RESUMO
AIM: The incidence of type 1 diabetes is increasing, and more people are going to live many years with the disease. Quality of life might become the most challenging long-term complication. The JUBILE study describes the quality of life of people living with type 1 diabetes for more than 40 years. METHODS: Patients were recruited from 35 French regional or university hospitals: patients and physicians completed questionnaires, validated by the Delphi method. From 1200 questionnaires circulated, 808 patients and their physicians returned questionnaires. RESULTS: The duration of type 1 diabetes was 49 ± 6 years (mean±SD), age at diagnosis 15 ± 10 years, HbA1c 7.4 ± 0.9% [58 ± 10 mmol/mol] and 52% were men. Macrovascular disease was present in 32%, 46% had no or only mild non proliferative retinopathy. Insulin pumps were used by 25% and insulin pen/syringe users injected 3.9 ± 2.1 times per day. Blood glucose was self monitored at least five times per day by 67% of patients. Men had 1.8 ± 1.2 children, women 1.4 ± 1.0. More than half (55%) of this population was working, 38% had a university degree. Patients still had a busy life, going out (59%), eating out (82%), playing sports (38%) and travelling (66%). No differences appeared based on age, duration of diabetes, demography or social features. CONCLUSIONS: Living a long and pleasant life is possible with type 1 diabetes. Diabetes does not prevent people from having children, working at highly qualified jobs, travelling abroad: a message of hope that is comforting for patients, their family, relatives and the medical teams.
Assuntos
Diabetes Mellitus Tipo 1/psicologia , Insulina/uso terapêutico , Qualidade de Vida , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored. METHODS: We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up. RESULTS: Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution. CONCLUSIONS: These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais , Neoplasias Colorretais/genética , Metilação de DNA , DNA de Neoplasias/sangue , DNA de Neoplasias/química , Neuropeptídeo Y/genética , Proteínas Repressoras/genética , Idoso , Biomarcadores Tumorais/genética , Metilação de DNA/genética , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVES: To independently evaluate unenhanced, contrast-enhanced perfusion and angiographic MR sequences for pulmonary embolism (PE) diagnosis. METHODS: Prospective investigation, including 274 patients who underwent perfusion, unenhanced 2D steady-state-free-precession (SSFP) and contrast-enhanced 3D angiographic MR sequences on a 1.5-T unit, in addition to CTA (CT angiography). Two independent readers evaluated each sequence independently in random order. Sensitivity, specificity, predictive values and inter-reader agreement were calculated for each sequence, excluding sequences judged inconclusive. Sensitivity was also calculated according to PE location. RESULTS: Contrast-enhanced angiographic sequences showed the highest sensitivity (82.9 and 89.7 %, reader 1 and reader 2, respectively), specificity (98.5 and 100 %) and agreement (kappa value 0.77). Unenhanced angiographic sequences, although less sensitive overall (68.7 and 76.4 %), were sensitive for the detection of proximal PE (92.7 and 100 %) and showed high specificity (96.1 and 99.1 %) and good agreement (kappa value 0.62). Perfusion sequences showed lower sensitivity (75.0 and 79.3 %), specificity (84.8 and 89.7 %) and agreement (kappa value 0.51), and a negative predictive value of 84.8 % at best. CONCLUSIONS: Compared with contrast-enhanced angiographic sequences, unenhanced sequences demonstrate lower sensitivity, except for proximal PE, but high specificity and agreement. The negative predictive value of perfusion sequences was insufficient to safely rule out PE. KEY POINTS: ⢠Unenhanced angiographic MR sequences are very specific and can identify proximal PE. ⢠Contrast-enhanced MR angiographic sequences show high sensitivity for PE diagnosis. ⢠A normal MR perfusion result does not exclude PE. ⢠Inter-reader agreement is better for angiographic than perfusion MR sequences.
Assuntos
Angiografia/métodos , Meios de Contraste/farmacologia , Imageamento por Ressonância Magnética/métodos , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/patologia , Adulto , Idoso , Feminino , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Movimento , Variações Dependentes do Observador , Perfusão , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Respiração , Sensibilidade e Especificidade , Fatores de TempoRESUMO
Cobimetinib combined with vemurafenib was available in France in 2015 through a 'Temporary Authorization for Use' program (TAU, preapproval access pending its marketing on 2016) for patients with v-raf murine sarcoma viral oncogene homolog B1-mutant advanced melanoma. This study aimed to provide real-world outcomes in patients previously registered in this TAU. This noninterventional, ambispective, multicentre French study, conducted in patients previously registered in TAU, aimed to estimate overall survival (OS) and progression-free survival (PFS) and to describe the tolerability of the therapeutic combination. At first cobimetinib intake (in combination with vemurafenib), 88% of the 185 evaluable patients had disease stage IV (brain metastasis: 70% of them), 31% had elevated lactate dehydrogenases, and 10% had an Eastern Cooperative Oncology Group (ECOG) index ≥2. Median OS was 16.1 months (95% CI, 12.5-20.7). Brain metastasis ( P < 0.001), ECOG index ≥2 ( P = 0.007), and hepatic impairment ( P = 0.037) were found as independent factors significantly associated with shorter survival. Median PFS was 7.3 months (95% CI, 5.2-8.4). ECOG index ≥2 ( P = 0.006) was significantly associated with shorter PFS. Between cobimetinib start and inclusion, increased CPK (3% of patients), retinal serous detachment (3%), decreased left ventricular ejection fraction (3%), increased transaminases (3%), and rash (3%) were the most reported serious adverse events. This study provides real-world outcomes in France for the vemurafenib-cobimetinib combination available in patients with BRAF-mutant-advanced melanoma. Our data tend to confirm in the real-life setting that this combination therapy is effective in such patients, with a safety profile consistent with previous interventional studies.
Assuntos
Neoplasias Encefálicas , Melanoma , Neoplasias Cutâneas , Adulto , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azetidinas , Neoplasias Encefálicas/tratamento farmacológico , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Camundongos , Mutação , Piperidinas , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Volume Sistólico , Vemurafenib/efeitos adversos , Função Ventricular EsquerdaRESUMO
OBJECTIVE: To perform a head-to-head comparison of coronary CT angiography (CCTA) and dobutamine-stress echocardiography (DSE) in patients presenting recent chest pain when troponin and ECG are negative. METHODS: Two hundred seventeen patients with recent chest pain, normal ECG findings, and negative troponin were prospectively included in this multicenter study and were scheduled for CCTA and DSE. Invasive coronary angiography (ICA), was performed in patients when either DSE or CCTA was considered positive or when both were non-contributive or in case of recurrent chest pain during 6month follow-up. The presence of coronary artery stenosis was defined as a luminal obstruction >50% diameter in any coronary segment at ICA. RESULTS: ICA was performed in 75 (34.6%) patients. Coronary artery stenosis was identified in 37 (17%) patients. For CCTA, the sensitivity was 96.9% (95% CI 83.4-99.9), specificity 48.3% (29.4-67.5), positive likelihood ratio 2.06 (95% CI 1.36-3.11), and negative likelihood ratio 0.07 (95% CI 0.01-0.52). The sensitivity of DSE was 51.6% (95% CI 33.1-69.9), specificity 46.7% (28.3-65.7), positive likelihood ratio 1.03 (95% CI 0.62-1.72), and negative likelihood ratio 1.10 (95% CI 0.63-1.93). The CCTA: DSE ratio of true-positive and false-positive rates was 1.70 (95% CI 1.65-1.75) and 1.00 (95% CI 0.91-1.09), respectively, when non-contributive CCTA and DSE were both considered positive. Only one missed acute coronary syndrome was observed at six months. CONCLUSIONS: CCTA has higher diagnostic performance than DSE in the evaluation of patients with recent chest pain, normal ECG findings, and negative troponine to exclude coronary artery disease.
