Multiple Interventions for Diabetic Foot Ulcer Treatment Trial (MIDFUT): study protocol for a randomised controlled trial.

INTRODUCTION: Diabetes affects more than 425 million people worldwide with a lifetime risk of diabetic foot ulcer (DFU) of up to 25%. Management includes wound debridement, wound dressings, offloading, treatment of infection and ischaemia, optimising glycaemic control; use of advanced adjuvant therapies is limited by high cost and lack of robust evidence. METHODS AND ANALYSIS: A multicentre, seamless phase II/III, open, parallel group, multi-arm multi-stage randomised controlled trial in patients with a hard-to-heal DFU, with blinded outcome assessment. A maximum of 447 participants will be randomised (245 participants in phase II and 202 participants in phase III). The phase II primary objective will determine the efficacy of treatment strategies including hydrosurgical debridement ± decellularised dermal allograft, or the combination with negative pressure wound therapy, as an adjunct to treatment as usual (TAU), compared with TAU alone, with patients randomised in a 1:1:1:2 allocation. The outcome is achieving at least 50% reduction in index ulcer area at 4 weeks post randomisation.The phase III primary objective will determine whether one treatment strategy, continued from phase II, reduces time to healing of the index ulcer compared with TAU alone, with participants randomised in a 1:1 allocation. Secondary objectives will compare healing status of the index ulcer, infection rate, reulceration, quality of life, cost-effectiveness and incidence of adverse events over 52 weeks post randomisation. Phase II and phase III primary endpoint analysis will be conducted using a mixed-effects logistic regression model and Cox proportional hazards regression, respectively. A within-trial economic evaluation will be undertaken; the primary economic analysis will be a cost-utility analysis presenting ICERs for each treatment strategy in rank order of effectiveness, with effects expressed as quality-adjusted life years.The trial has predefined progression criteria for the selection of one treatment strategy into phase III based on efficacy, safety and costs at 4 weeks. ETHICS AND DISSEMINATION: Ethics approval has been granted by the National Research Ethics Service (NRES) Committee Yorkshire and The Humber - Bradford Leeds Research Ethics Committee; approved 26 April 2017; (REC reference: 17/YH/0055). There is planned publication of a monograph in National Institute for Health Research journals and main trial results and associated papers in high-impact peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN64926597; registered on 6 June 2017.

Pressure Relieving Support Surfaces for Pressure Ulcer Prevention (PRESSURE 2): Clinical and Health Economic Results of a Randomised Controlled Trial.

BACKGROUND: Pressure ulcers (PUs) are complications of serious acute/chronic illness. Specialist mattresses used for prevention lack high quality effectiveness evidence. We aimed to compare clinical and cost effectiveness of 2 mattress types. METHODS: Multicentre, Phase III, open, prospective, parallel group, randomised controlled trial in 42 UK secondary/community in-patient facilities.2029 high risk (acutely ill, bedfast/chairfast and/or Category 1 PU/pain at PU site) adult in-patients were randomised (1:1, allocation concealment, minimisation with random element) factors including: centre, PU status, facility and consent type. Interventions were alternating pressure mattresses (APMs) or high specification foam (HSF) for maximum treatment phase 60 days. Primary outcome was time to development of new PU Category ≥ 2 from randomisation to 30 day post-treatment follow-up in intention-to treat population. Trial registration: ISRCTN 01151335. FINDINGS: Between August 2013 and November 2016, we randomised 2029 patients (1016 APMs: 1013 HSF) who developed 160(7.9%) PUs. There was insufficient evidence of a difference between groups for time to new PU Category ≥ 2 Fine and Gray Model Hazard Ratio HR = 0.76, 95%CI0.56-1.04); exact P = 0.0890; absolute difference 2%). There was a statistically significant difference in the treatment phase time to event sensitivity analysis, Fine and Gray model HR = 0.66, 95%CI, 0.46-0.93; exact P = 0.0176); 2.6% absolute difference). Economic analyses indicate that APM are cost-effective.There were no safety concerns. INTERPRETATION: In high risk (acutely ill, bedfast/chairfast/Category 1 PU/ pain on a PU site) in-patients, we found insufficient evidence of a difference in time to PU development at 30-day final follow-up, which may be related to a low event rate affecting trial power. APMs conferred a small treatment phase benefit. Patient preference, low PU incidence and small group differences suggests the need for improved targeting of APMs with decision making informed by patient preference/comfort/rehabilitation needs and the presence of potentially modifiable risk factors such as being completely immobile, nutritional deficits, lacking capacity and/or altered skin/Category1 PU.

Comparing alternating pressure mattresses and high-specification foam mattresses to prevent pressure ulcers in high-risk patients: the PRESSURE 2 RCT.

BACKGROUND: Pressure ulcers (PUs) are a burden to patients, carers and health-care providers. Specialist mattresses minimise the intensity and duration of pressure on vulnerable skin sites in at-risk patients. PRIMARY OBJECTIVE: Time to developing a new PU of category ≥ 2 in patients using an alternating pressure mattress (APM) compared with a high-specification foam mattress (HSFM). DESIGN: A multicentre, Phase III, open, prospective, planned as an adaptive double-triangular group sequential, parallel-group, randomised controlled trial with an a priori sample size of 2954 participants. Randomisation used minimisation (incorporating a random element). SETTING: The trial was set in 42 secondary and community inpatient facilities in the UK. PARTICIPANTS: Adult inpatients with evidence of acute illness and at a high risk of PU development. INTERVENTIONS AND FOLLOW-UP: APM or HSFM - the treatment phase lasted a maximum of 60 days; the final 30 days were post-treatment follow-up. MAIN OUTCOME MEASURES: Time to event. RESULTS: From August 2013 to November 2016, 2029 participants were randomised to receive either APM (n = 1016) or HSFM (n = 1013). Primary end point - 30-day final follow-up: of the 2029 participants in the intention-to-treat population, 160 (7.9%) developed a new PU of category ≥ 2. There was insufficient evidence of a difference between groups for time to new PU of category ≥ 2 [Fine and Gray model HR 0.76, 95% confidence interval (CI) 0.56 to 1.04; exact p-value of 0.0890 and 2% absolute difference]. Treatment phase sensitivity analysis: 132 (6.5%) participants developed a new PU of category ≥ 2 between randomisation and end of treatment phase. There was a statistically significant difference in the treatment phase time-to-event sensitivity analysis (Fine and Gray model HR 0.66, 95% CI 0.46 to 0.93; p = 0.0176 and 2.6% absolute difference). Secondary end points - 30-day final follow-up: new PUs of category ≥ 1 developed in 350 (17.2%) participants, with no evidence of a difference between mattress groups in time to PU development, (Fine and Gray model HR 0.83, 95% CI 0.67 to 1.02; p-value = 0.0733 and absolute difference 3.1%). New PUs of category ≥ 3 developed in 32 (1.6%) participants with insufficient evidence of a difference between mattress groups in time to PU development (Fine and Gray model HR 0.81, 95% CI 0.40 to 1.62; p = 0.5530 and absolute difference 0.4%). Of the 145 pre-existing PUs of category 2, 89 (61.4%) healed - there was insufficient evidence of a difference in time to healing (Fine and Gray model HR 1.12, 95% CI 0.74 to 1.68; p = 0.6122 and absolute difference 2.9%). Health economics - the within-trial and long-term analysis showed APM to be cost-effective compared with HSFM; however, the difference in costs models are small and the quality-adjusted life-year gains are very small. There were no safety concerns. Blinded photography substudy - the reliability of central blinded review compared with clinical assessment for PUs of category ≥ 2 was 'very good' (kappa statistic 0.82, prevalence- and bias-adjusted kappa 0.82). Quality-of-life substudy - the Pressure Ulcer Quality of Life - Prevention (PU-QoL-P) instrument meets the established criteria for reliability, construct validity and responsiveness. LIMITATIONS: A lower than anticipated event rate. CONCLUSIONS: In acutely ill inpatients who are bedfast/chairfast and/or have a category 1 PU and/or localised skin pain, APMs confer a small treatment phase benefit that is diminished over time. Overall, the APM patient compliance, very low PU incidence rate observed and small differences between mattresses indicate the need for improved indicators for targeting of APMs and individualised decision-making. Decisions should take into account skin status, patient preferences (movement ability and rehabilitation needs) and the presence of factors that may be potentially modifiable through APM allocation, including being completely immobile, having nutritional deficits, lacking capacity and/or having altered skin/category 1 PU. FUTURE WORK: Explore the relationship between mental capacity, levels of independent movement, repositioning and PU development. Explore 'what works for whom and in what circumstances'. TRIAL REGISTRATION: Current Controlled Trials ISRCTN01151335. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 52. See the NIHR Journals Library website for further project information.

Pressure ulcers (PUs) are patches of damaged skin, mainly caused by sitting/lying in one position. PUs are graded based on how serious they are, ranging from red patches (category 1) through small skin breaks/blisters (category 2) to serious wounds (category 4). Special mattresses are used to help prevent PUs. This study compared alternating pressure mattresses (APMs) with high-specification foam mattresses (HSFMs), to see which is better at preventing PUs. The study included adults admitted to hospital for acute illness who were at a high risk of developing PUs. Patients were randomly allocated to HSFM or APM. Nurses checked patients' skin and recorded changes. A total of 132 patients developed at least one new PU of category ≥ 2 before the end of treatment (60 days maximum). Of these, 53 patients were allocated to the APM arm and 79 to the HSFM arm, a difference of 2.6%. This is a small but significant difference. Nurses looked at patients' skin again 30 days after the patient had stopped using a trial mattress. At this point, 160 patients had at least one new PU (of category ≥ 2). Of these, 70 patients were allocated to the APM arm and 90 to the HSFM arm, a very small difference of 2.0%. Some patients asked to change mattresses; this happened more in the APM group. This study focused on high-risk patients; however, only a small number of people developed PUs, suggesting that prevention is possible with either mattress. Results also suggest that certain groups of patients may benefit more from APMs, for example people who cannot give consent or who have skin redness. When planning prevention and choosing mattresses, professionals and patients need to consider a number of factors, such as comfort, existing PUs and people's ability to self-care. Further research is recommended to understand what sort of prevention works, for whom and in what circumstances.

From embracing to managing risks.

OBJECTIVE: To assess developments over time in the capture, curation and use of quality and safety information in managing hospital services. SETTING: Four acute National Health Service hospitals in England. PARTICIPANTS: 111.5 hours of observation of hospital board and directorate meetings, and 72 hours of ward observations. 86 interviews with board level and middle managers and with ward managers and staff. RESULTS: There were substantial improvements in the quantity and quality of data produced for boards and middle managers between 2013 and 2016, starting from a low base. All four hospitals deployed data warehouses, repositories where datasets from otherwise disparate departmental systems could be managed. Three of them deployed real-time ward management systems, which were used extensively by nurses and other staff. CONCLUSIONS: The findings, particularly relating to the deployment of real-time ward management systems, are a corrective to the many negative accounts of information technology implementations. The hospital information infrastructures were elements in a wider move, away from a reliance on individual professionals exercising judgements and towards team-based and data-driven approaches to the active management of risks. They were not, though, using their fine-grained data to develop ultrasafe working practices.

Clinical evaluation of a new pressure ulcer risk assessment instrument, the Pressure Ulcer Risk Primary or Secondary Evaluation Tool (PURPOSE T).

