Placebo Side Research Articles

Effects of low‐level laser therapy on the rate of orthodontic tooth movement

To test the hypothesis that mechanical forces combined with low-level laser therapy stimulate the rate of orthodontic tooth movement. This study was a double blind, randomized placebo/control matched pairs clinical trial to test the efficacy of GaAlAs low-level laser therapy (LLLT) on 12 young adult patients who required retraction of maxillary canines into first premolar extraction spaces using tension coil springs with fixed edgewise appliance. LLLT was applied on the mucosa buccally, distally and palatally to the canine on the test side and using a pseudo-application on the placebo side. Dental impressions and casts were made at the commencement of the trial and at the end of the first, second and third months after starting the trial. Measurement of tooth movements was made on each stage model using a stereo microscope. There was no significant difference of means of the canine distal movement between the LLLT side and the placebo side for any time periods (p-value = 0.77). The energy density of LLLT (GaAlAs) at the surface level in this study (25 J/cm(2)) was probably too low to express either stimulatory effect or inhibitory effect on the rate of orthodontic tooth movement.

Brain Activity Associated with Expectancy-Enhanced Placebo Analgesia as Measured by Functional Magnetic Resonance Imaging

In this study, a well established expectancy manipulation model was combined with a novel placebo intervention, a validated sham acupuncture needle, to investigate the brain network involved in placebo analgesia. Sixteen subjects completed the experiment. We found that after placebo acupuncture treatment, subjective pain rating reduction (pre minus post) on the placebo-treated side was significantly greater than on the control side. When we calculated the contrast that subtracts the functional magnetic resonance imaging (fMRI) signal difference between post-treatment and pretreatment during pain application on placebo side from the same difference on control side [e.g., placebo (post - pre) - control (post - pre)], significant differences were observed in the bilateral rostral anterior cingulate cortex (rACC), lateral prefrontal cortex, right anterior insula, supramarginal gyrus, and left inferior parietal lobule. The simple regression (correlation) analysis between each subject's fMRI signal difference of post-treatment and pretreatment difference on placebo and control side and the corresponding subjective pain rating difference showed that significant negative correlation was observed in the bilateral lateral/orbital prefrontal cortex, rACC, cerebellum, right fusiform, parahippocampus, and pons. These results are different from a previous study that found decreased activity in pain-sensitive regions such as the thalamus, insula, and ACC when comparing the response to noxious stimuli applied to control and placebo cream-treated areas of the skin. Our results suggest that placebo analgesia may be configured through multiple brain pathways and mechanisms.

The short‐term effects of low‐level lasers as adjunct therapy in the treatment of periodontal inflammation

The aim of this split-mouth, double-blind controlled clinical trial was to study the effects of irradiation with low-level lasers as an adjunctive treatment of inflamed gingival tissue. Seventeen patients with moderate periodontitis were included. After clinical examination, all teeth were scaled and root planed (SRP). One week after SRP, we took samples of gingival crevicular fluid (GCF) and subgingival plaque. The laser therapy was started 1 week later and continued once a week for 6 weeks. One side of the upper jaw was treated with active laser and the other with a placebo. The test side was treated with two low-level lasers having wavelengths of 635 and 830 nm. The patients then underwent another clinical examination with sampling of GCF and plaque. The GCF samples were analysed for elastase activity, interleukin-1beta (IL-1beta) and metalloproteinase-8 (MMP-8). We examined the subgingival plaque for 12 bacteria using DNA probes. The clinical variables i.e. probing pocket depth, plaque and gingival indices were reduced more on the laser side than on the placebo one (p<0.01). The decrease in GCF volume was also greater on the laser side, 0, 12 microl, than on the placebo side, 0.05 microl (p=0.01). The total amount of MMP-8 increased on the placebo side but was slightly lower on the laser side (p=0.052). Elastase activity, IL-1beta concentration and the microbiological analyses showed no significant differences between the laser and placebo sides. Additional treatment with low-level lasers reduced periodontal gingival inflammation.

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis.

The placebo drug reactions from controlled trials were studied for the first time systematically for efficacy and the safety in drug data pooled from randomized, placebo-controlled, multicentre studies. The efficacy of placebo on clinical symptoms and outcome varied between the therapeutic indications. However, no placebo effects on laboratory values, as e.g. blood glucose or Hb1c in diabetics, were noted. The frequency and type of placebo-induced adverse reactions also varied between indication groups. The placebo side effect profile was largely similar to the side effect profile of the active treatment. The mechanisms of placebo effects are many fold and varied (e.g. endorphin release, conditioning), much lacks explanation. Since the prescription of non-evidence based medicines (= pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful. In clinical research, the judicious use of placebo remains essential to establish the efficacy and safety, safeguarding that patients receiving placebo will not be subject to harm and are fully informed.

