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

Short- and long-term effects of imatinib in hospitalized COVID-19 patients : A randomized trial

Objectives: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients. Methods: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients. Results: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47–3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78–1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32–1.63; low certainty evidence). Conclusions: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients.Peer 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