Royal Surrey County NHS Foundation Trust
Recent publications
Background Abbreviated breast MRI (abMRI) is being introduced in breast screening trials and clinical practice, particularly for women with dense breasts. Upscaling abMRI provision requires the workforce of mammogram readers to learn to effectively interpret abMRI. The purpose of this study was to examine the diagnostic accuracy of mammogram readers to interpret abMRI after a single day of standardised small-group training and to compare diagnostic performance of mammogram readers experienced in full-protocol breast MRI (fpMRI) interpretation (Group 1) with that of those without fpMRI interpretation experience (Group 2). Methods Mammogram readers were recruited from six NHS Breast Screening Programme sites. Small-group hands-on workstation training was provided, with subsequent prospective, independent, blinded interpretation of an enriched dataset with known outcome. A simplified form of abMRI (first post-contrast subtracted images (FAST MRI), displayed as maximum-intensity projection (MIP) and subtracted slice stack) was used. Per-breast and per-lesion diagnostic accuracy analysis was undertaken, with comparison across groups, and double-reading simulation of a consecutive screening subset. Results 37 readers (Group 1: 17, Group 2: 20) completed the reading task of 125 scans (250 breasts) (total = 9250 reads). Overall sensitivity was 86% (95% confidence interval (CI) 84–87%; 1776/2072) and specificity 86% (95%CI 85–86%; 6140/7178). Group 1 showed significantly higher sensitivity (843/952; 89%; 95%CI 86–91%) and higher specificity (2957/3298; 90%; 95%CI 89–91%) than Group 2 (sensitivity = 83%; 95%CI 81–85% (933/1120) p < 0.0001; specificity = 82%; 95%CI 81–83% (3183/3880) p < 0.0001). Inter-reader agreement was higher for Group 1 (kappa = 0.73; 95%CI 0.68–0.79) than for Group 2 (kappa = 0.51; 95%CI 0.45–0.56). Specificity improved for Group 2, from the first 55 cases (81%) to the remaining 70 (83%) ( p = 0.02) but not for Group 1 (90–89% p = 0.44), whereas sensitivity remained consistent for both Group 1 (88–89%) and Group 2 (83–84%). Conclusions Single-day abMRI interpretation training for mammogram readers achieved an overall diagnostic performance within benchmarks published for fpMRI but was insufficient for diagnostic accuracy of mammogram readers new to breast MRI to match that of experienced fpMRI readers. Novice MRI reader performance improved during the reading task, suggesting that additional training could further narrow this performance gap.
Purpose Although epidemiological studies have enhanced our understanding of acute kidney injury, defining the biologic processes corresponding to the clinical phenotype remains challenging. We have examined biomarkers associated with renal stress plus markers of glomerular function to assess whether this approach may aid prediction of AKI or other relevant endpoints. Materials & methods Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119–159 ² were analyzed in patients enrolled in the prospective, international, Sapphire study. Heterogenous critically ill patients (n = 723) were examined with a primary endpoint of development of KDIGO stage 2–3 within 12 h and a secondary endpoint of major adverse kidney events at 30 days (MAKE30). Results 100 patients (14%) reached the primary endpoint. Markers of renal stress outperformed those associated with glomerular function. Combining [TIMP-2]•[IGFBP7] with serum creatinine, but not the other functional markers, significantly (p = 0.02) increased the area under the ROC curve (AUC) from 0.80 (0.76–0.84) to 0.85 (0.81–0.89). In patients who did not develop AKI, all markers of glomerular filtration, but not [TIMP-2]·[IGFBP7], were significantly elevated in patients with a history of CKD (p < 0.05). Conclusions The combination of cell-cycle arrest biomarkers, TIMP-2 and IGFBP7, with serum creatinine but not cystatin C or PENK improved risk stratification for the development of stage 2 or 3 AKI over [TIMP-2]·[IGFBP7] alone.
Objective: To evaluate the psychometric properties of the Tinnitus Impact Questionnaire (TIQ), whose questions focus on assessing the impact of tinnitus on the patient's day to day activities, mood, and sleep, and not on hearing difficulties. Design: This was a retrospective cross-sectional study. Study sample: Data were included for 172 adult patients who attended a tinnitus and hyperacusis clinic in the UK within a six-month period and who had completed the TIQ. Results: Two items whose scores were very highly correlated with those for other items were removed, leaving seven items. Exploratory factor analysis suggested a single factor for the TIQ. A multiple causes multiple indicator model showed significant but very small direct effects of age on TIQ scores for two items, after adjustment for gender. The TIQ had excellent internal consistency, with Cronbach's alpha = 0.89. The total TIQ score was moderately to strongly correlated with scores for the Tinnitus Handicap Inventory, Screening for Anxiety and Depression-Tinnitus questionnaire, Hyperacusis Questionnaire, and Hyperacusis Impact Questionnaire, indicating convergent validity. The TIQ score was weakly correlated with the pure-tone average hearing threshold, indicating discriminant validity. Conclusions: The TIQ is a brief, valid and internally consistent questionnaire for assessing the impact of tinnitus.
Accurate and reliable intraoperative neuronavigation is crucial for achieving maximal safe resection of brain tumors. Intraoperative MRI (iMRI) has received significant attention as the next step in improving navigation. However, the immense cost and logistical challenge of iMRI precludes implementation in most centers worldwide. In comparison, intraoperative ultrasound (ioUS) is an affordable tool, easily incorporated into existing theatre infrastructure, and operative workflow. Historically, ultrasound has been perceived as difficult to learn and standardize, with poor, artifact-prone image quality. However, ioUS has dramatically evolved over the last decade, with vast improvements in image quality and well-integrated navigation tools. Advanced techniques, such as contrast-enhanced ultrasound (CEUS), have also matured and moved from the research field into actual clinical use. In this review, we provide a comprehensive and pragmatic guide to ioUS. A suggested protocol to facilitate learning ioUS and improve standardization is provided, and an outline of common artifacts and methods to minimize them given. The review also includes an update of advanced techniques and how they can be incorporated into clinical practice.
Background Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. Methods The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with (NCT00470236). Findings Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6–94·4%) in the no-boost group and 97·1% (95·6–98·1%) in the boost group (hazard ratio 0·47; 0·31–0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8–12%] vs 14% [12–17%], p=0·003) and induration (6% [5–8%] vs 14% [11–16%], p<0·001). Interpretation In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. Funding National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.
Background STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy (ADT). We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally-demonstrated surrogate for overall survival. Methods Standard-of-care (SOC) was ADT+/-radical prostate radiotherapy (RT). 460 SOC and 230 SOC+Doc were randomized 2:1. Standard survival methods and intention-to-treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time (RMST) if non-proportional (non-PH) hazards. mPFS (new metastases, skeletal-related events or prostate cancer death) had 70% power (α = 0.05) for HR = 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS) and progression-free survival (PFS: mPFS, locoregional progression). Results Median follow-up was 6.5 yr with 142 mPFS events on SOC (3 yr and 54% increases over previous report). There was no good evidence of an advantage to SOC+Doc on mPFS (HR = 0.89, 95%CI : 0.66–1.19, P = .43); with 5 yr mPFS 82% (95%CI : 78%–87%) SOC+Doc vs. 77% (95%CI : 73%–81%) SOC. Secondary outcomes showed evidence SOC+Doc improved FFS (HR = 0.70, 95%CI 0.55–0.88, P = .002) and PFS (non-PH P = .033, RMST difference = 5.8 m, 95%CI : 0.5–11.2, P = .031), but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95%CI : 0.64–1.21, P = .442). There was no evidence SOC+Doc increased late toxicity: post-1yr, 29% SOC and 30% SOC+Doc G3-5 toxicity. Conclusions There is robust evidence SOC+Doc improved FFS and PFS (previously shown to increase Quality-Adjusted-Life-Years), without excess late toxicity, which did not translates into benefit for longer-term outcomes. This may influence patient management in individual cases. Trial identification NCT00268476
Background Social media provides an opportunity for people to connect and form communities. This community architecture can help disseminate health-related information in the form of an awareness campaign. The European Society of Gynecological Oncology and the European Network of Gynecological Cancer Advocacy Groups initiated a global campaign, World Gynecologic Oncology Day, on September 20, 2020. We studied and analyzed the impact and reach of this Twitter campaign. Objectives To assess the impact and reach of the 2020 World Gynecologic Oncology Day Twitter campaign. Methods We analyzed Gynecological Oncology specific posts (Tweets) between 00:00 on September 17, 2020, to 23:59 on September 25, 2020 (Coordinated Universal Time), covering the days immediately prior and following World Gynecological Oncology Day (September 20, 2020), using Tweepy. European Network of Gynecological Cancer Advocacy Groups suggested hashtags (#GoForPurple, #WorldGODay, and #GoForCheckup) for this social media campaign used. We used these hashtags for our data (tweet) collection. Results Three hundred eighty-two Twitter accounts participated in this campaign, with 662 tweets including retweets. Twenty-two percent of participants were healthcare professionals. A total of 164 unique hashtags were identified, and #WorldGODay was the most frequently used among the Twitter accounts. #VaginalCancer, #CervicalCancer, and #VulvarCancer were used with the relation of the campaign. We identified five significant communities that contributed to raising awareness. Conclusions Twitter campaigns should be designed around a single short, easy-to-spell hashtag and coordinated with previously identified, influential accounts using timed tweets. #WorldGOday hashtag was relevant, easy to spell, memorable, and the most effective hashtag used in this campaign.
