PubMed · 15609516
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Zane Pollard, Pamela Berg. Distant diplopia.. https://doi.org/10.3928/01913913-20041101-12
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In many ways, adjustment for publication bias in meta-analysis parallels adjustment for ascertainment bias in genetic studies. We investigate a previously published simulation-based method for dealing with complex ascertainment bias and show that it can be modified for use in meta-analysis when publication bias is suspected. The method involves simulating sets of pseudo-data under the assumed model using guesses for the unknown parameters. The pseudo-data are subjected to the same selection criteria as are believed to have operated on the original data. A conditional likelihood is then used to estimate the adjusted values of the unknown parameters. This method is used to re-analyse a published meta-analysis of the effect of the MTHFR gene on homocysteine levels. Simulation studies show that the pseudo-data method is unbiased; they give an indication of the number of pseudo-data values required and suggest that a two-stage adjustment produces less variable estimates. This method can be thought of as an example of the selection model approach to publication bias correction. As the selection mechanism must be assumed, it is important to investigate the sensitivity of any conclusions to this assumption.
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BACKGROUND: Anticytomegalovirus (CMV) prophylaxis prevents the acute disease but its impact on subclinical infection and allograft outcome is unknown. We sought to determine whether CMV prophylaxis administered for three months after heart transplant would improve patient outcomes. METHODS: This prospective cohort study of 66 heart transplant recipients compared aggressive CMV prophylaxis (n = 21, CMV hyperimmune globulin [CMVIG] plus four weeks of intravenous ganciclovir followed by two months of valganciclovir); with standard prophylaxis (n = 45, intravenous ganciclovir for four weeks). Prophylaxis was based on pretransplant donor (D) and recipient (R) CMV serology: R-/D+ received aggressive prophylaxis; R+ received standard prophylaxis. Outcome measures were: CMV infection assessed by DNA-polymerase chain reaction on peripheral blood polymorphonuclear leukocytes, acute rejection, and cardiac allograft vascular disease (CAV) assessed by intravascular ultrasound. All patients completed one year of follow-up. RESULTS.: CMV infection was subclinical in all but four patients (two in each group). Aggressively treated patients had a lower incidence of CMV infection (73 +/- 10% vs. 94 +/- 4%; P = 0.038), and an independent reduced relative risk for acute rejection graded > or =3A (relative risk [95% CI] = 0.55 [0.26-0.96]; P = 0.03), as compared with the standard prophylaxis group. Aggressively prophylaxed patients also showed a slower progression of CAV, in terms of coronary artery lumen loss (lumen volume change=-21 +/- 13% vs. -10+/-14%; P = 0.05); and vessel shrinkage (vessel volume change = -15 +/- 11% vs. -3 +/- 18%; P = 0.03). CONCLUSIONS: Prolonged (val)ganciclovir plus CMVIG reduces viral levels, acute rejection, and allograft vascular disease, suggesting a role for chronic subclinical infection in the pathophysiology of the most common diseases affecting heart transplant recipients.