The Microbiota-Gut-Brain Axis.

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.

The Use of Anemia Control Model Is Associated with Improved Hemoglobin Target Achievement, Lower Rates of Inappropriate Erythropoietin Stimulating Agents, and Severe Anemia among Dialysis Patients.

INTRODUCTION: The Anemia Control Model (ACM) is a certified medical device suggesting the optimal ESA and iron dosage for patients on hemodialysis. We sought to assess the effectiveness and safety of ACM in a large cohort of hemodialysis patients. METHODS: This is a retrospective study of dialysis patients treated in NephroCare centers between June 1, 2013 and December 31, 2019. We compared patients treated according to ACM suggestions and patients treated in clinics where ACM was not activated. We stratified patients belonging to the reference group by historical target achievement rates in their referral centers (tier 1: <70%; tier 2: 70-80%; tier 3: >80%). Groups were matched by propensity score. RESULTS: After matching, we obtained four groups with 85,512 patient-months each. ACM had 18% higher target achievement rate, 63% smaller inappropriate ESA administration rate, and 59% smaller severe anemia risk compared to Tier 1 centers (all p < 0.01). The corresponding risk ratios for ACM compared to Tier 2 centers were 1.08 (95% CI: 1.08-1.09), 0.49 (95% CI: 0.47-0.51), and 0.64 (95% CI: 0.61-0.68); for ACM compared to Tier 3 centers, 1.01 (95% CI: 1.01-1.02), 0.66 (95% CI: 0.63-0.69), and 0.94 (95% CI: 0.88-1.00), respectively. ACM was associated with statistically significant reductions in ESA dose administration. CONCLUSION: ACM was associated with increased hemoglobin target achievement rate, decreased inappropriate ESA usage and a decreased incidence of severe anemia among patients treated according to ACM suggestion.

Better health-related quality of life is associated with prolonged survival and reduced hospitalization risk among dialysis-dependent chronic kidney disease patients: a historical cohort study.

RATIONALE & OBJECTIVE: End-stage kidney disease (ESKD) negatively affects patients' physical, emotional, and social functioning. Furthermore, adjustment to dialysis require substantial lifestyle changes that may further impact on patients physical and emotional well-being. However, the relationship between Health-Related Quality of life impairment with future adverse outcomes in dialysis is not well characterized. Our study aims to investigate the relationship between Health-Related Quality of Life (HRQoL) and patients' survival and hospitalization rates within a large European dialysis network. METHODS: A historical cohort study was conducted to evaluate association of HRQoL with hospitalization and mortality rates over a 12-month follow-up period. Patients responded to a self-administered survey as part of a Continuous Quality Improvement Program implemented in clinics affiliated with the Spanish FMC-Nephrocare organization. Health-Related Quality of Life (HRQoL) was measured with the KDQOL-36. Potential confounders included socio-demographic characteristics, comorbidities, biochemical parameters, dialysis treatment. We used Cox's Proportional Hazard regression to assess the hazard of death and Logistic Regression to assess the likelihood of hospital admissions during 12-month follow-up period. RESULTS: A total of 2280 (51.5%) completed the self-administrated survey, and 1838 patients met the inclusion/exclusion criteria of the study. Higher HRQoL scores were associated with significantly lower mortality and hospitalization risk. Risk estimates were robust to adjustment for potential confounders. CONCLUSIONS: Several dimensions of HRQoL are associated with patient-centered outcomes (i.e., mortality and hospitalizations at 1 year). Patient-Reported Outcomes contribute unique pieces of information characterizing patients' health. Residual confounding cannot be fully ruled out; moreover, the high attrition rate could result in selection bias, which may limit the generalizability of the findings to a broader population.

Approaching the Families of Potential Deceased Organ Donors: An Overview of Regulations and Practices in Council of Europe Member States.

The primary aim of this study was to describe regulations and practices concerning the family approach to discuss donation, specifically after the neurological determination of death, one of the most challenging steps in the donation pathway. A secondary objective was to assess the impact of legislation on consent rates for organ donation. The Council of Europe surveyed 39 member states about national regulations, practices, and consent rates; 34 replied. Opt-out legislation is present in 19, opt-in in 9 and a mixed system in six countries. An opt-out register is kept by 24 countries and an opt-in register by 18 countries, some keeping both. The mean consent rate was 81.2% of all family approaches. Most countries regulate how death using neurological criteria is confirmed (85.3%), while regulation of other aspects of the deceased donation pathway varies: the timing of informing the family about brain death (47.1%) and organ donation (58.8%), the profile of professional who discusses both topics with the family (52.9% and 64.7%, respectively) and the withdrawal of treatment after brain death (47.1%). We also noted a mismatch between what regulations state and what is done in practice in most countries. We suggest possible reasons for this disparity.

Association between sensory reactivity and feeding problems in school-aged children: InProS Study.

This study aimed to explore the association between sensory reactivity (SR) and feeding problems in children at 3-7 years of age. We analysed data from 589 Spanish children from the InProS project, a population-based cross-sectional study. SR was measured using the Short Sensory Profile (SSP) as a two-level categorical variable (SR or no SR) and feeding problems (food variety, texture problems, or both feeding problems) were collected using closed questions (yes or no). Multiple Poisson regression models were used to estimate associations adjusted for potential confounding variables. Results showed the following prevalence rates for SR: 29.0% (SSP total score <155), 11.4% (tactile sensitivity <30), 14.8% (taste/smell sensitivity <15), 22.1% (movement sensitivity <13), 49.1% (low responsiveness/seeking sensation <27), 43.6% (auditory filtering <23), 11.6% (low energy/weak <26), and 25.3% (visual/auditory sensitivity <19). Around a fifth of children (18.3%) consumed a limited variety of foods, 4.9% had difficulties in the transition/introduction of textures, and 3.9% had both feeding problems. The presence of taste/smell sensitivity was associated with difficulties in the transition/introduction of textures (PR = 1.17, 95%CI = 1.09-1.27), limited variety of foods (PR = 1.42, 95%CI = 1.31-1.53), and both feeding problems (PR = 1.31, 95%CI = 1.19-1.44). In addition, children with total SR or auditory filtering SR were associated with a higher prevalence of consuming a limited variety of foods (PR = 1.13, 95%CI = 1.06-1.20 and PR = 1.08, 95%CI = 1.02-1.15, respectively). These findings highlight the importance of considering SR as a potential predictor of feeding problems, especially in children with taste/smell sensitivity. However, further studies are needed to confirm these findings.

Diaphragmatic Activation Correlated with Lumbar Multifidus Muscles and Thoracolumbar Fascia by B-Mode and M-Mode Ultrasonography in Subjects with and without Non-Specific Low Back Pain: A Pilot Study.

Background and Objectives: The diaphragm, the lumbar multifidus muscles, and the thoracolumbar fascia (TLF) execute an important role in the stability of the lumbar spine and their morphology has been modified in subjects with non-specific low back pain (NS-LBP). While it is true that three structures correlate anatomically, the possible functional correlation between them has not been investigated previously in healthy subjects nor in subjects with NS-LBP. The aim of the present study was to examine this functional nexus by means of a comparison based on ultrasonographic parameters of the diaphragm, the lumbar multifidus muscles, and the TLF in subjects with and without NS-LBP. Materials and Methods: A sample of 54 (23 NS-LBP and 31 healthy) subjects were included in the study. The thickness and diaphragmatic excursion at tidal volume (TV) and force volume (FV), the lumbar multifidus muscles thickness at contraction and at rest, and the TLF thickness were evaluated using rehabilitative ultrasound imaging (RUSI) by B-mode and M-mode ultrasonography. The diaphragm thickening capacity was also calculated by thickening fraction (TF) at tidal volume and force volume. Results: There were no significant differences recorded between the activation of the diaphragm and the activation of the lumbar multifidus muscles and TLF for each variable, within both groups. However, there were significant differences recorded between both groups in diaphragm thickness and diaphragm thickening capacity at tidal volume and force volume. Conclusions: Diaphragmatic activation had no functional correlation with the activation of lumbar multifidus muscles and TLF for both groups. Nevertheless, subjects with NS-LBP showed a reduced diaphragm thickness and a lower diaphragm thickening capacity at tidal volume and force volume, compared to healthy subjects.

Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients.

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.

Implementation of specialised attention mechanisms: ICD-10 classification of Gastrointestinal discharge summaries in English, Spanish and Swedish.

Multi-label classification according to the International Classification of Diseases (ICD) is an Extreme Multi-label Classification task aiming to categorise health records according to a set of relevant ICD codes. We implemented PlaBERT, a new multi-label text classification head with per-label attention, on top of a BERT model. The model assessment is conducted on Electronic Health Records, conveying Discharge Summaries in three languages - English, Spanish, and Swedish. The study focuses on 157 diagnostic codes from the ICD. We additionally measure the labelling noise to estimate the consistency of the gold standard. Our specialised attention mechanism computes attention weights for each input token and label pair, obtaining the specific relevance of every word concerning each ICD code. The PlaBERT model outputs the computed attention importance for each token and label, allowing for visualisation. Our best results are 40.65, 38.36, and 41.13 F1-Score points on the English, Spanish and Swedish datasets, respectively, for the 157 gastrointestinal codes. Besides, Precision is the metric that most significantly improves owing to the attention mechanism of PlaBERT, with an increase of 44.63, 40.93, and 12.92 points, respectively, for the Spanish, Swedish and English datasets.

Reporting Quality in Abstracts of Randomized Controlled Trials Published in High-Impact Occupational Therapy Journals.

IMPORTANCE: Adequate reporting in the abstracts of randomized controlled trials (RCTs) is essential to enable occupational therapy practitioners to critically appraise the validity of findings. OBJECTIVE: To evaluate the reporting quality and characteristics of RCT abstracts published between 2008 and 2018 in the occupational therapy journals with the five highest impact factors in 2018. DESIGN: A descriptive cross-sectional study. DATA SOURCES: The American Journal of Occupational Therapy (AJOT), Australian Occupational Therapy Journal (AOTJ), Canadian Journal of Occupational Therapy (CJOT), Scandinavian Journal of Occupational Therapy (SJOT), and Physical and Occupational Therapy in Pediatrics (POTP) were identified using a Web of Science search. STUDY SELECTION AND DATA COLLECTION: We searched Scopus for abstracts in the five included journals. We used a 17-point scale based on the CONSORT for Abstracts (CONSORT-A) checklist to assess reporting quality. We also identified characteristics of the abstracts. FINDINGS: Seventy-eight RCT abstracts were assessed and showed moderate to low adherence to the CONSORT-A checklist (Mdn = 8, interquartile range = 7-9). Abstracts of articles with authors from a higher number of institutions, European first authors, and >200 words had higher CONSORT-A scores. The most underreported CONSORT-A items were trial design, blinding, numbers analyzed, outcome (results), harms, trial registration, and funding. CONCLUSIONS AND RELEVANCE: Between 2008 and 2018, the reporting quality in RCT abstracts from the five highest impact occupational therapy journals was moderate to low. Inadequate reporting in RCT abstracts raises the risk that occupational therapy practitioners will make ineffective clinical decisions based on misinterpretation of findings. What This Article Adds: Reporting quality in RCT abstracts in occupational therapy journals is moderate to low. Journal editors should require authors of RCTs to use the CONSORT-A checklist to promote optimal reporting and transparency in abstracts.

Danger in the Canopy. Comparative Proteomics and Bioactivities of the Venoms of the South American Palm Pit Viper Bothrops bilineatus Subspecies bilineatus and smaragdinus and Antivenomics of B. b. bilineatus (Rondônia) Venom against the Brazilian Pentabothropic Antivenom.

We report a structural and functional proteomics characterization of venoms of the two subspecies (Bothrops bilineatusbilineatus and B. b. smaragdinus) of the South American palm pit viper from the Brazilian state of Rondônia and B. b. smaragdinus from Perú. These poorly known arboreal and mostly nocturnal generalist predators are widely distributed in lowland rainforests throughout the entire Amazon region, where they represent an important cause of snakebites. The three B. bilineatus spp. venom samples exhibit overall conserved proteomic profiles comprising components belonging to 11 venom protein classes, with PIII (34-40% of the total venom proteins) and PI (8-18%) SVMPs and their endogenous tripeptide inhibitors (SVMPi, 8-10%); bradykinin-potentiating-like peptides (BBPs, 10.7-15%); snake venom serine proteinases (SVSP, 5.5-14%); C-type lectin-like proteins (CTL, 3-10%); phospholipases A2 (PLA2, 2.8-7.6%); cysteine-rich secretory proteins (CRISP, 0.9-2.8%); l-amino acid oxidases (LAO, 0.9-5%) representing the major components of their common venom proteomes. Comparative analysis of the venom proteomes of the two geographic variants of B. b. smaragdinus with that of B. b. bilineatus revealed that the two Brazilian taxa share identical molecules between themselves but not with Peruvian B. b. smaragdinus, suggesting hybridization between the geographically close, possibly sympatric, Porto Velho (RO, BR) B. b. smaragdinus and B. b. bilineatus parental populations. However, limited sampling does not allow determining the frequency of this event. The toxin arsenal of the South American palm pit vipers may account for the in vitro recorded collagenolytic, caseinolytic, PLA2, l-amino acid oxidase, thrombin-like and factor X-activating activities, and the clinical features of South American palm pit viper envenomings, i.e., local and progressively ascending pain, shock and loss of consciousness, spontaneous bleeding, and profound coagulopathy. The remarkable cross-reactivity of the Brazilian pentabothropic SAB antivenom toward the heterologous B. b. bilineatus venom suggests that the paraspecific antigenic determinants should have been already present in the venom of the last common ancestor of the Bothrops ″jararaca″ and ″taeniatus″ clades, about 8.5 Mya in the mid-late Miocene epoch of the Cenozoic era. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifiers PXD020043, PXD020026, and PXD020013.

The molecular basis of venom resistance in a rattlesnake-squirrel predator-prey system.

Understanding how interspecific interactions mould the molecular basis of adaptations in coevolving species is a long-sought goal of evolutionary biology. Venom in predators and venom resistance proteins in prey are coevolving molecular phenotypes, and while venoms are highly complex mixtures it is unclear if prey respond with equally complex resistance traits. Here, we use a novel molecular methodology based on protein affinity columns to capture and identify candidate blood serum resistance proteins ("venom interactive proteins" [VIPs]) in California Ground Squirrels (Otospermophilus beecheyi) that interact with venom proteins from their main predator, Northern Pacific Rattlesnakes (Crotalus o. oreganus). This assay showed that serum-based resistance is both population- and species-specific, with serum proteins from ground squirrels showing higher binding affinities for venom proteins of local snakes compared to allopatric individuals. Venom protein specificity assays identified numerous and diverse candidate prey resistance VIPs but also potential targets of venom in prey tissues. Many specific VIPs bind to multiple snake venom proteins and, conversely, single venom proteins bind multiple VIPs, demonstrating that a portion of the squirrel blood serum "resistome" involves broad-based inhibition of nonself proteins and suggests that resistance involves a toxin scavenging mechanism. Analyses of rates of evolution of VIP protein homologues in related mammals show that most of these proteins evolve under purifying selection possibly due to molecular constraints that limit the evolutionary responses of prey to rapidly evolving snake venom proteins. Our method represents a general approach to identify specific proteins involved in co-evolutionary interactions between species at the molecular level.

Neural negated entity recognition in Spanish electronic health records.

This work deals with negation detection in the context of clinical texts. Negation detection is a key for decision support systems since negated events (detection of absence of some events) help ascertain current medical conditions. For artificial intelligence, negation detection is a valuable point as it can revert the meaning of a part of a text and, accordingly, influence other tasks such as medical dosage adjustment, the detection of adverse drug reactions or hospital acquired diseases. We focus on negated medical events such as disorders, findings and allergies. From Natural Language Processing (NLP) background, we refer to them as negated medical entities. A novelty of this work is that we approached this task as Named Entity Recognition (NER) with the restriction that just negated medical entities must be recognized (in an attempt to help distinguish them from non-negated ones). Our study is driven with Electronic Health Records (EHRs) written in Spanish. A challenge to cope with is the lexical variability (alternative medical forms, abbreviations, etc.). To this end, we employed an approach based on deep learning. Specifically, the system combines character embeddings to cope with out-of-vocabulary (OOV) words, Long Short-Term Memory (LSTM) networks to model contextual representations and it makes use of Conditional Random Fields (CRF) to classify each medical entity as either negated or not given the contextual dense representation. Moreover, we explored both embeddings created from words and embeddings created from lemmas. The best results were obtained with the lemmatized embeddings. Apparently, this approach reinforced the capability of the LSTMs to cope with the high lexical variability. The f-measure for exact-match was 65.1 and 82.4 for the partial-match.

Validation of the Spanish version of the Oxford Cognitive Screen (S-OCS): psychometric properties of a short cognitive stroke-specific screening tool.

