奇正消痛贴治疗急性软组织损伤130例临床观察

目的观察奇正消痛贴治疗急性软组织损伤的临床疗效。方法将130例急性软组织损伤患者,随机分为治疗组和对照组,每组各65例,治疗组运用奇正消痛贴治疗,对照组予跌打镇痛膏治疗,观察两组疗效。结果治疗组治愈39例(60.0%),显效22例(23.8%),无效4例(6.2%);对照组治愈26例(40.0%),有效28例(43.1%),无效11例(16.9%)。两组疗效相比,治疗组总有效率明显优于对照组(P<0.05)。结论奇正消痛贴治疗急性软组织损伤的临床疗效满意。     

A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain

Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg; 2 tablets of ibuprofen 200 mg/codeine 12.8 mg; 2 tablets of paracetamol 500 mg/codeine 15 mg; or placebo. Results for the primary endpoint, the sum of the mean scores of pain relief combined with pain intensity differences over 12 hours, demonstrated that 1 and 2 tablets of the single-tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo (P < 0.0001) and paracetamol/codeine (P ? 0.0001); furthermore, 2 tablets offered significantly superior pain relief to ibuprofen/codeine (P = 0.0001), and 1 tablet was found noninferior to this combination. Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations. In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200 mg/paracetamol 500 mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics currently indicated for strong pain.     

Efficacy and tolerability of rizatriptan 10 mg in migraine: experience with 70 527 patient episodes

As patients who suffer from migraine need long-term treatment, the safety and consistent efficacy of such therapy is very important. Concurrent illness and additional medication can interfere with the treatment chosen for the attacks of migraine. The objective of this open-label study was to investigate the efficacy and tolerability of rizatriptan, in the treatment of up to three attacks of migraine, in the clinical setting. From October 1998 to July 1999, 6 174 doctors enrolled 33 147 patients into the study (26 644 women, 650 men). The mean age was 42.7 years. We were able to examine standardized migraine diaries relating to 25 501 patients and 70 537 migrainous episodes. Rizatriptan scored consistently high on efficacy and showed a consistently rapid onset. There was no evidence of tolerance to repeated use. An effect was reported within 1 hour of ingestion in 79% of attacks treated. In 27.8% of attacks, remission of headache was complete at 1 hour. Two hours after ingestion, 74% of attacks had subsided completely. Repeated administration of rizatriptan was well tolerated, and few adverse effects were seen. The most common unwanted effects were dizziness, weakness, fatigue, and nausea. No cardiovascular disturbance was seen. In the clinical setting, rizatriptan, 10 mg, is an effective and well-tolerated agent for the treatment of migraine attacks. Particularly noteworthy is the rapid onset of effect, with swift disappearance of headache. Rizatriptan has a favorable side effect profile, and, provided contraindications are observed, severe adverse cardiovascular complications are extremely unlikely.     

异甘草酸镁预防急性白血病患者化疗药物性肝损害的疗效观察

目的观察异甘草酸镁预防急性白血病患者化疗药物性肝损害的疗效。方法急性白血病患者66例,随机分为2组：预防组34例,对照组32例。预防组给予化疗药物＋异甘草酸镁;对照组仅使用化疗药物。结果预防组出现肝损害有15例次（9.6%）,对照组46例次（31.7%）,2组差异有统计学意义;预防组预防肝损害有效率82.7%,对照组有效率22.7%,2组比较差异显著。治疗过程中未出现与异甘草酸镁相关不良反应。结论异甘草酸镁对急性白血病患者的化疗药物性肝损害具有较好的防治作用,值得临床推广。     

Analgesic efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg compared with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg in patients with moderate to severe postoperative pain: a randomized, double-blind, placebo-controlled, single-dose, parallel-group study in a dental pain model

BACKGROUND: Combination therapy has been widely used for the clinical management of acute pain. By combining 2 drugs with different mechanisms of action, such therapy provides additive analgesic effects while reducing the risk for adverse effects. OBJECTIVE: This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo in a dental pain model. METHODS: This was a multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group, single-dose study in patients experiencing moderate to severe pain after surgical removal of > or = 2 ipsilateral impacted third molars. Patients were randomly assigned to receive oxycodone 5 mg/ibuprofen 400 mg, oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, or placebo. The primary outcome measures were total pain relief through 6 hours after dosing (TOTPAR6), sum of pain intensity differences through 6 hours (SPID6), and adverse events. Secondary efficacy measures included SPID3 and TOTPAR3, peak pain relief, peak pain intensity difference, time to onset of pain relief, time to use of rescue medication, proportion of patients reporting pain half gone, and the patient's global evaluation. RESULTS: Two hundred forty-nine patients (43.5% male; 87.5% white; mean age, 19.1 years; mean body weight, 153.6 pounds) were randomized to treatment as follows: 62 to oxycodone 5 mg/ibuprofen 400 mg, 61 to oxycodone 5 mg/acetaminophen 325 mg, 63 to hydrocodone 7.5 mg/acetaminophen 500 mg, and 63 to placebo. Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo (mean [SD] TOTPAR6, 14.98 [5.37], 9.53 [6.77], 8.36 [6.68], and 5.05 [6.49], respectively; P < 0.001, oxycodone 5 mg/ibuprofen 400 mg vs all other treatments). SPID6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg compared with all other treatments (mean: 7.78 [4.11], 3.58 [4.64], 3.32 [4.73], and 0.69 [4.85]; P < 0.001). Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points (P < 0.001, all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [P = 0.006]), with the exception of the time to onset of analgesia. The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg (6.5% and 3.2%, respectively) and placebo (3.2% and 1.6%). Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg (P = 0.011 and P = 0.009, respectively) but not with hydrocodone 7.5 mg/acetaminophen 500 mg. CONCLUSIONS: In this study in patients with moderate to severe pain after surgery to remove impacted third molars, oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/nonopioid combinations tested, and was associated with fewer adverse events.     

Comparative efficacy of a proprietary topical ibuprofen gel and oral ibuprofen in acute soft tissue injuries: a randomized,double-blind study

The efficacy of a novel, proprietary topical formulation of ibuprofen 5% gel (Ibugel) and ibuprofen 400 mg tablets (1200 mg daily) was compared in a double-blind, double-dummy, parallel group study in patients with acute soft tissue injuries. Patients received either active gel plus placebo tablets (n = 50) or active tablets plus placebo gel (n = 50) for at least 7 days. The gel was applied and one tablet was taken three times daily. The two treatments showed similar efficacy. There were no significant differences between the groups for either the primary efficacy endpoint, the median time for the injury to be rated as 'completely better' by the patients (>14 days active gel, 13.5 days active tablets; P = 0.59), or for other efficacy measures including the times to clinically significant relief from pain at rest or on movement and swelling. In summary, ibuprofen gel shows similar efficacy to oral ibuprofen 400 mg and may offer improved tolerability.     

口服蛋白酶体抑制剂伊沙佐米治疗多发性骨髓瘤的疗效和安全性研究

目的:评价口服蛋白酶体抑制剂伊沙佐米治疗多发性骨髓瘤的有效性及安全性。方法:选择2018年7月1日至2019年4月4日于复旦大学附属中山医院接受2周期或以上伊沙佐米治疗的多发性骨髓瘤患者(排除轻链淀粉样变性及浆细胞白血病患者)。治疗方案包括伊沙佐米单药以及联合其他药物(来那度胺、沙利度胺或地塞米松等)的两药或三药方案。伊沙佐米的起始剂量为4 mg,第1、8、15天口服,28 d为1个周期。治疗第2周期及第4周期后进行疗效和安全性评估。结果:共27例多发性骨髓瘤患者符合入选标准,包括复发/难治15例、初发12例。复发/难治患者总体反应率(ORR)为53.3%,其中2例完全缓解(CR)、1例非常好的部分缓解(VGPR)、5例部分缓解(PR);中位获得反应时间为53 d。其中,既往硼替佐米治疗难治者ORR为54.5%(6/11)。可评估初发患者9例,ORR 100.0%,2例CR、3例VGPR、4例PR;中位获得反应时间为38 d。伊沙佐米治疗3～4级不良事件发生率为29.6%。主要血液学毒性为淋巴细胞、血小板及中性粒细胞计数降低和贫血;其他常见不良反应包括乏力和胃肠道反应。所有患者未出现3～4级外周神经毒性。结论:在中国真实世界中,伊沙佐米对初诊及复发/难治的多发性骨髓瘤患者具有良好的疗效及安全性。     

Efficacy and tolerability of topiramate 200 mg/d in the prevention of migraine with/without aura in adults: a randomized, placebo-controlled, double-blind, 12-week pilot study

BACKGROUND: Several large, randomized, double-blind, placebo-controlled trials have found topiramate (TPM) to be effective and generally well tolerated as a preventive therapy for migraine. OBJECTIVE: This paper evaluates efficacy and safety data from a pilot study of TPM 200 mg/d as preventive therapy in adult subjects with a history of migraine with or without aura. METHODS: The pilot study had a randomized, double-blind, placebo-controlled design. Subjects were randomized in a 2:1 ratio to receive TPM 200 mg/d or placebo. The double-blind treatment phase consisted of an 8-week titration period (25 mg/d for the first week, followed by weekly increases of 25 mg) and a 12-week maintenance period. The primary efficacy measure was the change in mean monthly migraine frequency. Additional measures were the median percent reduction in monthly migraine frequency and the proportion of responders (those with > or =50%, > or =75%, or 100% reduction in monthly migraine frequency). RESULTS: The intent-to-treat (ITT) population included 211 subjects (138 TPM, 73 placebo; mean [SD] mean weight, 76.7 [18.7] kg). Of 45 subjects who discontinued the study in the TPM group, 21 discontinued during the titration period, compared with 3 of 13 subjects who discontinued in the placebo group. When the efficacy data were assessed using the per-protocol, analysis-of-covariance model, TPM 200 mg/d was not associated with a significant reduction in mean monthly migraine frequency compared with placebo. A post hoc analysis using a Poisson regression model in the ITT population suggested that TPM significantly reduced mean monthly migraine frequency compared with placebo (P=0.04). A significantly larger proportion of TPM-treated subjects had a > or =75% reduction in monthly migraine frequency compared with placebo (P=0.03). At least 1 adverse event was reported by 90.0% and 69.9% of the TPM and placebo groups, respectively. Treatment-emergent adverse events (AEs) occurring in > or =10% of subjects in the TPM group were paresthesia (45%), dizziness (16%), fatigue (16%), nausea (14%), and weight loss (14%). Most treatment-emergent AEs were rated mild or moderate in severity. Of 3 serious AEs (depression, abdominal pain, leg pain) occurring during the trial, none were considered related to either TPM or placebo. CONCLUSION: In this pilot study, mean monthly migraine frequency did not differ significantly between TPM and placebo.     

Efficacy and tolerability of buccal buprenorphine in opioid-naive patients with moderate to severe chronic low back pain

Objectives: Buprenorphine HCl buccal film has been developed for treating chronic pain utilizing BioErodible MucoAdhesive (BEMA^®) delivery technology. Buccal buprenorphine (BBUP; Belbuca^TM, Endo Pharmaceuticals) was evaluated for the management of moderate to severe chronic low back pain (CLBP) requiring around-the-clock analgesia in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-naive patients.

Methods: Patients (n = 749) were titrated to a dose of BBUP (range, 150–450 µg every 12 h) that was generally well tolerated and provided adequate analgesia for ≥14 days, and then randomized to BBUP (n = 229) or placebo (n = 232), respectively. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in the mean of daily average pain intensity scores (numeric rating scale from 0 [no pain] to 10 [worst pain imaginable]).

Results: Patients were experiencing moderate to severe pain at study entry: mean (SD) = 7.15 (1.05). Following titration, pain was reduced to the mild range; 2.81 (1.07). After randomization, mean (SD) pain scores increased from baseline to week 12 more with placebo (1.59 [2.04]) versus BBUP: (0.94 [1.85]) with a significant between-group difference (?0.67 [95% CI: ?1.07 to ?0.26]; p = 0.0012). A significantly larger percentage of patients receiving BBUP versus placebo had ≥30% pain reduction (63% vs 47%; p = 0.0012). During double-blind treatment, the most frequent adverse events (AEs) with BBUP were nausea (10%), constipation (4%) and vomiting (4%). The most common AEs with placebo were nausea (7%), upper respiratory tract infection (4%), headache (3%) and diarrhea (3%).

Conclusions: These findings demonstrate the efficacy and tolerability of BBUP among opioid-naive patients requiring around-the-clock opioid treatment for CLBP.     

来那度胺联合利妥昔单抗治疗1~3a级滤泡性淋巴瘤的疗效和安全性

目的：评价来那度胺联合利妥昔单抗治疗1～3a级滤泡性淋巴瘤的疗效和安全性。方法：选择2019年5月30日至2019年12月31日间于复旦大学附属中山医院血液科接受来那度胺联合利妥昔单抗（R2）治疗的1～3a级初发和复发滤泡性淋巴瘤（FL）患者。具体方案为来那度胺，25mg，第1～7天，第15～22天，口服，共12周期；利妥昔单抗注射液，375mg/m2，第1周期的第1、8、15、22天，第2～5周期的第1天，静脉滴注，共5周期；每28天为1个周期。每2～3个周期行疗效评价，主要评价指标为总体反应率（ORR），1年无进展生存（PFS）。每周期前后进行安全性评价。结果：共12例患者接受了R2治疗，10例疗效可评价，ORR为88.9%，1年PFS为87.5%，中位PFS未达到。3～4级中性粒细胞计数减少发生率为16.7%，3～4级肺部感染发生率为16.7%，未观察到3～4级的肝肾功能异常、皮疹、消化不良、周围神经病变。结论：隔周服用来那度胺的给药方式在来那度胺联合利妥昔单抗治疗1～3a级初发、复发FL患者中可取得良好疗效和安全性。     

基于单中心的波生坦治疗先天性心脏病相关肺动脉高压有效性及安全性分析

目的：回顾性观察波生坦治疗先天性心脏病相关肺动脉高压的远期有效性与安全性。 方法：经临床诊断后,纳入先天性心脏病相关肺动脉高压患者33例,其中2例为外科手术后患者,3例为介入封堵后患者,28例为临床诊断重度肺动脉高压存在手术禁忌症患者,我们对这些患者进行了5年左右的随访,波生坦的用量从62.5mg bid开始,4周后若无明显的副反应则加量至125mg bid。服药前分别进行6分钟步行试验（6MWD）,心超估测肺动脉压,评定心功能等级,肝功能检查,6个月后复查上述指标,之后每半年随访一次。平均随访年限为4.7±0.5年。 研究结果：33例患者（其中女性患者26例,平均年龄31岁,心功能II-IV级,5例接受封堵或修补手术）,死亡1例,接受波生坦口服治疗平均长达4.6年。随访至第三年时,患者6分钟步行试验距离从基线从303.0±88.1m增加至3年时的370.1±68m（P<0.001）;肺动脉收缩压（SPAP）从基线时的113.7±26.7mmHg降至92.9±31.8mmHg（P<0.001）;NYHA心功能分级从基线2.5±0.6降至2.2±0.6（P＝0.018）。肝功能指标：谷丙转氨酶（ALT）在随访期间均无显著性差异。但在3年随访之后,肺动脉收缩压,6分钟步行试验和心功能分级的改善情况开始明显减缓,甚至呈现“逆升高”趋势,服药五年后随访肺动脉收缩压、6分钟步行距离分别为101.0±32.8mmHg, 332±86m,较服药前基线数据仍有明显统计学差异（P=0.018,P=0.02）,患者心功能分级升至2.4±0.6,较服药前无明显统计学差异（P=0.43）。 结论：波生坦可以降低先天性心脏病相关重度肺动脉高压的肺动脉压力,有效控制其进行性升高趋势,改善心功能分级,提高患者的活动耐量,且对肝功能无明显影响。但在长期随访中,波生坦的作用逐步趋向下降,其长期效用仍待更多临床试验证实。     

Efficacy and tolerability of diclofenac potassium sachets in acute postoperative dental pain: a placebo-controlled, randomised, comparative study vs. diclofenac potassium tablets

This double-blind, randomised, parallel-group trial compared the analgesic efficacy of single 50 mg doses of diclofenac potassium sachets and tablets with placebo in 184 patients with moderate/severe pain after third molar extraction. The primary efficacy variable was the average pain reduction from baseline during the first 2-h postdose, using a visual analogue scale (VAS). During the first 2-h postdose, sachets and tablets significantly reduced pain (p < 0.05) vs. placebo with an incremental benefit seen for sachets over tablets (p < 0.05). Onset of analgesic effect (VAS) was at 30 min for sachets and 45 min for tablets. Pain reduction vs. placebo (VAS) was maintained for 8 h for sachets and tablets (p < 0.05). VAS-findings were confirmed by pain relief and intensity verbal scale assessments. Fewer patients re-medicated vs. placebo. No safety issues were identified. This study demonstrates that both diclofenac potassium sachets and tablets offer patients suffering from acute pain conditions an effective treatment with incremental analgesic benefits seen for sachets.     

Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced doses: a comparison with propranolol 160 mg daily

This was a phase-IV double-blind equivalence trial designed to assess the efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5 mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse events (n=58). The mean attack frequency in the double-blind period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The mean attack frequency in the last 28 days of the double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at least as effective as propranolol (P<0.001 in one-sided test). The percentage of responders (defined as subjects for whom attack frequency decreased by at least 50% compared to run-in) in the last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall, 190 subjects reported one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The results of this equivalence trial show that 10 mg flunarizine daily with a drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis of migraine for all evaluated parameters (one-sided equivalence tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective as 160 mg propranolol when looking at the mean attack frequency for both the whole double-blind period and the last 28 days of treatment. However, in the analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg flunarizine. In addition, no significant differences between the three treatments were found with regard to safety: all three treatments were generally well-tolerated and safe.     

国产硼替佐米（昕泰）治疗初治多发性骨髓瘤的初步研究

目的:初步评价国产硼替佐米(昕泰)治疗初治多发性骨髓瘤(multiple myeloma, MM)的有效性及安全性。方法:纳入确诊活动性MM,并接受昕泰治疗2个周期以上可评估疗效的初治患者。采用昕泰联合地塞米松的两药(BD)方案或两药基础上加用环磷酰胺的三药方案(VCD)。昕泰的起始剂量为每周1.3 mg/m~2。每2周期评价疗效和安全性。结果:2018年6月至2018年11月,共纳入14例MM患者,随访至2019年1月。全部患者可行2周期疗效评估,其中3例为非常好的部分缓解(VGPR)、9例部分缓解(PR)、1例微小缓解(MR)、1例疾病进展(PD),总反应率(ORR)为85.7%。6例患者可行4周期疗效评估,均为VGPR,ORR为100%。不良事件与原研药类似。主要血液学毒性包括血小板及淋巴细胞计数降低;非血液学毒性主要为消化系统不良反应,腹泻与便秘较多见。结论:昕泰治疗初治MM具有良好的疗效及安全性。     

地西他滨联合非血缘脐血移植治疗缓解后老年急性髓系白血病的疗效和安全性

目的:对比老年急性髓系白血病(EAML)经诱导治疗达到完全缓解后,用地西他滨联合非血缘脐血移植和传统方案巩固治疗的安全性和疗效。方法:回顾性分析2019年1月至2022年1月至盐城市第一人民医院和淮安市第一人民医院血液科就诊的经1-2周期诱导治疗获得完全缓解(CR)的老年AML患者52例,根据巩固治疗方案的不同分为观察组(24例)和对照组(28例),其中观察组接受地西他滨联合非血缘脐血移植巩固治疗,对照组接受传统巩固治疗,包括阿扎胞苷+维奈克拉、去甲氧柔红霉素+阿糖胞苷(IA)、阿柔比星+阿糖胞苷+粒细胞集落刺激因子(CAG)等。对比两组患者的临床疗效、造血恢复时间、不良反应、无复发生存期(RFS)、总生存期(OS)。结果:观察组中性粒细胞中位恢复时间12.54 d,对照组18.64 d,两组比较差异有统计学意义(P＜0．001);观察组血小板中位恢复时间12.67 d,对照组19.71 d,两组比较差异有统计学意义(P＜0.001)。观察组III-IV级骨髓抑制的发生率为95.83%,对照组为78.57%,差异无统计学意义(P＞0.05);两组非血液学毒性发生率分别为41.67%和42.86%,差异无统计学意义(P＞0.05)。观察组和对照组中位RFS分别为33和11个月,中位OS分别为36和24个月,两组比较差异均有统计学意义(P＜0.05)。结论:相较于传统巩固治疗方案,地西他滨联合非血缘脐血移植巩固治疗是老年AML患者诱导缓解后的有效治疗方案,可延长无复发生存时间(RFS),提高总生存率(OS)。     

Long-term tolerability of tramadol LP, a new once-daily formulation, in patients with osteoarthritis or low back pain

Introduction: Tramadol hydrochloride is a centrally acting analgesic, which possesses opioid agonist properties and activates monoaminergic spinal inhibition of pain. An oral, once a day, sustained release formulation of tramadol is thought to be advantageous compared with immediate release preparations as it prevents plasma peaks associated with increased side-effects of the drug. It may also improve compliance. The purpose of the study was to assess the long-term safety of a new sustained-release formulation of tramadol (tramadol LP) in patients with knee or hip osteoarthritis and in patients with refractory low back pain. Study design: The design was a phase III, open, multicentre, international, tolerability study with tramadol LP at a dose titrated by the patient between 100 and 400 mg once daily, according to the intensity of pain. The treatment was administered for a continuous period of 4 weeks followed by an intermittent intake of 5 months in 204 patients. The safety criteria for evaluation were recording of adverse events, laboratory tests, electrocardiogram, radiography, global tolerability assessed by the patient and the investigators. Results: Long-term use of tramadol LP was reasonably well tolerated. Most of the reported adverse events were expected and occurred within the first month of treatment. Roughly half of the patients (49%) reported adverse events, of which 66% were related to treatment. Gastrointestinal events (nausea and vomiting) were the most frequent. Serious adverse events were reported in 6·4% of patients, from which only two cases were related to treatment. There was no sign of tolerance development and the percentage of patients presenting withdrawal symptoms after the end of treatment was low (6%). Conclusion: Long-term treatment with tramadol LP once daily is generally safe in patients with osteoarthritis or refractory low back pain.     

Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections

Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7–14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1–90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4–96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3–69.7) with daptomycin and 47.4 % (95 % CI, 24.4–71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran–Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.     

Efficacy and tolerability of paracetamol/tramadol (325 mg/37.5 mg) combination treatment compared with tramadol (50 mg) monotherapy in patients with subacute low back pain: a multicenter, randomized, double-blind, parallel-group, 10-day treatment study

BACKGROUND: In various pain studies, the single-dose combination of paracetamol/tramadol (PIT) was found to be more effective than either agent alone. PIT could provide benefit in patients with subacute low back pain (LBP). OBJECTIVE: This study compared the efficacy and tolerability of PIT with tramadol alone (T) in patients with subacute LBP and assessed whether, under comparable analgesic conditions, PIT would be better tolerated. METHODS: This was a multicenter, randomized, double-blind, parallel-group study. Patients were enrolled if they suffered from nonspecific LBP lasting 10 to 42 days and experienced at least moderate pain (> or =40 mm on a 100-mm visual analog scale). Patients were randomized and treated for 10 days with PIT (325 mg/37.5 mg) or T (50 mg). The study outcomes were treatment efficacy (pain intensity, pain relief, patient satisfaction, physicians' assessment of pain control) and tolerability (adverse events [AEs], patients' tolerability judgment). RESULTS: A total of 119 patients were enrolled (PIT, n = 59; T, n = 60). Demographic characteristics of patients were comparable between the PIT and T groups in regard to age (mean, 56.5 vs 54.1 years, respectively), sex (women/men, 38121 vs 31129), race (white, 96.1% vs 94.2%), and body mass index (24.9 vs 26.1 kg/m2). Pain intensity (mean [SD] percentage of worst imaginable pain) improved from nearly identical levels at baseline (P/T, 67.5 [13.0] vs T, 65.3 [14.6]; P = NS) to similarly low levels at the final visit (P/T, 27.9 [22.7] vs T, 24.8 [21.6]; P = NS). The reduction in pain intensity was significant in both treatment groups (P < 0.001). Adequate pain relief (ie, "moderate," "important," or "complete") was observed in 81.6% (40149) of PIT patients versus 82.9% (39147) of T patients (P = NS). Comparably high rates of overall patient satisfaction (72.5% [37151] vs 72.9% [35148], respectively; P = NS) were achieved. Both treatment groups took a comparable number of daily units of study medication, which resulted in significantly (P < 0.001) lower daily doses of tramadol in the P/T group (mean [SD], 172.5 [46.6] mg) than in the T group (227.3 [59.7] mg). More P/T patients (84.3%) than T patients (68.8%) judged treatment tolerability as good or very good (P = NS). Significantly fewer AEs (P < 0.001) were observed in PIT patients, and the overall incidence of AEs (mostly opioid-typical AEs [eg, nausea, dizziness/vertigo, sleepiness/drowsiness, constipation, vomiting]) was much lower after P/T compared with T (P = 0.019). The most common AEs in the P/T and T groups were nausea (8159 vs 21160 patients, respectively; P = 0.012) and dizziness (3/59 vs 15/60 patients; P= 0.006). CONCLUSIONS: Tramadol, alone and in combination with paracetamol, provided highly effective analgesia for these patients with subacute LSP However, the combination of PIT, which resulted in 25% less tramadol than equianalgesic daily doses of T alone, considerably reduced the incidence of AEs and improved tolerability.     

Efficacy and tolerability of non-invasive ventilation delivered via a newly developed helmet in immunosuppressed patients with acute respiratory failure

OBJECTIVES: To assess efficacy and tolerability of a newly developed helmet for the delivery of non-invasive ventilation in patients with acute respiratory failure. PATIENTS AND METHODS: Ten consecutive immunocompromised patients with acute respiratory failure admitted to our intensive care unit were included in the study. The patients were equipped with the helmet and non-invasive ventilation (NIV) was performed. Oxygenation and tolerability were assessed during the first 24 hours of NIV. RESULTS: All patients tolerated the helmet well and their oxygenation improved. Two patients developed septic shock and had to be endotracheally intubated during the study period, eight patients survived to be weaned from NIV. CONCLUSIONS: NIV delivered via the helmet is effective and may serve as a better tolerated alternative to endotracheal intubation and to NIV via a standard face mask.     

肝动脉化疗栓塞术联合射频消融治疗肝癌患者的疗效及安全性

目的探讨肝动脉化疗栓塞术联合射频消融治疗肝癌患者的疗效及安全性。方法 124例肝癌患者分为对照组和观察组。对照组接受肝动脉化疗栓塞术治疗,观察组接受肝动脉化疗栓塞术联合射频消融治疗。比较2组影像检查、复发率及血液等指标。结果 2组甲胎蛋白、肿瘤最大直径有显著差异(P0.05)。观察组复发率较对照组低(P0.05)。观察组3、6个月的疗效、生存率明显优于对照组(P0.05)。结论肝动脉化疗栓塞术联合射频消融治疗可有效控制患者的病灶部位,降低复发率,提高生存率。