RESUMO
BACKGROUND: Tumor dynamics typically rely on the sum of the longest diameters (SLD) of target lesions, and ignore heterogeneity in individual lesion dynamics located in different organs. PATIENTS AND METHODS: Here we evaluated the benefit of analyzing lesion dynamics in different organs to predict survival in 900 patients with metastatic urothelial carcinoma treated with atezolizumab or chemotherapy (IMvigor211 trial). RESULTS: Lesion dynamics varied largely across organs, with lymph nodes and lung lesions showing on average a better response to both treatments than those located in the liver and locoregionally. A benefit of atezolizumab was observed on lung and liver lesion dynamics that was attributed to a longer duration of treatment effect as compared to chemotherapy (P value = 0.043 and 0.001, respectively). The impact of lesion dynamics on survival, assessed by a joint model, varied greatly across organs, irrespective of treatment. Liver and locoregional lesion dynamics had a large impact on survival, with an increase of 10 mm of the lesion size increasing the instantaneous risk of death by 12% and 10%, respectively. In comparison, lymph nodes and lung lesions had a lower impact, with a 10-mm increase in the lesion size increasing the instantaneous risk of death by 7% and 5%, respectively. Using our model, we could anticipate the benefit of atezolizumab over chemotherapy as early as 6 months before the end of the study, which is 3 months earlier than a similar model only relying on SLD. CONCLUSION: We showed the interest of organ-level tumor follow-up to better understand and anticipate the treatment effect on survival.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológicoRESUMO
BACKGROUND: The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS: All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS: In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION: In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.
Assuntos
Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/secundário , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Adulto JovemRESUMO
OBJECTIVE: To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management. DESIGN: Multicentre, double-blind, randomised placebo-controlled trial. SETTING: 30 French hospitals. POPULATION: Patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. METHODS: Within 30 minutes after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo. MAIN OUTCOME MEASURES: Failure as composite primary efficacy endpoint: at least 4 g/dl of haemoglobin decrease and/or transfusion of at least two units of packed red blood cells within 48 hours following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures and maternal morbidity-mortality within 6 ± 2 weeks after delivery. RESULTS: 437 patients were included: 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346 ml) and plasma fibrinogen (4.1 ± 0.9 g/l) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the fibrinogen and placebo groups, respectively (odds ratio [OR] = 0.99) after adjustment for centre and baseline plasma fibrinogen; (95% CI 0.66-1.47; P = 0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/l in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group versus two in the placebo group. CONCLUSIONS: As previous placebo-controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs or postpartum anaemia, but did prevent plasma fibrinogen decrease without any subsequent thromboembolic events. TWEETABLE ABSTRACT: Early systematic blind 3 g fibrinogen infusion in PPH did not reduce anaemia or transfusion rate, reduced hypofibrinogenaemia and was safe.
Assuntos
Parto Obstétrico/efeitos adversos , Fibrinogênio/administração & dosagem , Hemostáticos/administração & dosagem , Hemorragia Pós-Parto/tratamento farmacológico , Adulto , Transfusão de Sangue/estatística & dados numéricos , Parto Obstétrico/métodos , Método Duplo-Cego , Feminino , Humanos , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Gravidez , Prostaglandinas/administração & dosagem , Prevenção Secundária , Resultado do Tratamento , VaginaAssuntos
Neoplasias das Glândulas Suprarrenais , Histoplasmose , Fluordesoxiglucose F18 , Histoplasmose/diagnóstico por imagem , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
Background: Pseudomyxoma peritonei (PMP) is a rare clinical condition characterized by mucinous ascites, typically related to appendiceal or ovarian tumours. Current standard treatment involves cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but recurrences occur in 20-30 per cent of patients. The aim of this study was to define the timing and patterns of recurrence to provide a basis for modifying follow-up of these patients. Methods: This observational study examined a prospectively developed multicentre national database (RENAPE working group) to identify patients with recurrence after optimal CRS and HIPEC for PMP. Postoperative complications, long-term outcomes and potential prognostic factors were evaluated. Results: Of 1411 patients with proven PMP, 948 were identified who had undergone curative CRS and HIPEC. Among these patients, 229 first recurrences (24·2 per cent) were identified: 196 (20·7 per cent) occurred within the first 5 years (early recurrence) and 30 (3·2 per cent) occurred between 5 and 10 years. Three patients developed a first recurrence more than 10 years after the original treatment. The mean(s.d.) time to first recurrence was 2·36(2·21) years. Preoperative chemotherapy and high-grade pathology were significant factors for early recurrence. Overall survival for the entire group was 77·9 and 63·1 per cent at 5 and 10 years respectively. The principal site of recurrence was the peritoneum. Conclusion: Recurrence of PMP was rare after 5 years and exceptional after 10 years.
Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Adulto , Idoso , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Peritônio/patologia , Peritônio/cirurgia , Prognóstico , Estudos Prospectivos , Pseudomixoma Peritoneal/mortalidade , Pseudomixoma Peritoneal/patologia , Estudos Retrospectivos , Fatores de TempoRESUMO
INTRODUCTION: The development of outpatient surgery, cost-reduction pressures and instrumentation storage limitations have led to their use "just-in-time". A recent study showed that stoppage of surgical procedures immediately before the incision (No-Go) was often due to the management of supplies and implantable medical devices. To our knowledge, since the development of outpatient surgery and the shortening of hospital stays, managing the flow of instrumentation has not been optimized. At our hospital, we used a two-prong approach consisting of a tool to manage instrumentation and working group from the sterilization and orthopedic surgery units. The aims of this study were to: 1) evaluate whether this approach led to better notification of the risk of supply shortage for instrumentation and 2) determine whether it could reduce by at least half operating room disruptions such as delays or cancellation of surgical procedures. HYPOTHESIS: This approach results in better notification of the risk of supply shortage for instrumentation and reduces by at least half operating room disruptions such as delays or cancellation of surgical procedures. MATERIAL AND METHODS: A tool was developed to manage instrumentation flow based on a retrospective analysis of data from 2015. This tool consisted of: (1) a list of instrumentation needed for each surgical procedure from an analysis of the surgical schedule and verification of traceability labels of the instrumentation actually used, (2) a list of reasons for supply shortage identified from an analysis of non-conformities occurring in the sterilization process of instrumentation kits. These analyses resulted in the development of checklists for instrument sets for each procedure, while identifying those with a high risk of shortage. In 2017, a working group focused on instrumentation was set up with personnel from the sterilization unit and the orthopedic surgery unit. Based on the check-lists and the schedule 24hours before the surgery, the sterilization unit alerted the surgery unit by email of the risk of material shortage; the surgery ward replied with potential changes to the material or the surgery planning. This approach (instrumentation management tool and working group) was named just-in-time (JIT). The main outcome was the number of notifications of potential supply shortage with and without JIT over a 10-week period. The secondary outcomes were the number of notifications resolved in time and the occurrence of operating room disruptions (delay>30min or postponement of surgery) related to unavailable instrumentation. RESULTS: Nine reasons for potential supply shortage were identified such as instrumentation kits used for several types of procedures, those with fast rotation and low stock, or in double pathways (on loan and on deposit). The working group reported 163 potential shortages with JIT versus 41 without (p<10-5), of which 150 (92.5%) were resolved. Thirteen operating room disruptions occurred; only one was not detected by the JIT approach. CONCLUSION: Our JIT approach (instrumentation management tool and working group) is effective at preventing instrumentation supply shortages. LEVEL OF EVIDENCE: III, prospective comparative study.
Assuntos
Agendamento de Consultas , Procedimentos Ortopédicos/instrumentação , Ortopedia/organização & administração , Esterilização/organização & administração , Instrumentos Cirúrgicos/provisão & distribuição , Procedimentos Cirúrgicos Ambulatórios/instrumentação , Lista de Checagem , Humanos , Colaboração Intersetorial , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. OBJECTIVE: To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. MATERIAL AND METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. RESULTS: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. CONCLUSION: Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.
Assuntos
Neoplasias dos Ductos Biliares/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/terapia , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/secundário , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendênciasRESUMO
Major obstetric hemorrhage is a challenge for anesthesiologists because it remains responsible for over 10% of maternal deaths in high-income countries. A standardized multidisciplinary management, described in locally validated protocols and based on international guidelines is mandatory to prevent these deaths. The first difficulty relies on the systematic underestimation of the bleeding. Collection bags must be used to facilitate the diagnosis and therefore rapid management. The etiologies in antenatal or postpartum must be well-known in order to be treated adequately. A rapid recourse to prostaglandins (sulprostone in France) may reverse uterine atony. Invasive approach with surgery or radiology should be promptly implemented (uterine artery or internal iliac artery ligations±uterus plication) and hysterectomy should then be timely considered. Simultaneously, early and aggressive resuscitation with large-bore venous accesses should be implemented for rapid and massive transfusion (4:4:1 RBC:FFP:platelets ratio), along with an early use of fibrinogen concentrates and tranexamic acid. This transfusion strategy may be then guided by thromboelastography or thromboelastometry and bedside hemoglobin measurements. Activated factor VII remains indicated only before or after hysterectomy in case of uncontrolled bleeding. Management of placentation abnormalities (placenta previa, accreta, increta, percreta) must be well mastered as these etiologies may generate cataclysmic hemorrhages that can be and have to be anticipated.
Assuntos
Hemorragia Pós-Parto/terapia , Complicações na Gravidez/terapia , Hemorragia Uterina/terapia , Transfusão de Componentes Sanguíneos , Terapia Combinada , Dinoprostona/análogos & derivados , Dinoprostona/uso terapêutico , Fator VIIa/uso terapêutico , Feminino , Fibrinogênio/uso terapêutico , Humanos , Histerectomia , Artéria Ilíaca/cirurgia , Ligadura , Mortalidade Materna , Recuperação de Sangue Operatório , Placenta Acreta/fisiopatologia , Placenta Prévia/fisiopatologia , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/prevenção & controle , Hemorragia Pós-Parto/cirurgia , Gravidez , Complicações na Gravidez/prevenção & controle , Complicações na Gravidez/cirurgia , Proteínas Recombinantes/uso terapêutico , Ácido Tranexâmico/uso terapêutico , Artéria Uterina/cirurgia , Embolização da Artéria Uterina , Hemorragia Uterina/prevenção & controle , Hemorragia Uterina/cirurgia , Inércia Uterina/tratamento farmacológicoRESUMO
INTRODUCTION: Security and quality of the Medicinal Therapy are one of the most important objectives of the April 6th, 2011 order. The objective is to realize this study of the risks incurred by patients related to management and security of medicinal therapy in order to establish a plan to reduce the risks of drug's dispensation. MATERIALS AND METHOD: The method of the Preliminary Risk Analysis (PRA) has been implemented by a multidisciplinary group in a hospital service of orthopaedic surgery. The study focused on the dispensation phase of medicinal circuit. RESULTS: This analysis revealed 148 scenarii, 35 were criticality unacceptable. Fifty-four initial risk control actions were proposed and their stress levels to put them in place were evaluated. DISCUSSION: The main measures of risk management are: training, information, communication, computerization, automation, dual control, updating the documentation system, drug reconciliation and respect for Best Practices Hospitallers (BPH). CONCLUSIONS: Risk management requires a significant human and financial investment as well as, material resources and multidisciplinary expertise in order to offer the best solutions.
Assuntos
Tratamento Farmacológico/normas , Procedimentos Ortopédicos/normas , Ortopedia/normas , Gestão de Riscos/métodos , Sistemas Computacionais , Hospitais/normas , Humanos , Ortopedia/organização & administraçãoRESUMO
BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy. PATIENTS AND METHODS: Data from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT. RESULTS: In the training set, both dNLR ≥median (2) and duration of initial ADT Assuntos
Adenocarcinoma/patologia
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
, Neoplasias Ósseas/secundário
, Linfócitos/patologia
, Neutrófilos/patologia
, Neoplasias de Próstata Resistentes à Castração/patologia
, Adenocarcinoma/tratamento farmacológico
, Adenocarcinoma/mortalidade
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Neoplasias Ósseas/tratamento farmacológico
, Neoplasias Ósseas/mortalidade
, Docetaxel
, Seguimentos
, Humanos
, Agências Internacionais
, Masculino
, Pessoa de Meia-Idade
, Invasividade Neoplásica
, Estadiamento de Neoplasias
, Prednisona/administração & dosagem
, Prognóstico
, Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
, Neoplasias de Próstata Resistentes à Castração/mortalidade
, Taxa de Sobrevida
, Taxoides/administração & dosagem
RESUMO
BACKGROUND: Vasopressor administration is recommended to prevent hypotension during spinal anaesthesia (SA) for elective Caesarean delivery. We aimed to test the superior efficacy and ensure safety of a hydroxyethyl starch (HES) vs a Ringer's lactate (RL) preloading, when combined with a phenylephrine-based prophylaxis. METHODS: A total of 167 healthy parturients undergoing elective Caesarean delivery under SA were included in this multicentre, randomized, double-blind study. Patients received 500 ml of 6% HES (130/0.4)+500 ml of RL (HES group) or 1000 ml of RL (RL group) i.v. before SA. After SA, i.v. phenylephrine boluses were titrated when systolic arterial pressure (SAP) was below 95% of baseline. The primary outcome was the incidence of maternal hypotension (SAP <80% of baseline). RESULTS: The incidence of both hypotension and symptomatic hypotension (i.e. with dizziness, nausea/vomiting, or both) was significantly lower in the HES group vs the RL group: 36.6% vs 55.3% (one-sided P=0.025) and 3.7% vs 14.1%. There was no significant difference in total phenylephrine requirements [median (range): 350 (50-1800) vs 350 (50-1250) µg]. The decrease in maternal haemoglobin value the day after surgery was similar in the two groups [1.2 (1.0) vs 1.0 (0.9) g dl(-1)]. There was no detectable placental transfer of HES in six umbilical cord blood samples analysed in the HES group. Neonatal outcomes were comparable between the groups. CONCLUSIONS: Compared with a pure RL preloading, a mixed HES-RL preloading significantly improved prevention of both hypotension and symptomatic hypotension based on early phenylephrine bolus administration and did not induce adverse effects. CLINICAL TRIAL REGISTRATION: NCT00694343 (http://clinicaltrials.gov).
