Prevalence of early hip OA features on MRI in high-impact athletes. The femoroacetabular impingement and hip osteoarthritis cohort (FORCe) study.

OBJECTIVE: To compare early hip osteoarthritis (OA) features on magnetic resonance imaging (MRI) in high-impact athletes with and without hip and/or groin pain, and to evaluate associations between early hip OA features, the International Hip Outcome Tool (iHOT33) and Copenhagen Hip and Groin Outcome Score (HAGOS). DESIGN: This case-control study evaluated data of the femoroacetabular impingement and hip osteoarthritis cohort (FORCe). One hundred and eighty-two symptomatic (hip and/or groin pain >6 months and positive flexion-adduction-internal-rotation (FADIR) test) and 55 pain-free high-impact athletes (soccer or Australian football (AF)) without definite radiographic hip OA underwent hip MRI. The Scoring Hip Osteoarthritis with MRI (SHOMRI) method quantified and graded the severity of OA features. Each participant completed the iHOT33 and HAGOS. RESULTS: Hip and/or groin pain was associated with higher total SHOMRI (0-96) (mean difference 1.4, 95% CI: 0.7-2.2), labral score (adjusted incidence rate ratio (aIRR) 1.33, 95% CI: 1.1-1.6). Differences in prevalence of cartilage defects, labral tears and paralabral cysts between symptomatic and pain-free participants were inconclusive. There was a lower prevalence of effusion-synovitis in symptomatic participants when compared to pain-free participants (adjusted odds ratio (aOR) 0.46 (95% CI: 0.3-0.8). Early hip OA features were not associated with iHOT33 or HAGOS. CONCLUSIONS: A complex and poorly understood relationship exists between hip and/or groin pain and early hip OA features present on MRI in high-impact athletes without radiographic OA. Hip and/or groin pain was associated with higher SHOMRI and labral scores.

Bilateral ptosis: An unusual presentation of mid brain tuberculoma.

Central nervous system tuberculoma can have different clinical manifestations like headache, seizures, papilledema or other signs of raised intracranial pressure depending up on the site and number of tuberculoma. We report a case of 56 year old female reported with history of bilateral asymmetric ptosis of one month duration,with no other neurological defecit. Magnetic resonance imaging (MRI) brain revealed well defined ring enhancing lesion in the medial aspect of left hemi midbrain with diffuse disproportionate perilessional edema. Contrast Enhanced Computed Tomogram (CECT) of chest and abdomen revealed features of disseminated tuberculosis. She was diagnosed as a case of disseminated tuberculosis and started on antitubercular therapy with steroids and the ptosis almost resolved after 01 month of antitubercular therapy. Our case report is unique in the sense that only few cases of midbrain tuberculoma causing occulomotor abnormalities are reported in literature.

Diagnosing osteoarthritis from T2 maps using deep learning: an analysis of the entire Osteoarthritis Initiative baseline cohort.

OBJECTIVE: We aim to study to what extent conventional and deep-learning-based T2 relaxometry patterns are able to distinguish between knees with and without radiographic osteoarthritis (OA). METHODS: T2 relaxation time maps were analyzed for 4,384 subjects from the baseline Osteoarthritis Initiative (OAI) Dataset. Voxel Based Relaxometry (VBR) was used for automatic quantification and voxel-based analysis of the differences in T2 between subjects with and without radiographic OA. A Densely Connected Convolutional Neural Network (DenseNet) was trained to diagnose OA from T2 data. For comparison, more classical feature extraction techniques and shallow classifiers were used to benchmark the performance of our algorithm's results. Deep and shallow models were evaluated with and without the inclusion of risk factors. Sensitivity and Specificity values and McNemar test were used to compare the performance of the different classifiers. RESULTS: The best shallow model was obtained when the first ten Principal Components, demographics and pain score were included as features (AUC = 77.77%, Sensitivity = 67.01%, Specificity = 71.79%). In comparison, DenseNet trained on raw T2 data obtained AUC = 83.44%, Sensitivity = 76.99%, Specificity = 77.94%. McNemar test on two misclassified proportions form the shallow and deep model showed that the boost in performance was statistically significant (McNemar's chi-squared = 10.33, degree of freedom (DF) = 1, P-value = 0.0013). CONCLUSION: In this study, we presented a Magnetic Resonance Imaging (MRI)-based data-driven platform using T2 measurements to characterize radiographic OA. Our results showed that feature learning from T2 maps has potential in uncovering information that can potentially better diagnose OA than simple averages or linear patterns decomposition.

Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury.

OBJECTIVE: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. DESIGN: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. RESULTS: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. CONCLUSIONS: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.

Adherence to osteoporosis therapy after an upper extremity fracture: a pre-specified substudy of the C-STOP randomized controlled trial.

Despite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor. INTRODUCTION: To compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture. METHODS: Community-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients. RESULTS: By 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not. CONCLUSION: While both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01401556.

Harmonically Confined Particles with Long-Range Repulsive Interactions.

We study an interacting system of N classical particles on a line at thermal equilibrium. The particles are confined by a harmonic trap and repel each other via pairwise interaction potential that behaves as a power law ∝∑[under i≠j][over N]|x_{i}-x_{j}|^{-k} (with k>-2) of their mutual distance. This is a generalization of the well-known cases of the one-component plasma (k=-1), Dyson's log gas (k→0^{+}), and the Calogero-Moser model (k=2). Because of the competition between harmonic confinement and pairwise repulsion, the particles spread over a finite region of space for all k>-2. We compute exactly the average density profile for large N for all k>-2 and show that while it is independent of temperature for sufficiently low temperature, it has a rich and nontrivial dependence on k with distinct behavior for -21 and k=1.

Thymic Atrophy: Experimental Studies and Therapeutic Interventions.

The thymus is essential for T cell development and maturation. It is extremely sensitive to atrophy, wherein loss in cellularity of the thymus and/or disruption of the thymic architecture occur. This may lead to lower naïve T cell output and limited TCR diversity. Thymic atrophy is often associated with ageing. What is less appreciated is that proper functioning of the thymus is critical for reduction in morbidity and mortality associated with various clinical conditions including infections and transplantation. Therefore, therapeutic interventions which possess thymopoietic potential and lower thymic atrophy are required. These treatments enhance thymic output, which is a vital factor in generating favourable outcomes in clinical conditions. In this review, experimental studies on thymic atrophy in rodents and clinical cases where the thymus atrophies are discussed. In addition, mechanisms leading to thymic atrophy during ageing as well as during various stress conditions are reviewed. Therapies such as zinc supplementation, IL7 administration, leptin treatment, keratinocyte growth factor administration and sex steroid ablation during thymic atrophy involving experiments in animals and various clinical scenarios are reviewed. Interventions that have been used across different scenarios to reduce the extent of thymic atrophy and enhance its output are discussed. This review aims to speculate on the roles of combination therapies, which by acting additively or synergistically may further alleviate thymic atrophy and boost its function, thereby strengthening cellular T cell responses.

Effects of obesity and diabetes on rate of bone density loss.

In this large registry-based study, women with diabetes had marginally greater bone mineral density (BMD) loss at the femoral neck but not at other measurement sites, whereas obesity was not associated with greater BMD loss. Our data do not support the hypothesis that rapid BMD loss explains the increased fracture risk associated with type 2 diabetes and obesity observed in prior studies. INTRODUCTION: Type 2 diabetes and obesity are associated with higher bone mineral density (BMD) which may be less protective against fracture than previously assumed. Inconsistent data suggest that rapid BMD loss may be a contributing factor. METHODS: We examined the rate of BMD loss in women with diabetes and/or obesity in a population-based BMD registry for Manitoba, Canada. We identified 4960 women aged ≥ 40 years undergoing baseline and follow-up BMD assessments (mean interval 4.3 years) without confounding medication use or large weight fluctuation. We calculated annualized rate of BMD change for the lumbar spine, total hip, and femoral neck in relation to diagnosed diabetes and body mass index (BMI) category. RESULTS: Baseline age-adjusted BMD was greater in women with diabetes and for increasing BMI category (all P < 0.001). In women with diabetes, unadjusted BMD loss was less at the lumbar spine (P = 0.017), non-significantly greater at the femoral neck (P = 0.085), and similar at the total hip (P = 0.488). When adjusted for age and BMI, diabetes was associated with slightly greater femoral neck BMD loss (- 0.0018 g/cm2/year, P = 0.012) but not at the lumbar spine or total hip. There was a strong linear effect of increasing BMI on attenuated BMI loss at the lumbar spine with negligible effects on hip BMD. CONCLUSIONS: Diabetes was associated with slightly greater BMD loss at the femoral neck but not at other measurement sites. BMD loss at the lumbar spine was reduced in overweight and obese women but BMI did not significantly affect hip BMD loss.

