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1.
Front Psychol ; 14: 1229596, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37780169

RESUMEN

Getting 'stuck', literally and figuratively, is a common experience for autistic people. Literally 'stuck' means exhibiting limited response initiation due to immobility with tense muscles and inability to move. Figuratively 'stuck' means loneliness, passivity or captivity in activities that do not offer long-term satisfaction. To further conceptualize this complex phenomenon of limited response initiation in autistic individuals, we performed qualitative interviews and focus groups with autistic people and their family members, followed by brainstorm sessions and a Delphi study with input from a larger panel of experts from multiple backgrounds. We aimed to co-create the outline of an integrative approach to support autistic people in moving away from this 'stuck state' to more flexible, limber 'supple states' in order to live freer, more meaningful, satisfying and peaceful lives. Over time, in interaction with all participants, our shared insight grew. Based on this, we here stipulate a conceptual framework, in which the described 'stuck state' at the micro-level of the muscles/behavior of one individual, probably is caused by feeling/being 'stuck' or 'cramped' at several overarching (i.e., meso and macro) levels. For instance, stuck in relationships with unhealthy dynamics, stuck at home creating short-term calm, trance-like states (e.g., gaming), stuck at an educational level that might fit the individuals' current social-emotional state rather than their potential cognitive level, stuck in a job that pays the bills but does not feel meaningful, nor contributes to a satisfying life with opportunities for personal development. Stuck in a mental/public health care system where ever ongoing changes in policies hinder sustained support to suit care-needs. Stuck in a regulated societal system making it likely to repeatedly get stuck. Is this phenomenon specific to autism? Formally we have only conducted interviews with this population, but in another smaller, related project we also spoke to people from the general population with careers that are considered successful in the general society. These people actually voiced similar experiences. Therefore, we hypothesize that this numbing state of being or feeling 'stuck' may be a prevalent phenomenon that needs to be addressed. In this article, we discuss several types of interventive approaches (i.e., language-based talking therapies, affective experiential expressive therapies, physical therapies and systemic therapies), prevention as well as intervention programs, directed at different primary stakeholders, that can complement and enrich each other in an integrative policy, that leads to tailor-made, personalized trajectories of interdisciplinary support to enable people to live satisfying, meaningful, dignified and peaceful lives.

2.
J Am Soc Nephrol ; 32(9): 2362-2374, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34155059

RESUMEN

BACKGROUND: Renal involvement in ANCA-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. METHODS: In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value. RESULTS: We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. CONCLUSIONS: Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Arteritis/complicaciones , Arteritis/diagnóstico , Fallo Renal Crónico/epidemiología , Arteria Renal , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Arteritis/mortalidad , Supervivencia sin Enfermedad , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
3.
Eur Child Adolesc Psychiatry ; 30(8): 1263-1271, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32839872

RESUMEN

Antipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term treatment with antipsychotic drugs in this young population. We analysed a combined prospective and a retrospective observational cohort of Dutch children and adolescents, starting with risperidone, aripiprazole or pipamperone treatment. Linear mixed models were used to test whether sex, age, baseline body-mass-index (BMI) z score, type of antipsychotic, dose equivalent/kg, duration of use, previous antipsychotic use, ethnicity, physical exercise, IQ, concomitant medication, and psychiatric classification predicted the BMI z score for a follow-up of < 15 weeks, 15-52 weeks or > 52 weeks. A total of 144 patients were included with a median [interquartile range ([IQR)] age of 9 (4) years and median follow-up of 30 (73) weeks. During the complete follow-up, the median (IQR) weight gain was 0.37 (0.95) BMI z score points. Antipsychotic-induced weight gain was found to be most pronounced during the first 15 weeks of use (BMI z score increase per week ß = 0.02, 95% CI 0.01-0.03, p = 0.002). A higher baseline BMI z score and the absence of stimulant use were associated with a higher BMI z score during the entire follow-up and after 15 weeks, respectively. Previous treatment with an antipsychotic drug was associated with less weight gain during the first 15 weeks of treatment. Our findings underscore the importance of close patient monitoring during the first weeks of antipsychotic treatment with a focus on patients with a high baseline BMI z score.


