NobleBlocks

Hospital Del Mar

Hospital / health systemBarcelona, Spain

Research output, citation impact, and the most-cited recent papers from Hospital Del Mar (Spain). Aggregated across the NobleBlocks index of 300M+ scholarly works.

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17.5K
Citations
1.3M
h-index
345
i10-index
19.2K
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Hospital Del Mar

Top-cited papers from Hospital Del Mar

GSVA: gene set variation analysis for microarray and RNA-Seq data
Sonja Hänzelmann, Robert Castelo, Justin Guinney
2013· BMC Bioinformatics16.4Kdoi:10.1186/1471-2105-14-7

BACKGROUND: Gene set enrichment (GSE) analysis is a popular framework for condensing information from gene expression profiles into a pathway or signature summary. The strengths of this approach over single gene analysis include noise and dimension reduction, as well as greater biological interpretability. As molecular profiling experiments move beyond simple case-control studies, robust and flexible GSE methodologies are needed that can model pathway activity within highly heterogeneous data sets. RESULTS: To address this challenge, we introduce Gene Set Variation Analysis (GSVA), a GSE method that estimates variation of pathway activity over a sample population in an unsupervised manner. We demonstrate the robustness of GSVA in a comparison with current state of the art sample-wise enrichment methods. Further, we provide examples of its utility in differential pathway activity and survival analysis. Lastly, we show how GSVA works analogously with data from both microarray and RNA-seq experiments. CONCLUSIONS: GSVA provides increased power to detect subtle pathway activity changes over a sample population in comparison to corresponding methods. While GSE methods are generally regarded as end points of a bioinformatic analysis, GSVA constitutes a starting point to build pathway-centric models of biology. Moreover, GSVA contributes to the current need of GSE methods for RNA-seq data. GSVA is an open source software package for R which forms part of the Bioconductor project and can be downloaded at http://www.bioconductor.org.

Analysis of protein-coding genetic variation in 60,706 humans
Monkol Lek, Konrad J. Karczewski, Eric Vallabh Minikel, Kaitlin E. Samocha +4 more
2016· Nature10.3Kdoi:10.1038/nature19057

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.

The mutational constraint spectrum quantified from variation in 141,456 humans
Konrad J. Karczewski, Laurent C. Francioli, Grace Tiao, Beryl B. Cummings +4 more
2020· Nature10.1Kdoi:10.1038/s41586-020-2308-7

Abstract Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes 1 . Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases.

COSMIN guideline for systematic reviews of patient-reported outcome measures
C.A.C. Prinsen, Lidwine B. Mokkink, L.M. Bouter, Jordi Alonso +3 more
2018· Quality of Life Research3.3Kdoi:10.1007/s11136-018-1798-3

PURPOSE: Systematic reviews of patient-reported outcome measures (PROMs) differ from reviews of interventions and diagnostic test accuracy studies and are complex. In fact, conducting a review of one or more PROMs comprises of multiple reviews (i.e., one review for each measurement property of each PROM). In the absence of guidance specifically designed for reviews on measurement properties, our aim was to develop a guideline for conducting systematic reviews of PROMs. METHODS: Based on literature reviews and expert opinions, and in concordance with existing guidelines, the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) steering committee developed a guideline for systematic reviews of PROMs. RESULTS: A consecutive ten-step procedure for conducting a systematic review of PROMs is proposed. Steps 1-4 concern preparing and performing the literature search, and selecting relevant studies. Steps 5-8 concern the evaluation of the quality of the eligible studies, the measurement properties, and the interpretability and feasibility aspects. Steps 9 and 10 concern formulating recommendations and reporting the systematic review. CONCLUSIONS: The COSMIN guideline for systematic reviews of PROMs includes methodology to combine the methodological quality of studies on measurement properties with the quality of the PROM itself (i.e., its measurement properties). This enables reviewers to draw transparent conclusions and making evidence-based recommendations on the quality of PROMs, and supports the evidence-based selection of PROMs for use in research and in clinical practice.

