Placebos Research Papers - Academia.edu (original) (raw)

Background: This analysis was designed to assess the efficacy and safety of aripiprazole compared with placebo in subpopulations of patients with acute manic or mixed episodes of bipolar I disorder. Methods: Acutely manic patients experiencing DSM-IV manic/mixed episodes of bipolar I disorder were pooled from two randomized, three-week, flexible-dose, double-blind, placebo-controlled trials (N = 516) and stratified by disease severity (Young Mania Rating Scale, YMRS), episode type, presence or absence of psychotic features, episode frequency, age, gender, and baseline severity of depressive symptoms. Safety and treatment-emergent adverse-event analyses were also performed. Results: Aripiprazole significantly reduced mean YMRS total scores at end point compared with placebo in patients with more severe or less severe illness, with mixed or manic episodes, with or without psychotic features, or with a history of rapid or nonrapid cycling (p b 0.01 for each subpopulation); in men and women (p = 0.001 for both); in patients in the 18-40 and 41-55 year age groups (p ≤ 0.001 for both); and in three subgroups stratified by baseline severity of depressive symptoms using the Montgomery-Åsberg Depression Rating Scale (p b 0.05). The treatment-emergent adverse events reported in ≥ 5% of patients aged 18-40 years receiving aripiprazole were similar to those reported for the overall population. Limitations: This post hoc analysis utilized pooled data from two short-term studies. Conclusion: Efficacy of the second-generation antipsychotic aripiprazole was noted across a broad range of subpopulations often associated with treatment resistance in patients experiencing manic or mixed episodes of bipolar I disorder.

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- Bipolar Disorder, Treatment, Treatment Outcome, Adolescent

Aim: Non-insulin-dependent diabetes mellitus (type 2 diabetes) not responding to dietary treatment alone in patients with non-alcoholic liver cirrhosis is characterized by high postprandial hyperglycaemia. The control of postprandial hyperglycaemia in such patients, is generally achieved by the means of progressively higher doses of insulin, with an increasing risk of hypoglycaemia in the late postprandial period. The aim of this study was to evaluate the use of acarbose for the control of postprandial hyperglycaemia in 100 patients with wellcompensated liver cirrhosis and type 2 diabetes treated with insulin. Methods: The study was double blind with randomization of treatments into acarbose (52 patients) vs. placebo (48 patients) with parallel branches over a period of 28 weeks. Results: All patients tolerated the treatments well and no signi®cant variations in liver function tests were observed (< 5% vs. pretreatment). A signi®cant reduction of several parameters was observed only after acarbose treatment: fasting glycaemia (173 T 28 vs. 146 T 19 mg/dl; p < 0.01), postprandial glycaemia (230 T 24 vs. 148 T 20 mg/dl; p < 0.01), mean glycaemia (206 T 20 vs. 136 T 13 mg/dl; p < 0.01), mean variation (180 T 14 vs. 51 T 10 mg/dl; p < 0.01), HbA 1c (8.9 T 0.8 vs. 7.2 T 0.5; p < 0.05), C-peptide 2 h after a standard meal (4.5 T 1.9 vs. 2.8 T 1.7 ng/ml; p < 0.05), whereas the parameters did not change signi®cantly after the placebo. After acarbose treatment a signi®cant increase of intestinal voiding/week (+ 116% vs. + 10%; p < 0.01) and a parallel reduction of blood ammonia levels (± 52 T 9% vs. ± 9 T 5%; P < 0.01) were observed. Conclusions: The results clearly document the good tolerability and the absence of toxic effects of acarbose on liver, due to the lack of both intestinal absorption and hepatic metabolism of the drug at doses in the therapeutic range. In fact, acarbose increases the peristalsis movements of the gut, stimulates the proliferation of the saccarolytic bacteria and simultaneously reduces the proliferation of proteolytic bacteria, thus resulting active in the reduction of blood ammonia levels. These effects of acarbose may be advantageously exploited in the treatment of type 2 diabetic patients with well-compensated non-alcholic liver cirrhosis.

- by Salvatore Turco
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- Food, Blood Glucose, Liver Cirrhosis, Insulin
- by norman poole
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- Treatment, Catharsis, Benzodiazepines, Placebos

Background: is involved in the apical migration of epithelial cells during the development of periodontal pockets. Low-dose doxycycline (LDD) can therapeutically modulate the host response with its non-antimicrobial properties. In the present randomized, double-blind, placebo-controlled, parallel arm study, the effectiveness of LDD in combination with non-surgical periodontal therapy on gingival crevicular fluid (GCF) Ln-5 γ2 chain fragment levels and clinical parameters in patients with chronic periodontitis was examined over a 12-month period.

