J. E. Den Hartog

Are patient characteristics associated with the accuracy of hysterosalpingography in diagnosing tubal pathology? An individual patient data meta-analysis

BACKGROUND Conventional meta-analysis has estimated the sensitivity and specificity of hysterosalpingography (HSG) to be 65% and 83%. The impact of patient characteristics on the accuracy of HSG is unknown. The aim of this study was to assess by individual patient data meta-analysis whether the accuracy of HSG is associated with different patient characteristics. METHODS We approached authors of primary studies reporting on the accuracy of HSG using findings at laparoscopy as the reference. We assessed whether patient characteristics such as female age, duration of subfertility and a clinical history without risk factors for tubal pathology were associated with the accuracy of HSG, using a random intercept logistic regression model. RESULTS We acquired data of seven primary studies containing data of 4521 women. Pooled sensitivity and specificity of HSG were 53% and 87% for any tubal pathology and 46% and 95% for bilateral tubal pathology. In women without risk factors, the sensitivity of HSG was 38% for any tubal pathology, compared with 61% in women with risk factors (P = 0.005). For bilateral tubal pathology, these rates were 13% versus 47% (P = 0.01). For bilateral tubal pathology, the sensitivity of HSG decreased with age [factor 0.93 per year (P = 0.05)]. The specificity of HSG was very stable across all subgroups. CONCLUSIONS The accuracy of HSG in detecting tubal pathology was similar in all subgroups, except for women without risk factors in whom sensitivity was lower, possibly due to false-positive results at laparoscopy. HSG is a useful tubal patency screening test for all infertile couples.

Chlamydia antibody testing and diagnosing tubal pathology in subfertile women: an individual patient data meta-analysis

BACKGROUND The Chlamydia IgG antibody test (CAT) shows considerable variations in reported estimates of test accuracy, partly because of the use of different assays and cut-off values. The aim of this study was to reassess the accuracy of CAT in diagnosing tubal pathology by individual patient data (IPD) meta-analysis for three different CAT assays. METHODS We approached authors of primary studies that used micro-immunofluorescence tests (MIF), immunofluorescence tests (IF) or enzyme-linked immunosorbent assay tests (ELISA). Using the obtained IPD, we performed pooled receiver operator characteristics analysis and logistic regression analysis with a random effects model to compare the three assays. Tubal pathology was defined as either any tubal obstruction or bilateral tubal obstruction. RESULTS We acquired data of 14 primary studies containing data of 6191 women, of which data of 3453 women were available for analysis. The areas under the curve for ELISA, IF and MIF were 0.64, 0.65 and 0.75, respectively (P-value < 0.001) for any tubal pathology and 0.66, 0.66 and 0.77, respectively (P-value = 0.01) for bilateral tubal pathology. CONCLUSIONS In Chlamydia antibody testing, MIF is superior in the assessment of tubal pathology. In the initial screen for tubal pathology MIF should therefore be the test of first choice.

TLR9 KO MICE, HAPLOTYPES AND CPG INDICES IN CHLAMYDIA TRACHOMATIS INFECTION

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndrome undergoing percutaneous coronary intervention. Clopidogrel, in combination with aspirin, is associated with improvement in longterm vascular clinical outcomes in these patients and is currently the antiplatelet standard of care. However, a significant number of patients still experience secondary ischemic thrombotic events due to potential insufficient platelet inhibition or noncompliance. Therefore, the development of better and safer antiplatelet agents is of the utmost priority. Indeed, oral antiplatelet agents, such as aspirin in the ISIS-2 study and clopidogrel in the COMMIT mega trial, in moderate doses are among the very few classes of drugs that reduce absolute mortality in patients after acute vascular thrombotic events. Prasugrel (CS-747; LY-640315), an experimental third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet adenosine diphosphate P2Y(12) receptor. Preclinical and early phase clinical studies have shown that prasugrel has greater antiplatelet potency, lower variability in platelet response and faster onset of inhibition than clopidogrel. However, the doses of the drug chosen for further prasugrel developments are much higher (about 2.5-2.7 times higher) than those of conventional clopidogrel regimen(s). The recent TRITON trial assessed head-to-head prasugrel versus clopidogrel, both in addition to aspirin, and led to numerous controversies with regard to the fairness of the trial design, interpretation of its results, and the suitability of the high maintenance prasugrel dose for chronic preventive human use. We critically review various aspects of prasugrel development, focusing on the discrepancies between the official interpretation of the results and actual findings. We conclude that the benefits of prasugrel are exaggerated and that the risks are underestimated. Very careful maintenance dose selection and a flawless long-term safety profile for the new agents will become the keys to the success of future oral antiplatelet drug development.

Integration of patient characteristics and the results of Chlamydia antibody testing and hysterosalpingography in the diagnosis of tubal pathology: an individual patient data meta-analysis

BACKGROUND Tubal patency tests are routinely performed in the diagnostic work-up of subfertile patients, but it is unknown whether these diagnostic tests add value beyond the information obtained by medical history taking and findings at physical examination. We used individual patient data meta-analysis to assess this question. METHODS We approached authors of primary studies for data sets containing information on patient characteristics and results from tubal patency tests, such as Chlamydia antibody test (CAT), hysterosalpingography (HSG) and laparoscopy. We used logistic regression to create models that predict tubal pathology from medical history and physical examination alone, as well as models in which the results of tubal patency tests are integrated in the patient characteristics model. Laparoscopy was considered to be the reference test. RESULTS We obtained data from four studies reporting on 4883 women. The duration of subfertility, number of previous pregnancies and a history of previous pelvic inflammatory disease (PID), pelvic surgery or Chlamydia infection qualified for the patient characteristics model. This model showed an area under the receiver operating characteristic curve (AUC) of 0.63 [95% confidence interval (CI) 0.61-0.65]. For any tubal pathology, the addition of HSG significantly improved the predictive performance to an AUC of 0.74 (95% CI 0.73-0.76) (P < 0.001). For bilateral tubal pathology, the addition of both CAT and HSG increased the predictive performance to an AUC of 0.76 (95% CI 0.74-0.79). CONCLUSIONS In the work-up for subfertile couples, the combination of patient characteristics with CAT and HSG results gives the best diagnostic performance for the diagnosis of bilateral tubal pathology.