A seroprevalence study to determine the frequency of hantavirus infection in people exposed to wild and pet fancy rats in England.

Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9-45·7%) compared with 3·3% (95% CI 1·6-6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6-5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2-5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.

IL8 polymorphisms and overall survival in pazopanib- or sunitinib-treated patients with renal cell carcinoma.

BACKGROUND: We evaluated germline single nucleotide polymorphisms (SNPs) for association with overall survival (OS) in pazopanib- or sunitinib-treated patients with advanced renal cell carcinoma (aRCC). METHODS: The discovery analysis tested 27 SNPs within 13 genes from a phase III pazopanib trial (N=241, study 1). Suggestive associations were then pursued in two independent datasets: a phase III trial (COMPARZ) comparing pazopanib vs sunitinib (N=729, study 2) and an observational study of sunitinib-treated patients (N=89, study 3). RESULTS: In study 1, four SNPs showed nominally significant association (P≤0.05) with OS; two of these SNPs (rs1126647, rs4073) in IL8 were associated (P≤0.05) with OS in study 2. Because rs1126647 and rs4073 were highly correlated, only rs1126647 was evaluated in study 3, which also showed association (P≤0.05). In the combined data, rs1126647 was associated with OS after conservative multiple-test adjustment (P=8.8 × 10(-5); variant vs reference allele hazard ratio 1.32, 95% confidence interval: 1.15-1.52), without evidence for heterogeneity of effects between studies or between pazopanib- and sunitinib-treated patients. CONCLUSIONS: Variant alleles of IL8 polymorphisms are associated with poorer survival outcomes in pazopanib- or sunitinib-treated patients with aRCC. These findings provide insight in aRCC prognosis and may advance our thinking in development of new therapies.

Social needs screening in primary care: A tool in the fight for health equity?

Progress on addressing health inequalities is slow and in many places around the world the gap between the privileged and the disadvantaged is widening. This is driven largely by an unfair and unequal distribution of the social determinants of health. While upstream policy and agenda commitment is needed to improve social determinants of health at a population level, healthcare also has a role. Currently social information is sporadically collected and used in healthcare. Improving our understanding of social problems is crucial in targeting services and to reduce the overreliance on area-level measures of deprivation. This has the potential to improve patient care as well as more accurately capture socio-economic disadvantage. Here we argue that there is a role for primary care in screening for social needs to help address inequalities. Social needs screening, more commonly used in North America than Europe, aims to systematically collect social information in health and care settings. Healthcare professionals ask patients about social issues including employment, finances, housing, education and social isolation and this information is used to prompt referral to community services to address any need identified. Social needs screening has potential to address negative impacts of social determinants of health at an individual and population level. Providing a reliable measure of social need, screening gives healthcare professionals an opportunity to tailor and improve quality of care for patients and offer individualised support. It has been shown to improve individual social and health outcomes and positively impact healthcare utilisation. At a population level, social needs screening can improve the data on social determinants of health and therefore support policy makers and service delivery leaders to target resources and services more effectively to the communities most in need. Implementing social needs screening must take account of local healthcare service capacity and available community resources but where sustainable, effective programmes can be introduced, the potential benefits are manifold. While primary care alone cannot solve the root causes of health inequalities, we argue it could be a powerful actor in the fight for health equity.

Children and adolescents with SLE: not just little adults.

Juvenile-onset systemic lupus erythematosus (JSLE) represents 15-20% of all SLE cases. Whilst features of this chronic complex multisystem autoimmune disorder are highly variable, children and adolescents generally present with a more severe illness than adults and accrue greater disease damage over time. JSLE has a less striking female preponderance and differs from the adult form in pattern of major organ manifestations. Corticosteroids are used in almost all children with JSLE along with the majority requiring additional immunosuppressive medications. Making the diagnosis early and optimizing disease control are essential to ensure that normal childhood and adolescent development is not impeded. In this young population, special consideration must be given to the long-term sequelae of the disease and treatment-related toxicity. There is a current lack of paediatric-specific controlled trials and treatment strategies are generally guided by adult data. The enormous psychological and social impact of the disease and its treatments upon the child or young person and their family necessitates a comprehensive, holistic, specialized multidisciplinary approach to managing JSLE.