- by Gül Atilla
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- Dentistry, Periodontology, Low Dose, Chronic Disease
- by Edward Czerwiński
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- Medicine, TIME, Bone Density, Placebos

Context: Metformin is widely prescribed to pregnant women with polycystic ovary syndrome (PCOS) in an attempt to reduce pregnancy complications. Metformin is not approved for this indication, and evidence for this practice is lacking. ...... more

- by Angel Langdon
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- Endocrinology, Medicine, Biological Sciences, Gestational diabetes

Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids (PUFAs), including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents (red blood cell membrane, plasma, etc.) and dietary intake. However, more evidence is needed to support its relation. In this study, we conducted an 8-week, double-blind, placebo-controlled trial, comparing omega-3 PUFAs (9.6 g / day) with placebo, on the top of the usual treatment, in 28 patients with major depressive disorder. Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group (P,0.001). From the preliminary findings in this study, omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder.

- by Shih-Yi Huang
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- Treatment Outcome, Major Depressive Disorder, Placebos, Rating Scale

Background: A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood-brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX W co-administered with varenicline (Champix W) and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design: Two centers will include a total of 600 smokers who are motivated to quit smoking. At week −2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX W or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion: This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX W is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of nicotine vaccination for relapse prevention. Trial registration: ClinicalTrials.gov: (NCT00995033)

- by Matthew Kalnik
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- Research Design, Vaccines, Adolescent, Counseling

and attempted to extend and replicate the fmding that placebo responses can be conditioned in human subjects. Two groups of 10 subjects were told that they were receiving an analgesic which was in fact a placebo. During the conditionin& placebo administration was surreptitiously paired with an increase in the painful stimulus for half of the subjects and withadecrease for the other half. Subjects were tested pre and post conditioning for a placebo response. A second type of experimental pain was also used to determine stimulus generalization. The results confumed a previous finding that placebo responses can be conditioned in human subjects. The implications for clinical practice of a 1 earning model of placebo behavior are discussed.

- by Grahame Coleman
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- Pain, Classical Conditioning, Placebos, Analgesics

Acute tryptophan depletion (ATD) can be used to decrease serotonin levels in the brain. Traditionally, ATD has been established by administering amino acid (AA) mixtures and studies using this method showed that serotonin is involved in learning and memory processes. This study used a recently developed gelatin-based protein drink to examine whether it 1) is superior to the traditional AA method in controlling the tryptophan levels in the placebo condition, 2) impairs long-term memory and 3) differentially affects episodic and spatial memory. Sixteen healthy subjects participated in a double-blind, placebo-controlled study. Memory was assessed using a visual verbal learning test and an object relocation task (spatial memory). Tryptophan ratio significantly decreased after ATD and did not significantly increase in the placebo condition. Delayed recall in the verbal learning test and delayed relocation of objects to positions in the spatial task were impaired after ATD. Spatial short-term memory, however, improved. The current results indicate that the tryptophan levels were essentially neutral in the placebo condition compared with those in the traditional AA mixture. Our study provides further evidence that impairment in long-term episodic and elementary spatial memory after ATD is related to lowered tryptophan levels in plasma.

- by Wim Riedel
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- Psychopharmacology, Spatial Memory, Episodic Memory, Affect

Bacterial vaginosis (BV) is the most prevalent vaginal infection worldwide and is characterized by depletion of the indigenous lactobacilli. Antimicrobial therapy is often ineffective. We hypothesized that probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 might provide an adjunct to antimicrobial treatment and improve cure rates. Sixty-four Brazilian women diagnosed with BV were randomly assigned to receive a single dose of tinidazole (2 g) supplemented with either 2 placebo capsules or 2 capsules containing L. rhamnosus GR-1 and L. reuteri RC-14 every morning for the following 4 weeks. At the end of treatment (day 28), the probiotic group had a significantly higher cure rate of BV (87.5%) than the placebo group (50.0%) (p = 0.001). In addition, according to the Gram-stain Nugent score, more women were assessed with ''normal'' vaginal microbiota in the probiotic group (75.0% vs. 34.4% in the placebo group; p = 0.011). This study shows that probiotic lactobacilli can provide benefits to women being treated with antibiotics for an infectious condition.

