Copper(II) Affects the Biochemical Behavior of Proinsulin C-peptide by Forming Ternary Complexes with Serum Albumin.

Peptide hormones are essential signaling molecules with therapeutic importance. Identifying regulatory factors that drive their activity gives important insight into their mode of action and clinical development. In this work, we demonstrate the combined impact of Cu(II) and the serum protein albumin on the activity of C-peptide, a 31-mer peptide derived from the same prohormone as insulin. C-peptide exhibits beneficial effects, particularly in diabetic patients, but its clinical use has been hampered by a lack of mechanistic understanding. We show that Cu(II) mediates the formation of ternary complexes between albumin and C-peptide and that the resulting species depend on the order of addition. These ternary complexes notably alter peptide activity, showing differences from the peptide or Cu(II)/peptide complexes alone in redox protection as well as in cellular internalization of the peptide. In standard clinical immunoassays for measuring C-peptide levels, the complexes inflate the quantitation of the peptide, suggesting that such adducts may affect biomarker quantitation. Altogether, our work points to the potential relevance of Cu(II)-linked C-peptide/albumin complexes in the peptide's mechanism of action and application as a biomarker.

Biosimilars for the Treatment of Psoriasis: A Systematic Review of Clinical Trials and Observational Studies.

Importance: Biosimilars have the potential to reduce costs for the management of moderate-to-severe psoriasis compared with originators. However, the extrapolation of evidence enables the approval of a biosimilar for use in indications held by the originator without directly being studied in clinical trials. Thus, biosimilars can be approved for psoriasis based on extrapolated evidence from other diseases. The availability of evidence for the effectiveness and safety of biosimilars for the treatment of psoriasis is therefore unclear. Objective: To compare the efficacy/effectiveness and safety of biosimilars with originator biologics for the treatment of patients with psoriasis. Evidence Review: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and The European Union Clinical Trials Register were searched in August 2022. Eligible studies were appraised using the Cochrane Risk of Bias 2 and ROBINS-I tools. All analyses were conducted from September 2022 to November 2022. Findings: Fourteen trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) were included. Twelve trials compared biosimilars with originators in originator-naive patients (starters), and 11 trials compared switching from originator to biosimilar (switchers) with continuous originator treatments. There was no clinically or statistically significant difference in rates of achieving 75% improvement in Psoriasis Area and Severity Index scores and risks of adverse events (AEs) at week 16 and week 52 between the comparators. Two cohort studies showed no difference in effectiveness and safety outcomes between originators and biosimilars, whereas 1 study reported more AEs in patients who switched to biosimilars of adalimumab at 12 months. Three trials showed low risk of bias, whereas 11 trials had moderate risk of bias. All cohort studies had moderate to high risk of bias. Conclusions and Relevance: In this systematic review, there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators for the treatment of patients with psoriasis. Most of the available evidence was based on randomized clinical trials, although high-quality real-world evidence was lacking. Future studies are needed to examine the long-term effectiveness and safety of biosimilars for the treatment of patients with psoriasis.

A comparative analysis of non-invasive prenatal testing in Ontario and Quebec: the role of governing style in health technology innovation & adoption.

