Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities

Objective: Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited. In this study we aimed to report the experience of parents who administer, under supervision, oral cannabinoids to their children with ASD.Methods: After obtaining a license from the Israeli Ministry of Health, parents of children with ASD were instructed by a nurse practitioner how to administer oral drops of cannabidiol oil. Information on comorbid symptoms and safety was prospectively recorded biweekly during follow-up interviews. An independent group of specialists analyzed these data for changes in ASD symptoms and drug safety.Results: 53 children at a median age of 11 (4–22) year received cannabidiol for a median duration of 66 days (30–588). Self-injury and rage attacks (n = 34) improved in 67.6% and worsened in 8.8%. Hyperactivity symptoms (n = 38) improved in 68.4%, did not change in 28.9% and worsened in 2.6%. Sleep problems (n = 21) improved in 71.4% and worsened in 4.7%. Anxiety (n = 17) improved in 47.1% and worsened in 23.5%. Adverse effects, mostly somnolence and change in appetite were mild.Conclusion: Parents’ reports suggest that cannabidiol may improve ASD comorbidity symptoms; however, the long-term effects should be evaluated in large scale studies

Delayed versus classic orthostatic hypotension: clinical and prognostic implications

Purpose: Orthostatic hypotension (OH) is a common disorder, especially among hospitalised patients. Classic OH is defined as occurring 3 or less minutes of orthostatic stress, and delayed OH as occurring after 3 min of stress. We aimed to compare clinical characteristics and prognosis between inpatients with classic vs. delayed OH. Methods: We performed a retrospective analysis of data from 358 inpatients, aged ≥60 years, who were evaluated for the occurrence of OH at the initial phase of ambulation in four previous prospective studies in our department. Demographic, clinical and prognostic data were compared between patients with (n = 191) vs. without (n = 167) OH, classic (n = 138) vs. delayed (n = 53) OH and seated (n = 115) vs. standing (n = 76) OH. Results: Demographic characteristics, duration of bed rest, the main reasons for admission and the use of offending medications were comparable between the delayed and classic OH groups. Mean maximal postural diastolic (p < .001) and systolic (p = .063) blood pressure falls were higher among patients with classic v. delayed OH. No statistically significant difference between the patients with classic and delayed OH were observed in the occurrence of OH-related symptoms (62.3 vs. 69.8%, p = .42). During a median follow-up of 5.5 years, no statistically significant differences in survival were observed between patients with vs. without OH (p = .14), classic vs. delayed OH (p = .68) and seated vs. standing OH (p = .067). On multivariate analysis, these variables remained not significantly associated with decreased survival. Conclusions: Among inpatients, delayed OH is associated with a lesser magnitude of orthostatic blood pressure fall than classic OH. However, rates of symptomatic OH and long-term mortality were comparable between the groups. Thus, among hospitalised patients, delayed OH should be considered as posing the same severity as classic OH

A rise in mean platelet volume during hospitalization for community-acquired pneumonia predicts poor prognosis: a retrospective observational cohort study

Abstract Background Clinical characteristics and the prognostic significance of changes in mean platelet volume (MPV) during hospitalization for community-acquired pneumonia (CAP) have not been investigated. Methods Among 976 adults hospitalized for CAP, clinical characteristics, in-hospital outcomes (transfer to the intensive care unit, treatment with mechanical ventilation, prolonged hospital stay and death), and all-cause mortality following discharge, were compared according to ΔMPV (MPV on discharge minus MPV on admission): groups A (no rising MPV, ΔMPV < 0.6 fL) and B (rising MPV, ΔMPV ≥ 0.6 fL). Results Groups A and B comprised 83.8% and 16.2% of patients, respectively. Patients with a rise in MPV were more likely to be older, and to present with renal dysfunction, cerebrovascular disorder and severe pneumonia than were patients with no rise in MPV. On discharge, lower values of platelets and higher levels of neutrophils were observed in group B. Rising MPV strongly predicted a need for mechanical ventilation and in-hospital death (the respective relative risks: 2.62 and 6.79; 95% confidence intervals: 1.54–4.45 and 3.48–13.20). The respective 90-day, 3-year and total (median follow-up of 54 months) mortality rates were significantly higher in group B (29.1%, 43.0% and 50.0%) than group A (7.3%, 24.2% and 32.6%), p < 0.001 for all comparisons. A rise in MPV was a powerful predictor of all-cause mortality (relative risk 1.26 and 95% confidence interval 1.11–1.43). Conclusions Rising MPV during hospitalization for CAP is associated with a more severe clinical profile than no rise in MPV. A rise in MPV strongly predicts in-hospital and long-term mortality

Prognostic significance of platelet count changes during hospitalization for community-acquired pneumonia

The prognostic significance of platelet count (PC) changes during hospitalization for community-acquired pneumonia (CAP) has not been investigated. For 976 adults, clinical data during hospitalization for CAP and all-cause mortality following discharge were compared according to ΔPC (PC on discharge minus PC on admission): groups A (declining PC, ΔPC 50 × 109/l), and according to the presence of thrombocytopenia, normal PC, and thrombocytosis on admission/discharge. Groups A, B, and C comprised 7.9%, 46.5%, and 45.6% of patients, respectively. On hospital admission/discharge, thrombocytopenia, normal PC, and thrombocytosis were observed in 12.8%/6.4%, 84.1%/84.4%, and 3.1%/9.2% of patients, respectively. The respective 90-day, 3-year, and total (median follow-up of 54 months) mortality rates were significantly higher: in group A (40.3%, 63.6%, and 72.7%), compared to groups B (12.3%, 31.5%, and 39.0%) and C (4.9%, 17.3%, and 25.4%), p < 0.001; and in patients with thrombocytopenia at discharge (27.4%, 48.4%, and 51.6%), compared to those with normal PC (10.2%, 26.9%, and 35.4%) and thrombocytosis (8.9%, 17.8%, and 24.4%) at discharge (p < 0.001). Mortality rates were comparable among groups with thrombocytopenia, normal PC, and thrombocytosis at admission (p = 0.6). In the entire sample, each 100 × 109/l increment of ΔPC strongly predicted lower mortality (p < 0.001, relative risk 0.73, 95% confidence interval 0.64−0.83). In conclusion, PC changes are common among CAP inpatients. Rising PC throughout hospitalization is a powerful predictor of better survival, while declining PC predicts poor outcome. Evaluation of PC changes during hospitalization for CAP may provide useful prognostic information

DataSheet1_Medical cannabis for the treatment of comorbid symptoms in children with autism spectrum disorder: An interim analysis of biochemical safety.docx

Background: Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder and no effective treatment for the core symptoms is currently available. The present study is part of a larger clinical trial assessing the effects of cannabis oil on autism co-morbidities.Objectives: The aim of the present study was to assess the safety of a CBD-rich oil treatment in children and adolescents with ASD.Methods: Data from 59 children and young adults (ages 5–25 years) from a single-arm, ongoing, prospective, open-label, one center, phase III study was analyzed. Participants received the Nitzan Spectrum® Oil, with cannabis extracts infused in medium chain triglyceride (MCT) oil with a cannabidiol:THC ratio of 20:1, for 6 months. Blood analysis was performed before treatment initiation, and after 3 months. Complete blood count, glucose, urea, creatinine, electrolytes, liver enzymes (AST, ALT, gamma glutamyl transferase), bilirubin, lipid profile, TSH, FT4, thyroid antibodies, prolactin, and testosterone measurements were performed at baseline, prior to starting treatment and at study midpoint, after 3 months of treatment.Results: 59 children (85% male and 15% female) were followed for 18 ± 8 weeks (mean ±SD). The mean total daily dose was 7.88 ± 4.24 mg/kg body weight. No clinically significant differences were found in any of the analytes between baseline and 3 months follow up. Lactate dehydrogenase was significantly higher before treatment (505.36 ± 95.1 IU/l) as compared to its level after 3 months of treatment (470.55 ± 84.22 IU/L) (p = 0.003). FT4 was significantly higher after 3 months of treatment (15.54 ± 1.9) as compared to its level before treatment (15.07 ± 1.88) (p = 0.03), as was TSH [(2.34 ± 1.17) and (2.05 ± 1.02)] before and after 3 months of treatment, respectively (p = 0.01). However, all these values were within normal range. A comparison of the group with additional medications (n = 14) to those who received solely medical cannabis (n = 45) showed no difference in biochemical analysis, including liver enzymes, which remained stable, except for change in potassium level which was significantly higher in the group that did not receive additional medications (0.04 ± 0.37) compared to the group receiving concomitant drug therapy (-0.2 ± 0.33) (p = 0.04). A comparison of patients who received a high dose of the cannabis oil (upper quartile-16 patients), with those receiving a low dose (lower quartile—14 patients) showed no significant difference between the two groups, except for the mean change of total protein, which was significantly higher among patients receiving high dose of CBD (0.19 ± 2.74) compared to those receiving a low dose of CBD (1.71 ± 2.46 (p = 0.01), and mean change in number of platelets, that was significantly lower among patients who received high dose of CBD (13.46 ± 31.38) as compared to those who received low dose of CBD (29.64 ± 26.2) (p = 0.0007). However, both of these changes lack clinical significance.Conclusion: CBD-rich cannabis oil (CBD: THC 20:1), appears to have a good safety profile. Long-term monitoring with a larger number of participants is warranted.</p