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OBJECTIVES: To understand the facilitators and barriers to the implementation of renal tumour biopsy (RTB) in the diagnostic pathway for renal tumours in England. PATIENTS AND METHODS: Participants consisted of patients who had a renal tumour diagnosed and/or treated at one of five tertiary centres in England, healthcare professionals involved in the direct care of patients diagnosed with renal tumours, and clinical service managers and commissioners. The study employed a mixed-methods research methodology consisting of individual interviews and an on-line survey that explored the types of facilitators and barriers individuals perceived and experienced and the frequency in which these were reported. A public dissemination event took place following the completion of data collection; to facilitate discussion of potential solutions to implementing RTB. RESULTS: There were 50 participant interviews (23 patients, 22 clinicians, and five health service commissioners/operations managers). The patient on-line survey received 52 responses, and the clinician survey received 22 responses. Patients most frequently reported influences in choosing whether to undergo RTB pertained to wanting to know the diagnosis of their kidney mass (40%), the advice or information provided by healthcare professionals (40%), and not wishing to delay treatment (23%). Clinicians most frequently reported barriers to recommending RTB related to their uncertainty of diagnostic accuracy (56%), availability of appointments or hospital beds (52%), concerns of risk of bleeding (44%), risk of seeding (41%), and delays in meeting national cancer pathway targets (41%). The dissemination event was attended by 18 participants (seven patients and 11 clinicians). Suggestions to improve implementation included reducing variation and promotion of standardisation of practice by a consensus statement, increasing the evidence base (clinicians) and improved communication by developing better patient aids such as videos and diagrams (patients and clinicians). CONCLUSION: Implementation of RTB may be dependent on the quality of information provided, its format and perceived reliability of the information. Increased utilisation of RTB may be improved by development of a consensus statement on the role of biopsy, with patients expressing a preference for alternative information aids such as patient videos.
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This is a process evaluation of a large UK-based randomised controlled trial (RCT) (n = 5602) evaluating the effectiveness of recommending an alcohol reduction app, Drink Less, compared with usual digital care in reducing alcohol consumption in increasing and higher risk drinkers. The aim was to understand whether participants' engagement ('self-reported adherence') and behavioural characteristics were mechanisms of action underpinning the effectiveness of Drink Less. Self-reported adherence with both digital tools was over 70% (Drink Less: 78.0%, 95% CI = 77.6-78.4; usual digital care: 71.5%, 95% CI = 71.0-71.9). Self-reported adherence to the intervention (average causal mediation effect [ACME] = -0.250, 95% CI = -0.42, -0.11) and self-monitoring behaviour (ACME = -0.235, 95% CI = -0.44, -0.03) both partially mediated the effect of the intervention (versus comparator) on alcohol reduction. Following the recommendation (self-reported adherence) and the tracking (self-monitoring behaviour) feature of the Drink Less app appear to be important mechanisms of action for alcohol reduction among increasing and higher risk drinkers.
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BACKGROUND: The extent to which interventions are perceived as acceptable to users impacts engagement and efficacy. OBJECTIVE: In this study, we evaluated the acceptability of (1) the smartphone app Drink Less (intervention) and (2) the National Health Service (NHS) alcohol advice web page (usual digital care and comparator) among adult drinkers in the United Kingdom participating in a randomized controlled trial evaluating the effectiveness of the Drink Less app. METHODS: A subsample of 26 increasing- and higher-risk drinkers (Alcohol Use Disorders Identification Test score≥8) assigned to the intervention group (Drink Less; n=14, 54%; female: n=10, 71%; age: 22-72 years; White: n=9, 64%) or usual digital care group (NHS alcohol advice web page; n=12, 46%; female: n=5, 42%; age: 23-68 years: White: n=9, 75%) took part in semistructured interviews. The interview questions were mapped on to the 7 facets of acceptability according to the Theoretical Framework of Acceptability: affective attitude, burden, perceived effectiveness, ethicality, intervention coherence, opportunity costs, and self-efficacy. Alongside these constructs, we also included a question on perceived personal relevance, which previous research has linked to acceptability and engagement. Framework and thematic analysis of data was undertaken. RESULTS: The Drink Less app was perceived as being ethical, easy, user-friendly, and effective for the period the app was used. Participants reported particularly liking the tracking and feedback sections of the app, which they reported increased personal relevance and which resulted in positive affect when achieving their goals. They reported no opportunity cost. Factors such as negative affect when not meeting goals and boredom led to disengagement in the longer term for some participants. The NHS alcohol advice web page was rated as being easy and user-friendly with no opportunity costs. However, the information presented was not perceived as being personally relevant or effective in changing drinking behavior. Most participants reported neutral or negative affect, most participants thought the alcohol advice web page was accessible, and some participants reported ethical concerns around the availability of suggested resources. Some participants reported that it had acted as a starting point or a signpost to other resources. Participants in both groups discussed motivation to change and contextual factors such as COVID-19 lockdowns, which influenced their perceived self-efficacy regardless of their assigned intervention. CONCLUSIONS: Drink Less appears to be an acceptable digital intervention among the recruited sample. The NHS alcohol advice web page was generally considered unacceptable as a stand-alone intervention among the recruited sample, although it may signpost and help people access other resources and interventions.
