Fish oil (n-3 fatty acids) in drug resistant epilepsy: a randomised placebo-controlled crossover study.

Backgroundn-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models. High-dose fish oil has been explored in two randomised trials in drug resistant epilepsy with negative results. We performed a phase II randomised controlled crossover trial of low-dose and high-dose fish oil in participants with drug resistant epilepsy to explore whether low-dose or high-dose fish oil reduces seizures or improves cardiovascular health.MethodsRandomised placebo-controlled trial of low-dose and high-dose fish oil versus placebo (corn oil, linoleic acid) in 24 participants with drug resistant epilepsy. A three-period crossover design was utilised lasting 42 weeks, with three 10-week treatment periods and two 6-week washout periods. All participants were randomised in double-blind fashion to receive placebo, high dose or low dose in different sequences. The primary outcome was per cent change in total seizure frequency.FindingsLow-dose fish oil (3 capsules/day, 1080 mg eicosapentaenoic acid+docosahexaenoic acid) was associated with a 33.6% reduction in seizure frequency compared with placebo. Low-dose fish oil was also associated with a mild but significant reduction in blood pressure. High-dose fish oil was no different than placebo in reducing seizures or improving cardiac risk factors.InterpretationIn this phase II randomised crossover trial, low-dose fish oil was effective in reducing seizures compared with placebo. The magnitude of improvement is similar to that of recent antiepileptic drug trials in drug resistant epilepsy (DRE). The results indicate that low-dose fish oil may reduce seizures and improve the health of people with epilepsy. These findings justify a large multicentre randomised trial of low-dose fish oil (n-3 fatty acids <1080 mg/day) in drug resistant epilepsy.Trial registration numberNCT00871377

Ischemic Strokes Due to Large-Vessel Occlusions Contribute Disproportionately to Stroke-Related Dependence and Death: A Review

BackgroundSince large-vessel occlusion (LVO)-related acute ischemic strokes (AIS) are associated with more severe deficits, we hypothesize that the endovascular thrombectomy (ET) may disproportionately benefit stroke-related dependence and death.MethodsTo delineate LVO-AIS impact, systematic search identified studies measuring dependence or death [modified Rankin Scale (mRS) 3–6] or mortality following ischemic stroke among consecutive patients presenting with both LVO and non-LVO events within 24 h of symptom onset.ResultsAmong 197 articles reviewed, 2 met inclusion criteria, collectively enrolling 1,467 patients. Rates of dependence or death (mRS 3–6) within 3–6 months were higher after LVO than non-LVO ischemic stroke, 64 vs. 24%, odds ratio (OR) 4.46 (CI: 3.53–5.63, p < 0.0001). Mortality within 3–6 months was higher after LVO than non-LVO ischemic stroke, 26.2 vs. 1.3%, OR 4.09 (CI: 2.5–6.68), p < 0.0001. Consequently, while LVO ischemic events accounted for 38.7% (CI: 21.8–55.7%) of all acutely presenting ischemic strokes, they accounted for 61.6% (CI: 41.8–81.3%) of poststroke dependence or death and 95.6% (CI: 89.0–98.8%) of poststroke mortality. Using literature-based projections of LVO cerebral ischemia patients treatable within 8 h of onset, ET can be used in 21.4% of acutely presenting patients with ischemic stroke, and these events account for 34% of poststroke dependence and death and 52.8% of poststroke mortality.ConclusionLVOs cause a little more than one-third of acutely presenting AIS, but are responsible for three-fifths of dependency and more than nine-tenths of mortality after AIS. At the population level, ET has a disproportionate benefit in reducing severe stroke outcomes

Mechanical Ventilator Liberation of Patients With COVID-19 in Long-term Acute Care Hospital.

