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BACKGROUND: The classification of mental, behavioural and neurodevelopmental disorders in the World Health Organization's International Classification of Diseases 11th revision (ICD-11) includes a comprehensive set of behavioural indicators (BIs) within the neurodevelopmental disorders grouping. BIs can be used to assess the severity of disorders of intellectual development in situations in which standardised measures of intellectual functioning and adaptive behaviours are not available or feasible. This international study examines the implementation characteristics of the BIs and compares them to standardised measures for assessing the severity of intellectual impairment and adaptive behaviours in disorders of intellectual development and autism spectrum disorder (ASD). The clinical utility of the ICD-11 and the fidelity of its application in international clinical settings were also assessed. METHODS: A total of 116 children and adolescents (5-18 years old) with a suspected or established diagnosis of disorders of intellectual development were included across four sites [Italy (n = 18), Sri Lanka (n = 19) and two sites in India (n = 79)]. A principal component analysis was conducted to evaluate the application of the ICD-11 guidance for combining severity levels. RESULTS: Assessment using the BIs showed a higher proportion of individuals classified with mild severity, whereas the standardised measures indicated a higher proportion of severe ratings. Additionally, individuals with co-occurring ASD tended to have more severe impairments compared with those without ASD, as indicated by both BIs and standardised measures. Overall, the BIs were considered clinically useful, although more time and consideration were required when applying the guidelines for individuals with a co-occurring disorder of intellectual development and ASD. The principal component analysis revealed one principal component representing overall disorders of intellectual development severity levels. CONCLUSIONS: The ICD-11 BIs can be implemented as intended in international clinical settings for a broad range of presentations of individuals with neurodevelopmental disorders. Use of the BIs results in similar severity diagnoses to those made using standardised measures. The BIs are expected to improve the reliability of severity assessments in settings where appropriate standardised measures for intellectual and adaptive behaviours are not available or feasible.
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BACKGROUND: The COVID-19 pandemic has significantly impacted the delivery of diabetes in pregnancy care and general maternity care. This study aimed to explore the experiences and acceptability of telehealth use in diabetes in pregnancy care during the COVID-19 pandemic, from the perspectives of pregnant women and their clinicians. The secondary aim was to explore the experiences of pregnant women receiving general maternity care via telehealth during the COVID-19 pandemic. METHODS: In-depth qualitative semi-structured interviews were undertaken and analysed via thematic inductive approaches. The Nonadoption, Abandonment, and Challenges to the Scale-Up, Spread, and Sustainability of Health and Care Technologies Framework (NASSS) was applied. RESULTS: Eigthteen interviews were conducted with culturally and linguistically diverse pregnant women and 4 clinicians (endocrinologists and dietitians). All interviewees were satisfied with telehealth as a positive alternative to face-to-face consultations for diabetes care during the COVID-19 pandemic. Numerous benefits of delivering diabetes care via telehealth were discussed and themes centred around greater access to care, economic benefits and improved safety. Most barriers concerned the adopters (clinicians), yet, feasible and realistic suggestions to overcome barriers were voiced. The scope for technology adaptation and ongoing embedment into routine diabetes care was described. Overall, a hybrid flexible delivery model, predominantly consisting of telephone consultations, with some face-to-face consultations for initial diabetes appointments was recommended for future care. The use of telehealth in replacement of face-to-face appointments for general maternity care was perceived as reducing care quality. CONCLUSION: In this study, telehealth was viewed as acceptable to women and clinicians for diabetes in pregnancy care, supporting the ongoing delivery of a hybrid service model of telehealth and face-to-face care. These findings provide valuable information to improve diabetes in pregnancy services to meet the needs of women during the COVID-19 pandemic and beyond.
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COVID-19 , Diabetes Mellitus , Serviços de Saúde Materna , Telemedicina , Gravidez , Feminino , Humanos , COVID-19/prevenção & controle , Pandemias/prevenção & controleRESUMO
BACKGROUND: The World Health Organization (WHO) has approved the 11th Revision of the International Classification of Diseases (ICD-11). A version of the ICD-11 for Mental, Behavioural and Neurodevelopmental Disorders for use in clinical settings, called the Clinical Descriptions and Diagnostic Requirements (CDDR), has also been developed. The CDDR includes behavioural indicators (BIs) for assessing the severity of disorders of intellectual development (DID) as part of the section on neurodevelopmental disorders. Reliable and valid diagnostic assessment measures are needed to improve identification and treatment of individuals with DID. Although appropriately normed, standardised intellectual and adaptive behaviour assessments are considered the optimal assessment approach in this area, they are unavailable in many parts of the world. This field study tested the BIs internationally to assess the inter-rater reliability, concurrent validity, and clinical utility of the BIs for the assessment of DID. METHODS: This international study recruited a total of 206 children and adolescents (5-18 years old) with a suspected or established diagnosis of DID from four sites across three countries [Sri-Lanka (n = 57), Italy (n = 60) and two sites in India (n = 89)]. Two clinicians assessed each participant using the BIs with one conducting the clinical interview and the other observing. Diagnostic formulations using the BIs and clinical utility ratings were collected and entered independently after each assessment. At a follow-up appointment, standardised measures (Leiter-3, Vineland Adaptive Behaviour Scales-II) were used to assess intellectual and adaptive abilities. RESULTS: The BIs had excellent inter-rater reliability (intra-class correlations ranging from 0.91 to 0.97) and good to excellent concurrent validity (intra-class correlations ranging from 0.66 to 0.82) across sites. Compared to standardised measures, the BIs had more diagnostic overlap between intellectual and adaptive functioning. The BIs were rated as quick and easy to use and applicable across severities; clear and understandable with adequate to too much level of detail and specificity to describe DID; and useful for treatment selection, prognosis assessments, communication with other health care professionals, and education efforts. CONCLUSION: The inclusion of newly developed BIs within the CDDR for ICD-11 Neurodevelopmental Disorders must be supported by information on their reliability, validity, and clinical utility prior to their widespread adoption for international use. BIs were found to have excellent inter-rater reliability, good to excellent concurrent validity, and good clinical utility. This supports use of the BIs within the ICD-11 CDDR to assist with the accurate identification of individuals with DID, particularly in settings where specialised services are unavailable.
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Classificação Internacional de Doenças , Transtornos do Neurodesenvolvimento , Adaptação Psicológica , Adolescente , Criança , Pré-Escolar , Humanos , Itália , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.
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Diabetes Gestacional/terapia , Avaliação de Resultados em Cuidados de Saúde/normas , Cuidado Pré-Natal/normas , Consenso , Técnica Delphi , Feminino , Humanos , Cooperação Internacional , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Participação dos Interessados , Resultado do TratamentoRESUMO
INTRODUCTION: Women with polycystic ovary syndrome (PCOS) have increased risk of metabolic syndrome. The relative contribution of clinical, demographic or biochemical factors to metabolic syndrome in PCOS is not known. A literature search was conducted in MEDLINE, CINAHL, EMBASE and clinical trial registries. Of 4530 studies reviewed, 59 were included in the systematic review and 27 in the meta-analysis and meta-regression. In good and fair quality studies, women with PCOS had an overall increased prevalence of metabolic syndrome (odds ratio, OR 3.35, 95% confidence interval, CI 2.44, 4.59). Increased prevalence of metabolic syndrome occurred in overweight or obese women with PCOS (OR 1.88, 95% 1.16, 3.04) but not in lean women (OR 1.45, 95% CI 0.35, 6.12). In meta-regression analyses, the markers of metabolic syndrome diagnostic criteria (waist circumference, high-density lipoprotein cholesterol, triglyceride, blood pressure), BMI, glucose tolerance (2-hr oral glucose tolerance test) and surrogate markers of insulin resistance (HOMA-IR) but not markers of reproductive dysfunction (sex hormone binding globulin, testosterone, PCOS phenotypes) contributed significantly to the heterogeneity in the prevalence of metabolic syndrome. Women with PCOS have increased risk of metabolic syndrome which was associated with obesity and metabolic features but not with indices of hyperandrogenism.
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Resistência à Insulina/fisiologia , Síndrome Metabólica/complicações , Síndrome do Ovário Policístico/complicações , Glicemia , Índice de Massa Corporal , Feminino , Humanos , Síndrome Metabólica/metabolismo , Síndrome do Ovário Policístico/metabolismoRESUMO
BACKGROUND: Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity. OBJECTIVE AND RATIONALE: We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS. SEARCH METHODS: We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis. OUTCOMES: We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for diagnosing diabetes. The ethnicity-related difference retained its significance for Asia and Europe in BMI-matched subgroups. Clear contributors to heterogeneity did not emerge in meta-regression. WIDER IMPLICATIONS: Our findings underscore the importance of PCOS as a cause of dysglycemia with a higher prevalence of IGT and T2DM. They support the relevance of ethnicity and obesity and emphasize the need for accurate diagnostic methods for diabetes. PROSPERO REGISTRATION NUMBER: CRD42017056524.
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Diabetes Mellitus Tipo 2 , Etnicidade/estatística & dados numéricos , Intolerância à Glucose , Obesidade , Síndrome do Ovário Policístico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Feminino , Intolerância à Glucose/complicações , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/etnologia , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/etnologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/etnologia , PrevalênciaRESUMO
BACKGROUND: Problem behaviours (PBs) are a common cause for clinician contact in people with disorders of intellectual development and may be a common cause for the prescription of psychotropic medication. We aimed to use a large, multinational sample to define the prevalence of PBs, the associations with psychotropic medication use, and to assess for any potential 'diagnostic overshadowing' by the label of PBs in a population of people with disorders of intellectual development. METHOD: A multinational, multi-setting, cross-sectional service evaluation and baseline audit was completed. Data were collected from UK hospitals, UK community settings, Sri Lanka and Hong Kong. A semi-structured questionnaire was completed by treating clinicians, capturing demographic details, prevalence rates of intellectual disability and psychotropic medication use, alongside psychiatric co-morbidity. RESULTS: A sample size of 358 was obtained, with 65% of included participants treated in an inpatient setting. Psychotropic use was prevalent (90%) in our sample, particularly antipsychotics (74%). The prevalence of PB was high (83%). There was no statistically significant association between psychotropic prescription and recorded psychiatric co-morbidity, suggesting prevalent 'off-label' use for PBs, or poor recording of psychiatric co-morbidity. There was some evidence of possible diagnostic overshadowing due to the PB classification. A higher dose of psychotropic medication was associated with aggression toward others (P = 0.03). CONCLUSIONS: We found evidence of prevalent potential 'off-label' use for psychotropic medication, which may be due to PBs. We also found evidence of potential diagnostic-overshadowing, where symptoms of psychiatric co-morbidity may have been attributed to PBs. Our findings provide renewed importance, across borders and health systems, for clinicians to consider a holistic approach to treating PBs, and attempting to best understand the precipitants and predisposing factors before psychotropic prescribing.
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Sintomas Comportamentais , Deficiência Intelectual , Uso Off-Label , Psicotrópicos/uso terapêutico , Adulto , Antipsicóticos/uso terapêutico , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/tratamento farmacológico , Sintomas Comportamentais/epidemiologia , Sintomas Comportamentais/etiologia , Comorbidade , Estudos Transversais , Feminino , Hong Kong/epidemiologia , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/tratamento farmacológico , Deficiência Intelectual/epidemiologia , Masculino , Pessoa de Meia-Idade , Uso Off-Label/estatística & dados numéricos , Prevalência , Comportamento Problema , Sri Lanka/epidemiologia , Reino Unido/epidemiologiaRESUMO
Central nervous system (CNS) tuberculosis (TB) is a rare but catastrophic event in patients with systemic lupus erythematosus (SLE). Here we report a case of cerebral TB in a patient with lupus myocarditis and nephritis, following cyclophosphamide immunosuppression. To our knowledge this is the first reported case of cerebral TB in SLE in a non-endemic country. A 31-year-old female with SLE and a history of regular travel to Kenya presented to our centre with clinical features of acute heart failure. She was diagnosed with severe lupus myocarditis, and a renal biopsy also confirmed lupus nephritis. Prior to admission, she had also had a cough, fever and weight loss and was under investigation for suspected TB infection. She was treated with ivabradine, beta-blockers and diuretics together with methylprednisolone and cyclophosphamide immunosuppression. Subsequent sputum cultures confirmed TB and she was commenced on triple therapy. Despite this, she developed confusion, dizziness, blurred vision and fluctuating consciousness. Magnetic resonance imaging (MRI) and lumbar puncture revealed CNS TB infection resulting in meningitis. This was later complicated by obstructive hydrocephalus due to TB abscesses. A ventriculoperitoneal (VP) shunt was inserted and TB medications were given intravenously (IV) with dexamethasone. Following a prolonged hospital admission, the patient eventually recovered and rituximab treatment was used to control her SLE. TB infection has been associated with SLE flares. It is likely in this case that TB exacerbated a lupus flare and subsequent immunosuppression resulted in mycobacterial dissemination to the CNS. Systemic and CNS features of TB and SLE are difficult to distinguish and their contemporaneous management represents a diagnostic and therapeutic challenge.
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Ciclofosfamida/efeitos adversos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose do Sistema Nervoso Central/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Imageamento por Ressonância Magnética , Mycobacterium tuberculosis/efeitos dos fármacos , Escarro/microbiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tuberculose do Sistema Nervoso Central/diagnóstico , Tuberculose do Sistema Nervoso Central/imunologia , Tuberculose do Sistema Nervoso Central/terapia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/imunologia , Derivação VentriculoperitonealRESUMO
BACKGROUND: Aggressive challenging behaviour in people with intellectual disability (ID) is frequently treated with antipsychotic drugs, despite a limited evidence base. METHOD: A multi-centre randomised controlled trial was undertaken to investigate the efficacy, adverse effects and costs of two commonly prescribed antipsychotic drugs (risperidone and haloperidol) and placebo. RESULTS: The trial faced significant problems in recruitment. The intent was to recruit 120 patients over 2 years in three centres and to use a validated aggression scale (Modified Overt Aggression Scale) score as the primary outcome. Despite doubling the period of recruitment, only 86 patients were ultimately recruited. CONCLUSIONS: Variation in beliefs over the efficacy of drug treatment, difficulties within multidisciplinary teams and perceived ethical concerns over medication trials in this population all contributed to poor recruitment. Where appropriate to the research question cluster randomised trials represent an ethically and logistically feasible alternative to individually randomised trials.
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Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Deficiência Intelectual/tratamento farmacológico , Seleção de Pacientes , Risperidona/uso terapêutico , Transtornos do Comportamento Social/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Medicina Baseada em Evidências , Feminino , Haloperidol/efeitos adversos , Humanos , Deficiência Intelectual/psicologia , Masculino , Determinação da Personalidade/estatística & dados numéricos , Psicometria , Queensland , Risperidona/efeitos adversos , Transtornos do Comportamento Social/psicologia , Resultado do Tratamento , Reino UnidoRESUMO
OBJECTIVE(S): To assess the effects and cost-effectiveness of haloperidol, risperidone and placebo on aggressive challenging behaviour in adults with intellectual disability. DESIGN: A double-blind randomised controlled trial of two drugs and placebo administered in flexible dosage, with full, independent assessments of aggressive and aberrant behaviour, global improvement, carer burden, quality of life and adverse drug effects at baseline, 4, 12 and 26 weeks, and comparison of total care costs in the 6 months before and after randomisation. At 12 weeks, patients were given the option of leaving the trial or continuing until 26 weeks. Assessments of observed aggression were also carried out with key workers at weekly intervals throughout the trial. SETTING: Patients were recruited from all those being treated by intellectual disability services in eight sites in England, one in Wales and one in Queensland, Australia. PARTICIPANTS: Patients from all severity levels of intellectual disability; recruitment was extended to include those who may have been treated with neuroleptic drugs in the past. EXCLUSION CRITERIA: treatment with depot neuroleptics/another form of injected neuroleptic medication within the last 3 months; continuous oral neuroleptic medication within the last week; those under a section of the Mental Health Act 1983 or Queensland Mental Health Act 2000. INTERVENTIONS: Randomisation to treatment with haloperidol (a typical neuroleptic drug), risperidone (an atypical neuroleptic drug) or placebo using a permuted blocks procedure. Dosages were: haloperidol 1.25-5.0 mg daily; risperidone 0.5-2.0 mg daily. MAIN OUTCOME MEASURES: Primary: reduction in aggressive episodes between baseline and 4 weeks using Modified Overt Aggression Scale. Secondary: Aberrant Behaviour Checklist; Uplift/Burden Scale; 40-item Quality of Life Questionnaire; Udvalg for Kliniske Undersøgelser scale; Clinical Global Impressions scale. Economic costs recorded using a modified version of Client Service Receipt Inventory for 6 months before and after randomisation. RESULTS: There were considerable difficulties in recruitment because of ethical and consent doubts. Twenty-two clinicians recruited a total of 86 patients. Mean daily dosages were 1.07 mg rising to 1.78 mg for risperidone and 2.54 mg rising to 2.94 mg for haloperidol. Aggression declined dramatically with all three treatments by 4 weeks, with placebo showing the greatest reduction (79%, versus 57% for combined drugs) (p = 0.06). Placebo-treated patients showed no evidence of inferior response in comparison to patients receiving neuroleptic drugs. An additional study found that clinicians who had not participated in clinical trials before were less likely to recruit. Mean total cost of accommodation, services, informal care and treatment over the 6 months of the trial was 16,336 pounds for placebo, 17,626 pounds for haloperidol and 18,954 pounds for risperidone. CONCLUSIONS: There were no significant important benefits conferred by treatment with risperidone or haloperidol, and treatment with these drugs was not cost-effective. While neuroleptic drugs may be of value in the treatment of aggressive behaviour in some patients with intellectual disability, the underlying pathology needs to be evaluated before these are given. The specific diagnostic indications for such treatment require further investigation. Prescription of low doses of neuroleptic drugs in intellectual disability on the grounds of greater responsiveness and greater liability to adverse effects also needs to be re-examined.
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Agressão/efeitos dos fármacos , Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Pessoas com Deficiência Mental , Risperidona/uso terapêutico , Adolescente , Adulto , Idoso , Agressão/psicologia , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacologia , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Inglaterra , Feminino , Haloperidol/administração & dosagem , Haloperidol/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Placebos , Risperidona/administração & dosagem , Risperidona/farmacologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
CONTEXT: There are at least 24 missense, nonconservative mutations found in the ACTH receptor [melanocortin 2 receptor (MC2R)] that have been associated with the autosomal recessive disease familial glucocorticoid deficiency (FGD) type 1. The characterization of these mutations has been hindered by difficulties in establishing a functional heterologous cell transfection system for MC2R. Recently, the melanocortin 2 receptor accessory protein (MRAP) was identified as essential for the trafficking of MC2R to the cell surface; therefore, a functional characterization of MC2R mutations is now possible. OBJECTIVE: Our objective was to elucidate the molecular mechanisms responsible for defective MC2R function in FGD. METHODS: Stable cell lines expressing human MRAPalpha were established and transiently transfected with wild-type or mutant MC2R. Functional characterization of mutant MC2R was performed using a cell surface expression assay, a cAMP reporter assay, confocal microscopy, and coimmunoprecipitation of MRAPalpha. RESULTS: Two thirds of all MC2R mutations had a significant reduction in cell surface trafficking, even though MRAPalpha interacted with all mutants. Analysis of those mutant receptors that reached the cell surface indicated that four of six failed to signal, after stimulation with ACTH. CONCLUSION: The majority of MC2R mutations found in FGD fail to function because they fail to traffic to the cell surface.
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Glucocorticoides/deficiência , Receptor Tipo 2 de Melanocortina/genética , Receptores de Superfície Celular/genética , Animais , Western Blotting , Células CHO , Linhagem Celular , Cricetinae , Cricetulus , AMP Cíclico/fisiologia , Genes Reporter/genética , Humanos , Imunoprecipitação , Proteína Associada a Proteínas Relacionadas a Receptor de LDL/genética , Ligantes , Microscopia Confocal , Mutagênese Sítio-Dirigida , Mutação de Sentido Incorreto/genética , Transdução de Sinais/fisiologiaRESUMO
A reverse transcription nested polymerase chain reaction (RT-PCR) assay was developed and evaluated for detection of rubella virus (RV) RNA directly from clinical specimens using primers that amplified 592 nucleotides, of a variable region within the E1 gene. RV RNA was detected in pre- and post-natal congenital rubella samples and samples from patients with acute rubella, which suggests that it is a reliable technique for rubella diagnosis and surveillance. The sensitivity of the PCR was found to be equivalent to that of previously published assays, which amplify smaller regions of the E1 gene. This improved RT-PCR is much more specific for detection of the rubella genome compared to our previous PCR, where some primers were complementary to the human genome. The larger size of the PCR amplicon was also useful for molecular genotyping of virus strains.
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Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Vírus da Rubéola/isolamento & purificação , Rubéola (Sarampo Alemão)/diagnóstico , Rubéola (Sarampo Alemão)/epidemiologia , Sequência de Bases , Feminino , Genótipo , Humanos , Recém-Nascido , Dados de Sequência Molecular , Vigilância da População , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , RNA Viral/análise , RNA Viral/isolamento & purificação , Rubéola (Sarampo Alemão)/virologia , Síndrome da Rubéola Congênita/diagnóstico , Síndrome da Rubéola Congênita/virologia , Vírus da Rubéola/classificação , Vírus da Rubéola/genética , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: There has been a policy shift away from hospital to community in the services of all those with psychiatric disorders, including those with intellectual disability (ID), in the last 50 years. This has been accompanied recently by the growth of assertive outreach services, but these have not been evaluated in ID services. METHOD: In a randomized controlled trial we compared assertive outreach with 'standard' community care, using global assessment of function (GAF) as the primary outcome measure, and burden and quality of life as secondary measures. RESULTS: We recruited 30 patients, considerably less than expected; no significant differences were found between the primary and secondary outcomes in the two groups. The differences were so small that a Type II error was unlikely. CONCLUSIONS: Reasons for this lack of specific efficacy of the assertive approach are discussed and it is suggested that there is a blurring of the differences between standard and assertive approaches in practice.
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Serviços Comunitários de Saúde Mental/provisão & distribuição , Serviços Comunitários de Saúde Mental/estatística & dados numéricos , Deficiência Intelectual/terapia , Adolescente , Adulto , Idoso , Efeitos Psicossociais da Doença , Humanos , Deficiência Intelectual/diagnóstico , Inteligência , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: In an era of evidence-based medicine, practice is constantly monitored for quality in accordance with the needs of clinical governance (Oyebode et al. 1999). This is likely to lead to a dramatic change in the treatment of those with intellectual disability (ID), in which evidence for effective intervention is limited for much that happens in ordinary practice. As Fraser (2000, p. 10) has commented, the word that best explains "the transformation of learning disability practice in the past 30 years is 'enlightenment'." This is not enough to satisfy the demands of evidence, and Fraser exhorted us to embrace more research-based practice in a subject that has previously escaped randomized controlled trials (RCTs) of treatment because of ethical concerns over capacity and consent, which constitute a denial of opportunity which "is now at last regarded as disenfranchising". CONCLUSIONS: The present paper describes the difficulties encountered in setting up a RCT of a common intervention, i.e. assertive community treatment, and concludes that a fundamental change in attitudes to health service research in ID is needed if proper evaluation is to prosper.
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Medicina Baseada em Evidências , Pessoas com Deficiência Mental/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ética Médica , Humanos , Projetos de Pesquisa , Resultado do TratamentoRESUMO
The case of a 20 year old autistic woman with disabling repetitive behaviour that responded dramatically to treatment with fluvoxamine is reported. The connection between repetitive symptoms in autism and obsessive-compulsive disorder is considered, and the need for further evaluation of selective serotonin reuptake inhibitors in autism is discussed.