Performance of FRAX in clinical practice according to sex and osteoporosis definitions: the Manitoba BMD registry.

Among 62,275 women and 6455 men, FRAX stratified risk for incident major osteoporotic fracture (MOF) and incident hip fracture (HF) without sex interaction. Performance was good in those with osteoporosis regardless of how this was defined. INTRODUCTION: Some studies have reported that FRAX performance differs according to sex and/or osteoporosis definitions. We evaluated whether the performance of FRAX to predict incident MOF and HF in women and men was affected by the presence or absence of osteoporosis defined by World Health Organization (WHO) or National Osteoporosis Foundation (NOF) criteria. METHODS: We studied women and men age ≥ 40 years with baseline hip and spine DXA scans (1996-2013). Individuals were classified into four non-overlapping subgroups: osteoporosis by WHO criteria, osteoporosis exclusively by NOF criteria, high fracture risk by FRAX (MOF ≥ 20% or HF ≥ 3%, without osteoporosis), and low fracture risk (MOF < 20% and HF < 3% without osteoporosis). In each subgroup, we evaluated stratification (hazard ratios [HR]) and calibration (observed vs predicted 10-year fracture probability) for incident fracture. RESULTS: The population included 62,275 women (5345 MOF and 1471 HF) and 6455 men (405 MOF and 108 HF). FRAX scores were strongly predictive of MOF (HR per SD: women 2.12, 95% CI 2.06-2.18; men 1.89, 95% CI 1.73-2.08; sex interaction p value = 0.97) and HF (women 4.78, 95% CI 4.44-5.14; men 4.20, 95% CI 3.22-5.49; sex interaction p value = 0.71). FRAX scores gave similar HRs for MOF among the four subgroups (subgroup interaction p value 0.34 for women, 0.22 for men). Observed versus predicted 10-year MOF and HF probability for the defined subgroups demonstrated a high level of concordance for women and men (all r2 ≥ 0.9). CONCLUSIONS: FRAX was a strong and consistent predictor of MOF and HF in both women and men and performed well in those with osteoporosis whether defined by WHO or NOF criteria.

Risk of prostate cancer across different racial/ethnic groups in men with diabetes: a retrospective cohort study.

AIM: To examine the associations between prostate cancer, diabetes and race/ethnicity. METHODS: Using administrative data from British Columbia, Canada for the period 1994 to 2012, we identified men aged ≥50 years with and without diabetes. Validated surname algorithms identified men as Chinese, Indian or of other race/ethnicity. Multivariable Cox regression was used to estimate adjusted risks of prostate cancer according to diabetes status and race/ethnicity. RESULTS: Our cohort of 160 566 men had a mean (sd) age of 64.7 (9.4) years and a median of 9 years' follow-up. The incidence rates of prostate cancer among those with and without diabetes were 177.4 (171.7-183.4) and 216.0 (209.7-222.5) per 1000 person-years, respectively. The incidence among Chinese men was 120.9 (109.2-133.1), among Indian men it was 144.1 (122.8-169.0) and in men of other ethnicity it was 204.8 (200.2-209.5). Diabetes was independently associated with a lower risk of prostate cancer (adjusted hazard ratio 0.82, 95% CI 0.78-0.86), as was Chinese (adjusted hazard ratio 0.54, 95% CI 0.46,0.63) and Indian (adjusted hazard ratio 0.66, 95% CI 0.49,0.89) race/ethnicity; however, there was no statistically significant interaction between diabetes status and race/ethnicity (all P>0.1). CONCLUSION: Diabetes and Chinese and Indian race/ethnicity were each independently associated with a lower risk of prostate cancer.

Risk factors for pneumococcal endocarditis.