Revised International Prognostic Scoring System for Myelodysplastic Syndromes
Peter L. Greenberg, Heinz Tuechler, Julie Schanz, Guillermo Sanz +4 more
2012· Blood3.1Kdoi:10.1182/blood-2012-03-420489

The International Prognostic Scoring System (IPSS) is an important standard for assessing prognosis of primary untreated adult patients with myelodysplastic syndromes (MDS). To refine the IPSS, MDS patient databases from international institutions were coalesced to assemble a much larger combined database (Revised-IPSS [IPSS-R], n = 7012, IPSS, n = 816) for analysis. Multiple statistically weighted clinical features were used to generate a prognostic categorization model. Bone marrow cytogenetics, marrow blast percentage, and cytopenias remained the basis of the new system. Novel components of the current analysis included: 5 rather than 3 cytogenetic prognostic subgroups with specific and new classifications of a number of less common cytogenetic subsets, splitting the low marrow blast percentage value, and depth of cytopenias. This model defined 5 rather than the 4 major prognostic categories that are present in the IPSS. Patient age, performance status, serum ferritin, and lactate dehydrogenase were significant additive features for survival but not for acute myeloid leukemia transformation. This system comprehensively integrated the numerous known clinical features into a method analyzing MDS patient prognosis more precisely than the initial IPSS. As such, this IPSS-R should prove beneficial for predicting the clinical outcomes of untreated MDS patients and aiding design and analysis of clinical trials in this disease.

Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys
Ronald C. Kessler, Katie A. McLaughlin, Jennifer Green, Michael J. Gruber +4 more
2010· The British Journal of Psychiatry2.5Kdoi:10.1192/bjp.bp.110.080499

BACKGROUND: Although significant associations of childhood adversities with adult mental disorders are widely documented, most studies focus on single childhood adversities predicting single disorders. AIMS: To examine joint associations of 12 childhood adversities with first onset of 20 DSM-IV disorders in World Mental Health (WMH) Surveys in 21 countries. METHOD: Nationally or regionally representative surveys of 51 945 adults assessed childhood adversities and lifetime DSM-IV disorders with the WHO Composite International Diagnostic Interview (CIDI). RESULTS: Childhood adversities were highly prevalent and interrelated. Childhood adversities associated with maladaptive family functioning (e.g. parental mental illness, child abuse, neglect) were the strongest predictors of disorders. Co-occurring childhood adversities associated with maladaptive family functioning had significant subadditive predictive associations and little specificity across disorders. Childhood adversities account for 29.8% of all disorders across countries. CONCLUSIONS: Childhood adversities have strong associations with all classes of disorders at all life-course stages in all groups of WMH countries. Long-term associations imply the existence of as-yet undetermined mediators.

WHO World Mental Health Surveys International College Student Project: Prevalence and distribution of mental disorders.
Randy P. Auerbach, WHO WMH-ICS Collaborators, Philippe Mortier, Ronny Bruffaerts +4 more
2018· Journal of Abnormal Psychology2.4Kdoi:10.1037/abn0000362

Increasingly, colleges across the world are contending with rising rates of mental disorders, and in many cases, the demand for services on campus far exceeds the available resources. The present study reports initial results from the first stage of the WHO World Mental Health International College Student project, in which a series of surveys in 19 colleges across 8 countries (Australia, Belgium, Germany, Mexico, Northern Ireland, South Africa, Spain, United States) were carried out with the aim of estimating prevalence and basic sociodemographic correlates of common mental disorders among first-year college students. Web-based self-report questionnaires administered to incoming first-year students (45.5% pooled response rate) screened for six common lifetime and 12-month DSM-IV mental disorders: major depression, mania/hypomania, generalized anxiety disorder, panic disorder, alcohol use disorder, and substance use disorder. We focus on the 13,984 respondents who were full-time students: 35% of whom screened positive for at least one of the common lifetime disorders assessed and 31% screened positive for at least one 12-month disorder. Syndromes typically had onsets in early to middle adolescence and persisted into the year of the survey. Although relatively modest, the strongest correlates of screening positive were older age, female sex, unmarried-deceased parents, no religious affiliation, nonheterosexual identification and behavior, low secondary school ranking, and extrinsic motivation for college enrollment. The weakness of these associations means that the syndromes considered are widely distributed with respect to these variables in the student population. Although the extent to which cost-effective treatment would reduce these risks is unclear, the high level of need for mental health services implied by these results represents a major challenge to institutions of higher education and governments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Cross-national epidemiology of DSM-IV major depressive episode
Evelyn J. Bromet, Laura Helena Andrade, Irving Hwang, Nancy A. Sampson +4 more
2011· BMC Medicine2.2Kdoi:10.1186/1741-7015-9-90

BACKGROUND: Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low- to middle-income countries in the World Mental Health Survey Initiative. METHODS: Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults. RESULTS: The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2:1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low- to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed. CONCLUSIONS: MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.

