Reduce susceptibility to cefiderocol in gram negative bacteria in children: Is hope already lost before it's even arrived?

BACKGROUND: In last years the diffusion of carbapenem resistance in Gram-negative bacteria (CR-GNB) is increasing worldwide, mainly due to the expression of carbapenemases. Cefiderocol has molecular characteristics that ideally confers activity against all CR-GNB, but resistant strains have already been identified. We describe cefiderocol susceptibility profile among multi-drug resistant Gram-negative isolated from pediatric patients. METHODS: Prospective, single pediatric center study, 1st January 2020-15th June 2023. All GNB carbapenemases producers or phenotypically carbapenem-resistant isolated in the study period were tested for cefiderocol susceptibility. Clinical and microbiological data were collected. A descriptive analysis was performed, comparing the groups of cefiderocol-resistant vs. cefiderocol-susceptible Enterobacterales and non-fermenting Gram-negative bacteria (NF-GNB). RESULTS: Forty-seven GNB were tested for cefiderocol susceptibility; 38% were cefiderocol-resistant: 16/30 (52%) among Enterobacterales and 2/17 (12%) among NF-GNB. None of the patients were previously exposed to cefiderocol. Looking at Enterobacterales, resistance to ceftazidime/avibactam was higher among cefiderocol-resistant vs. cefiderocol-susceptible strains (62% vs 36%, respectively), as MBL expression (67% vs. 36%, respectively). Too few NF-GNB were cefiderocol-resistance to draw any conclusion. No difference in ICU admission and mortality was identified comparing cefiderocol-resistant vs. susceptible strains. Patients colonized/infected by cefiderocol-resistant strains had been previously hospitalized more frequently. CONCLUSION: In our cohort cefiderocol resistance was mostly registered among Enterobacterales, and especially among MBL producers' strains (that were alongside resistant to ceftazidime/avibactam). This could be explained by the known possible cross resistance mechanism among ceftazidime/avibactam and cefiderocol. Also, correlation of cefiderocol-resistance with previous hospitalization could be associated with horizontal resistance transmission. Looking at our data, we believe that cefiderocol should be use cautiously, especially empirically and in monotherapy, due to the high resistance rate.

Critical assessment of resource waste in staging and follow-up of breast cancer.

BACKGROUND: Breast cancer is a public health problem with both high incidence and cure rates. After treatment, patients are monitored for long periods of time due to the risk of recurrence. Thus, staging and follow-up strategies should consider not only the best results for the patient but also its costs for the public health system. OBJECTIVE: The objective of this study was to quantify the waste of resources on breast cancer follow-up and evaluate its impact on the public health system. METHODS: This is a retrospective analysis of consecutive medical records to identify the intervals between consultations and tests used for staging and during the first 2 years of follow-up of patients with breast cancer treated at a public hospital in Brazil. Data were compared with the guidelines of the main international consensus. RESULTS: Medical records of 60 consecutive patients treated in 2018 were selected, of whom 52 had 2 or more years of follow-up, and 8 had only 1 year of complete follow-up. A total of 34 patients (56.67%) underwent excessive examinations for stating. During follow-up, 125 surplus consultations were performed (33.6%). In this phase, 111 surplus exams were also performed, representing an increase of 100.9%. A total of 423 laboratory tests were performed for 18 patients in the first year and 229 tests for 14 patients in the second year. CONCLUSION: Excessive tests and consultations significantly burdened the Unified Health System without any benefit to patients. Better adherence to staging and follow-up recommendations could reduce costs and optimize the limited resources used in the public health system.

Real-Life Vancomycin Therapeutic Drug Monitoring in Coagulase-Negative Staphylococcal Bacteremia in Neonatal and Pediatric Intensive Care Unit: Are We Underestimating Augmented Renal Clearance?

