scholarly journals Risks and Biases in Case-Control Studies of Iatrogenic Creutzfeldt-Jakob Disease

2012 ◽  
Vol 39 (2) ◽  
pp. 147-147
Author(s):  
N. Venketasubramanian
2012 ◽  
Vol 39 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Jesús de Pedro Cuesta ◽  
María Ruiz Tovar ◽  
Hester Ward ◽  
Miguel Calero ◽  
Andrew Smith ◽  
...  

2008 ◽  
Vol 31 (4) ◽  
pp. 229-240 ◽  
Author(s):  
Ignacio Mahillo-Fernandez ◽  
Jesús de Pedro-Cuesta ◽  
Maria José Bleda ◽  
Mabel Cruz ◽  
Kåre Mølbak ◽  
...  

2020 ◽  
Vol 140 (6) ◽  
pp. 863-879
Author(s):  
Luke C. Dabin ◽  
Fernando Guntoro ◽  
Tracy Campbell ◽  
Tony Bélicard ◽  
Adam R. Smith ◽  
...  

AbstractPrion diseases are fatal and transmissible neurodegenerative disorders caused by the misfolding and aggregation of prion protein. Although recent studies have implicated epigenetic variation in common neurodegenerative disorders, no study has yet explored their role in human prion diseases. Here we profiled genome-wide blood DNA methylation in the most common human prion disease, sporadic Creutzfeldt–Jakob disease (sCJD). Our case–control study (n = 219), when accounting for differences in cell type composition between individuals, identified 38 probes at genome-wide significance (p < 1.24 × 10–7). Nine of these sites were taken forward in a replication study, performed in an independent case–control (n = 186) cohort using pyrosequencing. Sites in or close to FKBP5, AIM2 (2 probes), UHRF1, KCNAB2 successfully replicated. The blood-based DNA methylation signal was tissue- and disease-specific, in that the replicated probe signals were unchanged in case–control studies using sCJD frontal-cortex (n = 84), blood samples from patients with Alzheimer’s disease, and from inherited and acquired prion diseases. Machine learning algorithms using blood DNA methylation array profiles accurately distinguished sCJD patients and controls. Finally, we identified sites whose methylation levels associated with prolonged survival in sCJD patients. Altogether, this study has identified a peripheral DNA methylation signature of sCJD with a variety of potential biomarker applications.


2017 ◽  
Vol 22 (43) ◽  
Author(s):  
Fernando J García López ◽  
María Ruiz-Tovar ◽  
Javier Almazán-Isla ◽  
Enrique Alcalde-Cabero ◽  
Miguel Calero ◽  
...  

Background: Sporadic Creutzfeldt–Jakob disease (sCJD) is potentially transmissible to humans. Objective: This study aimed to summarise and rate the quality of the evidence of the association between surgery and sCJD. Design and methods: Firstly, we conducted systematic reviews and meta-analyses of case–control studies with major surgical procedures as exposures under study. To assess quality of evidence, we used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Secondly, we conducted a systematic review of sCJD case reports after sharing neurosurgical instruments. Results: Thirteen case–control studies met the inclusion criteria for the systematic review of case–control studies. sCJD was positively associated with heart surgery, heart and vascular surgery and eye surgery, negatively associated with tonsillectomy and appendectomy, and not associated with neurosurgery or unspecified major surgery. The overall quality of evidence was rated as very low. A single case–control study with a low risk of bias found a strong association between surgery conducted more than 20 years before disease onset and sCJD. Seven cases were described as potentially transmitted by reused neurosurgical instruments. Conclusion: The association between surgery and sCJD remains uncertain. Measures currently recommended for preventing sCJD transmission should be strongly maintained. Future studies should focus on the potential association between sCJD and surgery undergone a long time previously.


Neurology ◽  
1996 ◽  
Vol 46 (5) ◽  
pp. 1287-1287 ◽  
Author(s):  
D. P.W.M. Wientjens ◽  
Z. Davanipour ◽  
A. Hofman ◽  
K. Kondo ◽  
W. B. Matthews ◽  
...  

2020 ◽  
Author(s):  
Luke Child Dabin ◽  
Fernando Guntoro ◽  
Tracy Campbell ◽  
Tony Belicard ◽  
Adam R Smith ◽  
...  

Prion diseases are fatal and transmissible neurodegenerative disorders caused by the misfolding and aggregation of prion protein. Although recent studies have implicated epigenetic variation in common neurodegenerative disorders, no study has yet explored their role in human prion diseases. Here we profiled genome-wide blood DNA methylation in the most common human prion disease, sporadic Creutzfeldt-Jakob disease (sCJD). Our case-control study (n=219), when accounting for differences in cell type composition between individuals, identified 38 probes at genome-wide significance. Nine of these sites were taken forward in a replication study, performed in an independent case-control (n=186) cohort using pyrosequencing. Sites in or close to FKBP5, AIM2 (2 probes), UHRF1, KCNAB2, PRNP, ANK1 successfully replicated. The blood-based DNA methylation signal was tissue- and disease-specific, in that the replicated probe signals were unchanged in case-control studies using sCJD frontal-cortex (n=84), blood samples from patients with Alzheimer s disease, and from inherited and acquired prion diseases. Machine learning algorithms using blood DNA methylation array profiles accurately distinguished sCJD patients and controls. Finally, we identified sites whose methylation levels associated with prolonged survival in sCJD patients. Altogether, this study has identified a peripheral DNA methylation signature of sCJD with a variety of potential biomarker applications.


2001 ◽  
Vol 166 (12) ◽  
pp. 1057-1058 ◽  
Author(s):  
Jack E. Riggs ◽  
Shyam S. Moudgil ◽  
Gerald R. Hobbs

2008 ◽  
Vol 29 (3) ◽  
pp. 212-218 ◽  
Author(s):  
Jed A. Barash ◽  
Blair T. Johnson ◽  
David I. Gregorio

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


Author(s):  
Ruth H. Keogh ◽  
D. R. Cox

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