The global burden of mental disorders: An update from the WHO World Mental Health (WMH) Surveys
Ronald C. Kessler, Sergio Aguilar‐Gaxiola, Jordi Alonso, Somnath Chatterji +4 more
2009· Epidemiologia e Psichiatria Sociale1.9Kdoi:10.1017/s1121189x00001421

AIMS: The paper reviews recent findings from the WHO World Mental Health (WMH) surveys on the global burden of mental disorders. METHODS: The WMH surveys are representative community surveys in 28 countries throughout the world aimed at providing information to mental health policy makers about the prevalence, distribution, burden, and unmet need for treatment of common mental disorders. RESULTS: The first 17 WMH surveys show that mental disorders are commonly occurring in all participating countries. The inter-quartile range (IQR: 25th-75th percentiles) of lifetime DSM-IV disorder prevalence estimates (combining anxiety, mood, externalizing, and substance use disorders) is 18.1-36.1%. The IQR of 12-month prevalence estimates is 9.8-19.1%. Prevalence estimates of 12-month Serious Mental Illness (SMI) are 4-6.8% in half the countries, 2.3-3.6% in one-fourth, and 0.8-1.9% in one-fourth. Many mental disorders begin in childhood-adolescence and have significant adverse effects on subsequent role transitions in the WMH data. Adult mental disorders are found to be associated with such high role impairment in the WMH data that available clinical interventions could have positive cost-effectiveness ratios. CONCLUSIONS: Mental disorders are commonly occurring and often seriously impairing in many countries throughout the world. Expansion of treatment could be cost-effective from both employer and societal perspectives.

Trauma and PTSD in the WHO World Mental Health Surveys
Ronald C. Kessler, Sergio Aguilar‐Gaxiola, Jordi Alonso, Corina Benjet +4 more
2017· European journal of psychotraumatology1.6Kdoi:10.1080/20008198.2017.1353383

: Trauma exposure is common throughout the world, unequally distributed, and differential across trauma types with respect to PTSD risk. Although a substantial minority of PTSD cases remits within months after onset, mean symptom duration is considerably longer than previously recognized.

A Comparison of Four Methods of Weaning Patients from Mechanical Ventilation
Andrés Esteban, Fernando Frutos–Vivar, Martin J. Tobin, Inmaculada Alía +4 more
1995· New England Journal of Medicine1.6Kdoi:10.1056/nejm199502093320601

BACKGROUND: Weaning patients from mechanical ventilation is an important problem in intensive care units. Weaning is usually conducted in an empirical manner, and a standardized approach has not been developed. METHODS: We carried out a prospective, randomized, multicenter study involving 546 patients who had received mechanical ventilation for a mean (+/- SD) of 7.5 +/- 6.1 days and who were considered by their physicians to be ready for weaning. One hundred thirty patients had respiratory distress during a two-hour trial of spontaneous breathing. These patients were randomly assigned to undergo one of four weaning techniques: intermittent mandatory ventilation, in which the ventilator rate was initially set at a mean (+/- SD) of 10.0 +/- 2.2 breaths per minute and then decreased, if possible, at least twice a day, usually by 2 to 4 breaths per minute (29 patients); pressure-support ventilation, in which pressure support was initially set at 18.0 +/- 6.1 cm of water and then reduced, if possible, by 2 to 4 cm of water at least twice a day (37 patients); intermittent trials of spontaneous breathing, conducted two or more times a day if possible (33 patients); or a once-daily trail of spontaneous breathing (31 patients). Standardized protocols were followed for each technique. RESULTS: The median duration of weaning was 5 days for intermittent mandatory ventilation (first quartile, 3 days; third quartile, 11 days), 4 days for pressure-support ventilation (2 and 12 days, respectively), 3 days for intermittent (multiple) trials of spontaneous breathing (2 and 6 days, respectively), and 3 days for a once-daily trial of spontaneous breathing (1 and 6 days, respectively). After adjustment for other covariates, the rate of successful weaning was higher with a once-daily trial of spontaneous breathing than with intermittent mandatory ventilation (rate ratio, 2.83; 95 percent confidence interval, 1.36 to 5.89; P < 0.006) or pressure-support ventilation (rate ratio, 2.05; 95 percent confidence interval, 1.04 to 4.04; P < 0.04). There was no significant difference in the rate of success between once-daily trials and multiple trials of spontaneous breathing. CONCLUSIONS: A once-daily trial of spontaneous breathing led to extubation about three times more quickly than intermittent mandatory ventilation and about twice as quickly as pressure-support ventilation. Multiple daily trials of spontaneous breathing were equally successful.

Drinking Water Nitrate and Human Health: An Updated Review
Mary H. Ward, Rena R. Jones, Jean D. Brender, Theo de Kok +4 more
2018· International Journal of Environmental Research and Public Health1.5Kdoi:10.3390/ijerph15071557

Nitrate levels in our water resources have increased in many areas of the world largely due to applications of inorganic fertilizer and animal manure in agricultural areas. The regulatory limit for nitrate in public drinking water supplies was set to protect against infant methemoglobinemia, but other health effects were not considered. Risk of specific cancers and birth defects may be increased when nitrate is ingested under conditions that increase formation of N-nitroso compounds. We previously reviewed epidemiologic studies before 2005 of nitrate intake from drinking water and cancer, adverse reproductive outcomes and other health effects. Since that review, more than 30 epidemiologic studies have evaluated drinking water nitrate and these outcomes. The most common endpoints studied were colorectal cancer, bladder, and breast cancer (three studies each), and thyroid disease (four studies). Considering all studies, the strongest evidence for a relationship between drinking water nitrate ingestion and adverse health outcomes (besides methemoglobinemia) is for colorectal cancer, thyroid disease, and neural tube defects. Many studies observed increased risk with ingestion of water nitrate levels that were below regulatory limits. Future studies of these and other health outcomes should include improved exposure assessment and accurate characterization of individual factors that affect endogenous nitrosation.

Prediction of Postoperative Pulmonary Complications in a Population-based Surgical Cohort
Jaume Canet, L. Gallart, C. Gomar, Guillem Paluzie +4 more
2010· Anesthesiology1.5Kdoi:10.1097/aln.0b013e3181fc6e0a

BACKGROUND: Current knowledge of the risk for postoperative pulmonary complications (PPCs) rests on studies that narrowly selected patients and procedures. Hypothesizing that PPC occurrence could be predicted from a reduced set of perioperative variables, we aimed to develop a predictive index for a broad surgical population. METHODS: Patients undergoing surgical procedures given general, neuraxial, or regional anesthesia in 59 hospitals were randomly selected for this prospective, multicenter study. The main outcome was the development of at least one of the following: respiratory infection, respiratory failure, bronchospasm, atelectasis, pleural effusion, pneumothorax, or aspiration pneumonitis. The cohort was randomly divided into a development subsample to construct a logistic regression model and a validation subsample. A PPC predictive index was constructed. RESULTS: Of 2,464 patients studied, 252 events were observed in 123 (5%). Thirty-day mortality was higher in patients with a PPC (19.5%; 95% [CI], 12.5-26.5%) than in those without a PPC (0.5%; 95% CI, 0.2-0.8%). Regression modeling identified seven independent risk factors: low preoperative arterial oxygen saturation, acute respiratory infection during the previous month, age, preoperative anemia, upper abdominal or intrathoracic surgery, surgical duration of at least 2 h, and emergency surgery. The area under the receiver operating characteristic curve was 90% (95% CI, 85-94%) for the development subsample and 88% (95% CI, 84-93%) for the validation subsample. CONCLUSION: The risk index based on seven objective, easily assessed factors has excellent discriminative ability. The index can be used to assess individual risk of PPC and focus further research on measures to improve patient care.

Posttraumatic stress disorder in the World Mental Health Surveys
Karestan C. Koenen, Andrew Ratanatharathorn, Lauren C. Ng, Katie A. McLaughlin +4 more
2017· Psychological Medicine1.4Kdoi:10.1017/s0033291717000708

BACKGROUND: Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking. METHODS: Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics. RESULTS: The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed. CONCLUSIONS: PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.