BackgroundMechanical ventilation (MV) via tracheostomy is performed commonly for patients who are in long-term acute care hospitals (LTACHs) after respiratory failure. However, the outcome of MV in COVID-19-associated respiratory failure in LTACHs is not known.Research questionWhat is the ventilator liberation rate of patients who have received tracheostomy with COVID-19-associated respiratory failure compared with those with respiratory failure unrelated to COVID-19 in LTACHs?Study design and methodsIn this retrospective cohort study, we examined mechanically ventilated patients discharged between June 2020 and March 2021. Of 242 discharges, 165 patients who had undergone tracheostomy arrived and were considered for ventilator liberation. One hundred twenty-eight patients did not have COVID-19 and 37 patients were admitted for COVID-19.ResultsThe primary outcome of the study was ventilator liberation; secondary outcomes were functional recovery, length of stay (LOS) at the LTACH, and discharge disposition. After controlling for demographics, the number of comorbidities, hemodialysis, vasopressor need, thrombocytopenia, and the LOS at the short-term acute care hospital, our results indicated that patients with COVID-19 showed a higher adjusted ventilator liberation rate of 91.4% vs 56.0% in those without COVID-19. Functional ability was assessed with the change of Functional Status Score for the Intensive Care Unit (FSS-ICU) between admission and discharge. The adjusted mean change in FSS-ICU was significantly higher in the COVID-19 group than in the non-COVID-19 group: 9.49 (95% CI, 7.38-11.6) vs 2.08 (95% CI, 1.05-3.11), respectively (P < .001). Patients with COVID-19 experienced a shorter adjusted LOS at the LTACH with an adjusted hazard ratio of 1.57 (95% CI, 1.0-2.46; P = .05) compared with patients without COVID-19. We did not observe significant differences between the two groups regarding discharge location, but a trend toward need for lower level of care was found in patients with COVID-19.InterpretationOur study suggests that patients with COVID-19 requiring MV and tracheostomy have a higher chance for recovery than those without COVID-19

Defining Clinically Relevant Cerebral Hemorrhage After Thrombolytic Therapy for Stroke

Background and purposeSeveral definitions have been proposed to distinguish clinically relevant from incidental cerebral hemorrhagic transformation after thrombolytic therapy for acute ischemic stroke. We investigated which definition best identifies cerebral hemorrhages that alter long-term functional outcome in the National Institute of Neurological Disorders and Stroke (NINDS) tissue-type plasminogen activator (tPA) trials.MethodsWe analyzed 4 candidate hemorrhage definitions for which the NINDS tPA trials public data set had relevant data. For each, we identified tPA-treated patients having that hemorrhage type and compared their actual functional outcomes at 90 days with their predicted outcomes had they not received tPA and not had the hemorrhage. Projected outcomes without tPA were based on a 17-variable prognostic model derived from the NINDS tPA trials placebo group.ResultsAmong the 312 patients treated with intravenous tPA, 33 (10.6%) experienced any radiological intracerebral hemorrhage <36 hours of treatment, 16 (5.1%) a radiological parenchymal hematoma, 20 (6.4%) a NINDS tPA trials-defined symptomatic intracerebral hemorrhage, 12 (3.8%) an European-Australian Cooperative Acute Stroke Study 2 (ECASS2)-defined symptomatic intracerebral hemorrhage, and 6 (1.9%) a modified version of the Safe Implementation of Thrombolysis in Stroke Monitoring Study (mSITS-MOST)-defined symptomatic intracerebral hemorrhage. The ECASS2 and mSITS-MOST definitions identified the largest hemorrhage-related change in 90-day modified Rankin Scale scores (2.26-0.32=1.94, P=0.0001; 2.81-0.63=2.18, P=0.0002, respectively). These definitions also distinguished the largest hemorrhage-related change in 90-day mortality (64.7%-7.6%=57.1%; P=0.0004 for ECASS2; 68.4%-19.5%=48.9%; P=0.0152 for mSITS-MOST).ConclusionsThe ECASS2 and mSITS-MOST symptomatic intracerebral hemorrhage definitions, which combine radiological features and occurrence of substantial early neurological deterioration, best identify tPA hemorrhages that alter final patient outcome

Cardiovascular autonomic effects of electronic cigarette use: a systematic review.

