Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial

Background

There is little evidence from clinical trials that the use of adrenaline (epinephrine) in treating cardiac arrest improves survival, despite adrenaline being considered standard of care for many decades. The aim of our study was to determine the effect of adrenaline on patient survival to hospital discharge in out of hospital cardiac arrest.

Methods

We conducted a double blind randomised placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest. Identical study vials containing either adrenaline 1:1000 or placebo (sodium chloride 0.9%) were prepared. Patients were randomly allocated to receive 1 ml aliquots of the trial drug according to current advanced life support guidelines. Outcomes assessed included survival to hospital discharge (primary outcome), pre-hospital return of spontaneous circulation (ROSC) and neurological outcome (Cerebral Performance Category Score - CPC).

Results

A total of 4103 cardiac arrests were screened during the study period of which 601 underwent randomisation. Documentation was available for a total of 534 patients: 262 in the placebo group and 272 in the adrenaline group. Groups were well matched for baseline characteristics including age, gender and receiving bystander CPR. ROSC occurred in 22 (8.4%) of patients receiving placebo and 64 (23.5%) who received adrenaline (OR = 3.4; 95% CI 2.0-5.6). Survival to hospital discharge occurred in 5 (1.9%) and 11 (4.0%) patients receiving placebo or adrenaline respectively (OR = 2.2; 95% CI 0.7-6.3). All but two patients (both in the adrenaline group) had a CPC score of 1-2.

Conclusion

Patients receiving adrenaline during cardiac arrest had no statistically significant improvement in the primary outcome of survival to hospital discharge although there was a significantly improved likelihood of achieving ROSC.     

多学科协作背景下老年患者术后谵妄预防及护理管理策略的构建

目的 构建多学科协作背景下老年患者术后谵妄的预防及护理管理策略.方法 采用文献检索、质量评价、临床调研与专家小组讨论等方法,结合标准化护理语言-奥马哈系统及结果-过程-结果三维质量评价理论,初拟老年患者术后谵妄的预防及护理管理策略.采用德尔菲专家咨询法,经过两轮专家咨询,构建老年患者术后谵妄预防及护理管理体系.结果 建...     

老年患者术后神经认知障碍影响因素的研究进展

术后神经认知障碍是老年患者手术和麻醉后常出现的中枢神经系统并发症,是麻醉学和神经科学的研究热点。患者主要表现为认知功能衰减,可影响术后恢复,增加医疗负担。近年来,随着老年患者人数增多,术后神经认知障碍将成为一个严峻的临床及社会问题。本文旨在总结老年患者术后神经认知障碍相关影响因素,为临床和基础研究的实施提供参考,减少老年患者术后神经认知障碍的发生,减轻患者的医疗负担。     

Efficacy of memantine in the treatment of fibromyalgia: A double-blind,randomised, controlled trial with 6-month follow-up

Fibromyalgia (FM) is a prevalent and disabling chronic disease. Recent studies have found elevated levels of glutamate in several brain regions, leading to hypotheses about the usefulness of glutamate-blocking drugs such as memantine in the treatment of FM. The aim of this study was to evaluate the efficacy of memantine in the treatment of pain and other clinical variables (global function, clinical impression, depression, anxiety, quality of life) in FM patients. A double-blind, parallel randomised controlled trial was developed. A total of 63 patients diagnosed with FM were recruited from primary health care centres in Zaragoza, Spain. Memantine was administered at doses of 20 mg/d after 1 month of titration. Assessments were carried out at baseline, posttreatment, and 3- and 6-month follow-up. Compared with a placebo group, memantine significantly decreased ratings on a pain visual analogue scale (Cohen’s d = 1.43 at 6 months) and pain measured with a sphygmomanometer (d = 1.05). All other secondary outcomes except anxiety also improved, with moderate-to-large effect sizes at 6 months. Compared with placebo, the absolute risk reduction obtained with memantine was 16.13% (95% confidence interval = 2.0% to 32.6%), and the number needed to treat was 6.2 (95% confidence interval = 3 to 47). Tolerance was good, with dizziness (8 patients) and headache (4 patients) being the most frequent side effects of memantine. Although additional studies with larger sample sizes and longer follow-up times are needed, this study provides preliminary evidence of the utility of memantine for the treatment of FM.     

