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Dexketoprofen Trometamol and Tramadol Hydrochloride Fixed-Dose Combination in Moderate to Severe Acute Low Back Pain: A Phase IV, Randomized, Parallel Group, Placebo, Active-Controlled Study (DANTE). 右酮洛芬曲美他莫与盐酸曲马多固定剂量复方制剂治疗中度至重度急性腰痛:IV 期随机、平行组、安慰剂、活性对照研究 (DANTE)。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-26 DOI: 10.1007/s40122-024-00623-4
Giustino Varrassi, Magdi Hanna, Stefano Coaccioli, Paolo Fabrizzi, Simone Baldini, Ivan Kruljac, Carles Brotons, Serge Perrot

Introduction: Dexketoprofen/tramadol 25/75 mg (DKP/TRAM) is a fixed-dose combination of a cyclooxygenase inhibitor and opioid receptor agonist. To better understand the efficacy and safety of DKP/TRAM in the treatment of moderate to severe acute lower back pain (LBP) with or without radiculopathy, we carried out a large explorative phase IV international, multicenter, prospective, randomized, double-blind, parallel group, placebo-controlled study (DANTE).

Methods: A total of 538 patients with or without a history of LBP and experiencing acute LPB of moderate to severe intensity [Numerical Rating Scale-Pain Intensity (NRS-PI) score > 5] were randomized 4:4:1:1 to DKP/TRAM 25/75 mg every 8 h (n = 211), tramadol (TRAM) 100 mg (n = 207), placebo-matched DKP/TRAM (n = 59), or placebo-matched TRAM (n = 61).

Results: The proportion of patients achieving the primary endpoint, defined as the time to first achieve NRS-PI score < 4 or pain intensity reduction ≥ 30% from drug intake up to 8 h after the first dose, was higher in the DKP/TRAM arm than in the placebo group, but the difference was not statistically significant (46.1% vs. 42.6%, respectively; hazard ratio 1.11; 95% confidence interval 0.775, 1.595; p = 0.566). DKP/TRAM achieved superiority over TRAM in total pain relief at 4, 6, and 8 h (p < 0.05). Conversely, in relation to the secondary endpoints, a significantly greater reduction in NRS-PI score was seen with DKP/TRAM versus placebo starting from 1 h, and this reduction remained numerically lower throughout 8 h. Summed pain intensity difference values were also significantly lower at 4, 6, and 8 h with DKP/TRAM compared to TRAM (p < 0.05). Overall, DKP/TRAM was well tolerated.

Conclusion: Although the primary endpoint was not met, secondary efficacy analyses suggest the superiority of DKP/TRAM over placebo and TRAM alone in terms of total pain relief. DKP/TRAM can be considered to be an effective and safe option for the treatment of moderate to severe acute LBP.

Dante study registration: EudraCT number: 2019-003656-37; ClinicalTrials.gov Identifier: NCT05170841.

简介右酮洛芬/曲马多 25/75 毫克(DKP/TRAM)是一种环氧化酶抑制剂和阿片受体激动剂的固定剂量复方制剂。为了更好地了解 DKP/TRAM 治疗伴有或不伴有根神经病变的中重度急性下背痛(LBP)的疗效和安全性,我们开展了一项大型探索性 IV 期国际、多中心、前瞻性、随机、双盲、平行组、安慰剂对照研究(DANTE):共有538名患者,无论是否有腰痛病史,均患有中重度急性腰痛[数字评分量表-疼痛强度(NRS-PI)评分>5],他们按4:4:1:1的比例随机接受每8小时一次的DKP/TRAM 25/75毫克(n = 211)、曲马多(TRAM)100毫克(n = 207)、安慰剂匹配的DKP/TRAM(n = 59)或安慰剂匹配的TRAM(n = 61):结果:达到主要终点(定义为首次达到 NRS-PI 评分的时间)的患者比例达到了 100%:虽然未达到主要终点,但次要疗效分析表明,在疼痛完全缓解方面,DKP/TRAM 优于安慰剂和单独 TRAM。DKP/TRAM可被视为治疗中度至重度急性腰腿痛的有效而安全的选择:EudraCT编号:2019-003656-37;ClinicalTrials.gov标识符:NCT05170841:NCT05170841。
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引用次数: 0
Postoperative Dexmedetomidine Infusion and Chronic Postsurgical Pain in Thoracoscopic Pulmonary Nodule Surgery: A Retrospective Study with Propensity-Score-Matched Analysis. 胸腔镜肺结节手术术后右美托咪定输注与术后慢性疼痛:倾向分数匹配分析的回顾性研究
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-28 DOI: 10.1007/s40122-024-00611-8
Hang Sun, Yiwei Zhong, Min Wang, Shujie Niu, Rusong Yang, Yali Tian, Bingbing Li

Introduction: Patients frequently suffer from debilitating chronic postsurgical pain (CPSP) subsequent to thoracoscopic surgery. The impact of postoperative dexmedetomidine infusion on CPSP remains elusive. This study aimed to scrutinize the effect of dexmedetomidine on both 1-year incidence of CPSP and the quality of recovery after thoracoscopic pulmonary nodule surgery.

Methods: This retrospective analysis encompassed clinical and follow-up data from 1148 patients undergoing thoracoscopic pulmonary nodule surgery at our institution between September 2021 and August 2022. Depending on whether dexmedetomidine was infused intravenously or not on the first night after surgery, patients were stratified into the dexmedetomidine group or the control group, with propensity score matching applied to harmonize baseline characteristics. Comparative analysis sought to delineate distinctions of CPSP and recovery quality 1 year after surgery.

Results: Following propensity score matching, a cohort of 258 patients in each group underwent analysis. Comparisons after matching revealed no statistically significant disparities in 1-year CPSP incidence [76/258 (29.5%) versus 78/258 (30.2%), P = 0.847], moderate-to-severe pain occurrence [17/76 (22.4%) versus 22/78 (28.2%), P = 0.405], neuropathic pain occurrence [11/76 (14.5%) versus 11/78 (14.1%), P = 0.948], and postoperative recovery quality assessed by 12-Item Short Form Health Survey (SF-12) score (113.1 [107.2, 116.0] versus 113.0 [107.4, 116.0], P = 0.328). Multivariate logistic regression analysis encompassing the entire cohort identified being female [odds ratio (OR) 2.10, 95% confidence interval (CI) 1.59-2.79, P < 0.001) and postoperative rescue analgesia (OR 1.47, 95% CI 1.09-1.96, P = 0.010) as risk factors for CPSP, while intraoperative fentanyl dosage (OR 0.92, 95% CI 0.87-0.98, P = 0.006) emerged as a protective factor.

Conclusion: The prolonged administration of dexmedetomidine did not yield discernible amelioration in either 1-year CPSP or the recovery quality after thoracoscopic surgery. Noteworthy risk factors for CPSP encompassed female sex, postoperative rescue analgesia, and diminished fentanyl dosage intraoperatively.

