Can a Mendelian Randomization Study Predict the Results of a Clinical Trial? Yes and No
Pages 56-61
Antonio Abbate, Charles A. Dinarello, Mariangela Peruzzi, Sebastiano Sciarretta, Giacomo Frati and Giuseppe Biondi-Zoccai
DOI: http://dx.doi.org/10.6000/1929-6029.2016.05.01.6
Published: 08 January 2016

Abstract: Randomized controlled trials are considered at the top of the evidence hierarchy. However, in several cases randomized trials cannot be conducted or have not yet been completed. In such settings observational studies may provide important inference, yet traditional statistical adjustment methods fall short of controlling for all potential confounders, as unknown confounders cannot be taken care of by even the most sophisticated statistical tools. The mendelian randomization study is a type of research design which simultaneously exploits random transmission of genes and genetic linkage to obtain inferential estimates from the association between specific genetic variants known to modulate given risk factors and the corresponding outcomes of interests. Despite several developments in this field, there remain several areas of further research, and discrepancies between mendelian randomization studies and the corresponding randomized trials have already been recognized. Nonetheless, it is likely that this novel type of study will be used more commonly in the future, and a working knowledge of its pros, cons, and range of validity is crucial for conscientious interpretation and application. We thus aimed to concisely yet poignantly introduce the scholarly reader to this novel type of research design, notwithstanding that complementarity prevails in most cases over overlap between mendelian randomization studies and randomized trials.

Higher Performance of QuantiFERON TB Compared to Tuberculin Skin Test in Latent Tuberculosis Infection Prospective Diagnosis
Pages 62-70
Tarak Dhaouadi, Imen Sfar, Leila Mouelhi, Raoudha Tekaya, Ines Mahmoud, Jalila Bargaoui, Raoudha Daghbouj, Leila Abdelmoula, Taoufik Najjar, Taieb Ben Abdallah and Yousr Gorgi
DOI: http://dx.doi.org/10.6000/1929-6029.2016.05.01.7
Published: 08 January 2016

Abstract: The Tuberculin skin test (TST) has been used for years in the latent tuberculosis infection (LTBI) diagnosis, but it has, well-documented, low sensitivity and specificity. Interferon-γ release assays (IGRA) has been reported to be more sensitive and specific than TST. Therefore, this study aimed to evaluate the performance of a commercial IGRA, QuantiFERON^®-TB Gold In-Tube (QFT-GIT), comparatively to TST in LTBI diagnosis.

Patients and Methods: This study included 238 patients who were candidate for an anti-TNF therapy. The screening for LTBI was performed by both TST and QFT-GIT test for all patients. In order to evaluate the strength of associations, the odds ratios (OR) together with 95% confidence intervals (CI) were calculated. The correlation between QFT-GIT and TST was evaluated using κ statistics.

Results: Sixty-three (26.4%) sera were positive for QFT-GIT with a mean level of IFN-γ of about 1.18 IU/ml, while 81 (34%) patients were positive for TST. Agreement between QFT-GIT and TST was poor (37 QFT-GIT+/TST- and 55 QFT-GIT-/TST+), κ=0.09 (SD=0.065). The positivity of QFT-GIT was not influenced by BCG vaccination or by immunosuppression. Nevertheless, it was significantly associated to both history of an earlier tuberculosis disease (HETD) and its radiological sequel (RS), p=6E-7 and p=1E-8, respectively. Inversely, the TST results were not correlated to either HETD or RS, but the TST positivity was less frequent in immunosuppressed patients (45.5% vs. 73.9%), p=1E-5, OR (95% CI) = 0.29 [0.17-0.52]. Moreover, the extent of both the immunosuppression period and the time elapsed from the last BCG injection was significantly correlated to a lesser TST positivity, p=3E-12 and p=5E-7, respectively. Among the QFT-GIT-/TST+ patients (n=55) whom received an anti-TNF agent without any prophylactic treatment of LTBI, no tuberculosis was detected with a median follow-up of 78 weeks [56-109].

Conclusion: Our study suggests that the QFT-GIT has a higher performance comparatively to TST in the LTBI screening that is unaffected by either BCG vaccination or immunosuppression. Therefore, IGRAs has to replace TST especially in patients who are under consideration for an anti-TNF therapy.