Validity of the Functioning Assessment Short Tests (FAST), in patients with schizophrenia.

INTRODUCTION: Functional impairment in schizophrenia is one of the main features of the disorder and implies a great impact on the patient's quality of life. The Brief Functioning Assessment Scale (FAST), originally validated in bipolar disorder, has also been validated for its application in other mental disorders. However, we only found one study on the reliability and validity of the Brazilian version in schizophrenia. The purpose of this study was to analyze the psychometric properties of the Spanish version of the FAST in patients diagnosed with schizophrenia. MATERIAL AND METHODS: A total of 226 patients with a diagnosis of schizophrenia were evaluated by mean the FAST, the GAF and the self-care requirements scale (ERA). Scale properties were analyzed in terms of internal consistency, inter-observer agreement and test-retest reliability. Convergent validity with the GAF and ERA scales was also analyzed, as well as construct validity by means of a Confirmatory Factor Analysis (CFA). RESULTS: For the total scale, the results showed high internal consistency (Cronbach's Alpha of, 87), as well as good inter-observer (ICC=,86) and test-retest (ICC=,77) agreement. Concurrent validity with the GAF scale was discrete (r=-,32; P<,001) and with the ERA scale was moderate (r=,50; P<,001). CFA showed an internal structure that matched the six factors proposed by the original scale, with a good level of item saturation for each factor. CONCLUSIONS: The FAST scale showed good psychometric properties in terms of reliability and validity in its Spanish version for its application in patients with schizophrenia. It can be considered as a good tool to assess different areas of functional impairment in clinical practice and research.

Validación de la versión española de la Escala de funcionamiento breve (FAST) en pacientes diagnosticados de esquizofrenia / Validity of the Functioning Assessment Short Tests (FAST), in patients with schizophrenia

Introducción: El deterioro funcional es una de las principales características del curso de la esquizofrenia e implica un gran impacto en la calidad de vida del paciente. La Escala de funcionamiento breve (FAST), validada originalmente en trastorno bipolar, también ha sido validada para su aplicación en otros trastornos mentales, aunque solo encontramos un estudio sobre la fiabilidad y validez de la versión brasileña en esquizofrenia. El propósito de este estudio fue analizar las propiedades psicométricas de la versión española de la FAST en pacientes diagnosticados de esquizofrenia.Material y métodos: Un total de 226 pacientes con diagnóstico de esquizofrenia fueron evaluados, cumplimentando la FAST, la GAF y la Escala de requisitos de autocuidado (ERA). Se analizaron las propiedades de la escala en términos de consistencia interna, concordancia interobservador y fiabilidad test-retest. Se analizó también la validez convergente con las escalas GAF y ERA, y la validez de constructo mediante un análisis factorial confirmatorio.Resultados:Para el total del cuestionario los resultados mostraron una elevada consistencia interna (Cronbach's Alpha de 0,87), así como una buena concordancia interobservador (CCI=0,86) y test-retest (CCI=0,77). La validez concurrente con la escala GAF fue discreta (r=–0,32; p<0,001) y con la escala ERA moderada (r=0,50; p<0,001). El análisis factorial confirmatorio mostró una estructura interna que se ajustaba a los 6 factores de la escala original, con un buen nivel de saturación de los ítems para cada factor.Conclusiones: La escala FAST mostró buenas propiedades psicométricas en términos de fiabilidad y validez en su versión española para su aplicación en pacientes con esquizofrenia. Se puede considerar una buena herramienta para evaluar diferentes áreas del deterioro funcional en la práctica clínica y en investigación. (AU)

