Clinical and cost-effectiveness of PCF versus ACD in the treatment of cervical brachialgia (FORVAD trial).

BACKGROUND: Cervical radiculopathy occurs when a nerve root is compressed in the spine, if symptoms fail to resolve after 6 weeks surgery may be indicated. Anterior Cervical Discectomy (ACD) is the commonest procedure, Posterior Cervical Foraminotomy (PCF) is an alternative that avoids the risk of damage to anterior neck structures. This prospective, Phase III, UK multicentre, open, individually randomised controlled trial was performed to determine whether PCF is superior to ACD in terms of improving clinical outcome as measured by the Neck Disability Index (NDI) 52 weeks post-surgery. METHOD: Following consent to participate and collection of baseline data, subjects with cervical brachialgia were randomised to ACD or PCF in a 1:1 ratio on the day of surgery. Clinical outcomes were assessed on day 1 and patient reported outcomes on day 1 and weeks 6, 12, 26, 39 and 52 post-operation. A total of 252 participants were planned to be randomised. Statistical analysis was limited to descriptive statistics. Health economic outcomes were also described. RESULTS: The trial was closed early (n = 23). Compared to baseline, the median (interquartile range (IQR)) NDI score at 52 weeks reduced from 44.0 (36.0, 62.0) to 25.3 (20.0, 42.0) in the PCF group and increased from 35.6 (34.0, 44.0) to 45.0 (20.0, 57.0) in the ACD group. ACD may be associated with more swallowing, voice and other complications and was more expensive; neck and arm pain scores were similar. CONCLUSIONS: The trial was closed early, therefore no definitive conclusions on clinical or cost-effectiveness could be made.

Posterior cervical foraminotomy versus anterior cervical discectomy for Cervical Brachialgia: the FORVAD RCT.

Background: Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking. Objective: The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome. Design: This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals. Setting: National Health Service trusts. Participants: Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks. Interventions: Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data. Main outcome measures: The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow-Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation. Results: The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0-62.0 weeks) and 25.3 weeks (interquartile range 20.0-42.0 weeks), respectively, in the posterior cervical foraminotomy group (n = 14), and 35.6 weeks (interquartile range 34.0-44.0 weeks) and 45.0 weeks (interquartile range 20.0-57.0 weeks), respectively, in the anterior cervical discectomy group (n = 9). Scores appeared to reduce (i.e. improve) in the posterior cervical foraminotomy group, but not in the anterior cervical discectomy group. The median Eating Assessment Tool-10 items score for swallowing was higher (worse) after anterior cervical discectomy (13.5) than after posterior cervical foraminotomy (0) on day 1, but not at other time points, whereas the median Glasgow-Edinburgh Throat Scale score for globus was higher (worse) after anterior cervical discectomy (15, 7, 6, 6, 2, 2.5) than after posterior cervical foraminotomy (3, 0, 0, 0.5, 0, 0) at all postoperative time points. Five postoperative complications occurred within 6 weeks of surgery, all after anterior cervical discectomy. Neck pain was more severe on day 1 following posterior cervical foraminotomy (Numerical Rating Scale - Neck Pain score 8.5) than at the same time point after anterior cervical discectomy (Numerical Rating Scale - Neck Pain score 7.0). The median health-care costs of providing initial surgical intervention were £2610 for posterior cervical foraminotomy and £4411 for anterior cervical discectomy. Conclusions: The data suggest that posterior cervical foraminotomy is associated with better outcomes, fewer complications and lower costs, but the trial recruited slowly and closed early. Consequently, the trial is underpowered and definitive conclusions cannot be drawn. Recruitment was impaired by lack of individual equipoise and by concern about randomising on the day of surgery. A large prospective multicentre trial comparing anterior cervical discectomy and posterior cervical foraminotomy in the treatment of cervical brachialgia is still required. Trial registration: This trial is registered as ISRCTN10133661. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 21. See the NIHR Journals Library website for further project information.

Cervical brachialgia is pain that starts in the neck and passes down into the arm. Although most people with cervical brachialgia recover quickly, in some patients pain persists, and in 15% of patients pain is so severe that they are unable to work. In the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial, we investigated two neck surgeries used to treat this problem: posterior cervical foraminotomy (surgery from the back of the neck) and anterior cervical discectomy (surgery from the front of the neck). This trial aimed to find out if one of them is better than the other at relieving pain and more cost-effective for the National Health Service. We assessed patients' quality of life 1 year after their surgery and how their pain changed over the course of the year. We also measured the number of complications patients had in the first 6 weeks after their operation. Recruitment was slow and so the trial was stopped early, after only 23 patients from 11 hospitals had been randomly allocated to the two surgery groups. We had planned to recruit 252 participants to the trial; the number of participants we were able to recruit in practice was too small to enable us to determine which surgery is better at relieving pain. To find out why the trial had struggled to recruit, we asked hospital staff and participants about their experiences. We found that hospital staff sometimes struggled to organise everything needed to randomise patients on the day of surgery. Some staff also found it difficult to randomise patients as they had an opinion on which surgery they thought the patient should receive. The data collected in the trial will still be useful to help design future research. Finding out which surgery is better at relieving pain remains important, and the data we have collected will support answering this question in future.