导言:胸腔镜手术后,患者经常会出现令人衰弱的慢性术后疼痛(CPSP)。术后右美托咪定输注对 CPSP 的影响仍不明确。本研究旨在探讨右美托咪定对胸腔镜肺结节手术后1年CPSP发生率和恢复质量的影响:这项回顾性分析涵盖了2021年9月至2022年8月期间在我院接受胸腔镜肺结节手术的1148名患者的临床和随访数据。根据术后第一晚是否静脉输注右美托咪定,将患者分为右美托咪定组或对照组,并采用倾向评分匹配法统一基线特征。对比分析旨在明确术后一年 CPSP 和恢复质量的区别:经过倾向评分匹配后,对每组 258 名患者进行了分析。匹配后的比较显示,1 年 CPSP 发生率[76/258(29.5%)对 78/258(30.2%),P = 0.847]、中度至重度疼痛发生率[17/76(22.4%)对 22/78(28.2%),P = 0.405]、神经病理性疼痛发生率[11/76(14.5%)对 11/78(14.1%),P = 0.948],以及术后恢复质量评估(12 项简表健康调查 (SF-12) 评分)(113.1 [107.2, 116.0] 对 113.0 [107.4, 116.0],P = 0.328)。在对整个队列进行多变量逻辑回归分析后发现,女性患者的几率比(OR)为 2.10,95% 置信区间(CI)为 1.59-2.79,P 结论:女性患者的几率比男性患者低:长时间使用右美托咪定并未明显改善胸腔镜手术后1年的CPSP或恢复质量。值得注意的CPSP风险因素包括女性性别、术后抢救镇痛和术中减少芬太尼用量。
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引用次数: 0
Efficacy and Safety of Trazodone and Gabapentin Fixed-Dose Combination in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose-Finding Study. 曲唑酮和加巴喷丁固定剂量复方制剂对糖尿病痛性神经病变患者的疗效和安全性:随机对照剂量调查研究》。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-24 DOI: 10.1007/s40122-024-00624-3
Solomon Tesfaye, Ponnusamy Saravanan, Edvard Ehler, Karel Zinek, Ilona Palka-Kisielowska, Marcin Nastaj, Pierre Serusclat, Paola Lipone, Andrea Vergallo, Elisa Quarchioni, Fabrizio Calisti, Alessandro Comandini, Agnese Cattaneo
<p><strong>Introduction: </strong>Up to 50% of diabetic patients with neuropathy suffer from chronic pain, namely painful diabetic neuropathy (PDN), an unmet medical need with significant impact on quality of life. Gabapentin is widely used for PDN, albeit with frequent dose-limiting effects. Trazodone, an antidepressant with multi-modal action, has shown promising results when given at low doses as an add-on to gabapentin. Upon previous clinical trials and experimental evidence, a fixed-dose combination (FDC) of both compounds, at low doses, was developed for neuropathic pain.</p><p><strong>Methods: </strong>This was a phase II, randomized, double-blind, placebo and reference controlled, dose-finding, multicenter, international, prospective study. Male and female diabetic patients aged 18-75 years and affected by PDN were eligible for enrolment. Patients were randomized (1:1:1:1:2 ratio) to trazodone and gabapentin (Trazo/Gaba) 2.5/25 mg t.i.d. for 8 weeks, Trazo/Gaba 5/50 mg t.i.d. for 8 weeks, Trazo/Gaba 10/100 mg t.i.d. for 8 weeks, gabapentin (Gaba), or placebo (PLB). The aim of the study was to collect preliminary information on the effect of the 3 different FDCs of Trazo/Gaba on pain intensity based on the 11-point numeric rating score (NRS) after 8 weeks of treatment. The secondary objectives were the evaluation of the percentage of responders, neuropathic pain symptoms, anxiety, sleep, quality of life, safety, and tolerability. The primary efficacy endpoint was evaluated with last observation carried out forward (LOCF), using an analysis of covariance (ANCOVA), including treatment and centers as factors and baseline as covariate and applying linear contrast test, excluding the active treatment. Only if the linear contrast test was significant (p < 0.05), the step-down Dunnett test would be used to determine the minimum effective dose significantly different from PLB. If linearity was not verified, an adjusted ANCOVA model and comparisons with Dunnett test were performed. Before the application of the ANCOVA model, the non-significance of interaction treatment per baseline was verified.</p><p><strong>Results: </strong>A total of 240 patients were included in the modified intention-to-treat (m-ITT) population: 39 in Trazo/Gaba 2.5/25 mg, 38 in Trazo/Gaba 5/50 mg, 37 in Trazo/Gaba 10/100 mg, 83 in PLB, and 43 in Gaba. After 8 weeks of treatment, changes of the average daily pain score based on the 11-point NRS from baseline were - 2.52 ± 2.31 in Trazo/Gaba 2.5/25 mg group, - 2.24 ± 1.96 in Trazo/Gaba 5/50 mg group, - 2.46 ± 2.12 in Trazo/Gaba 10/100 mg group, - 1.92 ± 2.21 in Gaba group, and - 2.02 ± 1.95 in the PLB group. The linear contrast test did not result in significant differences (p > 0.05) among treatment groups. Consequently, the minimum effective dose against PLB was not determined. The multiple comparison with Dunnett adjustment did not show any statistically significant differences vs. PLB after 8 weeks of treatment: Trazo/Gab
导言:多达 50% 的糖尿病神经病变患者患有慢性疼痛,即糖尿病痛性神经病变 (PDN),这是一种尚未满足的医疗需求,对生活质量有重大影响。加巴喷丁被广泛用于治疗 PDN,但经常出现剂量限制效应。曲唑酮(Trazodone)是一种具有多模式作用的抗抑郁药,以小剂量作为加巴喷丁的辅助用药已显示出良好的效果。根据之前的临床试验和实验证据,我们开发出了这两种化合物的低剂量固定剂量复方制剂(FDC),用于治疗神经病理性疼痛:这是一项 II 期、随机、双盲、安慰剂和参照物对照、剂量调查、多中心、国际性、前瞻性研究。年龄在 18-75 岁之间、受 PDN 影响的男性和女性糖尿病患者均符合报名条件。患者被随机(1:1:1:1:1:2 的比例)分配到曲唑酮和加巴喷丁(Trazo/Gaba)2.5/25 毫克,每天三次,每次 8 周;曲唑/Gaba 5/50 毫克,每天三次,每次 8 周;曲唑/Gaba 10/100 毫克,每天三次,每次 8 周;加巴喷丁(Gaba)或安慰剂(PLB)。该研究的目的是收集3种不同的Trazo/Gaba FDCs在治疗8周后对疼痛强度(基于11点数字评分(NRS))影响的初步信息。次要目标是评估应答者比例、神经病理性疼痛症状、焦虑、睡眠、生活质量、安全性和耐受性。主要疗效终点的评估采用最后观察结果向前推移法(LOCF),使用协方差分析法(ANCOVA),将治疗和中心作为因子,基线作为协变量,并应用线性对比检验,排除积极治疗。只有当线性对比检验结果显著(P 结果)时,才会对其进行分析:共有 240 名患者被纳入改良意向治疗(m-ITT)人群:特拉佐/加巴 2.5/25 毫克 39 例、特拉佐/加巴 5/50 毫克 38 例、特拉佐/加巴 10/100 毫克 37 例、PLB 83 例、加巴 43 例。治疗8周后,基于11点NRS的每日平均疼痛评分与基线相比的变化情况为:Trazo/Gaba 2.5/25毫克组为- 2.52 ± 2.31,Trazo/Gaba 5/50毫克组为- 2.24 ± 1.96,Trazo/Gaba 10/100毫克组为- 2.46 ± 2.12,Gaba组为- 1.92 ± 2.21,PLB组为- 2.02 ± 1.95。线性对比试验结果表明,各治疗组之间没有显著差异(P > 0.05)。因此,未能确定对 PLB 的最小有效剂量。经过邓尼特调整的多重比较结果显示,治疗 8 周后,与 PLB 相比,各组间的差异无统计学意义:特拉佐/加巴 2.5/25 毫克(95% 置信区间 (CI) - 1.2739, 0.2026; p = 0.1539);特拉佐/加巴 5/50 毫克(95% 置信区间 (CI) - 0.9401, 0.5390; p = 0.5931);特拉佐/加巴 10/100 毫克(95% 置信区间 (CI) - 1.0342, 0.4582; p = 0.4471)。然而,接受最低剂量 Trazo/Gaba 2.5/25 毫克治疗的患者在治疗 6 周后与 PLB 相比有显著统计学差异(95% CI - 1.6648, - 0.2126; p = 0.0116)。在与疼痛、焦虑、抑郁、睡眠和生活质量相关的其他项目中,有反应的患者也发现了积极的结果,始终有利于最低特拉佐/加巴 FDC。发生了两例严重不良事件(SAE),但被判定与研究治疗无关。治疗突发不良事件(TEAEs)主要为轻度至中度,主要涉及神经系统、胃肠功能紊乱和检查:研究的主要终点是治疗 8 周后根据 11 点 NRS 得出的每日平均疼痛评分与基线相比的变化。虽然没有达到主要终点,但接受特拉佐/加巴 2.5/25 毫克(t.i.d.)治疗的患者在 6 周后疼痛和其他评分有了统计学意义上的显著改善,而且在整个研究期间,在主要终点和次要终点方面,与 PLB 相比都取得了更好的结果。根据这些结果,最低剂量的Trazo/Gaba FDC可能是进一步临床开发的最佳候选药物,以证实FDC药物治疗这种疾病的潜在疗效:临床试验注册:NCT03749642。
{"title":"Efficacy and Safety of Trazodone and Gabapentin Fixed-Dose Combination in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose-Finding Study.","authors":"Solomon Tesfaye, Ponnusamy Saravanan, Edvard Ehler, Karel Zinek, Ilona Palka-Kisielowska, Marcin Nastaj, Pierre Serusclat, Paola Lipone, Andrea Vergallo, Elisa Quarchioni, Fabrizio Calisti, Alessandro Comandini, Agnese Cattaneo","doi":"10.1007/s40122-024-00624-3","DOIUrl":"10.1007/s40122-024-00624-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Up to 50% of diabetic patients with neuropathy suffer from chronic pain, namely painful diabetic neuropathy (PDN), an unmet medical need with significant impact on quality of life. Gabapentin is widely used for PDN, albeit with frequent dose-limiting effects. Trazodone, an antidepressant with multi-modal action, has shown promising results when given at low doses as an add-on to gabapentin. Upon previous clinical trials and experimental evidence, a fixed-dose combination (FDC) of both compounds, at low doses, was developed for neuropathic pain.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was a phase II, randomized, double-blind, placebo and reference controlled, dose-finding, multicenter, international, prospective study. Male and female diabetic patients aged 18-75 years and affected by PDN were eligible for enrolment. Patients were randomized (1:1:1:1:2 ratio) to trazodone and gabapentin (Trazo/Gaba) 2.5/25 mg t.i.d. for 8 weeks, Trazo/Gaba 5/50 mg t.i.d. for 8 weeks, Trazo/Gaba 10/100 mg t.i.d. for 8 weeks, gabapentin (Gaba), or placebo (PLB). The aim of the study was to collect preliminary information on the effect of the 3 different FDCs of Trazo/Gaba on pain intensity based on the 11-point numeric rating score (NRS) after 8 weeks of treatment. The secondary objectives were the evaluation of the percentage of responders, neuropathic pain symptoms, anxiety, sleep, quality of life, safety, and tolerability. The primary efficacy endpoint was evaluated with last observation carried out forward (LOCF), using an analysis of covariance (ANCOVA), including treatment and centers as factors and baseline as covariate and applying linear contrast test, excluding the active treatment. Only if the linear contrast test was significant (p &lt; 0.05), the step-down Dunnett test would be used to determine the minimum effective dose significantly different from PLB. If linearity was not verified, an adjusted ANCOVA model and comparisons with Dunnett test were performed. Before the application of the ANCOVA model, the non-significance of interaction treatment per baseline was verified.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 240 patients were included in the modified intention-to-treat (m-ITT) population: 39 in Trazo/Gaba 2.5/25 mg, 38 in Trazo/Gaba 5/50 mg, 37 in Trazo/Gaba 10/100 mg, 83 in PLB, and 43 in Gaba. After 8 weeks of treatment, changes of the average daily pain score based on the 11-point NRS from baseline were - 2.52 ± 2.31 in Trazo/Gaba 2.5/25 mg group, - 2.24 ± 1.96 in Trazo/Gaba 5/50 mg group, - 2.46 ± 2.12 in Trazo/Gaba 10/100 mg group, - 1.92 ± 2.21 in Gaba group, and - 2.02 ± 1.95 in the PLB group. The linear contrast test did not result in significant differences (p &gt; 0.05) among treatment groups. Consequently, the minimum effective dose against PLB was not determined. The multiple comparison with Dunnett adjustment did not show any statistically significant differences vs. PLB after 8 weeks of treatment: Trazo/Gab","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"987-1006"},"PeriodicalIF":4.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
H-Wave® Device Stimulation for Chronic Neck Pain: A Patient-Reported Outcome Measures (PROMs) Study. H-Wave® 设备刺激治疗慢性颈痛:患者报告结果指标 (PROMs) 研究。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-11 DOI: 10.1007/s40122-024-00609-2
Ashim Gupta, David Han, Stephen M Norwood

