Setter hjernen på dagsordenen Johannessen, Lise Berit; Mathiesen, Ellisiv Bøgeberg
Tidsskrift for den Norske Lægeforening,
2004, Letnik:
124, Številka:
9
Journal Article
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.
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).
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).
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.
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.
En kvinne i 70-årene med langvarige gangvansker Flønes, Irene H; Haugarvoll, Kristoffer; Sundal, Christina ...
Tidsskrift for den Norske Lægeforening,
2015, 2015-00-00, Letnik:
135, Številka:
19
Journal Article
The study of consummatory responses during food intake represents a unique opportunity to investigate the physiological, psychological and neurobiological processes that control ingestive behavior. ...Recording the occurrence and temporal organization of individual licks across consumption, also called lickometry, yields a rich data set that can be analyzed to dissect consummatory responses into different licking patterns. These patterns, divided into trains of licks separated by pauses, have been used to deconstruct the many influences on consumption, such as palatability evaluation, incentive properties, and post-ingestive processes. In this review, we describe commonly used definitions of licking patterns and how various studies have defined and measured these. We then discuss how licking patterns can be used to investigate the impact of different physiological need states on processes governing ingestive behavior. We also present new data showing how licking patterns are changed in an animal model of protein appetite and how this may guide food choice in different protein-associated hedonic and homeostatic states. Thus, recording lick microstructure can be achieved relatively easily and represents a useful tool to provide insights, beyond the measurement of total intake, into the multiple factors influencing ingestive behavior.
Inactive interventions can have significant effects on cognitive performance. Understanding the generation of these cognitive placebo/nocebo effects is crucial for evaluating the cognitive impacts of ...interventional methods, such as non-invasive brain stimulation (NIBS). We report both cognitive placebo and nocebo effects on reward-based learning performance induced using an active sham NIBS protocol, verbal suggestions and conditioning in 80 healthy participants. Whereas our placebo manipulation increased both expected and perceived cognitive performance, nocebo had a detrimental effect on both. Model-based analysis suggests manipulation-specific strategic adjustments in learning-rates: Participants in the placebo group showed stronger learning from losses and reduced behavioral noise, participants in the nocebo group showed stronger learning from gains and increased behavioral noise. We conclude that experimentally induced expectancy can impact cognitive functions of healthy adult participants. This has important implications for the use of double-blind study designs that can effectively maintain blinding in NIBS studies.
Background
The serotonin receptor 2A (HTR2A) has been described as an important facilitation mediator of spinal nociceptive processing leading to central sensitization (CS) in animal models of ...chronic pain. However, whether HTR2A single nucleotide variants (SNVs) modulate neuropathic pain states in patients has not been investigated so far. The aim of this study was to elucidate the potential association of HTR2A variants with sensory abnormalities or ongoing pain in neuropathic pain patients.
Methods
At total of 240 neuropathic pain patients and 253 healthy volunteers were included. Patients were phenotypically characterized using standardized quantitative sensory testing (QST). Patients and controls were genotyped for HTR2A g.‐1438G > A (rs6311) and c.102C > T (rs6313). Genotype‐related differences in QST parameters were assessed considering QST profile clusters, principal somatosensory components and sex.
Results
There was an equal distribution of rs6313 and linked rs6311 between patients and controls. However, the rs6313 variant was significantly associated with a principal component of pinprick hyperalgesia and dynamic mechanical allodynia, indicating enhanced CS in patients with sensory loss (−0.34 ± 0.15 vs. +0.31 ± 0.11 vs., p < .001). In this cluster, the variant allele was also associated with single QST parameters of pinprick hyperalgesia (MPT, +0.64 ± 0.18 vs. −0.34 ± 0.23 p = .002; MPS, +0.66 ± 0.17 vs. −0.09 ± 0.23, p = .009) and ongoing pain was increased by 30%.
Conclusions
The specific association of the rs6313 variant with pinprick hyperalgesia and increased levels of ongoing pain suggests that the HTR2A receptor might be an important modulator in the development of CS in neuropathic pain.
Significance
This article presents new insights into serotonin receptor 2A‐mediating mechanisms of central sensitization in neuropathic pain patients. The rs6313 variant allele was associated with increased mechanical pinprick sensitivity and increased levels of ongoing pain supporting a contribution of central sensitization in the genesis of ongoing pain providing a possible route for mechanism‐based therapies.
Self-reported pain levels in patients with fibromyalgia may change according to weather conditions. Previous studies suggest that low barometric pressure (BMP) is significantly related to increased ...pain, but that the contribution of changes in BMP has limited clinical relevance. The present study examined whether BMP influenced variability in perceived stress, and if stress levels moderated or mediated the relationship between BMP and pain. Forty-eight patients with fibromyalgia enrolled in a randomized controlled trail (RCT) reported pain and emotional state three times daily with mobile phone messages for a 30-consecutive day period prior to the start of the treatment in the RCT. The patients were unaware that weather data were collected simultaneously with pain and emotional reports. The results showed that lower BMP and increased humidity were significantly associated with increased pain intensity and pain unpleasantness, but only BMP was associated with stress levels. Stress levels moderated the impact of lower BMP on pain intensity significantly, where higher stress was associated with higher pain. Significant individual differences were present shown by a sub-group of patients (n = 8) who reacted opposite compared to the majority of patients (n = 40) with increased pain reports to an increase in BMP. In sum, lower BMP was associated with increased pain and stress levels in the majority of the patients, and stress moderated the relationship between BMP and pain at the group-level. Significant individual differences in response to changes in BMP were present, and the relation between weather and pain may be of clinical relevance at the individual level.
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