In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The ...median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and >2 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed <6 months (5.7 months) compared with those relapsing ⩾12 months after ASCT (12.6 months, P=0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (P<0.0001), 10.0 (P=0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and >2: 5.3 months (P=0.0007). In multivariate analysis, tIPI >2, achievement of response and remission lasting <6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy.
Patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD) are at substantial risk of atherothrombotic events. The COMPASS trial showed that patients with stable CAD or PAD ...experienced significant benefits after treatment with rivaroxaban in combination with acetylsalicylic acid (ASA) compared with ASA alone. This paper aims to provide insight into the clinical and economic consequences of treatment with rivaroxaban from a Dutch societal perspective.
The clinical and economic implications of rivaroxaban in terms of the number of events prevented, costs, the incremental cost per life-years gained (LYG), and incremental cost per quality-adjusted life-years (QALYs) were determined based on a cost-effectiveness model for patients with stable CAD or PAD and in high-risk subgroups (i.e. patients with CAD and PAD, CAD and prior myocardial infarction and renal impairment, CAD and heart failure) using results from the Cardiovascular OutcoMes for People Using Anticoagulation Strategies (COMPASS) trial.
Patients treated with rivaroxaban have an expected increased discounted life expectancy of 0.67 years. In high-risk groups discounted incremental life expectancy ranged from 1.33 to 1.90 years. The incremental cost-effectiveness ratio for the full COMPASS population was €9,760/LYG and €12,033/QALY, whereas, for high-risk subgroups of patients with underlying conditions, incremental cost-effectiveness ratios ranged from €2,966/LYG to €5,052/LYG and from €3,940/QALY to €6,815/QALY. Results from the sensitivity analyses revealed that the model results were robust to variations in single or multiple input parameters at once.
The cost-effectiveness analysis showed that rivaroxaban in combination with ASA is a cost-effective treatment option in stable CAD or PAD patients. Rivaroxaban in combination with ASA is even more cost-effective in high-risk subgroups.
Treatment with escalated BEACOPP achieved a superior time to treatment failure over ABVD in patients with disseminated Hodgkin lymphoma. However, recent clinical trials have failed to confirm BEACOPP ...overall survival (OS) superiority over ABVD. In addition, the gain in low-risk patients is still a matter of debate.
We randomly compared ABVD (8 cycles) with BEACOPP (escalated 4 cycles ≥baseline 4 cycles) in low-risk patients with an International Prognostic Score (IPS) of 0–2. The primary end point was event-free survival (EFS). This parallel group, open-label phase 3 trial was registered under #RECF0219 at French National Cancer Institute.
One hundred and fifty patients were randomized in this trial (ABVD 80, BEACOPP 70): 28 years was the median age, 50% were male and IPS was 0–1 for 64%. Complete remission rate was 85% for ABVD and 90% for BEACOPP. Progression or relapses were more frequent in the ABVD patients than in the BEACOPP patients (17 versus 5 patients). With a median follow-up period of 5.5 years, seven patients died: six in the ABVD arm and one in the BEACOPP arm (HL 3 and 0, 2nd cancer 2 and 1, accident 1 and 0). The EFS at 5 years was estimated at 62% for ABVD versus 77%, for BEACOPP hazards ratio (HR) = 0.6, P = 0.07. The progression-free survival (PFS) at 5 years was 75% versus 93% (HR = 0.3, P = 0.007). The OS at 5 years was 92% versus 99% (HR = 0.18, P = 0.06).
Fewer progressions/relapses were observed with BEACOPP, demonstrating the high efficacy of the more intensive regimen, even in low-risk patients. However, additional considerations, balancing treatment-related toxicity and late morbidity due to salvage may help with decision-making with regard to treatment with ABVD or BEACOPP.
Self-mutilation, examined in samples of the general population, clinical groups, and self-identified self-mutilators, was reported by 4% of the general and 21% of the clinical sample, and was equally ...prevalent among males and females. Results suggest that such behavior is used to decrease dissociation, emotional distress, and posttraumatic symptoms. Childhood sexual abuse was associated with self-mutilation in both clinical and nonclinical samples.
