Depression, anxiety, and academic performance in COVID-19: a cross-sectional study.

Depression and anxiety are common after months of social isolation, and they can have a negative impact on anyone's quality of life if they are not treated promptly and appropriately. The aim of this study was to determine if the change to online modality courses and the presence of depression or anxiety symptoms during the COVID-19 pandemic was associated with a difference in the college student's academic achievement. This study was a cross-sectional survey in which we used the Patient Health Questionnaire-9 (PHQ-9) and the General Anxiety Disorder-7 (GAD-7). Also, we examined the students' perceptions of their academic performance using the Academic Self-Concept Scale (ASCS). A total of 610 students responded to the survey. The average score on the Academic Self-Concept Scale was 2.76 ± 0.35, the students presented a risk of 61.5% for possible depressive disorder and 52.1% for possible generalized anxiety disorder. The intensity of depression and anxiety symptoms had a significant effect on Academic Self-Concept Scale scores (p < 0.001 and p < 0.05, respectively). The findings indicate that the COVID-19 pandemic has had a direct effect on students' mental health and academic performance.

Effects of Oral Zafirlukast, Sildenafil, or Pirfenidone on the Formation of Postsurgical Intra-Abdominal Adhesions in an Experimental Rat Model.

INTRODUCTION: Intra-abdominal adhesions' main etiology is surgical procedures that commonly require reintervention. Oral treatments with sildenafil, zafirlukast, and pirfenidone have yielded decreased severity of fibrotic phenomena secondary to the introduction of foreign material. This study aimed to evaluate the efficacy of oral zafirlukast, sildenafil, or pirfenidone treatment on reducing or preventing intra-abdominal adhesions in an experimental rat model. METHODS: Four groups, each of 10 male Wistar rats weighing 250-300 g, were used. A midline laparotomy was used to excise an area of 1.5 × 1.5 cm and reconstructed with polypropylene mesh fixed to the abdominal wall. After 12 h, oral doses of zafirlukast (1.25 mg/kg, group B), sildenafil (15 mg/kg, group C), or pirfenidone (500 mg/kg, group D) were given every day for 8 days. The control group, A, received no treatment. At day 9, animals were reoperated. The implant was resected after ethically approved euthanasia, and specimens were fixed in 10% formaldehyde for histopathology. RESULTS: Control group A yielded adhesions with greater fibrovascular density and neighboring organ involvement than the other groups (p = 0.001), as well as intense inflammatory infiltrates and numerous granulomas (p = 0.04). Adhesions in group C had less fibrovascular density (p = 0.03) with decreased serosal injuries (p = 0.001) and less organ involvement. Group D had reduced adhesions without organ involvement (p < 0.01) and less inflammatory infiltrates, collagen fibers, and foreign body granulomas than group B or C (p < 0.01). CONCLUSIONS: Oral administration of these agents did not prevent adhesions but ameliorated them. Oral pirfenidone offered the best performance and could be recommended for human use.

Anxiety and COVID-19: Coronavirus Anxiety Scale scores in medical and non-medical personnel in urban hospitals in Guadalajara. A cross-sectional survey study.

The world is facing the worst health crisis in modern history. In addition to general concerns about the effects of COVID-19 on health, hospital personnel are developing numerous mental health conditions. This cross-sectional survey study evaluated the prevalence and severity of anxiety caused by the COVID-19 pandemic using the Coronavirus Anxiety Scale (CAS) in 2136 hospital employees. For the employees who presented scores ranging from 1-20 (n = 1090, 51%), the CAS mean score was 4.22 (SD = 3.95). The mean score was higher in women than men. By work category, non-clinical hospital personnel presented the highest CAS scores.

Principal sequence pattern analysis of episodes of excess mortality due to heat in the Barcelona metropolitan area.

The aim of the study is to classify the synoptic sequences associated with excess mortality during the warm season in the Barcelona metropolitan area. To achieve this purpose, we undertook a principal sequence pattern analysis that incorporates different atmospheric levels, in an attempt at identifying the main features that account for dynamic and thermodynamic atmospheric processes. The sequence length was determined by the short-term displacement between temperature and mortality. To detect this lag, we applied the cross-correlation function to the residuals obtained from the modelling of the daily temperature and mortality series of summer. These residuals were estimated by means of an autoregressive integrated moving average (ARIMA) model. A 7-day sequence emerged as the basic temporal unit for evaluating the synoptic background that triggers the temperature related to excess mortality in the Barcelona metropolitan area. The principal sequence pattern analysis distinguished three main synoptic patterns: two dynamic configurations produced by southern fluxes related to an Atlantic low, which can be associated with heat waves recorded in southern Europe, and a third pattern identified by a stagnation situation associated with the persistence of a blocking anticyclone over Europe, related to heat waves recorded in northern and central western Europe.

COVID-19 pandemic and its impact on medical interns' mental health of public and private hospitals in Guadalajara.

INTRODUCTION: Burnout syndrome is a global burden characterized by exhaustion, work detachment, and a sense of ineffectiveness. It affects millions of individuals worldwide, with a particularly high prevalence among medical students. Factors such as demanding education, exposure to suffering, and the COVID-19 pandemic have contributed to elevated stress levels. Addressing this issue is crucial due to its impact on well-being and health-care quality. MATERIALS AND METHODS: This cross-sectional survey study assessed fear of COVID-19 and burnout levels among medical student interns in hospitals in Guadalajara, Jalisco. The study used validated scales and collected data from September 2021 to September 2022. A snowball sampling method was employed and a minimum sample size of 198 participants was calculated. RESULTS: This study included 311 medical students (62.1% female and 37.9% male with a mean age of 23.51 ± 2.21 years). The majority were in their second semester of internship (60.5%) and from public hospitals (89.1%). Most students believed that the COVID-19 pandemic affected the quality of their internship (82.6%). Female students had higher personal burnout scores, while male students had higher work-related burnout scores. The mean score for fear of COVID-19 was 13.71 ± 6.28, with higher scores among women (p = 0.004) and those from public hospitals (p = 0.009). A positive weak correlation was found between COVID-19 scores and burnout subscales. CONCLUSION: Our study emphasizes the significant impact of various factors on burnout levels among medical students and health-care professionals during the COVID-19 pandemic. Prolonged exposure to COVID-19 patients, reduced staffing, and increased workload contributed to burnout, affecting well-being and quality of care. Targeted interventions and resilience-building strategies are needed to mitigate burnout and promote well-being in health-care settings.

Analysis of synoptic weather patterns of heatwave events.

Heatwaves (HWs) are expected to increase both in duration and intensity in the next decades, but little is known about their synoptic and mesoscalar behavior, which is especially important in mid-latitude regions. Most climate research has focused on temperature analysis to characterize HWs. We propose that a combination of temperature and synoptic patterns is a better way to define and understand HWs because including atmospheric circulation patterns provides information about different HW structures that can irregularly affect the territory, and illustrate this approach at the regional and urban scales using the Iberian Peninsula and the Metropolitan Area of Barcelona as case studies. We first select HW events from 1950 to 2020 and apply a multivariate analysis to identify synoptic patterns based on mean sea level pressure, geopotential height at 500 hPa, and maximum daily 2 m temperature. The results indicate that four synoptic patterns reproduce at least 50% of the variance in HWs, namely, "stationary and stable", "dynamic and advective", "stationary and advective", and "dynamic, advective and undulated". Next, we apply the analysis to the Representative Concentration Pathway future scenarios (RCPs) 4.5 and 8.5 from the Coordinated Regional Climate Downscaling Experiment (CORDEX) to determine how these synoptic trends can change in the future. The analysis shows that the four synoptic patterns continue to explain 55 to 60% of the variance in HWs. Future HW events will be characterized by an increase in geopotential height at 500 hPa due to the northward shift of the anticyclonic ridge. This is especially true for RCP8.5, which simulates business as usual incrementing fossil fuel use and additionally shows an increase in atmospheric dynamism in north advections from all directions in comparison with RCP4.5. These findings point to the importance of considering the geopotential height in HW prediction, as well as the direction of advections. Supplementary Information: The online version contains supplementary material available at 10.1007/s00382-023-06828-1.

Comparison of Fear of COVID-19 in Medical and Nonmedical Personnel in a Public Hospital in Mexico: a Brief Report.

The world is social distancing, and compulsory confinement has caused stress, psychological instability, stigmatization, fear, and discrimination in the general population. In this cross-sectional survey study, we administered the Fear of COVID-19 Scale (FCV-19S) to hospital medical and nonmedical personnel. A total of 1216 participants were surveyed from May 25 to May 29 of 2020. We asked all the staff for their participation in the study, and physical copies of the survey were distributed to the staff willing to participate. All surveys were answered anonymously. We found that the global FCV-19S mean score was 16.4 ± 6.1, with a significant difference between women and men's scores. Medical students presented higher scores than experienced medical personnel. Additionally, the medical and nursing personnel presented a higher level of fear than hospital staff who did not work directly with COVID-19 patients. Our findings suggest that greater knowledge of medicine or infectious diseases could decrease the overall psychological impact of the pandemic disease.

Flood impact on the Spanish Mediterranean coast since 1960 based on the prevailing synoptic patterns.

In a changing climate and in social context, tools and databases with high spatiotemporal resolution are needed for increasing the knowledge on the relationship between meteorological events and flood impacts; hence, analysis of high-resolution spatiotemporal databases with detailed information on the frequency, intensity, and impact of floods is necessary. However, the methodological nature of flood databases hinders relating specific flood events to the weather events that cause them; hence, methodologies for classifying flood cases according to the synoptic patterns that generate them are also necessary. Knowing which synoptic patterns are likely to generate risk situations allows for a probabilistic approach with high spatial resolution regarding the timing of occurrence, affected area, and expected damage from floods. To achieve these objectives, we use the SMC-Flood Database, a high-resolution spatiotemporal flood database covering the 1960-2015 period for all municipalities along the Spanish Mediterranean coast. To relate floods with the synoptic conditions that generated them, we used a multivariate analysis method on the corrected daily anomalies of the surface pressure fields, 850 hPa temperature, and 500 hPa geopotential height, all of which were obtained from the 20th Century Reanalysis Project V2. Results show that 12 atmospheric synoptic patterns can statistically explain the 3608 flood cases that occurred in the study area between 1960 and 2015. These flood cases were classified into 847 atmospherically induced flood events. These results reduce the uncertainty during decision making because of the classification of potential risk situations. The Mediterranean Basin is a region where floods have serious socioeconomic impacts; hence, this work helps improving prevention measures and providing information for policymakers, mainly regarding land use planning and early warning systems.

Convergence in critical fuel moisture and fire weather thresholds associated with fire activity in the pyroregions of Mediterranean Europe.

Wildfires are becoming an increasing threat to many communities worldwide. There has been substantial progress towards understanding the proximal causes of increased fire activity in recent years at regional and national scales. However, subcontinental scale examinations of the commonalities and differences in the drivers of fire activity across different regions are rare in the Mediterranean zone of the European Union (EUMed). Here, we first develop a new classification of EUMed pyroregions, based on grouping different ecoregions with similar seasonal patterns of burned area. We then examine the thresholds associated with fire activity in response to different drivers related to fuel moisture, surface meteorology and atmospheric stability. We document an overarching role for variation in dead fuel moisture content (FMd), or its atmospheric proxy of vapor pressure deficit (VPD), as the major driver of fire activity. A proxy for live fuel moisture content (EVI), wind speed (WS) and the Continuous Haines Index (CH) played secondary, albeit important, roles. There were minor differences in the actual threshold values of FMd (10-12%), EVI (0.29-0.36) and CH (4.9-5.5) associated with the onset of fire activity across pyroregions with peak fire seasons in summer and fall, despite very marked differences in mean annual burned area and fire size range. The average size of fire events increased with the number of drivers exceeding critical thresholds and reaching increasingly extreme values of a driver led to disproportionate increases in the likelihood of a fire becoming a large fire. For instance, the percentage of fires >500 ha increased from 2% to 25% as FMd changed from the wettest to the driest quantile. Our study is among the first to jointly address the roles of fuel moisture, surface meteorology and atmospheric stability on fire activity in EUMed and provides novel insights on the interactions across fire activity triggers.

Prognostic impact of renal function trajectories in patients with STEMI and kidney dysfunction undergoing primary percutaneous coronary intervention: An analysis of ten years all-comers registry.

BACKGROUND: Renal dysfunction in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) indicates a poor long-term prognosis. However, the prognostic value of the improvement or stabilisation of renal function during follow-up has not yet been assessed. This study aimed to investigate the long-term predictive impact of the improvement or stabilisation of renal function after one year of follow-up in patients with STEMI undergoing pPCI with renal dysfunction at discharge. METHODS: This prospective, single-centre cohort study included 2170 consecutive patients with STEMI who underwent pPCI. The glomerular filtration rate (GFR) was determined at hospital discharge and one-year follow-up. The median clinical follow-up was 72 months. RESULTS: Among the 2004 patients, 393 (19.6%) had a GFR <60 ml/min, and 1611 (80.4%) had a GFR ≥ 60 ml/min at discharge. Among patients with GFR <60 ml/min, data at one-year follow-up were available for 342. Of these patients, 127 (32%) showed improvement in renal function (defined as improvement in the Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification), 47 (12%) showed worsening of renal function (defined as worsening of the KDIGO CKD classification), and 168 (43%) showed no category changes. Improvement or stabilisation of GFR at one year of follow-up was associated with a reduction of major adverse cardiovascular events (MACE) [HR 0.51, 95% CI: 0.35-0.75, p = 0.001] and all-cause mortality [HR 0.54, 95% CI: 0.34-0.84, p = 0.007] during follow-up. CONCLUSIONS: The improvement or stabilisation of renal function at one-year follow-up in patients with STEMI and renal dysfunction is associated with a better long-term prognosis.

Misinformation About and Interest in Chlorine Dioxide During the COVID-19 Pandemic in Mexico Identified Using Google Trends Data: Infodemiology Study.

BACKGROUND: The COVID-19 pandemic has prompted the increasing popularity of several emerging therapies or preventives that lack scientific evidence or go against medical directives. One such therapy involves the consumption of chlorine dioxide, which is commonly used in the cleaning industry and is available commercially as a mineral solution. This substance has been promoted as a preventive or treatment agent for several diseases, including SARS-CoV-2 infection. As interest in chlorine dioxide has grown since the start of the pandemic, health agencies, institutions, and organizations worldwide have tried to discourage and restrict the consumption of this substance. OBJECTIVE: The aim of this study is to analyze search engine trends in Mexico to evaluate changes in public interest in chlorine dioxide since the beginning of the COVID-19 pandemic. METHODS: We retrieved public query data for the Spanish equivalent of the term "chlorine dioxide" from the Google Trends platform. The location was set to Mexico, and the time frame was from March 3, 2019, to February 21, 2021. A descriptive analysis was performed. The Kruskal-Wallis and Dunn tests were used to identify significant changes in search volumes for this term between four consecutive time periods, each of 13 weeks, from March 1, 2020, to February 27, 2021. RESULTS: From the start of the pandemic in Mexico (February 2020), an upward trend was observed in the number of searches compared with that in 2019. Maximum volume trends were recorded during the week of July 19-25, 2020. The search volumes declined between September and November 2020, but another peak was registered in December 2020 through February 2021, which reached a maximum value on January 10. Percentage change from the first to the fourth time periods was +312.85, -71.35, and +228.18, respectively. Pairwise comparisons using the Kruskal-Wallis and Dunn tests showed significant differences between the four periods (P<.001). CONCLUSIONS: Misinformation is a public health risk because it can lower compliance with the recommended measures and encourage the use of therapies that have not been proven safe. The ingestion of chlorine dioxide presents a danger to the population, and several adverse reactions have been reported. Programs should be implemented to direct those interested in this substance to accurate medical information.