Assuntos
Anestesia Obstétrica/métodos , Raquianestesia/métodos , Cesárea/métodos , Derivados de Hidroxietil Amido/administração & dosagem , Hipotensão/prevenção & controle , Soluções Isotônicas/administração & dosagem , Medicação Pré-Anestésica/métodos , Adulto , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Hipotensão/induzido quimicamente , Pessoa de Meia-Idade , Fenilefrina/uso terapêutico , Substitutos do Plasma/uso terapêutico , Lactato de Ringer , Resultado do Tratamento , Vasoconstritores/uso terapêutico , Adulto JovemRESUMO
Model-based drug development in oncology is still lagging despite a good momentum in the clinical pharmacology and pharmacometry community in the past few years. The failure rate of late-stage oncology studies is one of the highest across therapeutic areas. The modeling of the relationship between longitudinal tumor size and overall survival has been proposed to enhance learning in early clinical studies, to predict overall survival, and to simulate clinical trials. This approach has the potential to support proof of concept, early clinical decisions, and design of late-stage trials, but it is not yet widely integrated into the oncology drug development process. In this article, we review the state of these modeling efforts and discuss several key applications of these models. We conclude by suggesting a few paths forward.
Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Modelos Biológicos , Neoplasias/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Humanos , Neoplasias/patologia , Análise de Sobrevida , Fatores de TempoRESUMO
We report two deliveries in a patient with a Parkes-Weber syndrome. This parturient had a complex angiodysplasia including a soft tissue hypertrophy of a lower limb, a cutaneous angioma and arteriovenous malformations. The risk of perimedullar arteriovenous malformations was ruled out by angiographic magnetic resonance imaging of the spinal cord. We also describe other aspects of the management, including prepartum cardiovascular assessment, mode of delivery, the use of epidural analgesia and the prevention of haemorrhagia and thromboembolism.
Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Angiografia por Ressonância Magnética , Complicações na Gravidez , Gravidez de Alto Risco , Síndrome de Sturge-Weber , Adulto , Anticoagulantes/uso terapêutico , Malformações Arteriovenosas/etiologia , Malformações Arteriovenosas/terapia , Embolização Terapêutica , Enoxaparina/uso terapêutico , Feminino , Humanos , Hipertrofia , Recém-Nascido , Perna (Membro)/anormalidades , Perna (Membro)/irrigação sanguínea , Masculino , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Neoplasias Cutâneas , Medula Espinal/irrigação sanguínea , Tromboembolia/prevenção & controle , Trombofilia/tratamento farmacológico , Trombofilia/etiologiaRESUMO
OBJECTIVE: Pulmonary embolism remains a leading cause of maternal death in France and in other developed countries. Prevention is well codified, but management remains complex both for diagnosis and therapeutics. The objective of this review was to update the knowledge on diagnosis and treatment of pulmonary embolism during pregnancy. ARTICLE TYPE: Review. DATA SOURCE: Medline(®) database looking for articles published in English or French between 1965 and 2012, using pulmonary embolism, pregnancy, heparin, thrombolysis and vena cava filter as keywords. Editorials, original articles, reviews and cases reports were selected. DATA SYNTHESIS: Pulmonary embolism is one of the leading causes of maternal death in France. Clinical signs and biologic tests are not specific during pregnancy. Doppler ultrasound is helpful for diagnosis and avoids maternal and fetal radiation. Treatment is based on full anticoagulation. Low molecular weight heparin is the treatment of choice. A temporary vena cava filter may be proposed, especially at the end of pregnancy, or when heparin is contraindicated. In case of pulmonary embolism with cardiogenic shock, thrombolysis is an alternative treatment. CONCLUSION: Diagnostic approach is first based on the use of ultrasound- Doppler, and frequently on-to computed tomographic pulmonary angiography or ventilation-perfusion lung scanning. The treatment is based on low molecular weight heparin. Others therapeutics, such as thrombolysis or temporary vena cava filter, may be useful in certain circumstances.
Assuntos
Complicações na Gravidez/diagnóstico , Embolia Pulmonar/complicações , Anticoagulantes/uso terapêutico , Feminino , Fibrinolíticos/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico , Choque Cardiogênico/complicações , Choque Cardiogênico/tratamento farmacológico , Ultrassonografia Doppler , Filtros de Veia CavaRESUMO
Model-based estimates of tumor growth inhibition (TGI) metrics have the potential to enhance learning in early (phase II) clinical studies. They can be used as end points and biomarkers to predict treatment effect on clinical outcome measures-e.g., overall survival (OS)-and support phase II study design, end-of-phase II decisions, and phase III planning and execution. Efforts should be made to assess models in simulating independent studies with treatments of varying mechanisms of action.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Progressão da Doença , Neoplasias Renais/tratamento farmacológico , Modelos Estatísticos , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Niacinamida/uso terapêutico , SorafenibeRESUMO
OBJECTIVE: Incidence of breast cancer with brain metastases (BCBM) is increasing, especially among patients over-expressing HER2. Epidemiology on this sub-type of cancer is scarce, since cancer registries carry no information on the HER2 status. A retrospective database analysis was conducted to estimate the burden of BCBM, especially among HER2-positive patients in a secondary objective. METHODS: Patients with a new diagnosis of BCBM carried out between January and December 2008 were identified from the national hospital database using the International Disease Classification. Patients receiving a targeted anti-HER2 therapy were identified from the national pharmacy database. Hospital and pharmacy claims were linked to estimate the burden of HER2-positive patients. Data on hospitalizations were extracted to describe treatment patterns and healthcare costs during a 1-year follow-up. Predictors of treatment cost were analyzed through multi-linear regression analysis. RESULTS: Two thousand and ninety-nine BCBM patients were identified (mean age (SD) = 57.8 (13.6)), of whom 12.2% received a targeted anti-HER2 therapy; 79% of patients had brain metastases associated with extracranial metastases, and the attrition rate reached 82%. Patients received mostly palliative care (47.4%), general medical care (40.6%), and chemotherapy (35.0%). The total annual hospital cost of treatment was 8,426,392, representing a mean cost of 22,591 (±14,726) per patient, mainly influenced by extracranial metastases, surgical acts, and HER2-overexpression (p < 0.0001). CONCLUSIONS: The database linkage of hospital and pharmacy claims is a relevant approach to identify sub-type of cancer. Chemotherapy was widely used as a systemic treatment for breast cancer rather than for local treatment of brain metastases whose morbi-mortality remains high. The variability of treatment costs suggests clinical heterogeneity and, thus, extensive individualization of protocols.