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Consumo de Bebidas Alcoólicas , Aplicativos Móveis , Humanos , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Idoso , Reino Unido , Consumo de Bebidas Alcoólicas/prevenção & controle , Consumo de Bebidas Alcoólicas/psicologia , Adulto Jovem , Internet , Medicina Estatal , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Entrevistas como AssuntoRESUMO
BACKGROUND & AIMS: Although upper gastrointestinal endoscopy (EGD) remains the gold standard for detecting varices in cirrhosis, the Baveno VI criteria proposed a combination of transient elastography and platelet count that could rule out high-risk varices, therefore sparing the need for an endoscopy, with significant potential cost savings. We performed a cost-effectiveness analysis of the Baveno VI criteria compared with EGD in the diagnosis of high-risk varices in cirrhosis. METHODS: We built an analytical decision model to estimate the cost and benefits of using the Baveno VI criteria compared with EGD in patients with Child-Pugh A cirrhosis. The analysis was performed from the UK National Health Service perspective, over 1, 5, and 20 years. A Markov model was populated with data from published evidence. Outcomes were measured in terms of quality-adjusted life years (QALYs) and avoided deaths. The analyses were repeated for Canada and Spain, using relevant cost inputs. RESULTS: The Baveno VI criteria were cost effective compared with endoscopy in all analyses. For 1000 patients, they produced 0.16 additional QALYs at an incremental cost of £326 ($443.41) over 5 years, resulting in an incremental cost of £2081 ($2830) per additional QALY gained. The incremental net monetary benefit of Baveno VI compared with EGD was £2808 ($3819) over 5 years per patient. Baveno VI criteria also were cost effective in Canada and Spain. Deterministic and probabilistic sensitivity analysis supported these findings. CONCLUSIONS: The findings demonstrate that the Baveno VI criteria are cost effective, suggesting that they should be considered for widespread implementation on the basis of safety, appropriateness, and economic grounds.
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BACKGROUND: There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/- systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. METHODS: We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high-quality systematic reviews. FINDINGS: We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS + HIPEC + systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy probably decreases all-cause mortality compared to CRS + systemic chemotherapy. For colorectal cancer, CRS + HIPEC + systemic chemotherapy probably results in little to no difference in all-cause mortality and may increase the serious adverse events proportions compared to CRS +/- systemic chemotherapy, but probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone. INTERPRETATION: The role of CRS + HIPEC in gastric peritoneal metastases is uncertain. CRS + HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS + systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. PROSPERO REGISTRATION: CRD42019130504.
