Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

Epigenome-Wide Analysis of Methylation Changes in the Sequence of Gallstone Disease, Dysplasia, and Gallbladder Cancer.

BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a highly aggressive malignancy of the biliary tract. Most cases of GBC are diagnosed in low-income and middle-income countries, and research into this disease has long been limited. In this study we therefore investigate the epigenetic changes along the model of GBC carcinogenesis represented by the sequence gallstone disease → dysplasia → GBC in Chile, the country with the highest incidence of GBC worldwide. APPROACH AND RESULTS: To perform epigenome-wide methylation profiling, genomic DNA extracted from sections of formalin-fixed, paraffin-embedded gallbladder tissue was analyzed using Illumina Infinium MethylationEPIC BeadChips. Preprocessed, quality-controlled data from 82 samples (gallstones n = 32, low-grade dysplasia n = 13, high-grade dysplasia n = 9, GBC n = 28) were available to identify differentially methylated markers, regions, and pathways as well as changes in copy number variations (CNVs). The number and magnitude of epigenetic changes increased with disease development and predominantly involved the hypermethylation of cytosine-guanine dinucleotide islands and gene promoter regions. The methylation of genes implicated in Wnt signaling, Hedgehog signaling, and tumor suppression increased with tumor grade. CNVs also increased with GBC development and affected cyclin-dependent kinase inhibitor 2A, MDM2 proto-oncogene, tumor protein P53, and cyclin D1 genes. Gains in the targetable Erb-B2 receptor tyrosine kinase 2 gene were detected in 14% of GBC samples. CONCLUSIONS: Our results indicate that GBC carcinogenesis comprises three main methylation stages: early (gallstone disease and low-grade dysplasia), intermediate (high-grade dysplasia), and late (GBC). The identified gradual changes in methylation and CNVs may help to enhance our understanding of the mechanisms underlying this aggressive disease and eventually lead to improved treatment and early diagnosis of GBC.

Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data.

BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10-5 ) and Europeans (P = 9 × 10-5 ). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10-6 ). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk.

High CD8+ and absence of Foxp3+ T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival.

BACKGROUND: Gallbladder cancer (GBC), although infrequent in industrialized countries, has high incidence rates in certain world regions, being a leading cause of death among elderly Chilean women. Surgery is the only effective treatment, and a five-year survival rate of advanced-stage patients is less than 10%. Hence, exploring immunotherapy is relevant, although GBC immunogenicity is poorly understood. This study examined the relationship between the host immune response and GBC patient survival based on the presence of tumor-infiltrating lymphocytes at different disease stages. METHODS: Tumor tissues from 80 GBC patients were analyzed by immunohistochemistry for the presence of CD3+, CD4+, CD8+, and Foxp3+ T cell populations, and the results were associated with clinical stage and patient survival. RESULTS: The majority of tumor samples showed CD3+ T cell infiltration, which correlated with better prognosis, particularly in advanced disease stages. CD8+, but not CD4+, T cell infiltration correlated with improved survival, particularly in advanced disease stages. Interestingly, a < 1 CD4+/CD8+ T cell ratio was related with increased survival. Additionally, the presence of Foxp3+ T cells correlated with decreased patient survival, whereas a ≤ 1 Foxp3+/CD8+ T cell ratio was associated with improved patient survival. CONCLUSIONS: Depending on the disease stage, the presence of CD8+ and absence of Foxp3+ T cell populations in tumor tissues correlated with improved GBC patient survival, and thus represent potential markers for prognosis and management of advanced disease, and supports testing of immunotherapy.

Spirometry and respiratory oscillometry: Feasibility and concordance in schoolchildren with asthma.

