Monthly Archives: May 2010

Review: Challenges of Personalised Genomics Information for Health Management

The paper reviewed here is ‘From Utopia to Science: Challenges of Personalised Genomics Information for Health Management and Health Enhancement’ by  Hub Zwart, Professor of Philosophy and which is freely available here. I thought it would be interesting to look at this paper because the sequencing of human genomes is becoming increasingly accessible as sequencing technologies improve. Zwart addresses the use of information from the genome and gene therapy. I was particularly interested in the former. Zwart broadens the initial part of his inquiry by examining various forms of biotechnology and referencing Huxley’s classic ‘Brave New World’. He raises some intriguing questions about the evolution of culture and a move away from anthropomorphism. After reading this paper, there were a number of questions that seemed to suggest themselves.

What happens if a person has access to their full genome sequence outside of the medical environment?

Speculating, there are a number of possibilities

- A person will respond appropriately to this knowledge. The appropriate response will vary according to context. Having this level of information is unprecedented and it will take some time to identify what an ‘appropriate’ response is. For instance, it might be usual for a person to have an initial period of focusing on the information followed by a sharp decline in this focus but research will be needed to characterise this response.

- A person might become overly anxious about having this information. Even if they have no known illness disease  related alleles, they might anticipate further information becoming available about their alleles. The information might be incorporated into a prior somatoform disorder. I did a quick medline search combining ‘genetic counselling’ and ‘somatoform’ which produced one reference which didn’t seem too relevant. However a more detailed search might have picked up some relevant papers.

- A person might feel a loss of control if they are found to have a predisposition to a certain illness. Indeed this has been well explored and genetic counselling has been utilised for a number of genetic conditions. Outside of a supportive medical environment if a person learns of newly identified relationships between their alleles and specific diseases they might be unable to judge the appropriate risk.

- There may be a number of reasons why the information may be more complex – genes are differentially expressed in different tissues, there may be small inaccuracies in a genome sequence, the interactions between gene products may be more important than having the disease allele.

How will Health Services respond to Personal Genomics?

While this isn’t the case at the moment, it wouldn’t be too unreasonable to suppose that in 10 years time, a sizeable proportion of the population will have access to their genome sequences. People might approach health services to help them interpret this information. Thus there might be an increasing role for geneticists in managing this aspect of healthcare although this will depend on health service configuration and responses. Additionally primary care may develop specialised services for managing this aspect of healthcare. Within mental health services there may be a role for prevention although any service responses would need to be evidence based. Various studies have identified degrees of risk associated with specific genes but also emphasise the importance of the environment.

How will this impact on culture?

If a person has information to about their genome sequence then one important question is how will this influence their relationship with others? Obviously this will become exceedingly complicated and there will be countless examples that could not have been anticipated. There are a number of broad possibilities. Many people will want to keep this information private as with other aspects of their healthcare information.  Others may advertise this information to others if they think it will be to their advantage and certain self-selected ‘types’ will be known by the genes they do or do not have and it may therefore confer an additional layer of identity.  Many aspects of an emerging genomics culture have been examined in the film ‘Gattaca‘. This information may combine in complex ways with other technologies such as the internet.

One thing is clear and that is that this field will need to be regulated and the ethical implications engaged in ongoing debate.

Call for Authors: If you are interested in writing an article or series of articles for this blog please write to the e-mail address below. Copyright can be retained. Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Review: Behavioral Symptoms and Caregiver Burden in Dementia

The paper reviewed is ‘Behavioral Symptoms and Caregiver Burden in Dementia’ by Shaji and colleagues and freely available here.

Aims: The authors write that

The present study examines the prevalence of BPSD in a community sample of patients with dementia and its impact on the caregivers

Method: The study took place in a rural area in Kerala, India. Trained healthworkers identified cases which were then screened by clinicians using DSM-IV criteria and the Clinical Dementia Rating (CDR) scale. Subjects rated as moderate to severe on the CDR were included in the study. I didn’t notice any exclusion criteria and the population might therefore be representative of a clinical population (albeit with selection bias influencing the sample population characteristics). The subjects were also included in two other studies and three outcome measures were collected

  • BEHAVE-AD.
  • General Health Questionnaire-12.
  • Zaret Burden Interview (ZBI).

The statistical tests used for different data types are clearly stated.

Results:

  • 29 people were included in the study with a mean age of 78.3 and all living at home with their families.
  • The characteristics of the sample are described in table 1. 43.8% of the people received a diagnosis of Alzheimer’s Disease and 34.5% were diagnosed with Vascular Dementia. The other diagnosis or combinations are described. 79.3% of the sample were female.
  • The scores on BEHAVE-AD are described in table 2 with 28 of the subjects meeting the criteria for Behavioural and Psychological Symptoms in Dementia (BPSD). I noted that the standard deviations were relatively large.
  • Table 3 displays the prevalence of items on the BEHAVE-AD subscales. Particularly prominent are delusional ideation and disturbances of activity.
  • In Table 4 the researchers detail the incidence of delusion types.
  • Table 5 shows a comparison of vascular dementia and Alzheimer’s Disease.
  • Table 6 showed the characteristics of no/mild BEHAVE-AD symptoms v moderate/severe BEHAVE-AD symptoms. Here, I thought the significant results perhaps reflected their relationship to the BEHAVE-AD total as they are components.
  • Table 7 displayed the characteristics of 2 samples defined by GHQ score thresholds. There is a significant relationship between increasing GHQ scores and ZBI scores. I thought that causality might be difficult to interpret in view of the cross-sectional nature of the study.

Discussion:

The authors draw a number of conclusions. They note the absence of a relationship between BEHAVE-AD and GHQ-12 scores and suggest that a larger sample size may be helpful in exploring this relationship further.

Conclusions:

I thought this was a small but interesting study in a sample with family based care of people with moderate to severe dementia. There was found to be an association between GHQ scores in carers and ZBI scores although the direction of the link was unclear given the cross-sectional design of this study.

Call for Authors: If you are interested in writing an article or series of articles for this blog please write to the e-mail address below. Copyright can be retained. Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.

Review: Systematic Review of Safety and Tolerability of Donepezil, Rivastigmine and Galantamine

The paper reviewed here is ‘Safety and Tolerability of Donepezil, Rivastigmine and Galantamine for patients with Alzheimer’s Disease: Systematic Review of the ‘Real-World’ Evidence’ by Lockhart and colleagues and freely available here.

Aim: The aim of the study is clearly outlined and reflected in the title.

Method: The authors identify trials from the following sources

  • Medline database
  • EMBASE
  • Cochrane library

The researchers used the following search terms in MESH and the text of the abstract: Dementia, Alzheimer’s disease, Donepezil, Rivastigmine, Galantamine, cohort, retrospective, naturalistic. The researchers also hand-searched a number of conference proceedings. Primary outcome measures were

  • Incidence of individual AE’s reported
  • Withdrawal due to AE’s
  • Incidence of individual AE’s

The researchers opted for a qualitative analysis rather than a meta-analysis ‘due to potential heterogeneity in included studies’.

Study designs were assessed using the Newcastle-Ottawa Scale which is

designed to appraise the methodological quality of comparative cohort and case control studies

The researchers include a detailed list of inclusion and exclusion criteria in table 1. The impression I got from reading the criteria is that the diagnostic criteria, trial type (essentially randomised trials) and of course treatment were the most significant factors influencing inclusion. Thereafter the inclusion criteria were fairly broad meaning that there was an opportunity to include a relatively large number of papers.

Results: There were a number of steps involved in reaching the final number of 12 papers and the interested reader is referred to the original paper linked to above. The characteristics of the 12 studies are summarised in Table 2. In the identified studies, the numbers for the different acetylcholinesterase inhibitors were

Donepezil: Retrospective analysis – n=6294; Prospective analysis n=4034

Rivastigmine: Retrospective analysis n=1842; Prospective analysis n=2143

Galantamine: Retrospective analysis n=809; Prospective analysis n=418

Table 3 shows withdrawal from the medication to GI effects. There is a wide spread within the prospective study – withdrawal due to any GI AE category although the difference in sample sizes cause difficulties in interpretation. In a number of cases p values are given. I might have missed this, but I couldn’t identify what tests were being used to produce the p-values.

Table 4 shows withdrawal due to all non-GI adverse events. My impression from inspecting this table was that there was a broad range across the studies – both retrospective and prospective and this wasn’t summarised with mean and confidence intervals for aggregated data. Looking through the data further, the figures for withdrawal due to cardiovascular events ranged from 0 to 1.2%.

Table 5 shows an aggregation of GI and non-GI adverse events and here there are a number of consistent findings across various studies particularly in the GI studies although there are outliers in the dataset. Again the data is not pooled although this is explained in the methodology section.

Table 6 shows CNS adverse events. There were a lot of categories here but there were a relatively small number of data points for each category.

Table 7 shows ‘non-CNS-related AE’s’ which covers a number of cardiac and miscellaneous AE’s (excluding GI (with the exception of weight loss)). The De La Gastine study shows a higher incidence of cardiac arrythmias for the different ACHEI’s but has smaller sample sizes than the other studies. Here again I thought the use of confidence intervals and statistical comparison between groups would be helpful.

Conflict of Interest: I couldn’t identify a COI declaration and the authors identify their institutions as Pfizer and Abacus International, a health consultancy firm.

Conclusions: I thought the researchers had gathered a large amount of useful data. It would have been interesting to see the information displayed with the use of confidence intervals and for these to be used in a between-group comparison. Even a lack of difference between groups in itself would have been interesting and I thought would have been helpful in drawing firm conclusions. The researchers discuss why they have opted for a qualitative analysis.

Call for Authors: If you are interested in writing an article or series of articles for this blog please write to the e-mail address below. Copyright can be retained. Index: An index of the site can be found here. The page contains links to all of the articles in the blog in chronological order. Twitter: You can follow ‘The Amazing World of Psychiatry’ Twitter by clicking on this link. Podcast: You can listen to this post on Odiogo by clicking on this link (there may be a small delay between publishing of the blog article and the availability of the podcast). It is available for a limited period. TAWOP Channel: You can follow the TAWOP Channel on YouTube by clicking on this link. Responses: If you have any comments, you can leave them below or alternatively e-mail justinmarley17@yahoo.co.uk. Disclaimer: The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog.