Pharmacists in Trauma: a randomised controlled trial of emergency medicine pharmacists in trauma response teams.

BACKGROUND: Analgesia is an important component for patient well-being, but commonly delayed during trauma resuscitation. The Pharmacists in Trauma trial assessed the effects of integrating pharmacists into trauma response teams to improve analgesia delivery and medication management. METHODS: This unblinded randomised trial compared emergency medicine (EM) pharmacist involvement in trauma callouts versus standard care at an Australian level 1 trauma centre. Randomisation was performed via an online single sequence randomisation service. Eligible patients included those managed with a trauma callout during working hours of an EM pharmacist. Pharmacists were able to prescribe medications using a Partnered Pharmacist Medication Charting model. The primary outcome was the proportion of patients who had first dose analgesia within 30 min compared using the χ2 test. RESULTS: From 15 July 2021 until 31 January 2022, there were 119 patients randomised with 37 patients excluded as no analgesia was required. There were 82 patients included for analysis, 39 in the control arm and 43 in the intervention arm. The primary outcome was achieved in 25 (64.1%) patients in the control arm and 36 (83.7%) patients in the pharmacist arm (relative risk 1.31; 95% CI 1.0 to 1.71; p=0.042). Time to analgesia in the control arm was 28 (22-35) mins and 20 (15-26 mins) with pharmacist involvement; p=0.025. In the pharmacist arm, the initial dose of analgesia was prescribed by the pharmacist for 38 (88.4%) patients. There were 27 other medications prescribed by the pharmacist for the management of these patients. There were no differences in emergency and trauma centre or hospital length of stay. CONCLUSION: Addition of the EM pharmacist in trauma response teams improved time to analgesia. Involvement of an EM pharmacist in trauma reception and resuscitation may assist by optimising medication management, with members of the team more available to focus on other life-saving interventions. TRIAL REGISTRATION NUMBER: ACTRN12621000338864.

Pro-environmental behavior, personality and emotional intelligence in adolescents: a systematic review.

Introduction: Human behavior significantly contributes to environmental problems, making the study of pro-environmental behavior an important task for psychology. In this context, it is crucial to understand the pro-environmental behavior of adolescents, as young people play a fundamental role in facilitating long-term changes in environmental consciousness and encouraging decision-makers to take action. However, little is currently known about the pro-environmental behavior of adolescents. Recently, there has been growing interest in examining the influence of personality traits and emotional intelligence on pro-environmental behavior. Methods: We conducted a systematic review to enhance our understanding of adolescent pro-environmental behavior. Thus, this systematic review was designed to enhance understanding of adolescent's pro-environmental behavior by summarizing existing evidence on how it relates to personality and emotional intelligence. Results: Our findings suggest associations between specific personality traits and dimensions of emotional intelligence with adolescent pro-environmental behavior, aligning with similar studies conducted on adults. Discussion: While our findings offer valuable insights, further research is needed to establish causality and deepen our understanding of the interplay between multiple variables influencing pro-environmental behavior among adolescents. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023387836], identifier [CRD42023387836].

The Australian Traumatic Brain Injury Initiative: Systematic Review of the Effect of Acute Interventions on Outcome for People With Moderate-Severe Traumatic Brain Injury.

The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interventions with potential to modify clinical outcomes for people after msTBI, for inclusion in a data dictionary. Standardized searches were implemented across bibliographic databases from inception through April 2022. English-language reports of randomized controlled trials (RCTs) evaluating any association between any acute intervention and clinical outcome in at least 100 patients with msTBI, were included. A predefined algorithm was used to assign a value to each observed association. Consultation with AUS-TBI clinicians and researchers formed the consensus process for interventions to be included in a single data dictionary. Searches retrieved 14,455 records, of which 124 full-length RCTs were screened, with 35 studies included. These studies evaluated 26 unique acute interventions across 21 unique clinical outcomes. Only 4 interventions were considered to have medium modifying value for any outcome from the review, with an additional 8 interventions agreed upon through the consensus process. The interventions with medium value were tranexamic acid and phenytoin, which had a positive effect on an outcome; and decompressive craniectomy surgery and hypothermia, which negatively affected outcomes. From the systematic review and consensus process, 12 interventions were identified as potential modifiers to be included in the AUS-TBI national data resource.

Influence of Potentially Inappropriate Medication Use on Older Australians' Admission to Emergency Department Short Stay.

Older people in the emergency department (ED) often pose complex medical challenges, with a significant prevalence of polypharmacy and potentially inappropriate medicines (PIMs) in Australia. A retrospective analysis of 200 consecutive patients aged over 65 years admitted to the emergency short stay unit (ESSU) aimed to identify polypharmacy (five or more regular medications), assess PIM prevalence, and explore the link between pre-admission PIMs and ESSU admissions. STOPP/START version 2 criteria were used for the PIM assessment, with an expert panel categorizing associated risks. Polypharmacy was observed in 161 patients (80.5%), who were older (mean age 82 versus 76 years) and took more regular medications (median 9 versus 3). One hundred and eighty-five (92.5%) patients had at least one PIM, 81 patients (40.5%) had STOPP PIMs, and 177 patients (88.5%) had START omissions. Polypharmacy significantly correlated with STOPP PIM (OR 4.8; 95%CI: 1.90-12.1), and for each additional medication the adjusted odds of having a STOPP PIM increased by 1.20 (95%CI: 1.11-1.28). Nineteen admissions (9.5%) were attributed to one or more PIMs (total 21 PIMs). Of these PIMs, the expert panel rated eight (38%) as high risk, five (24%) as moderate risk, and eight (38%) as low risk for causing hospital admission. The most common PIMs were benzodiazepines, accounting for 14 cases (73.6%). Older ESSU-admitted patients commonly presented with polypharmacy and PIMs, potentially contributing to their admission.

Impact of antibiotic allergy labels on timely and appropriate antibiotics for sepsis in the emergency department.

Objectives: Time to initiation of effective antibiotic therapy is a strong predictor of survival for patients with sepsis presenting to the Emergency Department (ED). Antibiotic allergy labels (AALs) are a known barrier to timely sepsis management. The aim was to evaluate the influence of AALs on timely sepsis management for ED sepsis presentations in an Australian hospital. Methods: A retrospective cohort study was conducted for ED presentations requiring direct ICU admission for suspected sepsis, comparing patients with and without an AAL using propensity scores. Results: Between November 2018 and June 2021, 377 patients were included. The prevalence of an AAL was 29.6% (86/377). The median time to antibiotic administration was similar in the AAL versus non-AAL groups (51 versus 60 min, P = 0.11); there was no difference in mortality (14.1% versus 14.0%, P = 0.98) and length of stay (9.21 versus 10.10 days). The median time to antibiotic administration was shorter in those with Emergency Medicine (EM) pharmacist attendance versus those without (50 versus 92 min, P = 0.0001). Appropriateness of antibiotic prescription was 91.0% (343/377) for the overall cohort and was not associated with AALs, possibly due to our clear antimicrobial sepsis guidelines; however, EM pharmacist involvement was associated with increased antibiotic appropriateness (97.3% versus 88.4%, P = 0.00048). Conclusions: In our Australian ED, AALs were not found to impact timeliness of antibiotic administration in patients with sepsis. EM pharmacist involvement was associated with improved timeliness and appropriateness of antibiotic selection in patients presenting with sepsis.

Restriction of oxycodone in the emergency department (ROXY-ED): A randomised controlled trial.

