Making spatial-temporal marine ecosystem modelling better - A perspective.

Marine Ecosystem Models (MEMs) provide a deeper understanding of marine ecosystem dynamics. The United Nations Decade of Ocean Science for Sustainable Development has highlighted the need to deploy these complex mechanistic spatial-temporal models to engage policy makers and society into dialogues towards sustainably managed oceans. From our shared perspective, MEMs remain underutilized because they still lack formal validation, calibration, and uncertainty quantifications that undermines their credibility and uptake in policy arenas. We explore why these shortcomings exist and how to enable the global modelling community to increase MEMs' usefulness. We identify a clear gap between proposed solutions to assess model skills, uncertainty, and confidence and their actual systematic deployment. We attribute this gap to an underlying factor that the ecosystem modelling literature largely ignores: technical issues. We conclude by proposing a conceptual solution that is cost-effective, scalable and simple, because complex spatial-temporal marine ecosystem modelling is already complicated enough.

Non-Redfieldian dynamics driven by phytoplankton phosphate frugality explain nutrient and chlorophyll patterns in model simulations for the Mediterranean Sea.

The relative abundance of nitrate (N) over phosphate (P) measured as a molar ratio (N:P) is typically considered to determine the macronutrient limiting marine primary production. In low-complexity biogeochemical models, a simple threshold value is usually applied based on the canonical Redfield ratio (N:P = 16). However, the N:P ratio is not constant in many oceanic areas, especially marginal, semi-enclosed seas, such as the Mediterranean basin. In this work, a flexible definition of the N:P ratio based on the capacity of phytoplankton to modulate phosphate uptake according to its availability in seawater, the so-called Line of Frugality, is incorporated into the biogeochemical model MedERGOM. This modification allows the acquisition of a more realistic representation of the stoichiometry of nutrients in the Mediterranean basin and allows to better reproduce the observed phytoplankton biomass in productive areas such as the Gulf of Gabes and the Adriatic Sea. This approach is, thus, especially suitable for coastal areas in which basin-scale biogeochemical models fail to reproduce patterns observed by remote sensing or in situ measurements. Our results show that implementation of the stoichiometric flexibility of phytoplankton in a low-complexity biogeochemical model enhances the reproducibility of ecosystem dynamics without increasing the computational demand, representing a simple approximation easily implemented in models aiming to describe regions with a Non-Redfieldian stoichiometry.

Nutritional Status, Body Surface, and Low Lean Body Mass/Body Mass Index Are Related to Dose Reduction and Severe Gastrointestinal Toxicity Induced by Afatinib in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: The main reason for dose reduction of afatinib is gastrointestinal toxicity (GT). In a phase II study, we analyzed anthropometrical, nutritional, and biochemical factors associated with GT induced by afatinib. MATERIALS AND METHODS: Patients diagnosed with non-small cell lung cancer who progressed to prior chemotherapy received 40 mg of afatinib. Malnutrition was determined by Subjective Global Assessment, and lean body mass (LBM) was determined by computed tomography scan analysis using a pre-established Hounsfield unit threshold. Toxicity was obtained during four cycles by Common Terminology Criteria for Adverse Events. RESULTS: Eighty-four patients were enrolled. Afatinib was administered as the second, third, and fourth line of treatment in 54.8%, 38.1%, and 7.12% of patients, respectively. Severe diarrhea, mucositis, and overall severe GT were present in 38.9%, 28.8%, and 57.5%, respectively. Of the patients, 50% developed dose-limiting toxicity (DLT). Patients with malnutrition have higher risk for severe GT. Patients with lower LBM and body mass index developed more DLT (71.4% vs. 18.8%). CONCLUSION: Malnutrition is associated with a higher risk of severe GT induced by afatinib. Determination of nutritional status and body composition are helpful in identifying patients at higher risk of severe GT and could allow initiating treatment with lower doses according to tolerance.

