Alzheimer’s disease (AD) is a progressive and neurodegenerative illness which results in alterati... more Alzheimer’s disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent ...
The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NC... more The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NCT00227695) to investigate different rituximab monotherapy schedules in patients with follicular lymphoma (FL). Here, we report their long-term treatment outcome. Two-hundred and seventy FL patients were treated with 4 weekly doses of rituximab monotherapy (375 mg/m2); 165 of them, achieving at least a partial response, were randomly assigned to maintenance rituximab (375 mg/m2 every 2 months) on a short-term (4 administrations; n = 82) or a long-term (up to a maximum of 5 years; n = 83) schedule. The primary end point was event-free survival (EFS). At a median follow-up period of 10 years, median EFS was 3.4 years (95% confidence interval [CI], 2.1-5.5) in the short-term arm and 5.3 years (95% CI, 3.5-7.5) in the long-term arm. Using the prespecified log-rank test, this difference is not statistically significant (P = .39). There also was not a statistically significant difference in pro...
Nausea and vomiting are important symptoms observed in cancer patients. In a previous study, we s... more Nausea and vomiting are important symptoms observed in cancer patients. In a previous study, we showed that delayed chemotherapy-induced nausea and vomiting control could be potentially improved by skipping the administration of a 5-hydroxytryptamine 3 (5-HT3) antagonist on day 2. We report here a trial confirming our previous findings. A phase III randomized placebo-controlled trial was conducted in which patients received intravenously ondansetron 16 mg, dexamethasone 20 mg, and ranitidine 50 mg before highly/moderately emetogenic chemotherapy (day 1). Starting on day 2, all patients received metoclopramide 10 mg per oral every 8 hours (days 2, 3, and 4), dexamethasone 8 mg daily (days 2 and 3), and ranitidine 150 mg every 12 hours (days 2 and 3). Patients were randomized to receive either granisetron 0.5 mg per oral (days 2 and 3) (group A) or placebo instead of granisetron on day 2 and granisetron 0.5 mg on days 3 and 4 (group B). Seventy-three patients were enrolled. Groups were similar regarding clinical characteristics, despite better control during the acute phase of chemotherapy-induced nausea and vomiting in group A (P = 0.04). Complete delayed protection from nausea and vomiting (DCPNV) from day 2 to 5 was similar in both groups (30% vs. 32%; P = 0.5). Analyzing DCPNV by logistic regression multivariate analyses, acute complete protection from nausea and vomiting (P = 0.001) and study group (P = 0.06) were independently associated with DCPNV. Selecting patients who achieved acute complete protection from nausea and vomiting, we observed that group B had a superior DCPNV (85% vs. 50%, P = 0.02). DCPNV can be improved just by skipping day 2 of 5-HT3-antagonists. Future studies should compare this inexpensive strategy with NK1-antagonists or second generation 5-HT3-antagonists.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, Jan 22, 2018
Cancer treatment-induced bone loss (CTIBL) is a long-term side effect of breast cancer therapy. B... more Cancer treatment-induced bone loss (CTIBL) is a long-term side effect of breast cancer therapy. Both calcitriol and weight-bearing exercise improve bone metabolism for osteoporotic patients, but are unproven in a breast cancer population. We used a novel high-dose calcitriol regimen with an individualized exercise intervention to improve bone metabolism in breast cancer survivors. We accrued 41 subjects to this open label, 2 × 2 factorial, randomized feasibility trial. Breast cancer survivors were randomized to receive the following: (1) calcitriol (45 micrograms/week), (2) individualized exercise with progressive walking and resistance training, (3) both, or (4) a daily multivitamin (control condition) for 12 weeks. Primary outcomes included changes in biomarkers of bone formation, bone resorption, and the bone remodeling index, a composite measure of bone formation and resorption. Safety measures included clinical and biochemical adverse events. A main effect analysis was used for...
The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth f... more The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients. The aim of this study was to assess the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated NSCLC. For this cost-effectiveness analysis, we extracted individual patient data from the FLAURA randomized clinical trial and used findings of our earlier meta-analysis to develop a decision-analytic model and determine the cost-effectiveness of osimertinib (AZD9291) compared with first- and second-generation EGFR-TKIs over a 10-year time hor...
Summary Introduction: In patients with essential thrombocythemia (ET), the vascular complications... more Summary Introduction: In patients with essential thrombocythemia (ET), the vascular complications contribute to morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET-thrombosis) has recently been proposed. We present the application of this score and compare its results with the usual classification system. Method: We retrospectively evaluated the characteristics and risk factors for thrombosis of 46 patients with a diagnosis of ET seen in the last 6 years at Faculdade de Medicina do ABC (FMABC). Results: Thrombosis in the arterial territory was more prevalent than in venous sites. We observed that cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) were also risk factors for thrombosis (p<0.001). Age over 60 years and presence of JAK2 V617F mutation were not associated with the occurrence of thrombotic events. No patient clas...
Alzheimer’s disease (AD) is a progressive and neurodegenerative illness which results in alterati... more Alzheimer’s disease (AD) is a progressive and neurodegenerative illness which results in alterations in cognitive development. It is characterized by loss/dysfunction of cholinergic neurons, and formation of amyloid plaques, and formation of neurofibrillary tangles, among other changes, due to hyperphosphorylation of tau-protein. Exposure to pesticides in humans occurs frequently due to contact with contaminated food, water, or particles. Organochlorines, organophosphates, carbamates, pyrethroids and neonicotinoids are associated with the most diagnosed incidents of severe cognitive impairment. The aim of this study was to determine the effects of these pesticides on the phosphorylation of tau protein, and its cognitive implications in the development of AD. It was found that exposure to pesticides increased the phosphorylation of tau protein at sites Ser198, Ser199, Ser202, Thr205, Ser396 and Ser404. Contact with these chemicals altered the enzymatic activities of cyclin-dependent ...
