UK National Health Service Hospitals Research Articles

A Device for Prehabilitation of Total Knee Replacement Surgery (Slider): Usability Study.

Rehabilitation, or "prehabilitation," is essential in preparing for and recovering from knee replacement surgery. The recent demand for these services has surpassed available resources, a situation further strained by the COVID-19 pandemic, which has led to a pivot toward digital solutions such as web- or app-based videos and wearables. These solutions, however, face challenges with user engagement, calibration requirements, and skin contact issues. This study evaluated the practicality of a low-contact, gamified device designed to assist with prehabilitation exercises. The study aimed to assess the practicality and user-friendliness of a newly designed physiotherapy device (Slider) that enables exercise monitoring without the need for direct contact with the skin. A total of 17 patients awaiting knee replacement surgery at a UK National Health Service (NHS) hospital participated in this study. They used the device over a 2-week period and subsequently provided feedback through a usability and acceptability questionnaire. The study was completed by all participants, with a majority (13/17, 76%) finding the device intuitive and easy to use. The majority of patients were satisfied with the device's ability to meet their presurgery physiotherapy requirements (16/17, 94%) and expressed a willingness to continue using it (17/17, 100%). No safety issues or adverse effects were reported by the participants. The results indicate that the device was found to be a feasible option for patients to conduct presurgery physiotherapy exercises independently, away from a clinical setting. Further research involving a larger and more diverse group of participants is recommended to validate these findings more robustly.

Metformin in the prevention of type 2 diabetes after gestational diabetes in postnatal women (OMAhA): a UK multicentre randomised, placebo-controlled, double-blind feasibility trial with nested qualitative study

ObjectiveTo determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes.DesignA multicentre, placebo-controlled, double-blind randomised feasibility trial...

Compression therapy for NHS inpatients with leg ulcers: a literature review.

Leg ulcers are common, distressing and painful for patients, and are a significant financial burden to healthcare providers. Compression therapy is the mainstay of treatment for venous leg ulceration. Several studies have evaluated leg ulcer management and compression therapy in the community. However, little is known about the prevalence of leg ulceration and use of compression therapy in acute hospitals. The aim of this study was to explore the published literature on the use of compression therapy for inpatients with leg ulcers in UK National Health Service hospital settings. A literature search was undertaken to identify published papers reporting on inpatient leg ulcer populations and the use of compression therapy in hospitals using the following databases: CINAHL, MEDLINE Complete, Embase and PubMed. The literature review identified 364 articles, of which three met the eligibility criteria. These studies reported on the prevalence of leg ulceration, the number of Doppler assessments conducted for patients and the use of compression therapy. This review confirmed a lack of information on the prevalence of hospital inpatients with leg ulcers, and identified the need to conduct prevalence audits, establish leg ulcer services to streamline inpatient leg ulcer care and provide staff and patient education programmes.

What is the existing evidence base for adult medical same day emergency care in UK NHS hospitals? A scoping review protocol

ObjectivesSame day emergency care (SDEC) is a new model of care, which has emerged over the past 5 years, building on prior ambulatory care services. The National Health Service (NHS)...

Protocol for a multicentre randomised controlled trial examining the effects of temporarily pausing Bruton tyrosine kinase inhibitor therapy to coincide with SARS-CoV-2 vaccination and its impact on immune responses in patients with chronic lymphocytic leukaemia

IntroductionPeople who are immunocompromised have a poor biological response to vaccinations. This study aims to determine in patients with chronic lymphocytic leukaemia (CLL) if a 3-week pause in Bruton tyrosine...

Photodynamic Diagnosis-guided Transurethral Resection of Bladder Tumour in Participants with a First Suspected Diagnosis of Intermediate- or High-risk Non–muscle-invasive Bladder Cancer: Cost-effectiveness Analysis Alongside a Randomised Controlled Trial

BackgroundRecurrence of non–muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumour (TURBT). Photodynamic diagnosis (PDD) may reduce recurrence. PDD uses a photosensitiser in the bladder that causes the tumour to fluoresce to guide resection. PDD provides better diagnostic accuracy and allows more complete tumour resection. ObjectiveTo estimate the economic efficiency of PDD-guided TURBT (PDD-TURBT) in comparison to white light–guided TURNT (WL-TURBT) in individuals with a suspected first diagnosis of NMIBC at intermediate or high risk of recurrence on the basis of routine visual assessment before being scheduled for TURBT. Design, setting, and participantsThis is a health economic evaluation alongside a pragmatic, open-label, parallel-group randomised trial from a societal perspective. A total of 493 participants (aged ≥16 yr) were randomly allocated to PDD-TURBT (n = 244) or WL-TURBT (n = 249) in 22 UK National Health Service hospitals. Outcome measurements and statistical analysisCost effectiveness ratios were based on the use of health care resources associated with PDD-TURBT and WL-TURBT and quality-adjusted life years (QALYs) gained within the trial. Uncertainties in key parameters were assessed using sensitivity analyses. Results and limitationsOn the basis of the use of resources driven by the trial protocol, the incremental cost effectiveness of PDD-TURBT in comparison to WL-TURBT was not cost saving. At 3 yr, the total cost was £12 881 for PDD-TURBT and £12 005 for WL-TURBT. QALYs at three years were 2.087 for PDD-TURBT and 2.094 for WL-TURBT. The probability that PDD-TURBT is cost effective was never >30% above the range of societal cost-effectiveness thresholds. ConclusionsThere was no evidence of a difference in either costs or QALYs over 3-yr follow-up between PDD-TURBT and WL-TURBT in individuals with suspected intermediate- or high-risk NMIBC. PDD-TURBT is not supported for the management of primary intermediate- or high-risk NMIBC. Patient summaryWe assessed overall costs for two approaches for removal of bladder tumours in noninvasive cancer and measured quality-adjusted life years gained for each. We found that use of a photosensitiser in the bladder was not more cost effective than use of white light only during tumour removal.

Efficacy and safety of carbon dioxide insufflation for brain protection for patients undergoing planned left-sided open heart valve surgery: protocol for a multicentre, placebo-controlled, blinded, randomised controlled trial (the CO2 Study)

IntroductionBrain injury is common following open heart valve surgery. Carbon dioxide insufflation (CDI) has been proposed to reduce the incidence of brain injury by reducing the number of air microemboli...

Reverse shoulder arthroplasty versus hemiarthroplasty versus non-surgical treatment for older adults with acute 3- or 4-part fractures of the proximal humerus: study protocol for a randomised controlled trial (PROFHER-2: PROximal Fracture of Humerus Evaluation by Randomisation – Trial Number 2)

BackgroundProximal humerus fractures (PHF) are common and painful injuries, with the majority resulting from falls from a standing height. As with other fragility fractures, its age-specific incidence is increasing. Surgical treatment with hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA) have been increasingly used for displaced 3- and 4-part fractures despite a lack of good quality evidence as to whether one type of arthroplasty is superior to the other, and whether surgery is better than non-surgical management. The PROFHER-2 trial has been designed as a pragmatic, multicentre randomised trial to compare the clinical and cost-effectiveness of RSA vs HA vs Non-Surgical (NS) treatment in patients with 3- and 4-part PHF.MethodsAdults over 65 years of age presenting with acute radiographically confirmed 3- or 4-part fractures, with or without associated glenohumeral joint dislocation, who consent for trial participation will be recruited from around 40 National Health Service (NHS) Hospitals in the UK. Patients with polytrauma, open fractures, presence of axillary nerve palsy, pathological (other than osteoporotic) fractures, and those who are unable to adhere to trial procedures will be excluded. We will aim to recruit 380 participants (152 RSA, 152 HA, 76 NS) using 2:2:1 (HA:RSA:NS) randomisation for 3- or 4-part fractures without joint dislocation, and 1:1 (HA:RSA) randomisation for 3- or 4-part fracture dislocations. The primary outcome is the Oxford Shoulder Score at 24 months. Secondary outcomes include quality of life (EQ-5D-5L), pain, range of shoulder motion, fracture healing and implant position on X-rays, further procedures, and complications. Independent Trial Steering Committee and Data Monitoring Committee will oversee the trial conduct, including the reporting of adverse events and harms.DiscussionThe PROFHER-2 trial is designed to provide a robust answer to guide the treatment of patients aged 65 years or over who sustain 3- and 4-part proximal humeral fractures. The pragmatic design and recruitment from around 40 UK NHS hospitals will ensure immediate applicability and generalisability of the trial findings. The full trial results will be made available in a relevant open-access peer-reviewed journal.Trial registrationISRCTN76296703. Prospectively registered on 5th April 2018

The Achieving Self-directed Integrated Cancer Aftercare Intervention for Detection of Recurrent and Second Primary Melanoma in Survivors of Melanoma: Pilot Randomized Controlled Trial.

BackgroundMelanoma is common with increasing incidence. Guidelines recommend monthly total skin self-examinations (TSSEs) by survivors to detect recurrent and new primary melanomas. TSSE is underperformed despite evidence of benefit.ObjectiveThis study compares the effect on psychological well-being and TSSE practice of a self-directed digital intervention with treatment as usual in patients treated for a first stage 0 to IIC primary cutaneous melanoma within the preceding 60 months.MethodsThis randomized clinical trial was conducted at 2 UK National Health Service hospitals (Aberdeen Royal Infirmary, Grampian, and Addenbrooke’s, Cambridge). Adults (≥18 years) diagnosed with a first 0 to IIC primary cutaneous melanoma were randomized to receive Achieving Self-directed Integrated Cancer Aftercare (ASICA), a tablet-based intervention prompting and supporting TSSE in survivors of melanoma, or to usual care. The hypothesis was that ASICA would increase TSSE practice in users affected by melanoma and compared with controls without affecting psychological well-being. The main primary outcomes were melanoma worry (Melanoma Worry Scale), anxiety and depression (Hospital Anxiety and Depression Scale), and quality of life (EQ-5D-5L) as well as secondary outcomes collected using postal questionnaires 3, 6, and 12 months following randomization.ResultsA total of 240 recruits were randomized (1:1) into the ASICA (n=121, 50.4%) or control (n=119, 49.6%) groups. There were no significant differences between groups for melanoma worry at 12 months (mean difference: 0.12, 95% CI −0.6 to 0.84; P=.74), 3 months (0.23, 95% CI −0.31 to 0.78; P=.40), or 6 months (−0.1, 95% CI −0.7 to 0.51; P=.76). The ASICA group had lower anxiety scores at 12 months (−0.54, 95% CI −1.31 to 0.230; P=.17), 3 months (−0.13, 95% CI −0.79 to 0.54; P=.71), and significantly at 6 months (−1.00, 95% CI −1.74 to −0.26; P=.009). Depression scores were similar, being lower at 12 months (−0.44, 95% CI −1.11 to 0.23; P=.20) and 3 months (−0.24, 95% CI −0.84 to 0.35; P=.42) but only significantly lower at 6 months (−0.77, 95% CI −1.41 to −0.12; P=.02). The ASICA group had significantly higher quality of life scores at 12 months (0.044, 95% CI 0.003-0.085; P=.04) and 6 months (0.070, 95% CI 0.032-0.107; P<.001) and nonsignificantly at 3 months (0.024, 95% CI −0.006 to 0.054; P=.11). ASICA users reported significantly more regular (>5) TSSEs during the study year and significantly higher levels of self-efficacy in conducting TSSE. They also reported significantly higher levels of planning and intention to perform TSSE in the future.ConclusionsUsing ASICA for 12 months does not increase melanoma worry, can reduce anxiety and depression, and may improve quality of life. ASICA has the potential to improve the well-being and vigilance of survivors of melanoma and enable the benefits of regular TSSE.Trial RegistrationClinicalTrials.gov NCT03328247; https://clinicaltrials.gov/ct2/show/NCT03328247International Registered Report Identifier (IRRID)RR2-10.1186/s13063-019-3453-x

Prediction of hospital-onset COVID-19 infections using dynamic networks of patient contact: an international retrospective cohort study

