Dummy Treatment Research Articles

P-1354 - Comparative effects of venlafaxine and mirtazapine on sleep physiology measures in patients with major depresive disorder and insomnia

Sleep complaints are common in patients with major depressive disorder (MDD).Venlafaxine is an antidepressant of the serotonin -norepinephrine reuptake inhibitor class. Mirtazapine is a tetracyclic antidepressant (TeCA) used primarily in the treatment of depression. This study compares the effects of venlafaxine and mirtazapine on sleep continuity measures in DSM-IV MDD patients with insomnia. Patients (N = 37) received initial baseline polysomnography evaluations over 2 consecutive nights.Subjects were randomly assigned to either venlafaxine (75–150 mg/day) or mirtazapine (15–45mg/day)treatment for an 8 week,double -blind,double -dummy treatment trial.Single-night polysomnograms were conducted at weeks 1,2,and 8, with depression ratings assessed at baseline and weeks 1,2, 3,4, 6,and 8. Patients receiving mirtazapine (N = 20) had significant improvement in objective sleep physiology measures at 8 weeks.Improvement in sleep latency,sleep efficiency,and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment.No significant changes in sleep continuity measures were observed in the venlafaxine group (N = 17).Both groups improved clinicaly in mood and subjective sleep measures from baseline, with no differences between groups. These date demonstrate the differential effects of mirtazapine and venlafaxine with significant improvement in favor of mirtazapine ,on objective sleep parameters in MDD patients with insomnia.

Optimization of powder mixed electric discharge machining using dummy treated experimental design with analytic hierarchy process

The analytic hierarchy process (AHP) is widely used for the optimization of multiple responses from an experimental study. In the present study, a method to obtain more reliable global weight of different alternatives has been described for a powder-mixed electric discharge machining (EDM) process. Seven different process parameters were tested to study their effect on material removal rate (MRR), tool wear rate (TWR) and surface roughness (SR) using a specially designed Taguchi orthogonal array that could accommodate factors with varying number of levels. A three-level array L27 was modified to include two-level factors using dummy treatment. The process conditions that affected the three responses were identified and optimized together using AHP for high carbon high chromium (HCHCr), EN31 and hot die steel (HDS) workpiece material. Addition of powder in the dielectric improved the MRR as the electrical conductivity of powder reduces the dielectric insulating strength. Current, powder, and electrode material significantly affected the TWR. Kerosene as dielectric was observed to be a superior alternative than EDM oil. Graphite electrode worked best for HCHCr and EN31 and W–Cu electrode worked best for HDS as they globally optimize the three output variables. Also, Cu powder suspended in the dielectric resulted in an optimal solution for HCHCr and HDS and tungsten powder was seen to be a better choice for EN31 to globally optimize the responses. To overcome problems of poor finish at high current setting in EDM, the dielectric should be mixed with powder.

Hidden Administration of Drugs

In placebo-controlled trials, the placebo component of treatments is usually assessed by simulating a therapy through the administration of a dummy treatment (placebo) in order to eliminate the specific effects of the therapy. Recently, a radically different approach to the analysis of placebo responses has been implemented in which placebo responses are assessed without placebo groups. To do this, the placebo (psychological) component is eliminated by conducting hidden (unexpected) administrations of the active treatment. Compelling experimental evidence now shows that when the psychological component is eliminated through the administration of therapies unbeknownst to the patient, the effects of a variety of treatments are significantly reduced. Overall, the experimental data show that the action of different pharmacological agents can be modulated by cognitive and affective factors that can increase or decrease the effects of drugs. This experimental approach is thus a window into the complex interactions between psychology and pharmacodynamics.

Debriefing to placebo allocation: A phenomenological study of participants’ experiences in a randomized clinical trial

Question: Concealment is integral to placebo-controlled clinical trials and insures that participants remain blind to whether they are receiving real (verum) or dummy (placebo) treatment. While participants are routinely informed about and consent to be randomised to verum or placebo, they are typically never told which treatment they actually received: they are not debriefed to treatment allocation. Participants’ experiences of this aspect of trials have not been well-described. Methods: We therefore conducted an idiographic phenomenological study of four participants’ experiences of being blinded to and then debriefed to placebo allocation in a placebo-controlled clinical trial (conducted in the USA). Four participants in a trial of acupuncture for IBS were interviewed before, during, and after receiving a course of placebo treatments over 6 weeks. During the final interview they were debriefed to placebo allocation. Results: Each participant's experiences of being blinded to and then debriefed to placebo allocation are described in depth using a phenomenological approach based on the Sheffield School. All four thought they had received real acupuncture, and based their belief on a combination of embodied experiences during and after treatments, and their perceptions of their acupuncturists. They were all surprised to be told they had placebo, and did not unquestionably accept this news. Instead, they developed revised explanations that reconciled their lived experiences (of real acupuncture) with the conflicting news (of placebo acupuncture) from the interviewer. Conclusions: Our participants’ experiences of blinding and debriefing were embodied, related to their goals in undertaking the study, and social – embedded in trusting and valued relationships with acupuncturists, told to others outside the study, and described to an interviewer. This work suggests that debriefing to placebo allocation can and should be managed sensitively to facilitate positive outcomes for participants: further research should focus on developing best practice in this area.

Who controls the placebo? Introducing a Placebo Quality Checklist for pharmacological trials

Randomised placebo-controlled trials (RCT) are an invaluable tool for testing the efficacy of new treatment strategies. The choice of placebo in an RCT can affect not only patients' physical and psychological response to a particular intervention, but also the trial setting, the success of patient blinding to the intervention, and therefore the outcome of the study and the efficacy of treatment in general. Therefore the placebo is intrinsically tied to the trial's methodology and results. However, although placebos are an important component in randomised trials, their quality is often left unquestioned. A placebo which was not properly validated may even have specific effects that lead to false negative results. To address this deficit, we propose a measure of placebo quality using the term placebo to assess the physical aspect of a dummy treatment used in the placebo group of a randomised controlled trial (RCT). The Placebo Quality Checklist (PQC) described here may help investigators select an appropriate placebo and help both investigators and critical readers interpret the findings of studies with more care.

L’essai clinique contrôlé randomisé

It is generally agreed that the first comparative clinical trial in history was done by James Lind in 1747, in the treatment of scurvy. The general bases of modern experimental medicine were published by Claude Bernard in 1865. However, it is the development of new drugs and the evolution of methodological concepts that led to the first randomized controlled clinical trial, in 1948, which showed that the effects of streptomycin on pulmonary tuberculosis were significantly different from those of a placebo. Today, "evidence-based" medicine aims to rationalize the medical decision-making process by taking into account, first and foremost, the results of controlled randomized clinical trials, which provide the highest level of evidence. In the second half of the 20th century it became clear that different kinds of clinical trials might not provide the same level of evidence. Practitioners' intimate convictions must be challenged by the results of controlled clinical trials. Take the CAST trial for example, which, in 1989, tested antiarrhythmic drugs versus placebo in patients with myocardial infarction. It was well known that ventricular arrhythmias were a factor of poor prognosis in coronary heart disease, and it was therefore considered self-evident that drug suppression of these ventricular arrhythmias would reduce the mortality rate. In the event, the CAST trial showed the exact opposite, with an almost 3-fold increase in total mortality among patients with coronary heart disease who were treated with antiarrhythmic drugs. These results had a profound impact on the use of antiarrythmic drugs, which became contraindicated after myocardial infarction. A clinical trial has to fulfill certain methodological standards to be accepted as evidence-based medicine. First, a working hypothesis has to be formulated, and then the primary outcome measure must be chosen before beginning the study. An appropriate major endpoint for efficacy must be selected, in keeping with the primary outcome. One may choose either a single endpoint (for instance all-cause mortality; or a composite criterion taking into account various manifestations of the same health disorder (for instance cardiovascular mortality plus non lethal myocardial infarction plus non lethal ischemic stroke). The trial must be controlled, i.e. must compare the intervention with a standard or dummy treatment. A randomization process is used to ensure that the groups are comparable. The patients must be monitored and the results analyzed in double-blind manner The required number of patients is calculated based on the working hypothesis ("superiority" trial or "equivalence" trial), as well as the spontaneous variability of the main endpoint, and the alpha and beta statistical risks. The experimental design (cross-over or parallel groups) is chosen according to the primary outcome measure and the disease characteristics. Finally, the results must be analyzed in an intention-to-treat manner, taking into account all the patients who were initially randomized. The results of these methodologically sound trials form the basis for official therapeutic guidelines, which help physicians to choose the best treatments for their patients. However, extrapolating the results of randomized controlled clinical trials to the general patient population is not always straightforward. For instance, it is well known that patients who participate in clinical trials are highly selected and therefore somewhat unrepresentative. In addition, their numbers are limited and the treatment period is often much shorter than in routine management of a chronic disease. Finally, patients in clinical trials are monitored more closely than in routine practice. This is why we need post-marketing pharmacoepidemiological studies, in which cohorts of patients exposed to the treatment in question are monitored sufficiently long to determine the precise risk-benefit ratio. Controlled clinical trials are lacking in various fields of biomedical research, either because drug companies consider them unprofitable, or because they concern public health issues that are outside the scope of the private sector In such cases, controlled clinical trials must be undertaken and funded by the public sector Today, only North American institutions such as NIH and the National Heart Blood and Lung Institute are capable of sponsoring such trials. This creates a potential problem for extrapolation to European patient populations, which may be different. Large controlled clinical trials must start to be sponsored by public funding in Europe if European practitioners are to receive the evidence-based results they need to rationalize their medical practice.

Sunflower therapy for children with specific learning difficulties (dyslexia): A randomised, controlled trial

The aim of the study was to determine the clinical and perceived effectiveness of the Sunflower therapy in the treatment of childhood dyslexia. The Sunflower therapy includes applied kinesiology, physical manipulation, massage, homeopathy, herbal remedies and neuro-linguistic programming. A multi-centred, randomised controlled trial was undertaken with 70 dyslexic children aged 6-13 years. The research study aimed to test the research hypothesis that dyslexic children 'feel better' and 'perform better' as a result of treatment by the Sunflower therapy. Children in the treatment group and the control group were assessed using a battery of standardised cognitive, Literacy and self-esteem tests before and after the intervention. Parents of children in the treatment group gave feedback on their experience of the Sunflower therapy. Test scores were compared using the Mann Whitney, and Wilcoxon statistical tests. While both groups of children improved in some of their test scores over time, there were no statistically significant improvements in cognitive or Literacy test performance associated with the treatment. However, there were statistically significant improvements in academic self-esteem, and reading self-esteem, for the treatment group. The majority of parents (57.13%) felt that the Sunflower therapy was effective in the treatment of learning difficulties. Further research is required to verify these findings, and should include a control group receiving a dummy treatment to exclude placebo effects.

Quality of Fluidisation for the Drying of Forestry Biomass Particles in a Fluidised Bed

The objective of this work is to analyse three methods of forest biomass particles fluidisation, applied to the drying of solids. The techniques to promote fluidisation are: vibro-fluidised bed, mechanically agitated fluidised bed and fluidised bed with inert solids. The analysis of fluidisation quality was carried out by means of an orthogonal design with nested experiments and dummy treatment. The results indicated that the drying in the agitated fluidised bed is adapted to guarantee favourable conditions of homogeneity in the bed temperature: the average temperature differences in the bed were less than 0·3 °C. The high quality of fluidisation was also corroborated with high values of the coefficient of determination R 2 (0·997) for the drying curves during the period of constant drying rate.

Treatment at Random: The Ultimate Science or the Betrayal of Hippocrates?

Medicine’s principle contract with the patient has for centuries rested on traditional values espoused by the society and the physician: the restoration of health and dignity of the individual through compassionate care. The patient’s benefit has been the primary objective of medical intervention. This goal, unambiguously stated in the works of ancient Greek physicians, is explicitly declared in a code of medical practice that over the centuries has come down to us as the Hippocratic Oath. This simple principle of a beneficent medicine has secured the patient’s trust of the physician and has formulated a doctorpatient relationship with which individuals and society at large have been comfortable since antiquity. In return, society compliments the physician with high esteem. In Homer’s world of heroic deeds, “the physician is of the worth of many other men.” This relationship has been workable while the principal responsibility of care rests with the physician in a one-to-one exclusive affiliation with the patient. Corporate health care delivery, as it has evolved in the last century, whether provided by the state or the insurance company, is now challenging this unique relationship and is introducing new concepts of responsibility for the physician that are threatening to undermine medicine’s traditional character of beneficence. In the process of treating individuals, physicians are now required to consider the welfare of the state, of the society, or of the institution in which they practice. They are now asked to consider the value of life, the cost of life, and the worth of extended life! But how can the restoration of an individual’s health leave the society poorer? Why is it now necessary for the physician to declare a commitment to the interests of the society as well as to the individual patient? A practice that has emerged during the second half of the 20th century and continues unabated at the dawn of the 21st century is that of treatment allocated at random. This novel approach, often confused with therapy in the minds of physicians and unsuspecting patients, is in essence a research instrument in the service—many believe— of medical progress. Randomization involves a process by which the treatment to be allocated to an individual is not decided by the physician in charge, but by someone or something else (these days probably by a computer in a remote office that is not necessarily programmed to the individual patient’s welfare). This practice has been elevated to the “gold standard” of clinical science. This gold standard, the randomized trial, is a method of evaluation of the safety and efficacy of a novel treatment or diagnostic procedure in a group of individuals, half of whom will be subjected to the new procedure. The other half may receive a standard or established treatment, no treatment, or a dummy treatment known as a placebo. Who receives what, is a matter of chance. Why is randomization necessary? Because—it is argued—in this manner, bias in selecting patients with favorable prognostic factors for the treatment under investigation From the Parnassus, Park Hill, Loughton, Essex, United Kingdom.

Open versus hidden medical treatments: The patient's knowledge about a therapy affects the therapy outcome.

Any medical treatment has 2 components, the first being the specific effects of the treatment itself, the second, the knowledge that the treatment is being performed (the placebo effect). So far, the placebo effect has been studied by eliminating the specific effects of the therapy through the administration of a dummy treatment. In this study, the authors reversed this experimental approach. In fact, whereas the specific effects of the treatment were maintained constant, the patient's knowledge that the therapy was being performed was done away with. To do this, the authors performed hidden medical treatments and compared these with the open ones. The results show that the hidden administrations of pharmacological and nonpharmacological therapies are less effective than the open ones.

A simulation study of the nearest neighbour analysis method of papadakis

The relative performances of randomised block, balanced lattice squares and Papadakis nearest neighbour analyses were compared on two simulated fields whose soil heterogeneity profiles were generated, one with a few evenly spaced contours and the other with many unevenly spaced contours. Four levels of random error were generated to simulate different proportions of random error and soil heterogeneity. Dummy treatments, corresponding to 7 x 7 and 11 x 11 balanced lattice squares were applied to the fields. The results from simulated experiments showed an interaction of error mean square (EMS) between size of experiment (7 x 7, 11 x 11) and levels of soil heterogeneity in the lattice analyses, but no such interaction in the Papadakis analyses. The Papadakis EMS decreased as random error decreased but at a rate depending on the map andthe ratio of soil heterogeneity to random error.

Effects of agricultural cropping systems on micronutrients transformation

The effect of cropping systems of wheat-maize (WM), wheat-rice (WR), wheat-groundnut (WG), gram-bajra (GrB), potato-guara (PGu), and raya-mash (RaMa) in combination with treatments of dummy (uncultivated area) and applied Zn 0.0 (Zn0), 2.8 (Zn1), 5.6 (Zn2) 11.2 (Zn3) kg/ha was studied on the transformation of labile Zn fractions: exchangeable (Exch.), adsorbed (TAd) [weakly (WAd), moderately (MAd), strongly (SAd)], and organic matter (OM) in different layers of sandy loam soil. The added Zn stayed largely in the 0–30 cm layer and was associated with the WAd- and OM-Zn fractions. About 70% of the total labile Zn (PAv) remained in the WAd- and OM-Zn, that is, 33 and 39% in 0–15 cm layer, and 33–39% and 31–36% in 16–150 cm layer. All the Zn fractions in 0–15 cm layer, and only of WAd in 16–30 cm layer, significantly increased with rates of Zn addition. These were also significantly higher in Zn1–3 than Zn0 and dummy treatments because of the residual Zn. Diverse effects of cropping systems on soil properties, residual Zn, and labile Zn fractions were found. The influence was strong in 0–15 cm layer decreasing gradually with soil depth due largely to differences in Zn requirement, crop intake of various Zn fractions and the cultural practices of the systems. All the crops and rotations appreciabilly responded to Zn application. Uptake of Zn by crops markedly and successively increased with increasing rates of Zn application. The WR caused a significant increase in soil organic matter whereas WR and WM in CaCO3. The WR, WM and GrB resulted in a decrease in pH while WG and GrB in CaCO3. The RaMa and PGu maintained much higher residual Zn than other systems. The systems which caused the maximum decrease in Zn fractions were: cereal-cereal (WM) in Exch. legume-millet (GrB) in all the adsorbed, PAv and the Zn associated with CaCO3, vegetable-legume (PGu) also in MAd and SAd; and cereal-legume (WG) in OM and PAv. Hence GrB, WG and WM in that order will cause the deficiency of Zn much earlier than the other systems due to greater use and or transformation of WAd- andOM-Zn. Such effects were least under RaMa because it increased the WAd-, MAd- and OM-Zn.

306. Note: Some Aspects of 2 n Factorials with Dummy Treatments

306. Note: Some Aspects of 2 n Factorials with Dummy Treatments

Quality X Quantity Interaction

Fisher (4), in a reply to a query to this journal, has discussed the estimation of the effect of quality and of the quality X quantity interaction in the case of an experiment with 4 qualities of a fertiliser at 3 equally spaced levels, the lowest of which is not zero. As the originator of this query, my object was to obtain information concerning the general case of a situation common in experimentation. Textbooks are not very illuminating, since they all deal with the same special case, that of a number of qualities at 3 equally spaced levels, the lowest of which is zero, so that dummy treatments occur at the zero level. Thus Fisher (3) shows that the ordinary subdivision (based on a hypothesis of independent additive effects of the factors) of the sum of squares of such an interaction table into sums of squares for main effects, dummy effects, and interaction is unsatisfactory, and proposes the more natural hypothesis that quality differences are proportional to quantity applied instead of constant for all quantities. He describes his estimation of quality effects as e'calculating the 'regression' of the manurial response upon the manurial difference to which it is for the present purpose to be considered as proportional. An alternative orthogonal subdivision of the sums of squares for quality and for interaction of quality and quantity (as obtained in an ordinary interaction table) is based on the identity

Studies on the effects of temperature of irrigating water upon the growth and yields of rice plant

1) The main object of this experiment is to make sure whether the high temperature of irrigating water in the daytime of midsummer in the Kyushu region is harmful to rice plant or not and also to examine it's possibility of being a cause of “AKI-OCHI”.2) The rice plants were grown in 12 plots. They were divided into 3 plots according to the kind of treatment. Plot A: the irrigating water was kept hot about 40°C only in the daytime and kept in natural state daring the night. Plot B: the irrigating water was kept cold about 2°C merely in the daytime and kept in natural state during the night. Plot C: the check plot in natural state throughout all the day.Each plot was subdivided into 4 plots according to the period of treatment. Aw, Bw, Cw plots were treated from the early tillering stage till the heading. A1, B1, C1 plots were treated from the early tillering stage till the stage of highest number in tillers. A2, B2, C2 plots were treated from the end of A1, B1, C1 treatment till one week after ear formation period. A3, B3, C3 plots were treated from the end of A2, B2, C2 treatment till the heading. (Aw, A1, A2 and A3 plots are of dummy treatment.)3) The growth in plot A was suppressed during the treatment, but recovered soon after the treatment. The color of leaves became deep when the treatment began and the effect continued for a long time, and the heading came a little later. Most of the leaves therein had been kept green for 20 days after the heading and they began to wither a little later, but those in plot B a little earlier. The difference of the yield between plots A and C was not significant, and the yield in B plot was less than in C plot.The difference of the yield with the treated periods was not significant, but there was a tendency that plots Aw and Bw were slightly inferior, and plots A1 and A2 were a little superior to check plot.4) The harmful period of high temperature observed under natural conditions corresponds roughly to the period of treatment in plots A1 and A2. Precise conclusions can not be obtained unless the field experiment is carried out but the results of this experiment seem to show that the natural high temperature of irrigating water in midsummer in the Kyushu region has not a bad effect upon the rice plant.Cultivating race plants in constant temperature, many eminent investigators have obtained the results that the optimum temperature of irrigating water for rice plants is 30-34°C, and the temperature over 36°C is extremely harmful, and that the temperature 39°C shows only very meager growth. But it has been found that when the irrigating water is kept about 40°C in the daytime and in natural state during the night, the high temperature has not a remarkable bad effect upon the rice plant.