IntroductionThe rapid evolution of minimally invasive surgery has had a positive impact on patient outcomes; however, it is reported to be associated with work-related musculoskeletal symptoms (WMS) ...in surgeons. Currently there is no objective measure to monitor the physical and psychological impact of performing a live surgical procedure on the surgeon.Methods and analysisA single-arm observational study with the aim of developing a validated assessment tool to quantify the impact of surgery (open/laparoscopic/robotic-assisted) on the surgeon. Development and validation cohorts of major surgical cases of varying levels of complexity performed by consultant gynaecological and colorectal surgeons will be recruited. Recruited surgeons wear three Xsens DOT monitors (muscle activity) and an Actiheart monitor (heart rate). Salivary cortisol levels will be taken and questionnaires (WMS and State-Trait Anxiety Inventory) completed by the participants preoperatively and postoperatively. All the measures will be incorporated to produce a single score that will be called the 'S-IMPACT' score.Ethics and disseminationEthical approval for this study has been granted by the East Midlands Leicester Central Research Ethics Committee REC ref 21/EM/0174. Results will be disseminated to the academic community through conference presentations and peer-reviewed journal publications. The S-IMPACT score developed within this study will be taken forward for use in definitive multicentre prospective randomised control trials.
Abstract Aim To describe and evaluate risk assessment tools which detect those with pre-diabetes defined as either impaired glucose tolerance or impaired fasting glucose using an OGTT or as a raised ...HbA1c. Methods Tools were identified through a systematic search of PubMed and EMBASE for articles which developed a risk tool to detect those with pre-diabetes. Data were extracted using a standardised data extraction form. Results Eighteen tools met the inclusion criteria. Eleven tools were derived using logistic regression, six using decision trees and one using support vector machine methodology. Age, body mass index, family history of diabetes and hypertension were the most frequently included variables. The size of the datasets used and the number of events per variable considered were acceptable in all the tools. Missing data were not discussed for 8 (44%) of the tools, 10 (91%) of the logistic tools categorised continuous variables, external validation was carried out for only 7 (39%) of the tools and only 3 tools reported calibration levels. Conclusions Several risk scores are available to identify those with pre-diabetes. Before these are used in practice, the level of calibration and validity of the tools in the population of interest should be assessed.
IntroductionPersonalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (PERFORM) is a research programme that seeks to develop and evaluate a comprehensive exercise-based ...rehabilitation intervention designed for people with multimorbidity, the presence of multiple long-term conditions (MLTCs). This paper describes the protocol for a randomised trial to assess the feasibility and acceptability of the PERFORM intervention, study design and processes.Methods and analysisA multicentre, parallel two-group randomised trial with individual 2:1 allocation to the PERFORM exercise-based intervention plus usual care (intervention) or usual care alone (control). The primary outcome of this feasibility trial will be to assess whether prespecified progression criteria (recruitment, retention, intervention adherence) are met to progress to the full randomised trial. The trial will be conducted across three UK sites and 60 people with MLTCs, defined as two or more LTCs, with at least one having evidence of the beneficial effect of exercise. The PERFORM intervention comprises an 8-week (twice a week for 6 weeks and once a week for 2 weeks) supervised rehabilitation programme of personalised exercise training and self-management education delivered by trained healthcare professionals followed by two maintenance sessions. Trial participants will be recruited over a 4.5-month period, and outcomes assessed at baseline (prerandomisation) and 3 months postrandomisation and include health-related quality of life, psychological well-being, symptom burden, frailty, exercise capacity, physical activity, sleep, cognition and serious adverse events. A mixed-methods process evaluation will assess acceptability, feasibility and fidelity of intervention delivery and feasibility of trial processes. An economic evaluation will assess the feasibility of data collection and estimate the costs of the PERFORM intervention.Ethics and disseminationThe trial has been given favourable opinion by the West Midlands, Edgbaston Research Ethics Service (Ref: 23/WM/0057). Participants will be asked to give full, written consent to take part by trained researchers. Findings will be disseminated via journals, presentations and targeted communications to clinicians, commissioners, service users and patients and the public.Trial registration numberISRCTN68786622.Protocol version2.0 (16 May 2023).
Differences in patient demographic and tumour characteristics between patients of South Asian and White ethnicity diagnosed with an endometrial cancer (EC) and currently living in England are not ...well described. We undertook a retrospective study of EC cases diagnosed at the University Hospitals of Leicester, UK. A total of 1884 cases were included, with 13% of the patients being of South Asian ethnicity. South Asian women were diagnosed at a significantly younger age (mean age of 60.3 years) compared to women of White ethnicity (mean age of 66.9 years) with a mean difference of 6.6 years (95% CI 5.1 to 8.1, p < 0.001). Rising body mass index (BMI) in the White patient group was significantly correlated with younger age at diagnosis (p < 0.001); however, this association was not seen in South Asian patients. A linear regression that adjusted for diabetes status, BMI, and the interaction terms of diabetes status with BMI and ethnicity with BMI, highlighted a younger age of diagnosis in South Asian patients with a BMI less than 45 kg/m2. The difference was greatest at lower BMIs for both non-diabetics and diabetics. Further investigation is needed to explain these differences and to determine their impact on suspected cancer referral criteria.
BackgroundThere are a paucity of randomised data on the optimal timing of invasive coronary angiography (ICA) in higher-risk patients with non-ST elevation myocardial infarction (N-STEMI). ...International guideline recommendations for early ICA are primarily based on retrospective subgroup analyses of neutral trials.AimsThe RAPID N-STEMI trial aims to determine whether very early percutaneous revascularisation improves clinical outcomes as compared with a standard of care strategy in higher-risk N-STEMI patients.Methods and analysisRAPID N-STEMI is a prospective, multicentre, open-label, randomised-controlled, pragmatic strategy trial. Higher-risk N-STEMI patients, as defined by Global Registry of Acute Coronary Events 2.0 score ≥118, or >90 with at least one additional high-risk feature, were randomised to either: very early ICA±revascularisation or standard of care timing of ICA±revascularisation. The primary outcome is the proportion of participants with at least one of the following events (all-cause mortality, non-fatal myocardial infarction and hospital admission for heart failure) at 12 months. Key secondary outcomes include major bleeding and stroke. A hypothesis generating cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage and residual ischaemia post percutaneous coronary intervention. On 7 April 2021, the sponsor discontinued enrolment due to the impact of the COVID-19 pandemic and lower than expected event rates. 425 patients were enrolled, and 61 patients underwent CMR.Ethics and disseminationThe trial has been reviewed and approved by the East of England Cambridge East Research Ethics Committee (18/EE/0222). The study results will be submitted for publication within 6 months of completion.Trial registration numberNCT03707314; Pre-results.
To examine the feasibility of conducting a fully powered randomized controlled trial (RCT) of Individual Placement and Support (IPS). IPS is a form of supported employment which aims to put people ...into open employment quickly and in accordance with their preferences. It is delivered by employment specialists collocated within clinical teams, and provides time unlimited support for the individual and their employer, along with welfare benefits counselling.
A feasibility cluster RCT of treatment as usual (TAU) plus IPS versus TAU alone was conducted over 12 months among patients with offending histories in a community forensic setting in the UK. The feasibility criteria were to achieve 50% recruitment rate; 50% completion rate for IPS; 50% completion rate of all outcome measures; and 80% acceptability rating for IPS. The primary efficacy outcome was the proportion of people in open employment at 12 months. The secondary outcomes were other vocational and educational activities; Brief Psychiatric Rating Scale; Rosenberg's Self-esteem Scale; Client Service Receipt Inventory; quality of life using the SF12-v2 and EQ5-D3; Social Functioning Questionnaire; Work Limitation Questionnaire; and reoffending.
