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1.
BMC Med Res Methodol ; 23(1): 265, 2023 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951890

RESUMO

BACKGROUND: Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN. METHODS: TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials. RESULTS: TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units. CONCLUSION: TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing for effectiveness in a large cluster randomised trial is required.


Assuntos
Seleção de Pacientes , Projetos de Pesquisa , Humanos , Recém-Nascido , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Anaesthesia ; 78(7): 853-860, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37070957

RESUMO

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively.


Assuntos
Traumatismos Cardíacos , Hospitalização , Humanos , Estudos de Coortes , Sensibilidade e Especificidade , Curva ROC , Aprendizado de Máquina , Estudos Retrospectivos
3.
Mol Psychiatry ; 22(6): 900-909, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27137745

RESUMO

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.


Assuntos
Córtex Cerebral/patologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Adolescente , Adulto , Encéfalo/patologia , Córtex Cerebral/diagnóstico por imagem , Feminino , Lobo Frontal/patologia , Substância Cinzenta/patologia , Giro do Cíngulo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos , Neuroimagem/psicologia , Córtex Pré-Frontal/patologia , Lobo Temporal/patologia
4.
Mol Psychiatry ; 21(6): 806-12, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26122586

RESUMO

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.


Assuntos
Encéfalo/patologia , Transtorno Depressivo Maior/patologia , Adulto , Estudos de Casos e Controles , Feminino , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos
5.
Br J Surg ; 103(10): 1377-84, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27462835

RESUMO

BACKGROUND: The complexity of surgical interventions has major implications for the design of RCTs. Trials need to consider how and whether to standardize interventions so that, if successful, they can be implemented in practice. Although guidance exists for standardizing non-pharmaceutical interventions in RCTs, their application to surgery is unclear. This study reports new methods for standardizing the delivery of surgical interventions in RCTs. METHODS: Descriptions of 160 surgical interventions in existing trial reports and protocols were identified. Initially, ten reports were scrutinized in detail using a modified framework approach for the analysis of qualitative data, which informed the development of a preliminary typology. The typology was amended with iterative sequential application to all interventions. Further testing was undertaken within ongoing multicentre RCTs. RESULTS: The typology has three parts. Initially, the overall technical purpose of the intervention is described (exploration, resection and/or reconstruction) in order to establish its constituent components and steps. This detailed description of the intervention is then used to establish whether and how each component and step should be standardized, and the standards documented within the trial protocol. Finally, the typology provides a framework for monitoring the agreed intervention standards during the RCT. Pilot testing within ongoing RCTs enabled standardization of the interventions to be agreed, and case report forms developed to capture deviations from these standards. CONCLUSION: The typology provides a framework for use during trial design to standardize the delivery of surgical interventions and document these details within protocols. Application of this typology to future RCTs may clarify details of the interventions under evaluation and help successful interventions to be implemented.


Assuntos
Garantia da Qualidade dos Cuidados de Saúde/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa/normas , Procedimentos Cirúrgicos Operatórios/normas , Humanos , Garantia da Qualidade dos Cuidados de Saúde/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
6.
Br J Anaesth ; 115(2): 227-33, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26001837

RESUMO

BACKGROUND: Evidence suggests that cardiac output-guided haemodynamic therapy algorithms improve outcomes after high-risk surgery, but there is some concern that this could promote acute myocardial injury. We evaluated the incidence of myocardial injury in a perioperative goal-directed therapy trial. METHODS: Patients undergoing major gastrointestinal surgery (n=723) were randomly assigned to cardiac output-guided haemodynamic therapy (intervention group) or usual care as part of the OPTIMISE trial. At four participating sites, 288 patients were enrolled in a biomarker substudy. Serum high-sensitivity cardiac troponin I (TnI) concentration and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration were measured before and at 24 and 72 h after surgery. RESULTS: Median preoperative TnI and NT-ProBNP concentrations were 4.3 ng litre(-1) and 144 pg ml(-1), respectively. After surgery, 67 (46%) patients in the intervention group and 68 (48%) patients receiving usual care had TnI concentrations above the 99th centile upper reference limit (P=0.82). Peak serum TnI concentration was similar in the intervention and usual care groups (median [interquartile range]: 10.0 [5.3-21.5] vs 7.8 [5.0-21.8] ng litre(-1); P=0.85), and no differences were observed in serum TnI concentrations over 72 h (repeated-measures anova, P=0.51). Likewise, there were no differences in peak NT-proBNP concentration between intervention and usual care groups (645 [362-1169] vs 659 [381-1028] pg ml(-1); P=0.86) or in serial NT-proBNP concentrations over 72 h (P=0.20). CONCLUSIONS: Myocardial injury is common among patients undergoing major gastrointestinal surgery. In this study, the frequency was not affected by cardiac output-guided fluid and low-dose inotropic therapy.


Assuntos
Débito Cardíaco , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Cardiopatias/etiologia , Complicações Pós-Operatórias/etiologia , Idoso , Feminino , Hemodinâmica , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina I/sangue
7.
QJM ; 117(3): 187-194, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37878823

RESUMO

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.


Assuntos
Infarto do Miocárdio , Humanos , Biomarcadores , Estudos Prospectivos , Infarto do Miocárdio/diagnóstico , Troponina I , Valor Preditivo dos Testes , Serviço Hospitalar de Emergência , Algoritmos , Troponina T
8.
Br J Cancer ; 109(5): 1181-91, 2013 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-23928662

RESUMO

BACKGROUND: Breast reconstruction (BR) may improve psychosocial and cosmetic outcomes after mastectomy for breast cancer but currently, few women opt for surgery. Reasons for this are unclear. The aim of this qualitative study was to explore access to care and the provision of procedure choice to women seeking reconstructive surgery. METHODS: Semi-structured interviews with a purposive sample of patients who had undergone BR and professionals providing specialist care explored participants' experiences of information provision before BR. Interviews were transcribed verbatim and analysed using the constant comparative technique of grounded theory. Sampling, data collection and analysis were performed concurrently and iteratively until data saturation was achieved. RESULTS: Both patients and professionals expressed concerns about the provision of adequate procedure choice and access to care. Lack of information and/or time, involvement in decision making and issues relating to the evolution and organisation of reconstructive services, emerged as potential explanations for the inequalities seen. Interventions to improve cross-speciality collaboration were proposed to address these issues. CONCLUSION: Inequalities in the provision of choice in BR exist, which may be explained by a lack of integration between surgical specialities. Pathway restructuring, service reorganisation and standardisation of training may enhance cross-speciality collaboration and improve the patient experience.


Assuntos
Comportamento de Escolha , Tomada de Decisões , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Mamoplastia , Coleta de Dados , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Mamoplastia/métodos , Mamoplastia/psicologia , Mastectomia/psicologia , Padrões de Prática Médica , Inquéritos e Questionários
9.
J Intern Med ; 272(3): 224-39, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22724512

RESUMO

Air pollution is now recognized as an important independent risk factor for cardiovascular morbidity and mortality and may be responsible for up to 3 million premature deaths each year worldwide. The mechanisms underlying the observed effects are poorly understood but are likely to be multifactorial. Here, we review the acute and chronic effects of air pollution exposure on the cardiovascular system and discuss how these effects may explain the observed increases in cardiovascular morbidity and mortality.


Assuntos
Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/etiologia , Exposição Ambiental/efeitos adversos , Material Particulado , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Endotélio Vascular/fisiopatologia , Fibrinólise/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Inflamação/etiologia , Estresse Oxidativo/fisiologia , Rigidez Vascular/fisiologia , Vasoconstrição/fisiologia
10.
Curr Oncol ; 23(5): e436-e438, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27803602
11.
QJM ; 114(6): 374-380, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33769545

RESUMO

BACKGROUND: The COVID-19 pandemic is putting health professionals under increasing pressure. This population is already acknowledged to be at risk of burnout. AIM: We aim to provide a 'snapshot' of the levels of burnout, anxiety, depression and distress among healthcare workers during the COVID-19 pandemic. METHODS: We distributed an online survey via social media in June 2020 open to any UK healthcare worker. The primary outcome measure was symptoms of burnout measured using the Copenhagen Burnout Inventory. Secondary outcomes of depression, anxiety, distress and subjective measures of stress were also recorded. Multivariate logistic regression analysis was performed to identify factors associated with burnout, depression, anxiety and distress. RESULTS: A total of 539 persons responded to the survey; 90% female and 53% nurses. Participants with moderate-to-severe burnout were younger (49% vs. 33% under 40 years, P = 0.004), more likely to have pre-existing comorbidities (21% vs. 12%, P = 0.031), twice as likely to have been redeployed from their usual role (22% vs. 11%; P = 0.042), or to work in an area dedicated to COVID-19 patients (50% vs. 32%, P < 0.001) and were almost 4 times more likely to have previous depression (24% vs. 7%; P = 0.012). CONCLUSION: Independent predictors of burnout were being younger, redeployment, exposure to patients with COVID-19, being female and a history of depression. Evaluation of existing psychological support interventions is required with targeted approaches to ensure support is available to those most at risk.


Assuntos
COVID-19 , Pandemias , Esgotamento Psicológico , Estudos Transversais , Depressão/epidemiologia , Feminino , Pessoal de Saúde , Humanos , Masculino , SARS-CoV-2 , Reino Unido/epidemiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-32021696

RESUMO

PURPOSE: The purpose of this study is to assess the feasibility of conducting a large, multicentre randomised controlled trial (RCT) comparing needle fasciotomy with limited fasciectomy for treatment of Dupuytren's contractures. DESIGN: The design of this study is a parallel, two-arm, multicentre, randomised feasibility trial with embedded QuinteT Recruitment Intervention. PARTICIPANTS: Patients aged 18 years or over who were referred from primary to secondary care for treatment of a hand with Dupuytren's contractures of one or more fingers of more than 30° at the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints and well-defined cord(s). Patients were excluded if they had undergone previous Dupuytren's contracture surgery on the same hand. METHODS: Potential participants were screened for eligibility. Recruited participants randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy and followed-up for up to 6 months after treatment. Data on recruitment rates, completion of follow-up, and procedure costs were collected. Four patient reported outcome measures (PROMs) and objective outcome measures were collected before intervention and 6 weeks and 6 months afterwards. RESULTS: One hundred and fifty-three of 267 (57%) primary-care referrals for Dupuytren's contractures met the eligibility criteria for the study. Seventy-one of the 153 (46%) agreed to participate and were randomly allocated to treatment with needle fasciotomy or limited fasciectomy. Sixty-seven of these underwent their allocated treatment, two were crossovers from limited fasciectomy to needle fasciotomy, and two (both allocated limited fasciectomy) received no treatment. Fifty-nine participants (85%) completed 6-month follow-up PROMs. Participants felt the MYMOP, PEM and URAM PROMs allowed them to better describe how their treatment affected their hand function than the DASH PROM. The estimated costs of limited fasciectomy (in an operating theatre) and needle fasciotomy (in a clinic room) were £777 and £111 respectively. CONCLUSION: A large RCT comparing treatment of Dupuytren's contractures by needle fasciotomy and limited fasciectomy is feasible. Data from this study will help determine the number of sites and duration of recruitment required to complete an adequately powered RCT and will assist the selection of PROMs in future studies on the treatment of Dupuytren's contractures. (Level 1 feasibility study). TRIAL REGISTRATION: Trial registered with ISRCTN (registration number: ISRCTN11164292), date assigned - 28/08/2015.

13.
Clin Oncol (R Coll Radiol) ; 32(5): 292-297, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31813662

RESUMO

AIMS: Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to the development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. MATERIALS AND METHODS: This was a multicentre prospective observational cohort study. Female patients with newly diagnosed invasive breast cancer scheduled to receive anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was carried out before and 24 h after each cycle. Hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay. RESULTS: We recruited 78 women with a median (interquartile range) age of 52 (49-61) years. The median baseline troponin concentration was 1 (1-4) ng/l and the median cumulative epirubicin dose was 394 (300-405) mg/m2. Following an initial 33% fall 24 h after anthracycline dosing (P < 0.001), hs-cTnI concentrations increased by a median of 50% (P < 0.001) with each successive treatment cycle. In total, 45 patients had troponin measured immediately before the sixth treatment cycle, 21 (46.6%) of whom had hs-cTnI concentrations ≥16 ng/l, indicating myocardial injury. Plasma hs-cTnI concentrations before the second treatment cycle were a strong predictor of subsequent myocardial injury. CONCLUSIONS: Cardiotoxicity arising from anthracycline therapy is detectable in the earliest stages of breast cancer treatment and is cumulative with each treatment cycle. This injury is most reliably determined from blood sampling carried out before rather than after each treatment cycle.


Assuntos
Antraciclinas/efeitos adversos , Biomarcadores/sangue , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/diagnóstico , Troponina I/sangue , Neoplasias da Mama/patologia , Cardiotoxicidade/sangue , Cardiotoxicidade/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
14.
Hum Reprod ; 24(3): 619-25, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19088108

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs) are circulating mononuclear cells that participate in angiogenesis. The aim of this study was to determine the influence of the menstrual cycle on the number and function of EPCs, and to investigate their relationship with circulating concentrations of sex steroids and inflammatory mediators. METHODS: Ten healthy nulliparous, premenopausal, non-smoking women with regular menses were studied over a single menstrual cycle. Venepuncture was performed in the menstrual, follicular, peri-ovulatory and luteal phases. EPCs were quantified by flow cytometry (CD133(+)CD34(+)KDR(+) phenotype) and the colony-forming unit (CFU-EPC) functional assay. Circulating concentrations of estradiol, progesterone and inflammatory mediators (TNF-alpha, IL-6, sICAM-1 and VEGF) were measured by immunoassays. RESULTS: The numbers of CD133(+)CD34(+)KDR(+) cells were higher in the follicular phase (0.99 +/- 0.3 x 10(6) cells/l) compared with the peri-ovulatory phase (0.29 +/- 0.1 x 10(6) cells/l; P < 0.05). In contrast, the numbers of CFU-EPCs did not vary over the menstrual cycle. There were no correlations between EPCs and concentrations of either circulating sex steroids or inflammatory mediators. CONCLUSIONS: CD133(+)CD34(+)KDR(+) cells but not CFU-EPCs vary during the menstrual cycle. Our findings suggest a potential role for circulating EPCs in the normal cycle of physiological angiogenesis and repair of the uterine endometrium that is independent of circulating sex steroids or inflammatory mediators.


Assuntos
Células Endoteliais/patologia , Endotélio Vascular/patologia , Ciclo Menstrual , Células-Tronco/citologia , Antígeno AC133 , Adulto , Antígenos CD/biossíntese , Antígenos CD34/biossíntese , Células Endoteliais/citologia , Endotélio Vascular/citologia , Feminino , Citometria de Fluxo/métodos , Glicoproteínas/biossíntese , Humanos , Imunofenotipagem , Neovascularização Patológica , Peptídeos , Esteroides/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese
15.
Neuropediatrics ; 40(1): 1-5, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19639521

RESUMO

OBJECTIVE: Recent morphometric studies suggest that children with ADHD may demonstrate differential or delayed brain development compared with children without ADHD. This study examines the developmental course of brain activation patterns during the performance of an attention task. METHOD: Ten adolescents with ADHD and 14 healthy comparison adolescents performed a continuous performance task in an fMRI twice, one year apart. RESULTS: In the absence of performance differences, children with ADHD and healthy comparison subjects activated frontal-parietal regions while performing an attention task at initial testing. Children with ADHD appeared to require continued use of the right middle frontal gyrus during administration of testing one year apart while healthy comparison subjects did not activate this region at the time of the second testing. CONCLUSIONS: There appear to be developmental differences in brain activation patterns on an attentional task between ADHD and healthy controls. More research is needed for examining the longitudinal course of functional brain activation in children with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Atenção/fisiologia , Mapeamento Encefálico , Encéfalo/fisiopatologia , Adolescente , Análise de Variância , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Estudos de Casos e Controles , Criança , Feminino , Análise de Fourier , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Testes Neuropsicológicos , Oxigênio/sangue , Estimulação Luminosa/métodos , Desempenho Psicomotor , Tempo de Reação
16.
Bull Entomol Res ; 99(1): 83-96, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18662432

RESUMO

Host plant associated genetic differentiation is a common phenomenon in phytophagous insects, but the degree to which such associations sequentially drive diversification at higher trophic levels is not as well understood. A recent study examining neutral molecular markers in Hyalopterus aphids revealed that genetic structure in this genus is strongly determined by primary host plant use (Prunus spp.). In this paper, we take a similar approach to determine whether this host plant specificity has affected genetic structure in the parasitoid Aphidius transcaspicus, an important natural enemy of Hyalopterus spp. in the Mediterranean. Mitochondrial DNA (428 bp) and seven microsatellite loci were examined in parasitoids collected from aphid populations on almond, apricot, peach and plum trees from Spain and Greece. In contrast to the previous findings for Hyalopterus from the same regions, here we find no evidence for host associated diversification in A. transcaspicus at the species level or below, though geographic structure between regional populations is exceptionally high. These findings have several implications for our understanding of the ecology and evolution of A. transcaspicus as well as for its use as a biological control agent for Hyalopterus, suggesting that a consideration of host plant specificity may be less critical than factors such as climatic suitability or geographic origins of invasive populations.


Assuntos
Afídeos/parasitologia , Variação Genética , Repetições de Microssatélites/genética , Vespas/fisiologia , Animais , Complexo IV da Cadeia de Transporte de Elétrons/genética , Geografia , Interações Hospedeiro-Parasita , Filogenia , Vespas/genética
17.
Contemp Clin Trials Commun ; 14: 100335, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30949611

RESUMO

BACKGROUND: Recruitment to pediatric randomised controlled trials (RCTs) can be a challenge, with ethical issues surrounding assent and consent. Pediatric RCTs frequently recruit from a smaller pool of patients making adequate recruitment difficult. One factor which influences recruitment and retention in pediatric trials is patient and parent preferences for treatment. PURPOSE: To systematically review pediatric RCTs reporting treatment preference. METHODS: Database searches included: MEDLINE, CINAHL, EMBASE, and COCHRANE.Qualitative or quantitative papers were eligible if they reported: pediatric population, (0-17 years) recruited to an RCT and reported treatment preference for all or some of the participants/parents in any clinical area. Data extraction included: Number of eligible participants consenting to randomisation arms, number of eligible patients not randomised because of treatment preference, and any further information reported on preferences (e.g., if parent preference was different from child). RESULTS: Fifty-two studies were included. The number of eligible families declining participation in an RCT because of preference for treatment varied widely (between 2 and 70%) in feasibility, conventional and preference trial designs. Some families consented to trial involvement despite having preferences for a specific treatment. Data relating to 'participant flow and recruitment' was not always reported consistently, therefore numbers who were lost to follow-up or withdrew due to preference could not be extracted. CONCLUSIONS: Families often have treatment preferences which may affect trial recruitment. Whilst children appear to hold treatment preferences, this is rarely reported. Further investigation is needed to understand the reasons for preference and the impact preference has on RCT recruitment, retention and outcome.

18.
Thorax ; 63(7): 578-83, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18390635

RESUMO

BACKGROUND: The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy. METHODS: We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium dependent (acetylcholine 5-20 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators. RESULTS: Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r = -0.44, p = 0.002 and r = -0.43, p = 0.003) and sodium nitroprusside (r = -0.42, p = 0.009 and r = -0.37, p = 0.02). In comparison with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01). CONCLUSIONS: Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Pressão Positiva Contínua nas Vias Aéreas/métodos , Hipóxia/prevenção & controle , Apneia Obstrutiva do Sono/terapia , Acetilcolina/uso terapêutico , Adulto , Doenças Cardiovasculares/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitroprussiato/uso terapêutico , Substância P/uso terapêutico , Vasodilatação/fisiologia , Vasodilatadores/uso terapêutico
19.
Thorax ; 63(4): 306-11, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18024535

RESUMO

RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with a 2-3-fold increase in the risk of ischaemic heart disease, stroke and sudden death. The mechanisms responsible for this association are not clear and appear to be independent of smoking history. OBJECTIVE: We test the hypothesis that patients with COPD have increased arterial stiffness and blood pressure in comparison with age and smoking matched controls. METHODS: In a prospective case control study, we recruited 102 patients with COPD and 103 healthy controls matched for age and smoking status. Patients were assessed by clinical history and spirometry, with arterial stiffness and blood pressure determined using radial artery applanation tonometry and sphygmomanometry. RESULTS: Patients with COPD had increased arterial stiffness compared with matched controls, with elevated augmentation pressure (17 (1) vs 14 (1) mm Hg; p = 0.005) and a reduced time to wave reflection (131 (1) vs 137 (2) ms; p = 0.004). These differences were associated with increases in both diastolic (82 (1) vs 78 (1) mm Hg; p = 0.005) and systolic blood pressure (147 (2) vs 132 (2) mm Hg; p<0.001). Serum C reactive protein concentrations were threefold higher in patients (6.1 (0.9) vs 2.3 (0.4) mg/l; p = 0.001). Data are presented as mean (SEM). CONCLUSIONS: Patients with COPD have increased arterial stiffness and blood pressure in comparison with controls matched for age and smoking status. We speculate that increased systemic inflammation and vascular dysfunction could potentially explain the excess cardiovascular morbidity and mortality associated with COPD.


Assuntos
Morte Súbita Cardíaca/etiologia , Isquemia Miocárdica/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Acidente Vascular Cerebral/etiologia , Estudos de Casos e Controles , Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Pulso Arterial , Artéria Radial/fisiologia , Fatores de Risco , Acidente Vascular Cerebral/fisiopatologia , Resistência Vascular/fisiologia
20.
Health Technol Assess ; 11(8): iii-iv, ix-xii, 1-165, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17311735

RESUMO

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.


Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Programas de Rastreamento , Adolescente , Adulto , Infecções por Chlamydia/epidemiologia , Busca de Comunicante , Análise Custo-Benefício , Inglaterra/epidemiologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Programas de Rastreamento/economia , Programas de Rastreamento/psicologia , Programas de Rastreamento/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor Cross-Talk , Inquéritos e Questionários
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