OBJECTIVE: The purpose of this study was to describe the feasibility of respiratory oscillometry (RO) in schoolchildren with asthma, and the concordance of its results with those of spirometry, to determine its clinical usefulness. METHODS: RO and spirometry were performed in 154 children (6 to 14-year-old) with asthma, following strict quality criteria for the tests. Their feasibility (probability of valid test, time of execution, number of maneuvers needed to achieve a valid test, and perceived difficulty) was compared. The factors that influence feasibility were analyzed with multivariate methods. FEV1, FEV1/FVC, FVC and FEF25-75 for spirometry, and R5, AX and R5-19 for RO, were converted into z-scores and their concordance was investigated through intraclass correlation coefficients (ICC) and kappa indices for normal/abnormal values. RESULTS: There were no differences in the probability of obtaining a valid RO or spirometry (83.1% vs. 81.8%, p = 0.868). RO required a lower number of maneuvers [mean (SD) 4.2 (1.8) versus 6.0 (1.6), p < 0.001] and less execution time [5.1 (2.7) versus 7.6 (2.4) minutes, p < 0.001], and patients considered it less difficult. Age increased the probability of obtaining valid RO and spirometry. The concordance of results between RO and spirometry was low, and only between zFEV1 and zAX could it be considered moderate (ICC = 0.412, kappa = 0.427). CONCLUSION: RO and spirometry are feasible in children with asthma. RO has some practical advantages, but the concordance of its results with spirometry is low.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease.

For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions "Is Se deficiency related to heart inflammation and arrhythmogenesis in CCC?" and "Could Se be recommended as a therapeutic strategy for CCC?", we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-ß as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-ß pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients.

Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression.

Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence "gallstones → dysplasia → GBC". In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04-1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.

Familial Aggregation of Endemic Congenital Hypothyroidism Syndrome in Congo (DR): Historical Data.

Familial aggregation of endemic congenital hypothyroidism (CH) in an iodine-deficient population from northern Congo (Democratic Republic (DR)) was analysed on data collected four decades ago (1979-1980). During a systematic survey of 62 families, 46 endemic CH subjects (44 myxedematous and 2 neurological) were identified based on clinical evidence within a village cohort of 468 subjects. A distribution analysis showed that two families presented significant excess of cases versus a random background distribution. Both families were characterised by two healthy parents having all of their five offspring affected by some form of endemic CH. Goitre prevalence in endemic CH was lower than that in the general population, while goitre prevalence in the unaffected part of the cohort (parents and siblings) was similar to that of the general population. Some unidentified genetic/epigenetic factor(s) could contribute to the evolution of some iodine-deficient hypothyroid neonates through irreversible and progressive loss of thyroid functional capacity during early childhood (<5 years old). Besides severe iodine deficiency, environmental exposure to thiocyanate overload and selenium deficiency, factors not randomly distributed within families and population, intervened in the full expression of endemic CH. Further exploration in the field will remain open, as iodine deficiency in Congo (DR) was eliminated in the 1990s.

ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans.

BACKGROUND: The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. METHODS: This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. RESULTS: Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. CONCLUSION: Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.

[Health-related quality of life in cases of attention deficit hyperactivity disorder with and without pharmacological treatment]. / Calidad de vida relacionada con la salud en casos de trastorno por déficit de atención con hiperactividad con/sin tratamiento farmacológico.

INTRODUCTION: The health-related quality of life (HRQoL) questionnaire is important in order to assess the effects of therapeutic intervention. The aim of this study is to analyse HRQoL, comparing cases of attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (ADHD-T), untreated cases (ADHD-N), and controls. MATERIAL AND METHODS: The study included a sample of 228 participants between 8 and 14 years old (114 controls, 57 ADHD-T, and 57 ADHD-N). Consecutive sampling was used in ADHD according to DSM-IV criteria (ADHD Rating Scales IV), and random sampling of controls matched by gender and age. The evaluation of HRQoL was made by using KIDSCREEN-52 parent version. RESULTS: The intensity of ADHD symptoms is significantly lower in ADHD-T than in ADHD-N. There is a moderate significant correlation between greater intensity of ADHD symptoms and worse HRQoL. ADHD cases have significantly worse HRQoL than controls on psychic well-being, mood, relationship with parents and friends, school environment, and social acceptance. The cases of ADHD-T have significantly better HRQoL than ADHD-N in the school dimension, but do not differ significantly in other dimensions of KIDSCREEN-52. CONCLUSIONS: It would be advisable that the treatment of ADHD integrates multi-dimensional therapeutic models that improve the basic symptoms of the disorder, as well as the HRQoL.

Polyarthritis and membranoproliferative glomerulonephritis as paraneoplastic manifestation of Hodgkin's lymphoma: A case report and literature review. / Poliartritis y glomerulonefritis membranoproliferativa como manifestaciones paraneoplásicas de linfoma de Hodgkin: presentación de un caso y revisión de literatura.

Paraneoplastic syndromes can be presented in multiple ways, which include endocrinological, hematologic, rheumatologic and nephrologic manifestations. While most of the publications described solid tumors as responsible for these manifestations, hematologic neoplasms are important cause to consider as part of the differential diagnosis. We report the case of a 46 year-old man with seronegative symmetric polyarthritis of large and small joints associated with membranoproliferative glomerulonephritis with deposits of immune complexes and acute impairment of renal function, as part of a paraneoplastic syndrome secondary of a classical Hodgkin lymphoma with bone marrow invasion, which reversed completely with chemotherapy treatment.

[Effects of acute and chronic Trypanosoma cruzi infection in pregnant mice]. / Efectos de la infección aguda y crónica por Trypanosoma cruzi en la gestación de los ratones.

Pathogens may impair reproduction in association or not with congenital infections. We have investigated the effect of acute infection with Trypanosoma cruzi, the protozoan agent of Chagas disease, on reproduction of female mice. In the acute, parasitemic, phase of the infection, female mice were totally unable to reproduce. Most of them (80%) were infertiles and did not develop any gestation. In the few gravid infected mice, implantation numbers were as in uninfected control mice. However, their fetuses presented a weight meanly reduced by 40% as compared to those of uninfected females, and all of them died during the gestation or whithin 48 h after birth. Such massive mortality did not result from congenital infection, which did not occur. The infertility and the fetal mortality occuring early in gestation (resorptions) were significantly correlated with a high maternal parasitemia, whereas later fetal mortality was associated with the presence of intracellular parasites in the utero-placental unit. The decidua was particularly receptive to T. cruzi multiplication, since this tissue harboured 125 fold more amastigotes than the maternal heart or other placental tissues. In addition, placentas of dead fetuses presented histopathological lesions (inflammatory infiltrates, fibrine deposits and ischemic necrosis). Such harmfull effects of acute infection were not observed when female mice were in the chronic phase of the infection, since these reproduce normally. Their fetuses only suffered from moderate and reversible growth retardation. These results indicate that, following the maternal parasite burden, T. cruzi infection may induce very deleterious effects on gestation.

Progressive Chagas' cardiomyopathy is associated with low selenium levels.

Selenium (Se) deficiency is linked with some cardiomyopathies. Its status was determined in 170 patients with chronic Chagas' disease from 2 Brazilian regions (Rio de Janeiro and Belo Horizonte), clinically stratified into groups as follows: indeterminate or asymptomatic (IND); cardiac asymptomatic (CARDa); cardiac symptomatic with moderate to severe heart dysfunction (CARDb); and healthy adults (HA), used for comparison. In most HA, Se levels were normal, excluding an overall Se deficiency. Se was significantly lower in CARDb than in HA, IND, or CARDa patients. This was not associated with a concomitant decrease in activity of glutathione peroxidase. Thyrotropin was normal, excluding iodine deficiency. Se correlated positive and significantly with ventricular ejection fraction (assessed via echocardiography). Asymptomatic children with acute Chagas' disease had normal Se as well as 5 noninfectious cases of cardiomyopathy. Low Se was found in 6 of 10 chagasic patients with digestive megasyndromes. Thus, the decrease in Se in chagasic patients seems to be a biological marker for Trypanosoma cruzi infection and related to the progression of pathology.

