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Major bleeding in TSOACs when compared with warfarin: selected studies Risk of major Risk of GI Risk of intracranial Agent bleeding (95% CI) bleeding (95% CI) bleeding (95% CI) All AF32 RR 0 medicine used for pink eye generic aricept 10mg mastercard. They found that the incidence rate of ICH on and using the TIMI definition medicine x pop up order aricept with a visa, major bleeding occurred in 0 medications while breastfeeding purchase aricept discount. There was Most importantly for the clinician, it is clear that the HR for a signal suggesting an increased incidence of major GI bleeding of bleeding (compared with warfarin) is similar irrespective of defini- 34. Consis- Edoxaban tent with this, it appears that when major bleeding develops, those At the time of this writing, edoxaban is not yet available in the randomized to dabigatran have shorter intensive care unit stays and United States. The ENGAGE AF-TIMI 48 trial21 noted that the rate a trend toward improved mortality compared with patients on of major bleeding was 3. This highlights These drugs inhibit factor Xa, the first step in the common pathway the fact that, as with the other factor Xa inhibitors, the risk of of the coagulation cascade, in a dose-dependent fashion. The risk is slightly lower with factor Xa Overall, the risk of major bleeding associated with VTE therapy inhibitors than warfarin (OR 0. Impor- appears lower with TSOACs than with warfarin [relative risk tantly, the risk of the most severe type of bleeding, ICH, was 22 (RR) 0. Specific factors that modify this substantially lower with TSOACs (OR 0. Therefore, should be applied to those who are older, those with renal although this class of agents is associated with important major insufficiency, and those on concomitant antiplatelet agents or bleeding risks, these risks appear to be consistently lower than those NSAIDs. It is not yet clear whether there are clinically relevant differences in bleeding risks between different factor Xa inhibitors. Direct thrombin (factor IIa) inhibitors For patients on dabigatran for VTE, major bleeding appears to occur Rivaroxaban in 0. Rivaroxaban Apixaban For patients on rivaroxaban for VTE, major bleeding occurred in The ARISTOTLE trial highlighted how major bleeding risk can 0. Indirect comparisons Renal insufficiency Although numerous individual studies compare the bleeding rates Patients with renal insufficiency appear to be at increased major bleeding risk with anticoagulants. For example, the ROCKET-AF population showed higher CHADS2 scores than other trials, suggest- Those with moderate renal insufficiency are at even higher risk, ing a higher-risk population, so that the event rates for rivaroxaban with rates of major bleeding of 6. However, the apparent benefit of TSOACs was less obvious (OR for major bleeding 0. It is Some groups have attempted to compare different agents indi- likely that this finding is due to smaller numbers of patients with rectly using a common comparator (warfarin). However, the point estimate is similar risk to be lower with dabigatran than with rivaroxaban, but this and the trend toward lower bleeding rates with TSOACs is relatively was only significant for the lower 110 mg dose (OR 0. They also noted Some patients are at such increased thromboembolic risk that the risk of major bleeding to be lower with apixaban than with consideration is given to providing both an oral anticoagulant and high-dose dabigatran (OR 0. This issue appears to be most common after an rivaroxaban (OR 0. However, such an approach found similar results, with apixaban being associated with a should be considered with caution because concomitant therapy lower risk of major bleeding than dabigatran (RR 0. This trial was halted early because any benefit was gested that apixaban demonstrates a lower overall bleeding risk outweighed by major bleeding, which increased from 0. For the most part, unlike warfarin, no clinically available tools exist to detect drug levels of the TSOACs. However, it is likely that Advanced age plasma concentration influences bleeding risk. A substudy of the Older patients appear to be at consistently higher risk of bleeding RE-LY study of dabigatran for AF found that the risk of major complications while being anticoagulated. That said, such patients There has been concern that this information was not made available are also at higher risk for thromboembolism and can often derive in a timely manner to the public. Overall, serum concentrations of TSOACs, like high INR levels in warfarin it appears that TSOACs are associated with lower bleeding risks patients, carry elevated bleeding risks, it has been consistently than warfarin for younger patients (RR 0.

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Sensiti- vity and specificity of multimodal and ultrasound use of chemotherapeutic agents researched in clini- screening for ovarian cancer symptoms xanax overdose buy cheap aricept 10mg line, and stage distribution of cal trials in affluent societies may differ significantly detected cancers: results of the prevalence screen of the in less-developed countries due to differences in UK Collaborative Trial of Ovarian Cancer Screening genetic medicine quizlet order 5 mg aricept with mastercard, environmental treatment goals for depression buy discount aricept 5 mg, lifestyle and nutritional (UKCTOKS). Lancet Oncol 2009;10:327–40 factors and health service infrastructure in the 8. Ultrasound charac- teristics of different types of adnexal malignancies. Quality of life studies col Oncol 2006;102:41–8 assessing treatment effects in low-resourced com- 9. Prolonged hospi- statements on the management of ovarian cancer: final tal stay, treatment side-effects, lack of post-treatment document of the 3rd International Gynecologic Cancer support, for a disease with limited survival may be Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Neoadjuvant chemo- ACKNOWLEDGEMENT therapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010;363:943–53 Dr MEL van der Burg, PhD, medical oncologist, 11. Gynecol Oncol 1992;47:159–66 Guideline for staging surgery early-stage ovarian 12. Role of primary surgery in cancer stage FIGO IA–IIA advanced ovarian cancer. Impact of adjuvant • Inspection, palpation and resection chemotherapy and surgical staging in early-stage ovarian N Median abdominal laparotomy carcinoma: European Organisation for Research and N Cytologic whashing of ascites Treatment of Cancer-Adjuvant ChemoTherapy in Ovar- N Inspection and palpation of abdomen and ian Neoplasm trial. International pelvis Collaborative Ovarian Neoplasm trial 1: a randomized N Uterus and adnexal extirpation trial of adjuvant chemotherapy in women with early- N Omentectomy stage ovarian cancer. J Natl Cancer Inst 2003;95:125–32 N (Appendectomy at mucinous adenocarcino- 15. International ma) Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel • Staging biopsies randomized phase III trials of adjuvant chemotherapy in N Biopsy of all sites where the ovary was adhe- patients with early-stage ovarian carcinoma. J Natl sive Cancer Inst 2003;95:105–12 N Biopsy every lesion suspicious for tumor 16. Surgical stag- N ‘Blind’ biopsy of the peritoneum from: ing and treatment of early ovarian cancer: long-term analysis from a randomized trial. J Natl Cancer Inst 2010; • Bladder 102:982–7 • Pouch of Douglas 17. Protocol • Lateral pelvic sidewalls (fossa ovarica) development for ovarian cancer treatment in Kenya: a • Left and right paracolic grooves brief report. Int J Gynecol Cancer 2011;21:424–7 • Right diaphragmatic site 18. High dose cisplatin compared with high dose cyclophosphamide in the management • Lymph node dissection, or sampling of at least 2 of advanced epithelial ovarian cancer (FIGO stages III lymph nodes from the following sites: and IV): report from the North Thames Cooperative N Para-aortic lymph nodes Group. BMJ 1985;290:889–93 N Lymph nodes at the common iliac vessels 19. Randomized N Lymph nodes at the internal iliac vessels intergroup trial of cisplatin–paclitaxel versus cisplatin– cyclophosphamide in women with advanced epithelial N Lymph nodes at the external iliac vessels ovarian cancer: three-year results. J Natl Cancer Inst N Lymph nodes at the obturator fossa 2000;92:699–708 20. The International Collaborative Ovarian Neoplasm NOTE: In young patients with ovarian cancer lim- Group (ICON) Group. Paclitaxel plus carboplatin ver- ited to one ovary and who want to preserve their sus standard chemotherapy with either single agent fertility, tumor resection can be limited to one carboplatin or cyclophosphamide, doxorubicin, and cis- ovary + omentectomy and optimal surgical staging. Long-term follow-up confirms a survival advantage of the paclitaxel–cisplatin regimen over the cyclophospha- mide–cisplatin combination in advanced ovarian cancer. Intraperitoneal chemotherapy in patients with advanced ovarian cancer: the con view. The effect of debulking surgery after induction chemo- therapy on the prognosis in advanced epithelial ovarian cancer.

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