Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine.

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine. This living resource currently has more than 200,000 participants with ongoing recruitment. We highlight the clinical, laboratory, regulatory, and HIPAA-compliant informatics infrastructure along with our stakeholder engagement, consent, recontact, and participant engagement strategies. We characterize aspects of genetic and geographic diversity unique to the Rocky Mountain region, the primary catchment area for CCPM Biobank participants. We leverage linked health and demographic information of the CCPM Biobank participant population to demonstrate the utility of the CCPM Biobank to replicate complex trait associations in the first 33,674 genotyped individuals across multiple disease domains. Finally, we describe our current efforts toward return of clinical genetic test results, including high-impact pathogenic variants and pharmacogenetic information, and our broader goals as the CCPM Biobank continues to grow. Bringing clinical and research interests together fosters unique clinical and translational questions that can be addressed from the large EHR-linked CCPM Biobank resource within a HIPAA- and CLIA-certified environment.

A Cost-Utility Analysis of Robotic Arm-Assisted Total Hip Arthroplasty: Using Robotic Data from the Private Sector and Manual Data from the National Health Service.

Purpose: The aim was to assess the cost-effectiveness of robotic arm-assisted total hip arthroplasty (rTHA) compared with manual total hip arthroplasty (mTHA) and to assess the influence of annual volume on the relative cost-effectiveness of rTHA. Methods: A database of both rTHA (n = 48 performed in a private centre) and mTHA (n = 512 performed in the National Health Service) was used. Patient demographics, preoperative Oxford hip score, forgotten joint score, EuroQol 5-dimensional 3-level (EQ-5D), and postoperative EQ-5D were recorded. Two models for incremental cost-effectiveness ratios using cost per quality-adjusted life year (QALY) for rTHA were calculated based on a unit performing 100 rTHAs per year: 10-year follow-up and a lifetime time horizon (remaining life expectancy of a 69-year-old patient). Results: When adjusting for confounding factors, rTHA was independently associated with a 0.091 (p=0.029) greater improvement in the EQ-5D compared to mTHA. This resulted in a 10-year time horizon cost per QALY for rTHA of £1,910 relative to mTHA, which increased to £2,349 per QALY when discounted (5%/year). When using the 10-year time horizon cost per QALY was approximately £3,000 for a centre undertaking 50 rTHAs per year and decreased to £1,000 for centre undertaking 200 rTHAs per year. Using a lifetime horizon, the incremental unadjusted cost per QALY gained was £980 and £1432 when discounted (5%/year) for rTHA compared with mTHA. Conclusions: Despite the increased cost associated with rTHA, it was a cost-effective intervention relative to mTHA due to the associated greater health-related quality of health gain, according to the EQ-5D outcome measure.

Exposure to climate change drives stability or collapse of desert mammal and bird communities.

High exposure to warming from climate change is expected to threaten biodiversity by pushing many species toward extinction. Such exposure is often assessed for all taxa at a location from climate projections, yet species have diverse strategies for buffering against temperature extremes. We compared changes in species occupancy and site-level richness of small mammal and bird communities in protected areas of the Mojave Desert using surveys spanning a century. Small mammal communities remained remarkably stable, whereas birds declined markedly in response to warming and drying. Simulations of heat flux identified different exposure to warming for birds and mammals, which we attribute to microhabitat use. Estimates from climate projections are unlikely to accurately reflect species' exposure without accounting for the effects of microhabitat buffering on heat flux.

Robotic-assisted unicompartmental knee arthroplasty has a greater early functional outcome when compared to manual total knee arthroplasty for isolated medial compartment arthritis.

