Cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy for people with peritoneal metastases from colorectal, ovarian or gastric origin: A systematic review of randomized controlled trials.

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.

A study protocol for a feasibility randomised controlled trial investigating videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy in patients with penile cancer (VELRAD).

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.

Nephron Sparing Treatment (NEST) for Small Renal Masses: A Feasibility Cohort-embedded Randomised Controlled Trial Comparing Percutaneous Cryoablation and Robot-assisted Partial Nephrectomy.

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.

REFINE-Lung implements a novel multi-arm randomised trial design to address possible immunotherapy overtreatment.

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.

Protocol for a MULTI-centre feasibility study to assess the use of 99mTc-sestaMIBI SPECT/CT in the diagnosis of kidney tumours (MULTI-MIBI study).

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.

Cost-utility analysis of robotic-assisted radical cystectomy for bladder cancer compared to open radical cystectomy in the United Kingdom.

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.

NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer.

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.

Mixed methods evaluation of the Getting it Right First Time programme in elective orthopaedic surgery in England: an analysis from the National Joint Registry and Hospital Episode Statistics.

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.

Treatment of unresectable locally advanced pancreatic cancer with percutaneous irreversible electroporation (IRE) following initial systemic chemotherapy (LAP-PIE) trial: study protocol for a feasibility randomised controlled trial.

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.

Combined Endoscopic Stent-In-Stent Placement by Lumen-Apposing Metal Stents Through Self-Expanding Metal Stents for Simultaneous Malignant Biliary and Duodenal Obstruction.

The palliation of simultaneous biliary and duodenal obstruction in patients with advanced pancreatic cancer is a clinically and technically challenging scenario. Endoscopic procedures are a valid alternative to surgical or percutaneous transhepatic biliary drainage. The availability of self-expanding metal stents (SEMSs) and lumen-apposing metal stents (LAMS) have expanded therapeutic options. We describe a case in which biliary and duodenal obstructions were treated successfully with the combined use of SEMS and LAMS devices. Endoscopic ultrasound-guided biliary drainage with the use of new LAMS and a duodenal SEMS can be a valid option in expert hands as a palliative and minimally invasive treatment for gastric outlet and biliary obstruction.

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study.

BACKGROUND: It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts. METHODS: In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS<6 or computed tomography perfusion (CTP) ischemic core volume (rCBF<30%) ≥50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50 000 and $100 000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials. RESULTS: From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0-2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. CONCLUSIONS: In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. CLINICAL TRIAL REGISTRATION: NCT02446587.

Cytoreductive surgery (CRS) with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) versus standard of care (SoC) in people with peritoneal metastases from colorectal, ovarian or gastric origin: protocol for a systematic review and individual participant data (IPD) meta-analyses of effectiveness and cost-effectiveness.

INTRODUCTION: There is uncertainty about whether cytoreductive surgery (CRS)+hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared with standard of care (SoC) in people with peritoneal metastases who can withstand major surgery. PRIMARY OBJECTIVES: To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis. SECONDARY OBJECTIVES: To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services perspective using a model-based cost-utility analysis. METHODS AND ANALYSIS: We will perform a systematic review of literature by updating the searches from MEDLINE, Embase, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of intervention and control, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications and resource utilisation data. Using IPD, we will perform a two-step IPD, that is, calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses, meta-regression and sensitivity analyses. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting. ETHICS AND DISSEMINATION: This project was approved by the UCL Research Ethics Committee (Ethics number: 16023/001). We aim to present the findings at appropriate international meetings and publish the review, irrespective of the findings, in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019130504.

Cost-effectiveness of a melanoma screening programme using whole disease modelling.

OBJECTIVE: To assess the potential impact of a melanoma screening programme, compared with usual care, on direct costs and life expectancy in the era of targeted drugs and cancer immunotherapy. METHODS: Using a Whole Disease Model approach, a Markov simulation model with a time horizon of 25 years was devised to analyse the cost-effectiveness of a one-time, general practitioner-based melanoma screening strategy in the population aged over 20, compared with no screening. The study considered the most up-to-date drug therapy and was conducted from the perspective of the Veneto regional healthcare system within the Italian National Health Service. Only direct costs were considered. Sensitivity analyses, both one-way and probabilistic, were performed to identify the parameters with the greatest impact on cost-effectiveness, and to assess the robustness of our model. RESULTS: Over a 25-year time horizon, the screening intervention dominated usual care. The probabilistic sensitivity analyses confirmed the robustness of these findings. The key drivers of the model were the proportion of melanomas detected by the screening procedure and the adherence of the target population to the screening programme. CONCLUSIONS: The screening programme proved to be a dominant option compared with usual care. These findings should prompt serious consideration of the design and implementation of a regional or national melanoma screening strategy within a National Health Service.

