Urgent referral for suspected CNS cancer: which clinical features are associated with a positive predictive value of 3 % or more?

Background Urgent referral for suspected central nervous system (CNS) cancer is recommended, but little analysis of the referral criteria diagnostic performance has been conducted. New 2015 NICE guidance recommends direct brain imaging for patients with symptoms with positive predictive values (PPV) of 3 %, but further guidance is needed. Methods A 12-month retrospective evaluation of 393 patients referred under previous 2005 NICE 2-week rule criteria was conducted. Analysis was based on the three groups of symptoms forming the referral criteria, (1) CNS symptoms, (2) recent onset headaches, (3) rapidly progressive subacute focal deficit/cognitive/behavioural/personality change. Comparison was made with neuroimaging findings. Results Twelve (3.1 %) of 383 patients who attended clinic had CNS cancer suggesting the combination of clinical judgement and application of 2005 criteria matched the 2015 guideline’s PPV threshold. PPVs for the three groups of symptoms were (1) 4.1 % (95 % CIs 2.0 to 7.4 %), (2) 1.2 % (0.1 to 4.3 %) and (3) 3.7 % (0.1 to 19.0 %). Sensitivities were (1) 83.3 % (95 % CIs 51.6 to 97.9 %), (2) 16.7 % (2.1 to 48.4 %), and (3) 8.3 % (0.2 to 38.5 %); specificities were (1) 37.2 % (32.3 to 42.3 %), (2) 55.5 % (50.3 to 60.7 %) and (3) 93.0 % (89.9 to 95.4 %). Of 288 patients who underwent neuroimaging, 59 (20.5 %) had incidental findings, most commonly cerebrovascular disease. Conclusions The 2015 guidance is less prescriptive than previous criteria making clinical judgement more important. CNS symptoms had greatest sensitivity, while PPVs for CNS symptoms and rapidly progressive subacute deficit/cognitive/behavioural/personality change were closest to 3 %. Recent onset headaches had the lowest sensitivity and PPV

Real world hospital costs following stress echocardiography in the UK: a costing study from the EVAREST/BSE-NSTEP multi-entre study

Background: Stress echocardiography is widely used to detect coronary artery disease, but little evidence on downstream hospital costs in real-world practice is available. We examined how stress echocardiography accuracy and downstream hospital costs vary across NHS hospitals and identifed key factors that afect costs to help inform future clinical planning and guidelines. Methods: Data on 7636 patients recruited from 31 NHS hospitals within the UK between 2014 and 2020 as part of EVAREST/BSE-NSTEP clinical study, were used. Data included all diagnostic tests, procedures, and hospital admissions for 12 months after a stress echocardiogram and were costed using the NHS national unit costs. A decision tree was built to illustrate the clinical pathway and estimate average downstream hospital costs. Multi-level regression analysis was performed to identify variation in accuracy and costs at both patient, procedural, and hospital level. Linear regression and extrapolation were used to estimate annual hospital cost-savings associated with increasing predictive accuracy at hospital and national level. Results: Stress echocardiography accuracy varied with patient, hospital and operator characteristics. Hypertension, presence of wall motion abnormalities and higher number of hospital cardiology outpatient attendances annually reduced accuracy, adjusted odds ratio of 0.78 (95% CI 0.65 to 0.93), 0.27 (95% CI 0.15 to 0.48), 0.99 (95% CI 0.98 to 0.99) respectively, whereas a prior myocardial infarction, angiotensin receptor blocker medication, and greater operator experience increased accuracy, adjusted odds ratio of 1.77 (95% CI 1.34 to 2.33), 1.64 (95% CI 1.22 to 2.22), and 1.06 (95% CI 1.02 to 1.09) respectively. Average downstream costs were £646 per patient (SD 1796) with signifcant variation across hospitals. The average downstream costs between the 31 hospitals varied from £384–1730 per patient. False positive and false negative tests were associated with average downstream costs of £1446 (SD £601) and £4192 (SD 3332) respectively, driven by increased non-elective hospital admissions, adjusted odds ratio 2.48 (95% CI 1.08 to 5.66), 21.06 (95% CI 10.41 to 42.59) respectively. We estimated that an increase in accuracy by 1 percentage point could save the NHS in the UK £3.2 million annually. Conclusion: This study provides real-world evidence of downstream costs associated with stress echocardiography practice in the UK and estimates how improvements in accuracy could impact healthcare expenditure in the NHS. A real-world downstream costing approach could be adopted more widely in evaluation of imaging tests and interventions to refect actual value for money and support realistic planning

Lower Cancer Incidence in Amsterdam-I Criteria Families Without Mismatch Repair Deficiency: Familial Colorectal Cancer Type X

Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown

The Seventeenth Data Release of the Sloan Digital Sky Surveys: Complete Release of MaNGA, MaStar and APOGEE-2 Data

This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library (MaStar) accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) survey which publicly releases infra-red spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the sub-survey Time Domain Spectroscopic Survey (TDSS) data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey (SPIDERS) sub-survey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated Value Added Catalogs (VACs). This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper (MWM), Local Volume Mapper (LVM) and Black Hole Mapper (BHM) surveys

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Multi-Robot Boundary Tracking with Phase and Workload Balancing

