Simulation of survivorship bias in observational studies on plasma to red blood cell ratios in massive transfusion for trauma.

BACKGROUND: Observational studies on injured patients requiring massive transfusion have found a survival advantage associated with use of equivalent number of units of fresh frozen plasma (FFP) and packed red blood cells (RBCs) compared with use of FFP based on conventional guidelines. However, a survivorship bias might have favoured the higher use of FFP because patients who died early never had the chance to receive sufficient FFP to match the number of RBC units transfused. METHODS: A Markov model using trauma data from local hospitals was constructed and various FFP transfusion scenarios were applied in Monte Carlo simulations in which the relative risk of death associated with exposure to high FFP transfusion was set at 1.00, so that the FFP : RBC ratio had no influence on mortality outcome. RESULTS: Simulation results showed that the relative risk associated with exposure to high FFP transfusion was less than 1.00 (0.33-0.56 based on programmed delays in achieving an FFP : RBC ratio of 1 : 1-2), thus demonstrating a survivorship bias in favour of FFP : RBC equal to or more than 1 : 1-2 in certain observational trauma studies. This bias was directly proportional to the delay in achieving a FFP : RBC ratio of 1 : 1-2 during resuscitation. CONCLUSION: Some observational studies comparing low and high FFP administration in injured patients requiring massive transfusion probably involve survivorship bias that inflates or creates a survival advantage in favour of a higher FFP : RBC ratio.

The effect of dietary ascorbic acid and alpha-tocopherol on fecal mutagenicity.

The effect of supplemental ascorbic acid and alpha-tocopherol on fecal mutagenicity was examined in 2 studies involving 20 healthy human donors aged 22-55 years. The vitamins were given at a dose of 400 mg daily each. The mutagen was extracted from individual frozen feces samples with dichloromethane, and assayed with Salmonella Typhimurium tester strain TA100 without microsomal activation. In the first study, with a single donor on a controlled diet, the fecal mutagenicity decreased (P less than 0.001) on treatment to 21% of control. In the second study, with 19 donors on free-choice diets, the mutagenicity in producers on treatment decreased (P less than 0.01) to 26% of control. Addition of ascorbic acid and alpha-tocopherol directly to feces led to no change in mutagenicity. Antioxidants in the diet may have a role in lowering the body's exposure to endogenously produced mutagens.

Accuracy of central venous pressure monitoring during simultaneous continuous infusion through the same catheter.

Continuous central pressure monitoring and simultaneous continuous infusion via the same central venous catheter are sometimes necessary. Based on theoretical calculations and experimental measurements, we have determined that pressure monitoring is essentially unaffected if the continuous infusion rate is 50 ml.h(-1) or less for an adult and a paediatric central catheter. At rates > 200 ml.h(-1), the central venous pressure is exaggerated by up to 4 mmHg and 8 mmHg for the adult and paediatric catheters, respectively.

Strategies for dietary intervention studies in colon cancer.

As a result of many studies in descriptive and analytic epidemiology, in animal carcinogenesis, and in the direct examination of body fluids for mutagens/carcinogens, it is possible to develop a list of dietary factors that may be associated with the high rate of colon cancer and related cancers in Western countries. This paper is concerned with the design of intervention studies to clarify which of these factors is important. The size of such intervention trials is influenced primarily by two factors: the incidence of the disease outcome studied in a control population and the magnitude of risk reduction in a treated group. Calculations based on a variety of assumptions suggest that a randomized trial in which cancer mortality is measured as the outcome of the intervention in a healthy population is probably too costly to be justified by current evidence linking the disease to diet. However, precursor lesions can be considered as an alternative outcome. The choice of the precursor lesion depends on the link to the disease in question, the prevalence of the lesion in the population, and the ease of detection. Recent developments in the application of endoscopic methods and in the description of the pathologic process leading to cancer suggest the use of gastrointestinal polyps as "precursor lesions" as the outcome of a trial. We illustrate these points with a protocol for a study in progress, a randomized double-blind study of the effect of ascorbic acid and alpha-Tocopherol on the rate of recurrence of colorectal polyps.