Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method.

BACKGROUND: Epileptic seizures are an established comorbidity of Alzheimer's disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD. AIMS: 1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls. 2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD. 3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters. METHODS: Subjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs. RESULTS: We found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher's exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall-Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann-Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without. CONCLUSION: We confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04131491. 12/02/2020.

Impact of fatigue on anaesthesia providers: a scoping review.

BACKGROUND: Recently, fatigue has received more attention as a workplace hazard. This scoping review focuses on fatigue in anaesthesia providers. We explore the prevalence of fatigue in anaesthesia providers, and we examine how fatigue impacts their performance. METHODS: A literature search was independently conducted from December 2019 through March 2020. The following four databases were consulted: MEDLINE, CINAHL, EMBASE, and PubPsych. Only studies discussing fatigue in anaesthesia providers were eligible. RESULTS: The initial database search identified a total of 118 studies, of which 30 studies were included in the review. Eight articles concerned the prevalence of fatigue in anaesthesia providers, whereas 22 explored the impact of fatigue on the performance of anaesthesia providers. Up to 60.8% of anaesthesia providers suffered from severe excessive daytime sleepiness, and fatigue was denoted as a common workplace problem in up to 73.1% of anaesthesia providers. Fatigue had a negative influence on medication errors and vigilance, and it decreased the performance of anaesthesia providers during laboratory psychomotor testing. There was a decrease in non-technical skills (notably communication and teamwork) and worsening mood when fatigued. CONCLUSIONS: Based on this scoping review, fatigue is a prevalent a phenomenon that anaesthesia providers cannot ignore. A combination of deterioration in non-technical skills, increased medication errors, loss of sustained attention, and psychomotor decline can lead to poorer performance and cause patient harm. Concrete strategies to mitigate fatigue should be developed.

The role of COX-2 inhibitors in pain modulation.

NSAIDs are the analgesics that are most commonly used world-wide. In the past few years, there have been significant advances in explaining the mechanism of action and clinical efficacy of the drugs belonging to this pharmacological family. Recent data relating to the role of cyclo-oxygenase (COX)-2 in the development of neuronal hyperexcitability and pain hypersensitivity have opened new perspectives in our understanding of the therapeutic effects of these drugs in several painful conditions. The main objective of this brief review is to deal with some physiopathological and pharmacological aspects concerning the role of NSAIDs, with special reference to COX-2 inhibitors, in the treatment of pain.

Pharmacology of systemic analgesics.

Systemic administration of analgesic drugs is still the most widely used method for providing pain relief in acute painful situations. Opioids may be selected on the basis of their physicochemical characteristics and their diffusion index to the brain. But in clinical practice, their very steep concentration-analgesic effect relationship remains a critical aspect of opioid therapy. Thus, small fluctuations in plasma concentrations of opioids may lead to profound fluctuations in analgesic effect when their plasma and effect-site concentrations are near the minimum effective analgesic concentration (MEAC). Combining drugs acting on different mechanisms of nociceptive modulation offers benefits from additive/synergistic effects and will decrease the incidence of their adverse effects. Evidence-based reviews showed that effective pain relief using non-opioid analgesics relied on paracetamol supplemented with non-steroidal anti-inflammatory drugs (NSAIDs). The role of COX-2 selective inhibitors (CSIs) in acute pain relief still requires further evaluation. NSAIDs, CSIs and paracetamol share the property of morphine sparing in situations of severe (post-operative) pain. CSIs may be beneficial in patients in whom post-operative bleeding is a major surgical risk as the effects of NSAIDs on coagulation may last for days. Finally, low-dose ketamine infusions remain a worthwhile addition to opioid therapy. Analgesic concentrations of ketamine are 1/5th to 1/10th the anaesthetic concentration and exert significant inhibition on N-methyl-d-aspartate (NMDA) receptor activation.