Emergency Department point-of-care antiviral host response testing is accurate during periods of multiple respiratory virus co-circulation.

OBJECTIVES: FebriDx is a CE-marked, FDA-approved point-of-care test that detects the antiviral host response protein Myxovirus Resistance Protein A (MxA), in addition to C-reactive protein, using finger-prick blood. FebriDx MxA detection had a high negative predictive value for COVID-19 in symptomatic adults presenting to hospital in the first waves of the pandemic and was used subsequently as a 'rule out' triage tool in Emergency departments. The diagnostic accuracy of FebriDx MxA in the current context of co-circulation of influenza, SARS-CoV-2, and Respiratory Syncytial Virus (RSV), and in the era of COVID-19 vaccination, is unknown. METHODS: We retrospectively evaluated the diagnostic performance of FebriDx MxA in adults with acute respiratory symptoms presenting to the Emergency Department (ED) of a large UK teaching hospital using Reverse Transcription Polymerase Chain Reaction (RT-PCR) as the reference standard (Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV). RESULTS: Between March 9th 2022 and March 8th 2023, 5426 patients had both FebriDx and RT-PCR testing with valid results. 999 (18.4%) of patients had influenza detected, 520 (9.6%) SARS-CoV-2, and 190 (3.5%) RSV. Negative Predictive Value (NPV) of MxA detection by FebriDx was 97.5% (96.9-98.0) for influenza, 97.1% (96.4-97.7) for SARS-CoV-2, 98.1% (97.5-98.6) for RSV, and 92.8% (91.8-93.7) for all viruses combined. CONCLUSIONS: In symptomatic adults, FebriDx MxA had a high NPV for influenza and RSV, and retained a high NPV for SARS-CoV-2, in the context of virus co-circulation and widespread COVID-19 vaccination. FebriDx continues to be a useful 'rule out' triage tool in the ED and could potentially be scaled to provide a national triage solution for future viral pandemics.

Routine, molecular point-of-care testing for SARS-CoV-2 and other respiratory viruses within an acute oncology service improves patient care.

OBJECTIVES: COVID-19 has caused significant challenges for infection prevention measures and patient flow in hospital admission pathways. We aimed to assess the impact of replacing laboratory PCR with molecular point-of-care testing (mPOCT) for respiratory viruses including SARS-CoV-2, within an Acute Oncology Service (AOS). METHODS: This pre- and post-implementation study took place in the AOS of a large teaching hospital, in Southampton, UK. We collected data from two periods: November 25th, 2019 to November 24th, 2020, when respiratory virus testing utilised laboratory PCR, and December 1st, 2020 to May 31st, 2021 following the introduction of mPOCT. The primary outcome was the time to results. RESULTS: 2189 patients were tested in the pre-implementation period and 1540 in the post implementation period. Median (IQR) time to results was 5.8 h (4.2-10.6) pre-implementation and 1.9 h (1.5-3.0) post-implementation (difference -3.6 h [95%CI to -3.8 to -3.5]; p < 0.0001). Median time spent in assessment areas was 6.0 h (4.1-7.9) pre-implementation and 5.5 h (3.8-7.4) post-implementation (p < 0.0001). 20 (0.9%) patients admitted via AOS assessment unit developed hospital-acquired respiratory virus infection pre-implementation versus 0 (0%) post-implementation (p = 0.031). CONCLUSIONS: Routine mPOCT for respiratory viruses, including SARS-CoV-2, was associated with a reduced time to results, reduced time in assessment areas, and a reduction in the rates of hospital-acquired respiratory virus infection in an acute oncology assessment unit.

Is high sensitivity troponin, taken regardless of a clinical indication, associated with 1 year mortality in critical care patients?

