Amanda J. Edmondson

Candidate gene association studies of genes involved in neuronal cholinergic transmission in Alzheimer's disease suggests choline acetyltransferase as a candidate deserving further study

Consistent deficits in the cholinergic system are evident in the brains of Alzheimers Disease (AD) patients, including reductions in the activities of acetylcholine, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT), increased butyrylcholinesterase (BChE) activity, and a selective loss of nicotinic acetylcholine receptors (nAChRs). Accordingly, we have analyzed polymorphisms in the genes encoding AChE, ChAT, BChE, and several of the subunit genes from neuronal nAChRs, for genetic associations with late‐onset AD. A significant association for disease was detected for a non‐coding polymorphism in ChAT (allele χ12 = 12.84, P = 0.0003; genotype χ22 = 11.89, P = 0.0026). Although replication analysis did not confirm the significance of this finding when the replication samples were considered alone (allele χ12 = 1.02, P=0.32; genotype χ22 = 1.101, P = 0.58) the trends were in the correct direction and a significant association remained when the two sample sets were pooled (allele χ12 = 12.37, P = 0.0004; genotype χ22 = 11.61, P = 0.003). Previous studies have reported significant disease associations for both the K‐variant of BChE and the coding ChAT rs3810950 polymorphism with AD. Replication analyses of these two loci failed to detect any significant association for disease in our case‐control samples.

Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease

Consistent deficits in the cholinergic system are evident in Alzheimers disease (AD) patients, including selective loss of alpha4beta2 nicotinic acetylcholine receptors in the brains of AD patients. Knockout mice for the beta2 subunit have impaired neuronal survival in ageing. Accordingly, we have analysed polymorphisms in the genes that encode the alpha4 and beta2 subunits, CHRNA4 and CHRNB2 respectively, for genetic associations with late-onset AD. A significant association for disease was observed for a non-coding polymorphism in CHRNB2 (odds ratio=0.57, 95% confidence interval=0.35-0.95, P=0.024). Replication analysis was performed in two further sample sets. While these did not individually yield significant results, a significant association remained when all samples were pooled (odds ratio=0.70, 95% confidence interval=0.52-0.95, P=0.019). These data suggest that this variant warrants further examination in large case-control series.

The patients' experience of a bladder cancer diagnosis: a systematic review of the qualitative evidence.

PurposeBladder cancer (BC) is a common disease with disparate treatment options and variable outcomes. Despite the disease’s high prevalence, little is known of the lived experience of affected patients. National patient experience surveys suggest that those with BC have poorer experiences than those with other common cancers. The aim of this review is to identify first-hand accounts of the lived experiences of diagnosis through to survivorship.MethodThis is a systematic review of the qualitative evidence reporting first-hand accounts of the experiences of being diagnosed with, treated for and surviving bladder cancer. A thematic analysis and ‘best-fit’ framework synthesis was undertaken to classify these experiences.ResultsThe inconsistent nature of symptoms contributes to delays in diagnosis. Post-diagnosis, many patients are not actively engaged in the treatment decision-making process and rely on their doctor’s expertise. This can result in patients not adequately exploring the consequences of these decisions. Learning how to cope with a ‘post-surgery body’, changing sexuality and incontinence are distressing. Much less is known about the quality of life of patients receiving conservative treatments such as Bacillus Calmette-Guerin (BCG).ConclusionsThe review contributes to a greater understanding of the lived experience of bladder cancer. Findings reflect a paucity of relevant literature and a need to develop more sensitive patient-reported outcome measures (PROMs) and incorporate patient-reported outcomes in BC care pathways.Implications for cancer survivorsCollective knowledge of the patients’ self-reported experience of the cancer care pathway will facilitate understanding of the outcomes following treatment.

The Impact of Contact With Suicide-Related Behavior in Prison on Young Offenders

BACKGROUND Prison suicide rates are high, and suicide-related behaviors (SRBs) higher, but effects of contact with such behaviors in prison have not previously been examined. AIMS To compare the mental state of young men witnessing a peers suicide-related behavior in prison with that of men without such experience, and to test for factors associated with morbidity. METHOD Forty-six male prisoners (age 16-21 years) reporting contact with anothers suicide-related behavior in prison were interviewed 6 months after the incident, with validated questionnaires, as were 44 without such contact at least 6 months into their imprisonment. RESULTS Significantly higher levels of psychiatric morbidity and own suicide-related behaviors were found in the witness group, even after controlling for their higher levels of family mental illness and pre-exposure experience of in-prison bullying. Some personal factors were associated with higher morbidity; incident and institutional factors were not. CONCLUSIONS Findings of heightened vulnerabilities among young men exposed to suicide-related behaviors in prison suggest a need for longitudinal study to clarify temporal relationships and inform strategies to prevent or limit development of morbidity and further harm.

Using photo-elicitation to understand reasons for repeated self-harm: a qualitative study

BackgroundReasons for self-harm are not well understood. One of the reasons for this is that first-hand accounts are usually elicited using traditional interview and questionnaire methods. This study aims to explore the acceptability of using an approach (photo-elicitation) that does not rely on solely verbal or written techniques, and to make a preliminary assessment of whether people can usefully employ images to support a discussion about the reasons why they self-harm.MethodInterviews with eight participants using photo elicitation, a method in which photographs produced by the participant are used as a stimulus and guide within the interview.ResultsParticipants responded positively to using images to support a discussion about their self-harm and readily incorporated images in the interview. Four main themes were identified representing negative and positive or adaptive purposes of self-harm: self-harm as a response to distress, self-harm to achieve mastery, self-harm as protective and self-harm as a language or form of communication.ConclusionsEmploying this novel approach was useful in broadening our understanding of self-harm.