Risk and protective factors for suicide and suicidal behaviour: a literature review

The Scottish Development Centre for Mental Health, in partnership with the University of Edinburgh (Research Unit in Health, Behaviour and Change and General Practice Section) and the University of Stirling (Department of Applied Social Science and Department of Nursing and Midwifery), were commissioned by the then Scottish Executive to undertake a review of the literature on risk and protective factors for suicide and suicidal behaviour. The review had two overarching aims: first, to describe and assess current knowledge regarding the societal and cultural factors associated with increased incidence of suicide (risk factors), and to delineate the population subgroups that are at increased risk of suicidal behaviour; and second, to describe and assess current knowledge regarding factors that promote resilience and healthy survival against suicidal behaviour amongst people who are exposed to known suicidal risk conditions (protective factors)

Improving specific autobiographical memory in older adults:impacts on mood, social problem solving, and functional limitations

Older adults have difficulty recalling specific autobiographical events. This over-general memory style is a vulnerability factor for depression. Two groups receiving interventions that have previously been successful at reducing over-general memory in depressed populations were compared to a control group. Participants were healthy older adults aged ≥70 years: memory specificity training (MEST; n = 22), life review (n = 22), and control group (n = 22). There were significant improvements in autobiographical memory specificity in the MEST and life review groups at post-training, relative to the control group, suggesting that over-general memory can be reduced in older adults. Change in social problem solving ability and functional limitations were related to change in autobiographical memory specificity, supporting the suggested role of specific retrieval in generating solutions to social problems and maintaining independence. Qualitative analysis of participants’ feedback revealed that life review may be more appropriate for older adults, possibly because it involves integrating specific memories into a positive narrative

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes

Improving outcomes in adults with epilepsy and intellectual disability (EpAID) using a nurse-led intervention: study protocol for a cluster randomised controlled trial.

BACKGROUND: In adults with intellectual disability (ID) and epilepsy there are suggestions that improvements in management may follow introduction of epilepsy nurse-led care. However, this has not been tested in a definitive clinical trial and results cannot be generalised from general population studies as epilepsy tends to be more severe and to involve additional clinical comorbidities in adults with ID. This trial investigates whether nurses with expertise in epilepsy and ID, working proactively to a clinically defined role, can improve clinical and quality of life outcomes in the management of epilepsy within this population, compared to treatment as usual. The trial also aims to establish whether any perceived benefits represent good value for money. METHODS/DESIGN: The EpAID clinical trial is a two-arm cluster randomised controlled trial of nurse-led epilepsy management versus treatment as usual. This trial aims to obtain follow-up data from 320 participants with ID and drug-resistant epilepsy. Participants are randomly assigned either to a 'treatment as usual' control or a 'defined epilepsy nurse role' active arm, according to the cluster site at which they are treated. The active intervention utilises the recently developed Learning Disability Epilepsy Specialist Nurse Competency Framework for adults with ID. Participants undergo 4 weeks of baseline data collection, followed by a minimum of 20 weeks intervention (novel treatment or treatment as usual), followed by 4 weeks of follow-up data collection. The primary outcome is seizure severity, including associated injuries and the level of distress manifest by the patient in the preceding 4 weeks. Secondary outcomes include cost-utility analysis, carer strain, seizure frequency and side effects. Descriptive measures include demographic and clinical descriptors of participants and clinical services in which they receive their epilepsy management. Qualitative study of clinical interactions and semi-structured interviews with clinicians and participants' carers are also undertaken. DISCUSSION: The EpAID clinical trial is the first cluster randomised controlled trial to test possible benefits of a nurse-led intervention in adults with epilepsy and ID. This research will have important implications for ID and epilepsy services. The challenges of undertaking such a trial in this population, and the approaches to meeting these are discussed. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN96895428 version 1.1. Registered on 26 March 2013.Cambridgeshire and Peterborough NHS Foundation TrustThis is the final version of the article. It first appeared from BioMed Central via https://doi.org/10.1186/s13063-016-1429-

Training nurses in a competency framework to support adults with epilepsy and intellectual disability: the EpAID cluster RCT.

BACKGROUND: People with an intellectual (learning) disability (ID) and epilepsy have an increased seizure frequency, higher frequencies of multiple antiepileptic drug (AED) use and side effects, higher treatment costs, higher mortality rates and more behavioural problems than the rest of the population with epilepsy. The introduction of nurse-led care may lead to improvements in outcome for those with an ID and epilepsy; however, this has not been tested in a definitive clinical trial. OBJECTIVE: To determine whether or not ID nurses, using a competency framework developed to optimise nurse management of epilepsy in people with an ID, can cost-effectively improve clinical and quality-of-life outcomes in the management of epilepsy compared with treatment as usual. DESIGN: Cluster-randomised two-arm trial. SETTING: Community-based secondary care delivered by members of community ID teams. PARTICIPANTS: Participants were adults aged 18-65 years with an ID and epilepsy under the care of a community ID team and had had at least one seizure in the 6 months before the trial. INTERVENTIONS: The experimental intervention was the Learning Disability Epilepsy Specialist Nurse Competency Framework. This provides guidelines describing a structure and goals to support the delivery of epilepsy care and management by ID-trained nurses. MAIN OUTCOME MEASURES: The primary outcome was the seizure severity scale from the Epilepsy and Learning Disabilities Quality of Life questionnaire. Measures of mood, behaviour, AED side effects and carer strain were also collected. A cost-utility analysis was undertaken along with a qualitative examination of carers' views of participants' epilepsy management. RESULTS: In total, 312 individuals were recruited into the study from 17 research clusters. Using an intention-to-treat analysis controlling for baseline individual-level and cluster-level variables there was no significant difference in seizure severity score between the two arms. Altogether, 238 complete cases were included in the non-imputed primary analysis. Analyses of the secondary outcomes revealed no significant differences between arms. A planned subgroup analysis identified a significant interaction between treatment arm and level of ID. There was a suggestion in those with mild to moderate ID that the competency framework may be associated with a small reduction in concerns over seizure severity (standard error 2.005, 95% confidence interval -0.554 to 7.307;p = 0.092). However, neither subgroup showed a significant intervention effect individually. Family members' perceptions of nurses' management depended on the professional status of the nurses, regardless of trial arm. Economic analysis suggested that the competency framework intervention was likely to be cost-effective, primarily because of a reduction in the costs of supporting participants compared with treatment as usual. LIMITATIONS: The intervention could not be delivered blinded. Treatment as usual varied widely between the research sites. CONCLUSIONS: Overall, for adults with an ID and epilepsy, the framework conferred no clinical benefit compared with usual treatment. The economic analysis suggested that there may be a role for the framework in enhancing the cost-effectiveness of support for people with epilepsy and an ID. Future research could explore the specific value of the competency framework for those with a mild to moderate ID and the potential for greater long-term benefits arising from the continuing professional development element of the framework. TRIAL REGISTRATION: Current Controlled Trials ISRCTN96895428. FUNDING: This trial was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 22, No. 10. See the NIHR Journals Library website for further project information.This trial was funded by the NIHR Health Technology Assessment programm

What is the 'problem' that outreach work seeks to address and how might it be tackled? Seeking theory in a primary health prevention programme

<b>Background</b> Preventive approaches to health are disproportionately accessed by the more affluent and recent health improvement policy advocates the use of targeted preventive primary care to reduce risk factors in poorer individuals and communities. Outreach has become part of the health service response. Outreach has a long history of engaging those who do not otherwise access services. It has, however, been described as eclectic in its purpose, clientele and mode of practice; its effectiveness is unproven. Using a primary prevention programme in the UK as a case, this paper addresses two research questions: what are the perceived problems of non-engagement that outreach aims to address; and, what specific mechanisms of outreach are hypothesised to tackle these.<p></p> <b>Methods</b> Drawing on a wider programme evaluation, the study undertook qualitative interviews with strategically selected health-care professionals. The analysis was thematically guided by the concept of 'candidacy' which theorises the dynamic process through which services and individuals negotiate appropriate service use.<p></p> <b>Results</b> The study identified seven types of engagement 'problem' and corresponding solutions. These 'problems' lie on a continuum of complexity in terms of the challenges they present to primary care. Reasons for non-engagement are congruent with the concept of 'candidacy' but point to ways in which it can be expanded.<p></p> <b>Conclusions</b> The paper draws conclusions about the role of outreach in contributing to the implementation of inequalities focused primary prevention and identifies further research needed in the theoretical development of both outreach as an approach and candidacy as a conceptual framework

Durvalumab (MEDI 4736) in combination with extended neoadjuvant regimens in rectal cancer : a study protocol of a randomised phase II trial (PRIME-RT)

Acknowledgements We are grateful to Mr George Davidson and Ms Monica Jeffers for their input with writing the PRIME-RT protocol and patient information sheet. This study is co-sponsored by the University of Glasgow and NHS Greater Glasgow and Clyde. Funding PRIME-RT is funded by Astrazeneca and receives core funding from CRUK Clinical Trials Unit Glasgow for the purposes of trial set-up and data collection. The trial is co-sponsored by the University Of Glasgow and NHS Greater Glasgow and Clyde.Peer reviewedPublisher PD

The effectiveness of interventions to change six health behaviours: a review of reviews

Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency). Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis. Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities. Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p

Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa

Analyses of the population genetic structure of schistosomes under the “Schistosomiasis Consortium for Operational Research and Evaluation” (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent “biological hotspot” sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general

Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann-Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn's disease

OBJECTIVE: Patients with Niemann-Pick disease type C1 (NPC1), a lysosomal lipid storage disorder that causes neurodegeneration and liver damage, can present with IBD, but neither the significance nor the functional mechanism of this association is clear. We studied bacterial handling and antibacterial autophagy in patients with NPC1. DESIGN: We characterised intestinal inflammation in 14 patients with NPC1 who developed IBD. We investigated bacterial handling and cytokine production of NPC1 monocytes or macrophages in vitro and compared NPC1-associated functional defects to those caused by IBD-associated nucleotide-binding oligomerization domain-containing protein 2 (NOD2) variants or mutations in X-linked inhibitor of apoptosis (XIAP). RESULTS: Patients with the lysosomal lipid storage disorder NPC1 have increased susceptibility to early-onset fistulising colitis with granuloma formation, reminiscent of Crohn's disease (CD). Mutations in NPC1 cause impaired autophagy due to defective autophagosome function that abolishes NOD2-mediated bacterial handling in vitro similar to variants in NOD2 or XIAP deficiency. In contrast to genetic NOD2 and XIAP variants, NPC1 mutations do not impair NOD2-receptor-interacting kinase 2 (RIPK2)-XIAP-dependent cytokine production. Pharmacological activation of autophagy can rescue bacterial clearance in macrophages in vitro by increasing the autophagic flux and bypassing defects in NPC1. CONCLUSIONS: NPC1 confers increased risk of early-onset severe CD. Our data support the concept that genetic defects at different checkpoints of selective autophagy cause a shared outcome of CD-like immunopathology linking monogenic and polygenic forms of IBD. Muramyl dipeptide-driven cytokine responses and antibacterial autophagy induction are parallel and independent signalling cascades downstream of the NOD2-RIPK2-XIAP complex