Pharmacokinetics of cannabidiol in children with refractory epileptic encephalopathy

Growing interest in the clinical use of cannabidiol (CBD) as adjuvant therapy for pediatric refractory epileptic encephalopathy emphasizes the need for drug treatment optimization. The aim of this study was to characterize the pharmacokinetics of CBD in pediatric patients with refractory epileptic encephalopathy receiving an oil‐based oral solution. To evaluate CBD concentrations, six serial blood samples per patient were collected after the morning dose of CBD, at least 21 days after the beginning of treatment. Twelve patients who received a median (range) dose of 12.2 (5.3‐19.4) mg/kg/d (twice daily) were included in the analysis. Median (range) CBD time to maximum plasma concentration, maximum plasma concentration, and area under the concentration versus time curve up to 6 hours after dosing were 3.2 hours (1.9‐6.2), 49.6 ng/mL (14.4‐302.0), and 226.3 ng ? h/mL (70.5‐861.3), respectively. CBD systemic exposure parameters were in the lower range of previous reports in pediatric patients receiving doses in a similar range. Most of our patients (83%) showed little CBD plasma level fluctuation during a dosing interval, comparable to that encountered after oral administration of an extended release drug delivery system. CDB administration was generally safe and well tolerated, and a novel levothyroxine‐CBD interaction was recorded. Similar to other studies, large interindividual variability in CBD exposure was observed, encouraging the use of CBD therapeutic drug monitoring.     

CANVAS: a late onset ataxia due to biallelic intronic AAGGG expansions

Journal of Neurology - The ataxias are a group of disorders that manifest with balance, movement, speech and visual problems. They can arise due to dysfunction of the cerebellum, the vestibular...     

1324 prison suicides in 10 countries in South America: incidence,relative risks,and ecological factors

Purpose

Although suicide rates of prison populations and incidence factors have been reported for high-income countries, data from low- and middle-income regions are lacking. The purpose of the study was to estimate suicide rates among prison populations in South America, to examine prison-related factors, and to compare suicide rates between prison and general populations.

Methods

In this observational study, we collected the numbers of suicides in prison, rates of prison occupancy, and incarceration rates from primary sources in South America between 2000 and 2017. We compared suicide rates among prisoners with incidence rates in the general populations by calculating incidence rate ratios. We assessed the effect of gender, year, incarceration rates and occupancy on suicide rates in the prison populations using regression analyses.

Results

There were 1324 suicides reported during 4,437,591 person years of imprisonment between 2000 and 2017 in 10 South American countries. The mean suicide rate was 40 (95% CI 16–65) per 100,000 person years for male and female genders combined. The pooled incidence rate ratio of suicide between prison and general populations was 3.9 (95% CI 3.1–5.1) for both genders combined, 2.4 (95% CI 1.9–3.1) for men and a higher ratio in women (13.5, 95% CI 6.9–26.9). High occupancies of prisons were associated with lower incidence of suicide (β = − 58, 95% CI − 108.5 to − 7.1).

Conclusions

Suicides during imprisonment in South America are an important public health problem. Suicide prevention strategies need to target prison populations.

     

Genetic characterization of HA gene of low pathogenic H9N2 influenza viruses isolated in Israel during 2006–2012 periods

H9N2 influenza viruses are isolated in Israel since 2000 and became endemic. From November 2006 to the beginning of 2012, many H9N2 viruses were identified, all belonged to the Asian G1-like lineage represented by A/qu/Hong Kong/G1/97 (H9N2). In the present study, 66 isolates were selected for their hemagglutinin gene characterization. Most H9N2 isolates were distributed between two main groups, identified as the 4th and 5th introductions. The 5th introduction, was represented by a compact cluster containing viruses isolated in 2011–2012; the 4th introduction was subdivided into two subgroups, A and B, each containing at least two clusters, which can be identified as A-1, A-2, B-1, and B2, respectively. Genetic analysis of the deduced HA proteins of viruses, belonging to the 4th and 5th introductions, revealed amino acid variations in 79 out of 542 positions. All isolates had typical low pathogenicity motifs at the hemagglutinin (HA) cleavage site. Most viruses had leucine at position 216 in a receptor binding pocket that enables the virus to bind successfully with the cellular receptors intrinsic to mammals, including humans. It was shown that the differences between the HA proteins of viruses used for vaccine production and local field isolates increased in parallel with the duration and intensity of vaccine use, illustrating the genetic diversity of the H9N2 viruses in Israel.     

Sex-specific impact of severe obesity in the outcomes of hospitalized patients with COVID-19: a large retrospective study from the Bronx,New York

It has been demonstrated that obesity is an independent risk factor for worse outcomes in patients with COVID-19. Our objectives were to investigate which classes of obesity are associated with higher in-hospital mortality and to assess the association between obesity and systemic inflammation. This was a retrospective study which included consecutive hospitalized patients with COVID-19 in a tertiary center. Three thousand five hundred thirty patients were included in this analysis (female sex: 1579, median age: 65 years). The median body mass index (BMI) was 28.8 kg/m². In the overall cohort, a J-shaped association between BMI and in-hospital mortality was depicted. In the subgroup of men, BMI 35–39.9 kg/m² and BMI ≥40 kg/m² were found to have significant association with higher in-hospital mortality, while only BMI ≥40 kg/m² was found significant in the subgroup of women. No significant association between BMI and IL-6 was noted. Obesity classes II and III in men and obesity class III in women were independently associated with higher in-hospital mortality in patients with COVID-19. The male population with severe obesity was the one that mainly drove this association. No significant association between BMI and IL-6 was noted.