A randomised clinical trial of the effect of informed consent on the analgesic activity of placebo and naproxen in cancer pain. Does informed consent influence therapeutic outcome? A clinical trial of the hypnotic activity of placebo in patients admitted to hospital. Dynamics and significance of placebo response in primary dysmenorrhea. Double-blind, placebo-controlled trial of famotidine in children with abdominal pain and dyspepsia: global and quantitative assessment. Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study. Patient participation in the patient-provider interaction: the effects of patient question asking on the quality of interaction, satisfaction and compliance. Effect and placebo effect of acupressure (P6) on nausea and vomiting after outpatient gynaecological surgery. The use of analgesics in patients with acute abdominal pain. Randomized controlled trial of Gastrografin in adhesive small bowel obstruction. Effectiveness of a clinical intervention in improving pain control in outpatients with cancer treated by radiation therapy. Inducing placebo respiratory depressant responses in humans via opioid receptors. An investigation of the placebo effect and age-related factors in the report of needle pain from venipuncture in children. The influence of protocol pain and risk on patients' willingness to consent for clinical studies: a randomized trial. Placebo and naloxone can alter post-surgical pain by separate mechanisms. A randomized, placebo-controlled trial of intradiscal electrothermal therapy for the treatment of discogenic low back pain. Effect of intramuscular clebopride on postoperative nausea and vomiting. Determining the effectiveness of a clinical-practice intervention in improving the control of pain in outpatients with cancer. Morphine differentially affects the sensory and affective pain ratings in neurogenic and idiopathic forms of pain. A double-blind, placebo-controlled pilot study examining the effectiveness of intravenous ondansetron in the prevention of postoperative nausea and emesis. Pain and fatigue management: results of a nursing randomized clinical trial. Improving the quality of pain treatment by a tailored pain education programme for cancer patients in chronic pain. Impact of study quality on outcome in placebo-controlled trials of homeopathy. A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. A randomized trial investigating a chiropractic manual placebo: a novel design using standardized forces in the delivery of active and control treatments. Effects of valdecoxib in the treatment of chronic low back pain: results of a randomized, placebo-controlled trial. A randomized, placebo-controlled trial of exercise therapy in patients with acute low back pain. A double blind randomized study of oral clodronate in the treatment of bone metastases from tumors poorly responsive to chemotherapy. Randomization is important in studies with pain outcomes: systematic review of transcutaneous electrical nerve stimulation in acute postoperative pain. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Immediate influence of transcranial electrostimulation on pain and beta-endorphin blood levels: an active placebo-controlled study. The placebo effect of transcutaneous electrical stimulation. The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study. Nonpharmacologic treatment of postoperative nausea. A randomized controlled comparison of electro-acupoint stimulation or ondansetron versus placebo for the prevention of postoperative nausea and vomiting. The efficacy of metoclopramide in the treatment of migraine headache. Acupuncture compared to placebo-acupuncture for postoperative nausea and vomiting prophylaxis: a randomised placebo-controlled patient and observer blind trial. A placebo controlled double blind trial to evaluate the effectiveness of pulsed short wave therapy for osteoarthritic hip and knee pain. Pain reduction using transcranial electrostimulation: a double blind "active placebo" controlled trial. Repeated measurements of non-invasive ambulatory blood pressure: distinction between reproducibility and the proper effect of placebo. Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin. Antiemetic efficacy of ondansetron in laparoscopic cholecystectomy. A randomized, double-blind, placebo-controlled study. Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders. A comparison of behavioral and educational interventions for fibromyalgia. Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes. A randomized trial of exercise therapy in patients with acute low back pain. Efficacy on sickness absence. Two psychological interventions are effective in severely disabled, chronic back pain patients: a randomised controlled trial. Acute appendicitis: influence of early pain relief on the accuracy of clinical and US findings in the decision to operate--a randomized trial. Comparison of ondansetron and placebo for preventing postoperative nausea and emesis in gastrointestinal tract surgery: a multicenter randomized controlled trial. Can just-in-time, evidence-based "reminders" improve pain management among home health care nurses and their patients? The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study. Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. Betamethasone reduces postoperative pain and nausea after ambulatory surgery. The effects of an open design on trial participant recruitment, compliance and retention--a randomized controlled trial comparison with a blinded, placebo-controlled design. A six-month double-blind, placebo-controlled, randomized clinical trial of duloxetine for the treatment of fibromyalgia. A controlled study of amitriptyline in the treatment of chronic pain. Randomized clinical trial of morphine in acute abdominal pain. Placebo-controlled comparison of dolasetron and metoclopramide in preventing postoperative nausea and vomiting in patients undergoing hysterectomy. Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial. The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery. A comparative study of diazepam and acupuncture in patients with osteoarthritis pain: a placebo controlled study. Transcranial magnetic stimulation for pain control. Double-blind study of different frequencies against placebo, and correlation with motor cortex stimulation efficacy. Oral dolasetron mesylate for prevention of postoperative nausea and vomiting: a multicenter, double-blind, placebo-controlled study. The Oral Dolasetron PONV Prevention Study Group. Multimodal analgesia before thoracic surgery does not reduce postoperative pain. A placebo-controlled randomized clinical trial of nortriptyline for chronic low back pain. Evidence-based postoperative pain management in nursing: is a randomized-controlled trial the most appropriate design? A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Assessment of diclofenac or spinal manipulative therapy, or both, in addition to recommended first-line treatment for acute low back pain: a randomised controlled trial. Double-blind placebo-controlled comparison of the analgesic effects of single doses of lornoxicam and aspirin in patients with postoperative dental pain. Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. Effects of IV morphine in central pain: a randomized placebo-controlled study. A double-blind, placebo-controlled, randomized trial to evaluate the role of tetrachlorodecaoxide in the management of chemotherapy-induced oral mucositis. An educational intervention to improve physician reporting of adverse drug reactions: a cluster-randomized controlled trial. Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study. Intensive group training versus cognitive intervention in sub-acute low back pain: short-term results of a single-blind randomized controlled trial. A placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain. Efficacy of ondansetron in prophylaxis of postoperative nausea and vomiting in patients following infratentorial surgery: a placebo-controlled prospective double-blind study. Exposure in vivo versus operant graded activity in chronic low back pain patients: results of a randomized controlled trial. Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease. Acupressure for intrathecal narcotic-induced nausea and vomiting after caesarean section. Acupressure for chemotherapy-induced nausea and vomiting: a randomized clinical trial. A randomized controlled trial of intensive neurophysiology education in chronic low back pain. Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia. Impact of controlled-release oxycodone on efficacy beliefs and coping efforts among osteoarthritis patients with moderate to severe pain. Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. [Clebopride in premedication in ambulatory interventions in general anesthesia]. The symptomatic effect of cisapride in patients with irritable bowel syndrome and constipation. Treatment of anxiety, tension and restlessness states with Kava special extract WS 1490 in general practice: a randomized placebo-controlled double-blind multicenter trial. Feasibility study of Transcutaneous Electrical Nerve Stimulation (TENS) for cancer bone pain. Lacosamide in painful diabetic peripheral neuropathy: a phase 2 double-blind placebo-controlled study. Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II. [Ropivacaine infiltration during breast cancer surgery: postoperative acute and chronic pain effect]. Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design. A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. The antitussive effect of placebo treatment on cough associated with acute upper respiratory infection. The treatment of fibromyalgia with cranial electrotherapy stimulation. A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. The effect of opioids on phantom limb pain and cortical reorganization.
To determine whether informed consent in a therapeutic trial modifies the analgesic effect of naproxen and placebo, we conducted a prospective, randomised, single dose, placebo-controlled trial. Patients were randomly selected to receive or not information concerning the study. All patients included were then given a single dose of naproxen and placebo according to a crossover, double-blind design. Forty-nine patients with mild or moderate cancer pain which did not need narcotic analgesics entered the study. Twenty-five received both treatments without any information and constituted the uninformed group. Twenty-four had a complete information about the trial; six refused to participate. The 18 others constituted the informed-consent group. Visual analogue scales of pain before and 30, 60, 120 and 180 min after the intake of naproxen and placebo were recorded. As an analgesic, naproxen was more effective than placebo in both groups of patients (p = 0.001). For naproxen as well as for placebo, the analgesic effect was better in the informed-consent group compared to the uninformed group (p = 0.012). The difference in therapeutic activity between naproxen and placebo was moderately higher in the uninformed patients (p = 0.08). We concluded that, in contrast with parallel studies, giving information in a crossover, placebo-controlled trial may increase the apparent efficacy of both the tested agent and the placebo, and decrease the perceived difference the two. To examine whether written informed consent might influence the results of clinical trials the effect of placebo when given with or without informed consent to patients suffering from insomnia was studied. The study was a single blind observer blinded trial, and patients were paired according to sex, age, and hospital environment. Randomisation assigned the first patient of each pair to the control group (without informed consent) or the group to give informed consent. Of the 56 patients, 26 refused to give informed consent, and the age and sex distribution of these differed significantly (p less than 0.02) from the 30 pairs of patients ultimately enrolled into the study. In this "biased" sample, the hypnotic activity of placebo was significantly higher in the control group (p less than 0.05). It is concluded that the informed consent procedure biases the results of clinical trials and might affect their general applicability. A total of 55 patients with primary dysmenorrhea who had shown a favorable response to a preliminary treatment cycle with placebo were admitted to a double-blind study on placebo versus antiprostaglandin agents (naproxen and pirprofen). To evaluate the placebo effect and its duration, the treatment was given for 4 successive cycles. Whereas the antiprostaglandin agents were effective in most of the patients (in 80% of the pirprofen group and 85.7% of the naproxen group) and this efficacy was maintained throughout the study, a favorable response to placebo was observed in 84% in the first cycle, 29% in the second, 16% in the third and 10% in the fourth. The incidence of side effects was similar in the placebo and the active treatment groups (35.4% vs. 37.5%). It is postulated that a placebo effect in dysmenorrhea is due to a central analgesic mechanism mediated by endorphin release or possibly to psychological dynamics (mental or conditioning theories). However, this effect loses efficacy with time possibly due to a decreased susceptibility to the opioid action of the central nervous circuits responsible for menstrual pain perception or to deconditioning mechanisms. To determine the benefit of using an H2-receptor antagonist in children with abdominal pain and dyspepsia, 25 such children were enrolled in a double-blind, placebo-controlled trial of famotidine. Global and quantitative pain assessments were done before and after each treatment period. The quantitative assessment was calculated based on the abdominal pain score that was the sum of three components. Based on the global evaluation, there was a clear benefit of famotidine over placebo (68% vs 12%). Using the quantitative assessment, however, the mean improvement of the score using famotidine versus placebo was not statistically significant (3.37+/-3.53 vs 1.66+/-2.7). There was a significant improvement in this score during the first treatment period regardless of medication used (period effect: P = 0.05). A subset of patients with peptic symptoms demonstrated a significant drug effect that outweighed the period effect (drug effect: P = 0.01; period effect: P = 0.02). We conclude that famotidine subjectively improves the symptoms of children with recurrent abdominal pain but not objectively using the derived score. However, famotidine is significantly more effective than placebo among children with peptic symptoms. The use of this simple scoring scale may facilitate selecting those children who will benefit from H2-receptor antagonist therapy. To investigate whether including a placebo arm in a clinical trial of hormone replacement therapy influenced women's stated willingness to participate.
                Quasirandomised, interview based study. Setting: 10 group practices in the Medical Research Council's General Practice Research Framework.
                436 postmenopausal women aged 45-64 who had not had a hysterectomy.
                Stated willingness to enter a trial and reasons for the decisions made.
                Of 218 women told about the trial without a placebo arm, 85 (39%) indicated their willingness to enter compared with 65 (30%) of the 218 women told about the trial with the placebo arm (P=0.06). Part of this difference was due to explicit reluctance to take a placebo. Altruism and personal benefit were the reasons most frequently given for wanting to take part in a trial. The reasons most frequently cited for not wanting to take part were reluctance to restart periods, not wanting to take unknown or unnecessary tablets, or not wanting to interfere with present good health.
                For preventive trials the inclusion of a placebo arm may reduce patients' willingness to participate. The purpose of this study was to investigate the effectiveness, dynamics, and consequences of a health education intervention designed to increase patient question asking during the patient's medical visit. Data were collected at a Baltimore family and community health center which provides outpatient services to a low income, predominantly black and female population. The majority of the study participants were, in addition, elderly and chronically ill. A total of 294 patients and 3 providers took part in the study. The study design included random assignment of patients to experimental and placebo groups with two non-equivalent (non-randomized) control groups. Findings included: (1) The experimental group patients asked more direct questions and fewer indirect questions than did placebo group patients. (2) The experimental group patient-provider interaction was characterized by negative affect, anxiety, and anger, while the placebo group patient-provider interaction was characterized as mutually sympathetic. (3) The experimental group patients were less satisfied with care received in the clinic on the day of their visit than were placebo patients. (4) The experimental group patients demonstrated higher appointment-keeping ratios (an average number of appointments kept divided by an average number of appointments made) during a four-month prospective monitoring period. Acupuncture and acupressure have previously been reported to possess antiemetic effect. We wanted to investigate the "true" and placebo effect of acupressure in prevention of postoperative nausea and vomiting (PONV).
                Sixty women undergoing outpatient minor gynaecological surgery were entered into a double-blind and randomised study. One group received acupressure with bilateral stimulation of P6 (A), a second group received bilateral placebo stimulation (P) and a third group received no acupressure wrist band and served as a reference group (R). PONV was evaluated as number of patients with complete response (no PONV), nausea only or vomiting. In addition, the need for rescue antiemetic medication and nausea after 24 h was registered.
                Complete response was obtained in 11, 11 and 9 patients in groups, A, P and R, respectively. Nine, 7 and 6 patients had nausea before discharge home, and 1, 1 and 8 patients were nauseated (8 vs 1 patient: P < 0.05) 24 h after operation in A, P and R groups, respectively. When compared to placebo acupressure (2 patients vomited and 5 needed rescue), significantly (P < 0.05) fewer needed rescue antiemetic medication after acupressure at P6 (no vomiting or rescue medication). When compared to the observation group (5 vomited and 4 needed rescue antiemetics), significantly fewer vomited after acupressure (P < 0.05)
                In patients undergoing brief gynaecological surgery, placebo effect of acupressure decreased nausea after 24 h but vomiting and need of rescue antiemetics was reduced only by acupressure with the correct P6 point stimulation. Analgesics in patients with acute abdominal pain are often withheld for fear that they may change physical examination findings and thus may be unsafe. We conducted a randomized, prospective, placebo-controlled trial to investigate changes in physical examination following the administration of placebo, 5 mg, or 10 mg of morphine to 49 patients with acute abdominal pain. One patient was withdrawn secondary to inadequate documentation. Of the 48 patients who completed the trial, a statistically significant change in physical examination was noted in both groups receiving analgesics, but not in the placebo group. No adverse events or delays in diagnosis were attributed to the administration of analgesics. We conclude that physical examination does change after the administration of analgesics in patients with acute abdominal pain and that a larger study is needed to evaluate analgesic safety in this subpopulation of emergency department patients. Several previous studies have shown that Gastrografin can be utilized to triage patients with adhesive small bowel obstruction (ASBO) to an operative or a non-operative course. Previous studies assessing the therapeutic effect of Gastrografin have been confounded by post-administration radiology alerting the physician to the treatment group of the patient. Therefore the aim of the present paper was to test the hypothesis that Gastrografin hastens the non-operative resolution of (ASBO).