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Neoplasias Colorretais , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ovarianas , Neoplasias Peritoneais , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas , Humanos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Terapia Combinada , Hipertermia Induzida/métodosRESUMO
Background: Digital interventions, including apps and websites, can be effective for reducing alcohol consumption. However, many are not evidence- or theory-informed and have not been evaluated. We tested the effectiveness of the Drink Less app for reducing alcohol consumption compared with usual digital care in the UK. Methods: In this two-arm, parallel group, double-blind, randomised controlled trial, we enrolled increasing-and-higher-risk drinkers (AUDIT ≥ 8) in the UK, who were motivated to reduce their alcohol consumption and willing to use a digital intervention to do so, via online methods. Participants were randomly assigned (1:1), using an online algorithm, to receive a web link to download the Drink Less app (intervention) or to the NHS alcohol advice webpage (usual digital care). Researchers were masked to group allocation. Participants were followed up at one, three and six months. The primary outcome was self-reported weekly alcohol consumption at six months, adjusting for baseline consumption. The full analytic sample was used in most analyses, though missing data was treated in different ways. The primary, pre-registered intention-to-treat analysis assumed baseline-carried-forwards. Secondary pre-registered analyses also focused on the full analytic sample and used alternatives including multiple imputation and last observation carried forwards. This trial is registered with the ISRCTN registry, ISRCTN64052601. Findings: Between 07/13/2020 and 03/29/2022, 5602 people were randomly assigned to the Drink Less app (n = 2788) or comparator (n = 2814) groups. Six-month follow-up rates were 79% and 80%, respectively. The primary pre-registered conservative intention-to-treat approach assuming non-responders were drinking at baseline levels of consumption, found a non-significant greater reduction of 0.98 units in weekly alcohol consumption in the intervention group at 6-month follow-up (95% CI -2.67 to 0.70). The data were insensitive to detect the hypothesised effect (Bayes factor = 1.17). Data were not missing completely at random, with 6-month follow-up rates differing in terms of education, occupation, and income. We therefore conducted the pre-registered sensitivity analysis using multiple imputation, showing that the Drink Less app resulted in a 2.00-unit greater weekly reduction at 6-month follow-up compared with the NHS alcohol advice webpage (95% CI -3.76 to -0.24). Fewer than 0.1% of participants in both arms who responded to one, three or six-month follow-up reported adverse events linked to participation in the trial. Interpretation: The Drink Less app may be effective in reducing the alcohol consumption in increasing-and-higher-risk drinkers motivated to reduce their consumption. Funding: NIHR Public Health Research Programme.
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BACKGROUND: Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative. METHODS: A pragmatic, UK-wide multicentre feasibility randomised controlled trial (RCT), comparing videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy. Patients will be identified and recruited from supraregional multi-disciplinary team meetings (sMDT) and must be aged 18 or over requiring inguinal lymphadenectomy, with no contraindications to surgical intervention for their cancer. Participants will be followed up for 6 months following randomisation. The primary outcome is the ability to recruit patients for randomisation across all selected sites and the rate of loss to follow-up. Other outcomes include acceptability of the trial and intervention to patients and healthcare professionals assessed by qualitative research and obtaining resource utilisation information for health economic analysis. DISCUSSION: There are currently no other published RCTs comparing videoendoscopic versus open radical inguinal lymphadenectomy. Ongoing study is required to determine whether randomising patients to either procedure is feasible and acceptable to patients. The results of this study may determine the design of a subsequent trial. TRIAL REGISTRATION: Clinicaltrials.gov PRS registry, registration number NCT05592639. Date of registration: 13th October 2022, retrospectively registered.
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INTRODUCTION: Remote monitoring of home physiological measurements has been proposed as a solution to support patients with chronic diseases as well as facilitating virtual consultations and pandemic preparedness for the future. Daily home spirometry and pulse oximetry have been demonstrated to be safe and acceptable to patients with interstitial lung disease (ILD) but there is currently limited evidence to support its integration into clinical practice. AIM: Our aim is to understand the clinical utility of frequent remote physiological measurements in ILD and the impact of integrating these into clinical practice from a patient, clinical and health economic perspective. METHODS AND ANALYSIS: 132 patients with fibrotic ILD will be recruited and randomised to receive either usual care with remote digital monitoring of home spirometry and pulse oximetry or usual care alone for 12 months. All participants will complete health-related quality of life and experience questionnaires.The primary outcome compares the availability of spirometry measurements within the 2 weeks preceding planned clinic appointments. Secondary outcomes will explore other aspects of clinical and cost-effectiveness of the remote monitoring programme. ETHICS AND DISSEMINATION: The study has been approved by the Camden and Kings Cross Research Ethics Committee (22/LO/0309). All participants will provide informed consent.This study is registered with www. CLINICALTRIALS: gov (NCT05662124).The results of the study will be submitted for presentation at regional and national conferences and submitted for peer-reviewed publication. Reports will be prepared for study participants with the support from our public involvement representatives through the charity Action for Pulmonary Fibrosis.
