Continuous palliative sedation for patients with advanced cancer at a tertiary care cancer center.

BACKGROUND: Palliative sedation (PS) is an intervention to treat refractory symptoms and to relieve suffering at the end of life. Its prevalence and practice patterns vary widely worldwide. The aim of our study was to evaluate the frequency, clinical indications and outcomes of PS in advanced cancer patients admitted to our tertiary comprehensive cancer center. METHODS: We retrospectively studied the use of PS in advanced cancer patients who died between March 1st, 2012 and December 31st, 2014. PS was defined as the use of continuous infusion of midazolam or neuroleptics for refractory symptoms in the end of life. This study was approved by the Research Ethics Committee of our institution (project number 2481-15). RESULTS: During the study period, 552 cancer patients died at the institution and 374 met the inclusion criteria for this study. Main reason for exclusion was death in the Intensive Care Unit. Among all included patients, 54.2% (n = 203) received PS. Patients who received PS as compared to those not sedated were younger (67.8 vs. 76.4 years-old, p < 0.001) and more likely to have a diagnosis of lung cancer (23% vs. 14%, p = 0.028). The most common indications for sedation were dyspnea (55%) and delirium (19.7%) and the most common drugs used were midazolam (52.7%) or midazolam and a neuroleptic (39.4%). Median initial midazolam infusion rate was 0.75 mg/h (interquartile range - IQR - 0.6-1.5) and final rate was 1.5 mg/h (IQR 0.9-3.0). Patient survival (length of hospital stay from admission to death) of those who had PS was more than the double of those who did not (33.6 days vs 16 days, p < 0.001). The palliative care team was involved in the care of 12% (n = 25) of sedated patients. CONCLUSIONS: PS is a relatively common practice in the end-of-life of cancer patients at our hospital and it is not associated with shortening of hospital stay. Involvement of a dedicated palliative care team is strongly recommended if this procedure is being considered. Further research is needed to identify factors that may affect the frequency and outcomes associated with PS.

Does Time-to-Chemotherapy Impact the Outcomes of Resected Ovarian Cancer? Meta-analysis of Randomized and Observational Data.

OBJECTIVES: This study is a meta-analysis of prior publications evaluating the impact of time-to-chemotherapy (TTC) on disease recurrence and survival 3 years after the original surgery. METHODS: We performed a meta-analysis of studies published in PubMed (1950-2016) as of April 2016. Inclusion criteria were as follows: randomized controlled trials and prospective or retrospective cohorts that included patients with ovarian cancer who had undergone surgery with curative intent and use of adjuvant chemotherapy. We compared rates of disease recurrence and death according to the TTC ("early" vs "delayed") using a random-effects model and performed a metaregression to evaluate the impact of covariates on these outcomes. RESULTS: Of 239 abstracts in the original search, 12 were considered eligible. The cutoffs used for TTC were between 20 and 40 days. All studies used a platinum-based chemotherapy, and the rates of patients with suboptimal resection varied from 33% to 70%. A longer TTC was not associated with higher rates of disease recurrence (odds ratio, 0.89; 95% confidence interval, 0.63-1.24) or death at 3 years (odds ratio, 1.06; 95% confidence interval, 0.9-1.24). There was no evidence of significant publication bias (Egger test P = 0.472), but data were heterogeneous (I = 64.3%). Metaregression showed that the percentage of patients with suboptimal surgery and values used as cutoff to define "delayed" chemotherapy combined were a significant source of bias (residual I = 0%). CONCLUSIONS: In our analysis, TTC after surgery for ovarian cancer with curative intent was not associated with higher risk of disease recurrence or death. However, this association was influenced by the rate of optimal debulking and definition of "late" initiation of chemotherapy, so we must be careful when applying these data to patients with complete resection.

Higher overall survival in metastatic pancreatic cancer: the impact of where and how treatment is delivered / Maior sobrevida global em pacientes com câncer pancreático metastático: o impacto de onde e como o tratamento é realizado

Objective To determine the overall survival of patients with advanced pancreatic cancer and evaluate factors that impact prognosis in a private cancer center.Methods Data from the Hospital Cancer Registry at Hospital Israelita Albert Einstein were retrospectively collected. The patients enrolled had metastatic cancer at diagnosis or earlier staging and subsequent recurrence. Cases of neuroendocrine tumors were excluded.Results A total of 65 patients were evaluated, including 63 with adenocarcinoma. The median overall survival for patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV cancer, there was no evidence of a statistically significant association between median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age (p=0.152). However, the number of lines of chemotherapy was significantly associated with survival (log-rank p=0.013), with an estimated median survival of 10.2 months for patients who received up to two lines of treatment and 23.5 months for those receiving more than two lines of chemotherapy.Conclusion The survival of patients treated was longer than that reported in the literature. The only statistically significant factor related to increased survival was higher number of lines of chemotherapy received. We believe that the higher socioeconomic status of patients surveyed in this study, as well as their greater access to treatment options, may have influenced their overall survival.

Objetivo Determinar a sobrevida global dos pacientes com câncer pancreático avançado e avaliar fatores com impacto prognóstico em um centro de câncer privado.Métodos Foram coletados retrospectivamente os dados do Registro de Câncer do Hospital Israelita Albert Einstein. Os pacientes incluídos apresentaram câncer metastático ao diagnóstico ou em estádio mais precoce com recorrência subsequente. Os casos de tumores neuroendócrinos foram excluídos.Resultados Foram avaliados 65 pacientes, incluindo 63 com adenocarcinoma. A sobrevida global mediana dos pacientes em todos os estádios foi 20,7 meses (IC95%: 15,6-25,7), enquanto a sobrevida global de doença metastática foi de 13,3 meses. Entre os 33 casos com câncer em estádio IV, não houve evidência de associação estatisticamente significativa entre a sobrevida mediana e CA19-9 ao diagnóstico (p=0,212), localização do tumor (p=0,482), primeiro tratamento realizado (p=0,337), invasão vasculo-linfática (p=0,286) e idade (p=0,152). No entanto, o número de linhas de quimioterapia foi significativamente associado com a sobrevida (log-rankp=0,013), com uma sobrevida mediana estimada de 10,2 meses para os pacientes que receberam até duas linhas de tratamento e de 23,5 meses para os que receberam mais de duas linhas.Conclusão A sobrevida dos pacientes tratados foi maior do que o relatado na literatura. O único fator estatisticamente significativo relacionado à maior sobrevida foi maior número de linhas de quimioterapia recebidas. Acreditamos que o nível socioeconômico dos pacientes pesquisados neste estudo, assim como seu maior acesso a opções de tratamento, pode ter influenciado em sua sobrevivência global.

Higher overall survival in metastatic pancreatic cancer: the impact of where and how treatment is delivered.

OBJECTIVE: To determine the overall survival of patients with advanced pancreatic cancer and evaluate factors that impact prognosis in a private cancer center. METHODS: Data from the Hospital Cancer Registry at Hospital Israelita Albert Einstein were retrospectively collected. The patients enrolled had metastatic cancer at diagnosis or earlier staging and subsequent recurrence. Cases of neuroendocrine tumors were excluded. RESULTS: A total of 65 patients were evaluated, including 63 with adenocarcinoma. The median overall survival for patients in all stages was 20.7 months (95%CI: 15.6-25.7), while the overall survival of metastatic disease was 13.3 months. Among the 33 cases with stage IV cancer, there was no evidence of a statistically significant association between median survival and CA19-9 dosage (p=0.212), tumor location (p=0.482), first treatment performed (p=0.337), lymphovascular invasion (p=0.286), and age (p=0.152). However, the number of lines of chemotherapy was significantly associated with survival (log-rank p=0.013), with an estimated median survival of 10.2 months for patients who received up to two lines of treatment and 23.5 months for those receiving more than two lines of chemotherapy. CONCLUSION: The survival of patients treated was longer than that reported in the literature. The only statistically significant factor related to increased survival was higher number of lines of chemotherapy received. We believe that the higher socioeconomic status of patients surveyed in this study, as well as their greater access to treatment options, may have influenced their overall survival.

Assessment of adherence to the guidelines for the management of nausea and vomiting induced by chemotherapy.

