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1.
Aliment Pharmacol Ther ; 60(5): 604-612, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38943230

RESUMO

BACKGROUND: Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies. METHODS: We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy. RESULTS: From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants. CONCLUSIONS: Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent.


Assuntos
Colite Ulcerativa , Imunossupressores , Proctite , Sistema de Registros , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Proctite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Estudos Prospectivos
2.
Dig Liver Dis ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38839456

RESUMO

BACKGROUND: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context. METHODS: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment. RESULTS: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab. CONCLUSION: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles.

3.
Pharmaceutics ; 16(5)2024 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-38794292

RESUMO

Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.

4.
Dig Dis ; 42(3): 257-264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38452742

RESUMO

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.


Assuntos
Doenças Inflamatórias Intestinais , Pancreatite , Sistema de Registros , Humanos , Feminino , Pancreatite/induzido quimicamente , Pancreatite/genética , Masculino , Adulto , Estudos de Casos e Controles , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Pessoa de Meia-Idade , Predisposição Genética para Doença , Fatores de Risco , Variação Genética , Mercaptopurina/efeitos adversos , Mercaptopurina/uso terapêutico
5.
An Pediatr (Engl Ed) ; 100(2): 87-96, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38246835

RESUMO

INTRODUCTION: The aim of the study was to describe the neuropsychological profile of patients with attention deficit hyperactivity disorder (ADHD) and the impact of the disorder on executive functioning and academic performance. PATIENTS AND METHODS: We conducted a retrospective observational and analytical study. The sample consisted of 24 children with a diagnosis of ADHD (aged 6-15 years) without pharmacological treatment and 24 controls without ADHD (aged 7-15 years). A comprehensive neuropsychological evaluation was carried out, encompassing major cognitive domains, in addition to assessment of executive functioning and psychopathological symptoms through the administration of questionnaires to parents and teachers. RESULTS: The cognitive profile of the ADHD group was characterized by overall scores (including executive functions and academic abilities) in the normal range (z scores between -1 and 1), although significantly lower compared to the control group. Over half of the patients with ADHD (58%) had associated specific learning disorders. Furthermore, teachers tended to report executive function difficulties more frequently in male students. CONCLUSIONS: In the study sample, the group of patients with ADHD exhibited cognitive performance within the normal range, although with lower scores compared to controls. Behavioural rating scales provide valuable information about functioning outside the clinic, but may yield biased results on account of the focus on externalising symptoms. The neuropsychological evaluation is a useful tool that can facilitate the diagnosis of ADHD and an effective response to the needs and characteristics of patients and families.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Criança , Humanos , Masculino , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Função Executiva , Testes Neuropsicológicos , Estudos Retrospectivos , Inquéritos e Questionários , Adolescente , Feminino
6.
Interdisciplinaria ; 28(1): 73-91, jul. 2011.
Artigo em Espanhol | LILACS | ID: lil-633482

RESUMO

La ecolocación es una habilidad que usaría inconscientemente la mayoría de las personas. Resulta crucial para la movilidad independiente de la persona ciega e implica utilizar sonidos autoproducidos y sus reflexiones para localizar y reconocer objetos que no se ven. Dos nuevos paradigmas han enriquecido el estudio de esta sorprendente habilidad: el del acoplamiento sensoriomotor y el de la sustitución sensorial. El primero sostiene que los sistemas perceptivo y motor constituyen procesos acoplados que requieren un insoslayable tratamiento unificado. El segundo considera que es posible ver con los oídos o con la piel en virtud de la plasticidad cerebral. En esta segunda parte se presenta la temática en el contexto teórico de la cognición corporizada y de recientes avances en neurociencias; se desarrollan además los estudios realizados en el tercer período. En esta revisión se reflejan cambios paradigmáticos en las ciencias del comportamiento y el valor científico acrecentado de la ecolocación humana.


Echolocation is an ability that can be used daily by human beings, even without being conscious of it. It turns out to be crucial to the efficient independent mobility of the blind person, an aspect that is severely affected by blindness. It implies using the information that emerges from self-produced sounds and their reflexions in order to locate and recognize unseen objects. According to the new cognitive and ecological paradigms in perception, it is believed that the primary function of the auditory system is to determinate, i.e., to localize and recognize, the characteristics of the sound source through the sounds emitted by it. Within this context, it has been very recently argued that echolocation (i.e., the ability to locate and recognize biologically relevant secondary sound sources through the information contained in the direct-reflected couple) is a variant of that general process of primary sound sources determination. Two recently established scientific paradigms have specially enriched the study of this amazing ability: the sensorimotor contingency theory and the sensory substitution perspective. The first approach claims that the perceptual and motor systems are coupling processes that demand a thoroughly unified treatment. The second approach considers that, for example, vision loss does not mean loss of the ability to see since it is possible to see with the ears or the skin. The central idea is that the information usually captured by vision may instead be captured by touch or audition, on account of brain plasticity. In this way, in echolocation (which represents a kind of 'seeing with the ears' natural sensory substitution system that is part of the human endowment) action consists of the exploratory activity that the subject carries out through self-generation of sounds and head and/or cane movements while sensation refers to certain tonal or spatial percepts related to the presence and characteristics of the objects that the subject (implicitly) learns to perceive probably as auditory Gestalts. In the first part of this article the main theoretical aspects and a revision of the studies throughout two of the three delimited periods were developed: FIRST APPROACHES (1700 - 1935) and SIENTIFIC STUDY OF HUMAN ECHOLOCATION (1940 -1980). The questions that researchers formulated during these periods were firstly concerned with discovering if blind persons actually possessed this ability, which of the sense organs was involved and which sensory stimulation was its necessary and sufficient condition. Secondly, they inquired into the scopes of echolocation and its possible underlying psychoacoustic mechanisms. The thorough investigations carried out allowed to unequivocally establishing that audition is the sensory basis of this ability and that changes in pitch are its necessary and sufficient condition. It was also demonstrated that not only blind subjects but also appropriately trained sighted subjects were able to precisely localize and recognize the characteristics of the experimental objects. In this second part, we present the object of study within the context of theories of embodied cognition and recent developments in the field of the neurosciences; we also elaborate upon studies carried out during the third period, named RECENT STUDIES, that extends from 1990 to present days. We show how the blind person with good echolocation ability becomes an excellent experimental model to study behavioral and neurophysiological aspects involved in implicit learning. The article illustrates the paradigm shifts that occurred in recent scientific history through the study of this particular human ability that, within the mentioned recent theoretical context, has acquired a renewed interest.