Development and validation of the Diet Quality Tool for use in cardiovascular disease prevention settings.

The aim of this study was to develop and evaluate a dietary screening tool for use in a secondary cardiovascular disease (CVD) prevention setting to identify an individual's overall dietary quality. The Diet Quality Tool (DQT) was validated against a 4-day food diary for 37 individuals with established CVD attending cardiac rehabilitation. Construct validity was demonstrated for % energy from saturated fat (P=0.002, r=-0.500), dietary fibre (P<0.001, r=0.559) and omega-3 fatty acids (P=0.048, r=0.327). Criterion validity was established with a significant difference found between mean (95% CI) dietary intakes of fibre (28.2g, 4.4 to 17.3) and % total energy from saturated fat (10.6%, -4.8 to -0.8) for those with better DQT scores (>60%) versus those with poorer scores (≤60%) when compared with 4-day food diary nutrient values. The usefulness of the DQT was confirmed by both patients (n=25) and cardiac rehabilitation health professionals (n=8). The DQT was found to be a valid and useful dietary assessment tool with potential for use in a secondary CVD prevention setting. The tool has the capacity to be used in a wider variety of settings and further refinement of the tool would enable a greater amount of nutrients to be reliably screened.

Juvenile Dermatomyositis: what comes next? Long-term outcomes in childhood myositis from a patient perspective.

BACKGROUND: To describe long-term outcomes in JDM using patient questionnaires and link to longitudinal, prospectively collected data for each patient within the Juvenile Dermatomyositis Cohort and Biomarker Study, UK and Ireland (JDCBS) to determine outcome predictors.  METHODS: JDCBS participants aged ≥ 16y completed the SF36, HAQ and a questionnaire regarding current disease features, medications, education and employment. Data collected from the JDCBS included disease subtype, demographics, clinical and laboratory features. Intensity indices were calculated for physician VAS, modified skin DAS, CMAS and MMT8 by dividing area under the curve (AUC) from longitudinal score trajectories by duration of study follow-up (y). Relationships between questionnaire and JDCBS clinical / laboratory data were investigated fitting statistical models appropriate for cross sectional and longitudinal data. RESULTS: Of 190 questionnaires sent, 84 (44%) were returned. Average age of respondents was 20.6 years (SD 3.9), time since diagnosis was 12.4 years (SD 5.0), age at onset was 9.2 years (SD 4.3), female to male ratio 4.25:1. Forty-nine (59%) self-reported persistently active disease, 54 (65%) were still taking immunosuppressive medication. 14/32 at school/higher education reported myositis adversely affecting academic results. 18-24 year-olds were twice as likely to be unemployed compared the UK population (OR = 0.456, 95% CI 0.24, 0.84, p = 0.001). Participants ≥ 18 years were three times as likely to be living with a parent/guardian (OR = 3.39, p < 0.001). SF36 MCS and MMT8 intensity index scores were significantly correlated (ρ = 0.328, p = 0.007). CONCLUSIONS: After 12.4 years, questionnaire responders reported self-perceived high rates of persistently active disease and medication use, reduced rates of employment and were more likely to live with a parent/guardian. Perceived persistently active muscle disease appeared to affect quality of life in these patients and was the most significant contributor to long-term outcomes. Our findings highlight the importance of including the patient perspective in the assessment of long term outcomes, so that that we can start to target initial management strategies more effectively based on a combination of clinical and patient-reported data.

Adults with intellectual disabilities affected by cancer: critical challenges for the involvement agenda.

Cancer incidence and prevalence in people with intellectual disabilities are poorly documented. Changing demographic patterns, however, mirror those in the general population with increased longevity leading to higher numbers of people developing cancer in the future. Little is known about the service and support needs of this group, but there is a precedent to understand their experiences to inform research and service development if appropriately tailored approaches are to be adopted. This article outlines a project that sought to develop an advisory forum of adults with intellectual disabilities affected by cancer, to inform the development of a research agenda. The process of this work is described alongside a critical appraisal of the tensions in involving people with intellectual disabilities as advisors on cancer research and practice. We discuss and challenge the underlying ideologies, which lie in the path of fully engaging with marginalized patients.

