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Since its release the Power Threat Meaning Framework (PTMF) has received considerable interest and uptake. However, there have not yet been any attempts to review the scope of this emergent literature. This scoping review aimed to identify and synthesize: (1) all empirical research which utilized the PTMF in their methodologies, (2) the characteristics of these studies, (3) the different ways in which these studies utilized the PTMF, and (4) the key findings of these studies. This review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) scoping review extension (PRISMA-ScR). Following systematic searches of academic databases and grey literature, 17 studies meeting eligibility criteria were included. These papers were subject to critical appraisal, data charting, and narrative synthesis. This review identified four uses of the PTMF: (1) PTMF-informed data collection, (2) PTMF-informed data analysis, (3) Experiences of/views on the PTMF, and (4) PTMF-informed psychological practices. This evidence-base demonstrated the merits of utilizing the PTMF across a range of disciplines, settings, and populations. This heterogeneity also presents challenges for evidence synthesis. Implications for research (e.g. importance of the coherent and consistent approach to research) and practice/policy (e.g. professional training, collaboration, service-level barriers) are considered., (© 2024 The British Psychological Society.)

A hospital-wide point prevalence study investigated frailty and pain in patients with a cancer-related admission. Modifiable factors associated with frailty in people with cancer were determined through logistic regression. Forty-eight patients (19%) with cancer-related admissions were 2.65 times more likely to be frail and 2.12 more likely to have moderate pain. Frailty and pain were highly prevalent among cancer-related admissions, reinforcing the need for frailty screening and importance of pain assessment for patients with cancer., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Aims: To understand nurses' perceptions of volunteer support in health care settings., Background: Increasingly, volunteers provide specialised support to health care service users, requiring volunteers and nurses to work closely together. However, little is known about nurses' perceptions of volunteer support., Methods: A scoping review was conducted following the PRISMA-ScR checklist. A mixed-methods convergent integrative approach was taken guided by the JBI framework. Quantitative data were transformed into qualitative data for synthesis and descriptive thematic analysis. Six databases were searched (CINHAL+, EMBASE, PubMed, Scopus, PsycInfo, ProQuest Health and Medical Collection) on 24 January 2022 using terms related to nurses, perceptions, volunteers and care settings, followed by a manual search. The search was limited to English language articles published during 2000-2022. Studies were included if they reported nurses' perceptions of volunteers supporting care within any health care setting., Results: Of the 943 records identified, 12 met the inclusion criteria. All 12 were included in the review following critical appraisal. Five themes were identified: perceived benefits for patients, volunteers providing support for nursing staff, nurses' valuing volunteer support, nurses' understanding of the volunteer role and nurses' understanding of recruitment and training of volunteers., Conclusion: Nurses generally viewed volunteer support positively and perceived that it benefitted patients and assisted nurses. Some nurses raised concerns about the burden of additional supervision of volunteers and lacked knowledge of the volunteer role, recruitment and training. Emerging innovative models of nurse-led volunteer support can maximise the contribution of volunteers and help overcome barriers to volunteer acceptance., Implications: These findings will inform volunteer policies and provide guidance in developing volunteer support programs., (© 2022 International Council of Nurses.)

