Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis.

Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.

[Diagnostic Application of Invasive Cardiopulmonary Exercise Test in Patients with Unexplained Dyspnea].

OBJECTIVE: To explore the clinical diagnostic application of invasive cardiopulmonary exercise test (iCPET) in patients with unexplained dyspnea. METHODS: A retrospective analysis was conducted, covering patients with a chief complaint of exertional dyspnea between May 5, 2017 and October 1, 2020. Right cardiac catheterization examination was performed on patients whose cause had not been identified through routine examination, and further iCPET was performed on patients if no clear etiology was identified through right cardiac catheterization. According to the results and the diagnostic criteria of iCPET, patients showing no obvious abnormalities in the right cardiac catheterization examination were divided into four subgroups: exercise-induced pulmonary arterial hypertension (eiPAH), exercise-induced heart failure with preserved ejection fraction (eiHFpEF), preload failure, and oxidative myopathy. By comparing the lab test, echocardiography, right heart catheter and iCPET peak exercise data of the subgroups, the disease distribution and exercise hemodynamic characteristics of patients with unexplained dyspnea examined by iCPET were described. RESULTS: Of the 1 046 patients with exertional dyspnea, 771 were diagnosed with routine examination, while among the remaining 275 patients, 131 (47.6%) were diagnosed with right cardiac catheterization and 144 (52.4%) showed no clear etiology after routine examination and right cardiac catheterization. Of these 144 patients, 49 (34.0%) received iCPET with a median exercise time of 375 s. A total of 47 patients completed the examination, with a male-to-female ratio of 0.27∶1 and an average age of (47.9±14.4) years old. Among the 47 patients, 76.6% (36/47) aged between 20 and 59 and 78.7% (36/47) lived in urban areas. The preload failure group ( n=27) showed low right atrium pressure at peak exercise intensity. The eiHFpEF group ( n=9) showed high wedge pressure of pulmonary capillaries at peak of exercise intensity. The eiPAH group ( n=8) showed high average pulmonary artery pressure at peak exercise intensity. The oxidative myopathy group ( n=3) was characterized by impairment of tissue uptake and/or utilization of oxygen during exercise. According to the comparison among the three subgroups of the preload failure, eiHFpEF and eiPAH, the eiPAH group had the highest blood K + level in routine examination, while the preload failure group had the lowest blood K + level ( P=0.014). The iCPET of the three subgroups showed statistically significant ( P=0.001) difference in right atrial pressure increase during exercise. Among the three, the eiHFpEF group had the highest increase and the preload failure group had the lowest increase. Conclusion 　In unexplained dyspnea patients showing no abnormal results in right cardiac catheterization examination, the main cause was preload failure, which manifested as low right atrial pressure at peak exercise intensity. The study showed that iCPET was of important value for dyspnea cases when the cause of the condition was not revealed with right cardiac catheterization.