Polyurethane as a potential knee hemiarthroplasty biomaterial: an in-vitro simulation of its tribological performance.

Hemiarthroplasty is an attractive alternative to total joint replacement for the young active patient, when only one side of the synovial joint is damaged. In the development of a hemiarthroplasty prosthesis, a comprehensive understanding of the tribology of both the natural joint and the hemireplaced joint is necessary. The objectives of this study were to investigate the tribological response of polyurethane (PU) as a potential hemiarthroplasty material. Bovine medial compartmental knees were tested in a Prosim pendulum friction simulator, which applied physiologically relevant loading and motion. The healthy medial compartment was investigated as a negative control; a stainless steel hemiarthroplasty was investigated as a positive control; and three PU hemiarthroplasty plates of different moduli (1.4 MPa, 6.5 MPa, and 22 MPa) were also investigated. Using the lower-modulus PU caused reduced levels of contact stress and friction shear stress, which resulted in reduced levels of opposing cartilage wear. The two PU bearings with the lowest moduli demonstrated a similar tribological performance to the negative control. The higher-modulus PU (22 MPa) did demonstrate higher levels of friction shear stress, and wear resulted on the opposing cartilage, although not as severe as the wear from the stainless steel group. This study supports the use of compliant PU designs in future tribological experiments and hemiarthroplasty design applications.

Influence of the meniscus on friction and degradation of cartilage in the natural knee joint.

BACKGROUND: Total meniscectomy has been shown to cause early-onset arthritis in the underlying cartilage and bone in the knee joint, demonstrating that the meniscus plays an important protective role in the load carrying capacity. Relationships between friction and wear in synovial joints are complex due to the biphasic nature of articular cartilage and the time dependency of tribological responses. Determination of friction and wear in the whole natural joint in vitro or in vivo is technically difficult and the tribological effect of meniscectomy has not been previously studied in an articulating knee joint. OBJECTIVE: The aim of this study was to use a tribological simulation of the medial compartmental bovine knee, to investigate friction and wear, with and without the meniscus. We hypothesised that meniscectomy would lead to elevated contact stress and frictional coefficient across the joint. METHODS: Skeletally mature bovine medial compartmental knee joints were dissected and mounted in a pendulum friction simulator, which was used to apply physiologically relevant loading and motion. Wear was quantified using micro-MRI scans and surface profilometry. RESULTS: Knees tested with the intact meniscus showed no change in surface roughness and no detectable cartilage loss or deformation. However, increased contact stress and frictional coefficient upon removal of the meniscus, led to immediate surface fibrillation, biomechanical wear and permanent deformation of cartilage. CONCLUSIONS: This study presents, for the first time, an in vitro model simulation system to investigate the tribological effects of meniscectomy and meniscus repair and regeneration.

Evaluation of a mobile phone-based, advanced symptom management system (ASyMS) in the management of chemotherapy-related toxicity.

OBJECTIVES: To evaluate the impact of a mobile phone-based, remote monitoring, advanced symptom management system (ASyMS) on the incidence, severity and distress of six chemotherapy-related symptoms (nausea, vomiting, fatigue, mucositis, hand-foot syndrome and diarrhoea) in patients with lung, breast or colorectal cancer. DESIGN: A two group (intervention and control) by five time points (baseline, pre-cycle 2, pre-cycle 3, pre-cycle 4 and pre-cycle 5) randomised controlled trial. SETTING: Seven clinical sites in the UK; five specialist cancer centres and two local district hospitals. PARTICIPANTS: One hundred and twelve people with breast, lung or colorectal cancer receiving outpatient chemotherapy. INTERVENTIONS: A mobile phone-based, remote monitoring, advanced symptom management system (ASyMS). MAIN OUTCOME MEASURES: Chemotherapy-related morbidity of six common chemotherapy-related symptoms (nausea, vomiting, fatigue, mucositis, hand-foot syndrome and diarrhoea). RESULTS: There were significantly higher reports of fatigue in the control group compared to the intervention group (odds ratio = 2.29, 95%CI = 1.04 to 5.05, P = 0.040) and reports of hand-foot syndrome were on average lower in the control group (odds ratio control/intervention = 0.39, 95%CI = 0.17 to 0.92, P = 0.031). CONCLUSION: The study demonstrates that ASyMS can support the management of symptoms in patients with lung, breast and colorectal cancer receiving chemotherapy.