Introduction: Chronic neck pain (cNP) is one of the leading causes of disability worldwide, often being refractory to conventional forms of treatment. Various forms of electrical stimulation have been proposed to decrease pain and improve function. Patient-reported outcome measures (PROMs) for treatment of cNP have rarely been published.

Methods: An independent retrospective statistical analysis of PROMs data for users of H-Wave® device stimulation (HWDS), prospectively collected by the device manufacturer over a 4-year period, was conducted. Final surveys for 34,192 pain management patients were filtered for pain chronicity limited to 3-24 months and device use of 22-365 days, resulting in 11,503 patients with "all diagnoses"; this number was further reduced to 1482 patients with cNP, sprain, or strain.

Results: Neck pain was reduced by 3.13 points (0-10 pain scale), with significant (≥ 20%) relief in 86.6%. Function/activities of daily living (ADL) improved in 96.19%, while improved work performance was reported in 84.76%. Medication use decreased or stopped in 65.42% and sleep improved in 60.39%. Over 95% reported having expectations met or exceeded, service satisfaction, and confidence in device use, while no adverse events were reported. Subgroup analyses found positive benefit associations with longer duration of device use.

Conclusion: Near-equivalent outcomes were self-reported by cNP HWDS patients as for (previously published) chronic low back pain (cLBP) patients. HWDS provided effective and safe cNP relief, improvements in function and ADL, along with additional benefits including decreased medication use, better sleep, and improved work performance.

简介慢性颈部疼痛(cNP)是导致全球残疾的主要原因之一,传统治疗方法往往难以奏效。人们提出了各种形式的电刺激来减轻疼痛和改善功能。用于治疗 cNP 的患者报告结果测量(PROM)很少发表:方法:对 H-Wave® 设备刺激 (HWDS) 用户的 PROMs 数据进行了独立的回顾性统计分析。对 34,192 名疼痛治疗患者的最终调查进行了筛选,将疼痛慢性化时间限制在 3-24 个月,设备使用天数限制在 22-365 天,最终得出 11,503 名 "所有诊断 "患者;这一数字进一步减少到 1482 名 cNP、扭伤或劳损患者:颈部疼痛减轻了 3.13 分(0-10 级疼痛量表),86.6% 的患者颈部疼痛明显缓解(≥ 20%)。96.19%的患者功能/日常生活活动(ADL)有所改善,84.76%的患者工作表现有所改善。65.42%的人减少或停止用药,60.39%的人睡眠得到改善。超过 95% 的人表示达到或超过了预期,对服务感到满意,并对设备的使用充满信心,同时没有不良事件的报告。分组分析发现,使用装置时间越长,收益越大:cNP HWDS 患者自我报告的结果与(之前公布的)慢性腰背痛(cLBP)患者的结果几乎相同。HWDS 能有效、安全地缓解 cNP,改善功能和日常活动能力,还能带来更多益处,包括减少药物使用、改善睡眠和提高工作绩效。
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引用次数: 0
Efficacy and Adverse Effects of IV Morphine for Burn Pain Management in the Emergency Department: An Observational Study. 急诊科静脉注射吗啡治疗烧伤疼痛的疗效和不良反应:观察研究。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-05-25 DOI: 10.1007/s40122-024-00595-5
Francesco Coletta, Rossella Pirolli, Raffaele Annunziata, Manuela Nugnes, Antonio Tommasello, Romolo Villani, Luca Gregorio Giaccari, Maria Beatrice Passavanti, Maria Caterina Pace, Pasquale Sansone

Introduction: The management of pain following a burn is extremely complex because of the multifactorial nature of burn pain (nociceptive and neuropathic). In the pre-hospital setting and emergency department (ED), the main goal of acute pain management is to reduce the patient's pain, allowing them to maintain function and to prevent the chronification of pain. Opioids are used as first-line treatment in management of burn pain. The aim of our study was to evaluate the efficacy and adverse effects of intravenous (IV) morphine for burn pain management in the ED and to evaluate pain management in the pre-hospital setting.

Methods: In this single-center observational study, patients presenting with second- and third-degree burns were enrolled in our ED. Numerical Rating Scale (NRS) and Burn Specific Pain Anxiety Scale (BSPAS) were performed at ED admission and after 1 h. Pain medications administered before arrival in the ED were reported by the rescue team. All patients received IV acetaminophen every 8 h and IV morphine according NRS.

Results: Thirty patients were included in this study. At the time of arrival to the ED, > 90% of the patients reported severe pain; 95.8% of them received IV morphine to achieve pain relief. After 1 h, > 65% of patients had NRS < 3. The total amount of IV morphine was 18.12 ± 4.26 mg in the first hour. No adverse events were recorded. The BSPAS on admission to the ED was 34.8 ± 5.6, indicating severe anxiety. After 1 h, BSPAS was 12.8 ± 4.8, indicating mild anxiety.

Conclusion: IV morphine used for burn pain management in the emergency setting significantly improves patient outcomes in terms of pain. IV morphine also reduced anxiety scores at 1 h.

导言:烧伤后的疼痛治疗极为复杂,因为烧伤疼痛具有多因素性质(痛觉和神经病理性)。在院前环境和急诊科(ED)中,急性疼痛治疗的主要目标是减轻患者的疼痛,使他们能够保持功能,并防止疼痛慢性化。阿片类药物是治疗烧伤疼痛的一线药物。我们的研究旨在评估静脉注射吗啡治疗急诊室烧伤疼痛的疗效和不良反应,并评估院前环境中的疼痛管理:在这项单中心观察性研究中,我们在急诊室收治了二度和三度烧伤患者。入院时和入院 1 小时后分别进行了数字评定量表(NRS)和烧伤疼痛焦虑量表(BSPAS)。所有患者每 8 小时接受一次对乙酰氨基酚静脉注射,并根据 NRS 接受吗啡静脉注射:本研究共纳入 30 名患者。到达急诊室时,超过 90% 的患者报告有剧烈疼痛;其中 95.8% 的患者接受了静脉注射吗啡以缓解疼痛。1 小时后,超过 65% 的患者 NRS < 3。在第一小时内,静脉注射吗啡的总量为 18.12 ± 4.26 毫克。无不良反应记录。入院时的BSPAS为(34.8 ± 5.6),表明患者存在严重焦虑。1 小时后,BSPAS 为 12.8 ± 4.8,表明焦虑程度较轻:结论:在急诊环境中使用静脉注射吗啡治疗烧伤疼痛可明显改善患者的疼痛预后。静脉注射吗啡还能降低 1 小时后的焦虑评分。
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引用次数: 0
Transcutaneous Electrical Acupoint Stimulation Combined with Moderate Sedation of Remimazolam Tosilate in Gastrointestinal Endoscopy: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Trial. 胃肠道内窥镜检查中经皮电穴位刺激结合使用雷马唑仑托西酯中度镇静剂:一项前瞻性、随机、双盲、安慰剂对照临床试验。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-18 DOI: 10.1007/s40122-024-00618-1
Jian-Han Xu, Hai-Ling Tan, Li-Na Zhang, Zan-Gong Zhou, Li Yuan, Ling-Xin Kong, Ming-Quan Song, Li-Jie Qi, Xiang-Yu Ji

Introduction: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy.