Assuntos
Neoplasias Encefálicas/economia , Neoplasias Encefálicas/secundário , Neoplasias da Mama/economia , Neoplasias da Mama/patologia , Efeitos Psicossociais da Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/tratamento farmacológico , Bases de Dados Factuais , Feminino , França , Custos Hospitalares , Humanos , Revisão da Utilização de Seguros , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVES: A prophylactic anti-emetic strategy should depend on the number of nausea and vomiting risk factors. This study was undertaken to evaluate the practices of postoperative nausea and vomiting (PONV) prevention practices among obstetrician-gynaecologists, anaesthetists. STUDY DESIGN: A prospective, self-administered questionnaire survey was emailed to all Club d'Anesthésie Réanimation Obstétricale (Caro) members (French Obstetric and Gynaecology Anaesthetists' Association). METHODS: The questionnaire had closed-ended questions to evaluate each Caro member's prophylactic anti-emetic practices. Questions concerned demographic datas, prophylactic anti-emetic drugs administered to the patients with or without well known risk factors for developing PONV, the existence of protocol to prevent PONV in their own department of anaesthesiology and their awareness of the existence of French Society of Anaesthesia and Intensive Care (Sfar) PONV prevention guidelines 2007. RESULTS: Of 115 questionnaires, 66 respondents (57%) returned the questionnaires. Most of the respondents (74%) worked in a university hospital. Forty-two percent practiced exclusively in obstetric-gynaecology department. Fifty-six percent were anaesthetists for more than 20 years. Eighty-five percent of the physicians were well-informed about the SFAR's PONV prevention guidelines. Thirty seven percent of respondents assessed Apfel score systematically for all their patients. The percentages, which didn't calculate the probability of PONV with Apfel score or calculated only in cases of PONV history or travel sickness were 18% and 45% respectively. In cases of two or more risk factors, 63% used droperidol, dexamethasone and ondansetron in double or triple combinations. CONCLUSIONS: Although most surveyed practitioners were well informed about the new guidelines concerning PONV prevention, 27% not follow these guidelines regarding the administration of anti-emetic drugs. The calculation of Apfel score in the preoperative period must be also strengthened.
Assuntos
Anestesia Obstétrica , Antieméticos/uso terapêutico , Procedimentos Cirúrgicos em Ginecologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adolescente , Adulto , Idoso , Dexametasona/uso terapêutico , Droperidol/uso terapêutico , Feminino , França/epidemiologia , Fidelidade a Diretrizes , Guias como Assunto , Pesquisas sobre Atenção à Saúde , Hospitais/estatística & dados numéricos , Humanos , Masculino , Ondansetron/uso terapêutico , Médicos , Náusea e Vômito Pós-Operatórios/epidemiologia , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Four milliliters of distilled water was accidentally injected during labor epidural analgesia in a 32-year-old woman. This epidural injection resulted in severe and instantaneous thoracolumbar pain, which disappeared after epidural administration of NaCl 0.9% 5 mL followed by 20 ml of an analgesic mixture (ropivacaïne 0.1%+sufentanil 0.25 microg/ml). There was no evidence of any neurologic deficit or residual pain until discharge 10 days later. Although no other cases of accidental epidural injection of distilled water have been described up to now, a literature survey showed that it had been used previously as an old method to find the epidural space. However, few experimental data suggest that distilled water can be neurotoxic, which strictly contraindicates its use by epidural route. We used the Reason's systemic analysis model to identify each step that contributed to this error. Corrective measures were then implemented to avoid the recurrence of this error.
Assuntos
Anestesia Epidural/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Erros Médicos , Água , Adulto , Amidas , Analgésicos Opioides , Anestésicos Locais , Feminino , Humanos , Dor/induzido quimicamente , Gravidez , Ropivacaina , SufentanilRESUMO
The anaesthetic management and follow-up of well-characterised patients with pulmonary arterial hypertension presenting for noncardiothoracic nonobstetric surgery has rarely been described. The details of consecutive patients and perioperative complications during the period January 2000 to December 2007 were reviewed. Repeat procedures in duplicate patients were excluded. Longer term outcomes included New York Heart Association (NYHA) functional class, 6-min walking distance and invasive haemodynamics. A total of 28 patients were identified as having undergone major (57%) or minor surgery under general (50%) and regional anaesthesia. At the time of surgery, 75% of patients were in NYHA functional class I-II. Perioperative deaths occurred in 7%. Perioperative complications, all related to pulmonary hypertension, occurred in 29% of all patients and in 17% of those with no deaths during scheduled procedures. Most (n = 11, 92%) of the complications occurred in the first 48 h following surgery. In emergencies (n = 4), perioperative complication and death rates were higher (100 and 50%, respectively; p<0.005). Risk factors for complications were greater for emergency surgery (p<0.001), major surgery (p = 0.008) and a long operative time (193 versus 112 min; p = 0.003). No significant clinical or haemodynamic deterioration was seen in survivors at 3-6 or 12 months of post-operative follow-up. Despite optimal management in this mostly nonsevere pulmonary hypertension population, perioperative complications were common, although survivors remained stable. Emergency procedures, major surgery and long operations were associated with increased risk.