Multicenter Randomized Trial of Intermittently Scanned Continuous Glucose Monitoring Versus Self-Monitoring of Blood Glucose in Individuals With Type 2 Diabetes and Recent-Onset Acute Myocardial Infarction: Results of the LIBERATES Trial.

OBJECTIVE: To analyze the impact of modern glucose-monitoring strategies on glycemic and patient-related outcomes in individuals with type 2 diabetes (T2D) and recent myocardial infarction (MI) and assess cost effectiveness. RESEARCH DESIGN AND METHODS: LIBERATES was a multicenter two-arm randomized trial comparing self-monitoring of blood glucose (SMBG) with intermittently scanned continuous glucose monitoring (isCGM), also known as flash CGM, in individuals with T2D and recent MI, treated with insulin and/or a sulphonylurea before hospital admission. The primary outcome measure was time in range (TIR) (glucose 3.9-10 mmol/L/day) on days 76-90 post-randomization. Secondary and exploratory outcomes included time in hypoglycemia, hemoglobin A1c (HbA1c), clinical outcome, quality of life (QOL), and cost effectiveness. RESULTS: Of 141 participants randomly assigned (median age 63 years; interquartile range 53, 70), 73% of whom were men, isCGM was associated with increased TIR by 17 min/day (95% credible interval -105 to +153 min/day), with 59% probability of benefit. Users of isCGM showed lower hypoglycemic exposure (<3.9 mmol/L) at days 76-90 (-80 min/day; 95% CI -118, -43), also evident at days 16-30 (-28 min/day; 95% CI -92, 2). Compared with baseline, HbA1c showed similar reductions of 7 mmol/mol at 3 months in both study arms. Combined glycemic emergencies and mortality occurred in four isCGM and seven SMBG study participants. QOL measures marginally favored isCGM, and the intervention proved to be cost effective. CONCLUSIONS: Compared with SMBG, isCGM in T2D individuals with MI marginally increases TIR and significantly reduces hypoglycemic exposure while equally improving HbA1c, explaining its cost effectiveness. Studies are required to understand whether these glycemic differences translate into longer-term clinical benefit.

Rapid qualitative analysis in a mixed-methods evaluation of an infection prevention intervention in a UK hospital setting during the COVID-19 pandemic: A discussion of the CLEAN study methodology.

The COVID-19 pandemic created an urgent need for high-quality rapid research. One clinical challenge was how to minimise the risk of transmission in the hospital setting. The CLEAN study conducted a rapid evaluation of the potential utility of a spray-based disinfectant in a hospital setting. The study was undertaken between December 2020 and March 2021 and involved the implementation of the spray in 10 different clinical areas in one UK teaching hospital. A mixed-methods approach was adopted (including observations, surveys, and qualitative interviews) informed by the theories for understanding the implementation of new healthcare technologies. The evaluation found that while the spray had a number of perceived benefits when added to existing disinfection processes, other factors limited its potential utility. These findings informed a number of recommendations for future adoption within hospital settings. This paper describes and reflects on the rapid methodology that allowed us to undertake the study and deliver results in a short space of time. We experienced a number of pressures during set-up and fieldwork due to the challenging conditions caused by the pandemic, and the methodological approach had to evolve throughout the study because of the changing clinical context. The involvement of clinicians from the research setting as full members of the research team was key to the rapid delivery of the research. They provided an essential link to the implementation environment, and their experiential knowledge of the setting added an important perspective to the analysis. Balancing their involvement with their clinical roles was challenging, however, as was coordinating a large and diverse team of interviewers in such a short space of time. Overall, the study highlighted the value of rapid research to inform urgent healthcare decisions in a pandemic. Although our experience suggests that conducting such research requires some practical and methodological trade-offs, we found that there were also numerous benefits of using rapid methods and identified various opportunities to ensure their robustness.

Clinical and cost-effectiveness of Knee Arthroplasty versus Joint Distraction for Osteoarthritis (KARDS): protocol for a multicentre, phase III, randomised control trial.

INTRODUCTION: Knee replacement (KR) is a clinically proven procedure typically offered to patients with severe knee osteoarthritis (OA) to relieve pain and improve quality of life. However, artificial joints fail over time, requiring revision associated with higher mortality and inferior outcomes. With more young people presenting with knee OA and increasing life expectancy, there is an unmet need to postpone time to first KR. Knee joint distraction (KJD), the practice of using external fixators to open up knee joint space, is proposed as potentially effective to preserve the joint following initial studies in the Netherlands, however, has not been researched within an NHS setting. The KARDS trial will investigate whether KJD is non-inferior to KR in terms of patient-reported postoperative pain 12 months post-surgery. METHODS AND ANALYSIS: KARDS is a phase III, multicentre, pragmatic, open-label, individually randomised controlled non-inferiority trial comparing KJD with KR in patients with severe knee OA, employing a hybrid-expertise design, with internal pilot phase and process evaluation. 344 participants will be randomised (1:1) to KJD or KR. The primary outcome measure is the Knee Injury and Osteoarthritis Outcomes Score (KOOS) pain domain score at 12 months post-operation. Secondary outcome measures include patient-reported overall KOOS, Pain Visual Analogue Scale and Oxford Knee Scores, knee function assessments, joint space width, complications and further interventions over 24 months post-operation. Per patient cost difference between KR and KJD and cost per quality-adjusted life year (QALY) gained over 24 months will be estimated within trial, and incremental cost per QALY gained over 20 years by KJD relative to KR predicted using decision analytic modelling. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Research Ethics Committee (REC) and Health Research Authority (HRA). Trial results will be disseminated at clinical conferences, through relevant patient groups and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN14879004; recruitment opened April 2021.

Pro re nata prescribing and administration for neuropsychiatric symptoms and pain in long-term care residents with dementia and memory problems: a cross-sectional study.

Background Prescribing, dispensing and administering pro re nata (PRN; as needed or necessary, as determined by an individual) medicines to people with intermittent or short-term conditions is a potential area for medication errors and inappropriate prescribing and administration. In people with dementia, regular PRN medicines use can demonstrate good practice when appropriate or poor in situations where their use is not recommended. However, the frequency of PRN prescription and administration within long-term care settings (care homes) for people with dementia is largely unknown. A limited number of studies worldwide suggest variation between countries. Objective To describe the prescription and administration rates of PRN medicines for people with dementia in UK care homes. Setting Fifty UK care homes. Method Medication details were collected from review of residents' medicines records within the care home for the previous month. Main outcome measure Prescription and administration of PRN medicines for the treatment of behaviours associated with neuropsychiatric symptoms and pain. Results The most commonly prescribed PRN medicines were analgesics (35.3%), although lower levels of PRN prescription were observed compared to recent studies. The percentage of residents receiving PRN administrations varied, with 20% for antipsychotics, 50% for benzodiazepines, 59% for analgesics, and 85.7% for nonbenzodiazepine hypnotics being administered. Conclusion Further research is needed to understand the decision making in PRN prescription and administration within long-term care. The prescribing of potentially inappropriate medicines remains a problem in long-term care settings and pharmacists have a key role in reducing inappropriate polypharmacy by undertaking medication reviews that consider both regular and PRN medicines.

Promissory identities: Sociotechnical representations & innovation in regenerative medicine.

The field of regenerative medicine (RM) is championed as a potential source of curative treatments and economic wealth, and initiatives have been launched in several countries to facilitate innovation within the field. As a way of examining the social dimensions of innovation within regenerative medicine, this paper explores the sociotechnical representations of RM technologies in the UK, and the tensions, affordances and complexities these representations present for actors within the field. Specifically, the paper uses the Science and Technology Studies-inspired notions of 'technology identity' and 'development space' to examine how particular technologies are framed and positioned by actors, and how these positionings subsequently shape innovation pathways. Four developing RM technologies are used as case studies: bioengineered tracheas; autologous chondrocyte implantation; T-cell therapies; and a 'point-of-care' cell preparation device. Using these case studies we argue that there are particular identity aspects that have powerful performative effects and provide momentum to innovation projects, and we argue that there are particular stakeholders in the UK RM landscape who appear to have considerable power in shaping these technology identities and thus innovation pathways.

Use and reporting of restricted randomization: a review.

RATIONALE, AIMS AND OBJECTIVES: Restricted randomization, such as blocking or minimization, allows for the creation of balanced groups and even distribution of covariates, but it increases the risk of selection bias and technical error. Various methods are available to reduce these risks but there is limited evidence about their current usage, and there are also indications that reporting of these methods may not be adequate. This review aims to identify how frequently different methods of restriction are being used and to assess the reporting of these methods against established reporting standards. METHODS: 82 reports of randomized controlled trial were reviewed. For each trial, the reported method of randomization was recorded and the reporting of randomization was assessed. Where the method of randomization was not clear from the main paper, protocols and other published materials were also reviewed, and authors were contacted for further information. RESULTS: For 11% of trials the method of randomization was not reported in either the paper or a published protocol, and in a further 39% of cases the report omitted key details so that the predictability of the method could not be evaluated. In total, 88% of trials appear to have used some form of restricted randomization, and all of those that report the exact methods used either blocking or minimization. 15% of trials reported using blocks of six or less and 4% used minimization with no random element reported, both of which are highly predictable. CONCLUSION: Our results indicate that the majority of trials use some form of restriction, with many using relatively predictable methods that put them at greater risk of selection bias and technical error. Reporting of randomization methods often falls short of the minimum requirements set out by the CONSORT statement, leaving the reader unable to make an informed judgement about the risk of bias.