Reliability, validity, and responsiveness of the daily sleep interference scale among diabetic peripheral neuropathy and postherpetic neuralgia patients

To evaluate the psychometric characteristics of the Daily Sleep Interference Scale (DSIS) in patients with painful diabetic peripheral neuropathy (DPN) or postherpetic neuralgia (PHN), a post hoc secondary analysis of data from eight randomized clinical trials (four DPN and four PHN) was performed. Data were pooled within patient populations when assessment weeks were the same. The DSIS was completed by 1,124 DPN and 1,034 PHN patients. Patient-reported outcomes, including a Daily Pain Diary, the Short-Form McGill Pain Questionnaire, SF-36 Health Survey, Profile of Mood States, MOS-Sleep Scale (MOS-SS), EQ-5D, and Patient Global Impression of Change, were used to validate the DSIS. Test-retest reliability was high for both samples (intraclass correlation coefficient>0.90). The DSIS showed good construct validity, with moderate to high correlations between the DSIS and weekly mean pain scores (r=0.48-0.80), MOS-SS sleep disturbance subscale (r=0.45-0.64), MPQ-SF Pain Experience (r=0.37-0.61), and VAS (r=0.42-0.72). The DSIS showed good discriminant validity in both groups; high and low MOS-SS sleep disturbance groups had significantly different DSIS scores (P<0.001). DPN patients who improved minimally on the Patient Global Impression of Change and in pain scores improved 1.5-2 DSIS points on average; for PHN, patient scores improved an average of 1-2 points. The DSIS demonstrated robust test-retest reliability, good construct and discriminant validity and responsiveness in painful DPN and PHN patients. A 1-2 point change on the DSIS might be interpreted as an important difference.     

连续硬膜外输注消炎镇痛液治疗不同病程带状疱疹后遗神经痛的疗效研究

目的:比较连续硬膜外输注利多卡因和甲基强的松龙对不同病程带状疱疹后遗神经痛(PHN)患者的治疗效果。方法:胸腹部PHN患者70例,皮损位于T3-T11脊神经支配区。按照入院时疼痛持续的时间分为5组:Ⅰ组(n=13),疼痛持续1—2个月;Ⅱ组(n=15),疼痛持续2—3个月;Ⅲ组(n=16),疼痛持续3—6个月;Ⅳ组(n=12),疼痛持续6—12个月;Ⅴ组(n=14),疼痛持续12个月以上。所有患者在CT引导下置入硬膜外导管,采用硬膜外自控镇痛泵输注利多卡因和甲基强的松龙,连续输注18—20d,如果患者自控镇痛次数超过10次/d,则加用曲马多进行治疗。采用数字模拟评分法(NRS)评定疼痛强度。结果:硬膜外阻滞期间所有患者均达到满意镇痛,但Ⅲ组、Ⅳ组、Ⅴ组的镇痛泵使用数量和曲马多用量显著高于Ⅰ组、Ⅱ组;出院后7d,总有效率100%,组间无显著差异(P>0.05),但Ⅰ组和Ⅱ组的NRS评分明显低于Ⅴ组(P<0.05)。出院后3个月和6个月,Ⅰ组和Ⅱ组的有效率仍明显高于Ⅲ组、Ⅳ组和Ⅴ组(P<0.05);出院后3个月,Ⅲ组、Ⅳ组和Ⅴ组患者的NRS亦明显高于Ⅰ组和Ⅱ组(P<0.05)。出院后6个月,Ⅰ组患者的NRS明显低于其他4组(P<0.05);除Ⅰ组外,其余各组均有高于20%的患者治疗无效。患者的生存质量评分与疼痛程度密切相关(R2=0.945)。结论:连续硬膜外输注利多卡因和甲基强的松龙对病程<3个月的PHN患者的疗效优于病程≥3个月的患者。     

Randomized controlled trial of the combined monoaminergic and opioid investigational compound GRT9906 in painful polyneuropathy

