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The calcineurin pathway is often activated in mycosis fungoides. We aimed to assess the activity and safety of topical pimecrolimus, a calcineurin inhibitor, in patients with early mycosis fungoides.PimTo-MF was a single-arm, multicentre, phase 2 trial done at six medical centres in Spain. Patients (aged ≥18 years) had histologically confirmed early mycosis fungoides (stages IA-IIA) and an Eastern Cooperative Oncology Group performance status of 0-1. Key exclusion criteria included the use of concurrent treatments for mycosis fungoides, including sunbathing, topical or systemic corticosteroids, and other calcineurin inhibitors. Patients applied topical pimecrolimus 1% cream on their skin lesions twice daily for 16 weeks (1 g per 2% of body surface), with subsequent follow-up of 12 months. Dosage modifications were not allowed. To evaluate adherence to the treatment, patients were instructed to return all empty tubes to the hospital (as per drug accountability protocols). The primary endpoint was the overall response ratein the intention-to-treat population. PimTo-MF is registered with EudraCT, 2014-001377-14, and is complete.Between March 1, 2015, and Sept 30, 2016, 39 patients were enrolled. All patients were assessable, with a median age of 51·5 years (IQR 45-62), and the population was predominantly male (24 male [62%], 15 female [38%]). Median follow-up after baseline was 5·7 years (IQR 5·7-6·2). 22 (56%) of 39 patients had an overall response (one complete response, 21 partial responses). Responses were observed across IA (14 [54%] of 26 patients) and IB (eight [73%] of 11 patients) clinical stages, but not IIA. Topical pimecrolimus was well tolerated and no patient required a dose reduction or discontinued treatment because of unacceptable drug-related toxicity. No patients were lost to follow-up or discontinued treatment. 13 (33%) of 39 patients reported adverse events; transitory mild burning or pruritus (grade 1) was the most common, seen in eight (21%) patients. In three (8%) of these patients, the burning or pruritus was considered related to treatment. No grade 4 or 5 adverse events were observed.Pimecrolimus 1% cream seems active and safe in patients with early stage mycosis fungoides. Our findings should be taken with caution until long-term follow-up data are obtained that confirm the safety of this treatment. Further controlled clinical trials are warranted to confirm these results.Instituto de Salud Carlos III and the European Regional Development Fund.For the Spanish translation of the abstract see Supplementary Materials section.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Background Elderly patients with COVID-19 are among the most numerous populations being admitted in the ICU due to its high mortality rate and high comorbidity incidence. An early severity risk stratification at hospital admission could help optimize ICU usage towards those more vulnerable and critically ill patients. Methods Of 503 Spanish patients aged>64 years admitted in the ICU between 26 Feb and 02 Nov 2020 in two Spanish hospitals, we included 193 quality-controlled patients. The subphenotyping combined PCA and t-SNE dimensionality reduction methods to maximize non-linear correlation and reduce noise among age and full blood count tests (FBC) at hospital admission, followed by hierarchical clustering. Findings We identified five subphenotypes (Eld-ICU-COV19 clusters) with heterogeneous FBC patterns associated to significantly disparate 30-day ICU mortality rates ranging from 2% in a healthy cluster to 44% in a severe cluster, along three moderate clusters. Interpretations To our knowledge, this is the first study using age and FBC at hospital admission to early stratify the risk of death in ICU at 30 days in elderly patients. Our results provide guidance to comprehend the phenotypic classification and disparate severity patterns among elderly ICU patients with COVID-19, based only on age and FBC, that have the potential to establish target groups for early risk stratification or early triage systems to provide personalized treatments or aid the decision-making during resource allocation process for each target Eld-ICU-COV19 cluster, especially in those circumstances with resource scarcity problem. Funding FONDO SUPERA COVID-19 by CRUE-Santander Bank grant SUBCOVERWD-19. Research in context Evidence before this study We searched on PubMed and Google Scholar using the search terms “COVID-19”, “SARS-CoV2”, “phenotypes” for research published between 2020 to 2022, with no language restriction, to detect any published study identifying and characterizing phenotypes among ICU COVID-19 patients. A previous COVID-19 phenotyping study found three phenotypes from hospitalized patients associated with significantly disparate 30-day mortality rates (ranging from 2·5 to 60·7%). However, it seems to become harder to find phenotypes with discriminative mortality rates among ICU COVID-19 patients. For example, we found one study that uncovered two phenotypes from 39 ICU COVID-19 patients based on biomarkers with 39% and 63% mortality rates, but such difference was not statistically significant. We also found another study with more success that uncovered two ICU COVID-19 phenotypes using two different trajectories with somehow disparate 28-day mortality rates of 27% versus 37% (Ventilatory ratio trajectories) and of 25% versus 39% (mechanical power trajectories). Added value of this study To our knowledge, this is the first study that uses age and laboratory results at hospital admission (i.e., before ICU admission) in elderly patients to early stratify, prior ICU admission, the risk of death in ICU at 30 days. We classified 193 patients with COVID-19, based on age and ten Full Blood Count (FBC) tests, into five subphenotypes (one healthy, three moderate, and one severe) that showed significantly disparate 30-day ICU mortality rates from 2% to 44%. Implications of all the available evidence Identifying, from elderly ICU patients with COVID-19 (Eld-ICU-COV19), subphenotypes could spur further investigation to analyze the potential differences in their underlying disease mechanisms, acquire better phenotypical understanding among Eld-ICU-COV19 toward better decision-making in distributing the limited resources (including both logistic and medical) as well as shedding light on tailoring personalized treatment for each specific target subgroup in future medical research and clinical trial.