Evaluation of the efficacy of Withania somnifera (Ashwagandha) root extract in patients with obsessive-compulsive disorder: A randomized double-blind placebo-controlled trial

BackgroundObsessive-compulsive disorder (OCD) is a chronic psychiatric disorder that is causally linked to dysregulation of the serotonergic system. The aim of this study is to investigate the efficacy of Withania somnifera (W. somnifera) root extract as an adjunct therapy to standard OCD treatment.MethodsThirty patients with a confirmed diagnosis of OCD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria participated in this randomized double-blind placebo-controlled trial and were randomly assigned to the treatment group (W. somnifera extract, 120 mg/day; n = 15) or the placebo group (n = 15). All patients were under treatment with Selective Serotonin Re-uptake Inhibitors (SSRIs), and were instructed to take 4 capsules of the extract or placebo per day, preferably after meals, for a period of six weeks. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used in order to assess the severity of OCD symptoms at baseline and at the end of the trial. Statistical analyses were performed using SPSS software and Y-BOCS values were presented as median and range (Min-Max).ResultsComparison of the change in Y-BOCS score during the course of the trial revealed a significantly greater effect of W. somnifera (26 (14–40) [pre-treatment] versus 14 (4–40) [post-treatment]; change: −8 (−23 to 0)) versus placebo (18 (11–33) [pre-treatment] versus 16 (10–31) [post-treatment]; change: −2 (−4 to 0)) (P < 0.001). The extract was safe and no adverse event was reported during the trial.ConclusionW. somnifera extract may be beneficial as a safe and effective adjunct to SSRIs in the treatment of OCD.     

Perioperative plasma melatonin concentration in postoperative critically ill patients: Its association with delirium

Purpose

Delirium is a common complication in postoperative critically ill patients. Although abnormal melatonin metabolism is thought to be one of the mechanisms of delirium, there have been few studies in which the association between alteration of perioperative plasma melatonin concentration and postoperative delirium was assessed.

Materials

We conducted a prospective observational study to assess the association of perioperative alteration of plasma melatonin concentration with delirium in 40 postoperative patients who required intensive care for more than 48 hours. We diagnosed postoperative delirium using Confusion Assessment Method for the intensive care unit and measured melatonin concentration 4 times (before the operation as the preoperative value, 1 hour after the operation, postoperative day 1, and postoperative day 2).

Results

Postoperative delirium occurred in 13 (33%) of the patients. Although there was no significant difference in preoperative melatonin concentration, Δ melatonin concentration at 1 hour after the operation was significantly lower in patients with delirium than in those without delirium (− 1.1 vs 0 pg/mL, P = .036). After adjustment of relevant confounders, Δ melatonin concentration was independently associated with risk of delirium (odds ratio, 0.50; P = .047).

Conclusions

Delta melatonin concentration at 1 hour after the operation has a significant independent association with risk of postoperative delirium.     

Pregabalin in severe burn injury pain: a double-blind, randomised placebo-controlled trial

This randomised, double-blind, placebo-controlled trial assessed the efficacy and tolerability of pregabalin to alleviate the neuropathic component of moderate to severe burn pain. Patients aged 18 to 65 years admitted to a burns unit with a 5% or greater total body surface area burn injury were screened to participate in the trial. Using the Neuropathic Pain Scale (NPS), patients scoring 4 or higher on ‘hot’ pain or ‘sharp’ pain were invited to participate. Consenting patients were randomly assigned to receive pregabalin or placebo for 28 days with individual dose titration commencing at 75 mg twice daily to a maximum pregabalin dose of 300 mg twice daily. The primary outcome measure was the patients’ daily response to the sharp and hot pain of the NPS. Secondary outcome measures included the remaining elements of the NPS, daily opioid requirement, length of hospital stay, pain at 6 months, and side effects of nausea, vomiting, drowsiness and giddiness. For patients administered pregabalin, the primary outcome measures hot (P = .01) and sharp (P = .04) pain were significantly reduced compared with those in patients administered placebo. Secondary outcome measures of itch, unpleasantness, surface pain, and procedural pain were significantly lower (P < .05) in the pregabalin group. Adverse effects were uncommon, with no difference between the treatment groups. There was no significant difference between the pregabalin and placebo treatment groups with respect to opioid consumption, duration of hospital stay, or pain at 6 months. Pregabalin was efficacious and well tolerated in patients after severe burn injury and whose pain was characterised by features of acute neuropathic pain.     