Double-Blind, Half-Face Study Comparing Topical Vitamin C and Vehicle for Rejuvenation of Photodamage

BACKGROUND Aging of the population, in particular the “baby boomers,” has resulted in increased interest in methods of reversal of photodamage. Non-invasive treatments are in high demand, and our knowledge of mechanisms of photodamage to skin, protection of the skin, and repair of photodamage are becoming more sophisticated and complex. OBJECTIVE The objective of this study is to determine if the topical use of a vitamin C preparation can stimulate the skin to repair photodamage and result in clinically visible differences, as well as microscopically visible improvement. METHODS Ten patients applied in a double-blind manner a newly formulated vitamin C complex having 10% ascorbic acid (water soluble) and 7% tetrahexyldecyl ascorbate (lipid soluble) in an anhydrous polysilicone gel base to one-half of the face and the inactive polysilicone gel base to the opposite side. Clincial evaluation of wrinkling, pigmentation, inflammation, and hydration was performed prior to the study and at weeks 4, 8, and 12. Two mm punch biopsies of the lateral cheeks were performed at 12 weeks in four patients and stained with hematoxylin and eosin, as well as in situ hybridization studies using an anti-sense probe for mRNA for type I collagen. A questionnaire was also completed by each patient. RESULTS A statistically significant improvement of the vitamin C-treated side was seen in the decreased photoaging scores of the cheeks (P = 0.006) and the peri-oral area (P = 0.01). The peri-orbital area improved bilaterally, probably indicating improved hydration. The overall facial improvement of the vitamin C side was statistically significant (P = 0.01). Biopsies showed increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen. No patients were found to have any evidence of inflammation. Hydration was improved bilaterally. Four patients felt that the vitamin C-treated side improved unilaterally. No patient felt the placebo side showed unilateral improvement. CONCLUSION This formulation of vitamin C results in clinically visible and statistically significant improvement in wrinkling when used topically for 12 weeks. This clinical improvement correlates with biopsy evidence of new collagen formation.

REDUCTION IN PAIN ASSOCIATED WITH OPEN CARPAL TUNNEL DECOMPRESSION

Patients treated by open carpal tunnel decompression under local anaesthetic experience significant pain with the introduction of local anaesthetic before operation. A prospective double-blind randomized placebo controlled trial was carried out to assess whether this pain could be reduced with the pre-application of a topical lignocaine-prilocaine anaesthetic cream. Nineteen patients undergoing simultaneous bilateral operations were studied. Pain, measured with a visual analogue scale, was significantly reduced on the sides treated with anaesthetic cream. On a four point verbal scale the rating on the placebo side was “moderate” or “severe”, compared to “mild” on the anaesthetic cream side. The reduction in pain was greater in women, possibly due to a relatively thinner dermis. There were no adverse effects.

The Effect of Oral Pyridostigmine Bromide Nerve Agent Prophylaxis on Return of Twitch Height in Persons Receiving Succinylcholine

Prophylactic pyridostigmine is used for troops under threat of organophosphate exposure and can affect the neuromuscular blocking agent succinylcholine. The purpose of this study was to determine what effect pyridostigmine would have on neuromuscular blockade from succinylcholine. Thirty-nine subjects were enrolled in this double-blind, placebo-controlled investigation and assigned to either the pyridostigmine or the placebo group. All subjects were evaluated for pyridostigmine or placebo side effects and given an anesthesia induction that included the neuromuscular blocking agent succinylcholine. Neuromuscular blockade was measured by twitch height with a nerve stimulator. Interval data were analyzed using the chi 2 test and Student's t test. The pyridostigmine group demonstrated a prolonged recovery time to return of 25% (p = 0.003) and 75% (p = 0.028) of twitch height compared with the placebo group. No differences were noted for any other parameter measured. We conclude that the recovery from neuromuscular blockade after succinylcholine is prolonged while the intubating conditions remain unaffected.

Effect of 'Compound R' on thermal burn and full-depth wound contracture in fuzzy rats.

We evaluated the efficacy of Compound R emulsion on wound contraction in fuzzy rats. While the rats were under anesthesia, two mirror-image burn wounds were inflicted on the depilated back skin of each. Wounds were assigned randomly to treatment or placebo (oil), and the wound-scar areas were measured when they healed. A second set of wounds was created by taking two 6 millimeter punch biopsies from each rat and treated with Compound R or placebo. Under anesthesia, areas of the wound were measured on days 0, 5, 8 and on healing. Mean+/-SE areas for the healed burn wounds were: 151+/-24 mm2 for the treated and 102+/-26 mm2 for the placebo side (paired Student's t test, t=4.21, p=0.0015). Areas for Compound R-treated punch biopsy-induced wounds were significantly larger than placebo treated at each time point (p < 0.01). Results from this study show that Compound R impeded wound contraction.