- by Maristela Patta and +1
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- Microbiology, Probiotics, Medical Microbiology, Brazil

Promising data have suggested that retinoid chemoprevention may help to control second primary tumors (SPTs), recurrence, and mortality of stage I non-small-cell lung cancer (NSCLC) patients. We carried out a National Cancer Institute (NCI) Intergroup phase III trial (NCI #I91-0001) with 1166 patients with pathologic stage I NSCLC (6 weeks to 3 years from definitive resection and no prior radiotherapy or chemotherapy). Patients were randomly assigned to receive a placebo or the retinoid isotretinoin (30 mg/day) for 3 years in a double-blind fashion. Patients were stratified at randomization by tumor stage, histology, and smoking status. The primary endpoint (time to SPT) and the secondary endpoints (times to recurrence and death) were analyzed by log-rank test and the Cox proportional hazards model. All statistical tests were two-sided. After a median follow-up of 3.5 years, there were no statistically significant differences between the placebo and isotretinoin arms with respect to the time to SPTs, recurrences, or mortality. The unadjusted hazard ratio (HR) of isotretinoin versus placebo was 1.08 (95% confidence interval [CI] = 0.78 to 1.49) for SPTs, 0.99 (95% CI = 0.76 to 1.29) for recurrence, and 1.07 (95% CI = 0.84 to 1.35) for mortality. Multivariate analyses showed that the rate of SPTs was not affected by any stratification factor. Rate of recurrence was affected by tumor stage (HR for T(2) versus T(1) = 1.77 [95% CI = 1.35 to 2.31]) and a treatment-by-smoking interaction (HR for treatment-by-current-versus-never-smoking status = 3.11 [95% CI = 1.00 to 9.71]). Mortality was affected by tumor stage (HR for T(2) versus T(1) = 1.39 [95% CI = 1.10 to 1.77]), histology (HR for squamous versus nonsquamous = 1.31 [95% CI = 1.03 to 1.68]), and a treatment-by-smoking interaction (HR for treatment-by-current-versus-never-smoking = 4.39 [95% CI = 1.11 to 17.29]). Mucocutaneous toxicity (P&amp;lt;.001) and noncompliance (40% versus 25% at 3 years) were higher in the isotretinoin arm than in the placebo arm. Isotretinoin treatment did not improve the overall rates of SPTs, recurrences, or mortality in stage I NSCLC. Secondary multivariate and subset analyses suggested that isotretinoin was harmful in current smokers and beneficial in never smokers.

- by Fadlo Khuri
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- Multivariate Analysis, Smoking, Placebos, The

This study was designed to investigate the efficacy and tolerability of daily conjugated linoleic acid (CLA) in healthy exercising humans. This was a random-ized, double-blind, placebo-controlled study in 20 healthy humans of normal body weight and body mass index less than 25.0 kg/m2, who did standardized physical exercise in a gym for 90 min three times weekly. Participants took either placebo (hydrogel) or CLA 0.6 mg, three times daily, as two capsules during meals, for 12 weeks. Body fat, measured using near infrared light, was significantly reduced in the CLA group during the study, but not in the placebo group. No effects on body weight were observed. Tolerability was good and similar in the two groups. Compliance, as judged by the number of returned capsules, was more than 80 % of the recommended dose for all participants. Thus CLA reduces body fat but not body weight in healthy exercising humans of normal body weight.

- by O. Gudmundsen
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- Medicine, Adipose tissue, Key words, Exercise

Background: Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause. Despite its prevalence, there remains a significant lack of... more

The information needed to determine the internal and external validity of an experimental study is discussed. Internal validity is the degree to which a study establishes the cause-and-effect relationship between the treatment and the observed outcome. Establishing the internal validity of a study is based on a logical process. For a research report, the logical framework is provided by the report's structure. The methods section describes what procedures were followed to minimize threats to internal validity, the results section reports the relevant data, and the discussion section assesses the influence of bias. Eight threats to internal validity have been defined: history, maturation, testing, instrumentation, regression, selection, experimental mortality, and an interaction of threats. A cognitive map may be used to guide investigators when addressing validity in a research report. The map is based on the premise that information in the report evolves from one section to the...

- by Marion Slack
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- Research Design, Mortality, Placebos, Reproducibility of Results

To determine whether buccallsublingual administration of midazolam (MDL) would lead to detectable venous concentrations and EEG changes in 10 healthy volunteers. Methods: The study consisted of an open-label and a doubleblind phases. Subjects held 10 mg MDL in 2 ml peppermintflavored fluid or peppermint-flavored placebo in their mouth for 5 min and then spat it out. Cardiorespiratory and EEG monitoring was performed in all subjects. Results: Venous MDL concentrations measured on 10 occasions from 5 to 600 min after administration showed a rapid

- by Frank Besag
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- Treatment, Electroencephalography, Pharmacokinetics, Medicine

Objective: To evaluate the efficacy of Malva sylvestris L. flowers extract for treatment of FC. Method: Adults with FC were allocated to receive the M. sylvestris L. flowers aqueous extract syrup (MSL, 1 g extract/day) or placebo for four weeks. Frequency of constipation symptoms and stool forms were assessed every week. Self-reported improvement was assessed after treatment. Results: Compared with placebo, more increase was observed in defecation frequency (F ¼ 18.8, P < 0.001) and more decrease was observed in frequency of all constipation symptoms by MSL (F ¼ 16.5 to 25.3, all P values <0.001). Also, the MSL group experienced more reduction in frequency of hard stool forms (45.4% vs. 9.1%, P < 0.001) and reported more improvement in all symptoms (all P values <0.01) than placebo. Conclusion: The M. sylvestris L. flowers aqueous extract is efficacious and safe for the treatment of FC in adult patients. Investigating the mechanisms of action is warranted. IRCT2014031617032N1.

- by Mohammad Kamalinejad
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- Nursing, Complementary and Alternative Medicine, Constipation, Flowers

Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)--derived from broccoli sprout extracts--or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50-150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 1...

- by Jed W. Fahey
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- Biology, Treatment Outcome, Adolescent, Medicine

Agitation is common among patients with Alzheimer disease; safe, effective treatments are lacking. To assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation. Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score ≥4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed. In stage 1, 220 patients were randomized in a 3:4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified ...

- by Anton Porsteinsson
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- Treatment Outcome, Aggression, Placebos, Aged

Appropriate diagnosis is essential in providing proper and effective therapy. The field of diagnostic accuracy tests is dynamic with new tests being developed at a fast pace along with improvement in technology of existing tests on a continuous basis. Well-designed diagnostic test accuracy studies can help in making appropriate health care decisions, provided that they transparently and fully report their participants, tests, methods, and results. Exaggerated and biased results from poorly designed and reported diagnostic test studies can trigger their premature dissemination and lead physicians into making incorrect treatment decisions. Consequently, a diagnostic test is useful only to the extent that it distinguishes between conditions or disorders that might otherwise be confused. Since it is unlikely that clinicians, patients, and policy makers have the time, skills, and resources to find, appraise, and interpret the evidence and incorporate it into their health care decisions, ...

- by Laxmaiah Manchikanti
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- Research Design, Pain, Evidence Based Medicine, Medicine

The effectiveness of the short-and long-term use of crystallized theophylline in asthmatic children The bioavailability, duration of action, and efficacy of a crystallized tablet form of theophylline were studied in 16 nonsteroid-dependent asthmatic children. All required bronehodilator drugs daily for control of symptoms. Theophylline 125 rag, ephedrine S04 30 rag, T + E, or placetio were given in a randomized, double-blind, crossover design on four separate days. Pulmonary function tests (FVC, FEV, FEF25_7~) and serum T levels were determined at O, 4, 1, 2, 4, and 6 hours on both day one and after day 7 of a every-six-hour drug dosage schedule. Mean maximum T levels were achieved at two hours with a peak mean of 2.94 Izg/ml +_ 0.24 SEM on day one. On day 8, the maximum T levels were higher, with a peak mean at two hours of 4.69 I~g/ml + 0.49 SEM. Computer analyses for pharmokineties are compatible with 100% absorption of this preparation. Pulmonary function tests were significantly improved (FEV1 20% and FEF2~_75 15%) at T levels of 2 to 5 Ixg/ml. Addition of E to the T regimen further improved pulmonary funetion only on day one and had no effect on the last study day.

- by Roger Katz
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- Pediatrics, Asthma, Crystallization, Adolescent
- by diane sweeney
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- Evaluation, Immunohistochemistry, Antibodies, Dogs
- by Tatiana Moreno
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- Dentistry, Adolescent, Clinical, Follow-up studies

Since the somatosensory system is believed to be affected in focal dystonia, we focused on the modulation of the primary somatosensory cortex (SI) induced by repetitive transcranial magnetic stimulation (rTMS) in order to improve symptoms of writer's cramp. Patients with writer's cramp (N=9 in the pilot study and N=11 in the advanced study) were treated with 30-minute 1 Hz real- or sham-rTMS of the SI cortex every day for 5 days. Before and after rTMS, 1.5 T fMRI was examined during simple hand movements. While in the pilot study the rTMS coil was navigated over the SI cortex with a maximum of blood oxygenation-level dependent (BOLD) signal induced by passive movement, patients in the advanced study had the coil above the postcentral sulcus. After real-rTMS, 4 pilot study patients and 10 advanced study patients experienced subjective and objective improvement in writing, while only minimal changes were observed after sham-rTMS. Patients involved in the active movement task e...

- by Grégory Operto and +1
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- Radiation, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, Handwriting

Background. Diarrhea is the most common illness associated with international tourism. We evaluated the efficacy of a probiotic preparation of nonviable Lactobacillus acidophilus (hereafter referred to as LA) for the prevention of... more

- by Pierre Buffet and +1
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- Epidemiology, Probiotics, Diarrhea, Biological Sciences

Besides hyperglycemia and hypertension, a recently recognized risk factor for diabetic retinopathy (DR) appears to be hyperlipidemia. While studies using earlier generation lipid lowering agents in DR were disappointing, a randomized trial using HMG-CoA Reductase Inhibitors has strong rationale, though hitherto not attempted. The aim of the present study was to compare the HMG-CoA Reductase Inhibitor, simvastatin, with placebo in patients having DR in a double-blind randomized placebo-controlled trial. Fifty patients with diabetes mellitus (Type 1 and 2) with good glycemic control and hypercholesterolemia and having DR (non-clinically significant macular edema and visual acuity 6/24 or better) in either or both eyes were randomized to simvastatin 20-mg per day or placebo, and were followed up for 180 days. On simvastatin therapy, total cholesterol and low-density lipoprotein cholesterol (LDL-C) decreased (P B0.001, respectively), and the level of high-density lipoprotein cholesterol (HDL-C) increased (P B 0.001). VA improved in four patients using simvastatin, (not statistically different from placebo group) and worsening of VA occurred in seven patients in the placebo group and none in the simvastatin group (P = 0.009). Fundus fluorescein angiography and color fundus photograph showed improvement in one patient in the simvastatin group, while seven patients showed worsening in the placebo group (P = 0.009). The observations of the current study suggest that the HMG-CoA Reductase Inhibitor simvastatin significantly retards the progression of retinopathy in diabetic patients with hypercholesterolemia. The potential of this class of drugs for the primary prevention of DR and other microvascular complications needs to be explored further.

- by Atul Kumar
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- Photography, Randomization, Visual acuity, Macular Degeneration

Information provided to patients is thought to influence placebo and drug effects. In a prospective, withinsubjects, repeated-measures study of 66 subjects with episodic migraine, we investigated how variations in medication labeling modified placebo and drug effects. An initial attack with no treatment served as a control. In six subsequent migraine attacks, each participant received either placebo or Maxalt (10-mg rizatriptan) administered under three information conditions ranging from negative to neutral to positive (told placebo, told Maxalt or placebo, told Maxalt) (N = 459 documented attacks). Treatment order was randomized. Maxalt was superior to placebo for pain relief. When participants were given placebo labeled as (i) placebo, (ii) Maxalt or placebo, and (iii) Maxalt, the placebo effect increased progressively. Maxalt had a similar progressive boost when labeled with these three labels. The efficacies of Maxalt labeled as placebo and placebo labeled as Maxalt were similar. The efficacy of open-label placebo was superior to that of no treatment. Relative to no treatment, the placebo, under each information condition, accounted for more than 50% of the drug effect. Increasing "positive" information incrementally boosted the efficacy of both placebo and medication during migraine attacks. The benefits of placebo persisted even if placebo was honestly described. Whether treatment involves medication or placebo, the information provided to patients and the ritual of pill taking are important components of care.

