Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC).
The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients ...with locally advanced nonmetastatic CC.
This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery.
A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P < 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group.
Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients.
Aggressive blood pressure (BP) control has been advocated in patients with acute coronary syndrome, but few data exist in this population relative to cardiovascular outcomes.
We evaluated 4162 ...patients enrolled in the PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial (acute coronary syndrome patients randomized to pravastatin 40 mg versus atorvastatin 80 mg). The average follow-up BP (systolic and diastolic) was categorized into 10-mm Hg increments. The primary outcome was a composite of death due to any cause, myocardial infarction, unstable angina requiring rehospitalization, revascularization after 30 days, and stroke. The secondary outcome was a composite of death due to coronary heart disease, nonfatal myocardial infarction, or revascularization. The relationship between BP (systolic or diastolic) followed a J- or U-shaped curve association with primary, secondary, and individual outcomes, with increased events rates at both low and high BP values, both unadjusted and after adjustment for baseline variables, baseline C-reactive protein, and on-treatment average levels of low-density lipoprotein cholesterol. A nonlinear Cox proportional hazards model showed a nadir of 136/85 mm Hg (range 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic) at which the incidence of primary outcome was lowest. The curve was relatively flat for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg.
After acute coronary syndrome, a J- or U-shaped curve association existed between BP and the risk of future cardiovascular events, with lowest event rates in the BP range of approximately 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic and a relatively flat curve for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg, which suggests that too low of a pressure (especially <110/70 mm Hg) may be dangerous.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00382460.
Aim
Neoadjuvant chemotherapy has proven valuable in locally advanced resectable colon cancer (CC) but its effect on oncological outcomes is uncertain. The aim of the present paper was to report ...3‐year oncological outcomes, representing the secondary endpoints of the PRODIGE 22 trial.
Method
PRODIGE 22 was a randomized multicentre phase II trial in high‐risk T3, T4 and/or N2 CC patients on CT scan. Patients were randomized between 6 months of adjuvant FOLFOX (upfront surgery) or perioperative FOLFOX (four cycles before surgery and eight cycles after; FOLFOX perioperative). In wild‐type RAS patients, a third arm testing perioperative FOLFOX‐cetuximab was added. The primary endpoint was the tumour regression grade. Secondary endpoints were 3‐year overall survival (OS), disease‐free survival (DFS), recurrence‐free survival (RFS) and time to recurrence (TTR).
Results
Overall, 120 patients were enrolled. At interim analysis, the FOLFOX‐cetuximab arm was stopped for futility. The remaining 104 patients represented our intention‐to‐treat population. In the perioperative group, 96% received the scheduled four neoadjuvant cycles and all but one had adjuvant FOLFOX for eight cycles. In the control arm, 38 (73%) patients received adjuvant FOLFOX. The median follow‐up was 54.3 months. Three‐year OS was 90.4% in both arms hazard ratio (HR) = 0.85, 3‐year DFS, RFS and TTR were, respectively, 76.8% and 69.2% (HR=0.94), 73% and 69.2% (HR = 0.86) and 82% and 72% (HR = 0.67) in the perioperative and control arms, respectively. Forest plots did not show any subgroup with significant difference for survival outcomes. No benefit from adding cetuximab was observed.
Conclusion
Perioperative FOLFOX has no detrimental effect on long‐term oncological outcomes and may be an option for some patients with locally advanced CC.
Statins lower the levels of low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP). Whether this latter property affects clinical outcomes is unknown.
We evaluated relationships ...between the LDL cholesterol and CRP levels achieved after treatment with 80 mg of atorvastatin or 40 mg of pravastatin per day and the risk of recurrent myocardial infarction or death from coronary causes among 3745 patients with acute coronary syndromes.
