RESUMO
BACKGROUND: There is a lack of population-based information on the disease burden and management of alopecia areata (AA). OBJECTIVES: To describe the epidemiology of AA, focusing on incidence, demographics and patterns of healthcare utilization. METHODS: Population-based cohort study of 4·16 million adults and children, using UK electronic primary care records from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, 2009-2018. The incidence and point prevalence of AA were estimated. Variation in AA incidence by age, sex, deprivation, geographical distribution and ethnicity was examined. Patterns of healthcare utilization were evaluated in people with incident AA. RESULTS: The AA incidence rate was 0·26 per 1000 person-years. AA point prevalence in 2018 was 0·58% in adults. AA onset peaked at age 25-29 years for both sexes, although the peak was broader in females. People of nonwhite ethnicity were more likely to present with AA, especially those of Asian ethnicity [incidence rate ratio (IRR) 3·32 (95% confidence interval 3·11-3·55)]. Higher AA incidence was associated with social deprivation [IRR most vs. least deprived quintile 1·47 (1·37-1·59)] and urban living [IRR 1·23 (1·14-1·32)]. People of higher social deprivation were less likely to be referred for specialist dermatology review. CONCLUSIONS: By providing the first large-scale estimates of the incidence and point prevalence of AA, our study helps to understand the burden of AA on the population. Understanding the variation in AA onset between different population groups may give insight into the pathogenesis of AA and its management.
Assuntos
Alopecia em Áreas , Adulto , Alopecia em Áreas/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Atenção Primária à Saúde , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, debilitating, chronic inflammatory skin disease that affects the hands and feet. Clinical, immunological and genetic findings suggest a pathogenic role for interleukin (IL)-1. OBJECTIVES: To determine whether anakinra (an IL-1 receptor antagonist) delivers therapeutic benefit in PPP. METHODS: This was a randomized (1 : 1), double-blind, two-staged, adaptive, UK multicentre, placebo-controlled trial [ISCRTN13127147 (registered 1 August 2016); EudraCT number: 2015-003600-23 (registered 1 April 2016)]. Participants had a diagnosis of PPP (> 6 months) requiring systemic therapy. Treatment was 8 weeks of anakinra or placebo via daily, self-administered subcutaneous injections. Primary outcome was the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at 8 weeks. RESULTS: A total of 374 patients were screened; 64 were enrolled (31 in the anakinra arm and 33 in the placebo arm) with a mean (SD) baseline PPPASI of 17·8 (10·5) and a PPP investigator's global assessment of severe (50%) or moderate (50%). The baseline adjusted mean difference in PPPASI favoured anakinra but did not demonstrate superiority in the intention-to-treat analysis [-1·65, 95% confidence interval (CI) -4·77 to 1·47; P = 0·30]. Similarly, secondary objective measures, including fresh pustule count (2·94, 95% CI -26·44 to 32·33; favouring anakinra), total pustule count (-30·08, 95% CI -83·20 to 23·05; favouring placebo) and patient-reported outcomes, did not show superiority of anakinra. When modelling the impact of adherence, the PPPASI complier average causal effect for an individual who received ≥ 90% of the total treatment (48% in the anakinra group) was -3·80 (95% CI -10·76 to 3·16; P = 0·285). No serious adverse events occurred. CONCLUSIONS: No evidence for the superiority of anakinra was found. IL-1 blockade is not a useful intervention for the treatment of PPP.
Assuntos
Alopecia , Líquen Plano , Alopecia/epidemiologia , Estudos Transversais , Feminino , Fibrose , Humanos , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Hair and scalp problems are common. Unfortunately, many uncertainties exist around the most effective management and treatment strategies for these disorders. OBJECTIVES: To identify uncertainties in hair-loss management, prevention, diagnosis and treatment that are important to both people with hair loss and healthcare professionals. METHODS: A Hair Loss Priority Setting Partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in hair loss. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants; following exclusions 884 uncertainties relating to hair loss (excluding alopecia areata) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that was taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for hair loss (excluding alopecia areata) to guide researchers and funding bodies to support studies important to both patients and clinicians.
Assuntos
Alopecia/terapia , Pesquisa , Alopecia/diagnóstico , Alopecia/prevenção & controle , Consenso , Dermatologia/organização & administração , Pessoal de Saúde , Humanos , Relações Interprofissionais , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Alopecia areata (AA) is a common hair loss disorder that results in patchy to complete hair loss. Many uncertainties exist around the most effective treatments for this condition. OBJECTIVES: To identify uncertainties in AA management and treatment that are important to both service users (people with hair loss, carers and relatives) and healthcare professionals. METHODS: An AA priority setting partnership was established between patients, their carers and relatives, and healthcare professionals to identify the most important uncertainties in AA. The methodology of the James Lind Alliance was followed to ensure a balanced, inclusive and transparent process. RESULTS: In total, 2747 treatment uncertainties were submitted by 912 participants, of which 1012 uncertainties relating to AA (and variants) were analysed. Questions were combined into 'indicative uncertainties' following a structured format. A series of ranking exercises further reduced this list to a top 25 that were taken to a final prioritization workshop where the top 10 priorities were agreed. CONCLUSIONS: We present the top 10 research priorities for AA to guide researchers and funding bodies to support studies important to both patients and clinicians.
Assuntos
Alopecia em Áreas/terapia , Pesquisa , Cuidadores , Prioridades em Saúde , Inquéritos Epidemiológicos , Humanos , Relações Médico-Paciente , Relações Profissional-FamíliaRESUMO
Many emerging studies have implicated the Janus kinase/signal transducer and activator of transcription (JAK-STAT) cytokine signalling mechanism in disease pathogenesis. This signalling pathway is involved in haematopoiesis and immune development. Mutations in genes regulating JAK-STAT signalling can cause common inflammatory disorders and myeloproliferative disorders. JAK and STAT inhibitors are new management tools for disorders such as myelofibrosis and rheumatoid arthritis. Evidence suggests that the cytokine components of the JAK-STAT pathways play a crucial role in common skin disorders, including psoriasis and atopic dermatitis. We present an overview for the clinical dermatologist of the significance of these signalling pathways in various skin disorders, and introduce the potential application of JAK and STAT inhibition as a new therapeutic tool in dermatology.
Assuntos
Janus Quinases/fisiologia , Fatores de Transcrição STAT/fisiologia , Transdução de Sinais/fisiologia , Dermatopatias/fisiopatologia , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Fatores de Transcrição STAT/antagonistas & inibidores , Dermatopatias/tratamento farmacológicoRESUMO
BACKGROUND: Increasing evidence shows attachment security influences symptom expression and adaptation in people diagnosed with schizophrenia and other psychoses. AIMS: To describe the distribution of secure and insecure attachment in a cohort of individuals with first-episode psychosis, and to explore the relationship between attachment security and recovery from positive and negative symptoms in the first 12 months. METHOD: The study was a prospective 12-month cohort study. The role of attachment, duration of untreated psychosis (DUP), baseline symptoms and insight in predicting and mediating recovery from symptoms was investigated using multiple regression analysis and path analysis. RESULTS: Of the 79 participants, 54 completed the Adult Attachment Interview (AAI): 37 (68.5%) were classified as insecure, of which 26 (48.1%) were insecure/dismissing and 11 (20.4%) insecure preoccupied. Both DUP and insight predicted recovery from positive symptoms at 12 months. Attachment security, DUP and insight predicted recovery from negative symptoms at 12 months. CONCLUSIONS: Attachment is an important construct contributing to understanding and development of interventions promoting recovery following first-episode psychosis.
Assuntos
Apego ao Objeto , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Recuperação de Função Fisiológica , Adulto , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Avaliação de Sintomas , Resultado do TratamentoAssuntos
Alopecia em Áreas/tratamento farmacológico , Glucocorticoides/administração & dosagem , Triancinolona Acetonida/administração & dosagem , Administração Cutânea , Ensaios Clínicos Controlados como Assunto , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Injeções Intralesionais , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: This review sought to identify, summarise and critically evaluate studies that investigated attachment amongst individuals with psychosis. METHOD: The following computerised databases searched were CINAHL<1980 to December 2012; EMBASE<1980 to December 2012; Ovid MEDLINE (R)<1980 to December 2012; PsychINFO<1980 to December 2012; and Google Scholar<1980 to December 2012. RESULTS: We identified 22 papers describing 21 studies comprising 1453 participants, with a mean age of 35.0 years (range of 12-71 years), of whom 68.4% (n=994) were male. Of our sample, 1112 (76.5%) had a diagnosis of schizophrenia. We found small to moderate associations between greater attachment insecurity (as reflected in anxiety and avoidance) and poorer engagement with services, more interpersonal problems, more avoidant coping strategies, more negative appraisals of parenting experiences and more severe trauma. We also found small to modest associations between attachment insecurity and more positive and negative symptoms and greater affective symptom problems. CONCLUSION: Attachment theory may be useful as a means of understanding the developmental and interpersonal basis of recovery and adaptation in the context of psychosis. However, further research comprising more representative samples in their first episode and using prospective designs is required.
