Full agreement with global introspection was not found for any level of causality assessment. Confounding variables were found to be associated with low levels of agreement between decision algorithms and the GI method compromising the algorithms' sensitivity and specificity.

Decisional algorithms are sensitive methods for the detection of ADRs, but they present poor specificity. A reference method was not identified. Algorithms do not replace GI and are not definite alternatives in the individual causality assessment of suspected ADRs.

The head and neck squamous cell carcinoma (HNSCC) population consists mainly of high-risk for recurrence and locally advanced stage patients. Increased knowledge of the HNSCC genomic profile can improve early diagnosis and treatment outcomes. The development of models to identify consistent genomic patterns that distinguish HNSCC patients that will recur and/or develop metastasis after treatment is of utmost importance to decrease mortality and improve survival rates. In this study, we used array comparative genomic hybridization data from HNSCC patients to implement a robust model to predict HNSCC recurrence/metastasis. This predictive model showed a good accuracy (>80%) and was validated in an independent population from TCGA data portal. This predictive genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q and 17p, where several upstream and downstream members of signaling pathways that lead to an increase in cell proliferation and invasion are mapped. The introduction of genomic predictive models in clinical practice might contribute to a more individualized clinical management of the HNSCC patients, reducing recurrences and improving patients’ quality of life. The power of this genomic model to predict the recurrence and metastases development should be evaluated in other HNSCC populations.

This trial failed to demonstrate superiority of the novel ABM/P-15 hydrogel therapeutic modality over the standard ABM/ P-15 particulate graft in the treatment of intrabony periodontal defects.

It was not found any safety signal issued by drug regulatory agencies exclusively generated by DA. More research devoted to this issue is needed, since the value of these methods on drug safety signaling and their impact on drug regulation actions remains to be established.

Background/Objective: The Janus kinases are cytoplasmic tyrosine kinases associated with membrane cytokine receptors that mediate signaling of multiple cytokines and growth factors, contributing to the pathogenesis of multiple autoimmune disorders. Janus kinase inhibitors (JKIs) are a new class of targeted therapies with proven efficacy in treating rheumatoid arthritis but are associated with an increased risk of infections. This study is aimed at assessing the risk of cardiovascular and venous thromboembolic events associated with JKIs in patients with rheumatoid arthritis.Methods: PUBMED, EMBASE, Cochrane Library, and clinicaltrials.gov were searched to identify randomized controlled trials evaluating the efficacy and safety of JKIs in patients with rheumatoid arthritis. The outcomes assessed were the risk of major adverse cardiovascular events, venous thromboembolic events, and any cardiovascular event. Sensitivity analysis disaggregated the results according to background therapy, JKI licensed doses, and studies' methodological quality.Results: Forty-two randomized controlled trials met the inclusion criteria.No statistically significant risk differences were observed between the JKIs for any of the assessed outcomes. Compared with placebo, tofacitinib (odds ratio, 0.32; 95% confidence interval, 0.11-0.89) reduces the risk of venous thromboembolism. The results of the sensitivity analysis are in line with the initial findings.Conclusions: Current evidence suggests that the risk of cardiovascular and venous thromboembolic events is similar among the JKIs. Postmarketing pharmacovigilance evidence will be of utmost importance in confirming the cardiovascular safety of these drugs.

To study the contractile responses of the human basilar artery to 5-hydroxytryptamine (5-HT), sumatriptan, zolmitriptan and naratriptan, and to characterize the 5-HT receptor subtypes involved on those responses, human basilar artery rings were prepared for isometric contraction, protein isolation and Western blotting analysis. Concentration-response (CR) curves were made for all agonists in the absence or in the presence of selective antagonists at 5-HT1B (cyanopindolol), 5-HT1D (BRL 15,572) and 5-HT2 (ketanserin) receptors. We also used anti-5-HT1B and 5-HT1D receptor antibodies to search for the expression of protein of these receptor subtypes. From the CR curves, the relative intrinsic activity and potency of these agonists were determined. The ranking order for the intrinsic activity was 5-HT > or = sumatriptan > zolmitriptan > or = naratriptan, whereas that for the potency was zolmitriptan > or = 5-HT > or = sumatriptan > naratriptan. Our results also show that the human basilar artery seems to have a mixed population of 5-HT1B/1D receptors mediating the contractile response to triptans, which is also suggested by the expression of both receptor subtypes. There is also a population of 5-HT2 receptors for which the antimigraine drugs used have no apparent affinity. From this study, one can conclude that the second generation triptans have lower contractile capacity than sumatriptan, suggesting that they have a better cerebrovascular safety profile.

IN TRO DU ÇÃO O uso ra ci o nal dos me di ca men tos pres su põe que os doen tes re ce bam os me di ca men tos apro pria dos para as suas ne ces si da des tera pêu ti cas, em do ses e quan ti da des ajus tadas aos tem pos de tra ta men to e ao mais bai xo cus to possí vel. 1 As sim, a di men são das em ba la gens cons ti tui uma com po nen te da te ra pêu ti ca ra ci o nal, cuja ina de qua ção, ali a da à não ade são à te ra pêu ti ca, foi iden ti fi ca da como fac tor ge ra dor de ine fi ci ên cia na alo ca ção dos re cur sos de saú de. 2-9 Além do des per dí cio de re cur sos es cas sos, os me di ca men tos não uti li za dos po dem ain da re sul tar num ris co acres ci do de di mi nu i ção da efec ti vi da de, 10-13 in toxi ca ção aci den tal 14,15 ou con ta mi na ção am bien tal. 16-18