BACKGROUND: While processes of adoption and the impacts of various health technologies have been extensively studied by health services and policy researchers, the influence of policy makers' governing styles on these processes have been largely neglected. Through a comparative analysis of non-invasive prenatal testing (NIPT) in the Canadian provinces of Ontario and Quebec, this article examines how decisions about this technology were shaped by contrasting political ideologies, resulting in vastly different innovation and adoption strategies and outcomes. METHODS: A comparative qualitative investigation comprising of a document analysis followed by semi-structured interviews with key informants. Interview participants were researchers, clinicians, and private sector medical laboratory employees based in Ontario and Quebec, Canada. Interviews were conducted both in person and virtually- owing partly to the COVID-19 pandemic - to garner perspectives regarding the adoption and innovation processes surrounding non-invasive prenatal testing in both provinces. All interviews were recorded and transcribed verbatim and data were analyzed using thematic analysis. RESULTS: Through an analysis of 21 in-depth interview transcripts and key documents, the research team identified three central themes: 1) health officials in each province demonstrated a unique approach to using the existing scholarly literature on NIPT; 2) each provincial government demonstrated its own preference for service delivery, with Ontario preferring private and Quebec preferring public; and finally, 3) both Ontario and Quebec's strategies to NIPT adoption and innovation was contextualized within each province's unique financial positioning and concerns. These findings illustrate how both Quebec's nationalist focus and use of industrial policy and Ontario's 'New Public Management' style had implications for how this emerging healthcare technology was made available within each province's publicly-financed health system. CONCLUSIONS: Our study reveals how these governments' differing approaches to using data and research, public versus private service delivery, and financial goals and concerns resulted in distinct testing technologies, access, and timelines for NIPT adoption. Our analysis demonstrates the need for health policy researchers, policy makers, and others to move beyond analyses solely considering clinical and health economic evidence to understand the impact of political ideologies and governing styles.

Evidence Clearinghouses as Tools to Advance Health Equity: What We Know from a Systematic Scan.

Evidence clearinghouses evaluate and summarize literature to help decision-makers prioritize and invest in evidence-informed interventions. Clearinghouses and related practice-oriented tools are continuously evolving; however, it is unclear the extent to which these tools assess and summarize evidence describing an intervention's impact on health equity. We conducted a systematic scan to explore how clearinghouses communicated an intervention's equity impact and reviewed their underlying methods and how they defined and operationalized health equity. In 2021, we identified 18 clearinghouses that were US-focused, web-based registries of interventions that assigned an intervention effectiveness rating for improving community health and the social determinants of health. We reviewed each clearinghouse's website and collected publicly available information about their health equity impact review, review methods, and health equity definitions and values. We conducted a comparative analysis among select clearinghouses using qualitative methods. Among the 18 clearinghouses, fewer than half (only seven) summarized an intervention's potential impact on health equity. Overall, those seven clearinghouses defined and operationalized equity differently, and most lacked transparency in their review methods. Clearinghouses used one or more approaches to communicate findings from their review: summarize study findings on differential impact for subpopulations, curate interventions that reduce health disparities, and/or assign a disparity/equity rating to each intervention. Evidence clearinghouses can enhance equity-focused methods and be transparent in their underlying values to better support the uptake and implementation of evidence-informed interventions to advance health equity. However, clearinghouses are unable to do so without underlying equity-focused empirical evidence.

Investigation of metal modulation of oxytocin structure receptor-mediated signaling.

Oxytocin is a 9-amino acid peptide hormone. Since its discovery in 1954, it has most commonly been studied in relation to its role in stimulating parturition and lactation. However, it is now known that oxytocin has a widely diverse set of functions throughout the body including neuromodulation, bone growth, and inflammation. Previous research has suggested that divalent metal ions may be required for oxytocin activity, but the exact metal species and specific pathways have yet to be fully elucidated. In this work, we focus on characterizing copper and zinc bound forms of oxytocin and related analogs through far-UV circular dichroism. We report that Cu(ii) and Zn(ii) bind uniquely to oxytocin and all analogs investigated. Furthermore, we investigate how these metal bound forms may affect downstream signaling of MAPK activation upon receptor binding. We find that both Cu(ii) and Zn(ii) bound oxytocin attenuates the activation of the MAPK pathway upon receptor binding relative to oxytocin alone. Interestingly, we observed that Zn(ii) bound forms of linear oxytocin facilitate increased MAPK signaling. This study lays the foundation for future work on elucidating the metal effects on oxytocin's diverse bioactivity.

Evaluation of real-world outcomes associated with use of a prescription digital therapeutic to treat substance use disorders.

BACKGROUND AND OBJECTIVES: Digital therapeutics can expand the reach and fidelity of behavioral treatment for substance use disorders (SUDs). This analysis evaluated real-world engagement and clinical outcomes in patients diagnosed with SUD who were prescribed reSET®, an FDA-authorized prescription digital therapeutic (PDT). METHODS: Patients were prescribed a 12-week PDT comprising 61 therapy lessons (31 "core" and 30 "keep learning" lessons) and contingency management rewards (positive reinforcement message or monetary gift cards) based on lesson completion and negative urine drug screens. Engagement (defined as any activity in the PDT), retention (any activity in Weeks 9-12), and substance use data were collected automatically by the PDT and analyzed descriptively. Associations between early lesson completion and end-of-treatment outcomes were assessed. RESULTS: Six hundred and fifty-eight patients filled their prescription. Evaluated were 602 patients who were exposed to therapeutic content by completing at least one lesson (median age 37 years, 33% female, 41% male, 26% unreported sex). Median lessons completed was 33 (out of 61 possible), and 52% of patients completed all core modules. Retention in treatment during the last 4 weeks of treatment was 74%, and 62% were abstinent (missing data considered positive). [Correction added on 13 December 2022, after first online publication: In the preceding sentence, the treatment percentage values were revised from 74.6% to 74%.] DISCUSSION AND CONCLUSIONS: Patients with SUD exhibited robust engagement with a PDT, high rates of retention through 12 weeks, and substantial rates of abstinence at end of treatment when the therapeutic was used in a real-world setting. PDT's hold promise as a new way to access effective SUD treatment. SCIENTIFIC SIGNIFICANCE: This study is the first to report real-world PDT engagement and clinical outcomes data from a large, geographically diverse population of patients with SUDs.

Efficacy and toxicity of primary re-irradiation for malignant spinal cord compression based on radiobiological modelling: a phase II clinical trial.

BACKGROUND: The efficacy and safety of primary re-irradiation for MSCC are not known. Our aim was to establish the efficacy and safety of biologically effective dose-based re-irradiation. METHODS: Patients presenting with MSCC at a previously irradiated spine segment, and not proceeding with surgical decompression, were eligible. A 3 Gray per fraction experimental schedule (minimum 18 Gy/6 fractions, maximum 30 Gy/10 fractions) was used, delivering a maximum cumulative spinal dose of 100 Gy2 if the interval since the last radiotherapy was within 6 months, or 130 Gy2 if longer. The primary outcome was a change in mobility from week 1 to week 5 post-treatment, as assessed by the Tomita score. The RTOG SOMA score was used to screen for spinal toxicity, and an MRI performed to assess for radiation-induced myelopathy (RIM). RESULTS: Twenty-two patients were enroled, of whom eleven were evaluable for the primary outcome. Nine of eleven (81.8%) had stable or improved Tomita scores at 5 weeks. One of eight (12.5%) evaluable for late toxicity developed RIM. CONCLUSIONS: Re-irradiation is an efficacious treatment for MSCC. There is a risk of RIM with a cumulative dose of 120 Gy2. CLINICAL TRIAL REGISTRATION: Cancer Trials Ireland (ICORG 07-11); NCT00974168.

Design and implementation of an online admissions interview for selection to nursing and midwifery programmes: a partnership approach.

BACKGROUND: The recent surge in applications to nursing in the United Kingdom together with the shift towards providing virtual interviews through the use of video platforms has provided an opportunity to review selection methodologies to meet a new set of challenges. However there remains the requirement to use selection methods which are evidence-based valid and reliable even under these new challenges. METHOD: This paper reports an evaluation study of applicants to nursing and midwifery and reports on how to plan and use online interviews for in excess of 3000 applicants to two schools of nursing in Northern Ireland. Data is reported from Participants, Assessors and Administrators who were asked to complete an online evaluation using Microsoft Forms. RESULTS: A total of 1559 participants completed the questionnaire. The majority were aged 17-20. The findings provide evidence to support the validity and reliability of the online interview process. Importantly the paper reports on the design and implementation of a fully remote online interview process that involved a collaboration with two schools of nursing without compromising the rigour of the admissions process. The paper provides practical, quantitative, and qualitative reasons for concluding that the online remote selection process generated reliable data to support its use in the selection of candidates to nursing and midwifery. CONCLUSION: There are significant challenges in moving to online interviews and the paper discusses the challenges and reflects on some of the broader issues associated with selection to nursing and midwifery. The aim of the paper is to provide a platform for discussion amongst other nursing schools who might be considering major changes to their admissions processes.

Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific.

Introduction: Haematuria is a common red flag symptom of urinary tract cancer. Bladder cancer (BC) is the most common cancer to present with haematuria. Women presenting with haematuria are often underdiagnosed. Currently, no gender-specific tests are utilized in clinical practice. Considerable healthcare resources are needed to investigate causes of haematuria and this study was set up to help identify markers of BC. The aim of the study was to define biomarker algorithms in haematuria patients using an expanded panel of biomarkers to diagnose BC and investigate if the algorithms are gender-specific. Materials and Methods: A total of n=675 patients with a history of haematuria were recruited from Northern Ireland hospitals. Patients were collected on a 2:1 ratio, non-BC (control) n=474: BC n=201. A detailed clinical history, urine and blood samples were collected. Biomarkers, known to be involved in the pathobiology underlying bladder carcinogenesis were investigated. Biomarkers differentially expressed between groups were investigated using Wilcoxon rank sum and linear regression. Results: Biomarkers were gender specific. Two biomarker-algorithms were identified to triage haematuria patients; male - u_NSE, s_PAI-1/tPA, u_midkine, u_NGAL, u_MMP-9/TIMP-1 and s_prolactin (u=urine; s=serum); sensitivity 71.8%, specificity 72.8%; AUROC 0.795; and female urine biomarkers - IL-12p70, IL-13, midkine and clusterin; sensitivity 83.7%, specificity 79.7%; AUROC 0.865. Addition of the clinical variable infection to both algorithms increased both AUROC to 0.822 (DeLong p=0.014) and to 0.923 (DeLong p=0.004) for males and females, respectively. Combining clinical risk factors with biomarker algorithms would enable application of the algorithms to triage haematuria patients. Conclusion: Using gender-specific biomarker algorithms in combination with clinical risks that are associated with BC would allow clinicians to better manage haematuria patients and potentially reduce underdiagnosis in females. In this study, we demonstrate, for the first time, that blood and urine biomarkers are gender-specific when assessing risk of BC in patients who present with blood in their urine. Combining biomarker data with clinical factors could improve triage when referring patients for further investigations.

Diamond formation kinetics in shock-compressed C─H─O samples recorded by small-angle x-ray scattering and x-ray diffraction.

Extreme conditions inside ice giants such as Uranus and Neptune can result in peculiar chemistry and structural transitions, e.g., the precipitation of diamonds or superionic water, as so far experimentally observed only for pure C─H and H2O systems, respectively. Here, we investigate a stoichiometric mixture of C and H2O by shock-compressing polyethylene terephthalate (PET) plastics and performing in situ x-ray probing. We observe diamond formation at pressures between 72 ± 7 and 125 ± 13 GPa at temperatures ranging from ~3500 to ~6000 K. Combining x-ray diffraction and small-angle x-ray scattering, we access the kinetics of this exotic reaction. The observed demixing of C and H2O suggests that diamond precipitation inside the ice giants is enhanced by oxygen, which can lead to isolated water and thus the formation of superionic structures relevant to the planets' magnetic fields. Moreover, our measurements indicate a way of producing nanodiamonds by simple laser-driven shock compression of cheap PET plastics.

Clinical features and predictive biomarkers for bladder cancer in patients with type 2 diabetes presenting with haematuria.

AIMS: To identify clinical features and protein biomarkers associated with bladder cancer (BC) in individuals with type 2 diabetes mellitus presenting with haematuria. MATERIALS AND METHODS: Data collected from the Haematuria Biomarker (HaBio) study was used in this analysis. A matched sub-cohort of patients with type 2 diabetes and patients without diabetes was created based on age, sex, and BC diagnosis, using approximately a 1:2 fixed ratio. Randox Biochip Array Technology and ELISA were applied for measurement of 66 candidate serum and urine protein biomarkers. Hazard ratios and 95% confidence intervals were estimated by chi-squared and Wilcoxon rank sum test for clinical features and candidate protein biomarkers. Diagnostic protein biomarker models were identified using Lasso-based binominal regression analysis. RESULTS: There was no difference in BC grade, stage, and severity between individuals with type 2 diabetes and matched controls. Incidence of chronic kidney disease (CKD) was significantly higher in patients with type 2 diabetes (p = 0.008), and CKD was significantly associated with BC in patients with type 2 diabetes (p = 0.032). A biomarker model, incorporating two serum (monocyte chemoattractant protein 1 and vascular endothelial growth factor) and three urine (interleukin 6, cytokeratin 18, and cytokeratin 8) proteins, predicted incidence of BC with an Area Under the Curve (AUC) of 0.84 in individuals with type 2 diabetes. In people without diabetes, the AUC was 0.66. CONCLUSIONS: We demonstrate the potential clinical utility of a biomarker panel, which includes proteins related to BC pathogenesis and type 2 diabetes, for monitoring risk of BC in patients with type 2 diabetes. Earlier urology referral of patients with type 2 diabetes will improve outcomes for these patients. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN25823942.

Quantifying the Binding Interactions Between Cu(II) and Peptide Residues in the Presence and Absence of Chromophores.

Copper(II) is an essential metal in biological systems, conferring unique chemical properties to the biomolecules with which it interacts. It has been reported to directly bind to a variety of peptides and play both necessary and pathological roles ranging from mediating structure to electron transfer properties to imparting catalytic function. Quantifying the binding affinity and thermodynamics of these Cu(II)-peptide complexes in vitro provides insight into the thermodynamic driving force of binding, potential competitions between different metal ions for the peptide or between different peptides for Cu(II), and the prevalence of the Cu(II)-peptide complex in vivo. However, quantifying the binding thermodynamics can be challenging due to a myriad of factors, including accounting for all competing equilibria within a titration experiment, especially in cases where there are a lack of discrete spectroscopic handles representing the peptide, the d-block metal ion, and their interactions. Here, a robust set of experiments is provided for the accurate quantification of Cu(II)-peptide thermodynamics. This article focuses on the use of electronic absorption spectroscopy in the presence and absence of chromophoric ligands to provide the needed spectroscopic handle on Cu(II) and the use of label-free isothermal titration calorimetry. In both experimental techniques, a process is described to account for all competing equilibria. While the focus of this article is on Cu(II), the described set of experiments can apply beyond Cu(II)-peptide interactions, and provide a framework for accurate quantification of other metal-peptide systems under physiologically relevant conditions.

Characterization of West African Crystalline Macular Dystrophy in the Ghanaian Population.

OBJECTIVE: West African crystalline maculopathy (WACM) is characterized by the presence of macular hyperrefractile crystal-like deposits. Although the underlying pathophysiology has not been elucidated, a few biologic drivers have been proposed. We analyzed a large WACM case series to gain a more robust understanding of its features and etiology. DESIGN: Prospective, cross-sectional cohort study. SUBJECTS: Participants with WACM were selected from the large cohort recruited in the Ghana Age-Related Macular Degeneration Study. METHODS: Demographic and detailed medical histories, full ophthalmic examinations, digital color fundus photographs, and OCT images were obtained. All cases with WACM were evaluated by 3 retina experts. Crystal numbers, location, and distribution were determined. Associations between WACM and White age-related macular degeneration (AMD) risk variants were assessed using Firth's bias-reduced logistic regression, including age and sex as covariates. MAIN OUTCOME MEASURES: Phenotypic features of, and genetic associations with, WACM. RESULTS: West African crystalline maculopathy was identified in 106 eyes of 53 participants: 22 were bilateral and 24 were unilateral. Grading for AMD was not possible in 1 eye in 7 participants with WACM; therefore, laterality was not assessed in these subjects. Thirty-eight participants were women and were 14 men; sex was unrecorded for 1 participant. The mean age was 68.4 years (range, 45-101 years). Typical WACM crystals were demonstrated on OCT, which were more easily identified at high contrast and predominantly located at the inner limiting membrane. In eyes with copathology, crystals localized deeper in the inner retina, with wider retinal distribution over copathology lesions. There was no association with age or sex. A significant association was observed between the complement factor H (CFH) 402H risk variant and WACM. CONCLUSIONS: This study confirms the localization of crystals adjacent to the inner limiting membrane and distribution over lesions in eyes with copathology. The evaluation of OCT images under high contrast allows improved identification. West African crystalline maculopathy may be associated with the CFH-CFHR5 AMD risk locus identified among Whites; however, it is also possible that the combination of crystals and the CFH 402H allele increases the risk for developing late AMD. Further analyses using larger sample sizes are warranted to identify causalities between genotype and WACM phenotype.

The discourse of design: Patterns of TPACK Contribution during pre-service teacher learning design conversations.

Analysing pre-service teachers' learning design conversations in relation to Technological Pedagogical and Content Knowledge (TPACK) framework to understand their learning design practices has remained unexplored. This paper presents findings from a study of pre-service teachers' design discourses that identified how TPACK elements were used during their collaborative design of technology-enhanced lessons. Through thematic analysis of 81 design conversations in two cycles, it was found that pre-service teachers discussed design related issues, TPACK elements, and context in their design conversations with dominant references to design-related issues, substantial occurrences of single TPACK elements, and lower frequencies of integrated TPACK elements and context. Practical recommendations and a Design-TPACK or 'D-TPACK' framework were proposed to support pre-service teachers' learning design practices.

Thoracic ultrasound competence for ultrasound guided pleural procedures: The creation and validation of an assessment tool for use in the certification of basic thoracic ultrasound competence.

OBJECTIVES: Focused thoracic ultrasound (TUS) provides an increased safety profile when undertaking invasive pleural procedures. This has led to the requirement for defined curricula, high quality teaching and robust, validated assessment tools among physicians to ensure patient safety and clinical excellence. Current UK practice is based almost exclusively on expert consensus, but assessment methods employed have been shown to have low reliability and validity and are potentially open to bias. As a result, several assessment tools have been developed, although each has its own limitations. METHODS: This study aimed to develop and validate an assessment tool corresponding to those skills associated with the most basic level of practice, defined recently as an emergency level operator in the British Thoracic Society Training Standards for Thoracic Ultrasound. RESULTS: A total of 27 candidates were enrolled by two examiners based in Belfast and Oxford over a 10-month period between February and November 2019. Mean score of the inexperienced group was 44.3 (95% CI 39.2-49.4, range 28-54) compared with 74.9 (95% CI 72.8-77, range 64-80) in the experienced group providing an estimated mean difference of 30.7 between the two groups (95% CI 24.7-36.7; p < .001). CONCLUSIONS: This tool appears to discriminate between trainees with limited experience of TUS performance and those with no experience. It has the potential to form part of the assessment strategy for trainees in the United Kingdom and beyond, alongside well established assessment tools in postgraduate training.

Investigating the physical activity, health, wellbeing, social and environmental effects of a new urban greenway: a natural experiment (the PARC study).

BACKGROUND: Evidence for the health benefits of urban green space tends to stem from small, short-term quasi-experimental or cross-sectional observational research, whilst evidence from intervention studies is sparse. The development of an urban greenway (9 km running along 3 rivers) in Northern Ireland provided the opportunity to conduct a natural experiment. This study investigated the public health impact of the urban greenway on a range of physical activity, health, wellbeing, social, and perceptions of the environment outcomes. METHODS: A repeated cross-sectional household survey of adult residents (aged ≥16 years) who lived ≤1-mile radius of the greenway (intervention sample) and > 1-mile radius of the greenway (control sample) was conducted pre (2010/2011) and 6-months post implementation (2016/2017). We assessed changes in outcomes pre- and post-intervention follow-up including physical activity behaviour (primary outcome measure: Global Physical Activity Questionnaire), quality of life, mental wellbeing, social capital and perceptions of the built environment. Linear regression was used to calculate the mean difference between post-intervention and baseline measures adjusting for age, season, education, car ownership and deprivation. Multi-level models were fitted using a random intercept at the super output area (smallest geographical unit) to account for clustering within areas. The analyses were stratified by distance from the greenway and deprivation. We assessed change in the social patterning of outcomes over time using an ordered logit to make model-based outcome predictions across strata. RESULTS: The mean ages of intervention samples were 50.3 (SD 18.9) years at baseline (n = 1037) and 51.7 (SD 19.1) years at follow-up (n = 968). Post-intervention, 65% (adjusted OR 0.60, 95% CI 0.35 to 1.00) of residents who lived closest to the greenway (i.e., ≤400 m) and 60% (adjusted OR, 0.64 95% CI 0.41 to 0.99) who lived furthest from the greenway (i.e.,≥1200 m) met the physical activity guidelines - 68% of the intervention sample met the physical activity guidelines before the intervention. Residents in the most deprived quintiles had a similar reduction in physical activity behaviour as residents in less deprived quintiles. Quality of life at follow-up compared to baseline declined and this decline was significantly less than in the control area (adjusted differences in mean EQ5D: -11.0 (95% CI - 14.5 to - 7.4); - 30.5 (95% CI - 37.9 to - 23.2). Significant change in mental wellbeing was not observed despite improvements in some indicators of social capital. Positive perceptions of the local environment in relation to its attractiveness, traffic and safety increased. CONCLUSIONS: Our findings illustrate the major challenge of evaluating complex urban interventions and the difficulty of capturing and measuring the network of potential variables that influence or hinder meaningful outcomes. The results indicate at this stage no intervention effect for improvements in population-level physical activity behaviour or mental wellbeing. However, they show some modest improvements for secondary outcomes including positive perceptions of the environment and social capital constructs. The public health impact of urban greenways may take a longer period of time to be realised and there is a need to improve evaluation methodology that captures the complex systems nature of urban regeneration.

Ten-year outcomes following a cohort of ASR XL total hip arthroplasties.

AIMS: To determine the outcome at 10 years of a cohort of ASR XL total hip arthroplasties (THAs) and reasons for revision. METHODS: Between November 2005 and May 2007, 122 ASR XL THAs were implanted. All patients had a routine review at 6 weeks and 1 year, followed by a review in 2009 because of clinical concern and thereafter annual review up to 10 years with MRI. Review also included functional scores, radiographs, pain scores and blood metal ions. RESULTS: 67 (54.9%) ASR XLs had been revised by 11.1 years. Reasons for revision included pain (89.6%), high levels of cobalt and chromium ions (50.7%) and radiographic or MRI changes (80.6%). All 3 factors were present in 23 (34.3%). Pain at 1 year did not predict revision, but pain at the 2009 review did. At 10 years the revised patients had an average Oxford Hip Score (OHS) of 25.38 (12-42) and the non-revised 23.61 (2-21), the difference was not significant (p = 0.48). 3 patients (4.5%) have had a further revision; 2 for a previously unrevised stem and the other for instability. CONCLUSIONS: Our arthroplasty care practitioner service allowed us to identify increased pain and stop using the ASR XL over 3 years before the implant was recalled. The revised patients had similar functional outcome to those unrevised. Poorly performing implants need to be identified earlier.