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Background: The benefit of Self-monitoring of Blood Glucose (SMBG) in people with non-insulin treated type 2 diabetes remains unclear with inconsistent evidence from randomised controlled trials fuelling the continued debate. Lack of a consistent finding has been attributed to variations in study population and design, including the SMBG intervention. There is a growing consensus that structured SMBG, whereby the person with diabetes and health care provider are educated to detect patterns of glycaemic abnormality and take appropriate action according to the blood glucose profiles, can prove beneficial in terms of lowering HbA1c and improving overall well-being. Despite this, many national health agencies continue to issue guidelines restricting the use of SMBG in non-insulin treated type 2 diabetes. Methods: The SMBG Study is a 12 month, multi-centre, randomised controlled trial in people with type 2 diabetes not on insulin therapy who have poor glycaemic control (HbA1c ≥58 mmol/mol / 7.5%). The participants will be randomised into three comparative groups: Group 1 will act as a control group and receive their usual diabetes care; Group 2 will undertake structured SMBG with clinical review every 3 months; Group 3 will undertake structured SMBG with additional monthly telecare support from a trained study nurse. A total of 450 participants will be recruited from 16 primary and secondary care sites across Wales and England. The primary outcome measure will be HbA1c at 12 months with secondary measures to include weight, BMI, total cholesterol and HbA1c levels at 3, 6, 9 and 12 months. Participant well-being and attitude towards SMBG will be monitored throughout the course of the study. Recruitment began in December 2012 with the last participant visit due in September 2016. Discussion: This study will attempt to answer the question of whether structured SMBG provides any benefits to people with poorly controlled type 2 diabetes who are not being treated with insulin. The data will also clarify whether the telecare support provides additional value. The overall acceptability of SMBG as a tool for self-management will be assessed. Trial registration: UKCRN 12038 (Registered March 2012). ISRCTN21390608 (Retrospectively registered 15th May 2014). [ABSTRACT FROM AUTHOR]

While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are known to increase heart rate (HR), it is insufficiently recognized that the extent varies greatly between the various agonists and is affected by the assessment methods employed. Here we review published data from 24-h time-averaged HR monitoring in healthy individuals and subjects with type 2 diabetes mellitus (T2DM) treated with either short-acting GLP-1 RAs, lixisenatide or exenatide, or long-acting GLP-1 RAs, exenatide LAR, liraglutide, albiglutide, or dulaglutide (N = 1112; active-treatment arms). HR effects observed in two independent head-to-head trials of lixisenatide and liraglutide (N = 202; active-treatment arms) are also reviewed. Short-acting GLP-1 RAs, exenatide and lixisenatide, are associated with a transient (1-12 h) mean placebo- and baseline-adjusted 24-h HR increase of 1-3 beats per minute (bpm). Conversely, long-acting GLP-1 RAs are associated with more pronounced increases in mean 24-h HR; the highest seen with liraglutide and albiglutide at 6-10 bpm compared with dulaglutide and exenatide LAR at 3-4 bpm. For both liraglutide and dulaglutide, HR increases were recorded during both the day and at night. In two head-to-head comparisons, a small, transient mean increase in HR from baseline was observed with lixisenatide; liraglutide induced a substantially greater increase that remained significantly elevated over 24 h. The underlying mechanism for increased HR remains to be elucidated; however, it could be related to a direct effect at the sinus node and/or stimulation of the sympathetic nervous system, with this effect related to the duration of action of the respective GLP-1 RAs. In conclusion, this review indicates that the effects on HR differ within the class of GLP-1 RAs: short-acting GLP-1 RAs are associated with a modest and transient HR increase before returning to baseline levels, while some long-acting GLP-1 RAs are associated with a more pronounced and sustained increase during the day and night. Findings from recently completed trials indicate that a GLP-1 RA-induced increase in HR, regardless of magnitude, does not present an increased cardiovascular risk for subjects with T2DM, although a pronounced increase in HR may be associated with adverse clinical outcomes in those with advanced heart failure. [ABSTRACT FROM AUTHOR]

Background: Self-harm is common in the community with a lifetime prevalence of 13 %. It is associated with an elevated risk of overall mortality and suicide. People who harm themselves are high users of public services. Estimates of the 1-year risk of repetition vary between 5 and 15 % per year. Currently, limited evidence exists on the effectiveness of clinical interventions for young people who engage in self-harm. Recent reviews have failed to demonstrate any effect on reducing repetition of self-harm among adolescents receiving a range of treatment approaches. Family factors are particularly important risk factors associated with fatal and non-fatal self-harm among children and adolescents. Family therapy focuses on the relationships, roles and communication patterns between family members, but there have been relatively few studies of specifically family-focused interventions with this population. The Self-Harm Intervention: Family Therapy (SHIFT) Trial was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (grant no. 07/33/01) following a commissioned call for this research. Methods/Design: SHIFT is a pragmatic, phase III, multicentre, individually randomised, controlled trial comparing Family Therapy (FT) with treatment as usual (TAU) for adolescents aged 11 to 17 who have engaged in at least two episodes of self-harm. Both therapeutic interventions were delivered within the National Health Service (NHS) Child and Adolescent Mental Health Services (CAMHS) in England. Participants and therapists were, of necessity, aware of treatment allocation, but the researchers were blind to the allocations to allow unbiased collection of follow-up data. Primary outcome data (repetition of self-harm leading to hospital attendance 18 months post-randomisation) were collected from the Health and Social Care Information Centre (HSCIC), augmented by directed searches of medical records at Acute Trusts. Secondary outcome data (including suicidal intent, depression, hopelessness and health economics) were collected at 12 and 18 months post-randomisation via researcher-participant interviews and by post at 3 and 6 months. Discussion: SHIFT will provide a well-powered evaluation of the clinical and cost effectiveness of Family Therapy for young people who have self-harmed on more than one occasion. The study will be reported in 2016, and the results will inform clinical practice thereafter. [ABSTRACT FROM AUTHOR]

Background Around 150,000 people each year attend hospitals in England due to self-harm, many of them more than once. Over 5,000 people die by suicide each year in the UK, a quarter of them having attended hospital in the previous year because of self-harm. Self-harm is a major identifiable risk factor for suicide. People receive variable care at hospital; many are not assessed for their psychological needs and little psychological therapy is offered. Despite its frequent occurrence, we have no clear research evidence about how to reduce the repetition of self-harm. Some people who have self-harmed show less active ways of solving problems, and brief problem-solving therapies are considered the most promising psychological treatments. Methods/Design This is a pragmatic, individually randomised, controlled, feasibility study comparing interpersonal problem-solving therapy plus treatment-as-usual with treatment-as-usual alone, for adults attending a general hospital following self-harm. A total of 60 participants will be randomised equally between the treatment arms, which will be balanced with respect to the type of most recent self-harm event, number of previous self-harm events, gender and age. Feasibility objectives are as follows: a) To establish and field test procedures for implementing the problem-solving intervention; b) To determine the feasibility and best method of participant recruitment and follow up; c) To assess therapeutic delivery; d) To assess the feasibility of obtaining the definitive trial's primary and secondary outcomes; e) To assess the perceived burden and acceptability of obtaining the trial's self-reported outcome data; f) To inform the sample size calculation for the definitive trial. Discussion The results of this feasibility study will be used to determine the appropriateness of proceeding to a definitive trial and will allow us to design an achievable trial of interpersonal problem-solving therapy for adults who self-harm. Trial registration Current Controlled Trials (ISRCTN54036115) [ABSTRACT FROM AUTHOR]

Background: Methods for the dissemination, understanding and implementation of clinical guidelines need to be examined for their effectiveness to help doctors integrate guidelines into practice. The objective of this randomised controlled trial was to evaluate the effectiveness of an interactive online Diabetes Needs Assessment Tool (DNAT) (which constructs an e-learning curriculum based on individually identified knowledge gaps), compared with self-directed e-learning of diabetes guidelines. Methods: Health professionals were randomised to a 4-month learning period and either given access to diabetes learning modules alone (control group) or DNAT plus learning modules (intervention group). Participants completed knowledge tests before and after learning (primary outcome), and surveys to assess the acceptability of the learning and changes to clinical practice (secondary outcomes). Results: Sixty four percent (677/1054) of participants completed both knowledge tests. The proportion of nurses (5.4%) was too small for meaningful analysis so they were excluded. For the 650 doctors completing both tests, mean (SD) knowledge scores increased from 47.4% (12.6) to 66.8% (11.5) [intervention group (n = 321, 64%)] and 47.3% (12.9) to 67.8% (10.8) [control group (n = 329, 66%)], (ANCOVA p = 0.186). Both groups were satisfied with the usability and usefulness of the learning materials. Seventy seven percent (218/284) of the intervention group reported combining the DNAT with the recommended reading materials was "very useful"/"useful". The majority in both groups (184/287, 64.1% intervention group and 206/299, 68.9% control group) [95% CI for the difference (-2.8 to 12.4)] reported integrating the learning into their clinical practice. Conclusions: Both groups experienced a similar and significant improvement in knowledge. The learning materials were acceptable and participants incorporated the acquired knowledge into practice. Trial registration: ISRCTN: ISRCTN67215088 [ABSTRACT FROM AUTHOR]

Background: It has been proposed that different types of psychopathology in schizophrenia may reflect distinguishable pathological processes. In the current study we aimed to address such associations in the absence of confounders such as medication and disease chronicity by examining specific relationships between fMRI activation and individual symptom severity scores in unmedicated subjects at high genetic risk of schizophrenia. Methods: Associations were examined across two functional imaging paradigms: the Hayling sentence completion task, and an encoding/retrieval task, comprising encoding (at word classification) and retrieval (old word/new word judgement). Symptom severity was assessed using the positive and negative syndrome scale (PANSS). Items examined were hallucinations, delusions, and suspiciousness/persecution. Results: Associations were seen in the anterior middle temporal gyrus in relation to hallucination scores during the sentence completion task, and in the medial temporal lobe in association with suspiciousness/persecution scores in the encoding/retrieval task. Cerebellar activation was associated with delusions and suspiciousness/persecution scores across both tasks with differing patterns of laterality. Conclusion: These results support a role for the lateral temporal cortex in hallucinations and medial temporal lobe in positive psychotic symptoms. They also highlight the potential role of the cerebellum in the formation of delusions. That the current results are seen in un-medicated high risk subjects indicates these associations are not specific to the established illness and are not related to medication effects. [ABSTRACT FROM AUTHOR]

Background: We hypothesised that subjects at familial high risk of developing schizophrenia would have a reduction over time in grey matter, particularly in the temporal lobes, and that this reduction may predict schizophrenia better than clinical measurements. Methods: We analysed magnetic resonance images of 65 high-risk subjects from the Edinburgh High Risk Study sample who had two scans a mean of 1.52 years apart. Eight of these 65 subjects went on to develop schizophrenia an average of 2.3 years after their first scan. Results: Changes over time in the inferior temporal gyrus gave a 60% positive predictive value (likelihood ratio > 10) of developing schizophrenia compared to the overall 13% risk in the cohort as a whole. Conclusion: Changes in grey matter could be used as part of a predictive test for schizophrenia in people at enhanced risk for familial reasons, particularly for positive predictive power, in combination with other clinical and cognitive predictive measures, several of which are strong negative predictors. However, because of the limited number of subjects, this test requires independent replication to confirm its validity. [ABSTRACT FROM AUTHOR]

Background: There is evidence that groups of people with schizophrenia have deficits in Theory of Mind (ToM) capabilities. Previous studies have found these to be linked to psychotic symptoms (or psychotic symptom severity) particularly the presence of delusions and hallucinations. Methods: A visual joke ToM paradigm was employed where subjects were asked to describe two types of cartoon images, those of a purely Physical nature and those requiring inferences of mental states for interpretation, and to grade them for humour and difficulty. Twenty individuals with a DSM-IV diagnosis of schizophrenia and 20 healthy matched controls were studied. Severity of current psychopathology was measured using the Krawiecka standardized scale of psychotic symptoms. IQ was estimated using the Ammons and Ammons quick test. Results: Individuals with schizophrenia performed significantly worse than controls in both conditions, this difference being most marked in the ToM condition. No relationship was found for poor ToM performance and psychotic positive symptomatology, specifically delusions and hallucinations. Conclusion: There was evidence for a compromised ToM capability in the schizophrenia group on this visual joke task. In this instance this could not be linked to particular symptomatology. [ABSTRACT FROM AUTHOR]

Background: To reduce the likelihood of complications in persons with type 2 diabetes, it is critical to control hyperglycaemia. Monotherapy with metformin or insulin secretagogues may fail to sustain control after an initial reduction in glycemic levels. Thus, combining metformin with other agents is frequently necessary. These analyses model the potential long-term economic and health impact of using combination therapy to improve glycemic control. Methods: An existing model that simulates the long-term course of type 2 diabetes in relation to glycosylated haemoglobin (HbA1c) and post-prandial glucose (PPG) was used to compare the combination of nateglinide with metformin to monotherapy with metformin. Complication rates were estimated for major diabetes-related complications (macrovascular and microvascular) based on existing epidemiologic studies and clinical trial data. Utilities and costs were estimated using data collected in the United Kingdom Prospective Diabetes Study (UKPDS). Survival, life years gained (LYG), quality-adjusted life years (QALY), complication rates and associated costs were estimated. Costs were discounted at 6% and benefits at 1.5% per year. Results: Combination therapy was predicted to reduce complication rates and associated costs compared with metformin. Survival increased by 0.39 (0.32 discounted) and QALY by 0.46 years (0.37 discounted) implying costs of £6,772 per discounted LYG and £5,609 per discounted QALY. Sensitivity analyses showed the results to be consistent over broad ranges. Conclusion: Although drug treatment costs are increased by combination therapy, this cost is expected to be partially offset by a reduction in the costs of treating long-term diabetes complications. [ABSTRACT FROM AUTHOR]

Background: Although neuroanatomical and cognitive sequelae of low birthweight and preterm birth have been investigated, little is understood as to the likely prevalence of a history of low birthweight or preterm birth, or neuroanatomical correlates of such a history, within the special educational needs population. Our aim was to address these issues in a sample of young people receiving additional learning support.Methods: One hundred and thirty-seven participants aged 13-22 years, receiving additional learning support, were recruited via their schools or colleges and underwent structural magnetic resonance imaging (MRI). Obstetric records, available in 98 cases, included birthweight and gestational data in 90 and 95 cases, respectively. Both qualitative and quantitative voxel-based analyses of MRI data were conducted.Results: A history of low birthweight and preterm birth was present in 13.3% and 13.7% of cases, respectively. Low birthweight and preterm birth were associated with specific qualitative anomalies, including enlargement of subarachnoid cisterns and thinning of the corpus callosum. Low birthweight was associated with reduced grey matter density (GMD) in the superior temporal gyrus (STG) bilaterally, left inferior temporal gyrus and left insula. Prematurity of birth was associated with reduced GMD in the STG bilaterally, right inferior frontal gyrus and left cerebellar hemisphere. Comparison of subjects with no history of low birthweight or preterm birth with a previously defined control sample of cognitively unimpaired adolescents (n = 72) demonstrated significantly greater scores for several anomalies, including thinning of the corpus callosum, loss of white matter and abnormalities of shape of the lateral ventricles.Conclusion: Although a two-fold increased prevalence of a history of low birthweight and preterm birth exists within the special educational needs population, other aetiological factors must be considered for the overwhelming majority of cases. Neuroanatomical findings within this sample include qualitative anomalies of brain structure and grey matter deficits within temporal lobe structures and the cerebellum that persist into adolescence. These findings suggest a neurodevelopmental mechanism for the cognitive difficulties associated with these obstetric risk factors. [ABSTRACT FROM AUTHOR]

Background: Continuous medical education is traditionally reliant to a large extent on self-directed learning based on individuals' perceived learning priorities. Evidence suggests that this ability to self-assess is limited, and more so in the least competent. Therefore, it may be of benefit to utilise some form of external assessment for this purpose. Many diabetes educational programmes have been introduced, but few have been assessed for their benefit in a systematic manner. As diabetes is an increasingly prevalent disease, methods for the dissemination and understanding of clinical guidelines need to be explored for their effectiveness. This paper describes the study design of a randomised controlled trial to evaluate the effectiveness of using an interactive online Diabetes Needs Assessment Tool (DNAT), that builds a learning curriculum based on identified knowledge gaps, compared with conventional self-directed learning. The study assesses the effect of these interventions on health professionals' knowledge of diabetes management, evaluates the acceptability of this process of learning and self-reported changes in clinical practice as a result of this novel educational process., Methods: Following a baseline assessment, participants will be randomised to undergo a 4-month learning period where they will either be given access to the diabetes learning modules alone (control group) or a Diabetes Needs Assessment Tool (DNAT) plus the diabetes learning modules (intervention group). On completion of the DNAT, a personalized learning report will be created for each participant identifying needs alongside individualised recommendations of the most appropriate learning modules to meet those requirements. All participants will complete a Diabetes Knowledge Test before and immediately after the allocated learning and the primary outcome will be the state of knowledge at 4 months. Learners will also be surveyed immediately after the learning period to assess the acceptability of the learning formats and the perceived usefulness and usability of the materials. After a further month, all learners will receive a series of questions to evaluate self-reported changes in clinical practice as a result of this educational experience and asked to include specific examples of any changes in their diabetes care practice., Trial Registration: Current Controlled Trials ISRCTN67215088.

Background: It has been proposed that different types of psychopathology in schizophrenia may reflect distinguishable pathological processes. In the current study we aimed to address such associations in the absence of confounders such as medication and disease chronicity by examining specific relationships between fMRI activation and individual symptom severity scores in un-medicated subjects at high genetic risk of schizophrenia., Methods: Associations were examined across two functional imaging paradigms: the Hayling sentence completion task, and an encoding/retrieval task, comprising encoding (at word classification) and retrieval (old word/new word judgement). Symptom severity was assessed using the positive and negative syndrome scale (PANSS). Items examined were hallucinations, delusions, and suspiciousness/persecution., Results: Associations were seen in the anterior middle temporal gyrus in relation to hallucination scores during the sentence completion task, and in the medial temporal lobe in association with suspiciousness/persecution scores in the encoding/retrieval task. Cerebellar activation was associated with delusions and suspiciousness/persecution scores across both tasks with differing patterns of laterality., Conclusion: These results support a role for the lateral temporal cortex in hallucinations and medial temporal lobe in positive psychotic symptoms. They also highlight the potential role of the cerebellum in the formation of delusions. That the current results are seen in un-medicated high risk subjects indicates these associations are not specific to the established illness and are not related to medication effects.