The nuclear-encoded Krebs cycle enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDHB, -C and -D), act as tumour suppressors. Germline mutations in FH predispose individuals to ...leiomyomas and renal cell cancer (HLRCC), whereas mutations in SDH cause paragangliomas and phaeochromocytomas (HPGL). In this study, we have shown that FH-deficient cells and tumours accumulate fumarate and, to a lesser extent, succinate. SDH-deficient tumours principally accumulate succinate. In situ analyses showed that these tumours also have over-expression of hypoxia-inducible factor 1α (HIF1α), activation of HIF1αtargets (such as vascular endothelial growth factor) and high microvessel density. We found no evidence of increased reactive oxygen species in our cells. Our data provide in vivo evidence to support the hypothesis that increased succinate and/or fumarate causes stabilization of HIF1α a plausible mechanism, inhibition of HIF prolyl hydroxylases, has previously been suggested by in vitro studies. The basic mechanism of tumorigenesis in HPGL and HLRCC is likely to be pseudo-hypoxic drive, just as it is in von Hippel–Lindau syndrome.
Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, the ...strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted (P<0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs.
Two novel and simple mathematical models of arthropod temperature-dependent development are proposed. These models are easy to use and have 3 (equation 1) and 4 (equation 2) ecologically meaningful ...parameters, respectively. Each parameter can be estimated using nonlinear regression. These models were used to compare developmental rates at constant temperatures for our own experiments on Lobesia botrana (Dennis & Schiffermuller) and for data from 6 insect species described (a total of 13 stages). In all cases, we obtained an accurate nonlinear description of the rate of development against temperature given by the adjusted R2 (Kvalseth, 1985). The adjusted R2 calculated extended from 0.86 to 0.99 and were identical for our equations 1 and 2. In all cases, equation 2 provided the lowest residual sums of squares. The models gave upper TL and lower T temperature threshold estimations, and the estimations obtained were better by using equation 1 rather equation 2. Confidence intervals for each parameter were given and a comparison between estimated and observed temperature thresholds were presented.
A sample of 935 participants from the general population completed a mail‐out questionnaire containing the Trauma Symptom Inventory (J. Briere, 1995) and the Traumatic Events Survey (D. M. Elliott, ...1992). The lifetime seif‐reported prevalence of natural disasters in this sample was 22%. Although time from the last disaster to involvement in the study was an average of 13 years, previous disaster was associated with significantly higher scores on 6 of 10 symptom scales. Disaster characteristics (especially the presence of physical injury, fear of death, and property loss) were better predictors of symptomatology than was disaster type. Disaster exposure continued to predict symptomatology after controlling for interpersonal violence history, although interpersonal violence accounted for more overall symptom variance.
Previous research has suggested that, when interviewing young children, responses to yes/no questions are less reliable than responses to multiple-choice questions (Peterson & Grant, 2001). However, ...according to fuzzy trace theory, some forms of multiple-choice questions should elicit higher error rates than yes/no questions. Fuzzy trace theory is a theory of cognitive development that suggests there are two types of memory traces: Verbatim traces include exact details of an experience, whereas gist traces represent the patterns and meanings extracted from that experience. Based on the assumptions of this theory, we explored the effect of question format (yes/no vs. multiple-choice), temporal delay (short delay vs. long delay) and age (4- to 6-year-olds, 7- to 9-year-olds, and 10- to 12-year-olds) on children's suggestibility for a naturalistic, potentially stressful event; namely, a dental procedure. Following the dental procedure, and again after a 6- to 8-week delay, children (N = 68) were given 24 forced-choice questions regarding the dental event. Consistent with fuzzy trace theory, the findings suggest that (a) multiple-choice questions can be more problematic than yes/no questions, especially after a delay, and (b) younger children are more suggestible than older children, particularly when asked “no” and “absent feature” questions. The findings are discussed with respect to implications for interviewing children. (PsycINFO Database Record (c) 2016 APA, all rights reserved) (Source: journal abstract)
A widely accepted definition of resistance or intolerance to hydroxyurea (HU) in patients with essential thrombocythemia (ET) is lacking. An international working group (WG) was convened to develop a ...consensus formulation of clinically significant criteria for defining resistance/intolerance to HU in ET. To this aim, an analytic hierarchy process (AHP), a multiple-attribute decision-making technique, was used. The steps consisted of selecting the candidate criteria for defining resistance/intolerance; identifying the motivations that could influence the preference of the WG for any individual criterion; comparing the candidate criteria in a pair-wise manner; and grading them according their ability to fulfill the motivations. Every step in the model was derived by questionnaires or group discussion. The WG proposed that the definition of resistance/intolerance should require the fulfillment of at least one of the following criteria: platelet count greater than 600,000/micro l after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); platelet count greater than 400,000/micro l and WBC less than 2500/micro l or Hb less than 10 g/dl at any dose of HU; presence of leg ulcers or other unacceptable muco-cutaneous manifestations at any dose of HU; HU-related fever.
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