Bloodstream infections (BSI) from coagulase-negative-staphylococci (CoNS) are among the most frequent healthcare-related infections. Their treatment involves the use of vancomycin, a molecule whose optimal pharmacokinetic/pharmacodynamic (PK/PD) target for efficacy and safety is an area-under-curve/minimum inhibitory concentration (AUC/MIC) ratio ≥ 400 with AUC < 600. BSIs from CoNS in pediatric and neonatal intensive care unit that occurred at the Gaslini Institute over five years were evaluated to investigate the efficacy of vancomycin therapy in terms of achieving the desired PK/PD target and determining whether any variables interfere with the achievement of this target. AUC/MIC ≥ 400 with AUC < 600 at 48 and 72 h after therapy initiation was achieved in only 21% of the neonatal population and 25% of the pediatric population. In the pediatric population, an inverse correlation emerged between estimated glomerular filtration rate (eGFR) and achieved AUC levels. Median eGFR at 72 h was significantly higher (expression of hyperfiltration) in events with AUC < 400, compared with those with AUC ≥ 400 (p < 0.001). A cut-off value of eGFR in the first 72 h has been identified (145 mL/min/1.73 m2), beyond which it is extremely unlikely to achieve an AUC ≥ 400, and therefore a higher dose or a different antibiotic should be chosen.

Induction Therapy With Cisplatin, 5-Fluorouracil, Leucovorin, and Paclitaxel in Patients With Head and Neck Cancer.

BACKGROUND/AIM: This study aimed to evaluate the toxicities and response rate of a modified TPF (docetaxel, cisplatin, and 5-fluorouracil) protocol in patients with locally advanced head and neck cancer (ECOG performance status ≤1). PATIENTS AND METHODS: Induction treatment consisted of cisplatin 25 mg/m2/day as a 90 min infusion for three consecutive days, leucovorin 20 mg/m2/day as a bolus for four consecutive days, 5-fluorouracil (5-FU) 370 mg/m2/day as a bolus for four consecutive days, and paclitaxel 60 mg/m2 as a 1-h infusion on Days 1, 8, and 15, repeated every 3-4 weeks (twelve cycles to 6 patients). RESULTS: The main toxicities were grade 1 neuropathy, mucositis, and fatigue. There were four episodes of severe toxicities (grade ≥3). There was one early death, and 2 patients were discontinued due to hematological toxicity. Other side effects included neutropenia, nausea, diarrhea, and vomiting. CONCLUSION: Induction therapy with cisplatin, 5-fluorouracil, leucovorin, and paclitaxel in head and neck cancer is not feasible because of severe toxicity.

Critical assessment of resource waste in staging and follow-up of breast cancer

SUMMARY BACKGROUND: Breast cancer is a public health problem with both high incidence and cure rates. After treatment, patients are monitored for long periods of time due to the risk of recurrence. Thus, staging and follow-up strategies should consider not only the best results for the patient but also its costs for the public health system. OBJECTIVE: The objective of this study was to quantify the waste of resources on breast cancer follow-up and evaluate its impact on the public health system. METHODS: This is a retrospective analysis of consecutive medical records to identify the intervals between consultations and tests used for staging and during the first 2 years of follow-up of patients with breast cancer treated at a public hospital in Brazil. Data were compared with the guidelines of the main international consensus. RESULTS: Medical records of 60 consecutive patients treated in 2018 were selected, of whom 52 had 2 or more years of follow-up, and 8 had only 1 year of complete follow-up. A total of 34 patients (56.67%) underwent excessive examinations for stating. During follow-up, 125 surplus consultations were performed (33.6%). In this phase, 111 surplus exams were also performed, representing an increase of 100.9%. A total of 423 laboratory tests were performed for 18 patients in the first year and 229 tests for 14 patients in the second year. CONCLUSION: Excessive tests and consultations significantly burdened the Unified Health System without any benefit to patients. Better adherence to staging and follow-up recommendations could reduce costs and optimize the limited resources used in the public health system.

Ventriculitis and meningitis: by methicillin-resistant S. epidermidis: comparison of serum and CSF vancomycin concentrations and possible effect on MIC.

A case of HCAMV due to methicillin-resistant S. epidermidis (MRSE) in a new-born treated with vancomycin is described. Despite adequate vancomycin serum concentrations, an increase in vancomycin MIC (from 1 to 2 mg/L) in presence of persistently low CSF concentrations were observed. The eGFR during the treatment period was normal (no evidence of hyperfiltration). This report confirms the observation of a relationship among antibiotic PK/PD, cure of localized infections and resistance selection and specifically suggests the need for a first-line alternative to vancomycin in case of HCAMV due to CoNS with MIC ≥ 1 mg/L.

Medical Students' Perception of Risk Factors for Cancer.

To evaluate the perception of risk factors for cancer among medical students and how it varies among students in different years of their medical education. Cross-sectional study was conducted in 2019. The American Institute for Cancer Research Cancer Risk Awareness Survey questionnaire was administered to medical students at the Centro Universitário Saúde ABC. Students were divided into those in their 1st to 3rd year and those in their 4th to 6th year of medical education. Qualitative variables were described by frequency and percentage, and quantitative variables were described by mean and standard deviation or median and interquartile range. The scores of the groups on the questionnaire were compared using Student's t test. The 95% confidence interval was calculated, and p values < 0.05 were considered significant. We included 196 students, with approximately 30 to 35 students in each year of medical education. The median age was 22 (18 to 31), with 74% being female. Among risk factors for cancer, smoking (100%), cancer-causing genes (99.48%), and excessive sunlight exposure (99.48%) were the most cited by students. We observed a significant difference in the number of correct answers, favoring students in their 4th to the 6th year over those in their 1st to the 3rd year (mean = 16.46 vs. mean = 13.73, p < 0.001). Perception about risk factors for cancer is greater in the later years of medical education.

Malignant pericardial effusion as a primary manifestation of metastatic colon cancer: a case report.

BACKGROUND: Pericardial neoplastic involvement is rarely related to primary tumors of the pericardium and is most often caused by spread from other primary sites, such as lung and breast carcinomas, hematological malignancies (lymphoma and leukemia), and melanoma. Although pericardial metastasis from infradiaphragmatic tumors (such as colon cancers) are rare and poorly described in literature, any neoplasm has the potential to metastasize to the pericardium and heart by either contiguity, lymphatic, or hematological spread. CASE PRESENTATION: A 44-year-old previously healthy male Causasian patient had a sudden onset of dyspnea and wheezing. During investigation with echocardiogram, computed tomography and repeated pericardiocentesis, the cause of malignant pericardial effusion was confirmed as primary manifestation of metastatic colon cancer. The patient was treated with appropriate chemotherapy and presented satisfactory disease control. CONCLUSIONS: This report emphasizes the importance of considering the diagnostic hypothesis of occult neoplasia in a patient with pericardial effusion.

Depression, anxiety and spirituality in oncology patients.

OBJECTIVE To relate anxiety and depression levels to the spirituality levels of oncology patients in the ABC region. METHODS Cross-sectional study performed at the ABC University Center oncology outpatient clinics. For the evaluation of spirituality, the Religiosity, Spirituality, and Personal Beliefs instrument of the World Health Organization (SRPB-WHO) was applied. To evaluate the levels of depression and anxiety, the Hospital Anxiety and Depression Scale (HADS) was applied. Qualitative variables were described by frequency and percentage, and quantitative variables by mean and standard deviation or median and range. Relationships were established using either the T-test or Wilcoxon-Mann-Whitney test and correlations with Pearson or Spearman tests, depending on the normality assessed by the Shapiro-Wilk test. RESULTS We included 99 patients, 68% female, with a median age of 60 years (19 to 81). A total of 24% had high or borderline levels of anxiety and 21% of depression. There was a negative correlation between levels of depression and spirituality (rho = -0.44, p <0.001), and anxiety and spirituality (rho=-0.232, p=0.02). We found no significant difference between levels of anxiety, depression, or spirituality when stratified by schooling, income, ethnicity, or marital status. There was a positive correlation between levels of anxiety and depression (cor = 0.477, p <0.001). CONCLUSION Spirituality can be a complementary tool in the treatment of patients with cancer.

Depression, anxiety and spirituality in oncology patients

SUMMARY OBJECTIVE To relate anxiety and depression levels to the spirituality levels of oncology patients in the ABC region. METHODS Cross-sectional study performed at the ABC University Center oncology outpatient clinics. For the evaluation of spirituality, the Religiosity, Spirituality, and Personal Beliefs instrument of the World Health Organization (SRPB-WHO) was applied. To evaluate the levels of depression and anxiety, the Hospital Anxiety and Depression Scale (HADS) was applied. Qualitative variables were described by frequency and percentage, and quantitative variables by mean and standard deviation or median and range. Relationships were established using either the T-test or Wilcoxon-Mann-Whitney test and correlations with Pearson or Spearman tests, depending on the normality assessed by the Shapiro-Wilk test. RESULTS We included 99 patients, 68% female, with a median age of 60 years (19 to 81). A total of 24% had high or borderline levels of anxiety and 21% of depression. There was a negative correlation between levels of depression and spirituality (rho = -0.44, p <0.001), and anxiety and spirituality (rho=-0.232, p=0.02). We found no significant difference between levels of anxiety, depression, or spirituality when stratified by schooling, income, ethnicity, or marital status. There was a positive correlation between levels of anxiety and depression (cor = 0.477, p <0.001). CONCLUSION Spirituality can be a complementary tool in the treatment of patients with cancer.

RESUMO OBJETIVO Relacionar os níveis de ansiedade e depressão com os de espiritualidade dos pacientes oncológicos da região do ABC. MÉTODO Estudo transversal realizado nos ambulatórios de oncologia do Centro Universitário ABC. Para avaliação da espiritualidade, foi aplicado o questionário Religiosidade, espiritualidade e crenças pessoais da Organização Mundial da Saúde (SRPB-WHO). Para avaliar os níveis de depressão e ansiedade foi aplicado a Hospital Anxiety and Depression Scale (Hads). Variáveis qualitativas foram descritas por frequência e porcentagem, as quantitativas por média e desvio padrão ou mediana e intervalo. Relações foram feitas por meio do teste de t ou Wilcoxon-Mann-Whitney e correlações pelo teste de Pearson ou Spearman, a depender da normalidade avaliada pelo teste de Shapiro-Wilk. RESULTADO Foram incluídos 99 pacientes; 68% do sexo feminino, mediana de idade 60 (19 a 81); 24% tiveram níveis altos ou limítrofes para ansiedade e 21% para depressão. Foi observada correlação negativa entre os níveis de depressão e espiritualidade (rho=-0,44, p<0,001) e ansiedade e espiritualidade (rho=-0,232, p=0,02). Não foi observada diferença entre os níveis de ansiedade, depressão ou espiritualidade ao estratificar por escolaridade, renda, etnia ou estado civil. Houve correlação positiva entre os níveis de ansiedade e depressão (cor=0,477, p<0,001). CONCLUSÃO A espiritualidade pode ser uma ferramenta complementar a ser utilizada no tratamento do paciente com câncer.

Evaluation of the systemic and therapeutic repercussions caused by drug interactions in oncology patients.

INTRODUCTION: Drug interaction is an important cause of global morbidity. It is of particular importance in cancer patients since they are often in use of polypharmacy, related to interactions between the drugs and the chemotherapeutics used. OBJECTIVE: To evaluate the drug interaction between chemotherapy and other drugs in cancer patients. METHODS: a cross-sectional study carried out in the outpatient oncology department of a public tertiary hospital. Two hundred thirty-five patients were included, and the drugs they were using were identified. Using the MedScape and Epocrates database, we evaluated the interactions between medications and chemotherapy by defining their frequency and dividing their severity from interaction into mild, close monitoring necessity and severe. RESULTS: 161 patients had some drug interaction. We identified 9 types of mild interactions, 23 types of interactions with close monitoring necessity, and 2 types of serious interactions. The most frequent interactions were between fluorouracil and leucovorin (32 cases) and cyclophosphamide and doxorubicin (19 cases). Serious interactions were between aspirin and pemetrexed; and leucovorin and Bactrim. CONCLUSION: In the present study, drug interactions were frequent, including serious interactions with a potential increase in morbidity and mortality. Thus, it is necessary for oncologists to draw up a therapeutic plan considering potential interactions between prescribed chemotherapy and current medications in use by patients.

Evaluation of the systemic and therapeutic repercussions caused by drug interactions in oncology patients

SUMMARY INTRODUCTION: Drug interaction is an important cause of global morbidity. It is of particular importance in cancer patients since they are often in use of polypharmacy, related to interactions between the drugs and the chemotherapeutics used. OBJECTIVE: To evaluate the drug interaction between chemotherapy and other drugs in cancer patients. METHODS: a cross-sectional study carried out in the outpatient oncology department of a public tertiary hospital. Two hundred thirty-five patients were included, and the drugs they were using were identified. Using the MedScape and Epocrates database, we evaluated the interactions between medications and chemotherapy by defining their frequency and dividing their severity from interaction into mild, close monitoring necessity and severe. RESULTS: 161 patients had some drug interaction. We identified 9 types of mild interactions, 23 types of interactions with close monitoring necessity, and 2 types of serious interactions. The most frequent interactions were between fluorouracil and leucovorin (32 cases) and cyclophosphamide and doxorubicin (19 cases). Serious interactions were between aspirin and pemetrexed; and leucovorin and Bactrim. CONCLUSION: In the present study, drug interactions were frequent, including serious interactions with a potential increase in morbidity and mortality. Thus, it is necessary for oncologists to draw up a therapeutic plan considering potential interactions between prescribed chemotherapy and current medications in use by patients.