OBJECTIVE:: The aim of this study is to examine the psychometric properties of the Spanish version of the Oxford Cognitive Screen in a subacute stroke population. PARTICIPANTS AND SETTING:: Fifty-seven subacute stroke outpatients and 54 healthy individuals were recruited in Alicante province, Spain. MAIN MEASURE:: The Oxford Cognitive Screen. OTHER MEASURES:: The Montreal Cognitive Assessment, the Barcelona test, and the Barthel Index. DESIGN:: A validation study was conducted to analyze the inter-rater, intra-rater, test-retest, and internal consistency of the Spanish version of the Oxford Cognitive Screen. Concurrent validity was assessed using the Montreal Cognitive Assessment and the Barcelona test, and divergent validity using the Barthel index. Discriminant indices such as the sensitivity, specificity, predictive values, and optimal cut-offs were also estimated. RESULTS:: The subtests of the Spanish version of the Oxford Cognitive Screen showed excellent estimates for the inter-reliability (intraclass correlation coefficient (ICC) = 0.790 to 1.000; rs = 0.693 to 1.000), and acceptable-good for intra-reliability (ICC = 0.181 to 0.990) and test-retest reliability ( rs = 0.173 to 0.971). Internal consistency was also excellent (standardized Cronbach's α = 0.907). Spearman correlations for the concurrent validity were low-strong ( rs = -0.193 to 0.95) and low-moderate ( rs = -0.091 to 0.443) for divergent validity. The optimal cut-offs estimated for the subtests of the Spanish version of the Oxford Cognitive Screen showed good-high specificity (66.7%-100%) and positive predictive value (67.9%-100%), and low-good sensitivity (14.8%-83.3%) and moderate-good negative predictive value (53.5%-76.6%). Discriminant power as measured by the area under the curve indicated acceptable-good values (0.397 to 0.894). CONCLUSION:: Our findings support that the Spanish version of the Oxford Cognitive Screen is a reliable and valid tool for screening cognitive impairments in subacute stroke patients.

Recent advances in Swedish and Spanish medical entity recognition in clinical texts using deep neural approaches.

BACKGROUND: Text mining and natural language processing of clinical text, such as notes from electronic health records, requires specific consideration of the specialized characteristics of these texts. Deep learning methods could potentially mitigate domain specific challenges such as limited access to in-domain tools and data sets. METHODS: A bi-directional Long Short-Term Memory network is applied to clinical notes in Spanish and Swedish for the task of medical named entity recognition. Several types of embeddings, both generated from in-domain and out-of-domain text corpora, and a number of generation and combination strategies for embeddings have been evaluated in order to investigate different input representations and the influence of domain on the final results. RESULTS: For Spanish, a micro averaged F1-score of 75.25 was obtained and for Swedish, the corresponding score was 76.04. The best results for both languages were achieved using embeddings generated from in-domain corpora extracted from electronic health records, but embeddings generated from related domains were also found to be beneficial. CONCLUSIONS: A recurrent neural network with in-domain embeddings improved the medical named entity recognition compared to shallow learning methods, showing this combination to be suitable for entity recognition in clinical text for both languages.

Severe, life-threatening phenotype of primary Sjögren's syndrome: clinical characterisation and outcomes in 1580 patients (GEAS-SS Registry).

OBJECTIVES: To analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjögren's syndrome (SS). METHODS: The GEAS-SS multicentre registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included more than 20 Spanish reference centres with substantial experience in the management of SS patients. By January 2018, the database included 1580 consecutive patients fulfilling the 2002 classification criteria for primary SS. Severe, life-threatening systemic disease was defined as an activity level scored as "high" in at least one ESSDAI domain. RESULTS: Among 1580 patients, 208 (13%) were classified as presenting a severe, potentially life-threatening systemic disease: 193 presented one ESSDAI domain classified as high, 14 presented two high scored domains and only one presented three high activity domains. The ESSDAI domains involved consisted of lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 21 (10%), cutaneous in 19 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%). Patients with severe systemic disease were more frequently men (p=0.001) and had a higher frequency of anaemia (p<0.001), lymphopenia (p<0.001), rheumatoid factor (p=0.021), low C3 levels (p=0.015), low C4 levels (p<0.001) and cryoglobulins (p<0.001). From a therapeutic point of view, systemic patients received more frequently glucocorticoids (p<0.001), immunosuppressants (p<0.001), intravenous immunoglobulins (p=0.008) and rituximab (p<0.001). We found an overall mortality rate of 20% in severe systemic patients, a rate that reached to 33% in patients presenting two or more high systemic involvements; these patients had a higher frequency of low C4 levels (p=0.012) and cryoglobulins (p=0.001) in comparison with those with a single severe organ involved. CONCLUSIONS: 13% of patients with primary SS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases.

