Brain Tumor Imaging

Modern imaging techniques, particularly functional imaging techniques that interrogate some specific aspect of underlying tumor biology, have enormous potential in neuro-oncology for disease detection, grading, and tumor delineation to guide biopsy and resection; monitoring treatment response; and targeting radiotherapy. This brief review considers the role of magnetic resonance imaging and spectroscopy, and positron emission tomography in these areas and discusses the factors that limit translation of new techniques to the clinic, in particular, the cost and difficulties associated with validation in multicenter clinical trials

Protocol for the 'e-Nudge trial' : a randomised controlled trial of electronic feedback to reduce the cardiovascular risk of individuals in general practice [ISRCTN64828380]

Background: Cardiovascular disease (including coronary heart disease and stroke) is a major cause of death and disability in the United Kingdom, and is to a large extent preventable, by lifestyle modification and drug therapy. The recent standardisation of electronic codes for cardiovascular risk variables through the United Kingdom's new General Practice contract provides an opportunity for the application of risk algorithms to identify high risk individuals. This randomised controlled trial will test the benefits of an automated system of alert messages and practice searches to identify those at highest risk of cardiovascular disease in primary care databases. Design: Patients over 50 years old in practice databases will be randomised to the intervention group that will receive the alert messages and searches, and a control group who will continue to receive usual care. In addition to those at high estimated risk, potentially high risk patients will be identified who have insufficient data to allow a risk estimate to be made. Further groups identified will be those with possible undiagnosed diabetes, based either on elevated past recorded blood glucose measurements, or an absence of recent blood glucose measurement in those with established cardiovascular disease. Outcome measures: The intervention will be applied for two years, and outcome data will be collected for a further year. The primary outcome measure will be the annual rate of cardiovascular events in the intervention and control arms of the study. Secondary measures include the proportion of patients at high estimated cardiovascular risk, the proportion of patients with missing data for a risk estimate, and the proportion with undefined diabetes status at the end of the trial

Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis

BACKGROUND: Since the sterilising activity of new antituberculosis drugs is difficult to assess by conventional phase III studies, surrogate methods related to eventual relapse rates are required. METHODS: A suitable method is suggested by a retrospective analysis of viable counts of Mycobacterium tuberculosis in 12-hr sputum collections from 122 newly diagnosed patients with pulmonary tuberculosis in Nairobi, done pretreatment and at 2, 7, 14 and 28 days. Treatment was with isoniazid and streptomycin, supplemented with either thiacetazone (SHT) or rifampicin + pyrazinamide (SHRZ). RESULTS: During days 0–2, a large kill due to isoniazid occurred, unrelated to treatment or HIV status; thereafter it decreased exponentially. SHRZ appeared to have greater sterilising activity than SHT during days 2–7 (p = 0.044), due to rifampicin, and during days 14–28, probably due mainly to pyrazinamide. The greatest discrimination between SHRZ and SHT treatments was found between regression estimates of kill over days 2–28 (p = 0.0005) in patients who remained positive up to 28 days with homogeneous kill rates. No associations were found between regression estimates and the age, sex, and extent of disease or cavitation. An increased kill in HIV seropositive patients, unrelated to the treatment effect, was evident during days 2–28 (p = 0.007), mainly during days 2–7. CONCLUSIONS: Surrogate marker studies should either be in small groups treated with monotherapy during days 2 to about 7 or as add-ons or replacements in isoniazid-containing standard regimens from days 2 to 28 in large groups

Cardiovascular risk assessment scores for people with diabetes: a systematic review

People with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Multivariate cardiovascular risk scores have been used in many countries to identify individuals who are at high risk of CVD. These risk scores include those originally developed in individuals with diabetes and those developed in a general population. This article reviews the published evidence for the performance of CVD risk scores in diabetic patients by: (1) examining the overall rationale for using risk scores; (2) systematically reviewing the literature on available scores; and (3) exploring methodological issues surrounding the development, validation and comparison of risk scores. The predictive performance of cardiovascular risk scores varies substantially between different populations. There is little evidence to suggest that risk scores developed in individuals with diabetes estimate cardiovascular risk more accurately than those developed in the general population. The inconsistency in the methods used in evaluation studies makes it difficult to compare and summarise the predictive ability of risk scores. Overall, CVD risk scores rank individuals reasonably accurately and are therefore useful in the management of diabetes with regard to targeting therapy to patients at highest risk. However, due to the uncertainty in estimation of true risk, care is needed when using scores to communicate absolute CVD risk to individuals

A randomised trial into the effect of an isolated hip abductor strengthening programme and a functional motor control programme on knee kinematics and hip muscle strength

Background: Dynamic knee valgus and internal femoral rotation are proposed to be contributory risk factors for patellofemoral pain and anterior cruciate ligament injuries. Multimodal interventions including hip abductor strengthening or functional motor control programmes have a positive impact of pain, however their effect on knee kinematics and muscle strength is less clear. The aim of this study was to examine the effect of isolated hip abductor strengthening and a functional motor control exercise on knee kinematics and hip abductor strength. Methods: This prospective, randomised, repeated measures design included 29 asymptomatic volunteers presenting with increase knee valgus and femoral internal rotation. Participants completed either isolated hip abductor strengthening or a functional motor control exercise for 5 weeks. Knee kinematics were measured using inertial sensors during 2 functional activities and hip abductor strength measured using a load cell during isometric hip abduction. Results: There were no significant differences in dynamic knee valgus and internal rotation following the isolated hip abductor or functional motor control intervention, and no significant differences between the groups for knee angles. Despite this, the actual magnitude of reduction in valgus was 10° and 5° for the functional motor control group and strengthening group respectively. The actual magnitude of reduction in internal rotation was 9° and 18° for the functional motor control group and strengthening group respectively. Therefore there was a tendency towards clinically significant improvements in knee kinematics in both exercise groups. A statistically significant improvement in hip abductor strength was evident for the functional motor control group (27% increase; p = 0.008) and strengthening group (35% increase; p = 0.009) with no significant difference between the groups being identified (p = 0.475). Conclusions: Isolated hip strengthening and functional motor control exercises resulted in non-statistically significant changes in knee kinematics, however there was a clear trend towards clinically meaningful reductions in valgus and internal rotation. Both groups demonstrated similar significant gains in hip abductor strength suggesting\ud either approach could be used to strengthen the hip abductors

Cardiovascular risk assessment - From individual risk prediction to estimation of global risk and change in risk in the population

Cardiovascular disease is the most common cause of death and risk prediction formulae such as the Framingham Risk Score have been developed to easily identify patients at high risk that may require therapeutic interventions. Using cardiovascular risk formulae at a population level to estimate and compare average cardiovascular risk among groups has been recently proposed as a way to facilitate surveillance of net cardiovascular risk and target public health interventions. Risk prediction formulas may help to compare interventions that cause effects of different magnitudes and directions in several cardiovascular risk factors, because these formulas assess the net change in risk using easily obtainable clinical variables. Because of conflicting data estimates of the incidence and prevalence of cardiovascular disease, risk prediction formulae may be a useful tool to estimate such risk at a population level

Challenges to curing primary brain tumours

Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. In an attempt to encourage progress in our understanding and ability to successfully treat patients with brain tumours, Cancer Research UK convened an international panel of clinicians and laboratory-based scientists to identify challenges that must be overcome if we are to cure all patients with a brain tumour. The seven key challenges summarized in this Position Paper are intended to serve as foci for future research and investment

Targeting cancer metabolism: a therapeutic window opens

Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy.Burroughs Wellcome FundSmith Family FoundationStarr Cancer ConsortiumDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.