Bacteremia is one of the most common manifestations of invasive pneumococcal disease (IPD). One complication of bacteremia is endocarditis; yet, few studies have evaluated the overall incidence and risk factors for IPD-associated endocarditis. Thus, we evaluated the overall incidence and risk factors of endocarditis compared to those without endocarditis in a large population of IPD patients. We prospectively collected all IPD cases from 2000 to 2014 in Northern Alberta, Canada. Descriptive statistics were used to compare sociodemographic variables, clinical characteristics, and IPD-related outcomes between patients with and without endocarditis. Endocarditis complicated the course of only 28 (0.3%) of 3251 adult patients with IPD. Endocarditis patients were more likely to use illicit drugs and have a higher severity of illness at presentation (i.e., higher rate of altered mental status and rate of intensive care unit [ICU] utilization, p < 0.05); however, no other major risk factors were identified. New murmur development among endocarditis patients was common: 39.3% compared to 2.2% of non-endocarditis patients (p < 0.001). The mortality rate of 39.3% was more than twice that of the rate of 14.7% for the patients with IPD but without endocarditis. There was no pneumococcal serotype predilection for endocarditis. Endocarditis is an uncommon complication of IPD, but, when present, is associated with a significantly increased risk of mortality. Overall, few specific risk factors were identified for IPD-related endocarditis, with the exception of illicit drug use.

Effect of dietary manipulation and vaccination of turkey breeder hens on immunoglobulin levels of yolk, yolk sac and neonate poults.

Two hundred turkey breeder hens and 24 viable toms of 30-35 weeks age of small white variety were distributed into two treatment groups having four replicates of 25 hens and three toms in each treatment. First four replicates were offered a turkey breeder diet (Diet A) (Nutrient requirements of poultry, 1994, National Academic Press, Washington, DC) and the rest four replicates were maintained on a higher plane of nutrition (Diet B) for 8-week duration. After 6 weeks of experimental feeding, two replicates from each treatment groups were vaccinated with ND (R2 B) vaccine. Yolk sac of embryo from birds fed Diet B had a significantly higher (p < .05) IgG, IgM level and HI titre (log 2) than those fed Diet A. HI titre values of embryonic yolk sac from the vaccinated birds fed Diet B were significantly higher (p < .05) than that of the control groups. In addition, HI titre values were significantly higher (p < .05) in the day-old poults of the birds fed Diet B than that of those fed Diet A. There was significantly (p < .01) positive correlation between serum IgG and IgM of the breeder birds and day-old chicks. Similarly, there was significantly (p < .05) positive correlation between yolk IgG and IgM after 1-month experimental feeding and yolk sac IgG and IgM. Positive correlation (p < .05) also existed between yolk sac IgM and day-old chick serum IgM. Furthermore, the HI titres of breeder birds' serum at 14 days post-vaccination were positively correlated with their egg yolk after 10 and 15 days post-vaccination, yolk sac and day-old chicks. Thus, the study envisaged that a higher immunity in neonate poults from turkey breeders maintained on a higher plane of nutrition may be elicited as there was maternal transfer of antibodies from the serum of breeder birds to their offsprings through their yolk sac.

Cross-sectional and longitudinal study of the impact of posterior meniscus horn lesions on adjacent cartilage composition, patient-reported outcomes and gait biomechanics in subjects without radiographic osteoarthritis.

OBJECTIVE: The aim of this study was to assess cross-sectional and longitudinal effects of meniscal lesions on adjacent cartilage T1ρ and T2 relaxation times, patient-reported outcomes and gait biomechanics. DESIGN: Thirty patients with no cartilage morphological defects reported by Whole Organ MRI Score (WORMS) magnetic resonance imaging (MRI) grading and no radiographic osteoarthritis (OA) (Kellgren--Lawrence (KL) ≤ 1) were selected, 15 with posterior meniscus horn lesions and 15 matched controls without meniscal lesions. All were imaged on a 3T MR scanner for three consecutive years, except those who dropped from the study. Sagittal and frontal plane kinematic gait data were acquired at baseline. The Knee Injury and Osteoarthritis Outcome Score (KOOS) survey was taken each time. All images were automatically segmented and registered to an atlas for voxel-by-voxel cross-sectional and longitudinal analyses. RESULTS: Relaxation time comparisons between groups showed elevated T1ρ of the lateral tibia (LP) and elevated T2 of the medial tibia (MT) and LT at 1 and 2 years in the lesion group. Longitudinal comparisons within each group revealed greater relaxation time elevations over one and 2 years in the group with lesions. KOOS Quality of Life (QOL) was significantly different between the groups at all time points (P < 0.05), as were other KOOS subcategories. No significant differences in the frontal or sagittal biomechanics were observed between the groups at baseline. CONCLUSIONS: Individuals with healthy cartilage and posterior meniscal horn lesions have increased relaxation times when compared to matched controls, increased relaxation time changes over 2 years, and consistently report a lower KOOS QOL, yet show no difference in gait biomechanics.

The comparability of HR-pQCT bone measurements is improved by scanning anatomically standardized regions.

We investigated the sensitivity of distal bone density, structure, and strength measurements by high-resolution peripheral quantitative computed tomography (HR-pQCT) to variability in limb length. Our results demonstrate that HR-pQCT should be performed at a standard %-of-total-limb-length to avoid substantial measurement bias in population study comparisons and the evaluation of individual skeletal status in a clinical context. INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone do not account for anatomic variability in bone length: a 1-cm volume is acquired at a fixed offset from an anatomic landmark. Our goal was to evaluate HR-pQCT measurement variability introduced by imaging fixed vs. proportional volumes and to propose a standard protocol for relative anatomic positioning. METHODS: Double-length (2-cm) scans were acquired in 30 adults. We compared measurements from 1-cm sub-volumes located at the default fixed offset, and the average %-of-length offset. The average position corresponded to 4.0% ± 1.1 mm for radius, and 7.2% ± 2.2 mm for tibia. We calculated the RMS difference in bone parameters and T-scores to determine the measurement variability related to differences in limb length. We used anthropometric ratios to estimate the mean limb length for published HR-pQCT reference data, and then calculated mean %-of-length offsets. RESULTS: Variability between fixed vs. relative scan positions was highest in the radius, and for cortical bone in general (RMS difference Ct.Th = 19.5%), while individuals had T-score differentials as high as +3.0 SD (radius Ct.BMD). We estimated that average scan position for published HR-pQCT reference data corresponded to 4.0% at the radius, and 7.3% at tibia. CONCLUSION: Variability in limb length introduces significant bias to HR-pQCT measures, confounding cross-sectional analyses and limiting the clinical application for individual assessment of skeletal status. We propose to standardize scan positioning using 4.0 and 7.3% of total bone length for the distal radius and tibia, respectively.

Clinical performance of an updated trabecular bone score (TBS) algorithm in men and women: the Manitoba BMD cohort.

This is the first study to directly compare the original and recently updated versions of the trabecular bone score (TBS) algorithm. We confirmed improved performance of the new algorithm, especially among men. INTRODUCTION: Lumbar spine trabecular bone score (TBS) predicts major osteoporotic fractures (MOFs) and hip fractures (HFs) independent of bone density. The original TBS algorithm (version 1; [TBS-v1]) was optimized for women of average body size. Limitations were identified when used in men or extremes of body mass index (BMI). The current study evaluates an updated TBS algorithm (version 2; [TBS-v2]) modified to address these issues. METHODS: From a registry with all DXA results for Manitoba, Canada, we identified 47,736 women and 4348 men age ≥ 40 with baseline spine DXA (GE Prodigy, 1999-2011). Spine TBS was measured using both TBS-v1 and TBS-v2 algorithms. Risk stratification for incident fractures identified from population-based data was assessed from area under the receiver operating characteristic curve (AUROC). RESULTS: With the TBS-v1 algorithm, average TBS for men was significantly lower than for women (p < 0.001) and showed significant inverse correlations with BMI (Pearson r-0.40 in men, -0.18 in women [both p < 0.001]). With the TBS-v2 algorithm, average values for men were slightly greater than for women (p < 0.001) and there were no significant correlations with BMI (Pearson r 0.01 in men, -0.01 in women [both p > 0.1]). During mean follow-up of 5 years in men, there were 214 incident MOFs and 47 HFs; during 6 years mean follow-up in women, there were 2895 incident MOFs and 694 HFs. Improvements in fracture prediction were seen with TBS-v2 in both men (change in AUROC for MOFs +0.021 [p = 0.17], HFs +0.046 [p = 0.04]) and women (change in AUROC for MOFs +0.012 [p < 0.001], HFs +0.020 [p < 0.001]). CONCLUSION: The updated TBS algorithm is less affected by BMI, gives higher mean results for men than women consistent with their lower fracture risk, and improves fracture prediction in both men and women.