Frailty and pain in hospitalised patients are associated with adverse clinical outcomes. However, there is limited data on the associations between frailty and pain in this group of patients. Understanding the prevalence, distribution and interaction of frailty and pain in hospitals will help to determine the magnitude of this association and assist health care professionals to target interventions and develop resources to improve patient outcomes. This study reports the point prevalence concurrence of frailty and pain in adult patients in an acute hospital. A point prevalence, observational study of frailty and pain was conducted. All adult inpatients (excluding high dependency units) at an acute, private, 860-bed metropolitan hospital were eligible to participate. Frailty was assessed using the self-report modified Reported Edmonton Frail Scale. Current pain and worst pain in the last 24 h were self-reported using the standard 0-10 numeric rating scale. Pain scores were categorised by severity (none, mild, moderate, severe). Demographic and clinical information including admitting services (medical, mental health, rehabilitation, surgical) were collected. The STROBE checklist was followed. Data were collected from 251 participants (54.9% of eligible). The prevalence of frailty was 26.7%, prevalence of current pain was 68.1% and prevalence of pain in the last 24 h was 81.3%. After adjusting for age, sex, admitting service and pain severity, admitting services medical (AOR: 13.5 95% CI 5.7-32.8), mental health (AOR: 6.3, 95% CI 1. 9-20.9) and rehabilitation (AOR: 8.1, 95% CI 2.4-37.1) and moderate pain (AOR: 3.9, 95% CI 1. 6-9.8) were associated with increased frailty. The number of older patients identified in this study who were frail has implications for managing this group in a hospital setting. This indicates a need to focus on developing strategies including frailty assessment on admission, and the development of interventions to meet the care needs of these patients. The findings also highlight the need for increased pain assessment, particularly in those who are frail, for more effective pain management.Trial registration: The study was prospectively registered (ACTRN12620000904976; 14th September 2020)., (© 2023. The Author(s).)

Background: A fundamental tenent of treating developmental dysplasia of the hip is to identify patients with dislocated hips early so as to avoid the long-term sequelae of late diagnosis. The aim of this study was to develop a readily useable triage tool for patients with suspected hip dislocation, based on the clinical history and examination findings of the referring practitioner., Methods: All primary care referrals (n=934) over a 3-year period for suspected developmental dysplasia of the hip to a tertiary pediatric center were evaluated. Defined parameters with respect to history and clinical examination were evaluated. Multivariable logistic regression was used to establish predictors of hip dislocation, and from this a predictive model was derived which incorporated significant predictors of dislocation. An illustrative nomogram translated this predictive model into a usable numerical scoring system called the Children's Hip Prediction score, which estimates probability of hip dislocation., Results: There were 97 dislocated hips in 85 patients. The final predictive model included age, sex, family history, breech, gait concerns, decreased abduction, leg length discrepancy, and medical/neurological syndrome. The area under receiver operating curve for the model is 0.761. A Children's Hip Prediction score of≥5 corresponds to a sensitivity of 76.3% and a score of≥15 has a specificity of 97.8%, corresponding to an odds ratio of 27.3 for increased risk of dislocation., Conclusion: We found that a novel clinical prediction score, based on readily available history and examination parameters strongly predicted risk of dislocations in hip dysplasia referral. It is hoped that this tool could be utilized to optimize resource allocation and may be of particular benefit in less well-resourced health care systems., Level of Evidence: Level II., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Hospitalised older adults are prone to functional deterioration, which is more evident in frail older patients and can be further exacerbated by pain. Two interventions that have the potential to prevent progression of frailty and improve patient outcomes in hospitalised older adults but have yet to be subject to clinical trials are nurse-led volunteer support and technology-driven assessment of pain., Methods and Analysis: This single-centre, prospective, non-blinded, cluster randomised controlled trial will compare the efficacy of nurse-led volunteer support, technology-driven pain assessment and the combination of the two interventions to usual care for hospitalised older adults. Prior to commencing recruitment, the intervention and control conditions will be randomised across four wards. Recruitment will continue for 12 months. Data will be collected on admission, at discharge and at 30 days post discharge, with additional data collected during hospitalisation