AIMS: The primary aim of the study was to compare the knee-specific functional outcome of robotic unicompartmental knee arthroplasty (rUKA) with manual total knee arthroplasty (mTKA) for the management of isolated medial compartment osteoarthritis. Secondary aims were to compare length of hospital stay, general health improvement, and satisfaction between rUKA and mTKA. METHODS: A powered (1:3 ratio) cohort study was performed. A total of 30 patients undergoing rUKA were propensity score matched to 90 patients undergoing mTKA for isolated medial compartment arthritis. Patients were matched for age, sex, body mass index (BMI), and preoperative function. The Oxford Knee Score (OKS) and EuroQol five-dimension questionnaire (EQ-5D) were collected preoperatively and six months postoperatively. The Forgotten Joint Score (FJS) and patient satisfaction were collected six months postoperatively. Length of hospital stay was also recorded. RESULTS: There were no significant differences in the preoperative demographics (p ⩾ 0.150) or function (p ⩾ 0.230) between the groups. The six-month OKS was significantly greater in the rUKA group when compared with the mTKA group (difference 7.7, p < 0.001). There was also a greater six-month postoperative EQ-5D (difference 0.148, p = 0.002) and FJS (difference 24.2, p < 0.001) for the rUKA when compared to the mTKA. No patient was dissatisfied in the rUKA group and five (6%) were dissatisfied in the mTKA, but this was not significant (p = 0.210). Length of stay was significantly (p < 0.001) shorter in the rUKA group (median two days, interquartile range (IQR) 1 to 3) compared to the mTKA (median four days, IQR 3 to 5). CONCLUSION: Patients with isolated medial compartment arthritis had a greater knee-specific functional outcome and generic health with a shorter length of hospital stay after rUKA when compared to mTKA.Cite this article: Bone Joint Res 2019;9(1):15-22.

Sagittal alignment of the cemented femoral component in revision total knee arthroplasty influences the anterior and posterior condylar offset: Stem length does not affect these variables.

BACKGROUND: The position of the femoral component can influence knee kinematics by altering the posterior (PCO) and anterior condylar offset (ACO). The primary aim of this study was to assess whether the length of the cemented stem influences the sagittal position of the femoral component after revision total knee arthroplasty (rTKA). The secondary aim was to determine the influence of the sagittal position on PCO and ACO. METHODS: There were 172 consecutive patients over a seven-year period that underwent rTKA with a cemented semi-constrained prosthesis. The 172 patients were separated into two groups: 115 with short stems (50 mm) and 57 with longer stems (100 or 150 mm). Using rotationally acceptable lateral radiographs, the degree of flexion(+)/extension(-) of the femoral components, PCO, and ACO were measured. RESULTS: There was no significant difference (p > 0.25) between the two groups for sagittal position, PCO, or ACO. The average flexion of the femoral component with short stems was 2.2 ±â€¯4.1° and 2.2 ±â€¯3.4° for long stems (difference = 0.0, 95% confidence intervals (CI) -1.3 to 1.2). The average PCO ratio was 1.02 ±â€¯0.15 for short stems and 0.99 ±â€¯0.17 for long stems (difference = 0.03, 95% CI -0.02 to 0.08). The average ACO ratio was at 0.07 ±â€¯0.08 for short stems and 0.08 ±â€¯0.08 for long stems (difference = 0.01, 95% CI -0.01 to 0.04). There was a significant correlation between sagittal alignment of the femoral component and PCO (flexion increased PCO, r = 0.39, p < 0.0001) and ACO (flexion decreased ACO, r = -0.34, p < 0.0001). CONCLUSIONS: Cemented stem length does not influence the position of femoral component in the sagittal axis, PCO, or ACO. Surgical technique and sizing of the femoral component may be more predictive.

A religiously-tailored, multilevel intervention in African American churches to increase HIV testing: Rationale and design of the Taking It to the Pews cluster randomized trial.

