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INTRODUCTION: Participation in bowel cancer screening is lower in regions where there is high ethnic diversity and/or socioeconomic deprivation. Interventions, such as text message reminders and patient navigation (PN), have the potential to increase participation in these areas. As such, there is interest in the comparative effectiveness of these interventions to increase bowel cancer screening participation, as well as their relative cost-effectiveness. METHODS AND ANALYSIS: This study will use a three-arm randomised controlled trial design to compare the effectiveness and cost-effectiveness of text message reminders and PN to increase the uptake of bowel cancer screening in London. Participants will be individuals who have not returned a completed faecal immunochemical test kit within 13 weeks of receiving a routine invitation from the London bowel cancer screening hub. Participants will be randomised (in a 1:1:1 ratio) to receive either (1) usual care (ie, 'no intervention'), (2) a text message reminder at 13 weeks, followed by repeated text message reminders at 15, 17 and 19 weeks (in the event of non-response) or (3) a text message reminder at 13 weeks, followed by PN telephone calls at 15, 17 and 19 weeks in the event of non-response. The primary endpoint will be participation in bowel cancer screening, defined as 'the return of a completed kit by week 24'. Statistical analysis will use multivariate logistic regression and will incorporate pairwise comparisons of all three groups, adjusted for multiple testing. ETHICS AND DISSEMINATION: Approvals to conduct the research have been obtained from University College London's Joint Research Office (Ref: 150666), the Screening Research, Innovation and Development Advisory Committee ('RIDAC', Ref: 2223 014 BCSP Kerrison), the Health Research Authority (Ref: 22/WM/0212) and the Confidentiality Advisory Group (Ref: 22/CAG/0140). Results will be conveyed to stakeholders, notably those managing the screening programme and published in peer-reviewed journals/presented at academic conferences. TRIAL REGISTRATION NUMBER: ISRCTN17245519.
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Neoplasias Colorretais , Análise Custo-Benefício , Detecção Precoce de Câncer , Sangue Oculto , Navegação de Pacientes , Sistemas de Alerta , Telefone , Envio de Mensagens de Texto , Humanos , Londres , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/economia , Neoplasias Colorretais/diagnóstico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Current regulatory guidelines on drug-food interactions recommend an early assessment of food effect to inform clinical dosing instructions, as well as a pivotal food effect study on the to-be-marketed formulation if different from that used in earlier trials. Study waivers are currently only granted for BCS class 1 drugs. Thus, repeated food effect studies are prevalent in clinical development, with the initial evaluation conducted as early as the first-in-human studies. Information on repeated food effect studies is not common in the public domain. The goal of the work presented in this manuscript from the Food Effect PBPK IQ Working Group was to compile a dataset on these studies across pharmaceutical companies and provide recommendations on their conduct. Based on 54 studies collected, we report that most of the repeat food effect studies do not result in meaningful differences in the assessment of the food effect. Seldom changes observed were more than twofold. There was no clear relationship between the change in food effect and the formulation change, indicating that in most cases, once a compound is formulated appropriately within a specific formulation technology, the food effect is primarily driven by inherent compound properties. Representative examples of PBPK models demonstrate that following appropriate validation of the model with the initial food effect study, the models can be applied to future formulations. We recommend that repeat food effect studies should be approached on a case-by-case basis taking into account the totality of the evidence including the use of PBPK modeling.
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Interações Alimento-Droga , Modelos Biológicos , Humanos , Solubilidade , Simulação por Computador , AlimentosRESUMO
Artificial intelligence (AI) systems can now reliably assess surgeon skills through videos of intraoperative surgical activity. With such systems informing future high-stakes decisions such as whether to credential surgeons and grant them the privilege to operate on patients, it is critical that they treat all surgeons fairly. However, it remains an open question whether surgical AI systems exhibit bias against surgeon sub-cohorts, and, if so, whether such bias can be mitigated. Here, we examine and mitigate the bias exhibited by a family of surgical AI systems-SAIS-deployed on videos of robotic surgeries from three geographically-diverse hospitals (USA and EU). We show that SAIS exhibits an underskilling bias, erroneously downgrading surgical performance, and an overskilling bias, erroneously upgrading surgical performance, at different rates across surgeon sub-cohorts. To mitigate such bias, we leverage a strategy -TWIX-which teaches an AI system to provide a visual explanation for its skill assessment that otherwise would have been provided by human experts. We show that whereas baseline strategies inconsistently mitigate algorithmic bias, TWIX can effectively mitigate the underskilling and overskilling bias while simultaneously improving the performance of these AI systems across hospitals. We discovered that these findings carry over to the training environment where we assess medical students' skills today. Our study is a critical prerequisite to the eventual implementation of AI-augmented global surgeon credentialing programs, ensuring that all surgeons are treated fairly.
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Purpose: To examine the association between the quality of neurovascular bundle dissection and urinary continence recovery after robotic-assisted radical prostatectomy. Materials and Methods: Patients who underwent RARPs from 2016 to 2018 in two institutions with ≥1-year postoperative follow-up were included. The primary outcomes were time to urinary continence recovery. Surgical videos were independently assessed by 3 blinded raters using the validated Dissection Assessment for Robotic Technique (DART) tool after standardized training. Cox regression was used to test the association between DART scores and urinary continence recovery while adjusting for relevant patient features. Results: 121 RARP performed by 23 surgeons with various experience levels were included. The median follow-up was 24 months (95% CI 20 - 28 months). The median time to continence recovery was 7.3 months (95% CI 4.7 - 9.8 months). After adjusting for patient age, higher scores of certain DART domains, specifically tissue retraction and efficiency, were significantly associated with increased odds of continence recovery (p<0.05). Conclusions: Technical skill scores of neurovascular bundle dissection vary among surgeons and correlate with urinary continence recovery. Unveiling the specific robotic dissection skillsets which impact patient outcomes has the potential to focus surgical training.
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Inadequate definition of key terms and their relationships generates significant communication and analytical problems in environmental planning. In this work, we evaluate an ontological framework for environmental planning designed to combat these problems. After outlining the framework and issues addressed, we describe its evaluation by a group of experts representing a range of expertise and institutions. Experts rated their level of agreement with 12 propositions concerning the definitions and models underpinning the framework. These propositions, in turn, were used to assess three assumptions regarding the expected effectiveness of the framework and its contribution to addressing the abovementioned planning problems. In addition to point-based best estimates of their agreement with propositions, expert ratings were also captured on a continuous interval-valued scale. The use of intervals addresses the challenge of measuring and modelling uncertainty associated with complex assessments such as those provided by experts. Combined with written anonymous expert comments, these data provide multiple perspectives on the level of support for the approach. We conclude that the framework can complement existing planning approaches and strengthen key definitions and related models, thus helping avoid communication and analytical problems in environmental planning. Finally, experts highlighted areas that require further development, and we provide recommendations for improving the framework.
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Meio Ambiente , Técnicas de Planejamento , Comunicação , Humanos , Terminologia como AssuntoRESUMO
OBJECTIVE: To assess suitability of Comprehensive Complication Index (CCI®) vs. Clavien-Dindo classification (CDC) to capture 30-day morbidity after robot-assisted radical cystectomy (RARC). MATERIALS AND METHODS: A total of 128 patients with bladder cancer (BCa) undergoing intracorporeal RARC with pelvic lymph node dissection between 2015 and 2021 were included in a retrospective bi-institutional study, which adhered to standardized reporting criteria. Thirty-day complications were captured according to a procedure-specific catalog. Each complication was graded by the CDC and the CCI®. Multivariable linear regression (MVA) was used to identify predictors of higher morbidity. RESULTS: 381 complications were identified in 118 patients (92%). 55 (43%), 43 (34%), and 20 (16%) suffered from CDC grade I-II, IIIa, and ≥ IIIb complications, respectively. 16 (13%), 27 (21%), and 2 patients (1.6%) were reoperated, readmitted, and died within 30 days, respectively. 31 patients (24%) were upgraded to most severe complication (CCI® ≥ 33.7) when calculating morbidity burden compared to corresponding CDC grade accounting only for the highest complication. In MVA, only age was a positive estimate (0.44; 95% CI = 0.03-0.86; p = 0.04) for increased cumulative morbidity. CONCLUSION: The CCI® estimates of 30-day morbidity after RARC were substantially higher compared to CDC alone. These measurements are a prerequisite to tailor patient counseling regarding surgical approach, urinary diversion, and comparability of results between institutions.
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Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias da Bexiga Urinária , Derivação Urinária , Cistectomia/efeitos adversos , Cistectomia/métodos , Humanos , Morbidade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Derivação Urinária/métodosRESUMO
The quality of life (QoL) of men with optimal outcomes after robot-assisted radical prostatectomy (RARP) is largely unexplored. Thus we assessed meaningful changes of QoL measured with the EORTC QLQ-C30 24 months after RARP according to postsurgical Cancer of the Prostate Risk Assessment score (CAPRA-S) and pentafecta criteria. 2871 prostate cancer (PCa) patients with completed EORTC QLQ-C30 were stratified according to CAPRA-S, pentafecta (erectile function recovery, urinary continence recovery, biochemical-recurrence-free survival (BFS), negative surgical margins) and 90-day Clavien-Dindo-complications (CDC) ≤ 3a. Multivariable logistic regression analyses (LRM) aimed to predict improvement of EORTC QoL. Mean preoperative QoL values did not significantly differ between CAPRA-S low- (LR) vs. high-risk (HR, 75.7 vs. 75.2; p = 0.7) and pentafecta vs. non-pentafecta groups (75.6 vs. 75.2; p = 0.6). After RARP, stable QoL rates for CAPRA-S LR vs. HR and pentafecta were 30, 26 and 30%, respectively. Corresponding improved QoL rates were 44, 32 and 47%. In LRM, CAPRA-S and pentafecta criteria were independent predictors of improved QoL. We conclude that most favourable combined outcomes after RARP might confer stable or even improved QoL but up to one third of patients might experience deterioration. This warrants further investigation how to capture the underlying cause and to address and potentially solve these perceived negative effects despite successful RARP.
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Prostatectomia , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/efeitos adversos , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de Risco , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
â¢Behavioral economic-based interventions have been suggested to increase uptake in CRC screening programmes.â¢This study tested the effectiveness of six behavioral economic-based messages in two field trials.â¢None of the messages increased screening participation.
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BACKGROUND: To date, research exploring the public's awareness of bowel cancer has taken place with predominantly white populations. To enhance our understanding of how bowel cancer awareness varies between ethnic groups, and inform the development of targeted interventions, we conducted a questionnaire study across three ethnically diverse regions in Greater London, England. METHODS: Data were collected using an adapted version of the bowel cancer awareness measure. Eligible adults were individuals, aged 60+ years, who were eligible for screening. Participants were recruited and surveyed, verbally, by staff working at 40 community pharmacies in Northwest London, the Harrow Somali association, and St. Mark's Bowel Cancer Screening Centre. Associations between risk factor, symptom and screening awareness scores and ethnicity were assessed using multivariate regression. RESULTS: 1013 adults, aged 60+ years, completed the questionnaire; half were of a Black, Asian or Minority ethnic group background (n = 507; 50.0%). Participants recognised a mean average of 4.27 of 9 symptoms and 3.99 of 10 risk factors. Symptom awareness was significantly lower among all ethnic minority groups (all p's < 0.05), while risk factor awareness was lower for Afro-Caribbean and Somali adults, specifically (both p's < 0.05). One in three adults (n = 722; 29.7%) did not know there is a Bowel Cancer Screening Programme. Bowel screening awareness was particularly low among Afro-Caribbean and Somali adults (both p's < 0.05). CONCLUSION: Awareness of bowel cancer symptoms, risk factors and screening varies by ethnicity. Interventions should be targeted towards specific groups for whom awareness of screening and risk factors is low.
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Neoplasias Colorretais , Etnicidade , Idoso , Neoplasias Colorretais/diagnóstico , Inglaterra/epidemiologia , Humanos , Londres/epidemiologia , Pessoa de Meia-Idade , Grupos Minoritários , Inquéritos e QuestionáriosRESUMO
Colonoscopy is the gold standard test in the diagnosis of colorectal cancer. Despite this, many people across the world decline the procedure when invited for screening, surveillance or diagnostic evaluation. The aim of this review was to characterise the barriers and facilitators of colonoscopy use described in the qualitative literature. We searched PubMed and PsychInfo for studies that explored barriers and facilitators of colonoscopy use. To determine the eligibility of studies, we first reviewed titles, then abstracts, and finally the full paper. We started with a narrow search, which we expanded successively, until the number of new publications eligible after abstract review was <1% of the total number of publications identified. Papers were eligible if they: 1) focussed on an adult population, 2) used a qualitative research design and, 3) described at least one patient-related theme regarding colonoscopy use. We then extracted qualitative data from eligible papers and analysed using thematic synthesis. Fifty-seven studies met the inclusion criteria. Most explored barriers and facilitators of screening colonoscopy (n=53, 93.0%) and were conducted in the USA (n=48, 84.2%). Key psychological and social factors included: 'fear of pain and discomfort', 'concerns about doing the bowel preparation', and whether the test was recommended by the patient's physician. Key practical factors included cost, and whether colonoscopy was covered by the patient's healthcare insurance. Studies mostly focussed on screening colonoscopy in the USA, where there is no universal healthcare coverage. To better understand the barriers and facilitators in other contexts, further research is needed.
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Colonoscopia , Programas de Rastreamento , Adulto , Atenção à Saúde , Humanos , Pesquisa QualitativaRESUMO
OBJECTIVE: Coronavirus disease-19 (COVID-19) pandemic caused delays in definitive treatment of patients with prostate cancer. Beyond the immediate delay a backlog for future patients is expected. The objective of this work is to develop guidance on criteria for prioritisation of surgery and reconfiguring management pathways for patients with non-metastatic prostate cancer who opt for surgical treatment. A second aim was to identify the infection prevention and control (IPC) measures to achieve a low likelihood of coronavirus disease 2019 (COVID-19) hazard if radical prostatectomy (RP) was to be carried out during the outbreak and whilst the disease is endemic. METHODS: We conducted an accelerated consensus process and systematic review of the evidence on COVID-19 and reviewed international guidance on prostate cancer. These were presented to an international prostate cancer expert panel (n = 34) through an online meeting. The consensus process underwent three rounds of survey in total. Additions to the second- and third-round surveys were formulated based on the answers and comments from the previous rounds. The Consensus opinion was defined as ≥80% agreement and this was used to reconfigure the prostate cancer pathways. RESULTS: Evidence on the delayed management of patients with prostate cancer is scarce. There was 100% agreement that prostate cancer pathways should be reconfigured and measures developed to prevent nosocomial COVID-19 for patients treated surgically. Consensus was reached on prioritisation criteria of patients for surgery and management pathways for those who have delayed treatment. IPC measures to achieve a low likelihood of nosocomial COVID-19 were coined as 'COVID-19 cold' sites. CONCLUSION: Reconfiguring management pathways for patients with prostate cancer is recommended if significant delay (>3-6 months) in surgical management is unavoidable. The mapped pathways provide guidance for such patients. The IPC processes proposed provide a framework for providing RP within an environment with low COVID-19 risk during the outbreak or when the disease remains endemic. The broader concepts could be adapted to other indications beyond prostate cancer surgery.
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COVID-19/epidemiologia , Procedimentos Clínicos , Pandemias , Prostatectomia , Neoplasias da Próstata/cirurgia , Técnica Delphi , Alocação de Recursos para a Atenção à Saúde , Humanos , Controle de Infecções , Masculino , SARS-CoV-2 , Tempo para o TratamentoRESUMO
An elevated concentration of fibrinogen in blood is a significant risk factor during many pathological diseases, as it leads to an increase in red blood cells (RBC) aggregation, resulting in hemorheological disorders. Despite the biomedical importance, the mechanisms of fibrinogen-induced RBC aggregation are still debatable. One of the discussed models is the non-specific adsorption of fibrinogen macromolecules onto the RBC membrane, leading to the cells bridging in aggregates. However, recent works point to the specific character of the interaction between fibrinogen and the RBC membrane. Fibrinogen is the major physiological ligand of glycoproteins receptors IIbIIIa (GPIIbIIIa or αIIßß3 or CD41/CD61). Inhibitors of GPIIbIIIa are widely used in clinics for the treatment of various cardiovascular diseases as antiplatelets agents preventing the platelets' aggregation. However, the effects of GPIIbIIIa inhibition on RBC aggregation are not sufficiently well studied. The objective of the present work was the complex multimodal in vitro study of the interaction between fibrinogen and the RBC membrane, revealing the role of GPIIbIIIa in the specificity of binding of fibrinogen by the RBC membrane and its involvement in the cells' aggregation process. We demonstrate that GPIIbIIIa inhibition leads to a significant decrease in the adsorption of fibrinogen macromolecules onto the membrane, resulting in the reduction of RBC aggregation. We show that the mechanisms underlying these effects are governed by a decrease in the bridging components of RBC aggregation forces.
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Eritrócitos/patologia , Fibrinogênio/isolamento & purificação , Glicoproteínas/isolamento & purificação , Substâncias Macromoleculares/isolamento & purificação , Agregação Eritrocítica/genética , Eritrócitos/química , Eritrócitos/metabolismo , Fibrinogênio/genética , Citometria de Fluxo , Glicoforinas , Glicoproteínas/química , Glicoproteínas/ultraestrutura , Humanos , Lasers , Substâncias Macromoleculares/química , Substâncias Macromoleculares/ultraestrutura , Microfluídica/métodos , Pinças Ópticas , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologiaRESUMO
INTRODUCTION: After the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries. MATERIAL AND METHODS: An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses. RESULTS: 27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers-however, the number of COVID-19 patients and urologists did not reach double digits. CONCLUSION: The German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low.
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Infecções por Coronavirus/patologia , Pessoal de Saúde/psicologia , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Alemanha/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Internet , Pandemias , Equipamento de Proteção Individual , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Procedimentos Cirúrgicos Robóticos , SARS-CoV-2 , Inquéritos e Questionários , Doenças Urológicas/cirurgia , Urologistas/psicologiaRESUMO
BACKGROUND: In the UK, cancer-screening invitations are mailed with information styled in a standard, didactic way to allow for informed choice. Information processing theory suggests this "standard style" could be more appealing to people who prefer deliberative thinking. People less likely to engage in deliberative thinking may be disenfranchised by the design of current standard-style information. PURPOSE: To examine the distribution of preference for deliberative thinking across demographic groups (Study 1) and explore associations between preference for deliberative thinking and perceived usefulness of standard- and narrative-style screening information (Study 2). METHODS: In Study 1, adults aged 45-59 (n = 4,241) were mailed a questionnaire via primary care assessing preference for deliberative thinking and demographic characteristics. In Study 2, a separate cohort of adults aged 45-59 (n = 2,058) were mailed standard- and narrative-style leaflets and a questionnaire assessing demographic characteristics, preference for deliberative thinking, and perceived leaflet usefulness. Data were analyzed using multiple regression. RESULTS: In Study 1 (n = 1,783) and Study 2 (n = 650), having lower socioeconomic status, being a women, and being of nonwhite ethnicity was associated with lower preference for deliberative thinking. In Study 2, the standard-style leaflet was perceived as less useful among participants with lower preference for deliberative thinking, while perceived usefulness of the narrative-style leaflet did not differ by preference for deliberative thinking. CONCLUSIONS: Information leaflets using a standard style may disadvantage women and those experiencing greater socioeconomic deprivation. More work is required to identify design styles that have a greater appeal for people with low preference for deliberative thinking.
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Neoplasias Colorretais/diagnóstico , Comportamento do Consumidor/estatística & dados numéricos , Detecção Precoce de Câncer , Comunicação em Saúde , Folhetos , Preferência do Paciente/estatística & dados numéricos , Classe Social , Estudos de Coortes , Detecção Precoce de Câncer/normas , Feminino , Comunicação em Saúde/métodos , Comunicação em Saúde/normas , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente/etnologia , Fatores SexuaisRESUMO
OBJECTIVE: To determine the feasibility of specialist screening practitioners (SSPs) offering patient navigation (PN) to facilitate uptake of bowel scope screening (BSS) among patients who do not confirm or attend their appointment. DESIGN: A single-stage phase II trial. SETTING: South Tyneside District Hospital, Tyne and Wear, England, UK. PARTICIPANTS: Individuals invited for BSS at South Tyneside District Hospital during the 6-month recruitment period were invited to participate in the study. INTERVENTION: Consenting individuals were randomly assigned to either the PN intervention or usual care group in a 4:1 ratio. The intervention involved BSS non-attenders receiving a phone call from an SSP to elicit their reasons for non-attendance and offer educational, practical and emotional support as required. If requested by the patient, another BSS appointment was then scheduled. PRIMARY OUTCOME MEASURE: The number of non-attenders in the intervention group who were navigated and then rebooked and attended their new BSS appointment. SECONDARY OUTCOME MEASURES: Barriers to BSS attendance, patient-reported outcomes including informed choice and satisfaction with BSS and the PN intervention, reasons for study non-participation, SSPs' evaluation of the PN process and a cost analysis. RESULTS: Of those invited to take part (n=1050), 152 (14.5%) were randomised into the study: PN intervention=109; usual care=43. Most participants attended their BSS appointment (PN: 79.8%; control: 79.1%) leaving 22 eligible for PN: only two were successfully contacted. SSPs were confident in delivering PN, but were concerned that low BSS awareness and information overload may have deterred patients from taking part in the study. Difficulty contacting patients was reported as a burden to their workload. CONCLUSIONS: PN, as implemented, was not a feasible intervention to increase BSS uptake in South Tyneside. Interventions to increase BSS awareness may be better suited to this population. TRIAL REGISTRATION NUMBER: ISRCTN13314752; Results.
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Aceitação pelo Paciente de Cuidados de Saúde , Navegação de Pacientes/métodos , Sigmoidoscopia/estatística & dados numéricos , Adulto , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Navegação de Pacientes/economia , Satisfação do Paciente/estatística & dados numéricos , Sistemas de AlertaRESUMO
BACKGROUND: In the UK, patients with one or two adenomas, of which at least one is ≥ 10 mm in size, or three or four small adenomas, are deemed to be at intermediate risk of colorectal cancer (CRC) and referred for surveillance colonoscopy 3 years post polypectomy. However, colonoscopy is costly, can cause discomfort and carries a small risk of complications. OBJECTIVES: To determine whether or not annual faecal immunochemical tests (FITs) are effective, acceptable and cost saving compared with colonoscopy surveillance for detecting CRC and advanced adenomas (AAs). DESIGN: Diagnostic accuracy study with health psychology assessment and economic evaluation. SETTING: Participants were recruited from 30 January 2012 to 30 December 2013 within the Bowel Cancer Screening Programme in England. PARTICIPANTS: Men and women, aged 60-72 years, deemed to be at intermediate risk of CRC following adenoma removal after a positive guaiac faecal occult blood test were invited to participate. Invitees who consented and returned an analysable FIT were included. INTERVENTION: We offered participants quantitative FITs at 1, 2 and 3 years post polypectomy. Participants testing positive with any FIT were referred for colonoscopy and not offered further FITs. Participants testing negative were offered colonoscopy at 3 years post polypectomy. Acceptibility of FIT was assessed using discussion groups, questionnaires and interviews. MAIN OUTCOME MEASURES: The primary outcome was 3-year sensitivity of an annual FIT versus colonoscopy at 3 years for detecting advanced colorectal neoplasia (ACN) (CRC and/or AA). Secondary outcomes included participants' surveillance preferences, and the incremental costs and cost-effectiveness of FIT versus colonoscopy surveillance. RESULTS: Of 8008 invitees, 5946 (74.3%) consented and returned a round 1 FIT. FIT uptake in rounds 2 and 3 was 97.2% and 96.9%, respectively. With a threshold of 40 µg of haemoglobin (Hb)/g faeces (hereafter referred to as µg/g), positivity was 5.8% in round 1, declining to 4.1% in round 3. Over three rounds, 69.2% (18/26) of participants with CRC, 34.3% (152/443) with AAs and 35.6% (165/463) with ACN tested positive at 40 µg/g. Sensitivity for CRC and AAs increased, whereas specificity decreased, with lower thresholds and multiple rounds. At 40 µg/g, sensitivity and specificity of the first FIT for CRC were 30.8% and 93.9%, respectively. The programme sensitivity and specificity of three rounds at 10 µg/g were 84.6% and 70.8%, respectively. Participants' preferred surveillance strategy was 3-yearly colonoscopy plus annual FITs (57.9%), followed by annual FITs with colonoscopy in positive cases (31.5%). FIT with colonoscopy in positive cases was cheaper than 3-yearly colonoscopy (£2,633,382), varying from £485,236 (40 µg/g) to £956,602 (10 µg/g). Over 3 years, FIT surveillance could miss 291 AAs and eight CRCs using a threshold of 40 µg/g, or 189 AAs and four CRCs using a threshold of 10 µg/g. CONCLUSIONS: Annual low-threshold FIT with colonoscopy in positive cases achieved high sensitivity for CRC and would be cost saving compared with 3-yearly colonoscopy. However, at higher thresholds, this strategy could miss 15-30% of CRCs and 40-70% of AAs. Most participants preferred annual FITs plus 3-yearly colonoscopy. Further research is needed to define a clear role for FITs in surveillance. FUTURE WORK: Evaluate the impact of ACN missed by FITs on quality-adjusted life-years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18040196. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment programme, NIHR Imperial Biomedical Research Centre and the Bobby Moore Fund for Cancer Research UK. MAST Group Ltd provided FIT kits.
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Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodos , Sangue Oculto , Idoso , Colonoscopia/economia , Colonoscopia/métodos , Análise Custo-Benefício , Detecção Precoce de Câncer/psicologia , Detecção Precoce de Câncer/normas , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hemoglobinas/análise , Humanos , Imunoquímica/economia , Imunoquímica/métodos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente , Sensibilidade e Especificidade , Reino UnidoRESUMO
OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results.
Assuntos
Pólipos do Colo/cirurgia , Colonoscopia/métodos , Detecção Precoce de Câncer/métodos , Sangue Oculto , Adenoma/diagnóstico , Adenoma/cirurgia , Idoso , Pólipos do Colo/diagnóstico , Colonoscopia/economia , Neoplasias Colorretais/diagnóstico , Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Inglaterra , Reações Falso-Negativas , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodos , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: There is increasing interest in using a quantitative faecal immunochemical test (FIT) to rule out colorectal cancer (CRC) in patients with high-risk symptoms in primary care. AIM: This study aimed to investigate GPs' attitudes and willingness to use a FIT over an urgent 2-week wait (2WW) referral. DESIGN AND SETTING: A cross-sectional online survey involving 1024 GPs working across England. METHOD: Logistic regression models were used to explore the likelihood of GPs using a FIT instead of a 2WW referral, and reported using odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Just over one-third of GPs (n = 365) preferred to use a FIT as a rule-out test over a 2WW referral. GPs were more willing if they were: aged 36-45 years (OR 1.59 [95% CI = 1.04 to 2.44]); 46-55 years (OR 1.99 [95% CI = 1.14 to 3.47]); thought a FIT was highly accurate (OR 1.63 [95% CI = 1.16 to 2.29]); thought patients would benefit compared with having a colonoscopy (OR 2.02 [95% CI = 1.46 to 2.79]); and were highly confident about discussing the benefits of a FIT (OR 2.14 [95% CI = 1.46 to 3.16]). GPs were less willing if they had had >10 urgent referrals in the past year (OR 0.62 [95% CI = 0.40 to 0.94]) and thought that longer consultations would be needed (OR 0.61 [95% CI = 0.44 to 0.83]). CONCLUSION: The study findings suggest that the acceptability of using a FIT as a rule-out test in primary care is currently low, with less than half of GPs who perceived the test to be accurate preferring it over colonoscopy. Any potential guideline changes recommending a FIT in patients with high-risk symptoms, instead of urgent referral to rule out CRC, are likely to require intensive supporting educational outreach to increase GP confidence in the accuracy and application of a FIT in this context.
Assuntos
Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Fezes/química , Atenção Primária à Saúde , Encaminhamento e Consulta/estatística & dados numéricos , Adulto , Atitude do Pessoal de Saúde , Estudos Transversais , Inglaterra , Feminino , Humanos , Imunoquímica , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Razão de Chances , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Uptake of colorectal cancer screening is low in the English NHS Bowel Cancer Screening Programme (BCSP). Participation in screening is strongly associated with socioeconomic status. The aim of this study was to determine whether a supplementary leaflet providing the 'gist' of guaiac-based Faecal Occult Blood test (gFOBt) screening for colorectal cancer could reduce the socioeconomic status (SES) gradient in uptake in the English NHS BCSP. METHODS: The trial was integrated within routine BCSP operations in November 2012. Using a cluster randomised controlled design all adults aged 59-74 years who were being routinely invited to complete the gFOBt were randomised based on day of invitation. The Index of Multiple Deprivation was used to create SES quintiles. The control group received the standard information booklet ('SI'). The intervention group received the SI booklet and the Gist leaflet ('SI + Gist') which had been designed to help people with lower literacy engage with the invitation. Blinding of hubs was not possible and invited subjects were not made aware of a comparator condition. The primary outcome was the gradient in uptake across IMD quintiles. RESULTS: In November 2012, 163,525 individuals were allocated to either the 'SI' intervention (n = 79,104) or the 'SI + Gist' group (n = 84,421). Overall uptake was similar between the intervention and control groups (SI: 57.3% and SI + Gist: 57.6%; OR = 1.02, 95% CI: 0.92-1.13, p = 0.77). Uptake was 42.0% (SI) vs. 43.0% (SI + Gist) in the most deprived quintile and 65.6% vs. 65.8% in the least deprived quintile (interaction p = 0.48). The SES gradient in uptake was similar between the study groups within age, gender, hub and screening round sub-groups. CONCLUSIONS: Providing supplementary simplified information in addition to the standard information booklet did not reduce the SES gradient in uptake in the NHS BCSP. The effectiveness of the Gist leaflet when used alone should be explored in future research. TRIAL REGISTRATION: ISRCTN74121020 , registered: 17/20/2012.
Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Folhetos , Classe Social , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sangue OcultoRESUMO
Red blood cell (RBC) aggregation is an intrinsic property of the blood that has a direct effect on the blood viscosity and circulation. Nevertheless, the mechanism behind the RBC aggregation has not been confirmed and is still under investigation with two major hypotheses, known as "depletion layer" and "cross-bridging." We aim to ultimately understand the mechanism of the RBC aggregation and clarify both models. To measure the cell interaction in vitro in different suspensions (including plasma, isotonic solution of fibrinogen, isotonic solution of fibrinogen with albumin, and phosphate buffer saline) while moving the aggregate from one solution to another, an approach combining optical trapping and microfluidics has been applied. The study reveals evidence that RBC aggregation in plasma is at least partly due to the cross-bridging mechanism. The cell interaction strength measured in the final solution was found to be significantly changed depending on the initial solution where the aggregate was formed.