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BACKGROUND: Infective endocarditis (IE) is a serious condition which is difficult to diagnose and to treat, both medically and surgically. OBJECTIVES: The objective of this study was to evaluate the impact of the SARS-CoV-2 pandemic on the management of patients with IE. METHODS: We conducted a single-centre retrospective study including patients hospitalized for IE during the pandemic (Group 2) compared with the same period the year before (Group 1). We compared clinical, laboratory, imagery, therapeutic, and patient outcomes between the two groups. RESULTS: A total of 283 patients were managed for possible or definite IE (164 in Group 1 and 119 in Group 2). There were more intravenous drug-related IE patients in Group 2 (p = 0.009). There was no significant difference in surgery including intra-cardiac device extraction (p = 0.412) or time to surgery (p = 0.894). The one-year mortality was similar in both groups (16% versus 17.7%, p = 0.704). The recurrence rate was not significantly different between the two groups (5.9% in Group 2 versus 9.1% in Group 1, p = 0.311). CONCLUSIONS: The SARS-CoV-2 pandemic did not appear to have had a negative impact on the management of patients with IE. Maintenance of the activities of the endocarditis team within the referral centre probably contributed to this result. Nevertheless, the high proportion of intravenous drug-addicted patients in the pandemic cohort suggests that the SARS-CoV-2 pandemic had a major psychosocial impact.
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PURPOSE: To establish typical clinical and radiological profiles of primary low-grade parotid cancers in order to tailor therapeutic strategy. MATERIALS AND METHODS: Retrospective study of 57 patients operated on for primary parotid cancer between 2010 and 2021, with review of preoperative MRI and histopathology according to a standardized scoring grid. OBJECTIVE: To study prognostic factors and determine the preoperative clinical and radiological profile of low-grade cancers. RESULTS: Good prognostic factors for specific survival were: staging ≤ cT3 (p = 0.014), absence of adenopathy on cN0 MRI (p < 0.001), superficial lobe location (p = 0.033), pN0 (p < 0.001), absence of capsular rupture (p = 0.004), as well as the absence of peri-tumoral nodules (p = 0.033), intra-parotid adenopathies (p < 0.001), vascular emboli (p < 0.001), peri-neural sheathing (p = 0.016), nuclear atypia (p = 0.031), and necrosis (p = 0.002). It was not possible to define a reliable clinical and radiological profile for low-grade cancers (sensitivity 38%, specificity 79%). CONCLUSION: Our study demonstrated multiple factors of good prognosis, but it was not possible to define a clinical and radiological profile of patients likely to benefit from more limited surgery, nor to diagnose, a priori, low-grade cancers.
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Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/cirurgia , Neoplasias Parotídeas/patologia , Neoplasias Parotídeas/diagnóstico por imagem , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Adulto , Prognóstico , Idoso de 80 Anos ou mais , Cuidados Pré-Operatórios/métodos , Gradação de TumoresRESUMO
In the presence of competing causes of event occurrence (e.g., death), the interest might not only be in the overall survival but also in the so-called net survival, that is, the hypothetical survival that would be observed if the disease under study were the only possible cause of death. Net survival estimation is commonly based on the excess hazard approach in which the hazard rate of individuals is assumed to be the sum of a disease-specific and expected hazard rate, supposed to be correctly approximated by the mortality rates obtained from general population life tables. However, this assumption might not be realistic if the study participants are not comparable with the general population. Also, the hierarchical structure of the data can induces a correlation between the outcomes of individuals coming from the same clusters (e.g., hospital, registry). We proposed an excess hazard model that corrects simultaneously for these two sources of bias, instead of dealing with them independently as before. We assessed the performance of this new model and compared it with three similar models, using extensive simulation study, as well as an application to breast cancer data from a multicenter clinical trial. The new model performed better than the others in terms of bias, root mean square error, and empirical coverage rate. The proposed approach might be useful to account simultaneously for the hierarchical structure of the data and the non-comparability bias in studies such as long-term multicenter clinical trials, when there is interest in the estimation of net survival.