OBJECTIVE: To assess adherence of the prescribing physicians in a private cancer care center to the American Society of Clinical Oncology guideline for antiemetic prophylaxis, in the first cycle of antineoplastic chemotherapy. METHODS: A total of 139 chemotherapy regimens, of 105 patients, were evaluated retrospectively from 2011 to 2013. RESULTS: We observed 78% of non-adherence to the guideline rate. The main disagreements with the directive were the prescription of higher doses of dexamethasone and excessive use of 5-HT3 antagonist for low risk emetogenic chemotherapy regimens. On univariate analysis, hematological malignancies (p=0.005), the use of two or more chemotherapy (p=0.05) and high emetogenic risk regimes (p=0.012) were factors statistically associated with greater adherence to guidelines. Treatment based on paclitaxel was the only significant risk factor for non-adherence (p=0.02). By multivariate analysis, the chemotherapy of high emetogenic risk most correlated with adherence to guideline (p=0.05). CONCLUSION: We concluded that the adherence to guidelines is greater if the chemotherapy regime has high emetogenic risk. Educational efforts should focus more intensely on the management of chemotherapy regimens with low and moderate emetogenic potential. Perhaps the development of a computer generated reminder may improve the adherence to guidelines.

Assessment of adherence to the guidelines for the management of nausea and vomiting induced by chemotherapy / Avaliação da aderência à diretriz de cuidados para náuseas e vômitos induzidos por quimioterapia

ABSTRACT Objective: To assess adherence of the prescribing physicians in a private cancer care center to the American Society of Clinical Oncology guideline for antiemetic prophylaxis, in the first cycle of antineoplastic chemotherapy. Methods: A total of 139 chemotherapy regimens, of 105 patients, were evaluated retrospectively from 2011 to 2013. Results: We observed 78% of non-adherence to the guideline rate. The main disagreements with the directive were the prescription of higher doses of dexamethasone and excessive use of 5-HT3 antagonist for low risk emetogenic chemotherapy regimens. On univariate analysis, hematological malignancies (p=0.005), the use of two or more chemotherapy (p=0.05) and high emetogenic risk regimes (p=0.012) were factors statistically associated with greater adherence to guidelines. Treatment based on paclitaxel was the only significant risk factor for non-adherence (p=0.02). By multivariate analysis, the chemotherapy of high emetogenic risk most correlated with adherence to guideline (p=0.05). Conclusion: We concluded that the adherence to guidelines is greater if the chemotherapy regime has high emetogenic risk. Educational efforts should focus more intensely on the management of chemotherapy regimens with low and moderate emetogenic potential. Perhaps the development of a computer generated reminder may improve the adherence to guidelines. .

RESUMO Objetivo: Avaliar a adesão dos médicos prescritores, de um centro privado especializado em oncologia, à diretriz de antiêmese profilática da American Society of Clinical Oncology, no primeiro ciclo de quimioterapia antineoplásica. Métodos: Foram avaliados retrospectivamente 139 esquemas de quimioterapia, de 105 pacientes, tratados no período de 2011 a 2013. Resultados: Foram observados 78% de taxa de não adesão à diretriz. As principais discordâncias com a diretriz foram prescrição de doses mais elevadas de dexametasona e uso excessivo de antagonista 5-HT3 para regimes de quimioterapia de risco emetogênico baixo. Pela análise univariada, malignidades hematológicas (p=0,005), uso de dois ou mais quimioterápicos (p=0,05) e regimes de alto risco emetogênico (p=0,012) foram fatores estatisticamente associados a maior adesão à diretriz. O tratamento baseado em paclitaxel foi o único fator estatisticamente significativo para a não adesão (p=0,02). Pela análise multivariada, a quimioterapia de alto risco emetogênico apresentou maior correlação com a adesão à diretriz (p=0,05). Conclusão: Houve maior aderência para a quimioterapia de alto risco emetogênico. Esforços educacionais devem se concentrar mais intensamente na gestão de regimes de quimioterapia com potencial emetogênico baixo e moderado. Talvez o desenvolvimento de lembretes gerados por sistemas informatizados possa melhorar a aderência à diretriz. .

Antimicrobials and renal failure in neutropenic patients.

Antimicrobial treatment is often indicated to neutropenic patients. Although renal failure is a common complication of many antibiotics, no information could be found in the literature defining which are the best screening criteria for detecting renal injury. In this paper, the authors aim to assess the progress to renal failure in neutropenic patients on antimicrobial use and to compare different diagnostic criteria of renal failure in association to antimicrobial agents used. This is a cohort study conducted from February to August 2006 at the Hospital das Clínicas of the Universidade Federal de Minas Gerais, which included patients with neutropenia and antimicrobial therapy for the treatment of Healthcare Associated Infections notified by the Hospital Infection Control Committee. Renal injury has ensued in 25% of patients and no statistical difference between distinct criteria for renal injury was observed. Association of greater number of antimicrobials was associated with renal impairment. Time required for renal injury was independent of the antimicrobial regimen used, but mortality among patients with renal injury was higher when compared to those who had preserved renal function.

Neutropenic patients and their infectious complications at a University Hospital.

OBJECTIVE: The aim of this study was to analyze the characteristics and infectious complications of neutropenic patients in a referral hospital. METHODS: A cross-sectional study was carried out between April and September 2008, which enrolled all neutropenic patients identified by daily blood counts in the Universidade Federal de Minas Gerais. Demographic data and information on infections were obtained from the Hospital Infection Control Committee. Statistical analysis was performed using the Statistical Package for Social Sciences. RESULTS: One hundred and sixteen patients were followed up during 129 hospitalizations. The patients had a mean age of 48.7 years old. Sixty-four (55.2%) patients were male and 25 (21.6%) died during the follow-up. In 97 (75.2%) of the hospitalizations, patients had episodes of febrile neutropenia. Patients classified as low-risk had a mortality rate of 16.2% (n = 12) vs. 39.1% (n = 9) among high-risk patients (p-value = 0.02). The death rate of the patients who had been submitted to hematopoietic stem cell transplantation was 13.5% (n = 5) vs. 26.7% (n = 16) among patients not submitted to transplantation (p-value = 0.13). Of the 155 infections diagnosed, 45.5% were defined as clinically documented. The etiological agent most frequently isolated was Escherichia coli and the main topography reported was bloodstream infections. The most used antimicrobial agents were cefepime, vancomycin and fluconazole. Approximately 24% of patients evolved with impaired renal function during hospitalization. CONCLUSION: Most reported infections in neutropenic patients were defined as clinically documented, which shows the importance of suspicion in patients without specific signs and symptoms for early diagnosis and the need for the classification of risk for timely interventions.

Neutropenic patients and their infectious complications at a University Hospital

OBJECTIVE: The aim of this study was to analyze the characteristics and infectious complications of neutropenic patients in a referral hospital. METHODS: A cross-sectional study was carried out between April and September 2008, which enrolled all neutropenic patients identified by daily blood counts in the Universidade Federal de Minas Gerais. Demographic data and information on infections were obtained from the Hospital Infection Control Committee. Statistical analysis was performed using the Statistical Package for Social Sciences. RESULTS: One hundred and sixteen patients were followed up during 129 hospitalizations. The patients had a mean age of 48.7 years old. Sixty-four (55.2%) patients were male and 25 (21.6%) died during the follow-up. In 97 (75.2%) of the hospitalizations, patients had episodes of febrile neutropenia. Patients classified as low-riskhad a mortality rate of 16.2% (n = 12) vs. 39.1% (n = 9) among high-risk patients (p-value = 0.02). The death rate of the patients who had been submitted to hematopoietic stem cell transplantation was 13.5% (n = 5)vs. 26.7% (n = 16) among patients not submitted to transplantation (p-value = 0.13). Of the 155 infections diagnosed, 45.5% were defined as clinically documented. The etiological agent most frequently isolated was Escherichia coli and the main topography reported was bloodstream infections. The most used antimicrobial agents were cefepime, vancomycin and fluconazole. Approximately 24% of patients evolved with impaired renal function during hospitalization. CONCLUSION: Most reported infections in neutropenic patients were defined as clinically documented, which shows the importance of suspicion in patients without specific signs and symptoms for early diagnosis and the need for the classification of risk for timely interventions.