Patients in whom statin therapy resulted in LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter) had lower event rates than those with higher levels (2.7 vs. 4.0 events per 100 person-years, P=0.008). However, a virtually identical difference was observed between those who had CRP levels of less than 2 mg per liter after statin therapy and those who had higher levels (2.8 vs. 3.9 events per 100 person-years, P=0.006), an effect present at all levels of LDL cholesterol achieved. For patients with post-treatment LDL cholesterol levels of more than 70 mg per deciliter, the rates of recurrent events were 4.6 per 100 person-years among those with CRP levels of more than 2 mg per liter and 3.2 events per 100 person-years among those with CRP levels of less than 2 mg per liter; the respective rates among those with LDL cholesterol levels of less than 70 mg per deciliter were 3.1 and 2.4 events per 100 person-years (P<0.001). Although atorvastatin was more likely than pravastatin to result in low levels of LDL cholesterol and CRP, meeting these targets was more important in determining the outcomes than was the specific choice of therapy. Patients who had LDL cholesterol levels of less than 70 mg per deciliter and CRP levels of less than 1 mg per liter after statin therapy had the lowest rate of recurrent events (1.9 per 100 person-years).
Patients who have low CRP levels after statin therapy have better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol. Strategies to lower cardiovascular risk with statins should include monitoring CRP as well as cholesterol.
Alors que les troubles du langage parlé et leurs prises en soins dans l’aphasie sont largement décrits dans la littérature scientifique, ceux du langage écrits sont malheureusement moins explorés. Le ...langage parlé est souvent considéré comme prioritaire dans les traitements de l’aphasie au détriment du langage écrit. Pourtant, il est acquis que la littératie influence profondément le traitement du langage parlé : l’acquisition de la lecture établit une nouvelle interface entre la vision et le langage grâce à la plasticité cérébrale. Ainsi, voir la forme écrite d’un mot ou d’une phrase active l’ensemble des aires du langage parlé à l’exception du cortex auditif primaire et ses alentours, de même que le langage écrit participe au raffinement des représentations phonologiques par l’activation du planum temporal lors de l’écoute de phrases parlées. Chez le sujet sain, une capacité de lecture normale est associée à des capacités de traitement sémantique et phonologique intactes. Dans l’aphasie, les altérations du langage oral et du langage écrit sont fortement reliées et majoritairement imputables aux troubles sémantiques et/ou phonologiques observés dans le langage parlé, en d’autres termes, les difficultés linguistiques observées lors du langage parlé sont quasiment à l’identique pour le langage écrit, même si elles sont souvent plus sévères dans le langage écrit. Les influences des perturbations sémantiques et/ou phonologiques sur le langage écrit, peuvent assez schématiquement se décliner ainsi : l’alexie lexicale découle d’un trouble sémantique, une atteinte phonologique sévère est responsable d’une alexie sublexicale, l’alexie profonde résulte quant à elle d’une atteinte sémantique modérée et phonologique sévère. L’alexie globale est la conséquence d’une atteinte sévère sémantique et phonologique. La prise en soins des troubles de la production lexicale dans l’aphasie devrait tenir compte des liens fonctionnels du langage parlé et du langage écrit comme modalités qui se renforcent l’une et l’autre dans les prises en soins.
Our objective was to determine the timing of benefit with intensive statin therapy after an acute coronary syndrome (ACS) in two time windows: an early window soon after an ACS and a late window in ...more stable patients.
The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial showed that the use of intensive statin therapy improved clinical outcomes over two years in ACS patients versus standard therapy. The relative contributions of early or late effects to the overall clinical efficacy of intensive therapy are presently unclear.
A total of 4,162 patients with ACS were recruited in the PROVE IT-TIMI 22 trial. Patients were randomized to intensive statin therapy (atorvastatin, 80 mg) or standard therapy (pravastatin, 40 mg). The composite triple end point of death, MI, or rehospitalization for recurrent ACS was determined in each group at 30 days. The composite triple and primary end points were assessed in stable patients from six months to the end of study, after censoring for clinical events before six months.
The composite end point at 30 days occurred in 3.0% of patients receiving atorvastatin 80 mg versus 4.2% of patients receiving pravastatin 40 mg (hazard ratio HR = 0.72; 95% confidence interval CI, 0.52 to 0.99; p = 0.046). In stable patients, atorvastatin 80 mg was associated with a composite event rate of 9.6% versus 13.1% in the pravastatin 40 mg group (HR = 0.72; 95% CI, 0.58 to 0.89; p = 0.003).
Intensive statin therapy early after ACS leads to a reduction in clinical events at 30 days, consistent with greater early pleiotropic effects. In stable patients, intensive statin therapy provides long-term reduction in clinical events when compared with standard therapy. Thus, ACS patients should be started in-hospital and continued long-term on intensive statin therapy.