- by John Kelley
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- Treatment Outcome, Biological Sciences, Placebos, Triazoles

Objective-Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol... more

- by William Lovallo
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- Psychosomatic Medicine, Caffeine, Circadian Rhythm, Placebos

This study was designed to confirm our previous findings that nonalcoholic offspring from families with alcohol-dependent individuals have greater hypothalamic-pituitary-adrenal axis activation induced by opioid blockade compared with nonalcoholic subjects without a family history of alcohol dependence. Sixty-four nonalcoholic subjects aged 18 to 25 years were enrolled in the protocol. Twenty-seven subjects were offspring from families with alcohol dependence and were designated as family history-positive subjects (FHP). Thirty-seven subjects were biological offspring of non-alcohol-dependent parents and were designated as family history-negative subjects (FHN). Subjects received naloxone hydrochloride (0, 50, 125, 375, and 500 microg/kg) in double-blind, randomized order; adrenocorticotropin (ACTH) and cortisol were monitored over 120 min. No hormone differences at baseline or during placebo administration were identified between FHP and FHN subjects. FHP subjects had greater ACTH and cortisol response to opioid receptor blockade induced by naloxone hydrochloride compared with FHN subjects. These observations confirm previous findings that differences in ACTH and cortisol dynamics between FHP and FHN subjects can be unmasked by opioid receptor blockade.

- by Mary E McCaul
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- Psychology, Adolescent, Family history, Alcoholism

Six-month treatment of obesity with sibutramine 15 mg; a double-blind, placebo-controlled monocenter clinical trial in a hispanic population. Obes Res. 2000:8:71-82. Objective: To evaluate the safety and efficacy of sibutramine 15 mg by mouth once per day in obese patients over a period of 6 months. Research Methods and Procedures: A monocenter, double-blind, placebo controlled, parallel, prospective clinical trial was carried out. Sixty-nine male and female obese patients (body mass index [BMI] Ͼ 30 kg/m 2) aged 16 to 65 years entered the trial. Results: 22 of 35 patients in the sibutramine group and 9 of 34 patients in the placebo group completed the trial. The high dropout rate in the sibutramine group was due to adverse events in 3 cases, lack of efficacy (as judged by patients) in 7, loss to follow-up in 2, and an orthopedic device being worn in 1; in the placebo group the dropouts were ascribed to lack of efficacy (as judged by patients) in 17 cases and to loss to follow-up in 8 cases. Using the method of last observation carried forward, the weight loss in the sibutramine group was 10.27 kg (95% confidence intervals [95% CI] 7.66; 13.07) and 1.26 kg (95% CI 0.3; 2.23) in the placebo group. The BMI loss was 4.17 kg/m 2 (95% CI 3.11; 5.22) in the sibutramine group and 0.53 kg/m 2 (95% CI 0.13; 0.92) in the placebo group. The waist circumference reduction was 12.51 cm (95% CI 9.25; 15.77) in the sibutramine group and 3.26 cm (95% CI 1.38; 5.14) in the control group (p Ͻ 0.05 by paired Student's t test for all the intragroup comparisons). Twenty-three sibutramine patients had 34 adverse events, the most frequent adverse events in the sibutramine group were upper respiratory tract infections (n ϭ 6) and constipation (n ϭ 6); 16 placebo patients had 21 adverse events. Three sibutramine patients withdrew their informed consent when they had adverse events. Discussion: The results show that sibutramine induces significant loss of body weight and waist circumference. Cardiovascular function was not significantly affected by sibutramine. Sibutramine was well tolerated by most of the patients.

- by Maria Valentina RODRIGUEZ MONSALVE
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- Obesity, Clinical Trial, Informed Consent, Adolescent

Background: Statins are the most commonly prescribed drugs to reduce cardiometabolic risk. Besides the wellknown efficacy of such compounds in both preventing and treating cardiometabolic disorders, some patients experience statin-induced side effects. We hypothesize that the use of natural bergamot-derived polyphenols may allow patients undergoing statin treatment to reduce effective doses while achieving target lipid values. The aim of the present study is to investigate the occurrence of an enhanced effect of bergamot-derived polyphenolic fraction (BPF) on rosuvastatin-induced hypolipidemic and vasoprotective response in patients with mixed hyperlipidemia. Methods: A prospective, open-label, parallel group, placebo-controlled study on 77 patients with elevated serum LDL-C and triglycerides was designed. Patients were randomly assigned to a control group receiving placebo (n = 15), two groups receiving orally administered rosuvastatin (10 and 20 mg/daily for 30 days; n = 16 for ea...

- by Elzbieta Janda
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- Cardiology, Medicine, Prospective studies, Placebos

Downloaded from after the 15th treatment session and on day 45. In the HBO group there was a significant decrease in pain and oedema and a significant increase in the ROM of the wrist. When we compared the two groups, the HBO group had significantly better results with the exception of wrist extension. In conclusion, HBO is an effective and well-tolerated method for decreasing pain and oedema and increasing the ROM in patients with CRPS.

- by Hasan DURSUN
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- Pain, Adolescent, Pain Management, Placebos

This pilot randomized-controlled trial was designed to evaluate the effectiveness of an over-the-counter multistep herbal smoking cessation regimen, SmokeRx, that employs four different herbal formulations taken at different times during the program. Twenty-two subjects were randomized to a placebo group and 20 to the SmokeRx program. The results show that the odds of reduced or validated cessation of smoking were not significantly different between the groups at any juncture over the 6 months of the trial but that there was a trend for higher odds in the SmokeRx group. Subjects were also more likely to drop out of the placebo group (p = .06), suggesting a possible positive effect of the SmokeRx regimen. Overall, early dropouts (at 2 week follow-up) appeared less motivated to quit smoking, as they were more likely to be younger, had smoked more than 5 years, had greater difficulty refraining from smoking in places where it is forbidden, had fewer previous quit attempts, did not inte...

- by Gary D James
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- Nursing, Nutrition and Dietetics, Brazil, Herbal Medicine

Please cite this article in press as: Guatteo R, et al., Prevention of Coxiella burnetii shedding in infected dairy herds using a phase I C. burnetii inactivated vaccine, Vaccine (2008), 14 15 Keywords: 16 Coxiella burnetii 17 Dairy cow... more

- by Alain Joly
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- Survival Analysis, Biological Sciences, Cox Regression, Q Fever
- by Albert Figueras
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- Psychotherapy, Placebo Effect, Placebos, Mental Disorders

Non-freezing cold injury (NFCI) is a prevalent, but largely undiagnosed and poorly understood syndrome afflicting many who, as part of their work or leisure, expose their extremities to cold temperatures. The long term sequelae of NFCI are hyperhidrosis, cold-sensitivity and pain; these can last a lifetime. We tested the hypothesis that, in comparison with a placebo, sublingual glyceryl trinitrate (GTN) would increase the peripheral microcirculation during and after a mild cold challenge of individuals who had not been diagnosed with NFCI, but were cold-sensitive. Naive participants were categorised into two cohort groups: control (n = 7) or coldsensitive (n = 6). All participants undertook a standardised two minute cold exposure of their right foot while toe skin temperature (T sk ; infra-red thermograms) and blood flow (toe pad laser Doppler) were measured. GTN increased the rate of rewarming and absolute T sk of the coldest toe after the cold challenge in coldsensitive individuals. GTN also increased the blood flow in the great toe during rewarming in some coldsensitive individuals. We accept our hypothesis and suggest that the impairment in the vasodilatory response seen in individuals with cold-sensitivity can be overcome by the use of GTN, an endothelial-independent NO donor, and thereby improve the rewarming of cooled peripheral tissues.

- by Katrina Hope and +1
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- Microcirculation, Adolescent, Microvascular Physiology, Blood Pressure

Article abstract-Spasticity is a disorder of excess muscle tone associated with CNS disease. We hypothesized that botulinum toxin, a neuromuscular blocking agent, would reduce tone in spastic muscles after stroke. This randomized, double-blind, placebo-controlled, multicenter clinical trial evaluated the safety and efficacy of botulinum toxin type A (BTXA) in the treatment of chronic upper limb spasticity after stroke. Thirty-nine patients received IM injections of a total dose of either 75, 150, or 300 units of BTXA or placebo into the biceps, flexor carpi radialis, and flexor carpi ulnaris muscles. At baseline, patients demonstrated a mean wrist flexor tone of 2.9 and elbow flexor tone of 2.6 on the Ashworth Scale (0 to 4). Treatment with the 300-unit BTXA dose resulted in a statistically and clinically significant mean decrease in wrist flexor tone of 1.2 (p = 0.028), 1.1 ( p = 0.044), and 1.2 ( p = 0.026) points and elbow flexor tone of 1.2 ( p = 0.0241, 1.2 ( p = 0.028), and 1.1 ( p = 0.199) at weeks 2,4, and 6 postinjection. In the placebo group, tone reduction at the wrist was 0.3,0.2, and 0.0 and at the elbow was 0.3, 0.3, and 0.6 a t weeks 2,4, and 6 postinjection. BTXA groups reported significant