The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NC... more The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NCT00227695) to investigate different rituximab monotherapy schedules in patients with follicular lymphoma (FL). Here, we report their long-term treatment outcome. Two-hundred and seventy FL patients were treated with 4 weekly doses of rituximab monotherapy (375 mg/m2); 165 of them, achieving at least a partial response, were randomly assigned to maintenance rituximab (375 mg/m2 every 2 months) on a short-term (4 administrations; n = 82) or a long-term (up to a maximum of 5 years; n = 83) schedule. The primary end point was event-free survival (EFS). At a median follow-up period of 10 years, median EFS was 3.4 years (95% confidence interval [CI], 2.1-5.5) in the short-term arm and 5.3 years (95% CI, 3.5-7.5) in the long-term arm. Using the prespecified log-rank test, this difference is not statistically significant (P = .39). There also was not a statistically significant difference in pro...
Nausea and vomiting are important symptoms observed in cancer patients. In a previous study, we s... more Nausea and vomiting are important symptoms observed in cancer patients. In a previous study, we showed that delayed chemotherapy-induced nausea and vomiting control could be potentially improved by skipping the administration of a 5-hydroxytryptamine 3 (5-HT3) antagonist on day 2. We report here a trial confirming our previous findings. A phase III randomized placebo-controlled trial was conducted in which patients received intravenously ondansetron 16 mg, dexamethasone 20 mg, and ranitidine 50 mg before highly/moderately emetogenic chemotherapy (day 1). Starting on day 2, all patients received metoclopramide 10 mg per oral every 8 hours (days 2, 3, and 4), dexamethasone 8 mg daily (days 2 and 3), and ranitidine 150 mg every 12 hours (days 2 and 3). Patients were randomized to receive either granisetron 0.5 mg per oral (days 2 and 3) (group A) or placebo instead of granisetron on day 2 and granisetron 0.5 mg on days 3 and 4 (group B). Seventy-three patients were enrolled. Groups were similar regarding clinical characteristics, despite better control during the acute phase of chemotherapy-induced nausea and vomiting in group A (P = 0.04). Complete delayed protection from nausea and vomiting (DCPNV) from day 2 to 5 was similar in both groups (30% vs. 32%; P = 0.5). Analyzing DCPNV by logistic regression multivariate analyses, acute complete protection from nausea and vomiting (P = 0.001) and study group (P = 0.06) were independently associated with DCPNV. Selecting patients who achieved acute complete protection from nausea and vomiting, we observed that group B had a superior DCPNV (85% vs. 50%, P = 0.02). DCPNV can be improved just by skipping day 2 of 5-HT3-antagonists. Future studies should compare this inexpensive strategy with NK1-antagonists or second generation 5-HT3-antagonists.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, Jan 22, 2018
Cancer treatment-induced bone loss (CTIBL) is a long-term side effect of breast cancer therapy. B... more Cancer treatment-induced bone loss (CTIBL) is a long-term side effect of breast cancer therapy. Both calcitriol and weight-bearing exercise improve bone metabolism for osteoporotic patients, but are unproven in a breast cancer population. We used a novel high-dose calcitriol regimen with an individualized exercise intervention to improve bone metabolism in breast cancer survivors. We accrued 41 subjects to this open label, 2 × 2 factorial, randomized feasibility trial. Breast cancer survivors were randomized to receive the following: (1) calcitriol (45 micrograms/week), (2) individualized exercise with progressive walking and resistance training, (3) both, or (4) a daily multivitamin (control condition) for 12 weeks. Primary outcomes included changes in biomarkers of bone formation, bone resorption, and the bone remodeling index, a composite measure of bone formation and resorption. Safety measures included clinical and biochemical adverse events. A main effect analysis was used for...
The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth f... more The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients. The aim of this study was to assess the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated NSCLC. For this cost-effectiveness analysis, we extracted individual patient data from the FLAURA randomized clinical trial and used findings of our earlier meta-analysis to develop a decision-analytic model and determine the cost-effectiveness of osimertinib (AZD9291) compared with first- and second-generation EGFR-TKIs over a 10-year time hor...
Summary Introduction: In patients with essential thrombocythemia (ET), the vascular complications... more Summary Introduction: In patients with essential thrombocythemia (ET), the vascular complications contribute to morbidity and mortality. To better predict the occurrence of thrombotic events, an International Prognostic Score for Thrombosis in Essential Thrombocythemia (IPSET-thrombosis) has recently been proposed. We present the application of this score and compare its results with the usual classification system. Method: We retrospectively evaluated the characteristics and risk factors for thrombosis of 46 patients with a diagnosis of ET seen in the last 6 years at Faculdade de Medicina do ABC (FMABC). Results: Thrombosis in the arterial territory was more prevalent than in venous sites. We observed that cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) were also risk factors for thrombosis (p<0.001). Age over 60 years and presence of JAK2 V617F mutation were not associated with the occurrence of thrombotic events. No patient clas...
Uploads