Background: The prescription of opioids in emergency care has been associated with harm, including overdose and dependence. The aim of this trial was to assess restriction of access to oxycodone (ROXY), in combination with education and guideline modifications, versus education and guideline modifications alone (standard care) to reduce oxycodone administration in the Emergency Department (ED). Methods: An unblinded, active control, randomised controlled trial was conducted in an adult tertiary ED. Participants were patients aged 18-75 years who had analgesics administered in the ED. The primary intervention was ROXY, through removal of all oxycodone immediate release tablets from the ED imprest, with availability of a small supply after senior clinician approval. The intervention did not restrict prescription of discharge medications. The primary outcome measure was oxycodone administration rates. Secondary outcomes were administration rates of other analgesic medications, time to initial analgesics and oxycodone prescription on discharge. Results: There were 2258 patients eligible for analysis. Oxycodone was administered to 80 (6.1%) patients in the ROXY group and 221 (23.3%) patients in the standard care group (relative risk (RR) 0.26; 95% CI: 0.21 to 0.33; p < .001). Tapentadol was prescribed more frequently in the ROXY group (RR 2.17; 95% CI: 1.71-2.74), while there were no differences in prescription of other analgesic medications. On discharge, significantly fewer patients were prescribed oxycodone (RR 0.51; 95% CI: 0.39-0.66) and no differences were observed in prescription rates of other analgesic medications. There was no difference in time to first analgesic (HR 0.94; 95% CI: 0.86-1.02). Conclusions: Restricted access to oxycodone was superior to education and guideline modifications alone for reducing oxycodone use in the ED and reducing discharge prescriptions of oxycodone from the ED. The addition of simple restrictive interventions is recommended to enable rapid changes to clinician behaviour to reduce the potential harm associated with the prescribing of oxycodone in the ED.

Evaluating the effects of brain injury, disease and tasks on cognitive fatigue.

Because cognitive fatigue (CF) is common and debilitating following brain injury or disease we investigated the relationships among CF, behavioral performance, and cerebral activation within and across populations by combining the data from two cross-sectional studies. Individuals with multiple sclerosis (MS) were included to model CF resulting from neurological disease; individuals who had sustained a traumatic brain injury (TBI) were included to model CF resulting from neurological insult; both groups were compared with a control group (Controls). CF was induced while neuroimaging data was acquired using two different tasks. CF significantly differed between the groups, with the clinical groups reporting more CF than Controls-a difference that was statistically significant for the TBI group and trended towards significance for the MS group. The accrual of CF did not differ across the three groups; and CF ratings were consistent across tasks. Increasing CF was associated with longer response time for all groups. The brain activation in the caudate nucleus and the thalamus was consistently correlated with CF in all three groups, while more dorsally in the caudate, activation differed across the groups. These results suggest the caudate and thalamus to be central to CF while more dorsal aspects of the caudate may be sensitive to damage associated with particular types of insult.

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

Internet-delivered cognitive behavioural therapy programme to reduce depressive symptoms in patients with multiple sclerosis: a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and mortality. Despite its clinical relevance, there are few treatment options for depression associated with multiple sclerosis and confirmatory trials are scarce. We aimed to evaluate the safety and efficacy of a multiple sclerosis-specific, internet-based cognitive behavioural therapy (iCBT) programme for the treatment of depressive symptoms associated with the disease. METHODS: This parallel-group, randomised, controlled, phase 3 trial of an iCBT programme to reduce depressive symptoms in patients with multiple sclerosis was carried out at five academic centres with large outpatient care units in Germany and the USA. Patients with a neurologist-confirmed diagnosis of multiple sclerosis and depressive symptoms were randomly assigned (1:1:1; automated assignment, concealed allocation, no stratification, no blocking) to receive treatment as usual plus one of two versions of the iCBT programme Amiria (stand-alone or therapist-guided) or to a control condition, in which participants received treatment as usual and were offered access to the iCBT programme after 6 months. Masking of participants to group assignment between active treatment and control was not possible, although raters were masked to group assignment. The predefined primary endpoint, which was analysed in the intention-to-treat population, was severity of depressive symptoms as measured by the Beck Depression Inventory-II (BDI-II) at week 12 after randomisation. This trial is registered at ClinicalTrials.gov, NCT02740361, and is complete. FINDINGS: Between May 3, 2017, and Nov 4, 2020, we screened 485 patients for eligibility. 279 participants were enrolled, of whom 101 were allocated to receive stand-alone iCBT, 85 to receive guided iCBT, and 93 to the control condition. The dropout rate at week 12 was 18% (50 participants). Both versions of the iCBT programme significantly reduced depressive symptoms compared with the control group (BDI-II between-group mean differences: control vs stand-alone iCBT 6·32 points [95% CI 3·37-9·27], p<0·0001, effect size d=0·97 [95% CI 0·64-1·30]; control vs guided iCBT 5·80 points [2·71-8·88], p<0·0001, effect size d=0·96 [0·62-1·30]). Clinically relevant worsening of depressive symptoms was observed in three participants in the control group, one in the stand-alone iCBT group, and none in the guided iCBT group. No occurrences of suicidality were observed during the trial and there were no deaths. INTERPRETATION: This trial provides evidence for the safety and efficacy of a multiple sclerosis-specific iCBT tool to reduce depressive symptoms in patients with the disease. This remote-access, scalable intervention increases the therapeutic options in this patient group and could help to overcome treatment barriers. FUNDING: National Multiple Sclerosis Society (USA).

Geopolitical Considerations for Working with Medically Complex Patients: A Case Illustration.

OBJECTIVE: Becoming culturally competent healthcare providers depends on the ability of practitioners to acquire knowledge, awareness, and skills related to other cultures. In building these areas of competence, it is essential to consider geopolitical factors that may influence health and health-seeking behaviors, particularly when working with immigrant populations. When care is sought, they are likely to experience significant barriers to effective care, including lack of providers who speak their language and failure of practitioners to integrate cultural beliefs into treatment plans. This is further complicated by the presence of geopolitical issues, including immigration status, war/conflict in the patient's country of origin, and/or human rights violations. METHOD: The current study uses a sample case of a Burmese-speaking, Myanmar national to illustrate a culturally informed approach to the assessment of neurobehavioral changes within complex geopolitical circumstances. The sample represents an amalgam of several patients, designed to represent common presentations, sociodemographic situations, and concerns that arise during the neuropsychological assessment process. RESULTS: Description of relevant case information including background, clinical observations, and performance on testing is provided. DISCUSSION: Awareness of the impact of these life experiences not only has the potential to deepen our understanding of our patients but also results in a more holistic, accurate, and culturally competent conceptualization of their physical and mental health needs.

Introduction of an emergency medicine pharmacist-led sepsis alert response system in the emergency department: A cohort study.

OBJECTIVE: To determine effects of implementing a sepsis alert response system in the ED that included early intervention by emergency medicine (EM) pharmacists. METHODS: A prospective cohort (8 February 2016 to 28 February 2018) of patients after implementation of a sepsis alert response system in an Australian ED was compared to a retrospective cohort (3 January 2015 to 7 February 2016) of patients with sepsis who presented during EM pharmacist working hours and were admitted to the ICU. RESULTS: There were 184 patients, including 80 patients pre- and 104 patients post-implementation. The post-intervention cohort was triaged at a higher acuity, had higher quick Sepsis-related Organ Failure Assessment (qSOFA) scores and higher initial lactate measurements. After the intervention, antimicrobial agents were administered to patients within 60 min of presentation more often (21 [26.3%] to 85 [81.7%], P < 0.001). After adjusting for presenting triage category, admission lactate and presenting qSOFA scores, this association remained significant (adjusted odds ratio 9.99; 95% confidence interval 4.7-21.3). Significant improvements were observed for proportion of patients who had intravenous fluids initiated within 60 min (47.5% vs 72.1%); proportion of patients who had serum lactate measured within 60 min (50.0% vs 77.9%) and proportion of patients who had blood cultures performed within 60 min (52.5% vs 85.6%). CONCLUSION: Implementation of a sepsis alert response that included early involvement of the EM pharmacist was associated with improvement in time to antimicrobials and other components of the sepsis bundle. An upfront, multidisciplinary approach to patients presenting to the ED with suspected sepsis should be considered more broadly.

An Examination of Racial/Ethnic Differences on the Neurobehavioral Symptom Inventory Among Veterans Completing the Comprehensive Traumatic Brain Injury Evaluation: A Veterans Affairs Million Veteran Program Study.

OBJECTIVE: The purpose of this study was to explore racial/ethnic differences in neurobehavioral symptom reporting and symptom validity testing among military veterans with a history of traumatic brain injury (TBI). METHOD: Participants of this observational cross-sectional study (N = 9,646) were post-deployed Iraq-/Afghanistan-era veterans enrolled in the VA's Million Veteran Program with a clinician-confirmed history of TBI on the Comprehensive TBI Evaluation (CTBIE). Racial/ethnic groups included White, Black, Hispanic, Asian, Multiracial, Another Race, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander. Dependent variables included neurobehavioral symptom domains and symptom validity assessed via the Neurobehavioral Symptom Inventory (NSI) and Validity-10, respectively. RESULTS: Chi-square analyses showed significant racial/ethnic group differences for vestibular, somatic/sensory, and affective symptoms as well as for all Validity-10 cutoff scores examined (≥33, ≥27, ≥26, >22, ≥22, ≥13, and ≥7). Follow-up analyses compared all racial/ethnic groups to one another, adjusting for sociodemographic- and injury-related characteristics. These analyses revealed that the affective symptom domain and the Validity-10 cutoff of ≥13 revealed the greatest number of racial/ethnic differences. CONCLUSIONS: Results showed significant racial/ethnic group differences on neurobehavioral symptom domains and symptom validity testing among veterans who completed the CTBIE. An enhanced understanding of how symptoms vary by race/ethnicity is vital so that clinical care can be appropriately tailored to the unique needs of all veterans. Results highlight the importance of establishing measurement invariance of the NSI across race/ethnicity and underscore the need for ongoing research to determine the most appropriate Validity-10 cutoff score(s) to use across racially/ethnically diverse veterans.

Impact of the use of antibiotics on the clinical response to immune checkpoint inhibitors in patients with non-small cell lung cancer / Impacto del uso de antibióticos en la respuesta clínica de los inhibidores del punto de control en pacientes con carcinoma de pulmón no microcítico

Objectives. Recent research suggests that the use of antibiotics could reduce the efficacy of checkpoint inhibitors, in addition to other well-known factors. It could be due to gut microbiota modification, which impact over the immune system response. However, the information available so far is contradictory. The objective of this research was to clarify whether antibiotic use influences efficacy of checkpoint inhibitors treatments in non-small cell lung cancer patients in clinical practice. Methods. Therefore, a retrospective observational study was designed. Use of antibiotics among patients treated with atezolizumab, pembrolizumab or nivolumab was assessed within 2 months of checkpoint inhibitors treatments initiation. Results. A total of 140 patients were included, mostly men, with good performance status (ECOG 0-1), all of them previously treated with chemotherapy. An antibiotic prescription was identified in 31% of these patients, mainly fluoroquinolones or beta-lactams. The most frequent indication was respiratory infection. Both progression-free survival and overall survival were lower for patients treated with anti-infective drugs, although this difference was not statistically significant. Conclusion. More studies are needed to draw conclusions about the impact of antibiotics on the efficacy of immunotherapy. (AU)

Objetivos. Investigaciones recientes sugieren que el uso de antibióticos podría reducir la eficacia de los inhibidores del punto de control inmunológico, además de otros factores ya conocidos. Podría deberse a la modificación de la microbiota, por su impacto en la respuesta del sistema inmune. En cualquier caso, la información disponible hasta el momento es contradictoria. El objetivo de esta investigación es esclarecer si el uso de antibióticos influye en la eficacia de los inhibidores del punto de control para el tratamiento de pacientes con carcinoma de pulmón no microcítico en la práctica clínica. Métodos. Se diseñó un estudio observacional, retrospectivo. Se investigó el uso de antibióticos entre aquellos pacientes a tratamiento con atezolizumab, pembrolizumab o nivolumab en los 2 meses previos o posteriores a su inicio. Resultados. Se incluyeron 140 pacientes, principalmente hombres con aceptable estado general (ECOG 0-1), todos previamente tratados con quimioterapia. Se identificó una prescripción antibiótica en el 31% de la población, principalmente fluoroquinolonas o betalactámicos. La indicación más frecuente para dicha prescripción era la infección respiratoria. Tanto la supervivencia libre de progresión con la supervivencia global fue inferior en el grupo tratado con antiinfecciosos, aunque no se alcanzó significación estadística. Conclusiones. Son necesario más estudios para concluir acerca del impacto de los antibióticos en la eficacia de la inmunoterapia. (AU)

Recycled water acceptance: Data from two Spanish regions with opposite levels of scarcity.

The dataset presented in this paper were collected for testing a perceptive-axiological model of recycled water acceptance for low and high contact uses. Participants were selected by proportional random sampling by sex and age the two Spanish communities with the most extreme values of water stress (Galicia, the rainiest region and Murcia, the driest). Data were collected by a company specialized in market research using an online survey housed on Qualtrics. Participants who matched the specified profile were contacted by email. The company compensated them financially. The final sample size consisted of 726 valid responses. The survey collected data on a variety of variables related to three conceptual dimensions: the diagnosis of the environmental situation, the axiological influence and the public perceptions regarding recycled water. The survey also collected demographic data from respondents. The survey was designed and reviewed by four experts in social psychology and two experts in methodology. The dataset featured in this article provides the raw survey data plus sociodemographic distribution, survey items, and other statistical data. This is the first and most comprehensive set of comparative data known to the authors on public acceptance of water reuse for high and low contact uses comparing regions with and without water scarcity. The authors have published an open access paper based on this data set, which are linked to this paper. Water industry professionals, policymakers, researchers and other stakeholders aiming to implement wastewater reuse systems in society may be interested in using the data as a point of comparison for their own study on public acceptance of water reuse or examining the data for relationships not yet explored in the literature.

Associations of White Matter and Basal Ganglia Microstructure to Cognitive Fatigue Rate in Multiple Sclerosis.

Fatigue, including cognitive fatigue, is one of the most debilitating symptoms reported by persons with multiple sclerosis (pwMS). Cognitive fatigue has been associated with disruptions in striato-thalamo-cortical and frontal networks, but what remains unknown is how the rate at which pwMS become fatigued over time relates to microstructural properties within the brain. The current study aims to fill this gap in knowledge by investigating how cognitive fatigue rate relates to white matter and basal ganglia microstructure in a sample of 62 persons with relapsing-remitting MS. Participants rated their level of cognitive fatigue at baseline and after each block (x7) of a within-scanner cognitive fatigue inducing task. The slope of the regression line of all eight fatigue ratings was designated as "cognitive fatigue rate." Diffusional kurtosis imaging maps were processed using tract-based spatial statistics and regional analyses (i.e., basal ganglia) and associated with cognitive fatigue rate. Results showed cognitive fatigue rate to be related to several white matter tracts, with many having been associated with basal ganglia connectivity or the previously proposed "fatigue network." In addition, cognitive fatigue rate was associated with the microstructure within the putamen, though this did not survive multiple comparisons correction. Our approach of using cognitive fatigue rate, rather than trait fatigue, brings us closer to understanding how brain pathology may be impacting the experience of fatigue in the moment, which is crucial for developing interventions. These results hold promise for continuing to unpack the complex construct that is cognitive fatigue.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort.

Background: Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort. Methods: Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata. Results: A total of 57 patients were recruited, with median age of 63 years (IQR [53-81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age. Conclusion: In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Thalamic atrophy moderates associations among aerobic fitness, cognitive processing speed, and walking endurance in persons with multiple sclerosis.

BACKGROUND AND OBJECTIVES: Thalamic atrophy (TA) represents a biomarker of neurodegeneration and associated dysfunction/decline in physical and cognitive functioning among persons with multiple sclerosis (MS). Aerobic fitness, as an end point of exercise training, represents a promising target for restoring function in MS, but it is unknown if such effects differ by TA. This cross-sectional study examined whether aerobic fitness was differentially associated with cognitive processing speed and walking endurance in persons with MS who present with and without TA. METHODS: 44 fully ambulatory persons with MS completed a graded exercise test for measuring aerobic fitness (VO2peak) and underwent 3T MRI for measuring TA, the Symbol Digit Modalities Test (SDMT), and the 6-min walk (6MW). We performed Spearman correlations (rs) among VO2peak, SDMT, and 6MW scores overall, and in persons with and without TA. We applied Fisher's z-test for comparing correlations based on TA status. RESULTS: When controlling for age, EDSS score, and global MRI measures of atrophy, VO2peak was strongly associated with SDMT scores (prs = 0.74, p < 0.01) and 6MW performance (prs = 0.77, p < 0.01) in persons with TA, whereas VO2peak was not associated with SDMT scores (prs = - 0.01, p = 0.99) or 6MW performance (prs = 0.25, p = 0.38) in those without TA. The correlations between VO2peak and SDMT (z = 2.86, p < 0.01) and VO2peak and 6MW (z = 2.33, p = 0.02) were significantly stronger in the TA group. DISCUSSION: This study provides initial evidence of strong, selective associations among aerobic fitness, cognitive processing speed, and walking endurance in persons with TA as a biomarker for MS-related neurodegeneration. Such data support TA as a moderator of the association among aerobic fitness, cognitive processing speed, and walking endurance in persons with MS. Future research should carefully consider the role of TA when designing trials of aerobic exercise, cognition, and mobility in MS.

Correction: Transmembrane protease serine 2 (TMPRSS2) rs75603675, comorbidity and sex are the primary predictors of Covid-19 severity.

We identified an error in the abstract of the article: TPMRSS2 rs75603675 OR is incorrectly indicated. It should read (OR = 2.140) instead of (OR = 0.586). We apologize for this error. However, since the main text is correct, it has no impact on the results displayed in the study.

Transmembrane protease serine 2 (TMPRSS2) rs75603675, comorbidity, and sex are the primary predictors of COVID-19 severity.

By the end of December 2021, coronavirus disease 2019 (COVID-19) produced more than 271 million cases and 5.3 million deaths. Although vaccination is an effective strategy for pandemic control, it is not yet equally available in all countries. Therefore, identification of prognostic biomarkers remains crucial to manage COVID-19 patients. The aim of this study was to evaluate predictors of COVID-19 severity previously proposed. Clinical and demographic characteristics and 120 single-nucleotide polymorphisms were analyzed from 817 patients with COVID-19, who attended the emergency department of the Hospital Universitario de La Princesa during March and April 2020. The main outcome was a modified version of the 7-point World Health Organization (WHO) COVID-19 severity scale (WHOCS); both in the moment of the first hospital examination (WHOCS-1) and of the severest WHOCS score (WHOCS-2). The TMPRSS2 rs75603675 genotype (OR = 0.586), dyslipidemia (OR = 2.289), sex (OR = 0.586), and the Charlson Comorbidity Index (OR = 1.126) were identified as the main predictors of disease severity. Consequently, these variables might influence COVID-19 severity and could be used as predictors of disease development.

Signal Detection Theory as a Novel Tool to Understand Cognitive Fatigue in Individuals With Multiple Sclerosis.

Multiple Sclerosis (MS) affects 2.8 million persons worldwide. One of the most persistent, pervasive, and debilitating symptoms of MS is cognitive fatigue. While this has been known for over a century, cognitive fatigue has been difficult to study because patients' subjective (self-reported) cognitive fatigue has consistently failed to correlate with more objective measures, such as reaction time (RT) and accuracy. Here, we investigated whether more nuanced metrics of performance, specifically the metrics of Signal Detection Theory (SDT), would show a relationship to cognitive fatigue even if RT and accuracy did not. We also measured brain activation to see whether SDT metrics were related to activation in brain areas that have been shown to be sensitive to cognitive fatigue. Fifty participants (30 MS, 20 controls) took part in this study and cognitive fatigue was induced using four blocks of a demanding working memory paradigm. Participants reported their fatigue before and after each block, and their performance was used to calculate SDT metrics (Perceptual Certainty and Criterion) and RT and accuracy. The results showed that the SDT metric of Criterion (i.e., response bias) was positively correlated with subjective cognitive fatigue. Moreover, the activation in brain areas previously shown to be related to cognitive fatigue, such as the striatum, was also related to Criterion. These results suggest that the metrics of SDT may represent a novel tool with which to study cognitive fatigue in MS and other neurological populations. These results hold promise for characterizing cognitive fatigue in MS and developing effective interventions in the future.