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Neoplasias da Mama , Humanos , Feminino , Modelos de Riscos Proporcionais , Análise de Sobrevida , Simulação por Computador , ViésRESUMO
BACKGROUND: The excess mortality observed in Acute Myeloblastic Leukaemia (AML) patients, partly attributed to unequal access to curative treatments, could be linked to care pathways. METHODS: We included 1039 AML incident cases diagnosed between 2012-2016 from the 3 French blood cancer registries (3,625,400 inhabitants). We describe patients according to age, the medical entry unit and access to the specialised haematology unit (SHU) during follow-up. Multivariate logistic regression model was done to determine the association between covariables and access to SHU. A total of 713 patients (69%) had access to SHU during care. RESULTS: The most common care pathway concerned referral from the general practitioner to SHU, n = 459(44%). The univariate analysis observed a downward trend for the most deprived patients. Patients who consulted in SHU were younger (66 years vs. 83, p < 0.001), and 92% had access to cytogenetic analysis (vs. 54%, p < 0.001). They also had less poor prognosis AML-subtypes (AML-MRC, t-AML/MDS and AML-NOS) (38% vs. 69%); 77% with de novo AML (vs. 67%, p < 0.003)], more favourable cytogenetic prognostic status (23% vs. 6%, p < 0.001), less comorbidities (no comorbidity = 55% vs. 34%, p < 0.001) and treatments proposed were curative 68% (vs. 5.3%, p < 0.001). Factors limiting access to SHU were age over 80 years (OR, 0.14; 95% CI, 0.04-0.38), severe comorbidities (OR, 0.39; 95% CI, 0.21-0.69), emergency unit referral (OR, 0.28; 95% CI, 0.18-0.44) and non-SHU referral (OR, 0.12; 95% CI, 0.07-0.18). Consultation in an academic hospital increased access to SHU by 8.87 times (95% CI, 5.64-14.2). CONCLUSION: The high proportion of access to cytogenetic testing and curative treatment among patients admitted to SHU, and the importance of early treatment in AML underlines the importance of access to SHU for both diagnosis and treatment.
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Hematologia , Leucemia Mieloide Aguda , Humanos , Idoso de 80 Anos ou mais , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Prognóstico , Análise Citogenética , Assistência ao PacienteRESUMO
BACKGROUND: Animal studies have demonstrated that fetal exposure to high maternal cholesterol levels during pregnancy predisposes to aortic atheroma in the offspring. In humans, little is known about the consequences of this exposure on the development of atherosclerotic cardiovascular disease later in life. We wanted to assess whether maternal/paternal inheritance of familial hypercholesterolemia (FH) gene mutation could be associated with subclinical coronary atherosclerosis. METHODS: We retrospectively included 1350 patients, followed in the French registry of FH, with a documented genetic diagnosis. We selected 556 age- and sex-matched pair of patients based on the sex of the parents who transmitted the FH gene mutation, free of coronary cardiovascular event, and with a subclinical coronary atherosclerosis evaluation assessed using coronary artery calcium (CAC) score. We performed univariate and multivariate analysis to assess the individual effect of parental inheritance of the FH gene mutation on the CAC score. RESULTS: In the whole population, patients with maternal inheritance of FH gene mutation (n=639) less frequently had a family history of premature cardiovascular events (27.7% versus 45%, P<0.0001) and were 2 years older (46.9±16.8 versus 44.7±15.9 years old, P=0.02) than those with paternal inheritance (n=711). There was no difference in the prevalence of cardiovascular events between the two groups. In the matched subgroup, maternal inheritance was significantly associated with an increase in CAC score value by 86% (95% CI, 23%-170%; P=0.003), a 1.81-fold risk of having a CAC score ≥100 Agatston units (95% CI, 1.06-3.11; P=0.03), and a 2.72-fold risk of having a CAC score ≥400 Agatston units (95% CI, 1.39-5.51; P=0.004) when compared with paternal inheritance in multivariate analysis. CONCLUSIONS: Maternal inheritance of FH gene mutation was associated with more severe subclinical coronary atherosclerosis assessed by CAC score and may be considered as a potential cardiovascular risk factor.
