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Collateral Effect of Covid-19 on Stroke Evaluation in the United States
The authors reviewed an imaging database used to determine whether patients with acute stroke were eligible to undergo endovascular thrombectomy. They found a 39% decrease in daily use of this imaging from a 29-day prepandemic period in February 2020 to a 14-day early-pandemic period from late March through early April.
Journal Article
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (
n
= 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (
P
< 0.0001,
d
= 0.91) and to significantly decrease the SDS total score (
P
= 0.0116,
d
= 0.43). The mean change in CAPS-5 scores in participants completing treatment was −24.4 (s.d. 11.6) in the MDMA group and −13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.
Results from a phase 3, double-blind, randomized, placebo-controlled trial demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder.
Journal Article
Species-Specific Responses of Juvenile Rockfish to Elevated pCO2: From Behavior to Genomics
In the California Current ecosystem, global climate change is predicted to trigger large-scale changes in ocean chemistry within this century. Ocean acidification-which occurs when increased levels of atmospheric CO2 dissolve into the ocean-is one of the biggest potential threats to marine life. In a coastal upwelling system, we compared the effects of chronic exposure to low pH (elevated pCO2) at four treatment levels (i.e., pCO2 = ambient [500], moderate [750], high [1900], and extreme [2800 μatm]) on behavior, physiology, and patterns of gene expression in white muscle tissue of juvenile rockfish (genus Sebastes), integrating responses from the transcriptome to the whole organism level. Experiments were conducted simultaneously on two closely related species that both inhabit kelp forests, yet differ in early life history traits, to compare high-CO2 tolerance among species. Our findings indicate that these congeners express different sensitivities to elevated CO2 levels. Copper rockfish (S. caurinus) exhibited changes in behavioral lateralization, reduced critical swimming speed, depressed aerobic scope, changes in metabolic enzyme activity, and increases in the expression of transcription factors and regulatory genes at high pCO2 exposure. Blue rockfish (S. mystinus), in contrast, showed no significant changes in behavior, swimming physiology, or aerobic capacity, but did exhibit significant changes in the expression of muscle structural genes as a function of pCO2, indicating acclimatization potential. The capacity of long-lived, late to mature, commercially important fish to acclimatize and adapt to changing ocean chemistry over the next 50-100 years is likely dependent on species-specific physiological tolerances.
Journal Article
Analysis of Limiting Factors Across the Life Cycle of Delta Smelt (Hypomesus transpacificus)
AbstractWe developed a mechanistic life-cycle model derived from the elicitation of multiple factors influencing the success of individual life-stages of the imperiled delta smelt (Hypomesus transpacificus). We discuss the relevance of limiting factors in population ecology and problems with additive models in detecting them. We identify limiting factors and assess their significance using a non-linear optimization routine, combined with traditional metrics to assess the value of covariates and model performance. After reviewing previous conceptual models and multivariate analyses, we identified a set of factors that were consistent with conceptual models and useful in explaining the erratic fluctuations in a common abundance index: food at certain times in certain locations, predation by introduced species primarily in the spring, and entrainment. The analytical approach provides a transparent and intuitive framework in which to consider the contribution of covariates and consequences for population trends, and has the potential to assist with the evaluation of proposed recovery measures.
Journal Article
Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials
Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis.
We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0–1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis.
Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0·0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2·55 (95% CI 1·44–4·52) for 0–90 min, 1·64 (1·12–2·40) for 91–180 min, 1·34 (1·06–1·68) for 181–270 min, and 1·22 (0·92–1·61) for 271–360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5·2%) of 1850 patients assigned to alteplase and 18 (1·0%) of 1820 controls, with no clear relation to OTT (p=0·4140). Adjusted odds of mortality increased with OTT (p=0·0444) and were 0·78 (0·41–1·48) for 0–90 min, 1·13 (0·70–1·82) for 91–180 min, 1·22 (0·87–1·71) for 181–270 min, and 1·49 (1·00–2·21) for 271–360 min.
Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4·5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4·5 h, risk might outweigh benefit.
None.
Journal Article