A randomised controlled trial of energetic activity for depression in young people (READY): a multi-site feasibility trial protocol.

BACKGROUND: Prevalence of depression is increasing in young people, and there is a need to develop and evaluate behavioural interventions which may provide benefits equal to or greater than talking therapies or pharmacological alternatives. Exercise could be beneficial for young people living with depression, but robust, large-scale trials of effectiveness and the impact of exercise intensity are lacking. This study aims to test whether a randomised controlled trial (RCT) of an intervention targeting young people living with depression is feasible by determining whether it is possible to recruit and retain young people, develop and deliver the intervention as planned, and evaluate training and delivery. METHODS: The design is a three-arm cluster randomised controlled feasibility trial with embedded process evaluation. Participants will be help-seeking young people, aged 13-17 years experiencing mild to moderate low mood or depression, referred from three counties in England. The intervention will be delivered by registered exercise professionals, supported by mental health support workers, twice a week for 12 weeks. The three arms will be high-intensity exercise, low-intensity exercise, and a social activity control. All arms will receive a 'healthy living' behaviour change session prior to each exercise session and the two exercise groups are energy matched. The outcomes are referral, recruitment, and retention rates; attendance at exercise sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data; adverse events, all measured at baseline, 3, and 6 months; resource use; and reach and representativeness. DISCUSSION: UK National Health Service (NHS) policy is to provide young people with advice about using exercise to help depression but there is no evidence-based exercise intervention to either complement or as an alternative to medication or talking therapies. UK National Institute for Health and Care Excellence (NICE) guidelines suggest that exercise can be an effective treatment, but the evidence base is relatively weak. This feasibility trial will provide evidence about whether it is feasible to recruit and retain young people to a full RCT to assess the effectiveness and cost-effectiveness of an exercise intervention for depression. TRIAL REGISTRATION: ISRCTN, ISRCTN66452702 . Registered 9 April 2020.

18F-fluorodeoxyglucose positron emission tomography/computed tomography in the assessment of occult primary head and neck cancers--an audit and review of published studies.

AIMS: To assess the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with squamous cell and undifferentiated cancer neck nodes and no primary site on conventional assessment. MATERIALS AND METHODS: Seventy-eight patients with neck nodal metastases from an unknown primary cancer were studied. PET/CT was carried out in all patients, 1h after FDG injection. RESULTS: Uptake suspicious of an occult primary cancer was found in 46/78 (59.0%) patients. Subsequent investigations confirmed a primary site in the base of the tongue in 14, pharyngeal palatine tonsil in 14, post cricoid in one, lung in one. PET/CT diagnosed primary cancers in 30/78 patients (38.5%); sensitivity, specificity, positive predictive value, negative predictive value: 30/30 (100.0%), 32/48 (66.7%), 30/46 (65.2%), 32/32 (100.0%), respectively. PET/CT detected additional disease in four patients: contralateral nodal disease in two, mediastinal nodal disease in one and liver metastases in one. CONCLUSIONS: FDG PET/CT is of value in the assessment of patients with occult head and neck primary cancers. However, false-positive results remain a limitation of the investigation.

Shear-induced global thrombosis test of native blood: pivotal role of ADP allows monitoring of P2Y12 antagonist therapy.

BACKGROUND: It is claimed that in shear-induced platelet function tests, shear-stress is the sole agonist causing platelet activation and resultant thrombosis. However, the fact that red blood cells (RBC) are essential to achieve platelet aggregation in these tests supports recent evidence that ADP makes an important contribution to shear-induced platelet reaction. AIM: To establish the role of ADP in shear-induced thrombosis, and investigate whether a shear-induced thrombosis test can assess ADP-receptor (P2Y12) antagonist medication. METHODS: Blood from healthy volunteers was tested using the Global Thrombosis Test (GTT), before and after clopidogrel. To investigate the importance of contact of blood with plastic, the reactive part of the tube was primed with saline. We also investigated the effect of priming the tube with water, to cause localised haemolysis and ADP release. RESULTS: Saline-priming prolonged occlusion times (OT) by 25% (p<0.01) confirming ADP release from platelets and RBC as a result of contact. Water-priming shortened OT, accelerating the thrombotic reaction (accelerated GTT; aGTT) (OT 379 vs. 177s, p<0.01). Clopidogrel increased OT (379 vs. 477s, p<0.01), preventing the shortening of aGTT-OT (177 vs. 362s, pre- and post-clopidogrel; p<0.01). CONCLUSION: In addition to thrombin formation, ADP released from platelets and RBC in native blood subjected to high shear-stress makes an important contribution to the resultant thrombotic occlusion. The described aGTT sensitively detected the effect of clopidogrel and thus seems suitable for monitoring and individualizing ADP-receptor antagonist therapy. Parallel measurement of GTT and aGTT would allow assessment of both global thrombotic status and response to P2Y12 antagonist therapy.

Relationship between human tumour angiogenic profile and combretastatin-induced vascular shutdown: an exploratory study.

Combretastatin-A4-phosphate (CA4P) acts most effectively against immature tumour vasculature. We investigated whether histological angiogenic profile can explain the differential sensitivity of human tumours to CA4P, by correlating the kinetic changes demonstrated by dynamic MRI (DCE-MRI) in response to CA4P, with tumour immunohistochemical angiogenic markers. Tissue was received from 24 patients (mean age 59, range 32-73, 18 women, 6 men). An angiogenic profile was performed using standard immunohistochemical techniques. Dynamic MRI data were obtained for the same patients before and 4 h after CA4P. Three patients showed a statistically significant fall in K(trans) following CA4P, and one a statistically significant fall in IAUGC(60). No statistically significant correlations were seen between the continuous or categorical variables and the DCE-MRI kinetic parameters other than between ang-2 and K(trans) (P=0.044). In conclusion, we found no strong relationships between changes in DCE-MRI kinetic variables following CA4P and the immunohistochemical angiogenic profile.

Utility of N terminal pro brain natriuretic peptide in elderly patients.

OBJECTIVE: To evaluate the utility of N terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic marker for diastolic dysfunction or failure, systolic dysfunction, and significant valve disorders in patients over 75 years. DESIGN: Cohort study. SETTING: Outpatient echocardiography service in a district general hospital. PARTICIPANTS: 100 consecutive patients. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive values, negative predictive values, and area under receiver operating characteristic curve for NT-proBNP assay in the diagnosis of left ventricular diastolic dysfunction or failure, systolic dysfunction, and significant valve disorders. RESULTS: For diagnosis of systolic dysfunction NT-proBNP level of 424 pg/ml had a sensitivity of 96%, specificity of 45%, positive predictive value of 36%, and negative predictive value of 96%. The area under the curve was 0.71 (95% confidence intervals: 0.69 to 0.89). In valve heart disease, level of 227 pg/ml had sensitivity of 91%, specificity of 43%, positive predictive value of 40%, and negative predictive value of 92%. Patients with diastolic dysfunction/failure had lower plasma concentrations. CONCLUSIONS: This study showed that NT-proBNP had excellent negative predictive value for systolic dysfunction and significant valve disorders in very elderly patients. It increased significantly in systolic dysfunction, valve heart disease, and atrial fibrillation. NT-proBNP is not useful in the diagnosis of diastolic dysfunction or diastolic heart failure using standard echocardiography criteria.