Asunto(s)
Antipsicóticos , Adolescente , Antipsicóticos/efectos adversos , Índice de Masa Corporal , Niño , Humanos , Masculino , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Aumento de Peso/efectos de los fármacos
4.
Br J Clin Pharmacol ; 87(3): 1069-1081, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32643213

RESUMEN

AIM: Risperidone is the most commonly prescribed antipsychotic drug to children and adolescents worldwide, but it is associated with serious side effects, including weight gain. This study assessed the relationship of risperidone and 9-hydroxyrisperidone trough concentrations, maximum concentrations and 24-hour area under the curves (AUCs) with body mass index (BMI) z-scores in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side effects and effectiveness. METHODS: Forty-two children and adolescents (32 males) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side effects and effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including medication adherence and CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were measured. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 205 risperidone and 205 9-hydroxyrisperidone concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-hour AUCs were analysed to predict outcomes using generalized and linear mixed-effects models. RESULTS: A risperidone two-compartment model combined with a 9-hydroxyrisperidone one-compartment model best described the measured concentrations. Of all the pharmacokinetic parameters, higher risperidone sum trough concentrations best predicted higher BMI z-scores during follow-up (P < .001). Higher sum trough concentrations also predicted more sedation (P < .05), higher prolactin levels (P < .001) and more effectiveness measured with Aberrant Behavior Checklist irritability score (P < .01). CONCLUSION: Our results indicate a therapeutic window exists, which suggests that therapeutic drug monitoring of risperidone might increase safety and effectiveness in children and adolescents with ASD and behavioural problems.


Asunto(s)
Antipsicóticos , Trastorno del Espectro Autista , Adolescente , Antipsicóticos/efectos adversos , Trastorno del Espectro Autista/tratamiento farmacológico , Niño , Citocromo P-450 CYP2D6/genética , Humanos , Masculino , Palmitato de Paliperidona/efectos adversos , Risperidona/efectos adversos
5.
Clin J Am Soc Nephrol ; 15(8): 1103-1111, 2020 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-32723805

RESUMEN

BACKGROUND AND OBJECTIVES: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score. RESULTS: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P<0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In the meta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, and high-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study. CONCLUSIONS: The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.


Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Glomerulonefritis/patología , Riñón/patología , Insuficiencia Renal/etiología , Anciano , Biopsia , Progresión de la Enfermedad , Femenino , Glomerulonefritis/clasificación , Glomerulonefritis/complicaciones , Glomerulonefritis/inmunología , Humanos , Riñón/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Insuficiencia Renal/diagnóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo
6.
Clin Pharmacokinet ; 59(11): 1393-1405, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32394297

RESUMEN

BACKGROUND: Pipamperone is a frequently prescribed antipsychotic in children and adolescents in the Netherlands, Belgium, and Germany. However, pediatric pharmacokinetics and the relationship with side effects and efficacy are unknown. Currently, divergent pediatric dosing recommendations exist. OBJECTIVES: The objective of this study was to describe the population pharmacokinetics of pipamperone in children and adolescents; to correlate measured and predicted pipamperone trough concentrations and predicted 24-h area under the curves with effectiveness, extrapyramidal symptoms, and sedation; and to propose dose recommendations based on simulations. METHODS: Pipamperone concentrations were collected from Dutch pediatric patients in a prospective naturalistic trial (n = 8), and German pediatric patients in a therapeutic drug monitoring service (n = 22). A total of 70 pipamperone concentrations were used to develop a population pharmacokinetic model with non-linear mixed-effects modeling (NONMEM®). Additionally, an additional random sample of 21 German patients with 33 pipamperone concentrations from the same therapeutic drug monitoring service was used for external validation. Pharmacokinetic parameters were related to clinical improvement, sedation, and extrapyramidal symptoms. Simulations were performed to determine optimal dosages. RESULTS: In a one-compartment model, the apparent volume of distribution was 416 L/70 kg and the apparent clearance was 22.1 L/h/70 kg. Allometric scaling was used to correct for differences in bodyweight. The model was successfully externally validated. The median [25th-75th percentile] measured pipamperone trough concentrations were numerically higher in responders (98.0 µg/L [56.0-180.5 µg/L]) than in non-responders (58.0 µg/L [14.9-105.5 µg/L]), although non-significant (p = 0.14). A twice-daily 0.6-mg/kg dosage was better than a fixed dosage to attain the concentration range observed in responders. CONCLUSIONS: Our findings suggest that pipamperone therapeutic reference ranges may be lower for children with behavioral problems than recommended for adults with psychotic symptoms (100-400 µg/L). When dosing pipamperone in children and adolescents, bodyweight should be taken into account.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno del Espectro Autista , Butirofenonas/farmacocinética , Adolescente , Trastorno del Espectro Autista/tratamiento farmacológico , Butirofenonas/efectos adversos , Niño , Preescolar , Femenino , Alemania , Humanos , Masculino , Países Bajos , Estudios Prospectivos
7.
Front Immunol ; 10: 1405, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31297110

