在中国使用左乙拉西坦和卡马西平单药治疗部分性癫痫发作的比较:一项开放性、非劣效性试验的主要结果

目的针对≥16岁、新诊断或最近诊断为部分性癫痫发作的中国患者,比较左乙拉西坦和速释卡马西平(CBZ-IR)单药治疗的疗效。方法在Ⅲ期、随机分配、开放性试验N01364(NCT01954121)中,患者按1∶1的比例随机分配接受左乙拉西坦1 000 mg/d或CBZ-IR 400 mg/d,记录6个月无癫痫发作的患者比例及患者保留率、首次癫痫发作的时间、因不良事件或缺乏疗效导致首次癫痫发作/中止试验的时间、安全性和耐受性。结果在对符合方案集进行的分析中,接受左乙拉西坦治疗的186例患者中有88例(47.3%),接受CBZ-IR治疗的171例患者中有117例(68.4%)达到6个月无癫痫发作;校正后绝对差值为-22.9%(95%CI:-33.1%,-12.6%),其下限低于非劣效性界值-20%。左乙拉西坦组的患者保留率为48.4%,CBZ-IR组为70.2%。对于评估期首次癫痫发作时间,左乙拉西坦与CBZ-IR的风险比为2.686(95%CI:1.838,3.927);对于因不良事件或缺乏疗效导致首次癫痫发作/中止试验的时间,风险比为2.338(95%CI:1.629, 3.356)。使用左乙拉西坦在治疗中出现的不良事件(61.9%)略低于CBZ-IR(67.9%)。结论在低剂量单药治疗下,无法确定左乙拉西坦的疗效不低于CBZ-IR。左乙拉西坦的安全性/耐受性情况优于CBZ-IR。

Safety and Tolerance of Adefovir Dipivoxil in Chinese Healthy Volunteers: A PhaseⅠRandomized and Open-Label Trial

Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.

Is the Potential Interconnection between Antibiotic Susceptibility and Disinfectant Resistance a Threat to Food Safety?

The prevalence of antibiotic susceptibility and disinfectant resistance in bacterial pathogens causes a serious problem not only to food safety but also to public health, which directly or indirectly leads to treatment and disinfection failures. In this review, multidrug resistance, the mechanism of disinfectant resistance, the methods for detecting disinfectant resistance and the cross-resistance between an- tibiotics and disinfectants are summarized. More efforts should be devoted to explor- ing the professional guidance of using antibiotics and disinfectants, and to develop- ing the comprehensive detection with genetic and molecular methods is highly ex- pected.

Clinical utility,safety and tolerability of capsule endoscopy in urban Southeast Asian population

AIM:Capsule endoscopy has demonstrated its clinical utility in the evaluation of small bowel pathology in several Western studies.In this prospective study,we aimed to determine the clinical utility,safety and tolerability of capsule endoscopy in the evaluation of suspected small bowel disease in an urban Southeast Asian population. METHODS:We used the given (M2A) capsule endoscopy system in 16 consecutive patients with suspected small bowel pathology.In 9 patients the indication was obscure gastrointestinal bleeding,while in 6 patients it was to determine the extent of small bowel involvement in Crohn's disease.One patient underwent capsule endoscopy for evaluation of chronic abdominal pain.Patient's tolerability to the procedure was evaluated by standardized questionnaires and all patients were reviewed at one week to ensure that the capsule had been excreted without any adverse events. RESULTS:Abnormal findings were present in 8 patients (50%).The cause of obscure gastrointestinal bleeding was determined in 5 out of 9 patients.Findings included 2 cases of angiodysplasia,2 cases of jejunal ulcers and 1 case of both angiodysplasia and jejunal ulcer.One patient had small bowel erosions and loci of erythema of doubtful significance. Ileal lesions were diagnosed in 2 out of 6 patients with Crohn's disease.Capsule endoscopy was well tolerated by all patients.One patient with Crohn's disease had a complication of capsule retention due to terminal ileum stricture.The capsule eventually passed out spontaneously after i month. CONCLUSION:Our study,which represented the first Asian series,further confirms the diagnostic utility,safety and tolerability of wireless capsule endoscopy.

Safety and tolerability of intradermal influenza vaccination in patients with cardiovascular disease

Background It is well-established that influenza vaccination reduces adverse cardiovascular outcomes in patients with cardiovascular diseases （CVD）, however, the vaccine coverage rate in most countries remains low. The concern about the local adverse effects of intramus-cular injection, particularly in CVD patients receiving antithrombotic therapy, is one of the important impediments. This study was con-ducted to assess the safety, side effects and tolerability of intradermal influenza vaccine in CVD patients. Methods This was an observa-tional study in adult CVD patients who had undergone vaccination against seasonal influenza by intradermal vaccination between May 16th and May 30th, 2012 at Maharaj Nakorn Chiang Mai Hospital. The medical history, patients＇ acceptability and adverse effects were collected using a written questionnaire completed by the patient immediately following vaccination and by a telephone survey eight days later. Results Among 169 patients, 52.1%were women and the mean age was 63 ＆#177; 12 years. Coronary artery disease, valvular heart disease and dilated cardiomyopathy were present in 121 （71.6%）, 40 （23.7%） and 8 （4.7%）, respectively. Antithrombotics were used in 89.3%. After vaccination, the pain score was 0, 1 or 2 （out of 10） in 44.4%, 15.1%, and 27.6%of the patients, respectively. Eight days after vaccination, the common adverse reactions were itching 19 （11.9%）, swelling 9 （5.7%） and fatigue （4.7%）. No hematoma or bruising was reported. Conclusions The intradermal influenza vaccination is safe and well tolerates with high rates of satisfaction in CVD patients. This technique should be useful in expanding influenza vaccine coverage.

Safety and tolerability of isradipine in Phase I trial in Chinese population

Hypertension is one of the well-established risk factor for cardiovascular diseases. Calcium channel blockers（CCBs）, chemicals that could block voltage-gated calcium channels（VGCCs） in cardiac muscle and blood vessels, has been widely used for the treatment of hypertension. Isradipine, a second-generation CCB with high affinity for voltage-operated calcium channels, has not been marked in China. The purpose of this study was to investigate the efficacy, safety and tolerability of isradipine in a phase I clinical trial including 31 healthy Chinese subjects. All subjects received different doses of isradipine at 2.5, 5.0 and 10.0 mg in single-dose study. When the test is completed, subjects treated with 5.0 mg isradipine stayed at the research center for multiple-dose study（5.0 mg isradipine twice daily for 9 d）. Systolic blood pressure（SBP） and diastolic blood pressure（DBP） were measured pre-dose and post-dose（1, 2, 4, 6, 8, 12, 24, 36 and 48 h after isradipine treatment）. Electrocardiography（ECG） and peripheral edema were monitored pre-dose and 4, 8, 24 and 48 h after isradipine treatment. SBP and DBP in single-dose study decreased after isradipine treatment. SBP reached the lowest values 8 h after dosing with a decrease of（7.0±9.7） mmHg（5.4%, P = 0.111） in 2.5 mg group,（7.0±6.9） mmHg（6.0%, P = 0.008） in 5.0 mg group, and（14.0±10.5） mmHg（12.7%, P = 0.005） for 10.0 mg group respectively. Similarly, DBP also reached the lowest values 8 h after dosing with a decrease of（10.0±7.9） mmHg（12.8%, P = 0.004） in 2.5 mg group,（6.0±7.0） mmHg（8.6%, P = 0.003） in 5.0 mg group, and（11.0±4.1） mmHg（15.1%, P = 0.000） in 10.0 mg group respectively. No significant changes of SBP and DBP were observed in multiple-dose study. We detected mild adverse events（AEs）, such as increased transaminase and headache that resolved rapidly and spontaneously without intervention. No serious or potentially life-threatening AE was detected. Our results indicate that isradipin has a good safety and tolerability in Chinese healthy subjects. Long-term study with larger sample size is needed to confirm our conclusion.

Pharmacokinetics, safety and bioequivalence of intravenous and oral formulations of the antiepileptic drug levetiracetam in healthy Chinese volunteers

The intravenous formulation of levetiracetam (LEV)has been available in clinical practice worldwide for several years,but not in China.In the present study,we aimed to evaluate the bioequivalence of intravenous and oral LEV (tablet), an antiepileptic drug,in healthy Chinese volunteers.Two randomized,single-dose (1500mg),open-label,2-period crossover trials were conducted as follows:study A,15-min infusion;study B,45-min infusion.A total of 22healthy men participated in study A,and 24healthy men and woman were enrolled in study B.In study A,blood samples were collected after termination of each treatment.In study B,samples were collected after oral or after the start of the intravenous administration.Safety and the ratio of intravenous/oral LEV for AUC 0-t and Cmax were evaluated.The 90% confidence intervals of Cmax and AUC0-t ratios for LEV 1500-mg tablets versus 15-min intravenous administration were outside the bioequivalence limits (80.00%-125.00%). For LEV 45-min intravenous administration,bioequivalence versus 1500-mg tablets was within the range for Cmax and AUC 0-t. The most frequently adverse event (AE)was somnolence.A total of eight subjects experienced nine mild AEs in study A, and 19subjects experienced 29mild AEs in study B.Intravenous infusions (15 and 45 min)of 1500-mg LEV were as well tolerated as the oral tablet.Bioequivalence was demonstrated by 45-min infusions.Therefore,direct conversion from oral to intravenous LEV 1500 mg (45-min infusion),or vice versa,was possible.