RESUMO INTRODUÇÃO: Interação medicamentosa é uma importante causa de morbidade mundial. Apresenta especial importância em pacientes oncológicos, pois esses frequentemente estão em uso de polifarmácia, podendo haver interações entre os medicamentos e os quimioterápicos utilizados. OBJETIVO: Avaliar a interação medicamentosa entre a quimioterapia e outros medicamentos em pacientes oncológicos. MÉTODOS: Estudo transversal realizado em serviço ambulatorial de oncologia de um hospital público terciário. Foram incluídos 235 pacientes, identificando-se quais medicamentos eram utilizados por eles. Por meio do auxílio do banco de dados do MedScape e Epocrates, avaliaram-se as interações entre as medicações e os quimioterápicos, definindo sua frequência e dividindo sua gravidade da interação em leve, monitorização próxima e grave. RESULTADOS: Do total estudado, 161 pacientes apresentavam alguma interação medicamentosa, sendo nove tipos de interações leves, 23 tipos de interações com necessidade de monitorização próxima e dois tipos de interações graves. As interações mais frequentes foram entre fluoracil e leucovorin (32 casos) e ciclofosfamida e doxorrubicina (19 casos). As interações sérias foram entre aspirina e pemetrexed; e leucovorim e bactrim. CONCLUSÃO: No presente trabalho, interações medicamentosas foram frequentes, incluindo interações graves com potencial aumento de morbimortalidade. Assim, faz-se necessário que oncologistas tracem um plano terapêutico levando em consideração as possíveis interações medicamentosas entre a quimioterapia prescrita e demais medicações em uso pelos pacientes.

Time trend of breast cancer mortality in BRAZILIAN men: 10-year data analysis from 2005 to 2015.

BACKGROUND: Male Breast Cancer (MBC) is rare, which makes its understanding and treatment be extrapolated from what is known about the occurrence in women, with few epidemiological studies, with few epidemiological studies. Therefore, the aim of the present paper was to study breast cancer mortality in adult males in Brazil and its administrative regions between 2005 and 2015. METHODS: Ecological study with data on MBC mortality in adults between 2005 and 2015. Data were obtained from the Mortality Information System of the Department of Informatics of SUS (the Unified Health System of the country). Descriptive statistics were used for MBC mortality and linear regression to analyze the relationship between mortality and the country's administrative regions. Percentage Change (PC) and Annual Percentage Change (APC) were the trend measures used for MBC mortality for the period. RESULTS: Between 2005 and 2015, there were 1521 deaths due to MBC in adults in Brazil. Regarding mortality by region, there was great oscillation in the rates of the country as a whole (PC = 113,87; ß = 0,009 (IC95% 0,000 - 0,018); r2 = 0,381; P = 0,043). The highest increase in MBC mortality occurred in patients aged 80 years or older (PC = 161,04; ß = 0,201 (IC95% 0,640 - 0,339); r2 = 0,550; P = 0,009) and there was significant increase in deaths for the 50-54-year age group (PC = 224,01; ß = 0,135 (CI95% 0,052; 0,218); r2 = 0,601; P = 0,005). CONCLUSION: Mortality in adults due to MBC increased in Brazil during the study period with the highest percentage increase occurring for individuals aged 80 years or older.

Chemotherapy-induced fatigue is associated with changes in gene expression in the peripheral blood mononuclear cell fraction of patients with locoregional breast cancer.

PURPOSE: Chemotherapy-induced fatigue (CIF) is a frequent symptom that impairs patient functioning and quality of life. We aimed to evaluate whether systemic chemotherapy can induce a specific gene expression profile in peripheral blood mononuclear cells (PBMNC) of patients with locoregional breast cancer (LRBC) who develop CIF. METHODS: PBMNC were collected from 3 patients who developed CIF before and after their initial cycle of chemotherapy, and RNA-seq was performed in an Ion Torrent™ System. A total of 12.345 transcripts were sequenced, of which 26 were selected out of 71 that had significantly different expression before and after chemotherapy. The RNA-seq results were validated by RT-qPCR in a different group of 28 patients with LRBC who developed CIF after their first cycle of chemotherapy and in six patients who also received chemotherapy but did not develop CIF (controls). We assessed CIF according the BFI and Chalder Questionnaires. RESULTS: We observed a significant increase in expression of DUSP18 and RHOBTB1 and decreased expression of NCAN and RAET1G in patients who developed CIF after chemotherapy. Control patients only exhibited a significant decrease in NCAN expression. CONCLUSION: CIF induces specific changes in gene expression in the PBMNC of LRBC patients. Some of these changes, such as downregulation of NCAN expression, may reflect direct effects of chemotherapy since they are also observed in the controls. Furthermore, CIF may involve downregulation of skeletal muscle genes (RHOBT1, DUSP18) and immune systems (RAETG1), whereas NCAN downregulation may underlie the adverse cognitive effects of chemotherapy.