RESUMEN

Proteinuria has been identified as prognosticator of renal outcome in patients with ANCA-associated glomerulonephritis, but whether proteinuria is related to podocyte abnormalities in these patients is largely unknown. We here investigate podocyte foot process width and number of podocytes positive for the podocyte marker WT-1 in diagnostic renal biopsies of 25 Caucasian patients with ANCA-associated glomerulonephritis in relation to proteinuria. Control tissue was used from pre-transplantation donor kidney biopsies. Proteinuria at 10 weeks follow-up correlated significantly with foot process width (P = 0.04). Biopsies with foot process width ≥600 nm belonged more often to the crescentic or mixed class, whereas biopsies with a foot process width <600 nm were most often categorized as focal class (P = 0.03). The mean number of podocytes based upon expression of WT-1 was significantly lower in patients compared to controls (15 vs. 34 podocytes per glomerulus; P < 0.0001). The significant decrease in expression of the podocyte WT-1 marker in ANCA-associated glomerulonephritis is considered indicative of actual podocyte loss or at least, of a loss of functionality. Furthermore, our study indicates that podocyte foot process width at baseline could be indicative for proteinuria at short term follow up. For prognostic purposes, we therefore suggest to include a description of the foot process width in the diagnostic report of a biopsy with ANCA-associated glomerulonephritis.


Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Podocitos/inmunología , Proteinuria/inmunología , Adulto , Anciano , Biopsia , Estudios de Casos y Controles , Femenino , Glomerulonefritis/patología , Glomerulonefritis/cirugía , Humanos , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Podocitos/patología , Proteinuria/patología , Proteinuria/cirugía
9.
Clin J Am Soc Nephrol ; 13(1): 63-72, 2018 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-29162595

RESUMEN

BACKGROUND AND OBJECTIVES: Large studies on long-term kidney outcome in patients with anti-glomerular basement membrane (anti-GBM) GN are lacking. This study aimed to identify clinical and histopathologic parameters that predict kidney outcome in these patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective analysis included a total of 123 patients with anti-GBM GN between 1986 and 2015 from six centers worldwide. Their kidney biopsy samples were classified according to the histopathologic classification for ANCA-associated GN. Clinical data such as details of treatment were retrieved from clinical records. The primary outcome parameter was the occurrence of ESRD. Kidney survival was analyzed using the log-rank test and Cox regression analyses. RESULTS: The 5-year kidney survival rate was 34%, with an improved rate observed among patients diagnosed after 2007 (P=0.01). In patients with anti-GBM GN, histopathologic class and kidney survival were associated (P<0.001). Only one of 15 patients with a focal class biopsy sample (≥50% normal glomeruli) developed ESRD. Patients with a sclerotic class biopsy sample (≥50% globally sclerotic glomeruli) and patients with 100% cellular crescents did not recover from dialysis dependency at presentation. In multivariable analysis, dialysis dependency at presentation (hazard ratio [HR], 3.17; 95% confidence interval [95% CI], 1.59 to 6.32), percentage of normal glomeruli (HR, 0.97; 95% CI, 0.95 to 0.99), and extent of interstitial infiltrate (HR, 2.02; 95% CI, 1.17 to 3.50) were predictors of ESRD during follow-up. CONCLUSIONS: Dialysis dependency, low percentage of normal glomeruli, and large extent of interstitial infiltrate are associated with poor kidney outcome in anti-GBM GN. Kidney outcome has improved during recent years; the success rate doubled after 2007. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_11_21_CJASNPodcast_18_1_v.mp3.


Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Autoanticuerpos/inmunología , Membrana Basal/inmunología , Glomérulos Renales/inmunología , Adulto , Anciano , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/diagnóstico , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/fisiopatología , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/terapia , Biopsia , Progresión de la Enfermedad , Femenino , Humanos , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/patología , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Glomérulos Renales/patología , Glomérulos Renales/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Adulto Joven
10.
Curr Opin Rheumatol ; 30(1): 44-49, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28957961

RESUMEN

PURPOSE OF REVIEW: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have an increased malignancy risk compared with the general population. This review aims to evaluate recent evidence for changes in the incidence of malignancy in patients with AAV and to examine explanations for the association between AAV and malignancy. RECENT FINDINGS: The overall malignancy risk in patients with AAV has decreased, most likely as a result of recent changes in therapeutic regimen, that is, a decrease in the exposure to cyclophosphamide. The risk of nonmelanoma skin cancer (NMSC), however, remains increased, which is probably attributable to treatment with azathioprine. Malignancy risk in patients with AAV treated with rituximab was found to be lower than in cyclophosphamide-treated patients. The incidence of malignancy prior to AAV is not increased compared with the general population. SUMMARY: Continuing efforts to reduce the exposure to cyclophosphamide have led to a decrease in malignancy risk in patients with AAV, except for NMSC. Rituximab could be a well tolerated alternative for cyclophosphamide regarding the development of malignancies.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Neoplasias/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Azatioprina/uso terapéutico , Ciclofosfamida/uso terapéutico , Humanos , Incidencia , Factores de Riesgo , Rituximab/uso terapéutico , Neoplasias Cutáneas/epidemiología
11.
J Rheumatol ; 44(3): 314-318, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28089971

RESUMEN

OBJECTIVE: Previous studies have reported an increased malignancy risk preceding antineutrophil cytoplasmic antibody-associated vasculitis (AAV), suggesting common pathogenic pathways in these 2 entities. However, the study results were conflicting and often limited to patients with granulomatosis with polyangiitis (GPA). Here, we study the malignancy risk prior to AAV diagnosis [either GPA or microscopic polyangiitis (MPA)] to elaborate on the putative association between malignancy and AAV. METHODS: A total of 203 patients were selected for the current study. Malignancies prior to AAV diagnosis were identified using a nationwide pathology database, and their occurrence was verified by reviewing the medical files of 145 patients (71.4%). The malignancy incidence was compared to the general population by calculation of standardized incidence ratios (SIR), matching for sex, age, and time period. SIR were calculated for 2 intervals: < 2 years and ≥ 2 years prior to AAV diagnosis. Separate analyses were performed for GPA and MPA. RESULTS: The overall risk for malignancy prior to AAV diagnosis was similar to that of the general population (SIR 0.96, 95% CI 0.55-1.57), as was true when risks were analyzed by malignancy type, including skin, bladder, kidney, lung, stomach, rectum, and uterus (SIR ranged from 1.64 to 4.14). We found no significant difference in malignancy risk between patients with GPA and MPA. CONCLUSION: Our findings do not support the hypothesis that preceding malignancies and AAV have a causal relationship or shared pathogenic pathways.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Neoplasias/epidemiología , Adulto , Anciano , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad
12.
Autism ; 21(6): 646-658, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-27940569