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Aterosclerose , Doença da Artéria Coronariana , Hiperlipoproteinemia Tipo II , Humanos , Adulto , Pessoa de Meia-Idade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Cálcio , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Estudos Retrospectivos , Herança Materna , Aterosclerose/epidemiologia , Aterosclerose/genética , Aterosclerose/complicações , Mutação , Fatores de RiscoRESUMO
AIMS: To determine the prognosis of patients treated for infective endocarditis (IE) according to their healthcare pathway. To assess how the ESC guidelines are implemented concerning the performance of transoesophageal echocardiography, the use of antibiotic therapy, and the performance of valve surgery; and to compare the epidemiological profile of IE according to the type of centres in which the patients are hospitalized. METHODS AND RESULTS: In a prospective multicentric study including 22 hospitals in the South-East of France, 342 patients were classified into three groups according to their healthcare pathway: 119 patients diagnosed and taken care entirely in a reference centre or hospital with cardiac surgery [Referral Center (RC) group], 111 patients diagnosed and initially taken care in a non-RC (NRC), then referred in a centre including cardiac surgery [transferred to the Referral Center (TRC) group] and 112 patients totally taken care in the NRC (NRC group). One-year mortality was 26% (88 deaths) and was not significantly different between Groups 1 and 2 (20 vs. 21%, P = 0.83). Patients in the NRC group had a higher mortality (37%) compared with patients in the RC and TRC groups (P < 0.001). ESC guidelines were not implemented similarly depending on the healthcare pathway (P = 0.04). Patients in the NRC group were significantly older (P < 0.001) and had more comorbidities (P < 0.001) than patients treated in referral centres. CONCLUSION: Prognosis of patients with IE is influenced by their healthcare pathway. Patients treated exclusively in NRC have a worse prognosis than patients treated in referral or surgical centres.
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Endocardite Bacteriana , Endocardite , Antibacterianos/uso terapêutico , Atenção à Saúde , Endocardite/diagnóstico , Endocardite/epidemiologia , Endocardite/terapia , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/terapia , Mortalidade Hospitalar , Humanos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: To analyze worldwide practices regarding the initiation of oral feeding after total laryngectomy (TL). METHODS: Online survey. RESULTS: Among the 332 responses received, 278 from 59 countries were analyzed. Our results showed that 45.6% of respondents started water and 45.1% started liquid diet between postoperative days 7 and 10. Semi-solid feeds were initiated between days 10 and 14 for 44.9% of respondents and a free diet was allowed after day 15 for 60.8% of respondents. This timing was significantly delayed in cases of laryngo-pharyngectomy and after prior radiotherapy (p < 0.001). A greater proportion of respondents in Africa and Oceania allowed early oral feeding before day 6 as compared with the rest of the world (p < 0.001). CONCLUSION: Despite increasing number of publications, there is still a lack of evidence to support early oral feeding. The majority of respondents preferred to delay its initiation until at least 7 days after surgery.
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Laringe , Doenças Faríngeas , Humanos , Laringectomia , Faringectomia , Complicações Pós-OperatóriasRESUMO
OBJECTIVE: The indication of percutaneous renal transluminal angioplasty (PTRA) in fibromuscular dysplasia (FMD) is mainly based on renal artery stenosis (RAS) due to atherosclerosis criteria, which are not specific to FMD. Consequently, the selection of patients who could benefit from this treatment and its effectiveness remain uncertain. The aims of this study were to: (1) report the effects of PTRA guided by trans-stenotic pressure measurements on hypertension 7 months after treatment; (2) assess the impact of pressure measurement to guide treatment efficacy in comparison to visual angiographic parameters; and (3) evaluate the reproducibility and accuracy of the stenosis measurement using a 4F catheter in comparison to a pressure guidewire. METHODS: This prospective multi-centric study analyzed 24 patients with hypertension with RAS due to FMD that required PTRA. Clinical, duplex ultrasound, and angiographic indices were collected, and patients were followed up for 7 months (±1 month). Angiographic indices were measured twice both by a pressure guidewire and a 4F catheter. Assessment of procedural and clinical success of angioplasty was performed for all patients. RESULTS: Twenty-three patients (96%) had procedural success (considered as a post-PTRA translesional systolic gradient ≤10 mmHg or reduced by at least 80%) with a significant decrease in the systolic gradient after angioplasty (26.50 mmHg; [interquartile range, 16.75-38.75] vs 0.00 [interquartile range, 0.00-2.00]; P < .01). Three patients (12%) had complications, including two renal artery dissections and one partial renal infarction. Twenty-one patients (88%) were clinical responders to angioplasty at follow-up. Visual stenosis assessment showed a poor correlation with systolic gradient measurement before and after PTRA (R from -0.05 to 0.41; P = 0.06-0.82). High correlations were found between pressure measurements made by a 4F catheter and guidewire (R from 0.64 to 0.89; P ≤ .003). CONCLUSIONS: In patients selected by clinical indicators and duplex ultrasound, reaching a translesional systolic gradient ≤10 mmHg or reduced by at least 80% after angioplasty, promotes a high success rate for PTRA in hypertension due to FMD RAS.
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Angioplastia com Balão , Pressão Arterial , Displasia Fibromuscular/terapia , Hipertensão Renovascular/terapia , Obstrução da Artéria Renal/terapia , Artéria Renal/fisiopatologia , Adulto , Angioplastia com Balão/efeitos adversos , Determinação da Pressão Arterial/instrumentação , Angiografia por Tomografia Computadorizada , Feminino , Displasia Fibromuscular/complicações , Displasia Fibromuscular/diagnóstico , Displasia Fibromuscular/fisiopatologia , França , Humanos , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Estudos Prospectivos , Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/etiologia , Obstrução da Artéria Renal/fisiopatologia , Fatores de Tempo , Transdutores de Pressão , Resultado do Tratamento , Ultrassonografia Doppler em Cores , Dispositivos de Acesso VascularRESUMO
Recently, there has been a lot of development in relative survival field. In the absence of data on the cause of death, the research has tended to focus on the estimation of survival probability of a cancer (as a disease of interest). In many cancers, one nonfatal event that decreases the survival probability can occur. There are a few methods that assess the role of prognostic factors for multiple types of clinical events while dealing with uncertainty about the cause of death. However, these methods require proportional hazard or Markov assumptions. In practice, one or both of these assumptions might be violated. Violation of the proportional hazard assumption can lead to estimates that are biased, and difficult to interpret and violation of Markov assumption results in inconsistent estimators. In this work, we propose a semi-parametric approach to estimate the possibly time-varying regression coefficients in the likely non-Markov relative survival progressive illness-death model. The performance of the proposed estimator is investigated through simulations. We illustrate our approach using data from a study on rectal cancer resected for cure conducted in two French population-based digestive cancer registries.
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Neoplasias , Simulação por Computador , Humanos , Probabilidade , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: In survival analysis, data can be modeled using either a multiplicative hazards regression model (such as the Cox model) or an additive hazards regression model (such as Lin's or Aalen's model). While several diagnostic tools are available to check the assumptions underpinning each type of model, there is no defined procedure to fit these models optimally. Moreover, the two types of models are rarely combined in survival analysis. Here, we propose a strategy for optimal fitting of multiplicative and additive hazards regression models in survival analysis. METHODS: This section details our proposed strategy for optimal fitting of multiplicative and additive hazards regression models, with a focus on the assumptions underpinning each type of model, the diagnostic tools used to check these assumptions, and the steps followed to fit the data. The proposed strategy draws on classical diagnostic tools (Schoenfeld and martingale residuals) and less common tools (pseudo-observations, martingale residual processes, and Arjas plots). RESULTS: The proposed strategy is applied to a dataset of patients with myocardial infarction (TRACE data frame). The effects of 5 covariates (age, sex, diabetes, ventricular fibrillation, and clinical heart failure) on the hazard of death are analyzed using multiplicative and additive hazards regression models. The proposed strategy is shown to fit the data optimally. CONCLUSIONS: Survival analysis is improved by using multiplicative and additive hazards regression models together, but specific steps must be followed to fit the data optimally. By providing different measures of the same effect, our proposed strategy allows for better interpretation of the data.
