Hence, it is plausible that some cases of myopathy may have been due to undiagnosed rheumatic disease, although we would not expect this to inflate the RR associated with statin induced myopathy greatly. One key advantage of the case-crossover design is that it considerably reduces confounding as each case acts as its own control. Conventional confounders such as age, sex, BMI, and additional existing co morbidities such as renal and liver diseases can therefore be accounted for. However, if these change over time, it may be appropriate to calculate a ��propensity score�� for the individual which can included in the analyses and to test for confounding by exposure to other drugs. The case-crossover approach is particularly suitable for detecting acute conditions, such as ADRs of relatively acute onset. For case-crossover comparisons the main confounder is any secular trend in prescribing which will give rise to confounding by age. Analysis examining RR of statin associated myopathy, stratifying by calendar time periods showed possible secular trend of decreasing RR. The adjusted RR was similar to the crude estimate of RR; WY 14643 However the fall in RR from 28.7 to 18.8 may be explained by less use of concurrent fibrates with statins. The NVP-BEZ235 PI3K inhibitor difference in RR from 1995�C98 compared with 2003�C5 was found to be statistically significant RR 1.79, and was similar for longer periods of exposure RR 1.53. Where there are large RR associated with drug exposures; any contamination of unexposed with exposed groups will affect the estimates. This misclassification of exposure will mean that many cases classified as ����unexposed���� are in reality ����exposed����. So in effect we expect the true estimate for the RR of statin associated myopathy will be higher than 19.9. These and other techniques could be used to develop and apply methods for exploiting primary care databases to infer causal relationships between classes of drugs and classes of adverse events. In the longer term, the development of computerised integrated health records could allow the methods to applied to a much wider population and thus greatly improve the detection rates of ADRs. Because of the computerisation of general practice, the UK is well placed to develop these new methods and compare them with existing methods, although other European countries are also adapting to computerised medical records. This would lead to the development and testing of new methods of detecting adverse drug reactions, which if successfully introduced, would have great public health, clinical and economic benefits. This adaptation plays a key role in enabling a slow-growing, non-motile bacterium without a significant animal reservoir to spread across the globe and achieve its remarkable level of prevalence. Up to a third of all people are skin test positive for MTB infection. In addition, factors that promote TB latency may also be important during active TB disease. MTB in humans can be metabolically heterogeneous, with active and quiescent lesions adjacent to one another.