HIV continues to disproportionately impact African American (AA) communities. Due to delayed HIV diagnosis, AAs tend to enter HIV treatment at advanced stages. There is great need for increased access to regular HIV testing and linkage to care services for AAs. AA faith institutions are highly influential and have potential to increase the reach of HIV testing in AA communities. However, well-controlled full-scale trials have not been conducted in the AA church context. We describe the rationale and design of a 2-arm cluster randomized trial to test a religiously-tailored HIV testing intervention (Taking It to the Pews [TIPS]) against a standard information arm on HIV testing rates among AA church members and community members they serve. Using a community-engaged approach, TIPS intervention components are delivered by trained church leaders via existing multilevel church outlets using religiously-tailored HIV Tool Kit materials and activities (e.g., sermons, responsive readings, video/print testimonials, HIV educational games, text messages) to encourage testing. Church-based HIV testing events and linkage to care services are conducted by health agency partners. Control churches receive standard, non-tailored HIV information via multilevel church outlets. Secondarily, HIV risk/protective behaviors and process measures on feasibility, fidelity, and dose/exposure are assessed. This novel study is the first to fully test an HIV testing intervention in AA churches - a setting with great reach and influence in AA communities. It could provide a faith-community engagement model for delivering scalable, wide-reaching HIV prevention interventions by supporting AA faith leaders with religiously-appropriate HIV toolkits and health agency partners.

A systematic review of robotic-assisted unicompartmental knee arthroplasty: prosthesis design and type should be reported.

AIMS: Robotic-assisted unicompartmental knee arthroplasty (UKA) promises accurate implant placement with the potential of improved survival and functional outcomes. The aim of this study was to present the current evidence for robotic-assisted UKA and describe the outcome in terms of implant positioning, range of movement (ROM), function and survival, and the types of robot and implants that are currently used. MATERIALS AND METHODS: A search of PubMed and Medline was performed in October 2018 in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Search terms included "robotic", "knee", and "surgery". The criteria for inclusion was any study describing the use of robotic UKA and reporting implant positioning, ROM, function, and survival for clinical, cadaveric, or dry bone studies. RESULTS: A total of 528 articles were initially identified from the databases and reference lists. Following full text screening, 38 studies that satisfied the inclusion criteria were included. In all, 20 studies reported on implant positioning, 18 on functional outcomes, 16 on survivorship, and six on ROM. The Mako (Stryker, Mahwah, New Jersey) robot was used in 32 studies (84%), the BlueBelt Navio (Blue Belt Technologies, Plymouth, Minnesota) in three (8%), the Sculptor RGA (Stanmore Implants, Borehamwood United Kingdom) in two (5%), and the Acrobot (The Acrobot Co. Ltd., London, United Kingdom) in one study (3%). The most commonly used implant was the Restoris MCK (Stryker). Nine studies (24%) did not report the implant that was used. The pooled survivorship at six years follow-up was 96%. However, when assessing survival according to implant design, survivorship of an inlay (all-polyethylene) tibial implant was 89%, whereas that of an onlay (metal-backed) implant was 97% at six years (odds ratio 3.66, 95% confidence interval 20.7 to 6.46, p < 0.001). CONCLUSION: There is little description of the choice of implant when reporting robotic-assisted UKA, which is essential when assessing survivorship, in the literature. Implant positioning with robotic-assisted UKA is more accurate and more reproducible than that performed manually and may offer better functional outcomes, but whether this translates into improved implant survival in the mid- to longer-term remains to be seen. Cite this article: Bone Joint J 2019;101-B:838-847.

Patellofemoral arthroplasty versus total knee arthroplasty for patients with patellofemoral osteoarthritis: equal function and satisfaction but higher revision rate for partial arthroplasty at a minimum eight years' follow-up.

AIMS: The primary aim of this study was to compare the knee-specific functional outcome of patellofemoral arthroplasty with total knee arthroplasty (TKA) in the management of patients with patellofemoral osteoarthritis. PATIENTS AND METHODS: A total of 54 consecutive Avon patellofemoral arthroplasties were identified and propensity-score-matched to a group of 54 patients undergoing a TKA with patellar resurfacing for patellofemoral osteoarthritis. The Oxford Knee Score (OKS), the 12-Item Short-Form Health Survey (SF-12), and patient satisfaction were collected at a mean follow up of 9.2 years (8 to 15). Survival was defined by revision or intention to revise. RESULTS: There was no significant difference in the mean OKS (p > 0.60) or SF-12 scores (p > 0.28) between the groups. There was a lower rate of satisfaction at the final follow-up for the TKA group (78% vs 87%) but this was not statistically significant (odds ratio 0.56, p = 0.21). Length of stay was significantly shorter (p = 0.008) for the Avon group (difference 1.8 days, 95% confidence interval (CI) 0.4 to 3.2). The ten-year survival for the Avon group was 92.3% (95% CI 87.1 to 97.5) and for the TKA group was 100% (95% CI 93.8 to 100). This difference was not statistically significant (log-rank test, p = 0.10). CONCLUSION: Patients undergoing an Avon patellofemoral arthroplasty have a shorter length of stay, and a functional outcome and rate of satisfaction that is equal to that of TKA. The benefits of the Avon arthroplasty need to be balanced against the increased rate of revision when compared with TKA.

