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1.
Clin Med (Lond) ; 19(3): 201-204, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092511

RESUMO

The use of regular infusions of immunoglobulin is well established as a treatment for patients with antibody deficiency and for patients requiring immunomodulation. Although efficacy is believed to be equivalent for the different immunoglobulin products, it is generally regarded as best practice not to switch from one product to another unless there is a clinical reason to change. Changes in commissioning guidance and issues with the supply of some immunoglobulin products to the UK resulted in a requirement for a significant number of patients to switch between immunoglobulin products in 2017-2018. Data from the 2018 UK Primary Immunodeficiency census has been used to evaluate the clinical results of switching. Results from 30 immunology centres reported a total of 802 immunoglobulin product switches. Twelve reactions were recorded, none of which required admission to hospital, one patient was treated with oral corticosteroids, the others required either no treatment or treatment with oral antihistamines. This review of immunoglobulin product switch reactions gives a clearer indication regarding the safety of product switching than has previously been published.

2.
Artigo em Inglês | MEDLINE | ID: mdl-30170123

RESUMO

BACKGROUND: Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to nuclear factor κB, c-Jun N-terminal kinase, and mechanistic target of rapamycin complex 1. Germline CARD11 mutations cause several distinct primary immune disorders in human subjects, including severe combined immune deficiency (biallelic null mutations), B-cell expansion with nuclear factor κB and T-cell anergy (heterozygous, gain-of-function mutations), and severe atopic disease (loss-of-function, heterozygous, dominant interfering mutations), which has focused attention on CARD11 mutations discovered by using whole-exome sequencing. OBJECTIVES: We sought to determine the molecular actions of an extended allelic series of CARD11 and to characterize the expanding range of clinical phenotypes associated with heterozygous CARD11 loss-of-function alleles. METHODS: Cell transfections and primary T-cell assays were used to evaluate signaling and function of CARD11 variants. RESULTS: Here we report on an expanded cohort of patients harboring novel heterozygous CARD11 mutations that extend beyond atopy to include other immunologic phenotypes not previously associated with CARD11 mutations. In addition to (and sometimes excluding) severe atopy, heterozygous missense and indel mutations in CARD11 presented with immunologic phenotypes similar to those observed in signal transducer and activator of transcription 3 loss of function, dedicator of cytokinesis 8 deficiency, common variable immunodeficiency, neutropenia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome. Pathogenic variants exhibited dominant negative activity and were largely confined to the CARD or coiled-coil domains of the CARD11 protein. CONCLUSION: These results illuminate a broader phenotypic spectrum associated with CARD11 mutations in human subjects and underscore the need for functional studies to demonstrate that rare gene variants encountered in expected and unexpected phenotypes must nonetheless be validated for pathogenic activity.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30127805

RESUMO

Background: Hereditary angioedema (HAE) is a potentially life-threatening, bradykinin-mediated disease, often misdiagnosed and under-treated, with long diagnostic delays. There are limited real-world data on best-practice management of HAE in the UK. Objectives: To characterize the clinical profile, management and outcomes of patients with HAE type I and II from three specialist centres in the UK using data from the Icatibant Outcome Survey (IOS; Shire, Zug, Switzerland), an international observational study monitoring safety and effectiveness of icatibant, a selective bradykinin B2 receptor antagonist. Methods: We performed retrospective analyses of IOS data for patients with HAE type I and II from three centres in the UK and compared UK data with pooled IOS data from 10 countries (48 centres). Results: Analyses included 73 UK and 579 non-UK patients with HAE type I or II. Median diagnostic delay was 6.2 and 5.9 years, respectively. Analysis of data collected from February 2008 to July 2016 included 286 icatibant-treated attacks in 58 UK patients and 2553 icatibant-treated attacks in 436 non-UK patients (median of 3.0 attacks per patient in both groups). More attacks were treated by icatibant self-administration in UK patients (95.8%) than in non-UK patients (86.8%, p < 0.001). Time to icatibant treatment, time to resolution and attack duration were not significantly different in the UK versus non-UK patients. Conclusion: UK patients from the specialist centres studied report similar diagnostic delay and similar icatibant treatment outcomes to their non-UK counterparts. However, improvements in the timely diagnosis of HAE are still required.Trial registration ClinicalTrials.gov NCT01034969.

4.
J Clin Immunol ; 38(2): 204-213, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29423883

RESUMO

BACKGROUND: Immunologists are increasingly being asked to assess patients with non-classical and secondary antibody deficiency to determine their potential need for immunoglobulin replacement therapy (IGRT). Immunoglobulin is a limited, expensive resource and no clear guidance exists for this broad patient group. The purpose of this survey is to establish what factors influence the decision to commence IGRT in adult patients, when diagnostic criteria for primary antibody deficiency are not fulfilled. METHODS: Under the auspices of the United Kingdom Primary Immunodeficiency Network (UKPIN), a study group was established which circulated an online questionnaire to the consultant body across the UK and Ireland. Results provided a snapshot of the current clinical practice of 71% of consultant immunologists, from 30 centers. RESULTS: In order of importance, factors which influence the decision to commence IGRT include number of hospital admissions with infection, serum IgG level, bronchiectasis, radiologically proven pneumonia, number of positive sputum cultures, number of antibiotic courses, and results of immunization studies. The commonest test vaccine used was Pneumovax 23 with measurement of serotype-specific responses at 4 weeks, with a threshold of 0.35 µg/ml in 2/3 of serotypes measured. Eighty-six percent of patients are treated with a trial of prophylactic antibiotics prior to consideration of IGRT. Efficacy of IGRT trial is assessed at between 6 and 12 months. CONCLUSIONS: There was consistency in clinical practice using a combination of clinical history, evidence of infections, and vaccination testing for diagnosis. However, there was some variation in the implementation of this practice, particularly in vaccine choice and assessment of response to vaccination.

5.
J Clin Pathol ; 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29305517

RESUMO

AIM: To record the level of allergy teaching occurring in UK medical schools. The UK has experienced an 'allergy epidemic' during the last 3-4 decades. Previous government reviews have emphasised the importance of allergy education and training, treating common allergies in primary care with referral pathways to a specialist and the creation of regional networks. It is acknowledged that the delivery of allergy teaching in UK medical schools is variable, despite the well-recognised need. METHODS: All consultant members of the British Society for Allergy and Clinical Immunology involved in teaching medical students were invited to partake in qualitative research, employing an online questionnaire for data collection. Participants were asked to comment on the format of the allergy teaching delivered, the student participation and the clinical opportunities provided. Students were recruited to complete a similar survey as supporting evidence. RESULTS: 44 responses were collected, representing 64.7% of medical schools in the UK. Clinical allergy placements were compulsory in 31.8% of medical schools that responded. In 36.4%, it was reported that less than 10% of students had an opportunity to take an independent history from a patient with allergic disease, or practise using an epinephrine autoinjector. 90.9% responded that an allergy rotation was not offered to final year students. CONCLUSIONS: Allergy undergraduate teaching is suboptimal and heterogeneous in UK medical schools and there is a real need for standardisation as a means to enhance quality of care.

6.
Eur J Emerg Med ; 20(1): 10-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22976464

RESUMO

Angioedema is characterized by localized swelling of subcutaneous tissues or mucosa of the upper respiratory or gastrointestinal tract. Laryngeal involvement may threaten airway patency and can be fatal if not addressed promptly. There are several distinct subtypes of angioedema, caused by different pathological processes involving a range of proinflammatory mediators. In the emergency department, it is essential not only that acute angioedema is identified as quickly as possible but also that the likely working diagnosis is established so that the most effective treatment may be administered to resolve potentially life-threatening swelling. In this paper, we present an overview of the various types of angioedema, and offer a practical diagnostic and therapeutic approach to their management.


Assuntos
Angioedema/diagnóstico , Angioedema/terapia , Doença Aguda , Obstrução das Vias Respiratórias/etiologia , Algoritmos , Angioedema/complicações , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bradicinina/farmacologia , Degranulação Celular , Serviço Hospitalar de Emergência , Humanos , Doenças da Laringe/complicações , Mastócitos/imunologia , Mastócitos/fisiologia , Vasodilatadores/farmacologia
7.
BMC Res Notes ; 5: 103, 2012 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-22340023

RESUMO

BACKGROUND: Currently in the United Kingdom (UK), there is a mismatch between limited financial resources and the large proportion of patients with suspected allergies actually being referred to specialist allergy clinics. To better understand the case mix of patients being referred, we audited referrals to a regional allergy service over an 8 year period.The main source of data was consultant letters to General Practitioners (GP) summarising the diagnosis of patients, archived from January 2002 to September 2009. Letters were reviewed, extracting the clinic date, doctor seen, gender, date of birth, postcode, GP, and diagnoses. Diagnoses were classified into seven groups and illustrative cases for each group noted. FINDINGS: Data from 2,028 new referrals with suspected allergy were analysed. The largest group of patients (43%) were diagnosed with a type I hypersensitivity. The other diagnostic groups were chronic idiopathic (spontaneous) urticaria (35%), suspected type I hypersensitivity but no allergen identified (8%), idiopathic (spontaneous) angioedema (8%), physical urticaria (2.5%), non-allergic symptoms (1.6%), type IV hypersensitivity (0.8%) and ACE inhibitor sensitivity (0.5%). Two thirds of patients seen were female with a higher percentage of female patients in the non type-I hypersensitivity group (71%) than the type 1 hypersensitivity (66%) (χ2 = 5.1, 1df, p = 0.024). The type 1 hypersensitivity patients were younger than other patients (38 Vs 46 years, t = -10.8, p < 0.001) CONCLUSIONS: This study highlights the complexity of specialist allergy practice and the large proportion of patients referred with non-type I hypersensitivities, chronic idiopathic (spontaneous) urticaria being by far the largest group. Such information is critical to inform commissioning decisions, define referral pathways and in primary care education.