Barriers to mental health treatment: results from the WHO World Mental Health surveys
Laura Helena Andrade, Jordi Alonso, Zeina Mneimneh, J. Elisabeth Wells +4 more
2013· Psychological Medicine1.3Kdoi:10.1017/s0033291713001943

BACKGROUND: To examine barriers to initiation and continuation of mental health treatment among individuals with common mental disorders. METHOD: Data were from the World Health Organization (WHO) World Mental Health (WMH) surveys. Representative household samples were interviewed face to face in 24 countries. Reasons to initiate and continue treatment were examined in a subsample (n = 63,678) and analyzed at different levels of clinical severity. RESULTS: Among those with a DSM-IV disorder in the past 12 months, low perceived need was the most common reason for not initiating treatment and more common among moderate and mild than severe cases. Women and younger people with disorders were more likely to recognize a need for treatment. A desire to handle the problem on one's own was the most common barrier among respondents with a disorder who perceived a need for treatment (63.8%). Attitudinal barriers were much more important than structural barriers to both initiating and continuing treatment. However, attitudinal barriers dominated for mild-moderate cases and structural barriers for severe cases. Perceived ineffectiveness of treatment was the most commonly reported reason for treatment drop-out (39.3%), followed by negative experiences with treatment providers (26.9% of respondents with severe disorders). CONCLUSIONS: Low perceived need and attitudinal barriers are the major barriers to seeking and staying in treatment among individuals with common mental disorders worldwide. Apart from targeting structural barriers, mainly in countries with poor resources, increasing population mental health literacy is an important endeavor worldwide.

Development of Land Use Regression Models for PM<sub>2.5</sub>, PM<sub>2.5</sub> Absorbance, PM<sub>10</sub> and PM<sub>coarse</sub> in 20 European Study Areas; Results of the ESCAPE Project
Marloes Eeftens, Rob Beelen, Kees de Hoogh, Tom Bellander +4 more
2012· Environmental Science & Technology1.3Kdoi:10.1021/es301948k

Land Use Regression (LUR) models have been used increasingly for modeling small-scale spatial variation in air pollution concentrations and estimating individual exposure for participants of cohort studies. Within the ESCAPE project, concentrations of PM(2.5), PM(2.5) absorbance, PM(10), and PM(coarse) were measured in 20 European study areas at 20 sites per area. GIS-derived predictor variables (e.g., traffic intensity, population, and land-use) were evaluated to model spatial variation of annual average concentrations for each study area. The median model explained variance (R(2)) was 71% for PM(2.5) (range across study areas 35-94%). Model R(2) was higher for PM(2.5) absorbance (median 89%, range 56-97%) and lower for PM(coarse) (median 68%, range 32- 81%). Models included between two and five predictor variables, with various traffic indicators as the most common predictors. Lower R(2) was related to small concentration variability or limited availability of predictor variables, especially traffic intensity. Cross validation R(2) results were on average 8-11% lower than model R(2). Careful selection of monitoring sites, examination of influential observations and skewed variable distributions were essential for developing stable LUR models. The final LUR models are used to estimate air pollution concentrations at the home addresses of participants in the health studies involved in ESCAPE.

Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency
Piotr Ponikowski, Dirk J. van Veldhuisen, Josep Comín‐Colet, Georg Ertl +4 more
2014· European Heart Journal1.2Kdoi:10.1093/eurheartj/ehu385

AIM: The aim of this study was to evaluate the benefits and safety of long-term i.v. iron therapy in iron-deficient patients with heart failure (HF). METHODS AND RESULTS: CONFIRM-HF was a multi-centre, double-blind, placebo-controlled trial that enrolled 304 ambulatory symptomatic HF patients with left ventricular ejection fraction ≤45%, elevated natriuretic peptides, and iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL if transferrin saturation <20%). Patients were randomized 1 : 1 to treatment with i.v. iron, as ferric carboxymaltose (FCM, n = 152) or placebo (saline, n = 152) for 52 weeks. The primary end-point was the change in 6-min-walk-test (6MWT) distance from baseline to Week 24. Secondary end-points included changes in New York Heart Association (NYHA) class, Patient Global Assessment (PGA), 6MWT distance, health-related quality of life (QoL), Fatigue Score at Weeks 6, 12, 24, 36, and 52 and the effect of FCM on the rate of hospitalization for worsening HF. Treatment with FCM significantly prolonged 6MWT distance at Week 24 (difference FCM vs. placebo: 33 ± 11 m, P = 0.002). The treatment effect of FCM was consistent in all subgroups and was sustained to Week 52 (difference FCM vs. placebo: 36 ± 11 m, P < 0.001). Throughout the study, an improvement in NYHA class, PGA, QoL, and Fatigue Score in patients treated with FCM was detected with statistical significance observed from Week 24 onwards. Treatment with FCM was associated with a significant reduction in the risk of hospitalizations for worsening HF [hazard ratio (95% confidence interval): 0.39 (0.19-0.82), P = 0.009]. The number of deaths (FCM: 12, placebo: 14 deaths) and the incidence of adverse events were comparable between both groups. CONCLUSION: Treatment of symptomatic, iron-deficient HF patients with FCM over a 1-year period resulted in sustainable improvement in functional capacity, symptoms, and QoL and may be associated with risk reduction of hospitalization for worsening HF (ClinicalTrials.gov number NCT01453608).