Central sulcus is a barrier to causal propagation in epileptic networks.

the functional interactions of different brain regions are dependent of their underlying structural connectivity. These interactions are important for normal brain activity as well as in epileptic disorders where spontaneous epileptic discharges are generated. To understand the effects of brain topography on both normal and epileptic functional networks, we evaluated propagation frequency with respect to geodesic distance and the specific role of sulcal patterns in modulating these functional connections. We implemented a multimodal approach combining Electrocorticography (ECoG) and magnetic resonance imaging (MRI) to evaluate the relationships between epileptic and non-epileptic networks as they are related to structural connectivity in the human brain. We analyzed interictal ECoG along with MRI 3D reconstructions from seven epileptic patients and found that interictal full-dataset network propagations travel to both nearby and distant cortical locations, however with longer distance the propagations occurrence attenuates dramatically. We also discovered that the central sulcus acts as a strong barrier allowing only 30% of the propagation to cross central sulcus whereas the rest of the 70% propagations are observed on the same side of the sulcus. Epileptic spike propagations, however, were more highly localized with significantly less distant spread and had further reduction in spread across sulci. This is a novel approach to explore the structural influence of brain topography on the functional network and would help understand the interaction of different brain regions and how these are altered in patients with epilepsy. This approach could assist physician decision making during epilepsy surgery by revealing an appropriate brain network and cortical interactions.

Early functional outcomes after condylar-stabilizing (deep-dish) versus standard bearing surface for cruciate-retaining total knee arthroplasty.

AIMS: The primary study aim was to compare early knee-specific function of patients undergoing cemented total knee arthroplasty (TKA) with either a cruciate-retaining (CR) polyethylene insert or a highly congruent condylar-stabilizing (CS) insert. Secondary aims were to compare general health and satisfaction between the groups. METHODS: A total of 418 consecutive primary TKAs were identified retrospectively. Demographics and preoperative and 1-year postoperative patient-reported outcome measures (PROMs) were collected prospectively. PROMs consisted of Oxford Knee Scores, EuroQol-5 Dimensions scores, and Short Form-12 scores. RESULTS: A total of 54 (12.9%) patients received a CS insert and 364 patients received a CR TKA. The CS group had a significantly (odds ratio (OR) 2.9; p = 0.002) greater proportion of females (77.8% versus 54.9%). The only significant difference in postoperative PROMs was a higher Short Form-12 physical component score in the CR group (difference 3.1; 95% confidence interval (CI) 0.1 to 6.1; p = 0.04). Linear regression analysis demonstrated no significant difference for all postoperative PROMs (p > 0.25). There was no significant difference in satisfaction rate (OR 0.94; 95% CI 0.42 to 2.12; p = 0.56) or pain visual analogue score (difference 6.1; 95% CI -1.9 to 14.0; p = 0.14) between the groups. CONCLUSION: More congruent CS inserts have equivalent PROMs and patient satisfaction at 1 year compared with less congruent CR inserts. These represent an option for surgeons undertaking TKA where increased congruency is desired.

Patient-reported outcome metrics following total knee arthroplasty are influenced differently by patients' body mass index.