Methods: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam.

Results: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P.

Conclusions: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications.

Trial registration: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

简介:经皮穴位电刺激(TEAS)能否取代阿片类药物,并与瑞马唑仑联合使用,用于胃肠道内窥镜检查期间的镇静,还需要进一步的临床验证:共有108名门诊患者接受了诊断性消化内镜检查,他们被随机分为三组:芬太尼加瑞马唑仑组(C组)、TEAS加瑞马唑仑组(E组)和安慰剂-TEAS加瑞马唑仑组(P组)。患者满意度、医生满意度和检查过程中的疼痛量表评分构成研究的主要终点。次要终点是康复时间、正常行为功能恢复和出院时间、不良反应发生率和雷马唑仑剂量:与 C 组相比,E 组患者随访满意度的中位数得分更高,而医生满意度的中位数得分略低。E 组的疼痛评分略高于 C 组,但差异不显著。然而,C 组患者的低氧血症发生率、恶心发生率和眩晕严重程度均高于其他两组,出院并恢复正常行为功能的患者人数也多于其他两组。C组和E组的雷马唑仑剂量小于P组:结论:TEAS联合适度镇静的瑞马唑仑可提供理想的镇静效果,能较好地抑制消化道内镜检查引起的不适,且镇静相关并发症较少:试验注册:ID:NCT05485064;首次注册(2022 年 7 月 29 日);最后注册(2022 年 11 月 2 日)(Clinical Trials.gov)。
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引用次数: 0
Development of a Prediction Model and Corresponding Scoring Table for Postherpetic Neuralgia Using Six Machine Learning Algorithms: A Retrospective Study. 使用六种机器学习算法开发带状疱疹后神经痛的预测模型和相应评分表:回顾性研究
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-04 DOI: 10.1007/s40122-024-00612-7
Zheng Lin, Lu-Yan Yu, Si-Yi Pan, Yi Cao, Ping Lin

Introduction: Postherpetic neuralgia (PHN), a complication of herpes zoster, significantly impacts the quality of life of affected patients. Research indicates that early intervention for pain can reduce the occurrence or severity of PHN. This study aims to develop a predictive model and scoring table to identify patients at risk of developing PHN following acute herpetic neuralgia, facilitating informed clinical decision-making.

Methods: We conducted a retrospective review of 524 hospitalized patients with herpes zoster at The First Affiliated Hospital of Zhejiang Chinese Medical University from December 2020 to December 2023 and classified them according to whether they had PHN, collecting a comprehensive set of 30 patient characteristics and disease-related indicators, 5 comorbidity indicators, 2 disease score values, and 10 serological indicators. Relevant features associated with PHN were identified using the least absolute shrinkage and selection operator (LASSO). Then, the patients were divided into a training set and a test set in a 4:1 ratio, with comparability tested using univariate analysis. Six models were established in the training set using machine learning methods: support vector machines, logistic regression, random forest, k-nearest neighbor, gradient boosting, and neural network. The performance of these models was evaluated in the test set, and a nomogram based on logistic regression was used to create a PHN prediction score table.

Results: Eight non-zero characteristic variables selected from the LASSO regression results were included in the model, including age [area under the curve (AUC) = 0.812, p < 0.001], Numerical Rating Scale (NRS) (AUC = 0.792, p < 0.001), receiving treatment time (AUC = 0.612, p < 0.001), rash recovery time (AUC = 0.680, p < 0.001), history of malignant tumor (AUC = 0.539, p < 0.001), history of diabetes (AUC = 0.638, p < 0.001), varicella-zoster virus immunoglobulin M (AUC = 0.620, p < 0.001), and serum nerve-specific enolase (AUC = 0.659, p < 0,001). The gradient boosting model outperformed other classifier models on the test set with an AUC of 0.931, 95% confidence interval (CI) (0.882-0.980), accuracy of 0.886 (95% CI 0.809-0.940). In the test set, our predictive scoring table achieved an AUC of 0.820 (95% CI 0.869-0.970) with accuracy of 0.790 (95% CI 0.700-0.864).

Conclusion: This study presents a methodology for predicting the development of postherpetic neuralgia in shingles patients by analyzing historical case data, employing various machine learning techniques, and selecting the optimal model through comparative analysis. In addition, a logistic regression model has been used to create a scoring table for predicting the postherpetic neuralgia.

