174 research outputs found

    Telephone conversation impairs sustained visual attention via a central bottleneck

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    Recent research has shown that holding telephone conversations disrupts one's driving ability. We asked whether this effect could be attributed to a visual attention impairment. In Experiment 1, participants conversed on a telephone or listened to a narrative while engaged in multiple object tracking (MOT), a task requiring sustained visual attention. We found that MOT was disrupted in the telephone conversation condition, relative to single-task MOT performance, but that listening to a narrative had no effect. In Experiment 2, we asked which component of conversation might be interfering with MOT performance. We replicated the conversation and single-task conditions of Experiment 1 and added two conditions in which participants heard a sequence of words over a telephone. In the shadowing condition, participants simply repeated each word in the sequence. In the generation condition, participants were asked to generate a new word based on each word in the sequence. Word generation interfered with MOT performance, but shadowing did not. The data indicate that telephone conversation disrupts attention at a central stage, the act of generating verbal stimuli, rather than at a peripheral stage, such as listening or speaking

    Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants

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    Purpose: Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are neurotropic human alphaherpesviruses endemic worldwide. Upon primary infection, both viruses establish lifelong latency in neurons and reactivate intermittently to cause a variety of mild to severe diseases. Acute retinal necrosis (ARN) is a rare, sight-threatening eye disease induced by ocular VZV or HSV infection. The virus and host factors involved in ARN pathogenesis remain incompletely described. We hypothesize an underlying genetic defect in at least part of ARN cases. Methods: We collected blood from 17 patients with HSV-or VZV-induced ARN, isolated DNA and performed Whole Exome Sequencing by Illumina followed by analysis in Varseq with criteria of CADD score &gt; 15 and frequency in GnomAD &lt; 0.1% combined with biological filters. Gene modifications relative to healthy control genomes were filtered according to high quality and read-depth, low frequency, high deleteriousness predictions and biological relevance. Results: We identified a total of 50 potentially disease-causing genetic variants, including missense, frameshift and splice site variants and on in-frame deletion in 16 of the 17 patients. The vast majority of these genes are involved in innate immunity, followed by adaptive immunity, autophagy, and apoptosis; in several instances variants within a given gene or pathway was identified in several patients.Discussion: We propose that the identified variants may contribute to insufficient viral control and increased necrosis ocular disease presentation in the patients and serve as a knowledge base and starting point for the development of improved diagnostic, prophylactic, and therapeutic applications.</p

    Development and Validation of a Risk Score for Febrile Neutropenia After Chemotherapy in Patients With Cancer: The FENCE Score

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    Background: Febrile neutropenia (FN) after chemotherapy causes a high burden of morbidity and mortality. We aimed to develop and validate a risk score to predict FN in the first cycle of chemotherapy. Methods: We included patients with solid cancers and diffuse large B-cell lymphomas at Rigshospitalet, University of Copenhagen, 2010-2016. Predictors of FN were analyzed using Poisson regression and random split-sampling. Results: Among 6294 patients in the derivation cohort, 360 developed FN. Female sex, older age, cancer type, disease stage, low albumin, elevated bilirubin, low creatinine clearance, infection before chemotherapy, and number of and type of chemotherapy drugs predicted FN. Compared with those at low risk (n = 2520, 40.0%), the incidence rate ratio of developing FN was 4.8 (95% confidence interval [CI] = 2.9 to 8.1), 8.7 (95% CI = 5.3 to 14.1) and 24.0 (95% CI = 15.2 to 38.0) in the intermediate (n = 1294, 20.6%), high (n = 1249, 19.8%) and very high (n = 1231, 19.6%) risk groups, respectively, corresponding to a number needed to treat with granulocyte colony-stimulating factors to avoid one FN event in the first cycle of 284, 60, 34 and 14. The discriminatory ability (Harrell's C-statistic = 0.80, 95% CI = 0.78 to 0.82) was similar in the validation cohort (n = 3163) (0.79, 95% CI = 0.75 to 0.82). Conclusion: We developed and internally validated a risk score for FN in the first cycle of chemotherapy. The FENCE score is available online and provides good differentiation of risk groups

    Classification of death causes after transplantation (CLASS):Evaluation of methodology and initial results