7.
Interdisciplinaria ; 27(2): 335-348, dic. 2010.
Artigo em Espanhol | LILACS | ID: lil-633475

RESUMO

La ecolocación humana es una habilidad genuina, inexplorada y vinculada con la localización de sonidos reflejados, que resulta crucial en la movilidad independiente de la persona ciega. Se inscribe en el área poco estudiada de la audición cotidiana de sonidos no verbales e implica autoproducir sonidos para obtener información (reflexiones) a fin de localizar y reconocer objetos que no se ven. Se presenta una revisión histórica de estudios realizados sobre la temática, que refleja cambios paradigmáticos del devenir científico. Las conceptualizaciones históricas de la ecolocación resultan ejemplificadoras: al comienzo se la consideraba como un fenómeno paranormal mientras que en la actualidad, se la trata como una habilidad utilizada inconscientemente por la mayoría de las personas. En esta primera parte se exponen aspectos teóricos relevantes y los estudios realizados en dos de los tres períodos en que se ha dividido esta revisión histórica. El tercer período se presenta en la segunda parte de este artículo.


Echolocation is a genuinely human though greatly unexploited ability that is closely related to the localization of reflected sounds. It is part of the scarcely studied and promising field of the percept-cognitive processes involved in everyday audition of non-verbal sounds. It implies self-producing sounds (original or direct signal) with the specific purpose of obtaining auditory information (reflected signal) to detect, locate and recognize unseen objects. This ability turns out to be crucial to the blind person's independent mobility, an aspect that is severely affected by blindness. We present an historical revision of the main studies that have been carried out on this particular phenomenon, describing the paradigm changes that occurred in scientific history. The historical conceptualizations of echolocation are specially revealing: while it was initially considered a paranormal phenomenon, a kind of sixth sense, now it is treated as an ability that could be unconsciously used by most of us. In this first part of this paper we present relevant theoretical aspects and the studies carried out during two of the three periods this historical revision has been divided in: (a) First approaches (1700 - 1935) and (b) Scientific study of human echolocation (decades from 40s to 80s). The third period, named recent studies, is developed in the second part of this article. The questions that were initially asked were concerned the explanation of which of the sense organs was involved and which sensory stimulation was the necessary and sufficient condition for this ability. Some researchers and many blind persons were inclined to look for the answer in the sense of touch, from stimuli such as differences in pressure, air currents or differences in temperature upon the skin of the face; this originated the name of facial vision with which echolocation is also known. During the 40s a vast and rigorous research program was put forward in order to elucidate the sensory basis of echolocation. Experimental subjects (blind and blindfolded sighted participants) that took part of the program had to walk through a corridor and halt at the moment they perceived the presence of an obstacle (mobile panel); then they kept on walking approaching the obstacle as near as possible without making contact (first perception and final appraisal, respectively). A series of ingenious tests was designed in which tactile or auditory input was artificially suppressed, one at a time. None of the subjects was able to perceive the object in the case of auditory input suppression. To confirm this finding, other tests were conducted in extreme conditions: for example, the subject was in another room using a telephone communication device and he / she had to perform the same task but this time it was the experimenter that walked across the corridor instead of him / her. The performance was not significantly affected in this extreme condition. In this way, it was unequivocally established that audition is the sensory basis of this particular kind of ability and that changes in pitch are its necessary and sufficient condition. Later studies inquired into the discriminatory power of echolocation and its scopes. It was demonstrated that, on the one hand, blind subjects and appropriately trained blindfolded sighted subjects were able to accurately judge the position, distance, size, material and shape of the objects. On the other hand, for the first time, research about the spontaneous generation of sounds by blind persons was carried out. It was observed that they used clicks or vocalizations to detect presence /absence of the object and continuous sibilant sounds to perceive its borders. Their performance was not significantly affected when they used artificial sounds that mimicked their own or sound signals that they had described as not preferred. Around the end of the second period the underlying psychoacoustic mechanisms were studied and two auditory fusion phenomena were postulated: repetition pitch and the precedence effect.

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