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| 12. |
- Delcoigne, B, et al.
(författare)
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Feasibility of reusing time-matched controls in an overlapping cohort
- 2018
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 27:6, s. 1818-1829
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Tidskriftsartikel (refereegranskat)abstract
- The methods developed for secondary analysis of nested case-control data have been illustrated only in simplified settings in a common cohort and have not found their way into biostatistical practice. This paper demonstrates the feasibility of reusing prior nested case-control data in a realistic setting where a new outcome is available in an overlapping cohort where no new controls were gathered and where all data have been anonymised. Using basic information about the background cohort and sampling criteria, the new cases and prior data are “aligned” to identify the common underlying study base. With this study base, a Kaplan–Meier table of the prior outcome extracts the risk sets required to calculate the weights to assign to the controls to remove the sampling bias. A weighted Cox regression, implemented in standard statistical software, provides unbiased hazard ratios. Using the method to compare cases of contralateral breast cancer to available controls from a prior study of metastases, we identified a multifocal tumor as a risk factor that has not been reported previously. We examine the sensitivity of the method to an imperfect weighting scheme and discuss its merits and pitfalls to provide guidance for its use in medical research studies.
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| 13. |
- Michalon, Aubin, et al.
(författare)
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A human antibody selective for transthyretin amyloid removes cardiac amyloid through phagocytic immune cells
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Transthyretin amyloid (ATTR) cardiomyopathy is a debilitating disease leading to heart failure and death. It is characterized by the deposition of extracellular ATTR fibrils in the myocardium. Reducing myocardial ATTR load is a therapeutic goal anticipated to translate into restored cardiac function and improved patient survival. For this purpose, we developed the selective anti-ATTR antibody NI301A, a recombinant human monoclonal immunoglobulin G1. NI301A was cloned following comprehensive analyses of memory B cell repertoires derived from healthy elderly subjects. NI301A binds selectively with high affinity to the disease-associated ATTR aggregates of either wild-type or variant ATTR related to sporadic or hereditary disease, respectively. It does not bind physiological transthyretin. NI301A removes ATTR deposits ex vivo from patient-derived myocardium by macrophages, as well as in vivo from mice grafted with patient-derived ATTR fibrils in a dose- and time-dependent fashion. The biological activity of ATTR removal involves antibody-mediated activation of phagocytic immune cells including macrophages. These data support the evaluation of safety and tolerability of NI301A in an ongoing phase 1 clinical trial in patients with ATTR cardiomyopathy.
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