                Patients, diagnosed with ASBO on clinical and radiological grounds, were randomized to receive Gastrografin or placebo in a double-blinded fashion. Patients did not undergo further radiological investigation. If the patient required subsequent radiological intervention or surgical intervention they were excluded from the study. End-points were passage of time to resolution of ASBO (flatus and bowel motion), length of hospital stay and complications.
                Forty-five patients with ASBO were randomized to receive either Gastrografin or placebo. Two patients were excluded due to protocol violations. Four patients in each group required surgery. Eighteen of the remaining patients received Gastrografin and 17 received placebo. Patients who received Gastrografin had complete resolution of their ASBO significantly earlier than placebo patients (12 vs 21 h, P = 0.009) and this translated into a median of a 1-day saving in time in hospital (3 vs 4 days, P = 0.03).
                Gastrografin accelerates resolution of ASBO by a specific therapeutic effect. To determine the effectiveness of a multicomponent clinical intervention to reduce pain in outpatients with cancer.
                Sixty-four patients were randomly assigned to receive either a clinical intervention including an information session, the use of a pain diary, and the possibility to contact a physician to adjust the pain medication, or the usual treatment of pain by the staff radiation oncologist. All patients reported their average and worst pain levels at baseline and 2 and 3 weeks after the start of the intervention.
                The study groups were similar with respect to their baseline characteristics and pain levels at randomization. After 3 weeks, the average and worst pain experienced by patients randomized to the clinical intervention group was significantly inferior to the average pain experienced by patients in the control group (2.9/10 vs. 4.4/10 and 4.2/10 vs. 5.5/10, respectively). Results showed that the experimental group patients decreased their pain levels more than the control group patients did over time.
                An intervention including patient education, a pain diary, and defining a procedure for therapeutic adjustments can be effective to improve pain relief in outpatients with cancer. Several lines of evidence indicate that placebos produce analgesia through the activation of endogenous opioid systems. Recently, we showed that placebos may also produce respiratory depressant responses, a typical side-effect of narcotics, when a subject had a prior experience of respiratory depression in the course of narcotic treatment. In the present study, we report that the placebo respiratory depression can be induced after repeated administrations of the partial opioid agonist buprenorphine. The placebo respiratory depressant effect that resulted from the buprenorphine conditioning was completely blocked by a dose of 10 mg of naloxone, indicating that it was mediated by endogenous opioids. These findings show that placebos act, via the activation of opioid receptors, not only on pain mechanisms but on the respiratory centres as well, thus mimicking a typical side-effect of narcotics. In addition, the experimental procedure we used did not produce any expectation of respiratory depression and, similarly, the subjects did not notice any sign of respiratory discomfort. Thus, the placebo respiratory depression elicited in the present study cannot be explained on the basis of cognitive or motivational mechanisms. Rather, it appears to be a sequence effect due to learning, thus suggesting a conditioning mechanism mediated by endogenous opioids. To examine the potential role for a placebo cream in reducing reported needle pain severity in children, and the impact of age-related factors on pain self-report, a convenience sample of 117 children scheduled for venipuncture were randomly assigned to one of three treatments: (a) placebo cream with the suggestion that it might help reduce needle pain, (b) placebo cream with no indication as to the cream's purpose, and (c) no cream (control group). In allocation to treatment, children were stratified by age group, (3-7, 8-11, 12-17 years). They rated their needle pain severity (both predicted and reported) using the Faces Pain Scale, and rated their anxiety about the procedure using the Children's Anxiety and Pain Scale. Children in the cream groups were also asked whether they thought the cream had helped. Using video-tapes, an independent observer, blind to the placebo manipulation, rated each child's reaction to the needle. For the two groups receiving cream, 83% of those children told it might help stated that they believed it did, as compared with only 33% of children who received the cream but were told nothing of its purpose. These beliefs, however, were not reflected in self-report ratings of pain which showed no statistically significant treatment effect. Similarly, children who gave higher preprocedural anxiety ratings were no more likely to report less pain as a result of receiving the cream. There was, however, a treatment effect on the observer's ratings: children receiving cream plus suggestion were assigned significantly lower ratings of pain-related behaviour than those children who received the cream alone. While venipuncture was associated with only mild levels of pain, younger children, irrespective of treatment group, did report more pain than older children. Hierarchical regression analysis indicated that 60% of the variance in self-reported pain severity scores could be accounted for by how much the child thought the needle would hurt, how anxious the child was about receiving the needle, gender (higher pain ratings associated with girls), and estimated body surface area (higher pain ratings associated with smaller bodies). We conclude that the efficacy of placebo treatments for needle pain in children may depend on the suggestion of a possible benefit rather than upon treatment application per se. We tested the hypothesis that the risk or discomfort associated with a clinical trial influence patients' decisions to participate. Simultaneously, we evaluated factors likely to influence patients' decisions such as understanding of the risk and discomfort associated with the study, patient age, educational level, and psychological status. With IRB approval, participants, who believed they were being asked to participate in a real trial, were presented one of three sham protocols: no risk or pain (Control, n = 48), pain but no risk (Pain, n = 51), or risk but no pain (Risk, n = 51). Patients were debriefed at the end of the interview. Our major outcome measures were (a) understanding risk or pain associated with the proposed studies, (b) the extent to which patients felt pressured to participate, and (c) willingness to participate. Whereas understanding was similar in all groups (Control, 68%; Pain, 67%; and Risk, 72%), willingness to participate differed significantly (Control, 64%; Pain, 35%; Risk, 26%; P < 0.001). Patients who understood the level of risk or pain associated with the protocols were twice as likely to participate than those who did not (49% versus 24%; P = 0.003). Nine percent agreed to participate in the risky or painful protocols without understanding the risks involved. Patients who felt pressured did not agree to participate. Thus, the consent process protected patients, although for unexpected reasons. Understanding was poor, but patients who did not understand the risks or pain involved or who felt pressured rarely consented. Consequently, relatively few patients unknowingly agreed to participate in risky or painful studies. The discovery of an endogenous opioid-mediated analgesic system has led to the search for its physiological roles and how it might be activated in natural conditions. Environmental and surgical stress and certain forms of transcutaneous electrical stimulation or acupuncture appear to activate this system. Several studies also suggest that this opioid system mediates placebo analgesia. Placebo reduces post-surgical pain in comparison with no treatment, and this analgesia is apparently reversed by the opioid antagonist, naloxone. However, these studies did not indicate whether naloxone and placebo exert their effects by common or by separate mechanisms. By administering hidden infusions of naloxone (in subjects unaware that the medication was being given) separate from the administration of a placebo, we were able to assess the effects of these two treatments independently. We report here evidence that placebo analgesia can occur after blockade of opioid mechanisms by naloxone and that naloxone can produce hyperalgesia independent of the placebo effect. The combined action of these effects is sufficient to explain the reversal of placebo analgesia by naloxone. Intradiscal electrothermal therapy (IDET) is a treatment for discogenic low back pain the efficacy of which has not been rigorously tested.
                To compare the efficacy of IDET with that of a placebo treatment.
                Randomized, placebo-controlled, prospective trial.
                Patients were recruited by referral and the media. No inducements were provided to any patient in order to have them participate. Of 1,360 individuals who were prepared to submit to randomization, 260 were found potentially eligible after clinical examination and 64 became eligible after discography. All had discogenic low back pain lasting longer than 6 months, with no comorbidity. Thirty-seven were allocated to IDET and 27 to sham treatment. Both groups were satisfactorily matched for demographic and clinical features.
                IDET was performed using a standard protocol, in which the posterior annulus of the painful disc was heated to 90 C. Sham therapy consisted of introducing a needle onto the disc and exposing the patient to the same visual and auditory environment as for a real procedure. Thirty-two (85%) of the patients randomized to the IDET group and 24 (89%) of those assigned to the sham group complied fully with the protocol of the study, and complete follow-up data are available for all of these patients.
                The principal outcome measures were pain and disability, assessed using a visual analog scale for pain, the Short Form (SF)-36, and the Oswestry disability scale.
                Patients in both groups exhibited improvements, but mean improvements in pain, disability and depression were significantly greater in the group treated with IDET. More patients deteriorated when subjected to sham treatment, whereas a greater proportion showed improvements in pain when treated with IDET. The number needed to treat, to achieve 75% relief of pain, was five. Whereas approximately 40% of the patients achieved greater than 50% relief of their pain, approximately 50% of the patients experienced no appreciable benefit.
                Nonspecific factors associated with the procedure account for a proportion of the apparent efficacy of IDET, but its efficacy cannot be attributed wholly to a placebo effect. The results of this trial cannot be generalized to patients who do not fit the strict inclusion criteria of this study, but IDET appears to provide worthwhile relief in a small proportion of strictly defined patients undergoing this treatment for intractable low back pain. The antiemetic effect of clebopride, a new derivative of the orthopramide group, was compared with that of placebo in 298 women undergoing elective surgery. A group of 150 patients received premedication of 1 mg/kg of meperidine, administered intramuscularly (IM), and a group of 148 patients received premedication of 10 mg of diazepam IM. All patients received 0.5 mg of atropine IM. Anesthesia was induced with thiopental and maintained with halogenated N2O/O2. In a double-blind procedure, clebopride (2 mg) or placebo was injected IM at the end of anesthesia and whenever a patient had a second episode of vomiting. Clebopride appeared to be better than placebo in the prevention of nausea (P less than or equal to 0.05) and vomiting (P less than or equal to 0.001) during the 12-hour observation period. The frequency of side effects was virtually the same in patients given clebopride and patients given placebo. To determine the effectiveness of a clinical-practice intervention in improving the control of pain in outpatients with cancer.
                Between July 5 and September 30, 1995, a randomized, controlled trial of 510 cancer outpatients and 13 oncologists was conducted at 23 clinics in Indiana. All the patients completed assessments of their pain, their pain regimens, and the degrees of relief received; they were surveyed again by mail four weeks after their clinic visits. The intervention group's clinical charts contained a summary of the completed pain scales; the oncologists who treated these patients were instructed to review the summary sheet prior to an evaluation. This summary was not available for the oncologists treating the patients in the control group. Each patient's pain management index (PMI) was calculated: the patient's pain medication level was rated on a scale of 0 to 3; the patients's pain level was rated on a scale of 0 to 3 and then subtracted from the first rating. A negative PMI was interpreted as representing insufficient treatment. Data were analyzed with several statistical tests.
                In all, only 320 patients who reported cancer-related pain were used in the analysis: 160 to 260 in the control group and 160 of 250 in the intervention group. The groups were similar with respect to demographics, cancer sites, and performance status. A significant difference (p = .0162) in the physicians' prescription patterns was found. In the control group, prescriptions for 86% of the patients did not change, with no decrease in analgesic prescriptions; for 14% of the patients analgesic prescriptions increased. In the intervention group, analgesic prescriptions changed for 25% of the patients, decreasing for 5% and increasing for 20%. A decrease in the incidence of pain described as more than life's usual aches and pains was found for the intervention group (p = .05). No significant difference was found between the groups for the patients undertreated for pain, as measured by PMIs.
                Although analgesic regimens were altered significantly when the physicians understood more about the patient's pain, cancer pain management remains a complex problem. Future studies should focus on the long-term systematic incorporation of simple pain-assessment tools into daily outpatient oncology practices as well as on innovative ways to address other aspects of managing cancer pain. In a double-blind, placebo controlled crossover study, the effect of morphine on the affective and sensory pain ratings in different forms of chronic pain was investigated. Six patients suffering from central neurogenic pain, 8 from peripheral neurogenic pain and 6 from idiopathic pain participated in the study. Morphine (0.3 mg/kg bodyweight) and placebo (saline) were administered intravenously. Both the affective and sensory dimensions of pain sensation were assessed by means of the 101-point rating scale. From our results it appeared that morphine reduced the affective but not the sensory dimension of pain sensation in both groups of neurogenic pain patients. In the idiopathic pain group, neither the affective nor the sensory dimension of pain sensation were affected. The observed differences in opioid responsiveness were neither the result of differences in opioid consumption nor of differences in baseline pain levels. To compare the efficacy and safety profiles of ondansetron and a placebo when infused immediately prior to anesthesia induction for the prevention of postoperative nausea and emesis (vomiting or retching).
                Randomized, double-blind, placebo-controlled, parallel, multicenter pilot study.
                Three U.S. ambulatory surgical facilities.
                One hundred eighty ASA physical status I and II women scheduled to undergo ambulatory gynecologic surgical procedures while receiving general endotracheal anesthesia.
                Ondansetron 8 mg or a placebo (equivalent volume) was given intravenously (IV) prior to anesthesia induction to prevent postoperative nausea and vomiting.
                For the first 24 hours following emergency from anesthesia, patients were monitored in the postanesthesia care unit by a research observer and at home via telephone contact and diary cards. More patients in the ondansetron group (62%) than in the placebo group (40%) were emesis-free over the 24-hour study period (p = 0.005). Ondansetron also was more efficacious than the placebo over the 24-hour study period when a surgery duration of more than 45 minutes was considered in the analyses. For all patients, regardless of surgery duration, there was a low degree of nausea during the course of the study. In all instances, the degree of nausea was slightly lower for ondansetron-treated patients than for placebo-treated patients; however, in no instances were the differences statistically significant. Ondansetron and placebo had similar safety profiles as established by laboratory test results, vital sign monitoring, and adverse event reporting.
                Ondansetron, infused IV before anesthesia induction, appears to be safe and effective when used in the prevention of postoperative nausea and emesis. Through a randomized clinical trial, to compare patients undergoing an initial course of chemotherapy who report pain and fatigue at baseline and who are receiving conventional care alone with those receiving conventional care plus a nursing intervention on outcomes reported at 20 weeks.
                Chemotherapy clinics of two comprehensive and two community cancer centers.
                Interviews were conducted at baseline and 10 and 20 weeks. An 18-week, 10-contact nursing intervention utilizing problem-solving approaches to symptom management and improving physical functioning and emotional health was implemented.
                The sample consisted of 53 patients in the experimental arm and 60 in the control arm who reported pain and fatigue at baseline.
                Pain and fatigue, numbers of other symptoms, and physical role impact and social-functioning subscales from the Medical Outcomes Study 36 Short Form.
                Patients who received the intervention reported a significant reduction in the number of symptoms experienced and improved physical and social functioning. Fewer patients in the experimental arm reported both pain and fatigue at 20 weeks.
                Behavioral interventions targeted to patients with pain and fatigue can reduce symptom burden, improve the quality of the daily life of patients, and demonstrate the "value-added" role of nursing care for patients undergoing chemotherapy.