Patients' perceptions and experiences of using a mobile phone-based advanced symptom management system (ASyMS) to monitor and manage chemotherapy related toxicity.

Chemotherapy forms a core component of treatment for the majority patients with cancer. Recent changes in cancer services mean patients frequently receive such treatment as outpatients and are often required to manage side effects at home without direct support from oncology health professionals. Information technology continues to develop to support patients in the community; this study evaluated the impact of a mobile phone-based advanced symptom management system (ASyMS) on chemotherapy related toxicity in patients with lung, breast or colorectal cancer. One hundred and twelve patients were randomized from seven clinical sites across the UK; 56 patients used the mobile phone to record their symptoms, sending their reports directly to the nurses at their clinical site; 56 control group patients received standard care. Health professionals were alerted about any severe or life-threatening symptoms through the development of a chemotherapy symptom risk model. Patients' perceptions of ASyMS were evaluated pre and post participation. Patients reported many benefits of using ASyMS including improved communication with health professionals, improvements in the management of their symptoms, and feeling reassured their symptoms were being monitored while at home. ASyMS has the potential to positively impact on the management of symptoms in patients receiving chemotherapy treatment.

Effectiveness of infliximab in the treatment of refractory juvenile dermatomyositis with calcinosis.

OBJECTIVES: Some juvenile dermatomyositis (JDM) patients have a disease course which is refractory to multiple drug treatments. Prolonged disease activity is associated with increased mortality and morbidity. TNF-alpha has been identified in high levels in JDM patients who have a long disease course and calcinosis. We assessed the response of five refractory JDM patients to the anti-TNF-alpha monoclonal antibody, infliximab. METHODS: For all five patients intravenous infliximab was initially given at a dose of 3 mg/kg. Further doses were then given at weeks 2, 6 and every 8 weeks thereafter. The dose and frequency were tailored in accordance with clinical response. Clinical and laboratory data were collected prospectively. RESULTS: We report results between 8 and 30 months after starting infliximab. Improvements were seen in all five patients as shown by positive changes in physician visual analogue scale (VAS), Childhood Myositis Assessment Score (CMAS), Childhood Health Assessment Questionnaire (CHAQ), joint range of movement and, in some, regression of calcinosis and skin signs. There were no major side effects observed with addition of infliximab to the therapeutic regime. CONCLUSIONS: Major clinical benefit was demonstrated after the initiation of infliximab in all five cases of refractory JDM.

Nurse's perceptions and experiences of using of a mobile-phone-based Advanced Symptom Management System (ASyMS) to monitor and manage chemotherapy-related toxicity.

Many people diagnosed with cancer will receive chemotherapy as a core component of their care. Recent changes in the delivery of cancer services mean that patients frequently receive care on an out-patient basis and are therefore often required to manage related side effects at home without direct support from oncology health professionals. The use of information and communications technology may be seen as a means of supporting patients receiving chemotherapy in the home care setting. This mixed methods study, reports on the perceptions of nurses (n=35) who participated in a randomised controlled trial of a mobile phone based, Advanced Symptom Management System (ASyMS), in the management of chemotherapy-related toxicity in patients with breast, lung and colorectal cancer. Nurses' perceptions of ASyMS were evaluated at the start and the end of the study. Overall, they could see the benefits of ASyMS in the remote monitoring of chemotherapy toxicity and its role in facilitating early intervention and subsequent management, demonstrating the potential utility of the system within clinical practice.