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1.
J Clin Oncol ; : JCO1900456, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513482

RESUMO

PURPOSE: Off-label use of vemurafenib (VMF) to treat BRAFV600E mutation-positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated. PATIENTS AND METHODS: Fifty-four patients from 12 countries took VMF 20 mg/kg/d. They were classified according to risk organ involvement: liver, spleen, and/or blood cytopenia. The main evaluation criteria were adverse events (Common Terminology Criteria for Adverse Events [version 4.3]) and therapeutic responses according to Disease Activity Score. RESULTS: LCH extent was distributed as follows: 44 with positive and 10 with negative risk organ involvement. Median age at diagnosis was 0.9 years (range, 0.1 to 6.5 years). Median age at VMF initiation was 1.8 years (range, 0.18 to 14 years), with a median follow-up of 22 months (range, 4.3 to 57 months), whereas median treatment duration was 13.9 months (for 855 patient-months). At 8 weeks, 38 complete responses and 16 partial responses had been achieved, with the median Disease Activity Score decreasing from 7 at diagnosis to 0 (P < .001). Skin rash, the most frequent adverse event, affected 74% of patients. No secondary skin cancer was observed. Therapeutic plasma VMF concentrations (range, 10 to 20 mg/L) seemed to be safe and effective. VMF discontinuation for 30 patients led to 24 LCH reactivations. The blood BRAFV600E allele load, assessed as circulating cell-free DNA, decreased after starting VMF but remained positive (median, 3.6% at diagnosis, and 1.6% during VMF treatment; P < .001) and was associated with a higher risk of reactivation at VMF discontinuation. None of the various empirical therapies (hematopoietic stem-cell transplantation, cladribine and cytarabine, anti-MEK agent, vinblastine, etc) used for maintenance could eradicate the BRAFV600E clone. CONCLUSION: VMF seemed safe and effective in children with refractory BRAFV600E-positive LCH. Additional studies are needed to find effective maintenance therapy approaches.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31274239

RESUMO

AIM: No previous study has investigated interventions for homeless youth suffering from first episode psychosis and comorbid substance use disorder (HYPS). An intensive assertive community intervention team (IACIT) offering outreach interventions, housing support as well as integrated care for early psychosis and substance use disorder (SUD) was created in 2012 at the Centre Hospitalier de l'Université de Montréal (CHUM). To explore the impact of the addition of an IACIT to an early intervention for psychosis service (EIS) on housing stability, functional and symptomatic outcomes and mental health service use. METHODS: A two-year longitudinal study comparing the outcome of HYPS receiving combined EIS and IACIT since 2012, to a historical cohort of HYPS receiving EIS only between 2005 and 2011. Socio-demographic data, housing stability, functioning, illness severity, SUD severity, emergency room visits and hospitalizations were assessed at admission, at 1 month, and every 3 months thereafter. RESULTS: HYPS receiving EIS + IACIT achieved housing stability more rapidly and spent less time hospitalized than HYPS getting EIS only (RR 2.38, P = .017). HYPS with cocaine misuse were less likely to attain housing stability (RR 0.25, P = .04). No between-group differences were found for psychiatric symptoms, functioning and SUD outcomes. CONCLUSION: The addition of IACIT-HYPS to EIS was associated with earlier housing stability and reduced total hospitalization days compared to EIS alone.

4.
Can J Neurol Sci ; 46(3): 275-279, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30932801

RESUMO

ABSTRACTAmong healthy volunteers in psychiatric brain functional magnetic resonance imaging (fMRI) research studies, the prevalence of incidentalomas can be as high as 34%, of which 10% show clinical significance. An incidentaloma is a lesion found by coincidence without clinical symptoms or suspicion. Like lesions and other types of accidental findings, it is found in healthy individuals recruited to take part in psychiatric studies. The prevalence of these accidental findings among specific psychiatric populations remains unknown. However, a precise understanding of cerebral neuroanatomy, neuroradiological expertise, and an appropriate choice of fMRI exploration sequences will increase the sensitivity of identifying these accidental findings and enable researchers to address their clinical relevance and nature. We present recommendations on how to appropriately inform patients or participants of the accidental findings. Additionally, we propose specific suggestions pertaining to the clinical research setting aimed for investigators and psychiatrists. Unlike current articles pertaining to incidentaloma, the current report provides a distinct focus on psychiatric issues and specific recommendations for studies involving psychiatric patients.