BackgroundReal-time prediction is key to prevention and control of infections associated with health-care settings. Contacts enable spread of many infections, yet most risk prediction frameworks fail to account for their dynamics. We developed, tested, and internationally validated a real-time machine-learning framework, incorporating dynamic patient-contact networks to predict hospital-onset COVID-19 infections (HOCIs) at the individual level.MethodsWe report an international retrospective cohort study of our framework, which extracted patient-contact networks from routine hospital data and combined network-derived variables with clinical and contextual information to predict individual infection risk. We trained and tested the framework on HOCIs using the data from 51 157 hospital inpatients admitted to a UK National Health Service hospital group (Imperial College Healthcare NHS Trust) between April 1, 2020, and April 1, 2021, intersecting the first two COVID-19 surges. We validated the framework using data from a Swiss hospital group (Department of Rehabilitation, Geneva University Hospitals) during a COVID-19 surge (from March 1 to May 31, 2020; 40 057 inpatients) and from the same UK group after COVID-19 surges (from April 2 to Aug 13, 2021; 43 375 inpatients). All inpatients with a bed allocation during the study periods were included in the computation of network-derived and contextual variables. In predicting patient-level HOCI risk, only inpatients spending 3 or more days in hospital during the study period were examined for HOCI acquisition risk.FindingsThe framework was highly predictive across test data with all variable types (area under the curve [AUC]-receiver operating characteristic curve [ROC] 0·89 [95% CI 0·88–0·90]) and similarly predictive using only contact-network variables (0·88 [0·86–0·90]). Prediction was reduced when using only hospital contextual (AUC-ROC 0·82 [95% CI 0·80–0·84]) or patient clinical (0·64 [0·62–0·66]) variables. A model with only three variables (ie, network closeness, direct contacts with infectious patients [network derived], and hospital COVID-19 prevalence [hospital contextual]) achieved AUC-ROC 0·85 (95% CI 0·82–0·88). Incorporating contact-network variables improved performance across both validation datasets (AUC-ROC in the Geneva dataset increased from 0·84 [95% CI 0·82–0·86] to 0·88 [0·86–0·90]; AUC-ROC in the UK post-surge dataset increased from 0·49 [0·46–0·52] to 0·68 [0·64–0·70]).InterpretationDynamic contact networks are robust predictors of individual patient risk of HOCIs. Their integration in clinical care could enhance individualised infection prevention and early diagnosis of COVID-19 and other nosocomial infections.FundingMedical Research Foundation, WHO, Engineering and Physical Sciences Research Council, National Institute for Health Research (NIHR), Swiss National Science Foundation, and German Research Foundation.

Validation of the RCOphth and UKEGS glaucoma risk stratification tool ‘GLAUC-STRAT-fast’

Background/aimsThe aim of this study was to validate the Glaucoma Risk Stratification Tool (GLAUC-STRAT-fast) currently recommended by the Royal College of Ophthalmologists for the risk stratification of patients with glaucoma...

Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals

ObjectivesNosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study...

Flexibility and resistance exercises versus usual care for improving pain and function after distal radius fracture in adults aged 50 years or over: protocol for the WISE randomised multicentre feasibility trial

BackgroundDistal radius fractures represent about 1 in 5 of all fractures treated in UK hospitals. Most distal radius fractures occur in women aged 50 years or over after a fall. Distal radius fractures are managed using splints or casting, some are also treated with surgical fixation. Patients often experience long-term muscle weakness of the hand and arm that may impact their ability to do daily activities such as personal hygiene, routine household chores and food preparation. We propose a structured and tailored flexibility and resistance exercise programme for the hand and arm supplemented with behaviour change strategies to help perform daily exercise. The main aim of our study is to assess the feasibility of conducting a definitive randomised controlled trial.MethodsThis study is a multicentre, parallel-group individually randomised feasibility trial. We will recruit a minimum of 72 adults aged 50 years or over with distal radius fracture treated surgically or non-surgically from at least three UK National Health Service (NHS) hospitals. They will be randomised 1:1:1 to receive usual care, usual care and independent exercise with a single therapy session or usual care and supervised exercise with three therapy sessions over 12 weeks. Our primary feasibility objectives are (1) patient engagement assessed by recruitment, (2) acceptability of the interventions assessed by adherence and patient and clinician experience and (3) retention of participants in the trial. Outcome measures will be assessed at baseline, 3 months and at 6 months after randomisation. A qualitative sub-study will explore the experiences of the trial participants and therapists delivering the exercises.DiscussionA definitive trial will be considered feasible without major modifications if our progression criteria are met. If successful, the findings will inform the design of a future definitive RCT to evaluate the clinical and cost-effectiveness of the WISE exercise programme.Trial registrationISRCTN12290145.