Epidemiological profile of Brazilian oncological patients seen by a reference oncology center of the public health system and who migrate in search of adequate health care

SUMMARY INTRODUCTION Structural disparities between different Brazilian regions in public health system cause patients to migrate in search of better conditions to treat their diseases. Besides patient's discomfort, there is a concentration of care in large centres, causing overload to current capacity. OBJECTIVE To evaluate migratory flow and associated factors in a reference service in oncology. METHODS Cross-sectional study conducted at a referral oncology service in Great ABC region of São Paulo. Patients were interviewed, and clinical and demographic data collected. RESULTS Between March-July 2016, 217 patients were included. Analysis showed a divergence between the postal code registered in the medical record and that recorded during the interview in approximately 10% of cases. Of these, 42.9% were residents of other states. Search for treatment motivated most patients to seek service outside their city. CONCLUSION Results reflect the informal search for medical care outside the home area. Besides the direct impact on patients' quality of life, migratory flow has an economic-social impact because these patients place a burden and impose costs on services of cities where they do not perform their responsibilities as citizens. Confirmation of the existence of a significant migratory flow demonstrates the need to discuss restructuring public health policies.

RESUMO INTRODUÇÃO As disparidades estruturais entre diferentes regiões brasileiras no sistema de saúde pública fazem com que os pacientes migrem em busca de melhores condições para tratar suas doenças. Além do desconforto do paciente, há uma concentração de cuidados em grandes centros, causando sobrecarga da capacidade atual. OBJETIVO Avaliar o fluxo migratório e fatores associados em um serviço de referência em oncologia. MÉTODOS Estudo transversal realizado em um serviço de oncologia de referência na região do Grande ABC, em São Paulo. Os pacientes foram entrevistados e dados clínicos e demográficos coletados. RESULTADOS Entre março e julho de 2016 foram incluídos 217 pacientes. A análise mostrou uma divergência entre o código de endereçamento postal registrado no prontuário médico e o registrado durante a entrevista em aproximadamente 10% dos casos. Desses, 42,9% eram residentes de outros estados. A busca de tratamento motivou a maioria dos pacientes a buscar serviços fora de sua cidade. CONCLUSÃO Os resultados refletem a busca informal de cuidados médicos fora da área de residência. Além do impacto direto na qualidade de vida dos pacientes, o fluxo migratório tem um impacto econômico-social porque esses pacientes colocam um fardo e impõem custos aos serviços das cidades onde não executam suas responsabilidades como cidadãos. A confirmação da existência de um fluxo migratório significativo demonstra a necessidade de discutir a reestruturação das políticas de saúde pública.

Time trend and regional variability of mortality rate due to ovarian cancer in Brazil: a 15-year analysis.

Introduction: Ovarian cancer (OC) is the most lethal gynecological tumor. In Brazil, there are important regional differences regarding mortality rates for the same cancer type. Objectives: To analyze the progression of OC mortality rates in Brazil and its regions, in age groups over 50 years, between 2000 and 2015. Methods: Ecological longitudinal study carried out using secondary data from DATASUS (Brazil's public health system database) regarding deaths due to OC in women living in Brazil between 2000 and 2015. We calculated gross and adjusted mortality, estimated the impact of death of OC and proportional mortality rate of all cancer types in women between the age of 50 and 79 years. Results: There were 34.335 deaths due to OC in women in the referred age interval, with a 9% increase in mortality adjusted for age, a 0.05% (P = 0.012) trend and a 24.67% increase in the proportional mortality due to all causes with a 0.02% (P < 0.001) trend. There were statistically significant increases in mortality rates due to OC in the age groups of 50-54 (28,4%, P < 0,05) and 75-79 years (25,1%, P < 0,05). Conclusion: Although there are oscillations in mortality rates of OC in Brazil and its regions over the period studied, this parameter has remained relatively stable.

