Background Infection with the severe acute respiratory syndrome coronavirus-2 (SARSCoV-2), the virus which causes the corona virus disease-2019 (COVID-19) has substantial evidence that patients with pre-existing coronary artery disease (CAD) have an increased risk of serious illness, adverse coronary events, and mortality following infection. The COVID-CT registry will assess whether COVID-19 alters progression of coronary atherosclerotic plaque in patients with previously defined anatomic CAD on coronary computed tomographic angiography (CCTA). Mediators and covariates such as disease severity, inflammation, and neighborhood deprivation will also be assessed. Design The COVID-CT registry is a multicenter, longitudinal observational registry enrolling patients including patients with pre-pandemic atherosclerosis observed by CCTA from New York City and Long Island to determine the impact of COVID-19 infection. The primary aim is to test the hypothesis that patients with previously defined anatomic CAD by CCTA who are subsequently infected with SARS-CoV-2 have accelerated progression of total and noncalcified atherosclerotic plaque volumes when compared to uninfected patients. We hypothesize that systemic inflammation is a key promoter in the formation and progression of atherosclerotic plaque. Additionally, we will test whether measurement of the perivascular fat attenuation index detects high risk, coronary artery inflammation following COVID infection. Summary The impact of this first in-kind registry will be foundational for revising standard diagnostic pathways and risk assessment used to guide preventive care for millions of patients with CAD at increased risk from viral infection.

Estimating a patient's outcome after acute brain injury can inform clinical decision-making and support discussions with the patient's family. The objective of the ORANGE study,1 as stated in its protocol, was to predict poor extended Glasgow Outcome Score and mortality using the Neurological Pupil index (NPi); however, the reported analyses assessed the association of NPi with outcomes, not the actual predictive value of the NPi. The proposed NPi pathological threshold of 4 or less is based only on an association with mortality at 6 months in a multivariable Cox regression model.

Background Patient and public involvement (PPI) in clinical trial design contributes to ensuring the research objectives and outcome measures are relevant to patients. The minimal clinically important difference (MCID) in the primary outcome influences trial design and feasibility and should be predicated on PPI. We aimed to determine current practice of reporting PPI and the MCID in phase III/IV randomised controlled trials (RCTs). Methods Following a search of Medline, Embase, and the Cochrane Central Register of Controlled Trials, we included primary publications of phase III/IV RCTs, in English, inclusive of any medical specialty or type of intervention, that reported a health-related outcome. We excluded protocols and secondary publications of RCTs. We extracted RCT characteristics, the use of PPI, and use of the MCID. Results Between 1 July 2019 and 13 January 2020, 123 phase III/IV RCTs matched our eligibility criteria. Ninety percent evaluated a medical rather than surgical intervention. Oncology accounted for 21% of all included RCTs. Only 2.4% ( n = 3) and 1.6% ( n = 2) RCTs described PPI and the MCID respectively. Conclusions PPI and the MCID are poorly reported, so it is uncertain how these contributed to trial design. Improvement in the reporting of these items would increase confidence that results are relevant and clinically significant to patients, contributing to improving the overall trial design. Trial registration Not registered.

Background Hyponatraemia often occurs after subarachnoid haemorrhage (SAH). However, its clinical significance and optimal management are uncertain. We audited the screening, investigation and management of hyponatraemia after SAH. Methods We prospectively identified consecutive patients with spontaneous SAH admitted to neurosurgical units in the United Kingdom or Ireland. We reviewed medical records daily from admission to discharge, 21 days or death and extracted all measurements of serum sodium to identify hyponatraemia (<135 mmol/L). Main outcomes were death/dependency at discharge or 21 days and admission duration >10 days. Associations of hyponatraemia with outcome were assessed using logistic regression with adjustment for predictors of outcome after SAH and admission duration. We assessed hyponatraemia-free survival using multivariable Cox regression. Results 175/407 (43%) patients admitted to 24 neurosurgical units developed hyponatraemia. 5976 serum sodium measurements were made. Serum osmolality, urine osmolality and urine sodium were measured in 30/166 (18%) hyponatraemic patients with complete data. The most frequently target daily fluid intake was >3 L and this did not differ during hyponatraemic or non-hyponatraemic episodes. 26% (n/N=42/164) patients with hyponatraemia received sodium supplementation. 133 (35%) patients were dead or dependent within the study period and 240 (68%) patients had hospital admission for over 10 days. In the multivariable analyses, hyponatraemia was associated with less dependency (adjusted OR (aOR)=0.35 (95% CI 0.17 to 0.69)) but longer admissions (aOR=3.2 (1.8 to 5.7)). World Federation of Neurosurgical Societies grade I–III, modified Fisher 2–4 and posterior circulation aneurysms were associated with greater hazards of hyponatraemia. Conclusions In this comprehensive multicentre prospective-adjusted analysis of patients with SAH, hyponatraemia was investigated inconsistently and, for most patients, was not associated with changes in management or clinical outcome. This work establishes a basis for the development of evidence-based SAH-specific guidance for targeted screening, investigation and management of high-risk patients to minimise the impact of hyponatraemia on admission duration and to improve consistency of patient care.

Understanding the differences in outcomes based on study and patient characteristics can inform better research designs and improve the interpretation of translational glioblastoma studies. This study compared the clinical features and median overall survival (mOS) of 2,203 patients from two genomic cohorts (The Cancer Genome Atlas [TCGA] and the Chinese Glioma Genome Atlas [CGGA]) and two consecutive regional cohorts (Hong Kong [HK] and Southeast [SE] Scotland) with histologically confirmed glioblastoma. Differences in clinical characteristics reflected the distinct patient selection criteria for surgery. While the mOS were similar, the mOS of those who completed temozolomide chemoradiotherapy were 35.2 months in SE Scotland, 22.2 in HK, and 14.1 in the TCGA cohort. Survival functions were comparable in the multivariable survival analysis. Our findings highlight how a lack of clinical data impedes the translational value of research. Therefore, there is a need to develop common data elements to derive meaningful conclusions.

Abstract BACKGROUND Glioblastoma is the most common malignant primary brain tumour in adults and is usually incurable. Post-operative magnetic resonance imaging (MRI) is used to assess extent of resection, and subsequent follow-up MRI is used to monitor response to treatment and to detect progression. The benefit of regular, scheduled follow-up MRI on patient management and outcomes is unclear. MATERIAL AND METHODS In this multi-centre, retrospective observational cohort study we included patients with a histopathologically confirmed glioblastoma, operated between August 31, 2018 and February 1, 2019 who received any adjuvant oncological treatment. Follow-up MRI schedules, indications, and clinical outcomes were collected. The primary objective was to investigate the follow-up MRI surveillance practice after surgery for glioblastoma and assess compliance with recommendations from the National Institute for Health and Care Excellence (NICE) (Post-operative scan <72 hrs, MRI every 3-6 months). The secondary objectives were to determine indications for MRI scans and the association on overall survival (OS) and progression-free survival (PFS). RESULTS 754 patients, with a median age of 63 years (range: 21-84) from 26 neuro-oncology centres were included. Most patients had post-operative MRI within 72 hours of surgery (88.1%, N=407/462). The median number of subsequent follow-up MRI was 1 (Interquartile range 0-4). 28.1% of patients had follow-up MRI in accordance with NICE recommendations (N=212/754). Patients in this group were more likely to receive second-line chemotherapy (28.6% vs 19.5%, P=0.009). The median follow-up period was 10.5 months (IQR 5.3-19.4 months). Median overall survival was 15.1 months (95% CI 12.9-17.3) in the scheduled MRI group and 9.1 months (95% CI 7.8-10.4) in the non-compliant group. On multivariable cox regression analysis, regular, scheduled MRI was independently associated with longer overall survival (HR 1.67, 95% CI 1.33-2.10, P<0.001), but not PFS (HR 1.20, 95% CI 0.98-1.47, P=0.074). Patients with progression first detected on scheduled imaging had a significantly longer OS (18.4 vs 15.6 months, P=0.013) and PFS (9.9 months vs 7.9 months, P=0.041). CONCLUSION Following regular scheduled surveillance follow-up MRI for glioblastoma is associated with longer overall survival. Prospective trials are needed to determine whether regular or symptom-directed MRI influences survival outcomes and quality of life.

