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1.
J Interprof Care ; 37(3): 515-518, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36031805

RESUMO

Interprofessional education (IPE) interventions aiming to promote collaborative competence and improve the delivery of health and social care processes and outcomes continue to evolve. This paper reports on a protocol for an update review that we will conduct to identify and describe how the IPE evidence base has evolved in the last 7 years. We will identify literature through a systematic search of the following electronic databases: Medline, Embase, CINAHL, Education Source, ERIC, and BEI. We will consider all IPE interventions delivered to health professions students and accredited professionals. Peer-reviewed empirical research studies published in any language from June 2014 onwards will be eligible for inclusion. The outcomes of interest are changes in the reaction, attitudes/perceptions, knowledge/skills acquisition, behaviors, organizational practice, and/or benefits to patients. We will perform each task of screening, critical appraisal, data abstraction, and synthesis using at least two members of the review team. The review will enable an update and comprehensive understanding of the IPE evidence base to inform future IPE developments, delivery and evaluation across education and clinical settings.


Assuntos
Educação Interprofissional , Estudantes de Ciências da Saúde , Humanos , Ocupações em Saúde , Relações Interprofissionais , Cuidados Paliativos , Literatura de Revisão como Assunto
2.
Carcinogenesis ; 42(3): 369-377, 2021 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-33300568

RESUMO

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.


Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/genética , Somatomedinas/metabolismo , Adenocarcinoma/patologia , Idoso , Esôfago de Barrett/patologia , Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Fatores de Risco , Transdução de Sinais/genética
3.
Endoscopy ; 52(1): 29-36, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618768

RESUMO

BACKGROUND: The aims of this study were to compare neoplasia detection rates for nontargeted biopsies (Seattle protocol) versus acetic acid-targeted biopsies (Portsmouth protocol) during Barrett's surveillance and to explore feasibility, patient/clinician experience, acceptance, and barriers/enablers to study participation and implementation of the acetic acid technique. METHODS: This was a mixed-methods feasibility study including a pilot multicenter, randomized, crossover trial with qualitative interviews. Patients under Barrett's surveillance with no history of neoplasia were included. Patients underwent two endoscopies, one with each protocol, 8 weeks apart. Outcomes included recruitment and retention rates, neoplasia yield, and number of biopsies. RESULTS: 200 patients were recruited from 6 centers, and 174 (87.0 %) underwent both procedures. Neoplasia prevalence was 4.7 % (9/192). High grade dysplasia and cancer were detected with both protocols. Five low grade dysplasias were detected (two with acetic acid, four with nontargeted biopsies; one lesion was detected with both techniques). A total of 2139 biopsies were taken in the nontargeted arm and 226 in the acetic acid arm. Both patients and clinicians found the acetic acid technique acceptable. Based on these data, a noninferiority, tandem, crossover trial would require an estimated 2828 patients. CONCLUSIONS: We demonstrated the feasibility of performing a crossover endoscopy trial in Barrett's surveillance. Low neoplasia yield makes this design necessary and qualitative results demonstrated patient and clinician acceptance. The reduced numbers of biopsies suggest that the acetic acid technique could result in cost savings, providing the lack of missed pathology can be proven in a fully powered definitive trial.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Ácido Acético , Biópsia , Esofagoscopia , Estudos de Viabilidade , Humanos
4.
Cochrane Database Syst Rev ; 5: CD007334, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32442322

