Functional outcome and patient satisfaction with a 'self-care' protocol for minimally displaced distal radius fractures : a service evaluation.

AIMS: We introduced a self-care pathway for minimally displaced distal radius fractures, which involved the patient being discharged from a Virtual Fracture Clinic (VFC) without a physical review and being provided with written instructions on how to remove their own cast or splint at home, plus advice on exercises and return to function. METHODS: All patients managed via this protocol between March and October 2020 were contacted by a medical secretary at a minimum of six months post-injury. The patients were asked to complete the Patient-Rated Wrist Evaluation (PRWE), a satisfaction questionnaire, advise if they had required surgery and/or contacted any health professional, and were also asked for any recommendations on how to improve the service. A review with a hand surgeon was organized if required, and a cost analysis was also conducted. RESULTS: Overall 71/101 patients completed the telephone consultation; no patients required surgery, and the mean and median PRWE scores were 23.9/100 (SD 24.9) and 17.0/100 (interquartile range (IQR) 0 to 40), respectively. Mean patient satisfaction with treatment was 34.3/40 (SD 9.2), and 65 patients (92%) were satisfied or highly satisfied. In total there were 16 contact calls, 12 requests for a consultant review, no formal complaints, and 15 minor adjustment suggestions to improve patient experience. A relationship was found between intra-articular injuries and lower patient satisfaction scores (p = 0.025), however no relationship was found between PRWE scores and the nature of the fracture. Also, no relationship was found between the type of immobilization and the functional outcome or patient satisfaction. Cost analysis of the self-care pathway V traditional pathway showed a cost savings of over £13,500 per year with the new self-care model compared to the traditional model. CONCLUSION: Our study supports a VFC self-care pathway for patients with minimally displaced distal radius fractures. The pathway provides a good level of patient satisfaction and function. To improve the service, we will make minor amendments to our patient information sheet.Cite this article: Bone Jt Open 2022;3(9):726-732.

A pilot study investigating the effects of a manuka honey sinus rinse compared to a standard sinus rinse on sino-nasal outcome test scores in cystic fibrosis patients.

BACKGROUND: People with cystic fibrosis (CF) are prone to bacterial respiratory infections; these are often antibiotic resistant, are difficult to treat, and impact on the quality of life and lung function. The upper respiratory tract can act as a reservoir for these pathogens, and as part of clinical care, sinus rinses are used to alleviate symptoms in the upper airway. We have developed a sinus rinse containing manuka honey, to identify whether it can help improve symptoms or reduce the bacterial load. METHODS: We will undertake a randomised controlled trial where 30 adults with CF will be recruited and randomised to either the control or intervention group. Both groups will follow a sinus rinse protocol for 30 days (± 7 days); the control group will use the standard of care rinse, and the intervention group will use a manuka honey rinse. Both groups will provide samples at day 0 and day 30. The primary outcome measure will be a change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score. Secondary outcomes will include changes to quality of life (questionnaire), bacterial load/community composition, and sputum viscosity. DISCUSSION: This trial will look at the use of a manuka honey-infused sinus rinse solution on patients diagnosed with cystic fibrosis (CF) suffering with sinusitis; it will allow us to determine the efficacy of the manuka honey sinus rinse compared to standard rinse and will allow us to determine if molecular bacterial diversity analysis will provide in-depth information beyond the usual conventional microbiological. It will allow us to determine the feasibility of recruiting participants to this type of trial, allow us to check participant compliance with the protocol, and inform future studies. TRIAL REGISTRATION: Approval was obtained from the Research Ethics Committee Wales REC7 reference 18/WA/0319. Results of this study will be published at international conferences and in peer-reviewed journals; they will also be presented to the relevant stakeholders and research networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier NCT04589897 (retrospectively registered).

Measuring recovery after open lower limb fractures: combined objective functional tests and global perceived recovery outperform narrower metrics and a standard generic patient reported outcome measure.

BACKGROUND: Open lower limb fractures are serious injuries requiring combined ortho-plastic surgery and have significantly worse outcomes than similar closed fractures. There is little objective published data to determine which functional outcome measures best reflect progress or completeness of physical recovery. Our hypothesis was that objective measures combining strength, mobility and balance would better reflect recovery than isolated parameters (e.g. range of motion ROM) and would compare well to patients' perceived recovery. METHODS: Adult open lower limb fracture patients were reviewed 6 and 12 weeks, 6, 9 and 12 months post-injury. The mechanism, injury pattern, age, gender and treatment were recorded. Isolated parameter objective functional outcome measures (OFOMs) (ROM and MRC strength grade) were compared to combined OFOMs (timed up and go, comfortable gait speed and fast gait speed, Edgren Side Step Test (TUAG, CGS, FGS, ESST) and Single Leg balance. Patient reported outcomes were recorded (Global Perceived Effect (GPE) score and Disability Rating Index (DRI)). Statistical analysis used non-parametric tests (e.g. Spearman correlation) compared each with time since injury. RESULTS: Sixty-eight patients (54 male) with a median age of 45(20-75) years. Of the 19 isolated OFOMs, only knee flexion and ankle plantar flexion ROM and strength improved with time (Spearman correlation p = 0.042, 0.008, 0.032, 0.036 respectively). TUAG, ESST, CGS, FGS and GPE scores showed significant improvement (Spearman correlation p < 0.001). Patients' estimation of recovery paralleled these measures (Spearman correlation p < 0.001) with all but 2 patients achieving the minimum clinical important difference in DRI by 12 months compared to baseline. However, the GPE score had a higher proportion of improving responses than DRI at each time-point. DISCUSSION: Functional recovery is a key determinant in patients returning to work, providing for themselves and their family or resuming independent living for older patients. This study has demonstrated time-related improvements in combined OFOMs measuring mobility, strength, agility and balance paralleling patients' perception of recovery in the 12 months after open lower limb fractures. Over the same time-frame, the simple GPE score compared favourably with the DRI. Such parameters could become part of a defined core outcomes set. Focussing rehabilitation towards these combined OFOMs may help hasten recovery. TRIAL REGISTRATION: South West Wales REC 06/WMW02/10).

Utilisation of the STEAP protein family in a diagnostic setting may provide a more comprehensive prognosis of prostate cancer.

Prostate cancer is the second most common cancer diagnosed in men worldwide; however, few patients are affected by clinically significant disease within their lifetime. Unfortunately, the means to discriminate between patients with indolent disease and those who progress to aggressive prostate cancer is currently unavailable, resulting in over-treatment of patients. We therefore aimed to determine biomarkers of prostate cancer that can be used in the clinic to aid the diagnosis and prognosis. Immunohistochemistry analysis was carried out on prostate cancer specimens with a range of Gleason scores. Samples were stained and analysed for intensity of the Seven Transmembrane Epithelial Antigen of the Prostate (STEAP)-1, -2, -3, -4 and the Divalent Metal Transporter 1 (DMT1) proteins to determine suitable biomarkers for classification of patients likely to develop aggressive prostate cancer. Additionally, these proteins were also analysed to determine whether any would be able to predict future relapse using Kaplan Meier analysis. Data generated demonstrated that the protein expression levels of STEAP2 correlated significantly with Gleason score; furthermore, STEAP4 was a significant predictor of relapse. This data indicates that STEAP2 could be potential prognostic candidate for use in combination with the current prostate cancer detection methods and the presence of STEAP4 could be an indicator of possible relapse.

Developing a blood-based gene mutation assay as a novel biomarker for oesophageal adenocarcinoma.

The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastro-oesophageal reflux disease (GORD)-Barrett's metaplasia (BM)-oesophageal adenocarcinoma (OAC) model. Endoscopy patients underwent venipuncture and erythrocytes fluorescently stained for glycosyl phosphatidylinositol (GPI)-anchored proteins; CD55 and CD59. Using flow cytometry, GPI-anchor negative erythrocytes (mutants) were scored and compared amongst groups. The study enlisted 200 patients and 137 healthy volunteers. OAC patients had a three-fold increase in erythrocyte mutant frequency (EMF) compared to GORD patients (p < 0.001) and healthy volunteers (p < 0.001). In OAC patients, higher EMF was associated with worsening tumour staging (p = 0.014), nodal involvement (p = 0.019) and metastatic disease (p = 0.008). Chemotherapy patients demonstrated EMF's over 19-times higher than GORD patients. Patients were further classified into groups containing those with non-neoplastic disease and those with high-grade dysplasia/cancer with 72.1% of cases correctly classified by high EMF. Within the non-neoplastic group, aspirin users had lower EMF (p = 0.001) and there was a positive correlation between body mass index (p = 0.03) and age (p < 0.001) and EMF. Smokers had EMF's over double that of non-smokers (p = 0.011). Results suggest this test could help detect OAC and may be a useful predictor of disease progression.

The effects of a new Tendo-Achilles Pathway (TAP) on an orthopaedic department- A quality improvement study.

BACKGROUND: Achilles tendinopathy is a common pathology that is considered difficult to treat. At a time of austerity in the NHS it is essential to have carefully designed pathways that are monitored in terms of cost and effectiveness. However, a paucity of evidence exists for what the "best value" dedicated "joined up" pathway of care is for this difficult condition. OBJECTIVES: Design, implement and evaluate the impact of a new therapist lead pathway for Tendon- Achilles Pain (TAP).  METHODS: Process mapping, driver diagrams, stakeholder analysis and a series of Plan-Do-Study-Act cycles were used to design and implement TAP. To assess the impact of TAP, data was compared on whole system measures for 46 patients treated with referral to the traditional service (without TAP) and 46 patients managed according to the newly designed pathway (with TAP). A cost analysis was also conducted. RESULTS: A quality improvement approach led to the successful design and implementation of a therapist lead TAP. The impact of TAP included positive effects on patient satisfaction, a decrease in duplication of treatments, investigations and inappropriate reviews with consultants. No safety concerns were found. TAP was also £44,000 cheaper per annum than the previous service. CONCLUSION: Collaboration between orthopaedic and therapy services has resulted in a standardised pathway of care for patients with an Achilles tendinopathy.  It has removed unwanted variation, provided an opportunity to monitor the outcomes of treatments and resulted in decreased cost for the health board.

Does pre-operative anxiety and/or depression affect patient outcome after primary knee replacement arthroplasty?

BACKGROUND: Chronic pain is associated with psychological distress, most commonly manifested as anxiety and/or depression. METHODS: In order to investigate the effect of such distress on outcome from knee arthroplasty, we prospectively investigated the anxiety and depression levels of 104 patients undergoing a total of 107 primary knee arthroplasty procedures and the outcomes they achieved pre-operatively and at six weeks, one year and seven years post-operatively. The Hospital Anxiety and Depression Scale was used to record psychological status. Oxford Knee Score and American Knee Society Score were used to record functional outcomes. RESULTS: Forty-four percent (47/107) of the patients had an abnormal pre-operative anxiety and/or depression score. Mean anxiety and depression scores improved at six weeks and one year of follow-up, but then deteriorated slightly at seven years, albeit not back to baseline. Knee scores showed similar patterns over time. Regardless of pre-operative psychological status, mean AKSS Knee scores improved at six weeks and further improved at one year post-op. They then showed slight deterioration at seven years, but remained significantly better than pre-op. CONCLUSIONS: Psychological distress is common in our patients pre-operatively. Improvements in knee pain and function as a result of surgery correlate well with lower levels of psychological distress post-operatively. Knee replacement surgery positively influences all of the outcome measures studied rather than recovery being negatively influenced by pre-operative states. Knee replacement arthroplasty is not contra-indicated by pre-operative psychological distress. Successful knee replacement improves knee pain and function, as well as symptoms of anxiety and depression. These improvements persist for many years after the surgery.

STEAP2 Knockdown Reduces the Invasive Potential of Prostate Cancer Cells.

Six-transmembrane epithelial antigen of the prostate-2 (STEAP2) expression is increased in prostate cancer when compared to normal prostate, suggesting STEAP2 may drive prostate cancer progression. This study aimed to establish the functional role of STEAP2 in prostate tumourigenesis and evaluate if its knockdown resulted in reduced invasive potential of prostate cancer cells. PC3 and LNCaP cells were transfected with STEAP2 siRNA and proliferation, migration, invasion and gene expression analyses were performed. STEAP2 immunohistochemistry was applied to assess the protein expression and localisation according to Gleason score in 164 prostate cancer patients. Invasion significantly decreased in both cell lines following STEAP2 knockdown. PC3 proliferation and migration capacity significantly reduced, while LNCaP cell morphology and growth characteristics were altered. Additionally, STEAP2 downstream targets associated with driving invasion were identified as MMP3, MMP10, MMP13, FGFR4, IL1ß, KiSS1 and SERPINE1 in PC3 cells and, MMP7 in LNCaP cells, with CD82 altered in both. In patient tissues, STEAP2 expression was significantly increased in prostate cancer samples and this significantly correlated with Gleason score. These data demonstrate that STEAP2 drives aggressive prostate cancer traits by promoting proliferation, migration and invasion and significantly influencing the transcriptional profile of ten genes underlying the metastatic cascade.

Symbiont-mediated RNA interference in insects.

RNA interference (RNAi) methods for insects are often limited by problems with double-stranded (ds) RNA delivery, which restricts reverse genetics studies and the development of RNAi-based biocides. We therefore delegated to insect symbiotic bacteria the task of: (i) constitutive dsRNA synthesis and (ii) trauma-free delivery. RNaseIII-deficient, dsRNA-expressing bacterial strains were created from the symbionts of two very diverse pest species: a long-lived blood-sucking bug, Rhodnius prolixus, and a short-lived globally invasive polyphagous agricultural pest, western flower thrips (Frankliniella occidentalis). When ingested, the manipulated bacteria colonized the insects, successfully competed with the wild-type microflora, and sustainably mediated systemic knockdown phenotypes that were horizontally transmissible. This represents a significant advance in the ability to deliver RNAi, potentially to a large range of non-model insects.

Evaluation of 2 novel devices for calculation of fluid requirements in pediatric burns.

OBJECTIVES: The Parkland formula for maintenance and resuscitation fluid requirements in the first 24 hours after pediatric burns is widely used, but calculation errors frequently occur. Two different novel aids to calculation, a dedicated electronic device and a mechanical disc calculator, are described and compared with the conventional method of calculation (pen and paper, assisted by a general purpose calculator). METHODS: In a blinded randomized volunteer study, 21 participants performed a total of 189 calculations using simulated patient data to compare the accuracy and speed of 3 different methods for calculating resuscitation fluid requirements based on the pediatric Parkland formula. Bespoke software generated the simulated patient data and recorded accuracy and speed of all participant responses. RESULTS: Sixty-five percent of calculations with the electronic device, 35% using the disc and 44% using the pen/paper methods were within ±5% of the correct value and considered "correct" for clinical purposes. The method used strongly affected the tendency to make errors (logistic regression). With thresholds of error magnitude classed as very small (>5%), small (>25%), medium (>50%) and large (>100%) of the correct value respectively, the electronic method produced fewer errors than both disc and pen/paper methods at all error thresholds. Disc produced more errors than pen/paper at the greater than 5% threshold but fewer at the greater than 25%, greater than 50%, and greater than 100% thresholds. CONCLUSIONS: Both novel devices provide safer and faster alternatives to conventional methods for calculation of fluid requirements in pediatric burns.

Putative prognostic epithelial-to-mesenchymal transition biomarkers for aggressive prostate cancer.

Prostate cancer is the second most frequently diagnosed cancer worldwide and is the sixth leading cause of cancer deaths in men, yet it varies greatly in its aggressiveness. Currently, it is not possible to adequately differentiate between patients whose tumors will remain indolent and those patients whose disease will progress, resulting in unnecessary aggressive treatment. Consequently, there is an urgent need to identify markers of prostate cancer progression, invasiveness and metastasis to more accurately predict prognosis. The aim of this study was to assess the ability of key epithelial-to-mesenchymal transition molecules in identifying prostate cancer patients who are likely to develop aggressive tumors. Using 215 archival patient tissue samples, immunohistochemistry was applied to examine the expression and sub-cellular localization of E-Cadherin, Snail, Slug, Twist, Vimentin, BMP-2 and BMP-7. Of the seven markers assessed, a significantly increased expression of Snail protein was observed within the nucleus of prostate cancer cells and was strongly associated with increasing Gleason score and clinical stage. In addition, loss of E-Cadherin expression at the cellular membrane of prostate cancer cells was also significantly associated with increasing Gleason score, clinical stage, and additionally, a reduction in survival.

Comparison of three techniques for calculation of the Parkland formula to aid fluid resuscitation in paediatric burns.

CONTEXT: Inadequate fluid resuscitation of acute burns may result in hypovolaemic shock. Excessive fluid resuscitation may result in fluid overload. A nomogram which uses the popular Parkland formula and '4-2-1' regime has been recently described to facilitate the calculation of fluid requirements in children during the first 24 h following burn injury. OBJECTIVE: To compare the accuracy and speed of calculation of three different methods (pen and paper, electronic calculator and nomogram), which all use the Parkland formula and '4-2-1' regime to calculate maintenance and resuscitation fluid requirements for children in the first 24 h after burn injury. DESIGN: A randomised volunteer study using computer-generated simulated patient data. SETTING: Welsh Centre for Burns, ABM University Local Health Board, Swansea, UK. Data were collected between February 2011 and October 2011. PARTICIPANTS: The group consisted of 36 volunteers including trainee and consultant surgeons and anaesthetists. INTERVENTION: Thirty-six participants performed 318 calculations, using each of the three methods of calculation up to three times. MAIN OUTCOME MEASURES: Accuracy, speed and acceptability of the different methods. RESULTS: For nomogram, calculator and pen and paper: magnitude of error [low (≥25%), medium (≥50%) and high (≥75%)]: [5.7, 4.7 and 3.8%], [12.1, 12.1 and 7.5%], [28.6, 21.9 and 16.2%]; [P <0.001, P = 0.001 and P = 0.006]. Calculation time: [s; mean (SD)]: 121 (48), 109 (52) and 240 (140); P <0.001. The mean (SD) of the difficulty scores were 17.3 (13), 20.6 (13.4) and 62.2 (23.4); P <0.001. CONCLUSION: The nomogram was the most accurate method of calculating fluid requirements using the Parkland formula, was only slightly slower than the electronic calculator and was deemed the easiest to use. The nomogram is also low cost, robust, and provides a rapid means of detecting and preventing the large errors that we have shown can occur when an electronic device is used as the primary method of resuscitation fluid calculation. We, therefore, suggest that the nomogram is a suitable method for the calculation of the Parkland formula to guide resuscitation and maintenance fluid requirements in the first 24 h of paediatric burns or for cross-checking the results obtained by other means of calculation.

What is the best clinical test for Achilles tendinopathy?

BACKGROUND: Differential diagnosis of Achilles pathology is demanding. This study evaluates the diagnostic accuracy of clinical tests identified for a chronic mid body Achilles tendinopathy. Ultrasound scanning provides the reference standard. METHODS: Twenty-one participants with, and without, an Achilles tendinopathy, had an ultrasound scan followed immediately by the application of ten clinical tests. The accuracy and reproducibility of each test was determined. RESULTS: The most valid tests are; pain on palpation of the tendon (sensitivity 84%, specificity 73%, kappa 0.74-0.96) and the subjective reporting of pain 2-6 cm above the insertion into the calcaneum (sensitivity 78%, specificity 77%, kappa 0.75-0.81). CONCLUSION: Only location of pain and pain on palpation were found to be sufficiently reliable and accurate, to be recommended for use.

Influence of DNA repair on nonlinear dose-responses for mutation.

Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is one of the most mutagenic simple alkylators. Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents. Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0.0075 µg/ml (72.8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476). Mechanistic studies reveal that the NOGEL is dependent upon repair of O(6)-methylguanine (O(6)MeG) by the suicide enzyme O(6)MeG-DNA methyltransferase (MGMT). Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis.

Graduate entry medicine: selection criteria and student performance.

BACKGROUND: Graduate entry medicine raises new questions about the suitability of students with different backgrounds. We examine this, and the broader issue of effectiveness of selection and assessment procedures. METHODS: The data included background characteristics, academic record, interview score and performance in pre-clinical modular assessment for two years intake of graduate entry medical students. Exploratory factor analysis is a powerful method for reducing a large number of measures to a smaller group of underlying factors. It was used here to identify patterns within and between the selection and performance data. PRINCIPAL FINDINGS: Basic background characteristics were of little importance in predicting exam success. However, easily interpreted components were detected within variables comprising the 'selection' and 'assessment' criteria. Three selection components were identified ('Academic', 'GAMSAT', 'Interview') and four assessment components ('General Exam', 'Oncology', 'OSCE', 'Family Case Study'). There was a striking lack of relationships between most selection and performance factors. Only 'General Exam' and 'Academic' showed a correlation (Pearson's r = 0.55, p<0.001). CONCLUSIONS: This study raises questions about methods of student selection and their effectiveness in predicting performance and assessing suitability for a medical career. Admissions tests and most exams only confirmed previous academic achievement, while interview scores were not correlated with any consequent assessment.