Assuntos
Apego ao Objeto , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Humanos , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnósticoAssuntos
Adjuvantes Imunológicos/história , Alopecia em Áreas/história , Imunoterapia/história , Adjuvantes Imunológicos/administração & dosagem , Administração Tópica , Alérgenos/administração & dosagem , Alérgenos/história , Alopecia em Áreas/terapia , Haptenos/administração & dosagem , Haptenos/história , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Imunoterapia/métodos , Irritantes/administração & dosagem , Irritantes/históriaRESUMO
Pyoderma gangrenosum (PG) commonly occurs in association with various haematological and inflammatory disorders. We report a new association, a Janus kinase (JAK)2 mutation, in a 63-year-old patient with PG. We hypothesise that PG occurs by direct activation of JAK along with signal transducers and activators of transcription (STAT), a common mechanism involved in the pathogenesis of inflammatory and haematological diseases.
Assuntos
Janus Quinase 2/genética , Mutação , Pioderma Gangrenoso/genética , Humanos , Perna (Membro) , Masculino , Pessoa de Meia-IdadeRESUMO
This review summarizes clinically important findings from 17 systematic reviews and 2 guidelines on skin cancer indexed between April 2008 and April 2009. Melanoma primary-prevention measures, such as education, are more likely to be successful in younger children than adolescents, and general population screening for melanoma by whole-body examination is not currently supported by the evidence. A large systematic review of melanoma and pregnancy concluded that pregnancy does not affect prognosis. Two systematic reviews imply that sunburn later in life also increases the risk of melanoma, and that it is just as important as sunburn early in life. Three systematic reviews discussed the role of positron emission tomography and sentinel lymph-node biopsy for melanoma staging, but produced conflicting results. Superior diagnostic accuracy of dermatoscopy over naked-eye examination for melanoma was found in one review, while a second implied nonsignificantly higher sensitivity of computer-based diagnostic methods over dermatoscopy for melanoma but with reduced specificity. There were no identified randomized controlled trials of treatments for unresectable recurrent melanoma, and a review of immunotherapy with vaccines for melanoma failed to prove improved overall and disease-free survival. Guidelines for the management of basal cell carcinoma call for risk stratification, based on numerous factors including tumour size, site and histological subtype. Squamous cell carcinoma of the ear has been shown to spread to regional lymph nodes more commonly than to other sites, and may be predicted by depth of invasion, tumour size, cellular differentiation and completeness of excision.
Assuntos
Neoplasias Cutâneas/terapia , Adolescente , Adulto , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/terapia , Criança , Humanos , Melanoma/diagnóstico , Melanoma/etiologia , Melanoma/terapia , Guias de Prática Clínica como Assunto , Literatura de Revisão como Assunto , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/etiologiaAssuntos
Eritema/patologia , Dermatoses da Perna/patologia , Síndromes Paraneoplásicas/patologia , Eritema/etiologia , Feminino , Glucagonoma/complicações , Humanos , Dermatoses da Perna/etiologia , Pessoa de Meia-Idade , Necrose , Neoplasias Pancreáticas/complicações , Síndromes Paraneoplásicas/etiologia , Pele/patologiaRESUMO
We studied three lines of oxytocin (Oxt) and oxytocin receptor (Oxtr) knockout (KO) male mice [Oxt(-/-), total Oxtr(-/-) and partial forebrain Oxtr (Oxtr(FB/FB))] with established deficits in social recognition to further refine our understanding of their deficits with regard to stimulus female's strain. We used a modified social discrimination paradigm in which subjects are singly housed only for the duration of the test. Additionally, stimulus females are singly housed throughout testing and are presented within corrals for rapid comparison of investigation by subject males. Wild-type (WT) males from all three lines discriminated between familiar and novel females of three different strains (C57BL/6, BALB/c and Swiss-Webster). No KO males discriminated between familiar and novel BALB/c or C57BL/6 females. Male Oxt(-/-) and Oxtr(-/-) mice, but not Oxtr(FB/FB) mice, discriminated between familiar and novel Swiss-Webster females. As this might indicate a global deficit in individual recognition for Oxtr(FB/FB) males, we examined their ability to discriminate between females from different strains and compared performance with Oxtr(-/-) males. WT and KO males from both lines were able to distinguish between familiar and novel females from different strains, indicating the social recognition deficit is not universal. Instead, we hypothesize that the Oxtr is involved in 'fine' intrastrain recognition, but is less important in 'broad' interstrain recognition. We also present the novel finding of decreased investigation across tests, which is likely an artifact of repeated testing and not because of stimulus female's strain or age of subject males.