Introduction: Functional impairment in schizophrenia is one of the main features of the disorder and implies a great impact on the patient's quality of life. The brief functioning assessment scale (FAST), originally validated in bipolar disorder, has also been validated for its application in other mental disorders. However, we only found one study on the reliability and validity of the Brazilian version in schizophrenia. The purpose of this study was to analyze the psychometric properties of the Spanish version of the FAST in patients diagnosed with schizophrenia.Material and methods: A total of 226 patients with a diagnosis of schizophrenia were evaluated by mean the FAST, the GAF and the self-care requirements scale (ERA). Scale properties were analyzed in terms of internal consistency, inter-observer agreement and test–retest reliability. Convergent validity with the GAF and ERA scales was also analyzed, as well as construct validity by means of a Confirmatory Factor Analysis (CFA).Results: For the total scale, the results showed high internal consistency (Cronbach's Alpha of .87), as well as good inter-observer (ICC=.86) and test–retest (ICC=.77) agreement. Concurrent validity with the GAF scale was discrete (r=−.32; P<.001) and with the ERA scale was moderate (r=.50; P<.001). CFA showed an internal structure that matched the six factors proposed by the original scale, with a good level of item saturation for each factor.Conclusions: The FAST scale showed good psychometric properties in terms of reliability and validity in its Spanish version for its application in patients with schizophrenia. It can be considered as a good tool to assess different areas of functional impairment in clinical practice and research. (AU)

The negative consequences of sports betting opportunities on human capital formation: Evidence from Spain.

The proliferation of on-site betting shops has received enormous public attention, becoming one of the most alarming health policy issues in contemporary cities. However, there is little evidence on whether its growing presence nearby vulnerable populations produce social harm beyond its known adverse individual effects. This study provides new evidence on the negative societal effects of betting houses. Our research design takes advantage of a new wave of openings in Madrid (Spain), which created a sudden increase in the supply of on-site gambling. Using a differences-in-differences design, we find that new betting houses decline nearby high schools' educational performance, especially in public schools in less advantaged areas. This effect is neither trivial nor diminishing with time. This evidence suggests that betting houses increase inequality of educational opportunities. The ubiquity of betting houses around vulnerable populations in multiple regions drives us to think that these findings have relevant policy implications for many countries currently designing policies tackling the increase of problem gambling.

Matched cohort study on the efficacy of tocilizumab in patients with COVID-19.

BACKGROUND: Tocilizumab has been proposed as a treatment for the new disease COVID-19, however, there is not enough scientific evidence to support this treatment. The objective of this study is to analyze whether the use of tocilizumab is associated with respiratory improvement and a shorter time to discharge in patients with COVID-19 and lung involvement. METHODS: Observational study on a cohort of 418 patients, admitted to three county hospitals in Catalonia (Spain). Patients admitted consecutively were included and followed until discharge or up to 30 days of admission. A sub-cohort of patients treated with tocilizumab and a sub-cohort of control patients were identified, matched by a large number of risk factors and clinical variables. Sub-cohorts were also matched by the number of other treatments for COVID-19 that patients received. Increment in SAFI (inspired oxygen fraction / saturation) 48 h after the start of treatment, and time to discharge, were the primary outcomes. Mortality, which was a secondary outcome, was analyzed in the total cohort, by using logistic regression models, adjusted by confounders. RESULTS: There were 96 patients treated with tocilizumab. Of them, 22 patients could be matched with an equivalent number of control patients. The increment in SAFI from baseline to 48 h of treatment, was not significantly different between groups (tocilizumab: -0.04; control: 0.09; p = 0.636). Also, no difference in time to discharge was found between the two sub-cohorts (logrank test: p = 0.472). The logistic regression models, did not show an effect of tocilizumab on mortality (OR 0.99; p = 0.990). CONCLUSIONS: We did not find a clinical benefit associated with the use tocilizumab, in terms of respiratory function at 48 h of treatment, or time to discharge.

Association between COVID-19 prognosis and disease presentation, comorbidities and chronic treatment of hospitalized patients.