Participants' mean age was 39.2 years. The majority were male (88.9), White British (72.2), and single (72.2%). Over 72% had no higher qualification beyond secondary education; mean years in education was 10.4. Over one third had schizophrenia, one fifth had depression, and the rest had personality disorder as their primary diagnosis. Participants had a lifetime average of 7.5 convictions for 15.5 offences. The recruitment rate of all referrals was 38.3% (IPS n = 11; TAU n = 7). Completion rate for IPS was 54.5, with 45.5% acceptability rating. Completion rates for outcome measures for the groups at baseline and 12 months ranged from 22.2 to 100%. The proportion of people in open employment at 12 months were 9.1 and 0% for IPS and TAU respectively.
It is not feasible to conduct a full RCT of IPS in community forensic settings in the UK owing to recruitment and retention difficulties. Conducting a trial of this kind requires a large pool of patients from multiple sites and longer IPS implementation and recruitment periods than those of this study.
www.ClinicalTrials.gov, identifier NCT02442193.
IntroductionThe BRIGhTMIND study aims to determine the clinical effectiveness, cost-effectiveness and mechanism of action of connectivity guided intermittent theta burst stimulation (cgiTBS) versus ...standard repetitive transcranial magnetic stimulation (rTMS) in adults with moderate to severe treatment resistant depression.Methods and analysisThe study is a randomised double-blind controlled trial with 1:1 allocation to either 20 sessions of (1) cgiTBS or (2) neuronavigated rTMS not using connectivity guidance. A total of 368 eligible participants with a diagnosis of current unipolar major depressive disorder that is both treatment resistant (defined as scoring 2 or more on the Massachusetts General Hospital Staging Score) and moderate to severe (scoring >16 on the 17-item Hamilton Depression Rating Scale (HDRS-17)), will be recruited from primary and secondary care settings at four treatment centres in the UK. The primary outcome is depression response at 16 weeks (50% or greater reduction in HDRS-17 score from baseline). Secondary outcomes include assessments of self-rated depression, anxiety, psychosocial functioning, cognition and quality of life at 8, 16 and 26 weeks postrandomisation. Cost-effectiveness, patient acceptability, safety, mechanism of action and predictors of response will also be examined.Ethics and disseminationEthical approval was granted by East Midlands Leicester Central Research Ethics Committee (ref: 18/EM/0232) on 30 August 2018. The results of the study will be published in relevant peer-reviewed journals, and then through professional and public conferences and media. Further publications will explore patient experience, moderators and mediators of outcome and mechanism of action.Trial registration numberISRCTN19674644
Depression is a substantial health and economic burden. In approximately one-third of patients, depression is resistant to first-line treatment; therefore, it is essential to find alternative ...treatments. Transcranial magnetic stimulation (TMS) is a neuromodulatory treatment involving the application of magnetic pulses to the brain that is approved in the United Kingdom and the United States in treatment-resistant depression. This trial aims to compare the clinical effectiveness, cost-effectiveness, and mechanism of action of standard treatment repetitive TMS (rTMS) targeted at the F3 electroencephalogram site with a newer treatment-a type of TMS called theta burst stimulation (TBS) targeted based on measures of functional brain connectivity. This protocol outlines brain imaging acquisition and analysis for the Brain Imaging Guided Transcranial Magnetic Stimulation in Depression (BRIGhTMIND) study trial that is used to create personalized TMS targets and answer the proposed mechanistic hypotheses.
The aims of the imaging arm of the BRIGhTMIND study are to identify functional and neurochemical brain signatures indexing the treatment mechanisms of rTMS and connectivity-guided intermittent theta burst TMS and to identify imaging-based markers predicting response to treatment.
The study is a randomized double-blind controlled trial with 1:1 allocation to either 20 sessions of TBS or standard rTMS. Multimodal magnetic resonance imaging (MRI) is acquired for each participant at baseline (before TMS treatment) with T1-weighted and task-free functional MRI during rest used to estimate TMS targets. For participants enrolled in the mechanistic substudy, additional diffusion-weighted sequences are acquired at baseline and at posttreatment follow-up 16 weeks after treatment randomization. Core data sets of T1-weighted and task-free functional MRI during rest are acquired for all participants and are used to estimate TMS targets. Additional sequences of arterial spin labeling, magnetic resonance spectroscopy, and diffusion-weighted images are acquired depending on the recruitment site for mechanistic evaluation. Standard rTMS treatment is targeted at the F3 electrode site over the left dorsolateral prefrontal cortex, whereas TBS treatment is guided using the coordinate of peak effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. Both treatment targets benefit from the level of MRI guidance, but only TBS is provided with precision targeting based on functional brain connectivity.
Recruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023.
This trial will determine the impact of precision MRI guidance on rTMS treatment and assess the neural mechanisms underlying this treatment in treatment-resistant depressed patients.
ISRCTN Registry ISRCTN19674644; https://www.isrctn.com/ISRCTN19674644.
DERR1-10.2196/31925.
Aims. To apply and assess the suitability of a model consisting of commonly used cross-cultural translation methods to achieve a conceptually equivalent Gujarati language version of the Leicester ...self-assessment type 2 diabetes risk score. Methods. Implementation of the model involved multiple stages, including pretesting of the translated risk score by conducting semistructured interviews with a purposive sample of volunteers. Interviews were conducted on an iterative basis to enable findings to inform translation revisions and to elicit volunteers’ ability to self-complete and understand the risk score. Results. The pretest stage was an essential component involving recruitment of a diverse sample of 18 Gujarati volunteers, many of whom gave detailed suggestions for improving the instructions for the calculation of the risk score and BMI table. Volunteers found the standard and level of Gujarati accessible and helpful in understanding the concept of risk, although many of the volunteers struggled to calculate their BMI. Conclusions. This is the first time that a multicomponent translation model has been applied to the translation of a type 2 diabetes risk score into another language. This project provides an invaluable opportunity to share learning about the transferability of this model for translation of self-completed risk scores in other health conditions.
Curcumin is the main active ingredient of the spice turmeric, investigated extensively for putative anticancer properties.
This phase IIa open-labelled randomized controlled trial aimed to assess ...safety, efficacy, quality of life, neurotoxicity, curcuminoids, and C-X-C-motif chemokine ligand 1 (CXCL1) in patients receiving folinic acid/5-fluorouracil/oxaliplatin chemotherapy (FOLFOX) compared with FOLFOX + 2 g oral curcumin/d (CUFOX).
Twenty-eight patients aged >18 y with a histological diagnosis of metastatic colorectal cancer were randomly assigned (1:2) to receive either FOLFOX or CUFOX. Safety was assessed by Common Toxicity Criteria-Adverse Event reporting, and efficacy via progression-free survival (PFS) and overall survival (OS). Quality of life and neurotoxicity were assessed using questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and Functional Assessment of Cancer Treatment-Gynecologic Oncology Group-Neurotoxicity). Plasma curcuminoids were determined with liquid chromatography (LC) electrospray ionization tandem mass spectrometry and CXCL1 by ELISA.
Addition of daily oral curcumin to FOLFOX chemotherapy was safe and tolerable (primary outcome). Similar adverse event profiles were observed for both arms. In the intention-to-treat population, the HR for PFS was 0.57 (95% CI: 0.24, 1.36; P = 0.2) (median of 171 and 291 d for FOLFOX and CUFOX, respectively) and for OS was 0.34 (95% CI: 0.14, 0.82; P = 0.02) (median of 200 and 502 d for FOLFOX and CUFOX, respectively). There was no significant difference between arms for quality of life (P = 0.248) or neurotoxicity (P = 0.223). Curcumin glucuronide was detectable at concentrations >1.00 pmol/mL in 15 of 18 patients receiving CUFOX. Curcumin did not significantly alter CXCL1 over time (P = 0.712).
Curcumin is a safe and tolerable adjunct to FOLFOX chemotherapy in patients with metastatic colorectal cancer. This trial was registered at clinicaltrials.gov as NCT01490996 and at www.clinicaltrialsregister.eu as EudraCT 2011-002289-19.
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