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Chronic pain in people living with dementia: challenges to recognising and managing pain, and personalising intervention by phenotypePain is common in people with dementia, and pain can exacerbate the behavioural and psychological symptoms of dementia. Effective pain management is challenging, not least in people with dementia. Impairments of cognition, communication and abstract thought can make communicating pain unreliable or impossible. It is unclear which biopsychosocial interventions for pain management are effective in people with dementia, and which interventions for behavioural and psychological symptoms of dementia are effective in people with pain. The result is that drugs, physical therapies and psychological therapies might be either underused or overused. People with dementia and pain could be helped by assessment processes that characterise an individual's pain experience and dementia behaviours in a mechanistic manner, phenotyping. Chronic pain management has moved from a 'one size fits all' approach, towards personalised medicine, where interventions recommended for an individual depend upon the key mechanisms underlying their pain, and the relative values they place on benefits and adverse effects. Mechanistic phenotyping through careful personalised evaluation would define the mechanisms driving pain and dementia behaviours in an individual, enabling the formulation of a personalised intervention strategy. Central pain processing mechanisms are particularly likely to be important in people with pain and dementia, and interventions to accommodate and address these may be particularly helpful, not only to relieve pain but also the symptoms of dementia.
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Value of Drains in Soft-Tissue Tumour Surgery: A Specialist Regional Centre ExperienceBackground The mainstay of therapy in most soft-tissue tumours (STTs) is excision. However, this often results in blood/extracellular fluid collection within large dead spaces necessitating the use of surgical drains. Whether meticulous attention to haemostasis, careful closure of dead space, and use of compression bandage obviates the need for drains was investigated. This study aimed to compare postoperative outcomes in patients undergoing surgery for STTs with and without the use of drains. Methodology A retrospective analysis of patients undergoing STT surgery over five years was undertaken using a regional STT specialist service database. Patients were stratified into the following two groups: compression bandage alone (CB) versus compression bandage with drain (CBD). The chi-square test was used to examine associations with infection, seroma, and haematoma, while the unpaired t-test was used for associations with hospital stay and time to wound healing. The unpaired t-test with Bonferroni correction was used to account for tumour dimensions across both groups. Results A total of 81 CB and 25 CBD patients were included. The mean hospital stay was significantly lower in CB compared to CBD (4.9 days, SD = 8.574 vs. 9.8 days, SD = 7.647, p = 0.0125). None of the other variables was significantly different between the two groups, including infection (21.3% vs. 24.0%, p = 0.7804), seroma (25.0% vs. 36.0%, p = 0.2865), haematoma (0.026% vs. 2.0%, p = 0.2325), and time to wound healing (55.8 days, SD = 63.59 vs. 42.3 days, SD = 58.88, p = 0.3648). Conclusions Our findings suggest that the use of drains in patients undergoing STT tumour surgery lengthens hospital stay without reducing the incidence of postoperative complications/time to wound healing. A larger, prospective trial is needed.
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Influence of Social Support, Financial Status, and Lifestyle on the Disparity Between Inflammation and Disability in Rheumatoid Arthritis.Objective: To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). Methods: Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having "excess disability." Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN]). Results: Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (β = 0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (β = 0.24 [95% CI 0.14, 0.34]), less exercise (β = 0.17 [95% CI 0.09-0.25]), and less education (β = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN. Conclusion: Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade.
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Effects of haemodynamically atrio-ventricular optimized His-pacing on heart failure symptoms and exercise capacity: The His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomised, double-blind, cross-over trialAims: Excessive prolongation of PR interval impairs coupling of AV contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His-bundle pacing allows AV-delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV-optimized His pacing is preferable to no-pacing, in double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200ms and either QRS ≤140ms or right BBB. Methods and Results: Patients had atrial and His-bundle leads implanted (and an ICD lead if clinically indicated) and were randomized, to 6-months of pacing and 6-months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. 167 patients were randomized: 90% men, 69±10 years, QRS duration 124±26ms, PR interval 249±59ms, LVEF 33±9%. Neither peak VO 2 (+0.25 ml/min/kg, 95% CI -0.23 to +0.73, p=0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p=0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p=0.03). 76% of patients preferred His-bundle pacing-on and 24% pacing-off (p<0.0001). Conclusion: His-bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months
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Impact of radiographer immediate reporting of X-rays of the chest from general practice on the lung cancer pathway (radioX): a randomised controlled trialThe National Optimal Lung Cancer Pathway recommends rapid progression from abnormal chest X-rays (CXRs) to CT. The impact of the more rapid reporting on the whole pathway is unknown. The aim of this study was to determine the impact of immediate reporting of CXRs requested by primary care by radiographers on the time to diagnosis of lung cancer. Method: People referred for CXR from primary care to a single acute district general hospital in London attended sessions that were prerandomised to either immediate radiographer (IR) reporting or standard radiographer (SR) reporting within 24 hours. CXRs were subsequently reported by radiologists blind to the radiographer reports to test the reliability of the radiographer report. Radiographer and local radiologist discordant cases were reviewed by thoracic radiologists, blinded to reporter. Results: 8682 CXRs were performed between 21 June 2017 and 4 August 2018, 4096 (47.2%) for IR and 4586 (52.8%) for SR. Lung cancer was diagnosed in 49, with 27 (55.1%) for IR. The median time from CXR to diagnosis of lung cancer for IR was 32 days (IQR 19, 70) compared with 63 days (IQR 29, 78) for SR (p=0.03).8258 CXRs (95.1%) were reported by both radiographers and local radiologists. In the 1361 (16.5%) with discordance, the reviewing thoracic radiologists were equally likely to agree with local radiologist and radiographer reports. Conclusions: Immediate reporting of CXRs from primary care reduces time to diagnosis of lung cancer by half, likely due to rapid progress to CT. Radiographer reports are comparable to local radiologist reports for accuracy.