PURPOSE: This study investigated the impact of body mass index (BMI) on improvement in patient outcomes (pain, function, joint awareness, general health and satisfaction) following total knee arthroplasty (TKA). METHODS: Data were obtained for primary TKAs performed at a single centre over a 12-month period. Data were collected pre-operatively and 12-month postoperatively with the Oxford Knee Score (OKS) measuring pain and function, the EQ-5D-3L measuring general health status, the Forgotten Joint Score-12 (FJS-12) measuring joint awareness and a single question on treatment satisfaction. Change in scores following surgery was compared across the BMI categories identified by the World Health Organization (< 25.0, 25.0-29.9, 30.0-34.9, 35.0-39.9 and ≥ 40.0). Differences in postoperative improvement between the BMI groups were analysed with an overall Kruskal-Wallis test, with post hoc pairwise comparisons between BMI groups with Mann-Whitney tests. RESULTS: Of 402 patients [mean age 70.7 (SD 9.2); 55.2% women] 15.7% were normal weight (BMI < 25.0), 33.1% were overweight (BMI 25.0-29.9), 28.2% had class I obesity (BMI 30.0-34.9), 16.2% had class II obesity (BMI 35.0-39.9), and 7.0% had class III obesity (BMI ≥ 40.0). Postoperative change in OKS (n.s.) and EQ-5D-3L (n.s.) was not associated with BMI. Higher BMI group was associated with less improvement in FJS-12 scores (p = 0.010), reflecting a greater awareness of the operated joint during activity in the most obese patients. Treatment satisfaction was associated with BMI category (p = 0.029), with obese patients reporting less satisfaction. CONCLUSIONS: In TKA patients, outcome parameters are influenced differently by BMI. Our study showed a negative impact of BMI on postoperative improvement in joint awareness and satisfaction scores, but there was no influence on pain, function or general health scores. This information may be useful in terms of setting expectations expectation in obese patients planning to undergo TKA. LEVEL OF EVIDENCE: Level 1.

Cemented total hip arthroplasty following acetabular fracture.

AIMS: To evaluate the outcomes of cemented total hip arthroplasty (THA) following a fracture of the acetabulum, with evaluation of risk factors and comparison with a patient group with no history of fracture. PATIENTS AND METHODS: Between 1992 and 2016, 49 patients (33 male) with mean age of 57 years (25 to 87) underwent cemented THA at a mean of 6.5 years (0.1 to 25) following acetabular fracture. A total of 38 had undergone surgical fixation and 11 had been treated non-operatively; 13 patients died at a mean of 10.2 years after THA (0.6 to 19). Patients were assessed pre-operatively, at one year and at final follow-up (mean 9.1 years, 0.5 to 23) using the Oxford Hip Score (OHS). Implant survivorship was assessed. An age and gender-matched cohort of THAs performed for non-traumatic osteoarthritis (OA) or avascular necrosis (AVN) (n = 98) were used to compare complications and patient-reported outcome measures (PROMs). RESULTS: The mean time from fracture to THA was significantly shorter for patients with AVN (2.2 years) or protrusio (2.2 years) than those with post-traumatic OA (9.4 years) or infection (8.0 years) (p = 0.03). Nine contained and four uncontained defects were managed with autograft (n = 11), bulk allograft (n = 1), or trabecular metal augment (n = 1). Initial fracture management (open reduction and internal fixation or non-operative), timing of THA (>/< one year), and age (>/< 55 years) had no significant effect on OHS or ten-year survival. Six THAs were revised at mean of 12 years (5 to 23) with ten-year all-cause survival of 92% (95% confidence interval 80.8 to 100). THA complication rates (all complications, heterotopic ossification, leg length discrepancy > 10 mm) were significantly higher following acetabular fracture compared with atraumatic OA/AVN and OHSs were inferior: one-year OHS (35.7 versus 40.2, p = 0.026); and final follow-up OHS (33.6 versus 40.9, p = 0.008). CONCLUSION: Cemented THA is a reasonable option for the sequelae of acetabular fracture. Higher complication rates and poorer PROMs, compared with patients undergoing THA for atraumatic causes, reflects the complex nature of these cases. Cite this article: Bone Joint J 2017;99-B:1399-1408.