Cupriavidus spp. and other waterborne organisms in healthcare water systems across the UK

Cupriavidus pauculus is a rare clinical pathogen, cases of which have been linked to contaminated hospital water systems. An outbreak of three cases of C.pauculus and other waterborne organisms was reported in a Glasgow hospital in 2018. To determine whether Cupriavidus spp. are present in hospital water systems elsewhere in Scotland and the UK, and to ascertain the optimal laboratory methodology for detection. This study also sought to establish where in the water system these organisms are detected, and whether a selective media could be developed for isolation. In addition, water samples were tested for the presence of other Gram-negative waterborne organisms. Water samples were received from 10 UK National Health Service hospitals and from various parts of the water system. Isolates were plated on to tryptone soya agar (TSA) and Pseudomonas isolation agar, and were further identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and 16S polymerase chain reaction. Cupriavidus spp. were detected in four of 10 hospitals tested, and all five isolates were from the periphery of the water system. All hospitals had evidence of other opportunistic premise plumbing pathogens. Cupriavidus spp. were identified using TSA, with some isolates growing on Pseudomonas isolation agar; as such, they may be detected inadvertently when testing water specifically for Pseudomonas aeruginosa. Isolation of Cupriavidus spp. was not unique to the Glasgow incident, and these bacteria are present in hospital water systems elsewhere in the UK. Water testing in response to clinical cases is recommended. Consideration should also be given to water testing following bacteraemias due to other rare and unusual water-borne pathogens.

Use of the Quality of Interactions Schedule (QuIS) in assessing negative staff-patient interactions in acute care settings for older people: A content validation study.

The Quality of Interactions Schedule (QuIS) is an observational tool to assess the quality of staff-patient interactions in a healthcare context. QuIS is a promising measure for the evaluation of compassionate care, particularly where care is being delivered to patient populations, such as older people, who may be excluded from self-completion data collection methods. This study investigates the content validity of QuIS in identification of negative staff-patient interactions in acute care. Staff-patient interactions (n=1598) on adult inpatient units with a high proportion of older patients in two UK National Health Service hospitals were observed and rated using QuIS. When rating interactions as negative quality, observers recorded brief field notes to explain the rating. Content analysis was used to develop categories of negative interaction type. These categories were compared with the QuIS negative interaction definitions. Eighty-eight negative ratings were accompanied by a field note that could be used in the analysis. Five interaction categories were identified: Patient calls for help, call not acknowledged; Staff focused on task and appear to ignore/not hear patient; Patient-led interactions appear dismissed or ignored; Patient prevented from doing something without explanation; Staff interact with each other or talk to relatives, not including patient. There was clear association between the derived categories and QuIS guidance for negative ratings. These findings support the validity of QuIS data in relation to measurement of interaction quality in acute care settings. Extending the research to a wider range of settings would be useful.

The STAR care pathway for patients with pain at 3 months after total knee replacement: a multicentre, pragmatic, randomised, controlled trial

SummaryBackgroundApproximately 20% of people experience chronic pain after total knee replacement, but effective treatments are not available. We aimed to evaluate the clinical effectiveness and cost-effectiveness of a new care pathway for chronic pain after total knee replacement.MethodsWe did an unmasked, parallel group, pragmatic, superiority, randomised, controlled trial at eight UK National Health Service (NHS) hospitals. People with chronic pain at 3 months after total knee replacement surgery were randomly assigned (2:1) to the Support and Treatment After Replacement (STAR) care pathway plus usual care, or to usual care alone. The STAR intervention aimed to identify underlying causes of chronic pain and enable onward referrals for targeted treatment through a 3-month post-surgery assessment with an extended scope practitioner and telephone follow-up over 12 months. Co-primary outcomes were self-reported pain severity and pain interference in the replaced knee, assessed with the Brief Pain Inventory (BPI) pain severity and interference scales at 12 months (scored 0–10, best to worst) and analysed on an as-randomised basis. Resource use, collected from electronic hospital records and participants, was valued with UK reference costs. Quality-adjusted life-years (QALYs) were calculated from EQ-5D-5L responses. This trial is registered with ISRCTN, ISRCTN92545361.FindingsBetween Sept 6, 2016, and May 31, 2019, 363 participants were randomly assigned to receive the intervention plus usual care (n=242) or to receive usual care alone (n=121). Participants had a median age of 67 years (IQR 61 to 73), 217 (60%) of 363 were female, and 335 (92%) were White. 313 (86%) patients provided follow-up data at 12 months after randomisation (213 assigned to the intervention plus usual care and 100 assigned to usual care alone). At 12 months, the mean between-group difference in the BPI severity score was −0·65 (95% CI −1·17 to −0·13; p=0·014) and the mean between-group difference in the BPI interference score was −0·68 (−1·29 to −0·08; p=0·026), both favouring the intervention. From an NHS and personal social services perspective, the intervention was cost-effective (greater improvement with lower cost), with an incremental net monetary benefit of £1256 (95% CI 164 to 2348) at £20 000 per QALY threshold. One adverse reaction of participant distress was reported in the intervention group.InterpretationSTAR is a clinically effective and cost-effective intervention to improve pain outcomes over 1 year for people with chronic pain at 3 months after total knee replacement surgery.FundingNational Institute for Health Research.

Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer's disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial

SummaryBackgroundDrugs modifying angiotensin II signalling could reduce Alzheimer's disease pathology, thus decreasing the rate of disease progression. We investigated whether the angiotensin II receptor antagonist losartan, compared with placebo, could reduce brain volume loss, as a measure of disease progression, in clinically diagnosed mild-to-moderate Alzheimer's disease.MethodsIn this double-blind, multicentre, randomised controlled trial, eligible patients aged 55 years or older, previously untreated with angiotensin II drugs and diagnosed (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria) with mild-to-moderate Alzheimer's disease, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts. After undergoing a 4-week, open-label phase of active treatment then washout, participants were randomly assigned (1:1) oral over-encapsulated preparations of either 100 mg losartan (after an initial two-dose titration stage) or matched placebo daily for 12 months. Randomisation, minimised by age and baseline medial temporal lobe atrophy score, was undertaken online or via pin-access service by telephone. Participants, their study companions, and study personnel were masked to group assignment. The primary outcome, analysed by the intention-to-treat principle (ie, participants analysed in the group to which they were randomised, without imputation for missing data), was change in whole brain volume between baseline and 12 months, measured using volumetric MRI and determined by boundary shift interval (BSI) analysis. The trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN93682878) and the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT 2012–003641–15), and is completed.FindingsBetween July 22, 2014, and May 17, 2018, 261 participants entered the open-label phase. 211 were randomly assigned losartan (n=105) or placebo (n=106). Of 197 (93%) participants who completed the study, 171 (81%) had complete primary outcome data. The mean brain volume (BSI) reduction was 19·1 mL (SD 10·3) in the losartan group and 20·0 mL (10·8) in the placebo group. The difference in total volume reduction between groups was –2·29 mL (95% CI –6·46 to 0·89; p=0·14). The number of adverse events was low (22 in the losartan group and 20 in the placebo group) with no differences between treatment groups. There was one treatment-related death per treatment group.Interpretation12 months of treatment with losartan was well tolerated but was not effective in reducing the rate of brain atrophy in individuals with clinically diagnosed mild-to-moderate Alzheimer's disease. Further research is needed to assess the potential therapeutic benefit from earlier treatment in patients with milder cognitive impairment or from longer treatment periods.FundingEfficacy and Mechanism Evaluation Programme (UK Medical Research Council and National Institute for Health Research).

Early detection of neovascular age-related macular degeneration: an economic evaluation based on data from the EDNA study

Background/aimsTo evaluate the cost-effectiveness of non-invasive monitoring tests to detect the onset of neovascular age-related macular degeneration (nAMD) in the unaffected second eye of patients receiving treatment for unilateral nAMD...