                These data support the "value-added" role of nursing interventions for symptom management and improved quality of life during the course of cancer treatment. Educational interventions, aiming to increase patients' knowledge and attitude regarding pain, can affect pain treatment. The purpose of this study was to evaluate the effects of a Pain Education Programme (PEP), on adequacy of pain treatment, and to describe characteristics predicting change in adequacy. The PEP consists of a multi-method approach in which patients are educated about the basic principles regarding pain, instructed how to report pain in a pain diary, how to communicate about pain, and how to contact healthcare providers. The effects of the PEP were evaluated taking into consideration the lack of well-established outcome measures to evaluate adequacy of pain treatment, the lack of long-term follow-up, and the influence of missing data.A prospective, randomized study was utilized in which 313 chronic cancer patients were followed-up until 8 weeks postdischarge. Adequacy of pain treatment was evaluated by means of the Amsterdam Pain Management Index (APMI), consisting of an integrated score of patients' Present Pain Intensity, Average Pain Intensity, and Worst Pain Intensity, corrected for patients' Tolerable Present Pain, with the analgesics used by the patient. At pretest, 60% of the patients in the hospital were treated inadequately for their pain. Postdischarge, the control group patients were significantly more inadequately treated at 2 weeks after discharge (56% vs 41%), at 4 weeks after discharge (62% vs 42%) and at 8 weeks after discharge (57% vs 51%) than the intervention group patients. While the level of inadequacy in the control groups remained relatively stable at all assessment points, a slight increase in the percentage of patients being treated inadequately was found in the intervention group patients over time. A beneficial effect of the PEP was found for patients both with and without district nursing. Variables predicting an improvement in adequacy of pain treatment consisted of the PEP, the APMI score at baseline, patients' level of physical functioning, patients' level of social functioning, the extent of adherence to pain medication, patients' pain knowledge, and the amount of analgesics used. These findings suggest that quality of pain treatment in cancer patients with chronic pain can be enhanced by educating patients about pain and improving active participation in their own pain treatment. The benefit from the PEP, however, decreases slightly over time, pointing at a need for ongoing education.
                Copyright 2001 European Federation of Chapters of the International Association for the Study of Pain. We investigated the influence of indicators of methodological quality on study outcome in a set of 89 placebo-controlled clinical trials of homoeopathy in three different ways: (1) The results of studies meeting single criteria (explicit statement of random allocation, allocation concealment, double-blinding, completeness of follow-up) of methodological quality were compared with those of studies not meeting the criteria in univariate and multivariate analyses; (2) The results of studies scoring above and below predefined scores in two quality assessment scales were compared; (3) Primary studies were consecutively entered into a cumulative meta-analysis according to the summary scores derived from the quality assessment scales. All analyses were performed using meta-regression methods. Studies that were explicitly randomized and were double-blind as well as studies scoring above the cut-points yielded significantly less positive results than studies not meeting the criteria. In the cumulative meta-analyses, there was a trend for increasing effect sizes when more studies with lower-quality scores were added. However, there was no linear relationship between quality scores and study outcome. We conclude that in the study set investigated, there was clear evidence that studies with better methodological quality tended to yield less positive results. Because summarizing disparate study features into a single score is problematic, meta-regression methods simultaneously investigating the influence of single study features seem the best method for investigating the impact of study quality on outcome. To evaluate the efficacy and safety of pregabalin for symptomatic relief of pain associated with fibromyalgia (FM) and for management of FM.
                This multicenter, double-blind, placebo-controlled trial randomly assigned 748 patients with FM to receive placebo or pregabalin 300, 450, or 600 mg/day (dosed twice daily) for 13 weeks. The primary outcome variable for study objective 1, symptomatic relief of pain associated with FM, was comparison of endpoint mean pain scores between each pregabalin group and placebo. The outcome variable for study objective 2, management of FM, included endpoint mean pain scores, Patient Global Impression of Change (PGIC), and Fibromyalgia Impact Questionnaire (FIQ)-Total Score. Secondary outcomes included assessments of sleep, fatigue, and mood disturbance.
                Patients in all pregabalin groups showed statistically significant improvement in endpoint mean pain score and in PGIC response compared with placebo. Improvements in FIQ-Total Score for the pregabalin groups were numerically but not significantly greater than those for the placebo group. Compared with placebo, all pregabalin treatment groups showed statistically significant improvement in assessments of sleep and in patients' impressions of their global improvement. Dizziness and somnolence were the most frequently reported adverse events.
                Pregabalin at 300, 450, and 600 mg/day was efficacious and safe for treatment of pain associated with FM. Pregabalin monotherapy provides clinically meaningful benefit to patients with FM. To evaluate the proposed manual placebo in terms of success in blinding patients to treatment group assignment and outcomes between the treatment groups.
                Randomized controlled trial.
                A chiropractic college research clinic in the midwestern United States.
                One hundred and eleven (111) individuals aged 18 years and over with subacute or chronic lowback pain.
                The active treatment consisted of flexion-distraction chiropractic manipulation and trigger point therapy and the control treatment of sham manipulation and effleurage; both groups received eight treatments over a 3-week period. The application of prescribed ranges of biomechanical forces for each treatment was standardized using specialized computerized equipment. "Nontreatment" aspects of the clinical encounter were to be standardized across groups. A primary clinician blinded to treatment assignment provided interpersonal interactions and treating clinicians delivered treatments with a minimum of interaction.
                The accuracy of the patient's perception of group assignment at visit 4 and the mean change in the Pain Disability Index (PDI) over the treatment period were the primary outcome variables.
                Patients in the control group were more likely to perceive their treatment assignment accurately than those in the active group (78% versus 54%, respectively). Patients in both treatment groups improved on the PDI and the Roland-Morris Questionnaire; there were no significant differences in improvement between the groups. Age, gender, prior chiropractic experience and expectation of treatment at baseline had no effect on outcomes.
                Patients in the control group were not successfully blinded; however, patients' perceptions of treatment group assignment did not significantly affect outcomes. The clinically significant improvement in both groups, independent of patient or clinician expectations, suggests the presence of therapeutic factors common to both groups, other than biomechanical force. Further studies examining other aspects of the clinical encounter, considered separately from biomechanical force, are warranted before arbitrarily designating any intervention as a "placebo." Valdecoxib, a cyclooxygenase (COX)-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and primary dysmenorrhea. Therapeutic doses of COX-2 specific inhibitors are as effective as nonspecific nonsteroidal anti-inflammatory drugs in reducing inflammatory pain while sparing the gastrointestinal and platelet toxicity associated with nonspecific COX-1 inhibition.
                The aim of this study was to assess the analgesic efficacy and tolerability of valdecoxib 40 mg/d compared with placebo in the treatment of chronic low back pain.
                This 4-week, prospective, randomized, double-blind placebo-controlled, parallel-group study was conducted at 37 centers across the United States and 5 centers in Canada. Patients aged > or =18 years with chronic low back pain in flare were enrolled. Patients were randomized to receive valdecoxib 40-mg/d or placebo tablets, once daily for 4 weeks. Patients rated low back pain intensity on a visual analog scale and completed the Roland-Morris Disability Questionnaire and the modified Brief Pain Inventory-Short Form (mBPI-SF) at each visit.
                Two hundred ninety-three patients were enrolled. The valdecoxib group comprised 148 patients (81 women, 67 men; mean [SD] age, 48.6 [13.3] years; mean [SD] body weight, 86.6 [20.9] kg), and the placebo group included 145 patients (85 women, 60 men; mean [SD] age, 48.7 [12.6] years; mean [SD] body weight, 85.6 [19.9] kg). Of the enrolled patients, 249 completed the study: 134 patients (91%) who received valdecoxib and 115 patients (79%) who received placebo. No statistically significant differences in patient baseline characteristics were noted between treatment groups, except in response to 1 mBPI-SF question; patients in the valdecoxib group reported significantly greater interference in relations with other people due to pain than did those in the placebo group (P = 0.048). Changes from baseline in low back pain intensity were significantly greater in valdecoxib-treated patients at each assessment (all, P < 0.001 vs placebo). Pain scores on the mBPI-SF indicated significantly greater pain relief with valdecoxib at each assessment (all, P < or = 0.014 vs placebo). Improvements in mean Roland-Morris Disability Questionnaire score with valdecoxib were significantly greater than with placebo at each assessment (all, P < or = 0.003). Although the overall incidence of adverse events (AEs) was significantly higher among patients receiving valdecoxib than those receiving placebo (35.1% vs 24.1%, respectively; P = 0.042), no significant differences were found between groups for the incidence of any individual AE. Most AEs (89% [77/87 total events]) were mild or moderate in severity.
                In this study of patients with chronic low back pain, valdecoxib 40 mg/d provided rapid relief (within 1 week) and consistent relief (over 4 weeks). In addition, significant improvement in function and decreased disability were found with valdecoxib compared with placebo. To assess the efficacy of exercise therapy for acute low back pain, a randomized, placebo-controlled trial was performed in 40 Dutch general practices. Patients received either exercise instruction with advice for daily life by a physiotherapist; placebo ultrasound therapy by a physiotherapist; or usual care by the general practitioner. All patients received analgesic agents and information on low back pain before randomization. Four hundred seventy-three patients were included. No differences in number of recurrences, functional health status, or medical care usage could be found among the three groups. In the exercise group, duration of recurrences was shorter and patients were less tired during the first 3 months than in the usual care group, but no differences were found between the exercise and placebo groups. It was concluded that exercise therapy for patients with acute low back pain has no advantage over usual care from the general practitioner. Bisphosphonates are used in oncology as a means of decreasing complications due to bone metastases, in association with anticancer treatment, especially in patients with breast cancer, prostate cancer and myeloma. Little is known about the effects of bisphosphonates on bone metastases from other tumors and in particular from tumors for which no effective treatment is available. We conducted a randomized, double-blind placebo-controlled trial of oral clodronate in patients with bone metastases from tumors poorly responsive to chemotherapy, with the aims of evaluating the effects of this drug on symptoms control and bone metastases evolution. Sixty-six patients with poorly responsive tumors such as non-small cell lung cancer (NSCLC), bladder cancer, gastrointestinal cancers, kidney cancer, melanoma and metastatic carcinoma of unknown origin entered the study. Patients were randomized to receive either clodronate 1,600 mg/day for one year or identical placebo-containing tablets. Various parameters such as Karnofsky performance status, pain score (measured by a visual-analogue scale) and analgesic requirement were recorded at monthly intervals. Of the 66 patients enrolled, 9 were observed for one month or less; 7 were followed for two months; only 50 patients were followed for more than 2 months and could be adequately evaluated. At 3 months both clodronate and placebo-treated patients had a decrease in Karnofsky performance status, with the decrease being more evident in the placebo group. Mean pain scores showed an increase of pain in patients receiving placebo and a decrease of pain in patients receiving clodronate, although the difference failed to be statistically significant. Analgesics requirement increased in both groups, but significantly more in patients receiving placebo (p = 0.042), in whom increase in opioid requirements was particularly evident. Toxicity was low, with occasional gastroenteric discomfort in both groups. The main problem of this study was the difficulty in recruiting an adequate number of patients and following them for a sufficient period of time: general conditions rapidly deteriorated in many patients, and approximately 25% of the 66 enrolled were not considered evaluable; few patients survived for the length of the study, one year. This might partly account for the lack of significance of some of the parameters under study. With these limits, oral clodronate demonstrated some efficacy in symptom control and in reducing the need for analgesics. We set out to examine the evidence for the importance of randomization of transcutaneous electrical nerve stimulation (TENS) in acute postoperative pain. Controlled studies were sought; randomization and analgesic and adverse effect outcomes were summarized. Forty-six reports were identified by searching strategies. Seventeen reports with 786 patients could be regarded unequivocally as randomized controlled trials (RCT) in acute postoperative pain. No meta-analysis was possible. In 15 of 17 RCT, we judged there to be no benefit of TENS compared with placebo. Of the 29 excluded trials, 19 had pain outcomes but were not RCT; in 17 of these 19 TENS studies, the authors concluded that TENS had a positive analgesic effect. No adverse effects were reported. Non-randomized studies overestimated treatment effects. Homoeopathy is widely used, but specific effects of homoeopathic remedies seem implausible. Bias in the conduct and reporting of trials is a possible explanation for positive findings of trials of both homoeopathy and conventional medicine. We analysed trials of homoeopathy and conventional medicine and estimated treatment effects in trials least likely to be affected by bias.
                Placebo-controlled trials of homoeopathy were identified by a comprehensive literature search, which covered 19 electronic databases, reference lists of relevant papers, and contacts with experts. Trials in conventional medicine matched to homoeopathy trials for disorder and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate and outcomes coded so that odds ratios below 1 indicated benefit. Trials described as double-blind, with adequate randomisation, were assumed to be of higher methodological quality. Bias effects were examined in funnel plots and meta-regression models.
                110 homoeopathy trials and 110 matched conventional-medicine trials were analysed. The median study size was 65 participants (range ten to 1573). 21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65-1.19) for homoeopathy (eight trials) and 0.58 (0.39-0.85) for conventional medicine (six trials).
                Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects. Stimulation of the antinociceptive system by noninvasive electrical current from electrodes placed on the head is a renewed method of pain relief.
                We conducted a randomized, double-blind, placebo-controlled study on 20 chronic back pain patients. They were treated with either transcranial electrostimulation (TCES) or an active placebo device. Pain level and serum beta-endorphin levels were measured before and after treatment.
                beta-Endorphin level increased in seven of the ten patients from the treatment group and did not change in eight of ten patients from control group (P = 0.057 between groups). Pain level decreased in eight treated patients and seven control patients (significant decrease for each group, no significant difference between groups).
                Transcranial electrostimulation is a nonpharmacologic method of pain relief accompanied or mediated by beta-endorphin release. The comparable degree of the initial clinical response emphasizes the powerful placebo effect on reported pain not mediated by endorphin release. This preliminary study shows that noninvasive electrical stimulation is a safe treatment with a positive effect on beta-endorphin blood levels. The placebo effect of transcutaneous electrical stimulation was studied in 93 patients in a double-blind cross-over trial using a genuine stimulator and a placebo machine. Placebo analgesic effect occurred in 32% of trials, as compared with 48% for actual stimulation. The placebo effect of the transcutaneous electrical stimulator is similar to the placebo effect that is noted in other double-blind studies in which medications are used. The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks.
                Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli.
                A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo.
                The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures. Nausea is the most common postoperative complication of anesthesia. Appropriately applied acupressure offers a safe and cost-effective nursing approach to the prevention of this problem. This study tested the effect of acupressure on the incidence of postoperative nausea in same-day surgery patients.
                Ninety outpatient surgery patients were randomly assigned to one of three groups. The treatment group (n = 30) received bilateral elastic bands designed to exert pressure on the appropriate location on the distal aspect of the wrist during the perioperative period. The placebo group (n = 30) had elastic bands incapable of acupressure placed on their wrists. The control group (n = 30) received routine nursing and medical interventions for nausea and vomiting. Antiemetics were prescribed by the anesthesiologist and administered to patients in all three groups if nausea persisted and/or emesis occurred. The incidences of nausea or vomiting were tabulated separately for operating room, PACU phase I, and PACU phase II, and compared using Fisher's Exact Test.
                The incidence of nausea and vomiting did not differ overall in the OR or PACU phase I. However, in PACU phase II the incidence was 10% in the treatment group, 20% in the placebo group, and 50% in the control group (overall, P = .0001). Treatment wrist bands reduced the incidence of nausea and vomiting as compared with the control group (P = .0001), as did the placebo wrist bands (P = .0033). The numerical trend suggests that the incidence is reduced by half. The incidence of nausea can be significantly reduced by the use of placebo and suggests that further reduction can be obtained by using acupressure. In this study we evaluated the efficacy of electro-acupoint stimulation, ondansetron versus placebo for the prevention of postoperative nausea and vomiting (PONV). Patients undergoing major breast surgery under general anesthesia were randomized into active electro-acupoint stimulation (A), ondansetron 4 mg IV (O), or sham control (placement of electrodes without electro-acupoint stimulation; placebo [P]). The anesthetic regimen was standardized. The incidence of nausea, vomiting, rescue antiemetic use, pain, and patient satisfaction with management of PONV were assessed at 0, 30, 60, 90, 120 min, and at 24 h. The complete response (no nausea, vomiting, or use of rescue antiemetic) was significantly more frequent in the active treatment groups compared with placebo both at 2 h (A/O/P = 77%/64%/42%, respectively; P = 0.01) and 24 h postoperatively (A/O/P = 73%/52%/38%, respectively; P = 0.006). The need for rescue antiemetic was less in the treatment groups (A/O/P = 19%/28%/54%; P = 0.04). Specifically, the incidence and severity of nausea were significantly less in the A group compared with the other groups, and in the O group compared with the P group (A/O/P = 19%/40%/79%, respectively). The A group experienced less pain in the postanesthesia care unit, compared with the O and P groups. Patients in the treatment groups were more satisfied with their management of PONV compared with placebo. When used for the prevention of PONV, electro-acupoint stimulation or ondansetron was more effective than placebo with greater degree of patient satisfaction, but electro-acupoint stimulation seems to be more effective in controlling nausea, compared with ondansetron. Stimulation at P6 also has analgesic effects. By evaluating the efficacy of metoclopramide alone and in combination with ibuprofen versus placebos, this study was designed to both evaluate the efficacy of metoclopramide and elucidate its mechanism of action in the treatment of migraine headache.
                The study was conducted over a two-year period and was a randomized, double-blind, placebo-controlled study.
                An urban teaching hospital.
                Patients enrolled were at least 18 years old and had recurring headaches with one or more of the following characteristics: unilateral, preceded by neurologic symptoms, significant nausea and vomiting, or mood changes and photophobia.
                Ten milligrams of metoclopramide or an equal volume of IV normal saline was given and 600 mg of ibuprofen or identical-appearing placebo was given orally at time 0. Patients rated their pain and nausea at time 0, 30 minutes, and 60 minutes using visual-analog scales.
                The differences in pain and nausea scores for the metoclopramide + placebos group versus the other three groups were tested using exact nonparametric (Mann-Whitney) statistical procedures. The metoclopramide + placebos group had significantly better relief of pain compared with the placebos + ibuprofen and placebos + placebos groups. The metoclopramide + placebos group had significantly better relief of nausea than the ibuprofen + placebos group; nausea scores for the placebos + placebos group could not be analyzed due to excessive variance from the other groups at baseline. The differences between the metoclopramide + placebos group and the metoclopramide + ibuprofen group were not statistically significant with regard to either pain or nausea.
                Metoclopramide is efficacious in the treatment of both the pain and nausea of migraine headache. This is a direct action that is not dependent on the concomitant administration of another agent. This randomised, placebo-controlled, patient and observer blinded trial was conducted to determine whether acupuncture at the acupuncture point P6 is effective in preventing postoperative nausea and vomiting (PONV) compared to placebo acupuncture. Female patients (n = 220) scheduled for gynaecological or breast surgery were randomly assigned to two groups receiving either acupuncture (n = 109) or placebo acupuncture (n = 111). Each group was stratified for type of surgery and included two subgroups receiving intervention either before or after induction of anaesthesia. The incidence of PONV and/or antiemetic rescue medication within 24 h after surgery was the main outcome measure which showed no statistically significant difference between groups (43.7% acupuncture, 50.9% placebo, p = 0.27). The differences were more pronounced for patients having gynaecological surgery (48.9% acupuncture, 67.6% placebo, p = 0.07) than for those having breast surgery (38.7% acupuncture, 40.3% placebo, p = 0.86). The secondary outcome, vomiting, was significantly reduced by acupuncture from 39.6% to 24.8% (p = 0.03). Subgroup analysis showed no difference between applications of acupuncture before compared to after induction of anaesthesia. The aim of this study was to investigate the effectiveness of pulsed short wave (PSW) in the relief of pain in osteoarthritis of the hip and knee. Ninety-two patients, mean age 63 years, (34 men and 58 women) were randomly allocated to one of three groups: (1) Active PSW, using the dosage found in a pilot study to be non-significantly most effective, (2) Placebo PSW, (3) No treatment control group. Nine sessions of treatment were provided over a 3-week period, each application lasting for 15 min. The machine was modified by the manufacturers so that the therapist was able to administer the treatment and carry out assessments without being aware of the treatment allocation. Outcome measures included sensory and affective pain diary reports averaged over days and weeks, self-reported benefit and the General Health Questionnaire. Analysis of variance with repeated measures over time was used to find out if the active treatment had a specific effect, incremental to the placebo effect. There were no significant differences between the active and placebo groups over time. According to the pain diary reports, both active and placebo groups tended to improve slightly during treatment, but worsened after its withdrawal. Patients who were given the placebo application tended to report more benefit than those who had the active treatment, although this did not quite reach statistical significance (P < 0.06). Patients who were not on a waiting list for surgery did significantly better over time than those who were (P < 0.03). There were no significant differences between the groups over time for the other outcome variables. Any treatment effect on this patient population appears to have been largely placebo-mediated. No evidence was found therefore for the specific effectiveness of PSW for treatment of osteoarthritic hip or knee pain. To examine the efficacy of transcranial electrical stimulation a non-invasive method of reducing pain.
                A randomized, double-blind, placebo-controlled trial.
                A total of 119 patients with chronic pain.
                Patients were treated with either transcranial electrical stimulation or an active placebo device. Short- and long-term follow-ups were evaluated for treatment efficacy with 4 ordinal scale variables: visual analogue scale (pain level), SLEEP (how often does pain disturb sleep), FREQ (frequency of pain) and MED (frequency of use of medications to relieve pain).
                Pain level decreased significantly in the transcranial electrical stimulation-treated group compared with the active-placebo group 3 weeks after the end of treatment (p = 0.0017 between groups). Other parameters did not demonstrate significant differences. Three months after the end of treatment this effect was maintained and other treatment parameters showed similar improvements.
                Transcranial electrical stimulation is an effective non-invasive method for pain relief. The active placebo device has a powerful effect on reported pain, which diminishes in the long-term. The involvement of possible neural mechanisms is discussed. OBJECTIVE: To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements. METHOD: Thirty-four essential hypertensive outpatients were randomly allocated after a 4-week preselection period in two groups in a cross-over study design. One group received placebo for 4 weeks while the other formed the control group (reproducibility), then the treatments were exchanged for another 4 weeks. Clinic and ambulatory blood pressures were measured at three different times for each patient, namely bnefore the random allocation to groups and at the end of each period, using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring. RESULTS: Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures (by 3.4+/-13 and 3.6+/-8 mmHg, respectively), but not in 24 h, daytime and night-time blood pressures. Circadian hourly blood pressure and heart rate curves were virtually superimposable. In the 13 placebo responder patients selected on the basis of clinic blood pressure, placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures, mainly during the day period (by 5.2+/-6.2 and 4.89+/-7.8 mmHg, respectively). This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference. To characterize at baseline the placebo responder patients, comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group. CONCLUSION: The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo (placebo responders); the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis. This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs. This was a multicenter, double-blind (DB), placebo-controlled, randomized discontinuation trial to evaluate the efficacy of pregabalin monotherapy for durability of effect on fibromyalgia (FM) pain. The trial included a 6-week open-label (OL) pregabalin-treatment period followed by 26-week DB treatment with placebo or pregabalin. Adults with FM and 40-mm score on 100-mm pain visual analog scale (VAS) were eligible. During OL weeks 1-3, patients received escalating dosages of pregabalin to determine their optimal dosages. During OL weeks 4-6, patients received their optimal fixed dosages (300, 450, 600mg/d). To be randomized, patients must have had 50% decrease in pain VAS and a self-rating of "much" or "very much" improved on Patient Global Impression of Change (PGIC) at the end of OL. Double-blind treatment was with placebo or the patient's optimal fixed dosage of pregabalin. Primary outcome was time to loss of therapeutic response (LTR), defined as <30% reduction in pain (from OL baseline) or worsening of FM. A total of 1051 patients entered OL; 287 were randomized to placebo, 279 to pregabalin. Time to LTR was longer for pregabalin versus placebo (P<.0001). Kaplan-Meier estimates of time-to-event showed half the placebo group had LTR by Day 19; half the pregabalin group still had not lost response by trial end. At the end of DB, 174 (61%) placebo patients met LTR criteria versus 90 (32%) pregabalin patients. Pregabalin was well tolerated, though 178 (17%) discontinued during OL for treatment-related adverse events (AE), and more pregabalin than placebo patients discontinued for AEs during DB. In those who respond, pregabalin demonstrated durability of effect for relieving FM pain. to assess the effectiveness of ondansetron in preventing postoperative nausea and vomiting after elective laparoscopic cholecystectomy, and the effect of this anesthetic on hospital stay.
                this randomized, double-blind, placebo-controlled study was done in the General Surgery Service of the Getafe University Hospital. Patients who were scheduled for laparoscopic cholecystectomy to treat uncomplicated cholelithiasis, and who had an ASA status of I-II, were recruited. Before surgery the patients received either ondansetron 4 mg or placebo intravenously. This study was approved by the local ethics committee.
                56 patients were included, 29 in the ondansetron group and 27 in the placebo group. In the latter, 4 patients were later excluded because of conversion to open surgery. Postoperative nausea and emetic episodes were experienced by 7% of the patients in the ondansetron group and 47% in the placebo group (p = 0.0007). Oral intake started 7 h after surgery in the ondansetron group and 11 h after surgery in the placebo group (p = 0.04), with a mean difference of 4 h. Hospital stay was 30 h and 48 h respectively (p = 0.01), with a mean difference of 18 h.
                ondansetron given prior to surgery at a dose of 4 mg prevents postoperative nausea and vomiting after laparoscopic cholecystectomy, and reduces hospital stay. There are no prospective, multicenter, double-blind, placebo-controlled, randomized pharmacologic trials for the treatment of pain-predominant functional gastrointestinal disorders in children. The aim of this study was to evaluate the efficacy of amitriptyline in children with pain-predominant functional gastrointestinal disorders.
                In this multicenter placebo-controlled trial, children with irritable bowel syndrome, functional abdominal pain, or functional dyspepsia were randomized to 4 weeks of placebo or amitriptyline (10 mg/d, weight <35 kg; 20 mg/d, weight >35 kg). Assessment of gastrointestinal symptoms, psychological traits, and daily activities occurred before and after intervention. Pain was assessed daily with self-report diaries. The primary outcome was overall response to treatment (child's assessment of pain relief and sense of improvement). Secondary outcomes were effect on psychosocial traits and daily functioning.
                Ninety children were enrolled, and 83 completed the study (placebo, 40 children [30 girls]; drug, 43 children [35 girls]). A total of 63% of patients reported feeling better and 5% feeling worse in the amitriptyline arm compared with 57.5% feeling better and 2.5% feeling worse in the placebo arm (P = .63). Pain relief was excellent in 7% and good in 38% of children receiving placebo compared with excellent in 15% and good in 35% of children treated with amitriptyline (P = .85). Logistic regression analysis of those reporting excellent or good response versus fair, poor, or failed response showed no difference between amitriptyline and placebo (P = .83). Children who had more severe pain at baseline in both groups (P = .0065) had worse outcome. Amitriptyline reduced anxiety scores (P < .0001).
                Both amitriptyline and placebo were associated with excellent therapeutic response. There was no significant difference between amitriptyline and placebo after 4 weeks of treatment. Patients with mild to moderate intensity of pain responded better to treatment. To compare a comprehensive behavioral intervention with an education/control condition in the treatment of patients with fibromyalgia (FM), and to explore the role of mediators of clinical improvement in both groups.
                The effects of the behavioral and education/control interventions were evaluated across a 10 week treatment period and at 6 month followup on measures of pain, depression, disability, pain behaviors, and intervening variables. The behavioral intervention focused on the development of diverse pain coping skills, while the education/control condition presented information on a range of health related topic without emphasizing skill acquisition.
                Although improvement across time was found in depression, self-reported pain behaviors, observed pain behaviors, and myalgia scores, no differences in these criteria were found between the behavioral and education/control conditions. Multiple regression analyses revealed that changes in helplessness and passive coping were associated with improvement in a number of clinical outcomes.
                The findings illustrate the value of psychoeducational interventions in decreasing the psychological and behavioral effect of FM, and the value of reducing dysfunctional coping and helplessness in future intervention research. To assess, against placebo, the pain-relieving effects of high-rate repetitive transcranial magnetic stimulation (rTMS) on neuropathic pain.
                Double-blind, randomized, cross-over study of high-rate rTMS against placebo in 28 patients. The effect of a change in coil orientation (posteroanterior vs lateromedial) on different subtypes of neuropathic pain was further tested in a subset of 16 patients. Pain relief was evaluated daily during 1 week.
                High-frequency, posteroanterior rTMS decreased pain scores significantly more than placebo. Posteroanterior rTMS also outmatched placebo in a score combining subjective (pain relief, quality of life) and objective (rescue drug intake) criteria of treatment benefit. Changing the orientation of the coil from posteroanterior to lateromedial did not yield any significant pain relief. The analgesic effects of posteroanterior rTMS lasted for approximately 1 week. The pain-relieving effects were observed exclusively on global scores reflecting the most distressing type of pain in each patient. Conversely, rTMS did not modify specifically any of the pain subscores that were separately tested (ongoing, paroxysmal, stimulus-evoked, or disesthesic pain).
                Posteroanterior repetitive transcranial magnetic stimulation (rTMS) was more effective than both placebo and lateromedial rTMS. When obtained, pain relief was not specific of any particular submodality, but rather reduced the global pain sensation whatever its type. This is in accord with recent models of motor cortex neurostimulation, postulating that its analgesic effects may derive in part from modulation of the affective appraisal of pain, rather than a decrease of its sensory components. A randomized, placebo-controlled trial in which patients received either usual care by a general practitioner (information and analgesics), or placebo physiotherapy given by a physiotherapist, or exercise therapy given by a physiotherapist.
                To assess the efficacy of exercise therapy on sickness absence from work in patients with acute low back pain.
                Exercise therapy during the nonchronic phase of back pain is considered to reduce sickness absence, but this opinion is controversial.
                Patients with acute nonspecific low back pain and a paid job were included for analysis. Sickness absence (number of days) was checked monthly during the 1-year follow-up period and compliance was also assessed.
                From 40 general practices 363 patients who were gainfully employed were included. In the exercise therapy group the percentage of patients with sickness absence was higher and the duration of absence was longer than in the placebo and usual care groups, but these differences were not significant. Indications of more absence in the exercise therapy group appeared to be based largely on a greater number of patients with absences during the first 3 months. Patients in the exercise group who had not reported sick at entry had more sickness absences during the follow-up year than patients in the usual care and placebo group. Good compliance did not affect the results.
                Exercise therapy for patients with acute low back pain does not reduce sickness absence. Many pain patients appreciate biofeedback interventions because of the integration of psychological and physiological aspects. Therefore we wanted to investigate in a sample of chronic back pain patients whether biofeedback ingredients lead to improved outcome of psychological interventions.
                One hundred and twenty-eight chronic back pain patients were randomly assigned to cognitive-behavioural therapy (CBT), cognitive-behavioural therapy including biofeedback tools (CBT-B) or waitlist control (WLC). The sample was recruited from a highly disabled group including many patients with low education status and former back surgeries. Measures on pain, physical functioning, emotional functioning, coping strategies and health care utilisation were taken at pretreatment, posttreatment and 6 months of follow-up.
                The results indicated significant improvements on most outcome measures for CBT-B and CBT in comparison to WLC. CBT-B and CBT were equally effective (e.g. ITT effect sizes for pain intensity: CBT-B, 0.66 (95% CI 0.39-0.95); CBT, 0.60 (95% CI 0.33-0.87)).
                In conclusion, biofeedback ingredients did not lead to improved outcome of a psychological intervention. Cognitive-behavioural treatment as a "package" of respondent, operant and cognitive interventions was effective for ameliorating pain-related symptoms for chronic back pain patients treated in an outpatient setting. The high treatment acceptability associated with biofeedback ingredients can also be achieved with pure psychological interventions. To determine the influence of early pain relief on the diagnostic performance of ultrasonography (US) and on the appropriateness of the surgical decision.
                A prospective randomized, double-blind placebo-controlled trial with morphine was conducted. A visual analog scale was used to evaluate pain in 340 patients aged 16 years or older. US was performed with a standardized protocol. Diagnosis was confirmed at histologic analysis or, in the patients released without surgery, at follow-up.
                One hundred seventy-five patients were injected with morphine, and 165 were injected with the placebo. Pain relief was stronger in the morphine group. In the morphine group, US had lower (71.1%) sensitivity (difference, -9.5%; 95% CI, -18.5%, -0.5%) and higher (65.2%) specificity (difference, 11.4%; 95% CI, 1.0%, 21.8%). This group had also a higher positive predictive value (64.6%) and a lower negative predictive value (71.4%), but the differences between this group and the placebo group were not statistically significant. Among female patients, the decision to operate was appropriate more often in the morphine group (75.8%), but the difference between this group and the placebo group was not statistically significant (5.1%; 95% CI, -7.4%, 17.6%). In male patients and overall, opiate analgesia did not influence the appropriateness of the decision. The appropriateness to discharge patients without surgery was 100% in all groups.
                Morphine does not improve US-based diagnosis of appendicitis. Nausea and emesis are undesirable events that may cause discomfort and suffering in the postoperative period. This study was carried out to evaluate the efficacy and safety of ondansetron for preventing postoperative nausea and vomiting in patients undergoing gastrointestinal tract surgery.
                Using a randomized double-blind study design, 408 surgical patients (163 male and 245 female) receiving general endotracheal anesthesia were studied at five medical centers in Bangkok. Ondansetron (4 mg) or placebo was administered prior to induction of anesthesia. Episodes of nausea and vomiting, adverse events and laboratory tests (complete blood count and liver function test) were evaluated during 24 hours after study drug administration.
                The incidence of postoperative nausea and vomiting in the placebo group (42.7 and 35.2%) were significantly higher than the ondansetron group (23.9 and 15.4%). However, no significant differences occurred in the incidence of adverse events or changes in laboratory tests in the ondansetron group compared to the placebo group.
                Ondansetron 4 mg given intravenously before surgery is safe and effective for preventing postoperative nausea and emesis following gastrointestinal tract surgery. The purpose of this randomized, controlled, home care intervention was to test the effectiveness of two nurse-targeted, e-mail-based interventions to increase home care nurses' adherence to pain assessment and management guidelines, and to improve patient outcomes. Nurses from a large urban non-profit home care organization were assigned to usual care or one of two interventions upon identification of an eligible cancer patient with pain. The basic intervention consisted of a patient-specific, one-time e-mail reminder highlighting six pain-specific clinical recommendations. The augmented intervention supplemented the initial e-mail reminder with provider prompts, patient education material, and clinical nurse specialist outreach. Over 300 nurses were randomized and outcomes of 673 of their patients were reviewed. Data collection involved clinical record abstraction of nurse care practices and patient interviews completed approximately 45 days after start of care. The intervention had limited effect on nurse-documented care practices but patient outcomes were positively influenced. Patients in the augmented group improved significantly over the control group in ratings of pain intensity at its worst, whereas patients in the basic group had better ratings of pain intensity on average. Other outcomes measures were also positively influenced but did not reach statistical significance. Our findings suggest that although reminders have some role in improving cancer pain management, a more intensive approach is needed for a generalized nursing workforce with limited recent exposure to state-of-the-art pain management practices. Forty-three patients with peripheral neuropathic pain, exclusively pain reduced by spinal cord stimulation (SCS), were switched into a painful state after SCS inactivation. This mode was used to assess the pain-relieving effect of carbamazepine (CMZ) and opioids in a double-blinded, placebo-controlled trial. In Phase 1, the patients were randomly allocated to receive either CMZ (600 mg/d) or placebo during an SCS-free period of 8 days. In Phase 2, after a CMZ elimination interval of 7 days, 38 patients received either sustained-release morphine (90 mg/d) or placebo for 8 days. In cases of intolerable pain, the patients were authorized to reactivate their SCS. The pain intensity was rated on a numeric analog scale. In 38 patients who completed Phase 1, significant delay in pain increase was observed in the CMZ group as compared with placebo (P = 0.038). In Phase 2, the trend observed with morphine was insignificant (P = 0.41). Two CMZ patients and one morphine patient showed complete pain relief and preferred to continue the medication. Thirty-five patients returned to SCS. We conclude that CMZ is effective in peripheral neuropathic pain. Morphine obviously requires larger individually titrated dosages than those used in this study for results to be adequately interpreted. To investigate the effects of systemic administration of lidocaine on different components of neuropathic central pains by quantitative sensory testing.
                The efficacy of systemic lidocaine (5 mg/kg IV over 30 minutes) was evaluated in a double-blind, placebo-controlled, and cross-over fashion, on both spontaneous ongoing pain and evoked pains (allodynia and hyperalgesia) in 16 patients with chronic poststroke (n = 6) or spinal cord injury (n = 10) related pain.
                Lidocaine was significantly superior to the placebo (saline) in reducing the intensity of spontaneous ongoing pain for up to 45 minutes after the injection: 10 of 16 patients (62.5%) receiving lidocaine showed a significant reduction in spontaneous pain, whereas only six patients showed this after the placebo. Lidocaine also significantly reduced the intensity of brush-induced allodynia and mechanical hyperalgesia, but was no better than the placebo against thermal allodynia and hyperalgesia. In general, the side effects were moderate and consisted mainly of lightheadedness (44%).
                Systemic lidocaine can induce a significant and selective reduction of several components of pain caused by CNS injuries. The observed preferential antihyperalgesic and antiallodynic effects of this drug suggest a selective central action on the mechanisms underlying these evoked pains. Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo-controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression. The aims of this study were to evaluate the effects of a single-dose glucocorticoid on the incidence and severity of pain and nausea and vomiting (PONV) after ambulatory surgery. Seventy-eight ASA physical status I-III patients scheduled for hemorrhoidectomy or hallux valgus correction were studied using a randomized, double-blind, placebo-controlled protocol. One group received 12 mg of betamethasone i.m. 30 min before the start of surgery (Group B), whereas the placebo group (Group P) received saline. General anesthesia was induced with propofol and fentanyl and maintained with isoflurane in both groups. Pain (measured using a visual analog scale, verbal score, and analgesic requirements), PONV, and other side effects were evaluated postoperatively. Patients in Group B experienced significantly less postoperative pain, less PONV, and better patient satisfaction during the first 24 h after surgery. In conclusion, a single dose of betamethasone (12 mg) seemed to produce analgesic and antiemetic effects after day-case surgery. Implications: In a placebo-controlled study, the use of corticosteroid prophylaxis (betamethasone) produced a significant reduction in both postoperative pain and nausea in outpatients who received the corticosteroid injection before ambulatory foot or hemorrhoid operations. In randomized trials there may be no overriding reason whether or not to have a placebo control.
                We assessed the effects of an open trial design (no placebo and people know what tablets they are given) compared with a blinded, placebo-controlled design on recruitment, compliance and retention within a randomized trial of secondary osteoporotic fracture prevention.
                We undertook a randomized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture, recruited in a UK teaching hospital. Randomization was 2:1 in favour of the blinded, placebo-controlled trial design.
                From 180 eligible participants randomized to receive information based on the open trial design, 134 (74.4%) consented to take part, compared with 233 (65.1%) of 358 people randomized to the blinded, placebo-controlled design (difference 9.4%, 95% confidence interval 1.3-17.4%). Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded, placebo-controlled design. There was no significant difference in tablet compliance. Open trial participants were more likely to remain in the trial for one year (difference 13.9%, 95% confidence interval 3.1-24.6%), mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group (difference 23.6%, 95% confidence interval 11.9-35.2%). The odds ratio for reporting an adverse event in the open trial compared to the blinded, placebo-controlled design was 0.64 (95% confidence interval 0.28-1.49), and for reporting a fracture was 0.81 (0.36-1.85).
                We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power, but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial. Assess the efficacy of duloxetine 60/120 mg (N = 162) once daily compared with placebo (N = 168) in the treatment of patients with fibromyalgia, during six months of treatment.
                This was a phase-III, randomized, double-blind, placebo-controlled, parallel-group study assessing the efficacy and safety of duloxetine.
                There were no significant differences between treatment groups on the co-primary efficacy outcome measures, change in the Brief Pain Inventory (BPI) average pain severity from baseline to endpoint (P = 0.053) and the Patient's Global Impressions of Improvement (PGI-I) at endpoint (P = 0.073). Duloxetine-treated patients improved significantly more than placebo-treated patients on the Fibromyalgia Impact Questionnaire pain score, BPI least pain score and average interference score, Clinical Global Impressions of Severity scale, area under the curve of pain relief, Multidimensional Fatigue Inventory mental fatigue dimension, Beck Depression Inventory-II total score, and 36-item Short Form Health Survey mental component summary and mental health score. Nausea was the most common treatment-emergent adverse event in the duloxetine group. Overall discontinuation rates were similar between groups.
                Although duloxetine 60/120 mg/day failed to demonstrate significant improvement over placebo on the co-primary outcome measures, in this supportive study, duloxetine demonstrated significant improvement compared with placebo on numerous secondary measures. This paper reports a study in which a double-blind controlled cross-over study of amitriptyline vs. placebo was carried out in a group of patients referred to a multidisciplinary pain clinic for the management of chronic intractable pain for which no substantial organic cause could be demonstrated. Of 52 patients entering the 12-week trial, 20 withdrew before completion. No differences were found in terms of global improvement on either agent. Subjective reports indicated a greater reduction in pain at 2 and 4 weeks on amitriptyline, but no difference at 6 weeks. None of the baseline measures was predictive of response. Administration of analgesia to patients with acute abdominal pain is controversial. We test the hypothesis that morphine given to emergency department (ED) patients with acute abdominal pain will reduce discomfort and improve clinically important diagnostic accuracy.
                Pain was measured with a standard 0- to 100-mm visual analog scale. ED patients with acute abdominal pain were randomized in a double-blind fashion to 0.1 mg/kg intravenous morphine or placebo. The primary endpoint was the difference between the 2 study arms in clinically important diagnostic accuracy. Clinically important diagnostic accuracy was defined a priori by its complement, clinically important diagnostic error, using 2 independent, blinded investigators to identify any discordance between the provisional and final diagnoses that might adversely affect the patient's health status. The provisional diagnosis was provided by an ED attending physician, who examined the patient only once, 15 minutes after administration of the study agent. The final diagnosis was obtained through follow-up at least 6 weeks after the index ED visit.
                We randomized 160 patients, of whom 153 patients were available for analysis, 78 patients in the morphine group and 75 patients in the placebo group. Baseline features were similar in both groups, including initial median visual analog scale scores of 98 mm and 99 mm. The median decrease in visual analog scale score at 15 minutes was 33 mm in the morphine group and 2 mm in the placebo group. There were 11 instances of diagnostic discordance in each group, for a clinically important diagnostic accuracy of 86% (67/78) in the morphine group and 85% (64/75) in the placebo group. The difference in clinically important diagnostic accuracy between the 2 groups was 1% (95% confidence interval [CI] -11% to 12%). Analysis by efficacy and intention to treat yielded similar results. Kappa for interobserver concordance in classification of clinically important diagnostic accuracy was 0.94 (95% CI 0.79 to 1.00). No patients required naloxone.
                Although administration of intravenous morphine to adult ED patients with acute abdominal pain could lead to as much as a 12% difference in diagnostic accuracy, equally favoring opioid or placebo, our data are most consistent with the inference that morphine safely provides analgesia without impairing clinically important diagnostic accuracy. In a randomized, placebo-controlled, double-blind trial, we compared the efficacy of dolasetron and metoclopramide in preventing postoperative nausea and vomiting in women undergoing hysterectomy.
                Patients were allocated randomly to one of three groups: group A (n = 50) received 50 mg dolasetron orally, group B (n = 50) received 20 mg metoclopramide intravenously and placebo orally, group C (n = 50) received placebo orally. If patients complained of retching or vomiting, or if patients demanded an antiemetic, 1.25 mg droperidol was administrated intravenously. To quantify postoperative nausea and vomiting the following score was used: 0 = no nausea, 1 = nausea, 2 = retching, 3 = single vomiting, 4 = multiple vomiting. The Raatz test was used to analyse postoperative nausea and vomiting (PONV) scores.
                Dolasetron reduced the postoperative nausea and vomiting score significantly (P < 0.02 vs. metoclopramide; P < 0.0001 vs. placebo). Metoclopramide also reduced the postoperative nausea and vomiting score (P < 0.02 vs. placebo). Fisher's exact test showed a significant reduction of vomiting in the dolasetron group compared with metoclopramide-treated patients (P < 0.007) and placebo-treated patients (P < 0.000006) and a significantly lower rate of nausea in comparison to the placebo group (P < 0.009). There were no significant differences between the metoclopramide and the placebo groups (in Fisher's exact test). The use of postoperative droperidol per patient was significantly lower in the dolasetron group (P < 0.04 vs. metoclopramide; P < 0.0001 vs. placebo) than in the metoclopramide (P < 0.02 vs. placebo) and in the placebo groups.
                Oral dolasetron is more effective than either metoclopramide given intravenously or placebo for preventing vomiting after hysterectomy. It also was significantly superior to either metoclopramide or placebo concerning the PONV score and the need for droperidol rescue. The purpose is to investigate an additional antiemetic effect to ondansetron with needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture in patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation.
                Eighty patients who were admitted to hospital for high-dose chemotherapy and autologous peripheral blood stem cell transplantation were included into a randomized placebo-controlled single-blind trial. The patients were randomized to receive acupuncture (n = 41) or noninvasive placebo acupuncture (n = 39) at the acupuncture point P6 30 min before first application of high-dose chemotherapy and the day after. All patients received 8 mg ondansetron/day i.v. as basic antiemetic prophylaxis. The main outcome measure was the rate of patients who either had at least one episode of vomiting or required any additional antiemetic drugs on the first 2 days of chemotherapy.