Protocol for a feasibility study of a cohort embedded randomised controlled trial comparing NEphron Sparing Treatment (NEST) for small renal masses.

INTRODUCTION: Small renal masses (SRMs; ≤4 cm) account for two-thirds of new diagnoses of kidney cancer, the majority of which are incidental findings. The natural history of the SRM seems largely indolent. There is an increasing concern regarding surgical overtreatment and the associated health burden in terms of morbidity and economy. Observational data support the safety and efficacy of percutaneous cryoablation but there is an unmet need for high-quality evidence on non-surgical management options and a head-to-head comparison with standard of care is lacking. Historical interventional trial recruitment difficulties demand novel study conduct approaches. We aim to assess if a novel trial design, the cohort embedded randomised controlled trial (RCT), will enable carrying out such a comparison. METHODS AND ANALYSIS: Single-centre prospective cohort study of adults diagnosed with SRM (n=200) with an open label embedded interventional RCT comparing nephron sparing interventions. Cohort participants will be managed at patient and clinicians' discretion and agree with longitudinal clinical data and biological sample collection, with invitation for trial interventions and participation in comparator control groups. Cohort participants with biopsy-proven renal cell carcinoma eligible for both percutaneous cryoablation and partial nephrectomy will be randomly selected (1:1) and invited to consider percutaneous cryoablation (n=25). The comparator group will be robotic partial nephrectomy (n=25). The primary outcome of this feasibility study is participant recruitment. Qualitative research techniques will assess barriers and recruitment improvement opportunities. Secondary outcomes are participant trial retention, health-related quality of life, treatment complications, blood transfusion rate, intensive care unit admission and renal replacement requirement rates, length of hospital stay, time to return to pre-treatment activities, number of work days lost, and health technologies costs. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 19/EM/0004). Study outputs will be presented and published. TRIAL REGISTRATION: ISRCTN18156881; Pre-results.

Obstetric brachial plexus injuries (OBPIs): health-related quality of life in affected adults and parents.

BACKGROUND: Obstetric brachial plexus injuries (OBPIs) are rare but can have significant implications for those affected, their caregivers and the health system. Symptoms can range from restricted movement to complete paralysis of the arm. We investigated health-related quality of life in adults with OBPIs and parents of children with permanent OBPIs, compared these with population norms, and investigated whether certain socio-demographic or clinical factors were associated with the quality of life in these cohorts. METHODS: A cross-sectional study examined 50 affected adults and 78 parents. Participants completed EQ-5D-5 L and characteristics questionnaires. EQ-5D-5 L responses were mapped onto an EQ-5D-3 L value set to generate utility scores. Mean utility scores were compared with English population norms. Univariable and multivariable linear regression models were conducted to assess for associations between participant characteristics and the utility scores. RESULTS: The overall mean utility scores for affected adults and parents were 0.56 (SD 0.28) and 0.80 (SD 0.19) respectively. Affected adults (95% CI (- 0.38, - 0.22), p < 0.001) and parents of children with permanent OBPIs (95% CI (- 0.10, - 0.02), p = 0.007) had lower mean utility scores, and therefore quality of life, compared to English population norms. For affected adults, previous OBPI surgery (95% CI (0.01, 0.25), p = 0.040), employment in non-manual work (95% CI (0.06, 0.30), p = 0.005) and having a partner (95% CI (0.04, 0.25), p = 0.009) appeared to be positively associated with the utility score. Affected adults receiving disability benefits related to OBPIs appeared to have worse utility scores than those not receiving any disability benefits (95% CI (- 0.31, - 0.06), p = 0.005). For parents, employment was associated with better utility scores (95% CI (0.02, 0.20), p = 0.024) but the presence of one or more medical condition appeared to be associated with worse utility scores (95% CI (- 0.16, - 0.04), p = 0.001). CONCLUSIONS: Adults with OBPIs and parents of children with permanent OBPIs reported worse utility scores, and therefore quality of life, compared to the English general population. We also identified certain characteristics as possible factors to consider when dealing with utility scores in these cohorts. The utility scores in this study can be used in future economic evaluations related to OBPIs.