5.
Am J Geriatr Psychiatry ; 27(5): 548-558, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30527274

RESUMO

OBJECTIVE: Major depressive disorder (MDD) is a prevalent condition in older adults. Although antidepressant drugs are commonly prescribed, efficacy is variable, and older patients are more prone to side effects. Repetitive transcranial magnetic stimulation (rTMS) is an alternative therapy used increasingly in the treatment of MDD. Even though recent studies have shown efficacy of rTMS in elderly depressed patients, the safety and efficacy of accelerated rTMS has not been studied in this population. METHODS: Data were retrospectively analyzed for adults with treatment-resistant depression (N = 73, n = 19 ≥60years, n = 54 <60 years) who underwent an accelerated protocol of 30 sessions (2 sessions per day) of left dorsolateral prefrontal cortex high-frequency (20 Hz) rTMS. RESULTS: There were statistically significant improvements in depression and anxiety symptoms from baseline to post-treatment in both age groups, but those 60years and older showed statistically greater improvement in depression and anxiety symptom scores (p = 0.01) than those less than 60. There were significantly more responders (p = 0.001) and remitters (p = 0.023) in the older group. The age groups did not differ significantly in clinical and demographic characteristics or severity of current depressive episode, although baseline anxiety was less severe in those 60years and older. Unipolar and bipolar patients had a similar clinical response, and treatment appeared to be well tolerated by all patients. CONCLUSION: Our results suggest that accelerated rTMS protocol is a safe and effective treatment for unipolar and bipolar depressed subjects, including older adults.

6.
Br J Haematol ; 183(4): 608-617, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30421536

RESUMO

Neurodegenerative (ND) complications in Langerhans cell histiocytosis (LCH) are a late-onset but dramatic sequelae for which incidence and risk factors are not well defined. Based on a national prospective registry of paediatric LCH patients, we determined the incidence rate of clinical ND LCH (cND-LCH) and analysed risk factors, taking into account disease extent and molecular characteristics. Among 1897 LCH patients, 36 (1·9%) were diagnosed with a cND-LCH. The 10-year cumulative incidence of cND-LCH was 4·1%. cND-LCH typically affected patients previously treated for a multisystem, risk organ-negative LCH, represented in 69·4% of cND-LCH cases. Pituitary gland, skin and base skull/orbit bone lesions were more frequent (P < 0·001) in cND-LCH patients compared to those without cND-LCH (respectively 86·1% vs. 12·2%, 75·0% vs. 34·2%, and 63·9% vs. 28·4%). The 'cND susceptible patients' (n = 671) i.e., children who had experienced LCH disease with pituitary or skull base or orbit bone involvement, had a 10-year cND risk of 7·8% vs. 0% for patients who did not meet these criteria. Finally, BRAFV 600E status added important information among these cND susceptible patients, with the 10-year cND risk of 33·1% if a BRAFV 600E mutation was present compared to 2·9% if it was absent (P = 0·002).

8.
J ECT ; 34(4): 283-290, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29870432

RESUMO

BACKGROUND: Treatment-resistant depression (TRD) is a serious chronic condition disabling patients functionally and cognitively. Chronic vagus nerve stimulation (VNS) is recognized for the management of TRD, but few studies have examined its long-term effects on cognitive dysfunction in unipolar and bipolar resistant depression. OBJECTIVE: The purpose of this study was to assess the course of cognitive functions and clinical symptoms in a cohort of patients treated with VNS for TRD. METHODS: In 14 TRD patients with VNS, standardized clinical and neuropsychological measures covering memory, attention/executive functions, and psychomotor speed were analyzed prestimulation and up to 2 years poststimulation. RESULTS: Vagus nerve stimulation patients significantly improved on cognitive and clinical measures. Learning and memory improved rapidly after 1 month of stimulation, and other cognitive functions improved gradually over time. Cognitive improvements were sustained up to 2 years of treatment. At 1 month, improvement in Montgomery-Åsberg Depression Rating Scale scores was not correlated with changes in any of the cognitive scores, whereas at 12 months, the change in Montgomery-Åsberg Depression Rating Scale score was significantly correlated with several measures (Stroop interference, verbal fluency, and Rey-Osterrieth Complex Figure delayed recall). CONCLUSIONS: In recent years, a growing interest in cognitive dysfunction in depression has emerged. Our results suggest that chronic VNS produces sustained clinical and cognitive improvements in TRD patients, with some mental functions improving as soon as 1 month after the initiation of the VNS therapy. Vagus nerve stimulation seems a very promising adjunctive therapy for TRD patients with cognitive impairment.

9.
Br J Haematol ; 178(3): 457-467, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28444728

RESUMO

The BRAFV600E mutation is reported in half of patients with Langerhans cell histiocytosis (LCH). This study investigated the detection of the BRAFV600E allele in circulating cell-free (ccf) DNA in a paediatric LCH cohort. Children with BRAFV600E -mutated LCH were investigated to detect ccf BRAFV600E at diagnosis (n = 48) and during follow-up (n = 17) using a picolitre-droplet digital PCR assay. At diagnosis, ccf BRAFV600E was positive in 15/15 (100%) patients with risk-organ positive multisystem (RO+ MS) LCH, 5/12 (42%) of patients with RO- MS LCH and 3/21 (14%) patients with single-system (SS) LCH (P < 0·001, Fisher's exact test). The positive BRAFV600E load was higher for RO+ patients (mean, 2·90%; range, 0·04-11·4%) than for RO- patients (mean, 0·16%; range, 0·01-0·39) (P = 0·003, Mann-Whitney U test). After first-line vinblastine-steroid induction therapy, 7/7 (100%) of the non-responders remained positive for ccf BRAFV600E compared to 2/4 (50%) of the partial-responders and 0/4 of the complete responders (P = 0·002, Fisher's exact test). Six children treated with vemurafenib showed a clinical response that was associated with a decrease in the ccf BRAFV600E load at day 15. Thus, ccf BRAFV600E is a promising biomarker for monitoring the response to therapy for children with RO+ MS LCH or RO- LCH resistant to first-line chemotherapy.


Assuntos
Histiocitose de Células de Langerhans/diagnóstico , Proteínas Proto-Oncogênicas B-raf/sangue , Adolescente , Alelos , Biomarcadores/sangue , Sistema Livre de Células/metabolismo , Criança , Pré-Escolar , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/genética , Humanos , Indóis/uso terapêutico , Lactente , Masculino , Mutação , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/uso terapêutico , Vemurafenib , Vimblastina/uso terapêutico
11.
J Clin Oncol ; 34(25): 3023-30, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27382093

RESUMO

PURPOSE: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia with a broad spectrum of clinical manifestations and outcomes in children. The somatic BRAF(V600E) mutation occurs frequently, but clinical significance remains to be determined. PATIENTS AND METHODS: BRAF(V600E) mutation was investigated in a French LCH cohort. We analyzed associations between mutation status and clinical presentation, extent of disease, reactivation rate, response to therapy, and long-term permanent sequelae. RESULTS: Among 315 patients with successfully determined BRAF status, 173 (54.6%) carried a BRAF(V600E) mutation. Patients with BRAF(V600E) manifested more severe disease than did those with wild-type BRAF. Patients with BRAF(V600E) comprised 87.8% of patients (43 of 49) with multisystem LCH with risk organ involvement (liver, spleen, hematology), 68.6% of patients (35 of 51) with multisystem LCH without risk organ involvement, 43.9% of patients (86 of 196) with single-system LCH, and 42.1% of patients (8 of 19) with lung-involved LCH (P < .001). BRAF(V600E) mutation was also associated with organ involvement that could lead to permanent, irreversible damage, such as neurologic (75%) and pituitary (72.9%) injuries. Compared with patients with wild-type BRAF, patients with BRAF(V600E) more commonly displayed resistance to combined vinblastine and corticosteroid therapy (21.9% v 3.3%; P = .001), showed a higher reactivation rate (5-year reactivation rate, 42.8% v 28.1%; P = .006), and had more permanent, long-term consequences from disease or treatment (27.9% v 12.6%; P = .001). CONCLUSION: In children with LCH, BRAF(V600E) mutation was associated with high-risk features, permanent injury, and poor short-term response to chemotherapy. Further population-based studies should be undertaken to confirm our observations and to assess the impact of BRAF inhibitors for this subgroup of patients who may benefit from targeted therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Corticosteroides/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Criança , Pré-Escolar , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos , Feminino , França/epidemiologia , Histiocitose de Células de Langerhans/enzimologia , Histiocitose de Células de Langerhans/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sistema de Registros , Vimblastina/administração & dosagem
12.
Br J Haematol ; 174(6): 887-98, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27273725

RESUMO

The French national cohort of children with Langerhans cell histiocytosis (LCH) has included 1478 patients since it was established in 1983. LCH therapeutic strategies substantially changed in 1998, so we have divided the cohort into two 15-year periods. Starting in 1998, therapy duration increased from 6 to 12 months, repeated induction therapy was performed in cases showing a poor response to the first induction with vinblastine and steroids, and refractory disease in a risk organ (RO+) was treated with cladribine and cytarabine. A total of 483 (33%) patients were enrolled before 1998, and 995 (67%) after 1998. Five-year survival was 96·6% (95% confidence interval: 95·4-97·5%) overall, improving from 92% pre-1998 to 99% post-1998 (P < 0·001 adjusted to disease extent). This change was supported by an increase in 5-year survival from 60% to 92% in the RO+ group. Survival was particularly associated with cladribine and cytarabine among refractory RO+ patients. Disease reactivation was slightly less frequent after 1998, due to better enrolment of single-system patients, extended therapy duration, and more efficient second-line therapy. The crude rates of endocrine and neurological sequelae (the most frequent sequelae) appeared to improve over time, but this difference was not observed when the analysis was stratified by disease extent.