comprising records of pain assessment and volunteer support activity. The primary outcome of this study will be the change in frailty between both admission and discharge, and admission and 30 days, and secondary outcomes include length of stay, adverse events, discharge destination, quality of life, depression, cognitive function, functional independence, pain scores, pain management intervention (type and frequency) and unplanned 30-day readmissions. Stakeholder evaluation and an economic analysis of the interventions will also be conducted., Ethics and Dissemination: Ethical approval has been granted by Human Research Ethics Committees at Ramsay Health Care WA|SA (number: 2057) and Edith Cowan University (number: 2021-02210-SAUNDERS). The findings will be disseminated through conference presentations, peer-reviewed publications and social media., Trial Registration Number: ACTRN12620001173987., Competing Interests: Competing interests: KG is the director of clinical services at Hollywood Private Hospital. JH and MA are two of the originators of PainChek, which is marketed by PainChek. They both have share holdings in PainChek Ltd (ASX:PCK), which is a publicly listed company in the Australian Share Securities. They also have a granted patent entitled ‘A pain assessment method and system’ (PCT/AU2015/000501) in Australia, Japan, China and the USA, which was assigned to PainChek. JH holds the position of chief scientific officer of PainChek and is also an emeritus Professor at Curtin Medical School, Curtin University. MA previously held the position of a senior research scientist (October 2018 to May 2020) at PainChek and is currently serving the position of a Research and Practice Lead at The Dementia Centre, HammondCare, and is also an adjunct lecturer at Curtin Medical School, Curtin University., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Frailty and pain are associated with adverse patient clinical outcomes and healthcare system costs. Frailty and pain can interact, such that symptoms of frailty can make pain assessment difficult and pain can exacerbate the progression of frailty. The prevalence of frailty and pain and their concurrence in hospital settings are not well understood, and patients with cognitive impairment are often excluded from pain prevalence studies due to difficulties assessing their pain. The aim of this study is to determine the prevalence of frailty and pain in adult inpatients, including those with cognitive impairment, in an acute care private metropolitan hospital in Western Australia., Methods and Analysis: A prospective, observational, single-day point prevalence, cross-sectional study of frailty and pain intensity of all inpatients (excluding day surgery and critical care units) will be undertaken. Frailty will be assessed using the modified Reported Edmonton Frail Scale. Current pain intensity will be assessed using the PainChek smart-device application enabling pain assessment in people unable to report pain due to cognitive impairment. Participants will also provide a numerical rating of the intensity of current pain and the worst pain experienced in the previous 24 hours. Demographic and clinical information will be collected from patient files. The overall response rate of the survey will be reported, as well as the percentage prevalence of frailty and of pain in the sample (separately for PainChek scores and numerical ratings). Additional statistical modelling will be conducted comparing frailty scores with pain scores, adjusting for covariates including age, gender, ward type and reason for admission., Ethics and Dissemination: Ethical approval has been granted by Ramsay Health Care Human Research Ethics Committee WA/SA (reference: 2038) and Edith Cowan University Human Research Ethics Committee (reference: 2020-02008-SAUNDERS). Findings will be widely disseminated through conference presentations, peer-reviewed publications and social media., Trial Registration Number: ACTRN12620000904976., Competing Interests: Competing interests: KG is the Director of Clinical Services at Hollywood Private Hospital. Professor Jeff Hughes and Mr Mustafa Atee are two of the originators PainChek, which is marketed by PainChek. Both have shareholdings in PainChek Ltd (ASX:PCK), which is a publicly listed company in the Australian Share Securities. They have a granted patent entitled 'A pain assessment method and system” (PCT/AU2015/000501) in Australia, Japan, China and the USA. JH holds the position of Chief Scientific Officer of PainChek while serving as a Professor at the School of Pharmacy and Biomedical Sciences, Curtin University. MA formerly served (October 2018–May 2020) as a Research Scientist for PainChek. He is also PhD Candidate with the School of Pharmacy and Biomedical Sciences, Curtin University., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Vascular calcification (VC) and renal osteodystrophy are important complications of advanced chronic kidney disease (CKD). High resolution peripheral quantitative computed tomography (HRpQCT) is able to assess bone microstructure in renal osteodystrophy and lower leg arterial calcification (LLAC) is usually seen as an incidental finding. LLAC can be a useful quantitative assessment of VC in CKD but the relationship between LLAC and vascular biomarkers and bone is unknown. We aimed to assess the relationship between LLAC and biomarkers, bone turnover and microstructure., Methods: In this cross-sectional study, fasting blood samples were taken from 69 CKD stages 4-5D patients and 68 healthy controls. HRpQCT of distal tibia and radius were performed. 