RESUMEN

In order to shed more light on why referred girls are less likely to be diagnosed with autism spectrum disorder than boys, this study examined whether behavioral characteristics influence the probability of an autism spectrum disorder diagnosis differently in girls versus boys derived from a multicenter sample of consecutively referred children aged 2.5-10 years. Based on information from the short version of the Developmental, Dimensional and Diagnostic Interview and the Autism Diagnostic Observation Schedule, 130 children (106 boys and 24 girls) received a diagnosis of autism spectrum disorder according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) criteria and 101 children (61 boys and 40 girls) did not. Higher overall levels of parent-reported repetitive and restricted behavior symptoms were less predictive of an autism spectrum disorder diagnosis in girls than in boys (odds ratio interaction = 0.41, 95% confidence interval = 0.18-0.92, p = 0.03). In contrast, higher overall levels of parent-reported emotional and behavioral problems increased the probability of an autism spectrum disorder diagnosis more in girls than in boys (odds ratio interaction = 2.44, 95% confidence interval = 1.13-5.29, p = 0.02). No differences were found between girls and boys in the prediction of an autism spectrum disorder diagnosis by overall autistic impairment, sensory symptoms, and cognitive functioning. These findings provide insight into possible explanations for the assumed underidentification of autism spectrum disorder in girls in the clinic.


Asunto(s)
Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/psicología , Niño , Conducta Infantil/psicología , Preescolar , Cognición , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Probabilidad , Factores Sexuales
13.
Ann Rheum Dis ; 76(6): 1064-1069, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27899372

RESUMEN

OBJECTIVES: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with cyclophosphamide have an increased malignancy risk compared with the general population. We investigated whether treatment with rituximab instead of cyclophosphamide has decreased the malignancy risk in patients with AAV. METHODS: The study included patients with AAV treated at a tertiary vasculitis referral centre between 2000 and 2014. The malignancy incidence in these patients was compared with the incidence in the general population by calculating standardised incidence ratios (SIRs), adjusted for sex, age and calendar year. Malignancy incidence was compared between rituximab-treated and cyclophosphamide-treated patients. RESULTS: Of the 323 included patients, 33 developed a total of 45 malignancies during a mean follow-up of 5.6 years. This represented a 1.89-fold increased (95% CI 1.38 to 2.53) malignancy risk, and a non-significantly increased risk if non-melanoma skin cancer was excluded (SIR, 1.09; 95% CI 0.67 to 1.69). The risk of non-melanoma skin cancer was 4.58-fold increased (95% CI 2.96 to 6.76). Cyclophosphamide-treated patients had an increased malignancy risk compared with the general population (SIR, 3.10; 95% CI 2.06 to 4.48). In contrast, rituximab-treated patients had a malignancy risk similar to the general population (SIR, 0.67; 95% CI 0.08 to 2.43). The malignancy risk in cyclophosphamide-treated patients was 4.61-fold higher (95% CI 1.16 to 39.98) than in rituximab-treated patients. CONCLUSIONS: The malignancy risk in patients with AAV was lower in rituximab-treated patients than in cyclophosphamide-treated patients. Notably, rituximab treatment was not associated with an increased malignancy risk compared with the general population. Rituximab could therefore be a safe alternative to cyclophosphamide in the treatment of AAV.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Ciclofosfamida/uso terapéutico , Neoplasias/epidemiología , Rituximab/uso terapéutico , Adulto , Anciano , Antirreumáticos/administración & dosificación , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Rituximab/administración & dosificación , Neoplasias Cutáneas/epidemiología
14.
Kidney Int Rep ; 2(6): 1018-1031, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29634043

RESUMEN

The 2016 European Vasculitis Society (EUVAS) meeting, held in Leiden, the Netherlands, was centered around phenotypic subtyping in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). There were parallel meetings of the EUVAS petals, which here report on disease assessment; database; and long-term follow-up, registries, genetics, histology, biomarker studies, and clinical trials. Studies currently conducted will improve our ability to discriminate between different forms of vasculitis. In a project that involves the 10-year follow-up of AAV patients, we are working on retrieving data on patient and renal survival, relapse rate, the cumulative incidence of malignancies, and comorbidities. Across Europe, several vasculitis registries were developed covering over 10,000 registered patients. In the near future, these registries will facilitate clinical research in AAV on a scale hitherto unknown. Current studies on the genetic background of AAV will explore the potential prognostic significance of genetic markers and further refine genetic associations with distinct disease subsets. The histopathological classification of ANCA-associated glomerulonephritis is currently evaluated in light of data coming out of a large international validation study. In our continuous search for biomarkers to predict clinical outcome, promising new markers are important subjects of current research. Over the last 2 decades, a host of clinical trials have provided evidence for refinement of therapeutic regimens. We give an overview of clinical trials currently under development, and consider refractory vasculitis in detail. The goal of EUVAS is to stimulate ongoing research in clinical, serological, and histological management and techniques for patients with systemic vasculitis, with an outlook on the applicability for clinical trials.

