Comparison of Verbal Episodic Memory Measures: Consortium to Establish a Registry for Alzheimer's Disease—Neuropsychological Assessment Battery (CERAD-NAB) versus California Verbal Learning Test (CVLT)

Episodic memory is affected early in the course of dementia. Two well-established tests to assess verbal episodic memory functioning are the Word List task from the Consortium to Establish a Registry for Alzheimer's disease Neuropsychological Assessment Battery (CERAD-NAB) and the California Verbal Learning Test (CVLT). In clinical and/or research settings, patients are typically administered either one or the other test, making statistical comparisons difficult. This study aimed to (i) compare the z-scores of these two tests in patients with MCI and different types of dementia and (ii) establish formulae to transform CERAD-NAB scores into CVLT scores and vice versa. Sixty-five patients completed both tests for the first time and within 10 days of each other. Pearson correlation coefficients indicated that the two tests assess similar aspects of episodic memory and that the CVLT is more sensitive to subtle episodic memory impairments. Finally, conversion formulae are provided and their implementation illustrate

The Influence of HIV on the Evolution of Mycobacterium tuberculosis.

HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery--a randomized controlled trial

OBJECTIVE: Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. DESIGN:: Double-blind, randomized, placebo-controlled trial. SETTING: One Swiss University Hospital. PATIENTS: One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTION: Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. MEASUREMENTS AND MAIN RESULTS: The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. CONCLUSION: This negative or, because of methodologic issues, possibly failed trial does no support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass

Evaluation of a summary score of cognitive performance for use in trials in perioperative and critical care.

Background/Aims: Cognitive dysfunction after medical treatment is increasingly being recognized. Studies on this topic require repeated cognitive testing within a short time. However, with repeated testing, practice effects must be expected. We quantified practice effects in a demographically corrected summary score of a neuropsychological test battery repeatedly administered to healthy elderly volunteers. Methods: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychological Assessment Battery (for which a demographically corrected summary score was developed), phonemic fluency tests, and trail-making tests were administered in healthy volunteers aged 65 years or older on days 0, 7, and 90. This battery allows calculation of a demographically adjusted continuous summary score. Results: Significant practice effects were observed in the CERAD total score and in the word list (learning and recall) subtest. Based on these volunteer data, we developed a threshold for diagnosis of postoperative cognitive dysfunction (POCD) with the CERAD total score. Conclusion: Practice effects with repeated administration of neuropsychological tests must be accounted for in the interpretation of such tests. Ignoring practice effects may lead to an underestimation of POCD. The usefulness of the proposed demographically adjusted continuous score for cognitive function will have to be tested prospectively in patients

Long-term neurological symptoms after acute COVID-19 illness requiring hospitalization in adult patients: insights from the ISARIC-COVID-19 follow-up study

in this study we aimed to characterize the type and prevalence of neurological symptoms related to neurological long-COVID-19 from a large international multicenter cohort of adults after discharge from hospital for acute COVID-19

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities