Progress in Detection and Projection of Climate Change in Spain since the 2010 CLIVAR-Spain regional climate change assessment report

The Iberian Peninsula region offers a challenging benchmark for climate variability studies for several reasons. It exhibits a wide variety of climatic regimes, ranging from wet Atlantic climates with annual precipitation around 2000 mm, to extensive semiarid regions with severe hydrological stress, to even cold alpine environments in some isolated areas

Ten-year follow-up of clinical governance implementation in primary care : Improving screening, diagnosis and control of cardiovascular risk factors

Altres ajuts: CAM was awarded a predoctoral scholarship from the Fundació Institut Universitari per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol) (http: //www.idiapjordigol.com/index.php/ca/) (7Z06/003).protective effect of having a cardiovascular event (hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.44-0.94) or death (HR = 0.55, 95% CI = 0.35-0.88) was observed in patients from centres where general practitioners received high frequency feedback. Additionally, these PCCs presented improved cardiovascular health indicators and lower incidence and mortality by CVD, illustrating the impact of this intervention. Current improvement strategies for the control of cardiovascular risk factors (CRFs) in Europe are based on quality management policies. With the aim of understanding the effect of interventions delivered by primary healthcare systems, we evaluated the impact of clinical governance on cardiovascular health after ten years of implementation in Catalonia. A cohort study that included 1878 patients was conducted in 19 primary care centres (PCCs). Audits that comprised 13 cardiovascular health indicators were performed and general practitioners received periodic (annual, biannual or monthly) feedback about their clinical practice. We evaluated improvement in screening, diagnosis and control of the main CRFs and the effects of the feedback on cardiovascular risk (CR), incidence of cardiovascular disease (CVD) and mortality, comparing baseline data with data at the end of the study (after a 10-year follow-up). The impact of the intervention was assessed globally and with respect to feedback frequency. General improvement was observed in screening, percentage of diagnoses and control of CRFs. At the end of the study, few clinically significant differences in CRFs were observed between groups. However, the reduction in CR was greater in the group receiving high frequency feedback, specifically in relation to smoking and control of diabetes and cholesterol (Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL)). A

Expression of p53 protein isoforms predicts survival in patients with multiple myeloma

Loss and/or mutation of the TP53 gene are associated with short survival in multiple myeloma, but the p53 landscape goes far beyond. At least 12 p53 protein isoforms have been identified as a result of a combination of alternative splicing, alternative promoters and/or alternative transcription site starts, which are grouped as α, β, γ, from transactivation domain (TA), long, and short isoforms. Nowadays, there are no studies evaluating the expression of p53 isoforms and its clinical relevance in multiple myeloma (MM). We used capillary nanoimmunoassay to quantify the expression of p53 protein isoforms in CD138‐purified samples from 156 patients with newly diagnosed MM who were treated as part of the PETHEMA/GEM2012 clinical trial and investigated their prognostic impact. Quantitative real‐time polymerase chain reaction was used to corroborate the results at RNA levels. Low and high levels of expression of short and TAp53β/γ isoforms, respectively, were associated with adverse prognosis in MM patients. Multivariate Cox models identified high levels of TAp53β/γ (hazard ratio [HR], 4.49; p < .001) and high‐risk cytogenetics (HR, 2.69; p < .001) as independent prognostic factors associated with shorter time to progression. The current cytogenetic‐risk classification was notably improved when expression levels of p53 protein isoforms were incorporated, whereby high‐risk MM expressing high levels of short isoforms had significantly longer survival than high‐risk patients with low levels of these isoforms. This is the first study that demonstrates the prognostic value of p53 isoforms in MM patients, providing new insights on the role of p53 protein dysregulation in MM biology

Multiple perspectives on the attribution of the extreme European summer of 2012 to climate change

Summer 2012 was very wet in northern Europe, and unusually dry and hot in southern Europe. We use multiple approaches to determine whether anthropogenic forcing made the extreme European summer of 2012 more likely. Using a number of observation- and model-based methods, we find that there was an anthropogenic contribution to the extremes in southern Europe, with a qualitative consensus across all methodologies. There was a consensus across the methodologies that there has been a significant increase in the risk of hot summers in southern Europe with climate change. Most approaches also suggested a slight drying, but none of the results were statistically significant. The unusually wet summer in northern Europe was made more likely by the observed atmospheric circulation pattern in 2012, but no evidence was found for a long-term trend in circulation

Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin

Single nucleotide polymorphisms (SNPs) in the multiple drug resistance protein 1 (MRP1) and P-glycoprotein 1 (MDR1) genes modulate their ability to mediate drug resistance. We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and/or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin (PLD). The MRP1/R723Q polymorphism was found in five subjects among the 279 patient study population, all of whom received PLD + bortezomib. Its presence was associated with a longer time to progression (TTP; median 330 vs. 129 days; p = 0.0008), progression-free survival (PFS; median 338 vs. 129 days; p = 0.0006), and overall survival (p = 0.0045). MDR1/3435(C > T), which was in Hardy–Weinberg equilibrium, showed a trend of association with PFS (p = 0.0578), response rate (p = 0.0782) and TTP (p = 0.0923) in PLD + bortezomib patients, though no correlation was found in the bortezomib arm. In a recessive genetic model, MDR1/3435 T was significantly associated with a better TTP (p = 0.0405) and PFS (p = 0.0186) in PLD + bortezomib patients. These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and/or refractory myeloma patients treated with PLD + bortezomib. Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients

Melflufen and dexamethasone in heavily pretreated relapsed and refractory multiple myeloma

Clinical trial information: NCT02963493Altres ajuts: Oncopeptides A

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever

Background Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. Methods Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. Results The incidence of NF among the groups was reduced (64%, 44%, and 24%; P2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05). Conclusions G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial

Multiple myeloma and SARS-CoV-2 infection : clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19

Evidence of coupling in ocean-atmosphere dynamics over the North Atlantic

Coupling between the ocean and the atmosphere is investigated in reanalysis data sets. Projecting the data sets onto a dynamically defined subspace allows one to isolate the dominant modes of variability of the coupled system. This coupled projection is then analyzed using multichannel singular spectrum analysis. The results suggest that a dominant low-frequency signal with a 25-30 year period already mentioned in the literature is a common mode of variability of the atmosphere and the ocean. A new score for evaluating the internal nature of the common variability is then introduced, and it confirms the presence of coupled dynamics in the ocean-atmosphere system that impacts the atmosphere at large scale. The physical nature of this coupled dynamics is then discussed