Inclusion bias

Assuming such preclinical studies did show such beneficial effects to combination treatment, how would a clinical trial of such combination treatment be designed Because hypothermia is not an easily blinded treatment, special care will be needed to ensure the avoidance of bias. This might include use of separate blinded evaluators of neurological outcome unrelated to the patients care. Inclusion criteria for the trial should also ensure that patients are neither too severely disabled, nor too mild affected neurologically, to avoid ceiling and floor effects. 

In such cases, we recommend that parametric statistics be applied to the latency data as long as a minimum of 4 animals show convulsions, to avoid score bias by inclusion of floor and ceiling effects. 

To overcome the bias resulting from uneven dispersal of tracer or inhibitor, sediment rate measurements are often made in slurries, which destroy the gradient structure of sediments, which is essential to the in situ fluxes. Slurries may provide useful information on potential rates, but not in situ rates. Potential nitrification rates and rates measured in intact cores were not correlated in estuarine sediments (Caffrey et ah, 2003). The lack of correlation was explained by the inclusion of variable amounts of anoxic sediments in the slurries from which the potential rates were derived. 

In a retrospective review of 37 patients with chronic non-malignant pain (mostly from failed lumbosacral spine surgery) treated with intrathecal hydromorphone there was an analgesic response in six of the 16 patients who were switched from morphine to hydromorphone because of poor pain relief (1). Opioid-related adverse effects, such as nausea, vomiting, pruritus, and sedation, were also reduced by hydromorphone in the 21 patients who were switched to hydromorphone because of morphine-related adverse effects, especially 1 month after use. These results should be treated cautiously, because of the limitations of a retrospective study that lacks strict inclusion criteria, with obvious population bias and under-reporting, and without standardized procedures for rotation to hydromorphone. 

Simulated annealing refinement is usually unable to correct very large errors in the atomic model or to correct for missing parts of the structure. The atomic model needs to be corrected by inspection of a difference Fourier map. In order to improve the quality and resolution of the difference map, the observed phases are often replaced or combined with calculated phases, as soon as an initial atomic model has been built. These combined electron density maps are then used to improve and to refine the atomic model. The inclusion of calculated phase information brings with it the danger of biasing the refinement process towards the current atomic model. This model bias can obscure the detection of errors in atomic models if sufficient experimental phase information is unavailable. In fact during the past decade several cases of incorrect or partly incorrect atomic models have been reported where model bias may have played a role [67]. 

Systematic reviews are recent additions to the medical literature. In contrast to traditional narrative reviews, these reviews aim to answer a precisely defined clinical question and to do so in a way that is transparent and designed to minimize bias. Some of the defining features of systematic reviews are (1) a clear definition of the clinical question to be addressed, (2) an extensive and explicit strategy to find ail studies (published or unpublished) that may be eligible for inclusion in the review, (3) criteria by which studies are included and excluded, (4) a mechanism to assess the quahty of each study and, in some cases, (5) synthesis of results by use of statistical techniques of meta-analysis. By contrast, traditional reviews are subjective, are rarely well focused on a clinical question, lack explicit criteria for selection of studies to be reviewed, do not indicate criteria to assess the quality of included studies, and rarely can use meta-analysis. 

Timmer et al. (148) reviewed the efficacy of P. sidoides extract for acute respiratoiy tract infections and identified 12 trials meeting their inclusion criteria (randomized trials against a control intervention with complete resolution of symptoms as primary outcome criteria). Fom trials were excluded from the analyses due to high risk of bias. They reviewed eight trials... 

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