43 CKD patients had trans-iliac bone biopsy after tetracycline labelling., Results: LLAC was more severe in CKD than controls (median [IQR] 1.043 [0.05-16.52] vs 0 [0-0.55] mgHA, p < 0.001). CKD patients with diabetes (28%) had significantly higher LLAC compared to non-diabetic CKD (median [IQR] 24.07 [3.42-61.30] vs 0.23 [0-3.78] mgHA, p < 0.001). LLAC mass in CKD correlated with serum phosphate (rho = 0.29, p < 0.05), calcium x phosphate product (rho = 0.31, p < 0.05), intact parathyroid hormone (rho = 0.38, p < 0.01), intact fibroblast growth factor-23 (iFGF23) (rho = 0.40, p = 0.001), total alkaline phosphatase (rho = 0.41, p < 0.001), bone alkaline phosphatase (rho = 0.29, p < 0.05), osteocalcin (rho = 0.32, p < 0.05), osteoprotegerin (rho = 0.40, p = 0.001) and dephosphorylated-uncarboxylated matrix Gla protein (rho = 0.31, p < 0.05). LLAC in CKD also correlated with worse distal tibia cortical bone mineral density, thickness and porosity. No association was found between LLAC and bone turnover, mineralization or volume on biopsy in CKD. In multivariate analysis, only age, diabetes, iPTH and iFGF23 were independently associated with LLAC in CKD., Conclusions: High levels of PTH and FGF23, along with older age and the presence of diabetes may all play independent roles in the development of LLAC in advanced CKD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Bone biopsy is the gold standard test to diagnose renal osteodystrophy (ROD). There is a preference to perform bone biopsy during renal transplantation but tetracycline bone labelling is usually not possible. We aimed to test if histomorphometry static parameters can identify low and high bone turnover as assessed by dynamic measurement using double tetracycline labelling., Methods: 43 CKD stages 4-5D had trans-iliac bone biopsy using a 4 mm Jamshidi trephine and needle after tetracycline labelling. Quantitative histomorphometry was performed using the Bioquant Osteo histomorphometry system. Normal bone turnover was defined as bone formation rate/bone surface (BFR/BS) of 18-38 μm 3 /μm 2 /year. Static parameters of bone turnover included osteoblast surface/bone surface (Ob.S/BS, %), osteoclast surface/bone surface (Oc.S/BS, %) and erosion surface/bone surface (ES/BS, %). Receiver operating characteristics (ROC) analysis was used to evaluate diagnostic accuracy of these static parameters for low and high bone turnover (based on BFR/BS)., Results: Median (IQR) for BFR/BS in this study was 32.12 (17.76-48.25) μm 3 /μm 2 /year. 26% of patients had low, 34% had normal and 40% had high bone turnover. The area under the ROC curve (AUC) for Ob.S/BS, Oc.S/BS and ES/BS were non-significant indicating poor accuracy for identifying low bone turnover. The AUC for Ob.S/BS was 0.697 (95% CI 0.538 to 0.827) indicating fair accuracy for identifying high bone turnover. Oc.S/BS and ES/BS had non-significant AUCs for high bone turnover., Conclusions: Static histomorphometry parameters for bone turnover are unable to replace dynamic parameter in diagnosing ROD. Tetracycline bone labelling is still required., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We describe the first radiographic clinic in the literature for DDH and how this novel clinic can significantly improve the efficiency and cost-effectiveness of service in a tertiary referral centre., Aims: A radiographic clinic for the management of developmental dysplasia of the hip was introduced in 2017 in our institution. We performed a detailed cost analysis to assess the economic savings made with the introduction of this new clinic. We assessed the efficiency of the service by identifying how many unnecessary outpatient visits were prevented. We also assessed the difference in times from referral to review between the two clinics., Methods: Analysis of the clinic activity in 2017 was possible as all data was collected prospectively by the DDH CNS and stored in our database. Cost analysis was performed, and the savings made per patient along with the financial benefit to our institution was recorded., Results: The new radiographic clinic reduced the cost of reviewing one patient by €162.51 per patient. There was a 73% discharge rate from the clinic which prevented 251 unnecessary patient visits to the outpatient department over the course of the year. There was a significant 11-day reduction in waiting times between referral and review when comparing the radiographic to the conventional clinic (p < 0.05)., Conclusions: A radiographic clinic for the management of developmental dysplasia of the hip has a significant effect on the efficiency and overall cost-effectiveness of service provision in a tertiary referral centre.

