Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
1.
JAMA Neurol ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33900360

RESUMO

Importance: Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and prevent relapse. Objective: To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the treatment of patients with active IIH. Design, Setting, and Participants: This 5-year randomized clinical trial (Idiopathic Intracranial Hypertension Weight Trial) enrolled women with active IIH and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or higher at 5 National Health Service hospitals in the UK between March 1, 2014, and May 25, 2017. Of 74 women assessed for eligibility, 6 did not meet study criteria and 2 declined to participate; 66 women were randomized. Data were analyzed from November 1, 2018, to May 14, 2020. Interventions: Bariatric surgery (n = 33) or CWM intervention (Weight Watchers) (n = 33). Main Outcomes and Measures: The primary outcome was change in intracranial pressure measured by lumbar puncture opening pressure at 12 months, as assessed in an intention-to-treat analysis. Secondary outcomes included lumbar puncture opening pressure at 24 months as well as visual acuity, contrast sensitivity, perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey) at 12 and 24 months. Because the difference in continuous outcomes between groups is presented, the null effect was at 0. Results: Of the 66 female participants (mean [SD] age, 32.0 [7.8] years), 64 (97.0%) remained in the clinical trial at 12 months and 54 women (81.8%) were included in the primary outcome analysis. Intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -6.0 [1.8] cm cerebrospinal fluid [CSF]; 95% CI, -9.5 to -2.4 cm CSF; P = .001) and at 24 months (adjusted mean [SE] difference, -8.2 [2.0] cm CSF; 95% CI, -12.2 to -4.2 cm CSF; P < .001) compared with the CWM arm. In the per protocol analysis, intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -7.2 [1.8] cm CSF; 95% CI, -10.6 to -3.7 cm CSF; P < .001) and at 24 months (adjusted mean [SE] difference, -8.7 [2.0] cm CSF; 95% CI, -12.7 to -4.8 cm CSF; P < .001). Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -21.4 [5.4] kg; 95% CI, -32.1 to -10.7 kg; P < .001) and at 24 months (adjusted mean [SE] difference, -26.6 [5.6] kg; 95% CI, -37.5 to -15.7 kg; P < .001). Quality of life was significantly improved at 12 months (adjusted mean [SE] difference, 7.3 [3.6]; 95% CI, 0.2-14.4; P = .04) and 24 months (adjusted mean [SE] difference, 10.4 [3.8]; 95% CI, 3.0-17.9; P = .006) in the bariatric surgery arm. Conclusions and Relevance: In this randomized clinical trial, bariatric surgery was superior to a CWM intervention in lowering intracranial pressure. The continued improvement over the course of 2 years shows the impact of this intervention with regard to sustained disease remission. Trial Registration: ClinicalTrials.gov Identifier: NCT02124486.

2.
Brain Commun ; 2(1): fcz050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32954315

RESUMO

Treatment options for idiopathic intracranial hypertension are limited. The enzyme 11ß-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11ß-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18-55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: -2.8, 95% confidence interval: -7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: -4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: -0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11ß-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11ß-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest.

3.
ANZ J Surg ; 90(7-8): 1396-1401, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32564498

RESUMO

BACKGROUND: Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is well validated in the staging of pre-treatment head and neck squamous cell carcinoma (HNSCC), although the impact of human papilloma virus (HPV) status and node size on accuracy remains unclear. The aim of this study was to assess the diagnostic accuracy of PET/CT based on HPV status and node size and determine the effects of maximum standardized uptake value thresholds on sensitivity, specificity and positive predictive value. METHODS: A total of 38 patients with primary HNSCC were recruited. All patients underwent primary tumour resection and cervical node dissection following FDG-PET/CT. RESULTS: A total of 38 patients including 68 dissected necks, representing 353 nodal levels and a total of 2701 lymph nodes were included. Histopathological analysis revealed lymph node metastases in 4.3% (116/2701) of dissected lymph nodes. Forty-four percent of patients had HPV-positive tumours. Sixty-four percent of involved lymph nodes were <1 cm. The sensitivity and specificity for HPV-positive nodes were 67.2% and 99.3% versus 35.6% and 98.2% in HPV-negative nodes, respectively (P < 0.001). Mean maximum standardized uptake value in HPV-positive nodes was 6.3 versus 3.5 in HPV-negative nodes (P < 0.001). Sensitivity and specificity were 30.7% and 99.2% in <1 cm nodes versus 90.2% and 84.8% in ≥1 cm nodes, respectively (P < 0.001). CONCLUSION: FDG-PET/CT has significantly higher diagnostic accuracy in determining nodal metastases in HPV-positive HNSCC versus HPV-negative disease. Accuracy was lower in <1 versus ≥1 cm nodes.