The cost-effectiveness of temporary single-patient rooms to reduce risks of healthcare-associated infection

The use of single rooms for patient isolation often forms part of a wider bundle to prevent certain healthcare-associated infections (HAIs) in hospitals. Demand for single rooms often exceeds what is available and the use of temporary isolation rooms may help resolve this. Changes to infection prevention practice should be supported by evidence showing that cost-effectiveness is plausible and likely. To perform a cost-effectiveness evaluation of adopting temporary single rooms into UK National Health Service (NHS) hospitals. The cost-effectiveness of a decision to adopt a temporary, single-patient, isolation room to the current infection prevention efforts of an NHS hospital was modelled. Primary outcomes are the expected change to total costs and life-years from an NHS perspective. The mean expected incremental cost per life-year gained (LYG) is £5,829. The probability that adoption is cost-effective against a £20,000 threshold per additional LYG is 93%, and for a £13,000 threshold the probability is 87%. The conclusions are robust to scenarios for key model parameters. If a temporary single-patient isolation room reduces risks of HAI by 16.5% then an adoption decision is more likely to be cost-effective than not. Our estimate of the effectiveness reflects guidelines and reasonable assumptions and the theoretical rationale is strong. Despite uncertainties about the effectiveness of temporary isolation rooms for reducing risks of HAI, there is some evidence that an adoption decision is likely to be cost-effective for the NHS setting. Prospective studies will be useful to reduce this source of uncertainty.

Targeting synovial fibroblast proliferation in rheumatoid arthritis (TRAFIC): an open-label, dose-finding, phase 1b trial.

SummaryBackgroundCurrent rheumatoid arthritis therapies target immune inflammation and are subject to ceiling effects. Seliciclib is an orally available cyclin-dependent kinase inhibitor that suppresses proliferation of synovial fibroblasts—cells not yet targeted in rheumatoid arthritis. Part 1 of this phase 1b/2a trial aimed to establish the maximum tolerated dose of seliciclib in patients with active rheumatoid arthritis despite ongoing treatment with TNF inhibitors, and to evaluate safety and pharmacokinetics.MethodsPhase 1b of the TRAFIC study was a non-randomised, open-label, dose-finding trial done in rheumatology departments in five UK National Health Service hospitals. Eligible patients (aged ≥18 years) fulfilled the 1987 American College of Rheumatology (ACR) or the 2010 ACR–European League Against Rheumatism classification criteria for rheumatoid arthritis and had moderate to severe disease activity (a Disease Activity Score for 28 joints [DAS28] of ≥3·2) despite stable treatment with anti-TNF therapy for at least 3 months before enrolment. Participants were recruited sequentially to a maximum of seven cohorts of three participants each, designated to receive seliciclib 200 mg, 400 mg, 600 mg, 800 mg, or 1000 mg administered in 200 mg oral capsules. Sequential cohorts received doses determined by a restricted, one-stage Bayesian continual reassessment model, which determined the maximum tolerated dose (the primary outcome) based on a target dose-limiting toxicity rate of 35%. Seliciclib maximum concentration (Cmax) and area under the plasma concentration time curve 0–6 h (AUC0–6) were measured. This study is registered with ISRCTN, ISRCTN36667085.FindingsBetween Oct 8, 2015, and Aug 15, 2017, 37 patients were screened and 15 were enrolled to five cohorts and received seliciclib, after which the trial steering committee and the data monitoring committee determined that the maximum tolerated dose could be defined. In addition to a TNF inhibitor, ten (67%) enrolled patients were taking conventional synthetic disease modifying antirheumatic drugs. The maximum tolerated dose of seliciclib was 400 mg, with an estimated dose-limiting toxicity probability of 0·35 (90% posterior probability interval 0·18–0·52). Two serious adverse events occurred (one acute kidney injury in a patient receiving the 600 mg dose and one drug-induced liver injury in a patient receiving the 400 mg dose), both considered to be related to seliciclib and consistent with its known safety profile. 65 non-serious adverse events occurred during the trial, 50 of which were considered to be treatment related. Most treatment-related adverse events were mild; 20 of the treatment-related non-serious adverse events contributed to dose-limiting toxicities. There were no deaths. Average Cmax and AUC0–6 were two-times higher in participants developing dose-limiting toxicities.InterpretationThe maximum tolerated dose of seliciclib has been defined for rheumatoid arthritis refractory to TNF blockade. No unexpected safety concerns were identified to preclude ongoing clinical evaluation in a formal efficacy trial.FundingUK Medical Research Council, Cyclacel, Research into Inflammatory Arthritis Centre (Versus Arthritis), and the National Institute of Health Research Newcastle and Birmingham Biomedical Research Centres and Clinical Research Facilities.