Thomas V. Inglesby, MD
Two scientific teams have recently engineered the H5N1 virus to make it readily transmissible between ferrets. Given that ferrets are considered the most reliable animal surrogate for human influenza infection, the newly engineered H5N1 strain is probably transmissible between humans as well. The potential consequences of an engineered human-transmissible H5N1 strain are stunning. Although seasonal flu infects as much as 20% of the world's population—more than 1 billion persons—each year, only a small fraction of those with seasonal flu dies, most often the oldest, youngest, and sickest. If the newly engineered strain were to escape the laboratory (either by design or by accident) and spread as widely as seasonal flu with anywhere near the current confirmed H5N1 human case-fatality rate, it could endanger the lives of hundreds of millions of persons. The possible benefits of this work do not justify taking such risks. As clinicians, we have a stake in this issue with our responsibilities for the diagnosis and treatment of influenza. We embrace the principle of free and open exchange of scientific information, but we also believe in the principle of “first, do no harm.” These 2 principles have come into a moment of rare conflict. It seems most reasonable and prudent to request that the involved scientific community and its institutions exercise restraint by restricting dissemination of the experimental results and discontinuing work on the engineered H5N1 strains. If a highly compelling case is made for continued work on this strain despite the risks, the work should be controlled and should merit the greatest scrutiny.
Sandra P., Silveiro, MD, Sandra P. Silveiro, Ariana A. Soares, Leticia S. Weinert, Eduardo G. Camargo
Hospital de Clinicas de Porto Alegre, RS, Brazil
February 13, 2012
Estimating equations for glomerular filtration rate in the era of creatinine standardization - a systematic review
TO THE EDITOR: Early and colleagues have elegantly presented the results of a timely systematic review "Estimating equations for glomerular filtration rate in the era of creatinine standardization - a systematic review" (1), concluding that the performance of the CKD-EPI and MDRD study equations varies across populations and GFR ranges.The authors required, as inclusion criteria to their review, the minimum number of a 100 individuals, the use of a glomerular filtration rate (GFR) reference method and the use of an IDMS traceable creatinine method. As the review encompassed the period of 1999 up to October 2011, we would like to share our results published in the November 2011 issue of Diabetes Care (2), because not only our data fulfills the required inclusion criteria, but also describes the findings of a South-Brazilian population, not evaluated in the systematic review. In our cross-sectional study, we evaluated 105 patients with type 2 diabetes, with a mean age of 57 years; 53 (50%) men and 90 (86%) white. Forty-six (44%) patients had microalbuminuria, and 14 (13%) had macroalbuminuria - all patients had GFRs >60 mL/min/1.73 m2, as measured by 51Cr-EDTA single-injection method. Measured 51Cr-EDTA GFR was 103 +/- 23, CKD-EPI GFR was 83 +/- 15 (bias: 20), and MDRD GFR was 78 +/- 17 mL/min/1.73 m2 (bias: 24). Accuracy P30 (95%CI) was 67% (58-74) for CKD-EPI and 64% (56-75) for MDRD. We concluded that both equations pronouncedly underestimated GFR in type 2 diabetic patients with GFR above 60 mL/min/1.73 m2. These findings confirmed our previous report of a significantly worse performance of both equations in patients with diabetes when compared with healthy individuals, mainly due to the fact that diabetic patients had higher serum creatinine levels than the healthy group, even after matched by GFR (3). In contrast, when previously analyzing a group of 96 healthy volunteers with normal GFR, we observed the improved accuracy (P30) of CDK-EPI equation as compared to the MDRD equation (85% vs. 69%, respectively, P <0.001) (4). We congratulate the authors on the excellent job of reporting the situation of estimating equations on the nowadays scenario. A more appropriated interpretation of the equations performance allows the eventual development of strategies to improve the identified misrepresentations.
1)Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K. Estimating equations for glomerular filtration rate in the era of creatinine standardization - A systematic review. Early release. Ann Intern Med 2012.
2)Silveiro SP, Araujo GN, Ferreira MN, Souza FD, Yamaguchi HM, Camargo EG. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation pronouncedly underestimates glomerular filtration rate in type 2 diabetes. Diabetes Care. 2011;34(11):2353-5.
3)Camargo EG, Soares AA, Detanico AB, Weinert LS, Veronese FV, Gomes EC, Silveiro SP. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is less accurate in patients with Type 2 diabetes when compared with healthy individuals. Diabet Med. 2011;28(1):90-5.
4)Soares AA, Eyff TF, Campani RB, Ritter L, Weinert LS, Camargo JL, Silveiro SP. Performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations in healthy South Brazilians. Am J Kidney Dis. 2010;55(6):1162-3.
Hugh, Mann, Physician
Eagle Rock, Mo 65641
March 27, 2012
The lady doth protest too much (Hamlet)
The US Institute of Medicine's squeaky clean bill of health for the troubled vaccine industry is all too predictable. As the sacred cow and cash cow of modern medicine, vaccines enjoy both scientific and legal immunity. How ironic that vaccines enjoy more immunity than they convey.
Inglesby TV. Engineered H5N1: A Rare Time for Restraint in Science. Ann Intern Med. 2012;156:460–462. doi: https://doi.org/10.7326/0003-4819-156-6-201203200-00387
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Published: Ann Intern Med. 2012;156(6):460-462.
Infectious Disease, Influenza.
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