PurposeElectronic cigarettes (ECs) are the fastest growing tobacco product in the USA, and ECs, like tobacco cigarettes (TCs), have effects on the cardiovascular autonomic nervous system, with clinical implications. The purpose of this review was to collect and synthesize available studies that have investigated the autonomic cardiovascular effects of EC use in humans. Special attention is paid to the acute and chronic effects of ECs, the relative contributions of the nicotine versus non-nicotine constituents in EC emissions and the relative effects of ECs compared to TCs.MethodsUsing the methodology described in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement, we conducted a literature search of the Ovid PubMed and Embase databases on 6 December 2019 using keywords in titles and abstracts of published literature. Acute (minutes to hours) and chronic (days or longer) changes in heart rate variability (HRV), heart rate (HR) and blood pressure (BP) were used as estimates of cardiovascular autonomic effects.ResultsNineteen studies were included in this systematic review, all of which used earlier generation EC devices. Acute EC vaping increased HR and BP less than acute TC smoking. Nicotine but not non-nicotine constituents in EC aerosol were responsible for the sympathoexcitatory effects. The results of chronic EC vaping studies were consistent with a chronic sympathoexcitatory effect as estimated by HRV, but this did not translate into chronic increases in HR or BP.ConclusionsElectronic cigarettes are sympathoexcitatory. Cardiac sympathoexcitatory effects are less when vaping using the earlier generation ECs than when smoking TCs. Additional studies of the latest pod-like EC devices, which deliver nicotine similarly to a TC, are necessary

Defining Clinically Relevant Cerebral Hemorrhage After Thrombolytic Therapy for Stroke

Background and purposeSeveral definitions have been proposed to distinguish clinically relevant from incidental cerebral hemorrhagic transformation after thrombolytic therapy for acute ischemic stroke. We investigated which definition best identifies cerebral hemorrhages that alter long-term functional outcome in the National Institute of Neurological Disorders and Stroke (NINDS) tissue-type plasminogen activator (tPA) trials.MethodsWe analyzed 4 candidate hemorrhage definitions for which the NINDS tPA trials public data set had relevant data. For each, we identified tPA-treated patients having that hemorrhage type and compared their actual functional outcomes at 90 days with their predicted outcomes had they not received tPA and not had the hemorrhage. Projected outcomes without tPA were based on a 17-variable prognostic model derived from the NINDS tPA trials placebo group.ResultsAmong the 312 patients treated with intravenous tPA, 33 (10.6%) experienced any radiological intracerebral hemorrhage <36 hours of treatment, 16 (5.1%) a radiological parenchymal hematoma, 20 (6.4%) a NINDS tPA trials-defined symptomatic intracerebral hemorrhage, 12 (3.8%) an European-Australian Cooperative Acute Stroke Study 2 (ECASS2)-defined symptomatic intracerebral hemorrhage, and 6 (1.9%) a modified version of the Safe Implementation of Thrombolysis in Stroke Monitoring Study (mSITS-MOST)-defined symptomatic intracerebral hemorrhage. The ECASS2 and mSITS-MOST definitions identified the largest hemorrhage-related change in 90-day modified Rankin Scale scores (2.26-0.32=1.94, P=0.0001; 2.81-0.63=2.18, P=0.0002, respectively). These definitions also distinguished the largest hemorrhage-related change in 90-day mortality (64.7%-7.6%=57.1%; P=0.0004 for ECASS2; 68.4%-19.5%=48.9%; P=0.0152 for mSITS-MOST).ConclusionsThe ECASS2 and mSITS-MOST symptomatic intracerebral hemorrhage definitions, which combine radiological features and occurrence of substantial early neurological deterioration, best identify tPA hemorrhages that alter final patient outcome