Western General Hospital
  • Edinburgh, United Kingdom
Recent publications
Latitude and season determine exposure to ultraviolet radiation and correlate with population blood pressure. Evidence for Vitamin D causing this relationship is inconsistent, and temperature changes are only partly responsible for BP variation. In healthy individuals, a single irradiation with 20 J/cm2 UVA mobilises NO from cutaneous stores to the circulation, causes arterial vasodilatation, and elicits a transient fall in BP. We, therefore, tested whether low-dose daily UVA phototherapy might be an effective treatment for mild hypertension. 13 patients with untreated high-normal or stage 1 hypertension (BP 130-159/85-99 mm Hg), confirmed by 24-h ambulatory blood pressure (ABP), were recruited. Using home phototherapy lamps they were either exposed to 5 J/cm2 full body UVA (320–410 nm) radiation each day for 14 days, or sham-irradiated with lamps filtered to exclude wavelengths <500 nm. After a washout period of 3 ± 1 week, the alternate irradiation was delivered. 24-h ABP was measured on day 0 before either irradiation sequence and on day 14. Clinic BP was recorded on day 0, and within 90 min of irradiation on day 14. There was no effect on 24-h ABP following UVA irradiation. Clinic BP shortly after irradiation fell with UVA (−8.0 ± 2.9/−3.8 ± 1.1 mm Hg p = 0.034/0.029) but not sham irradiation (1.1 ± 3.0/0.9 ± 1.5 mm Hg). Once daily low-dose UVA does not control mildly elevated BP although it produces a transient fall shortly after irradiation. More frequent exposure to UVA might be effective. Alternatively, UVB, which photo-releases more NO from skin, could be tried.
Background & Aims Healthcare service provision in inflammatory bowel disease (IBD) is often designed to meet targets set by healthcare providers rather than those of patients. It is unclear whether this meets the needs of patients, as assessed by patients themselves. This nationwide study assessed patients' experience of IBD and the healthcare they received, aiming to identify factors in IBD healthcare provision associated with perceived high‐quality care. Methods Using the 2019 IBD Standards as a framework, a national benchmarking tool for quality assessment in IBD was developed by IBD UK, comprising a Patient Survey and Service Self‐Assessment. Results In all, 134 IBD services and 9757 patients were responded. Perceived quality of care was lowest in young adults then increased with age, was higher in males and those >2 years since diagnosis. No hospital services met all the National IBD Standards for recommended workforce numbers. Key metrics associated with patient‐reported high‐quality care were as follows: identification as a tertiary centre, patient information availability, shared decision‐making, rapid response to contact for advice, access to urgent review, joint medical/surgical clinics and access to research (all p < 0.001). Higher numbers of IBD nurse specialists in a service was strongly associated with patients receiving regular reviews and having confidence in self‐management and reporting high‐quality care. Conclusions This extensive patient and healthcare provider survey emphasises the importance of aspects of care less often measured by clinicians, such as communication, shared decision‐making and provision of information, and demonstrates that IBD nurse specialists are crucial to meeting the needs of people living with IBD.
Difficult airway management continues to adversely affect patient care and clinical outcomes and is poorly predicted. Previous difficult airway management is the most accurate predictor of future difficulty. The Difficult Airway Society initiated a national airway database to allow clinicians to access details of previous difficult airway episodes in patients issued with a difficult airway alert card. We aimed to analyse this database, reporting patient characteristics, airway management and patient outcomes. We included all living adult patients reported in the first 5 years of the database (n = 675). Clinical airway assessment was reported in 634 (94%) patients, with three or more parameters assessed in 488 (72%). A history of difficult airway was known in 136 (20%) patients and difficult airway management was anticipated in 391 (58%). In all, 75 (11%) patients had an airway‐related critical incident, with 1 in 29 being awoken from anaesthesia, 1 in 34 requiring unplanned or prolonged stay in the intensive care unit and 1 in 225 needing an emergency front‐of‐neck airway or had a cardiac arrest/peri‐arrest episode. Airway‐related critical incidents were associated with out‐of‐hours airway management, but no other associations were apparent. Our data report the first analysis of a national difficult airway database, finding that unanticipated difficult airway management continues to occur despite airway assessment, and the rate of critical incidents in this cohort of patients is high. This database has the potential to improve airway management for patients in the future.
Objectives: Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. Methods: At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications ('red shading' in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. Results: Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3-8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40-7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08-0.65) for 2015-2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). Conclusion: In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12.