Background Elevated standardised mortality ratio of cardiovascular diseases (CVD) in patients with brain tumours may result from differences in the CVD incidences and cardiovascular risk factors. We compared the risk of CVD among patients with a primary malignant or non-malignant brain tumour to a matched general population cohort, accounting for other co-morbidities. Methods Using data from the Secured Anonymised Information Linkage (SAIL) Databank in Wales (United Kingdom), we identified all adults aged ≥ 18 years in the primary care database with first diagnosis of malignant or non-malignant brain tumour identified in the cancer registry in 2000–2014 and a matched cohort (case-to-control ratio 1:5) by age, sex and primary care provider from the general population without any cancer diagnosis. Outcomes included fatal and non-fatal major vascular events (stroke, ischaemic heart disease, aortic and peripheral vascular diseases) and venous thromboembolism (VTE). We used multivariable Cox models adjusted for clinical risk factors to compare risks, stratified by tumour behaviour (malignant or non-malignant) and follow-up period. Results There were 2869 and 3931 people diagnosed with malignant or non-malignant brain tumours, respectively, between 2000 and 2014 in Wales. They were matched to 33,785 controls. Within the first year of tumour diagnosis, malignant tumour was associated with a higher risk of VTE (hazard ratio [HR] 21.58, 95% confidence interval 16.12–28.88) and stroke (HR 3.32, 2.44–4.53). After the first year, the risks of VTE (HR 2.20, 1.52–3.18) and stroke (HR 1.45, 1.00–2.10) remained higher than controls. Patients with non-malignant tumours had higher risks of VTE (HR 3.72, 2.73–5.06), stroke (HR 4.06, 3.35–4.93) and aortic and peripheral arterial disease (HR 2.09, 1.26–3.48) within the first year of diagnosis compared with their controls. Conclusions The elevated CVD and VTE risks suggested risk reduction may be a strategy to improve life quality and survival in people with a brain tumour.

Background Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. Methods This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. Findings In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1-8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95% CI:1.5-3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8-20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2-0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Interpretation Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. Copyright (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

The coronary vascular volume to left ventricular mass (V/M) ratio assessed by coronary computed tomography angiography (CCTA) is a promising new parameter to investigate the relation of coronary vasculature to the myocardium supplied. It is hypothesized that hypertension decreases the ratio between coronary volume and myocardial mass by way of myocardial hypertrophy, which could explain the detected abnormal myocardial perfusion reserve reported in patients with hypertension. Individuals enrolled in the multicenter ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry who underwent clinically indicated CCTA for analysis of suspected coronary artery disease with known hypertension status were included in current analysis. The V/M ratio was calculated from CCTA by segmenting the coronary artery luminal volume and left ventricular myocardial mass. In total, 2,378 subjects were included in this study, of whom 1,346 (56%) had hypertension. Left ventricular myocardial mass and coronary volume were higher in subjects with hypertension than normotensive patients (122.7 ± 32.8 g vs 120.0 ± 30.5 g, p = 0.039, and 3,105.0 ± 992.0 mm3 vs 2,965.6 ± 943.7 mm3, p <0.001, respectively). Subsequently, the V/M ratio was higher in patients with hypertension than those without (26.0 ± 7.6 mm3/g vs 25.3 ± 7.3 mm3/g, p = 0.024). After correcting for potential confounding factors, the coronary volume and ventricular mass remained higher in patients with hypertension (least square) mean difference estimate: 196.3 (95% confidence intervals [CI] 119.9 to 272.7) mm3, p <0.001, and 5.60 (95% CI 3.42 to 7.78) g, p <0.001, respectively), but the V/M ratio was not significantly different (least square mean difference estimate: 0.48 (95% CI -0.12 to 1.08) mm3/g, p = 0.116). In conclusion, our findings do not support the hypothesis that the abnormal perfusion reserve would be caused by reduced V/M ratio in patients with hypertension.

Aims Patients with cauda equina syndrome (CES) require emergency imaging and surgical decompression. The severity and type of symptoms may influence the timing of imaging and surgery, and help predict the patient's prognosis. Categories of CES attempt to group patients for management and prognostication purposes. We aimed in this study to assess the inter -rater reliability of dividing patients with CES into categories to assess whether they can be reliably applied in clinical practice and in research. Methods A literature review was undertaken to identify published descriptions of categories of CES. A total of 100 real anonymized clinical vignettes of patients diagnosed with CES from the Understanding Cauda Equina Syndrome (UCES) study were reviewed by consultant spinal surgeons, neurosurgical registrars, and medical students. All were provided with published category definitions and asked to decide whether each patient had 'suspected CES'; 'early CES'; 'incomplete CES'; or 'CES with urinary retention'. Inter -rater agreement was assessed for all categories, for all raters, and for each group of raters using Fleiss's kappa. Results Each of the 100 participants were rated by four medical students, five neurosurgical registrars, and four consultant spinal surgeons. No groups achieved reasonable inter -rater agreement for any of the categories. CES with retention versus all other categories had the highest inter -rater agreement (kappa 0.34 (95% confidence interval 0.27 to 0.31); minimal agreement). There was no improvement in inter -rater agreement with clinical experience. Across all categories, registrars agreed with each other most often (kappa 0.41), followed by medical students (kappa 0.39). Consultant spinal surgeons had the lowest inter -rater agreement (kappa 0.17). Conclusion Inter -rater agreement for categorizing CES is low among clinicians who regularly manage these patients. CES categories should be used with caution in clinical practice and research studies, as groups may be heterogenous and not comparable.

AimsPatients with cauda equina syndrome (CES) require emergency imaging and surgical decompression. The severity and type of symptoms may influence the timing of imaging and surgery, and help predict the patient’s prognosis. Categories of CES attempt to group patients for management and prognostication purposes. We aimed in this study to assess the inter-rater reliability of dividing patients with CES into categories to assess whether they can be reliably applied in clinical practice and in research.MethodsA literature review was undertaken to identify published descriptions of categories of CES. A total of 100 real anonymized clinical vignettes of patients diagnosed with CES from the Understanding Cauda Equina Syndrome (UCES) study were reviewed by consultant spinal surgeons, neurosurgical registrars, and medical students. All were provided with published category definitions and asked to decide whether each patient had ‘suspected CES’; ‘early CES’; ‘incomplete CES’; or ‘CES with urinary retention’. Inter-rater agreement was assessed for all categories, for all raters, and for each group of raters using Fleiss’s kappa.ResultsEach of the 100 participants were rated by four medical students, five neurosurgical registrars, and four consultant spinal surgeons. No groups achieved reasonable inter-rater agreement for any of the categories. CES with retention versus all other categories had the highest inter-rater agreement (kappa 0.34 (95% confidence interval 0.27 to 0.31); minimal agreement). There was no improvement in inter-rater agreement with clinical experience. Across all categories, registrars agreed with each other most often (kappa 0.41), followed by medical students (kappa 0.39). Consultant spinal surgeons had the lowest inter-rater agreement (kappa 0.17).ConclusionInter-rater agreement for categorizing CES is low among clinicians who regularly manage these patients. CES categories should be used with caution in clinical practice and research studies, as groups may be heterogenous and not comparable.Cite this article: Bone Joint J 2023;105-B(9):1007–1012.

Abstract Background This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors.

Introduction Intraoperative feedback can be associated with improved surgical performance. Quality feedback can reduce the time required by trainees to achieve proficiency in psychomotor skills. Operative training time has become increasingly limited, and it has become imperative to use surgical training time effectively. Aim In this survey, we assessed trainees’ perspectives of intraoperative feedback. We included several aspects of feedback including its occurrence, quality, and potential barriers. Methods All surgical trainees in a single centre were invited to complete an electronic questionnaire. Participants were anonymised. We summarised data using descriptive statistics. Results Most trainees (85%) reported they had the opportunity to share their training goals with trainers. Just under three-quarters of trainees felt they always or sometimes got timely feedback. Only half of the trainees were signposted to feedback and 23% felt feedback was not part of their department's culture. Half of the trainees did not always feel comfortable asking for feedback from their trainers stating their reasons as fear of criticism, lack of time and competing clinical commitments. Conclusion There is no denying the importance of feedback on operative performance, however, this survey shows that many of the pillars of quality feedback are poorly adhered to.

Introduction: Cauda equina syndrome (CES) has significant medical, social, and legal consequences. Understanding the number of people presenting with CES and their demographic features is essential for planning healthcare services to ensure timely and appropriate management. We aimed to establish the incidence of CES in a single country and stratify incidence by age, gender, and socioeconomic status. As no consensus clinical definition of CES exists, we compared incidence using different diagnostic criteria. Methods: All patients presenting with radiological compression of the cauda equina due to degenerative disc disease and clinical CES requiring emergency surgical decompression during a 1-year period were identified at all centres performing emergency spinal surgery across Scotland. Initial patient identification occurred during the emergency hospital admission, and case ascertainment was checked using ICD-10 diagnostic coding. Clinical information was reviewed, and incidence rates for all demographic and clinical groups were calculated. Results: We identified 149 patients with CES in 1 year from a total population of 5.4 million, giving a crude incidence of 2.7 (95% CI: 2.3–3.2) per 100,000 per year. CES occurred more commonly in females and in the 30–49 years age range, with an incidence per year of 7.2 (95% CI: 4.7–10.6) per 100,000 females age 30–39. There was no association between CES and socioeconomic status. CES requiring catheterization had an incidence of 1.1 (95% CI: 0.8–1.5) per 100,000 adults per year. The use of ICD-10 codes alone to identify cases gave much higher incidence rates, but was inaccurate, with 55% (117/211) of patients with a new ICD-10 code for CES found not to have CES on clinical notes review. Conclusion: CES occurred more commonly in females and in those between 30 and 49 years and had no association with socioeconomic status. The incidence of CES in Scotland is at least four times higher than previous European estimates of 0.3–0.6 per 100,000 population per year. Incidence varies with clinical diagnostic criteria. To enable comparison of rates of CES across populations, we recommend using standardized clinical and radiological criteria and standardization for population structure.

Objective To assess the outcome measures used in studies investigating cervical spine fractures in adults, with or without associated spinal cord injury, to inform development of a core outcome set. Methods Medline, Embase and Scopus were searched for relevant studies until May 28, 2022, without a historic limit on study date. Study characteristics, population characteristics and outcomes reported were extracted and analyzed. Results Our literature search identified 536 studies that met criteria for inclusion, involving 393,266 patients. Most studies were single center (87.3%), retrospective studies (88.9%) and involved a median of 40 patients (range 6–167,278). Treatments assessed included: surgery (55.2%), conservative (6.2%), halo immobilization (4.9%), or a mixture (33.2%). Median study duration was 84 months (range 3–564 months); the timing of clinical and/or radiological follow-up assessment after injury was reported in 56.7%. There was significant heterogeneity in outcomes used, with 79 different reported outcomes measures. Differences in use were identified between smaller/larger, retro-/prospective and single/multicenter cohorts. Over time, the use of radiological outcomes has declined with greater emphasis on patient-reported outcome measures (PROMs). Studies of conservative management were more likely to detail PROMs and mortality, whereas surgical studies reported Frankel/ASIA grade, radiological fusion, complication rates, duration of hospital stay and re-operation rates more frequently. In studies assessing the elderly population (> 65 years), use of PROMs, mortality, hospital stay and discharge destination were more common, whereas fusion was reported less often. Response rates for outcome assessments were lower in studies assessing elderly patients, and studies using PROMs. Conclusions We have classified the various outcome measures used for patients with cervical spine fractures based on the COMET outcome taxonomy. We also described the contexts in which different outcomes are more commonly employed to help guide decision-making when designing future research endeavors.

Background The Dose Adjustment for Normal Eating (DAFNE) course teaches insulin dose adjustment to match dietary carbohydrates and improve glycaemic control in participants with type 1 diabetes mellitus (T1DM). We investigated the association between socioeconomic deprivation and reduction in HbA1c as a marker of sustained glycaemic control, after attending DAFNE education. Methods This retrospective observational study identified adults with T1DM who attended DAFNE training in NHS Lothian, South East Scotland. We extracted age, sex, postcode-based Scottish Index of Multiple Deprivation (SIMD) quintiles and annual HbA1c measurements available four years before and after course attendance. We calculated mean HbA1c before (baseline) and after attendance at DAFNE, across four annual measurements. Change in mean HbA1c (mmol/mol) was categorised into three groups: decrease (>= - 2.5), no change (<+/- 2.5), increase (>= + 2.5). We used multivariable ordinal logistic regression, with baseline mean HbA1c as a covariate, to investigate the association of SIMD quintile with reduction in mean HbA1c. Results 335 participants were included. Age and sex distribution were similar across SIMD quintiles (Mean age = 45, range 21-91, 59% women). Lower SIMD quintiles (greater deprivation) had higher baseline mean HbA1c (SIMD 1: 76.0, SIMD 5: 69.0). Higher SIMD quintiles (lower deprivation) were associated with lower odds of no change/increase in mean HbA1c (SIMD 5, odds ratio = 0.25, 95% confidence interval 0.10, 0.58, p = 0.001, multivariable analysis). Conclusion Socioeconomic deprivation was associated with higher baseline mean HbA1c and lower reduction in HbA1c following DAFNE education. Future research could explore causes and how best to support participants from deprived areas. Previous submissions This work has not been previously submitted to a journal. This work was presented as a poster at The ABCD Conference 2021 and the abstract (of no more than 300 words) from the meeting has been published: Innes CWD, Henshall DE, Wilson B, Poon M, Morley SD, Ritchie SA. Socioeconomic deprivation is associated with reduced efficacy of an insulin adjustment education programme for people with type 1 diabetes. Br J Diabetes. 2021; 21: 293-296.