                The main outcome measure showed no significant difference (P = 0.82): 61% failure in the acupuncture group and 64% in the placebo acupuncture group (95% confidence interval of 3% difference: -18.1 and 24.3%). Comparing nausea, episodes of vomiting or retching and number of additionally required antiemetic drugs did not provide any discrepancy with the main result.
                This study suggests that in combination with ondansetron i.v., invasive needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture has no additional effect for the prevention of acute nausea and vomiting in high-dose chemotherapy. Nonpharmacologic techniques may be effective in preventing postoperative nausea and vomiting (PONV). This sham-controlled, double-blinded study was designed to examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation (TAES) in a surgical population at high risk of developing PONV. We studied 221 outpatients undergoing laparoscopic cholecystectomy with a standardized general anesthetic technique in this randomized, multicenter trial. In the TAES group, an active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively. The ReliefBand was applied after completion of electrocautery and remained in place for 9 h after surgery. The incidence of PONV and need for "rescue" medication were evaluated at predetermined time intervals. TAES was associated with a significantly decreased incidence of moderate-to-severe nausea as denoted on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11% for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and Placebo groups, respectively). TAES was also associated with a larger proportion of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for Sham and Placebo groups, respectively; P < 0.05). However, there were no statistically significant differences among the three groups with regard to incidence of vomiting or the need for rescue antiemetic drugs. We conclude that TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting, after laparoscopic cholecystectomy.
                Transcutaneous acupoint electrical stimulation at the P6 acupoint reduced postoperative nausea, but not vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures. Forty-four patients with chronic cervical osteoarthritis took part in this study. Patients were treated with acupuncture, sham-acupuncture, diazepam or placebo-diazepam in randomized order. Pain was rated on visual analogue scales before, during, and after treatment. Two scales were separately used to rate the intensity (sensory component) and the unpleasantness (affective component) of pain. The results analyzed from these trials show that diazepam, placebo-diazepam, acupuncture and sham-acupuncture have a more pronounced effect on the affective than on the sensory component of pain. Acupuncture was significantly more effective than placebo-diazepam (p less than 0.05), but not significantly more effective than diazepam or sham-acupuncture. To assess, using a double-blind procedure, the pain-relieving effects of rTMS against placebo, and their predictive value regarding the efficacy of implanted motor cortex stimulation (MCS).
                Three randomised, double-blinded, 25 min sessions of focal rTMS (1 Hz, 20 Hz and sham) were performed in 12 patients, at 2 weeks intervals. Effects on pain were estimated from daily scores across 5 days before, and 6 days after each session. Analgesic effects were correlated with those of subsequent implanted motor cortex stimulation (MCS).
                Immediately after the stimulating session, pain scores were similarly decreased by all rTMS modalities. Conversely, during the following week, 1 Hz stimulation provided significantly less analgesia than 20 Hz and placebo, and was pro-algesic in some patients. Placebo and 20 Hz rTMS were effective on different patients, and only 20 Hz rTMS predicted the efficacy of subsequent MCS, with no false positives.
                While 1Hz rTMS should not be used with analgesic purposes, high-frequency rTMS may become useful to select candidates for MCS. Placebo effects are powerful and should be controlled for. Immediate results after a single rTMS session are misleading.
                Defining rTMS parameters is a crucial step before proposing rTMS as predictive test of SCM efficacy in clinical practice. To examine the safety and effectiveness of a range of single oral doses of dolasetron mesylate for the prevention of postoperative nausea and vomiting.
                Randomized, double-blind, placebo-controlled trial.
                32 hospitals.
                789 female ASA physical status I, II, and III patients, ages 18 to 60 years, weighing between 45 and 100 kg, scheduled for major gynecologic surgery (including abdominal hysterectomy, gynecologic laparotomy, or vaginal hysterectomy) with general anesthesia.
                25, 50, 100, or 200 mg oral doses of dolasetron mesylate or placebo were administered 1 to 2 hours before induction of anesthesia. Efficacy was assessed for 24 hours postrecovery by measuring complete response (no emetic episodes, no rescue medication), total response (complete response with no nausea), time to first emetic episode or rescue, and patient visual analog scale evaluations of nausea severity and satisfaction with antiemetic therapy.
                Complete response rates for the 50, 100, and 200 mg dose groups were statistically greater than placebo (p < or = 0.018). Likewise, total response rates were statistically greater in the 50, 100, and 200 mg dose groups than in the placebo group (p = 0.012). Percentage of patients with no nausea and patient satisfaction scores were significantly higher for each dolasetron dose group than placebo (p < or = 0.047 and p < or = 0.004, respectively). Efficacy peaked at the 50 mg dose. The incidence of adverse events was similar in the placebo (30.1%) and dolasetron groups (29.4%). Headache was the most frequent treatment-related adverse event, with 2% to 5% incidence across groups. Incidence of adverse events did not increase with increasing dolasetron doses. Dose-related decreases in blood pressure at acute time points were not clinically significant.
                Single oral doses of dolasetron, administered 1 to 2 hours before induction of anesthesia, are safe and effective for preventing postoperative nausea and vomiting in this patient sample. Maximal antiemetic response was seen with the 50 mg oral dolasetron dose. Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain. To assess the efficacy of nortriptyline, a tricyclic antidepressant, as an analgesic in chronic back pain without depression, we conducted a randomized, double-blind, placebo-controlled, 8-week trial in 78 men recruited from primary care and general orthopedic settings, who had chronic low back pain (pain at T-6 or below on a daily basis for 6 months or longer). Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects. The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression (50-150 ng/ml). The main outcome endpoints were pain (Descriptor Differential Scale), disability (Sickness Impact Profile), health-related quality of life (Quality of Well-Being Scale), mood (Beck Depression Inventory, Spielberger State Anxiety Inventory, Hamilton Anxiety/Depression Rating Scales), and physician rated outcome (Clinical Global Impression). Reduction in pain intensity scores was significantly greater for participants randomized to nortriptyline (difference in mean change 1.68, 95%-0.001, CI -3.36, P = 0.050), with a reduction of pain by 22% compared to 9% on placebo. Reduction in disability marginally favored nortriptyline (P = 0.055), but health-related quality of life, mood, and physician ratings of overall outcome did not differ significantly between treatments. Subgroup analyses of study completers supported the intent-to-treat analysis. Also, completers with radicular pain on nortriptyline (n = 5) had significantly (P < 0.05) better analgesia and overall outcome than did those on placebo (n = 6). The results suggest noradrenergic mechanisms are relevant to analgesia in back pain. This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression. There is an increasing drive to make nursing care evidence-based. High quality evidence from systematic reviews relevant to postoperative pain relief exists, yet pain after surgery remains poorly controlled for many patients. This study aimed to assess whether implementing evidence-based pain management improved postoperative pain outcomes. Pain on a 0-10 scale was the primary outcome and analgesic consumption a secondary outcome. A baseline audit was undertaken on four surgical wards to establish whether there was a need for the study. A randomized-controlled trial was then designed to assess the effects of implementing an evidence-based approach to postoperative pain management. The four wards were randomized to receive the intervention or act as a control. Outcomes were assessed 3 months after the intervention on both intervention and control wards. The intervention (implementation of an oral analgesic algorithm derived from systematic reviews) was then implemented on the control wards and outcomes reassessed after 3 months on the control wards. The intervention was designed using an evidence-based approach to effective implementation. Four interactive sessions covered: (1) detailed feedback of baseline data and discussion (utilizing audit and feedback), (2) why systematic reviews, analgesic league tables and choice of drugs to develop an analgesic algorithm (see Figure 1), (3) principles of evidence based health care (EBHC), including critical appraisal and (4) facilitation and change workshop. The findings revealed no significant differences in pain level or drug use between the intervention and control wards. However, the control wards also changed during the control period. Possible explanations for this are discussed. When looking at changes compared with baseline, both intervention and control wards increased their use of algorithm drugs and reduced use of non-algorithm drugs during the study. No effects were found on pain in the intervention wards. Pain ratings at rest since surgery, on movement since surgery and worst pain on movement were significantly reduced compared with baseline in the control wards. Although there are many pressures to utilize a randomized-controlled trial study design in the culture of evidence-based health care, there will be times, especially when implementing complex changes in practice that other types of design should be considered. Recent evidence suggests that fibromyalgia is a disorder characterized by dysfunctional brain activity. Because transcranial direct current stimulation (tDCS) can modulate brain activity noninvasively and can decrease pain in patients with refractory central pain, we hypothesized that tDCS treatment would result in pain relief in patients with fibromyalgia.
                Thirty-two patients were randomized to receive sham stimulation or real tDCS with the anode centered over the primary motor cortex (M1) or the dorsolateral prefrontal cortex (DLPFC) (2 mA for 20 minutes on 5 consecutive days). A blinded evaluator rated the patient's pain, using the visual analog scale for pain, the clinician's global impression, the patient's global assessment, and the number of tender points. Other symptoms of fibromyalgia were evaluated using the Fibromyalgia Impact Questionnaire and the Short Form 36 Health Survey. Safety was assessed with a battery of neuropsychological tests. To assess potential confounders, we measured mood and anxiety changes throughout the trial.
                Anodal tDCS of the primary motor cortex induced significantly greater pain improvement compared with sham stimulation and stimulation of the DLPFC (P < 0.0001). Although this effect decreased after treatment ended, it was still significant after 3 weeks of followup (P = 0.004). A small positive impact on quality of life was observed among patients who received anodal M1 stimulation. This treatment was associated with a few mild adverse events, but the frequency of these events in the active-treatment groups was similar to that in the sham group. Cognitive changes were similar in all 3 treatment groups.
                Our findings provide initial evidence of a beneficial effect of tDCS in fibromyalgia, thus encouraging further trials. We aimed to investigate whether the addition of non-steroidal anti-inflammatory drugs or spinal manipulative therapy, or both, would result in faster recovery for patients with acute low back pain receiving recommended first-line care.
                240 patients with acute low back pain who had seen their general practitioner and had been given advice and paracetamol were randomly allocated to one of four groups in our community-based study: diclofenac 50 mg twice daily and placebo manipulative therapy (n=60); spinal manipulative therapy and placebo drug (n=60); diclofenac 50 mg twice daily and spinal manipulative therapy (n=60); or double placebo (n=60). The primary outcome was days to recovery from pain assessed by survival curves (log-rank test) in an intention-to-treat analysis. This trial was registered with the Australian Clinical Trials Registry, ACTRN012605000036617.
                Neither diclofenac nor spinal manipulative therapy appreciably reduced the number of days until recovery compared with placebo drug or placebo manipulative therapy (diclofenac hazard ratio 1.09, 95% CI 0.84-1.42, p=0.516; spinal manipulative therapy hazard ratio 1.01, 95% CI 0.77-1.31, p=0.955). 237 patients (99%) either recovered or were censored 12 weeks after randomisation. 22 patients had possible adverse reactions including gastrointestinal disturbances, dizziness, and heart palpitations. Half of these patients were in the active diclofenac group, the other half were taking placebo. One patient taking active diclofenac had a suspected hypersensitivity reaction and ceased treatment.
                Patients with acute low back pain receiving recommended first-line care do not recover more quickly with the addition of diclofenac or spinal manipulative therapy. The pain experienced after third molar surgery was used as a model to evaluate the analgesic efficacy of a new non-steroidal anti-inflammatory drug, lornoxicam, in a Phase II study. One hundred and fifty fit, young adults participated in this randomised, single dose, double-blind, parallel group clinical study. Three doses of lornoxicam (2 mg, 4 mg, and 8 mg) were compared with aspirin 650 mg and placebo. Patients suffering from moderate to severe pain following surgery were monitored for up to 8 hours. All indices of efficacy showed similar results, all active treatments being associated with highly significant (P less than 0.0001) reductions in pain during the study period. Lornoxicam 8 mg demonstrated significant analgesic efficacy as compared with placebo. The two lower doses of lornoxicam and aspirin all showed apparent degrees of efficacy intermediate between that of placebo and lornoxicam 8 mg, although the trial proved to have inadequate power to show significant differences between these three treatments. Lornoxicam was very well tolerated at all three doses studied, with no adverse events definitely attributable to its administration. In a randomized double-blind study the efficacy of neurolytic coeliac plexus block (NCPB) was compared with pharmacological therapy in the treatment of pain from pancreatic cancer.
                Twenty-four patients were divided into two groups: 12 patients underwent NCPB (group 1) and 12 were treated with pharmacological therapy (group 2). Immediate and long-term efficacy, mean analgesic consumption, mortality and morbidity were evaluated at follow-up. Statistical analysis was performed with the unpaired t test, Mann-Whitney U test and Fisher's exact test.
                Immediately after the block, patients in group 1 reported significant pain relief compared with those in group 2 (P < 0.05), but long-term results did not differ between the groups. Mean analgesic consumption was lower in group 1. There were no deaths. Complications related to NCPB were transient diarrhoea and hypotension (P not significant between groups). Drug-related adverse effects were constipation (five of 12 patients in group 1 versus 12 of 12 in group 2), nausea and/or vomiting (four of 12 patients in group 1 versus 12 of 12 in group 2) (P < 0.05), one gastric ulcer and one gluteal abscess in group 2.
                NCPB was associated with a reduction in analgesic drug administration and drug-related adverse effects, representing an effective tool in the treatment of pancreatic cancer pain. To investigate the efficacy and tolerability of galantamine, using a slow dose escalation schedule of up to 8 weeks, in 978 patients with mild to moderate AD.
                A 5-month multicenter, placebo-controlled, double-blind trial. Following a 4-week placebo run-in, patients were randomized to one of four treatment arms: placebo or galantamine escalated to final maintenance doses of 8, 16, or 24 mg/day. Outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus), the AD Cooperative Study Activities of Daily Living inventory, and the Neuropsychiatric Inventory. Standard safety evaluations and adverse event monitoring were carried out.
                After 5 months, the galantamine-placebo differences on ADAS-cog were 3.3 points for the 16 mg/day group and 3.6 points for the 24 mg/day group (p < 0.001 versus placebo, both doses). Compared with placebo, the galantamine 16- and 24-mg/day groups also had a significantly better outcome on CIBIC-plus, activities of daily living, and behavioral symptoms. Treatment discontinuations due to adverse events were low in all galantamine groups (6 to 10%) and comparable with the discontinuation rate in the placebo group (7%). The incidence of adverse events in the galantamine groups, notably gastrointestinal symptoms, was low and most adverse events were mild.
                Galantamine 16 and 24 mg/day significantly benefits the cognitive, functional, and behavioral symptoms of AD as compared with placebo. Slow dose escalation appears to enhance the tolerability of galantamine, minimizing the incidence and severity of adverse events. To evaluate the effectiveness and safety of samarium-153 (153Sm) lexidronam (EDTMP) in a double-blind, placebo-controlled study.
                Patients with painful bone metastases secondary to a variety of primary malignancies were randomized to receive 153Sm-EDTMP 0.5 or 1.0 mCi/kg, or placebo. Treatment was unblinded for patients who did not respond by week 4, with those who had received placebo eligible to receive 1.0 mCi/kg of active drug in an open-label manner. Patient and physician evaluations were used to assess pain relief, as was concurrent change in opioid analgesia.
                One hundred eighteen patients were enrolled onto the study. Patients who received 1.0 mCi/kg of active drug had significant reductions in pain during each of the first 4 weeks in both patient-rated and physician-rated evaluations. Pain relief was observed in 62% to 72% of those who received the 1.O-mCi/kg dose during the first 4 weeks, with marked or complete relief noted in 31% by week 4. Persistence of pain relief was seen through week 16 in 43% of patients who received 1.0 mCi/kg, of active drug. A significant correlation (P = .01) was observed between reductions in opioid analgesic use and pain scores only for those patients who received 1.0 mCi/kg 153Sm-EDTMP. Bone marrow suppression was mild, reversible, and not associated with grade 4 toxicity.
                A single dose of 1.0 mCi/kg of 153Sm-EDTMP provided relief from pain associated with bone metastases. Pain relief was observed within 1 week of administration and persisted until at least week 16 in the majority of patients who responded. To investigate the effects of IV morphine on central pain syndromes through quantitative sensory testing and to assess the long-term benefit of oral morphine.
                After an initial open titration phase aiming to determine the maximal tolerated dosage of IV morphine, the efficacy of morphine infusion (9-30 mg; mean dosage, 16 mg) was assessed in a double-blind, placebo-controlled and crossover fashion in 15 patients with poststroke- (6 patients) or spinal cord injury- (9 patients) related pain. All of the patients subsequently received sustained oral morphine.
                Morphine significantly reduced the intensity of brush-induced allodynia but had no effect on other evoked pains (i.e., static mechanical and thermal allodynia/hyperalgesia). The effects of morphine on ongoing pain were not significantly different from those of the placebo, but 7 patients (46%) responded to morphine. There was a correlation between the effects of morphine on spontaneous pain and the decrease of the responses to suprathreshold thermal stimuli on the nonpainful contralateral side, suggesting that these effects were related to the general antinociceptive activity of the drug. The effects of IV morphine were correlated with those of oral morphine at 1 month, but only 3 patients (20%) were still taking morphine after 1 year.
                IV morphine induces analgesic effects on some components of central neuropathic pain syndromes, but only a minority of patients may benefit from long-term opioid treatment. We conducted a double-blind, placebo-controlled, randomized trial to evaluate the efficacy and safety of tetrachlorodecaoxide (TCDO) in patients with chemotherapy-induced mucositis. Sixty-two patients with World Health Organization grade II-IV oral mucositis were eligible for the study. They were randomized to receive TCDO or placebo, 10 ml, twice daily, swish and swallow, for 7 days. Patients were evaluated for oral pain, dysphagia, and oral intake. Downgrading and total duration of mucositis were documented. Thirty-two were randomized to receive TCDO. Thirty received the placebo. All were evaluable. Both arms were well matched for age, gender, type of underlying neoplasm, and prior history of oral mucositis. Intensity of initial symptoms, degree of mucositis, and time period between delivery of chemotherapy and development of mucositis were also similar. Post-therapy evaluation revealed no significant difference in the mean grade of oral and esophageal pain, or dysphagia between TCDO and placebo. Downgrading or total duration of mucositis did not differ between the two groups. Oral intake improved significantly in patients taking TCDO. Time to subjective improvement in oral pain was significantly shorter with TCDO (3.1 versus 3.6 days). Evaluation on day 3 revealed that 77% of those receiving TCDO were free of oral pain in comparison to 46% receiving placebo (P = 0.05). These results indicate that TCDO may be helpful in palliating some of the symptoms related to oral mucositis. The therapeutic benefit, however, is small and needs to be confirmed in a larger trial. Data on the adverse effects of newly marketed drugs are limited. Voluntary reporting is an important part of postmarketing surveillance but is underused by physicians.
                To evaluate the effectiveness of educational outreach visits for improving adverse drug reaction (ADR) reporting by physicians.
                A cluster-randomized controlled trial covering all National Health System physicians in the north of Portugal, with intervention in March 2004 through July 2004, and 13 to 16 months of follow-up. A total of 1388 physicians were assigned in 4 spatial clusters to the intervention group, and 5063 were assigned in 11 clusters to the control group.
                One-hour educational outreach visits tailored to training needs identified in a previous study.
                Change in total number of reported ADRs and number of serious, high-causality, unexpected, and new-drug-related ADRs, using generalized linear mixed models adjusted for baseline ADR reporting, age, specialty, and work setting.
                At baseline, ADR reporting rates (per 1000 physician-years) did not differ significantly between the intervention groups and the control groups in reporting ADRs overall (7.6 vs 11.3), nor did they differ significantly by category: serious, 4.3 vs 6.0; high-causality, 5.4 vs 7.6; unexpected, 1.6 vs 3.5; and new-drug-related ADRs, 3.7 vs 3.8. (P>.05 for all comparisons). The control group had no significant increase in ADR reports during follow-up. The adjusted increase in ADR reporting rates attributable to intervention was 90.19 for total ADRs (95% confidence interval [CI], 54.51-125.87; relative risk [RR], 10.23; 95% CI, 3.81-27.51), 30.16 for serious ADRs (95% CI, 18.84-41.47; RR, 6.32; 95% CI, 2.09-19.16), 64.90 for high-causality ADRs (95% CI, 38.38-91.42; RR, 8.75; 95% CI, 3.05-25.07), 28.04 for unexpected ADRs (95% CI, 16.25-39.83; RR, 30.21; 95% CI, 4.54-200.84), and 42.17 for new-drug-related ADRs (95% CI, 21.58-62.76; RR, 8.05; 95% CI, 2.10 -30.83). The greatest difference occurred during the first 4 months after intervention, but differences remained statistically significant for 12 months.
                A targeted outreach program may improve high-quality reporting of ADRs among physicians. A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400 mg/day. The study comprised a run-in period of two weeks, two treatment periods of five weeks separated by a three weeks' washout period. The primary efficacy variable was the change in the mean pain intensity score from baseline to the last week of treatment. Other variables included pain relief, health related quality of life (SF-36), interference of sleep by pain, Clinician and Patient Global Impression of Change, and adverse effects. Nine centers randomized a total of 120 patients, 22 of whom withdrew. There was no statistically significant difference between the treatments for the primary outcome efficacy variable. However, gabapentin provided significantly better pain relief (p=0.015) compared with placebo. More patients had at least a 30% pain reduction with gabapentin compared with placebo (p=0.040) and pain interfered significantly less with sleep during gabapentin treatment compared with placebo (p=0.0016). Both the Patient (p=0.023) and Clinician (p=0.037) Global Impression of Change indicated a better response with gabapentin compared with placebo. Gabapentin was well tolerated. The most common adverse effects were dizziness and tiredness. To evaluate the short-term effect of physical exercise and a cognitive intervention in low back pain.
                Randomized controlled trial.
                Ninety-three patients sick-listed for 8-12 weeks for sub-acute low back pain were randomized to an exercise regime (n = 30), a cognitive intervention (n = 34) or a control group (n = 29).
                Primary outcome measures were pain, disability, sick-listing and satisfaction with care. Secondary outcome measures were self-efficacy for pain and for function, fear-avoidance beliefs, emotional distress, generic health status and life satisfaction.
                Eighteen percent of subjects dropped out. Drop-out was most frequent in the exercise group. At 18 weeks after inclusion fear-avoidance beliefs were reduced in both intervention groups. The cognitive group demonstrated significant improvement in disability, self-efficacy for pain, emotional distress, general health and life satisfaction. Patients in the exercise group were significantly more satisfied with the treatment, and patients following the exercise protocol reduced pain significantly. No effect on sick-listing was seen.
                Cognitive intervention improved disability and may be feasible for most patients sick-listed in the sub-acute phase. Physical exercise reduced patients' symptoms, but requires high motivation by patients. Despite positive effects in intervention groups on variables considered as negative prognostic factors for long-term disability and sickness absence, interventions had no effect on sick-listing. In the present study we investigated the effect of the N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine (30 mg/d) on the intensity of chronic phantom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by the patients on a visual analog scale during baseline and both treatment periods. At the same time points, the functional organization of the primary somatosensory cortex (SI) was determined by neuromagnetic source imaging. In comparison to baseline and placebo, the NMDA receptor antagonist had no effect on the intensity of chronic PLP. In none of the periods were significant changes in the functional organization of SI observed. Although the conclusions regarding the clinical effect are limited because of the small sample size, the data indicate that in the studied dosage the NMDA receptor antagonist memantine is ineffective in the treatment of chronic PLP and is also ineffective for the reduction of associated neural plasticity in the primary SI.
                NMDA receptors play a substantial role in central nervous system changes underlying neuropathic pain. In a placebo-controlled double-blinded study we tested the effect of 30 mg memantine on chronic phantom limb pain and pain-associated cortical reorganization. In a prospective double blind placebo-controlled study, 45 patients scheduled for infratentorial surgery were randomly allocated into two groups. Five patients were later excluded from the study because of various reasons. Out of 40 analyzable patients, 20 received IV Ondansetron (4 mg), whereas the other 20 received the matching placebo approximately 1 hour before the skin closure. After conclusion of surgery and tracheal extubation, all patients were monitored in the recovery room for post operative nausea and vomiting (PONV) for 48 hours. The incidence of PONV within the first 24 hours was found to be 50% and 10% in the placebo and ondansetron groups, respectively (p<0.05). After 24 hours, however, both groups were comparable in relation to the incidence of emesis. Rescue antiemetic (RAE) was required in nine (45%) patients in the placebo group and in two (10%) patients in the Ondansetron group (p<0.05). A significantly higher number of patients remained sedated postoperatively in the Ondansetron group than in the placebo group (p<0.05). One patient in the Ondansetron group had protracted diarrhea for 48 hours postoperatively. These results indicate that administration of IV Ondansetron (4 mg) 1 hour before skin closure effectively reduces PONV after infratentorial surgery, and does not have significant adverse effects. Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. It was demonstrated that EXP, despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities, was equally effective as GA in improving functional disability and main complaints, although the group difference almost reached statistical significance favouring EXP. Both treatment conditions did not differ in pain intensity and daily activity levels either. Nor was EXP superior to GA in the subgroup of highly fearful patients. Irrespective of treatment, approximately half the patients reported clinically relevant improvements in main complaints and functional disability, although for the latter outcome the group difference was almost significant favouring EXP. Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed. To assess the efficacy and safety of lansoprazole in treating infants with symptoms attributed to gastroesophageal reflux disease (GERD) that have persisted despite a >or= 1-week course of nonpharmacologic management.
                This multicenter, double-blind, parallel-group study randomized infants with persisting symptoms attributed to GERD to treatment with lansoprazole or placebo for 4 weeks. Symptoms were tracked through daily diaries and weekly visits. Efficacy was defined primarily by a >or= 50% reduction in measures of feeding-related crying and secondarily by changes in other symptoms and global assessments. Safety was assessed based on the occurrence of adverse events (AEs) and clinical/laboratory data.
                Of the 216 infants screened, 162 met the inclusion/exclusion criteria and were randomized. Of those, 44/81 infants (54%) in each group were responders--identical for lansoprazole and placebo. No significant lansoprazole-placebo differences were detected in any secondary measures or analyses of efficacy. During double-blind treatment, 62% of lansoprazole-treated subjects experienced 1 or more treatment-emergent AEs, versus 46% of placebo recipients (P= .058). Serious AEs (SAEs), particularly lower respiratory tract infections, occurred in 12 infants, significantly more frequently in the lansoprazole group compared with the placebo group (10 vs 2; P= .032).
                This study detected no difference in efficacy between lansoprazole and placebo for symptoms attributed to GERD in infants age 1 to 12 months. SAEs, particularly lower respiratory tract infections, occurred more frequently with lansoprazole than with placebo. In this randomized double-blind trial we investigated the effect of acupressure on the incidence of nausea and vomiting after caesarean section under spinal anaesthesia with added intrathecal morphine. Parturients wore either acupressure or placebo wristbands during surgery and postoperatively for at least 10 h. There was no significant difference overall between the two groups in the incidence of intra- or postoperative nausea or vomiting/retching. Demand for antiemetic medication was also similar in the two groups. However, in the sub-group of parturients who gave a previous history of postoperative nausea or vomiting, there was a statistically significant reduction in both postoperative nausea and vomiting/retching in the acupressure group. Further investigations are needed to see whether acupressure may be an effective non-pharmacological, non-invasive treatment for a common problem in this sub-group of patients. To compare differences in the chemotherapy-induced nausea and vomiting (CINV) among three groups of women (acupressure, placebo acupressure, and usual care) undergoing chemo-therapy for breast cancer.
                A multicenter, longitudinal, randomized clinical trial throughout one cycle of chemotherapy.
                Ten community clinical oncology programs associated with the M.D. Anderson Cancer Center and nine independent sites located throughout the United States.
                160 women who were beginning their second or third cycle of chemotherapy for breast cancer treatment and had moderate nausea intensity scores with their previous cycles.
                Subjects were randomized to one of three groups: acupressure to P6 point (active), acupressure to SI3 point (placebo), or usual care only. Subjects in the acupressure group were taught to apply an acupressure wrist device by research assistants who were unaware of the active acupressure point. All subjects completed a daily log for 21 days containing measures of nausea and vomiting and recording methods (including antiemetics and acupressure) used to control these symptoms.
                Acute and delayed nausea and vomiting.
                No significant differences existed in the demographic, disease, or treatment variables among the treatment groups. No significant differences were found in acute nausea or emesis by treatment group. With delayed nausea and vomiting, the acupressure group had a statistically significant reduction in the amount of vomiting and the intensity of nausea over time when compared with the placebo and usual-care groups. No significant differences were found between the placebo and usual-care groups in delayed nausea or vomiting.
                Acupressure at the P6 point is a value-added technique in addition to pharmaceutical management for women undergoing treatment for breast cancer to reduce the amount and intensity of delayed CINV.
                Acupressure is a safe and effective tool for managing delayed CINV and should be offered to women undergoing chemotherapy for breast cancer. Cognitive-behavioral pain management programs typically achieve improvements in pain cognitions, disability, and physical performance. However, it is not known whether the neurophysiology education component of such programs contributes to these outcomes. In chronic low back pain patients, we investigated the effect of neurophysiology education on cognitions, disability, and physical performance.
                This study was a blinded randomized controlled trial. Individual education sessions on neurophysiology of pain (experimental group) and back anatomy and physiology (control group) were conducted by trained physical therapist educators. Cognitions were evaluated using the Survey of Pain Attitudes (revised) (SOPA(R)), and the Pain Catastrophizing Scale (PCS). Behavioral measures included the Roland Morris Disability Questionnaire (RMDQ), and 3 physical performance tasks; (1) straight leg raise (SLR), (2) forward bending range, and (3) an abdominal "drawing-in" task, which provides a measure of voluntary activation of the deep abdominal muscles. Methodological checks evaluated non-specific effects of intervention.
                There was a significant treatment effect on the SOPA(R), PCS, SLR, and forward bending. There was a statistically significant effect on RMDQ; however, the size of this effect was small and probably not clinically meaningful.
                Education about pain neurophysiology changes pain cognitions and physical performance but is insufficient by itself to obtain a change in perceived disability. The results suggest that pain neurophysiology education, but not back school type education, should be included in a wider pain management approach. Non-invasive unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex induces analgesic effects in focal chronic pain syndromes, probably by modifying central pain modulatory systems. Neuroimaging studies have shown bilateral activation of a large number of structures, including some of those involved in pain processing, suggesting that such stimulation may induce generalized analgesic effects. The goal of this study was to assess the effects of unilateral rTMS of the motor cortex on chronic widespread pain in patients with fibromyalgia. Thirty patients with fibromyalgia syndrome (age: 52.6 +/- 7.9) were randomly assigned, in a double-blind fashion, to two groups, one receiving active rTMS (n = 15) and the other sham stimulation (n = 15), applied to the left primary motor cortex in 10 daily sessions. The primary outcome measure was self-reported average pain intensity over the last 24 h, measured at baseline, daily during the stimulation period and then 15, 30 and 60 days after the first stimulation. Other outcome measures included: sensory and affective pain scores for the McGill pain Questionnaire, quality of life (assessed with the pain interference items of the Brief Pain Inventory and the Fibromyalgia Impact Questionnaire), mood and anxiety (assessed with the Hamilton Depression Rating Scale, the Beck Depression Inventory and the Hospital Anxiety and Depression Scale). We also assessed the effects of rTMS on the pressure pain threshold at tender points ipsi- and contralateral to stimulation. Follow-up data were obtained for all the patients on days 15 and 30 and for 26 patients (13 in each treatment group) on day 60. Active rTMS significantly reduced pain and improved several aspects of quality of life (including fatigue, morning tiredness, general activity, walking and sleep) for up to 2 weeks after treatment had ended. The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety. The effects of rTMS were more long-lasting for affective than for sensory pain, suggesting differential effects on brain structures involved in pain perception. Only few minor and transient side effects were reported during the stimulation period. Our data indicate that unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia. This study examines the impact of controlled-release oxycodone (OxyContin) on cognitive-behavioral indicators of efficacy beliefs and coping efforts in patients with osteoarthritis who experience persistent pain.
                This was a double-blind, placebo-controlled study of 104 male and female patients with osteoarthritis who experienced moderate to severe pain. Pain assessment, arthritis helplessness, and coping efforts were assessed before and after for treatment and placebo control groups.
                Examination of differences between treatment and control groups after 2 weeks revealed significant reductions in reported pain, improvements in coping efficacy, and reductions in helplessness and passive coping in response to controlled-release oxycodone treatment compared to placebo. Changes in pain partially mediated the effects on coping in subsequent assessments.
                The findings indicate that controlled-release oxyco- done treatment accounted for improvements in coping with pain beyond that of placebo controls. This medication may be most beneficial to osteoarthritis patients when incorporated as part of a multidisciplinary approach to pain management. Pain intensity, muscle strength, static muscle endurance, pressure pain threshold, and pain tolerance at tender points and control points were assessed in 31 patients with fibromyalgia (FM), before and after intravenous administration of morphine (9 patients), lidocaine (11 patients), and ketamine (11 patients). The three different studies were double-blind and placebo-controlled. The patients were classified as placebo-responders, responders (decrease in pain intensity by > 50%) and non-responders. The morphine test did not show any significant changes. The lidocaine test showed a pain decrease during and after the infusion. The ketamine test showed a significant reduction in pain intensity during and after the test period. Tenderness at tender points decreased and endurance increased significantly, while muscle strength remained unchanged. The present results support the hypothesis that the NMDA receptors are involved in pain mechanisms in fibromyalgia. These findings also suggest that central sensitization is present in FM and that tender points represent secondary hyperalgesia. The authors examine the antiemetic effects of 1 mg clebopride administered iv after surgery, vs a placebo, by making a double blind randomized study on two groups of 40 women comparable by age and weight. The 2 groups of outpatients, admitted for short gynecological surgery, underwent diagnostic uterine curettage. They were anaesthetized with a cocktail of 2.5 mcg/kg fentanyl and 0.25 mg/kg ketamine, on spontaneous respiration. Nausea, vomiting and the other side effects were evaluated 3-6 hours after surgery. Statistically, clebopride proved more effective than placebo against nausea and vomiting (P ranging between 0.05-0.01), with no relevant side effects. Cisapride improves symptoms in patients with idiopathic constipation. This trial compares the effect of cisapride with that of placebo in patients with irritable bowel syndrome (IBS) and constipation.
                Seventy patients were randomized to 12 weeks' treatment with 5 mg cisapride three times daily or placebo in a double-blind trial. The dose could be doubled after 4 weeks in patients without satisfactory improvement. The patients scored their symptoms on a 100-mm visual analogue scale (VAS) (0 = best, 100 = worst), and the investigators evaluated the symptomatic effect.
                The dose was doubled in 17 and 23 patients in the cisapride and placebo groups, respectively, after 4 weeks. The patients' mean VAS score for global evaluation of IBS symptoms in the cisapride and placebo groups was 73 and 71 mm, respectively, at the start of treatment and 47 and 41 mm at the end. The difference between cisapride and placebo at the end was 6 mm in favour of placebo (95% confidence interval (CI), -6, 18) (NS). The investigators evaluated the effect as good or excellent in 39.2% and 58.8% in the cisapride and placebo groups, respectively. The difference in favour of placebo was 19.5% (95% CI, -5, 44) (NS). Nor were any statistically significant differences seen between cisapride and placebo in the other effect factors.
                The trial seems to exclude a clinically significant effect of 15-30 mg cisapride daily in patients with IBS and constipation during a 12-week treatment period. The efficacy and tolerability of 150 mg/d Kava special extract WS 1490 were investigated in a randomized, placebo-controlled, double-blind multicenter study in patients suffering from neurotic anxiety (DSM-III-R diagnoses 300.02, 300.22, 300.23, 300.29, or 309.24). 141 adult, male and female out-patients received 3 x 1 capsule of 50 mg/d WS 1490 or placebo for four weeks, followed by two weeks of observation without study-specific treatment. During randomized treatment the total score of the Anxiety Status Inventory (ASI) observer rating scale showed more pronounced decreases in the WS 1490 group than in the placebo group. Although a treatment group comparison of the post-treatment ASI scores was not significant (p > 0.05), an exploratory analysis of variance across the differences between treatment end and baseline, with center as a second factor, showed superiority of the herbal extract over placebo (p < 0.01, two-sided). 73% of the patients treated with WS 1490 exhibited ASI score decreases > 5 points versus baseline, compared to 56% for placebo. Significant advantages for WS 1490 were also evident in a structured well-being self-rating scale (Bf-S) and the Clinical Global Impressions (CGI), while the Erlangen Anxiety, Tension and Aggression Scale (EAAS) and the Brief Test of Personality Structure (KEPS) showed only minor treatment group differences. Although the results show consistent advantages for WS 1490 over placebo in several psychiatric scales and indicate significant improvements in the patients' general well-being, the differences versus placebo were not as large as in previous trials which employed 300 mg/d of the same extract. WS 1490 was well tolerated, with no influence on liver function tests and only one trivial adverse event (tiredness) attributable to the study drug. This multicenter study assessed the feasibility of conducting a phase III trial of transcutaneous electrical nerve stimulation (TENS) in patients with cancer bone pain recruited from palliative care services. Eligible patients received active and placebo TENS for 1 hour at site of pain in a randomized crossover design; median interval between applications 3 days. Responses assessed at 30 and 60 minutes included numerical and verbal ratings of pain at rest and on movement, and pain relief. Recruitment, tolerability, adverse events, and effectiveness of blinding were also evaluated. Twenty-four patients were randomised and 19 completed both applications. The intervention was well tolerated. Five patients withdrew: 3 due to deteriorating performance status, and 2 due to increased pain (1 each following active and placebo TENS). Confidence interval estimation around the differences in outcomes between active and placebo TENS suggests that TENS has the potential to decrease pain on movement more than pain on rest. Nine patients did not consider that a placebo was used; the remaining 10 correctly identified placebo TENS. Feasibility studies are important in palliative care prior to undertaking clinical trials. Our findings suggest that further work is required on recruitment strategies and refining the control arm before evaluating TENS in cancer bone pain.
                Cancer bone pain is common and severe, and partly mediated by hyperexcitability. Animal studies suggest that Transcutaneous Electrical Nerve Stimulation can reduce hyperalgesia. This study examined the feasibility of evaluating TENS in patients with cancer bone pain in order to optimize methods before a phase III trial.
                Copyright 2010 American Pain Society. Published by Elsevier Inc. All rights reserved. Peripheral diabetic neuropathy affects between 20% and 45% of patients with diabetes.
                To ascertain the effect of lacosamide on pain associated with peripheral diabetic neuropathy.
                One hundred nineteen patients with a 1 to 5-year history of pain attributed to diabetic neuropathy and a score of > or =4 on the Likert pain scale entered the multicenter, randomized, double-blind, placebo-controlled trial. Lacosamide (N=60) titrated from 100 to 400 mg/d or maximum tolerated dose and placebo (N=59) were the trial interventions. Primary efficacy criterion was change in pain score on the 11-point Likert pain scale. Secondary assessments included Short-Form McGill Pain and Short-Form-36 Quality of Life Questionnaires, sleep/activity interference, pain intensity, Patient and Clinical Global Impression of Change, and Profile of Mood. Patients receiving at least 1 dose of medication underwent safety evaluation.
                Ninety-four patients (lacosamide 46; placebo 48) completed the trial. Lacosamide had significantly (P=0.039) better pain relief versus placebo (primary outcome). Improvements were also seen in secondary outcome measures. Adverse events occurred in 52 lacosamide and 44 placebo patients. Common adverse events, occurring in > or =5% of patients, were headache (lacosamide 18%, placebo 22%), dizziness (lacosamide 15%, placebo 8%), and nausea (lacosamide 12%, placebo 7%). Five lacosamide and 3 placebo patients withdrew for adverse events.
                Lacosamide seems to attenuate pain in diabetic neuropathy in doses up to 400 mg/d and improves quality of life issues. Several lines of evidence suggest that neuropathic pain (including Complex Regional Pain Syndrome [CRPS] I and CRPS II) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. This study sought to characterize the effects of intravenous lidocaine (a sodium channel blocker) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II.
                This study used a randomized, double-blind, placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia. Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week. A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1, 2, and 3 microg/ml. At baseline and at each plasma level, spontaneous and evoked pain scores and neurosensory testing within the painful area were measured. The neurosensory testing consisted of thermal thresholds, tactile thresholds and the area of allodynia to punctate, and stroking and thermal stimuli.
                Intravenous lidocaine and diphenhydramine had no significant effect on the cool, warm, or cold pain thresholds. However, lidocaine caused a significant elevation of the hot pain thresholds in the painful area. Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area. There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level.
                This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain. There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli. Decrease acute pain after breast cancer surgery by an infiltration of ropivacaine. Analyse effect on chronic pain.
                Prospective randomised double blind versus placebo study.
                Eighty-one patients randomised between two groups received wound infiltration with 40 ml of ropivacaine 4.75 mg/ml or placebo. Acute pain was assessed during 24h with analogical visual scale and antalgic consumption. One year later, telephonic interviews looked for chronic pain and evaluate it with McGill Pain Questionnaire.
                Analogical visual scale pain score, antalgic consumption and chronic pain incidence were similar between groups.
                Ropivacaine scar infiltration provided no acute or chronic pain relief after breast cancer surgery. In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P=0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design. The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT.
                Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam.
                The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms.
                Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL. The objective of this study was to determine the effects of a placebo treatment on cough in patients with cough associated with acute upper respiratory tract infection (URTI).
                Patients with dry or slightly productive cough associated with a history of URTI were recruited. Cough frequency (CF) over 15 minutes was recorded by means of a microphone connected to a pen recorder. Cough suppression time (CST) was recorded when patients were instructed by means of a red light to try not to cough. Patients received either a single dose of vitamin E (placebo treatment) or no treatment. CF and CST were recorded before and 15 minutes after treatment.
                Twenty-seven patients were randomized to placebo treatment and 27 to the no-treatment group (mean age 22.6 years). The median difference between post- and pretreatment CF was -3 in the no-treatment group and -18 in the placebo group (p = .0003). There was a significant increase in CST in the placebo group compared with no treatment (p = .027).
                The results demonstrate that placebo treatment has significant antitussive activity. This placebo effect may be related to generation of central neurotransmitters such as endogenous opioids. In cranial electrotherapy stimulation (CES), micro-current levels of electrical stimulation are passed across the head via electrodes clipped to the ear lobes. After successful clinical use of CES with fibromyalgia patients in our clinic, it was decided to test these results with a double-blind, placebo-controlled study in which 60 randomly assigned patients were given 3 weeks of 1-hour-daily CES treatments, sham CES treatments, or were held as wait-in-line controls for any placebo effect in the sham-treated patients. Treated patients showed a 28% improvement in tender point scores, and a 27% improvement in self-rated scores of general pain level. The number of subjects rating their quality of sleep as poor dropped from 60% at the beginning of the study to 5%. In addition, there were significant gains in the self-rated feelings of well-being and quality of life, plus gains in six stress-related psychological test measures. No placebo effect was found among the sham-treated controls. A theoretical role of CES in affecting the brain's pain message mechanisms and/or neurohormonal control systems is discussed. It is concluded that CES is as effective as the drug therapies in several trials, with no negative side effects, and deserves further consideration as an additional agent for the treatment of fibromyalgia. Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome chronic symptom that has no proven pharmacologic treatment. The purpose of this double-blind randomized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem.
                Patients with CIPN were randomized to baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) versus placebo (PLO) to determine its effect on numbness, tingling, pain, and function. The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks.
                Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory (p = 0.053) and motor subscales (p = 0.021). The greatest improvements were related to the symptoms of tingling, cramping, and shooting/burning pain in the hands as well as difficulty in holding a pen. There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity.
                Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN. This topical gel was well tolerated, without evident systemic toxicity. Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN. The efficacy of oral retarded morphine sulphate (MST) was tested against placebo in a double-blind crossover design in 12 patients with phantom limb pain after unilateral leg or arm amputation. Two counterbalanced treatment phases of 4 weeks each were initiated with an intravenous test infusion of MST or Placebo. The titration phase was 2 weeks. The dose of MST was titrated to at least 70 mg/day and at highest 300 mg/day. Pain intensity was assessed hourly on visual analog scales during a 4-week treatment-free phase, both treatment phases and at two follow-ups (6 and 12 months). Reorganization of somatosensory cortex, electric perception and pain thresholds as well as selective attention were measured pre- and post-treatment. A significant pain reduction was found during MST but not during placebo. A clinically relevant response to MST (pain reduction of more than 50%) was evident in 42%, a partial response (pain reduction of 25-50%) in 8% of the patients. Neuromagnetic source imaging of three patients showed initial evidence for reduced cortical reorganization under MST concurrent with the reduction in pain intensity. Perception and pain thresholds were not significantly altered whereas attention was significantly lower under MST. Thus, opioids show efficacy in the treatment of phantom limb pain and may potentially influence also cortical reorganization. These data need to be replicated in larger patient samples.
We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.