Effect of mono/dual antiretroviral therapy on suppression of HCV and HIV during treatment of HCV infection in HIV/HCV-coinfected patients

ObjectiveData of hepatitis C treatment with direct-acting antivirals (DAAs) in HIV infected patients are limited to a few number of antiretroviral therapies (ART). The aim of this study was to assess the effectiveness and safety of non-conventional ART as monotherapy or dual therapy (MDT) when combined with DAA.MethodsRetrospective review of HIV/HCV-coinfected patients treated with DAAs during one year in 3 centers. Sustained virologic response 12 weeks after therapy (SVR) and maintenance of HIV viral suppression were compared between patients receiving triple ART (TT) or MDT.ResultsOverall 485 patients were included (359 receiving TT and 126 MDT). HCV SVR was 93.4% (95%CI, 90.8% to 95.3%) in the intention-to-treat analysis without differences between groups: 92.8% on TT vs 95.2% on MDT (p = 0.3). HCV virological failure was associated with lower CD4 + cell count at baseline (for every 100-cell/μl increment: OR, 0.8; 95%CI, 0.7-0.9; p = 0.01) and with liver stiffness (for every 10-unit increment: OR, 1.5; 95%CI 1.2-1.8; p< 0.01). HIV-RNA during HCV treatment or 12 weeks after was detectable in 23 patients on TT (6.6%) and 9 (7.2%) patients on MDT (p = 0.8). The median (IQR) change in CD4 + cell count was not significantly different between the groups: 15 (–55 to 115) in TT vs –12 (–68 to 133) cells/μl in MDT (p = 0.8).ConclusionDAAs obtain high rates of SVR among HIV/HCV-coinfected patients independently of whether TT or non-conventional ART is used. Suppression of HIV was maintained in both groups.     

High-dose-rate brachytherapy with two or three fractions as monotherapy in the treatment of locally advanced prostate cancer

BackgroundTo evaluate late urinary (GU) and gastrointestinal (GI) adverse events (AEs) and biochemical control of disease after high-dose rate brachytherapy (HDR-BT) in locally advanced prostate cancer.Patients and methods227 consecutive patients were treated with 3 × 10.5 Gy (n = 109) or 2 × 13 Gy (n = 118) HDR-BT alone. Biochemical failure was assessed using the Phoenix definition of PSA nadir + 2 μg/l and late AEs using the RTOG scoring system and the International Prostate Symptom Score (IPSS).ResultsKaplan–Meier estimates and prevalence of late events indicate that urinary, bowel and IPSS symptoms are higher after 31.5 Gy than after 26 Gy, however differences are significant only for Grade 1 and 2 urinary toxicity. Kaplan–Meier estimates of morbidity are consistently and considerably higher than time-point estimates of prevalence; which reflects the transient nature of most symptoms. At 3 years 93% and 97% of patients treated with 26 and 31.5 Gy, respectively, were free from biochemical relapse (p = 0.5) and 91% for the latter regimen at 5 years. In univariate and multivariate analysis risk-category was the only significant predictor of relapse (p < 0.03).ConclusionThese HDR-BT schedules achieved high levels of biochemical control of disease in patients with advanced prostate cancer with few severe complications seen throughout the first 3 years.     

拉莫三嗪单药治疗新诊断小儿癫(癎)的临床疗效

目的:观察拉莫三嗪对新诊断小儿癫(癎)的疗效和安全性.方法:选取80例新诊断小儿癫痫患者,给予拉莫三嗪单药治疗.起始剂量0.5 mg/(kg·d),每周增加0.5 mg/kg,至第4周加至目标剂量4.0～5.0 mg/(kg·d),分2次口服.观察药物的不良反应及药物疗效.结果:80例患儿中完全控制31例,显效27例,有效8例,无效14例,总有效率为82.5％.病程≤1年患儿的疗效好于≥6年的患儿,差异有统计学意义(P＜0.01),各发作类型中以强直阵挛发作疗效最佳,总有效率为95％.不良反应以皮疹、头痛、嗜睡较为多见,对症治疗后症状消失.结论:拉莫三嗪治疗小儿癫(癎)总有效率较高,不良反应出现率低,是治疗小儿癫(癎)的一种安全、有效药物.     

左乙拉西坦单药治疗老年癫癎的临床研究

目的：研究左乙拉西坦（LEV）治疗老年癫癎患者的临床疗效、安全性及对生活质量的影响.方法：采用前瞻性研究对42例不同类型老年癫癎患者（男24例,女18例;年龄60～82岁）,使用LEV单药治疗.LEV起始剂量：500 mg,每日2次,根据疗效调整剂量,比较不同发作类型老年癫癎患者的疗效、安全性及对生活质量的影响.结果：42例老年癫癎患者用LEV后无发作13例（31%）,显效9例（22%）,有效14例（33%）,无效6例（14%）,采用癫癎患者生活质量量表-31（QOLIE-31）评定,LEV治疗后在对发作的担忧、精力/疲乏、认知功能、药物影响及社会功能方面得分与治疗前比较差异有统计学意义（P〈0.05）,有7例（17%）出现与LEV可能有关的不良反应,其中嗜睡2例,急躁3例,注意力不集中、攻击行为各1例,上述不良反应均未经特殊处理,在1～2个月内自行消失,无1例因不良反应退出治疗.结论：LEV单药治疗各型老年癫癎均有疗效,显著减少发作频率,安全耐受性好,无明显认知毒性,能够提高老年癫癎患者的生活质量.     

A multicenter, outpatient, open-label study to evaluate the dosing, effectiveness, and safety of topiramate as monotherapy in the treatment of epilepsy in clinical practice

This 24-week, multicenter, open-label trial was designed to evaluate the dosing, effectiveness, and safety of topiramate monotherapy for epilepsy and to identify patient and clinical characteristics predictive of optimally effective stabilized monotherapy doses. Of 406 randomized patients, 244 comprised the evaluable-for-efficacy population (12 weeks of treatment and stabilized topiramate dose during final 28 days); 213 were on topiramate monotherapy at the end of the trial. The mean stabilized daily dose of topiramate over the last 28 days of treatment (primary endpoint) was significantly lower for patients reporting one to three seizures (low seizure frequency, n = 147) than for those reporting more than three seizures (high seizure frequency, n = 66) during a 3-month retrospective baseline period (191 mg vs 239 mg, P = 0.003). Patients in the low-seizure-frequency group reached a stable topiramate dose after a median of 36 days, compared with 53 days for patients in the high-seizure-frequency group. Linear and stepwise regression analyses showed baseline seizure frequency and lifetime seizure count to be significant (P < 0.05) predictors of the stabilized dosage. Most treatment-emergent adverse events (TEAEs) were mild to moderate; those occurring with cumulative incidence rates >10% in either seizure frequency group were paresthesia, fatigue, anorexia, dizziness, somnolence, headache, and hypoesthesia; 18.2% of patients discontinued topiramate because of a TEAE, 5.1% reported serious TEAEs, and no deaths were reported during the study.     

Treatments and limitations for methicillin-resistant Staphylococcus aureus: A review of current literature

Methicillin-resistant Staphylococcus aureus (MRSA) has remained a major threat to healthcare; in both hospital and community settings over the past five decades. With the current use of antibiotics for a variety of infections, including MRSA, emerging resistance is a major concern. Currently available treatments have restrictions limiting their use. These issues include, but are not limited to, side effects, cross-resistance, lack of understanding of pharmacokinetics and clinical pharmacodynamics, gradual increment in minimal inhibitory concentration over the period (MIC creep) and ineffectiveness in dealing with bacterial biofilms. Despite availability of various therapeutic options for MRSA, the clinical cure rates remain low with high morbidity and mortality. Given these challenges with existing treatments, there is a need for development of novel agents for MRSA. Along with prompt infection control strategies and strict implementation of antibiotic stewardship, cautious use of newer anti-MRSA agents will be of utmost importance. This article reviews the treatments and limitations of MRSA management and highlights the future path.     

核苷类似物单药口服预防肝移植术后乙型病毒性肝炎复发的研究

目的探讨核苷类似物单药口服预防肝移植术后乙型病毒性肝炎(乙肝)复发的有效性和安全性。方法回顾性分析1999年10月至2014年4月在广东佛山市第一人民医院行肝移植的32例乙肝相关性疾病患者的临床资料。根据供体来源分为两个阶段。第一阶段为1999年10月至2007年9月的6例无心跳供体肝移植,供肝的乙型肝炎病毒(HBV)血清标志物均为(-),受体术前血清乙型肝炎表面抗原(HBsAg)、乙型肝炎核心抗体(抗-HBc)均为(+),其中2例合并乙型肝炎e抗原(HBeAg)(+),1例合并乙型肝炎e抗体(抗-HBe)(+),5例受体术前血清HBV脱氧核糖核酸(DNA)1 000 copies/ml,1例HBV DNA1 000 copies/ml。给予拉米夫定(100 mg/d)单药口服预防肝移植术后乙肝复发。第二阶段为2011年11月至2014年4月的26例心脏死亡器官捐献供体肝移植(其中1例为肝肾联合移植);供肝血清HBsAg(+)6例、(-)20例,乙型肝炎表面抗体(抗-HBs)(+)15例,HBeAg(+)2例,抗-HBc(+)14例,抗-HBe(+)5例;11例受体术前血清HBV DNA500 copies/ml,15例HBV DNA500 copies/ml;25例给予恩替卡韦0.5 mg/d、1例给予替比夫定600 mg/d单药口服预防乙肝复发。结果第一阶段肝移植受体中位随访时间为104个月,全部受体术后血清HBsAg和HBV DNA均转阴,至今未见乙肝复发。第二阶段肝移植受体中位随访时间为50周,20例接受HBsAg(-)供肝,其中1例于术后39周出现一过性HBsAg(+),随后又转阴;另1例肝肾联合移植受体在移植术后28周发生乙肝复发,但血清HBV DNA(-);其中15例采用抗-HBc(+)供体肝移植术后均未见乙肝复发。6例采用HBsAg(+)供体的肝移植受体术后HBsAg均未转阴。所有随访受体均存活,术后均未见HBV DNA复制,亦未发现核苷类似物相关不良反应。结论核苷类似物单药口服预防肝移植术后乙肝的复发是有效和安全的。     

Use of ezetimibe results in more patients reaching lipid targets without side effects

BackgroundEzetimibe's mechanism of action, complementary to that of statins, makes it a useful therapeutic option in patients intolerant of lipid-lowering drugs or in those not achieving target lipid levels.ObjectivesTo evaluate the efficacy and safety of ezetimibe in a longterm follow-up of lipid clinic patients with emphasis on motivation for use and the impact on achievement of target lipid levels.MethodsTwo hundred and ninety-five clinic patients who were prescribed and took ezetimibe in the 13-month period following the drug's availability in Canada were identified from our database. Patients’ history and laboratory data were collected before and at first visit after the ezetimibe therapy was started. Paired t-test and chi-square test were used for statistical comparisons of ezetimibe's effect on lipid parameters and the achievement of target lipid-levels respectively.ResultsEzetimibe treatment increased significantly the proportion of patients achieving lipid targets (by 25% for LDL-C and by 21.7% for TC/HDL-C) significantly by 18% (p < 0.001) and TC/HDL-C by 15% (p < 0.011). The effect of ezetimibe in combination with other lipid-lowering therapies was similar; LDL-C decreased by 22% (p < 0.001) and TC/HDL-C by 15.4% (p < 0.011). The same lipid-lowering effect was seen in patients with diabetes. In this subgroup, addition of ezetimibe to ongoing therapy led to three- and two-fold increase in LDL-C and TC/HDL-C target levels achievement, respectively. Only 7% of patients discontinued ezetimibe treatment due to side effects.ConclusionIn patients referred to the lipid clinic (typically because of side effects or failure to reach targets on other lipid-lowering therapy) treatment with ezetimibe significantly increased proportion of those achieving their target lipid levels. This was not accompanied by significant side effects.     

Evaluation of drug treatment outcome in epilepsy: a clinical perspectiv

This article provides a comprehensive discussion of clinical outcome measures used in trials aimed at assessing the efficacy and safety of antiepileptic drugs. For efficacy, assessment still relies on careful documentation of changes in ictal activity as determined by seizure counts based on patients recall, direct clinical observation and (for absence seizures) EEG monitoring. In selected cases, assessment of seizure severity may also be indicated. The precise choice of outcome measures is largerly dependent upon the specific trial design. In shortterm regulatory trials, parameters such as time to nth seizure after randomization (or after achievement of target dosage) may be used as an index of antiepileptic efficacy, but the clinical relevance of such measures is questionable. In addon trials in refractory patients, changes in seizure counts and proportion of patients achieving 50%, 75% and 100% reduction in seizure frequency may be appropriate. For longterm monotherapy trials in newly diagnosed patients, proportion of patients achieving prolonged remission (1year or longer) usually represents the most clinically meaningful efficacy outcome. Retention of patients on the allocated treatment over time is also a valuable measure, but it should be regarded as a composite endpoint because decision to continue treatment is dependent on both efficacy and tolerability. At present, there is no universally accepted method for evaluating side effects, particularly those which can not be documented objectively. Spontaneous reports of symptoms or use of specific checklists have advantages and disadvantages. Studies aimed at ensuring greater standardization in safety assesment should be encouraged, especially with respect to need of obtaining quantitative estimates, and information on both prevalence and incidence of side effects should be reported in all trials.