Ovarian cancer is one of the most common gynecologic cancers and has the highest mortality rate of any other cancer of the female reproductive system. Epithelial ovarian cancer (EOC) accounts for approximately 90% of all ovarian malignancies. The standard therapeutic strategy includes cytoreductive surgery accompanied by pre- or postoperative platinum-based chemotherapy. Nevertheless, up to 80% of the patients relapse within the following 12–18 months from the completion of the treatment and then receive first-line chemotherapy depending on platinum sensitivity. Mutations in BRCA1/2 genes are the most significant molecular aberrations in EOC and serve as prognostic and predictive biomarkers. Poly ADP-ribose polymerase (PARP) inhibitors exploit defects in the DNA repair pathway through synthetic lethality. They have also been shown to trap PARP1 and PARP2 on DNA, leading to PARP-DNA complexes. Olaparib, rucaparib, and niraparib have all obtained Food and Drug Administration (FDA) and/or the European Medicine Agency (EMA) approval for the treatment of EOC in different settings. Immune checkpoint inhibitors (ICI) have improved the survival of several cancers and are under evaluation in EOC. However, despite the success of immunotherapy in other malignancies, the use of antibodies inhibiting the immune checkpoint programmed cell death (PD-1) or its ligand (PD-L1) obtained modest results in EOC so far, with median response rates of up to 10%. As such, ICI have not yet been approved for the treatment of EOC. We herein provided a comprehensive insight into the most recent progress in synthetic lethality PARP inhibitors, along with the mechanisms of resistance. We also summarised data regarding the role of immune checkpoint inhibitors, the use of vaccination therapy, and adoptive immunotherapy in treating epithelial ovarian cancer.
Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.
Background: Hyperacusis can be defined as intolerance of certain everyday sounds, which are perceived as too loud or uncomfortable and which cause significant distress and impairment in the individual's day-to-day activities. Misophonia is defined as a high magnitude of emotional and behavioural reaction to certain sounds produced by human beings, such as eating sounds and breathing sounds. Several psychometric instruments have been developed to assess symptoms and the impact of hyperacusis and misophonia; however, to the author's knowledge, no study has evaluated and compared the methodological quality of the studies on psychometric properties of the existing instruments. Purpose: To systematically review the research studies assessing the psychometric properties of the instruments used for hyperacusis and misophonia and assess the quality and appropriateness of the methodologies used. Research design: Systematic review. Data collection and analysis: A systematic literature search was performed using five electronic literature databases (PubMed, Scopus, PsycINFO, Google Scholar and Web of Science). Studies were included if they were written in English and reported information about the psychometric properties of instruments measuring hyperacusis or misophonia symptoms or their impact. The quality of the studies and that of the psychometric instruments were evaluated using the consensus-based standards for the selection of health measurement instruments (COSMIN) tool. Results: The title and abstracts of 916 articles were screened and 39 articles were selected for full-text evaluation, with 14 articles meeting the inclusion criteria. From these 14 articles, eight different instruments (5 for hyperacusis and 3 for misophonia) were identified and reviewed comprising: (1) Hyperacusis Questionnaire (HQ), (2) Inventory of Hyperacusis Symptoms (IHS), (3) questionnaire on hypersensitivity to sound (GUF), (4) Hyperacusis Handicap Questionnaire (HHQ), (5) Short Hyperacusis Questionnaire, (6) Amsterdam Misophonia Scale (A-MISO-S), (7) MisoQuest, and (8) the Misophonia Questionnaire (MQ). Conclusion: None of the papers reviewed reported all the information required to meet the COSMIN standards. The studies' methodological quality varied between 'very good' and 'inadequate' depending on their grade on the COSMIN tool. There is a need for further research on the psychometric properties of the instruments included in this review.
Background: Divergence between deterioration to life–threatening COVID–19 or clinical improvement occurs for most within the first 14 days of symptoms. Life–threatening COVID–19 shares clinical similarities with Macrophage Activation Syndrome, which can be driven by elevated Free Interleukin–18 (IL–18) due to failure of negative-feedback release of IL–18 binding protein (IL–18bp). We therefore designed a prospective, longitudinal cohort study to examine IL–18 negative–feedback control in relation to COVID–19 severity and mortality from symptom day 15 onwards. Methods: 662 blood samples, matched to time from symptom onset, from 206 COVID–19 patients were analysed by enzyme–linked immunosorbent assay for IL–18 and IL–18bp, enabling calculation of free IL–18 (fIL–18) using the updated dissociation constant (K d ) of 0.05 nanomoles. Adjusted multivariate regression analysis was used to assess the relationship between highest fIL–18 and outcome measures of COVID-19 severity and mortality. Results: Up to symptom day 14, mean fIL–18 levels increase in all patients. Levels in survivors declined thereafter, but remained elevated in non–survivors, due to IL–18 production without commensurate IL–18bp release. Adjusted regression analysis from symptom day 15 onwards showed a 100 mmHg decrease in Pa02/Fi02 (primary outcome) for each 37.7 pg/ml increase in highest fIL–18 (p < 0.03). Per 50 pg/ml increase in highest fIL–18, adjusted logistic regression gave an odds–ratio (OR) for crude 60–day mortality of 1.41 (1.1 – 2.0) (p < 0.03), and an OR for death with hypoxaemic respiratory failure of 1.90 [1.3 – 3.1] (p < 0.01). Highest fIL–18 was associated also with organ failure, with an increase of 63.67 pg/ml for every additional organ supported (p < 0.01) in patients with hypoxaemic respiratory failure. In this same sub-group, highest fIL–18 showed a direct correlation with Neutrophil/Lymphocyte ratio, with an increase in fIL–18 by 3.54 pg/ml (p < 0.03) for each unit increase. Conclusions: Loss of IL–18 negative–feedback control, from symptom day 15 onwards is associated with COVID–19 severity and mortality. ISRCTN: #13450549; registration date: 30/12/2020.
Muscle wasting is implicated in the pathogenesis of intensive care unit acquired weakness (ICU-AW), affecting 40% of patients and causing long-term physical disability. A repetitive vascular occlusion stimulus (RVOS) limits muscle atrophy in healthy and orthopaedic subjects, thus, we explored its application to ICU patients. Adult multi-organ failure patients received standard care +/- twice daily RVOS {4 cycles of 5 min tourniquet inflation to 50 mmHg supra-systolic blood pressure, and 5 min complete deflation} for 10 days. Serious adverse events (SAEs), tolerability, feasibility, acceptability, and exploratory outcomes of the rectus femoris cross-sectional area (RFCSA), echogenicity, clinical outcomes, and blood biomarkers were assessed. Only 12 of the intended 32 participants were recruited. RVOS sessions (76.1%) were delivered to five participants and two could not tolerate it. No SAEs occurred; 75% of participants and 82% of clinical staff strongly agreed or agreed that RVOS is an acceptable treatment. RFCSA fell significantly and echogenicity increased in controls (n = 5) and intervention subjects (n = 4). The intervention group was associated with less frequent acute kidney injury (AKI), a greater decrease in the total sequential organ failure assessment score (SOFA) score, and increased insulin-like growth factor-1 (IGF-1), and reduced syndecan-1, interleukin-4 (IL-4) and Tumor necrosis factor receptor type II (TNF-RII) levels. RVOS application appears safe and acceptable, but protocol modifications are required to improve tolerability and recruitment. There were signals of possible clinical benefit relating to RVOS application.
Enteropathy-associated T-cell lymphoma (EATL) is a rare but serious complication of celiac disease. Diagnosis is challenging. Patients can present with weight loss, abdominal pain, and diarrhea or acutely with bowel perforation or obstruction. Patients often present with advanced disease. Malnutrition further limits treatment options. Early diagnosis is important to start aggressive treatment strategies. However, even with prompt diagnosis, prognosis remains poor with a high mortality rate. We report the first documented case of sole tonsillar involvement, a rare extraintestinal and extranodal site of disease, leading to EATL diagnosis. We also highlight some of the challenges in diagnosing EATL.
This paper evaluates the proportion and the audiological and other characteristics of patients with symptoms of misophonia among a population seeking help for tinnitus and/or hyperacusis at an audiology clinic (n = 257). To assess such symptoms, patients were asked “over the last 2 weeks, how often have you been bothered by any of the following problems? Feeling angry or anxious when hearing certain sounds related to eating noises, lip-smacking, sniffling, breathing, clicking sounds, tapping?”. The results of routine audiological tests and self-report questionnaires were gathered retrospectively from the records of the patients. Measures included: pure tone audiometry, uncomfortable loudness levels (ULLs), and responses to the tinnitus impact questionnaire (TIQ), the hyperacusis impact questionnaire (HIQ), and the screening for anxiety and depression in tinnitus (SAD-T) questionnaire. The mean age of the patients was 53 years (SD = 16) (age range 17 to 97 years). Fifty four percent were female. Twenty-three percent of patients were classified as having misophonia. The presence and frequency of reporting misophonia symptoms were not related to audiometric thresholds, except that a steeply sloping audiogram reduced the likelihood of frequent misophonia symptoms. Those with more frequent misophonia symptoms had lower values of ULLmin (the across-frequency average of ULLs for the ear with lower average ULLs) than those with less frequent or no reported symptoms. The reported frequency of experiencing misophonia symptoms increased with increasing impact of tinnitus (TIQ score ≥9), increasing impact of hyperacusis (HIQ score >11), and symptoms of anxiety and depression (SAD-T score ≥4). It is concluded that, when assessing individuals with tinnitus and hyperacusis, it is important to screen for misophonia, particularly when ULLmin is abnormally low or the TIQ, HIQ or SAD-T score is high. This will help clinicians to distinguish patients with misophonia, guiding the choice of therapeutic strategies.
Background Concurrent with its evolution as medical and surgical sub-speciality, pancreatic disease is now recognised as a speciality within dietetics. Recent national guidelines have highlighted the importance of nutritional assessment and intervention in both pancreatic cancer and pancreatitis, but there is a lack of timely and appropriate nutritional support for many patients with pancreatic disease. Methods The Nutrition Interest Group of the Pancreatic Society of Great Britain and Ireland developed a training course for non-specialist dietitians in 2014. Improvement in knowledge was assessed using questionnaires carried out before and after the training course, and results assessed against pre-agreed targets. Comprehensive evaluation of each aspect of the course was collated. Results Over four years, 1,215 dietitians attended the course in 32 different locations throughout the United Kingdom. Eight three percent completed knowledge questionnaires before and after the course. There was a significant improvement in test scores (22.2 ± 5.3 vs. 35.8 ± 4.0, P<0.0001), with 94% of delegates achieving the target score for non-specialists. The course was well evaluated with 98% of all markers graded as ‘good’ or ‘excellent’. Conclusions Targeted educational initiatives delivered outside of normal working hours are an effective means of training and educating a large number of health care professionals over a large geographical area within a short timeframe.
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311 members
Ben Creagh-Brown
  • Intensive Care Medicine
Robert W Laing
  • Department of Oncology
Nima Abbassi-Ghadi
  • Department of Surgery
Thumuluru Kavitha Madhuri
  • Department of Gynaecological Oncology
Matthew Chares Dickinson
  • Anaesthesia, Perioperative Medicine & Pain
Guildford, United Kingdom