Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.Peer reviewe

Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.publishedVersionPeer reviewe

Cardiovascular regulation in epilepsy with emphasis on the interictal state

Abstract Epilepsy is associated with changes in autonomic cardioregulatory function. Ictally, autonomic disturbances may be evident with significant changes in heart rate (HR), blood pressure (BP) and respiration. However, interictal dysfunction of autonomic cardiovascular system may be subtle and it may be recognized only by delicate tools designed for that purpose. The aim of this study was to evaluate the function of the cardiovascular autonomic regulatory system in patients with epilepsy. Cardiovascular reflex tests were performed on patients with partial or idiopathic generalized epilepsies. Special attention was paid to temporal lobe epilepsy (TLE). An association of refractory and well controlled TLE and hippocampal sclerosis with altered cardioregulation was evaluated by using cardiovascular reflex tests and an analysis of spectral and non-linear analysis of heart rate variation (HRV). Cardiovascular reflexes were altered both in patients with partial and idiopathic generalized epilepsies who had been treated for epilepsy with antiepileptic drugs (AEDs), whereas patients with newly, untreated epilepsy did not differ from the control subjects. Diminished cardiovascular reflexes also seemed to be associated with carbamazepine (CBZ) treatment. Various parameters of cardiovascular reflex tests and analysis of spectral and dynamic measures of HRV were diminished in patients with TLE compared to the control subejcts. These results indicate that epilepsy, especially TLE, is associated with interictal changes of autonomic cardioregulation. Although these changes seem to be evident in patients with severe form of TLE, patients with well controlled TLE and patients without hippocampal sclerosis also have altered autonomic cardioregulatory function. These results suggest that dysfunction of the cardioregulatory system is rather associated with functional than structural changes of the inner temporal lobe in patients with TLE

Heart rate dynamics in refractory and well controlled temporal lobe epilepsy

Objectives: Disorders of cardiovascular and other autonomic nervous system functions are often found in patients with temporal lobe epilepsy (TLE). Cardiovascular dysregulation in TLE has previously been quantified assessing traditional time and frequency domain measures of heart rate (HR) variability from short term ECG recordings. However, new complexity and fractal measures of HR variability based on non-linear dynamics and fractals ("chaos theory") may disclose certain patterns of HR dynamics that cannot be detected using only conventional measures. Methods: In addition to the traditional spectral and non-spectral components of HR variability, fractal correlation properties, approximate entropy (ApEn) of RR interval dynamics, and the slope of the power law relation were measured from 24 hour ambulatory ECG recordings to evaluate interictal autonomic cardiovascular regulatory function in 19 patients with refractory TLE, 25 patients with well controlled TLE, and in 34 healthy age and sex matched control subjects. Results: The traditional time and frequency domain measures were lower in patients with TLE than in controls (p<0.05). In addition, the power law slope (p<0.005) and ApEn (p<0.05) were also reduced in TLE patients. Furthermore, ApEn was smaller in patients with refractory TLE than in patients with well-controlled TLE ( p<0.01), whereas the long term fractal correlation value α2 was lower in patients with well controlled TLE (p<0.05). An altered HR variation was not associated with any particular AED regimen. Conclusions: In addition to reduced overall HR variability, the long term fractal organisation and complexity of HR dynamics seem to be altered in TLE. These abnormalities in HR behaviour may partly contribute to the occurrence of adverse cardiovascular events, such as life threatening arrhythmias in patients with TLE

Suppressed circadian heart rate dynamics in temporal lobe epilepsy

Objectives: To measure interictal circadian rhythm of heart rate (HR) variability in patients with temporal lobe epilepsy (TLE) using a 24 hour ECG recording. Methods: Various conventional and dynamic fractal measures of HR variability were analysed in 17 patients with refractory TLE, 20 patients with well controlled TLE, and 37 healthy age and sex matched control subjects. Results: The SD of all RR intervals (p<0.01), the measured power spectral components of HR variability (low frequency power (p<0.01), high frequency power (p<0.05)), and the SD(1) (p<0.05) and SD(2) (p<0.01) Poincaré two dimensional vector analysis measurements were suppressed in the patients. This suppression was observed during both day and night time; however, it was more pronounced at night, and nocturnal increase in HR variability usually seen in the normal population could not be detected in the patients. The HR variability measures did not correlate with the duration of epilepsy, the age of the patients, or with the anti-epileptic drugs used. Conclusion: TLE was associated with reduced HR variability, which was more pronounced during night than day, and the nocturnal increase in HR variability was abolished in patients with TLE. The alteration in autonomic regulation of HR variability was similar in patients with both refractory and well controlled TLE

Medical students’ experience of emotions and success in neurological studies:what do they tell us?

Abstract Background: There is a need to develop effective educational experience in neurology to improve the students’ skills in diagnosing and managing patients with neurological symptoms or disease. The aim of this study was to investigate the medical students’ attitudes and emotions towards neurology before and after the four week clinical course at two Finnish Universities in order to find elements to improve effective learning by decreasing the emotional stress in medical studies. Methods: In this two-stage study, 58 medical students participated in an internet survey with open-ended questions after completing a clinical neurology course. In the content analysis of this survey 20 students (35%) were identified with negative anticipation towards neurology before undertaking the clinical neurology course. In the second phase of the study, the narrative analysis method was used to analyse the face-to-face interviews. Two of these interviews are described in this paper and represent cases who expressed negative emotions in both online survey and narrative interview. Results: According to the content analysis, the principal emotions that were experienced at the beginning of the clinical neurology course were insecurity about personal performance (𝑛 = 19, 95%) anxiety (𝑛 = 9, 45%) and fear (𝑛 = 6, 30%). During the course the combined negative emotions (insecurity, anxiety, and fear) decreased in 80% of students (16/20 cases), remained unchanged in 15% (3/20) and could not be evaluated in 1 (5%) case. The main reasons for the observed negative anticipation were the complexity of neurology and challenges in the interpretation of clinical findings. Based on content analysis and narratives, elements that were evaluated as the most significant contributors in reducing this included small group teaching with real patients, teachersʼ expertise and the increase in self-confidence. Conclusion: Teaching with appropriate didactic methodology and feedback, and plenty of practical training can improve effective learning in neurology. We suggest that the pedagogic competence of the clinical teacher influences a student’s motivation and proficiency and reduce stress in neurology-related learning tasks

Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy

Abstract Background: Narcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascending arousal network (AAN), which regulates arousal via release of neurotransmitters like noradrenalin. Brain pulsations are thought to drive intracranial cerebrospinal fluid flow linked to brain metabolite transfer that sustains homeostasis. This flow increases in sleep and is suppressed by noradrenalin in the awake state. Here we tested the hypothesis that narcolepsy is associated with altered brain pulsations, and if these pulsations can differentiate narcolepsy type 1 from healthy controls. Methods: In this case-control study, 23 patients with narcolepsy type 1 (NT1) were imaged with ultrafast fMRI (MREG) along with 23 age- and sex-matched healthy controls (HC). The physiological brain pulsations were quantified as the frequency-wise signal variance. Clinical relevance of the pulsations was investigated with correlation and receiving operating characteristic analysis. Results: We find that variance and fractional variance in the very low frequency (MREGvlf) band are greater in NT1 compared to HC, while cardiac (MREGcard) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREGvlf shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREGcard variance (R = −0.48, p = 0.0249). Conclusions: We suggest that our novel results reflect impaired CSF dynamics that may be linked to altered glymphatic circulation in narcolepsy type 1

Lag analysis of fast fMRI reveals delayed information flow between the default mode and other networks in narcolepsy

Abstract Narcolepsy is a chronic neurological disease characterized by dysfunction of the hypocretin system in brain causing disruption in the wake-promoting system. In addition to sleep attacks and cataplexy, patients with narcolepsy commonly report cognitive symptoms while objective deficits in sustained attention and executive function have been observed. Prior resting-state functional magnetic resonance imaging (fMRI) studies in narcolepsy have reported decreased inter/intranetwork connectivity regarding the default mode network (DMN). Recently developed fast fMRI data acquisition allows more precise detection of brain signal propagation with a novel dynamic lag analysis. In this study, we used fast fMRI data to analyze dynamics of inter resting-state network (RSN) information signaling between narcolepsy type 1 patients (NT1, n = 23) and age- and sex-matched healthy controls (HC, n = 23). We investigated dynamic connectivity properties between positive and negative peaks and, furthermore, their anticorrelative (pos-neg) counterparts. The lag distributions were significantly (P &lt; 0.005, familywise error rate corrected) altered in 24 RSN pairs in NT1. The DMN was involved in 83% of the altered RSN pairs. We conclude that narcolepsy type 1 is characterized with delayed and monotonic inter-RSN information flow especially involving anticorrelations, which are known to be characteristic behavior of the DMN regarding neurocognition