Mixed methods evaluation of the Getting it Right First Time programme - improvements to NHS orthopaedic care in England: study protocol.

BACKGROUND: Orthopaedic procedures, such as total hip replacement and total knee replacement, are among the commonest surgical procedures in England. The Getting it Right First Time project (GIRFT) aims to deliver improvements in quality and reductions in the cost of NHS orthopaedic care across the country. We will examine whether the planned changes have delivered improvements in the quality of care and patient outcomes. We will also study the processes involved in developing and implementing changes to care, and professional and organisational factors influencing these processes. In doing so, we will identify lessons to guide future improvement work in other services. METHODS/DESIGN: We will evaluate the implementation of the GIRFT programme, and its impact on outcomes and cost, using a mixed methods design. Qualitative methods will be used to understand the programme theory underlying the approach and study the effect of the intervention on practice, using a case study approach. This will include an analysis of the central GIRFT programme and local provider responses. Data will be collected via semi-structured interviews, non-participant observation, and documentary analysis. Quantitative methods will be used to examine 'what works and at what cost?' We will also conduct focus groups with patients and members of the public to explore their perceptions of the GIRFT programme. The research will draw on theories of adoption, diffusion, and sustainability of innovation; its characteristics; and contextual factors at provider-level that influence implementation. DISCUSSION: We will identify generalisable lessons to inform the organisation and delivery of future improvement programmes, to optimise their implementation and impact, both within the UK and internationally. Potential challenges involved in conducting the evaluation include the phased implementation of the intervention in different provider organisations; the inclusion of both retrospective and prospective components; and the effects of ongoing organisational turbulence in the English NHS. However, these issues reflect the realities of service change and its evaluation.

Gallstone ileus treated with non-surgical conservative methods: a case report.

INTRODUCTION: The preoperative diagnosis of gallstone ileus is challenging due to the variability of its presentation, often resulting in late diagnosis. Controversy remains regarding the management of gallstone ileus; surgery is the standard treatment, but also less invasive approaches have proven to be successful. We present an unusual case of gallstone ileus and its conservative treatment. CASE PRESENTATION: We describe the case of a 49-year-old Caucasian woman with a bowel sub-occlusion, treated conservatively. The imaging technique (plain abdominal X-ray and computed tomography scan) led to a diagnosis of gallstones ileus. A surgical intervention was not performed. Instead, she underwent extracorporeal shock-wave lithotripsy to fragment the stones, mechanical intestinal dilatation for ileocolic stenosis and endoscopic removal of the gallstone. The presence of an apricot shell contributed to the bowel occlusion and was removed. The intervention was successful and without complications. CONCLUSIONS: Given the variability of the gallstone ileus presentation, surgery could not be the only treatment for our patient. In our case report, we show that colonoscopy could be a non-invasive approach that allows for diagnosis and treatment at the same time. The available data do not show a higher rate of recurrent biliary disease in cases where this method has been used, therefore in select patients, a conservative treatment could be an effective solution.

Screenee perception and health-related quality of life in colorectal cancer screening: a review.

Screening for colorectal cancer (CRC) has become established to varying degrees in several Western countries for the past 30 years. Because of its effectiveness, screening has been adopted or is planned in a number of other countries. In most countries, the screening method (e.g., fecal occult blood test [FOBT], sigmoidoscopy) is followed by colonoscopy, for verification. In other countries (e.g., United States, Germany), colonoscopy is the preferred first-line investigation method. However, because colonoscopy is considered to be invasive, might be poorly tolerated, and can be associated with complications, the idea of adopting colonoscopy as the primary screening method suffers. Negative effects of screening methods can reduce participation in programs and thereby negate the desired effect on individual and societal health. At present, there is no generally accepted method either to assess the perception and satisfaction of patients screened or the outcome of the screening procedures in CRC. In this review, we discuss the past development and present availability of instruments to measure health-related quality of life (HRQoL), the scarce studies in which such instruments have been used in screening campaigns, and the findings. We suggest the creation of a specific instrument for the assessment of HRQoL in CRC screening.