Efficacy and safety of modafinil in patients with idiopathic hypersomnia without long sleep time: a multicenter,randomized, double-blind,placebo-controlled,parallel-group comparison study

BackgroundFew treatments are available for patients with idiopathic hypersomnia (IH). Modafinil, an established treatment for narcolepsy, was tested for efficacy and safety in Japanese patients with IH without long sleep time.MethodsThis multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted at 20 institutions in Japan. Patients who met the diagnostic criteria of IH in the International Classification of Sleep Disorders (second edition) were included. The study comprised a ≥17-day observation period and a 3-week treatment period during which modafinil (200 mg) or placebo was administered orally once daily (in the morning). The primary efficacy endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Adverse events (AEs) were also recorded to evaluate safety.ResultsIn total, 123 patients were screened and 71 were randomized to receive modafinil (N = 34) or placebo (N = 37). Patients treated with modafinil experienced a significantly prolonged mean sleep latency on the MWT at the end of the study compared with placebo (5.02 min, 95% confidence interval: 3.26–6.77 min; p < 0.001). AEs occurred in 58.8% (20/34) and 27.0% (10/37) of patients in the modafinil and placebo groups, respectively. Frequent AEs in the modafinil group were headache (n = 6), dry mouth (n = 3), and nausea (n = 3); no clinically significant AEs occurred.ConclusionModafinil was shown to be an effective and safe treatment for excessive daytime sleepiness in patients with IH without long sleep time.Clinical trial registrationJapicCTI; 142539.     

维持性血液透析患者自主神经功能异常与透析中低血压的关系

目的以心率变异性(heart rate variability,HRV)为观察指标,分析维持性血液透析(maintenance hemodialysis,MHD)患者的自主神经功能异常与透析中低血压(intradialytichypotension,IDH)的关系.方法在透析过程中同步监测患者的血压和动态心电图,依据是否发生IDH将60例患者分为2组(血压下降组和对照组),比较2组的HRV指标,其中LFn代表交感神经活性,HFn代表迷走神经活性,LF/HF代表2者之间的平衡状态.以发生IDH为结果变量,以性别、年龄、透析龄、原发病是否糖尿病、心脏指数、中心血容量占体质量百分比、超滤量占体质量百分比和透析前LFn为预测变量,建立Logistic回归模型分析LFn对IDH的预测价值.结果对照组在透析过程中LFn水平和LF/HF比值逐渐升高,且升高趋势稳定(LFn中位数:透析开始时65.47nu,210min时73.79nu,P=0.001;LF/HF中位数:开始时2.17,210min时3.98,P＜0.001),HFn的水平则逐渐减低(HFn中位数:透析开始30.06nu,210min时19.43nu,P=0.002),而血压下降组的上述指标变化趋势不稳定,其中LFn在整个透析过程中都始终低于对照组.logistic回归模型显示,在校正了上述人口学特征和临床基础情况后,LFn对IDH的发生仍有预测价值,OR值为0.943(95%CI0.894～0.966).结论维持性血液透析患者交感神经活性在透析过程不能随血容量的下降持续、稳定的增高,与IDH的发生有密切关系;透析前交感神经活性的基础水平减低是IDH的独立危险因素,表明自主神经功能异常是导致透析中低血压的重要原因之一.     

Maintaining and repeating tocolysis: A reflection on evidence

It is inherent to human logic that both doctors and patients want to suppress uterine contractions when a woman presents in threatened preterm labor. Tocolysis is widely applied in women with threatened preterm labor with a variety of drugs. According to literature, tocolysis is indicated to enable transfer to a tertiary center as well as to ensure the administration of corticosteroids for fetal maturation. There is international discrepancy in the content and the implementation of guidelines on preterm labor. Tocolysis is often maintained or repeated. Nevertheless, the benefit of prolonging pregnancy has not yet been proven, and it is not impossible that prolongation of the pregnancy in a potential hostile environment could harm the fetus. Here we reflect on the use of tocolysis, focusing on maintenance and repeated tocolysis, and compare international guidelines and practices to available evidence. Finally, we propose strategies to improve the evaluation and use of tocolytics, with potential implications for future research.     

Randomized Trial of Interferon-Alpha plus Ursodeoxycholic Acid versus Interferon plus Placebo in Patients with Chronic Hepatitis C Resistant to Interferon

Background: Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA. Methods: Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months. Results: At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P &lt; 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids. Conclusions: An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids.     

Rotavirus vaccination compliance and completion in a Medicaid infant population

We examined completion and compliance rates of rotavirus (RV) vaccination according to the recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Food and Drug Administration approved Prescribing Information (PI) for Rotarix^® (RV1, GlaxoSmithKline Vaccines) and RotaTeq^® (RV5, Merck and Co.) among infants under one year of age covered by Medicaid programs. Healthcare claims data from state Medicaid programs that constituted the Truven Health MarketScan^® Multi-State Medicaid Database were retrieved from May 2008–June 2012. Infants were grouped under PI and ACIP cohorts based on the dosing regimens followed. The overall compliance per PI (n = 673,956) and ACIP (n = 695,612) recommendations were 24.5% and 28.2%, respectively; completion rates were 30.3% and 32.6%, respectively. In the PI cohort, infants who received RV1 had significantly higher compliance as compared with infants who received RV5 (65.2% vs. 31.3%; p < 0.0001); completion rates among infants receiving RV1 and RV5 were 65.3% and 46.4%, respectively (p < 0.0001). In the ACIP cohort, compliance with RV1 was significantly higher than RV5 (68.8% vs. 45.9%; p < 0.0001) as was the overall completion rate (73.5% vs. 48.8%; p < 0.0001). While compliance is increasing year over year, overall compliance of RV vaccines is suboptimal, with over 40% of eligible infants unvaccinated in both populations. The 2-dose RV vaccine showed better completion rates and higher compliance than the 3-dose RV vaccine in the United States. Public health initiatives focusing on suboptimal compliance and completion rates of RV vaccination in the Medicaid population could improve these metrics, thereby offering protection against RV infection.     

PICC导管在血液恶性肿瘤化疗中的应用与护理

目的：探究PICC导管在血液恶性肿瘤化疗中的应用与护理。方法选取治疗且需要长期化疗的血液恶性肿瘤患者76例并使用PICC导管。结果76例患者中,发生机械性静脉炎7例,导管脱出2例,导管堵塞1例,导管材料过敏2例,拔管9例,放弃治疗1例,平均置管时间（113.38±11.5）d。进行化疗后,无患者发生穿刺点感染和局部渗血等并发症。结论使用PICC导管并正确维护能够有效保护患者的血管,对患者进行合理有效的护理是进行PICC置管的关键。