Objective Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD. Design Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study. Results Geometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001). Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and were predicted by SARS-CoV-2 antinucleocapsid concentrations after the initial infection. We did not observe persistent oropharyngeal carriage of SARS-CoV-2. Hospitalisations and deaths were uncommon in both groups. Conclusions Following a third dose of an mRNA-based vaccine, infliximab was associated with attenuated serological responses and more SARS-CoV-2 breakthrough infection and reinfection which were not predicted by the magnitude of anti-S RBD responses, indicative of vaccine escape by the Omicron variant. Trial registration number ISRCTN45176516 .
Background: Villous atrophy is an indication for small bowel capsule endoscopy (SBCE). However, SBCE findings are not described uniformly and atrophic features are sometimes not recognized; Methods: The Delphi technique was employed to reach agreement among a panel of SBCE experts. The nomenclature and definitions of SBCE lesions suggesting the presence of atrophy were decided in a core group of 10 experts. Four images of each lesion were chosen from a large SBCE database and agreement on the correspondence between the picture and the definition was evaluated using the Delphi method in a broadened group of 36 experts. All images corresponded to histologically proven mucosal atrophy; Results: Four types of atrophic lesions were identified: mosaicism, scalloping, folds reduction, and granular mucosa. The core group succeeded in reaching agreement on the nomenclature and the descriptions of these items. Consensus in matching the agreed definitions for the proposed set of images was met for mosaicism (88.9% in the first round), scalloping (97.2% in the first round), and folds reduction (94.4% in the first round), but granular mucosa failed to achieve consensus (75.0% in the third round); Conclusions: Consensus among SBCE experts on atrophic lesions was met for the first time. Mosaicism, scalloping, and folds reduction are the most reliable signs, while the description of granular mucosa remains uncertain.
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
Lay Summary We assessed the impact of a dedicated inflammatory bowel disease flare clinic. Attenders had more changes to maintenance medications made and less steroid use than inflammatory bowel disease patients reviewed at the Acute Receiving Unit. This model of care may potentially reduce hospital admissions.
Background In 2010, a national enquiry into elderly patient outcomes after surgery identified that only 36% received ‘good’ care. Guidance was subsequently published by the Association of Anaesthetists of Great Britain and Ireland regarding perioperative care of the elderly and those with dementia; this study aims to assess current adherence to these guidelines in anaesthetic departments across Scotland. Methods A web-based survey was sent to all Scottish departments. The questions assessed department patient demographic, access to specialist pre-assessment services, availability of multidisciplinary input, perioperative care of patients with cognitive impairment and departmental training on geriatric perioperative care. Results Responses were collected from November-December 2020 with a 92.6% response rate. A total of 64% of departments stated that > 50% of their workload involved patients over 75. One department had a lead clinician for geriatric anaesthesia, whilst 20% could access a geriatric specialist when coordinating perioperative care. Specialist geriatric pre-assessment services operate in 20% of centres. A total of 60% of respondents used a clinical frailty score when pre-assessing patients over 75, with 48% specifically screening for cognitive impairment. The vast majority of centres, 76%, did not routinely provide information regarding post-operative delirium and 24% ‘never or very rarely’ invite caregivers to accompany patients with dementia into the department. Education sessions regarding perioperative elderly care had occurred in 56% of departments. Conclusions Elderly patients represent a significant proportion of anaesthetic workload in Scotland. Despite this, adherence to recommended practice is low. The vast majority of centres lack access to specialist multidisciplinary input or specialist pre-assessment services which are essential to providing good care. Reported screening for frailty and cognitive impairment is variable, with opportunities for improvement in communication and education (patient and clinician) surrounding these conditions.
Objective It is unclear how the compounding prevalence of inflammatory bowel disease (IBD) has translated into the causes and rates of hospitalisation, particularly in an era of increased biologic prescribing. We aimed to analyse these trends in a population‐based IBD cohort over the last 10 years. Design The Lothian IBD registry is a complete, validated, prevalent database of IBD patients in NHS Lothian, Scotland. ICD‐10 coding of hospital discharge letters from all IBD patient admissions to secondary care between 1 January 2010 and 31 December 2019 was interrogated for admission cause, with linkage to local/national data sets on death and prescribed drugs. Results Fifty‐seven per cent (4673/8211) of all IBD patients were admitted to secondary care for >24 h between 1 January 2010 and 31 December 2019. In patients <40 years, IBD was the commonest reason for admission (38% of admissions), whereas infection was the most common cause in those >60 years (19% of admissions). Three per cent (243/8211) of IBD patients accounted for 50% of the total IBD bed‐days over the study period. Age‐standardised IBD admission rates fell from 39.4 to 25.5 admissions per 100,000 population between 2010 and 2019, an average annual percentage reduction of 3% (95% CI −4.5% to −2.1%, p < 0.0001). Non‐IBD admission rates were unchanged overall (145–137 per 100,000 population) and specifically for serious (hospitalisation) and severe (ITU admission or death) infection over the same period. Conclusion Despite compounding prevalence and increased biologic use, IBD admission rates are falling. The cause of admission varies with age, with infection the predominant cause in older patients.