老年患者术后谵妄风险预测模型的范围综述

目的 对老年患者术后谵妄风险预测模型进行范围综述,为临床工作及未来研究提供借鉴。方法 聚焦老年患者术后谵妄风险预测模型,检索中英文数据库,获取与老年患者术后谵妄相关的风险预测模型文献。结果 共纳入26项研究,老年患者术后谵妄发生率为4.6%~39.7%。模型构建方法包括Logistic回归及多种机器学习算法,模型呈现形式多样,年龄、痴呆史、术前认知功能水平、麻醉分级、糖尿病史、麻醉时间、查尔森合并症指数、术前血清白蛋白水平是老年患者术后谵妄风险预测模型中重要的预测因子。结论 临床护理人员应关注老年患者术后谵妄的高危因素,重视规范、科学的预测模型构建及验证流程,未来应探索更加科学精准、性能良好、易于推广的老年患者术后谵妄风险预测模型。     

老年髋部骨折术后血容量改变与谵妄的相关分析

目的探讨谵妄与老年髋部骨折患者术后血容量改变的相关性,为治疗和预防提供参考。方法连续性观察150例接受手术治疗的老年髋部骨折患者。谵妄的评估采用CAM（confusionassessmentmethod）量表。收集其术前、术中及术后的数据,用Logistic回归分析血容量改变与谵妄的相关性。结果59例患者（男28例,女31例）术后出现了谵妄,发生率为39．3％（59／150）。谵妄组平均年龄（77．71±6．63）岁,高于无谵妄组患者（73．79±5．42）岁,两组比较差异有统计学意义（t=-3．958,P〈0．001）。谵妄组患者术前及术后第7天平均血红蛋白浓度、红细胞比容均低于未出现谵妄组[术前分别为（117．80±16．59）、（123．92±14．61）g／L,t=2．378,P=0．019;0．355±0．154、0．372±0．210,t=2．291,P=0．023;术后第7天（98．15±11．51）、（102．33±9．88）g／L,t=2．369,P=0．019;0．296±0．040、0．306±0．030,t=-3．958,P〈0．001]。两组间在性别、骨折类型、手术方式、手术时间、失血量及术后1、3d血红蛋白浓度间差异无统计学意义（P均〉0．05）。经Logistic回归分析,患者的年龄、教育程度及术后第7天血红蛋白含量在是否出现谵妄两组间差异有统计学意义（OR分别为3．28、1．097、0．389,P均〈0．05）。结论高龄髋部骨折患者发生谵妄是一个多因素结果,高龄、术后持续低血红蛋白浓度、受教育程度低患者的谵妄发生概率高。     

Effect of vitamin D on musculoskeletal pain and headache: A randomized,double-blind,placebo-controlled trial among adult ethnic minorities in Norway

Immigrants from South Asia, the Middle East, and Africa living in Northern Europe frequently have low vitamin D levels and more pain compared to the native Western population. The aim of this study was to examine whether daily vitamin D₃ (25 μg/d or 10 μg/d) supplementation for 16 weeks would improve musculoskeletal pain or headache compared to placebo. This randomized, double-blind, placebo-controlled, parallel-group trial recruited 251 participants aged 18 to 50 years, and 215 (86%) attended the follow-up visit. The pain measures were occurrence, anatomical localization, and degree of musculoskeletal pain, as measured by visual analogue scale (VAS) score during the past 2 weeks. Headache was measured with VAS and the Headache Impact Test (HIT-6) questionnaire. At baseline, females reported more pain sites (4.7) than males (3.4), and only 7% reported no pain in the past 2 weeks. During the past 4 weeks, 63% reported headache with a high mean HIT-6 score of 60 (SD 7). At follow-up, vitamin D level, measured as serum 25(OH)D₃, increased from 27 nmol/L to 52 nmol/L and from 27 nmol/L to 43 nmol/L in the 25-μg and 10-μg supplementation groups, respectively, whereas serum 25(OH)D₃ did not change in the placebo group. Pain scores and headache scores were improved at follow-up compared with baseline. The use of vitamin D supplements, however, showed no significant effect on the occurrence, anatomical localization, and degree of pain or headache compared to placebo.     

右美托咪定预防全麻术后躁动和咽喉疼痛的作用

目的探讨右美托咪啶在预防全麻术后躁动和咽喉疼痛方面的应用价值,以提高全身麻醉的安全性。方法选取接受全麻手术治疗的患者114例,通过随机数字表法将其分为观察组和对照组各57例。两组均采用相同的药物进行全身麻醉,观察组在手术结束前半个小时静脉泵入右美托咪啶,对照组则静脉泵入相同体积的0.9%氯化钠注射液。对比两组患者恢复自主呼吸的时间和拔除气管插管时间以及术后躁动和咽喉疼痛的发生率。结果两组患者恢复自主呼吸时间、拔除气管插管时间的对比,差异无统计学意义(P0.05)。在术后躁动方面,观察组0级的有53例,躁动率为7.02%;对照组0级的有34例,躁动率为40.35%。观察组躁动率显著低于对照组(P0.05)。在术后咽喉疼痛方面,观察组0级的有46例,咽喉疼痛率为19.30%;对照组0级的有30例,咽喉疼痛率为47.37%。观察组咽喉疼痛率显著低于对照组(P0.05)。结论右美托咪啶对全麻术后躁动和咽喉疼痛具有良好的预防作用,同时不会增加呼吸抑制的风险,值得在临床上推广应用。     

Sumatriptan nasal spray in adolescent migraineurs: a randomized, double-blind, placebo-controlled, acute study

OBJECTIVE: To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. BACKGROUND: Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P = .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. METHODS: This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with > or = 6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. RESULTS: Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P = .046) and 2 hours (68% vs. 58%; P = .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P = .087) or for sustained headache relief from 1 to 24 hours (P = .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). CONCLUSIONS: This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population.     

A dose-ranging study of midazolam for postoperative sedation of patients: a randomized,double-blind,placebo-controlled trial

OBJECTIVE: To evaluate the dose range, efficacy, and safety of midazolam for induction of sedation of mechanically ventilated postoperative patients in the intensive care unit. DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: Thirteen intensive care units in Japan. PATIENTS: We included 98 patients undergoing general surgery who were ASA physical status I-III. The following inclusion criteria were applied to the patients after surgery: under mechanical ventilation, sedation level 2 or 3 on the Ramsay Sedation Scale, and any pain level but 4 on the Pybus and Torda Pain Scale. MEASUREMENTS AND RESULTS: Of the 98 patients initially enrolled in the study, 95 patients received one of the study medications: placebo (n = 24), 0.015 mg/kg midazolam (n = 21), 0.03 mg/kg midazolam (n = 26), or 0.06 mg/kg midazolam (n = 24). Level of sedation was assessed by using the Ramsay Sedation Scale before and 10 mins after medication. The proportions of patients with sedation level 4 or deeper after medication were 4.3%, 14.3%, 52.0%, and 90.9% in the placebo and the midazolam 0.015 mg/kg, 0.03 mg/kg, and 0.06 mg/kg groups, respectively. Safety was assessed by routine monitoring of body functions and monitoring for adverse events. Although midazolam dose-dependently reduced mean systolic arterial pressure, the changes in this variable were small; only one or two patients in each treatment group had decreases in systolic arterial pressure of >20%. No clear dose dependency was found for changes in other body functions measured in the intensive care unit. CONCLUSION: The proportion of patients who achieved a satisfactory level of sedation increased with an increasing dose of midazolam. Intravenous bolus injection of midazolam also dose-dependently reduced mean systolic arterial pressure. This study indicated that, balancing sedative efficacy and safety, from 0.03 to 0.06 mg/kg of midazolam provides relatively safe sedation in postoperative patients.     

The effectiveness of traditional Thai massage versus massage with herbal compress among elderly patients with low back pain: A randomised controlled trial

ObjectivesTo determine the effectiveness of including an herbal compress in a traditional Thai massage regimen for the care of low back pain in the elderly.Design and methodsThis study was a randomised controlled trial. The sample consisted of 140 patients suffering from non-specific chronic low back pain, who were randomly assigned to either the TTM (n = 70) or TMH (n = 70) group. The primary outcome was pain intensity (Visual Analogue Scale), and the secondary outcomes were disability, back performance and quality of life. The outcome measurements were assessed at baseline, 6 weeks and 15 weeks.ResultsThere were no statistically significant differences in the primary and secondary outcomes between the two study groups (p-value > 0.05). Although improvement was observed for both groups in pain intensity, disability, quality of life, and back performance.ConclusionsThere was no additional benefit of including an herbal compress in a regimen of Thai massage for the care of low back pain in the elderly.     

Efficacy of a standardized echinacea preparation (Echinilin) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial

BACKGROUND: Recently, echinacea has regained popularity as one of the treatments chosen most commonly by consumers with the expectation that it will reduce the severity and duration of the common cold. However, the results from a limited number of clinical trials for this application have thus far been inconclusive. This incongruity may be the result of investigators utilizing poorly standardized echinacea products, likely devoid of sufficient quantities of active constituents necessary to exert a definitive clinical effect. Therefore, a formulation containing alkamides, cichoric acid, and polysaccharides at concentrations of 0.25, 2.5, and 25 mg/mL, respectively, was prepared from freshly harvested Echinacea purpurea plants (commercially available as Echinilin, Natural Factors Nutritional Products, Inc., Vancouver, BC, Canada). The objective of this study was to test the efficacy of this highly standardized formulation in reducing the severity and duration of symptoms of a naturally acquired common cold. METHODS: In a randomized, double-blind, placebo-controlled trial, 282 subjects aged 18-65 years with a history of two or more colds in the previous year, but otherwise in good health, were recruited. The subjects were randomized to receive either echinacea or placebo. They were instructed to start the echinacea or placebo at the onset of the first symptom related to a cold, consuming 10 doses the first day and four doses per day on subsequent days for 7 days. Severity of symptoms (10-point scale: 0, minimum; 9, maximum) and dosing were recorded daily. A nurse examined the subjects on the mornings of days 3 and 8 of their cold. RESULTS: A total of 128 subjects contracted a common cold (59 echinacea, 69 placebo). The total daily symptom scores were found to be 23.1% lower in the echinacea group than in placebo in those who followed all elements of the study protocol (P<0.01). Throughout the treatment period, the response rate to treatments was greater in the echinacea group. A few adverse event profiles were observed in both groups. CONCLUSIONS: Early intervention with a standardized formulation of echinacea resulted in reduced symptom severity in subjects with naturally acquired upper respiratory tract infection. Further studies with larger patient populations appear to be warranted.     

Medicinal seeds Ziziphus spinosa for insomnia: A randomized,placebo-controlled,cross-over,feasibility clinical trial

ObjectivesTo evaluate the feasibility of implementing a clinical trial protocol of the herbal seeds Ziziphus spinosa (ZS) for people with insomnia.Design and settingA randomized, double-blind, placebo controlled, cross-over feasibility trial in Melbourne, Australia.InterventionsAfter two-week run-in participants were randomized to either ZS (encapsulated granules; 2 g daily) or placebo for four weeks. After four-weeks wash-out, participants swapped to the other treatment for four weeks.Main outcome measuresSleep quality assessed by the Insomnia Severity Index and Pittsburgh Sleep Quality Index (PSQI). Quality of life, mood, functional impairment and sleep parameters were also assessed.ResultsTwelve participants were randomized and completed both periods of cross-over (six in each sequence). Feasibility endpoints were acceptable. Improvements for sleep quality measured on the PSQI were statistically significant during the ZS treatment periods compared to placebo (t = −2.276, df = 10, 95 % CI −3.3 to −0.04, p = 0.046). There was no evidence of any significant carryover effects. However, there were period effects. Other outcomes showed no statistically significant difference between the treatments. Subjective sleep parameters measured on sleep diaries showed improvements after ZS in terms of total sleep time, sleep efficiency and sleep onset latency, but not after placebo. ZS was well tolerated with only minor adverse events.ConclusionsZS is an acceptable and well-tolerated herbal candidate for the treatment of insomnia. The feasibility objectives of this study were achieved and ZS improved both subjective sleep quality and quantity compared to placebo. ZS should be explored in future clinical trials.