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Doenças Pulmonares Intersticiais , Qualidade de Vida , Humanos , Análise Custo-Benefício , Resultado do Tratamento , Doenças Pulmonares Intersticiais/diagnóstico , Oximetria , Espirometria , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Importance: The diagnosis of rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical features that are not recognized even by experienced clinicians. Next-generation sequencing technologies, such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), have greatly enhanced the diagnosis of genetic diseases by expanding the ability to sequence a large part of the genome, rendering a cost-effectiveness comparison between them necessary. Objective: To assess the cost-effectiveness of WGS compared with WES and conventional testing in children with suspected genetic disorders. Design, Setting, and Participants: In this economic evaluation, a bayesian Markov model was implemented from January 1 to June 30, 2023. The model was developed using data from a cohort of 870 pediatric patients with suspected genetic disorders who were enrolled and underwent testing in the Ospedale Pediatrico Bambino Gesù, Rome, Italy, from January 1, 2015, to December 31, 2022. The robustness of the model was assessed through probabilistic sensitivity analysis and value of information analysis. Main Outcomes and Measures: Overall costs, number of definitive diagnoses, and incremental cost-effectiveness ratios per diagnosis were measured. The cost-effectiveness analyses involved 4 comparisons: first-tier WGS with standard of care; first-tier WGS with first-tier WES; first-tier WGS with second-tier WES; and first-tier WGS with second-tier WGS. Results: The ages of the 870 participants ranged from 0 to 18 years (539 [62%] girls). The results of the analysis suggested that adopting WGS as a first-tier strategy would be cost-effective compared with all other explored options. For all threshold levels above 29 800 (US $32 408) per diagnosis that were tested up to 50â¯000 (US $54â¯375) per diagnosis, first-line WGS vs second-line WES strategy (ie, 54.6%) had the highest probability of being cost-effective, followed by first-line vs second-line WGS (ie, 54.3%), first-line WGS vs the standard of care alternative (ie, 53.2%), and first-line WGS vs first-line WES (ie, 51.1%). Based on sensitivity analyses, these estimates remained robust to assumptions and parameter uncertainty. Conclusions and Relevance: The findings of this economic evaluation encourage the development of policy changes at various levels (ie, macro, meso, and micro) of international health systems to ensure an efficient adoption of WGS in clinical practice and its equitable access.
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Genoma , Feminino , Humanos , Criança , Masculino , Sequenciamento do Exoma , Análise Custo-Benefício , Teorema de Bayes , Sequenciamento Completo do GenomaRESUMO
There is a paucity of high-level evidence on small renal mass (SRM) management, as previous classical randomised controlled trials (RCTs) failed to meet accrual targets. Our objective was to assess the feasibility of recruitment to a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN). A total of 200 participants were recruited to the cohort, of whom 50 were enrolled in the RCT. In the CRA intervention arm, 84% consented (95% confidence interval [CI] 64-95%) and 76% (95% CI 55-91%) received CRA; 100% (95% CI 86-100%) of the control arm underwent RPN. The retention rate was 90% (95% CI 79-96%) at 6 mo. In the RPN group 2/25 (8%) were converted intra-operative to radical nephrectomy. Postoperative complications (Clavien-Dindo grade 1-2) occurred in 12% of the CRA group and 29% of the RPN group. The median length of hospital stay was shorter for CRA (1 vs 2 d; p = 0.019). At 6 mo, the mean change in renal function was -5.0 ml/min/1.73 m2 after CRA and -5.8 ml/min/1.73 m2 after RPN. This study demonstrates the feasibility of a cohort-embedded RCT comparing CRA and RPN. These data can be used to inform multicentre trials on SRM management. PATIENT SUMMARY: We assessed whether patients with a small kidney tumour would consent to a trial comparing two different treatments: cryoablation (passing small needles through the skin to freeze the kidney tumour) and surgery to remove part of the kidney. We found that most patients agreed and a full trial would therefore be feasible.