This study sought to evaluate the safety and efficacy of achieving very low calculated low-density lipoprotein (LDL) levels with intensive statin therapy.
Intensive statin therapy reduces clinical ...events occurring after acute coronary syndrome (ACS) and may result in LDL levels markedly lower than guideline levels. Prior epidemiologic and preclinical studies raise concerns about the safety of very low cholesterol levels.
The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study compared intensive therapy (atorvastatin, 80 mg) and moderate therapy (pravastatin, 40 mg) in patients after ACS. Patients treated with atorvastatin were divided by four-month LDL values into groups: >100, >80 to 100 (reference-range-meeting guidelines), >60 to 80, >40 to 60, and <40 mg/dl. Baseline, clinical, and safety data were compared among groups achieving guideline recommendation levels or lower.
Among 1,825 patients with four-month LDL, 91% were at goal (<100 mg/dl). The distribution was >80 to 100 mg/dl (14%), >60 to 80 mg/dl (31%), >40 to 60 mg/dl (34%), and <40 mg/dl (11%). Those with lower LDL levels were more often male, older, and diabetic, and had lower baseline LDL levels. They had prior statin therapy and fewer prior myocardial infarctions (MI). There were no significant differences in safety parameters, including muscle, liver, or retinal abnormalities, intracranial hemorrhage, or death, in the very low LDL groups. The <40 mg/dl and 40 to 60 mg/dl groups had fewer major cardiac events (death, MI, stroke, recurrent ischemia, revascularization).
Compared with patients treated with an accepted LDL goal (80 to 100 mg/dl), there was no adverse effect on safety with lower achieved LDL levels, and apparent improved clinical efficacy. These data identify no intrinsic safety concern of achieving low LDL and, therefore, a strategy of intensive treatment need not be altered in patients achieving very low LDL levels.
Young adulthood is a critical life period for health and health behaviours. Related measurements collected before and after birth, and during childhood and adolescence can provide a life-course ...analysis of important factors that contribute to health and behaviour in young adulthood. The Western Australian Pregnancy Cohort (Raine) Study has collected a large number of such measurements during the fetal, perinatal, infancy, childhood and adolescence periods and plans to relate them to common health issues and behaviours in young adults, including spinal pain, asthma, sleep disorders, physical activity and sedentary behaviour and, work absenteeism and presenteeism. The aim of this paper is to describe the rationale, design and methods of the 22 year follow-up of the Raine Study cohort.
The Raine Study is a prospective cohort study. Participants still active in the cohort (n = 2,086) were contacted around the time of their 22nd birthday and invited to participate in the 22 year follow-up. Each was asked to complete a questionnaire, attend a research facility for physical assessment and an overnight sleep study, wear activity monitors for a week, and to maintain a sleep and activity diary over this week. The questionnaire was broad and included questions related to sociodemographics, medical history, quality of life, psychological factors, lifestyle factors, spinal pain, respiratory, sleep, activity and work factors. Physical assessments included anthropometry, blood pressure, back muscle endurance, tissue sensitivity, lung function, airway reactivity, allergic status, 3D facial photographs, cognitive function, and overnight polysomnography.
Describing the prevalence of these health issues and behaviours in young adulthood will enable better recognition of the issues and planning of health care resources. Providing a detailed description of the phenotype of these issues will provide valuable information to help educate health professionals of the needs of young adults. Understanding the life-course risk factors of health issues and behaviours in young adulthood will have important health planning implications, supporting the development of targeted interventions to improve current health status and reduce the onset and development of further ill-health across adulthood.
Provider: - Institution: - Data provided by Europeana Collections- Presentació a la Llibreria 22 del llibre "La enfermedad de escribir" editat i traduït per Abel Debritto. Intervenen a la presentació ...Lluís Llamas i Abel Debritto.- 00:00:00 Jordi Gispert s'adreça als presents. Imatges de l'aparador de la llibreria 22.
00:00:13 Lluís Llamas explica la trajectòria d'Abel Debritto i anuncia que el Festival Pepe Sales que organitza la Penyora va sobre la figura de Charles Bukowski. Imatges del públic a l'interior de la llibreria.
00:02:15 Abel Debritto parla de l'edició del llibre i de la figura de Charles Bukowski.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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