Longer-term health and social care strategies for stroke survivors and their carers: the LoTS2Care research programme including cluster feasibility RCT

This is the final version. Available on open access from the NIHR Journals Library via the DOI in this recordData-sharing statement Workstreams in this programme grant involved qualitative methodologies; therefore, the data generated are not suitable for sharing beyond those contained in this report. Further information can be obtained from the corresponding author. As WS5 was a feasibility trial to inform a definitive trial, sharing of the trial data set is not anticipated; however, any data requests should be sent to the corresponding author and would be subject to review by a subgroup of the trial team, which will include the data guarantor, Professor Farrin. All data-sharing activities would require a data-sharing agreement.Abstract Background It is reported that the longer-term outcomes for stroke survivors are poor, with a range of unmet needs identified. Objectives The aims were to develop and test a longer-term stroke care strategy focused on improving the quality of life of stroke survivors and their carers by addressing unmet needs, and maintenance and enhancement of participation (i.e. involvement in life situations). Design Five overlapping workstreams were undertaken – (1) refinement of content by semistructured interviews with stroke survivors and their carers and by a review of the literature to inform content and delivery of the care strategy; (2) exploration of service models by national survey and focus groups with purposely selected services; (3) intervention development by interaction with a reference group of stroke survivors, carers, and health and social care professionals; (4) refinement and pilot implementation of the developed intervention in three stroke services (case studies); and (5) a cluster randomised controlled feasibility trial in 10 stroke services across England and Wales. Setting The intervention development work and feasibility trial were in stroke services (inclusive of primary, secondary, community and social care provision) across England and Wales. Participants Participants were stroke survivors resident in the community and their carers, and health and social care professionals in the included stroke services. Data sources Interviews with 28 stroke survivors and their carers at least 9 months post stroke ascertained their needs and the barriers to and facilitators of addressing those needs. Additional literature reviews identified 23 needs. No evidence-based interventions to address these needs were reported; self-management was highlighted as a possible delivery mechanism. In workstream 2, a national survey revealed that the most common model of stroke service provision was care up to 12 months post stroke, reported by 46 (40%) services. Thirty-five (30%) services provided care up to 6 months post stroke and 35 (30%) provided care beyond 12 months, thus identifying 6 months post stroke as an appropriate delivery point for a new intervention. Through focus groups in a range of services, stroke survivors’ perceived unmet needs and the barriers to and enablers of service provision were identified. Intervention Using information obtained in workstreams 1 and 2 and working closely with a stakeholder reference group, we developed an intervention based on the unmet needs prioritised by stroke survivors and their carers (workstream 3). In workstream 4, action groups (clinicians, stroke survivors and researchers) were established in three stroke services that led implementation in their service and contributed to the iterative refinement of the intervention, associated training programme and implementation materials. The intervention (called New Start) was delivered at 6 months post stroke. Key components were problem-solving self-management with survivors and carers, help with obtaining usable information, and helping survivors and their carers build sustainable, flexible support networks. Results A cluster randomised feasibility trial (workstream 5) was successfully implemented in 10 stroke services across England and Wales, with associated process and health economic evaluations. Five services were randomised to provide New Start, while five continued with usual care; 269 participants were recruited. Progression criteria – in terms of our pre-determined (red, amber, green) criteria for progress to a full trial: target stroke survivor recruitment rates were achieved, on average, across sites (24.1 per site over 6 months, green); 216 (80.3%) registered stroke survivors returned follow-up questionnaires at 9 months (84.1% in the intervention arm and 75.8% in the usual care arm, green); according to data reported by sites, overall, 95.2% of registered stroke survivors were offered at least one session of the intervention (green); all five intervention sites had at least two facilitators deemed competent, delivered the New Start intervention and provided it to stroke survivors (green). However, at some sites, there were concerns regarding the number of stroke survivors being offered, accepting and receiving the intervention. Only small differences in outcomes and costs were observed between the New Start and usual care groups, and considerable uncertainty around the cost-effectiveness remains. Conclusions We report a complex programme of work that has described the longer-term needs of stroke survivors and highlighted evidence and service gaps. Working closely with stroke survivors, an intervention was developed that has been refined in three services and feasibility tested in a cluster randomised controlled trial. Further refinement of the target population and optimisation of the intervention materials is required prior to a full randomised controlled trial evaluation. Future work Optimisation of the intervention, and clearer specification of recipients, are required prior to a full trial evaluation. Trial registration Current Controlled Trials ISRCTN38920246.National Institute for Health Research (NIHR