Purified Dry Paullinia cupana (PC-18) Extract for Chemotherapy-Induced Fatigue: Results of Two Double-Blind Randomized Clinical Trials.

Fatigue is frequent among oncologic patients. Unpurified Paullinia cupana dry extract showed encouraging results for chemotherapy-induced fatigue in our previous studies. We report two randomized, double-blind studies with a standardized dry purified Paullinia cupana extract named PC-18. For both studies, we recruited early breast cancer patients who had an increase in their fatigue scores after their first cycle of adjuvant chemotherapy. In the first study, we compared an oral dose of 37.5 mg of PC-18 twice daily with placebo. In the second study, we examined PC-18 at either 7.5 or 12.5 mg orally twice daily versus placebo. In both studies, PC-18 was not superior to placebo as assessed by both Chalder and Brief Fatigue Inventory (BFI) fatigue questionnaires, probably reflecting unexpectedly good placebo antifatigue activity. Since all capsules employed in both studies contained about 100 mg of magnesium silicate as an excipient, we retrospectively evaluated frozen serum samples from the second study and found a significant increase in magnesium levels after patients received placebo. By multivariate analysis, higher prerandomization magnesium levels and higher BFI scores together with the use of a 12.5 mg dose of PC-18 all correlated significantly with higher posttreatment BFI scores. We observed no significant toxicities in any of the trials. We conclude that the absence of differences between PC-18 and placebo may be due to the unexpectedly high antifatigue activity of the placebo in these studies. Further studies evaluating the role of magnesium supplementation for chemotherapy-induced fatigue are needed.

Curcuma longa (Turmeric) for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Pilot Study.

Hand-foot syndrome (HFS) is common and frequently occurs in the first cycle of treatment in approximately 40% to 50% of patients who receive capecitabine. Turmeric (Curcuma longa) is a plant used in Ayurvedic medicine with clinical activity in various inflammatory conditions. Our objective was to evaluate whether turmeric was active for the prevention of capecitabine-induced HFS. We included patients older than 18 years of age without previous exposure to capecitabine who were scheduled to receive this medication. Before starting treatment, after three weeks and at the end of six weeks, we evaluated dermatologic toxicity, conducted quality-of-life questionnaires (EORTC-QLQC30 and DLQI) and collected serum inflammatory biomarkers (inerleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), C-reactive protein (CRP), and albumin). We administered turmeric at a dose of 4 g/day (2 pills 12 hours apart) starting at the beginning of capecitabine treatment and lasting six weeks. We included 40 patients whose mean age was 62 years. Most were female (80%), 52% had breast cancer, and 47.5% had GI tumors. After the first cycle of capecitabine treatment, we observed that 11 of 40 patients developed HFS (27.5%; 95% CI [15, 42]), whereas four patients developed HFS equal or superior to grade 2 (10%; 95% CI [3.3, 23]). We did not find any correlations between the inflammatory markers tested and HFS. We show that turmeric combined with capecitabine seems to produce a lower rate of HFS, especially grade 2 or higher. These findings need to be reproduced in larger controlled studies.

Epidemiological profile of Brazilian oncological patients seen by a reference oncology center of the public health system and who migrate in search of adequate health care.

INTRODUCTION: Structural disparities between different Brazilian regions in public health system cause patients to migrate in search of better conditions to treat their diseases. Besides patient's discomfort, there is a concentration of care in large centres, causing overload to current capacity. OBJECTIVE: To evaluate migratory flow and associated factors in a reference service in oncology. METHODS: Cross-sectional study conducted at a referral oncology service in Great ABC region of São Paulo. Patients were interviewed, and clinical and demographic data collected. RESULTS: Between March-July 2016, 217 patients were included. Analysis showed a divergence between the postal code registered in the medical record and that recorded during the interview in approximately 10% of cases. Of these, 42.9% were residents of other states. Search for treatment motivated most patients to seek service outside their city. CONCLUSION: Results reflect the informal search for medical care outside the home area. Besides the direct impact on patients' quality of life, migratory flow has an economic-social impact because these patients place a burden and impose costs on services of cities where they do not perform their responsibilities as citizens. Confirmation of the existence of a significant migratory flow demonstrates the need to discuss restructuring public health policies.