Calidad percibida por ostomizados en la utilización de un nuevo producto que contiene miel de manuka / Quality perceived by ostomized on the use of a new product containing manuka hone

La calidad es un concepto fundamental en el avance de todo producto sanitario. Objetivo. Evaluar el grado de calidad percibida por los usuarios en una bolsa colectora con miel de Manuka integrada en el protector cutáneo para ostomías. Metodología. Estudio descriptivo transversal comparativo realizado entre diciembre de 2017 y marzo de 2018, en distintos centros españoles. Criterios de selección: ser portador de una ostomía intestinal temporal o permanente, ≥18 años y no haber utilizado el nuevo producto. Se empleó un cuestionario autodiseñado con 16 ítems. Las variables analizadas fueron: tipo de estoma del paciente, cambio de frecuencia de bolsa, manejo del nuevo dispositivo, estado de la piel periestomal, nivel de satisfacción del usuario y necesidad del uso de accesorios complementarios. Resultados. Se incluyeron 31 pacientes. El 58% era portador de una ileostomía. El 71% consideró que la nueva bolsa era mejor o mucho mejor con un filtro más efectivo y una muy buena calidad del apósito (61,3%). Un 25,6% indicó haber reducido el número de cambios precisado. El 87,10% indicó que la bolsa era más fácil de colocar y al 64,5% le resultó más fácil despegarla con menor presencia de residuos (67,7%). Un 25,8% señaló requerir un número menor de accesorios. Conclusiones. La reducción en el número de cambios de bolsas y el mayor nivel de confort se relaciona con la rápida adherencia a la piel y la ventana de inspección. El mayor nivel de satisfacción se relaciona con la buena calidad del apósito y del filtro, la mejor adaptación a la piel y el cuidado de esta

Objective. To evaluate the level of quality perceived by users on a collection bag with Manuka honey integrated into the ostomy skin protector. Methodology. Descriptive transversal study realised between December 2017 and March 2018, in different Spanish centers. Selection criteria: To be a carrier of a temporary or permanent intestinal ostomy, ≥ 18 years old and not to have used the new product. The patients answered a self-designed questionnaire with 16 items. The variables analyzed were: Type of patient stoma, change of bag frequency, use of the new product, peristomal skin condition, level of user satisfaction and need for the use of complementary accessories. Results. 31 patients were included. 58% were carriers of an ileostomy. The 71% considered that the new bag was better or much better with a more effective filter and a very good quality of the dressing (61.3%). A 25.6% indicated that they had reduced the number of changes of the bag. The 87.10% indicated that the bag was easier to place and 64.5% said that it was easier to take off with less presence of waste (67.7%). A 25.8% pointed that the new bag required less accessories. Conclusions. The reduction in the number of bag changes and the higher level of comfort is related to the quick adherence to the skin and the inspection window. The highest level of satisfaction is related to the good quality of the dressing and the filter, the best adaptation to the skin and the care of it

Prevalence of oppositional defiant disorder in Spain.

INTRODUCTION: Oppositional defiant disorder (ODD) is characterized by a pattern of negative, defiant, disobedient and hostile behavior toward authority figures. ODD is one of the most frequent reasons for clinical consultation on mental health during childhood and adolescence. ODD has a high morbidity and dysfunction, and has important implications for the future if not treated early. OBJECTIVE: To determine the prevalence of ODD in schoolchildren aged 6-16 years in Castile and Leon (Spain). MATERIAL AND METHODS: Population study with a stratified multistage sample, and a proportional cluster design. Sample analyzed: 1,049. Cases were defined according to DSM-IV criteria. RESULTS: An overall prevalence rate of 5.6% was found (95% CI: 4.2%-7%). Male gender prevalence=6.8%; female=4.3%. Prevalence in secondary education=6.2%; primary education=5.3%. No significant differences by gender, age, grade, type of school, or demographic area were found. ODD prevalence without considering functional impairment, such as is performed in some research, would increase the prevalence to 7.4%. ODD cases have significantly worse academic outcomes (overall academic performance, reading, maths and writing), and worse classroom behavior (relationship with peers, respect for rules, organizational skills, academic tasks, and disruption of the class). CONCLUSIONS: Castile and Leon has a prevalence rate of ODD slightly higher to that observed in international publications. Depending on the distribution by age, morbidity and clinical dysfunctional impact, an early diagnosis and a preventive intervention are required for health planning.