The aim of this study was to assess whether high sensitivity troponin (hs-cTnI) is associated with 1 year mortality in critical care (CC). One year mortality data were obtained from NHS Digital for a consecutive cohort of patients admitted to general CC unit (GCCU) and neuroscience CC unit (NCCU) who had hs-cTnI tests performed throughout their CC admission, regardless of whether the test was clinically indicated. Cox proportional hazards were used to estimate the risk of 1-year mortality. A landmark analysis was undertaken to assess whether any relationship at 1 year was driven by mortality within the first 30 days. A total of 1033 consecutive patients were included. At 1 year 254 (24.6%) patients had died. The admission log(10)hs-cTnI concentration in the entire cohort (HR 1.35 (95% CI 1.05-1.75) p = 0.009 with a bootstrap of 1000 samples) was independently associated with 1 year mortality. On landmark analysis the association with 1 year mortality was driven by 30 day mortality. These results indicate that admission hs-cTnI concentration is independently associated with 1 year mortality in CC and this relationship may be driven by differences in mortality at 30 days.

A hyperinflammation clinical risk tool, HI5-NEWS2, stratifies hospitalised COVID-19 patients to associate risk of death and effect of early dexamethasone in an observational cohort.

BACKGROUND: The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. METHODS: Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. FINDINGS: Of 1265 patients, high risk of HI (high HI5-NEWS2) (n = 367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n = 455, 36.0%). An intermediate risk group (n = 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p = 0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p = 0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p = 0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p = 0.31). INTERPRETATION: Higher HI5-NEWS2 scores measured at COVID-19 diagnosis, strongly associate with increased mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention in all cases.

Impact of direct-access IBD physician delivered endoscopy on clinical outcomes: a pre-implementation and post-implementation study.

Introduction: Patients with suspected inflammatory bowel disease (IBD) referred from primary care often face diagnostic and treatment delays. This study aimed to compare a novel direct-access IBD endoscopy pathway with the traditional care model. Method: Single centre real-world study analysing primary care referrals with suspected IBD. Group A: patients triaged to direct-access IBD endoscopy. Group B: patients undergoing traditional outpatient appointments before the availability of direct-access IBD endoscopy. Demographics, fecal calprotectin (FCP), C-reactive protein (CRP), disease activity score, endoscopy findings, treatment and follow-up were collected and statistically analysed. Ranked semantic analysis of IBD symptoms contained within referral letters was performed. Results: Referral letters did not differ significantly in Groups A and B. Demographic data, FCP and CRP values were similar. Referral to treatment time (RTT) at the time of IBD endoscopy was reduced from 177 days (Group B) to 24 days (Group A) (p<0.0001). Diagnostic yield of IBD was 35.6% (Group B) versus 62.0% (Group A) (p=0.0003). 89.2% of patients underwent colonoscopy in Group B versus 46.4% in Group A. DNA rates were similar in both groups. The direct to IBD endoscopy pathway saved 100% of initial IBD consultant clinics with a 2.5-fold increase in IBD nurse-led follow-up. Conclusion: Our novel pathway resulted in an 86% reduction in RTT with associated increased diagnostic yield while saving 100% of initial IBD consultant outpatient appointments. Replication in other trusts may improve patient experience and accelerate time to diagnosis/treatment while optimising the use of healthcare resources.

Molecular point-of-care testing for lower respiratory tract pathogens improves safe antibiotic de-escalation in patients with pneumonia in the ICU: Results of a randomised controlled trial.

