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Unlabelled: To assess whether joint pain or radiographic osteoarthritis (ROA) of the knee and hand is associated with all-cause and disease-specific mortality in middle-aged women.Methods: Four subgroups from the prospective community-based Chingford Cohort Study were identified based on presence/absence of pain and ROA at baseline: (Pain-/ROA-; Pain+/ROA-; Pain-/ROA+; Pain+/ROA+). Pain was defined as side-specific pain in the preceding month, while side-specific ROA was defined as Kellgren-Lawrence grade ≥2. All-cause, cardiovascular disease (CVD) and cancer-related mortality over the 23-year follow-up was based on information collected by the Office for National Statistics. Associations between subgroups and all-cause/cause-specific mortality were assessed using Cox regression, adjusting for age, body mass index, typical cardiovascular risk factors, occupation, past physical activity, existing CVD disease, glucose levels and medication use.Results: 821 and 808 women were included for knee and hand analyses, respectively. Compared with the knee Pain-/ROA- group, the Pain+/ROA- group had an increased risk of CVD-specific mortality (HR 2.93 (95% CI 1.47 to 5.85)), while the knee Pain+/ROA+ group had an increased HR of 1.97 (95% CI 1.23 to 3.17) for all-cause and 3.57 (95% CI 1.53 to 8.34) for CVD-specific mortality. We found no association between hand OA and mortality.Conclusion: We found a significantly increased risk of all-cause and CVD-specific mortality in women experiencing knee pain with or without ROA but not ROA alone. No relationship was found between hand OA and mortality risk. This suggests that knee pain, more than structural changes of OA is the main driver of excess mortality in patients with OA. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess uptake of community-based capillary thyroid stimulating hormone (TSH) screening in Scotland and determine the optimal frequency of screening, the justification for preschool screening and strategies for treatment. METHODS: Subjects with Down's syndrome aged 1-19 years underwent capillary TSH measurement. Clinical and biochemical data were collected using proformas. RESULTS: 5742 capillary TSH tests were performed on 1329 children in 1997-2009, increasing from 183 children from two health boards tested in 1997 to 630 from 13 health boards tested in 2009. Of 132 children referred by the screening laboratory with elevated capillary TSH, 98 (M:F ratio 1:1.2, median (range) age 8.9 (0.9-17.9) years) had adequate documentation and 76 had thyroid dysfunction (defined as venous TSH >6 mU/l), giving a prevalence of not less than 5.7%. Fifty-six (57%) had tested negative during the previous year, 8 (8%) tested positive on their first screening test and 23/67 (34%) were thyroid peroxidase autoantibody negative on initial venous blood. Two of the 13 (13%) preschool children were severely hypothyroid (venous TSH 71 and 283 mU/l). Of patients with venous TSH 6-10.9 (n=27), 11.0-20.9 (n=25) and >= 21.0 mU/l (n=24) following referral, initial/subsequent treatment with thyroxine was given in 3/8, 15/5 and 21/1, respectively. CONCLUSION: Capillary TSH screening in Down's syndrome is eminently feasible and should be performed annually from 1 year of age. Nearly all subjects with initial venous TSH >= 11.0 mU/l will require thyroxine treatment but most with TSH 6-10 mU/l only require surveillance initially. [ABSTRACT FROM AUTHOR]

Introduction Liver cirrhosis and the development of portal hypertension is associated with significant morbidity and mortality. It is widely accepted that patients with liver disease have a hyperdynamic circulation that is associated with an increased cardiac output. We have previously proposed that, rather than a generalised systemic vasodilatation, there is selective splanchnic vasodilatation with concomitant vasoconstriction in other vascular beds: the so-called “splanchnic steal” phenomenon. Aim To measure regional visceral blood flow using 3T magnetic resonance imaging in patients with liver disease. Method Single centre pilot study of 19 subjects (10 healthy controls, nine patients with liver disease). Arterial and venous phase magnetic resonance angiograms were obtained using a Siemens 3T Verio MR scanner with gadolinium contrast. From these MRA's, ECG-gated phase contrast flow measurement MR data were then positioned and measured in the hepatic artery, portal vein, superior mesenteric artery, descending thoracic aorta, distal abdominal aorta, and the renal and carotid arteries. Results Mean MELD score in patient group was 14 (range 7–21) with a range of aetiologies: alcoholic (6), non-alcoholic fatty (1), autoimmune (1), hepatitis C virus (1). In comparison to controls, flow in the descending thoracic aorta was increased by 43% in patients with liver disease (4.74 vs 3.32 L/min; p=0.021) consistent with an increased cardiac output. Hepatic artery flow showed a trend towards increase in patients (0.47 vs 0.27 L/min; p=0.11) whereas portal vein flow decreased dramatically (0.20 vs 1.20 L/min; p=0.006). Overall, in patients with liver disease, there was a 46% reduction in total liver blood flow (0.67 vs 1.47 L/min; p=0.037) and a reversal of hepatic artery/portal vein flow ratio (4.15 vs 0.33 L/min; p=0.009). Although superior mesenteric artery flow was three times greater in patients (0.54 vs 0.15 L/min; p=0.001), renal blood flow showed a trend towards reduction of 32% (0.42 vs 0.62 L/min; p=0.053), no change in carotid blood flow (0.75 vs 0.62 L/min; p=0.129) and no change in inferior aortic flow (1.45 vs 1.12 L/min; p=0.28). Conclusion There are marked derangements in regional visceral blood flow in patients with liver cirrhosis. Our findings strongly support the splanchnic steal hypothesis that dysregulated splanchnic vasodilatation and porto-systemic shunting induce a high cardiac output state associated with extra-splanchnic vasoconstriction including the renal circulation. [ABSTRACT FROM PUBLISHER]

Introduction: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in patients with anaemia of chronic kidney disease may lead to increased ESA doses to achieve target haemoglobin levels; however, elevated doses may be associated with increased mortality. Furthermore, patients with hyporesponsiveness to ESAs have poorer clinical outcomes than those who respond well to ESAs. Incidence and clinical characteristics of patients with ESA hyporesponsiveness were explored in a real-world setting., Methods: This was a retrospective study of electronic medical records of adults with stage 5 chronic kidney disease receiving renal replacement therapy and ESA treatment, from 1 January 2015 to 31 December 2021. The primary objective was ESA hyporesponsiveness rate/1000 days, with a hyporesponsive event defined as ESA use at an elevated dose, according to National Institute for Health and Care Excellence (NICE) criteria. Other hyporesponsiveness definitions applied were erythropoietin resistance index-defined ESA hyporesponsiveness (ERI) Kidney Disease Improving Global Outcomes (KDIGO) and a clinical practicality algorithm., Results: In total, 85,259 patients were included in the analysis; 59.9% were male, median (interquartile range) ESA starting dose was 733.3 (400.0, 1200.0) IU/week and follow-up duration was 2.2 (1.0, 4.2) years. Incidence of ESA hyporesponsiveness varied when applying different definitions; NICE 0.05/1000 days (5.2% of patients), ERI 0.40/1000 days (40.7%), KDIGO 0.15/1000 days (15.4%), and clinical practicality algorithm 0.48/1000 days (47.9%). ESA doses remained higher in hyporesponsive versus responsive patients, yet haemoglobin levels were similar between groups., Conclusion: The results from this study, which applied multiple hyporesponsiveness definitions to a large, geographically diverse population of patients with anaemia of CKD, showed variation in ESA hyporesponsiveness incidence rates depending on definitions used and higher ESA doses in hyporesponsive versus responsive patients. These results underscore the need for individualised clinical assessment and thorough evaluation when considering ESA dose adjustments to reach haemoglobin targets. Graphical abstract available for this article., Trial Registration: NCT05530291., Competing Interests: Declarations. Conflict of Interest: Hans-Jürgen Aren, Luca Neri, Astrid Feuersenger, Mario Garbelli and Otto Arkossy are employees of Fresenius Medical Care, contracted by Astellas Pharma Global Development Inc. to conduct the study. Hans-Jürgen Aren reports Fresenius Medical Care stock shares. Christopher Atzinger and Alina Jiletcovici are employees of Astellas Pharma Global Development Inc. Alina Jiletcovici reports Eli Lilly stock shares. Robert Snijder is an employee of Astellas Pharma Europe B.V. Kirsten Leyland, Najib Khalife and Mahmood Ali are employees of Astellas Pharma Europe Ltd. Ethical Approval: All data were pseudonymised and all patients provided written informed consent for access and secondary use of their pseudonymised clinical data for research purposes. According to the National Institutes of Health definition of human subject research, this study falls under the exempt human subjects research category [27]., (© 2024. The Author(s).)

Background: Joint injury is a major risk factor for osteoarthritis and provides an opportunity to prospectively examine early processes associated with osteoarthritis. We investigated whether predefined baseline demographic and clinical factors, and protein analytes in knee synovial fluid and in plasma or serum, were associated with clinically relevant outcomes at 2 years after knee injury., Methods: This longitudinal cohort study recruited individuals aged 16-50 years between Nov 1, 2010, and Nov 28, 2014, across six hospitals and clinics in London, UK. Participants were recruited within 8 weeks of having a clinically significant acute knee injury (effusion and structural injury on MRI), which was typically treated surgically. We measured several predefined clinical variables at baseline (eg, time from injury to sampling, extent and type of joint injury, synovial fluid blood staining, presence of effusion, self-reported sex, age, and BMI), and measured 12 synovial fluid and four plasma or serum biomarkers by immunoassay at baseline and 3 months. The primary outcome was Knee Injury and Osteoarthritis Outcome Score (KOOS 4 ) at 2 years, adjusted for baseline score, assessed in all patients. Linear and logistic regression models adjusting for predefined covariates were used to assess associations between baseline variables and 2-year KOOS 4 . This study is registered with ClinicalTrials.gov, number NCT02667756., Findings: We enrolled 150 patients at a median of 17 days (range 1-59, IQR 9-26) after knee injury. 123 (82%) were male, with a median age of 25 years (range 16-50, IQR 21-30). 98 (65%) of 150 participants completed a KOOS 4 at 2 (or 3) years after enrolment (50 participants were lost to follow-up and two were withdrawn due to adverse events unrelated to study participation); 77 (51%) participants had all necessary variables available and were included in the core variable adjusted analysis. In the 2-year dataset mean KOOS 4 improved from 38 (SD 18) at baseline to 79 (18) at 2 years. Baseline KOOS 4, medium-to-large knee effusion, and moderate-to-severe synovial blood staining and their interaction significantly predicted 2-year KOOS 4 (n=77; coefficient -20·5, 95% CI -34·8 to -6·18; p=0·0060). The only predefined biomarkers that showed independent associations with 2-year KOOS 4 were synovial fluid MCP-1 (n=77; -0·015, 0·027 to -0·004 per change in 1 pg/mL units; p=0·011) and IL-6 (n=77; -0·0005, -0·0009 to -0·0001 per change in 1 pg/mL units; p=0·017). These biomarkers, combined with the interaction of effusion and blood staining, accounted for 39% of outcome variability. Two adverse events occurred that were linked to study participation, both at the time of blood sampling (one presyncopal episode, one tenderness and pain at the site of venepuncture)., Interpretation: The combination of effusion and haemarthrosis was significantly associated with symptomatic outcomes after acute knee injury. The synovial fluid molecular protein response to acute knee injury (best represented by MCP-1 and IL-6) was independently associated with symptomatic outcomes but not with structural outcomes, with the biomarkers overall playing a minor role relative to clinical predictors. The relationship between symptoms and structure after acute knee injury and their apparent dissociation early in this process need to be better understood to make clinical progress., Funding: Versus Arthritis, Kennedy Trust for Rheumatology Research, and NIHR Oxford Biomedical Research Centre., Competing Interests: TLV reports consultancy fees from GlaxoSmithKline, UCB, and Mundipharma and has also received research grants from Galapagos, Fidia, and Samumed. NKA reports consultancy fees from Pfizer/Lilly and received a grant in a related area of research from Merck. AJ reports consultancy fees from Freshfields Bruckhaus Deringer and from Anthera Pharmaceuticals. AW is a board member and holds stock in Fortius Clinic, has received research grants from Smith and Nephew, is a board member and shareholder in Innovate Orthopaedics, and a shareholder in DocComs. FEW has received clinical study grants from Pfizer and Astellas Pharma, reports consultancy fees from Pfizer, and is part of a consortium receiving some of its research funding from Galapagos, Fidia, and Samumed. All other authors report no competing interests., (© 2021 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Osteoarthritis-related changes in joint space measurements over time are small and sensitive to measurement error. The Reliable Change Index (RCI) determines whether the magnitude of change observed in an individual can be attributed to true change. This study aimed to examine the RCI as a novel approach to estimating osteoarthritis progression., Methods: Data were from 167 men and 392 women with knee osteoarthritis (diagnosed using the American College of Rheumatology criteria) randomized to the placebo arm of the 3-year Strontium Ranelate Efficacy in Knee Osteoarthritis trial (SEKOIA) and assessed annually. The RCI was used to determine whether the magnitude of change in joint space width (JSW) on radiographs between study years was likely to be true or due to measurement error., Results: Between consecutive years, 57-69% of participants had an apparent decrease (change <0) in JSW, while 31-43% of participants had annual changes indicating improvement in JSW. The RCI identified JSW decreases in only 6.0% of patients between baseline and year 1, and in 4.5% of patients between the remaining study years. The apparent increases in JSW were almost eliminated between baseline and year 1, and between years 1 and 2 only 1.3% of patients had a significant increase, dropping to 0.9% between years 2 and 3., Conclusion: The RCI provides a method to identify change in JSW, removing many apparent changes that are likely to be due to measurement error. This method appears to be useful for assessing change in JSW from radiographs in clinical and research settings., (© 2018, American College of Rheumatology.)

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., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: Malalignment is associated with knee osteoarthritis (KOA), however, the optimal anatomic axis (AA) knee alignment measurement on a standard limb radiograph (SLR) is unknown. This study compares one-point (1P) and two-point (2P) AA methods using three knee joint centre locations and examines cross-sectional associations with symptomatic radiographic knee osteoarthritis (SRKOA), radiographic knee osteoarthritis (RKOA) and knee pain., Methods: AA alignment was measured six different ways using the KneeMorf software on 1058 SLRs from 584 women in the Chingford Study. Cross-sectional associations with principal outcome SRKOA combined with greatest reproducibility determined the optimal 1P and 2P AA method. Appropriate varus/neutral/valgus alignment categories were established using logistic regression with generalised estimating equation models fitted with restricted cubic spline function., Results: The tibial plateau centre displayed greatest reproducibility and associations with SRKOA. As mean 1P and 2P values differed by >2°, new alignment categories were generated for 1P: varus <178°, neutral 178-182°, valgus >182° and for 2P methods: varus <180°, neutral 180-185°, valgus >185°. Varus vs neutral alignment was associated with a near 2-fold increase in SRKOA and RKOA, and valgus vs neutral for RKOA using 2P method. Nonsignificant associations were seen for 1P method for SRKOA, RKOA and knee pain., Conclusions: AA alignment was associated with SRKOA and the tibial plateau centre had the strongest association. Differences in AA alignment when 1P vs 2P methods were compared indicated bespoke alignment categories were necessary. Further replication and validation with mechanical axis alignment comparison is required., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

Objectives: We sought to describe the effect of alterations in hip morphology with respect to worsening hip OA in a community-based sample including African American (AA) and white men and women., Methods: This nested case-control study defined case hips as Kellgren Lawrence grade (KLG) <3 on baseline supine pelvis radiographs and KLG ≥3 or THR for OA at the 1st or 2nd follow-up visit (mean 6 and 13 years, respectively); control hips had KLG <3 at both visits, with gender/race distribution similar to cases. Hip morphology was assessed using HipMorf software (Oxford, UK). Descriptive means and standard errors were obtained from generalized estimating equation (GEE) models. Sex-stratified GEE regression models (accounting for within-person correlation), adjusted for age, race, BMI, and side were then employed., Results: A total of 120 individuals (239 hips; 71 case/168 control) were included (25% male, 26% AA, mean age 62 years, BMI 30 kg/m(2)). Case hips tended to have greater baseline AP alpha angles, smaller minimum joint space width (mJSW) and more frequent triangular index signs. Adjusted results among men revealed that higher AP alpha angle, Gosvig ratio, and acetabular index were positively associated with case hips; coxa profunda was negatively associated. Among women, greater AP alpha angle, smaller mJSW, protrusio acetabuli, and triangular index sign were associated with case hips., Conclusions: We confirmed an increased risk of worsening hip OA due to baseline features of cam deformity among men and women, as well as protrusio acetabuli among women, and provide the first estimates of these measures in AAs., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: To analyze data from the Scottish capillary thyroid stimulating hormone (TSH) screening program for hypothyroidism in Down syndrome to identify a threshold for capillary TSH elevation below which low venous free thyroxine (fT4) (<9 pmol/L) and/or frank venous TSH elevation (>10 mU/L) range is unlikely., Study Design: Review of proformas prospectively submitted on all children with Down syndrome referred via the screening program between 2003 and 2013., Results: Ninety-nine patients with Down syndrome (50 females, 49 males) were identified, 76 school-age (≥ 5 years) and 23 preschool (<5 years), mean (range) age at referral 9.4 (0.9-18.1) years. Pearson correlation between capillary TSH and venous TSH was 0.814; between capillary TSH and venous fT4 -0.522 (P = .01). Receiver operator curve analysis showed that capillary TSH values of 4 and 6 mU/L were 95.9% and 73.5% sensitive, 5.8% and 80.8% specific, respectively, in predicting venous TSH >10 mU/L. Fifty-three children had capillary TSH values of 4-5.9 mU/L of whom only one, a boy of 15.8 years, had subnormal venous fT4 (<9 pmol/L), and venous TSH >10 mU/L was found in 13 (4 preschool)., Conclusions: Venous fT4 is normal in almost all patients with Down syndrome with capillary TSH 4-6 mU/L. We propose an algorithm incorporating rescreening by finger prick after 6 months, rather than venepuncture, in school-aged children with borderline capillary TSH elevation. Further data are needed before this approach can be recommended for preschool children., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between body mass index (BMI) and foot joint pain (FJP) over a 5-year period in a community-based cohort., Methods: We examined a subset of women from the Chingford Women's Study, a community cohort followed up for 20 years. From a baseline of 1,003 female participants, we reviewed data from 639 women (64%) for whom complete data sets for FJP and BMI were obtained over a 5-year period between year 10 (Y10) and year 15 (Y15). Descriptive statistics, binary regression modeling, and odds ratios (ORs) were used to examine the longitudinal relationship between BMI and FJP., Results: For Y10 and Y15, the median age was 61 years (interquartile range [IQR] 57-67) and 66 years (IQR 62-72), respectively, and the mean ± SD BMI was 26.7 ± 4.6 kg/m(2) and 27.2 ± 4.8 kg/m(2) , respectively. FJP prevalence was 21.6% at Y10 and 26.6% at Y15. Longitudinal analyses showed that both BMI and FJP increased significantly from Y10 to Y15 (P < 0.001). The odds of having FJP after a 5-year period increased by 4.9% for each BMI unit increase 5 years earlier (OR 1.049 [95% confidence interval (95% CI) 1.011-1.089], P = 0.012). This remained significant when adjusted for age, diabetes mellitus, and rheumatoid arthritis (OR 1.051 [95% CI 1.011-1.091], P = 0.012)., Conclusion: This is the first large longitudinal cohort study demonstrating that, in middle-aged women, a high BMI precedes and is predictive of FJP independent of age. Evidence from our findings can be used to identify those individuals at risk of developing FJP., (© 2014 The Authors. Arthritis Care & Research is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.)

Some major themes over the past year in clinical research of osteoarthritis (OA) include obesity, muscle strength, pain mechanisms, novel disease modifying drugs, and risk factors for poor outcomes of joint replacement surgery. A systematic literature search was performed using PubMed from January 2012 to December 2012. The articles selected for this review represent topics the authors thought best highlight recent clinical OA research., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The sensory, motor, educational and emotional/behavioral outcomes in 32 survivors of childhood brain tumors were evaluated by examination, interview, questionnaires on emotion/behavior and the Health Utilities Index Mark 2 (HUI 2). Thirty-eight percent had moderate/severe disability, and this was associated closely with special educational provision. Pre- and peri-operative factors were the commonest determinants of disability. Fifty percent had a high score on the emotion/behavior questionnaires, suggesting a high risk of an emotional or behavioral problem. The HUI 2 discriminated well between those survivors who had and those who had not had special provision made for their education but poorly between those with high and those with low scores on the emotion/behavior questionnaires. Previous studies have found self-reported health-related quality of life to be related more closely to emotional/behavioral sequelae than to disability. Possible uses and limitations of the HUI 2 in this clinical context are discussed., (Copyright 1999 Wiley-Liss, Inc.)