can someone have a look at this please before i add references etc
Aside from these crucial methodological issues, other plausible alternative explanations for the findings are not explicitly discussed. Foremost among these is reverse causality: Patients with poor general health because of CFS may be more susceptible to viral and other infections.Well-conducted case-control studies provide important insights into disease pathogenesis. Lombardi et al. (1) demonstrated an apparent association between chronic fatigue syndrome (CFS) and the presence, infectivity of, and immune response to the human gammaretrovirus, xenotropic murine leukemia virus–related virus (XMRV).
I am surprised that Sudlow begins with such loose terminology.Lobardi et al reported a statistically significant correlation beween patients who fulfilled the Canadian Consensus criteria for diagnosing a person as suffering from ME,cfs defined as a neurological disorder by the world health authority and the presence of XMRV.
First, although the CFS cases studied fulfilled broadly accepted diagnostic criteria,
Again I am surprised by this comment. The CCC diagnostic criteria are the only clinical diagnostic guidelines in the world.All others are research guidelines.The FUKUDA guidelines are internationally agreed and recognised.The research guidelines(The Oxford criteria) used to diagnose people in the European studies are not. The Oxford criteria has fatigue as the only mandatory diagnostic criteria(sharpe et al 1991).This a strange way of diagnosing a neurological disorder.The CCC guidelines on the other hand have neuroimmunoendocrine symptoms as mandatory.
Sudlow also seems to be unaware of the fact that CFS is not an objective diagnosis.
It is a socially constructed label driven by the diagnostic criteria applied by the diagnoser.Different doctors apply different diagnostic criteria and thus produce objectively different patient cohorts which are unfortunately given the same label.
I am astonished that someone who purports to be an epidemiologist does not seem to realise this.
Second, to avoid selection bias, the CFS-free controls should have been drawn from the same background population as the cases and selected independent of the exposure (in this case, a viral infection) under study (2, 3). Put simply, the controls should ideally have been people who would have been cases in the study if they had CFS.
Sudlow is assuming that XMRV is not causative.Put simply if XMRV is causative then Sudlows design would leave us with no way of telling XMRV levels in patients with CFS compared to controls.They would all have equal levels of the virus .Selection bias is all to obvious in the Imperial college study because all the patients were supplied by one psychiatrist using diagnostic critera constructed by himself and his colleagues which are not internationally recognised.Sudlow is completely silent on this subject.
However, the control subjects are not described in (1) beyond a mention that they were healthy donors. Third, the lack of clinical data for cases and controls makes it impossible to assess the potential for confounding by numerous other characteristics that may independently influence XMRV status, including age, sex, social deprivation status, medical history (e.g., of prostate cancer), and area of residence.
None of these parameters are described in the European studies.She seems to be accepting,albeit tacitly, that there is a link between XMRV and prostate cancer while questioning the link between XMRV and ME/cfs which is in statistical terms about a hundred times stronger.There is no clinical data supplied in the European studies for any of the patients control groups or otherwise.
Fourth, Lombardi et al. do not explain whether identical and contemporaneous laboratory sample storage, handling, and analysis procedures were used for both cases and controls. Differences in these could be another potentially important source of confounding. Fifth, even if identical laboratory procedures for cases and controls were intended, researchers exploring an exciting new hypothesis of a viral cause for CFS in a laboratory established to explore biological causes of CFS will be understandably eager for positive results. This so-called "expectation bias" may lead to completely unconscious and nondeliberate differences in sample handling and data interpretation between cases and controls; it can be avoided only if researchers are blinded to the case-control status of the samples. However, this is not described in (1).
Expectation bias arises as a result of the self biasing nature of mental representations.This leads us to interpret things according to the nature of our beliefs world views and expectations.In neurocognitive terms it is called top down processing. This is one of the main reasons why the scientific method is constructed in such a way that to test a hypothesis is to actively try to disprove it. Lombardi et al far from displaying expectation bias challenged their hypothesis by attempting to find XMRV using 4 different methods.Had any one of their approaches failed then their hypothesis would have been invalidated.That is robust science.Contrast that to the approach used in the imperial; college study when the author of the study on the basis of one study claimed that”there is no XMRV in the UK.That in objective terms corresponds to the scientific definition of expectation bias.By not extending the scope of her analysis to the other studies in this area Sudlow appears to be displaying cognitive biases of her own.
Aside from these crucial methodological issues, other plausible alternative explanations for the findings are not explicitly discussed. Foremost among these is reverse causality: Patients with poor general health because of CFS may be more susceptible to viral and other infections.
The conclusion in the study by Lombardi et al was that there was a statistically significant correlation between the presence of XMRV and peopled diagnosed with ME,cfs according to the CCC criteria. There were a myriad of counfounding vatiables in the design of the European studies which made the results impossible to interpret and the conclusions reached unfalsifyable. Surely an epidemiologist would note that point.
Finally it is extremely common that people in very poor health because of a retroviral infection fall prey to secondary pathogens.This is what happens in patients suffering from Aids.So it is far more likely that a retroviral infection accounts for the poor health seen in patients with ME,cfs.I feel that a scientist should offer that as an alternative explanation especially as she is so keen on plausible alternative explanations been put forward