BACKGROUND: Effective treatment of pneumonia requires timely administration of appropriate antimicrobials but standard diagnostic tests take around 48 h to generate results. Highly accurate, rapid molecular tests have been developed for identifying organisms in lower respiratory tract samples, however their impact on antibiotic use is unknown. The aim of this study was to assess the impact of syndromic molecular point-of-care testing compared to conventional diagnostic testing, on antibiotic use. METHODS: In this pragmatic, randomised controlled trial, we enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy. RESULTS: 200 patients were randomly assigned to point-of-care testing (n = 100) or the control group (n = 100). 85 patients had community acquired pneumonia (42 in the mPOCT group and 43 in the control group), 69 hospital acquired pneumonia (30 in mPOCT and 39 in control) and 46 ventilator associated pneumonia (28 in mPOCT and 18 in control). The median [IQR] time to results was 1.7 [1.6-1.9] hours for point-of-care testing and 66.7 [56.7-88.5] hours for standard diagnostics (difference of -65.0 h, 95%CI -68.0 to -62.0; p < 0.0001). 71 (71%) patients in the point-of-care testing arm had pathogens detected compared to 51 (51%) in the control arm (difference of 20%, 95%CI 7 to 33; p = 0.004). 80 (80%) of patients in the point-of-care group received results-directed therapy, compared with 29 (29%) of 99 in the control group (difference of 51%, 95%CI 39-63; p < 0.0001). Time to results-directed therapy was 2.3 [1.8-7.2] hours in the mPOCT group and 46.1 [23.0-51.5] hours in the control group (difference of -43.8 h, 95% CI -48.9 to -38.6; p < 0.0001). 42 (42%) patients in mPOCT group had antibiotics de-escalated compared with 8 (8%) of 98 in the control group (difference of 34%, 95%CI 23-45; p < 0.0001). Time to de-escalation was 4.8 [2.4-13.0] hours in the mPOCT group compared with 46.5 [26.3-48.6] hours in the control group (difference of -41.4 h, 95%CI -53 to -29.7; p < 0.0001). There was no major difference in antibiotic duration or in clinical or safety outcomes between the two groups. CONCLUSIONS: Use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.

Evidence of a genetically driven metabolomic signature in actively inflamed Crohn's disease.

Crohn's disease (CD) is characterised by chronic inflammation. We aimed to identify a relationship between plasma inflammatory metabolomic signature and genomic data in CD using blood plasma metabolic profiles. Proton NMR spectroscopy were achieved for 228 paediatric CD patients. Regression (OPLS) modelling and machine learning (ML) approaches were independently applied to establish the metabolic inflammatory signature, which was correlated against gene-level pathogenicity scores generated for all patients and functional enrichment was analysed. OPLS modelling of metabolomic spectra from unfasted patients revealed distinctive shifts in plasma metabolites corresponding to regions of the spectrum assigned to N-acetyl glycoprotein, glycerol and phenylalanine that were highly correlated (R2 = 0.62) with C-reactive protein levels. The same metabolomic signature was independently identified using ML to predict patient inflammation status. Correlation of the individual peaks comprising this metabolomic signature of inflammation with pathogenic burden across 15,854 unselected genes identified significant enrichment for genes functioning within 'intrinsic component of membrane' (p = 0.003) and 'inflammatory bowel disease (IBD)' (p = 0.003). The seven genes contributing IBD enrichment are critical regulators of pro-inflammatory signaling. Overall, a metabolomic signature of inflammation can be detected from blood plasma in CD. This signal is correlated with pathogenic mutation in pro-inflammatory immune response genes.

Routine molecular point-of-care testing for SARS-CoV-2 reduces hospital-acquired COVID-19.

OBJECTIVES: Risk of hospital-acquired COVID-19 (HA-COVID-19) infection is increased by cohorting infected and non-infected patients together in assessment areas, whist awaiting laboratory PCR results. Molecular point-of-care tests (mPOCT) reduce time to results and improve patient flow but the impact on HA-COVID-19 is unknown. METHODS: In this pre and post implementation study patients were evaluated across two time periods: March 1st to August 13th 2020, prior to the introduction of mPOCT in medical admissions areas, and 14th August 2020 to 1st April 2021, after mPOCT introduction. The primary outcome was proportion of HA-COVID-19 infection among all COVID-19 positive patients. Secondary outcome measures included time to SARS-CoV-2 results, length of time spent in the medical assessment area and comparison of local, regional and national proportions of HA-COVID-19. RESULTS: 1988 patients were admitted through the acute medicine admission cohorting area and tested for SARS-CoV-2 prior to introducing mPOCT and 4640 afterwards. Median (IQR) time to SARS-CoV-2 result was 6.5 (2.1-17.9) hours prior to introducing mPOCT and 1.0 (0.8-1.3) hours afterwards (p < 0.0001). Median (IQR) duration in the assessment cohort area was 12.0 (4.8-20.6) hours prior to introduction of POCT and 3.2 (2.0-5.6) hours afterwards (p < 0.0001). The proportion of hospital-acquired COVID-19 cases was 108 (16.5%) of 654 prior to introducing mPOCT compared with 168 (9.4%) of 1782 afterwards, (HR 0.55, 95%CI 0.43-0.70; p < 0.0001). In the period following the introduction of mPOCT up to 1st April 2021 the median proportion of HA-COVID-19 was 13.6% (95%CI 8.2-18.9%) locally, compared with 43.8% (95%CI 37.8-49.9%) for all acute NHS trusts regionally and 30.9% (95%CI 28.4-33.5%) for all NHS trusts nationally. CONCLUSIONS: Routine mPOCT for SARS-CoV-2 was associated with reduced time to results, time spent in admission cohort areas, and hospital-acquired COVID-19, compared to laboratory PCR.

Biomarker identification using dynamic time warping analysis: a longitudinal cohort study of patients with COVID-19 in a UK tertiary hospital.

OBJECTIVES: COVID-19 is a heterogeneous disease, and many reports have described variations in demographic, biochemical and clinical features at presentation influencing overall hospital mortality. However, there is little information regarding longitudinal changes in laboratory prognostic variables in relation to disease progression in hospitalised patients with COVID-19. DESIGN AND SETTING: This retrospective observational report describes disease progression from symptom onset, to admission to hospital, clinical response and discharge/death among patients with COVID-19 at a tertiary centre in South East England. PARTICIPANTS: Six hundred and fifty-one patients treated for SARS-CoV-2 between March and September 2020 were included in this analysis. Ethical approval was obtained from the HRA Specific Review Board (REC 20/HRA/2986) for waiver of informed consent. RESULTS: The majority of patients presented within 1 week of symptom onset. The lowest risk patients had low mortality (1/45, 2%), and most were discharged within 1 week after admission (30/45, 67%). The highest risk patients, as determined by the 4C mortality score predictor, had high mortality (27/29, 93%), with most dying within 1 week after admission (22/29, 76%). Consistent with previous reports, most patients presented with high levels of C reactive protein (CRP) (67% of patients >50 mg/L), D-dimer (98%>upper limit of normal (ULN)), ferritin (65%>ULN), lactate dehydrogenase (90%>ULN) and low lymphocyte counts (81%

FebriDx host response point-of-care testing improves patient triage for coronavirus disease 2019 (COVID-19) in the emergency department.

OBJECTIVES: Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED). DESIGN: We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm. SETTING: Emergency department of a university teaching hospital. PATIENTS: Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a 'high-risk' area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area. RESULTS: Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34-92) for FebriDx-negative patients and 203 minutes (IQR, 142-255) for FebriDx-positive patients (difference of -134 minutes; 95% CI, -144 to -122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%-97%). CONCLUSIONS: FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2-positive patients.

Incidence and 1-year outcome of periprocedural myocardial infarction following cardiac surgery: are the Universal Definition and Society for Cardiovascular Angiography and Intervention criteria fit for purpose?

OBJECTIVES: The diagnosis and clinical implications of periprocedural myocardial infarction (PPMI) following coronary artery bypass grafting (CABG) are contentious, especially the importance of PPMI in the interpretation of trial data. METHODS: Consecutive patients admitted to a cardiothoracic critical care unit over a 6-month period following open cardiac surgery had high-sensitivity cardiac troponin I assay performed on admission and every day for 48 h, regardless of whether there was a request by the supervising clinical team. Patients were categorized as PPMI using both the Universal Definition of Myocardial Infarction (UDMI) and Society of Cardiovascular Angiography and Interventions (SCAI) criteria. Multivariable Cox regression analysis was performed to assess whether any relationships between PPMI diagnoses and 1-year mortality were independent. RESULTS: There were 2 groups of consecutive patients: (i) after CABG (n = 245) and (ii) after non-CABG surgery (n = 243). Of the CABG patients, 20.4% met criteria for UDMI PPMI and 87.6% for SCAI PPMI. The diagnosis of UDMI PPMI was independently associated with 1-year mortality on multivariable Cox regression analysis [hazard ratio 4.16 (95% confidence interval 1.28-13.49)]. Of 243 patients who had non-CABG cardiac surgery, 11.4% met criteria for UDMI PPMI and 85.2% for SCAI PPMI but neither were associated with 1-year mortality. CONCLUSIONS: The incidence of SCAI PPMI in a real-world cohort of cardiac surgery patients is so high as to be of limited clinical value. In contrast, a diagnosis of UDMI PPMI post-CABG is independently associated with 1-year mortality, so may have clinical (and research) utility.

Wave comparisons of clinical characteristics and outcomes of COVID-19 admissions - Exploring the impact of treatment and strain dynamics.

OBJECTIVES: Dexamethasone has now been incorporated into the standard of care for COVID-19 hospital patients. However, larger intensive care unit studies have failed to show discernible improvements in mortality in the recent wave. We aimed to investigate the impacts of these factors on disease outcomes in a UK hospital study. METHODS: This retrospective observational study reports patient characteristics, interventions and outcomes in COVID-19 patients from a UK teaching hospital; cohort 1, pre 16th June-2020 (pre-dexamethasone); cohort 2, 17th June to 30th November-2020 (post-dexamethasone, pre-VOC 202,012/01 as dominant strain); cohort 3, 1st December-2020 to 3rd March-2021 (during establishment of VOC202012/01 as the dominant strain). RESULTS: Dexamethasone treatment was more common in cohorts 2 and 3 (42.7% and 51.6%) compared with cohort 1 (2.5%). After adjusting for risk, odds of death within 28 days were 2-fold lower in cohort 2 vs 1 (OR:0.47,[0.27,0.79],p = 0.006). Mortality was higher cohort 3 vs 2 (20% vs 14%); but not significantly different to cohort 1 (OR: 0.86,[0.64, 1.15],p = 0.308). CONCLUSIONS: The real world finding of lower mortality following dexamethasone supports the published trial evidence and highlights ongoing need for research with introduction of new treatments and ongoing concern over new COVID-19 variants.

Impact of the COVID-19 pandemic on routine surveillance for adults with chronic hepatitis B virus (HBV) infection in the UK.

Background: To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load). Methods: We used anonymized electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK National Health Service (NHS) Trusts. Results: We report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID-19 years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient. Conclusions: These results demonstrate the real-time utility of HIC data in monitoring health-care provision, and support interventions to provide catch-up services to minimise the impact of the pandemic. Further investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes.

Secondary haemophagocytic lymphohistiocytosis in hospitalised COVID-19 patients as indicated by a modified HScore is infrequent and high scores do not associate with increased mortality.

A significant proportion of COVID-19 patients show evidence of hyperinflammation (HI), of which secondary haemophagocytic lymphohistiocytosis (sHLH) is the most severe manifestation and diagnosed with HScore. Using a COVID-relevant modification of the HScore (%HScore), we set out to determine the prevalence of sHLH in 567 COVID-19 inpatient cases.The overall incidence of individuals with an 80% probability of sHLH in our COVID-19 cohort was 1.59% on admission and only rose to 4.05% if calculated at any time during admission. This small cohort as defined by %HScore showed no excess mortality compared with the whole cohort. Overall, %HScores were lower in older patients (p<0.0001) and did not reliably predict outcome at any cut-off value (AUROC 0.533, p=0.211, odds ratio 0.99).Our study demonstrates that a modified version (%HScore) of the conventional sHLH scoring system (HScore) does not enable risk stratification in people hospitalised with COVID. We propose further work is needed to develop novel approaches to predict HI and improve trial stratification for HI directed therapy in people with COVID-19.

SARS-CoV-2 viral load at presentation to hospital is independently associated with the risk of death.

