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01, p less then 0.01). CONCLUSION Within academic medical schools, women remain under-represented in obstetrics and gynecology departmental and cancer center leadership. Potential benefits to gynecologic oncology divisions of inclusion women and surgically focused leadership were identified. OBJECTIVE Low-risk non-metastatic gestational trophoblastic neoplasia (GTN) has been treated with single agent chemotherapy, but second curettage is emerging as an alternative strategy with reported cure rates of 40%. We sought to estimate the cost-effectiveness of second curettage as the first line treatment of low-risk GTN. METHODS A decision-analytic model was created using TreeAge software to compare costs and outcomes for women with WHO staged low-risk GTN undergoing treatment with 5-day methotrexate (MTX), biweekly pulsed actinomycin-D, or second curettage. Probabilities were derived from the literature. Outcomes of interest included side effects from chemotherapy, need for additional agents, hemorrhage, uterine perforation, and cure rates. Utilities were applied to discounted life expectancy at a rate of 3% to generate quality adjusted life years (QALYs). https://www.selleckchem.com/products/tegatrabetan.html Sensitivity analyses were then performed in order to assess the robustness of our assumptions. RESULTS Of the three treatment arms, MTX was associated with the lowest cost and had similar QALYs to the other studied modalities. Second curettage was associated with 49 additional cures when applied to a theoretic cohort of 1000 women, as well as an additional 83 hemorrhages and 17 uterine perforations. Sensitivity analysis on the cure rate of second curettage revealed that second curettage was not cost-effective over MTX unless its probability of cure was 98%. CONCLUSION Our study found 5-day MTX was the cost-effective strategy for treatment of women with low-risk, non-metastatic GTN when compared to second curettage and actinomycin-D. In a carefully selected patient population, second curettage may be an additional treatment strategy. OBJECTIVE To assess the incidence of vulvar high-grade precancerous lesions and cancer in Denmark during 1997-2018. METHODS We identified incident vulvar cancer cases in the Danish Cancer Registry and incident cases of vulvar precancerous lesions in the Danish Pathology Register. We calculated age-standardized incidence rates of vulvar squamous cell carcinoma (VSCC), non-SCC and precancerous lesions, and age-specific incidence rates of VSCC and precancerous lesions. Incidence trends were evaluated using linear Poisson regression to estimate the average annual percentage change (AAPC). For vulvar precancerous lesions, trends were evaluated in the period before (1997-2007) and after (2008-2018) implementation of HPV vaccination. RESULTS In the 22-year study period, the age-standardized incidence rate of VSCC increased from 1.23 (1997-1998) to 1.98 per 100,000 (2017-2018), corresponding to an average yearly increase of 2.95% (95%CI 2.15-3.75). The incidence of non-SCC increased only slightly. Overall, the incidence of vulvar precancerous lesions increased (AAPC = 2.38%; 95%CI 1.75-3.02). After implementation of HPV vaccination, the incidence of vulvar precancerous lesions decreased significantly in women aged less then 20 (AAPC = -22.10% (95%CI -35.27 to -6.26)) and 20-29 years (AAPC = -6.57, 95% CI -10.63 to -2.33), whereas the incidence increased in the majority of age groups ≥50 years. CONCLUSIONS Overall, the incidence of VSCC and vulvar precancerous lesions increased during 1997-2018. However, after introduction of HPV vaccination, the incidence of vulvar precancerous lesions decreased among women aged less then 20 and 20-29 years, pointing towards a possible effect of HPV vaccination in this group. This development should be followed in the future. The clinicopathological and prognostic significance of olfactomedin-4 (OLFM4) expression has not yet been elucidated in extrahepatic bile duct carcinomas (EBDCs). Immunohistochemical analysis of OLFM4 expression in 31 normal biliary epithelia, 33 biliary intraepithelial neoplasias (BilINs), and 180 surgically resected EBDCs (54 perihilar and 126 distal) was performed and was used to analyze clinicopathological variables including patient survival. The expression of OLFM4 showed a progressive increase from normal biliary epithelia (0.2 ± 0.4) to BilINs (2.8 ± 3.2) to EBDCs (4.6 ± 4.2; P less then 0.001). OLFM4 was highly expressed in 26.1% (47/180) of the EBDC cases, and high OLFM4 levels were more frequently observed in tumors with nodular growth (P = 0.029), well differentiation (P = 0.011), and lower T-category (P = 0.025) and stage grouping (P = 0.013). Patients with EBDC having high expression of OLFM4 had better survival than those with low expression of OLFM4 (median, 43.3 vs. 29.2 months; P = 0.037). OLFM4 might play an important role in carcinogenesis and in the progression from BilINs to EBDCs. High OLFM4 expression predicted less aggressive clinical behavior in patients with EBDC. Neuropathic pain remains a significant unmet medical need. Several recommendations have recently been proposed concerning pharmacotherapy, neurostimulation techniques and interventional management, but no comprehensive guideline encompassing all these treatments has yet been issued. We performed a systematic review of pharmacotherapy, neurostimulation, surgery, psychotherapies and other types of therapy for peripheral or central neuropathic pain, based on studies published in peer-reviewed journals before January 2018. The main inclusion criteria were chronic neuropathic pain for at least three months, a randomized controlled methodology, at least three weeks of follow-up, at least 10 patients per group, and a double-blind design for drug therapy. Based on the GRADE system, we provide weak-to-strong recommendations for use and proposal as a first-line treatment for SNRIs (duloxetine and venlafaxine), gabapentin and tricyclic antidepressants and, for topical lidocaine and transcutaneous electrical nerve stimulation specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a second-line treatment for pregabalin, tramadol, combination therapy (antidepressant combined with gabapentinoids), and for high-concentration capsaicin patches and botulinum toxin A specifically for peripheral neuropathic pain; a weak recommendation for use and proposal as a third-line treatment for high-frequency rTMS of the motor cortex, spinal cord stimulation (failed back surgery syndrome and painful diabetic polyneuropathy) and strong opioids (in the absence of an alternative). Psychotherapy (cognitive behavioral therapy and mindfulness) is recommended as a second-line therapy, as an add-on to other therapies. An algorithm encompassing all the recommended treatments is proposed.
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