Abstract
Purpose
Diagnostic delay is a major problem concerning common variable immunodeficiency (CVID). We aimed to determine the pattern of general practitioner (GP) consultations in individuals diagnosed with CVID within 3 years before the diagnosis and whether the risk of diagnosis was associated with the frequency of consultations or character of examinations.
Methods
We conducted a nested case-control study, identifying 132 adult CVID patients and 5940 age- and gender-matched controls from national registers during 1997–2013. We used conditional logistic regression to calculate the odds ratios (OR) and 95% confidence intervals (95%CI).
Results
The median number of consultations among individuals with CVID was more than twice that of the controls in all 3 years (3rd, 10; 2nd, 11.5; and 1st, 15.4 vs. 4). We found a statistically significant association between the number of consultations and the risk of a subsequent CVID diagnosis, independent of age and gender, but strongest in the individuals < 40 years. In the 3rd year before diagnosis, having 9–15 consultations compared with 1–4 was associated with an OR (95%CI) of 5.0 (2.3–10.9), 2.4 (1.1–5.4), and 1.3 (0.3–5.3) for those aged 18–40, 41–60, and > 60, respectively. Several examinations (i.e., blood tests for inflammation/infection and pulmonary function test) were associated with increased odds of a subsequent CVID diagnosis.
Conclusion
The risk of a CVID diagnosis was highly related to both the number of consultations and the character of examinations performed by the GP. CVID should be a differential diagnosis among patients with multiple consultations, especially in patients < 40 years old.
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Acknowledgments
The authors of this study greatly appreciate the work of Eva Sandberg and Sören Möller (Odense Patient Data Explorative Network), for independent statistical guidance and supervision, as well as counseling on register-based research conducted in Denmark. We are grateful to all physicians who have provided data to the Danish adult CVID cohort, as well as the patients included in this study. This study could not have been completed without the help of the Danish adult CVID cohort.
Data Availability Statement
The datasets for this manuscript are not publicly available as the data on both cases and controls are confidential, and access to the raw data would allow for the identification of personal microdata. To review the raw data, as well as .do files, a data handler agreement with the Danish state (the Danish Data Protection Agency) is needed. If access to the datasets is to be uptrained anyways, a request should be sent to Frederik V. Antonsen (Frederik.veitland.antonsen2@rsyd.dk). The request has to be processed by the Danish Protection Agency, and FA will serve as a correspondent between the parties.
Funding
FI received funding from the University of Southern Denmark as salary for 6 months. The study was mainly funded by the Department of Infectious Diseases at Odense University Hospital and in part funded by an independent grant from Odense University Hospital.
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As the principal investigator, FI had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. IJ and LR are responsible for the study concept and design. FI, RI, and LR are responsible for the analysis and interpretation of data. FI is responsible for drafting of the manuscript.FI, LR, RI, TK, AH, CL, IJ, LW, and TN are responsible for the critical revision of the manuscript for important intellectual content. LW, CL, TK, AH, and TN are responsible for obtaining patient data. IJ and LR are responsible for the study supervision.
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TK has served as a lecturer and attended conferences sponsored by Baxter, Baxalta, Shire, and CSL Behring. CL has served as a lecturer and attended conferences sponsored by Shire, CSL Behring, and Octapharma. AH has received an unrestricted research grant from CSL Behring. All other authors declare that they have no conflict of interest.
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Ilkjær, F.V., Rasmussen, L.D., Martin-Iguacel, R. et al. How to Identify Common Variable Immunodeficiency Patients Earlier: General Practice Patterns. J Clin Immunol 39, 641–652 (2019). https://doi.org/10.1007/s10875-019-00666-9
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DOI: https://doi.org/10.1007/s10875-019-00666-9