AIM: To test the psychometric properties and clinical usability of a new Pressure Ulcer Risk Assessment Instrument including inter-rater and test-retest reliability, convergent validity and data completeness. BACKGROUND: Methodological and practical limitations associated with traditional Pressure Ulcer Risk Assessment Instruments, prompted a programme to work to develop a new instrument, as part of the National Institute for Health Research funded, Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056). DESIGN: Observational field test. METHOD: For this clinical evaluation 230 patients were purposefully sampled across four broad levels of pressure ulcer risk with representation from four secondary care and four community NHS Trusts in England. Blinded and simultaneous paired (ward/community nurse and expert nurse) PURPOSE-T assessments were undertaken. Follow-up retest was undertaken by the expert nurse. Field notes of PURPOSE-T use were collected. Data were collected October 2012-January 2013. RESULTS: The clinical evaluation demonstrated "very good" (kappa) inter-rater and test-retest agreement for PURPOSE-T assessment decision overall. The percentage agreement for "problem/no problem" was over 75% for the main risk factors. Convergent validity demonstrated moderate to high associations with other measures of similar constructs. CONCLUSION: The PURPOSE-T evaluation facilitated the initial validation and clinical usability of the instrument and demonstrated that PURPOSE-T is suitable of use in clinical practice. Further study is needed to evaluate the impact of using the instrument on care processes and outcomes.

Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2): study protocol for a randomised controlled trial.

BACKGROUND: Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual's functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. METHODS/DESIGN: PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 'high-risk' patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. DISCUSSION: The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design. TRIAL REGISTRATION: ISRCTN01151335 . Registered on 14 May 2013. Protocol version: 5.0, dated 25 September 2015 Trial sponsor: Clare Skinner, Faculty Head of Research Support, University of Leeds, Leeds, LS2 9JT; 0113 343 4897; C.E.Skinner@leeds.ac.uk.

Developing a pressure ulcer risk factor minimum data set and risk assessment framework.

AIM: To agree a draft pressure ulcer risk factor Minimum Data Set to underpin the development of a new evidenced-based Risk Assessment Framework. BACKGROUND: A recent systematic review identified the need for a pressure ulcer risk factor Minimum Data Set and development and validation of an evidenced-based pressure ulcer Risk Assessment Framework. This was undertaken through the Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research and incorporates five phases. This article reports phase two, a consensus study. DESIGN: Consensus study. METHOD: A modified nominal group technique based on the Research and Development/University of California at Los Angeles appropriateness method. This incorporated an expert group, review of the evidence and the views of a Patient and Public Involvement service user group. Data were collected December 2010-December 2011. FINDINGS: The risk factors and assessment items of the Minimum Data Set (including immobility, pressure ulcer and skin status, perfusion, diabetes, skin moisture, sensory perception and nutrition) were agreed. In addition, a draft Risk Assessment Framework incorporating all Minimum Data Set items was developed, comprising a two stage assessment process (screening and detailed full assessment) and decision pathways. CONCLUSION: The draft Risk Assessment Framework will undergo further design and pre-testing with clinical nurses to assess and improve its usability. It will then be evaluated in clinical practice to assess its validity and reliability. The Minimum Data Set could be used in future for large scale risk factor studies informing refinement of the Risk Assessment Framework.

Methods to assess cost-effectiveness and value of further research when data are sparse: negative-pressure wound therapy for severe pressure ulcers.

Health care resources are scarce, and decisions have to be made about how to allocate funds. Often, these decisions are based on sparse or imperfect evidence. One such example is negative-pressure wound therapy (NPWT), which is a widely used treatment for severe pressure ulcers; however, there is currently no robust evidence that it is effective or cost-effective. This work considers the decision to adopt NPWT given a range of alternative treatments, using a decision analytic modeling approach. Literature searches were conducted to identify existing evidence on model parameters. Given the limited evidence base, a second source of evidence, beliefs elicited from experts, was used. Judgments from experts on relevant (uncertain) quantities were obtained through a formal elicitation exercise. Additionally, data derived from a pilot trial were also used to inform the model. The 3 sources of evidence were collated, and the impact of each on cost-effectiveness was evaluated. An analysis of the value of further information indicated that a randomized controlled trial may be worthwhile in reducing decision uncertainty, where from a set of alternative designs, a 3-arm trial with longer follow-up was estimated to be the most efficient. The analyses presented demonstrate how allocation decisions about medical technologies can be explicitly informed when data are sparse and how this kind of analyses can be used to guide future research prioritization, not only indicating whether further research is worthwhile but what type of research is needed and how it should be designed.