Assuntos
Histiocitose de Células de Langerhans/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , França/epidemiologia , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/mortalidade , Histiocitose de Células de Langerhans/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Vigilância da População , Padrão de Cuidado , Análise de Sobrevida , Resultado do Tratamento
13.
J Neurophysiol ; 112(10): 2505-28, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25143539

RESUMO

We tested the hypothesis that the same spinal interneuronal pathways are activated by the reticulospinal system during locomotion and reaching. If such were the case, we expected that microstimulation within the pontomedullary reticular formation (PMRF) would evoke qualitatively similar responses in muscles active during both behaviors. To test this, we stimulated in 47 sites within the PMRF during both tasks. Stimulation during locomotion always produced a strongly phase-dependent, bilateral pattern of activity in which activity in muscles was generally facilitated or suppressed during one phase of activity (swing or stance) and was unaffected in the other. During reaching, stimulation generally activated the same muscles as during locomotion, although the modulation of the magnitude of the evoked responses was less limb dependent than during locomotion. An exception was found for some forelimb flexor muscles that were strongly facilitated by stimulation during the swing phase of locomotion but were not influenced by stimulation during the transport phase of the reach. We suggest that during locomotion the activity in interneuronal pathways mediating signals from the reticulospinal system is subject to strong modulation by the central pattern generator for locomotion. During reach, we suggest that, for most muscles, the same spinal interneuronal pathways are used to modify muscle activity but are not as strongly gated according to limb use as during locomotion. Finally, we propose that the command for movement during discrete voluntary movements suppresses the influence of the reticulospinal system on selected forelimb flexor muscles, possibly to enhance fractionated control of movement.


Assuntos
Atividade Motora/fisiologia , Formação Reticular/fisiologia , Medula Espinal/fisiologia , Caminhada/fisiologia , Animais , Gatos , Geradores de Padrão Central/fisiologia , Estimulação Elétrica/métodos , Eletrodos Implantados , Eletromiografia , Membro Anterior/fisiologia , Membro Posterior/fisiologia , Masculino , Músculo Esquelético/fisiologia , Vias Neurais/fisiologia
14.
J Child Health Care ; 18(4): 369-77, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23939722

RESUMO

This qualitative study examines what contributes to the development of personal identity among refugee adolescents of African origin who have immigrated to Québec. For this purpose, 12 adolescents participated in individual interviews and in self-recorded interviews. The research findings show that the development of young people's personal identity is directly and indirectly influenced by personal characteristics, the environmental, and the interpersonal relationships. We identify both elements that facilitate the development of personal identity and obstacles to such development so as to provide better support for health education among refugee adolescents.


Assuntos
Desenvolvimento da Personalidade , Psicologia do Adolescente , Refugiados/psicologia , Autoimagem , Aculturação , Adolescente , Desenvolvimento do Adolescente , Feminino , Humanos , Relações Interpessoais , Masculino , Pesquisa Qualitativa , Quebeque
15.
Rech Soins Infirm ; (112): 26-35, 2013 Mar.
Artigo em Francês | MEDLINE | ID: mdl-23671984

RESUMO

INTRODUCTION: There has been remarkable growth in research on adolescents in the last decade, particularly in nursing science. OBJECTIVE: The goal of this article is to produce a synthesis of findings justifying the use of qualitative methods in collecting data from adolescents. METHOD: A literature review identified relevant articles (N : 27) from digital databases. FINDINGS: While the studies done on adolescents were on different topics, the data collection methods were often similar. Most of the studies used more than one technique to reconcile scientific rigour and the way the adolescents expressed themselves. In order to understand a phenomenon, its context and the meaning given to the experience proved essential. CONCLUSION: In qualitative research on adolescents, it is important to use data collection methods that make it possible to clearly target the experience explored and to orient and guide the individual in deepening that experience in order to favour the emergence of his or her point of view. Data collection methods based on written communication have to be complemented with other methods more focused on oral communication so as to draw out interpretations reflecting adolescents' points of view as accurately as possible.


Assuntos
Psiquiatria do Adolescente , Coleta de Dados/métodos , Pesquisa Qualitativa , Adolescente , Humanos
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