Estrogen regulation of adipose tissue lipoprotein lipase—Possible mechanism of body fat distribution

OBJECTIVE: The purpose of this study was to evaluate the regulation of lipoprotein lipase activity, protein mass, and messenger ribonucleic acid by estradiol. STUDY DESIGN: Premenopausal women not taking exogenous sex steroids had transdermal 17β-estradiol and placebo patches placed in the gluteal region during the early follicular phase of the menstrual cycle. Adipose biopsies were performed from beneath the patches. Adipose tissue lipoprotein lipase activity was determined by a radiometric assay, protein mass was determined by enzyme-linked immunosorbent assay, and messenger ribonucleic acid level was determined by Northern analysis. Comparisons between the treated and placebo sides were analyzed by nonparametric statistics. RESULTS: Adipose tissue from beneath the 17β-estradiol patch had significantly decreased lipoprotein lipase activity and extracellular protein mass than did adipose tissue from beneath the placebo patch. There was no difference in lipoprotein lipase messenger ribonucleic acid levels. CONCLUSIONS: Estrogen decreases lipoprotein lipase activity by a posttranscriptional modification of protein levels. A hypothesis of sex steroid regulation of body fat distribution is proposed. (Am J Obstet Gynecol 1998;178:101-7.)

The effect of soft-laser application on postoperative pain and swelling: A double-blind, crossover study

The effect of soft-laser application on postoperative pain and swelling was evaluated in a double-blind, crossover study. Twenty-five healthy adults with bilateral identically impacted lower third molars were selected for this study. The teeth were removed in two separate operations. Laser treatment was tested in comparison with placebo laser, with a 40-mW, 830-nm Biophoton laser (Roenvig Dental, Denmark). All surgical procedures and measurements were done by the same surgeon. The following features were statistically analyzed: swelling, trismus, and subjective registration of pain on a visual analog scale. No statistically significant differences were observed in comparison of the experimental side with the placebo side. It may be concluded that soft-laser treatment has no beneficial effect on swelling, trismus, and pain after third molar surgery.

A randomised double blind comparative study of low level laser therapy following surgical extraction of lower third molar teeth

A randomised, double blind comparative study was undertaken to assess the efficacy of low level laser therapy in the reduction of postoperative pain and swelling in patients undergoing the extraction of bilaterally impacted mandibular third molar teeth. Healing of the sockets was also compared after 1 week. A group of 64 patients had one randomly-selected operation side treated with a semi-conductor laser and the other side with an apparently identical but non-operating model. Complete data were obtained from 52 of the 64 patients. The results showed that there was no evidence of a difference in pain and swelling on the third day after operation between laser and placebo sides. There was no difference between the two sides when they were assessed for healing 7 days after surgery.

Mutans streptococci in saliva and interdental spaces after topical applications of an antibacterial varnish in schoolchildren

The effect of a chlorhexidine-containing varnish on the levels of mutans streptococci in saliva and in interdental spaces was investigated in 33 15-year-old schoolchildren. Each child was treated with an active (1% chlorhexidine; 1% thymol) and a placebo varnish preparation following the split-mouth technique. The varnishes were applied twice in small amounts into upper interdental areas with a 2-d interval. Mutans streptococci in saliva and interdental plaque was sampled and enumerated during 3 months. The results showed an immediate reduction of the number of interdental mutans streptococci on both test and placebo side after the varnish applications. The levels, however, were significantly lower in the test quadrants compared with the placebo-treated sides after 8, 30 and 90 d. Thus, the findings indicate a slower recolonization in interdental spaces treated with the active preparation. The levels of mutans streptococci in saliva were significantly reduced 1 and 3 months after varnish treatment, suggesting a long-term effect of the antibacterial varnish.

Probability and nature of misattribution of drug side effects

AbstractThere are situations in which physicians must rely on drug side effects to identify a preparation, and in drug research, the blind condition is often compromised owing to assumptions based on side effects. This study sought to sensitize practitioners and researchers to the “pharmacologic” action of placebos inclusive of side effects. In a survey of practicing physicians, a cluster of typically reported placebo side effects was presented with the task of identifying the pharmacologic‐therapeutic category to which this unidentified contributing preparation might belong. Only 5% correct identification was evidenced, and a significant bias toward classification of placebo side effects as representative of antihistamine or autonomic preparations was noted. These specific biases were evident both when considering a chance distribution of classification responses and national prescription patterns. Implications for practice and research are discussed.