Assuntos
Angioedema/diagnóstico , Grupos Diagnósticos Relacionados , Hipersensibilidade Imediata/diagnóstico , Urticária/diagnóstico , Alérgenos/análise , Alérgenos/imunologia , Instituições de Assistência Ambulatorial/organização & administração , Angioedema/tratamento farmacológico , Angioedema/imunologia , Antialérgicos/uso terapêutico , Auditoria Clínica , Feminino , Humanos , Hipersensibilidade Imediata/tratamento farmacológico , Hipersensibilidade Imediata/imunologia , Masculino , Atenção Primária à Saúde/organização & administração , Encaminhamento e Consulta/tendências , Fatores Sexuais , Reino Unido , Urticária/tratamento farmacológico , Urticária/imunologia
8.
Eur J Emerg Med ; 19(4): 271-4, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22008588

RESUMO

Patients with hereditary angioedema may present to the emergency department (ED) with subcutaneous and submucosal swellings, the most important being the development of laryngeal oedema, which can rapidly obstruct the airways and cause death. The aim of this study was to establish whether local guidelines exist for the management of such patients and to determine where the C1 inhibitor concentrate (C1 INHC) was kept in the trusts. A questionnaire survey of the availability and use of C1 INHC was sent to 35 EDs across the UK with established immunology services within their trusts. A hundred percent response was received. Thirty-three trusts had a supply of the drug C1 INHC in varying quantities. Nineteen trusts had it in their ED. Only 17 departments had any guidance with regard to their use. There is a significant lack of guidance for C1 INHC use in the EDs surveyed. A guideline was developed as a result that can be used by EDs across Europe.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Complemento C1s/antagonistas & inibidores , Serviço Hospitalar de Emergência , Guias de Prática Clínica como Assunto , Algoritmos , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/imunologia , Complemento C4/antagonistas & inibidores , Pesquisas sobre Serviços de Saúde , Humanos , Reino Unido
9.
Medicine (Baltimore) ; 89(6): 403-25, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21057262

RESUMO

Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 patients with MyD88 deficiency, from 37 kindreds in 15 countries.The clinical features of IRAK-4 and MyD88 deficiency were indistinguishable. There were no severe viral, parasitic, and fungal diseases, and the range of bacterial infections was narrow. Noninvasive bacterial infections occurred in 52 patients, with a high incidence of infections of the upper respiratory tract and the skin, mostly caused by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. The leading threat was invasive pneumococcal disease, documented in 41 patients (68%) and causing 72 documented invasive infections (52.2%). P. aeruginosa and Staph. aureus documented invasive infections also occurred (16.7% and 16%, respectively, in 13 and 13 patients, respectively). Systemic signs of inflammation were usually weak or delayed. The first invasive infection occurred before the age of 2 years in 53 (88.3%) and in the neonatal period in 19 (32.7%) patients. Multiple or recurrent invasive infections were observed in most survivors (n = 36/50, 72%).Clinical outcome was poor, with 24 deaths, in 10 cases during the first invasive episode and in 16 cases of invasive pneumococcal disease. However, no death and invasive infectious disease were reported in patients after the age of 8 years and 14 years, respectively. Antibiotic prophylaxis (n = 34), antipneumococcal vaccination (n = 31), and/or IgG infusion (n = 19), when instituted, had a beneficial impact on patients until the teenage years, with no seemingly detectable impact thereafter.IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation. Patients and families should be informed of the risk of developing life-threatening infections; empiric antibacterial treatment and immediate medical consultation are strongly recommended in cases of suspected infection or moderate fever. Prophylactic measures in childhood are beneficial, until spontaneous improvement occurs in adolescence.


Assuntos
Quinases Associadas a Receptores de Interleucina-1/deficiência , Fator 88 de Diferenciação Mieloide/deficiência , Adolescente , Antibacterianos/uso terapêutico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/prevenção & controle , Criança , Pré-Escolar , Suscetibilidade a Doenças , Feminino , Humanos , Imunidade , Lactente , Quinases Associadas a Receptores de Interleucina-1/genética , Masculino , Mutação , Fator 88 de Diferenciação Mieloide/genética , Receptores de Interleucina-1/metabolismo , Receptores Toll-Like/metabolismo
10.
Allergy Asthma Clin Immunol ; 6(1): 22, 2010 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-20667125

RESUMO

Hereditary angioedema (C1 inhibitor deficiency, HAE) is associated with intermittent swellings which are disabling and may be fatal. Effective treatments are available and these are most useful when given early in the course of the swelling. The requirement to attend a medical facility for parenteral treatment results in delays. Home therapy offers the possibility of earlier treatment and better symptom control, enabling patients to live more healthy, productive lives. This paper examines the evidence for patient-controlled home treatment of acute attacks ('self or assisted administration') and suggests a framework for patients and physicians interested in participating in home or self-administration programmes. It represents the opinion of the authors who have a wide range of expert experience in the management of HAE.

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