Movement therapy without moving - First results on isometric movement training for post-stroke rehabilitation of arm function.

This study explores the use of isometric movement training for arm rehabilitation after stroke. The aim of this approach is to enhance movement skill even when the person training is not moving. This is accomplished by deceptively displaying virtual motions, exploiting known cross-modal sensory interactions between vision and proprioception. This approach can be advantageous in situations where actual movement is prohibitive due to weakness, spasticity, instability, or unsafe conditions. We present early insights on usability of and tolerance to this training approach and quantitative results that can power future clinical trials.

Outcomes following osteosynthesis of periprosthetic hip fractures around cemented tapered polished stems.

We retrospectively reviewed outcomes of 79 patients with periprosthetic hip fractures around cemented tapered polished stem (CTPS) implants treated with osteosynthesis between January 1997 and July 2011. All patients underwent open reduction and fixation using a broad dynamic compression plate (DCP). Seventy two (91%) of fractures united. There were seven (9%) non-unions with failure of metal work, three (4%) as a result of infection and four (5%) due to mechanical failure. Significant subsidence (>5mm) of the implant was seen in seven (9%) of cases. Ten (13%) cases developed post-operative infection. Non-anatomic reduction and infection were identified as predictors of poor outcome. This is the largest series of a very specific group of periprosthetic fractures treated with osteosynthesis. Open reduction internal fixation with a broad dynamic compression plate for patients with periprosthetic hip fractures around the tip of cemented tapered polished stems is a suitable treatment provided there is no bone loss and the fracture can be precisely, anatomically, reduced and adequately fixed.

Validation of the English language Forgotten Joint Score-12 as an outcome measure for total hip and knee arthroplasty in a British population.

AIMS: To validate the English language Forgotten Joint Score-12 (FJS-12) as a tool to evaluate the outcome of hip and knee arthroplasty in a United Kingdom population. PATIENTS AND METHODS: All patients undergoing surgery between January and August 2014 were eligible for inclusion. Prospective data were collected from 205 patients undergoing total hip arthroplasty (THA) and 231 patients undergoing total knee arthroplasty (TKA). Outcomes were assessed with the FJS-12 and the Oxford Hip and Knee Scores (OHS, OKS) pre-operatively, then at six and 12 months post-operatively. Internal consistency, convergent validity, effect size, relative validity and ceiling effects were determined. RESULTS: Data for the TKA and THA patients showed high internal consistency for the FJS-12 (Cronbach α = 0.97 in TKAs, 0.98 in THAs). Convergent validity with the Oxford Scores was high (r = 0.85 in TKAs, r = 0.79 for THAs). From six to 12 months, the change was higher for the FJS-12 than for the OHS in THA patients (effect size d = 0.21 versus -0.03). Ceiling effects at one-year follow-up were low for the FJS-12 with just 3.9% (TKA) and 8.8% (THA) of patients achieving the best possible score. CONCLUSION: The FJS-12 has strong measurement properties in terms of validity, internal consistency and sensitivity to change in TKA and THA patients. Low ceiling effects and good relative validity allow the monitoring of longer term outcomes, particularly in well-performing groups after total joint arthroplasty. Cite this article: Bone Joint J 2017;99-B:218-24.

Directional selection effects on patterns of phenotypic (co)variation in wild populations.

Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient.

Discovery of an L-alanine ester prodrug of the Hsp90 inhibitor, MPC-3100.

Various types of Hsp90 inhibitors have been and continue to undergo clinical investigation. One development candidate is the purine-based, synthetic Hsp90 inhibitor 1 (MPC-3100), which successfully completed a phase I clinical study. However, further clinical development of 1 was hindered by poor solubility and consequent formulation issues and promoted development of a more water soluble prodrug. Towards this end, numerous pro-moieties were explored in vitro and in vivo. These studies resulted in identification of L-alanine ester mesylate, 2i (MPC-0767), which exhibited improved aqueous solubility, adequate chemical stability, and rapid bioconversion without the need for solubilizing excipients. Based on improved physical characteristics and favorable PK and PD profiles, 2i mesylate was selected for further development. A convergent, scalable, chromatography-free synthesis for 2i mesylate was developed to support further clinical evaluation.

