Amitriptyline for post-COVID headache: effectiveness, tolerability, and response predictors.

BACKGROUND: Headache is one of the most frequently reported symptoms in post-COVID patients. The clinical phenotype of COVID-19 headache combines phenotypic features of both tension-type headache (TTH) and migraine. We aimed to assess the effectiveness, side effects and predictors of amitriptyline (AMT) response in a real-world study setting. METHODS: We performed an observational multicentric study with a retrospective cohort. All consecutive patients with confirmed COVID-19 infection who received AMT for post-COVID headache from March 2020 to May 2021 were included. Response was evaluated by the reduction in the number of headache days per month (HDM) between weeks 8 and 12, compared with the baseline. We explored which variables were associated with a higher probability of response to AMT. RESULTS: Forty-eight patients were eligible for the study, 40/48 (83.3%) females, aged 46.85 (SD: 13.59) years. Patients had history of migraine 15/48 (31.3%) or TTH 5/48 (10.4%). The mean reduction of HDM was 9.6 (SD: 10.9; 95% CI 6.5, 12.7) days. Only 2/48 (5%) of patients discontinued AMT due to poor tolerability. History of TTH (10.9, 95% CI 1.3, 20.6) and nausea (- 8.5, 95% CI - 14.6, - 2.5) were associated with AMT response. CONCLUSIONS: This study provides real-world evidence of the potential benefit of AMT in patients with post-COVID-19 headache, especially in patients with history of TTH and without concomitant nausea.

Assessment of Neutrophil Extracellular Traps in Coronary Thrombus of a Case Series of Patients With COVID-19 and Myocardial Infarction.

IMPORTANCE: Severe coronavirus disease 2019 (COVID-19) is characterized by the intense formation of neutrophil extracellular traps (NETs), leading to the occlusion of microvessels, as shown in pulmonary samples. The occurrence of ST-elevated myocardial infarction (STEMI) is a serious cardiac manifestation of COVID-19; the intrinsic mechanism of coronary thrombosis appears to still be unknown. OBJECTIVE: To determine the role of NETs in coronary thrombosis in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This was a consecutive series of patients with COVID-19 at an academic tertiary hospital in Madrid, Spain, who underwent primary coronary interventions for STEMI in which coronary aspirates were obtained in the catheterization laboratory using a thrombus aspiration device. Patients with COVID-19 who experienced a STEMI between March 23 and April 11, 2020, from whom coronary thrombus samples were aspirated during primary coronary intervention, were included in the analysis. These patients were compared with a series conducted from July 2015 to December 2015 of patients with STEMI. MAIN OUTCOMES AND MEASURES: The presence and quantity of NETs in coronary aspirates from patients with STEMI and COVID-19. The method for the analysis of NETs in paraffin-embedded coronary thrombi was based on the use of confocal microscopy technology and image analysis for the colocalization of myeloperoxidase-DNA complexes and citrullinated histone H3. Immunohistochemical analysis of thrombi was also performed. Clinical and angiographic variables were prospectively collected. RESULTS: Five patients with COVID-19 were included (4 men [80%]; mean [SD] age, 62 [14] years); the comparison group included 50 patients (44 males [88%]; mean [SD] age, 58 [12] years). NETs were detected in the samples of all 5 patients with COVID-19, and the median density of NETs was 61% (95% CI, 43%-91%). In the historical series of patients with STEMI, NETs were found in 34 of 50 thrombi (68%), and the median NET density was 19% (95% CI, 13%-22%; P < .001). All thrombi from patients with COVID-19 were composed of fibrin and polymorphonuclear cells. None of them showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture. CONCLUSIONS AND RELEVANCE: In this small case series of patients with COVID-19 and myocardial infarction, NETs seem to play a major role in the pathogenesis of STEMI in COVID-19 disease. Our findings support the idea that targeting intravascular NETs might be a relevant goal of treatment and a feasible way to prevent coronary thrombosis in patients with severe COVID-19 disease.

Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis.

