Data_Sheet_1_Dual orexin receptor antagonists for treatment of insomnia: A systematic review and meta-analysis on randomized, double-blind, placebo-controlled trials of suvorexant and lemborexant.PDF

Study objectivesRecent treatment guidelines for chronic insomnia recommend pharmacological and non-pharmacological therapies. One of the contemporary drug options for insomnia includes dual orexin receptor antagonist (DORA), such as suvorexant and lemborexant. We conducted a systematic review and meta-analysis for the treatment of insomnia with suvorexant and lemborexant based on randomized, double-blind, placebo-controlled Trials.MethodsWe conducted a comprehensive search on three databases (PubMed/Medline, Web of Science, and Cochrane Library) till August 14, 2021, without any restrictions to retrieve the relevant articles. The effect sizes were computed presenting the pooled mean difference or risk ratio along with 95% confidence interval of each outcome.ResultsOur search showed eight articles (five for suvorexant and three for lemborexant). Results of diary measures, rating scales, polysomnography results, treatment discontinuation, and adverse events were measured. All efficacy outcome measures favorably and significantly differed in the suvorexant compared to placebo. Safety profile did not differ significantly except for somnolence, excessive daytime sleepiness/sedation, fatigue, back pain, dry mouth, and abnormal dreams. Important adverse events including hallucinations, suicidal ideation/behavior and motor vehicle accidents did not differ between suvorexant and placebo. All the efficacy outcomes significantly differed between lemborexant 5 and lemborexant 10 compared to placebo. Somnolence rate for lemborexant 5 and lemborexant 10 and nightmare for lemborexant 10 were significantly higher than placebo.ConclusionThe present meta-analysis reported that suvorexant and lemborexant are efficacious and safe agents for the patients with insomnia. Further data in patients with insomnia and various comorbid conditions are needed.</p

Additional file 1 of High-density lipoprotein cholesterol efflux capacity in patients with obstructive sleep apnea and its relation with disease severity

Additional file 1: S Figure 1. Cholesterol efflux capacities according to sex. a) Total, b) non-ABCA1, and c) ABCA1 CEC displayed no statistically remarkable difference between females and males in the whole population. d) Total CEC, e) Non-ABCA1 CEC, and f) ABCA1 CEC indicated no remarkable difference in males compared to females in both OSA patients and controls

Additional file 2 of High-density lipoprotein cholesterol efflux capacity in patients with obstructive sleep apnea and its relation with disease severity

Additional file 2: S Figure 2. Cholesterol efflux capacities according to BMI categories. a) Total, b) Non-ABCA1, and c) ABCA1 CEC have shown no considerable change between normal weight (BMI  25) in the whole population. d) Total CEC, e) Non-ABCA1 CEC, and f) ABCA1 CEC demonstrated no change in normal weight (BMI  25) in both OSA patients and controls

Raw data.

Backgroundobstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with increased risk factors for cardiovascular diseases (CVDs). Oxidative stress, insulin resistance, inflammation, and endothelial dysfunction are increased in OSA patients and microRNAs (miRs) are regulatory elements that influence these pathological mechanisms. miR125a, miR126, and miR146a-5p play a role in these pathological mechanisms and have not been evaluated in patients with OSA.MethodThis case-control study was performed on 90 OSA patients and 34 controls. Circulating levels of miR125a, miR126, and miR146a-5 were determined using real-time PCR, and serum levels of hsCRP, ICAM-1, and VCAM-1 were evaluated using ELISA kits.ResultsmiR125a and miR146a were elevated in patients with OSA compared to controls while miR126 decreased significantly. All three miRs indicated a remarkable difference between the mild-OSA group compared to the severe-OSA group. Furthermore, patients with OSA showed elevated levels of hsCRP, ICAM-1, and VCAM-1. Multiple linear regression indicated an independent association of miR125a with ICAM-1 and hsCRP, miR126 associated with VCAM-1 and total cholesterol, and miR146a-5p represented an association with apnea-hypopnea index and ICAM-1. Furthermore, miR146a-5p illustrated a good diagnostic ability to differentiate between OSA and controls.ConclusionsCirculating miR125a, miR126, and miR146a-5p fluctuations in patients with OSA and their relations with markers of endothelial dysfunction provide in vivo evidence and suggest a potential role for these miRs with endothelial dysfunction in patients with OSA.</div

Pearson correlation of miR125a, miR126, and miR146a-5p with other variables.

Pearson correlation of miR125a, miR126, and miR146a-5p with other variables.</p

The basic characteristic of the studied population.

The basic characteristic of the studied population.</p

Odds ratio (OR) of the OSA presence according to circulating levels of miRs.

Odds ratio (OR) of the OSA presence according to circulating levels of miRs.</p

Circulating levels of miRs.

a) miR125a levels increased in patients with OSA compared to controls, and in the severe-OSA group compared to the mild-OSA group. b) miR126 concentration was lower in OSA compared to controls and in the severe-OSA group compared to the mild-OSA group. c) circulating mi146a were found to be higher in OSA patients in comparison to controls, and mild-OSA had a lower concentration of miR146a-5p compared with moderate-OSA and severe-OSA groups. ns, not significant; * p<0.05, ** p<0.01, *** p<0.001 and **** p<0.0001.</p

Fig 3 -

ROC curve for the diagnostic ability of a) miR125a, b) miR126, and c) miR146a-5p.</p

Serum levels of hsCRP, ICAM-1, and VCAM-1.

a) Serum levels of hsCRP were elevated in OSA patients compared to controls, and the severe-OSA group represents a higher concentration of hsCRP compared with mild-OSA and moderate-OSA groups. b) Serum concentration of ICAM-1 was higher in the OSA group compared to controls, and the severe-OSA group indicated higher ICAM-1 compared to the mild-OSA group. c) Patients with OSA were found to have a higher concentration of VCAM-1 compared to controls. ns, not significant; * p<0.05, ** p<0.01, *** p<0.001 and **** p<0.0001.</p