Making the Oxford Hip and Knee Scores meaningful at the patient level through normative scoring and registry data.

OBJECTIVES: The Oxford Hip and Knee Scores (OHS, OKS) have been demonstrated to vary according to age and gender, making it difficult to compare results in cohorts with different demographics. The aim of this paper was to calculate reference values for different patient groups and highlight the concept of normative reference data to contextualise an individual's outcome. METHODS: We accessed prospectively collected OHS and OKS data for patients undergoing lower limb joint arthroplasty at a single orthopaedic teaching hospital during a five-year period. T-scores were calculated based on the OHS and OKS distributions. RESULTS: Data were obtained from 3203 total hip arthroplasty (THA) patients and 2742 total knee arthroplasty (TKA) patients. The mean age of the patient was 68.0 years (sd 11.3, 58.4% women) in the THA group and in 70.2 (sd 9.4; 57.5% women) in the TKA group. T-scores were calculated for age and gender subgroups by operation. Different T-score thresholds are seen at different time points pre and post surgery. Values are further stratified by operation (THA/TKA) age and gender. CONCLUSIONS: Normative data interpretation requires a fundamental shift in the thinking as to the use of the Oxford Scores. Instead of reporting actual score points, the patient is rated by their relative position within the group of all patients undergoing the same procedure. It is proposed that this form of transformation is beneficial (a) for more appropriately comparing different patient cohorts and (b) informing an individual patient how they are progressing compared with others of their age and gender. Cite this article: Bone Joint Res 2015;4:137-144.

Dealing with the predicted increase in demand for revision total knee arthroplasty: challenges, risks and opportunities.

Worldwide rates of primary and revision total knee arthroplasty (TKA) are rising due to increased longevity of the population and the burden of osteoarthritis. Revision TKA is a technically demanding procedure generating outcomes which are reported to be inferior to those of primary knee arthroplasty, and with a higher risk of complication. Overall, the rate of revision after primary arthroplasty is low, but the number of patients currently living with a TKA suggests a large potential revision healthcare burden. Many patients are now outliving their prosthesis, and consideration must be given to how we are to provide the necessary capacity to meet the rising demand for revision surgery and how to maximise patient outcomes. The purpose of this review was to examine the epidemiology of, and risk factors for, revision knee arthroplasty, and to discuss factors that may enhance patient outcomes.

Diet-induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration.

AIM: Obesity is classified as a metabolic disorder that is associated with delayed muscle regeneration following damage. For optimal skeletal muscle regeneration, inflammation along with extracellular matrix remodelling and muscle growth must be tightly regulated. Moreover, the regenerative process is dependent on the activation of myogenic regulatory factors (MRFs) for myoblast proliferation and differentiation. The purpose of this study was to determine how obesity alters inflammatory and protein synthetic signalling and MRF expression at the onset of muscle regeneration in mice. METHODS: Forty-eight male C57BL/6J mice (3 weeks old) were randomly assigned to either a high-fat diet (HFD, 60% fat) or a lean diet (10% fat) for 12 weeks. At 15 weeks, bupivacaine was injected into the tibialis anterior (TA) of the injured group (n = 5-8/group) and PBS was injected into the control (n = 5-6). The TA was excised 3 or 28 days after injection. RESULTS: We demonstrated impaired muscle regeneration in obese mice. The obese mice had reduced IL-6, MyoD and IGF-1 mRNA abundance compared to the lean mice (P < 0.05). Three days following muscle damage, TNF-α mRNA and protein levels of P-STAT3 and P-Akt were 14-fold, fourfold and fivefold greater in the lean mice respectively. However, there were no differences observed in the obese injured group compared to the uninjured group. Moreover, p70S6K1 was threefold greater in lean injured mice compared to uninjured but was reduced by 28% in the obese injured mice. CONCLUSION: Obese mice have impaired inflammatory and protein synthetic signalling that may negatively influence muscle regeneration.