The frontal assessment battery in clinical practice: a systematic review.

BACKGROUND: The frontal assessment battery (FAB) is a brief tool designed to evaluate executive function. Some studies have particularly focused on assessing its applicability addressing two issues: first, on detecting the brain regions responsible for the FAB performance, and second, on determining its capability for differential diagnosis. Our aim was to summarize and analyze critically the studies that assessed the neuroanatomical correspondence and the differential diagnostic value of the FAB in several study populations suffering from different pathologies. METHODS: We completed a literature search in MEDLINE (via PubMed) database by using the term "frontal assessment battery" and the combination of this term with "applicability" or "use" or "usefulness". The search was limited to articles in English or Spanish languages, published between 1 September 2000 and 30 September 2016, human studies, and journal articles. RESULTS: A total of 32 studies met inclusion criteria. Seventeen studies were aimed at identifying the brain regions or the neural substrates involved in executive functions measured by the FAB and 15 studies at verifying that the FAB was an appropriate tool for the differential diagnosis in neurological diseases. CONCLUSION: Our study showed that the FAB may be an adequate assessment tool for executive function and may provide useful information for differential diagnosis in several diseases. Given that the FAB takes short time and is easy to administer, its usage may be of great interest as part of a full neuropsychological assessment in clinical settings. Copyright © 2017 John Wiley & Sons, Ltd.

Neural Basis of Cognitive Assessment in Alzheimer Disease, Amnestic Mild Cognitive Impairment, and Subjective Memory Complaints.

INTRODUCTION: Interpreting cognitive tests is often challenging. The same test frequently examines multiple cognitive functions, and the functional and anatomical basis underlying test performance is unknown in many cases. This study analyses the correlation of different neuropsychological test results with brain metabolism in a series of patients evaluated for suspected Alzheimer disease. METHODS: 20 healthy controls and 80 patients consulting for memory loss were included, in which cognitive study and 18F-fluorodeoxyglucose PET were performed. Patients were categorized according to Reisberg's Global Deterioration Scale. Voxel-based analysis was used to determine correlations between brain metabolism and performance on the following tests: Free and Cued Selective Reminding Test (FCSRT), Boston Naming Test (BNT), Trail Making Test, Rey-Osterrieth Complex Figure test, Visual Object and Space Perception Battery (VOSP), and Tower of London (ToL) test. RESULTS: Mean age in the patient group was 73.9 ± 10.6 years, and 47 patients were women (58.7%). FCSRT findings were positively correlated with metabolism in the medial and anterior temporal region bilaterally, the left precuneus, and posterior cingulate. BNT results were correlated with metabolism in the middle temporal, superior, fusiform, and frontal medial gyri bilaterally. VOSP results were related to the occipital and parietotemporal regions bilaterally. ToL scores were correlated to metabolism in the right temporoparietal and frontal regions. CONCLUSIONS: These results suggest that different areas of the brain are involved in the processes required to complete different cognitive tests. Ascertaining the functional basis underlying these tests may prove helpful for understanding and interpreting them.

Semi-supervised medical entity recognition: A study on Spanish and Swedish clinical corpora.

OBJECTIVE: The goal of this study is to investigate entity recognition within Electronic Health Records (EHRs) focusing on Spanish and Swedish. Of particular importance is a robust representation of the entities. In our case, we utilized unsupervised methods to generate such representations. METHODS: The significance of this work stands on its experimental layout. The experiments were carried out under the same conditions for both languages. Several classification approaches were explored: maximum probability, CRF, Perceptron and SVM. The classifiers were enhanced by means of ensembles of semantic spaces and ensembles of Brown trees. In order to mitigate sparsity of data, without a significant increase in the dimension of the decision space, we propose the use of clustered approaches of the hierarchical Brown clustering represented by trees and vector quantization for each semantic space. RESULTS: The results showed that the semi-supervised approaches significantly improved standard supervised techniques for both languages. Moreover, clustering the semantic spaces contributed to the quality of the entity recognition while keeping the dimension of the feature-space two orders of magnitude lower than when directly using the semantic spaces. CONCLUSIONS: The contributions of this study are: (a) a set of thorough experiments that enable comparisons regarding the influence of different types of features on different classifiers, exploring two languages other than English; and (b) the use of ensembles of clusters of Brown trees and semantic spaces on EHRs to tackle the problem of scarcity of available annotated data.

On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning.