Hodgkin lymphoma treatment with ABVD in the US and the EU: neutropenia occurrence and impaired chemotherapy delivery.

BACKGROUND: In newly diagnosed patients with Hodgkin lymphoma (HL) the effect of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD)-related neutropenia on chemotherapy delivery is poorly documented. The aim of this analysis was to assess the impact of chemotherapy-induced neutropenia (CIN) on ABVD chemotherapy delivery in HL patients. STUDY DESIGN: Data from two similarly designed, prospective, observational studies conducted in the US and the EU were analysed. One hundred and fifteen HL patients who started a new course of ABVD during 2002-2005 were included. The primary objective was to document the effect of neutropenic complications on delivery of ABVD chemotherapy in HL patients. Secondary objectives were to investigate the incidence of CIN and febrile neutropenia (FN) and to compare US and EU practice with ABVD therapy in HL. Pooled data were analysed to explore univariate associations with neutropenic events. RESULTS: Chemotherapy delivery was suboptimal (with a relative dose intensity < or = 85%) in 18-22% of patients. The incidence of grade 4 CIN in cycles 1-4 was lower in US patients (US 24% vs. EU 32%). Patients in both the US and the EU experienced similar rates of FN across cycles 1-4 (US 12% vs. EU 11%). Use of primary colony-stimulating factor (CSF) prophylaxis and of any CSF was more common in the US than the EU (37% vs. 4% and 78% vs. 38%, respectively). The relative risk (RR) of dose delays was 1.54 (95% confidence interval [CI] 1.08-2.23, p = 0.036) for patients with vs. without grade 4 CIN and the RR of grade 4 CIN was 0.35 (95% CI 0.12-1.06, p = 0.046) for patients with vs. without primary CSF prophylaxis. CONCLUSIONS: In this population of HL patients, CIN was frequent and FN occurrence clinically relevant. Chemotherapy delivery was suboptimal. CSF prophylaxis appeared to reduce CIN rates.

Dealing with Immigration in the Context of EU Enlargement: the Case of Transitional Provisions

This analysis addresses the issue of immigration in the context of the European Union enlargement. Focusing on the use of transitional provisions, it attempts to explain why and when EU leaders give workers from new member countries access to their labor market. Building on the observation that EU leaders seem not to use provisions in the spirit of the law, I gauge the importance of domestic political stakes in the use of those provisions. The empirical results suggest that although EU leaders implement and repeal provisions based on economic circumstances, political factors do intervene in the decision-making process. However, it remains uncertain whether those political factors are institutional or purely electoral.

Reliving, emotions, and fragmentation in the autobiographical memories of veterans diagnosed with PTSD

Fifty veterans diagnosed with posttraumatic stress disorder (PTSD) each recalled four autobiographical memories: one from the 2 years before service, one non-combat memory from the time in service, one from combat, and one from service that had often come as an intrusive memory. For each memory, they provided 21 ratings about reliving, belief, sensory properties, reexperiencing emotions, visceral emotional responses, fragmentation, and narrative coherence. We used these ratings to examine three claims about traumatic memories: a separation of cognitive and visceral aspects of emotion, an increased sense of reliving, and increased fragmentation. There was evidence for a partial separation of cognitive judgments of reexperiencing an emotion and reports of visceral symptoms of the emotion, with visceral symptoms correlating more consistently with scores on PTSD tests. Reliving, but not fragmentation of the memories, increased with increases in the trauma relatedness of the event and with increases in scores on standardized tests of PTSD severity. Copyright © 2004 John Wiley & Sons, Ltd.

Genetic variants in the TEP1 gene are associated with prostate cancer risk and recurrence.

BACKGROUND: Telomere-related genes play an important role in carcinogenesis and progression of prostate cancer (PCa). It is not fully understood whether genetic variations in telomere-related genes are associated with development and progression in PCa patients. METHODS: Six potentially functional single-nucleotide polymorphisms (SNPs) of three key telomere-related genes were evaluated in 1015 PCa cases and 1052 cancer-free controls, to test their associations with risk of PCa. Among 426 PCa patients who underwent radical prostatectomy (RP), the prognostic significance of the studied SNPs on biochemical recurrence (BCR) was also assessed using the Kaplan-Meier analysis and Cox proportional hazards regression model. The relative telomere lengths (RTLs) were measured in peripheral blood leukocytes using real-time PCR in the RP patients. RESULTS: TEP1 rs1760904 AG/AA genotypes were significantly associated with a decreased risk of PCa (odds ratio (OR): 0.77, 95% confidence interval (CI): 0.64-0.93, P=0.005) compared with the GG genotype. By using median RTL as a cutoff level, RP patients with TEP1 rs1760904 AG/AA genotypes tended to have a longer RTL than those with the GG genotype (OR: 1.55, 95% CI: 1.04-2.30, P=0.031). A significant interaction between TEP1 rs1713418 and age in modifying PCa risk was observed (P=0.005). After adjustment for clinicopathologic risk factors, the presence of heterozygotes or rare homozygotes of TEP1 rs1760904 and TNKS2 rs1539042 were associated with BCR in the RP cohorts (hazard ratio: 0.53, 95% CI: 0.36-0.79, P=0.002 and hazard ratio: 1.67, 95% CI: 1.07-2.48, P=0.017, respectively). CONCLUSIONS: These data suggest that genetic variations in the TEP1 gene may be biomarkers for risk of PCa and BCR after RP.