GRT9906 is an investigational novel compound with μ‐opioid receptor agonism and inhibition of noradrenalin/serotonin re‐uptake. In this randomized, double‐blind, placebo‐controlled, three‐way cross‐over trial in painful polyneuropathy, the efficacy and safety of GRT9906 was assessed and compared with tramadol. During 4‐week treatment periods, daily oral doses of either GRT9906 120–240 mg, or placebo, or tramadol 200–400 mg were given. These were separated by 1‐week washout periods. The primary endpoint was the average pain intensity (average of daily current pain intensity over the last 3 days of each treatment period rated on a 0 to 10‐point numeric rating scale). One hundred seventeen patients were enrolled and 64 were randomized to one of six treatment sequences. Forty‐seven patients qualified for the per protocol analysis. GRT9906 reduced average pain intensity by 2.1 points compared with a reduction of 0.6 points on placebo (p < 0.0001) and 2.4 points on tramadol. GRT9906 also improved scores on the sleep problem scale and the neuropathic pain symptom inventory and scored better than placebo on the patient global impression of change. Numbers needed to treat to obtain one patient with more than 50% pain relief was 3.9 (95% CI 2.4–11.5) for both GRT9906 and tramadol. The most frequently reported adverse events were nausea, fatigue, constipation and sleep disorder for GRT9906 and tramadol. Four patients dropped out due to adverse events during both GRT9906 and tramadol treatment and two dropped out during placebo treatment. In conclusion, in painful polyneuropathy, GRT9906 demonstrated analgesic efficacy with a magnitude of effect comparable with tramadol and was well tolerated.     

A Pooled Analysis of Two Randomized,Double‐Blind,Placebo‐Controlled Trials of Milnacipran Monotherapy in the Treatment of Fibromyalgia

Milnacipran has been shown to significantly improve the pain, global well‐being, and physical function of fibromyalgia (FM), and is approved by the U.S. Food and Drug Administration for the management of this disorder. Post hoc analyses of data from two pivotal trials were conducted to further assess the clinical benefits of milnacipran, to determine the impact of baseline pain severity on treatment outcomes, and to confirm the safety and tolerability of this medication in patients with FM. Patients in these trials were randomized to placebo (n = 624), milnacipran 100 mg/day (n = 623), or milnacipran 200 mg/day (n = 837). Two different composite responder analyses were used to evaluate efficacy: a 2‐measure analysis, requiring ≥ 30% improvement from baseline visual analog scale 24‐hour recall pain scores and a Patient Global Impression of Change (PGIC) score of “very much improved” or “much improved”; and a 3‐measure analysis, requiring a ≥ 6‐point improvement from baseline in SF‐36 Physical Component Summary scores in addition to the pain and PGIC criteria. Additionally, a pooled analysis of mean changes from baseline pain scores was conducted in order to evaluate the efficacy of milnacipran over the entire course of treatment. At 3 months, composite responder rates were significantly higher in the milnacipran treatment groups than in the placebo group (2‐ and 3‐measure composite responder analyses: P ≤ 0.001, both doses vs. placebo). These improvements were not dependent on baseline pain severity. Similar composite responder results were observed in patients who continued treatment for up to 6 months. Significant improvements in mean pain scores were seen with both doses of milnacipran vs. placebo as early as 1 week after treatment initiation and were sustained for up to 6 months of milnacipran treatment. The most common adverse events associated with milnacipran were nausea, headache, and constipation.     

Exercise blood pressure and endothelial dysfunction in hypertension

Background: Hypertensive patients with persistent endothelial dysfunction have adverse cardiovascular prognosis. However, current methods aimed to assess endothelial dysfunction in those patients who possess clinical applicability. We hypothesised that such individuals could potentially be identified by an exaggerated systolic blood pressure (BP) response to a submaximal exercise. Methods: We studied 22 male patients with essential hypertension who were categorised into two age‐matched groups depending on their exercise systolic BP (ExSBP) rise during the 3‐min exercise step test; the exaggerated ExSBP group [hyper‐responders (≥ 40 mmHg)] and the low ExSBP responder group [hypo‐responders (≤ 20 mmHg)]. Eleven healthy volunteers matched for age were used as control. Clinic and daytime ambulatory BP were assessed after 14 days of anti‐hypertensive treatment withdrawal, which were not significantly different between groups. Vascular reactivity in response to intra‐arterial infusions of acetylcholine, N^G‐monomethyl‐l ‐arginine (l ‐NMMA) and sodium nitroprusside was assessed using forearm venous occlusion plethysmography. Results: The hyper‐responder group had significantly less forearm vasodilatation to acetylcholine compared with the hypo‐responder group [percentage change in the forearm blood flow 125 (17) vs. 260 (28), mean (SEM); p < 0.001]. Similarly, the vasoconstrictive response to l ‐NMMA was significantly impaired in the hyper‐responder group in comparison to the hypo‐responder group [?30 (2) vs. ?45 (4); p < 0.05]. In contrast, the vascular response to sodium nitroprusside was not different between groups suggesting preserved endothelial‐independent vasodilatation. Conclusions: Despite similar ambulatory and office BP, the exaggerated ExSBP group had significantly worse endothelial function compared with the low ExSBP responder group. This simple and non‐invasive test may be useful in routine clinical practice to aid risk stratification in hypertensive patients.     

Postoperative pain relief in the morbidly obese patient: Feasibility study of a combined dipyrone/tramadol infusion

The aim of the prospective clinical study was to test the feasibility of a dipyrone/tramadol combination for pain therapy after laparoscopic and open obesity surgery. The study group was made up of 29 surgical patients; 14 following a median laparotomy and 15 following a laparoscopic approach. All received a continuous intravenous infusion of dipyrone (metamizol) and tramadol for pain relief.

The surgical procedure (laparotomy or laparoscopy), body mass index, postoperative analgesic requirement and pain intensity (visual analogue scale (VAS 1–10)) were documented.

Following laparotomy, the combination infusion provided effective analgesia. On the first and fourth postoperative days, the pain scores at rest were 1.5 and 2.3 respectively. The pain scores did not increase significantly with movement (2.7 and 2.2 respectively).

Following laparoscopic gastric banding the pain scores were less than 2.0 at rest and with movement on the first postoperative day. On the fourth postoperative day the pain scores at rest and with movement were 0.2.

This feasibility study suggests that a combination of the strong non-opioid dipyrone and the atypical opioid tramadol provides good analgesia following laparotomy and laparoscopic surgery for morbid obesity.     

大鼠电针镇痛的个体差异性及其与基础痛阈的关系

电针镇痛具有个体差异性。我们采用聚类分析的统计学方法,以１００Ｈｚ电针３０分钟内辐射热甩尾潜伏期升高百分数之平均值为指标,将１６８例大鼠分为优针效和劣地效两个群体,其针效至少在两之内保持相对稳定。电针镇痛效果与基础痛阈呈显著正相关。即优针效鼠的基础痛阈显著高于劣针效鼠。     

Attributes of response in depressed patients switched to treatment with duloxetine