This paper discusses the use of a cooperative multiple robot system as applied to distributed tracking and sampling of a boundary edge. Within this system the boundary edge is partitioned into subsegments, each allocated to a particular robot such that workload is balanced across the robots. Also, to minimize the time between sampling local areas of the boundary edge, it may be desirable to minimize the difference between each robots progression (i.e. phase) along its allocated sub segment of the edge. The paper introduces a new distributed controller that handles both workload and phase balancing. Simulation results are used to illustrate the effectiveness of the controller in an Autonomous Underwater Vehicle (AUV) under ice edge sampling application. Successful results from experimentation with three iRobot Creates are also presented

Storage and sharing of large 3D imaging datasets

The scientific and engineering communities are investing in the generation of large voxel datasets. Procedures and standards to record acquisition, sample condition, processing algorithms and imaging parameters are vital to maintain long-term data value. Even when these are conserved, data remains largely inaccessible to the wider community, hindering both business and research exploitation, an issue increasingly recognised by funding bodies. Engaging imaging communities in the use and development of standards-compliant schemas and ontologies is therefore essential. Tools to then conserve significant volumes of 3D data are discussed, including Cloud compute and storage opportunities. Policy and practical issues are considered in relation to institutional and disciplinary repository models for managing and exposing datasets. The real value will become apparent as Semantic technologies become established, at which stage the ever-increasing body of experimental data will provide new opportunities for knowledge discovery within and across disciplines

Phenotypical differences of C9ORF72 gene-positive and negative amyotrophic lateral sclerosis:A comparative case series

Background Hexanucleotide repeat expansions of C9ORF72 account for a significant proportion of autosomal dominant neurodegenerative diseases in the amyotrophic lateral sclerosis (ALS)-frontotemporal dementia spectrum. In the absence of a family history, clinical identification of such patients remains difficult. We aimed to identify differences in demographics and clinical presentation between patients with C9ORF72 gene-positive ALS (C9pALS) versus C9ORF72 gene-negative ALS (C9nALS), to aid identification of these patients in the clinic and examine differences in outcomes including survival. Methods We retrospectively reviewed the clinical presentations of 32 patients with C9pALS and compared their characteristics with a cohort of 46 patients with C9nALS from the same tertiary neurosciences centre. Results Patients with C9pALS more commonly presented with mixed upper and lower motor signs (C9pALS 87.5%, C9nALS 65.2%; p=0.0352), but less frequently presented with purely upper motor neuron signs (C9pALS 3.1%, C9nALS 21.7%; p=0.0226). The C9pALS cohort had a higher frequency of cognitive impairment (C9pALS 31.3%, C9nALS 10.9%; p=0.0394) and bulbar disease (C9pALS 56.3%, C9nALS 28.3%; p=0.0186). There were no differences between cohorts in age at diagnosis, gender, limb weakness, respiratory symptoms, presentation with predominantly lower motor neuron signs or overall survival. Discussion Analysis of this ALS clinic cohort at a UK tertiary neurosciences centre adds to the small but growing understanding of the unique clinical features of patients with C9pALS. In the age of precision medicine with expanding opportunities to manage genetic diseases with disease-modifying therapies, clinical identification of such patients is increasingly important as focused therapeutic strategies become available.</p

Urgent referral for suspected CNS cancer: which clinical features are associated with a positive predictive value of 3 % or more?

Abstract Background Urgent referral for suspected central nervous system (CNS) cancer is recommended, but little analysis of the referral criteria diagnostic performance has been conducted. New 2015 NICE guidance recommends direct brain imaging for patients with symptoms with positive predictive values (PPV) of 3 %, but further guidance is needed. Methods A 12-month retrospective evaluation of 393 patients referred under previous 2005 NICE 2-week rule criteria was conducted. Analysis was based on the three groups of symptoms forming the referral criteria, (1) CNS symptoms, (2) recent onset headaches, (3) rapidly progressive subacute focal deficit/cognitive/behavioural/personality change. Comparison was made with neuroimaging findings. Results Twelve (3.1 %) of 383 patients who attended clinic had CNS cancer suggesting the combination of clinical judgement and application of 2005 criteria matched the 2015 guideline’s PPV threshold. PPVs for the three groups of symptoms were (1) 4.1 % (95 % CIs 2.0 to 7.4 %), (2) 1.2 % (0.1 to 4.3 %) and (3) 3.7 % (0.1 to 19.0 %). Sensitivities were (1) 83.3 % (95 % CIs 51.6 to 97.9 %), (2) 16.7 % (2.1 to 48.4 %), and (3) 8.3 % (0.2 to 38.5 %); specificities were (1) 37.2 % (32.3 to 42.3 %), (2) 55.5 % (50.3 to 60.7 %) and (3) 93.0 % (89.9 to 95.4 %). Of 288 patients who underwent neuroimaging, 59 (20.5 %) had incidental findings, most commonly cerebrovascular disease. Conclusions The 2015 guidance is less prescriptive than previous criteria making clinical judgement more important. CNS symptoms had greatest sensitivity, while PPVs for CNS symptoms and rapidly progressive subacute deficit/cognitive/behavioural/personality change were closest to 3 %. Recent onset headaches had the lowest sensitivity and PPV