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Criocirurgia , Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Criocirurgia/efeitos adversos , Estudos de Viabilidade , Nefrectomia/efeitos adversos , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Néfrons/patologia , Resultado do Tratamento , Estudos Retrospectivos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes. DESIGN: A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation. SETTING: Three inner-city UK National Health Service hospitals in London. PARTICIPANTS: Pregnant women with gestational diabetes treated with medication. INTERVENTIONS: 2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally. PRIMARY OUTCOME MEASURES: Rates of recruitment, randomisation, follow-up, attrition and adherence to the intervention. SECONDARY OUTCOME MEASURES: Preliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs. RESULTS: Out of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders. CONCLUSIONS: It is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention. TRIAL REGISTRATION NUMBER: ISRCTN20930880.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Metformina , Feminino , Humanos , Gravidez , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Gestacional/prevenção & controle , Diabetes Gestacional/tratamento farmacológico , Estudos de Viabilidade , Medicina Estatal , Método Duplo-Cego , Reino UnidoRESUMO
Increasing evidence suggests that some immunotherapy dosing regimens for patients with advanced cancer could result in overtreatment. Given the high costs of these agents, and important implications for quality of life and toxicity, new approaches are needed to identify and reduce unnecessary treatment. Conventional two-arm non-inferiority designs are inefficient in this context because they require large numbers of patients to explore a single alternative to the standard of care. Here, we discuss the potential problem of overtreatment with anti-PD-1 directed agents in general and introduce REFINE-Lung (NCT05085028), a UK multicentre phase 3 study of reduced frequency pembrolizumab in advanced non-small-cell lung cancer. REFINE-Lung uses a novel multi-arm multi-stage response over continuous interventions (MAMS-ROCI) design to determine the optimal dose frequency of pembrolizumab. Along with a similarly designed basket study of patients with renal cancer and melanoma, REFINE-Lung and the MAMS-ROCI design could contribute to practice-changing advances in patient care and form a template for future immunotherapy optimisation studies across cancer types and indications. This new trial design is applicable to many new or existing agents for which optimisation of dose, frequency, or duration of therapy is desirable.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Qualidade de Vida , Pulmão , Imunoterapia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Perinatal mental health difficulties affect up to 27% of birthing parents during pregnancy and the first postnatal year, and if untreated are associated with difficulties in bonding and long-term adverse outcomes to children. There are large evidence gaps related to psychological treatment, particularly in group therapy approaches and parent-infant interventions. One intervention showing preliminary efficacious findings and user acceptability is Circle of Security-Parenting (COS-P), which is a brief, weekly, group programme. However, these studies were underpowered and predominantly non-randomised, and there has never been a research trial in England or with birthing parents experiencing severe and complex perinatal mental health difficulties. The aim of the research is to conduct a randomised control trial to test whether COS-P will reduce perinatal mental health symptoms in birthing parents accessing NHS perinatal mental health services, compared to treatment as usual (TAU). Secondary objectives include exploring whether the intervention improves parenting sensitivity, emotion regulation skills, attachment security and infant development. Additionally, the project aims to examine whether the intervention is acceptable to parents and NHS staff, and whether it is cost-effective. METHODS: COSI is an individually randomised, single-blind parallel arm controlled trial with an embedded internal pilot aiming to recruit 369 participants in a 2:1 ratio (intervention: TAU). Participants will be recruited from ten NHS community perinatal mental health services in England and screened based on clinical levels of both mental health symptoms (average CORE-OM score ≥ 1.1) and postnatal bonding difficulties (total PBQ score ≥ 12). This trial has 90% power to detect a MCID of 5 points on the CORE-OM. Primary and secondary outcomes will be measured at baseline, 3, 7 and 12 months after baseline. Service use and quality of life measures will also be collected alongside a process evaluation of parents' and interveners' views and experiences. DISCUSSION: This will be the first large pragmatic trial to test whether COS-P is effective for birthing parents with severe and complex perinatal mental health difficulties in improving their mental health symptoms. If shown to be effective, the intervention could be delivered widely across the NHS and other similar services globally. TRIAL REGISTRATION: ISRCTN, ISRCTN18308962. Registered 18 February 2022.