简介:带状疱疹后遗神经痛(PHN)是带状疱疹的一种并发症,严重影响患者的生活质量。研究表明,对疼痛进行早期干预可降低 PHN 的发生率或严重程度。本研究旨在开发一种预测模型和评分表,以识别急性带状疱疹神经痛后有可能发展为 PHN 的患者,从而帮助患者做出明智的临床决策:我们对浙江中医药大学附属第一医院 2020 年 12 月至 2023 年 12 月的 524 例带状疱疹住院患者进行了回顾性研究,并根据是否患有 PHN 对患者进行了分类,收集了 30 项患者特征和疾病相关指标、5 项合并症指标、2 项疾病评分值和 10 项血清学指标。使用最小绝对缩小和选择算子(LASSO)确定了与 PHN 相关的特征。然后,按照 4:1 的比例将患者分为训练集和测试集,并使用单变量分析检验可比性。在训练集中使用机器学习方法建立了六个模型:支持向量机、逻辑回归、随机森林、k-近邻、梯度提升和神经网络。在测试集中评估了这些模型的性能,并使用基于逻辑回归的提名图创建了 PHN 预测评分表:结果:从 LASSO 回归结果中选出的 8 个非零特征变量被纳入了模型,包括年龄[曲线下面积(AUC)= 0.812,P 结论:该研究提出了一种预测 PHN 的方法:本研究通过分析带状疱疹患者的历史病例数据,采用各种机器学习技术,并通过比较分析选择最佳模型,提出了一种预测带状疱疹患者发生带状疱疹后遗神经痛的方法。此外,研究还利用逻辑回归模型创建了带状疱疹后遗神经痛预测评分表。
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引用次数: 0
The Use of High-Dose Intravenous L-Ascorbate in Pain Therapy: Current Evidence from the Literature. 在疼痛治疗中使用大剂量静脉注射 L-抗坏血酸:目前的文献证据
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-12 DOI: 10.1007/s40122-024-00622-5
Rudolf Likar, Ruth Poglitsch, Štěpán Bejvančický, Ludwig Carl, Miroslav Ferencik, Alfred Klein-Watrycz, Monika Rieger, Keveen Salirrosas Flores, Astrid Schumich, Zoe Vlamaki, Marc Werner

Introduction: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of L-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.

Methods: The current literature on the therapeutic effect of L-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous L-ascorbate.

Results: A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of L-ascorbate in pain treatment.

Discussion: Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. L-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.

Conclusions: L-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.

导言疼痛是最常见的就医原因。尽管开展了广泛的研究工作并使用了有效的镇痛药来调节疼痛,但在解决疼痛根源方面仍存在重大治疗差距。疼痛与氧化应激引起的组织损伤以及大量摄入抗氧化剂后诱发的炎症介质有关。抗氧化剂的作用,尤其是左旋抗坏血酸的作用,在日常临床实践中仍存在争议和低估:方法:在循证医学的背景下,对目前关于左旋抗坏血酸、抗坏血酸和维生素 C 对各种疼痛症状的治疗效果的文献进行了评估。两位独立专家对从 PubMed 上系统搜索到的这些文章进行了严格评估,并从证据水平和方法质量方面进行了评分。这项工作的主要目的是为静脉注射左旋抗坏血酸制定具体的疼痛治疗指南:在 PubMed 上搜索发现了 14 篇合适的文章,包括对照临床试验和荟萃分析。通过二手文献还可以找到另外 10 篇文献。有支持性证据表明,抗坏血酸治疗对炎症性疼痛、复杂性区域疼痛综合征、带状疱疹后神经痛、神经性疼痛、术后疼痛和肿瘤相关疼痛具有疗效。然而,所考虑的研究在给药类型、剂量、治疗时间以及研究质量方面都存在差异。尽管所有研究都不尽相同,但高科学质量的研究显然支持左旋抗坏血酸在疼痛治疗中的疗效:讨论:氧化应激几乎存在于所有疼痛病症中。由于大多数维生素 C 的口服配方不能提供生物利用率,因此应首选肠外给药,在没有静脉治疗的日子里,可通过口服高生物利用率的剂量来支持肠外给药。肠外大剂量给药应首选左旋抗坏血酸,而不是抗坏血酸,因为左旋抗坏血酸在生理条件下不会释放酸价:结论:L-抗坏血酸是一种有效、安全、经济的综合治疗方案,可治疗各种疼痛病症,从根本上解决组织损伤和炎症介质爆发问题。
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引用次数: 0
Rizatriptan as an Over-the-Counter Triptan in the Treatment of Migraine Attacks. 治疗偏头痛发作的非处方药利扎曲普坦
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-17 DOI: 10.1007/s40122-024-00625-2
Carl H Göbel, Axel Heinze, Anna Cirkel, Hartmut Göbel

Around 91% of migraine patients use over-the-counter medicines to treat attacks, often without further treatment or medical consultation. This therapeutic principle is established in most countries, regardless of how the healthcare system is otherwise structured or financed. Using Germany as an example, the basis for an expansion of attack therapy with rizatriptan as an over-the-counter triptan is described. To achieve the best possible tolerability and safety in the context of self-medication, the lowest possible dose should be selected to provide the most favourable tolerability and safety profile in the context of self-medication through low dosages. The lowest approved dose of rizatriptan is 5 mg. This was investigated in three randomized controlled trials with 752 patients. The results show that rizatriptan at a dose of 5 mg is more effective than the triptans naratriptan 2.5 mg, almotriptan 12.5 mg and sumatriptan 50 mg, which were previously available for self-medication in Germany. There was no significant difference in the frequency of adverse events with rizatriptan 5 mg compared to placebo. Rizatriptan 5 mg does not have a higher side effect potential than sumatriptan 50 mg, which is already exempt from the prescription requirement. The reasons given show that rizatriptan in a dose of 5 mg for the treatment of acute migraine attacks fulfils the requirements for a transfer from prescription to pharmacy-only status at least as well as sumatriptan 50 mg, naratriptan 2.5 mg and almotriptan 12.5 mg. From a clinical care perspective, it is desirable for affected patients to have other options available for self-medication. Non-responders to other substances also have a further treatment option with rizatriptan 5 mg, with the same or even better risk-benefit profile, to treat migraine attacks safely, effectively and in a tolerable manner as part of self-medication.