4.
Eur J Endocrinol ; 181(5): R185-R197, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31416048

RESUMO

Visual dysfunction is an important element in the morbidity encountered in patients with pituitary adenoma leading to functional impairment and compromised quality of life. It consists of many parameters (even in the absence of reported symptomatology) as a result of tumour growth in proximity to structures critical for vision (anterior visual pathway, cranial nerves within cavernous sinuses), and as an adverse consequence of therapeutic interventions. Adenoma resection leads to high rates of visual improvement and possibly continues beyond a year post surgery, but the exact timing of maximum effect requires elucidation. Retinal nerve fibre layer measurement may be a reliable, objective parameter predicting favourable visual outcomes, although its prognostic value when pathological, needs to be confirmed. For compromised vision after pituitary apoplexy, early surgical decompression remains usual practice until evidence-based guidance becomes available. The risk of radiation-induced visual toxicity is mainly influenced by total and per fraction dose of radiation and treatment modality. Careful selection of cases and of radiotherapy technique/planning are of major importance in minimising this risk. Dopamine agonists lead to visual recovery in a considerable number of prolactinoma patients. Visual morbidity should be considered a vital indicator in the metrics of quality of service/care in pituitary disease making regular, full ophthalmic examination an essential component of modern management of pituitary pathology at all time points of patient pathway. Well-designed studies minimising effects of bias and using tools and scoring systems reliably reflecting visual status will provide robust evidence on valid prognostication and patient stratification guiding clinical decision making.


Assuntos
Adenoma/complicações , Adenoma/epidemiologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/epidemiologia , Transtornos da Visão/epidemiologia , Transtornos da Visão/etiologia , Humanos , Planejamento de Assistência ao Paciente , Transtornos da Visão/patologia
5.
BMJ Open ; 7(9): e017426, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28963303

RESUMO

INTRODUCTION: Effective treatments are lacking for idiopathic intracranial hypertension (IIH), a condition characterised by raised intracranial pressure (ICP) and papilloedema, and found primarily in obese women. Weight loss and lowering body mass index (BMI) have been shown to lower ICP and improve symptoms in IIH; however, weight loss is typically not maintained, meaning IIH symptoms return. The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) will assess whether bariatric surgery is an effective long-term treatment for patients with IIH with a BMI over 35 kg/m2. The National Institute for Health and Care Excellence recommends bariatric surgery in people with a BMI over 35 kg/m2 and a qualifying comorbidity; currently IIH does not qualify as a comorbidity. METHODS AND ANALYSIS: IIH:WT is a multicentre, open-label, randomised controlled clinical trial of 64 participants with active IIH and a BMI over 35 kg/m2. Participants will be randomised in a 1:1 ratio to bariatric surgery or a dietary weight loss programme and followed up for 5 years. The primary outcome measure is ICP at 12 months. Secondary outcome measures include ICP at 24 and 60 months, and IIH symptoms, visual function, papilloedema, headache, quality of life and cost-effectiveness at 12, 24 and 60 months. TRIAL REGISTRATION NUMBER: IIH:WT is registered as ISRCTN40152829 and on ClinicalTrials.gov as NCT02124486 and is in the pre-results stage.


Assuntos
Cirurgia Bariátrica , Índice de Massa Corporal , Obesidade/terapia , Pseudotumor Cerebral/complicações , Programas de Redução de Peso , Peso Corporal , Análise Custo-Benefício , Feminino , Humanos , Modelos Lineares , Pseudotumor Cerebral/fisiopatologia , Qualidade de Vida , Projetos de Pesquisa , Resultado do Tratamento , Reino Unido , Perda de Peso
6.
Pract Neurol ; 14(6): 380-90, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24809339

RESUMO

Adult patients who present with papilloedema and symptoms of raised intracranial pressure need urgent multidisciplinary assessment including neuroimaging, to exclude life-threatening causes. Where there is no apparent underlying cause for the raised intracranial pressure, patients are considered to have idiopathic intracranial hypertension (IIH). The incidence of IIH is increasing in line with the global epidemic of obesity. There are controversial issues in its diagnosis and management. This paper gives a practical approach to assessing patients with papilloedema, its investigation and the subsequent management of patients with IIH.


Assuntos
Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/terapia , Humanos , Papiledema/diagnóstico , Papiledema/etiologia , Pseudotumor Cerebral/complicações
8.
J Appl Res Intellect Disabil ; 26(1): 14-25, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23255375

RESUMO

BACKGROUND: Creative use of legislation can produce positive change in the lives of people with intellectual disabilities. This may be 'bottom-up' or 'top-down' or at multiple levels and with multiple stakeholders. METHOD: Using a human rights-based approach (HRBA), four initiatives to improve services for people with intellectual disabilities in the UK are described. RESULTS: The first example explains the process of co-producing a DVD and board game to enable people with intellectual disabilities to understand their human rights. The second example considers the impact of organizational culture in the process of embedding a pilot evaluation of practical, human rights-based risk assessment and management tools. A third pilot project examines how the guiding principles of Mental Health Act (MHA) (2007) for England and Wales can be operationalized using an HRBA. Finally, improving equitable access to health care through a 'top-down' process of change involving the Green Light Toolkit is reported. CONCLUSION: The authors consider how to approach the process and where to focus in the system, to realize meaningful change.


Assuntos
Política de Saúde , Direitos Humanos/legislação & jurisprudência , Deficiência Intelectual , Serviços de Saúde Mental/organização & administração , Participação do Paciente , Medicina Estatal/organização & administração , Adulto , Atitude do Pessoal de Saúde , Internação Compulsória de Doente Mental/legislação & jurisprudência , Internação Compulsória de Doente Mental/normas , Inglaterra , Jogos Experimentais , Acesso aos Serviços de Saúde/organização & administração , Acesso aos Serviços de Saúde/normas , Humanos , Serviços de Saúde Mental/legislação & jurisprudência , Serviços de Saúde Mental/normas , Cultura Organizacional , Inovação Organizacional , Educação de Pacientes como Assunto/métodos , Projetos Piloto , Gestão de Riscos/organização & administração , Medicina Estatal/legislação & jurisprudência , Medicina Estatal/normas , País de Gales
10.
N Z Med J ; 123(1323): 58-74, 2010 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-20930913

RESUMO

AIMS: The aim of this project was to employ interdepartmental and cross district health board collaboration to reach a regional consensus on the management of patients who may benefit from carotid endarterectomy. METHODS: All regional stroke physicians, neurologists, and vascular surgeons met to review relevant literature and local audits and to discuss best management strategies suited to the region. RESULTS: A consensus statement was agreed upon and is presented here along with a summary of the supporting scientific evidence. DISCUSSION: Regional interdisciplinary collaboration proved an effective way to reach a carotid endarterectomy management consensus across a wider geographical area that is served by a single vascular surgery department. This approach could serve as a model for other regional initiatives.


Assuntos
Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/normas , Acidente Vascular Cerebral/prevenção & controle , Anticoagulantes/uso terapêutico , Ponte de Artéria Coronária , Diagnóstico por Imagem , Feminino , Humanos , Masculino , Nova Zelândia , Seleção de Pacientes , Complicações Pós-Operatórias/prevenção & controle
12.
J Neuroophthalmol ; 25(2): 113-5, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15937434

RESUMO

A 68-year-old woman with chronic lymphocytic leukemia (CLL) had acute optic neuropathy associated with cerebrospinal fluid evidence of meningeal spread of CLL. There was no evidence of a hematologic relapse. After undergoing four weekly doses of intrathecal methotrexate, vision improved dramatically and spinal fluid became normal. Four years later, she has near normal vision in the affected eye and remains in hematologic remission. This is the first reported case of successful treatment of optic neuropathy in CLL with intrathecal methotrexate alone.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Metotrexato/uso terapêutico , Neoplasias do Nervo Óptico/tratamento farmacológico , Acuidade Visual/fisiologia , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Feminino , Humanos , Injeções Espinhais , Leucemia Linfocítica Crônica de Células B/fisiopatologia , Metotrexato/administração & dosagem , Neoplasias do Nervo Óptico/fisiopatologia , Recuperação de Função Fisiológica , Campos Visuais
14.
Am J Ophthalmol ; 135(1): 102-3, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12504711

RESUMO

PURPOSE: We report an unusual paradoxical effect of brimonidine. DESIGN: Observational case report. METHODS: A 70-year-old woman with bilateral normal tension glaucoma was treated with topical brimonidine and followed in an outpatient setting. The main outcome measured was intraocular pressure (IOP) in mm Hg. RESULTS: Brimonidine was observed to cause IOP elevation, confirmed on rechallenge, scoring 8 (strong probability) on an adverse drug reaction probability score. CONCLUSION: Under certain circumstances topical brimonidine can cause paradoxical raised IOP necessitating vigilance in follow-up of patients on topical brimonidine.


Assuntos
Agonistas alfa-Adrenérgicos/efeitos adversos , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/induzido quimicamente , Quinoxalinas/efeitos adversos , Idoso , Tartarato de Brimonidina , Feminino , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos
15.
J Virol ; 76(12): 6083-92, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12021341

RESUMO

Drug-resistant mutants with a methionine-to-valine substitution at position 184 of reverse transcriptase (M184V) emerged within 5 weeks of initiation of therapy in four newborn macaques infected with simian immunodeficiency virus (SIVmac251) and treated with lamivudine (3TC) or emtricitabine [(-)-FTC] (two animals per drug). Thus, this animal model mimics the rapid emergence of M184V mutants of HIV-1 during 3TC therapy of human patients. One animal of each treatment group developed fatal immunodeficiency at 12 weeks of age, which is similar to the rapid disease course seen in most untreated SIVmac251-infected infant macaques. To further evaluate the effect of the M184V mutation on viral fitness and virulence, groups of juvenile macaques were inoculated with the molecular clone SIVmac239 with either the wild-type sequence (group A [n = 5]) or the M184V sequence (SIVmac239-184V; group B [n = 5] and group C [n = 2]). The two SIVmac239-184V-infected animals of group C did not receive any drug treatment, and in both animals the virus population reverted to predominantly wild type (184M) by 8 weeks after inoculation. The other five SIVmac239-184V-infected animals (group B) were treated with (-)-FTC to prevent reversion. Although virus levels 1 week after inoculation were lower in the SIVmac239-184V-infected macaques than in the SIVmac239-infected animals, no significant differences were observed from week 2 onwards. Two animals in each group developed AIDS and were euthanized, while all other animals were clinically stable at 46 weeks of infection. These data demonstrate that the M184V mutation in SIV conferred a slightly reduced fitness but did not affect disease outcome.


Assuntos
Desoxicitidina/análogos & derivados , Mutação , DNA Polimerase Dirigida por RNA/genética , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Vírus da Imunodeficiência Símia/fisiologia , Vírus da Imunodeficiência Símia/patogenicidade , Animais , Animais Recém-Nascidos , Fármacos Anti-HIV/uso terapêutico , Desoxicitidina/uso terapêutico , Farmacorresistência Viral , Emtricitabina , Lamivudina/uso terapêutico , Macaca mulatta , Inibidores da Transcriptase Reversa/uso terapêutico , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/enzimologia , Vírus da Imunodeficiência Símia/genética , Virulência , Replicação Viral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...