression symptoms increased, the degree of medication nonadherence also increased (beta = -1.89; p = 0.011). Conclusions The prevalence of depression and medication nonadherence is high in cSLE, and these factors have a direct relationship. Interventions that better recognize and treat depression and increase rates of medication adherence are needed to improve outcomes in cSLE.

First detection of Edwardsiella ictaluri (Proteobacteria: Enterobacteriaceae) in wild Australian catfish.

The bacterium Edwardsiella ictaluri is considered to be one of the most significant pathogens of farmed catfish in the United States of America and has also caused mortalities in farmed and wild fishes in many other parts of the world. E. ictaluri is not believed to be present in wild fish populations in Australia, although it has previously been detected in imported ornamental fishes held in quarantine facilities. In an attempt to confirm freedom from the bacterium in Australian native fishes, we undertook a risk-based survey of wild catfishes from 15 sites across northern Australia. E. ictaluri was detected by selective culturing, followed by DNA testing, in Wet Tropics tandan (Tandanus tropicanus) from the Tully River, at a prevalence of 0.40 (95% CI 0.21-0.61). The bacterium was not found in fishes sampled from any of the other 14 sites. This is the first report of E. ictaluri in wild fishes in Australia.

Cross-cultural adaptation and implementation of Good Life with osteoarthritis in Denmark (GLA:D™): group education and exercise for hip and knee osteoarthritis is feasible in Canada.

OBJECTIVE: Adapt and evaluate the feasibility of implementing Good Life with osteoArthritis in Denmark (GLA:DTM) in Canada for people with mild to severe hip/knee osteoarthritis. METHODS: Patients triaged to non-surgical management participated in two education sessions and 12 supervised, neuromuscular exercise classes. We used the RE-AIM implementation framework evaluating outcomes of Reach, Effectiveness/Efficacy, Adoption, Implementation and Maintenance. Patients completed surveys pre-program and at 3 months follow-up. Program fidelity was evaluated at four observations against a priori criteria. We conducted semi-structured interviews with therapists post-program. RESULTS: 72 patients consented to participate, 59 started the program and one withdrew on physician advice. The remaining 58 provided follow-up data. Mean age was 67 years; 78% were female and 52% had body mass index (BMI) >25. The effect of the program was demonstrated: 40% improvement in pain with 59% achieving a clinically important improvement of ≥2 points on the Numeric Pain Rating scale. Statistically significant improvement also occurred in the Hip disability/Knee injury and Osteoarthritis Outcome Score subscales. 24% reported increased physical activity. Program fidelity was demonstrated with all criteria met. Therapists emphasized that rolling recruitment allowed appropriate supervision and resulted in participants encouraging each other. 99% of participants indicated they benefitted from and were satisfied with the program and 90% reported using the knowledge daily. 52% were willing to pay >$250 Cdn for the program. CONCLUSION: GLA:DTM implementation was feasible in the Canadian context with results similar to those of >7,000 participants in Denmark. Implementation and evaluation of GLA:DTM Canada is now occurring nationally.

Pharmacogenomics-Based Point-of-Care Clinical Decision Support Significantly Alters Drug Prescribing.

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk. The influence of pharmacogenomic alerts on prescribing behaviors was the primary endpoint. In all, 2,279 outpatient encounters were analyzed. Independent of other potential prescribing mediators, medications with high pharmacogenomic risk were changed significantly more often than prescription drugs lacking pharmacogenomic information (odds ratio (OR) = 26.2 (9.0-75.3), P < 0.0001). Medications with cautionary pharmacogenomic information were also changed more frequently (OR = 2.4 (1.7-3.5), P < 0.0001). No pharmacogenomically high-risk medications were prescribed during the entire study when physicians consulted the CDS tool. Pharmacogenomic information improved prescribing in patterns aimed at reducing patient risk, demonstrating that enhanced prescription decision-making is achievable through clinical integration of genomic medicine.

A prospective cohort study examining medical and social factors associated with engagement in life activities following total hip replacement.

OBJECTIVES: Studies show limited improvement in the frequency of engaging in life activities after joint replacement. However, there is a paucity of research that has examined factors, including other life events, which influence engagement following total hip replacement (THR). This research sought to identify factors associated with engaging in life activities following THR. METHODS: A prospective cohort study was conducted with 376 people who had a THR for osteoarthritis (OA). Data were collected pre-surgery and 1 year post-surgery. The primary outcome was change in frequency in engagement in life activities (Late Life Disability Index (LLDI): higher scores indicate higher frequency of engagement (range 0-80)). Analyses included multivariable regression. Factors considered included: positive/negative life events, a new comorbidity, another joint replacement and complications post-surgery. RESULTS: Participants' mean age was 64 years; 46% were male. 68% of participants had at least one comorbidity pre-surgery; 36% reported at least one new comorbidity after surgery. The mean change in LLDI frequency was an increase of 6.29 (±8.10). 36% reported one or more positive impact life events in the year following surgery; 63% reported one or more negative life events. The number of positive life events (beta = 1.24; 95% CI: 0.49, 1.99) was significantly associated with change in LLDI frequency after adjusting for age, sex, education, body mass index (BMI), comorbidities pre-surgery, number of symptomatic joints and pre-surgery pain and function, LLDI limitations and depression. CONCLUSIONS: These findings highlight the significant influence of social factors and life circumstances on engagement in life activities following THR.

Patient Perceptions of Care as Influenced by a Large Institutional Pharmacogenomic Implementation Program.

Despite growing clinical use of genomic information, patient perceptions of genomic-based care are poorly understood. We prospectively studied patient-physician pairs who participated in an institutional pharmacogenomic implementation program. Trust/privacy/empathy/medical decision-making (MDM)/personalized care dimensions were assessed through patient surveys after clinic visits at which physicians had access to preemptive pharmacogenomic results (Likert scale, 1 = minimum/5 = maximum; mean [SD]). From 2012-2015, 1,261 surveys were issued to 507 patients, with 792 (62.8%) returned. Privacy, empathy, MDM, and personalized care scores were significantly higher after visits when physicians considered pharmacogenomic results. Importantly, personalized care scores were significantly higher after physicians used pharmacogenomic information to guide medication changes (4.0 [1.4] vs. 3.0 [1.6]; P < 0.001) compared with prescribing visits without genomic guidance. Multivariable modeling controlling for clinical factors confirmed personalized care scores were more favorable after visits with genomic-influenced prescribing (odds ratio [OR] = 3.26; 95% confidence interval [CI] = (1.31-8.14); P < 0.05). Physicians seem to individualize care when utilizing pharmacogenomic results and this decision-making augmentation is perceived positively by patients.

Improved radiological diagnosis of palmar osteochondral disease in the Thoroughbred racehorse.

BACKGROUND: Palmar osteochondral disease (POD) is common in the Thoroughbred racehorse yet difficult to diagnose by radiography alone. OBJECTIVES: To improve the sensitivity and specificity for diagnosing POD from radiographs. STUDY DESIGN: Prospective, longitudinal study. METHODS: Radiographs in nine different projections were made of metacarpophalangeal joints (MCPJ) of 50 Thoroughbreds. Post-mortem, MCPJs were dissected and gross pathology was scored. Three experienced Thoroughbred clinicians read each radiograph and recorded their findings. Another clinician reviewed each radiograph alongside the related gross specimens in order to correlate radiological findings with joint pathology. This served as a 'gold standard'. The performance of each clinician at detecting POD was compared with the 'gold standard'. Radiological features associated with POD were identified and presented to the clinicians in a training manual, prior to them re-reading the radiographs. The ability of each clinician to diagnose POD was reassessed. RESULTS: Palmar osteochondral disease was a common finding (88/100 joints). All three clinicians demonstrated low sensitivity and low specificity at detecting POD (mean 0.37 and 0.75, respectively). Conversely, the sensitivity and specificity for POD in the 'gold standard' was high (0.95 and 1.0). POD was associated with primary radiological features (e.g. focal radiolucencies in the palmar condyles, disruption of the outline of subchondral bone and focal sclerosis of the palmar condyles) and secondary features (e.g. basilar and apical osteophytes on the proximal sesamoid bones, flattening of the palmar condyles and cavitation of the dorso-distal aspect of the third metacarpal bone). Secondary radiographic features were often easier to detect. Following training the performance of clinicians at identifying POD was significantly improved. MAIN LIMITATIONS: Only two clinicians completed the study; low proportion of POD negative cases in the study. CONCLUSIONS: Clinicians frequently overlook key radiological features related to POD. Alerting clinicians to relevant radiological features improved the sensitivity and specificity of diagnosis.

A Novel Mechanism for Human Cardiac Ankyrin-B Syndrome due to Reciprocal Chromosomal Translocation.

BACKGROUND: Cardiac rhythm abnormalities are a leading cause of morbidity and mortality in developed countries. Loss-of-function variants in the ANK2 gene can cause a variety of cardiac rhythm abnormalities including sinus node dysfunction, atrial fibrillation and ventricular arrhythmias (called the "ankyrin-B syndrome"). ANK2 encodes ankyrin-B, a molecule critical for the membrane targeting of key cardiac ion channels, transporters, and signalling proteins. METHODS AND RESULTS: Here, we describe a family with a reciprocal chromosomal translocation between chromosomes 4q25 and 9q26 that transects the ANK2 gene on chromosome 4 resulting in loss-of-function of ankyrin-B. Select family members with ankyrin-B haploinsufficiency due to the translocation displayed clinical features of ankyrin-B syndrome. Furthermore, evaluation of primary lymphoblasts from a carrier of the translocation showed altered levels of ankyrin-B as well as a reduced expression of downstream ankyrin-binding partners. CONCLUSIONS: Thus, our data conclude that, similar to previously described ANK2 loss-of-function "point mutations", large chromosomal translocations resulting in ANK2 haploinsufficiency are sufficient to cause the human cardiac ankyrin-B syndrome. The unexpected ascertainment of ANK2 dysfunction via the discovery of a chromosomal translocation in this family, the determination of the familial phenotype, as well as the complexities in formulating screening and treatment strategies are discussed.

Cross-cultural validation of the ICOAP and physical function short forms of the HOOS and KOOS in a multi-country study of patients with hip and knee osteoarthritis.

OBJECTIVE: To evaluate the internal consistency and construct validity of the Physical Function short-forms for the Hip and Knee Injury Osteoarthritis Outcome Scores (HOOS-PS/KOOS-PS) and the Intermittent and Constant Osteoarthritis Pain (ICOAP) in a nine country study of patients consulting for total hip or knee replacement (THR or TKR). METHODS: Patients completed HOOS-PS or KOOS-PS, ICOAP and Western Ontario and McMaster Universities' Osteoarthritis Index (WOMAC) pain and physical function subscales at their consultation visit. Internal consistency was calculated using Cronbach's alpha. The association of HOOS-PS/KOOS-PS and ICOAP with WOMAC pain and function subscales was calculated with Spearman correlation coefficients with 95% confidence intervals. RESULTS: HOOS-PS/KOOS-PS and ICOAP demonstrated high internal consistency across countries (alpha 0.75-0.96 (hip) and 0.76-0.95 (knee)). Both HOOS-PS and KOOS-PS demonstrated high correlations (0.76-0.90 and 0.75-0.91, respectively) with WOMAC function in all countries. ICOAP exhibited moderate to high correlations with WOMAC pain and function subscales (0.53-0.84 (hip) and 0.43-0.84 (knee)). CONCLUSION: The psychometric properties of the HOOS-PS/KOOS-PS, and ICOAP were maintained across all countries.

Multiplanar lumbopelvic control in patients with low back pain: is multiplanar assessment better than single plane assessment in discriminating between patients and healthy controls?

OBJECTIVES: Patients with low back pain (LBP) commonly have lumbopelvic control deficits. Lumbopelvic assessment during sagittal motion is incorporated into commonly used clinical examination algorithms for Treatment Based Classification. The purpose of this study was to investigate whether combined assessment of lumbopelvic control during sagittal and frontal plane motion discriminates between people with and without LBP better than single plane assessment alone. METHODS: Nineteen patients with LBP and 18 healthy control participants volunteered for this study. The active straight leg raise (ASLR) and active hip abduction (AHAbd) tests were used to assess lumbopelvic control during sagittal and frontal plane motion, respectively. The tests were scored as positive or negative using published scoring criteria. Contingency tables were created for each test alone and for the combined tests (both positive/both negative) with presence/absence of LBP as the reference standard to calculate accuracy statistics of sensitivity (sn), specificity (sp), likelihood (+LR and -LR), and diagnostic odds ratios (OR). RESULTS: Active straight leg raise and AHAbd tests alone had sn of 0·63, 0·74, respectively, sp of 0·61, 0·50, respectively, and OR of 2·7, 2·8, respectively. The combined tests had sn = 0·89, sp = 0·60, and OR = 12·0. Forty percent of patients with LBP had control deficits in both planes of motion. DISCUSSION: The AHAbd and ALSR tests appear to have greater diagnostic discrimination when used in combination than when used independently. A percentage of patients with LBP had control deficits in both planes, while others demonstrated uniplanar deficits only. These findings highlight the importance of multiplanar assessment in patients with LBP.