Objectives Previous studies have suggested that SARS-CoV-2 viral load, measured on upper respiratory tract samples at presentation to hospital using PCR Cycle threshold (Ct) value, has prognostic utility. However, these studies have not comprehensively adjusted for factors known to be intimately related to viral load. We aimed to evaluate the association between Ct value at admission and patient outcome whilst adjusting carefully for covariates. Methods We evaluated the association between Ct value at presentation and the outcomes of ICU admission and death, in patients hospitalised during the first wave of the pandemic in Southampton, UK. We adjusted for covariates including age, duration of illness and antibody sero-status, measured by neutralisation assay. Results 185 patients were analysed, with a median [IQR] Ct value of 27.9 [22.6-32.1]. On univariate analysis the Ct value at presentation was associated with the risk of both ICU admission and death. In addition, Ct value significantly differed according to age, the duration of illness at presentation and antibody sero-status. On multivariate analysis, Ct value was independently associated with risk of death (aOR 0.84, 95% CI 0.72-0.96; p = 0.011) but not ICU admission (aOR 1.04, 95% CI 0.93-1.16; p = 0.507). Neutralising antibody status at presentation was not associated with mortality or ICU admission (aOR 10.62, 95% CI 0.47-889; p = 0.199 and aOR 0.46, 95% CI 0.10-2.00; p = 0.302, respectively). Conclusions SARS-CoV-2 Ct value on admission to hospital was independently associated with mortality, when comprehensively adjusting for other factors and could be used for risk stratification.

Cervical spinal degenerative disease in multiple sclerosis.

BACKGROUND AND PURPOSE: Root and cord irritation from cervical spinal degenerative disease (SDD) may share clinical features with progressive multiple sclerosis (MS), so diagnostic overshadowing may occur. We hypothesized that cervical stenotic SDD is commoner in people with progressive MS, compared to controls. METHODS: A retrospective case-control study of 111 cases (56 with progressive MS and 55 age- and sex-matched controls) was conducted. Five types of cervical SDD (disc degeneration, posterior disc protrusion, endplate changes, canal stenosis and foraminal stenosis) were assessed objectively on magnetic resonance imaging using published scales. Multivariable regression analysis was performed. RESULTS: Moderate-to-severe cervical spinal degeneration occurred more frequently in progressive MS, compared to controls. In multivariable regression, foraminal stenosis was three times more likely in progressive MS (odds ratio 3.20, 95% confidence interval 1.27, 8.09; p = 0.014), and was more severe (p = 0.009). This finding was confirmed on retrospective evaluation of clinical radiology reports in the same population. Foraminal stenosis was twice as likely in progressive MS, compared to relapsing-remitting MS. CONCLUSIONS: People with progressive MS are susceptible to foraminal stenosis. A higher index of suspicion for cervical SDD is required when appropriate neurological symptoms occur in the setting of progressive MS, to guide appropriate treatment or monitoring.

Distribution of High-Sensitivity Troponin Taken Without Conventional Clinical Indications in Critical Care Patients and Its Association With Mortality.

OBJECTIVES: To describe the distribution of high-sensitivity troponin in a consecutive cohort of patients in critical care units, regardless of clinical indication, and its association with clinical outcomes. DESIGN: Prospective observational study. SETTING: Single-center teaching hospital. PATIENTS: Consecutive patients admitted to two adult critical care units (general critical care unit and neuroscience critical care unit) over a 6-month period. INTERVENTIONS: All patients had high-sensitivity troponin tests performed at admission and tracked throughout their critical care stay, regardless of whether the supervising team felt there was a clinical indication. The results were not revealed to patients or clinicians unless clinically requested. MEASUREMENTS AND MAIN RESULTS: There were 1,033 patients in the study cohort (general critical care unit 750 and neuroscience critical care unit 283). The median high-sensitivity troponin was 21 ng/L (interquartile range, 7-86 ng/L), with 560 patients (54.2%) above the upper limit of normal as defined by the manufacturer. Admission high-sensitivity troponin concentrations above the upper limit of normal in general critical care unit and neuroscience critical care unit were associated with increasing age, comorbidity, markers of illness severity, and the need for organ support. On adjusted analysis, the high-sensitivity troponin concentration remained an independent predictor of critical care mortality in general critical care unit and neuroscience critical care unit. CONCLUSIONS: High-sensitivity troponin elevation, taken outside the context of conventional clinical indications, was common in the critically ill. Such elevations were associated with increasing age, comorbidity, illness severity, and the need for organ support. Admission high-sensitivity troponin concentration is an independent predictor of critical care mortality and as such may represent a novel prognostic biomarker at admission.