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Is Surgery a Risk Factor for Creutzfeldt-Jakob Disease? Outcome Variation by Control Choice and Exposure Assessments

  • Jed A. Barash (a1), Blair T. Johnson (a2) and David I. Gregorio (a3)



To determine whether methodological differences explain divergent results in case-control studies examining surgery as a risk factor for Creutzfeldt-Jakob disease (CJD).


After case-control studies were systematically identified using PubMed, we performed a homogeneity analysis and applied models to effect sizes (odds ratio [OR] with 95% confidence interval [CI]) using 2 parameters: type of control subject used and consistency of data ascertainment. The hospitals and communities were located in Europe, Japan, and Australia. Patients were CJD case subjects and age- and sex-matched control subjects in the hospital or community. Because of the natural history of the disease, CJD subjects are not considered reliable sources of information for these studies. Therefore, individuals who are considered close to the subjects and who have knowledge of their medical history, including spouses and relatives, are necessarily identified as proxy informants for the surgical record of the case subjects.


Overall, the effect sizes lacked homogeneity (P<.0001). Three studies that used control subjects from the community revealed a significantly elevated risk of CJD for patients who underwent surgery (OR, 1.82; 95% CI, 1.41-2.35 [P<.0001 ]), whereas 3 investigations that used control subjects from the hospital revealed a significantly reduced risk (OR, 0.69; 95% CI, 0.52-0.90 [P = .0069]). Two studies that used proxy informants to acquire information about case subjects and control subjects (consistent ascertainment) found that the risk of CJD was significantly lower in those subjects who underwent surgery (OR, 0.65; 95% CI, 0.48-0.87 [P = .0043]). Conversely, 4 studies in which proxy informants acted only on behalf of case subjects (inconsistent data ascertainment) found a significant positive association between surgery and CJD (OR, 1.67; 95% CI, 1.32-2.12 [P<.0001 ]). Both models fit the data very well, leaving no remaining variance in effect sizes to explain.


Variation in the type of control subjects used and in exposure assessment in case-control studies may partially explain conflicting data regarding the association between surgery and CJD. However, there was almost complete confounding of these 2 parameters, making interpretation more difficult. Planning of future investigations must carefully consider these design elements.


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1.Jubelt, B. Prion diseases. In: Rowland, LP, ed. Merritt's Neurology. 11th ed. Philadelphia: Lippincott, Williams, and Wilkins; 2005:264270.
2.Brown, P. Transmissible spongiform encephalopathy. In: Goetz, CG, ed. Textbook of Clinical Neurology. 2nd ed. Philadelphia: WB Saunders; 2003:945954.
3.Brown, P, Preece, M, Brandel, JP, et al.Iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 2000;55:10751081.
4.Wientjens, DPWM, Davanipour, Z, Hofman, A, et al.Risk factors for Creutzfeldt-Jakob disease: a reanalysis of case-control studies. Neurology 1996;46:12871291.
5.Kondo, K, Kuroiwa, Y. A case control study of Creutzfeldt-Jakob disease: association with physical injuries. Ann Neurol 1982;11:377381.
6.Davanipour, Z, Alter, M, Sobel, E, Asher, D, Gajdusek, DC. Creutzfeldt-Jakob disease: possible medical risk factors. Neurology 1985;35:14831486.
7.Harries-Jones, R, Knight, R, Will, RG, Cousens, S, Smith, PG, Matthews, WB. Creutzfeldt-Jakob disease in England and Wales, 1980-1984: a case-control study of potential risk factors. J Neurol Neurosurg Psychiatry 1988;51:11131119.
8.van Duijn, CM, Delasnerie-Laupretre, N, Masullo, C, et al.Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95. Lancet 1998;351:10811085.
9.Collins, S, Law, MG, Fletcher, A, Boyd, A, Kaldor, J, Masters, CL. Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study. Lancet 1999;353:693697.
10.Zerr, I, Brandel, JP, Masullo, C, et al.European surveillance on Creutzfeldt-Jakob disease: a case control study for medical risk factors. J Clin Epidemiol 2000;53:747754.
11.Nakamura, Y, Oki, I, Tanihara, S, et al.A case-control study of Creutzfeldt-Jakob disease in Japan: transplantation of cadaveric dura mater was a risk factor. J Epidemiol 2000;10:399402.
12.Ward, HJT, Everington, D, Croes, EA, et al.Sporadic Creutzfeldt-Jakob disease and surgery: a case-control study using community controls. Neurology 2002;59:543548.
13.Masters, CL, Harris, JO, Gajdusek, DC, Gibbs, CJ, Bernoulli, C, Asher, DM. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol 1979;5:177188.
14.Hedges, LV, Olkin, I. Statistical Methods for Meta-analysis. Orlando, Florida: Academic Press; 1985.
15.Johnson, BT, Eagly, AH. Quantitative synthesis of social psychological research. In: Reis, HT, Judd, CM, eds. Handbook of Research Methods in Social and Personality Psychology. London: Cambridge University Press;2000:496528.
16.Lipsey, MW, Wilson, DB. Practical Meta-analysis. Thousand Oaks, California: Sage Publications; 2001.
17.Bradburn, MJ, Deeks, JJ, Altman, DG. sbe24: metan—an alternative meta-analysis command. Stata Technical Bulletin 1998;44:415.
18.S-Juan, P, Ward, HJT, De Silva, R, Knight, RSG, Will, RG. Ophthalmic surgery and Creutzfeldt-Jakob disease. Br J Ophthalmol 2004;88:446449.
19.Lewis, V, Boyd, A, Masters, CL, Collins, SJ. Apparently sporadic CJD and covert health-care transmissions. Lancet Neurol 2002;1:470471.
20.Moritz, DJ, Kelsey, JL, Grisso, JA. Hospital controls versus community controls: differences in inferences regarding risk factors for hip fracture. Am J Epidemiol 1997;145:653660.
21.Schlesselman, JJ, Stolley, PD. Case-Control Studies. New York: Oxford University Press; 1982.
22.Ward, HJT, Cousens, SN, Smith-Bathgate, B, et al.Obstacles to conducting epidemiological research in the UK general population. BMJ 2004;329:277279.
23.Wacholder, S, McLaughlin, JK, Silverman, DT, Mandel, JS. Selection of controls in case-control studies. I. Principles. Am J Epidemiol 1992;135:10191028.
24.Debanne, SM, Petot, GJ, Li, J, et al.On the use of surrogate respondents for controls in a case-control study of Alzheimer's disease. J Am Geriatr Soc 2001;49:980984.
25.Ward, HJT, Everington, D, Cousens, SN, et al.Risk factors for variant Creutzfeldt-Jakob disease: a case-control study. Ann Neurol 2006;59:111120.

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Is Surgery a Risk Factor for Creutzfeldt-Jakob Disease? Outcome Variation by Control Choice and Exposure Assessments

  • Jed A. Barash (a1), Blair T. Johnson (a2) and David I. Gregorio (a3)


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