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Dor no Peito/sangue , Dor no Peito/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/normas , Dobutamina/administração & dosagem , Ecocardiografia sob Estresse/normas , Eletrocardiografia/normas , Troponina/sangue , Idoso , Dor no Peito/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-CegoRESUMO
OBJECTIVES: To determine the costs and cost-effectiveness of a diagnostic strategy including computed tomography coronary angiography (CTCA) in comparison with invasive conventional coronary angiography (CA) for the detection of significant coronary artery disease from the point of view of the healthcare provider. METHODS: The average cost per CTCA was determined via a micro-costing method in four French hospitals, and the cost of CA was taken from the 2011 French National Cost Study that collects data at the patient level from a sample of 51 public or not-for-profit hospitals. RESULTS: The average cost of CTCA was estimated to be 180
Assuntos
Angiografia Coronária/economia , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada por Raios X/economia , Análise Custo-Benefício , Humanos , Tempo de Internação , Medição de RiscoRESUMO
OBJECTIVES: Arterial stiffness is related to age and collagen properties of the arterial wall and can be indirectly evaluated by the pulse wave velocity (PWV). Ultrafast ultrasound imaging, a unique ultrahigh frame rate technique (>10,â000 images/s), recently emerged enabling direct measurement of carotid PWV and its variation over the cardiac cycle. Our goal was to characterize the carotid diastolic-systolic arterial stiffening using ultrafast ultrasound imaging in healthy individuals and in vascular Ehlers-Danlos syndrome (vEDS), in which collagen type III is defectuous. METHODS: Ultrafast ultrasound imaging was performed on common carotids of 102 healthy individuals and 37 consecutive patients with vEDS. Results are meanâ±âstandard deviation. RESULTS: Carotid ultrafast ultrasound imaging PWV in healthy individuals was 5.6â±â1.2 in early systole and 7.3â±â2.0â m/s in end systole, and correlated with age (râ=â0.48; Pâ<â0.0001 and râ=â0.68; Pâ<â0.0001, respectively). Difference between early and end-systole PWV increased with age independently of blood pressure (râ=â0.54; Pâ<â0.0001). In patients with vEDS, ultrafast ultrasound imaging PWV was 6.0â±â1.5 in early systole and 6.7â±â1.5 âm/s in end systole. Carotid stiffness change over the cardiac cycle was lower than in healthy people (0.021 vs. 0.057 âm/s per mmHg; Pâ=â0.0035). CONCLUSION: Ultrafast ultrasound imaging can evaluate carotid PWV and its variation over the cardiac cycle. This allowed to demonstrate the age-induced increase of the arterial diastolic-systolic stiffening in healthy people and a lower stiffening in vEDS, both characterized by arterial complications. We believe that this easy-to-use technique could offer the opportunity to go beyond the diastolic PWV to better characterize arterial stiffness change with age or other collagen alterations.
Assuntos
Artérias Carótidas/fisiopatologia , Síndrome de Ehlers-Danlos/fisiopatologia , Rigidez Vascular/fisiologia , Adolescente , Adulto , Idoso , Pressão Sanguínea/fisiologia , Artérias Carótidas/diagnóstico por imagem , Síndrome de Ehlers-Danlos/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVE: Epicardial adipose tissue (EAT) is suggested to correlate with metabolic risk factors and to promote plaque development in the coronary arteries. We sought to determine whether EAT thickness was associated or not with the presence and extent of angiographic coronary artery disease (CAD). METHODS: We measured epicardial fat thickness by computed tomography and assessed the presence and extent of CAD by coronary angiography in participants from the prospective EVASCAN study. The association of EAT thickness with cardiovascular risk factors, coronary artery calcification scoring and angiographic CAD was assessed using multivariate regression analysis. RESULTS: Of 970 patients (age 60.9 years, 71% male), 75% (nâ=â731) had CAD. Patients with angiographic CAD had thicker EAT on the left ventricle lateral wall when compared with patients without CAD (2.74±2.4 mm vs. 2.08±2.1 mm; pâ=â0.0001). The adjusted odds ratio (OR) for a patient with a LVLW EAT value ≥2.8 mm to have CAD was ORâ=â1.46 [1.03-2.08], pâ=â0.0326 after adjusting for risk factors. EAT also correlated with the number of diseased vessels (pâ=â0.0001 for trend). By receiver operating characteristic curve analysis, an EAT value ≥2.8 mm best predicted the presence of>50% diameter coronary artery stenosis, with a sensitivity and specificity of 46.1% and 66.5% respectively (AUC:0.58). Coronary artery calcium scoring had an AUC of 0.76. CONCLUSION: Although left ventricle lateral wall EAT thickness correlated with the presence and extent of angiographic CAD, it has a low performance for the diagnosis of CAD.