Background Three-dimensional relationships within the limbic and paralimbic areas are often hard to grasp. Relevant anatomical structures exhibit a complicated architecture and connectivity and therefore surgical approaches targeting lesions or functional resections in this area pose a distinct challenge. Purpose To provide an educational, comprehensive, systematic and stepwise manual for the dissection and illustration of major limbic structures since there is a gap in the pertinent literature. Further, we aim to offer a thorough yet simplified roadmap for laboratory and intraoperative dissections. Methods Twenty (20) normal adult, formalin-fixed cerebral hemispheres were studied through the fiber dissection technique and under the microscope. Stepwise and in tandem medial to lateral and lateral to medial dissections were performed in all specimens aiming to reveal the morphology and spatial relationships of major limbic and paralimbic areas. Results Fourteen (14) consecutive, discrete and easily reproducible laboratory anatomical steps are systematically described to reveal the intricate anatomy of the limbic and paralimbic structures and their main connections. Conclusion This study offers for the first time in the pertinent literature a focused, step-by-step laboratory manual for the dissection and illustration of the limbic and paralimbic structures. The overreaching goal is to supplement the novice and experienced anatomist and neurosurgeon with a thorough and systematic reference to facilitate laboratory or intraoperative dissections.
A female patient presented with fever of unknown origin, night sweats and weight loss. She had no pulmonary symptoms. Investigations revealed bilateral ground glass lung lesions which were subsequently followed-up with imaging. Two years later, a follow-up CT scan revealed an increase in the size of the lesions which exhibited a more solid appearance. A diagnostic biopsy was difficult to perform, and the patient underwent a left upper lobectomy for suspected primary lung malignancy. Histological examination showed lung involvement by Castleman’s disease of plasma cell type which displayed a multifocal distribution. There was no evidence of nodal involvement. Following discussion at the multidisciplinary team meeting and correlation with radiology, a diagnosis of multicentric Castleman’s disease of the lung was made. Here, we present an unusual case of multicentric Castleman’s disease of the lung mimicking primary lung carcinoma. Our case highlights the importance of considering this entity in the differential diagnosis of multifocal lung lesions with a ground glass-like appearance to allow early diagnosis and management.
Congenital diaphragmatic hernia (CDH) can occur in isolation or in conjunction with other birth defects (CDH+). A molecular etiology can only be identified in a subset of CDH cases. This is due, in part, to an incomplete understanding of the genes that contribute to diaphragm development. Here, we used clinical and molecular data from 36 individuals with CDH+ who are cataloged in the DECIPHER database to identify genes that may play a role in diaphragm development and to discover new phenotypic expansions. Among this group, we identified individuals who carried putatively deleterious sequence or copy number variants affecting CREBBP, SMARCA4, UBA2, and USP9X. The role of these genes in diaphragm development was supported by their expression in the developing mouse diaphragm, their similarity to known CDH genes using data from a previously published and validated machine learning algorithm, and/or the presence of CDH in other individuals with their associated genetic disorders. Our results demonstrate how data from DECIPHER, and other public databases, can be used to identify new phenotypic expansions and suggest that CREBBP, SMARCA4, UBA2, and USP9X play a role in diaphragm development.
The therapeutic armamentarium for rheumatoid arthritis has increased substantially over the last 20 years. Historically antirheumatic treatment was started late in the disease course and frequently included prolonged high-dose glucocorticoid treatment which was associated with accelerated generalised bone loss and increased vertebral and non-vertebral fracture risk. Newer biologic and targeted synthetic treatments and a combination of conventional synthetic DMARDs prevent accelerated systemic bone loss and may even allow repair of cortical bone erosions. Emerging data also gives new insight on the impact of long-term conventional synthetic DMARDs on bone health and fracture risk and highlights the need for ongoing studies for better understanding of “established therapeutics”. An interesting new antirheumatic treatment effect is the potential of erosion repair with the use of biologic DMARDs and janus kinase inhibitors. Although several newer anti-rheumatic drugs seem to have favorable effects on bone mineral density in RA patients, these effects are modest and do not seem to influence the fracture risk thus far. We summarize recent developments and findings of the impact of anti-rheumatic treatments on localized and systemic bone integrity and health.