Background: This study was designed to assess clinical and functional outcomes associated with switching to duloxetine treatment in patients with major depressive disorder (MDD) experiencing emotional and painful physical symptoms in their current episode. Methods: In this 8‐week, multinational, multicentre, single‐arm, open‐label clinical trial, 242 MDD patients were switched to duloxetine 60 mg/day after selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) treatment. The primary analysis compared mean change from baseline in Brief Pain Inventory – Modified Short Form (BPI‐SF) interference score between initial responders [≥ 50% reduction from baseline on the 17‐item Hamilton Depression Rating Scale (HAMD₁₇) Maier subscale] and initial non‐responders after 4 weeks. Initial responders continued with duloxetine 60 mg/day. Initial non‐responders received duloxetine 120 mg/day for the remaining 4 weeks. Depression, pain, anxiety and functional outcomes were also compared after 8 weeks. Results: BPI‐SF interference decreased from baseline in initial responders (n = 108) and initial non‐responders (n = 85) after 4 weeks of duloxetine treatment, with greater reductions in initial responders [BPI‐SF mean difference in reduction: 1.01 (95% CI 0.42–1.61); p < 0.001]. Reductions in pain interference favouring initial responders were also apparent after 8 weeks [0.68 (95% CI: 0.03–1.33); p = 0.042]. Depression, pain, anxiety and function improved over 8 weeks across patient groups. Conclusions: Elements of core mood and pain are important residual symptoms following poor treatment response in MDD. Early improvement in these symptoms after switching to duloxetine indicated an increased chance of functional recovery.     

曲马多与阿米替林治疗带状疱疹后遗神经痛的疗效比较

目的：研究曲马多对带状疱疹后遗神经痛的临床疗效、剂量控制以及主要的不良反应。方法：将50例带状疱疹后遗痛患者分为曲马多组（n=30）和阿米替林组（n=20）,对患者的疼痛程度（visual analog scale,VAS）、疼痛缓解程度、不良反应、日常生活等进行8周的随访。结果：曲马多治疗后8周VAS较治疗前显著下降（P〈0.01）。第1～3周曲马多较阿米替林能够更好的减轻患者的疼痛程度（P〈0.05）。第4～8周两者疗效无显著差异（P〉0.05）。曲马多最常见的不良反应为便秘、乏力、恶心及嗜睡;80%的患者用曲马多后生活质量得到改善。结论：曲马多或阿米替林都能够减轻带状疱疹后遗神经痛。曲马多能够快速的缓解患者疼痛,疗效稳定。大部分患者可以耐受曲马多的不良反应且生活质量得到了改善。曲马多可以作为带状疱疹后遗神经痛的主要镇痛药物。     

Pain Responder Analysis: Use of Area Under the Curve to Enhance Interpretation of Clinical Trial Results

Interpretation of results on patient-reported pain outcomes from clinical trials should be meaningful to patients and healthcare providers. This study applied an area-under-the-curve (AUC) analysis to responder profiles in a clinical trial of pregabalin for the treatment of fibromyalgia (FM). Data were from a 14-week, randomized, placebo-controlled trial of pregabalin (300, 450, or 600 mg/day) for the treatment of FM in patients meeting American College of Rheumatology criteria for FM and with a baseline pain score of at least 40 mm on the 100-mm pain visual analogue scale. Pain was evaluated in a daily diary by patients using an 11-point numeric rating scale (0 = no pain, 10 = worst possible pain). Response profiles on pain improvement scores and their differences between pregabalin and placebo were assessed using the AUC (derived using the trapezoidal rule) from the responder curve (vertical axis, proportion of subjects; horizontal axis, minimum percent improvement in pain). The AUC can be interpreted as if all responders were improved by the same percentage equal to the AUC divided by 100. The AUCs (2,100 for placebo, and 2,944, 3,170, and 3,349 for pregabalin 300, 450, and 600 mg, respectively) can be considered as if every responder improved by 21, 29, 31, and 33.5% in the responder's respective treatment group. Pain improvement was significantly better with pregabalin ( P  < 0.05), with pregabalin responders improving by 8.4% (300 mg/day), 10.7% (450 mg/day), and 12.5% (600 mg/day) more than placebo responders. This novel approach demonstrates that responder profiles can provide an enhanced interpretation of pain outcomes for patient care and symptom management.     

Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial

This study was designed to assess the efficacy and safety of pregabalin-a novel alpha(2)-delta ligand with analgesic, anxiolytic, and anticonvulsant activity-for treating neuropathic pain in patients with post-herpetic neuralgia (PHN). Two hundred and thirty-eight patients were randomised into this multicentre, doubleblind, placebo-controlled trial to receive 150 (n=81), 300 mg/day (n=76) pregabalin, or placebo (n=81) for 8 weeks. Among the exclusion criteria was failure to respond to previous treatment for PHN with gabapentin at doses > or =1200 mg/day. Endpoint mean pain scores were significantly reduced in patients receiving 150 or 300 mg/day pregabalin compared with placebo. Efficacy was observed as early as week 1 and was maintained throughout the study. Significantly more patients in both pregabalin groups (150 mg, 26%; 300 mg, 28%) were responders (> or =50% decrease in mean pain score from baseline to endpoint) than in the placebo group (10%). Additionally, by week 1 and for the study's duration, 150 and 300 mg/day pregabalin significantly reduced weekly mean sleep interference scores. More pregabalin-treated patients than placebo-treated patients reported that they were 'much improved' or 'very much improved'. Health-related quality-of-life (HRQoL) measurements using the SF-36 Health Survey demonstrated improvement in the mental health domain for both pregabalin dosages, and bodily pain and vitality domains were improved in the 300 mg/day group. The most frequent adverse events were dizziness, somnolence, peripheral oedema, headache, and dry mouth. Pregabalin efficaciously treated the neuropathic pain of PHN. Additionally, pregabalin was associated with decreased sleep interference and significant improvements in HRQoL measures.     

剖宫产术后患者三种不同药物静脉镇痛效果比较

目的：观察和比较地佐辛、盐酸曲马朵和酒石酸布托啡诺用于剖宫产术后静脉自控镇痛（PCIA）的镇痛效果。方法将150例剖宫产产妇随机分为地佐辛组（A组）、盐酸曲马朵组（B组）、酒石酸布托啡诺组（C组）,每组50例。三组产妇均在腰硬联合麻醉下施术,术中麻醉效果满意,术毕立即接静脉输注镇痛泵,药物配方为A组：地佐辛50 mg＋盐酸托烷司琼5 mg＋0.9%氯化钠注射液100 ml;B组：盐酸曲马朵1000 mg＋盐酸托烷司琼5 mg＋0.9%氯化钠注射液共100 ml;C组：酒石酸布托啡诺10 mg＋盐酸托烷司琼5 mg＋0.9%氯化钠注射液共100 ml。观察各组术后4 h、12 h、24 h、36 h、48 h各时间点的静息疼痛和动态疼痛,并采用视觉疼痛模拟评分法（VAS）进行评分,记录各种不良反应的发生。结果静息疼痛VAS评分：4 h、12 h A组低于B、C 组,差异有统计学意义（P＜0.05）,B、C组各时间点组间差异无统计学意（P＞0.05）。动态疼痛VAS评分：4 h、12 h、24 h A组低于B、C 组,差异有统计学意义（P＜0.05）,B、C 组各时间点组间差异无统计学意义（P＞0.05）。不良反应（恶心呕吐、头晕头痛、嗜睡）C组的发生率高于A组,差异有统计学意义（P＜0.05）。结论三种药物可安全用于剖宫产术后静脉镇痛,效果可靠,其中地佐辛联合盐酸托烷司琼镇痛效果良好,且不良反应相对较少。     

A Meta‐Analysis of Pain Response in the Treatment of Fibromyalgia

Objective: This meta‐analysis compared efficacy (pain response) of drugs that are licensed or commonly used in the treatment of fibromyalgia. A meta‐analysis of safety measured via discontinuation because of adverse events was also performed. Methods: We conducted a meta‐analysis of 21 clinical trials to estimate treatment differences vs. placebo, separately, for duloxetine, fluoxetine, gabapentin, milnacipran, pramipexole, pregabalin, either of two tricyclic antidepressants, and tramadol plus paracetamol. Indirect treatment comparisons using mixed treatment comparisons methodology were conducted for all pairwise comparisons. Pain response was analyzed as improvement of at least 30%, and separately of 50%, from baseline. Results: When compared with placebo, statistically significant pain responses (improvement of 30% and 50%) were observed for patients treated with duloxetine, milnacipran 200 mg/day, pregabalin 300 or 450 mg/day, and tramadol plus paracetamol. Treatment with fluoxetine, gabapentin, or milnacipran 100 mg/day resulted in significant findings for the 30% improvement in pain response. The meta‐analysis showed a statistically increased risk of discontinuation because of adverse events for milnacipran 100 and 200 mg/day (both P < 0.001), and pregabalin 300 and 450 mg/day (P = 0.009 and P < 0.001, respectively). All other treatments, except fluoxetine, showed numerically increased risk over placebo for discontinuation because of adverse events. In the indirect comparisons, no pairwise comparison of active treatments reached statistical significance for either pain response end point. Conclusion: All eight active treatments displayed evidence suggesting improvement over placebo in the treatment of pain in patients suffering from fibromyalgia. Indirect comparison of active treatments found no strong differences.     

氯诺昔康及曲马多行术后自控镇痛的临床应用

目的评价氯诺昔康及曲马多用于患者术后自控镇痛(PCA)的安全性及有效性,寻找较好的术后自控镇痛方法从而减轻术后护理的工作量和提高患者术后护理质量。方法50例在全麻下行胆囊切除术和单侧乳癌根治术的患者,随机分为氯诺昔康组(L组)和曲马多组(T组),每组各25例。将所配制药液注入PCA泵,PCA泵给药速率为2ml/h,术毕时启动PCA泵进行镇痛,术毕前予首量。镇痛结束时,由患者完成疼痛的评分,记录PCA期间出现的副作用。结果L组患者的镇痛效果优于T组,差异有统计学意义。T组恶心与呕吐的发生率为36.0%,L组为8.0%,T组明显高于L组(P<0.05)。结论氯诺昔康术后自控镇痛的效果优于曲马多,恶心、呕吐少,能减少术后护理工作量,更适用于治疗术后急性疼痛。     

Current antiviral combination therapy for chronic hepatitis C patients who failed to interferon alfa-based treatment

What is known and Objective: Interferon‐alfa‐based therapy is effective in the treatment of Hepatitis C. However, some patients fail to respond and others relapse, after initially responding. Our objective was to assess the efficacy, safety and predictive factors for sustained virological response (SVR) to peginterferon plus ribavirin in chronic hepatitis C patients who failed to interferon‐alfa (IFNα)‐based therapy. Methods: Seventy‐five consecutive patients who failed to IFNα‐based therapy were retreated with peginterferon plus ribavirin. Of these patients, 85% were infected by genotype 1. The primary endpoint was SVR. Results and Discussion: Of 75 non‐responder (n = 54) or relapser patients (n = 21), 50 were previously treated with IFNα‐monotherapy and 25 with IFNα plus ribavirin. Global SVR rate was 41·3%: for patients re‐treated with IFNα the response was 48% whilst for those retreated with IFNα plus ribavirin, it was 28%. For previous non‐responders the SVR rate was 37% and for relapsers it was 52·4%. What is new and Conclusion: Retreatment with peginterferon plus ribavirin is an effective option for some chronic hepatitis C non‐responder or relapser patients. Higher SVR rate was achieved in relapsers and in those patients who received IFNα monotherapy previously.     

Association of depression and anxiety with reduced quality of life in patients with predialysis chronic kidney disease

Aim: Although depression and anxiety are the most common psychological problems among dialysis patients, little is known about the association between depression, anxiety and quality of life (QOL) in patients with predialysis chronic kidney disease (CKD). Therefore, we assessed the prevalence of depression and anxiety, and their association with QOL in patients with predialysis CKD. Methods: Two hundred and eight predialysis patients (male 61.1%) with a mean age of 55.7 ± 13.7 years and an estimated glomerular filtration rate < 60 ml/min/1.73 m² were enrolled. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. Patients with anxiety and depression scores ≥ 8 were diagnosed with anxiety and depression disorders respectively. The WHOQOL‐BREF questionnaire was used to assess patient QOL. Results: The prevalence of depression (47.1%) and anxiety (27.6%) did not differ across CKD stages. Depression correlated positively with age, employment, income, education, comorbidity index, haemoglobin level, albumin concentration and anxiety score, and negatively with all WHOQOL‐BREF domain scores. Anxiety correlated significantly with QOL, but not with socioeconomic factors. In a multiple regression analysis, haemoglobin level, anxiety and QOL were independent factors associated with depression. In a linear regression analysis, depression and anxiety independently correlated with QOL after we adjusted for age, alcohol use, employment, income, education, haemoglobin level and albumin concentration. Conclusions: Patients with predialysis CKD have a high prevalence of depression and anxiety, which are associated with reduced QOL. Early detection of depression and anxiety and active interventions should be considered to improve the QOL of these patients.     

The impact of tramadol and dihydrocodeine treatment on quality of life of patients with cancer pain

Background: Tramadol and dihydrocodeine (DHC) are analgesics of step 2 WHO analgesic ladder (opioids for mild to moderate pain, weak opioids) frequently used in the treatment of cancer pain of moderate intensity. The aim of the study was to assess the impact of tramadol and DHC treatment on quality of life (QL) and performance status (PS) of patients with cancer pain. Patients and methods: Randomised, cross‐over, clinical study of 40 opioid‐naive patients with nociceptive cancer pain who received tramadol or DHC controlled release tablets for 7 days, and then drugs were switched and administered for another 7 days. Pain was assessed by visual analogue scale (VAS), QL by EORTC QLQ C 30, and PS by Eastern Cooperative Oncology Group (ECOG) and Karnofsky. Results: From 40 patients recruited, 30 completed the study. DHC treatment provided better analgesia (VAS). In QL functional scales, better emotional functioning in tramadol group and better global QL and cognitive functioning in DHC group were observed. In symptom scales, less fatigue, pain and sleep disturbances, less nausea and vomiting and better appetite in DHC group were noted. In tramadol group, less constipation and less financial problems were observed. No differences in dyspnoea and diarrhoea were noted. ECOG and Karnofsky PS were low and did not differ between tramadol and DHC groups. Conclusions: Dihydrocodeine treatment was associated with better global QL, cognitive functioning, analgesia and appetite, less fatigue, sleep disturbances, nausea and vomiting. Tramadol therapy was connected with better emotional functioning, less constipation and financial problems. PS deteriorated in both tramadol and DHC groups.     

持续硬膜外输注镇痛结合交感神经射频热凝治疗四肢带状疱疹后遗神经痛的疗效

摘要 目的：观察CT 引导下四肢带状疱疹后遗神经痛（PHN）持续硬膜外输注镇痛结合交感神经射频热凝治疗的临床结果。 方法：32例四肢带状疱疹后遗神经痛患者随机分为对照组（A组,采用硬膜外置管持续输注镇痛治疗,n=17）和联合治疗组（B组,采用持续硬膜外置管镇痛3—4周后行交感神经射频热凝治疗3次,n=15）,比较治疗前后7d、1个月、6个月、1年的视觉模拟评分（VAS）、疼痛缓解率、生存质量评分（QOL）、麻木评分、肌力下降发生率。 结果：治疗后两组患者的VAS评分均较治疗前明显降低（P<0.05）;治疗后6个月、1年,B组的VAS、QOL、疼痛缓解率均优于A组（P<0.05）,同时A、B两组的麻木发生率和麻木评分均无显著性差异（P>0.05）,治疗后两组均无肌力下降发生。 结论：四肢带状疱疹后遗神经痛持续硬膜外镇痛结合交感神经射频毁损治疗可有效缓解疼痛,长期疗效高于单纯持续硬膜外镇痛,同时并不增加麻木及肌力下降的发生率。     

Impact of CYP2D6 genotype on postoperative tramadol analgesia

Genetic polymorphisms result in absent enzyme activity of CYP2D6 (poor metabolizers, PM) in about 10% of the Caucasian population. This study investigates whether the PM genotype has an impact on the response to tramadol analgesia in postoperative patients. A prospective study design was used and 300 patients recovering from abdominal surgery were enrolled. After titration of an individual loading dose, patients could self-administer 1 ml bolus doses of the drug combination tramadol 20 mg/ml, dipyrone 200 mg/ml and metoclopramide 0.4 mg/ml via patient-controlled analgesia (PCA). Patients' genotype was analyzed considering the most prevalent PM associated CYP2D6 mutations using a real-time PCR and hybridization based genotyping method. Demographic data, surgery related variables, pain scores, analgesic consumption and need for rescue medication were compared between extensive metabolizers (EM) and PM. The primary outcome criterion 'response' was defined as responder or non-responder status by the need for rescue medication and patients' satisfaction at the final interview. Demographic and surgery related data were comparable between EM (n=241) and PM (n=30). The percentage of non-responders was significantly higher in the PM group (46.7%) compared with the EM group (21.6%; p=0.005). Tramadol loading dose amounted to 108.2+/-56.9 and 144.7+/-22.6 mg (p<0.001) in EM and PM, respectively. More patients displaying the PM genotype needed rescue medication in the recovery room and during PCA period than patients with at least one wild type allele (21.6 versus 43.3%, p=0.02). PM for CYP2D6 showed a lower response rate to postoperative tramadol analgesia than EM. Therefore, CYP2D6 genotype has an impact on analgesia with tramadol. Pharmacogenetics may explain some of the varying response to pain medication in postoperative patients.     

Comparison of postoperative pain management using two patient-controlled analgesia methods: nursing perspective

Title. Comparison of postoperative pain management using two patient‐controlled analgesia methods: nursing perspective. Aim. To compare the effect of fentanyl iontophoretic transdermal system and morphine intravenous patient‐controlled analgesia on the time‐efficiency and convenience of postoperative patient care. Background. Intravenous patient‐controlled analgesia with morphine is effectively used to manage postoperative pain; however, it takes time to set up and administer. Methods. Nurses evaluated patient‐care tasks with fentanyl iontophoretic transdermal system and/or morphine intravenous patient‐controlled analgesia in two phase IIIb studies (n = 1305) using a nurse ease‐of‐care questionnaire. A responder for time‐efficiency and convenience responded with one of the top three positive choices on all items; for satisfaction, a responder chose one of the top two positive choices on both items. Data were collected between March 2004 and April 2005. Findings. In both studies, greater proportions of nurses were responders for fentanyl iontophoretic transdermal system than for morphine intravenous patient‐controlled analgesia, respectively, for time‐efficiency [total hip replacement surgery, 80·9% (250/309) vs. 57·7% (172/298), P < 0·001; abdominal/pelvic surgery, 84·8% (162/191) vs. 57·7% (113/196), P < 0·001], convenience [total hip replacement surgery, 85·5% (271/317) vs. 64·1% (191/298), P < 0·001; abdominal/pelvic surgery, 89·2% (166/186) vs. 62·8% (123/196), P < 0·001], and satisfaction [total hip replacement surgery, 66·6% (247/371) vs. 33·3% (108/324), P < 0·001; abdominal/pelvic surgery, 67·4% (155/230) vs. 38·2% (84/220), P < 0·001]. Higher proportions of nurses favoured fentanyl iontophoretic transdermal system than morphine intravenous patient‐controlled analgesia in both studies (P < 0·001). Conclusion. The fentanyl iontophoretic transdermal system appears to be simpler, easier to use, and more satisfactory for nurses than morphine intravenous patient‐controlled analgesia.