Assuntos
Tecido Adiposo/fisiologia , Doença da Artéria Coronariana/diagnóstico , Tecido Adiposo/diagnóstico por imagem , Idoso , Área Sob a Curva , Índice de Massa Corporal , Cálcio/metabolismo , Dor no Peito , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etiologia , Vasos Coronários/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/fisiologia , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Circunferência da CinturaRESUMO
Computed tomographic coronary angiography (CTCA) has been proposed as a noninvasive test for significant coronary artery disease (CAD), but only limited data are available from prospective multicenter trials. The goal of this study was to establish the diagnostic accuracy of CTCA compared to coronary angiography (CA) in a large population of symptomatic patients with clinical indications for coronary imaging. This national, multicenter study was designed to prospectively evaluate stable patients able to undergo CTCA followed by conventional CA. Data from CTCA and CA were analyzed in a blinded fashion at central core laboratories. The main outcome was the evaluation of patient-, vessel-, and segment-based diagnostic performance of CTCA to detect or rule out significant CAD (≥50% luminal diameter reduction). Of 757 patients enrolled, 746 (mean age 61 ± 12 years, 71% men) were analyzed. They underwent CTCA followed by CA 1.7 ± 0.8 days later using a 64-detector scanner. The prevalence of significant CAD in native coronary vessels by CA was 54%. The rate of nonassessable segments by CTCA was 6%. In a patient-based analysis, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of CTCA were 91%, 50%, 68%, 83%, 1.82, and 0.18, respectively. The strongest predictors of false-negative results on CTCA were high estimated pretest probability of CAD (odds ratio [OR] 1.97, p <0.001), male gender (OR 1.5, p <0.002), diabetes (OR 1.5, p <0.0001), and age (OR 1.2, p <0.0001). In conclusion, in this large multicenter study, CTCA identified significant CAD with high sensitivity. However, in routine clinical practice, each patient should be individually evaluated, and the pretest probability of obstructive CAD should be taken into account when deciding which method, CTCA or CA, to use to diagnose its presence and severity.
Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Doença da Artéria Coronariana/epidemiologia , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To examine the impact of oncologist awareness of palliative care (PC), the intervention of the PC team (PCT) and multidisciplinary decision-making on three quality indicators of end-of-life (EOL) care. SETTING: Cochin Academic Hospital, Paris, 2007-2008. DESIGN AND PARTICIPANTS: A 521 decedent case series study nested in a cohort of 735 metastatic cancer patients previously treated with chemotherapy. Indicators were location of death, number of emergency room (ER) visits in last month of life and chemotherapy administration in last 14 days of life. Multivariable logistic regression models were used to estimate associations between indicators and oncologist's awareness of PC, PCT intervention and case discussions at weekly onco-palliative meetings (OPMs). RESULTS: 58 (11%) patients died at home, 45 (9%) in an intensive care unit or ER, and 253 (49%) in an acute care hospital; 185 (36%) patients visited the ER in last month of life and 75 (14%) received chemotherapy in last 14 days of life. Only the OPM (n=179, 34%) independently decreases the odds of receiving chemotherapy in last 14 days of life (OR 0.5, 95% CI 0.2 to 0.9) and of dying in an acute care setting (0.3, 0.1 to 0.5). PCT intervention (n=300, 58%) did not independently improve any indicators. Among patients seen by the PCT, early PCT intervention had no impact on indicators, whereas the OPM reduced the odds of persistent chemotherapy in the last 14 days of life. CONCLUSION: Multidisciplinary decision-making with oncologists and the PCT is the most critical parameter for improving EOL care.