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Neoplasias da Mama , Feminino , Humanos , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
In cancer epidemiology using population-based data, regression models for the excess mortality hazard is a useful method to estimate cancer survival and to describe the association between prognosis factors and excess mortality. This method requires expected mortality rates from general population life tables: each cancer patient is assigned an expected (background) mortality rate obtained from the life tables, typically at least according to their age and sex, from the population they belong to. However, those life tables may be insufficiently stratified, as some characteristics such as deprivation, ethnicity, and comorbidities, are not available in the life tables for a number of countries. This may affect the background mortality rate allocated to each patient, and it has been shown that not including relevant information for assigning an expected mortality rate to each patient induces a bias in the estimation of the regression parameters of the excess hazard model. We propose two parametric corrections in excess hazard regression models, including a single-parameter or a random effect (frailty), to account for possible mismatches in the life table and thus misspecification of the background mortality rate. In an extensive simulation study, the good statistical performance of the proposed approach is demonstrated, and we illustrate their use on real population-based data of lung cancer patients. We present conditions and limitations of these methods and provide some recommendations for their use in practice.
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Simulação por Computador , Tábuas de Vida , Modelos de Riscos Proporcionais , Viés , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , MasculinoRESUMO
OBJECTIVE: The aim of this study was to evaluate the recurrence rate of lithiasis following minimally invasive surgery to identify risk factors and mechanisms for recurrence of salivary gland lithiasis. STUDY DESIGN: Retrospective case series. METHODS: A retrospective study was conducted including all patients treated for salivary gland lithiasis by minimally invasive surgery, such as sialendoscopy, intracorporeal lithotripsy, extracorporeal lithotripsy, transoral approach, and combined approach in our Department. We analyzed the recurrence rate of salivary lithiasis, their topography and timeline. RESULT: Three hundred four patients were included in this study, the mean age was 49 years (range 12-90 years), and the mean duration of follow-up was 19.8 months (range 0-66 months). Fifteen patients (5%) presented secondary lithiasis. In all but one case, recurrences involved the same gland as primary lithiasis, and most frequently the submandibular gland. Recurrences occurred from 3 to 46 months postoperatively. Fourteen patients, who presented recurrence, had been initially treated by transoral approach. Recurrent lithiasis were treated by transoral approach or submandibulectomy. CONCLUSION: Salivary gland lithiasis recurrence was rare after minimally invasive salivary gland surgery. This study reinforced the concept that salivary gland lithiasis should be considered as a duct pathology. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:794-799, 2021.
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Procedimentos Cirúrgicos Minimamente Invasivos , Cálculos das Glândulas Salivares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Endoscopia , Feminino , Humanos , Incidência , Litotripsia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Pembrolizumab, a humanized immunoglobulin monoclonal antibody directed against the programmed cell death 1 receptor, demonstrated robust efficacy and a manageable safety profile across multiple tumor types in clinical trials. AIM: To investigate the efficacy and safety of first-line pembrolizumab for patients with non-small cell lung cancers (NSCLCs) in clinical practice. METHODS: In this observational monocentric retrospective study, 38 patients with PD-L1 >50% were enrolled between November 2017 and November 2018. RESULTS: The global median overall survival was 11.08 months (95% confidence interval [CI], 5.98-not reached) and the global median progression-free survival was 6 months (95% CI, 3-not reached). In the univariate analysis, clinical performance status score and the development of immune-related adverse events were the only 2 clinical factors significantly correlated with overall survival. CONCLUSION: The results of the present study suggest that pembrolizumab seems less effective in the real-life population than in the pivotal clinical trials in patients with NSCLC but remains an effective treatment option for patients with NSCLC. Longer follow-up is needed.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
BACKGROUND: To describe the characteristics of the largest European study of MEC of salivary glands and to determine the prognostic factors for overall and disease free survival. PATIENTS AND METHODS: Patients with MEC were prospectively included in the Réseau d'Expertise Français sur les Cancers ORL Rares (REFCOR, French Network of Rare Head and Neck Tumors) database between 2009 and 2015. RESULTS: A total of 292 patients were included. Tumors were classified as low grade in 175 cases (60%), intermediate in 39 (13%) and high grade in 78 (27%). Median follow-up was 26 months. The 5-year OS and DFS rates were respectively 83% and 69%. In multivariate analysis, age (pâ¯=â¯0.004), diabetes (pâ¯=â¯0.02) and advanced stage (pâ¯=â¯0.03) were found to have a significant negative impact on OS. Diabetes (pâ¯=â¯0.001), alcohol consumption (pâ¯=â¯0.003) and advanced stage (pâ¯=â¯0.001) were found to have a significant negative impact on DFS. Compare to low grade, high grade tended to have a negative impact on OS (pâ¯=â¯0.05) and had a significant effect on DFS (0.002) while intermediate grade had no significant influence on survival. The surgical treatment had a positive impact on both OS (pâ¯=â¯0.00005) and DFS (pâ¯=â¯0.0005). Postoperative radiotherapy had no impact in multivariate analysis. CONCLUSION: Advanced clinical stage, high grade tumor, high age, the impossibility of carrying out a complete surgical resection, and diabetes are the main prognostic factors in this prospective series of patients with MEC. Such findings open new research perspectives on the influence of these components on initial patient care.
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Carcinoma Mucoepidermoide/secundário , Carcinoma Mucoepidermoide/terapia , Recidiva Local de Neoplasia/patologia , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/terapia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Quimiorradioterapia Adjuvante , Bases de Dados Factuais , Complicações do Diabetes/complicações , Intervalo Livre de Doença , Seguimentos , França , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Esvaziamento Cervical , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Radioterapia Adjuvante , Taxa de Sobrevida , Adulto JovemRESUMO
In central Senegal, malaria incidence declined in response to scaling-up of control measures from 2000 to 2010 and has since remained stable, making elimination unlikely in the short term. Additional control measures are needed to reduce transmission. We simulated chemoprophylaxis interventions targeting malaria hotspots using a metapopulation mathematical model, based on a differential-equation framework and incorporating human mobility. The model was fitted to weekly malaria incidence from 45 villages. Three approaches for selecting intervention targets were compared: (a) villages with malaria cases during the low transmission season of the previous year; (b) villages with highest incidence during the high transmission season of the previous year; (c) villages with highest connectivity with adjacent populations. Our results showed that intervention strategies targeting hotspots would be effective in reducing malaria incidence in both targeted and untargeted areas. Regardless of the intervention strategy used, pre-elimination (1-5 cases per 1000 per year) would not be reached without simultaneously increasing vector control by more than 10%. A cornerstone of malaria control and elimination is the effective targeting of strategic locations. Mathematical tools help to identify those locations and estimate the impact in silico.
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Malária , Quimioprevenção , Humanos , Incidência , Malária/epidemiologia , Malária/prevenção & controle , Modelos Teóricos , Estações do Ano , Senegal/epidemiologiaRESUMO
BACKGROUND: Methods for estimating relative survival are widely used in population-based cancer survival studies. These methods are based on splitting the observed (the overall) mortality into excess mortality (due to cancer) and background mortality (due to other causes, as expected in the general population). The latter is derived from life tables usually stratified by age, sex, and calendar year but not by other covariates (such as the deprivation level or the socioeconomic status) which may lack though they would influence background mortality. The absence of these covariates leads to inaccurate background mortality, thus to biases in estimating the excess mortality. These biases may be avoided by adjusting the background mortality for these covariates whenever available. METHODS: In this work, we propose a regression model of excess mortality that corrects for potentially inaccurate background mortality by introducing age-dependent multiplicative parameters through breakpoints, which gives some flexibility. The performance of this model was first assessed with a single and two breakpoints in an intensive simulation study, then the method was applied to French population-based data on colorectal cancer. RESULTS: The proposed model proved to be interesting in the simulations and the applications to real data; it limited the bias in parameter estimates of the excess mortality in several scenarios and improved the results and the generalizability of Touraine's proportional hazards model. CONCLUSION: Finally, the proposed model is a good approach to correct reliably inaccurate background mortality by introducing multiplicative parameters that depend on age and on an additional variable through breakpoints.
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Neoplasias , Viés , Simulação por Computador , Humanos , Modelos de Riscos Proporcionais , Projetos de PesquisaAssuntos
Carcinoma Mucoepidermoide/terapia , Neoplasias das Glândulas Salivares/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Mucoepidermoide/mortalidade , Carcinoma Mucoepidermoide/patologia , Terapia Combinada , Feminino , França , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Taxa de SobrevidaRESUMO
Net survival is used in epidemiological studies to assess excess mortality due to a given disease when causes of death are unreliable. By correcting for the general population mortality, it allows comparisons between regions or periods and thus evaluation of health policies. The Pohar-Perme non-parametric estimator of net survival has been recently proposed, soon followed by an appropriate log-rank-type test. However, log-rank tests are known to be under-optimal in non-proportional settings (e.g. crossing of the hazard functions). In classical survival analysis, one solution is to compare the restricted mean survival times. A difference in restricted mean survival time represents a life benefit or loss over the studied period. In the present article the restricted mean net survival time was used to derive a specific test statistic to compare net survivals in proportional and non-proportional hazards settings. The new test was generalized to more than two groups and to stratified analysis. The test performance was assessed on simulation study, compared to the log-rank-type test, and its use illustrated on a population-based colorectal cancer registry. The new test for net survival comparisons proved robust to non-proportionality and well-performing in proportional hazards situations. Furthermore, it is also suited to the classical survival framework.
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Taxa de Sobrevida , Causalidade , Simulação por Computador , Humanos , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: Net survival, a measure of the survival where the patients would only die from the cancer under study, may be compared between treatment groups using either "cause-specific methods", when the causes of death are known and accurate, or "population-based methods", when the causes are missing or inaccurate. The latter methods rely on the assumption that mortality due to other causes than cancer is the same as the expected mortality in the general population with same demographic characteristics derived from population life tables. This assumption may not hold in clinical trials where patients are likely to be quite different from the general population due to some criteria for patient selection. METHODS: In this work, we propose and assess the performance of a new flexible population-based model to estimate long-term net survival in clinical trials and that allows for cause-of-death misclassification and for effects of selection. Comparisons were made with cause-specific and other population-based methods in a simulation study and in an application to prostate cancer clinical trial data. RESULTS: In estimating net survival, cause-specific methods seemed to introduce important biases associated with the degree of misclassification of cancer deaths. The usual population-based method provides also biased estimates, depending on the strength of the selection effect. Compared to these methods, the new model was able to provide more accurate estimates of net survival in long-term clinical trials. CONCLUSION: Finally, the new model paves the way for new methodological developments in the field of net survival methods in multicenter clinical trials.
Assuntos
Ensaios Clínicos como Assunto/métodos , Confiabilidade dos Dados , Neoplasias da Próstata/mortalidade , Análise de Sobrevida , Idoso , Causas de Morte , Simulação por Computador , Dietilestilbestrol/uso terapêutico , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Projetos de PesquisaRESUMO
Nivolumab, a fully human immunoglobulin monoclonal antibody inhibiting the programmed cell death protein-1 receptor, demonstrated robust efficacy and a manageable safety profile across multiple tumor types in clinical trials. The aim of the present study was to investigate the efficacy and safety of nivolumab for pretreated patients with non-small cell lung cancers in clinical practice. In this observational monocentric retrospective study, 98 patients were enrolled between February 2015 and February 2016. The global median overall survival was 6.34 months (95% confidence interval (CI) : 4.11-10.88) and the global median progression free survival was 1.84 months (95% CI: 1.68-2.73). In the univariate analysis, clinical performance status score was the only factor significantly correlated with overall survival. The safety profile of nivolumab is consistent with that described in prior studies, with only 7% undesirable effects requiring the discontinuation of treatment. The results of the present study demonstrate that nivolumab affords clinical efficacy and manageable tolerability in patients with non-small cell lung cancers.