AE, D ST and their SuperMAG Counterparts : the effect of improved spatial resolution in geomagnetic indices

For decades, geomagnetic indices have been used extensively to parameterize space weather events, as input to various models and as space weather specifications. The auroral electrojet (AE) index and disturbance storm time index (DST) are two such indices that span multiple solar cycles and have been widely studied. The production of improved spatial coverage analogs to AE and DST is now possible using the SuperMAG collaboration of ground‐based magnetometers. SME is an electrojet index that shares methodology with AE. SMR is a ring current index that shares methodology with DST. As the number of magnetometer stations in the SuperMAG network increases over time, so does the spatial resolution of SME and SMR. Our statistical comparison between the established indices and their new SuperMAG counterparts finds that, for large excursions in geomagnetic activity, AE systematically underestimates SME for later cycles. The difference between distributions of recorded AE and SME values for a single solar maximum can be of the same order as changes in activity seen from one solar cycle to the next. We demonstrate that DST and SMR track each other but are subject to an approximate linear shift as a result of the procedure used to map stations to the magnetic equator. We explain the observed differences between AE and SME with the assistance of a simple model, based on the construction methodology of the electrojet indices. We show that in the case of AE and SME, it is not possible to simply translate between the two indices

Statistical analysis applied to multidecadal geomagnetic index records : AE, Dst, and their SuperMAG counterparts

The overall level of solar activity varies within and between successive solar cycles. Geomagnetic indices such as the auroral electrojet (AE) index and disturbance storm time (Dst) index span multiple solar cycles. Using a global network of magnetometers, the SuperMAG collaboration compiles the SME and SMR indices with higher spatial and temporal resolution than their traditional counterparts. A statistical comparison between the established indices and their newer SuperMAG counterparts is presented. AE systematically under-samples when compared to SME for later solar cycles. AE and SME differ at the same scale as cycle-to-cycle variability. Dst and hourly SMR track each other with a small systematic linear shift. The observed differences between AE and SME are explained with the assistance of a simple model. The statistics of bursts and the observed values of the AE and SMR indices are examined in relation to solar cycle variation. Average burst duration, ￣τ, and burst return period ￣ R form an activity parameter, ￣τ/R￣ which characterizes the fraction of time the magnetosphere spends, on average, in an active state for a given burst threshold. Level crossing theory directly relates ￣τ/R￣ to the observed index value cumulative distribution function. Solar cycle ordering is identified for empirical distributions of burst parameters and underlying time series observations. Extreme value theory is applied to the SMR index for the first time. The amplitude of extreme events resolved by SMR systematically exceeds that resolved by the classical Dst 1-hour index. The severity of the 1 in 100 year event based on SMR is ∼ 25% larger than that estimated from Dst. Accurate estimates of return levels such as the 1 in 100 year event are central to resilience planning for a wide range of systems that underpin our society. i

Extreme event statistics in Dst, SYM‐H, and SMR geomagnetic indices

Extreme space weather events are rare, and quantifying their likelihood is challenging, often relying on geomagnetic indices obtained from ground‐based magnetometer observations that span multiple solar cycles. The Dst index ring‐current monitor, derived from an hourly average over four low‐latitude stations, is a benchmark for extreme space weather events, and has been extensively studied statistically. We apply extreme value theory (EVT) to two geomagnetic ring current indices: SYM‐H (derived from 6 stations) and SMR (derived from up to 120 stations). EVT analysis reveals a divergence between the return level found for Dst, and those for SYM‐H and SMR, that increases non‐linearly with return period. For return periods below 10 years, hourly averaged SYM‐H and SMR have return levels similar to Dst, but at return periods of 50 and 100 years, they respectively exceed that of Dst by about 10% and 15% (SYM‐H) and about 7% and 12% (SMR). One minute resolution SYM‐H and SMR return levels progressively exceed that of Dst; their 5, 10, 50, and 100 year return levels exceed that of Dst by about 10%, 12%, 20% and 25% respectively. Our results indicate that consideration should be given to the differences between the indices if selecting one to use as a bench mark in model validation or resilience planning for the wide range of space weather sensitive systems that underpin our society

Quantification of magnetosphere–ionosphere coupling timescales using mutual information : response of terrestrial radio emissions and ionospheric–magnetospheric currents

Auroral kilometric radiation (AKR) is a terrestrial radio emission excited by the same accelerated electrons which excite auroral emissions. Although it is well correlated with auroral and geomagnetic activity, the coupling timescales between AKR and different magnetospheric or ionospheric regions have yet to be determined. Estimation of these coupling timescales is non-trivial as a result of complex, non-linear processes which rarely occur in isolation. In this study, the mutual information between AKR intensity and different geomagnetic indices is used to assess the correlation between variables. Indices are shifted to different temporal lags relative to AKR intensity, and the lag at which the variables have the most shared information is found. This lag is interpreted as the coupling timescale. The AKR source region receives the effects of a shared driver before the auroral ionosphere. Conversely, the polar ionosphere reacts to a shared driver before the AKR source region. Bow shock interplanetary magnetic field BZ is excited about 1 h before AKR enhancements. This work provides quantitatively determined temporal context to the coupling timelines at Earth. The results suggest that there is a sequence of excitation following the onset of a shared driver: first, the polar ionosphere feels the effects, followed by the AKR source region and then the auroral ionosphere

Characterisation of the pro-inflammatory cytokine signature in severe COVID-19

Clinical outcomes from infection with SARS-CoV-2, the cause of the COVID-19 pandemic, are remarkably variable ranging from asymptomatic infection to severe pneumonia and death. One of the key drivers of this variability is differing trajectories in the immune response to SARS-CoV-2 infection. Many studies have noted markedly elevated cytokine levels in severe COVID-19, although results vary by cohort, cytokine studied and sensitivity of assay used. We assessed the immune response in acute COVID-19 by measuring 20 inflammatory markers in 118 unvaccinated patients with acute COVID-19 (median age: 70, IQR: 58-79 years; 48.3% female) recruited during the first year of the pandemic and 44 SARS-CoV-2 naïve healthy controls. Acute COVID-19 was associated with marked elevations in nearly all pro-inflammatory markers, whilst eleven markers (namely IL-1β, IL-2, IL-6, IL-10, IL-18, IL-23, IL-33, TNF-α, IP-10, G-CSF and YKL-40) were associated with disease severity. We observed significant correlations between nearly all markers elevated in those infected with SARS-CoV-2 consistent with widespread immune dysregulation. Principal component analysis highlighted a pro-inflammatory cytokine signature (with strongest contributions from IL-1β, IL-2, IL-6, IL-10, IL-33, G-CSF, TNF-α and IP-10) which was independently associated with severe COVID-19 (aOR: 1.40, 1.11-1.76, p=0.005), invasive mechanical ventilation (aOR: 1.61, 1.19-2.20, p=0.001) and mortality (aOR 1.57, 1.06-2.32, p = 0.02). Our findings demonstrate elevated cytokines and widespread immune dysregulation in severe COVID-19, adding further evidence for the role of a pro-inflammatory cytokine signature in severe and critical COVID-19

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

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

Evaluating patient attitudes to increased patient engagement with antimicrobial stewardship: a quantitative survey

BackgroundAntimicrobial stewardship (AMS) describes interventions designed to optimize antimicrobial therapy, minimize adverse treatment consequences and reduce the spread of antimicrobial resistance (AMR). Previous research has investigated the patient’s role in healthcare infection prevention but the patient’s role in AMS has not been extensively explored. ObjectivesTo investigate the willingness of hospital inpatients to question staff about prudent antimicrobial use in an Irish hospital and evaluate the impact of patient and public involvement in research (PPI) on this study. MethodsA survey was co-designed with the hospital Patient Representative Group (PRG) to evaluate patient willingness to engage with prudent antimicrobial treatment. A random sample of 200 inpatients was selected to self-complete the survey using pen and paper. PRG members provided feedback on their involvement. ResultsOf the 200 inpatients randomly selected to participate, 120 did not fulfil the inclusion criteria. Of the remaining 80, 67 participated (response 84%). Median respondent age was 58 years, 30% were employed and 30% had a third-level education degree. Over 90% had not heard of AMS while just over 50% had not heard of AMR. Patients preferred asking factual questions rather than challenging ones but did not have a preference in asking questions of doctors compared with nurses. Older patients were less likely to ask questions. PRG members reported an overall positive experience as research collaborators. Conclusions Future patient-centred AMS interventions should empower patients to ask about antimicrobial treatment, in particular the older patient cohort. PPI is a valuable component of patient-centred research.</div

Hepatitis C in the era of direct-acting antivirals: real-world costs of untreated chronic hepatitis C; a cross-sectional study

Background: Recent advances in Hepatitis C therapeutics offer the possibility of cure but will be expensive. The cost of treatment may be partially offset by the avoidance of advanced liver disease. We performed a micro-costing study of the ambulatory healthcare utilisation of patients with Hepatitis C supplemented with inpatient diagnosis related group costs.Methods: The staff utilisation costs associated with a Hepatitis C ambulatory visit were measured and combined with the costs of investigations to establish a mean cost per consultation. An annualised estimate of cost was produced by multiplying this by the number of consultations accessed, stratified by degree of liver impairment. Inpatient costs were established by identifying the number of inpatient episodes and multiplying by Irish diagnosis related group costs. Non-parametric bootstrapping was performed to derive mean and 95% CI values.Results: Two hundred and twenty-five patients were identified. The cost of an outpatient medical review was (sic) 136 ((sic)3.60 SD). The cost of a Hepatitis C nursing review was (sic) 128 ((sic)7.30 SD). The annual mean costs of care were as follows (95% CI): Mild (sic) 398 ((sic) 336, (sic) 482), Moderate (sic) 417((sic) 335, (sic) 503), Compensated cirrhosis (sic) 1790 ((sic) 990, (sic) 3164), Decompensated cirrhosis (sic) 8302 ((sic) 3945, (sic) 14,637), Transplantation Year 1 (sic) 137,176 ((sic) 136,024, (sic) 138,306), Transplantation after Year 1 (sic) 5337 ((sic) 4942, (sic) 5799), Hepatocellular carcinoma (sic)21,992 ((sic)15,222, (sic)29,467), Sustained virological response (sic)44 ((sic)16, (sic)73).Conclusions: The direct medical cost associated with Hepatitis C care in Ireland is substantial and increases exponentially with progression of liver disease. The follow-up costs of patients with a sustained virological response in this cohort were low in comparison to patients with chronic infection