Background: Significant health disparities exist between members of the Travelling community and those of the general population. Barriers to Traveller engagement with health services include the experience or perception of discrimination, and cultural and health literacy barriers. Experience of skin disease and interactions with healthcare providers has not been widely explored in this ethnic minority. The formation of positive relationships between the Travelling community and healthcare providers is important in the promotion of treatment adherence and improving health outcomes., Objectives: To investigate Travellers' experience of skin disease and their relationships with healthcare providers., Methods: Focus groups were conducted with a purposive sample of female members of the Irish Travelling community with experience of skin health issues, between January 2018 and April 2018. Three focus groups were conducted at three separate locations with 10 participants in each group. Themes were identified from the focus group transcripts using an inductive thematic analysis framework., Results: Emergent themes surrounding relationships between Travellers and healthcare providers included health literacy, discrimination, information inconsistency, trust and communication. Factors that were valued in the creation of positive relationships included an appreciation of varying degrees of health literacy, the provision of sufficient information tailored to an individual's needs and a demonstration of cultural competence., Conclusions: Dermatologists are well placed to provide practical, customized, treatment guidance and engage patients while integrating their culturally based beliefs., (© 2019 British Association of Dermatologists.)

Background Renal osteodystrophy is common in advanced CKD, but characterization of bone turnover status can only be achieved by histomorphometric analysis of bone biopsy specimens (gold standard test). We tested whether bone biomarkers and high-resolution peripheral computed tomography (HR-pQCT) parameters can predict bone turnover status determined by histomorphometry. Methods We obtained fasting blood samples from 69 patients with CKD stages 4-5, including patients on dialysis, and 68 controls for biomarker analysis (intact parathyroid hormone [iPTH], procollagen type 1 N-terminal propeptide [PINP], bone alkaline phosphatase [bALP], collagen type 1 crosslinked C-telopeptide [CTX], and tartrate-resistant acid phosphatase 5b [TRAP5b]) and scanned the distal radius and tibia of participants by HR-pQCT. We used histomorphometry to evaluate bone biopsy specimens from 43 patients with CKD. Results Levels of all biomarkers tested were significantly higher in CKD samples than control samples. For discriminating low bone turnover, bALP, intact PINP, and TRAP5b had an areas under the receiver operating characteristic curve (AUCs) of 0.82, 0.79, and 0.80, respectively, each significantly better than the iPTH AUC of 0.61. Furthermore, radius HR-pQCT total volumetric bone mineral density and cortical bone volume had AUCs of 0.81 and 0.80, respectively. For discriminating high bone turnover, iPTH had an AUC of 0.76, similar to that of all other biomarkers tested. Conclusions The biomarkers bALP, intact PINP, and TRAP5b and radius HR-pQCT parameters can discriminate low from nonlow bone turnover. Despite poor diagnostic accuracy for low bone turnover, iPTH can discriminate high bone turnover with accuracy similar to that of the other biomarkers, including CTX., (Copyright © 2018 by the American Society of Nephrology.)

Objective: A review of the current literature evaluating trauma nursing education., Background: A variety of trauma nursing courses exist, to educate nurses working in trauma settings, and to maintain their continuing professional development. Despite an increase in the number of courses delivered, there appears to be a lack of evidence to demonstrate the effectiveness of trauma nursing education and in particular the justification for this resource allocation., Design: Integrative literature review., Data Sources: A search of international literature on trauma nursing education evaluation published in English from 1985 to 2015 was conducted through electronic databases CINAHL Plus, Google Scholar, PubMed, Austhealth, Science Citation Index Expanded (Web of Science), Sciverse Science Direct (Elsevier) & One file (Gale). Only peer reviewed journal articles identifying trauma course and trauma nursing course evaluation have been included in the selection criteria., Review Methods: An integrative review of both quantitative and qualitative literature guided by Whittemore and Knafl's theoretical framework using Bowling's and Pearson's validated appraisal checklists, has been conducted for three months., Results: Only 17 studies met the inclusion criteria, including 14 on trauma course evaluation and 3 on trauma nursing course evaluation. Study findings are presented as two main themes: the historical evolution of trauma nursing education and evaluation of trauma nursing education outcomes., Conclusion: Trauma nursing remains in its infancy and education in this specialty is mainly led by continuing professional development courses. The shortage of evaluation studies on trauma nursing courses reflects the similar status in continuing professional development course evaluation. A trauma nursing course evaluation study will address the gap in this under researched area., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The degradation of the main fibrillar collagens, collagens I and II, is a crucial process for skeletal development. The most abundant dipeptides generated from the catabolism of collagens contain proline and hydroxyproline. In humans, prolidase is the only enzyme able to hydrolyze dipeptides containing these amino acids at their C-terminal end, thus being a key player in collagen synthesis and turnover. Mutations in the prolidase gene cause prolidase deficiency (PD), a rare recessive disorder. Here we describe 12 PD patients, 9 of whom were molecularly characterized in this study. Following a retrospective analysis of all of them a skeletal phenotype associated with short stature, hypertelorism, nose abnormalities, microcephaly, osteopenia and genu valgum, independent of both the type of mutation and the presence of the mutant protein was identified. In order to understand the molecular basis of the bone phenotype associated with PD, we analyzed a recently identified mouse model for the disease, the dark-like (dal) mutant. The dal/dal mice showed a short snout, they were smaller than controls, their femurs were significantly shorter and pQCT and μCT analyses of long bones revealed compromised bone properties at the cortical and at the trabecular level in both male and female animals. The differences were more pronounce at 1 month being the most parameters normalized by 2 months of age. A delay in the formation of the second ossification center was evident at postnatal day 10. Our work reveals that reduced bone growth was due to impaired chondrocyte proliferation and increased apoptosis rate in the proliferative zone associated with reduced hyperthrophic zone height. These data suggest that lack of prolidase, a cytosolic enzyme involved in the final stage of protein catabolism, is required for normal skeletogenesis especially at early age when the requirement for collagen synthesis and degradation is the highest., (Copyright © 2014 Elsevier Inc. All rights reserved.)

This report illustrates how the uncertainty about food safety metrics may influence the selection of a performance objective (PO). To accomplish this goal, we developed a model concerning Listeria monocytogenes in ready-to-eat (RTE) deli meats. This application used a second order Monte Carlo model that simulates L. monocytogenes concentrations through a series of steps: the food-processing establishment, transport, retail, the consumer's home and consumption. The model accounted for growth inhibitor use, retail cross contamination, and applied an FAO/WHO dose response model for evaluating the probability of illness. An appropriate level of protection (ALOP) risk metric was selected as the average risk of illness per serving across all consumed servings-per-annum and the model was used to solve for the corresponding performance objective (PO) risk metric as the maximum allowable L. monocytogenes concentration (cfu/g) at the processing establishment where regulatory monitoring would occur. Given uncertainty about model inputs, an uncertainty distribution of the PO was estimated. Additionally, we considered how RTE deli meats contaminated at levels above the PO would be handled by the industry using three alternative approaches. Points on the PO distribution represent the probability that - if the industry complies with a particular PO - the resulting risk-per-serving is less than or equal to the target ALOP. For example, assuming (1) a target ALOP of -6.41 log10 risk of illness per serving, (2) industry concentrations above the PO that are re-distributed throughout the remaining concentration distribution and (3) no dose response uncertainty, establishment PO's of -4.98 and -4.39 log10 cfu/g would be required for 90% and 75% confidence that the target ALOP is met, respectively. The PO concentrations from this example scenario are more stringent than the current typical monitoring level of an absence in 25 g (i.e., -1.40 log10 cfu/g) or a stricter criteria of absence in 125 g (i.e., -2.1 log10 cfu/g). This example, and others, demonstrates that a PO for L. monocytogenes would be far below any current monitoring capabilities. Furthermore, this work highlights the demands placed on risk managers and risk assessors when applying uncertain risk models to the current risk metric framework., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Early Intervention in Psychosis Services (EIS) for young people in England experiencing first-episode psychosis (FEP) were commissioned in 2002, based on an expected incidence of 15 cases per 100 000 person-years, as reported by schizophrenia epidemiology in highly urban settings. Unconfirmed reports from EIS thereafter have suggested higher than anticipated rates. The aim of this study was to compare the observed with the expected incidence and delineate the clinical epidemiology of FEP using epidemiologically complete data from the CAMEO EIS, over a 6-year period in Cambridgeshire, for a mixed rural-urban population., Method: A population-based study of FEP (ICD-10, F10-39) in people aged 17-35 years referred between 2002 and 2007; the denominator was estimated from mid-year census statistics. Sociodemographic variation was explored by Poisson regression. Crude and directly standardized rates (for age, sex and ethnicity) were compared with pre-EIS rates from two major epidemiological FEP studies conducted in urban English settings., Results: A total of 285 cases met FEP diagnoses in CAMEO, yielding a crude incidence of 50 per 100 000 person-years [95% confidence interval (CI) 44.5-56.2]. Age- and sex-adjusted rates were raised for people from black ethnic groups compared with the white British [incidence rate ratio (IRR) 2.1, 95% CI 1.1-3.8]. Rates in our EIS were comparable with pre-EIS rates observed in more urban areas after age, sex and ethnicity standardization., Conclusions: Our findings suggest that the incidence observed in EIS is far higher than originally anticipated and is comparable to rates observed in more urban settings prior to the advent of EIS. Sociodemographic variation due to ethnicity and other factors extend beyond urban populations. Our results have implications for psychosis aetiology and service planning.

Prostate, breast and lung cancers readily develop bone metastases which lead to fractures, hypercalcemia and pain. Malignant growth in the bones depends on osteoclast-mediated bone resorption and in this regard bisphosphonate compounds, which have high-bone affinity and inhibit osteoclast activity, have been found to alleviate bone cancer symptoms. In this study, the bisphosphonate risedronate and its phosphonocarboxylate derivative NE-10790 was tested in a murine bone cancer pain model. Risedronate decreased bone cancer-related bone destruction and pain-related behavior and decreased the spinal expression of glial fibrillary acidic protein, whereas NE-10790 had no effect on these parameters. Furthermore, risedronate but not NE-10790 induced dose-dependent toxicity in NCTC-2472 cells in vitro. Furthermore, the direct toxic effect of risedronate on tumor cells observed in vitro opens the possibility that a direct toxic effect on tumor cells may also be present in vivo and be related to the efficacy of bisphosphonate compounds. In conclusion, these results suggest that risedronate treatment may lead to an increased life quality, in patient suffering from bone cancer, in terms of decreased osteolysis and pain, and merits further study., (2009 UICC.)

During the last decade, a central role for insulin-like growth factor 1 (IGF-1) in the pathophysiology of multiple myeloma (MM) has been well established. IGF-I provided by the tumor-microenvironment interaction may directly and indirectly facilitate the migration, survival and expansion of the MM cells in the bone marrow (BM). The inhibition of the IGF-1R-mediated signaling pathway has recently been suggested to be a possible new therapeutic principle in MM. Using the mouse 5T2MM model, we now demonstrate that targeting the IGF-1R using picropodophyllin (PPP) in a therapeutical setting not only has strong antitumor activity on the established MM tumor but also influences the BM microenvironment by inhibiting angiogenesis and bone disease, having a profound effect on the survival of the mice. At therapeutically achievable concentrations of PPP, the average survival was 180 days for the PPP-treated mice as compared to 100 days for vehicle-treated mice. PPP used as single drug treatment in the 5T2MM model resulted in a decrease of tumor burden by 65% while the paraprotein concentrations were reduced by 75%. This decrease was associated with a significant inhibition of tumor-associated angiogenesis and osteolysis. The present studies on the biological effects of PPP in the 5T2MM model constitute an important experimental platform for future therapeutic implementation., ((c) 2007 Wiley-Liss, Inc.)

A buckle fracture is a stable fracture where there is a dorsal cortex compression of the distal radius. A total of 117 children with buckle fracture treated at our institution were randomised prospectively into two treatment groups: soft cast or rigid cast. The rigid cast group attended clinic after three weeks for removal of the cast. In the soft cast group, the cast was removed by parents at home after three weeks. Telephone follow-up was carried out after 4 to 5 weeks post fracture. Both groups had full recovery as compared to the uninjured side and parents were satisfied with the treatment. Only one patient in the soft cast group had a problem as compared to 5 in the rigid cast group (p = 0.035, using chi square test). When given a choice, parents of children in both groups opted for future treatment with a soft cast (p < 0.01 using chi square test). Our study showed that buckle fractures of the distal radius can safely be treated with a soft cast without the need for more than one fracture clinic appointment.

Multiple myeloma is a B-cell malignancy characterized by the uncontrolled growth of plasma cells in the bone marrow and the development of osteolytic bone disease. Myeloma cells express the receptor activator of nuclear factor kappaB ligand (RANKL), induce RANKL expression in the bone marrow, and down-regulate expression of the decoy receptor osteoprotegerin, thereby promoting bone resorption. Targeting this system in myeloma has clear therapeutic potential. However, osteoprotegerin also binds tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and prevents TRAIL-induced apoptosis of myeloma cells. Whether or not osteoprotegerin can bind TRAIL and prevent apoptosis in vivo and the relative importance of osteoprotegerin binding to TRAIL and RANKL are unclear. In the present study, we have investigated the ability of an osteoprotegerin-like peptidomimetic (OP3-4), designed to block the RANKL/RANK interaction, to inhibit osteoclastic bone resorption and TRAIL-induced apoptosis in vitro and myeloma bone disease in vivo. OP3-4 inhibited osteoclast formation (P < 0.01) and bone resorption (P < 0.01) in vitro. However, OP3-4 had no effect on TRAIL-induced apoptosis of RPMI 8226 myeloma cells. Treatment of 5T2MM myeloma-bearing mice with OP3-4 decreased osteoclast number and the proportion of bone surface covered by osteoclasts (P < 0.05). Treatment also prevented the tumor-induced decrease in cancellous bone area and the development of osteolytic lesions (P < 0.05). OP3-4 also reduced tumor burden when compared with the control (P < 0.05). These data suggest that OP3-4 and the selective inhibition of RANKL, but not TRAIL activity, are effective in preventing myeloma bone disease and offer a novel therapeutic approach to treating this aspect of myeloma. [Cancer Res 2007;67(1):202-8].

Background: Demonstrating specific cognitive impairments in psychotic disorders is difficult. However, specific deficits in memory and executive functions have often been claimed. The Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks of IDED attention-shifting (an executive task) and visuospatial paired associates learning (PAL, a memory task) require intact frontal and temporo-hippocampal functioning, respectively; both have been suggested as markers of disease progress in psychosis., Method: Seventy-one subjects with a first-episode psychosis or at-risk mental state were assessed on these two tasks during referral to a specialist service, the Cambridge-based CAMEO early intervention team., Results: Performance on the two tasks was dissociated. Poor performance on the PAL test was associated with increased symptom levels and poorer global function, while failure on the IDED executive test was not found to have significant clinical associations. Duration of illness was not associated with performance on either task., Conclusions: Visuospatial PAL failure may be a marker of clinical severity at the onset of psychosis while IDED performance may reflect a more stable, trait-like impairment. Dissociated performance on the executive and associative learning tasks may reflect independent, neurally dissociated impairments that do not arise in a fixed order. This may explain some of the heterogeneity of cognitive function seen in early psychosis.

The article describes the development of guidelines for the management of first episode psychosis, over the first few years of the illness. Such guidelines advocate the use of low dose medication (be this with typical or atypical anti-psychotics) as well as psychological techniques, and assertive case management. The paper will review the development of these guidelines, describe them, and suggest outcome measures for the treatment of first and early episodes.