Biogeochemical control of marine productivity in the Mediterranean Sea during the last 50 years.

The temporal dynamics of biogeochemical variables derived from a coupled 3-D model of the Mediterranean Sea are evaluated for the last 50 years (1960-2010) against independent data on fisheries catch per unit effort (CPUE) for the same time period. Concordant patterns are found in the time series of all of the biological variables (from the model and from fisheries statistics), with low values at the beginning of the series, a later increase, with maximum levels reached at the end of the 1990s, and a posterior stabilization. Spectral analysis of the annual biological time series reveals coincident low-frequency signals in all of them. The first, more energetic signal peaks around the year 2000, while the second, less energetic signal peaks near 1982. Almost identical low-frequency signals are found in the nutrient loads of the rivers and in the integrated nutrient levels in the surface marine ecosystem. Nitrate concentration shows a maximum level in 1998, with a later stabilization to present-day values, coincident with the first low-frequency signal found in the biological series. Phosphate shows maximum concentrations around 1982 and a posterior sharp decline, in concordance with the second low-frequency signal observed in the biological series. That result seems to indicate that the control of marine productivity (plankton to fish) in the Mediterranean is principally mediated through bottom-up processes that could be traced back to the characteristics of riverine discharges. The high sensitivity of CPUE time series to environmental conditions might be another indicator of the overexploitation of this marine ecosystem. KEY POINTS: Biogeochemical evolution of the Mediterranean over the past 50 yearsRiver nutrient loads drive primary and secondary productionsStrong link between low trophic levels and fisheries.

A European community pharmacy-based survey to investigate patterns of prescription fraud through identification of falsified prescriptions.

AIM: To identify prescription drugs involved in falsified prescriptions in community pharmacies in 6 European countries. METHODS: A cross-sectional survey among 2,105 community pharmacies in Belgium, France, Italy, the Netherlands, Spain and Sweden was carried out to collect all suspect prescription forms. For each reported drug, the number of reported falsified prescriptions per thousand inhabitants was estimated. A falsification ratio was calculated by dividing the number of reports by the number of defined daily doses per 1,000 inhabitants per day for this drug, computed from national sale or reimbursement data. RESULTS: On 862 prescription forms, benzodiazepines (zolpidem, bromazepam, alprazolam), buprenorphine (as an opioid maintenance drug) and tramadol were the most frequently reported. Depending on their level of use in each country, methylphenidate, morphine and flunitrazepam presented the highest falsification ratios, particularly in Spain, Belgium and France. CONCLUSIONS: Stimulants, opioids and some benzodiazepines were the most frequently reported drugs in this survey on falsified prescriptions, but differences between countries were observed.

Potential polyunsaturated aldehydes in the Strait of Gibraltar under two tidal regimes.

Diatoms, a major component of the large-sized phytoplankton, are able to produce and release polyunsaturated aldehydes after cell disruption (potential PUAs or pPUA). These organisms are dominant in the large phytoplankton fraction (>10 µm) in the Strait of Gibraltar, the only connection between the Mediterranean Sea and the Atlantic Ocean. In this area, the hydrodynamics exerts a strong control on the composition and physiological state of the phytoplankton. This environment offers a great opportunity to analyze and compare the little known distribution of larger sized PUA producers in nature and, moreover, to study how environmental variables could affect the ranges and potential distribution of these compounds. Our results showed that, at both tidal regimes studied (Spring and Neap tides), diatoms in the Strait of Gibraltar are able to produce three aldehydes: Heptadienal, Octadienal and Decadienal, with a significant dominance of Decadienal production. The PUA released by mechanical cell disruption of large-sized collected cells (pPUA) ranged from 0.01 to 12.3 pmol from cells in 1 L, and from 0.1 to 9.8 fmol cell⁻¹. Tidal regime affected the abundance, distribution and the level of physiological stress of diatoms in the Strait. During Spring tides, diatoms were more abundant, usually grouped nearer the coastal basin and showed less physiological stress than during Neap tides. Our results suggest a significant general increase in the pPUA productivity with increasing physiological stress for the cell also significantly associated to low nitrate availability.

Proof of concept for a new sensor to monitor marine litter from space.

Worldwide, governments are implementing strategies to combat marine litter. However, their effectiveness is largely unknown because we lack tools to systematically monitor marine litter over broad spatio-temporal scales. Metre-sized aggregations of floating debris generated by sea-surface convergence lines have been reported as a reliable target for detection from satellites. Yet, the usefulness of such ephemeral, scattered aggregations as proxy for sustained, large-scale monitoring of marine litter remains an open question for a dedicated Earth-Observation mission. Here, we track this proxy over a series of 300,000 satellite images of the entire Mediterranean Sea. The proxy is mainly related to recent inputs from land-based litter sources. Despite the limitations of in-orbit technology, satellite detections are sufficient to map hot-spots and capture trends, providing an unprecedented source-to-sink view of the marine litter phenomenon. Torrential rains largely control marine litter inputs, while coastal boundary currents and wind-driven surface sweep arise as key drivers for its distribution over the ocean. Satellite-based monitoring proves to be a real game changer for marine litter research and management. Furthermore, the development of an ad-hoc sensor can lower the minimum detectable concentration by one order of magnitude, ensuring operational monitoring, at least for seasonal-to-interannual variability in the mesoscale.

Life expectancy after surgical aortic valve replacement for low-gradient aortic stenosis with preserved ejection fraction.

INTRODUCTION AND OBJECTIVES: Surgical aortic valve replacement (SAVR) can modify the natural history of severe aortic stenosis (SAS). However, compared with the general population, these patients have a loss of life expectancy. The life expectancy of patients who undergo SAVR due to low-gradient SAS with preserved left ventricular ejection fraction (LVEF) is unknown. METHODS: We included all patients between 50 and 65 years who underwent isolated SAVR in 27 Spanish centers during an 18-year period. We analyzed observed and expected survival at 18 years in patients with low-gradient SAS with preserved LVEF and all other types of SAS. We used propensity score matching to compare the life expectancy of patients with low-gradient SAS with preserved LVEF vs those with high-gradient SAS with preserved LVEF. RESULTS: We analyzed 5084 patients, of whom 413 had low-gradient SAS with preserved LVEF. For these patients, observed survival at 10, 15 and 18 years was 86.6% (95%CI, 85.3-87.8), 75% (95%CI, 72.7-77.2), and 63.5% (95%CI, 58.8-67.8). Expected survival at 10, 15 and 18 years was 90.2%, 82.1%, and 75.7%. In the matched sample, survival of patients with low-gradient SAS with preserved LVEF was similar to that of patients with high-gradient with preserved LVEF, log-rank test, P=.95; HR=1 (95%CI, 0.7-1.4; P=.95). CONCLUSIONS: There is a loss of life expectancy in patients with all types of SAS undergoing SAVR. This loss is higher in patients with left ventricular dysfunction and lower in patients with low-gradient or high-gradient aortic stenosis with preserved LVEF. The benefit of surgery is similar between these last 2 groups.

Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial.

PURPOSE: Hypoxia has been associated with chemoradioresistance secondary to vascular endothelial growth factor receptor induced by hypoxia-induced factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in tissues, and this may have antiangiogenic, proapoptotic, and antiefflux effects. Particularly, epidermal growth factor-mutated (EGFRm) tumor cell lines have been shown to overexpress both vascular endothelial growth factor and HIF. In this phase 2 study, we evaluated the effect of transdermal NTG plus whole brain radiation therapy (WBRT) in patients with non-small cell lung cancer (NSCLC) with brain metastases (BM). METHODS: This was an open-label, phase 2 clinical trial with 96 patients with NSCLC and BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. The primary endpoint was intracranial objective response rate (iORR) evaluated 3 months posttreatment. NTG was administered using a transdermal 36-mg patch from Monday through Friday throughout WBRT administration (10 days). The protocol was retrospectively registered at ClinicalTrials.gov (NCT04338867). RESULTS: Fifty patients were allocated to the control group, and 46 were allocated to the experimental group (NTG); among these, 26 (52%) had EGFRm in the control group and 21 (45.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response compared with controls (56.5% [n = 26/46 evaluable patients] vs 32.7% [n = 16/49 evaluable patients]; relative risk, 1.73; 95% confidence interval [CI], 1.08-2.78; P = .024). Additionally, patients who received NTG + WBRT had an independently prolonged intracranial progression-free survival (ICPFS) compared with those who received WBRT alone (27.7 vs 9.6; hazard ratio [HR], 0.5; 95% CI, 0.2-0.9; P = .020); this positively affected overall progression-free survival among patients who received systemic therapy (n = 88; HR, 0.5; 95% CI, 0.2-0.9; P = .043). The benefit of ICPFS (HR, 0.4; 95% CI, 0.2-0.9; P = .030) was significant in the EGFRm patient subgroup. No differences were observed in overall survival. A significantly higher rate of vomiting presented in the NTG arm of the study (P = .016). CONCLUSIONS: The concurrent administration of NTG and radiation therapy improves iORR and ICPFS among patients with NSCLC with BM. The benefit in ICPFS is significant in the EGFRm patient subgroup.

Model based estimate of transboundary litter pollution on Mediterranean coasts.

Plastic litter pollution is one of the major concerns for the health of marine ecosystems worldwide. This pervasive form of pollution affects all oceans and seas and it's interacting with multiple levels of the marine food webs. In the European context, several pieces of legislation try to fight against this pervasive and ubiquitous form of pollution. Recently, EU Member States have agreed to a maximum threshold of litter items per coast length (20 items/100 m coastline). One major concern among stakeholders to reach this consensus was the transboundary litter, as measures need to be implemented in the country of origin. Henceforth, a solid method to estimate the amounts of the transboundary litter to a given Member State's coasts is needed. In this contribution, we use a combination of hydrodynamic and Lagrangian models for the Mediterranean Sea in order to understand the origin of coastal litter. Simulations show that the amount of transboundary litter in Mediterranean countries could be as large as 30% although both regional and seasonal differences could be significant.

Modelling the Mediterranean Sea ecosystem at high spatial resolution to inform the ecosystem-based management in the region.

Cumulative pressures are rapidly expanding in the Mediterranean Sea with consequences for marine biodiversity and marine resources, and the services they provide. Policy makers urge for a marine ecosystem assessment of the region in space and time. This study evaluates how the whole Mediterranean food web may have responded to historical changes in the climate, environment and fisheries, through the use of an ecosystem modelling over a long time span (decades) at high spatial resolution (8 × 8 km), to inform regional and sub-regional management. Results indicate coastal and shelf areas to be the sites with highest marine biodiversity and marine resources biomass, which decrease towards the south-eastern regions. High levels of total catches and discards are predicted to be concentrated in the Western sub-basin and the Adriatic Sea. Mean spatial-temporal changes of total and commercial biomass show increases in offshore waters of the region, while biodiversity indicators show marginal changes. Total catches and discards increase greatly in offshore waters of the Western and Eastern sub-basins. Spatial patterns and temporal mean changes of marine biodiversity, community biomasses and trophic indices, assessed in this study, aim at identifying areas and food web components that show signs of deterioration with the overall goal of assisting policy makers in designing and implementing spatial management actions for the region.

Life expectancy after aortic valve replacement in young patients.

INTRODUCTION AND OBJECTIVES: In young patients with severe aortic stenosis, it is unknown whether their life expectancy restored after aortic valve replacement (AVR) is unknown. METHODS: We analyzed all patients aged between 50 and 65 years who underwent isolated AVR in 27 Spanish centers during an 18-year period. We compared observed and expected survival at 15 years of follow-up. We repeated all analyses for patients without complications in the postoperative period. RESULTS: A total of 5084 patients were analyzed. For the overall sample, observed survival at 10 and 15 years was 85.3% (95%CI, 84.1%-86.4%) and 73.7% (95%CI, 71.6%-75.6%), respectively. Expected survival was 90.1% and 82.1%. Cumulative relative survival for 1, 5, 10 and 15 years of follow-up was 97.4% (95%CI, 96.9%-97.9%), 96.5% (95%CI, 95.7%-97.3%), 94.7% (95%CI, 93.3%-95.9%), and 89.8% (95%CI, 87.3%-92.1%). For patients without complications, cumulative relative survival for 1, 5, 10 and 15 years was 100.3% (95%CI, 99.8%-100.5%), 98.9% (95%CI 97.6% -99.9%), 97.3% (95%CI, 94.9%-99.4%), and 91.9% (95%CI, 86.5%-96.8%). CONCLUSIONS: Life expectancy in young patients who have severe aortic stenosis and undergo AVR is lower than that of the general population. Life expectancy of individuals without complications during the postoperative period is also reduced. Therefore, baseline characteristics are likely the main factors that explain the reduction in life expectancy.

Differences in life expectancy between men and women after aortic valve replacement.

OBJECTIVES: Some researchers have observed an increased number of deaths during the follow-up of young patients who undergo aortic valve replacement due to severe aortic stenosis, suggesting that this procedure does not restore their life expectancy. Our goal was to confirm these findings and explore sex-based differences. METHODS: All patients between 50 and 65 years of age who underwent isolated aortic valve replacement in 27 Spanish centres during an 18-year period were included. We compared observed and expected survival at 15 years of follow-up and estimated the cumulative incidence of death from a competing risks point of view. We stratified by sex and analysed if being a woman was an independent risk factor for death. RESULTS: For men, the observed survival at 10 and 15 years of follow-up was 85% [95% confidence interval (CI) 83.6%-86.4%] and 72.3% (95% CI 69.7%-74.7%), respectively whereas the expected survival was 88.1% and 78.8%. For women, the observed survival at 10 and 15 years was 85% (95% CI 82.8%-86.9%) and 73% (95% CI 69.1%-76.4%), whereas the expected survival was 94.6% and 89.4%. At 15 years of follow-up, the cumulative incidence of death due to the disease in men and women was 8.2% and 16.7%, respectively. In addition, being a woman was an independent risk factor for death (hazard ratio = 1.23 (95% CI 1.02-1.48; P = 0.03). CONCLUSIONS: After the aortic valve replacement, men and women do not have their life expectancy restored, but this loss is much higher in women than in men. In addition, being a woman is a risk factor for long-term death. Reasons for these findings are unknown and must be investigated.

Biological or mechanical prostheses for isolated aortic valve replacement in patients aged 50-65 years: the ANDALVALVE study.

OBJECTIVES: The decision about whether to use a biological or a mechanical prosthesis for aortic valve replacement remains controversial in patients between 50 and 65 years of age and has yet to be addressed in a Mediterranean population. This research aimed to analyse long-term survival and major morbidity rates (30-day mortality, stroke, any prosthetic reoperation and major bleeding) within this population. METHODS: Our multicentre observational retrospective study included all subjects aged 50-65 years who had a primary isolated aortic valve replacement due to severe aortic stenosis at 7 public hospitals from Andalusia (Spain) between 2000 and 2015. Concomitant surgery, reoperations and endocarditis were the exclusion criteria. A total of 1443 patients were enrolled in the study (272 with biological and 1171 with mechanical valves). Multivariate analyses including a 2:1 propensity score matching (506 mechanical and 257 biological prostheses) were conducted. RESULTS: Bioprostheses were implanted in 18.8% (n = 272): 35% were women; the mean EuroSCORE-I was 3%. The mean follow-up was 8.1 ± 4.9 years in a matched sample: 8.8 ± 4.9 years in those receiving a mechanical vs 7.1 ± 4.5 years in those receiving a biological prosthesis (P = 0.001). In the paired sample, the 15-year survival rate was 73% in those who had a biological vs 76% in those who had a mechanical valve [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.54-1.20; P = 0.159]. No significant differences were observed in patients ≥55 years old (74% of 15-year survival in both groups: HR 0.88, 95% CI 0.56-1.34; P = 0.527). A higher rate of major bleeding was found in patients with a mechanical prosthesis (P = 0.004), whereas reoperation was more frequent among those with a biological prosthesis (P = 0.01). CONCLUSIONS: Long-term survival was comparable in patients above 55 years of age. Mechanical prostheses were associated with more major bleeding and bioprostheses, with more reoperations. A bioprosthesis in patients above 55 years old is a reasonable choice. CLINICAL TRIAL REGISTRATION NUMBER: NCT03239509.

Deep winter convection and phytoplankton dynamics in the NW Mediterranean Sea under present climate and future (horizon 2030) scenarios.

Deep water convection (DC) in winter is one of the major processes driving open-ocean primary productivity in the Northwestern Mediterranean Sea. DC is highly variable in time, depending on the specific conditions (stratification, circulation and ocean-atmosphere interactions) of each specific winter. This variability also drives the interannual oscillations of open-ocean primary productivity in this important region for many commercially-important fish species. We use a coupled model system to 1) understand to what extent DC impacts phytoplankton seasonality in the present-day and 2) to explore potential changes in future scenarios (~2030). Our model represents quite accurately the present-day characteristics of DC and its importance for open-ocean phytoplankton blooms. However, for the future scenarios the importance of deep nutrients in fertilizing the euphotic layer of the NW Mediterranean decreases. The model simulates changes in surface density and on the levels of kinetic energy that make mesoscale activity associated with horizontal currents to become a more important fertilization mechanism, inducing subsequently phenological changes in seasonal plankton cycles. Because of our focus on the open-sea, an exact quantification of the impact of those changes on the overall biological production of the NW Mediterranean cannot be made at the moment.

Hydrological and biogeochemical response of the Mediterranean Sea to freshwater flow changes for the end of the 21st century.

We evaluate the changes on the hydrological (temperature and salinity) and biogeochemical (phytoplankton biomass) characteristics of the Mediterranean Sea induced by freshwater flow modifications under two different scenarios for the end of the 21st century. An ensemble of four regional climate model realizations using different global circulation models at the boundary and different emission scenarios are used to force a single ocean model for the Mediterranean Sea. Freshwater flow is modified according to the simulated changes in the precipitation rates for the different rivers' catchment regions. To isolate the effect resulting from a change in freshwater flow, model results are evaluated against a 'baseline' simulation realized assuming a constant inflow equivalent to climatologic values. Our model results indicate that sea surface salinity could be significantly altered by freshwater flow modification in specific regions and that the affected area and the sign of the anomaly are highly dependent on the used climate model and emission scenario. Sea surface temperature and phytoplankton biomass, on the contrary, show no coherent spatial pattern but a rather widespread scattered response. We found in open-water regions a significant negative relationship between sea surface temperature anomalies and phytoplankton biomass anomalies. This indicates that freshwater flow modification could alter the vertical stability of the water column throughout the Mediterranean Sea, by changing the strength of vertical mixing and consequently upper water fertilization. In coastal regions, however, the correlation between sea temperature anomalies and phytoplankton biomass is positive, indicating a larger importance of the physiological control of growth rates by temperature.

Gynaecomastia associated with proton pump inhibitors: a case series from the Spanish Pharmacovigilance System.

OBJECTIVE: Proton pump inhibitors (PPIs) are widely used in the management of peptic ulcer and related symptoms. They have been linked to certain endocrine adverse reactions, including gynaecomastia. The aim of the present study is to investigate the association between the use of PPIs and the development of gynaecomastia. METHODS: Reports of cases of gynaecomastia that had putatively been induced by PPIs and that had been collected by the Spanish Pharmacovigilance System via the 'yellow card' scheme, were analysed. Reporting odds ratios (RORs) were calculated as a measure of disproportionality. RESULTS: Twenty-four cases of gynaecomastia associated with PPIs were identified in the database of the Spanish Pharmacovigilance System. Overall, there was a clear temporal sequence of events in all cases and the adverse effect disappeared after drug withdrawal in most of the cases; 14 patients were also receiving other drugs at the time of the adverse effect. The ROR for omeprazole exposure versus no exposure, but not that for other PPIs, showed a statistically significant elevation (ROR adjusted for age 5.23; 95% CI 3.32, 8.26). CONCLUSION: Considering the widespread use of PPIs, gynaecomastia may affect a large number of patients. In most cases, the condition seems to be reversible with drug withdrawal. Doctors should be aware of this potential adverse reaction when prescribing PPIs to their patients over long periods of time.

Historical changes of the Mediterranean Sea ecosystem: modelling the role and impact of primary productivity and fisheries changes over time.

The Mediterranean Sea has been defined "under siege" because of intense pressures from multiple human activities; yet there is still insufficient information on the cumulative impact of these stressors on the ecosystem and its resources. We evaluate how the historical (1950-2011) trends of various ecosystems groups/species have been impacted by changes in primary productivity (PP) combined with fishing pressure. We investigate the whole Mediterranean Sea using a food web modelling approach. Results indicate that both changes in PP and fishing pressure played an important role in driving species dynamics. Yet, PP was the strongest driver upon the Mediterranean Sea ecosystem. This highlights the importance of bottom-up processes in controlling the biological characteristics of the region. We observe a reduction in abundance of important fish species (~34%, including commercial and non-commercial) and top predators (~41%), and increases of the organisms at the bottom of the food web (~23%). Ecological indicators, such as community biomass, trophic levels, catch and diversity indicators, reflect such changes and show overall ecosystem degradation over time. Since climate change and fishing pressure are expected to intensify in the Mediterranean Sea, this study constitutes a baseline reference for stepping forward in assessing the future management of the basin.

HMG CoA reductase inhibitors and impotence: two case series from the Spanish and French drug monitoring systems.

OBJECTIVE: HMG CoA Reductase inhibitors, more commonly called statins, are used in the pharmacological management of hyperlipidaemia. At present, the use of these drugs is increasing worldwide. They have been linked to certain adverse drug reactions, including impotence. The aim of the present study is to explore the basis of the association between statin use and impotence using data from spontaneous reports. METHOD: We analysed the cases of impotence associated with statins that were collected by the Spanish and French pharmacovigilance systems. We used cases of impotence as a numerator and consumption data as a denominator to estimate the cumulative reported incidence of impotence. RESULTS: Thirty-eight cases of impotence associated with statins have been identified in the database of the Spanish pharmacovigilance system; overall, there was a temporal sequence of events in all cases and the adverse reaction disappeared after drug withdrawal in 93% of the cases. Sixteen patients had also been treated with other drugs. In France, 37 cases were collected. In 85% of these cases recovery from the adverse reaction was observed after drug withdrawal; there was a positive rechallenge in five cases, and 15 patients were receiving other drugs at the same time. No significant differences among reported incidences with different statins were found. CONCLUSION: Considering the widespread use of this drug class and the under-reporting of this particular reaction it could affect a large number of patients. The reaction seems to be reversible in most of the cases after drug withdrawal. Doctors should be aware of this potential adverse reaction when prescribing statins to their patients.