15.
Nephrol Dial Transplant ; 30 Suppl 1: i31-6, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25805748

RESUMEN

In the early 1990s, an international working group of experienced renal pathologists, the Renal Histology group, set up a scoring system for biopsies with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis. This scoring system subdivided glomerular, interstitial and vascular lesions and served as a tool for the evaluation of all renal biopsies from studies of the European Vasculitis Study Group (EUVAS). Histopathological studies gave new insights into the prediction of renal outcome in patients with ANCA-associated glomerulonephritis. Percentage of normal glomeruli and a selected number of interstitial parameters were reliable predictors of long-term follow-up glomerular filtration rate in all studies. Out of these results, a histopathological classification distinguishing focal, crescentic, mixed and sclerotic classes of ANCA-associated glomerulonephritis was developed. Until today, 13 studies have validated this classification system. Future studies will try to determine if and how renal histology could be helpful in guiding treatment of ANCA-associated glomerulonephritis.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/historia , Anticuerpos Anticitoplasma de Neutrófilos/historia , Glomerulonefritis/historia , Histocitoquímica/historia , Sociedades Médicas/historia , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/clasificación , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Europa (Continente) , Glomerulonefritis/clasificación , Historia del Siglo XX , Historia del Siglo XXI , Humanos
16.
J Autism Dev Disord ; 45(7): 2076-91, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25682078

RESUMEN

The current study aimed to investigate the Autism Diagnostic Interview-Revised (ADI-R) algorithms for toddlers and young preschoolers (Kim and Lord, J Autism Dev Disord 42(1):82-93, 2012) in a non-US sample from ten sites in nine countries (n = 1,104). The construct validity indicated a good fit of the algorithms. The diagnostic validity was lower, with satisfactorily high specificities but moderate sensitivities. Young children with clinical ASD and lower language ability were largely in the mild-to-moderate or moderate-to-severe concern ranges of the ADI-R, nearly half of the older and phrase speech ASD-group fell into the little-to-no concern range. Although broadly the findings support the toddler algorithms, further work is required to understand why they might have different properties in different samples to further inform research and clinical use.


Asunto(s)
Trastorno Autístico/diagnóstico , Entrevista Psicológica , Algoritmos , Preescolar , Femenino , Humanos , Lactante , Lenguaje , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
17.
Res Dev Disabil ; 39: 32-42, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25635383

RESUMEN

In order to understand typical and atypical developmental trajectories it is important to assess how strengths or weaknesses in one domain may be affecting performance in other domains. This study examined longitudinal relations between early fine motor functioning, visuospatial cognition, exploration, and language development in preschool children with ASD and children with other developmental delays/disorders. The ASD group included 63 children at T1 (Mage = 27.10 months, SD = 8.71) and 46 children at T2 (Mage = 45.85 months, SD = 7.16). The DD group consisted of 269 children at T1 (Mage = 17.99 months, SD = 5.59), and 121 children at T2 (Mag e= 43.51 months, SD = 3.81). A subgroup nested within the total sample was randomly selected and studied in-depth on exploratory behavior. This group consisted of 50 children, 21 children with ASD (Mage = 27.57, SD = 7.09) and 29 children with DD (Mage = 24.03 months, SD = 6.42). Fine motor functioning predicted language in both groups. Fine motor functioning was related to visuospatial cognition in both groups and related to object exploration, spatial exploration, and social orientation during exploration only in the ASD group. Visuospatial cognition and all exploration measures were related to both receptive and expressive language in both groups. The findings are in line with the embodied cognition theory, which suggests that cognition emerges from and is grounded in the bodily interactions of an agent with the environment. This study emphasizes the need for researchers and clinicians to consider cognition as emergent from multiple interacting systems.