Calidad de vida relacionada con la salud en casos de trastorno por déficit de atención con hiperactividad con/sin tratamiento farmacológico / Health-related quality of life in cases of attention deficit hyperactivity disorder with and without pharmacological treatment

Introducción: La calidad de vida relacionada con la salud (CVRS) es un marcador relevante para valorar los efectos de una intervención terapéutica. El objetivo del estudio es analizar la CVRS comparando casos con trastorno por déficit de atención con hiperactividad (TDAH) tratados farmacológicamente con metilfenidato (TDAH-T), casos no tratados (TDAH-N) y controles. Material y métodos: Muestra de 228 participantes entre 8 y 14 años (114 controles, 57 TDAH-T y 57 TDAH-N). Muestreo consecutivo de TDAH según DSM-IV (ADHD Rating Scales IV) y muestreo aleatorio de controles emparejados por sexo y edad. Evaluación de CVRS mediante KIDSCREEN-52 versión padres. Resultados: La intensidad de síntomas de TDAH es significativamente menor en TDAH-T que en TDAH-N y se observa correlación significativa moderada entre mayor intensidad de síntomas de TDAH y peor CVRS. Los casos de TDAH tienen significativamente peor CVRS que los controles en bienestar psíquico, estado de ánimo, relación con padres, relación con amigos, entorno escolar y aceptación social. Los casos de TDAH-T presentan significativamente mejor CVRS que TDAH-N en la dimensión escolar, pero no se diferencian significativamente en otras dimensiones del KIDSCREEN-52. Conclusiones: Sería recomendable que el tratamiento del TDAH integrase modelos terapéuticos multidimensionales que mejoren los síntomas básicos del trastorno y la CVRS

Introduction: The health-related quality of life (HRQoL) questionnaire is important in order to assess the effects of therapeutic intervention. The aim of this study is to analyse HRQoL, comparing cases of attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (ADHD-T), untreated cases (ADHD-N), and controls. Material and methods: The study included a sample of 228 participants between 8 and 14 years old (114 controls, 57 ADHD-T, and 57 ADHD-N). Consecutive sampling was used in ADHD according to DSM-IV criteria (ADHD Rating Scales IV), and random sampling of controls matched by gender and age. The evaluation of HRQoL was made by using KIDSCREEN-52 parent version. Results: The intensity of ADHD symptoms is significantly lower in ADHD-T than in ADHD-N. There is a moderate significant correlation between greater intensity of ADHD symptoms and worse HRQoL. ADHD cases have significantly worse HRQoL than controls on psychic well-being, mood, relationship with parents and friends, school environment, and social acceptance. The cases of ADHD-T have significantly better HRQoL than ADHD-N in the school dimension, but do not differ significantly in other dimensions of KIDSCREEN-52. Conclusions: It would be advisable that the treatment of ADHD integrates multi-dimensional therapeutic models that improve the basic symptoms of the disorder, as well as the HRQoL

Criterion validity and clinical usefulness of Attention Deficit Hyperactivity Disorder Rating Scale IV in attention deficit hyperactivity disorder (ADHD) as a function of method and age / Validez de criterio y utilidad clínica del Attention Deficit Hiperactivity Disorder Rating Scales IV en el Trastorno por Déficit de Atención con Hiperactividad en función del método y la edad

BACKGROUND: The aim of this research is to analyze Attention Deficit Hyperactivity Disorder Rating Scales IV (ADHD RS-IV) criteria validity and its clinical usefulness for the assessment of Attention Deficit Hyperactivity Disorder (ADHD) as a function of assessment method and age. METHODOLOGY: A sample was obtained from an epidemiological study (n = 1095, 6-16 years). Clinical cases of ADHD (ADHD-CL) were selected by dimensional ADHD RS-IV and later by clinical interview (DSM-IV). ADHD-CL cases were compared with four categorical results of ADHD RS-IV provided by parents (CATPA), teachers (CATPR), either parents or teachers (CATPAOPR) and both parents and teachers (CATPA&PR). Criterion validity and clinical usefulness of the answer modalities to ADHD RS-IV were studied. RESULTS: ADHD-CL rate was 6.9% in childhood, 6.2% in preadolescence and 6.9% in adolescence. Alternative methods to the clinical interview led to increased numbers of ADHD cases in all age groups analyzed, in the following sequence: CATPAOPR> CATPRO> CATPA> CATPA&PR> ADHD-CL. CATPA&PR was the procedure with the greatest validity, specificity and clinical usefulness in all three age groups, particularly in the childhood. CONCLUSIONS: Isolated use of ADHD RS-IV leads to an increase in ADHD cases compared to clinical interview, and varies depending on the procedure used

ANTECEDENTES: se estudia la validez de criterio y utilidad clínica del Attention Deficit Hiperactivity Disorder Rating Scales IV (ADHD RS-IV) en el Trastorno por Déficit de Atención con Hiperactividad (TDAH) en función del método y edad. MÉTODO: muestra extraída de un estudio epidemiológico (n = 1095, 6-16 años). Los casos de TDAH clínico (TDAH-CL) fueron seleccionados mediante ADHD RS-IV dimensional y entrevista clínica (DSM-IV) y fueron comparados con cuatro modalidades categoriales de respuesta al ADHD RS-IV implementado por padres (CATPA), profesores (CATPR), padres o profesores indistintamente (CATPAOPR) y/o conjuntamente (CATPAYPR). Se estudió la validez de criterio y utilidad clínica de las modalidades de respuesta. RESULTADOS: la tasa de TDAHCL es 6,9% en infancia, 6,2% en preadolescencia y 6,9% en adolescencia. Los procedimientos alternativos a la entrevista clínica aumentan los casos de TDAH en los tres grupos de edad, siguiendo la sucesión CATPAOPR > CATPRO > CATPA > CATPAYPR > TDAH-CL. El procedimiento con mayor índice de validez, especifidad, utilidad clínica y capacidad predictiva de TDAH fue CATPAYPR. CONCLUSIONES: la utilización de una versión categorial del ADHD RS-IV produce un incremento de casos de TDAH respecto a la entrevista clínica que varía en función del método utilizado

Poliartritis y glomerulonefritis membranoproliferativa como manifestaciones paraneoplásicas de linfoma de Hodgkin: presentación de un caso y revisión de literatura / Polyarthritis and membranoproliferative glomerulonephritis as paraneoplastic manifestation of Hodgkin's lymphoma: a case report and literature review

Los síndromes paraneoplásicos pueden presentarse de múltiples maneras, dentro de las cuales destacan las manifestaciones endocrinológicas, reumatológicas, hematológicas y nefrológicas. Si bien la mayoría de las publicaciones describen los tumores sólidos como responsables de dichos cuadros, las neoplasias hematológicas son causa importante a considerar como parte del diagnóstico diferencial. Se presenta el caso de un varón de 46 años con un cuadro de poliartritis simétrica seronegativa de grandes y pequeñas articulaciones, asociado a glomerulonefritis membranoproliferativa con depósitos de inmunocomplejos y deterioro agudo de la función renal, como parte de un síndrome paraneoplásico secundario a un linfoma de Hodgkin clásico con invasión medular, el cual revirtió completamente con el tratamiento de quimioterapia (AU)