Resumen Introduccion y objetivos La ivabradina es un inhibidor de la corriente If, principal determinante de la funcion marcapasos del nodulo sinusal, aprobado como antianginoso y para tratar la insuficiencia cardiaca. Existen indicios sobre su capacidad para inhibir la conduccion a traves del nodulo auriculoventricular (NAV). Sobre esta base, el proyecto BRAKE-AF plantea el uso de ivabradina como agente cronotropico negativo en fibrilacion auricular (FA). Metodos Se realizara un ensayo clinico multicentrico de fase III, aleatorizado, abierto, en paralelo, con diseno de no inferioridad, para comparar la ivabradina frente a la digoxina en 232 pacientes con FA permanente no controlada con bloqueadores beta o antagonistas del calcio; el objetivo primario es la reduccion de la frecuencia cardiaca media diurna en un Holter de 24 h a los 3 meses. El ensayo se apoyara en un estudio electrofisiologico que analizara el efecto de la ivabradina en el potencial de accion del NAV humano, utilizando un modelo experimental en celulas de ovario de hamster chino transfectadas con el ADN que codifica la expresion de los distintos canales que componen dicho potencial de accion, registrando las corrientes ionicas mediante la tecnica del parche de membrana. Resultados Se obtendra informacion tanto del efecto de la ivabradina en las corrientes ionicas y el potencial de accion del NAV como de su eficacia y su seguridad en pacientes con FA permanente. Conclusiones Los resultados del proyecto BRAKE-AF podrian permitir que la ivabradina se incluyera en el limitado arsenal de farmacos disponibles actualmente para el control de frecuencia en la FA. Ensayo registrado en ClinicalTrials.gov (Identificador: NCT03718273).

Introduction and objectives Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF). Methods A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques. Results New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF. Conclusions The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF. Clinical trial registration: http://www.clinicaltrials.gov . Identifier: NCT03718273 .

Objective:To determine the association between ultra-processed food (UPF) intake and all-cause mortality in a representative sample of Spanish population.Design:Prospective cohort design in which follow-up lasted from baseline (1991) to mortality date or 31 December 2017, whichever was first. Dietary information was collected using a validated frequency questionnaire and categorised following the NOVA classification according to the extent of food processing. The association between consumption of UPF and mortality was analysed using Cox models. Isoenergetic substitution models were constructed to compare the health effects of the NOVA groups.Setting:Cohort from the Diet and Risk of Cardiovascular Diseases (CVD) in Spain (DRECE) study, representative of the Spanish populationParticipants:Totally, 4679 subjects between 5 and 59 years old.Results:Average consumption of UPF was 370·8 g/d (24·4 % of energy intake). After a median follow-up of 27 years, 450 deaths occurred. Those who consumed the highest amount of UPF had higher risk of mortality. For every 10 % of the energy intake from UPF consumption, an increase of 15 % in the hazard of all-cause mortality was observed (HR 1·15; (95 % CI 1·03, 1·27); P-value = 0·012). Substitution of UPF with minimally processed foods was significantly associated with a decreased risk of mortality.Conclusions:An increase in UPF consumption was associated with higher risk of all-cause mortality in a representative sample of the Spanish population. Moreover, the theoretical substitution of UPF with unprocessed or minimally processed foods leads to a decrease in mortality. These results support the need to promote diets based on unprocessed or minimally processed foods.

The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF.To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis.We analysed different objective health measures and SPH as RF for dementia and AD incidence in 4569 participants of the NEDICES cohort by means of Cox-regression models. The mean follow-up period was 3.2 (range: 0.03-6.6) years.Ageing, low education, history of stroke, and "poor" SPH were the main RF for dementia and AD incidence, whereas physical activity was protective. "Poor" SPH had a hazard ratio = 1.66 (95% CI 1.17-2.46; p = 0.012) after controlling for different confounders.According to data from NEDICES cohort, SPH is a better predictor of dementia and AD than other more objective health status proxies. SPH should be considered a holistic and biologically rooted indicator of health status, which can predict future development of dementia and AD in older adults.Our data indicate that it is worthwhile to include the SPH status as a RF in the studies of dementia and AD incidence and to explore the effect of its improvement in the evolution of this incidence.

Front-of-pack labels can improve the ability of consumers to identify which foods are healthier, making them a useful public health tool. Nutri-Score is a front-of-pack labelling system adopted by several European countries. This system ranks foods according to their nutritional quality, but does not consider other dimensions such as the degree of food processing. The aim of this study is to compare the nutritional quality (as assessed by Nutri-Score) and the ultra-processing (as assessed by the NOVA classification) of foods in the Open Food Facts database. A simple correspondence analysis was carried out to study the relationship between the two systems. Ultra-processed foods (NOVA 4) were found in all Nutri-Score categories, ranging from 26.08% in nutritional category A, 51.48% in category B, 59.09% in category C, 67.39% in category D to up to 83.69% in nutritional category E. Given the negative effect that the consumption of ultra-processed foods has on different aspects of health, front-of-pack labelling with Nutri-Score should at least be accompanied by complementary labelling indicating the level of processing, such as the NOVA classification.

Background To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). Methods We did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739), and is ongoing. Findings Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p

Purpose Heart failure (HF) is a chronic, frequent and disabling condition but with a modifiable course and a large potential for improving. The aim of this study was to validate the two available clinical prediction rules for mortality at one year in patients with primo-hospitalization for decompensated HF: PREDICE and AHEAD. The secondary aim was to evaluate in our setting the changes in the clinical pattern of HF in the last decade in patients hospitalized for a first episode of the disease. Patients and methods A prospective multicenter cohort study, which included 180 patients hospitalized with "de novo" HF was conducted to validate the PREDICE score. Calibration and discrimination measurements were calculated for the PREDICE model and the PREDICE score (using the validation cohort of the PREDICE) and the AHEAD score (using both the development and the validation cohort of the PREDICE). Results For the PREDICE models, the area under the curve (AUC) was 0.68 (95% confidence interval [CI]: 0.57-0.79) and the calibration slope 0.65 (95% CI: 0.21-1.20). For the PREDICE score AUC was 0.59 (95% CI: 0.47-0.71) and slope 0.42 (95% CI: -0.20-1.17). For the AHEAD score the AUC was 0.68 (95% CI: 0.62-0.73) and slope 1.38 (95% CI: 0.62-0.73) when used the development cohort of PREDICE and the AUC was 0.58 (95% CI: 0.49-0.67), and slope 0.68 (95% CI: -0.06 to 1.47) when used its validation cohort. Conclusion The present study shows that the two risk scores available for patients with primo-hospitalization for decompensated HF (PREDICE and AHEAD) are not currently valid for predicting mortality at one-year. In our setting the clinical spectrum of hospitalized patients with new-onset HF has been modified over time. The study underscores the need to validate the prognostic models before clinical implementation.

Mediterranean Diet (MedDiet) is broadly aknowledged as healthy. Different scoring systems of adherence to MedDiet have been developed. These indexes share components, but also disagree and don’t correlate as expected. So, methodological issues arise when comparing studies using different MedDiet adherence scores. Furthermore, scoring calculus is time consuming and prone to error. We develop this package as a reproducible and easy-to-use way of calculating different scores of adherence to MedDiet and provide a methodological improvement to nutriepidemiological studies using adherence scores. Each function in MedDietCalc package computes a single score according to its authors published scoring schema. Implementation: R package. Main feature is a group of calculators of 14 literature available MedDiet scores, with several implementations to ease their use. It also includes a sample dataset from DRECE 6 study and FRESCO cardiovascular risk score calculator. Available from the Comprehensive R Archive Network [ CRAN.R-project.org ] under the name “MedDietCalc”, licensed with General Public License 3. We provide the first software to compute and compare different MedDiet scores, which can also be used with datasets. Different scores to measure adherence to MedDiet exist, with no gold standard. In the provided sample just 3 score pairs were highly correlated, and most of them were moderately or poorly correlated. This disagreement limits our understanding of the effects of MedDiet on health status. Comparability of studies could be improved if adherence to MedDiet were reported with more than a single score.

Objective The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting. Methods We enrolled 31 participants recently diagnosed with PD who were due to start dopaminergic treatment and 30 age-matched controls. We remotely monitored their typing pattern during a 6-month (24 weeks) follow-up period before and while dopaminergic medications were being titrated. The typing data were used to develop a novel algorithm based on recursive neural networks and detect participants' responses to medication. The latter were defined by the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) minimal clinically important difference. Furthermore, we tested the accuracy of the algorithm to predict the final response to medication as early as 21 weeks prior to the final 6-month clinical outcome. Results The score on the novel algorithm based on recursive neural networks had an overall moderate kappa agreement and fair area under the receiver operating characteristic (ROC) curve with the time-coincident UPDRS-III minimal clinically important difference. The participants classified as responders at the final visit (based on the UPDRS-III minimal clinically important difference) had higher scores on the novel algorithm based on recursive neural networks when compared with the participants with stable UPDRS-III, from the third week of the study onward. Conclusions This preliminary study suggests that remotely gathered unsupervised typing data allows for the accurate detection and prediction of drug response in PD. © 2019 International Parkinson and Movement Disorder Society.

