Sunday, January 29, 2012

Broderick delivers a slap to Van Der Meer and Lloyd

We believe that a prime cause of inconsistent and confusing research findings in this heterogeneous patient population has been the use of overly inclusive criteria for CFS such as the Oxford and Reeves criteria, because each study may include very different patient sets. This dilutes the results, makes them difficult to confirm, leads to scepticism and thus inhibits progress. Jason et al. found the Reeves empirical criteria to be flawed because it was possible to meet the CFS criteria without any physical symptoms, only 10% actually had ME/CFS and 38% of patients with Major Depressive Disorder were misclassified as having CFS. The increased estimates of CFS from 0.24% (Fukuda) to 2.54% (Reeves, USA) and 2.6% (UK) confirm that the Reeves and Oxford criteria select patient sets that are approximately ten times larger and more inclusive than those selected by the Fukuda criteria. Whilst some general information about fatigue may be ascertained using these inclusive criteria, it is not productive to try to study the mechanisms of ME if up to 90% of the research patient set do not meet the criteria for ME. …

… If the same symptoms consistently flare in response to exertion, they are more likely to share a common cause. For example, if a patient consistently experiences flu-like symptoms, sore throat and tender lymph nodes in response to exertion, it suggests that immune activation is a component of their underlying pathophysiology, which then can be studied scientifically. Given that the Oxford criteria are based on general chronic fatigue and it is possible to meet the Reeves criteria without having any physical symptoms, it is surprising that the ICC was admonished for its use of subjective symptoms. Symptoms by definition are subjective; however, the clinician can observe visible signs that accompany symptoms such as swollen lymph nodes, crimson crescents in tonsillar fossae, abnormal accommodation responses of the pupils, abnormal body temperature or blood pressure, abnormal tandem gait and positive Romberg test, thus confirming symptoms. …

The ICC identify patients who have measurable and reproducible pathophysiological abnormalities in response to exertion, which people with general fatigue or depression do not have. In contrast, the Reeves and Oxford criteria do not require postexertional malaise or exhaustion in their definitions, and it is optional in the Fukuda criteria. The more general and stereotypic the criteria, the less useful they become because lumping together patients whose chronic fatigue is an integral part of many other diseases skews both clinical and research findings. It is prudent to study patients who have various kinds of adverse pathophysiological reactions to exertion to isolate various pathogeneses responsible for them and determine appropriate treatments. The use of patient sets selected by relevant, well-defined and consistent ICC for ME in research will thus advance science, provide greater clarity of understanding and elicit more reproducible scientific results. This will also allow a selection of more homogeneous sets of ME patients, given the current knowledge, which can then be compared with other populations. Whether patients with less severe conditions represent a continuum, faulty diagnosis or different disease entities can only be determined by future studies.

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