Background: Anthracyclines are effective cytotoxic drugs used in the treatment of breast cancer and lymphoma but are associated with myocardial injury, left ventricular dysfunction, and heart failure. Anthracycline-induced cardiotoxicity is highly variable in severity and without a proven therapeutic intervention. β-Adrenergic receptor blockers and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients. Methods: The Cardiac CARE trial is a multicentre prospective randomized open-label blinded end point trial of combination β-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapy in patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy that is associated with myocardial injury. Patients at higher risk of cardiotoxicity with plasma high-sensitivity cTnI (cardiac troponin I) concentrations in the upper tertile at the end of chemotherapy are randomized to standard of care plus combination candesartan and carvedilol therapy or standard of care alone. All patients undergo cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. The primary end point is the change in left ventricular ejection fraction at 6 months after chemotherapy. In low-risk nonrandomized patients, left ventricular ejection fraction before and 6 months after anthracycline will be compared with define the specificity of the high-sensitivity cTnI assay for identifying low-risk participants who do not develop left ventricular systolic dysfunction. Discussion: Cardiac CARE will examine whether cardiac biomarker monitoring identifies patients at risk of left ventricular dysfunction following anthracycline chemotherapy and whether troponin-guided treatment with combination candesartan and carvedilol therapy prevents the development of left ventricular dysfunction in these high-risk patients.
Aim To gain consensus on the patient assessment skills required by pharmacist independent prescribers prescribing immunomodulators in myeloma across National Health Service Scotland. Methods This was a two-phase study which used nominal group technique to gain local consensus followed by a two-round eDelphi questionnaire to gain national consensus across all cancer networks. Setting This project was conducted across the three cancer networks within NHS Scotland: South East Scotland Cancer Network; West of Scotland Cancer Network and North Cancer Alliance. Subjects Participants were invited from each cancer network (South East Scotland Cancer Network, West of Scotland Cancer Network and North Cancer Alliance) and included haematology consultants, haematology specialist registrars, haematology advanced nurse practitioners and haematology pharmacists. Results There were five participants in the nominal group technique. Twenty-two out of 31 patient assessment skills gained local consensus, seven patient assessment skills did not gain consensus and two patient assessment skills were deemed irrelevant. There were 12 and 14 participants in round one and two of the eDelphi questionnaire, respectively. Twenty-nine patient assessment skills were included in the first-round questionnaire and 21 gained consensus. The remaining eight patient assessment skills were included in round two where seven did not achieve consensus and one achieved disagreement consensus. Conclusion This research outlines 21 patient assessment skills required for pharmacist independent prescribers to prescribe immunomodulators for myeloma patients according to haematology specialists in Scotland. Discussion on patient assessment skills without consensus showed that the pharmacist independent prescribers would have a shared responsibility with the consultant. This work should inform the development of a competency framework to allow training of pharmacist independent prescribers in Scotland. Some patient assessment skills could be transferrable for pharmacist independent prescribers prescribing systemic anti-cancer therapy for other haematological malignancies.
Background Surgery for renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the renal vein (RV) and/or inferior vena cava (IVC) has high peri-surgical morbidity/mortality. NAXIVA assessed the response of VTT to axitinib, a potent tyrosine kinase inhibitor. Methods NAXIVA was a single-arm, multi-centre, Phase 2 study. In total, 20 patients with resectable clear cell RCC and VTT received upto 8 weeks of pre-surgical axitinib. The primary endpoint was percentage of evaluable patients with VTT improvement by Mayo level on MRI. Secondary endpoints were percentage change in surgical approach and VTT length, response rate (RECISTv1.1) and surgical morbidity. Results In all, 35% (7/20) patients with VTT had a reduction in Mayo level with axitinib: 37.5% (6/16) with IVC VTT and 25% (1/4) with RV-only VTT. No patients had an increase in Mayo level. In total, 75% (15/20) of patients had a reduction in VTT length. Overall, 41.2% (7/17) of patients who underwent surgery had less invasive surgery than originally planned. Non-responders exhibited lower baseline microvessel density (CD31), higher Ki67 and exhausted or regulatory T-cell phenotype. Conclusions NAXIVA provides the first Level II evidence that axitinib downstages VTT in a significant proportion of patients leading to reduction in the extent of surgery. Clinical trial registration NCT03494816.
Institution pages aggregate content on ResearchGate related to an institution. The members listed on this page have self-identified as being affiliated with this institution. Publications listed on this page were identified by our algorithms as relating to this institution. This page was not created or approved by the institution. If you represent an institution and have questions about these pages or wish to report inaccurate content, you can contact us here.
69 members
Yasuko Maeda
  • Department of Colorectal Surgery
Wayne Lam
  • Clinical Genetics Service
Thomas Raymond Shaw
  • Department of Cardiology
Martin Eastwood
  • Gastroenterology
Edinburgh, United Kingdom