A structural variation reference for medical and population genetics
Ryan L. Collins, Harrison Brand, Konrad J. Karczewski, Xuefang Zhao +4 more
2020· Nature1.2Kdoi:10.1038/s41586-020-2287-8

Abstract Structural variants (SVs) rearrange large segments of DNA 1 and can have profound consequences in evolution and human disease 2,3 . As national biobanks, disease-association studies, and clinical genetic testing have grown increasingly reliant on genome sequencing, population references such as the Genome Aggregation Database (gnomAD) 4 have become integral in the interpretation of single-nucleotide variants (SNVs) 5 . However, there are no reference maps of SVs from high-coverage genome sequencing comparable to those for SNVs. Here we present a reference of sequence-resolved SVs constructed from 14,891 genomes across diverse global populations (54% non-European) in gnomAD. We discovered a rich and complex landscape of 433,371 SVs, from which we estimate that SVs are responsible for 25–29% of all rare protein-truncating events per genome. We found strong correlations between natural selection against damaging SNVs and rare SVs that disrupt or duplicate protein-coding sequence, which suggests that genes that are highly intolerant to loss-of-function are also sensitive to increased dosage 6 . We also uncovered modest selection against noncoding SVs in cis -regulatory elements, although selection against protein-truncating SVs was stronger than all noncoding effects. Finally, we identified very large (over one megabase), rare SVs in 3.9% of samples, and estimate that 0.13% of individuals may carry an SV that meets the existing criteria for clinically important incidental findings 7 . This SV resource is freely distributed via the gnomAD browser 8 and will have broad utility in population genetics, disease-association studies, and diagnostic screening.

Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the Di@bet.es Study
Federico Soriguer, Albert Goday, Anna Bosch-Comas, Elena Bordiú +4 more
2011· Diabetologia1.2Kdoi:10.1007/s00125-011-2336-9

AIMS/HYPOTHESIS: The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation. METHODS: A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75 g). RESULTS: Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG-IGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p < 0.0001), and was higher in men than in women (p < 0.001). CONCLUSIONS/INTERPRETATION: The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.

A 14-Item Mediterranean Diet Assessment Tool and Obesity Indexes among High-Risk Subjects: The PREDIMED Trial
Miguel Ángel Martínez‐González, Ana García‐Arellano, Estefanía Toledo, Jordi Salas‐Salvadó +4 more
2012· PLoS ONE1.1Kdoi:10.1371/journal.pone.0043134

OBJECTIVE: Independently of total caloric intake, a better quality of the diet (for example, conformity to the Mediterranean diet) is associated with lower obesity risk. It is unclear whether a brief dietary assessment tool, instead of full-length comprehensive methods, can also capture this association. In addition to reduced costs, a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies. Another relevant question is which individual items of such a brief tool are responsible for this association. We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index, waist circumference and waist-to-height ratio (WHtR) as outcomes. DESIGN: Cross-sectional assessment of all participants in the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. SUBJECTS: 7,447 participants (55-80 years, 57% women) free of cardiovascular disease, but with either type 2 diabetes or ≥ 3 cardiovascular risk factors. Trained dietitians used both a validated 14-item questionnaire and a full-length validated 137-item food frequency questionnaire to assess dietary habits. Trained nurses measured weight, height and waist circumference. RESULTS: Strong inverse linear associations between the 14-item tool and all adiposity indexes were found. For a two-point increment in the 14-item score, the multivariable-adjusted differences in WHtR were -0.0066 (95% confidence interval, -0.0088 to -0.0049) for women and -0.0059 (-0.0079 to -0.0038) for men. The multivariable-adjusted odds ratio for a WHtR>0.6 in participants scoring ≥ 10 points versus ≤ 7 points was 0.68 (0.57 to 0.80) for women and 0.66 (0.54 to 0.80) for men. High consumption of nuts and low consumption of sweetened/carbonated beverages presented the strongest inverse associations with abdominal obesity. CONCLUSIONS: A brief 14-item tool was able to capture a strong monotonic inverse association between adherence to a good quality dietary pattern (Mediterranean diet) and obesity indexes in a population of adults at high cardiovascular risk.