RESUMO

BACKGROUND: Barrett's oesophagus is one of the most common pre-malignant lesions in the world. Currently the mainstay of therapy is surgical management of advanced cancer but this has improved the five-year survival very little since the 1980s. As a consequence, improved survival relies on early detection through endoscopic surveillance programmes. Success of this strategy relies on the fact that late-stage pre-malignant lesions or very early cancers can be cured by intervention. Currently there is considerable controversy over which method is best: that is conventional open surgery or endotherapy (techniques involving endoscopy). OBJECTIVES: We used data from randomised controlled trials (RCTs) to examine the effectiveness of endotherapies compared with surgery in people with Barrett's oesophagus, those with early neoplasias (defined as high-grade dysplasia (HGD) and those with early cancer (defined as carcinoma in-situ, superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm (T1-b)). SEARCH METHODS: We used the Cochrane highly sensitive search strategy to identify RCTs in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, EBMR, Controlled Trials mRCT and ISRCTN, and LILACS, in July and August 2008. The searches were updated in 2009 and again in April 2012. SELECTION CRITERIA: Types of studies: RCTs comparing endotherapies with surgery in the treatment of high-grade dysplasia or early cancer. All cellular types of cancer were included (i.e. adenocarcinomas, squamous cell carcinomas and more unusual types) but will be discussed separately. TYPES OF PARTICIPANTS: patients of any age and either gender with a histologically confirmed diagnosis of early neoplasia (HGD and early cancer) in Barrett's or squamous lined oesophagus. Types of interventions; endotherapies (the intervention) compared with surgery (the control), all with curative intent. DATA COLLECTION AND ANALYSIS: Reports of studies that meet the inclusion criteria for this review would have been analysed using the methods detailed in Appendix 9. MAIN RESULTS: We did not identify any studies that met the inclusion criteria. In total we excluded 13 studies that were not RCTs but that compared surgery and endotherapies. AUTHORS' CONCLUSIONS: This Cochrane review has indicated that there are no RCTs to compare management options in this vital area, therefore trials should be undertaken as a matter of urgency. The problems with such randomised methods are standardising surgery and endotherapies in all sites, standardising histopathology in all centres, assessing which patients are fit or unfit for surgery and making sure there are relevant outcomes for the study (i.e. long-term survival (over five or more years)) and no progression of HGD.


Assuntos
Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/métodos , Lesões Pré-Cancerosas/cirurgia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Humanos , Lesões Pré-Cancerosas/patologia
5.
Lancet ; 392(10145): 400-408, 2018 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-30057104

RESUMO

BACKGROUND: Oesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus. METHODS: The Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77. FINDINGS: Between March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2-9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01-1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98-1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01-1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14-2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events. INTERPRETATION: High-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus. FUNDING: Cancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Esôfago de Barrett/tratamento farmacológico , Esomeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Esomeprazol/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Adulto Jovem
6.
Gastrointest Endosc ; 89(4): 680-689, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30076843

RESUMO

BACKGROUND AND AIMS: Endoscopic resection (ER) is safe and effective for Barrett's esophagus (BE) containing high-grade dysplasia (HGD) or mucosal adenocarcinoma (T1A). The risk of metachronous neoplasia is reduced by ablation of residual BE by using radiofrequency ablation (RFA) or argon plasma coagulation (APC). These have not been compared directly. We aimed to recruit up to 100 patients with BE and HGD or T1A confirmed by ER over 1 year in 6 centers in a randomized pilot study. METHODS: Randomization was 1:1 to RFA or APC (4 treatments allowed at 2-month intervals). Recruitment, retention, dysplasia clearance, clearance of benign BE, adverse events, healthcare costs, and quality of life by using EQ-5D, EORTC QLQ-C30, or OES18 were assessed up to the end of the trial at 12 months. RESULTS: Of 171 patients screened, 76 were randomized to RFA (n = 36) or APC (n = 40). The mean age was 69.7 years, and 82% were male. BE was <5 cm (n = 27), 5 to 10 cm (n = 45), and >10 cm (n = 4). Sixty-five patients completed the trial. At 12 months, dysplasia clearance was RFA 79.4% and APC 83.8% (odds ratio [OR] 0.7; 95% confidence interval [CI], 0.2-2.6); BE clearance was RFA 55.8%, and APC 48.3% (OR 1.4; 95% CI, 0.5-3.6). A total of 6.1% (RFA) and 13.3% (APC) had buried BE glands. Adverse events (including stricture rate after starting RFA 3/36 [8.3%] and APC 3/37 [8.1%]) and quality of life scores were similar, but RFA cost $27491 more per case than APC. CONCLUSION: This pilot study suggests similar efficacy and safety but a cost difference favoring APC. A fully powered non-inferiority trial is appropriate to confirm these findings. (Clinical trial registration number: NCT01733719.).


Assuntos
Adenocarcinoma/cirurgia , Coagulação com Plasma de Argônio , Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Ablação por Radiofrequência , Adenocarcinoma/patologia , Idoso , Coagulação com Plasma de Argônio/efeitos adversos , Coagulação com Plasma de Argônio/economia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/patologia , Estenose Esofágica/etiologia , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Projetos Piloto , Qualidade de Vida , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/economia , Resultado do Tratamento
7.
Gut ; 66(10): 1739-1747, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27486097

RESUMO

OBJECTIVE: Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA. DESIGN: We used data from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207 controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling, oxidative stress, human leucocyte antigen and nuclear factor-κB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. RESULTS: We identified a significant signal for the COX pathway in relation to BE risk (p=0.0059, false discovery rate q=0.03), and in gene-level analyses found an association with microsomal glutathione-S-transferase 1 (MGST1); (p=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Four of these were subsequently confirmed (p<5.5×10-5) in a meta-analysis encompassing an independent set of 1851 BE cases and 3496 controls, and are known strong expression quantitative trait loci for MGST1. Three such variants were associated with similar elevations in OA risk. CONCLUSIONS: This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/OA and suggests that variants in MGST1 influence disease susceptibility.


Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Neoplasias Esofágicas/genética , Mutação em Linhagem Germinativa , Glutationa Transferase/genética , Idoso , Citocinas/metabolismo , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos HLA/metabolismo , Humanos , Inflamação/genética , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Análise de Componente Principal , Prostaglandina-Endoperóxido Sintases/metabolismo , Fatores de Risco , Transdução de Sinais/genética
8.
Endoscopy ; 49(2): 121-129, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28103621

RESUMO

Background and study aims Acetic acid chromoendoscopy (AAC) enhances the ability to correctly identify Barrett's neoplasia, and is increasingly used by both expert and nonexpert endoscopists. Despite its increasing use, there is no validated training strategy to achieve competence. The aims of our study were to develop a validated training tool in AAC-assisted lesion recognition, to assess endoscopists' baseline knowledge of AAC-assisted lesion recognition, and to evaluate the efficacy and impact of this training tool. Methods A validated assessment of 40 images and 20 videos was developed. A total of 13 endoscopists with experience of Barrett's endoscopy but no formal training in AAC were recruited to the study. Participants underwent: baseline assessment 1, online training, assessment 2, interactive seminar, assessment 3. Results Baseline assessment demonstrated a sensitivity of 83 % and a negative predictive value (NPV) of 83 %. The online training intervention significantly improved sensitivity to 95 % and NPV to 94 % (P < 0.01). Further improvement was seen after a 1-day interactive seminar including live cases, with sensitivity increasing to 98 % and NPV to 97 %. Conclusions The data demonstrate the need for training in AAC-assisted lesion recognition as baseline performance, even by Barrett's experts, was poor. The online training and testing tool for AAC for Barrett's neoplasia was successfully developed and validated. The training intervention improved performance of endoscopists to meet ASGE PIVI standards. The training tool increases the endoscopist's degree of confidence in the use of AAC. The training tool also leads to shift in attitudes of endoscopists from Seattle protocol towards AAC-guided biopsy protocol for Barrett's surveillance.


Assuntos
Ácido Acético/administração & dosagem , Esôfago de Barrett/patologia , Esofagoscopia/educação , Esofagoscopia/normas , Indicadores e Reagentes/administração & dosagem , Biópsia/métodos , Competência Clínica , Esofagoscopia/métodos , Humanos , Desenvolvimento de Programas
9.
Future Oncol ; 13(26): 2363-2382, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29121775

RESUMO

To improve outcomes for patients with cancer, in terms of both survival and a reduction in the morbidity and mortality that results from surgical resection and treatment, there are two main areas that require improvement. Accurate early diagnosis of the cancer, at a stage where curative and, ideally, minimally invasive treatment is achievable, is desired as well as identification of tumor margins, lymphatic and distant disease, enabling complete, but not unnecessarily extensive, resection. Optical imaging is making progress in achieving these aims. This review discusses the principles of optical imaging, focusing on fluorescence and spectroscopy, and the current research that is underway in GI tract carcinomas.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/cirurgia , Imagem Óptica , Cirurgia Assistida por Computador , Animais , Meios de Contraste , Diagnóstico Diferencial , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos , Imagem Óptica/métodos , Cirurgia Assistida por Computador/métodos
10.
J Interprof Care ; 31(4): 529-532, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28486026

RESUMO

Interprofessional collaborative practice is widely documented as a strategy to improve quality of healthcare. To develop collaborative practitioners, educators need interprofessional curricula with proper cognitive demand and methods of delivery and assessment. The University of the Western Cape in South Africa incorporated an Interprofessional Core Courses Curriculum for all undergraduate students enrolled in the health sciences faculty. The objective of this study was to analyse the curriculum content to determine its cognitive rigor. Cognitive rigor can be measured by the quantitative content analysis method using the Depth of Knowledge (DOK) framework. This approach tests whether the rigor of instructional activities and assessments is aligned with learning outcomes. The curriculum content evaluated in this study found that assessment activities were less demanding than instructional activities and infrequently aligned with learning outcomes. This approach may be useful to other educators seeking to evaluate and plan interprofessional curriculum.


Assuntos
Currículo , Ocupações em Saúde/educação , Relações Interprofissionais , Aprendizagem , Comportamento Cooperativo , Promoção da Saúde/organização & administração , Humanos , Atenção Primária à Saúde/organização & administração , Avaliação de Programas e Projetos de Saúde , África do Sul
11.
Lancet Oncol ; 17(10): 1363-1373, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27527254

RESUMO

BACKGROUND: Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barrett's oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barrett's oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barrett's oesophagus and oesophageal adenocarcinoma. METHODS: We did a meta-analysis of all genome-wide association studies of Barrett's oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10-8). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches-including functional annotation databases and gene-based and pathway-based methods-to identify pathophysiologically relevant cellular mechanisms. FINDINGS: Our sample comprised 6167 patients with Barrett's oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barrett's oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10-10), MSRA (rs17749155; p=5·2 × 10-10), LINC00208 and BLK (rs10108511; p=2·1 × 10-9), KHDRBS2 (rs62423175; p=3·0 × 10-9), TPPP and CEP72 (rs9918259; p=3·2 × 10-9), TMOD1 (rs7852462; p=1·5 × 10-8), SATB2 (rs139606545; p=2·0 × 10-8), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10-8). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10-8) and was independent of Barrett's oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10-6) belonged to muscle cell differentiation and to mesenchyme development and differentiation. INTERPRETATION: Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barrett's oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barrett's oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barrett's oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. FUNDING: US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.


Assuntos
Adenocarcinoma/genética , Esôfago de Barrett/genética , Neoplasias Esofágicas/genética , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , Risco
12.
Gastroenterology ; 148(2): 367-78, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25447851

RESUMO

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.


Assuntos
Esôfago de Barrett/genética , Proteínas Morfogenéticas Ósseas/genética , Predisposição Genética para Doença , Fatores de Diferenciação de Crescimento/genética , Polimorfismo de Nucleotídeo Único , Proteínas com Domínio T/genética , Esôfago de Barrett/etiologia , Neoplasias Esofágicas/genética , Estudo de Associação Genômica Ampla , Humanos , Risco
13.
Hum Resour Health ; 14(1): 49, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27523088

RESUMO

Across the globe, a "fit for purpose" health professional workforce is needed to meet health needs and challenges while capitalizing on existing resources and strengths of communities. However, the socio-economic impact of educating and deploying a fit for purpose health workforce can be challenging to evaluate. In this paper, we provide a brief overview of six promising strategies and interventions that provide context-relevant health professional education within the health system. The strategies focused on in the paper are:1. Distributed community-engaged learning: Education occurs in or near underserved communities using a variety of educational modalities including distance learning. Communities served provide input into and actively participate in the education process.2. Curriculum aligned with health needs: The health and social needs of targeted communities guide education, research and service programmes.3. Fit for purpose workers: Education and career tracks are designed to meet the needs of the communities served. This includes cadres such as community health workers, accelerated medically trained clinicians and extended generalists.4. Gender and social empowerment: Ensuring a diverse workforce that includes women having equal opportunity in education and are supported in their delivery of health services.5. Interprofessional training: Teaching the knowledge, skills and attitudes for working in effective teams across professions.6. South-south and north-south partnerships: Sharing of best practices and resources within and between countries.In sum, the sharing of resources, the development of a diverse and interprofessional workforce, the advancement of primary care and a strong community focus all contribute to a world where transformational education improves community health and maximizes the social and economic return on investment.


Assuntos
Serviços de Saúde Comunitária , Educação Profissionalizante/métodos , Pessoal de Saúde/educação , Características de Residência , Agentes Comunitários de Saúde , Currículo , Recursos em Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Comunicação Interdisciplinar , Cooperação Internacional , Área Carente de Assistência Médica , Médicos , Atenção Primária à Saúde , Competência Profissional , Fatores Socioeconômicos , Direitos da Mulher , Recursos Humanos
14.
Med Teach ; 38(7): 656-68, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27146438

RESUMO

BACKGROUND: Interprofessional education (IPE) aims to bring together different professionals to learn with, from, and about one another in order to collaborate more effectively in the delivery of safe, high-quality care for patients/clients. Given its potential for improving collaboration and care delivery, there have been repeated calls for the wider-scale implementation of IPE across education and clinical settings. Increasingly, a range of IPE initiatives are being implemented and evaluated which are adding to the growth of evidence for this form of education. AIM: The overall aim of this review is to update a previous BEME review published in 2007. In doing so, this update sought to synthesize the evolving nature of the IPE evidence. METHODS: Medline, CINAHL, BEI, and ASSIA were searched from May 2005 to June 2014. Also, journal hand searches were undertaken. All potential abstracts and papers were screened by pairs of reviewers to determine inclusion. All included papers were assessed for methodological quality and those deemed as "high quality" were included. The presage-process-product (3P) model and a modified Kirkpatrick model were employed to analyze and synthesize the included studies. RESULTS: Twenty-five new IPE studies were included in this update. These studies were added to the 21 studies from the previous review to form a complete data set of 46 high-quality IPE studies. In relation to the 3P model, overall the updated review found that most of the presage and process factors identified from the previous review were further supported in the newer studies. In regard to the products (outcomes) reported, the results from this review continue to show far more positive than neutral or mixed outcomes reported in the included studies. Based on the modified Kirkpatrick model, the included studies suggest that learners respond well to IPE, their attitudes and perceptions of one another improve, and they report increases in collaborative knowledge and skills. There is more limited, but growing, evidence related to changes in behavior, organizational practice, and benefits to patients/clients. CONCLUSIONS: This updated review found that key context (presage) and process factors reported in the previous review continue to have resonance on the delivery of IPE. In addition, the newer studies have provided further evidence for the effects on IPE related to a number of different outcomes. Based on these conclusions, a series of key implications for the development of IPE are offered.


Assuntos
Atenção à Saúde/organização & administração , Pessoal de Saúde/educação , Relações Interprofissionais , Atitude do Pessoal de Saúde , Comportamento , Comportamento Cooperativo , Atenção à Saúde/normas , Docentes/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Aprendizagem , Qualidade da Assistência à Saúde
15.
J Interprof Care ; 30(6): 747-753, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27797631

RESUMO

Whilst interest in interprofessional learning (IPL) in practice contexts has grown in recent years, the complexities involved have led many universities to rely on IPL in the classroom, online, and/or simulated contexts. Curtin University's Faculty of Health Sciences has successfully implemented a multi-award winning, large-scale Interprofessional Practice Programme. This programme, which began with five small pilots in 2009, provides team-based interprofessional practice placements for over 550 students from nine professions per annum. Drawing on both the literature and Curtin University's experience, this Interprofessional Education and Practice Guide aims to assist university and practice-based educators to "weigh the case" for introducing team-based interprofessional placements. The key lessons learned at Curtin University are identified to offer guidance to others towards establishing a similar programme for students during their prequalifying courses in health, social care, and related fields.


Assuntos
Docentes , Relações Interprofissionais , Universidades , Humanos
17.
Am J Gastroenterol ; 110(5): 662-82; quiz 683, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25869390

RESUMO

OBJECTIVES: Barrett's esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research.


Assuntos
Esôfago de Barrett/patologia , Esôfago de Barrett/terapia , Biomarcadores Tumorais/análise , Consenso , Técnica Delphi , Neoplasias Esofágicas/patologia , Esôfago/patologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/terapia , Técnicas de Ablação , Fatores Etários , Biópsia , Metilação de DNA , Esofagoscopia , Humanos , Lesões Pré-Cancerosas/química , Lesões Pré-Cancerosas/genética , Fatores de Risco , Fatores Sexuais , Conduta Expectante/métodos
19.
Analyst ; 140(7): 2215-23, 2015 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-25594077

RESUMO

We report results from a study utilizing infrared spectral cytopathology (SCP) to detect abnormalities in exfoliated esophageal cells. SCP has been developed over the past decade as an ancillary tool to classical cytopathology. In SCP, the biochemical composition of individual cells is probed by collecting infrared absorption spectra from each individual, unstained cell, and correlating the observed spectral patterns, and the variations therein, against classical diagnostic methods to obtain an objective, machine-based classification of cells. In the past, SCP has been applied to the analysis and classification of cells exfoliated from the cervix and the oral cavity. In these studies, it was established that SCP can distinguish normal and abnormal cell types. Furthermore, SCP can differentiate between truly normal cells, and cells with normal morphology from the vicinity of abnormalities. Thus, SCP may be a valuable tool for the screening of early stages of dysplasia and pre-cancer.


Assuntos
Esôfago/citologia , Esôfago/patologia , Imagem Óptica , Esôfago de Barrett/diagnóstico , Esôfago de Barrett/patologia , Humanos , Espectrofotometria Infravermelho
20.
Surg Endosc ; 29(2): 417-24, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25007975

RESUMO

BACKGROUND: The uptake of minimally invasive oesophagectomy (MIO) in the UK has increased dramatically in recent years. Post-oesophagectomy diaphragmatic hernias (PODHs) are rare, but may be influenced by the type of approach to resection. The aim of this study was to compare the incidence of symptomatic PODH following open and MIO in a UK specialist centre. METHODS: Consecutive patients undergoing oesophagectomy for malignant disease between 1996 and 2012 were included. A standardised, radical approach to the abdominal phase was employed, irrespective of the type of procedure undertaken. Patient demographics, details of surgery and post-operative complications were collected from patient records and a prospective database. RESULTS: A total of 273 oesophagectomies were performed (205 open; 68 MIO). There were 62 hybrid MIOs (laparoscopic abdomen and thoracotomy) and six total MIOs. Seven patients required conversion and were analysed as part of the open cohort. Nine patients (13.2 %) developed a PODH in the MIO cohort compared with two patients (1.0 %) in the open cohort, (p < 0.001). Five patients developed hernias in the early post-operative period (days 2-10): all following MIO. Both PODHs in the open cohort occurred following transhiatal oesophagectomy. All PODHs were symptomatic and required surgical repair. CT thorax confirmed the diagnosis in 10 patients. Seven hernias were repaired laparoscopically, including two cases in the early post-operative period. PODHs were repaired using the following techniques: suture (n = 6), mesh reinforcement (n = 4) and omentopexy to the anterior abdominal wall without hiatal closure (n = 1). There were two recurrences (18 %). CONCLUSIONS: The incidence of symptomatic PODH may be higher following MIO compared to open surgery. The reasons for this are unclear and may not be completely explained by the reduction in adhesion formation. Strategies such as fixation of the conduit to the diaphragm and omentopexy to the abdominal wall may reduce the incidence of herniation.


Assuntos
Esofagectomia/efeitos adversos , Hérnia Diafragmática/etiologia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias , Toracotomia/efeitos adversos , Idoso , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Feminino , Seguimentos , Hérnia Diafragmática/diagnóstico , Hérnia Diafragmática/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Reino Unido/epidemiologia
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