Data mining for signals in spontaneous reporting databases: proceed with caution

PURPOSE: To provide commentary and points of caution to consider before incorporating data mining as a routine component of any Pharmacovigilance program, and to stimulate further research aimed at better defining the predictive value of these new tools as well as their incremental value as an adjunct to traditional methods of post-marketing surveillance. METHODS/RESULTS: Commentary includes review of current data mining methodologies employed and their limitations, caveats to consider in the use of spontaneous reporting databases and caution against over-confidence in the results of data mining. CONCLUSIONS: Future research should focus on more clearly delineating the limitations of the various quantitative approaches as well as the incremental value that they bring to traditional methods of pharmacovigilance.     

Time-course analyses addressing the acquisition of DBA lectin reactivity in mouse lymphoid organs and uterus during the first week of pregnancy

Terminal differentiation of uterine natural killer (uNK) cells is induced in humans and mice at the time of endometrial decidualization. In mice, commitment to this lineage is first recognized at gestation day (gd)5.5 when small, non-granulated lymphocytes in the mesometrial decidua basalis become histochemically reactive with the lectin Dolichlos biflorus agglutinin (DBA). Transplantation experiments in mice have shown that the self-renewing progenitors of uNK cells are present in peripheral rather than uterine tissues. While lymphoid tissues of virgin mice lack DBA lectin reactive putative uNK cell precursors or progenitors, peripheral organs have not been systematically examined in female mice during early pregnancy while the uNK cell population is becoming established. Here we report such a study in gd0.5–7.5 random bred mice. Only mesenteric lymph nodes showed a transient gain in DBA lectin reactive lymphocytes between gd0.5 and 4.5. These cells had cytoplasmic but almost no surface DBA lectin reactivity. This study indicates that the decidual environment is unique and locally promotes DBA lectin surface expression in terminally differentiating uNK cells.     

Evaluation and management of recurrent early pregnancy loss

Recurrent pregnancy loss affects up to 5% of couples trying to establish a family. Evaluation classically begins after 3 consecutive miscarriages of less than 10 weeks of gestation but may be warranted earlier if a prior miscarriage was found to be euploid, or if there is concomitant infertility and/or advancing maternal age. The evaluation begins with an extensive history and physical, followed by a diagnostic screening protocol. Management must be evidence-based; unproven treatments should be avoided. If no factor is identified, many couples will still eventually have a successful pregnancy outcome with supportive therapy alone.