Asunto(s)
Trastorno Autístico/fisiopatología , Cognición , Discapacidades del Desarrollo/fisiopatología , Conducta Exploratoria , Desarrollo del Lenguaje , Destreza Motora , Procesamiento Espacial , Trastorno Autístico/psicología , Preescolar , Estudios de Cohortes , Discapacidades del Desarrollo/psicología , Femenino , Humanos , Estudios Longitudinales , Masculino , Actividad Motora , Países Bajos , Estudios Prospectivos
18.
Autism ; 19(5): 588-603, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24919961

RESUMEN

In a randomized controlled trial, we evaluated the early intervention program Video-feedback Intervention to promote Positive Parenting adapted to Autism (VIPP-AUTI) with 78 primary caregivers and their child (16-61 months) with Autism Spectrum Disorder. VIPP-AUTI is a brief attachment-based intervention program, focusing on improving parent-child interaction and reducing the child's individual Autism Spectrum Disorder-related symptomatology in five home visits. VIPP-AUTI, as compared with usual care, demonstrated efficacy in reducing parental intrusiveness. Moreover, parents who received VIPP-AUTI showed increased feelings of self-efficacy in child rearing. No significant group differences were found on other aspects of parent-child interaction or on child play behavior. At 3-months follow-up, intervention effects were found on child-initiated joint attention skills, not mediated by intervention effects on parenting. Implementation of VIPP-AUTI in clinical practice is facilitated by the use of a detailed manual and a relatively brief training of interveners.


Asunto(s)
Trastorno Autístico , Retroalimentación Formativa , Relaciones Padres-Hijo , Responsabilidad Parental , Padres/educación , Grabación en Video , Adulto , Atención , Trastorno del Espectro Autista , Preescolar , Intervención Educativa Precoz , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad
19.
Eur Child Adolesc Psychiatry ; 23(11): 1005-21, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24913785

RESUMEN

A large number of studies have reported on the validity of autism spectrum disorder (ASD) screening procedures. An overall understanding of these studies' findings cannot be based solely on the level of internal validity of each, since screening instruments might perform differently according to certain factors in different settings. Europe has led the field with the development of the first screening tool and first prospective screening study of autism. This paper seeks to provide an overview of ASD screening studies and ongoing programmes across Europe, and identify variables that have influenced the outcomes of such studies. Results show that, to date, over 70,000 children have been screened in Europe using 18 different screening procedures. Differences among findings across studies have enabled us to identify ten factors that may influence screening results. Although it is impossible to draw firm conclusions as to which screening procedure is most effective, this analysis might facilitate the choice of a screening method that best fits a specific scenario, and this, in turn, may eventually improve early ASD detection procedures.


Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Tamizaje Masivo/métodos , Niño , Preescolar , Europa (Continente) , Humanos , Lactante , Estudios Prospectivos , Reproducibilidad de los Resultados
20.
Res Dev Disabil ; 35(2): 423-8, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24361810

RESUMEN

The present study examined whether atypical visual processing is related to the level of social skills in children with autism spectrum disorder (ASD). Thirty-eight young children with ASD (29 boys, 9 girls) were included. Atypical visual processing was assessed by coding the number of lateral glances and the amount of object grouping behavior on videotaped observations of the ADOS (aged 35 ± 9 months). The level of social skills was measured using the subscale interpersonal relationships of the Vineland SEEC (32 ± 7 months). A negative relationship with a medium effect size was found between lateral glances and interpersonal relationships. Object grouping behavior and interpersonal relationships were not related. This study suggests that visual perception may be a mechanism in the development of interpersonal relationships in ASD, which is in accordance with an embodied approach to social cognition.


Asunto(s)
Trastorno Autístico/fisiopatología , Trastornos de la Percepción/fisiopatología , Conducta Social , Percepción Visual/fisiología , Trastorno Autístico/psicología , Trastornos Generalizados del Desarrollo Infantil/fisiopatología , Trastornos Generalizados del Desarrollo Infantil/psicología , Preescolar , Femenino , Fijación Ocular , Humanos , Relaciones Interpersonales , Masculino , Trastornos de la Percepción/psicología , Grabación de Cinta de Video
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