Comparative risk of acute myocardial infarction for anti-osteoporosis drugs in primary care: a meta-analysis of propensity-matched cohort findings from the UK Clinical Practice Research Database and the Catalan SIDIAP Database.

The aim of this study was to evaluate the risk of acute myocardial infarction in patients taking osteoporosis medication. Patients were taken from the SIDIAP or CPRD database and were matched using propensity scores. Patients with diabetes and chronic kidney disease taking SERMs were at an increased risk. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment. INTRODUCTION: This study aims to evaluate the comparative safety of anti-osteoporosis drugs based on the observed risk of acute myocardial infarction while on treatment in a primary care setting. METHODS: This is a propensity-matched cohort study and meta-analysis. This study was conducted in two primary care record databases covering UK NHS (CPRD) and Catalan healthcare (SIDIAP) patients during 1995-2014 and 2006-2014, respectively. The outcome was acute myocardial infarction while on treatment. Users of alendronate (reference group) were compared to those of (1) other oral bisphosphonates (OBP), (2) strontium ranelate (SR), and (3) selective oestrogen receptor modulator (SERM), after matching on baseline characteristics (socio-demographics, fracture risk factors, comorbidities, and concomitant drug use) using propensity scores. Multiple imputation was used to handle missing data on confounders and competing risk modelling for the calculation of relative risk (sub-distribution hazard ratios (SHR)) according to therapy. Country-specific data were analysed individually and meta-analysed. RESULTS: A 10% increased risk of acute myocardial infarction was found in users of other bisphosphonates as compared to alendronate users within CPRD. The meta-analysis of CPRD and SIDIAP results showed a 9% increased risk in users of other bisphosphonate as compared to alendronate users. Sensitivity analysis showed SERMS users with diabetes and chronic kidney disease were at an elevated risk. CONCLUSIONS: This study provides additional data on the risk of acute myocardial infarction in patients receiving osteoporosis treatment. The results favour the cardiovascular safety of alendronate as a first-line choice for osteoporosis treatment.

Industry 4.0 for pharmaceutical manufacturing: Preparing for the smart factories of the future.

Over the last two centuries, medicines have evolved from crude herbal and botanical preparations into more complex manufacturing of sophisticated drug products and dosage forms. Along with the evolution of medicines, the manufacturing practices for their production have advanced from small-scale manual processing with simple tools to large-scale production as part of a trillion-dollar pharmaceutical industry. Today's pharmaceutical manufacturing technologies continue to evolve as the internet of things, artificial intelligence, robotics, and advanced computing begin to challenge the traditional approaches, practices, and business models for the manufacture of pharmaceuticals. The application of these technologies has the potential to dramatically increase the agility, efficiency, flexibility, and quality of the industrial production of medicines. How these technologies are deployed on the journey from data collection to the hallmark digital maturity of Industry 4.0 will define the next generation of pharmaceutical manufacturing. Acheiving the benefits of this future requires a vision for it and an understanding of the extant regulatory, technical, and logistical barriers to realizing it.

Influences of puff protocols and upper airway anatomy on cannabis pharmacokinetics: A CFPD-PK study.

Predicting the optimal administration doses of the inhaled Δ9-tetrahydrocannabinol (THC), i.e., one of the major natural compounds in cannabis, is critical for maximizing the therapeutic outcomes and minimizing the toxic side effects. Thus, it is essential to developing an aerosol dosimetry model to simulate the transport, deposition, and translocation of inhaled THC aerosols from the human respiratory system to the systemic region. In this study, a computational fluid-particle dynamics (CFPD) plus pharmacokinetics (PK) model was developed and validated to quantify the localized vapor and particle uptake rates of THC and the resultant THC-plasma concentrations using two human upper airway geometries. In addition, two different puff protocols (4.0/10.0 s and 1.6/11.4 s as the inhalation/holding time ratios) were employed, associated with two different inhaled THC doses (2.0 mg and 8.82 mg, respectively). The computational results demonstrated that multiple parameters had noticeable influences on THC particle deposition and vapor absorption in the upper airways, as well as the resultant pharmacokinetic behaviors. These factors include anatomical features of the upper airway, puff flow rate, duration, and holding time. The results indicated that puff protocol with 4.0/10.0 s inhalation/holding time ratio would be recommended if the treatment needs THC delivery to the deeper lung. Furthermore, the inhaled THC dose had a dominant effect on the THC-plasma PK profiles, which could override the influences of anatomical variability and puff protocols. The developed CFPD-PK modeling framework has the potential to provide localized lung absorption data and PK profiles for in vitro-in vivo correlation, as well as supporting the development and assessment of drug products containing cannabis or cannabis-derived compounds.

Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review.

OBJECTIVE: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. DESIGN: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle-Ottawa Scale (NOS) for risk of bias assessment. RESULTS: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). CONCLUSIONS: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations.

Lifetime occupation is not associated with radiographic osteoarthritis of the first metatarsophalangeal joint in a cohort study of UK women.

OBJECTIVE: The study aim was to determine whether lifetime occupation was associated with the presence of radiographic osteoarthritis (ROA) of the first metatarsophalangeal joint (MTPJ) in women. METHOD: Data were collected from the prospective, population-based Chingford 1000 Women study. This cohort of women, aged 45-64 years at inception, was established in 1989 from a single general practice in Chingford, UK. Data has subsequently been collected repeatedly. Data from baseline, year six and year ten was used for the purposes of this cross-sectional study. The primary outcome was the presence of dorsal view ROA of the first MTPJ. The main exposure was lifetime occupation, categorised according to levels of occupation previously defined via international consensus: 1. Sedentary, 2. Light, 3. Light manual, 4. Heavy manual. Logistic regression analyses were conducted to quantify the relationship between lifetime occupation type and the presence of ROA of the first MTPJ, adjusting for age, body mass index and lifetime high-heeled footwear use as potential interactive variables for each decade. RESULTS: Data for 209 women were included within this study. The mean (SD) age was 57 (±5.2) years. Predominant lifetime occupation was reported as sedentary by 51.7%, as light by 0%, as light manual by 33.5% and as heavy manual by 14.8% of participants. There were no statistical associations between lifetime occupation type and the presence of ROA of the first MTPJ in either the unadjusted (OR = 0.99, CI = 0.78-1.26,P = 0.96) partially adjusted (for age and BMI; OR = 1.00, CI = 0.78-1.29, P = 0.99) or fully adjusted models (for age, BMI and lifetime high heel footwear use for each decade of working life (OR = 1.02, CI = 0.79-1.31, P = 0.91); high-heel footwear use up to 20s (OR = 0.83, CI = 0.71-1.31, P = 0.83); high-heel footwear use in 20-30s (OR = 1.00, CI = 0.75-1.3, P = 0.98); high-heel footwear use in 30-40s (OR = 1.00, CI = 0.70-1.42, P = 0.99); high-heel footwear use in 40-50s (OR = 0.90, CI = 0.58-1.40, P = 0.65); high-heel footwear use in 50s (OR = 0.63,CI = 0.36-1.09, P = 0.10). CONCLUSIONS: The findings suggest that lifetime occupation is not associated with the presence of ROA of the fist metatarsophalangeal joint. There does not appear to be any interactive effect between lifetime occupation, lifetime high-heel footwear use, age or BMI and ROA of the first MTPJ. In later life a positive trend towards increased ROA in those who reported lifetime high-heel footwear use was noted and this may be worthy of further research.

A consensus-based framework for conducting and reporting osteoarthritis phenotype research.

BACKGROUND: The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. METHODS: A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. RESULTS: Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. CONCLUSIONS: This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients.

Association between Bone marrow lesions & synovitis and symptoms in symptomatic knee osteoarthritis.

OBJECTIVE: Bone marrow lesions (BMLs) on MRI are typically subchondral in location, however, a proportion occur at knee ligament attachments and also include a cyst-like component. Our aim was to determine whether the volume of BML subtypes and synovial tissue volume (STV) was associated with symptoms in symptomatic knee OA. METHOD: Images were acquired in a sub-sample who had taken part in a randomised trial of vitamin D therapy in knee OA (UK-VIDEO). Contrast-enhanced (CE) MRI was performed annually. In those who had ≥1 follow-up and a baseline scan (N = 50), STV and BML volume was assessed. BMLs were categorised by location and by the presence/absence of a cyst-like component. WOMAC was assessed annually. We used fixed-effects panel-regression modelling to examine the association between volume and symptoms. RESULTS: There was no association between knee pain and total subchondral BML volume (b = 0.3 WOMAC units, 95% CI -0.3 to 1.0) or total ligament-based BML volume (b = 1.9, 95% CI -1.6 to 5.3). The volume of subchondral BMLs with a cyst-like component was not associated with pain (b = 0.8, 95% CI -0.5 to 2.1) however, the volume of the cyst-like component itself was associated with pain (b = 51.8, 95% CI 14.2 to 89.3). STV was associated with pain (b = 2.2, 95% CI 0.6 to 3.7). CONCLUSION: The volume of the cyst-like component from subchondral BMLs with a cyst-like component was associated with knee pain. BML location, however, did not influence symptoms. STV was also associated with knee symptoms.

Differences between race and sex in measures of hip morphology: a population-based comparative study.

OBJECTIVE: This paper aims to (i) identify differences in measures of hip morphology between four racial groups using anteroposterior (AP) hip x-rays, and (ii) examine whether these differences vary by sex. METHODS: 912 hip x-rays (456 individuals) from four racial groups (European Caucasians, American Caucasians, African Americans and Chinese) were obtained. Males and females (45-75 years) with no radiographic hip OA (Kellgren and Lawrence < Grade 2 or Croft < Grade 1) were included. Eleven features of hip joint morphology were analysed. Linear regression with generalised estimating equations (GEE) was used to determine race and sex differences in hip morphology. Post-hoc Bonferroni procedure was used to adjust for multiple comparisons. RESULTS: The final analysis included 875 hips. Chinese hips showed significant differences for the majority of measures to other racial groups. Chinese were characterised by more shallow and narrow acetabular sockets, reduced femoral head coverage, smaller femoral head diameter, and a lesser angle of alignment between the femoral neck and shaft. Variation was found between other racial groups, but with few statistically significant differences. The average of lateral centre edge angle, minimum neck width and neck length differed between race and sex (p-value for interaction < 0.05). CONCLUSIONS: Significant differences were found in measures of morphology between Chinese hips compared to African Americans or Caucasian groups; these may explain variation in hip OA prevalence rates between these groups and the lower rate of hip OA in Chinese. Sex differences were also identified, which may further explain male-female prevalence differences for OA.

Considering "clonality": A regulatory perspective on the importance of the clonal derivation of mammalian cell banks in biopharmaceutical development.

There has been much recent focus on the regulatory emphasis and the relative importance surrounding clonal derivation of mammalian production cell lines used in the manufacture of recombinant DNA-derived biopharmaceuticals. This interest has led to an ongoing discussion between regulators and industry on how this topic is evaluated and the role it plays in the development of a new biopharmaceutical. Herein the authors describe that the clonal derivation of the production cell line is a factor with potential impact on product quality, and thus should not be considered separately from, but rather in the context of all elements comprising the control strategy necessary to support approval of a regulatory application. Considerations for how clonal derivation of cell banks and clonal variation thereof may be viewed during the lifecycle of a biopharmaceutical product is provided.

OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis.

OBJECTIVE: To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. METHODS: We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. RESULTS: Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. CONCLUSION: These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.

The impact of BMI and smoking on risk of revision following knee and hip replacement surgery: evidence from routinely collected data.

OBJECTIVE: The aim of this study was to assess the association of body mass index (BMI) and smoking with risk of revision following total knee replacement (TKR) and total hip replacement (THR). DESIGN: Primary care data, from the Clinical Practice Research Datalink (CPRD), was linked to inpatient hospital records, from Hospital Episode Statistics Admitted Patient Care (HES APC), and covered 1997 to 2014. Parametric survival models, with BMI and smoking status included as explanatory variables, were estimated for 10-year risk of revision and mortality, and were extrapolated to estimate lifetime risk of revision. FINDINGS: TKR and THR cohorts included 10,260 and 10,961 individuals, respectively. For a change in BMI from 25 to 35, the 10-year risk of revision is expected change from 4.6% (3.3-6.4%) to 3.7% (2.6-5.1%) for TKR and 3.7% (2.8-5.1%) to 4.0% (2.8-5.7%) for THR for an otherwise average patient profile. Meanwhile, changing from a non-smoker to a current smoker is expected to change the risk of revision from 4.1% (3.1-5.5%) to 2.8% (1.7-4.7%) for TKR and from 3.8% (2.8-5.3%) to 2.9% (1.9-4.7%) for THR for an otherwise average patient profile. Estimates of lifetime risk were also similar for different values of BMI or smoking status. CONCLUSIONS: Obesity and smoking do not appear to have a meaningful impact on the risk of revision following TKR and THR.

Sensory experience remodels genome architecture in neural circuit to drive motor learning.

Neuronal-activity-dependent transcription couples sensory experience to adaptive responses of the brain including learning and memory. Mechanisms of activity-dependent gene expression including alterations of the epigenome have been characterized1-8. However, the fundamental question of whether sensory experience remodels chromatin architecture in the adult brain in vivo to induce neural code transformations and learning and memory remains to be addressed. Here we use in vivo calcium imaging, optogenetics and pharmacological approaches to show that granule neuron activation in the anterior dorsal cerebellar vermis has a crucial role in a delay tactile startle learning paradigm in mice. Of note, using large-scale transcriptome and chromatin profiling, we show that activation of the motor-learning-linked granule neuron circuit reorganizes neuronal chromatin including through long-distance enhancer-promoter and transcriptionally active compartment interactions to orchestrate distinct granule neuron gene expression modules. Conditional CRISPR knockout of the chromatin architecture regulator cohesin in anterior dorsal cerebellar vermis granule neurons in adult mice disrupts enhancer-promoter interactions, activity-dependent transcription and motor learning. These findings define how sensory experience patterns chromatin architecture and neural circuit coding in the brain to drive motor learning.

Impact of a national enhanced recovery after surgery programme on patient outcomes of primary total knee replacement: an interrupted time series analysis from "The National Joint Registry of England, Wales, Northern Ireland and the Isle of Man".

OBJECTIVE: We aimed to test whether a national Enhanced Recovery After Surgery (ERAS) Programme in total knee replacement (TKR) had an impact on patient outcomes. DESIGN: Natural-experiment (April 2008-December 2016). Interrupted time-series regression assessed impact on trends before-during-after ERAS implementation. SETTING: Primary operations from the UK National Joint Registry (NJR) were linked with Hospital Episode Statistics (HES) data which contains inpatient episodes undertaken in National Health Service (NHS) trusts in England, and Patient Reported Outcome Measures (PROMs). PARTICIPANTS: Patients undergoing primary planned TKR aged ≥18 years. INTERVENTION: ERAS implementation (April 2009-March 2011). OUTCOMES: Regression coefficients of monthly means of Length of stay (LOS), bed day costs, change in Oxford knee scores (OKS) 6-months after surgery, complications (at 6 months), and rates of revision surgeries (at 5 years). RESULTS: 486,579 primary TKRs were identified. Overall LOS and bed-day costs decreased from 5.8 days to 3.7 and from £7607 to £5276, from April 2008 to December 2016. Oxford knee score (OKS) change improved from 15.1 points in April 2008 to 17.1 points in December 2016. Complications decreased from 4.1 % in April 2008 to 1.7 % in March 2016. 5-year revision rates remained stable at 4.8 per 1000 implants years in April 2008 and December 2011. After ERAS, declining trends in LOS and bed costs slowed down; OKS improved, complications remained stable, and revisions slightly increased. CONCLUSIONS: Different secular trends in outcomes for patients having TKR have been observed over the last decade. Although patient outcomes are better than a decade ago ERAS did not improve them at national level.

Publisher Correction: Sensory experience remodels genome architecture in neural circuit to drive motor learning.

In this Letter, '≥' should be '≤' in the sentence: "Intra-chromosomal reads were further split into short-range reads (≥1 kb) and long-range reads (>1 kb)". This error has been corrected online.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Association of metabolic syndrome with knee and hand osteoarthritis: A community-based study of women.

OBJECTIVE: It is unclear whether the association between osteoarthritis (OA) and metabolic syndrome (MetS) varies with the site of the affected joint and the presence of pain. Our aim was to describe the association between MetS and radiographic OA (ROA) affecting the knee or the hand in the presence or absence of concurrent joint pain. METHODS: Cross-sectional data of 952 women, aged 45-65years from the Chingford study, a population-based longitudinal cohort of middle-aged women initiated in 1988-1989 in London (UK), was analysed. MetS was defined using the National Cholesterol Education Program Treatment Panel III criteria. Data was collected on components of MetS: waist circumference, triglycerides, high-density lipoprotein (HDL), blood pressure and blood glucose. The outcome was four knee and hand OA groups: painful ROA, ROA only, pain only and neither ROA nor pain (reference category). Multinomial logistic regression models adjusted for age and body mass index (BMI) were used to evaluate the effect of presence of MetS and its individual components on OA subgroups for knee and hand separately. RESULTS: 952 eligible women, aged 45-65years was analysed. A significant association was observed between the presence and the number of MetS with painful knee ROA when adjusted for age; however, this association disappeared when BMI was included in the model. In contrast, the presence and the number of MetS were associated with painful interphalangeal (IPJ) OA after adjusting for both age and BMI. Four out of the five MetS components, including triglycerides, HDL-c, hypertension and glucose, were associated with painful IPJ OA. CONCLUSIONS: MetS is associated with painful IPJ OA but not with knee OA once BMI is taking into consideration. Further attention to MetS and OA at different sites is needed to understand the metabolic phenotype in OA.

Development and validation of a clinical prediction model for patient-reported pain and function after primary total knee replacement surgery.

To develop and validate a clinical prediction model of patient-reported pain and function after undergoing total knee replacement (TKR). We used data of 1,649 patients from the Knee Arthroplasty Trial who received primary TKR across 34 centres in the UK. The external validation included 595 patients from Southampton University Hospital, and Nuffield Orthopaedic Centre (Oxford). The outcome was the Oxford Knee Score (OKS) 12-month after TKR. Pre-operative predictors including patient characteristics and clinical factors were considered. Bootstrap backward linear regression analysis was used. Low pre-operative OKS, living in poor areas, high body mass index, and patient-reported anxiety or depression were associated with worse outcome. The clinical factors associated with worse outcome were worse pre-operative physical status, presence of other conditions affecting mobility and previous knee arthroscopy. Presence of fixed flexion deformity and an absent or damaged pre-operative anterior cruciate ligament (compared with intact) were associated with better outcome. Discrimination and calibration statistics were satisfactory. External validation predicted 21.1% of the variance of outcome. This is the first clinical prediction model for predicting self-reported pain and function 12 months after TKR to be externally validated. It will help to inform to patients regarding expectations of the outcome after knee replacement surgery.

Harmonising measures of knee and hip osteoarthritis in population-based cohort studies: an international study.

OBJECTIVE: Population-based osteoarthritis (OA) cohorts provide vital data on risk factors and outcomes of OA, however the methods to define OA vary between cohorts. We aimed to provide recommendations for combining knee and hip OA data in extant and future population cohort studies, in order to facilitate informative individual participant level analyses. METHOD: International OA experts met to make recommendations on: 1) defining OA by X-ray and/or pain; 2) compare The National Health and Nutrition Examination Survey (NHANES)-type OA pain questions; 3) the comparability of the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) scale to NHANES-type OA pain questions; 4) the best radiographic scoring method; 5) the usefulness of other OA outcome measures. Key issues were explored using new analyses in two population-based OA cohorts (Multicenter Osteoarthritis Study; MOST and Osteoarthritis Initiative OAI). RESULTS: OA should be defined by both symptoms and radiographs, with symptoms alone as a secondary definition. Kellgren and Lawrence (K/L) grade ≥2 should be used to define radiographic OA (ROA). The variable wording of pain questions can result in varying prevalence between 41.0% and 75.4%, however questions where the time anchor is similar have high sensitivity and specificity (91.2% and 89.9% respectively). A threshold of 3 on a 0-20 scale (95% CI 2.1, 3.9) in the WOMAC pain subscale demonstrated equivalence with the preferred NHANES-type question. CONCLUSION: This research provides recommendations, based on expert agreement, for harmonising and combining OA data in existing and future population-based cohorts.

Toward classification criteria for early osteoarthritis of the knee.

OBJECTIVE: To propose draft classification criteria for early stage osteoarthritis (OA) of the knee for use in a primary care setting. METHODS: A group of basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists in a workshop setting discussed potential classification criteria for early osteoarthritis of the knee. The workshop was divided into sessions around relevant topics with short state of the art presentations followed by breakout sessions, consensus discussions, and consolidation into a consensus document. RESULTS: Three classes of criteria were agreed: (1) Pain, symptoms/signs, self-reported function, and quality of life using tools such as KOOS: scoring ≤85% in at least 2 out of these 4 categories; (2) Clinical examination: at least 1 present out of joint line tenderness or crepitus; (3) Knee radiographs: Kellgren & Lawrence (KL) grade of 0 or 1. MRI is at present not recommended as an aid to identify or define early OA in routine clinical practice or primary care, in light of the absence of validated consensus criteria and the high population prevalence of structural joint changes detected by this method. Biomarkers may have future utility in early OA classification, but no individual or set of biomarkers is yet robust enough. CONCLUSION: Based on our consensus proposal, draft classification criteria for early OA of the knee for use in clinical studies should include patient reported outcomes such as pain and function, together with clinical signs and KL grade 0-1 on radiographs.

Population-based prevalence of multiple radiographically-defined hip morphologies: the Johnston County Osteoarthritis Project.

OBJECTIVE: To provide the first prevalence estimates of different radiographic hip morphologies relevant to dysplasia and femoroacetabular impingement in a well-characterized USA population-based cohort. METHODS: Cross-sectional data were from the baseline examination (1991-1997) of a large population-based prospective longitudinal cohort study (The Johnston County Osteoarthritis Project). HipMorf software (Oxford, UK) was used to assess hip morphology on anteroposterior (AP) pelvis radiographs. Weighted, sex-stratified prevalence estimates and 95% confidence intervals for four key hip morphologies (AP alpha angle, triangular index sign, lateral center edge angle (LCEA), and protrusio acetabula) were derived and further stratified by age, race and body mass index (BMI). RESULTS: A total of 5192 hips from 2596 individuals were included (31% African American, 43% male, mean age 63 years, mean BMI 29 kg/m2). Cam morphology was seen in more than 25% of men and 10% of women. Mild dysplasia was present in about 1/3 of men and women, while pincer morphology was identified in 7% of men and 10% of women. Femoral side (cam) morphologies were more common and more frequently bilateral among men, while pincer morphologies were more common in women; mixed morphologies were infrequent. African-Americans were more likely to have protrusio acetabula than whites. CONCLUSION: We report the first population-based prevalence estimates of radiographic hip morphologies relevant to femoroacetabular impingement (FAI) and dysplasia in the USA. These morphologies are very common, with » men and 1/10 women having cam morphology, 1/3 of all adults having mild dysplasia, and 1/15 men and 1/10 women having pincer morphology in at least one hip.

Bone density and body composition in newly licenced professional jockeys.

The primary objective is the description of bone mineral density (BMD) and body composition in newly licensed jockeys. One in three male, flat jockeys has a very low bone mineral density. Further research is needed to assess the short-term risk of fractures and long-term health implications of these findings. INTRODUCTION: Describe bone mineral density (BMD) and body composition in entry-level male and female, flat and jump jockeys in Great Britain. METHODS: Data was collected on jockeys applying for a professional jockey license between 2013 and 2015. Areal BMD at the spine, femoral neck (FN), total hip and body composition were assessed by dual-energy X-ray absorptiometry (DXA) scan. We examined differences between BMD and body composition by gender and race type (flat or jump). Volumetric bone mineral apparent density (BMAD) of the spine and FN was also calculated to account for group differences in bone size. RESULTS: Seventy-nine male flat jockeys (age 18.5 ± 1.9, BMI 19.0 ± 1.4), 69 male jump (age 20.7 ± 2.0, BMI 20.6 ± 1.3) and 37 female flat jockeys (age 19.3 ± 2.0, BMI 20.8 ± 1.7) took part in this study. Spine BMD Z-scores ≤-2 for male flat, male jump and female flat jockeys were 29, 13 and 2.7%, respectively. Spine BMD was lower in male than female flat jockeys (p<0.001). All BMD scores were lower in male flat compared to male jump jockeys (p<0.001). Body fat percent (BF %) was lower in male flat jockeys compared to male jump and female flat jockeys (p<0.05). Lean mass index (LMI) was lower in male flat compared to male jump jockeys (p<0.001). CONCLUSIONS: Male flat jockeys had a significantly lower BMD, LMI and BF% compared to jump jockeys and female flat jockeys. Male flat jockeys had lower spine BMD scores than females. Individual bone maturation may influence these findings. Further investigation into the relevance of low BMD and altered body composition on jockey health is required.