Background: There are no immunological data on SARS-CoV-2 heterologous vaccinations schedules in humans. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, Astra Zeneca). Methods: We did a phase 2, open-label, adaptive, randomised, controlled clinical trial on adults under 60 years old, vaccinated with a single dose of ChAdOx1-S between 8 and 12 weeks before screening, and no history of SARS-CoV-2 infection (EudraCT No. 2021-001978-37 and NCT04860739). Participants were randomly assigned (2:1) to receive BNT162b2 (0.3 mL, single intramuscular injection) or observation. The primary outcomes were 7-day reactogenicity and 14-day anti-spike IgG response, measured by immunoassays covering SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibodies functionality and cellular immune response were assessed using a pseudovirus neutralization assay and IFN-gamma immunoassay, respectively. Findings: Between April 24 and April 30, 2021, 676 individuals were randomized (n=450 intervention group, n=226 control group) at 5 sites in Spain, and 663 (441 and 222, respectively) completed the study up to day 14 (mean age 44 [SD 9], 56·5% female). In the intervention group, geometric mean titres (GMT) of IgG-RBD increased from 71·46 BAU/mL (95% CI 59·84-85·33) at baseline to 7756·68 (7371·53; 8161·96) at day 14 (p < 0·0001). IgG against trimeric spike-protein increased from 98·4 [85.69–112.99] to 3684·87 [3429·87–3958·83]). 100% participants exhibited neutralizing antibodies 14 days after BNT162b2 administration, in comparison to 34.1% at enrolment. A 4-fold increase in cellular immune response was also observed. Reactions were predominantly mild (68·3%) or moderate (29·9%), and consisted more frequently on injection site pain (88·2%), induration (35·5%), headache (44·4%) and myalgia (43·3%). No serious adverse events were reported. Interpretation: BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response with an acceptable and manageable reactogenicity profile. Clinical Trial Registration Details: EudraCT No. 2021-001978-37 and NCT04860739. Funding Information: Funded by Instituto de Salud Carlos III (ISCIII). Declaration of Interests: CB is the Deputy General Manager of the ISCIII. JRA has received fees from Janssen, outside of the submitted work. AMB is principal investigator of clinical trials sponsored by GSK, Daiichi-Sankyo, Janssen and Farmalider, outside of the submitted work. The other authors declare no competing interests. Ethics Approval Statement: All the participants provided written informed consent before enrolment. The trial complies with the principles of the Declaration of Helsinki and Good Clinical Practice. This study was approved by the Spanish Agency of Medicines and Healthcare Products (AEMPS) and by the Ethics Committee at University Hospital La Paz.

Objetivo: Evaluar la pérdida celular endotelial en pacientes operados mediante facoemulsificación de catarata no complicada, comparando datos de cirujanos noveles y cirujanos expertos. Método: Se realizó un estudio observacional y prospectivo en el que se evaluaron 50 ojos consecutivos aleatorizados en dos grupos de 25 ojos cada uno. Se realizó a cada ojo recuento de células endoteliales mediante microscopía especular preoperatoriamente y al mes de la cirugía. Los ojos con cataratas complicadas fueron excluidos. Resultados: La mayoría de los pacientes eran mujeres, con una edad media de 75.5 años. La disminución de la densidad celular al mes de la cirugía fue significativa tanto en ojos operados por cirujanos expertos como por cirujanos noveles, con una pérdida del 14.8% y el 15.6%, respectivamente, sin diferencia estadísticamente significativa (p = 0.491). Además, la correlación entre la pérdida de ambos grupos fue de 0.58 (p = 0.0094). La pérdida celular en ojos operados por cirujanos noveles demostró una buena correlación (0.577) con la energía acumulada disipada del ultrasonido durante la facoemulsificación (p = 0.0025), frente a los expertos, en los que no pudo demostrarse esta asociación. El total de energía acumulada disipada empleada por cirujanos noveles fue significativamente mayor (p = 0.045), un 63% más que los expertos. Conclusiones: La diferencia en el recuento endotelial tras cirugía de catarata se demuestra asociada a la propia cirugía, con cifras similares para cirujanos noveles y expertos, y se observa una buena correlación entre ambos grupos. Teniendo en cuenta la pérdida de celularidad endotelial corneal, la seguridad del procedimiento realizado por cirujanos noveles es equivalente a la del realizado por expertos.

Resumen Introduccion y objetivos Estudiar la validez de la funcion SCORE original de bajo riesgo sin y con colesterol unido a lipoproteinas de alta densidad y SCORE calibrada en poblacion espanola. Metodos Analisis agrupado con datos individuales de 12 estudios de cohorte de base poblacional. Se incluyo a 30.919 participantes de 40-64 anos sin enfermedades cardiovasculares en el momento del reclutamiento, que se siguieron durante 10 anos para la mortalidad cardiovascular contemplada en el proyecto SCORE. La validez de las funciones se analizo mediante el area bajo la curva ROC (discriminacion) y el test de Hosmer-Lemeshow (calibracion), respectivamente. Resultados Se dispuso de 286.105 personas/ano. La mortalidad a 10 anos por causas cardiovasculares fue del 0,6%. La razon de casos esperados/observados fue de 9,1, 6,5 y 9,1 en varones y de 3,3, 1,3 y 1,9 en mujeres con las funciones SCORE original de bajo riesgo sin y con colesterol unido a lipoproteinas de alta densidad y SCORE calibrada, respectivamente; diferencias estadisticamente significativas con el test de calibracion de Hosmer-Lemeshow entre la mortalidad predicha con SCORE y la observada (p Conclusiones Todas las versiones de las funciones SCORE disponibles en Espana sobreestiman significativamente la mortalidad cardiovascular observada en la poblacion espanola. A pesar de la aceptable capacidad de discriminacion, la prediccion del numero de acontecimientos cardiovasculares mortales (calibracion) fue significativamente imprecisa.

The effect of above-normal body mass index (BMI) on health outcomes is controversial because it is difficult to distinguish from the effect due to BMI-associated cardiovascular risk factors. The objective was to analyze the impact on 10-year incidence of cardiovascular disease, cancer deaths and overall mortality of the interaction between cardiovascular risk factors and BMI. We conducted a pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79years old at basal examination. Body mass index was measured at baseline being the outcome measures ten-year cardiovascular disease, cancer and overall mortality. Multivariable analyses were adjusted for potential confounders, considering the significant interactions with cardiovascular risk factors. We included 54,446 individuals (46.5% with overweight and 27.8% with obesity). After considering the significant interactions, the 10-year risk of cardiovascular disease was significantly increased in women with overweight and obesity [Hazard Ratio=2.34 (95% confidence interval: 1.19-4.61) and 5.65 (1.54-20.73), respectively]. Overweight and obesity significantly increased the risk of cancer death in women [3.98 (1.53-10.37) and 11.61 (1.93-69.72)]. Finally, obese men had an increased risk of cancer death and overall mortality [1.62 (1.03-2.54) and 1.34 (1.01-1.76), respectively]. In conclusion, overweight and obesity significantly increased the risk of cancer death and of fatal and non-fatal cardiovascular disease in women; whereas obese men had a significantly higher risk of death for all causes and for cancer. Cardiovascular risk factors may act as effect modifiers in these associations.

BACKGROUND: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.METHODS: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose–response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th–95th percentile 1·04–13·5]) from 71 011 participants from 37 studies.FINDINGS: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10–1·17), coronary disease excluding myocardial infarction (1·06, 1·00–1·11), heart failure (1·09, 1·03–1·15), fatal hypertensive disease (1·24, 1·15–1·33); and fatal aortic aneurysm (1·15, 1·03–1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91–0·97). In comparison to those who reported drinking >0–≤100 g per week, those who reported drinking >100–≤200 g per week, >200–≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1–2 years, or 4–5 years, respectively.INTERPRETATION: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.FUNDING: UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

Background Knowledge about the harmful effects of high levels of low-density lipoprotein cholesterol (cLDL) in adults increased after the publication of various guidelines, leading to closer control and more treatment. We hypothesized that these health care changes would result in an overall improvement in the lipid profile of the population. Objective To determine the evolution of the lipid profile in the population of Spain from the Diet and Risk of Cardiovascular Disease in Spain cohort. Methods A comparison was made between the baseline population-based probabilistically sampled DRECE cohort (DRECE 1 study, 1992–1994, n = 4787) and its 13 years later revisit (DRECE 3 study, 2005–2007). A cross-sectional comparison was made of the overall population of DRECE1 and DRECE3, including only individuals aged 20 to 60 years (inter-individual variations). For subjects participating in both DRECE1 and DRECE3 (n = 1039), individual variations over time (intra-individual analyses) were examined. Results In the overall population, the prevalence of lipid-lowering therapy increased from 3.8% in DRECE1 to 10.7% in DRECE3. Comparing the lipid profile of the population aged 20–60 years in DRECE1 with the same age group in DRECE3, an overall decrease is observed in total cholesterol from a mean of 203.31 mg/dl (SD 43.51) in 1992–1994 to 196.31 mg/dl (SD 38.53) in 2005–2007, and in cLDL from a mean of 125.78 mg/dl (SD 38.53) to 121.37 mg/dl (SD 34.22). The proportion of the population with total cholesterol >200 mg/dl decreased from 51% in DRECE1 to 47% in DRECE3, although this difference did not reach statistical significance (p = 0.077). As regards the intra-individual analyses, total cholesterol increased from DRECE1 to DRECE3 in men and women younger than 40 years at baseline, but decreased in those who were older. Index of individuality for total cholesterol, cLDL, cHDL and triglycerides ranged from 0.53 to 0.87. Conclusions The lipid profile of the Spanish population improved between 1992–1994 and 2005–2007. Within individuals, lipid concentrations, especially total cholesterol and cLDL have increased, although the trend is favorable in the middle-age group (40–59 years). These changes seem to be due to several causes, impacted by dietary and lifestyle factors, and also by a greater emphasis in lipid-lowering therapy in middle-aged people. Lipid parameters had a low index of individuality, which limits their usefulness as population reference values.

Resumen Objetivo Analizar las caracteristicas cosmeticas de 12 geles comercializados y utilizados habitualmente en consultas para el tratamiento del acne y determinar cuales son las preferencias de los pacientes. Material y metodos Estudio observacional, descriptivo en 50 pacientes valorados en consultas de forma consecutiva en el Hospital del Sureste entre el 1 de febrero y el 30 de abril de 2015. Se proporciono a cada uno de los participantes 12 envases transparentes con los distintos productos y evaluaron el olor, color, la facilidad para extenderse, el residuo que el gel dejaba sobre la piel y el grado de sensacion pegajosa tras su aplicacion. Asi mismo otorgaron una puntuacion global a cada gel. Resultados Hemos encontrado diferencias muy significativas en cuanto a la valoracion cosmetica de los diferentes geles. Hemos descubierto que el olor y la capacidad pegajosa de los tratamientos son los 2 factores con mayor peso para evaluar un gel por parte de los pacientes. Conclusion La percepcion general acerca de la cosmetica de los diferentes geles actualmente comercializados para el tratamiento del acne varia de forma significativa en funcion del gel utilizado.

The area under the receiver operating characteristic (ROC) curve is a measure of discrimination ability used in diagnostic and prognostic research. The ROC plot is usually represented without additional information about decision thresholds used to generate the graph. In our article, we show that adding at least one or more informative cutoff points on the ROC graph facilitates the character- ization of the test and the evaluation of the discriminatory capacities, which can result in more informed medical decisions. We use the rocreg and rocregplot commands. Copyright 2016 by StataCorp LP.

Introduction Surgery is one of the high-risk areas for the occurrence of adverse events (AE). The purpose of this study is to know the percentage of hospitalization-related AE that are detected by the “Global Trigger Tool” methodology in surgical patients, their characteristics and the tool validity. Materials and methods Retrospective, observational study on patients admitted to a general surgery department, who underwent a surgical operation in a third level hospital during the year 2012. The identification of AE was carried out by patient record review using an adaptation of “Global Trigger Tool” methodology. Once an AE was identified, a harm category was assigned, including the grade in which the AE could have been avoided and its relation with the surgical procedure. Results The prevalence of AE was 36.8%. There were 0.5 AE per patient. 56.2% were deemed preventable. 69.3% were directly related to the surgical procedure. The tool had a sensitivity of 86% and a specificity of 93.6%. The positive predictive value was 89% and the negative predictive value 92%. Conclusions Prevalence of AE is greater than the estimate of other studies. In most cases the AE detected were related to the surgical procedure and more than half were also preventable. The adapted “Global Trigger Tool” methodology has demonstrated to be highly effective and efficient for detecting AE in surgical patients, identifying all the serious AE with few false negative results.

Resumen Introduccion La cirugia supone una de las areas de alto riesgo para la aparicion de efectos adversos (EA). El objetivo de este estudio es conocer el porcentaje de EA en hospitalizacion que se detectan mediante la metodologia «Global Trigger Tool» en pacientes de cirugia general, las caracteristicas de los mismos y la validez de la herramienta. Material y metodos Estudio retrospectivo, observacional y descriptivo sobre pacientes ingresados en cirugia general de un hospital de tercer nivel, sometidos a intervencion quirurgica durante el ano 2012. La identificacion de EA se lleva a cabo mediante una revision de historias clinicas empleando una adaptacion de la metodologia «Global Trigger Tool» Una vez identificado el EA, se le asigno una categoria de dano y se determino el grado en el que este podria haber sido evitado asi como su relacion con el procedimiento quirurgico. Resultados La prevalencia de EA fue de 36,8%. Con un numero de EA por paciente de 0,5. El 56,2% se consideraron evitables. Y un 69,3% se relacionaron directamente con el procedimiento quirurgico. La herramienta demostro una sensibilidad del 86% y una especificidad del 93,6%. El valor predictivo positivo fue de 89%, el valor predictivo negativo de 92%. Conclusiones La prevalencia de EA es mas alta de lo estimado en otros estudios. La mayoria de los EA detectados estan relacionados con el procedimiento quirurgico, y mas de la mitad son evitables. La metodologia «Global Trigger Tool» adaptada ha demostrado ser altamente eficaz y eficiente para la deteccion de EA en cirugia, identificando todos los EA graves y con pocos falsos negativos.

Objective To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. Method Pooled analysis of 11 population-based Spanish cohorts (1992–2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. Results The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. Conclusions The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

Objective To externally validate the prognostic models for predicting the time-dependent outcome in patients with locally advanced cervical cancer (LACC) who were treated with concurrent chemoradiotherapy in an independent cohort. Methods A historical cohort of 297 women with LACC who were treated with radical concurrent chemoradiotherapy from 1999 to 2014 at the 12 de Octubre University Hospital (H12O), Madrid, Spain. The external validity of prognostic models was quantified regarding discrimination, calibration, measures of overall performance, and decision curve analyses. Results The review identified 8 studies containing 13 prognostic models. Different (International Federation of Gynecology and Obstetrics [FIGO] stages, parametrium involvement, hydronephrosis, location of positive nodes, and race) but related cohorts with validation cohort (5-year overall survival [OS]=70%; 5-year disease-free survival [DFS]=64%; average age of 50; and over 79% squamous cell) were evaluated. The following models exhibited good external validity in terms of discrimination and calibration but limited clinical utility: the OS model at 3 year from Kidd et al.'s study (area under the receiver operating characteristic curve [AUROC]=0.69; threshold of clinical utility [TCU] between 36% and 50%), the models of DFS at 1 year from Kidd et al.'s study (AUROC=0.64; TCU between 24% and 32%) and 2 years from Rose et al.'s study (AUROC=0.70; TCU between 19% and 58%) and the distant recurrence model at 5 years from Kang et al.'s study (AUROC=0.67; TCU between 12% and 36%). Conclusion The external validation revealed the statistical and clinical usefulness of 4 prognostic models published in the literature.

It has often been suggested that cardiovascular mortality and their geographical heterogeneity are associated with nutrients intake patterns and also lipid profile. The large Spanish study Dieta y Riesgo de Enfermedades Cardiovasculares en España (DRECE) investigated this theory from 1991 to 2010. Out of the 4,783 Spanish individuals making up the DRECE cohort, 220 subjects (148 men and 72 women) died (4.62%) during the course of the study. The mean age of patients who died from cardiovascular causes (32 in all) was 61.08 years 95% CI (57.47-64.69) and 70.91% of them were males. The consumption of nutrients and the lipid profile by geographical area, studied by geospatial models, showed that the east and southern area of the country had the highest fat intake coupled to a high rate of unhealthy lipid profile. It was concluded that the spatial geographical analysis showed a relationship between high fat intake, unhealthy lipid profile and cardiovascular mortality in the different geographical areas, with a high variability within the country.

Background: Cumulative risk of stroke recurrence is about 26% at five years, with overall mortality rate of 38%. Objective: to develop a user-friendly clinical prediction algorithm of ischemic stroke recurrence to help in the design of long-term strategies for secondary prevention. Design: Historical Cohort study. Setting: Tertiary urban hospital-based practice. Patients: Subjects admitted to the hospital for a first-ever ischemic stroke. Measurements: Variables studied were clinical picture and management, previous vascular risk factors and comorbidity, Stroke subtype and severity. Predictors were determined by statistical models based on Cox regression and recursive partition analysis. The internal validity was calculated via boots trapping and its performance (predictive ability) by the statistic C. Results: 303 patients were analyzed. They were classified as having: 1) ＂high or very high＂ risk of recurrence (probability ＞ 51%) (those with left ventricular hypertrophy/hypertensive cardiomyopathy or chronic kidney disease) (21% of patients; 2) 'Intermediate' risk (probability 21-50%) (44% of patients); and 3) 'low' risk (those with age under 70 years without left ventricular hypertrophy/hypertensive cardiomyopathy nor coronary heart disease or age over 70 years, but starting therapy with anticoagulants due to an underlying embolic condition) (probability ＜21%) (35% of patients). The C statistic was 0.7557 (95% CI: 0.697-0.813) demonstrating a good predictive ability. Conclusion: A few variables organized into a clinical prediction rule, could help physician's assessment of patients with a first stroke episode admitted to a health center to improve and facilitate the decision making and course of action.

Enteral nutrition (EN) is controversial in patients with circulatory compromise. This study assesses the feasibility and safety of EN given early after cardiac surgery in patients with hemodynamic failure.Prospective observational study conducted in a surgical intensive care unit (ICU) of a tertiary hospital over 17 months.Cardiac surgery patients with hemodynamic failure (dependence on 2 or more vasoactive drugs and/or mechanical circulatory support) requiring more than 24 hours of mechanical ventilation. Variables Examined: Descriptive data, daily hemodynamic data, and variables related to the efficacy and safety of EN. EN was performed according to our EN protocol.Of 642 patients admitted to the ICU, 37 (5.8%) met the inclusion criteria. Of these, 11 (29.7%) required mechanical circulatory support, and 25 (68.0%) met the criteria for early multiorgan dysfunction. Mortality was 13.5%. Mean EN duration was 12.3 days (95% confidence interval [CI], 9.6-15.0). The mean EN diet volume delivered/patient/d was 1199 mL (95% CI, 1118.7-1278.8), and mean EN energy delivered/patient/d was 1228.4 kcal (95% CI, 1145.8-1311). The set energy target was achieved in 15 patients (40.4%). The most common EN-related complication was constipation. No case of mesenteric ischemia was detected.Our findings indicate that early EN is feasible in this type of patients and not associated with serious complications. However, it is difficult to attain an appropriate energy target by EN alone. These observations point to a need for monitoring of daily energy delivery and balance, as well as careful monitoring of warning signs of intestinal ischemia.

Introduction and objectives To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. Methods Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. Results Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. Conclusions All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate.

Objective To describe the development of a novel on-line database aimed to serve as a source of information concerning healthcare interventions appraised for their clinical value and appropriateness by several initiatives worldwide, and to present a retrospective analysis of the appraisals already included in the database. Methods and Findings Database development and a retrospective analysis. The database DianaHealth.com is already on-line and it is regularly updated, independent, open access and available in English and Spanish. Initiatives are identified in medical news, in article references, and by contacting experts in the field. We include appraisals in the form of clinical recommendations, expert analyses, conclusions from systematic reviews, and original research that label any health care intervention as low-value or inappropriate. We obtain the information necessary to classify the appraisals according to type of intervention, specialties involved, publication year, authoring initiative, and key words. The database is accessible through a search engine which retrieves a list of appraisals and a link to the website where they were published. DianaHealth.com also provides a brief description of the initiatives and a section where users can report new appraisals or suggest new initiatives. From January 2014 to July 2015, the on-line database included 2940 appraisals from 22 initiatives: eleven campaigns gathering clinical recommendations from scientific societies, five sets of conclusions from literature review, three sets of recommendations from guidelines, two collections of articles on low clinical value in medical journals, and an initiative of our own. Conclusions We have developed an open access on-line database of appraisals about healthcare interventions considered of low clinical value or inappropriate. DianaHealth.com could help physicians and other stakeholders make better decisions concerning patient care and healthcare systems sustainability. Future efforts should be focused on assessing the impact of these appraisals in the clinical practice.

OBJECTIVES: Evaluate whether an intervention applied to general practitioners to prevent clinical inertia had an impact on pain, functionality, and health-related quality of life (HRQoL) of patients with hip and/or knee osteoarthritis. DESIGN: This was a cluster-based, multicentre, prospective, randomized, parallel-group study. Clusters of physicians working were assigned to one of two study groups. Physicians in Group 1 received a training session while those in Group 2 did not. SETTING: Primary Care Health centers representative of the entire Spanish territory. PARTICIPANTS: 329 general practitioners of primary healthcare centre. INTERVENTIONS: The intervention consists of a motivational session to propose a proactive care, based on current recommendations. MEASUREMENTS: Visual analogue scale (VAS); functionality (WOMAC scale) and global perception of health by SF-12. Effects were measured in two visits six months apart. RESULTS: A total of 1361 physicians, and 4076 patients participated in the study. No significant differences were observed in the clinical benefit obtained between patients assigned to Group 1 and Group 2. Nevertheless, a significant improvement was observed in the combined population (Groups 1 + 2) in the VAS (p

Background: The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. Methods: We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. Results: For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators. Conclusion: Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved.

Antonio Martinez-Salio a, , Agustin Gomez De la Camara , Maria Victoria Ribera Canudas , Jordi Montero Homs , Emilio Blanco Tarrio , Antonio Collado Cruz , Avelino Ferrero Mendez , Joan Molet Teixido , Angel Oteo-Alvaro , Rafael Galvez Mateos , Enric Zamorano Bayarri , Andres Pena Arrebola f y Julio Pardo Fernandez a a Sociedad Espanola de Neurologia (SEN), Madrid, Espana b Unidad de Investigacion, Hospital )12 de Octubre* , Madrid, Espana c Sociedad Espanola del Dolor (SED), Madrid, Espana d Sociedad Espanola de Medicos de Atencion Primaria (SEMERGEN), Madrid, Espana e Sociedad Espanola de Reumatologia (SER), Madrid, Espana f Sociedad Espanola de Rehabilitacion y Medicina Fisica (SERMEF), Madrid, Espana g Sociedad Espanola de Neurocirugia (SENEC), Madrid, Espana h Sociedad Espanola de Cirugia Ortopedica y Traumatologia (SECOT), Madrid, Espana

Fundamento y objetivos Los antipsicoticos atipicos se han relacionado en los ultimos anos con la hiperglucemia, la diabetes mellitus, el aumento de peso y las alteraciones de lipidos en algunos pacientes. El objetivo de este estudio es analizar si el tratamiento continuado con risperidona, olanzapina o clozapina altera el metabolismo de los lipidos y la glucosa en los pacientes esquizofrenicos. Pacientes y metodo Este estudio incluyo a pacientes esquizofrenicos que habian recibido tratamiento psiquiatrico en monoterapia con clozapina, olanzapina o risperidona durante un periodo de 1-3 anos. Los pacientes diagnosticados de diabetes durante el tratamiento psiquiatrico y los que presentaron cifras de glucemia en ayunas ≥ 126 mg/dl en dos determinaciones consecutivas constituyeron el grupo de casos. Los demas pacientes esquizofrenicos en tratamiento que no presentaron estas alteraciones fueron incluidos en el grupo control. Resultados Segun el analisis ajustado de regresion logistica multivariante para determinar el efecto del tratamiento antipsicotico sobre la presencia de diabetes –que incluyo tambien como factores de evaluacion la edad y el indice de masa corporal– la odds ratio (OR) para olanzapina respecto de risperidona fue de 2,22 (intervalo de confianza [IC] del 95%, 1,12-4,22; p = 0,0228); y para clozapina en relacion con risperidona, de 2,87 (IC del 95%, 1,19-6,93; p = 0,0192). Ambos resultados muestran que los pacientes tratados con olanzapina o clozapina presentan un riesgo de diabetes mellitus significativamente superior en comparacion con los pacientes tratados con risperidona. El riesgo de aumento de trigliceridos vario significativamente en los pacientes tratados con olanzapina (OR = 1,34; p = 0,0075) o clozapina (OR = 1,58; p = 0,0028). Conclusiones El riesgo de diabetes mellitus en los pacientes tratados con olanzapina es dos veces veces mas elevado que el de los tratados con risperidona y, en el caso de los tratados con clozapina, el riesgo es praticamente tres veces superior al de risperidona. La risperidona ofrece al parecer un mejor perfil de seguridad a largo plazo respecto al riesgo de alteraciones del metabolismo de los lipidos y la glucosa.

Fundamento y objetivo Los pacientes con sindrome del aceite toxico son una poblacion de riesgo de padecer hipertension arterial pulmonar. La elevacion anomala de la presion sistolica pulmonary (PSP) durante el ejercicio podria considerarse un marcador temprano de hipertension pulmonar en poblaciones de riesgo. El objetivo del presente estudio ha sido analizar mediante ecocardiografia la respuesta de la PSP al ejercicio en pacientes con sindrome del aceite toxico. Pacientes y metodo Se estudio a 50 pacientes con sindrome del aceite toxico y a 20 voluntarios sanos con ecocardiograma en reposo y en el maximo ejercicio (cicloergometro semisupino) y se midio la PSP. En los pacientes se determino la capacidad de difusion de monoxido de carbono. Resultados No se observaron diferencias en el valor medio de la PSP en el ejercicio entre los pacientes y los voluntarios sanos. En un 8% de los primeros se observo un valor igual o superior a 80 mmHg, lo que se asocio a hipertension pulmonar leve en reposo, disminucion de la funcion ventricular derecha y trastornos de la difusion pulmonar. Un valor de corte de la PSP en reposo igual o superior a 27 mmHg tuvo una sensibilidad del 100% y una especificidad del 71% para predecir una PSP pico de 80 mmHg o superior. Conclusiones Una minoria de pacientes con sindrome del aceite toxico muestra hipertension pulmonar grave con el ejercicio. Este tipo de respuesta anormal se asocia a otros marcadores de vasculopatia pulmonar. Futuros estudios han de esclarecer la relacion entre estas anomalies y el riesgo de desarrollar ulteriormente hipertension arterial pulmonar.