Involvement of Plasma Melatonin in Medication-Overuse Headache: A Cross-Sectional Study.

OBJECTIVES: Patients with medication-overuse headache (MOH) are often complicated with anxiety, depression, and sleep disorders and are associated with dependence behavior and substance abuse. Melatonin has physiological properties including analgesia, regulation of circadian rhythms, soporific, and antidepressant and affects drug preference and addiction. This study aimed to investigate the role of melatonin in MOH compared with episodic migraine (EM) and healthy controls and to verify the relationship between plasma melatonin levels and psychiatric symptoms. METHODS: Thirty patients affected by MOH, 30 patients with EM, and 30 matched healthy controls were enrolled. All subjects completed a detailed headache questionnaire and scales including the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index, the Leeds Dependence Questionnaire. Melatonin levels in plasma samples were measured by enzyme immunoassay method. RESULTS: The levels of plasma melatonin were significantly different among 3 groups of subjects (MOH, 7.74 [5.40-9.89]; EM, 9.79 [8.23-10.62]; Control, 10.16 [8.60-17.57]; H = 13.433; P = 0.001). Significantly lower levels of melatonin were found in MOH patients compared with healthy controls ( P = 0.001). The level of plasma melatonin inversely correlated with the scores of HADS-Anxiety ( r = -0.318, P = 0.002), HADS-Depression ( r = -0.368, P < 0.001), Pittsburgh Sleep Quality Index ( r = -0.303, P = 0.004), and Leeds Dependence Questionnaire ( r = -0.312, P = 0.003). CONCLUSIONS: This study innovatively detects the plasma melatonin levels in MOH patients and explores the association between melatonin levels and psychiatric symptoms. Melatonin may be potential complementary therapy in the treatment of MOH considering its comprehensive role in multiple aspects of MOH.

Trans-arterial chemoembolization combined with Jinlong capsule for advanced hepatocellular carcinoma: a PRISMA-compliant meta-analysis in a Chinese population.

CONTEXT: Jinlong capsule (JLC) is an animal-derived traditional Chinese medical preparation for advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is still not well investigated. OBJECTIVE: This study summarizes the efficacy and safety of JLC combined with trans-arterial chemoembolization (TACE) for patients with HCC. METHODS: The databases PubMed, Cochrane Library, Web of Science, EMBASE, Medline, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database and Chinese Biological Medicine Database were systematically searched from the date of their inception until February 2020. Jinlong capsule, trans-arterial chemoembolization, and hepatocellular carcinoma were the key terms searched. Randomized controlled trials and high-quality prospective cohort trials comparing the combined use of JLC and TACE versus TACE for HCC were included. Data were pooled using random or fixed effect models depending on heterogeneity. RESULTS: Data from 19 articles with 1,725 HCC patients were analysed. Compared with TACE treatment alone, the combination of TACE and JLC significantly prolonged patients' 6-36 month overall survival (p < 0.05), and markedly improved the overall response rate (RR = 1.37, 95% CI = 1.24-1.52, p < 0.00001) and disease control rate (RR = 1.11, 95% CI = 1.06-1.17, p < 0.0001) of patients. The liver function, quality of life, and immune function of patients were significantly improved; the partial adverse events related to TACE were also effectively relieved after the combination treatment. CONCLUSION: This meta-analysis suggests that the combination of TACE and JLC is more effective in the treatment of HCC than treatment with TACE alone.

Effectiveness of transcutaneous electrical nerve stimulation for the treatment of migraine: a meta-analysis of randomized controlled trials.

BACKGROUND: Migraine is now ranked as the second most disabling disorder worldwide reported by the Global Burden of Disease Study 2016. As a noninvasive neurostimulation technique, transcutaneous electrical nerve stimulation(TENS) has been applied as an abortive and prophylactic treatment for migraine recently. We conduct this meta-analysis to analyze the effectiveness and safety of TENS on migraineurs. METHODS: We searched Medline (via PubMed), Embase, the Cochrane Library and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials, which compared the effect of TENS with sham TENS on migraineurs. Data were extracted and methodological quality assessed independently by two reviewers. Change in the number of monthly headache days, responder rate, painkiller intake, adverse events and satisfaction were extracted as outcome. RESULTS: Four studies were included in the quantitative analysis with 161 migraine patients in real TENS group and 115 in sham TENS group. We found significant reduction of monthly headache days (SMD: -0.48; 95% CI: -0.73 to - 0.23; P < 0.001) and painkiller intake (SMD: -0.78; 95% CI: -1.14 to - 0.42; P < 0.001). Responder rate (RR: 4.05; 95% CI: 2.06 to 7.97; P < 0.001) and satisfaction (RR: 1.85; 95% CI: 1.31 to 2,61; P < 0.001) were significantly increased compared with sham TENS. CONCLUSION: This meta-analysis suggests that TENS may serve as an effective and well-tolerated alternative for migraineurs. However, low quality of evidence prevents us from reaching definitive conclusions. Future well-designed RCTs are necessary to confirm and update the findings of this analysis. SYSTEMATIC REVIEW REGISTRATION: Our PROSPERO protocol registration number: CRD42018085984 . Registered 30 January 2018.

Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.

Unintended inhibition of the cardiac potassium channel human ether-a-go-go-related gene (hERG) is considered the main culprit in drug-induced arrhythmias known as torsades de pointes. Electrophysiology is the most reliable in vitro screening method for identifying potential cardiac hERG liabilities, but only the recent advent of planar electrode-based voltage clamp electrophysiology promises sufficient throughput to support the drug testing needs of most drug discovery programs. We have assessed the reliability of this new format of the voltage clamp technology in measuring the activity of small molecules on the hERG channel. Based on the results herein of a screening against a panel of well-characterized hERG-active and -inactive molecules, we demonstrate that planar electrode electrophysiology, utilizing the Sealchip and PatchXpress technology platform (AVIVA Biosciences Corp., San Diego, CA), is comparable to traditional electrophysiology based on glass micropipettes in its reliability and data content. The new technology will allow significantly higher throughput and more thorough testing of pharmaceutical compounds.