IMPORTANCE: The rapid pandemic expansion of the disease caused by the new SARS-CoV-2 virus has compromised health systems worldwide. Knowledge of prognostic factors in affected patients can help optimize care. OBJECTIVE: The objective of this study was to analyze the relationship between the prognosis of COVID-19 and the form of presentation of the disease, the previous pathologies of patients and their chronic treatments. DESIGN, PARTICIPANTS AND LOCATIONS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia (Spain). As primary outcomes, severe disease (need for oxygen therapy via nonrebreather mask or mechanical ventilation) and death were studied. Multivariate binary logistic regression models were performed to study the association between the different factors and the results. RESULTS: Advanced age, male sex and obesity were independent markers of poor prognosis. The most frequent presenting symptom was fever, while dyspnea was associated with severe disease and the presence of cough with greater survival. Low oxygen saturation in the emergency room, elevated CRP in the emergency room and initial radiological involvement were all related to worse prognosis. The presence of eosinophilia (% of eosinophils) was an independent marker of less severe disease. CONCLUSIONS: This study identified the most robust markers of poor prognosis for COVID-19. These results can help to correctly stratify patients at the beginning of hospitalization based on the risk of developing severe disease.

Observational study of azithromycin in hospitalized patients with COVID-19.

BACKGROUND: The rapid spread of the disease caused by the novel SARS-CoV-2 virus has led to the use of multiple therapeutic agents whose efficacy has not been previously demonstrated. The objective of this study was to analyze whether there is an association between the use of azithromycin and the evolution of the pulmonary disease or the time to discharge, in patients hospitalized with COVID-19. METHODS: This was an observational study on a cohort of 418 patients admitted to three regional hospitals in Catalonia, Spain. As primary outcomes, we studied the evolution of SAFI ratio (oxygen saturation/fraction of inspired oxygen) in the first 48 hours of treatment and the time to discharge. The results were compared between patients treated and untreated with the study drug through subcohort analyses matched for multiple clinical and prognostic factors, as well as through analysis of non-matched subcohorts, using Cox multivariate models adjusted for prognostic factors. RESULTS: There were 239 patients treated with azithromycin. Of these, 29 patients treated with azithromycin could be matched with an equivalent number of control patients. In the analysis of these matched subcohorts, SAFI at 48h had no significant changes associated to the use of azithromycin, though azithromycin treatment was associated with a longer time to discharge (10.0 days vs 6.7 days; log rank: p = 0.039). However, in the unmatched cohorts, the increased hospital stay associated to azithromycin use, was no significant after adjustment using Multivariate Cox regression models: hazard ratio 1.45 (IC95%: 0.88-2.41; p = 0.150). This study is limited by its small sample size and its observational nature; despite the strong pairing of the matched subcohorts and the adjustment of the Cox regression for multiple factors, the results may be affected by residual confusion. CONCLUSIONS: We did not find a clinical benefit associated with the use of azithromycin, in terms of lung function 48 hours after treatment or length of hospital stay.

Traumatic Microbleeds in the Hippocampus and Corpus Callosum Predict Duration of Posttraumatic Amnesia.

OBJECTIVE: Radiologic predictors of posttraumatic amnesia (PTA) duration are lacking. We hypothesized that the number and distribution of traumatic microbleeds (TMBs) detected by gradient recalled echo (GRE) magnetic resonance imaging (MRI) predicts PTA duration. SETTING: Academic, tertiary medical center. PARTICIPANTS: Adults with traumatic brain injury (TBI). DESIGN: We identified 65 TBI patients with acute GRE MRI. PTA duration was determined with the Galveston Orientation and Amnesia Test, Orientation Log, or chart review. TMBs were identified within memory regions (hippocampus, corpus callosum, fornix, thalamus, and temporal lobe) and control regions (internal capsule and global). Regression tree analysis was performed to identify radiologic predictors of PTA duration, controlling for clinical PTA predictors. MAIN MEASURES: TMB distribution, PTA duration. RESULTS: Sixteen patients (25%) had complicated mild, 4 (6%) had moderate, and 45 (69%) had severe TBI. Median PTA duration was 43 days (range, 0-240 days). In univariate analysis, PTA duration correlated with TMBs in the corpus callosum (R = 0.29, P = .02) and admission Glasgow Coma Scale (GCS) score (R = -0.34, P = .01). In multivariate regression analysis, admission GCS score was the only significant contributor to PTA duration. However, in regression tree analysis, hippocampal TMBs, callosal TMBs, age, and admission GCS score explained 26% of PTA duration variance and distinguished a subgroup with prolonged PTA. CONCLUSIONS: Hippocampal and callosal TMBs are potential radiologic predictors of PTA duration.