Impact of operators experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry.

BACKGROUND: The Watchman FLX is a device upgrade of the Watchman 2.5 that incorporates several design enhancements intended to simplify left atrial appendage occlusion (LAAO) and improve procedural outcomes. This study compares peri-procedural results of LAAO with Watchman FLX (Boston Scientific, Marlborough, Massachusetts) in centers with varying degrees of experience with the Watchman 2.5 and Watchman FLX. METHODS: Prospective, multicenter, "real-world" registry including consecutive patients undergoing LAAO with the Watchman FLX at 26 Spanish sites (FLX-SPA registry). Implanting centers were classified according to the center's prior experience with the Watchman 2.5. A further division of centers according to whether or not they had performed ≤ 10 or > 10Watchman FLX implants was prespecified at the beginning of the study. Procedural outcomes of institutions stratified according to their experience with the Watchman 2.5 and FLX devices were compared. RESULTS: 359 patients [mean age 75.5 (SD8.1), CHA2DS2-VASc 4.4 (SD1.4), HAS-BLED 3.8(SD0.9)] were included. Global success rate was 98.6%, successful LAAO with the first selected device size was achieved in 95.5% patients and the device was implanted at first attempt in 78.6% cases. There were only 9(2.5%) major peri-procedural complications. No differences in efficacy or safety results according to the centers previous experience with Watchman 2.5 and procedural volume with Watchman FLX existed. CONCLUSIONS: The Watchman FLX attains high procedural success rates with complete LAA sealing in unselected, real-world patients, along with a low incidence of peri-procedural complications, regardless of operators experience with its previous device iteration or the number of Watchman FLX devices implanted.

Substance Use and Psychological Distress in Mexican Adults during COVID-19 Pandemic: A Cross-Sectional Study.

OBJECTIVES: This observational cross-sectional study examined changes in substance use during the coronavirus disease 2019 (COVID-19) pandemic in the Mexican population and evaluated whether depression or anxiety was associated with these new consumption patterns. METHODS: An online survey was distributed to the general population. Participants were questioned about their demographics, situation during the COVID-19 pandemic, and substance consumption patterns. The Patient Health Questionnaire-9 for depression and the Coronavirus Anxiety Scale were used. RESULTS: A total of 866 individuals completed the survey. The mean scores for the Patient Health Questionnaire-9 and Coronavirus Anxiety Scale were 8.89 ± 6.20 and 3.48 ± 3.22, respectively. The preferred substances were alcohol (19%), tobacco (16.5%), and marijuana (5.6%). Consumption of alcohol (p = 0.042) significantly increased during the pandemic and it was higher in women than in men (p = 0.040). CONCLUSIONS: Substance use patterns were affected by the pandemic, with an increase in the number of users and consumption rate, as well as the reported psychiatric symptoms.

Preventive measures against the COVID-19 pandemic in Mexico: A cross-sectional study.

Introduction: Understanding how Mexicans behave during the pandemic could present a complete picture of the phenomenon in our country and provide better management of it. Objective: This study aimed to analyze the Mexican population's behavior and preventive measures. Methods: This was a cross-sectional study in which a total of 4,004 participants from the general population responded to the survey. Results: Almost 99% of the participants mentioned knowing the symptoms of COVID-19. Although 77.5% of participants considered that they followed proper social distancing measures, 60% of them mentioned that they knew at least six individuals who did not follow social distancing measures. Furthermore, 96.2% of participants reported using preventive measures at least 50% of the time. Only 51.3% used a certified mask. Conclusion: The COVID-19 pandemic outcomes in Mexico are the result of multiple negative factors, such as high rates of comorbidities, high number of people living together at home, many people breaking social isolation, and most of the population using non-certified preventive measures that may not be effective enough.

Prognostic impact of left ventricular ejection fraction recovery in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: analysis of an 11-year all-comers registry.

AIMS: Left ventricular ejection fraction (LVEF) recovery after an ST-segment elevation myocardial infarction (STEMI) identifies a group of patients with a better prognosis. However, the association between long-term outcomes and LVEF recovery among patients with STEMI undergoing primary percutaneous coronary intervention (PCI) has not yet been well investigated. Our study aims to detect differences in long-term all-cause and cardiovascular mortality between patients who recover LVEF at 1-year post-PCI and those who do not, and search for predictors of LVEF recovery. METHODS AND RESULTS: This is a retrospective, single-centre study of 2170 consecutive patients admitted for STEMI in which primary PCI is performed. LVEF was determined at admission and at 1-year follow-up. The primary outcomes were long-term all-cause and cardiovascular mortality. Among the 2168 patients with baseline LVEF data, 822 (38%) had a LVEF < 50% and 1346 (62%) ≥ 50%. Among those with LVEF < 50%, LVEF data at 1-year were available in 554, and 299 (54.0%) presented with complete recovery (LVEF ≥ 50%). LVEF recovery was associated with a reduction in long-term all-cause and cardiovascular mortality (P < 0.0001). Female sex, treatment with ACEIs, lower creatinine levels, infarct-related artery different from the left main or left anterior descendent artery, and absence of prior ischaemic heart disease were independently associated with LVEF recovery. CONCLUSIONS: Nearly 40% of patients with STEMI undergoing primary PCI presented with LVEF depression at hospital admission. Among them, LVEF recovery at 1-year occurred in more than 50% and was independently associated with a significant decrease in long-term all-cause and cardiovascular mortality.

Hyaluronic Acid Reduces Fibrosis in a Rabbit Model of Urethral Anastomosis.

INTRODUCTION: Urethral stricture caused by fibrosis is a common medical condition, but top-line therapy for this pathology has a high recurrence rate. This study aimed to determine the efficacy of hyaluronic acid (HA) treatment in preventing the development of fibrosis in a rabbit model of urethral anastomosis. MATERIALS AND METHODS: This experimental study involved 20 rabbits. HA (0.5 mL, 25 µg/mL) was applied in the experimental group (n = 10) during an experimental urethral anastomosis, and sterile saline (0.9%) solution was applied in the control group (n = 10). Animals underwent reoperation 12 weeks later for urethral resection. Fibrosis, inflammation, and urethral diameter were measured by two blinded pathologists at the site of the anastomosis. RESULTS: The amount of inflammatory infiltrate was similar in both groups. The thicknesses of the collagen fiber band were 275.9 ± 62.3 and 373.4 ± 44.3 µm in the study and control groups (p = 0.001), respectively, and the urethral lumen diameters at the anastomosis site at follow-up were 2575 ± 167 and 2382 ± 214 µm, respectively (p = 0.04). CONCLUSION: HA treatment reduced fibrosis at the anastomosis site during this experiment; we suggest further research to corroborate its efficacy in the treatment of urethral stricture.

Impact of significant paravalvular leaks after transcatheter aortic valve implantation on anaemia and mortality.

OBJECTIVE: The aim of this work is to assess the relationship between significant paravalvular leak (SPL) after transcatheter aortic valve implantation (TAVI) on anaemia and their impact on prognosis. METHODS: Observational analytic study developed at two university hospitals, including all consecutive patients who underwent TAVI during a 10-year period (2009 to 2018). A logistic regression model was created to determine independent predictors of anaemia at 3 months. Time to event outcomes were analysed with Cox regression. Median follow-up was 21.3±21.9 months. RESULTS: 788 patients were included. 5.3% had SPL. SPL was an independent predictor of anaemia 3 months after TAVI (OR: 8.31, 95% CI: 2.06 to 33.50). SPL and anaemia at 3 months were independently associated with long-term mortality (HR: 1.82, 95% CI: 1.16 to 2.85; HR: 2.07, 95% CI: 1.39 to 3.08). CONCLUSION: SPL is an independent predictor of anaemia at 3 months after TAVI, a condition that doubles long-term mortality. Our findings could explain in part the worse prognosis of SPL after TAVI. Further pathophysiological studies are necessary to explain this association.

The extreme floods in the Ebro River basin since 1600 CE.

Reliable and complete knowledge of the historical floods is necessary for understanding the extreme hydrological dynamics of the rivers, their natural variability and anthropic changes. In this work we reconstruct the most important floods of the Ebro basin during the last 400 years in different areas of the basin. The analysis is based on four different areas: the Ebro River at Zaragoza, the Cinca River at Fraga, the Segre River at Lleida, and the Ebro River near its mouth at Tortosa. Based on a documentary research, we have first obtained relevant information about the initial conditions (rainfall duration and distribution, snow cover influence) and the maximum flood heights that allow to reconstruct the maximum peak flows by using hydraulic models and to calculate the subbasins contributions. The results show four main types of extreme floods: a) those affecting simultaneously all the subbasins with the highest peak discharges (Ebro at Tortosa in 1787: 0.15 m3 s-1 km-2); b) those originated at the western basin, upstream from Zaragoza, with an Atlantic origin, presenting moderate maximum peak flows, caused by persistent winter rainfall and where snowmelt significantly contributes to the flood; c) those originating at the central Pyrenean subbasins, with Mediterranean origin, occurring, with high peak discharges. These mainly occur during autumn as a consequence of rainfalls of different duration (between 3 days and 1 month), and without significant snow thawing and d) finally, less frequent but very intense flash floods events centered in the Lower Ebro area with low peak flows. In terms of frequency, two different periods can be distinguished: from 1600 until 1850, the frequency of events is low; since 1850 the frequency of events is clearly higher, due to an increase of the climatic variability during last stages of the Little Ice Age. From the 1960's reservoirs construction modifies discharges regime.

Survival outcomes of the NeoALTTO study (BIG 1-06): updated results of a randomised multicenter phase III neoadjuvant clinical trial in patients with HER2-positive primary breast cancer.

BACKGROUND: Lapatinib (L) plus trastuzumab (T) with weekly paclitaxel significantly increased the pathologic complete response (pCR) rate compared with the anti-human epidermal growth factor receptor 2 (HER2) agent alone plus paclitaxel. The event-free survival (EFS) and overall survival (OS) by the treatment arms L + T vs. T and L vs. T and the relationship between pCR and EFS/OS both in the whole study population and according to hormone receptor-negative and hormone receptor-positive cohorts after a median follow-up of 6.7 years were assessed. PATIENTS AND METHODS: Four hundred fifty-five patients with HER2-positive early breast cancer randomly received L 1500 mg/day (n = 154), T (common dose, n = 149) or L 1000 mg/day plus T (n = 152) for 6 weeks, followed by the assigned anti-HER2 treatment combined with paclitaxel weekly × 12. After surgery, patients received 3 cycles of fluorouracil, epirubicin and cyclophosphamide. The primary end-point was pCR (ypT0/is; for current analysis, it is ypT0/is ypN0), and the secondary end-points were EFS and OS. RESULTS: Six-year EFS rates were 67%, 67% and 74% with L, T and L + T, respectively (L vs T: hazard ratio [HR], 0.98 [95% confidence interval {CI}, 0.64-1.51; P = .93]; L + T vs T: HR, 0.81 [95% CI, 0.52-1.26; P = .35]). Six-Year OS rates were 82%, 79% and 85% for L, T and L + T, respectively (L vs T: HR, 0.85 [95% CI, 0.49-1.46; P = .56]; L + T vs T: HR, 0.72 [95% CI, 0.41-1.27; P = .26]). In landmark analyses, patients with a pCR had a significantly higher 6-year EFS (77% and 65%) and OS (89% and 77%) compared with those without a pCR for both overall and the hormone receptor-negative cohort. CONCLUSION: Achieving a pCR is important in HER2-positive disease and translates into better long-term outcome with regard to EFS and OS.