Pressure ulcer related pain in community populations: a prevalence survey.

BACKGROUND: Pressure ulcers are costly to the healthcare provider and can have a major impact on patient's quality of life. One of the most distressing symptoms reported is pain. There is very little published data on the prevalence and details of pain experienced by patients with pressure ulcers, particularly in community populations. The study was conducted in two community NHS sites in the North of England. METHODS: The aim was to estimate the prevalence of pressure area related pain within a community population. We also explored the type and severity of the pain and its association with pressure ulcer classification. A cross-sectional survey was performed of community nurses caseloads to identify adult patients with pressure ulcers and associated pain. Consenting patients then had a full pain assessment and verification of pressure ulcer grade. RESULTS: A total of 287 patients were identified with pressure ulcers (0.51 per 1000 adult population). Of the 176 patients who were asked, 133 (75.6%) reported pain. 37 patients consented to a detailed pain assessment. Painful pressure ulcers of all grades and on nearly all body sites were identified. Pain intensity was not related to number or severity of pressure ulcer. Both inflammatory and neuropathic pain were reported at all body sites however the proportion of neuropathic pain was greater in pressure ulcers on lower limbs. CONCLUSIONS: This study has identified the extent and type of pain suffered by community patients with pressure ulcers and indicates the need for systematic and regular pain assessment and treatment

Using Cognitive Pre-Testing Methods in the Development of a New Evidenced-Based Pressure Ulcer Risk Assessment Instrument

Background: Variation in development methods of Pressure Ulcer Risk Assessment Instruments has led to inconsistent inclusion of risk factors and concerns about content validity. A new evidenced-based Risk Assessment Instrument, the Pressure Ulcer Risk Primary Or Secondary Evaluation Tool - PURPOSE-T was developed as part of a National Institute for Health Research (NIHR) funded Pressure Ulcer Research Programme (PURPOSE: RP-PG-0407-10056). This paper reports the pre-test phase to assess and improve PURPOSE-T acceptability, usability and confirm content validity. Methods: A descriptive study incorporating cognitive pre-testing methods and integration of service user views was undertaken over 3 cycles comprising PURPOSE-T training, a focus group and one-to-one think-aloud interviews. Clinical nurses from 2 acute and 2 community NHS Trusts, were grouped according to job role. Focus group participants used 3 vignettes to complete PURPOSE-T assessments and then participated in the focus group. Think-aloud participants were interviewed during their completion of PURPOSE-T. After each pre-test cycle analysis was undertaken and adjustment/improvements made to PURPOSE-T in an iterative process. This incorporated the use of descriptive statistics for data completeness and decision rule compliance and directed content analysis for interview and focus group data. Data were collected April 2012-June 2012. Results: Thirty-four nurses participated in 3 pre-test cycles. Data from 3 focus groups, 12 think-aloud interviews incorporating 101 PURPOSE-T assessments led to changes to improve instrument content and design, flow and format, decision support and item-specific wording. Acceptability and usability were demonstrated by improved data completion and appropriate risk pathway allocation. The pre-test also confirmed content validity with clinical nurses. Conclusions: The pre-test was an important step in the development of the preliminary PURPOSE-T and the methods used may have wider instrument development application. PURPOSE-T proposes a new approach to pressure ulcer risk assessment, incorporating a screening stage, the inclusion of skin status to distinguish between those who require primary prevention and those who require secondary prevention/treatment and the use of colour to support pathway allocation and decision making. Further clinical evaluation is planned to assess the reliability and validity of PURPOSE-T and it’s impact on care processes and patient outcomes

Computational modelling of wound healing insights to develop new treatments

About 1% of the population will suffer a severe wound during their life. Thus, it is really important to develop new techniques in order to properly treat these injuries due to the high socioeconomically impact they suppose. Skin substitutes and pressure based therapies are currently the most promising techniques to heal these injuries. Nevertheless, we are still far from finding a definitive skin substitute for the treatment of all chronic wounds. As a first step in developing new tissue engineering tools and treatment techniques for wound healing, in silico models could help in understanding the mechanisms and factors implicated in wound healing. Here, we review mathematical models of wound healing. These models include different tissue and cell types involved in healing, as well as biochemical and mechanical factors which determine this process. Special attention is paid to the contraction mechanism of cells as an answer to the tissue mechanical state. Other cell processes such as differentiation and proliferation are also included in the models together with extracellular matrix production. The results obtained show the dependency of the success of wound healing on tissue composition and the importance of the different biomechanical and biochemical factors. This could help to individuate the adequate concentration of growth factors to accelerate healing and also the best mechanical properties of the new skin substitute depending on the wound location in the body and its size and shape. Thus, the feedback loop of computational models, experimental works and tissue engineering could help to identify the key features in the design of new treatments to heal severe wounds

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

BACKGROUND: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. METHODS: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). FINDINGS: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p<0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p<0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). INTERPRETATION: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. FUNDING: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas

Treatment of skin lesions in newborn children: meeting the needs of nursing staff

Objective To understand, together with nursing staff, the care needed to treat skin lesions in newborn children hospitalized in a neonatal unit. Method Qualitative research, of the convergent care type. The data was collected through semi-structured interviews, which were conducted from November to December 2012, in the neonatal unit of a hospital in southern Brazil. The participants were four auxiliary nurses, six nursing technicians and four nurses. Results The following three categories were designated: questions about what can be used in relation to newborn children; hospitalization can cause lesions on the skin of newborn children; and knowledge about care promotes professional autonomy. Conclusion There is an urgent need for staff to know more about the treatment of skin lesions, which would provide safer care for newborn children and would also support the autonomy of professional nurses in providing that care

Using a modified Delphi methodology to gain consensus on the use of dressings in chronic wounds management

Objective: Managing chronic wounds is associated with a burden to patients, caregivers, health services and society and there is a lack of clarity regarding the role of dressings in improving outcomes. This study aimed to provide understanding on a range of topics, including: the definition of chronicity in wounds, the burden of illness, clinical outcomes of reducing healing time and the impact of early interventions on clinical and economic outcomes and the role of matrix metalloproteinases (MMPs) in wound healing. Method: A systematic review of the literature was carried out on the role of dressings in diabetic foot ulcer (DFU), and venous leg ulcer (VLU) management strategies, their effectiveness, associated resource use/cost, and quality of life (QoL) impact on patients. From this evidence-base statements were written regarding chronicity in wounds, burden of illness, healing time, and the role of MMPs, early interventions and dressings. A modified Delphi methodology involving two iterations of email questionnaires followed by a face-to-face meeting was used to validate the statements, in order to arrive at a consensus for each. Clinical experts were selected, representing nurses, surgeons, podiatrists, academics, and policy experts. Results: In the first round, 38/47 statements reached or exceeded the consensus threshold of 80% and none were rejected. According to the protocol, any statement not confirmed or rejected had to be modified using the comments from participants and resubmitted. In the second round, 5/9 remaining statements were confirmed and none rejected, leaving 4 to discuss at the meeting. All final statements were confirmed with at least 80% consensus. Conclusion: This modified Delphi panel sought to gain clarity from clinical experts surrounding the use of dressings in the management of chronic wounds. A full consensus statement was developed to help clinicians and policy makers improve the management of patients with these conditions

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p&lt;0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p&lt;0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (&lt;1%) with standard of care in the abiraterone trial). Interpretation: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Funding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas