Ketotifen in childhood asthma: a double-blind placebo controlled trial.

In a three week double-blind cross-over controlled trial in twenty asthmatic children, ketotifen (HC 20-511, 'Zaditen', Sandoz) showed no significant difference from placebo, although there was a consistent trend in favour of the active drug.     

Homeopathy in HIV infection: a trial report of double-blind placebo controlled study.

OBJECTIVE: This study was aimed to evaluate the immuno-modulator role of homeopathic remedies in Human Immunodeficiency Virus (HIV) infection. METHODOLOGY: A randomised double blind clinical trial was conducted to compare the effect of homeopathic remedies with placebo, on CD4+ve T-lymphocytes in HIV infected individuals, conforming to Centres for Disease Control (CDC) stage II & III. 100 HIV+ve individuals between 18-50 y (71% males) were included in the study. 50 cases conformed to CDC stage II--Asymptomatic HIV infection, and 50 cases to CDC stage III--Persistent Generalised Lymphadenopathy (PGL). Cases were stratified according to their clinical status and CD4+ve lymphocyte counts. The randomisation charts were prepared much before the start of the trial by randomly assigning placebo and verum codes to registration numbers from 1 to 50. A single individualised homeopathic remedy was prescribed in each case and was followed up at intervals of 15 d to one month. A six months study was performed for each registered case. Assessment of progress was made by evaluation of CD+ve lymphocyte counts, which was the prospectively-defined main outcome measure of the study; the results were compared with the base line immune status. RESULTS: In PGL, a statistically significant difference was observed in CD+ve T-lymphocyte counts between pre and post trial levels in verum group (P < 0.01). In the placebo group a similar comparison yielded non-significant results. (P = 0.91). Analysis of change in the pre and post trial counts of CD4+ve cells between groups was also statistically significant (P = 0.04). In asymptomatic HIV infection, differences in absolute CD4+ve lymphocyte counts between pre and post trial levels were not significant. Analysis of changes in pre and post trial CD4 levels of placebo and verum groups for combined strata of asymptomatic and PGL groups was also not significant. CONCLUSION: The study suggests a possible role of homeopathic treatment in HIV infection in symptomatic phase, as evidenced by a statistically significant elevation of base line immune status in persistent generalised lymphadenopathy.     

No more tears: a randomized controlled double-blind trial of Amethocaine gel vs. placebo in the management of procedural pain in neonates

AIM: During a comparative double-blind study, the efficacy of Amethocaine local anaesthetic gel was compared with that of a placebo gel to establish their effect on the reduction of behavioural and physiological responses to pain in neonates. METHOD: Forty infants were included in the trial, 20 being randomly assigned to each group. After topical application of either Amethocaine or the placebo for 30 minutes, cannulation was performed using a 24 gauge cannula. Assessment of pain was made with the aid of four point assessment tool incorporating facial expression, cry and heart rate changes and ease of cannulation. Additional baseline data were obtained including sex, gestation, weight and previous experience of cannulation, and analysed using Statistical Package for Social Sciences (SPSS). RESULTS: Good analgesic effects were demonstrated in the Amethocaine group, as there was a high level of significance (P < 0.01) in the difference in pain scores between the two groups using a Mann-Whitney U-test. There was no correlation between gestation or weight and the degree of pain experienced during painful procedures. No significant relationship was found between cannulation and the degree of pain experienced. CONCLUSION: It can, therefore, be concluded that Amethocaine gel is an effective local anaesthetic in the management of skin puncturing procedural pain in neonates, and that all infants regardless of maturity, weight or previous experiences probably experience a similar degree of pain and therefore warrant effective and appropriate analgesic intervention.     

Tramadol relieves pain and allodynia in polyneuropathy: a randomised, double-blind, controlled trial.

It is generally believed that opioids relieve neuropathic pain less effectively than nociceptive pain and that they have no effect on some of the key characteristics of neuropathic pain such as touch-evoked pain (allodynia). Tramadol is an analgesic drug acting directly on opioid receptors and indirectly on monoaminergic receptor systems. The aim of this trial was to determine whether tramadol relieved painful polyneuropathy and reduced allodynia. The study design was randomised, double-blind, placebo-controlled and cross-over. After baseline observations, 45 patients were assigned to one of the two treatment sequences. The dose of tramadol slow-release tablets was titrated to at least 200 mg/day and at highest 400 mg/day. During the two treatment periods of 4 weeks duration, patients rated pain, paraesthesia and touch-evoked pain by use of 0-10 point numeric rating scales. Mechanical allodynia induced by stimulation with an electronic toothbrush was rated at the end of each treatment period with a similar scale. Thirty-four patients completed the study. Their ratings for pain (median 4 vs. 6, P=0.001), paraesthesia (4 vs. 6, P=0.001) and touch-evoked pain (3 vs. 5, P<0.001) were lower on tramadol than on placebo, as were their ratings of allodynia (0 vs. 4, P=0.012). The number needed to treat to obtain one patient with >/=50% pain relief was 4.3 (95% confidence interval 2.4-20). It is concluded that tramadol appears to relieve both ongoing pain symptoms and the key neuropathic pain feature allodynia in polyneuropathy.     

Plasmapheresis in severe sepsis and septic shock: a prospective,randomised, controlled trial

OBJECTIVE: To determine the therapeutic efficacy and safety of plasmapheresis in the treatment of patients with severe sepsis and septic shock. DESIGN: Prospective, randomised, clinical trial with a planned, midstudy, interim analysis. SETTING: Intensive care unit in a university hospital in Archangels, Russia. PATIENTS: Consecutive patients with severe sepsis or septic shock. INTERVENTIONS: One hundred and six patients were randomised to receive either standard therapy or an add-on treatment with plasmapheresis. MEASUREMENTS AND RESULTS: The primary endpoint was 28-day survival. Septic shock was diagnosed in 57% of the plasmapheresis-treated patients and 54% of the control patients. Mean APACHE III score at entry was 56.4 in the plasmapheresis group and 53.5 in the control group. The 28-day, all-cause mortality rate was 33.3% (18/54) in the plasmapheresis group and 53.8% (28/52) in the control group. This represents a relative risk for fatal outcome in the plasmapheresis group of 0.61, an absolute risk reduction of 20.5% and a number of patients needed to treat of 4.9. Apart from six transient episodes of hypotension and one allergic reaction to fresh frozen plasma, no adverse reactions were attributable to the plasmapheresis treatment in this study. CONCLUSIONS: Plasmapheresis may be an important adjuvant to conventional treatment to reduce mortality in patients with severe sepsis or septic shock. Plasmapheresis is a safe procedure in the treatment of septic patients. A prospective randomised multicentre trial is warranted to confirm our results and to determine which subgroups of septic patients will benefit most from this treatment modality.     

Predicting outcome of TENS in chronic pain: a prospective, randomized, placebo controlled trial

Transcutaneous electrical nerve stimulation (TENS) is an easy to use non-invasive analgesic intervention applied for diverse pain states. However, effects in man are still inconclusive, especially for chronic pain. Therefore, to explore the factors predicting result of TENS treatment in chronic pain we conducted a prospective, randomized, placebo-controlled trial (n = 163), comparing high frequency TENS (n = 81) with sham TENS (n = 82). Patients’ satisfaction (willingness to continue treatment; yes or no) and pain intensity (VAS) were used as outcome measures. The origin of pain and cognitive coping strategies were evaluated as possible predictors for result of TENS treatment. Results: Fifty-eight percent of the patients in the TENS group and 42.7% of the sham-TENS group were satisfied with treatment result (chi square = 3.8, p = 0.05). No differences were found for pain intensity. Patients diagnosed with osteoarthritis and related disorders (especially of the vertebral column) or peripheral neuropathic pain were less satisfied with high frequency TENS (OR = 0.12 (95% CI 0.04–0.43) and 0.06 (95% CI 0.006–0.67), respectively). Injury of bone and soft tissue (especially postsurgical pain disorder) provided the best results. Treatment modality or interactions with treatment modality did not predict intensity of pain as a result of treatment. We conclude, that predicting the effect of high frequency TENS in chronic pain depends on the choice of outcome measure. Predicting patients’ satisfaction with treatment result is related to the origin of pain. Predicting pain intensity reflects mechanisms of pain behavior and perceived control of pain, independent of treatment modality. Pain catastrophizing did not predict TENS treatment outcome.     

Optimal refresher training intervals for AED and CPR skills: a randomised controlled trial

AIM: To determine the optimal refresher training interval for lay volunteer responders in the English National Defibrillator Programme who had previously undertaken a conventional 4-h initial class and a first refresher class at 6 months. METHODS: Subjects were randomised to receive either two additional refresher classes at intervals of 7 and 12 months or one additional refresher class after 12 months. RESULTS: Greater skill loss had occurred when the second refresher class was undertaken at 12 compared with 7 months. Skill retention however, was higher in the former group, ultimately resulting in no significant difference in final skill performance. There was no significant difference in performance between subjects attending two versus three refresher classes. On completion of refresher training all subjects were able to deliver countershocks, time to first shock decreased by 17s in both groups, and the proportion of subjects able to perform most skills increased. The execution of several important interventions remained poor, regardless of the total number of classes attended or the interval between them. These included CPR skills, defibrillation pad placement, and pre-shock safety checks. Refresher classes held more frequently and at shorter intervals increased subjects' self-assessed confidence, possibly indicating greater preparedness to use an AED in a real emergency. CONCLUSIONS: This study shows that the ability to deliver countershocks is maintained whether the second refresher class is held at seven or 12 months after the first. To limit skill deterioration between classes, however, refresher training intervals should not exceed 7 months. The quality of instruction given should be monitored carefully. Learning and teaching strategies require review to improve skill acquisition and maintenance.     

Massage or music for pain relief in labour: A pilot randomised placebo controlled trial

Research on massage therapy for maternal pain and anxiety in labour is currently limited to four small trials. Each used different massage techniques, at different frequencies and durations, and relaxation techniques were included in three trials. Given the need to investigate massage interventions that complement maternal neurophysiological adaptations to labour and birth pain(s), we designed a pilot randomised controlled trial (RCT) to test the effects of a massage programme practised during physiological changes in pain threshold, from late pregnancy to birth, on women's reported pain, measured by a visual analogue scale (VAS) at 90min following birth. To control for the potential bias of the possible effects of support offered within preparation for the intervention group, the study included 3 arms – intervention (massage programme with relaxation techniques), placebo (music with relaxation techniques) and control (usual care). The placebo offered a non‐pharmacological coping strategy, to ensure that use of massage was the only difference between intervention and placebo groups. There was a trend towards slightly lower mean pain scores in the intervention group but these differences were not statistically significant. No differences were found in use of pharmacological analgesia, need for augmentation or mode of delivery. There was a trend towards more positive views of labour preparedness and sense of control in the intervention and placebo groups, compared with the control group. These findings suggest that regular massage with relaxation techniques from late pregnancy to birth is an acceptable coping strategy that merits a large trial with sufficient power to detect differences in reported pain as a primary outcome measure.     

Endotracheal suctioning versus minimally invasive airway suctioning in intubated patients: a prospective randomised controlled trial

STUDY OBJECTIVE: Endotracheal suctioning in intubated patients is routinely applied in most ICUs but may have negative side effects. We hypothesised that on-demand minimally invasive suctioning would have fewer side effects than routine deep endotracheal suctioning, and would be comparable in duration of intubation, length of stay in the ICU, and ICU mortality. DESIGN: Randomised prospective clinical trial. SETTING: In two ICUs at University Hospital Groningen, the Netherlands. PATIENTS: Three hundred and eighty-three patients requiring endotracheal intubation for more than 24 h. INTERVENTIONS: Routine endotracheal suctioning (n=197) using a 49-cm suction catheter was compared with on-demand minimally invasive airway suctioning (n=186) using a suction catheter only 29 cm long. MEASUREMENTS AND RESULTS: No differences were found between the routine endotracheal suctioning group and the minimally invasive airway suctioning group in duration of intubation [median (range) 4 (1-75) versus 5 (1-101) days], ICU-stay [median (range) 8 (1-133) versus 7 (1-221) days], ICU mortality (15% versus 17%), and incidence of pulmonary infections (14% versus 13%). Suction-related adverse events occurred more frequently with RES interventions than with MIAS interventions; decreased saturation: 2.7% versus 2.0% (P=0.010); increased systolic blood pressure 24.5% versus 16.8% (P<0.001); increased pulse pressure rate 1.4% versus 0.9% (P=0.007); blood in mucus 3.3% versus 0.9% (P<0.001). CONCLUSIONS: This study demonstrated that minimally invasive airway suctioning in intubated ICU-patients had fewer side effects than routine deep endotracheal suctioning, without being inferior in terms of duration on intubation, length of stay, and mortality.     

Gabapentin in postherpetic neuralgia: a randomised, double blind, placebo controlled study.

A multicentre double blind, randomised, placebo controlled 7-week study evaluated the efficacy and safety of gabapentin 1800 or 2400 mg/day in treating postherpetic neuralgia. Three hundred and thirty-four men and women aged at least 18 years (mean 73) received gabapentin 1800 or 2400 mg daily or placebo in three divided doses with a forced titration schedule. The primary outcome measure was change in average daily pain diary score (baseline week v final week). Secondary outcomes included mean weekly sleep interference score; Short Form-McGill Pain Questionnaire (SF-MPQ); Clinician and Patient Global Impression of Change (CGIC/PGIC); Short Form-36 Health Survey (SF-36). From week 1, pain scores showed a significantly greater improvement with gabapentin: the final difference v baseline was -34.5% for the 1800 mg dose, -34.4% for the 2400 mg dose compared with -15.7% for the placebo group. The difference vs. placebo was 18.8% for the 1800 mg dose (95% confidence interval 10.9-26.8%; P<0.01) and 18.7% for the 2400 mg dose (10.7-26.7%; P<0.01). Sleep interference diaries showed a similar pattern. There were significant differences in favour of gabapentin for number of patients reporting >50% reduction in their pain intensity, in the CGIC and PGIC, in the sensory and total scores of the SF-MPQ (both doses), in the visual analogue scale of pain of the SF-MPQ (2400 mg only) and in the vitality, bodily pain and mental health domains of the SF-36. Overall gabapentin was well tolerated. The most common adverse events were dizziness and somnolence, particularly during the titration phase. Thus, this study confirms the role of gabapentin as an efficacious and well-tolerated treatment for postherpetic neuralgia.     

Efficacy of low-level laser therapy applied at acupuncture points in knee osteoarthritis: a randomised double-blind comparative trial

Objective

To evaluate the efficacy of low-level laser therapy (LLLT) applied to acupuncture points on the knee joint in combination with exercise and advice in patients with knee osteoarthritis.

Design

Randomised, double-blind, comparative clinical trial.

Participants

Forty-nine patients with knee osteoarthritis were assigned at random into two groups: active laser group (n = 26) and placebo laser group (n = 23).

Intervention

Using a gallium aluminium arsenide laser device, patients received either active or placebo LLLT at five acupuncture points on the affected knee during nine sessions.

Outcome measures

Patients were assessed using a visual analogue scale (VAS) and the Saudi Knee Function Scale (SKFS) at baseline, the fifth treatment session, the last treatment session, 6 weeks post intervention and 6 months post intervention.

Results

VAS scores showed a significant improvement in the active laser group compared with the placebo laser group at 6 weeks post intervention [mean difference −1.3, 95% confidence interval (CI) of the difference −2.4 to −0.3; P = 0.014] and 6 months post intervention (mean difference −1.8, 95% CI of the difference −3.0 to −0.7; P = 0.003) using the independent samples test. SKFS scores also showed a significant improvement in the active laser group compared with the placebo laser group at the last treatment session (median difference −15, 95% CI of the difference −27 to −2; P = 0.035) and 6 months post intervention (median difference −21, 95% CI of the difference −34 to −7; P = 0.006) using the Mann–Whitney U test.

Conclusions

The results demonstrate that short-term application of LLLT to specific acupuncture points in association with exercise and advice is effective in reducing pain and improving quality of life in patients with knee osteoarthritis.     

Prediction of extubation outcome: a randomised, controlled trial with automatic tube compensation vs. pressure support ventilation

Introduction  

Tolerance of a spontaneous breathing trial is an evidence-based strategy to predict successful weaning from mechanical ventilation. Some patients may not tolerate the trial because of the respiratory load imposed by the endotracheal tube, so varying levels of respiratory support are widely used during the trial. Automatic tube compensation (ATC), specifically developed to overcome the imposed work of breathing because of artificial airways, appears ideally suited for the weaning process. We further evaluated the use of ATC in this setting.     

Clinical consequences of alterations in platelet transfusion dose: a prospective, randomized, double-blind trial

BACKGROUND: The dose-response relationship for platelet transfusion has become increasingly important as the use of platelet transfusion has grown. STUDY DESIGN AND METHODS: One hundred fifty-eight prophylactic apheresis platelet transfusions were administered to 46 patients undergoing high-dose therapy followed by hematopoietic progenitor cell transplantation in a prospective, randomized, double-blind, multiple-crossover study. Transfusions were administered in pairs, differing only in platelet content. Each pair consisted of a lower-dose platelet component (LDP) and a higher-dose platelet component (HDP) administered in random order to the same patient. LDPs contained a mean of 3.1 x 10(11) platelets (range, 2.3-3.5 x 10(11)), and HDPs contained a mean of 5.0 x 10(11) platelets (range, 4.5-6.1 x 10(11)). Patients with active bleeding and those who were refractory to platelet transfusions were excluded. RESULTS: The mean posttransfusion platelet count increment with LDP was 17,010 per microL, and that with HDP was 31,057 per microL (p<0.0001). Only 37 percent of LDPs resulted in platelet count increments of at least 20,000 per microL, whereas 81 percent of HDPs resulted in increments above this level (p<0.0001). The mean transfusion-free interval with LDP was 2.16 days, whereas that with HDP was 3.03 days (p<0.01). Administration of LDPs was associated with a 39 to 82 percent increase in the relative risk (per day) of requiring subsequent platelet transfusions (p<0.0001). CONCLUSION: As compared to the administration of HDPs, the administration of LDPs for prophylactic transfusion in hematopoietic progenitor cell transplant patients results in a lower platelet count increment, a lower likelihood of obtaining a posttransfusion platelet increment >20,000 per microL, a shorter transfusion-free interval, and a greater relative risk per day of requiring additional transfusions.     

Positive impact of crisis resource management training on no-flow time and team member verbalisations during simulated cardiopulmonary resuscitation: a randomised controlled trial

Objectives

To evaluate the impact of video-based interactive crisis resource management (CRM) training on no-flow time (NFT) and on proportions of team member verbalisations (TMV) during simulated cardiopulmonary resuscitation (CPR). Further, to investigate the link between team leader verbalisation accuracy and NFT.

Methods

The randomised controlled study was embedded in the obligatory advanced life support (ALS) course for final-year medical students. Students (176; 25.35 ± 1.03 years, 63% female) were alphabetically assigned to 44 four-person teams that were then randomly (computer-generated) assigned to either CRM intervention (n = 26), receiving interactive video-based CRM-training, or to control intervention (n = 18), receiving an additional ALS-training. Primary outcomes were NFT and proportions of TMV, which were subdivided into eight categories: four team leader verbalisations (TLV) with different accuracy levels and four follower verbalisation categories (FV). Measurements were made of all groups administering simulated adult CPR.

Results

NFT rates were significantly lower in the CRM-training group (31.4 ± 6.1% vs. 36.3 ± 6.6%, p = 0.014). Proportions of all TLV categories were higher in the CRM-training group (p < 0.001). Differences in FV were only found for one category (unsolicited information) (p = 0.012). The highest correlation with NFT was found for high accuracy TLV (direct orders) (p = 0.06).

Conclusions

The inclusion of CRM training in undergraduate medical education reduces NFT in simulated CPR and improves TLV proportions during simulated CPR. Further research will test how these results translate into clinical performance and patient outcome.     

The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial

Objective  To determine if statin therapy reduces the incidence of severe sepsis and the levels of inflammatory cytokines in patients with acute bacterial infection. Design  Double-blind placebo controlled randomized clinical trial. Setting  Department of medicine and medical intensive care unit in a tertiary university medical center. Patients and participants  A total of 83 patients with suspected or documented bacterial infection were enrolled. We randomly assigned 42 patients to receive 40 mg of simvastatin orally, followed by 20 mg of simvastatin, and 41 to receive matching placebo. Measurements and results  The study was prematurely terminated due to slow recruitment rate. Here we report the analysis of the secondary outcome: change in cytokines levels at 72 h. Both groups were evenly matched in terms of co-morbidity and severity of illness on admission. Four of the 83 patients enrolled developed severe sepsis, two in each group. No difference was observed in other clinical variables and there were no mortalities. Cytokine levels were randomly assessed in 40 patients (20 in each group). Both TNF-α and IL-6 levels were significantly reduced in the simvastatin group (p = 0.02 and p = 0.02, respectively), while no such difference was observed in the placebo group (p = 0.35 and 0.39, respectively). Conclusions  Statin therapy may be associated with a reduction in the levels of inflammatory cytokines in patients with acute bacterial infections. Large controlled trials will determine if this reduction will translate into a clinical benefit. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.