Paraneoplastic syndromes can be presented in multiple ways, which include endocrinological, hematologic, rheumatologic and nephrologic manifestations. While most of the publications described solid tumors as responsible for these manifestations, hematologic neoplasms are important cause to consider as part of the differential diagnosis. We report the case of a 46 year-old man with seronegative symmetric polyarthritis of large and small joints associated with membranoproliferative glomerulonephritis with deposits of immune complexes and acute impairment of renal function, as part of a paraneoplastic syndrome secondary of a classical Hodgkin lymphoma with bone marrow invasion, which reversed completely with chemotherapy treatment (AU)

Prevalencia del trastorno negativista desafiante en España / Prevalence of oppositional defiant disorder in Spain

Introducción: El trastorno negativista desafiante (TND) se caracteriza por un patrón de comportamiento negativista, desafiante, desobediente y hostil, dirigido a las figuras de autoridad. El TND es uno de los motivos más frecuentes de consulta clínica en salud mental durante la infancia y adolescencia. Presenta gran morbilidad y disfuncionalidad, mostrando repercusiones futuras si no es tratado de forma temprana. Objetivo: Determinar la tasa de prevalencia de TND en escolares de 6-16 años de Castilla y León (España). Material y métodos: Estudio epidemiológico poblacional, con diseño muestral polietápico estratificado, proporcional y por conglomerados. Muestra analizada: 1.049 sujetos. Casos definidos según criterios DSM-IV. Resultados: La prevalencia de TND es 5,6% (IC 95%: 4,2-7%). Prevalencia género masculino = 6,8%; femenino = 4,3%. Prevalencia educación secundaria = 6,2%; educación primaria = 5,3%. No existen diferencias significativas en función del sexo, edad, tipo de centro, ni por zona sociodemográfica. La prevalencia de TND sin considerar deterioro funcional aumentaría al 7,4%. Los casos de TND presentan significativamente peores resultados académicos (resultados académicos globales, lectura, matemáticas y expresión escrita) y peor conducta en clase (relación con compañeros, respeto a las normas, destrezas de organización, realización de tareas académicas e interrupción de la clase). Conclusiones: Castilla y León presenta una tasa de prevalencia de TND levemente superior a la observada en publicaciones internacionales. En función de su distribución por edad, morbilidad y repercusión clínica disfuncional, parece necesaria una planificación sanitaria que incida en un diagnóstico temprano e intervención preventiva (AU)

Introduction: Oppositional defiant disorder (ODD) is characterized by a pattern of negative, defiant, disobedient and hostile behavior toward authority figures. ODD is one of the most frequent reasons for clinical consultation on mental health during childhood and adolescence. ODD has a high morbidity and dysfunction, and has important implications for the future if not treated early. Objective: To determine the prevalence of ODD in schoolchildren aged 6-16 years in Castile and Leon (Spain). Material and methods: Population study with a stratified multistage sample, and a proportional cluster design. Sample analyzed: 1,049. Cases were defined according to DSM-IV criteria. Results: An overall prevalence rate of 5.6% was found (95% CI: 4.2%---7%). Male gender prevalence = 6.8%; female = 4.3%. Prevalence in secondary education = 6.2%; primary education = 5.3%. No significant differences by gender, age, grade, type of school, or demographic area were found. ODD prevalence without considering functional impairment, such as is performed in some research, would increase the prevalence to 7.4%. ODD cases have significantly worse academic outcomes (overall academic performance, reading, maths and writing), and worse classroom behavior (relationship with peers, respect for rules, organizational skills, academic tasks, and disruption of the class). Conclusions: Castile and Leon has a prevalence rate of ODD slightly higher to that observed in international publications. Depending on the distribution by age, morbidity and clinical dysfunctional impact, an early diagnosis and a preventive intervention are required for health planning (AU)