This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products. The systematic search took place in February/2017 and updated in December/2017 using the keywords "epilepsy" or "Dravet" or "Lennox-Gastaut" or "CDKL5" combined with "Cannabis," "cannabinoid," "cannabidiol," or "CBD" resulting in 199 papers. The qualitative assessment resulted in 11 valid references, with an average impact factor of 8.1 (ranging from 1.4 to 47.8). The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months). Two thirds of patients reported improvement in the frequency of seizures (399/622, 64%). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71%) than patients treated with purified CBD (81/175, 46%), [corrected] with statistical significance (p < 0.0001). Nevertheless, when the standard clinical threshold of a "50% reduction or more in the frequency of seizures" was applied, only 39% of the individuals were considered "responders," and there was no difference (p = 0.52) [corrected] between treatments with CBD-rich extracts (122/330, 37%) [corrected] and purified CBD (94/223, 42%). Patients treated with CBD-rich extracts reported lower average dose (6.0 mg/kg/day) [DOSAGE ERROR CORRECTED] than those using purified CBD (25.3 mg/kg/day). [DOSAGE ERROR CORRECTED] The reports of mild (158/216 76% vs. 148/447, 33% p < 0.001) and severe (41/155, 26% vs. 23/328, 7% p < 0.0001) [corrected] adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts. CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy. The roots of this difference is likely due to synergistic effects of CBD with other phytocompounds (aka Entourage effect), but this remains to be confirmed in controlled clinical studies.

Corrigendum: Potential Clinical Benefits of CBD-Rich Cannabis Extracts Over Purified CBD in Treatment-Resistant Epilepsy: Observational Data Meta-analysis.

[This corrects the article DOI: 10.3389/fneur.2018.00759.].

Genetic variation for growth and selection in adult plants of Eucalyptus badjensis.

The aim of this study was to evaluate Eucalyptus badjensis concerning the genetic variation for growth traits and the potential of the species in supporting a breeding programme. The field trial was a provenance/progeny test established in Campina da Alegria, Santa Catarina, Brazil (latitude 26°52'05.1″ S, longitude 51°48'47.5″ W, altitude 1,015 m) in a soil classified as Latossolic Alumino-Ferric Brown Nitosol. The experiment comprised 60 open-pollinated progenies from the provenances Glenbog and Badja State Forest, New South Wales, Australia. Ten replicates and plots with six plants in row were used. At the age of 17 years, 279 trees were assessed for diameter of the bole at breast height (DBH), total tree height (H) and volume of wood with bark (Vol). After submitting the data to statistical genetic analysis, the overall means for DBH, H and Vol were 45.17 cm, 33.30 m and 2.84 m3, and the estimates of additive coefficient of variation [ C V a(%)] were 12.59%, 5.91% and 26.51%, respectively. Heritability coefficients of additive effects ( h a 2) were also estimated and the following values were found: 0.443, 0.312 and 0.358. Thirty-nine trees from 25 different progenies were selected. The expected means of the provenances after improvement were 50.02 cm, 34.35 m and 3.47 m3 for DBH, H and Vol, respectively.

El alcoholismo: algunos aspectos epidemiológicos y sociales en la población atendida en 2 consultorios del médico de la familia / Alcoholism: some epidemiologic and social aspects in a target population of two family physician practices

Se realiza un estudio epidemiológico en 2 consultorios del Médico de la Familia correspondientes al Policlínico Docente "Bayamo Oeste" municipio Bayamo, provincia Granma, sobre el alcoholismo, en pacientes dispensarizados como tales. Se estudiaron distintas variables como edad, sexo, ocupación, nivel educacional, estado civil y edad de comienzo de la ingestión del tóxico. Predominó el sexo masculino entre 20 a 40 años, en el nivel educacional secundario y en el grupo de los solteros. Se encontró un gran porcentaje de desocupados y llamó la atención que comenzaron a ingerir las bebidas alcohólicas antes de los 25 años en el 89,5 % de la muestra