CIHR Canadian HIV Trials Network Co-Infection and Concurrent Diseases Core: Updated Canadian guidelines for the treatment of hepatitis C infection in HIV-hepatitis C coinfected adults

BACKGROUND:Hepatitis C virus (HCV) coinfection occurs in 20% to 30% of Canadians living with HIV and is responsible for a heavy burden of morbidity and mortality. Management of HIV-HCV coinfection is more complex due to the accelerated progression of liver disease, the timing and nature of antiretroviral and HCV therapy, mental health and addictions management, socioeconomic obstacles and drug-drug interactions between new HCV direct-acting antiviral therapies and antiretroviral regimens.OBJECTIVE:To update national standards for the management of HCV-HIV coinfected adults in the Canadian context.METHODS:A standing working group with specific clinical expertise in HIV-HCV coinfection was convened by The Canadian Institute of Health Research HIV Trials Network to review recently published data regarding HCV antiviral treatments and to update the Canadian HIV-HCV coinfection guidelines.RESULTS:Recent data suggest that the gap in sustained virological response rates between HCV monoinfection and HIV-HCV coinfection has been eliminated with newer HCV antiviral regimens. All HIV-HCV coinfected individuals should be assessed for HCV therapy. First-line treatment for genotypes 1 through 6 includes pegylated interferon and weight-based ribavirin dosing plus the nucleotide sofosbuvir for 12 weeks. Sofosbuvir in combination with the protease inhibitor simeprevir is another first-line consideration for genotype 1 infection. Sofosbuvir with ribavirin for 12 weeks (genotype 2) and 24 weeks (genotype 3) is also recommended as first-line treatment.DISCUSSION:Recommendations may not supersede individual clinical judgement.     

Randomized Controlled Trial of Bixalomer Versus Sevelamer Hydrochloride in Hemodialysis Patients With Hyperphosphatemia

Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease. Bixalomer is a nonabsorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract. This study compared the efficacy and safety of bixalomer versus sevelamer hydrochloride for controlling hyperphosphatemia in hemodialysis patients. This was a multicenter, randomized open‐label, non‐inferiority study. The primary endpoint was serum phosphate on completion of treatment. Administration of bixalomer was started at 1.5 g/day and adjusted to a maximum of 7.5 g/day depending on the serum phosphate level. Sevelamer hydrochloride was started at 3.0 or 6.0 g/day and adjusted to a maximum of 9.0 g/day. Treatment was continued for 12 weeks. Fifty‐five patients were randomized to each treatment group. After 12 weeks, the baseline adjusted mean serum phosphate level was 5.87 mg/dL in the bixalomer group and 5.55 mg/dL in the sevelamer group, with a difference of 0.31 mg/dL and 95% confidence interval (CI) of [?0.13 to 0.76]. The upper limit of the 95%CI for the difference of the mean serum phosphate level between the two groups was <1.0 mg/dL, which was the non‐inferiority margin in this study. Thus, non‐inferiority of bixalomer to sevelamer was confirmed. The incidence of adverse events was lower in the bixalomer group, and bixalomer did not promote acidosis. Bixalomer achieved a similar reduction of serum phosphate to sevelamer, while causing fewer adverse reactions. Consequently, the usefulness of bixalomer for treating hyperphosphatemia was confirmed.     

微量白蛋白尿与急性缺血性卒中的严重程度和转归的关系

目的 探讨微量白蛋白尿(microalbuminuria,MAU)与急性缺血性卒中的危险因素、病情严重程度及转归的关系.方法 前瞻性纳入连续的急性缺血性卒中患者,根据尿白蛋白/肌酐比率(urine albumin/creatinine ratio,UACR)分为MAU阳性组(≥30 mg/g)和MAU阴性组(＜30 mg/g),根据改良Rankin量表(modified Rankin Scale,mRS)评分分为转归良好组(0～2分)和转归不良组(＞2分),对各项人口统计学和临床资料进行比较,并分析急性缺血性卒中转归不良和MAU阳性的独立因素.结果 共纳入156例急性缺血性卒中患者,其中男性84例,女性72例;年龄53～ 78岁,平均(65.4±6.2)岁;发病至入院时间为1.5～28 h;94例转归良好,62例转归不良,无死亡病例;76例MAU阳性,80例MAU阴性.多变量logistic回归分析显示,高龄[优势比(odds ratio,OR)1.992,95％可信区间(c onfidence interval,CI)1.108～2.374;P=0.015]、合并糖尿病(OR 2.497,95％ CI1.177～5.298;P =0.017)和心房颤动(OR 2.338,95％ CI1.062 ～5.148;P=0.035)、高血清高半胱氨酸(homocysteine,Hcy)水平(OR 2.541,95％ CI 1.073～6.02;P=0.047)和UACR(OR 2.130,95％ CI1.396 ～3.017;P =0.001)、MAU阳性(OR 3.291,95％ CI1.681 ～6.444;P=0.001)、高基线美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale,NIHSS)评分(OR9.196,95％ CI2.828～19.815;P ＜0.001)是急性缺血性卒中患者转归不良的独立危险因素.MAU阳性组合并糖尿病的患者比例(P=0.038)以及空腹血糖水平(P=0.025)、血清Hcy水平(P=0.022)和颈动脉内膜-中膜厚度(intima-media thickness,IMT)(P=0.019)与MAU阴性组存在显著性差异.MAU阳性组前循环梗死比例较低(P=0.033),基线NIHSS评分(P=0.003)和转归不良率较高(P＜0.001).多变量logistic回归分析显示,合并糖尿病(OR 2.237,95％ CI1.036 ～4.829;P =0.040)以及空腹血糖(OR 1.223,95％ CI1.145 ～1.673;P=0.027)和Hcy水平(OR 2.542,95％ CI 1.047～6.612;P=0.025)、颈动脉IMT(OR1.295,95％ CI1.106 ～1.362;P=0.023)和基线NIHSS评分(OR1.206,95％ CI1.044 ～1.219;P =0.023)增高与急性缺血性卒中患者MAU阳性独立相关.结论 MAU阳性是急性缺血性卒中转归不良的独立危险因素之一,且与急性缺血性卒中的部分危险因素密切相关,并对急性缺血性卒中病情严重程度和转归有着显著的影响.     

输血相关性急性肺损伤研究进展

输血相关性急性肺损伤（transfusion-related acute lung injury,TRALI）是输血相关性疾病中最常见的类型.其发病率及病死率高,定义基于临床和影像学参数.TRALI分为免疫介导性和非免疫介导性,患者基础情况和输血因素共同决定着TRALI的发生.TRALI的预防主要包括避免使用女性供血者血浆制品及避免输注多个供血者的混合血浆.但目前所有预防措施只能减少而不是消除TRALI的发生,且对于这种危及生命的综合征尚无明确治疗方法,因此防治TRALI的工作任重而道远.本文对TRALI的定义、发病率、发病机制、临床表现、预防及治疗作一综述.     

ALI/ARDS的治疗进展

关于ALI和ARDS发病机制的研究和探讨众多.主要集中在炎症反应、氧化应激损伤、凝血纤溶系统失衡、细胞损伤及凋亡、肺泡液体清除异常、医疗操作损伤等层面.针对这些因素所带来的机体损伤,人们进行了大量的实验室及临床的研究与治疗,虽然表现出一定的治疗效果,但是单独应用的适用范围仍有限.     

隐源性机化性肺炎18例临床分析

目的 分析我院经活检确认的18例隐源性机化性肺炎患者,总结其在临床、治疗及预后方面的特点.方法 收集我院2008年1月至2012年10月间经肺活检证实的18例隐源性机化性肺炎患者的所有资料,回顾性分析本组患者的临床资料、易患因素、影像学表现、病理、实验室检查等的特点.结果 18例患者平均年龄（59±11）岁.本组18例患者临床症状主要为咳嗽、咳痰、胸闷、气短等呼吸系统症状,少数有盗汗、乏力、消瘦等全身症状.影像学表现多种多样,可有斑片影、实变影、磨玻璃样变影等,最初发病多以斑片影为主.肺功能表现为轻度限制性通气功能障碍,弥散功能受损.14例（77.8％）患者治愈,4例（22.2％）患者复发,对糖皮质激素效果较好.结论 隐源性机化性肺炎容易误诊为肺部感染,诊断需要综合临床-影像-病理三方面分析,病理具有早期指导治疗作用,但是本病预后良好.     

支气管哮喘和慢性阻塞性肺疾病重叠的治疗策略

支气管哮喘（简称哮喘）和COPD两者的定义都表现为气流受限,但它们的危险因素及临床表现有所不同。然而,大量的临床观察发现哮喘患者表现出COPD表型,反过来,在COPD患者中也存在哮喘表型。流行病学资料表明老年慢性阻塞性气道疾病的患者中,一半或以上患者中存在哮喘和COPD重叠的现象,而这部分人被排除在目前各种临床药物试验之外。因此,对哮喘和COPD重替的研究有助于更好地解决哮喘COPD重叠患者的“特殊”临床特点,同时为COPD发病机制提供新的观点,亦为更好地预防、治疗及管理该重叠综合征作出最佳的选择。     

Castleman病相关性嗜血细胞综合征一例报道并文献复习

背景　Castleman病（CD）及嗜血细胞综合征（HPS）均是罕见淋巴增生性疾病,病死率高,迄今尚缺乏标准的治疗方案。目的　加强对CD相关性HPS的认识,提高临床医师对该病的诊疗水平。方法　报道2017-08-22贵州省黔西南州人民医院收治的1例CD相关性HPS的患儿,结合相关文献,总结其诊断及治疗特点。结果　本例患儿表现为反复高热、肝脾大、淋巴结肿大伴全身水肿,曾误诊为败血症、传染性单核细胞增多症、淋巴瘤,并予反复抗感染、大剂量激素、丙种球蛋白等冲击治疗,病情无明显好转;通过正电子发射断层显像/计算机断层成像（PET-CT）检查及颈部淋巴结活检符合淋巴结多中心CD,且骨髓细胞学检查提示,嗜血细胞增多,最终考虑CD相关性HPS。针对白介素6（IL-6）通路靶向治疗后临床症状得到持续缓解。结论　CD是一种较为罕见的疾病,进展迅速,预后较差,且明确诊断需行组织病理学检查,而针对IL-6通路靶向治疗可能成为CD患者有效治疗方案。     

Post-treatment outcomes in a double-blind, randomized trial of sertraline for alcohol dependence

Background: Pharmacotherapy studies in alcohol dependence (AD) are generally of short duration and do not include post‐treatment follow‐up. We examined the durability of treatment effects in a placebo‐controlled trial of sertraline for AD. Methods: As previously reported, patients received 12 weeks of treatment with sertraline (n = 63) or placebo (n = 71), followed by assessments at 3 and 6 months post‐treatment ( Kranzler et al., 2011 , J Clin Psychopharmacol 31:22–30). We examined the main and interaction effects with time of 3 between‐subject factors (medication group, age of onset of AD [late‐onset alcoholics, LOAs, vs. early‐onset alcoholics, EOAs], and the tri‐allelic 5‐HTTLPR genotype) on drinking days (DDs) and heavy drinking days (HDDs). Results: The medication group effect, which was significant during treatment, remained significant during the 3‐month follow‐up period for L’/L’ LOAs, with the sertraline group having fewer DDs than the placebo group (p = 0.027). However, the medication group effect seen in L’/L’ EOAs during treatment was no longer significant (p = 0.48). There were no significant effects in S’ carriers at the 3‐month follow‐up visit, or in either genotype group at the 6‐month follow‐up. Conclusions: The beneficial effects of sertraline observed in LOAs during treatment persisted during the 3‐month post‐treatment period. Additional studies are needed to validate these pharmacogenetic findings, which together with the effects seen during active treatment support the use of sertraline only in LOAs.