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Laboratory practice is central to earlier myeloma diagnosis: Utilizing a primary care diagnostic tool and laboratory guidelines integrated into haematology services
No full textTreatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis.Published version, accepted version (12 month embargo), submitted versionRD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted
The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study
No full textCONTEXT: The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood. OBJECTIVE: We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D. METHODS: We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D. RESULTS: Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes. CONCLUSION: These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. See the journal About page for additional terms.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Family centeredness of care: a cross-sectional study in intensive care units part of the European society of intensive care medicine
No full textPURPOSE: To identify key components and variations in family-centered care practices. METHODS: A cross-sectional study, conducted across ESICM members. Participating ICUs completed a questionnaire covering general ICU characteristics, visitation policies, team-family interactions, and end-of-life decision-making. The primary outcome, self-rated family-centeredness, was assessed using a visual analog scale. Additionally, respondents completed the Maslach Burnout Inventory and the Ethical Decision Making Climate Questionnaire to capture burnout dimensions and assess the ethical decision-making climate. RESULTS: The response rate was 53% (respondents from 359/683 invited ICUs who actually open the email); participating healthcare professionals (HCPs) were from Europe (62%), Asia (9%), South America (6%), North America (5%), Middle East (4%), and Australia/New Zealand (4%). The importance of family-centeredness was ranked high, median 7 (IQR 6-8) of 10 on VAS. Significant differences were observed across quartiles of family centeredness, including in visitation policies availability of a waiting rooms, family rooms, family information leaflet, visiting hours, night visits, sleep in the ICU, and in team-family interactions, including daily information, routine day-3 conference, and willingness to empower nurses and relatives. Higher family centeredness correlated with family involvement in rounds, participation in patient care and end-of-life practices. Burnout symptoms (41% of respondents) were negatively associated with family-centeredness. Ethical climate and willingness to empower nurses were independent predictors of family centeredness. CONCLUSIONS: This study emphasizes the need to prioritize healthcare providers' mental health for enhanced family-centered care. Further research is warranted to assess the impact of improving the ethical climate on family-centeredness.Published version, accepted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embarg
Does randomised evidence alter clinical practise? The react qualitative study
No full textBACKGROUND: In 2015, the results of the 'Small bites versus large bites for closure of abdominal midline incisions (STITCH) Trial' were published in The Lancet. This demonstrated the superiority of small bite laparotomy closure over mass closure for the reduction of incisional hernias; despite this most surgeons have not changed their practice. Previous research has shown the time taken for the implementation of evidenced based practise within medicine takes an average of 17 years. This study aims to understand the reasons why surgeons have and have not changed their practice with regards to closure of midline laparotomy. METHODS: Semi-structured interviews were completed with surgical consultants and registrars at a single institution in South West England. The interview topic guide was informed by a review of the published literature, which identified barriers to adopting evidence into surgical practice. Interview transcripts underwent thematic analysis with themes identified following discussions within the research team, exploring views on published data and clinical practise. RESULTS: Nine interviews with general surgical and urological consultants as well as registrars in training were performed. Three themes were identified; 'Trusting the Evidence & Critical Appraisal', 'Surgical Attitude to Risk' and 'Adopting Evidence in Practise', that reflected barriers to the introduction of evidenced based practise to clinical work. CONCLUSION: Identification of the themes highlights possible areas for intervention to decrease the adoption time for evidence, for example from randomised controlled trials. The continued updating of clinical practise allows clinicians to provide best evidenced based care for patients and improve their outcomes.Published vesionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
False Positive Rate from Prospective Studies of PET-CT in Cutaneous Malignant Melanoma: A Systematic Review and Meta-Analysis
No full textBACKGROUND: Cutaneous malignant melanoma (CMM) is increasing in prevalence and possesses the highest mortality rate of any skin cancer. Positron Emission Tomography and Computed Tomography (PET-CT) may be utilised in either radiological staging or surveillance, primarily in stage III-IV disease. False positive (FP) results lead to patient distress, increased costs, and unnecessary follow-up. The FP rate in CMM literature varies widely, altering calculations of positive predictive value and has not undergone pooled meta-analytic. MATERIALS AND METHODS: A systematic review and meta-analysis of FP results in prospective studies of PET-CT in CMM was performed in accordance with PRISMA guidelines. RESULTS: The systematic review produced 14 trials for inclusion. Patient-based reporting had the lowest pooled proportion of FP results with 5.8 % (95 % CI = 3.3 % to 8.8 %), lesion-based was highest with 9.1 % (95 % CI = 3.4 % to 17.2 %) and combined was 6.1 % (95 % CI = 4.3 % to 8.1 %). Bias was low to unclear other than for FP reporting. Heterogeneity (I2) was variable across all analyses. FP findings were mainly lymphatic, dermatological, respiratory, or skeletal. Diagnostic information was not provided. CONCLUSIONS: This study was the first attempt to quantify the pooled proportion of FP results from PET-CT in CMM. A small number of studies (n = 14) were available due to the predominance of retrospective methodology. Due to inconsistent reporting the true proportion of FP results is unclear. Systemic distribution was expected but limited diagnostic information was provided. Repeat meta-analysis using retrospective work should be performed. Future work should be prospective with clearly documented FP proportion, distribution, diagnosis, and follow-up.Not hel
Progressive unilateral facial asymmetry in a young girl
No full textPublished version, accepted version (12 months embrago)The article is available via Open Access. Click on the 'Additional link' above to access the full-text
Optimizing Oxford Shoulder Scores with computerized adaptive testing reduces redundancy while maintaining precision
No full textAIMS: The Oxford Shoulder Score (OSS) is a 12-item measure commonly used for the assessment of shoulder surgeries. This study explores whether computerized adaptive testing (CAT) provides a shortened, individually tailored questionnaire while maintaining test accuracy. METHODS: A total of 16,238 preoperative OSS were available in the National Joint Registry (NJR) for England, Wales, Northern Ireland, the Isle of Man, and the States of Guernsey dataset (April 2012 to April 2022). Prior to CAT, the foundational item response theory (IRT) assumptions of unidimensionality, monotonicity, and local independence were established. CAT compared sequential item selection with stopping criteria set at standard error (SE) 0.90). Monotonicity, measured by H value, yielded 0.482, signifying good monotonic trends. Local independence was generally met, with Yen's Q3 statistic > 0.2 for most items. The median item count for completing the CAT simulation with a SE of 0.32 was 3 (IQR 3 to 12), while for a SE of 0.45 it was 2 (IQR 2 to 6). This constituted only 25% and 16%, respectively, when compared to the 12-item full-length questionnaire. CONCLUSION: Calibrating IRT for the OSS has resulted in the development of an efficient and shortened CAT while maintaining accuracy and reliability. Through the reduction of redundant items and implementation of a standardized measurement scale, our study highlights a promising approach to alleviate time burden and potentially enhance compliance with these widely used outcome measures.UnknownJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Exercise-based cardiac rehabilitation for adults with heart failure
No full textBACKGROUND: People with heart failure experience substantial disease burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous 2018 Cochrane review reported that exercise-based cardiac rehabilitation (ExCR) compared to no exercise control shows improvement in HRQoL and hospital admission amongst people with heart failure, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane review include the following: (1) most trials were undertaken in patients with heart failure with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with heart failure with preserved (= 45%) ejection fraction (HFpEF) were under-represented; and (2) most trials were undertaken in a hospital or centre-based setting. OBJECTIVES: To assess the effects of ExCR on mortality, hospital admission, and health-related quality of life of adults with heart failure. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and Web of Science without language restriction on 13 December 2021. We also checked the bibliographies of included studies, identified relevant systematic reviews, and two clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared ExCR interventions (either exercise only or exercise as part of a comprehensive cardiac rehabilitation) with a follow-up of six months or longer versus a no-exercise control (e.g. usual medical care). The study population comprised adults (= 18 years) with heart failure - either HFrEF or HFpEF. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, mortality due to heart failure, all-cause hospital admissions, heart failure-related hospital admissions, and HRQoL. Secondary outcomes were costs and cost-effectiveness. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 60 trials (8728 participants) with a median of six months' follow-up. For this latest update, we identified 16 new trials (2945 new participants), in addition to the previously identified 44 trials (5783 existing participants). Although the existing evidence base predominantly includes patients with HFrEF, with New York Heart Association (NYHA) classes II and III receiving centre-based ExCR programmes, a growing body of trials includes patients with HFpEF with ExCR undertaken in a home-based setting. All included trials employed a usual care comparator with a formal no-exercise intervention as well as a wide range of active comparators, such as education, psychological intervention, or medical management. The overall risk of bias in the included trials was low or unclear, and we mostly downgraded the certainty of evidence of outcomes upon GRADE assessment. There was no evidence of a difference in the short term (up to 12 months' follow-up) in the pooled risk of all-cause mortality when comparing ExCR versus usual care (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.71 to 1.21; absolute effects 5.0% versus 5.8%; 34 trials, 36 comparisons, 3941 participants; low-certainty evidence). Only a few trials reported information on whether participants died due to heart failure. Participation in ExCR versus usual care likely reduced the risk of all-cause hospital admissions (RR 0.69, 95% CI 0.56 to 0.86; absolute effects 15.9% versus 23.8%; 23 trials, 24 comparisons, 2283 participants; moderate-certainty evidence) and heart failure-related hospital admissions (RR 0.82, 95% CI 0.49 to 1.35; absolute effects 5.6% versus 6.4%; 10 trials; 10 comparisons, 911 participants; moderate-certainty evidence) in the short term. Participation in ExCR likely improved short-term HRQoL as measured by the Minnesota Living with Heart Failure (MLWHF) questionnaire (lower scores indicate better HRQoL and a difference of 5 points or more indicates clinical importance; mean difference (MD) -7.39 points, 95% CI -10.30 to -4.77; 21 trials, 22 comparisons, 2699 participants; moderate-certainty evidence). When pooling HRQoL data measured by any questionnaire/scale, we found that ExCR may improve HRQoL in the short term, but the evidence is very uncertain (33 trials, 37 comparisons, 4769 participants; standardised mean difference (SMD) -0.52, 95% CI -0.70 to -0.34; very-low certainty evidence). ExCR effects appeared to be consistent across different models of ExCR delivery: centre- versus home-based, exercise dose, exercise only versus comprehensive programmes, and aerobic training alone versus aerobic plus resistance programmes. AUTHORS' CONCLUSIONS: This updated Cochrane review provides additional randomised evidence (16 trials) to support the conclusions of the previous 2018 version of the review. Compared to no exercise control, whilst there was no evidence of a difference in all-cause mortality in people with heart failure, ExCR participation likely reduces the risk of all-cause hospital admissions and heart failure-related hospital admissions, and may result in important improvements in HRQoL. Importantly, this updated review provides additional evidence supporting the use of alternative modes of ExCR delivery, including home-based and digitally-supported programmes. Future ExCR trials need to focus on the recruitment of traditionally less represented heart failure patient groups including older patients, women, and those with HFpEF.Published version (12 month embargo), accepted version (12 month embargo)The article is available via Open Access. Click on the 'Additional link' above to access the full-text
Does proactive care in care homes improve survival? A quality improvement project
No full textBACKGROUND: NHS England's 'Enhanced Health in Care Homes' specification aims to make the healthcare of care home residents more proactive. Primary care networks (PCNs) are contracted to provide this, but approaches vary widely: challenges include frailty identification, multidisciplinary team (MDT) capability/capacity and how the process is structured and delivered. AIM: To determine whether a proactive healthcare model could improve healthcare outcomes for care home residents. DESIGN AND SETTING: Quality improvement project involving 429 residents in 40 care homes in a non-randomised crossover cohort design. The headline outcome was 2-year survival. METHOD: All care home residents had healthcare coordinated by the PCN's Older Peoples' Hub. A daily MDT managed the urgent healthcare needs of residents. Proactive healthcare, comprising information technology-assisted comprehensive geriatric assessment (i-CGA) and advanced care planning (ACP), were completed by residents, with prioritisation based on clinical needs.Time-dependent Cox regression analysis was used with patients divided into two groups:Control group: received routine and urgent (reactive) care only.Intervention group: additional proactive i-CGA and ACP. RESULTS: By 2 years, control group survival was 8.6% (n=108), compared with 48.1% in the intervention group (n=321), p<0.001. This represented a 39.6% absolute risk reduction in mortality, 70.2% relative risk reduction and the number needed to treat of 2.5, with little changes when adjusting for confounding variables. CONCLUSION: A PCN with an MDT-hub offering additional proactive care (with an i-CGA and ACP) in addition to routine and urgent/reactive care may improve the 2-year survival in older people compared with urgent/reactive care alone.Published version, accepted version, submitted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
No full textBACKGROUND: Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. METHODS: RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided a of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. FINDINGS: Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60-69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0-10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612-0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6-75·7) in the short-course ADT group and 78·1% (74·2-81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. INTERPRETATION: Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. FUNDING: Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society.Published version, accepted versionRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted