First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib [NCT00267215]

Cyclo-oxygenase-2 selective inhibitors are frequently used to manage osteoarthritis. We compared the analgesic efficacy of the novel cyclo-oxygenase-2 selective inhibitor lumiracoxib (Prexige) versus placebo and celecoxib in patients with knee osteoarthritis. This seven day, double-blind, placebo and active comparator controlled, parallel group study included 364 patients aged > or = 50 years with moderate-to-severe symptomatic knee osteoarthritis. Patients received lumiracoxib 400 mg/day (four times the recommended chronic dose in osteoarthritis; n = 144), placebo (n = 75), or celecoxib 200 mg twice daily (n = 145). The primary variable was actual pain intensity difference (100 mm visual-analogue scale) between baseline and the mean of three hour and five hour assessments after the first dose. Actual pain intensity difference, average and worst pain, pain relief and functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were measured over seven days. Patients also completed a global evaluation of treatment effect at study end or premature discontinuation. For the primary variable, the superiority of lumiracoxib versus placebo, the noninferiority of lumiracoxib versus celecoxib, and the superiority of lumiracoxib versus celecoxib were assessed by closed test procedure adjusting for multiplicity, thereby maintaining the overall 5% significance level. In addition, celecoxib was assessed versus placebo in a predefined exploratory manner to assess trial sensitivity. Lumiracoxib provided better analgesia than placebo 3-5 hours after the first dose (P = 0.004) through to study end. The estimated difference between lumiracoxib and celecoxib 3-5 hours after the first dose was not significant (P = 0.185). Celecoxib was not significantly different from placebo in this analysis (P = 0.069). At study end 13.9% of lumiracoxib-treated patients reported complete pain relief versus 5.5% and 5.3% of celecoxib and placebo recipients, respectively. WOMAC total and subscales improved for both active treatments versus placebo except for difficulty in performing daily activities, for which celecoxib just failed to achieve significance (P = 0.056). In the patient's global evaluation of treatment effect, 58.1% of patients receiving lumiracoxib rated treatment as 'excellent' or 'good', versus 48.6% of celecoxib and 25.3% of placebo patients. Lumiracoxib was well tolerated. The overall incidence of adverse events was similar across treatment groups.     

Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor,to patients with knee osteoarthritis: a randomized, 12-month,double-blind,placebo-controlled study

We performed a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-response study of the efficacy and safety of the oral administration of PG-116800, a matrix metalloproteinase (MMP) inhibitor, in patients with mild to moderate knee osteoarthritis. The primary efficacy endpoints included the progression of joint space narrowing in the osteoarthritic knee, as measured by microfocal radiography with fluoroscopic positioning, and the reduction of symptoms (pain and stiffness) and/or the improvement of function, as measured by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Four hundred and one patients were randomly assigned to either placebo (n = 80) or one of fourdoses of PG-116800: 25 mg (n = 81), 50 mg (n = 80), 100 mg (n = 80), or 200 mg (n = 80) taken twice daily for 12 months. During the study, the 200-mg dose was discontinued based on an increased frequency of musculoskeletal adverse effects. After 1 year of treatment, no statistically significant difference was observed between placebo and PG-116800 with regard to mean changes in minimum joint space width of the knee or to WOMAC scores. The most frequent adverse effect was arthralgia (35%). Twenty-three percent of evaluable patients had at least a 30% decrease from baseline of at least onerange-of-motion measurement of either shoulder at a follow-up visit. The percentage of patients with reduction in range of motion was significantly greater in the twohighest dose groups relative to placebo. Thirteen percent of patients, half of whom were in the 200-mg group, reported hand adverse events (oedema, palmar fibrosis, Dupuytren contracture, or persistent tendon thickness or nodules). The threemost frequent shoulder adverse events were reversible arthralgia, stiffness, and myalgia, which mostly affected the twohighest dose groups. The unfavorable risk-benefit balance of the MMP inhibitor PG-116800 in patients with knee osteoarthritis precludes further development of the compound for this indication. This study adds to the weight of evidence suggesting that side effect profiles of MMP inhibitors in general make them unsuitable for use in osteoarthritis.     

Short- and long-term effects of mud-bath treatment on hand osteoarthritis: a randomized clinical trial

The aim of this study was to evaluate both the short-term and the long-term effectiveness of spa therapy in patients with primary hand osteoarthritis (OA). This was a prospective randomized, single blind controlled trial. Sixty outpatients with primary bilateral hand OA were included in the study and randomized to one of two groups. One group (n?=?30) was treated with 12 daily local mud packs and generalized thermal baths with a sulfate-calcium-magnesium-fluorides mineral water added to usual treatment. The control group (n?=?30) continued regular outpatient care routine (exercise, NSAIDs and/or analgesics). Each patient was examined at baseline, after 2 weeks, and after 3, 6, 9 and 12 months. Primary outcome measures were global spontaneous hand pain on a visual analogue scale (VAS) and the functional index for hand osteoarthritis (FIHOA) score; secondary outcomes were health assessment questionnaire (HAQ), duration of morning stiffness, medical outcomes study 36-item short form (SF-36) and symptomatic drugs consumption. Our results demonstrated that the efficacy of spa therapy was significant in all the assessed parameters, both at the end of therapy and after 3 months; the values of FIHOA, HAQ and drugs consumption continued to be significantly better after 6 months in comparison with baseline. There were no significant modifications of the parameters throughout the follow-up in the control group. Differences between the two groups were significant for all parameters at the 15th day and at 3 months follow-up; regarding FIHOA, HAQ, and symptomatic drugs consumption, the difference between the two groups persisted and was significant at 6month follow-up. Tolerability of spa therapy seemed to be good. In conclusion, our results confirm that the beneficial effects of spa therapy in patients with hand OA last over time.     

Comparison of outpatient and inpatient spa therapy in knee osteoarthritis

Osteoarthritis (OA) is a common condition that impacts many people worldwide and involves weight-bearing joints, resulting in chronic pain. In this study, we aimed to compare the effectiveness of inpatient and outpatient physical therapy modalities and spa combination treatments on pain and functional status in patients with knee osteoarthritis. Seventy-four patients diagnosed with primary knee osteoarthritis were included in this study. The patients were randomized into two groups, inpatient (n?=?37) and outpatient (n?=?37) physical therapy. All patients received a physical therapy program (superficial heater + deep heater + transcutaneous electrical nerve stimulation) for 2 weeks and spa therapy. All cases were evaluated clinically, laboratory, and radiographically. In order to evaluate pain and functional status, the Visual Analogue Scale (VAS), Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and Timed Up and Go (TUG) test were used before and after treatment. There was no significant difference between the two groups in the TUG test and WOMAC scores (p?>?0.05). However, a significant difference was found in VAS scores in favor of the outpatient group (p?<?0.05). As a result, although there was a significant improvement in pain scores in the outpatient group, multicenter studies with larger patient groups may provide more evidence.

     

盐酸氨基葡萄糖片联合玻璃酸钠治疗颞下颌关节骨关节炎的疗效观察

目的:研究盐酸氨基葡萄糖片联合玻璃酸钠治疗颞下颌关节骨关节炎(TMJOA)的临床疗效,为临床治疗提供依据。方法:选取2012年11月到2015年11月我院收治的TMJOA患者60例,按照随机数字表法将患者分为研究组和对照组,每组30例,两组均给予玻璃酸钠关节腔注射,研究组在此基础上给予盐酸氨基葡萄糖片治疗,应用视觉模拟评分法(VAS)评价关节疼痛情况,比较两组临床疗效和不良反应,比较治疗前后两组最大张口度、张口VAS评分和张口偏斜。结果:研究组总有效率为83.33%(25/30),显著高于对照组的56.67%(17/30),比较差异具有统计学意义(P0.05);治疗后两组张口VAS评分和张口偏斜显著降低,最大张口度显著增高,且研究组显著优于对照组,比较差异具有统计学意义(P0.05);两组不良反应发生率比较差异无统计学意义(P0.05)。结论:盐酸氨基葡萄糖片联合玻璃酸钠治疗TMJOA具有较好的临床疗效,能有效改善患者关节功能。     

The quality of clinical trials with Harpagophytum procumbens

OBJECTIVE: To examine systematically the quality of the clinical trials investigating the effectiveness of Harpagophytum products. METHODS: Literature searches and enquiries to experts identified 20 studies of treatment with various Harpagophytum products (powder, aqueous and ethanolic extracts) for exacerbations of chronic musculoskeletal pain. Eight were open uncontrolled observational studies, one comparing progress under treatment for pain in back, knee and hip pain. Two were open comparisons with conventional treatment, only one of which was randomised. Ten were double-blinded, randomised controlled comparisons, 8 with placebo and 2 with NSAID comparator treatments. Indices of the internal and external validities were examined by reference to a checklist to see how well the studies answered the questions: do Harpagophytum products work and do they work as well as more conventional comparator treatments? RESULTS: The uncontrolled trials, though providing useful preliminary estimates of the possible effect of treating various conditions, could not separate the effects of the Harpagophytum product from whatever placebo effect might have been exerted in the circumstances of the study. The 2 open comparisons were open to performance, detection and/or selection bias. Of the 8 randomised double blinded controlled comparisons with placebo, 6 were marred by lack of transparency, one could not provide definitive evidence from its pre-selected principal outcome measure, and one provided good quality evidence of a dose dependent superiority of effect over placebo, though this was with a product that is not generally available for clinical practice. One of the randomised controlled comparisons with comparator (Doloteffin versus rofecoxib) was intended only as a pilot and studied too few patients for definitive conclusions whereas the other did provide good evidence that the powder, Harpadol is not importantly less effective than the weak NSAID diacerhein. CONCLUSIONS: Evidence of effectiveness of Harpagophytum products is not transferrable from product to product. The results of some studies suggest some effectiveness for some products, but for none of the clinically available products is the quality of evidence totally satisfactory. It is better so far with products that contain at least 50 mg of harpagoside in the daily dosage than with products (which happen to be of ethanolic extraction) that contain less.     

Differences between the tolerance characteristics of two anticonvulsant benzodiazepines in the amygdaloid-kindled rat

The characteristics of the development of tolerance to the anticonvulsant effects of chronic treatment by dipotassium clorazepate and diazepam using amygdaloid-kindled rats were investigated. Dipotassium clorazepate (5 mg/kg) or diazepam (5 mg/kg) were intraperitoneally administered for 10 consecutive days. Tolerance to the anticonvulsant effect of dipotassium clorazepate developed in seizure stage on day 6, after-discharge duration on day 7 and seizure latency on day 4. In contrast, tolerance to the effects of diazepam developed more rapidly in seizure stage on day 4, after-discharge duration on day 4 and seizure latency on day 3. Thus tolerance to the anticonvulsive effect of dipotassium clorazepate developed relatively slower than that to diazepam. All rats had stage 5 convulsions 24 hr after cessation of the administration of dipotassium clorazepate and diazepam. Concomitant determinations of plasma concentrations of the main metabolite of dipotassium clorazepate and diazepam, desmethyldiazepam, showed no statistical difference during treatment, suggesting that the developed tolerance was not metabolic but functional.     

膝关节镜下有限清理与广泛清理术治疗膝关节骨关节炎的临床疗效

目的:研究膝关节镜下有限清理与广泛清理术治疗膝关节骨关节炎的临床疗效。方法:选择2012年2月至2013年2月我院收治的80例膝关节骨关节炎患者,按随机数字表法平均分为研究组及对照组各40例,研究组行膝关节镜下有限清理术,对照组行广泛清理术;比较两组患者治疗优良率、手术前及术后1年膝关节功能评分及手术时间、住院时间等。结果:研究组患者治疗优良率为80.00%(32/40)高于对照组的75.00%(30/40),但差异无统计学意义(P0.05);研究组手术时间及住院时间分别为(30.4±14.8)h及(8.9±4.3)d,明显低于对照组的(60.6±16.9)h及(15.6±6.8)d,比较差异具有统计学意义(P0.05);两组术后1年膝关节功能评分较治疗前均明显改善,研究组术后Lysholm评分为(73.2±12.3)分,与对照组的(73.7±11.9)分比较差异无统计学意义(P0.05);两组患者均未出现术后感染等并发症,对照组2例出现术后下肢静脉血栓,研究组无严重并发症发生,两组比较差异无统计学意义(P0.05)。结论:膝关节镜下有限清理术治疗膝关节骨关节炎与广泛清理术疗效相当,但可明显缩短手术时间及住院时间,患者恢复快,值得推广应用。     

不同剂量甲氨蝶呤联合不同剂量叶酸治疗活动期类风湿关节炎的临床研究

摘要 目的：探讨不同剂量甲氨蝶呤（MTX）联合不同剂量的叶酸治疗活动期类风湿关节炎（RA）的疗效与安全性。方法：选取100例符合纳入、排除标准的RA患者,按照28关节疾病活动指数（DAS28）分为高疾病活动度组（使用MTX 15 mg 每周1次）50例和低疾病活动度组（使用MTX 10 mg 每周1次）50例。高疾病活动度组按叶酸使用10 mg 每周1次 或5 mg 每周1次随机分为两组。低疾病活动度组按叶酸使用5 mg 每周1次或不使用随机分为两组,对比治疗6个月后的临床疗效和安全性。结果：治疗后,高疾病活动度叶酸5 mg组DAS28评分、视觉模拟评分量表（VAS）评分、血沉（ESR）、超敏C反应蛋白（hs-CRP）以及总有效率均优于叶酸10 mg组（P<0.05）,但是两组健康评定问卷（HAQ）评分、不良反应发生率和MTX浓度比较无明显差异（P>0.05）。低疾病活动度叶酸5 mg 组与无叶酸组患者治疗后hs-CRP、ESR、MTX浓度比较差异有统计学意义（P<0.05）,但是两组总有效率和不良反应发生率比较无明显差异（P>0.05）。结论：RA高疾病活动时,使用MTX 15 mg 每周1次联合叶酸5 mg 每周1次疗效更优,且不良反应发生率及MTX浓度变化不明显。RA低疾病活动时,MTX 10 mg 每周1次,与是否使用叶酸在疗效和安全性上无显著差异,但未使用叶酸患者的MTX浓度更高。     

Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports

The objective was to improve understanding of adverse events occurring with celecoxib in the treatment of osteoarthritis and rheumatoid arthritis. Data were extracted from company clinical trial reports of randomised trials of celecoxib in osteoarthritis or rheumatoid arthritis lasting 2 weeks or more. Outcomes were discontinuations (all cause, lack of efficacy, adverse event, gastrointestinal adverse event), endoscopically detected ulcers, gastrointestinal or cardio-renal events, and major changes in haematological parameters. The main comparisons were celecoxib (all doses) versus placebo, paracetamol (acetaminophen) 4,000 mg daily, rofecoxib 25 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs) (naproxen, diclofenac, ibuprofen, and loxoprofen). For NSAIDs, celecoxib was compared both at all doses and at licensed doses (200 to 400 mg daily). Thirty-one trials included 39,605 randomised patients. Most patients had osteoarthritis and were women of average age 60 years or above. Most trials lasted 12 weeks or more. Doses of celecoxib were 50 to 800 mg/day. Compared with placebo, celecoxib had fewer discontinuations for any cause or for lack of efficacy, fewer serious adverse events, and less nausea. It had more patients with dyspepsia, diarrhoea, oedema, more adverse events that were gastrointestinal or treatment related, and more patients experiencing an adverse event. There were no differences for hypertension, gastrointestinal tolerability, or discontinuations for adverse events. Compared with paracetamol, celecoxib had fewer discontinuations for any cause, for lack of efficacy, or diarrhoea, but no other differences. Compared with rofecoxib, celecoxib had fewer patients with abdominal pain and oedema, but no other differences. Compared with NSAIDs, celecoxib had fewer symptomatic ulcers and bleeds, endoscopically detected ulcers, and discontinuations for adverse events or gastrointestinal adverse events. Fewer patients had any, or a gastrointestinal, or a treatment-related adverse event, or vomiting, abdominal pain, dyspepsia, or reduced haemoglobin or haematocrit. Discontinuations for lack of efficacy were higher. No differences were found for all-cause discontinuations, serious adverse events, hypertension, diarrhoea, nausea, oedema, myocardial infarction, cardiac failure, or raised creatinine. Company clinical trial reports present much more information than published papers. Adverse event information is clearly presented in company clinical trial reports, which are an ideal source of information for systematic review and meta-analysis.     

不同周期大剂量地塞米松对初诊ITP的疗效和安全性分析

目的：比较单周期、双周期、三周期大剂量地塞米松治疗初诊原发免疫性血小板减少症（ITP）的疗效和安全性。方法：93名初诊患者按1∶1∶1随机接受单周期（A组：地塞米松每次40 mg每天1次,第1日至第4日）、双周期（B组：地塞米松每次40 mg每天1次,第1日至第4日、第15日至第18日）、三周期大剂量地塞米松（C组：地塞米松每次40 mg每天1次,第1日至第4日、第15日至第18日、第29日至第32日）治疗,比较三组患者的疗效和安全性。结果：93名初诊原发免疫性血小板减少症患者,A组、B组、C组各31名患者,就短期疗效而言,三组相比,停药第7日完全反应率、第14日完全反应率差异均无统计学意义,但是,停药第7日ABC三组的有效率（41.9%vs 70.0%vs 90.0%,P<0.01）、第14日有效率（16.1%vs 36.70%vs 63.3%,P<0.01）差异有统计学意义;就长期疗效而言,三组之间治疗第120日有效率、第60日完全反应率、第90日完全反应率、第120日完全反应率、第90日复发率、第120日复发率差异无统计学意义,但是,第60日有效率（10.0%vs 26.6%vs 53.3%,P<0.01）、第90日有效率（0.0%vs 13.3%vs 30.0%,P<0.01）和第60日复发率（88.9.0%vs 73.3%vs 46.7%,P<0.01）差异有统计学意义,三组治疗相关的不良反应多较轻微,患者大多可耐受。结论：增加大剂量地塞米松的周期,虽没有提高ITP患者的完全反应率,但提高了3月内的有效率,且不良反应可以耐受,可以作为临床用药的参考。     

UKA与TKA治疗膝关节内侧单间室骨性关节炎的临床对比

目的:探究膝关节单髁置换术(UKA)与全膝关节置换术(TKA)治疗膝关节内侧单间室骨性关节炎的临床治疗效果。方法:将2011年4月-2015年7月期间因膝关节单间室骨性关节炎入院接受治疗的89例患者纳入本研究,随机分为研究组和对照组,研究组44例,行UKA手术,对照组45例,采用TKA手术方式治疗。对两组患者进行术后随访,对比临床治疗效果。结果:两组术前均有明显膝关节疼痛,术后膝关节疼痛均明显改善,组间差别无显著统计学意义(X2=1.323,P=0.2500.05);术后膝关节屈曲角度、HSS评分相对于术前均显著改善,研究组术后膝关节屈曲角度(111.2±18.8)度高于对照组的(98.6±14.7)度,差异有统计学意义(P0.05);HSS评分(87.6±13.7)分高于对照组的(73.2±16.8)分,差异有统计学意义(P0.05);研究组膝关节屈曲至90度时间比对照组短,数据差异有统计学差异(t=-2.303,P=0.0240.05)。结论:膝关节内侧单间室骨性关节炎采用UKA与TKA均能取得一定临床效果,减轻患者痛苦,改善膝关节功能,但UKA临床疗效较好,手术创伤较小,术后恢复较快。     

Gait characteristics of patients with knee osteoarthritis.

The knee kinematics and kinetics of 139 patients (47 males and 92 females) with Grade II knee osteoarthritis (OA) were measured during level walking, stair ascent and stair descent. There was no significant difference in knee motion between the patients and normal subjects. The patients with knee OA had a significantly reduced internal knee extensor moment compared to normal subjects. This difference reflects the patient's compensation to reduce the knee joint loading. Further, subjects with OA and a higher body mass index have a lower knee extensor moment. The female subjects had significantly greater knee flexion and a greater knee extensor moment. This gender difference may partially explain the increased prevalence of OA in females. Most tests of OA treatments are assessed by criteria that do not reflect functional activities. This study demonstrates that objective gait analysis can be used to document gait adaptations used by patients with knee OA.     

经颅磁刺激联合高压氧（HBO)治疗脑梗死240 例临床疗效分析

目的:观察经颅磁刺激(transcranial magnetic stimulation,TMS)联合高压氧(hyperbaricoxygen,HBO)治疗脑梗死的临床疗效。方法:采用随机数字表法将240例脑梗死患者分为联合治疗组、HBO组及常规组,每组80例。常规组患者给予常规治疗,HBO组患者在常规干预基础上辅以HBO治疗,联合治疗组患者则在常规干预基础上辅以HBO及TMS联合治疗。上述治疗均以10 d为1个疗程,共治疗2个疗程。于治疗前、治疗2个疗程后比较各组患者神经功能缺损程度,并同时于上述时间点检测各组患者中枢运动传导时间(CMCT)及血清中脑源性神经营养因子(BDNF)、神经生长因子(NGF)表达情况。结果:各组患者分别经2个疗程治疗后,发现联合治疗组NIHSS评分、总有效率均显著优于HBO组及常规组水平(均P0.05);另外联合治疗组血清中BDNF含量与NGF含量均较治疗前明显升高(P0.05),与常规组及HBO组间差异亦具有统计学意义(均P0.05)。结论:TMS联合HBO治疗脑梗死具有协同作用,能进一步改善患者受损神经功能及日常生活质量,其治疗机制可能与增强神经营养因子表达有关。     

椎体后凸成形术治疗骨质疏松性椎体压缩骨折的临床研究

摘要目的：随着老龄人口的增多,老年骨质疏松性椎体压缩性骨折（Osteoporotic Vertebral Compression Fracture,ovcr）的发病率也逐年增高。本文探讨椎体后凸成形术（PercutaneousKyphoplasty,PKP）对0VCF的疼痛缓解及功能改善等方面的临床疗效,并探讨其发展过程、作用机理及并发症的防治。方法：回顾性分析2007年1月至2011年12月应用PKP治疗的OVCF158例患者,其中男55例,女103例;患者年龄52--87岁,平均68．7岁。对患者术前、术后1日、术后3个月随访时的疼痛（VAs）及功能情况（ODD进行评价,并对以上数据进行配对t检验。结果：全部病例均顺利完成手术,3例出现椎体间隙渗漏,5例渗漏至椎体周缘,2例骨水泥渗漏至椎管内,无神经根和脊髓受压症状。VAS评分评价,术前（7．60±0．95）分,术后1日（1．00±0．74）分,术后三个月（0．20±0．48）分,术后疼痛缓解有统计学意义（P〈0．01）;ODI,术前（84．94±4-36）％,术后1日（20．47±3．61）％,术后三个月（9．85±3．43m,术后功能恢复有统计学意义（P〈0．01）。结论：PKP术后1日患者疼痛及功能较术前均有明显改善,术后3个月较术后1日亦有进一步的改观。术后后续应用治疗骨质疏松药物及康复治疗可改善患者骨质,预防相邻椎体及其他部位骨质骨折,使疗效更加满意。PKP为治疗OVCF提供了一种安全、有效的方法,可以迅速缓解疼痛,改善功能,具有广阔的应用前景。     

Phytalgic®, a food supplement, vs placebo in patients with osteoarthritis of the knee or hip: a randomised double-blind placebo-controlled clinical trial

Introduction

The medicinal treatment of osteoarthritis (OA) is mostly symptomatic to relieve pain and incapacity with analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), drugs with well-known risks. Complementary medicines might reduce the symptoms of OA and decrease the need for NSAIDs. This study tested the effects of a food supplement, Phytalgic^®, on pain and function in patients with osteoarthritis and their use of analgesic and NSAIDs.

Methods

A randomized double-blind parallel-groups clinical trial compared Phytalgic^® (fish-oil, vitamin E, Urtica dioica) to a placebo for three months, in 81 patients with OA of the knee or hip using NSAIDs and/or analgesics regularly. The main outcome measures were use of NSAIDs (in Defined Daily Doses per day - DDD/day) or analgesics (in 500 mg paracetamol-equivalent tablets per week (PET/week) measured each month, and Western Ontario-McMaster University Osteo-Arthritis Index (WOMAC) function scales.

Results

After three months of treatment, the mean use of analgesics in the active arm (6.5 PET/week) vs. the placebo arm (16.5) was significantly different (P < 0.001) with a group mean difference of -10.0 (95% CI: -4.9 to -15.1). That of NSAIDs in the active arm (0.4 DDD/day) vs the placebo arm (1.0 DDD/day) was significantly different (P = 0.02) with a group mean difference of - 0.7 DDD/day (95% CI: -0.2 to -1.2). Mean WOMAC scores for pain, stiffness and function in the active arm (respectively 86.5, 41.4 and 301.6) vs the placebo arm (resp. 235.3, 96.3 and 746.5) were significantly different (P < 0.001) with group mean differences respectively of -148.8 (95% CI: -97.7 to -199.9), -54.9 (95% CI: -27.9 to -81.9) and -444.8 (95% CI: -269.1 to -620.4).

Conclusions

The food supplement tested appeared to decrease the need for analgesics and NSAIDs and improve the symptoms of osteoarthritis.

Trial registration

Clinicaltrials.gov NCT00666523.     

Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review.

OBJECTIVES--To assess whether adding codeine to paracetamol has an additive analgesic effect; to assess the safety of paracetamol-codeine combinations versus paracetamol alone. DESIGN--Systematic literature review with meta-analysis, methodological quality of published trials being scored by means of 13 predefined criteria. TRIALS--24 of 29 trials that met the inclusion criteria. Models studied in the trials were postsurgical pain (21), postpartum pain (one), osteoarthritic pain (one), and experimentally induced pain (one). INTERVENTIONS--Dosages ranged from 400 to 1000 mg paracetamol and 10 to 60 mg codeine. MAIN OUTCOME MEASURES--The sum pain intensity difference (efficacy analysis) and the proportion of patients reporting a side effect (safety analysis). RESULTS--Most trials were considered of good to very good quality. Only the single dose studies could be combined for analysis of analgesic efficacy. Pooled efficacy results indicated that codeine added to paracetamol provided a 5% increase in analgesia on the sum pain intensity difference. This effect was comparable to the difference in analgesic effect between codeine and placebo. The cumulative incidence of side effects with each treatment was comparable in the single dose trials. In the multidose studies a significantly higher proportion of side effects occurred with paracetamol-codeine preparations. CONCLUSION--The difference is analgesic effect between paracetamol-codeine combinations and paracetamol alone was small but statistically significant. In the multidose studies the proportion of patients reporting a side effect was significantly higher with paracetamol-codeine combinations. For occasional pain relief a paracetamol-codeine combination might be appropriate but repeated use increases the occurrence of side effects.     

The clinical and economic efficacies of short courses of azithromycin in acute sinusitis]

A randomized study of a 3-day course of azithromycin therapy (500 mg once daily) vs. a 10-day course of co-amoxiclav therapy (625 mg thrice daily) in patients with acute sinusitis was performed with an account of the GCP criteria. One hundred patients in 2 groups each of 50 persons were enrolled. The estimates of the patient body temperature, headache, pain on palpation in the area of the accessory nasal sinuses, nasal cavity stuffing, nasal discharge nature and the nose mucous membrane appearance were recorded prior to the treatment, in 72 hours and on the 10th-12th and 26th-30th days of the treatment. The microbiological analysis of the punctate from the accessory nasal sinuses was undertaken before the antibiotic therapy and 72 hours after its start. The economic analysis included the cost of the antibiotic therapy course, hospitalization term, medical manipulations and laboratory tests as well as the cost/efficacy index. The frequency of the relapses within 6 months after the cure was estimated in the two groups compared. In 72 hours and on the 10th-12th days after the treatment start the efficacy of azithromycin was significantly higher than that of co-amoxiclav. The cure was stated in 41 (82 per cent) and 26 (52 per cent) patients on the 10th-12th days, in 6 (12 per cent) and 21 (42 per cent) patients the improvement was stated and the fail was stated in 3 (6 per cent) and 2 (4 per cent) patients respectively. The efficacy of the drugs on the 26th-30th days after the treatment start did not differ. The isolates of Staphylococcus aureus and Streptococcus pyogenes were the main pathogens. The bacteriologic eradication was recorded in 29 (90.6 per cent) patients treated with azithromycin and only in 18 (69.2 per cent) patients treated with co-amoxiclav. Adverse reactions and relapses of the disease within 6 months after the cure were more frequent in the patients treated with co-amoxiclav. The cost of the azithromycin therapy was significantly lower. It was shown that the shortened course of the azithromycin therapy provided earlier cure of the patients with acute sinusitis, better tolerance of the drug, less frequent adverse reactions, lower cost as compared to the use of co-amoxiclav and no relapses.     

Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distorsions: results of a multicenter, randomized, placebo-controlled, double-blind study.

Comfrey (Symphytum officinale L.) is a medicinal plant with anti-inflammatory, analgesic and tissue regenerating properties. In a double-blind, multicenter, randomized, placebo-controlled, group comparison study on patients suffering from unilateral acute ankle sprains (n = 142, mean age 31.8 years, 78.9% male), the percutaneous efficacy of an ointment of comfrey extract (Kytta-Salbe f, four treatments per day for 8 days) was confirmed decisively. Compared to placebo, the active treatment was clearly superior regarding the reduction of pain (tonometric measurement, p<0.0001, as the primary efficacy variable) and ankle edema (figure-of-eight method, p = 0.0001). Statistically significant differences between active treatment and placebo could also be shown for ankle mobility (neutral zero method), and global efficacy. Under active treatment, no adverse drug reactions were reported. The good local and global tolerance of the trial medication could also be confirmed. The study results are consistent with the known pre-clinical and clinical data concerning comfrey.     

A double blind,randomized, placebo controlled study of the efficacy and safety of 5-Loxin<Superscript>®</Superscript>for treatment of osteoarthritis of the knee

Introduction

5-Loxin^® is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin^® in the treatment of osteoarthritis (OA) of the knee.

Methods

Seventy-five OA patients were included in the study. The patients received either 100 mg (n = 25) or 250 mg (n = 25) of 5-Loxin^® daily or a placebo (n = 25) for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne''s Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. Additionally, the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients. Measurement of a battery of biochemical parameters in serum and haematological parameters, and urine analysis were performed to evaluate the safety of 5-Loxin^® in OA patients.

Results

Seventy patients completed the study. At the end of the study, both doses of 5-Loxin^® conferred clinically and statistically significant improvements in pain scores and physical function scores in OA patients. Interestingly, significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin^® as early as 7 days after the start of treatment. Corroborating the improvements in pain scores in treatment groups, we also noted significant reduction in synovial fluid matrix metalloproteinase-3. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups.

Conclusion

5-Loxin^® reduces pain and improves physical functioning significantly in OA patients; and it is safe for human consumption. 5-Loxin^® may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators, and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients.

Trail Registration

(Clinical trial registration number: ISRCTN05212803.)