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Serviços Comunitários de Saúde Mental , Poder Familiar , Criança , Feminino , Gravidez , Humanos , Poder Familiar/psicologia , Análise Custo-Benefício , Qualidade de Vida , Método Simples-Cego , Inglaterra , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
INTRODUCTION: The incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding. As a result, benign masses are often unnecessarily surgically resected. 99mTc-sestamibi SPECT/CT has shown high diagnostic accuracy for benign renal oncocytomas and other oncocytic renal neoplasms of low malignant potential in single-centre studies. The primary aim of MULTI-MIBI is to assess feasibility of a multicentre study of 99mTc-sestamibi SPECT/CT against a reference standard of histopathology from surgical resection or biopsy. Secondary aims of the study include obtaining estimates of 99mTc-sestamibi SPECT/CT sensitivity and specificity and to inform the design and conduct of a future definitive trial. METHODS AND ANALYSIS: A feasibility prospective multicentre study of participants with indeterminate, clinical T1 renal tumours to undergo 99mTc-sestamibi SPECT/CT (index test) compared with histopathology from biopsy or surgical resection (reference test). Interpretation of the index and reference tests will be blinded to the results of the other. Recruitment rate as well as estimates of sensitivity, specificity, positive and negative predictive value will be reported. Semistructured interviews with patients and clinicians will provide qualitative data to inform onward trial design and delivery. Training materials for 99mTc-sestamibi SPECT/CT interpretation will be developed, assessed and optimised. Early health economic modelling using a decision analytic approach for different diagnostic strategies will be performed to understand the potential cost-effectiveness of 99mTc-sestamibi SPECT/CT. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 20/YH/0279) protocol V.5.0 dated 21/6/2022. Study outputs will be presented and published nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN12572202.
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Neoplasias Renais , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Estudos de Viabilidade , Neoplasias Renais/diagnóstico por imagem , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Life expectancy and the number of ultra-octogenarians increased significantly, thus making crucial the appropriateness of several endoscopic procedures in elderly patients. The aim of our study was to provide a retrospective analysis of the efficacy and safety of capsule endoscopy (CE) in patients aged over 80 years. METHODS: In this single-centre study, 900 patients underwent capsule endoscopy between 2002 and 2015 for different indications; of these 106 patients aged ≥80 years (group A) and 99 patients aged 40-60 years (control group B) were retrospectively selected. RESULTS: Occult gastrointestinal bleeding accounted for 62.1% of all indications for capsule endoscopy in group B, compared to 95.2% in group A (P<0.001). Although not statistically significant, the diagnostic yield was higher in group A (71%) vs. group B (62%). The percentages of reaching the cecum and the median gastric transit time were uniform within the two groups. In contrast, small bowel transit time was longer in group A vs. B. Small bowel preparation was similar in the two groups. The exam was generally well tolerated in both groups, with capsule aspiration being one of the main adverse events, which occurred in two elderly patients. CONCLUSIONS: Our data expand previous findings confirming that capsule endoscopy can be performed safely even in very old patients and show that the diagnostic yield is similar to that of younger patients.
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Endoscopia por Cápsula , Idoso , Idoso de 80 Anos ou mais , Humanos , Estudos Retrospectivos , Endoscopia por Cápsula/efeitos adversos , Endoscopia por Cápsula/métodos , Octogenários , Intestino Delgado , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologiaRESUMO
Postoperative bacterial endophthalmitis is an infection of the eye's internal tissues resulting from an intraocular procedure. The condition is uncommon but can cause severe and irreversible impairment of sight. Standard management involves administration of antibiotics with or without subsequent removal of the infected vitreous gel by vitrectomy surgery. Surgical intervention is typically reserved for infections that persist despite a period of medical management alone. We aim to determine whether outcomes can be improved by performing surgery without delay. To explore the feasibility of a definitive randomised controlled trial and to determine the number of participants required, we will conduct a multicentre feasibility trial. This trial will include 40 affected individuals, allocated randomly to either standard of care, being intravitreal antibiotic administration alone, or to early vitrectomy surgery in addition to antibiotic administration. We will determine the feasibility and size of a definitive trial by evaluating the participants and the outcomes for their sight. Research Ethics Committee approval (REC 20/WM/0264). Here we describe the trial protocol. Trial registration number:ClinicalTrials.gov NCT04522661.