- by Michele Tagliati
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- Cognitive Science, Neurology, Skeletal muscle biology, Movement
- by Jonathan Adachi
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- Risk, Antibodies, Bone Density, Placebos
- by Gianluca Serafini
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- Psychology, Cognitive Science, Depression, Human

Background: The minimum dose of food protein to which subjects with food allergy have reacted in double-blind, placebo-controlled food challenges is between 50 and 100 mg. However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. Objective: We sought to determine whether adults previously proven by challenge to be allergic to peanut react to very low doses of peanut protein. Methods: We used a randomized, double-blind, placebo-controlled food challenge of 14 subjects allergic to peanuts with doses of peanut ranging from 10 ixg to 50 mg, administered in the form of a commercially available peanut fiour. Results: One subject had a systemic reaction to 5 mg of peanut protein, and two subjects had mild objective reactions to 2 mg and 50 mg of peanut protein, respectively. Five subjects had mild subjective reactions (1 to 5 mg and 4 to 50 mg). All subjects with convincing abjective reactions had short-lived subjective reactions to preceding doses, as low as 100 p~g in two cases. Five subjects did not react to any dose up to 50 mg. Conclusion: Even in a group of well-characterized, highly sensitive subjects with peanut allergy, the threshold dose of peanut protein varies. As little as 100 ptg of peanut protein provokes symptoms in some subjects with peanut ailergy. (J Allergy Clin Immunol 1997;100:596-600.)

- by Julie Nordlee
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- Immunology, Food Allergy, Allergy, Low Dose

The purpose of this study was to compare the effectiveness of habit reversal with a placebo control as a treatment for chronic nail biting in adults. Thirty adults with a chronic nail-biting problem (occurring > or = 5 times/day nearly every day for > or = 4 weeks and causing physical damage or social impairment) were randomly assigned to a placebo control or habit reversal group. Five participants withdrew from the study prior to the completion of treatment. The remaining individuals in both groups received a total of 2 hours of treatment over 3 sessions. Individuals in the habit reversal group (N = 13) received the components of awareness training, competing response training, and social support. Individuals in the placebo control group (N = 12) simply discussed their nail biting. At pretreatment, posttreatment, and a 5-month follow-up, nail length was measured, photographs were taken of the damaged nails and later rated by independent observers, and data on participant depr...

- by Brook Marcks
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- Anxiety Disorders, Depression, Treatment, Treatment Outcome

Objective: A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request (symptoms of most concern to patient/caregiver), which may be diluted in change scores of multisymptom scales. Method: In the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network 8-week double-blind trial of risperidone versus placebo, the chief concerns of parents were collected at 0, 4, and 8 weeks (endpoint), in addition to standardized primary measures. Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale (1 = normalized, 5 = unchanged, 9 = disastrous); 94 participants had usable data. Results:

- by Benedetto Vitiello
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- Assessment, Research Design, Autism, Clinical Trial

The use of placebo may have accompanied healing and medical practices since their origins (Plato; Charmides, 155-156). Recent experimental data indicate that we would be well advised to further consider placebo eVects in future therapeutic strategies, with a better knowledge of their potency, psychological basis and underlying neurobiological mechanisms. Current research in the areas of pain, depression and Parkinson's disease has uncovered some of the potential neurobiological mechanisms of placebo eVects. These data indicate that conscious expectation and unconscious behavioral conditioning processes appear to be the major neurobiological mechanisms capable of releasing endogenous neurotransmitters and/or neurohormones that mimic the expected or conditioned pharmacological eVects. To date, research on placebo responses aVecting immune-related diseases is scarce, but there are consistent indications that skin and mucosal inXammatory diseases, in particular, are strongly modulated by placebo treatments. However, the brain's capability to modulate peripheral immune reactivity has been impressively demonstrated by paradigms of behavioral conditioning in animal experiments and human studies. Thus, placebo eVects can beneWt end organ functioning and the overall health of the individual through positive expectations and behavioral conditioning processes.

- by Gustavo Pacheco-López
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- Psychology, Immunology, PSYCHONEUROIMMUNOLOGY, Placebo Effect