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Association of pain and risk of falls in community-dwelling adults: a prospective study in the Survey of Health, Ageing and Retirement in Europe (SHARE).Purpose: To investigate the longitudinal associations between pain and falls risks in adults. Methods: Prospective cohort study on data from 40,636 community-dwelling adults ≥ 50 years assessed in Wave 5 and 6 in the Survey of Health, Ageing and Retirement in Europe (SHARE). Socio-demographic and clinical information was collected at baseline (Wave 5). At 2-year follow-up (Wave 6), falls in the previous 6 months were recorded. The longitudinal associations between pain intensity, number of pain sites and pain in specific anatomic sites, respectively, and falls risk were analysed by binary logistic regression models; odds ratios (95% confidence intervals) were calculated. All analyses were adjusted for socio-demographic and clinical factors and stratified by sex. Results: Mean age was 65.8 years (standard deviation 9.3; range 50-103); 22,486 (55.3%) participants were women. At follow-up, 2805 (6.9%) participants reported fall(s) in the previous 6 months. After adjustment, participants with moderate and severe pain at baseline had an increased falls risk at follow-up of 1.35 (1.21-1.51) and 1.52 (1.31-1.75), respectively, compared to those without pain (both p < 0.001); mild pain was not associated with falls risk. Associations between pain intensity and falls risk were greater at younger age (p for interaction < 0.001). Among participants with pain, pain in ≥ 2 sites or all over (multisite pain) was associated with an increased falls risk of 1.29 (1.14-1.45) compared to pain in one site (p < 0.001). Conclusions: Moderate, severe and multisite pain were associated with an increased risk of subsequent falls in adults.
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Amlodipine induced hyponatraemiaHyponatraemia (serum sodium <135 mmol/L) is a common finding in clinical practice. Patients with hyponatraemia have increased morbidity and mortality compared with patients without hyponatraemia. Hyponatraemia is often iatrogenic and avoidable. These can be classified into 5 main types: hypovolaemic hyponatraemia, euvolaemic hyponatraemia, hypervolaemic hyponatraemia, hypertonic hyponatraemia and pseudohyponatraemia. Patients can be asymptomatic to severe cerebral oedema, leading to brainstem herniation, respiratory arrest and death.
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Tumour-induced osteomalacia.Phosphate is important for normal mineralisation of bone. Phosphate is important in its own right for neuromuscular function, and profound hypophosphataemia can be accompanied by encephalopathy, muscle weakness and cardiomyopathy. Hypophosphataemia can be due to intracellular uptake of phosphate from the extracellular fluid, reduced intestinal phosphate absorption, increased renal excretion, decreased renal tubular absorptive capacity and genetic defects in renal tubule phosphate transporters.
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IBRUTINIB AND RITUXIMAB AS FIRST LINE THERAPY FOR MANTLE CELL LYMPHOMA: A MULTICENTRE, REAL-WORLD UK STUDY.Background: Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this combination in the frontline setting, randomised phase 3 and real-world data are currently lacking. Aims: To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity profile of IBR +/- R in adult patients with previously untreated MCL. Methods: Following institutional approval, adults commencing IBR +/- R for untreated MCL under interim Covid-19 arrangements were prospectively identified by contributing centres. Hospital records were interrogated for demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT. Results: Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53 mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in 56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6), pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment. New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively.
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THE ASSOCIATION of PAINFUL and NON-PAINFUL COMORBIDITIES with CENTRAL MECHANISMS of KNEE PAIN.Background Central mechanisms of knee pain occur in the central nervous system and may intensify and prolong pain. Central pain mechanisms might be facilitated by ongoing nociceptive input. A link between multimorbidity and central mechanisms of knee pain is proposed; ongoing sensory inputs due to comorbidities may trigger changes in pain processing by the CNS. This might be particularly expected with painful comorbidities. Objectives To investigate potential relationships of painful and non-painful multimorbidity with central mechanisms of knee pain. Methods Cross-sectional analysis of self-report data from participants of the Investigating Musculoskeletal Health and Wellbeing cohort, who reported knee as their most bothersome site of joint pain over the previous month, with pain rated ≥1/10, and who had completed FRAIL and CAP-Knee (1) questionnaires. Two indirect measures suggesting central mechanisms involvement in knee pain were used as dependent variables; pain intensity (0-10 numerical rating scale) and CAP-Knee score (0-16 scale). Comorbidities were assigned either “painful comorbidity” or “non-painful comorbidity” status based on IASP classification of chronic pain criteria (2). Multivariable linear regression models, adjusted for age and sex, were employed to explore associations of comorbidity counts with pain intensity and CAP-Knee score. Results 736 participants satisfied inclusion criteria. 55% were female, mean age 71 (range 40 to 95). Painful comorbidity count and non-painful comorbidity count each had positive associations with pain intensity (β=0.42, 95% CI=0.29 to 0.54, p<0.001; and β=0.31, 95%CI=0.16 to 0.45, p<0.001, respectively). Painful and non-painful comorbidity counts each also were associated with CAP-Knee score (β=0.80, 95% CI=0.59 to 1.01, p<0.001; and β=0.52, 95% CI=0.27 to 0.77, p<0.001, respectively). Painful and non-painful comorbidity counts each remained significantly associated both with pain intensity and with CAP-Knee scores when both types of comorbidity count were included in the same multivariable model. Conclusion Both painful and non-painful comorbidities were positively associated with central mechanisms of knee pain, providing further insight into the interconnectedness of pain processing systems and the rest of the body. The explanation behind these relationships may depend on more than just ongoing nociceptive input. Future work should address possible contributions from genetic, pathophysiological, psychological, and pharmacological factors associated with comorbid diagnosis.
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Critical care usage after major gastrointestinal and liver surgery: a prospective, multicentre observational study.Background: Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods: This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy. Results: Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI. Conclusions: After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.
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A colitis bundle initiative to improve the outcome of acute IBD colitis patientsIntroduction Early detection and assessment of the severity are crucial in the management of an IBD flare-ups. This is so steroid therapy, the initial remission-inducing treatment can be administered at that right time. However, in those with severe colitis where steroid therapy is inadequate, often rescue therapy, either in the form of biologics or surgery is required. Simple measures during flare-ups would help to achieve this and potentially be life-saving. Methods This project aims to review the current performance against the IBD management NICE guideline and to introduce a trust-wide Colitis bundle to ensure junior doctors and consultants can make important decisions regarding colitis patient care. A retrospective audit was carried out on 40 In-patients with a diagnosis of an acute flare of ulcerative and Crohn’s colitis over the year 2021. A proforma was created based on the latest colitis management guidelines. This reviewed step-by-step management plans over the first 3 days period – which, if perfectly followed, will ensure deliverance of rescue therapy safely by day 3 or day 4. Results The results showed a delay in managing acute IBD flare-ups, in which the initial steroid therapy was given to only 82.8% and the VTE prophylaxis was commenced only on 65.7% of the cases. Recognition of colitis severity as defined by Truelove and Witt’s score was also poor as it happened in only 20% of the cases. This downplayed the urgency of acknowledging the need for an escalated treatment strategy, which subsequently resulted in a delay in pre-biologics screening test – this happened in 25.7% of cases only within the first 2 days of diagnosis. As this test was essential in those requiring rescue biologic therapies, this resulted in an overall delay in its initiation as demonstrated in Figure 1. Abstract P21 Figure 1 Time between the biologic therapy decision and its first dose administration Conclusions The quality improvement project has demonstrated poor recognition and assessment of acute IBD flare-ups as recommended by the NICE guideline. This subsequently led to a delay in initiation of the steroid therapy, pre-biologic screening test, and initiation of rescue biologic therapies in those with severe colitis. This is due to the lack of exposure among junior and senior doctors towards the guideline. As a response, a mass education at a Trust level for the doctors was recommended and a colitis bundle was constructed, which comprised of evidence-based action plans checklist divided into Day 1 to Day 3 to make sure that all the aspects are not missed.
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Routine Pressure Wire Assessment Versus Conventional Angiography in the Management of Patients With Coronary Artery Disease: The RIPCORD 2 TrialBackground: Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone. Methods: We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non-ST-segment-elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events. Results: In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3-5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613-£7015); and angiography+FFR, £4510 (£2721-£7415; P=0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60-87); and angiography+FFR, 75 (interquartile range, 60-90; P=0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR (P=0.64). Conclusions: A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life.
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Considering the impact of patient ethnicity on cystic fibrosis related bone disease.We found the article “Bone accrual and structural changes over one year in youth with cystic fibrosis” by Rosara M.Bass et al [1] to be of great interest. The study investigated bone changes over one year in individuals aged 5–18 with both cystic fibrosis (CF). The aim of this was to see how much bone development in youth and emerging adults contributes to cystic fibrosis related bone disease (CFBD). The study accounted for the following patient demographics: weight, height, age, pubertal status, and gender [1]. Although these are important factors, we believe it is important to consider the impact of patient ethnicity on the development of structural changes in the bone. Several studies across western countries have found that vitamin D deficiencies are more prevalent in ethnic minority groups, including South Asian and Black African-Caribbean populations [2], [3]. This is thought to be due to skin pigmentation being a factor which impacts the levels of vitamin D produced in the skin after sun exposure [2]. Furthermore, vitamin D deficiency is also the most recognised cause of CFBD [4]. Therefore, it is important to recognise the potential impact of ethnicity on changes in bone development in patients with CF. Additionally, it is important to note that studies have demonstrated that CF patients from ethnic minority backgrounds are more likely to experience worse outcomes compared to white patients [5]. For example, a study in the United States found that Hispanic and Black patients with CF had worse respiratory function compared to white patients [5]. We therefore propose that future studies should include ethnicity as a patient demographic. Further research into the impact of ethnicity on CFBD will enable a more inclusive and holistic approach towards diagnosis and treatment of CF.
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Improving the delivery of acute NIV at Kings Mill Hospital: A closed loop quality improvement project.Background: The British Thoracic Society (BTS) Acute Non-Invasive Ventilation (NIV) standards state all patients who require acute NIV should be initiated on NIV within two hours of hospital admission. The delivery of acute NIV is a time critical intervention as prompt application of acute NIV substantially reduces mortality for patients with acute hypercapnic respiratory failure. Objective: This audit aimed to assess the number of patients for whom there is a delay in the initiation of acute NIV. We also assessed the outcome of admission for patients started on acute NIV. Methods: Data was collected on patients admitted to Kings Mill Hospital for acute NIV between 1/2/2019 and 31/3/2019. Awareness and knowledge of acute NIV was highlighted as an area for improvement. E-learning packages on 'Acute NIV' were designed and sent to medical-staff. The audit was repeated for patients admitted for acute NIV between 1/2/2020 and 31/3/2020 and analysed using chi-square tests. Results: 25 patients were included in the initial audit and 30 patients in the re-audit. Prior to intervention 31% of patients had a delay in the initiation of acute NIV, which increased to 77% post-intervention (p < 0.0001). Prior to intervention there was a mortality rate of 17% and a mortality rate of 13% post-intervention (p > 0.05). Conclusion: Further work is required to ensure the sustained delivery of acute NIV to BTS standards, however variable achievements in the targets does not seem to have a significant adverse effect on patient outcomes.
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Antibiotic prophylaxis in breast surgery: a meta-analysis to identify the optimal strategy to reduce infection rates in breast surgery.Intro: Breast surgeries are an increasingly frequent operation, with an exponential rise in breast cancer diagnoses, and women opting for cosmetic surgeries. SSIs are the most common post-operative complication with many negative consequences including sepsis and even death. These are treated with prophylactic antibiotics prior to surgery. Breast surgery is currently defined as 'clean', although literature indicates that the infection rate is higher than should be expected for this classification. The aim of this meta-analysis is to evaluate whether pre-operative antibiotics reduce SSI frequency and which class of antibiotics achieve the best reduction. Methods: A literature search through online libraries was used to find clinical trials investigating pre-breast-surgery antibiotics and SSI frequency. These were grouped all together and separately by class of antibiotics. Additionally studies investigating breast cancer surgeries and non-cancer surgeries were grouped separately. A forest-plot was created for each group to calculate an estimated effect, these were then compared against each other. Results: Use of antibiotics resulted in a reduction in SSI frequency by 3.55% overall, and reduced frequency in all types of surgeries performed. Cephalosporins reduced SSI frequency by 2.23%, Beta-lactamase inhibitors 4.17% and macrolides achieved the greatest effect with a 14.58% reduction. Conclusion: This meta-analysis proves that antibiotics reduce SSI frequency in breast surgery and supports the notion to remove the 'clean' classification. This definition may result in failure to provide prophylaxis, resulting in patients suffering from preventable SSIs and their negative consequences. Macrolides were the most effective followed by beta-lactamase inhibitors and cephalosporins, this may be implemented in structuring new guidelines favouring use of macrolides before conducting breast surgery.