This study aims to assess the feasibility of a trial to determine the benefit of prompt surgery for "endophthalmitis", which is a rare but blinding eye infection resulting from invasive eye procedures. Endophthalmitis can cause rapidly progressive, severe pain and irreversible loss of sight. Antibiotic administration alone may be insufficient to control the infection and in up to 50% of cases surgery is subsequently performed to improve the outcome by removing the infected vitreous gel (vitrectomy). Usual care involves intensive and extended inpatient and outpatient management over a 6-month period in specialist tertiary centres at considerable cost to the NHS. Surgical intervention is typically reserved for infections that persist despite a period of medical management with intravitreal antibiotics alone. We aim to determine whether outcomes can be improved by performing surgery to remove infected vitreous gel without delay by removing infected vitreous material at the first opportunity. Early vitrectomy surgery has the potential to improve the outcome for people's sight and well-being, and to reduce the associated financial costs to the NHS, and assist in endeavours to reduce antibiotic usage. To find out if earlier surgery can improve the outcome, we first need to determine if an appropriate clinical trial is feasible and decide how it should best be designed. Postoperative endophthalmitis is typically unexpected, causes considerable distress and places demand on urgent clinical services. We need to confirm that a sufficient number of affected people would be willing to participate in such a trial and that the hospitals providing care would have the capacity to perform early surgery. Participants will be randomly allocated to vitrectomy performed at an earlier stage of the condition, or later if needs be in accordance with standard care. Standard follow-up for both arms will continue for a six-month period.
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BACKGROUND: Bladder cancer is the tenth most common cancer in the United Kingdom. Currently, open radical cystectomy (ORC) is the gold standard. Due to the risk of complications and a 2.3-8% mortality rate1, there is growing interest in the use of robot-assisted radical cystectomy (RARC). The aim of this study is to perform a cost-utility analysis, comparing RARC to ORC for bladder cancer patients from the perspective of the National Health Service England. METHODS: A three-stage decision tree: surgery, post-surgery transfusions and complications, in a 90-day time horizon, was produced to simulate possible pathways of patients. The incremental cost-effectiveness ratio (ICER) was calculated based on data derived from current literature. Multiple univariate sensitivity analysis was carried out to evaluate influences of varying costs of RARC and ORC on the ICER. RESULTS: The ICER for RARC compared to ORC resulted in £25,536/QALY. At the lower threshold of £20,000/QALY, RARC resulted in a negative NMB (£-4,843.32) and at the upper threshold of £30,000/QALY, a positive NMB (£624.61) compared to ORC. Threshold analysis showed that the intervention costs of £13,497 and £14,403 are met at the lower and upper threshold respectively. The univariate sensitivity analysis showed that the intervention costs of RARC or ORC, and the probabilities of complications, had the greatest impact on the ICER. CONCLUSION: As the resultant ICER did not fall below the £20,000/QALY threshold, our study did not provide a definitive recommendation for RARC for bladder cancer. Negative values for the NMB at the lower threshold indicated the intervention was not feasible from a cost perspective. At the upper threshold of £30,000/QALY, this situation was reversed. The intervention became cost-effective. Therefore, further research is needed to justify the intervention.
Assuntos
Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Análise Custo-Benefício , Cistectomia , Humanos , Medicina Estatal , Reino Unido , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients' quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. METHODS: NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. DISCUSSION: NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. TRIAL REGISTRATION: NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.
Assuntos
Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Disfunção Erétil/etiologia , Humanos , Masculino , Margens de Excisão , Estudos Multicêntricos como Assunto , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Incontinência Urinária/etiologiaRESUMO
OBJECTIVE: To evaluate the impact of the 'Getting it Right First Time' (GIRFT) national improvement programme in orthopaedics, which started in 2012. DESIGN: Mixed-methods study comprising statistical analysis of linked national datasets (National Joint Registry; Hospital Episode Statistics; Patient-Reported Outcomes); economic analysis and qualitative case studies in six National Health Service (NHS) Trusts. SETTING: NHS elective orthopaedic surgery in England. PARTICIPANTS: 736 088 patients who underwent primary hip or knee replacement at 126 NHS Trusts between 1 April 2009 and 31 March 2018, plus 50 NHS staff. INTERVENTION: Improvement bundle including 'deep dive' visits by senior clinician to NHS Trusts, informed by bespoke set of routine performance data, to discuss how improvements could be made locally. MAIN OUTCOME MEASURES: Number of procedures conducted by low volume surgeons; use of uncemented hip implants in patients >65; arthroscopy in year prior to knee replacement; hospital length of stay; emergency readmissions within 30 days; revision surgery within 1 year; health-related quality of life and functional status. RESULTS: National trends demonstrated substantial improvements beginning prior to GIRFT. Between 2012 and 2018, there were reductions in procedures by low volume surgeons (ORs (95% CI) hips 0.58 (0.53 to 0.63), knees 0.77 (0.72 to 0.83)); uncemented hip prostheses in >65 s (OR 0.56 (0.51 to 0.61)); knee arthroscopies before surgery (OR 0.48 (0.41 to 0.56)) and mean length of stay (hips -0.90 (-1.00 to -0.81), knees -0.74 days (-0.82 to -0.66)). The additional impact of visits was mixed and comprised an overall economic saving of £431 848 between 2012 and 2018, but this was offset by the costs of the visits. Staff reported that GIRFT's influence ranged from procurement changes to improved regional collaboration. CONCLUSION: Nationally, we found substantial improvements in care, but the specific contribution of GIRFT cannot be reliably estimated due to other concurrent initiatives. Our approach enabled additional analysis of the discrete impact of GIRFT visits.
Assuntos
Artroplastia do Joelho , Ortopedia , Inglaterra , Hospitais , Humanos , Qualidade de Vida , Sistema de Registros , Medicina EstatalRESUMO
BACKGROUND: Approximately 30% of patients with pancreas cancer have unresectable locally advanced disease, which is currently treated with systemic chemotherapy. A new treatment option of irreversible electroporation (IRE) has been investigated for these patients since 2005. Cohort studies suggest that IRE confers a survival advantage, but with associated, procedure-related complications. Selection bias may account for improved survival and there have been no prospective randomised trials evaluating the harms and benefits of therapy. The aim of this trial is to evaluate the feasibility of a randomised comparison of IRE therapy with chemotherapy versus chemotherapy alone in patients with locally advanced pancreatic cancer (LAPC). METHODS AND ANALYSIS: Eligible patients with LAPC who have undergone first-line 5-FluoroUracil, Leucovorin, Irinotecan and Oxaliplatin chemotherapy will be randomised to receive either a single session of IRE followed by (if indicated) further chemotherapy or to chemotherapy alone (standard of care). Fifty patients from up to seven specialist pancreas centres in the UK will be recruited over a period of 15 months. Trial follow-up will be 12 months. The primary outcome measure is ability to recruit. Secondary objectives include practicality and technical success of treatment, acceptability of treatment to patients and clinicians and safety of treatment. A qualitative study has been incorporated to evaluate the patient and clinician perspective of the locally advanced pancreatic cancer with percutaneous irreversible electroporation trial. It is likely that the data obtained will guide the structure, the primary outcome measure, the power and the duration of a subsequent multicentre randomised controlled trial aimed at establishing the clinical efficiency of pancreas IRE therapy. Indicative procedure-related costings will be collected in this feasibility trial, which will inform the cost evaluation in the subsequent study on efficiency. ETHICS AND DISSEMINATION: The protocol has received approval by London-Brent Research Ethics Committee reference number 21/LO/0077.Results will be analysed following completion of trial recruitment and follow-up. Results will be presented to international conferences with an interest in oncology, hepatopancreaticobiliary surgery and interventional radiology and be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN14986389.