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    Correct classification of death causes is an important component of transplant trials.We aimed to develop and validate a system to classify causes of death in hematopoietic stem cell (HSCT) and solid organ (SOT) transplant recipients.Case record forms (CRF) of fatal cases were completed, including investigator-designated cause of death. Deaths occurring in 2010 to 2013 were used for derivation; and were validated by deaths occurring in 2013 to 2015. Underlying cause of death (referred to as recorded underlying cause) was determined through a central adjudication process involving 2 external reviewers, and subsequently compared with the Danish National Death Cause Registry.Three hundred eighty-eight recipients died 2010 to 2015 (196 [51%] SOT and 192 [49%] HSCT). The main recorded underlying causes of death among SOT and HSCT were classified as cancer (20%, 48%), graft rejection/failure/graft-versus-host-disease (35%, 28%), and infections (20%, 11%). Kappa between the investigator-designated and the recorded underlying cause of death was 0.74 (95% CI 0.69-0.80) in derivation and comparable in the validation cohort. Death causes were concordant with the Danish National Death Cause Registry in 37.2% (95% CI 31.5-42.9) and 38.4% (95% CI 28.8-48.0) in the derivation and validation cohorts, respectively.We developed and validated a method to systematically and reliably classify the underlying cause of death among transplant recipients. There was a high degree of discordance between this classification and that in the Danish National Death Cause Registry

    Incidence Rates and Risk Factors of Clostridioides difficile Infection in Solid Organ and Hematopoietic Stem Cell Transplant Recipients

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    BACKGROUND: Transplant recipients are an immunologically vulnerable patient group and are at elevated risk of Clostridioides difficile infection (CDI) compared with other hospitalized populations. However, risk factors for CDI post-transplant are not fully understood. // METHODS: Adults undergoing solid organ (SOT) and hematopoietic stem cell transplant (HSCT) from January 2010 to February 2017 at Rigshospitalet, University of Copenhagen, Denmark, were retrospectively included. Using nationwide data capture of all CDI cases, the incidence and risk factors of CDI were assessed. // RESULTS: A total of 1687 patients underwent SOT or HSCT (1114 and 573, respectively), with a median follow-up time (interquartile range) of 1.95 (0.52–4.11) years. CDI was diagnosed in 15% (164) and 20% (114) of the SOT and HSCT recipients, respectively. CDI rates were highest in the 30 days post-transplant for both SOT and HSCT (adjusted incidence rate ratio [aIRR], 6.64; 95% confidence interval [CI], 4.37–10.10; and aIRR, 2.85; 95% CI, 1.83–4.43, respectively, compared with 31–180 days). For SOT recipients, pretransplant CDI and liver and lung transplant were associated with a higher risk of CDI in the first 30 days post-transplant, whereas age and liver transplant were risk factors in the later period. Among HSCT recipients, myeloablative conditioning and a higher Charlson Comorbidity Index were associated with a higher risk of CDI in the early period but not in the late period. // CONCLUSIONS: Using nationwide data, we show a high incidence of CDI among transplant recipients. Importantly, we also find that risk factors can vary relative to time post-transplant

    Impact of Plasmodium falciparum infection on the frequency of moderate to severe anaemia in children below 10 years of age in Gabon

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    BACKGROUND: Improving the understanding of childhood malarial anaemia may help in the design of appropriate management strategies. METHODS: A prospective observational study over a two-year period to assess the burden of anaemia and its relationship to Plasmodium falciparum infection and age was conducted in 8,195 febrile Gabonese children. RESULTS: The proportion of children with anaemia was 83.6% (n = 6830), higher in children between the ages of six and 23 months. Those under three years old were more likely to develop moderate to severe anaemia (68%). The prevalence of malaria was 42.7% and P. falciparum infection was more frequent in children aged 36-47 months (54.5%). The proportion of anaemic children increased with parasite density (p 60%), but was unrelated to P. falciparum parasitaemia. CONCLUSION: Malaria is one of the main risk factors for childhood anaemia which represents a public health problem in Gabon. The risk of severe malarial anaemia increases up the age of three years. Efforts to improve strategies for controlling anaemia and malaria are needed

    Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

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    Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health
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