喜炎平注射液治疗慢性阻塞性肺疾病急性加重期的Meta-分析

目的 评价喜炎平注射液治疗慢性阻塞性肺疾病急性加重期（AECOPD）的疗效与安全性。方法 检索PubMed、EMbase、The Cochrane Library、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普中文期刊全文数据库（VIP）和万方数据库中发表的关于喜炎平注射液治疗AECOPD的临床随机对照试验（RCT）,从建库起至2020年2月20日,采用Jadad量表对纳入的文献进行质量评价,运用RevMan 5.3软件进行Meta-分析。结果 共纳入19项RCTs,包括1 500例患者。Meta-分析结果显示：喜炎平注射液组在总有效率[WMD=3.68,95%CI=（2.68,5.06）,P<0.000 01]、呼吸困难的消失时间[WMD=-2.25,95%CI=（-2.53,-1.97）,P<0.000 01]、白细胞计数[WMD=0.95,95%CI=（0.67,1.23）,P<0.000 01]、中性粒细胞比值[WMD=3.16,95%CI=（-0.42,6.74）,P=0.08]、二氧化碳分压[WMD=3.76,95%CI=（1.75,5.77）,P=0.000 3]、氧分压[WMD=5.64,95%CI=（4.75,6.52）,P<0.000 01]、FEV₁占预计值百分比[WMD=3.46,95%CI=（0.47,6.46）,P=0.02]、C反应蛋白[WMD=6.93,95%CI=（4.28,9.58）,P<0.000 01]等指标的结果均优于对照组。结论 临床治疗AECOPD时加用喜炎平注射液可取得更好疗效,但本研究所纳入的文献质量偏低,需要更多规范的临床研究进一步印证。     

大剂量布地奈德对慢性阻塞性肺疾病急性加重期疗效和安全性的Meta-分析

目的 系统评价大剂量布地奈德治疗慢性阻塞性肺病急性加重期（AECOPD）的疗效和安全性,为临床合理用药提供参考。方法 检索Cochrane Library、PubMed、Embase、万方数据库、中国学术期刊全文数据库（CNKI）和中国生物医学文献数据库（CBM）等专业数据库,收集大剂量布地奈德（试验组）对比常规剂量布地奈德（对照组）治疗AECOPD的随机对照试验（RCT）,时间从建库到2019年5月。提取相关资料并评价文献质量,使用RevMan 5.3软件进行Meta-分析。结果 共纳入12项RCTs,878例患者。Meta-分析结果显示,试验组患者在改善临床症状评分［MD=-1.00,95% CI（-1.44,-0.56）,P<0.01］、升高动脉血氧分压（PaO₂）［MD=5.71,95% CI（5.03,6.38）,P<0.01］、降低动脉血二氧化碳分压（PaCO₂）［MD=-5.75,95% CI（-7.24,-4.26）,P<0.01］、升高1 s用力呼气量（FEV1）［MD=0.20,95% CI（0.10,0.30）,P<0.01］及FEV1占用力肺活量（FVC）的百分比（FEV1/FVC）［MD=5.69,95% CI（1.46,9.91）,P<0.01］均显著优于对照组。但试验组患者口腔真菌发生率［RR=3.18,95% CI（1.18,8.55）,P=0.02］也显著大于对照组。结论 大剂量布地奈德治疗AECOPD与常规剂量相比,临床疗效更优,但增加口腔真菌感染的风险。     

免疫球蛋白治疗新生儿感染性肺炎疗效和免疫功能的系统评价

目的 系统评价免疫球蛋白治疗新生儿感染性肺炎的疗效、安全性,及对免疫功能的影响。方法 计算机检索PubMed、EMbase、The Cochrane Library、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和维普中文期刊全文数据库（VIP）和万方数据库,检索年限为从建库至2020年4月,搜集免疫球蛋白治疗新生儿感染性肺炎的临床随机对照试验（RCT）,筛选文献后提取数据,采用Jadad量表进行文献质量评价,通过RevMan 5.3软件对临床有效率、临床体征改善时间、血气分析指标、炎性因子指标、免疫球蛋白水平、T淋巴细胞水平和不良反应发生率进行Meta-分析。结果 共纳入13项研究,1 185例患者。Meta-分析结果显示：试验组（免疫球蛋白）的临床有效率比对照组高[RR=1.19,95%CI（1.13,1.24）,P<0.01];退热时间[MD=-1.45,95%CI（-1.58,-1.32）]、咳嗽咳喘消失时间[MD=-2.06,95%CI（-2.23,-1.89）]、肺部啰音消失时间[MD=-1.85,95%CI（-2.00,-1.69）]和住院时间[MD=-2.37,95%CI（-2.59,-2.16）]均显著小于对照组（P<0.01）;氧气分压（PO₂）提高[MD=2.31,95%CI（1.56,2.89）]、二氧化碳分压（PCO₂）下降[MD=-1.49,95%CI（-2.01,-0.97）]和动脉血氧饱和度（SaO₂）提高[MD=1.08,95%CI（0.46,1.70）]均显著优于对照组（P<0.01）;降钙素原下降[SMD=-1.39,95%CI（-2.48,-0.31）]和C-反应蛋白下降[SMD=-1.85,95%CI（-2.87,-0.84）]均优于对照组（P<0.01）;免疫球蛋白IgG水平升高[SMD=1.80,95%CI（1.39,2.20）]显著优于对照组（P<0.01）;CD3⁺增加值[MD=2.13,95%CI（1.08,3.19）]、CD4⁺增加值[MD=3.97,95%CI（2.88,5.06）,P<0.01]、CD8⁺增加值[MD=1.33,95%CI（0.25,2.90）,P=0.01]和CD4⁺/CD8⁺增加值[MD=0.33,95%CI（0.03,0.63）,P=0.03]均显著优于对照组;不良反应发生率与对照组相当[RR=1.16,95%CI（0.57,2.35）,P=0.69]。结论 免疫球蛋白能迅速减轻新生儿感染性肺炎临床症状、显著改善血氧含量、炎性因子水平和免疫功能,且安全性较好。     

Phase I trial of oblimersen (Genasense®) and gemcitabine in refractory and advanced malignancies

Background: Overexpression of Bcl-2 is associated with worse prognosis for a number of cancer types. The present study was designed to determine the maximum tolerated dose (MTD) of oblimersen (antisense Bcl-2) and gemcitabine when administered to patients with refractory malignancies. Materials and methods: Sixteen patients with advanced solid tumors refractory to standard therapies were treated with escalating doses of oblimersen continuous, 120-h intravenous infusion given every 14 days, with a fixed-dose-rate intravenous infusion of gemcitabine administered on day 5 of each cycle. Serial plasma samples were collected to calculate the pharmacokinetics of oblimersen and gemcitabine, and also to measure the effect of oblimersen on Bcl-2 expression. Results: 7 women and 9 men, median age 55 years (range 35–74 years), received a 5-day infusion of oblimersen at dose levels of 5 mg/kg/day (n = 4) or 7 mg/kg/day (n = 12). On the 5th day of the infusion, gemcitabine was given at 10 mg/m²/h for a total dose of 1,000 mg/m² (n = 7; cohorts I and II), 1,200 mg/m² (n = 3; cohort III), or 1,500 mg/m² (n = 6; cohort IV). Edema was the dose-limiting toxicity (DLT), necessitating expansion of cohort IV. No subsequent DLTs were noted. Thus, the maximum planned doses were well tolerated, and a formal MTD was not determined. Most hematologic toxicities were grade 1 or 2. There was low-grade fatigue, nausea/vomiting, and myalgias/arthralgias. Oblimersen C_ss and AUC increased in relation to the dose escalation, but gemcitabine triphosphate levels did not correlate well with dose. There were no objective responses, though 5 patients had stable disease. A >75% reduction in Bcl-2 expression in peripheral blood mononuclear leucocytes was seen more frequently in patients who achieved stable disease than in progressing patients. Conclusions: The maximal planned dose levels of oblimersen and gemcitabine in combination were well tolerated. Only one DLT (edema) occurred. There was a correlation between Bcl-2 reduction and stable disease. The recommended doses of the drugs for future studies are 7 mg/kg/day of oblimersen on days 1–5, and gemcitabine 1,500 mg/m² on day 5, every two weeks.     

普乐安片联合萘哌地尔治疗前列腺增生的疗效观察

目的分析普乐安片联合萘哌地尔治疗前列腺增生的临床效果。方法选择2014年3月-2017年3月在焦作市妇幼保健院治疗的前列腺增生患者88例,随机分为对照组(44例)和治疗组(44例)。对照组患者口服萘哌地尔片,25mg/次,1次/d。治疗组在对照组的基础上口服普乐安片,4片/次,3次/d。两组患者均治疗30d。观察两组患者临床疗效,同时比较治疗前后两组患者残余尿量、尿流速、国际前列腺症状评分(IPSS)和QOL评分。结果治疗后,对照组和治疗组临床有效率分别为75.00%和93.18%,两组比较差异具有统计学意义(P<0.05)。治疗后,两组残余尿量明显减少(P<0.05),而平均尿流速(Qave)和最大尿流速(Qmax)均明显增加(P<0.05),且治疗组残余尿量和尿流速明显优于对照组(P<0.05)。治疗后,两组IPSS和QOL评分均显著降低(P<0.05),且治疗组明显低于对照组(P<0.05)。结论普乐安片联合萘哌地尔治疗前列腺增生患者临床效果较好,可明显改善患者排尿情况,优化前列腺功能,提高患者生活质量。     

阿托伐他汀对心肌梗死后心力衰竭临床疗效的系统评价

目的 评价阿托伐他汀治疗心肌梗死后心力衰竭患者的有效性，为该病患者的循证治疗提供证据。方法 计算机检索PubMed、Cochrane图书馆、EMbase、中国学术期刊全文数据库（CNKI）、万方数据库（Wanfang）、维普中文科技期刊数据库（VIP）等数据库中的随机对照试验（RCT），检索时限均从建库至2018年10月。采用RevMan 5.3软件进行Meta-分析，客观评价其临床疗效。结果 共纳入22个RCTs，10 971例患者。对其中20个RCTs进行Meta-分析，结果显示：（1）与常规治疗组相比，阿托伐他汀组的左室射血分数（LVEF）、6 min步行距离明显增加[MD=7.56，95% CI（4.13，10.98），P<0.000 1；MD=20.06，95% CI（9.77，30.35），P=0.000 1]，N末端脑钠肽（NT-proBNP）、脑钠肽（BNP）、左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）值明显减小[MD=-153.23，95% CI（-186.97，-119.49），P<0.00001；MD=-96.74，95% CI（-117.10，-76.38），P<0.00001；MD=-5.69，95% CI（-8.11，-3.27），P<0.000 01；MD=-6.80，95% CI（-8.65，-4.95），P<0.000 01]；（2）有7个研究涉及阿托伐他汀的剂量，与40 mg治疗组相比20 mg治疗组的LVEDD、LVESD、NT-proBNP、BNP明显减少[MD=-5.13，95% CI（-6.05，-4.21），P<0.000 01；MD=-0.84，95% CI（-1.50，-0.17），P=0.01；MD=-26.53，95% CI（-47.68，-5.37），P=0.01；MD=-17.63，95% CI（-32.66，-2.59），P=0.02]，LVEF及6 min步行距离明显增加[MD=9.13，95% CI（7.95，10.31），P<0.000 01；MD=22.24，95% CI（7.06，37.43），P=0.0004]。定性分析结果显示阿托伐他汀可有效改善心肌梗死后心力衰竭的临床症状及患者心功能状况。结论 阿托伐他汀对心肌梗死后心力衰竭患者治疗效果显著，且可以有效预防无症状型心力衰竭进一步发展，但上述结论尚需更多大样本高质量的临床试验加以验证。     

Pharmacokinetics of bupivacaine enantiomers in sheep: Influence of dosage regimen and study design

Bupivacaine is used as a racemate. In previous studies the mean total body clearance ofR(+)-bupivacaine was found to be greater thanS(−)-bupivacaine by 65% after iv bolus dose of separate enantiomers and by 20% after iv infusion to steady state of racemate. The present studies were performed to determine whether different study designs using different iv dosage regimens could influence the pharmacokinetic parameters determined for either bupivacaine enantiomer. rac-Bupivacaine·HCl was administered iv to 6 adult Merino ewes by bolus, brief infusion, and prolonged infusion. Arterial blood concentrations ofR(+)- andS(−)-bupivacaine were measured by enantioselective HPLC. These regimens consistently produced lower arterial blood concentrations ofR(+)-bupivacaine thanS(−)-bupivacaine due toR(+)-bupivacaine having a greater initial dilution volume by 16 (95%CI=3–29)%, volume of distribution at steady state equilibrium by 32 (95%CI=17–32)% and mean total body clearance by 28 (95%CI=21–35)%. The slow half-life ofR(+)-bupivacaine, however, was found to be 15 (95%CI=0–31)% longer than that ofS(−)-bupivacaine. The difference between enantiomers in mean total body clearance thus was similar to the previous study based upon infusion to steady state of rac-bupivacaine. Differences in pharmacokinetics attributable to the dosage regimen consisted of a greater mean total body clearance forR(+)-bupivacaine along with a smaller terminal half life with the bolus regimen and a longer half-life ofS(−)-bupivacaine after prolonged infusion. Differences in pharmacokinetics between the bupivacaine enantiomers occurred consistently in both distribution and clearance but the magnitude of the effect was less than 50% in each case. Systematic differences in pharmacokinetics associated with the dosage regimen were found mainly in terminal half-life. Dosage regimen, thus, was found to influence the pharmacokinetic results found experimentally and is therefore a significant variable in its own right. The study was supported by the National Health and Medical Research Council of Australia and by the Australian New Zealand College of Anaesthetists by way of award of inaugural Douglas Joseph Professorship in Anaesthesia (to L.E.M.).     

Phase II study of gemcitabine in combination with vinorelbine versus gemcitabine followed by vinorelbine for metastatic breast cancer

Background No clear data are available concerning the superiority of combination chemotherapy to sequential therapy using agents beyond 1st or 2nd line chemotherapy for treating patients with metastatic breast cancer. Methods Patients were randomized to receive a combination of gemcitabine and vinorelbine or gemcitabine until disease progression followed by vinorelbine monotherapy. Quality of life was assessed using EORTC QLQ-C30 questionnaires. Results Forty-two patients were randomized to the combination arm and 40 were randomized to the sequential arm. Baseline characteristics were well balanced between the arms. The median number of chemotherapy cycles was 4 (range, 1–23) for the combination arm and 6 (range, 1–25) for the sequential arm. Patients receiving combination therapy had a higher composite response rate (26.8% vs. 12.5%; P = 0.106) but a shorter median time to treatment failure (3.6 vs. 4.4 months, P = 0.252) as compared to patients receiving sequential monotherapy. Median overall survival for the combination and sequential arms was 10.6 months and 8.9 months, respectively (P = 0.436). Toxicities were manageable and similar in both arms. Quality of life measurements in global health, role, and social function were superior in the combination arm (P < 0.05). Conclusions Combined gemcitabine and vinorelbine therapy appears comparable to sequential monotherapy for heavily pretreated patients with metastatic breast cancer as demonstrated by improved quality of life outcomes with similar therapeutic efficacies and incidences of adverse events.     

醒脑静治疗急性重症颅脑损伤昏迷患者疗效及安全性的Meta-分析

目的 系统评价醒脑静治疗急性重症颅脑损伤昏迷的疗效和安全性。方法 计算机检索中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普中文期刊全文数据库（VIP）、万方数据库、PubMed及Embase数据库,检索时间均从建库至2019年5月。收集醒脑静治疗急性重型颅脑损伤昏迷的随机对照试验。对符合纳入标准的临床研究进行质量评价和资料提取后,采用Rev Man 5.3软件进行Meta-分析。结果 共纳入15项研究,包括1 173例患者。Meta-分析结果显示：试验组的清醒率（OR=2.50,95%CI=1.79～3.49）、清醒时间（MD=-4.20,95%CI=-5.45～-2.96）、GCS评分变化（MD=2.68,95%CI=2.44～2.93）、NHISS评分变化（MD=-6.12,95%CI=-7.46～-4.77）、APACHE-Ⅱ（MD=-3.61,95%CI=-4.37～-2.86）、预后较好率（OR=2.37,95%CI=1.81～3.10）、预后不良率（OR=0.46,95%CI=0.34～0.62）及血清炎性因子（TNF-a、IL-8、IL-6）均优于对照组,差异均有统计学意义（P<0.01）。结论 现有研究证据显示,醒脑静能显著提高重症颅脑损伤昏迷患者清醒率、缩短清醒时间、提高GCS评分、降低NIHSS评分和APACHE-Ⅱ评分,提高预后良好率。     

Strychnine-sensitive glycine receptors inducing [3H]-acetylcholine release in rat caudatoputamen: a new site of action of ethanol?

In the present study acute effects of ethanol on [³H]-acetylcholine ([³H]-ACh) release induced by activation of strychnine-sensitive glycine receptors in superfused slices of rat caudatoputamen were investigated. The glycine-evoked [³H]-ACh release (lg EC₅₀ = –4.10, CI₉₅ = [–4.14, –4.05]) was inhibited by strychnine in a competitive manner (pA₂ = 6.86, CI₉₅ = [6.61, 7.08]). Release of [³H]-ACh could also be induced by L-serine. L-serine was less potent than glycine (lg EC₅₀ = –2.61, CI₉₅ = [–2.69, –2.52]). Both glycine and L-serine showed similar maximum effects (E_max(glycine) = 1.34, CI₉₅ = [1.24, 1.45]; E_{max(L-serine)} = 1.19, CI₉₅ = [1.09, 1.32]). Ethanol at concentrations of 2‰ (= 34 mM) and 4‰ (= 68 mM) inhibited glycine-evoked [³H]-ACh release in a manner like the competitive antagonist strychnine, however with lower potency. The pA₂ of ethanol was 1.19, CI₉₅ = [0.85, 1.41], at 2‰ [v/v] and 1.51, CI₉₅ = [1.19, 1.78] at 4‰ ethanol. Similar to its action on glycine-evoked [³H]-ACh release, ethanol at 4‰ [v/v] also inhibited L-serine-evoked transmitter release in a competitive-like fashion (pA₂ = 0.83, CI₉₅ = [–0.15, 1.18]). We conclude, that strychnine-sensitive glycine receptors, mediating [³H]-ACh release in the rat caudatoputamen, might represent a new site of action of ethanol. Received: 15 May 1997 / Accepted: 4 September 1997     

A phase II open-label trial of bortezomib in patients with multiple myeloma who have undergone an autologous peripheral blood stem cell transplant and failed to achieve a complete response

Background A majority of multiple myeloma (MM) patients fail to achieve complete response (CR) to peripheral blood stem cell transplantation (PBSCT); effective options following autologous transplantation are needed. Bortezomib (B) is active against MM. This study was conducted to determine the feasibility, safety, tolerability, and efficacy of B following high-dose melphalan therapy and PBSCT. Methods Fifty patients enrolled (48 evaluable) and 49 were treated (safety population). Treatment: 4 cycles B 1.3 mg/m² Days 1, 4, 8, and 11/21-days; 4 additional cycles were permitted for stable or responding patients. Results Median age was 55 years (range, 38–73), 68% male, 64% ECOG PS = 0, 44% Durie-Salmon Stage IIIA prior to induction, 42% had symptomatic IgG MM; 74% had prior single transplant (26% tandem). Responses post-transplant: 70% PRs, 18% MRs. A median of 4 cycles (range, 2–8) of B were administered. Responses: CR 8%, uCR 2%, PR 23%, uPR 19%, MR 10%, and no change 35%; median time-to-treatment failure (TTF) was 6.2 months (range, 1.0–19.4). Three deaths occurred (n = 1 sepsis, n = 2 disease progression). Grade 3–4 treatment-related toxicities included: thrombocytopenia, neuropathy (14%, each); asthenia, neutropenia (10%, each); and nausea (4%). Twelve patients (24%) discontinued treatment due to toxicity and 30 patients (60%) completed the study; 20 patients started new treatment (median 5.8 months [range, 1.5–20.3]). Conclusions The study closed early due to widespread availability of B, and the lack of B-na?ve patients. Bortezomib monotherapy after melphalan and autologous PBSCT was feasible, safe and well-tolerated (toxicities were manageable), but failed to produce the hypothesized response rates.     

A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials

Purpose To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. Methods This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and April 2008. Trabectedin was administered intravenously as 1 of 3 schedules: 24-hour infusion every 3 weeks (q3wk 24-h; n = 570/2,818 cycles), 3-hour infusion every 3 weeks (q3wk 3-h; n = 258/1,003 cycles), and 3-hour infusion for three consecutive weeks every 4 weeks (qwk 3-h; n = 304/1,198 cycles). Results The majority of patients (90%) had received previous chemotherapy. Patients were given a median of three treatment cycles of trabectedin (range, 1–59). Nausea, fatigue and vomiting were the most common trabectedin-related adverse events, reported in ≥20% of patients. Reversible myelosuppression (mainly neutropenia) and transient reversible transaminase increases were the most common laboratory abnormalities seen with trabectedin, with a very low incidence of relevant clinical consequences. Deaths associated with drug-related adverse events were infrequent, occurring in 19 (1.7%) patients. Conclusion Single-agent trabectedin treatment was reasonably well tolerated. Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time.     