Assuntos
Química Encefálica/genética , Encéfalo/metabolismo , Ocitocina/metabolismo , Receptores de Ocitocina/metabolismo , Comportamento Social , Animais , Comportamento Animal/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Caracteres Sexuais , Comportamento Sexual Animal/fisiologia , Especificidade da EspécieRESUMO
Spatial memory, anxiety and central monoaminergic activities were measured in non-pregnant (NP) and pregnant females during two time periods of pregnancy: gestational days 7-9 (GD7, GD9) and gestation days 16-18 (GD16, GD18). Pregnant females discriminated between object locations on both test days on an object placement task, whereas NP females were unable to discriminate between locations. Pregnant females displayed decreased anxiety on the elevated plus maze on GD9 compared to NP females, followed by increased anxiety-like behavior on the elevated plus maze on GD18. Monoamine levels and activity (as indexed by turnover ratio) were measured in prefrontal cortex (PFC), CA1 and CA3 regions of the hippocampus (areas important for memory), and medial preoptic area (mPOA, an area important in display of maternal behaviors). In the PFC, NP females generally had higher monoamine levels and turnover ratios; however, norepinephrine (NE) turnover was higher in pregnant females at GD18. In the CA1 and CA3 regions of the hippocampus, monoamine levels and turnover ratios were generally higher during pregnancy, particularly on GD9. In the mPOA, pregnancy was associated with increases in NE activity, a previously unreported finding. The present study expands upon existing research indicating that pregnancy is beneficial to spatial memory and may decrease anxiety. Changes in monoamine levels and activity in specific brain regions indicate that the dopamine, norepinephrine and serotonin systems may contribute to the observed behavioral differences.
Assuntos
Ansiedade/metabolismo , Monoaminas Biogênicas/metabolismo , Encéfalo/metabolismo , Memória/fisiologia , Gravidez/metabolismo , Percepção Espacial/fisiologia , Animais , Ansiedade/fisiopatologia , Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/fisiopatologia , Encéfalo/anatomia & histologia , Cognição/fisiologia , Feminino , Hipocampo/metabolismo , Comportamento Materno/fisiologia , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Vias Neurais/anatomia & histologia , Vias Neurais/metabolismo , Neurotransmissores/metabolismo , Norepinefrina/metabolismo , Córtex Pré-Frontal/metabolismo , Gravidez/psicologia , Área Pré-Óptica/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismoRESUMO
OBJECTIVE: To systematically review the relationship of premorbid adjustment to symptomatology in first episode psychosis (FEP), taking into account the influence of duration of untreated psychosis (DUP). METHOD: Electronic databases were searched to identify relevant studies. RESULTS: A variety of approaches to the reporting of premorbid adjustment were identified. There was no significant association between premorbid adjustment and DUP, supporting the proposition that they are independent constructs. The effect of premorbid adjustment upon positive symptomatology was negligible. Premorbid adjustment had a modest effect upon negative symptoms and quality of life, increasing over duration of follow-up. CONCLUSION: Premorbid adjustment remains a valid construct in the study of FEP. Both premorbid adjustment and DUP confer independent effects on aspects of symptomatology in FEP. Results for premorbid adjustment are similar to previous findings in more chronic samples. The potential for conceptualizing premorbid functioning by developmental, academic/social and typological approaches is currently underexploited.
Assuntos
Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Qualidade de Vida/psicologia , Ajustamento Social , Diagnóstico Diferencial , Progressão da Doença , Humanos , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Índice de Gravidade de DoençaAssuntos
Adjuvantes Imunológicos/efeitos adversos , Calcinose/induzido quimicamente , Interferon beta/efeitos adversos , Dermatopatias/induzido quimicamente , Adulto , Feminino , Humanos , Injeções Subcutâneas , Interferon beta-1a , Esclerose Múltipla/tratamento farmacológico , Gravidez , Complicações na Gravidez/tratamento farmacológico , Fatores de Tempo , Resultado do TratamentoRESUMO
Carotid artery thrombosis in young patients without evidence of premature atherosclerosis prompts investigation of unusual forms of carotid disease in addition to a workup for cardiac and arch vessel sources for emboli. Noninvasive imaging and conventional angiographic techniques play an important part in the diagnostic evaluation looking for potential vascular sources. Physicians should also be aware that, in addition, hypercoagulable conditions may predispose to carotid thrombosis. One such patient is presented with bilateral carotid thrombosis and stroke. The management of the problem is reviewed, as well as the investigation of potential hypercoagulable conditions, with a primary focus on qualitative and quantitative platelet abnormalities.