Methodological issues in drug assessment research

AbstractIncreased sensitivity to methodological issues in drug assessment research is needed in light of challenges to research design, conduct, and outcomes. Major issues presented include (a) the nature and adequacy of placebo controls, (b) problems in maintaining the integrity of “blind” conditions, and (c) the potential design‐compromising effects of informed consent. The necessity of true matching placebos, particularly concerning physical/perceptual characteristics and the ability to produce transitory changes in subjects, was stressed. Though the double‐blind condition has conceptual integrity, the operation of drug and placebo side effects and associated guess bias may confound research results. Use of a triple‐blind condition and addition of a drug‐disguised group is suggested. Last, the issue of informed consent and its implications for the integrity of drug research is a problem deserving more attention.

How disturbing are side effects of beta blockers.

Drug side effects are notoriously difficult to evaluate accurately. In this particular context there are further problems arising from the exclusion of many patients in some of the few published series of populations exposed to beta-blocking drugs. In some of these same series, placebo side effects appear to affect almost as many patients as the active drug. However, detailed breakdown of these side effects show significant differences in the actual complaints made by patients of each group. Apart from the well known major complications of beta-blocking drugs, the lesser but still disturbing ones to mention include generalized fatigue, muscle weakness, cold extremities, nightmares and impotence. A change of beta-blocking preparation or else lowering the dosage often ameliorates these problems.

The Use of Prophylactic Penicillin in Periodontal Surgery

In an attempt to prevent postoperative sequellae dentists often prescribe penicillin or other antibiotics following periodontal surgery. A review of the literature shows conflicting reports about this procedure. This study investigated the efficacy of prophylactic penicillin in 19 human subjects undergoing periodontal surgery. Following initial therapy, flap surgery was undertaken in at least two comparable quadrants in each patient. Using a split mouth technique, patients were either given phenoxymethyl penicillin or a placebo following flap surgery for 5 days. Pain, infection, plaque levels, gingivitis and crevicular fluid flow were measured during a 4 week period. There were no differences between the placebo or penicillin sides in any of the parameters studied, except that the pain experience was significantly lower on the penicillin operated side. Within the limitations of this study it is difficult to substantiate the routine use of antibiotics following periodontal surgery.

Tranexamic acid in alveolar sockets in the prevention of alveolitis sicca dolorosa

The effect of trans-4-amino-methyl-cyclohexane acid (AMCA) and a placebo preparation on the development of alveolitis sicca dolorosa (ASD) was investigated in a double-blind designed experiment. The preoperative registrations were age, sex, use of oral contraceptives, menstrual cycle, smoking, degree of impaction and operation time. The study included 120 healthy persons. Each person had bilateral impacted mandibular molars removed surgically at one session. AMCA (160 mg/extraction site) or placebo was applied in each socket after the operation. The postoperative course was evaluated on average 5 days later by the use of 13 different variables describing local and general discomfort. The incidence of ASD was 7.5 % in the AMCA side and 5.0 % in the placebo side. The result shows that a local inhibition of plasminogen activation by AMCA is insufficient to prevent the development of ASD. The occurrence of ASD and postoperative discomfort was not increased in women operated during the menstrual period. The usage of oral contraceptives is known to be associated with a high frequency of ASD. Women taking oral contraceptives may therefore postpone the operation to the withdrawal period of the pill, to reduce the risk of developing ASD. Postoperative pains and the consumption of analgetics were significantly increased in patients who were habitual smokers.

The effect of attributing internal arousal to an external source upon test anxiety and performance.

Summary Schachter's (13) theory of emotions as cognitive “labels” attached to undifferentiated states of internal arousal was applied to findings of Sarason (10) and his colleagues concerning the performance effects of test anxiety. The results supported Sarason's data in indicating that, under ordinary circumstances, the high-anxious individual performs less well than the low on a difficult and threatening task. It was further predicted and discovered that the highly test anxious person who was led to ascribe his internal arousal to the side effects of a placebo performed as well as less anxious subjects and better than other highly test anxious people who were unable to attribute their anxiety symptoms to placebo side effects.

Clindamycin and Colitis

Comments and Correction1 February 1975Clindamycin and ColitisANDREW S JACOBANDREW S JACOBSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-2-279_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The report of Tedesco, Barton, and Alpers (Ann Intern Med81:429-433, 1974) of an association of colitis with clindamycin use is lacking a placebo group as a necessary control. The authors report a 21% incidence of diarrhea and a 10% incidence of pseudomembranous colitis in patients given clindamycin. However, when these patients were begun on the drug, they were "interviewed with special attention given to bowel habits." It is possible that placebo side effects, caused by physician concern about the patient's bowel habits, are responsible for the side effects. The inclusion, in their study, of a similarly...