Phase I study of gemcitabine, docetaxel and imatinib in refractory and relapsed solid tumors

Purpose: In a phase I study, the combination of gemcitabine and imatinib was well tolerated with broad anticancer activity. This phase I trial evaluated the triplet of docetaxel, gemcitabine and imatinib. Experimental Design: Imatinib was administered at 400 mg daily on days 1–5, 8–12 and 15–19. Gemcitabine was started at 600 mg/m² at a rate of 10 mg/min on days 3 and 10 and docetaxel at 30 mg/m² on day 10, on a 21-day cycle. Diffusion and dynamic contrast-enhanced perfusion MRI was performed in selected patients. Results: Twenty patients with relapsed/refractory solid tumors were enrolled in this IRB-approved study. The mean age was 64, and mean ECOG PS was 1. Two patients were evaluated by diffusion/perfusion MRI. After two grade 3 hematological toxicities at dose level 1, the protocol was amended to reduce the dose of imatinib. MTDs were 600 mg/ m² on days 3 and 10 for gemcitabine, 30 mg/ m² on day 10 for docetaxel, and 400 mg daily on days 1–5 and 8–12 for imatinib. Dose limiting toxicities after one cycle were neutropenic fever, and pleural and pericardial effusions. The best response achieved was stable disease, for six cycles, in one patient each with mesothelioma and non small cell lung cancer (NSCLC) at the MTD. Two patients with NSCLC had stable disease for four cycles. Discussion: An unexpectedly low MTD for this triplet was identified. Our results suggest drug-drug interactions that amplify toxicities with little evidence of improved tumor control.     

丙酸倍氯米松对比布地奈德雾化吸入治疗儿童哮喘急性发作的Meta-分析

目的 系统评价丙酸倍氯米松对比布地奈德雾化吸入治疗儿童哮喘急性发作的临床疗效和安全性。方法 计算机检索PubMed、EMbase、The Cochrane Library、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和维普中文期刊全文数据库（VIP）和万方数据库,检索时限均为2000年1月-2019年12月,搜集丙酸倍氯米松联用特布他林（试验组）对比布地奈德联用特布他林（对照组）雾化吸入治疗儿童哮喘急性发作的随机对照研究,对符合纳入标准的临床研究进行资料提取和质量评价,采用RevMan 5.3软件对纳入文献进行质量评价和Meta-分析。结果 共纳入11篇文献（3篇英文文献和8篇中文文献）,1 227例患儿。Meta-分析结果显示：试验组临床有效率[RR=0.98,95%CI=0.92~1.04]、哮喘缓解率[RR=0.97,95%CI=0.92~1.01]、临床症状评分[SMD=0.09,95%CI=-0.06~0.24]、咳嗽消失时间[SMD=0.02,95%CI=-0.32~0.36]、呼吸困难改善时间[SMD=-0.03,95%CI=-0.29~0.24]和肺部哮鸣音消失时间[SMD=0.15,95%CI=-0.11~0.41]、住院时间[SMD=0.04,95%CI=-0.09~0.17]、呼气流量峰值[SMD=-0.32,95%CI=-0.85~0.20]和不良反应发生率[RR=1.41,95%CI=0.74~2.69]与对照组比较均无显著性差异（P>0.05）。结论 现有证据显示,丙酸倍氯米松雾化吸入治疗儿童哮喘急性发作的临床疗效和安全性与布地奈德相当,值得临床推广。     

依那普利叶酸片对比依那普利片治疗心力衰竭的Meta-分析

目的 系统评价依那普利叶酸片对比依那普利片治疗心力衰竭的疗效和安全性,为临床推广提供循证医学证据。方法 计算机检索中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普中文科技期刊数据库（VIP）、万方医学期刊全文数据库、PubMed及Cochrane library等数据库,收集有关依那普利叶酸片对比依那普利片治疗心力衰竭的随机对照研究（RCT）,采用Revman 5.3软件对各研究的N-末端B型利钠肽前体（NT-proBNP）、同型半胱氨酸（Hcy）、血浆和肽素水平、心脏超声指标、ADR等进行分析。结果 共纳入12项RCT,1 259例患者。Meta-分析显示：与依那普利片比较,依那普利叶酸片能进一步降低NT-proBNP水平（MD=-0.41,95% CI=-0.43~-0.40,P<0.01）、血浆和肽素水平（MD=-3.02,95% CI=-4.37~-1.68,P<0.01）和Hcy水平（MD=-3.36,95% CI=-4.04~-2.68,P<0.01）;显著增加LVEF/%（MD=5.00,95% CI=3.58~6.43,P<0.01）,降低LVEDD （MD=-4.07,95% CI=-5.74~-2.40,P<0.01）和LVESDD （MD=-3.49,95% CI=-5.23~-1.76,P<0.01）;ADR发生率（OR=1.00,95% CI=0.42~2.36,P>0.05）无显著性差异。结论 依那普利叶酸片降低心力衰竭患者NT-proBNP、Hcy和血清和肽素水平,改善心脏功能均优于依那普利片,两种药物安全性相当。     

Phase I study of a 3-drug regimen of gemcitabine/cisplatin/pemetrexed in patients with metastatic transitional cell carcinoma of the urothelium

Summary Objectives: Gemcitabine (G) plus cisplatin (C) is standard care for metastatic transitional cell carcinoma (TCC) of the urothelium. Pemetrexed (P), alone or in combination with G, is active in metastatic TCC. However, the safety and efficacy of P combined with GC therapy is unknown. This phase I trial was designed to determine the maximum tolerated dose (MTD) of GC followed by P + G in patients with metastatic TCC. Methods: Cohorts of 3 to 6 patients received escalating doses 28-day cycles (maximum 6 cycles): G 800–1,000 mg/m² on days 1 and 15; P 400–500 mg/m² on day 15; and C 50–70 mg/m² on day 1. All patients received folic acid, vitamin B₁₂, and full supportive care. The 3+3 standard phase I escalation rule was used to determine MTD. Results: Fifteen patients registered: 13/15 white males; median age 70 years (range, 53–82); 11/15 had KPS ≥ 90. At dose level 0, 2/4 patients experienced unrelated DLTs, and 1 patient was replaced (completed <1 cycle). Dose escalation proceeded to dose level 1. At level 1, 4/6 patients experienced DLTs; dosing decreased to level 0 and 4/5 patients experienced DLTs. The MTD was not determined. The 2 patients that completed 6 cycles both had partial responses. Grades 3–4 hematologic toxicities included neutropenia (60%), leukopenia (20%), and febrile neutropenia (13%). Conclusion: Adding P to the standard GC regimen as first-line therapy for metastatic TCC produced no benefit. The MTD exceeded therapeutic gemcitabine and cisplatin doses for urothelial cancer and thus the study was aborted.     

Dyadic analysis of criminal justice involvement and hiv risks among couples who inject drugs and their intimate partners in almaty,kazakhstan

BackgroundIncarceration increases HIV risk behaviors and strains intimate partnerships of couples of people who inject drugs (PWID) in Kazakhstan. Studies are yet to examine dyadic relationships between criminal justice involvement and injection drug and sexual HIV risk behaviors of couples who inject drugs in Kazakhstan. This study examined associations between individual and partner level criminal justice involvement and injection drug and sexual HIV risk behaviors among 216 intimate dyads (n = 432) of PWID in Almaty, Kazakhstan.MethodsThe Actor Partner Interdependence Model (APIM) using structural equation modeling examined individual (actor), partner and dyadic patterns (actor-partner) of associations between arrest, incarceration and drug crime conviction of dyads of male and female intimate partners of PWID using baseline data from Project Renaissance, a couples-focused HIV prevention intervention for PWID and their intimate partners.ResultsResults from the APIM identified significant associations between lifetime (β=0.10, CI_95%=0.01.20, p=.021) and recent (β=0.12, CI_95%=0.01.26, p=.045) arrest and increased risk of injection drug use with any partner for female partners. Partner-only effects were identified in which male PWID's recent arrest was associated with an increase in their study partners’ injection drug risk behaviors (β=0.10 CI_95%=0.02, 0.20, p=.044). For female partners, prior incarceration was associated with increased engagement in injection drug risk behaviors (β=0.10 CI_95% =0.02, 0.20, p=.035) with any partner. For male partners’ prior incarceration was associated with injection drug risk behaviors with their study partners (β=0.10 CI_95%= 0.02, 0.20. p<.05). Female partners prior drug crime conviction was associated with their own (β=0.14 CI_95%=0.01, 0.28, p=.048) and their intimate partners’ (β=0.18, CI_95%=0.03, 0.33, p=.024) engagement in injection drug risk behaviors with any injecting partner. Recent drug crime conviction (β=0.12, CI_95%=0.01, 0.24, p=.038) and arrest (β=0.13, CI_95%, p=.022) was associated with increased engagement in sexual risk behaviors among female partners.ConclusionFindings from this study identified differences in how criminal justice involvement impacts sexual and injection drug and sexual risk behaviors between male and female partners of PWID. Future research must investigate how structural interventions at the dyadic level could address the negative impact of criminal justice involvement on sexual and injection drug HIV risks within the contexts of couples who are PWID.     

Phase II study of irinotecan/S-1 combination chemotherapy for patients with oxaliplatin-refractory colorectal cancer

To determine the efficacy and tolerance of irinotecan in combination with S-1 (IRIS) for patients whose disease progressed after treatment with an oxaliplatin-based therapy for colorectal cancer (CRC). Each patient’s disease had progressed after the administration of a regimen containing oxaliplatin and 5-FU. S-1 was administered orally at a fixed dose of 40mg/m² twice daily on days 1–14 and 21–35. Irinotecan (150 mg/m²) was administered via intravenous infusion on days 1, 15, and 29. Courses were repeated every 6 weeks. 20 patients were enrolled in this study between April 2006 and March 2008. The median age was 63 years (range: 34–74), and the dominant metastasis sites were the liver, lung, and lymph nodes. The objective response rate was 20%; 1 patient registered complete response and 3 patients registered partial responses; 7 patients were stabilized (35%); and 9 evidenced progression of disease (45%). Median progression-free survival was 3.0 months (95% CI, 2.1–3.9 months) and median overall survival was 9.8 months (95% CI, 6.3–13.3 months). For the 41 cycles analyzed, the most commonly detected hematologic toxicity was grade I–II anemia (63.4%). Leukopenia occurred in 18 cycles (41.5%), including eight cycles (19.5%) of grade 3–4 leukopenia. Frequently observed non-hematologic toxicities included the following: grade I vomiting was reported in 4 patients (20%), grade 2 neuropathy occurred in 3 patients (15%), and grade 2 mucositis was noted in 2 patients (10%). Two patients died from sepsis and hematemesis during treatment. Although the response rate in stage I reached the target (≥ 3/18, p0 = 10%) established for movement to stage II, this study had to be discontinued because two patients died during treatment. Additionally, the follow-up loss rate was higher (16.6%) than we had anticipated (<10%). Even though a regime consisting of irinotecan combined with S-1 (IRIS) has proven effective in oxaliplatin-pretreated patients with advanced CRC, treatment-related mortalities and the high follow-up loss rate suggested that this IRIS protocol should result in early closure and modification.     

The influence of hepatic impairment on the pharmacokinetics of the dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptin

Objective Vildagliptin is a potent and selective dipeptidyl peptidase-IV (DPP-4) inhibitor that improves glycemic control in patients with type 2 diabetes mellitus by increasing α- and β-cell responsiveness to glucose. This study investigated the pharmacokinetics of vildagliptin in patients with hepatic impairment compared with healthy subjects. Methods This was an open-label, parallel-group study in patients with mild (n = 6), moderate (n = 6) or severe (n = 4) hepatic impairment and healthy subjects (n = 6). All subjects received a single 100-mg oral dose of vildagliptin, and plasma concentrations of vildagliptin and its main pharmacologically inactive metabolite LAY151 were measured up to 36 h post-dose. Results Exposure to vildagliptin (AUC_0–∞ and C_max) decreased non-significantly by 20 and 30%, respectively, in patients with mild hepatic impairment [geometric mean ratio (90% CI): AUC_0–∞, 0.80 (0.60, 1.06), p = 0.192; C_max, 0.70 (0.46, 1.05), p = 0.149]. Exposure to vildagliptin was also decreased non-significantly in patients with moderate hepatic impairment [−8% for AUC_0–∞, geometric mean ratio (90% CI): 0.92 (0.69, 1.23), p = 0.630; −23% for C_max, geometric mean ratio (90% CI): 0.77 (0.51, 1.17), p = 0.293]. In patients with severe hepatic impairment, C_max was 6% lower than that in healthy subjects [geometric mean ratio (90% CI): 0.94 (0.59, 1.49), p = 0.285], whereas AUC_0–∞ was increased by 22% [geometric mean ratio (90% CI): 1.22 (0.89, 1.68), p = 0.816). Across the hepatic impairment groups, LAY151 AUC_0–∞ and C_max were increased by 29–84% and 24–63%, respectively, compared with healthy subjects. The single 100-mg oral dose of vildagliptin was well tolerated by patients with hepatic impairment. Conclusions There was no significant difference in exposure to vildagliptin in patients with mild, moderate or severe hepatic impairment; therefore, no dose adjustment of vildagliptin is necessary in patients with hepatic impairment.