Total small vessel disease burden and brain network efficiency in cerebral amyloid angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is associated with hemorrhagic and nonhemorrhagic markers small vessel disease (SVD). A composite score to quantify the total burden of SVD on MRI specifically for CAA patients was recently developed. Brain network alterations related to individual MRI markers of SVD in CAA were demonstrated. OBJECTIVES: Considering diffusion based network measures sensitive to detect different relevant SVD-related brain injury, we investigated if increased overall SVD injury on MRI corresponds to worse global brain connectivity in CAA. METHODS: Seventy-three patients (79.5% male, mean age 70.58±8.22years) with a diagnosis CAA were considered. SVD markers in total MRI SVD score included: lobar cerebral microbleeds, cortical superficial siderosis (cSS), white matter hyperintensities (WMH) and centrum semiovale-enlarged perivascular spaces. Diffusion imaging based network reconstruction was made. The associations between total MRI SVD score and global network efficiency (GNE) were analyzed. RESULTS: A modest significant inverse correlation between total MRI SVD score and GNE existed (p=0.013; R2=0.07). GNE was related with the presence of cSS and moderate-severe WMHs. CONCLUSIONS: An increased burden of SVD neuroimaging markers corresponds to more reductions in global brain connectivity, implying a possible cumulative effect of overall SVD markers on disrupted physiology. GNE was related with some components of the score, specifically cSS and moderate-severe WMHs.

Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal.

BACKGROUND: Recovery of functional independence is possible in patients with brainstem traumatic axonal injury (TAI), also referred to as "grade 3 diffuse axonal injury," but acute prognostic biomarkers are lacking. We hypothesized that the extent of dorsal brainstem TAI measured by burden of traumatic microbleeds (TMBs) correlates with 1-year functional outcome more strongly than does ventral brainstem, corpus callosal, or global brain TMB burden. Further, we hypothesized that TMBs within brainstem nuclei of the ascending arousal network (AAN) correlate with 1-year outcome. METHODS: Using a prospective outcome database of patients treated for moderate-to-severe traumatic brain injury at an inpatient rehabilitation hospital, we retrospectively identified 39 patients who underwent acute gradient-recalled echo (GRE) magnetic resonance imaging (MRI). TMBs were counted on the acute GRE scans globally and in the dorsal brainstem, ventral brainstem, and corpus callosum. TMBs were also mapped onto an atlas of AAN nuclei. The primary outcome was the disability rating scale (DRS) score at 1 year post-injury. Associations between regional TMBs, AAN TMB volume, and 1-year DRS score were assessed by calculating Spearman rank correlation coefficients. RESULTS: Mean ± SD number of TMBs was: dorsal brainstem = 0.7 ± 1.4, ventral brainstem = 0.2 ± 0.6, corpus callosum = 1.8 ± 2.8, and global = 14.4 ± 12.5. The mean ± SD TMB volume within AAN nuclei was 6.1 ± 18.7 mm3. Increased dorsal brainstem TMBs and larger AAN TMB volume correlated with worse 1-year outcomes (R = 0.37, p = 0.02, and R = 0.36, p = 0.02, respectively). Global, callosal, and ventral brainstem TMBs did not correlate with outcomes. CONCLUSIONS: These findings suggest that dorsal brainstem TAI, especially involving AAN nuclei, may have greater prognostic utility than the total number of lesions in the brain or brainstem.

GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

BACKGROUND AND PURPOSE: Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. METHODS: We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method. RESULTS: The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P=9×10-03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (P=3.2×10-09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score (P=0.03). CONCLUSIONS: The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population.

Microinfarct disruption of white matter structure: a longitudinal diffusion tensor analysis.

OBJECTIVE: To evaluate the local effect of small asymptomatic infarctions detected by diffusion-weighted imaging (DWI) on white matter microstructure using longitudinal structural and diffusion tensor imaging (DTI). METHODS: Nine acute to subacute DWI lesions were identified in 6 subjects with probable cerebral amyloid angiopathy who had undergone high-resolution MRI both before and after DWI lesion detection. Regions of interest (ROIs) corresponding to the site of the DWI lesion (lesion ROI) and corresponding site in the nonlesioned contralateral hemisphere (control ROI) were coregistered to the pre- and postlesional scans. DTI tractography was additionally performed to reconstruct the white matter tracts containing the ROIs. DTI parameters (fractional anisotropy [FA], mean diffusivity [MD]) were quantified within each ROI, the 6-mm lesion-containing tract segments, and the entire lesion-containing tract bundle. Lesion/control FA and MD ratios were compared across time points. RESULTS: The postlesional scans (performed a mean 7.1 ± 4.7 months after DWI lesion detection) demonstrated a decrease in median FA lesion/control ROI ratio (1.08 to 0.93, p = 0.038) and increase in median MD lesion/control ROI ratio (0.97 to 1.17, p = 0.015) relative to the prelesional scans. There were no visible changes on postlesional high-resolution T1-weighted and fluid-attenuated inversion recovery images in 4 of 9 lesion ROIs and small (2-5 mm) T1 hypointensities in the remaining 5. No postlesional changes in FA or MD ratios were detected in the 6-mm lesion-containing tract segments or full tract bundles. CONCLUSIONS: Asymptomatic DWI lesions produce chronic local microstructural injury. The cumulative effects of these widely distributed lesions may directly contribute to small-vessel-related vascular cognitive impairment.

Role of the MMP9 gene in hemorrhagic transformations after tissue-type plasminogen activator treatment in stroke patients.

BACKGROUND AND PURPOSE: Despite the benefits of tissue-type plasminogen activator treatment, some stroke patients experience adverse hemorrhagic transformations (HT). Plasma protein levels of MMP9 have been associated with HT occurrence. We aimed to analyze the association of the MMP9 gene with HT occurrence. METHODS: We analyzed the MMP9 gene in blood samples from 885 stroke patients treated with tissue-type plasminogen activator by tag-SNP, imputed SNP, direct sequencing, and RNA expression. RESULTS: We did not observe any significant association between MMP9 genetic variations or MMP9 expression and HT occurrence. Moreover, no association was found between MMP9 expression and MMP9 polymorphisms. CONCLUSIONS: Genetic variations in the MMP9 gene are not associated with HT occurrence in tissue-type plasminogen activator-treated patients.

A predictive clinical-genetic model of tissue plasminogen activator response in acute ischemic stroke.

OBJECTIVE: Wide interindividual variability exists in response to tissue plasminogen activator (t-PA) treatment in the acute phase of ischemic stroke. We aimed to find genetic variations associated with hemorrhagic transformation (HT) and mortality rates after t-PA. We then generated a clinical-genetic model for predicting t-PA response. METHODS: Our prospective study used SNPlex to genotype 140 single nucleotide polymorphisms (SNPs) from 97 candidate genes in 3 patient cohorts. The cohorts included 1,172 patients who were treated with t-PA; 20.9% of them developed HT as evaluated by systematic brain computed tomography scan, and 10.6% died. A predictive model was generated by logistic regression (LR). Functional studies included real time quantitative polymerase chain reaction, nephelometry, and Western blot for alpha-2-macroglobulin (A2M) and activated partial thromboplastin time measurement for coagulation factor XII (FXII). RESULTS: Replication analysis revealed that the SNP rs669 (Val1000Ile) in A2M was associated with HT, and rs1801020 (-4C>T) of F12 was associated with in-hospital death. The rs669 SNP withstood Bonferroni correction for HT (p < 3.57E-4). LR-based scores predicted HT occurrence (p = 9.13E-15) and in-hospital mortality (p = 8.7E-9) and were validated in an independent cohort. Val1000Ile modified A2M serum levels at baseline and after t-PA infusion, but not mRNA expression or protein structure; -4C>T affected FXII activity both prior to and after t-PA treatment. INTERPRETATION: Two functional polymorphisms were consistently associated with t-PA safety. Our validated LR-based score predicts t-PA safety in the Spanish population.

Evaluación crítica de las guías de práctica clínica / Critical evaluation of clinical practice guidelines

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Relationship between the efficacy of rivastigmine and apolipoprotein E (epsilon4) in patients with mild to moderately severe Alzheimer disease.

Alzheimer disease is the most common form of dementia in Western countries and the leading cause of disability in the over-65 population. Apolipoprotein E (APOE) is a multifunctional protein implied in lipid metabolism and neurobiology. Polymorphisms of the APOE gene have been associated with a variety of medical disorders, from arteriosclerosis to AD. A high frequency of the APOE epsilon4 allele has been found in patients with AD and they seem to have a higher risk of developing the disease. Various authors have suggested a possible relationship between the efficacy of cholinesterase inhibitors and the presence of the APOE epsilon4 allele. The purpose of the present study was to compare prospectively the efficacy of rivastigmine in patients with mild to moderately severe AD presenting different polymorphisms of the APOE gene on chromosome 19 and to determine if there was a difference in the response to rivastigmine treatment in AD patients with the APOE epsilon4 allele (heterozygous or homozygous) versus patients who had other forms of APOE, such as epsilon2 and epsilon3. This was an open-label, nonrandomized, multicenter study in patients over 50 years of age diagnosed with mild to moderately severe AD. The results of the analysis of this study indicate that the presence of at least one APOE epsilon4 allele does not determine a difference in the response to treatment with rivastigmine. The data indicate that knowledge of the patient's genotype is not necessary for treatment with rivastigmine. It would be interesting in the future to analyze the interaction between these 2 factors using other available anticholinesterase drugs.

Nifedipine versus ritodrine for suppression of preterm labor. Comparison of their efficacy and secondary effects.

OBJECTIVES: To compare the efficacy of nifedipine and ritodrine in prolonging pregnancy beyond 48 h, 1 week and 36.0 weeks and to evaluate maternal side effects and adverse perinatal outcome. STUDY DESIGN: Non-blinded, randomized controlled trial. Eighty patients with singleton pregnancies admitted for preterm labor with intact membranes between 22 and 35 weeks of gestation were included in the study. Preterm labor was defined as the persistence of at least two symptomatic uterine contractions within a 10 min period during 60 min after admission and despite bed rest. RESULTS: Forty women received oral nifedipine and forty intravenous ritodrine. Two patients, one from each group, were excluded because of loss to follow-up after discharge. Therefore, 39 women in the nifedipine and the ritodrine groups, respectively, were evaluable for the final analysis. Baseline characteristics were comparable in both groups. The percentage of initial response, the speed of onset of action and the rate of successful treatment within 48 h were significantly better in the ritodrine group. However, prolongation of pregnancy beyond 7 days and 36 weeks of pregnancy was similar with a significantly lower rate of side effects in the nifedipine group. CONCLUSIONS: In this small trial, ritodrine provided more effective tocolysis within the first 48 h than nifedipine at the doses used in this study, although with a significantly higher rate of side effects.