约91%的偏头痛患者使用非处方药物治疗偏头痛发作,通常无需进一步治疗或就诊。无论医疗系统的结构或资金来源如何,大多数国家都确立了这一治疗原则。本文以德国为例,介绍了将利扎曲普坦作为非处方三苯氧胺来扩大发作治疗范围的基础。为了在自行用药的情况下实现最佳的耐受性和安全性,应选择尽可能低的剂量,以便通过低剂量自行用药实现最有利的耐受性和安全性。利扎曲普坦的最低批准剂量为 5 毫克。三项随机对照试验共对752名患者进行了研究。结果表明,5 毫克剂量的利扎曲普坦比之前在德国可用于自我药疗的那曲普坦 2.5 毫克、阿莫曲坦 12.5 毫克和舒马曲坦 50 毫克更有效。与安慰剂相比,5 毫克利扎曲普坦的不良反应发生率没有明显差异。利扎曲普坦 5 毫克的副作用并不比舒马曲普坦 50 毫克高,后者已经免于处方要求。上述理由表明,用于治疗偏头痛急性发作的5毫克剂量的利扎曲普坦至少与舒马曲坦50毫克、那拉曲普坦2.5毫克和阿莫曲坦12.5毫克一样,符合从处方药转为药房专用药的要求。从临床治疗的角度来看,患者最好有其他自我治疗的选择。对其他药物无应答的患者还可以选择使用5毫克利扎曲普坦,其风险-效益特征与其他药物相同甚至更好,可以安全、有效、可耐受地治疗偏头痛发作,作为自我药物治疗的一部分。
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引用次数: 0
Effect of Intravenous Sodium Pentobarbital on Pain and Sensory Abnormalities in Patients with Chronic Non-Cancer Pain: Narrative Literature Review, Research Study, and Illustrative Case Reports. 静脉注射戊巴比妥钠对慢性非癌性疼痛患者的疼痛和感觉异常的影响:文献综述、研究和说明性病例报告。
IF 4.1 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-08-01 Epub Date: 2024-06-20 DOI: 10.1007/s40122-024-00621-6
Shehnaz Fatima Lakha, Angela Mailis

Introduction: Sodium pentobarbital (SP), a short- to intermediate-acting barbiturate, has limited information in the existing literature. The objectives of this study are to describe (a) the effect of intravenous (IV) SP infusion on pain and sensory abnormalities, and (b) its utility in the diagnosis and management of patients with chronic pain.

Methods: A narrative review of barbiturate applications for chronic pain was followed by a pragmatic study of 176 consecutive patients admitted to an inpatient pain unit (2004-2009). We collected demographic information upon admission, diagnoses retrieved from chart review, and pain ratings and sensory abnormalities at baseline and after blinded infusion of normal saline (NS) followed by SP.

Results: The study group consisted of 83 men and 93 women (mean age 41 ± 11 years); the mean NS dose was 7.8 ± 2.3 (range 2-10 ml), the SP dose was 223.8 ± 88 mg (range 40-420), and the numeric rating scale (NRS) baseline pain score was 6.0 ± 2. The mean reduction in NRS reached both statistical and clinical significance in 150 responders to either NS/SP or SP only. Collectively, we found (a) an extremely high rate of response to IV SP irrespective of the underlying pathology, (b) greater response for pain than for sensory abnormalities (sensory gains or deficits), (c) greater response for sensory gain than for sensory deficit, and (d) greater response for allodynia than for pinprick hyperalgesia. Illustrative case reports are also presented.

Discussion: IV SP infusion is a diagnostic tool that assists in elucidating pain generators and the nature of sensory abnormalities (central vs. peripheral), with effects similar to those of IV sodium amytal. The test cannot be viewed as a tell-all diagnostic modality and must be used in conjunction with clinical judgment, investigations, and psychological reports.

简介:戊巴比妥钠(SP)是一种短效至中效巴比妥酸盐,现有文献中的相关信息十分有限。本研究旨在描述(a)静脉注射(IV)戊巴比妥钠对疼痛和感觉异常的影响,以及(b)戊巴比妥钠在诊断和治疗慢性疼痛患者中的作用:方法:对巴比妥类药物在慢性疼痛中的应用进行了叙述性回顾,然后对疼痛住院病房连续收治的 176 名患者进行了实用性研究(2004-2009 年)。我们收集了患者入院时的人口统计学信息、病历中的诊断信息、基线时和盲注生理盐水(NS)后的疼痛评分和感觉异常:研究组包括 83 名男性和 93 名女性(平均年龄为 41 ± 11 岁);NS 平均剂量为 7.8 ± 2.3(范围为 2-10 毫升),SP 剂量为 223.8 ± 88 毫克(范围为 40-420),数字评分量表(NRS)基线疼痛评分为 6.0 ± 2。在 150 名仅对 NS/SP 或 SP 有反应的患者中,NRS 平均值的降低达到了统计学和临床意义。总之,我们发现:(a) 无论潜在病理情况如何,静脉注射 SP 的反应率极高;(b) 对疼痛的反应大于对感觉异常(感觉增强或缺失)的反应;(c) 对感觉增强的反应大于对感觉缺失的反应;(d) 对异动症的反应大于对针刺痛的反应。讨论:讨论:静脉注射 SP 是一种诊断工具,有助于阐明疼痛的产生和感觉异常的性质(中枢与外周),其效果与静脉注射阿米妥钠相似。该测试不能被视为万能的诊断方式,必须与临床判断、调查和心理报告结合使用。
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Pain and Therapy
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