Economic evaluation of a population-based osteoporosis intervention for outpatients with non-traumatic non-hip fractures: the "Catch a Break" 1i [type C] FLS.

Fracture liaison services (FLS) are advocated to improve osteoporosis treatment after fragility fracture, but there are few economic analyses of different models. A population-based 1i [=type C] FLS for non-hip fractures was implemented and it costs $44 per patient and it was very cost-effective ($9200 per QALY gained). Small operational changes would convert it from cost-effective to cost-saving. INTRODUCTION: After fragility fracture, <20% of patients receive osteoporosis treatment. FLS are recommended to address this deficit but there are very few economic analyses of different FLS models. Therefore, we conducted an economic analysis of a 1i (=type C) FLS called "Catch a Break (CaB)." METHODS: CaB is a population-based FLS in Alberta, Canada, that case-finds older outpatients with non-traumatic upper extremity, spine, pelvis, or "other" non-hip fractures and provides telephonic outreach and printed educational materials to patients and their physicians. Cost-effectiveness was assessed using Markov decision-analytic models. Costs were expressed in 2014 Canadian dollars and effectiveness based on model simulations of recurrent fractures and quality-adjusted life years (QALYs). Perspective was healthcare payer; horizon was lifetime; and costs and benefits were discounted 3%. RESULTS: Over 1 year, CaB enrolled 7323 outpatients (mean age 67 years, 75% female, 69% upper extremity) at average cost of $44 per patient. Compared with usual care, CaB increased rates of bisphosphonate treatment by 4.3 to 17.5% (p < 0.001). Over their lifetime, for every 10,000 patients enrolled in CaB, 4 hip fractures (14 fractures total) would be avoided and 12 QALYs gained. Compared with usual care, incremental cost-effectiveness of CaB was estimated at $9200 per QALY. CaB was cost-effective in 85% of 10,000 probabilistic simulations. Sensitivity analyses showed if "other" fractures were excluded and intervention costs reduced 25% that CaB would become cost-saving. CONCLUSIONS: A relatively inexpensive population-based 1i (=type C) FLS was implemented in Alberta and it was very cost-effective. If CaB excluded "other" fractures and decreased intervention costs by 25%, it would be cost-saving, as would any FLS that was more effective and less expensive.

FRAX for fracture prediction shorter and longer than 10 years: the Manitoba BMD registry.

In a large clinical registry for the province of Manitoba, Canada, FRAX predicted incident MOF and hip fracture from 1 to 15 years following baseline assessment. A simple linear rescaling of FRAX outputs seems useful for predicting both short- and long-term fracture risk in this population. INTRODUCTION: FRAX® estimates 10-year probability of major osteoporotic fracture (MOF) and hip fracture. We examined FRAX predictions over intervals shorter and longer than 10 years. METHODS: Using a population-based clinical registry for Manitoba, Canada, we identified 62,275 women and 6455 men 40 years and older with baseline dual-energy X-ray absorptiometry scans and FRAX scores. Incident MOF and hip fracture were assessed up to 15 years from population-based data. We assessed agreement between estimated fracture probability from 1 to 15 years using linearly rescaled FRAX scores and observed cumulative fracture probability. The gradient of risk for FRAX probability and incident fracture was examined overall and for 5-year intervals. RESULTS: FRAX predicted incident MOF and hip fracture for all time intervals. There was no attenuation in the gradient of risk for MOF even for years >10. Gradient of risk was slightly lower for hip fracture prediction in years >10 vs years <5, though HRs remained high. Linear agreement was seen in the relationships between observed vs predicted (rescaled) FRAX probabilities (R 2 0.95-1.00). Among women, there was near-perfect linearity in MOF predictions. Deviations from linearity, with a slightly higher observed than predicted MOF probability, were most evident in the first years following a fracture event and after 10 years for hip fracture prediction in women using FRAX with BMD. Simulations showed that results were robust to large differences in fracture rates and moderate differences in mortality rates. CONCLUSIONS: FRAX predicts incident MOF and hip fracture up to 15 years and could be adapted to predict fracture over time periods shorter and longer term than 10 years in populations with fracture and mortality epidemiology similar to Canada.

Understanding fragility fracture patients' decision-making process regarding bisphosphonate treatment.

We aimed to understand how patients 50 years and older decided to persist with or stop osteoporosis (OP) treatment. Processes related to persisting with or stopping OP treatments are complex and dynamic. The severity and risks and harms related to untreated clinical OP and the favorable benefit-to-risk profile for OP treatments should be reinforced. INTRODUCTION: Older adults with fragility fracture and clinical OP are at high risk of recurrent fracture, and treatment reduces this risk by 50 %. However, only 20 % of fracture patients are treated for OP and half stop treatment within 1 year. We aimed to understand how older patients with new fractures decided to persist with or stop OP treatment over 1 year. METHODS: We conducted a grounded theory study of patients 50 years and older with upper extremity fracture who started bisphosphonates and then reported persisting with or stopping treatment at 1 year. We used theoretical sampling to identify patients who could inform emerging concepts until data saturation was achieved and analyzed these data using constant comparison. RESULTS: We conducted 21 interviews with 12 patients. Three major themes emerged. First, patients perceived OP was not a serious health condition and considered its impact negligible. Second, persisters and stoppers differed in weighting the risks vs benefits of treatments, where persisters perceived less risk and more benefit. Persisters considered treatment "required" while stoppers often deemed treatment "optional." Third, patients could change treatment status even 1-year post-fracture because they re-evaluated severity and impact of OP vs risks and benefits of treatments over time. CONCLUSIONS: The processes and reasoning related to persisting with or stopping OP treatments post-fracture are complex and dynamic. Our findings suggest two areas of leverage for healthcare providers to reinforce to improve persistence: (1) the severity and risks and harms related to untreated clinical OP and (2) the favorable benefit-to-risk profile for OP treatments.

Operator variability in scan positioning is a major component of HR-pQCT precision error and is reduced by standardized training.

In this study, we determined that operator positioning precision contributes significant measurement error in high-resolution peripheral quantitative computed tomography (HR-pQCT). Moreover, we developed software to quantify intra- and inter-operator variability and demonstrated that standard positioning training (now available as a web-based application) can significantly reduce inter-operator variability. INTRODUCTION: HR-pQCT is increasingly used to assess bone quality, fracture risk, and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection ("scout view image") and define the region to be scanned by positioning a "reference line" on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators. METHODS: To evaluate the operator in vivo measurement precision, we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner's software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled six new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group. RESULTS: In vivo precision errors were up to threefold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. The inter-operator precision errors were significantly greater than the short-term intra-operator precision (p < 0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators and lower inter-operator reproducibility (p < 0.001). Precision errors were significantly greater for the radius than for the tibia. CONCLUSION: Operator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online ( http://webapps.radiology.ucsf.edu/refline/ ).

Prevalence and impact of obesity in people with haemophilia: Review of literature and expert discussion around implementing weight management guidelines.

Obesity affects more than 35% of Americans, increasing the risk of more than 200 comorbid conditions, impaired quality of life and premature mortality. This review aimed to summarize literature published over the past 15 years regarding the prevalence and impact of obesity in people with haemophilia (PWH) and to discuss implementing general guidelines for weight management in the context of the haemophilia comprehensive care team. Although few studies have assessed the effects of obesity on haemophilia-specific outcomes, existing evidence indicates an important impact of weight status on lower extremity joint range of motion and functional disability, with potentially important effects on overall quality of life. Data regarding bleeding tendency in PWH with coexisting obesity are largely inconclusive; however, some individuals may experience reduced joint bleeds following moderate weight loss. Additionally, conventional weight-based dosing of factor replacement therapy leads to increased treatment costs for PWH with obesity or overweight, suggesting pharmacoeconomic benefits of weight loss. Evidence-based recommendations for weight loss include behavioural strategies to reduce caloric intake and increase physical activity, pharmacotherapy and surgical therapy in appropriate patients. Unique considerations in PWH include bleed-related risks with physical activity; thus, healthcare professionals should advise patients on types and intensities of, and approaches to, physical activity, how to adjust treatment to accommodate exercise and how to manage potential activity-related bleeding. Increasing awareness of these issues may improve identification of PWH with coexisting obesity and referral to appropriate specialists, with potentially wide-ranging benefits in overall health and well-being.