Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine A Report of the International Placebo Symposium Working Group

Compared with other specialties, the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments. The best way to change this disadvantage is through a well conducted clinical research, such as standard placebo- or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in physical and rehabilitation medicine that ultimately translates to better clinical care. To address the challenges for the use of placebo in physical and rehabilitation medicine and randomized clinical trials and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in physical and rehabilitation medicine, (2) challenges for the use of placebo in physical and rehabilitation medicine, (3) bioethics, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group.

Nutritional recommendation alone does not change the obesity profile of health professionals

Objective: To evaluate the frequency of overweight and obesity in health professionals, before and after a single specialized dietary recommendation. Methods: Anthropometric measures of 579 workers of a general hospital in the city of Sao Paulo, Brazil were taken. The weight (f), height (h) and waist circumference (wc) were interpreted according to the WHO and NCEP ATP III guidelines. Nutrition specialist provided dietary and behavioral recommendations. The entire sample underwent a new evaluation one year later. Results: At the first evaluation, 79 employees presente WC >= 102 cm (male) or WC >= 88 cm (female). The association between WC >= 102 cm (men) or WC >= 88 cm (women) and BMI >= 30 kg/m(2) was found in 12.8 % (69 subjects). The BMI distribution per age group indicated that the increase in overweight and obesity was directly proportional to the age increase. Physical activities were not practiced by 75% of the subjects studied. A year later, the evaluation indicated lack of statistical differences regarding the BMI and waist circumference of the sample and only 2.8% started to practice a physical activity. Conclusion: Dietary recommendation alone failed to promote changes in the eating habits of health professionals who work at a general hospital or to encourage them to practice exercise.

Can eccentric arterial plaques alone cause flow stagnation points and favour thrombus incorporation?

We have used an experimental model of aorta stenosis, with a Plexiglas plug, simulating a stable atheromatous plaque that promotes local turbulence and thrombosis. With animal survival of more than 24 h, we followed the partial fibrinolysis of the thrombus as well as its posterior organization and incorporation to the arterial wall as a neointima for up to 30 days. The mushroom plug form permitted the development of recirculation and stasis areas around it, favouring this evolution. Despite noted limitations, this study demonstrates that thrombus incorporation can contribute to plaque extension, as it can promote recirculation and stasis areas.

Processing Speed and Working Memory Span: Their Differential Role in Superficial and Deep Memory Processes in Schizophrenia

Previous work has suggested that decrement in both processing speed and working memory span plays a role in the memory impairment observed in patients with schizophrenia. We undertook a study to examine simultaneously the effect of these two factors. A sample of 49 patients with schizophrenia and 43 healthy controls underwent a battery of verbal and visual memory tasks. Superficial and deep encoding memory measures were tallied. We conducted regression analyses on the various memory measures, using processing speed and working memory span as independent variables. In the patient group, processing speed was a significant predictor of superficial and deep memory measures in verbal and visual memory. Working memory span was an additional significant predictor of the deep memory measures only. Regression analyses involving all participants revealed that the effect of diagnosis on all the deep encoding memory measures was reduced to non-significance when processing speed was entered in the regression. Decreased processing speed is involved in verbal and visual memory deficit in patients, whether the task require superficial or deep encoding. Working memory is involved only insofar as the task requires a certain amount of effort. (JINS, 2011, 17, 485-493)

Comparison of the effects of tramadol, codeine, and ketoprofen alone or in combination on postoperative pain and on concentrations of blood glucose, serum cortisol, and serum interleukin-6 in dogs undergoing maxillectomy or mandibulectomy

Objective-To compare analgesic effects of tramadol, codeine, and ketoprofen administered alone and in combination and their effects on concentrations of blood glucose, serum cortisol, and serum interleukin (IL)-6 in dogs undergoing maxillectomy or mandibulectomy. Animals-42 dogs with oral neoplasms. Procedures-30 minutes before the end of surgery, dogs received SC injections of tramadol (2 mg/kg), codeine (2 mg/kg), ketoprofen (2 mg/kg), tramadol + ketoprofen, or codeine + ketoprofen (at the aforementioned dosages). Physiologic variables, analgesia, and sedation were measured before (baseline) and 1, 2, 3, 4, 5, and 24 hours after surgery. Blood glucose, serum cortisol, and serum IL-6 concentrations were measured 1, 3, 5, and 24 hours after administration of analgesics. Results-All treatments provided adequate postoperative analgesia. Significant increases in mean +/- SD blood glucose concentrations were detected in dogs receiving tramadol (96 +/- 14 mg/dL), codeine (120 +/- 66 mg/dL and 96 +/- 21 mg/dL), ketoprofen (105 +/- 22 mg/dL), and codeine + ketoprofen (104 +/- 16 mg/dL) at 5, 1 and 3, 5, and 3 hours after analgesic administration, respectively, compared with preoperative (baseline) values. There were no significant changes in physiologic variables, serum IL-6 concentrations, or serum cortisol concentrations. Dogs administered codeine + ketoprofen had light but significant sedation at 4, 5, and 24 hours. Conclusions and Clinical Relevance-Opioids alone or in combination with an NSAID promoted analgesia without adverse effects during the 24-hour postoperative period in dogs undergoing maxillectomy or mandibulectomy for removal of oral neoplasms. (Am J Vet Res 2010;71:1019-1026)

Accuracy of working length determination using 3 electronic apex locators and direct digital radiography

Objectives. The objectives of this study were to assess the accuracy of working length determination using 3 electronic apex locators and direct digital radiography and to compare the results with those obtained using the visual method (control measurement). Study design. Twenty extracted human maxillary premolars were selected: 17 two-rooted and 3 single-rooted (total of 37 canals). Working length was measured using electronic apex locators Elements Diagnostic, Root ZX, and Just II. Subsequently, teeth were positioned in the alveolar bone of a dry skull and submitted to direct digital radiography. A variation of +/- 1 mm was considered as acceptable. Results were analyzed using the Wilcoxon and the chi(2) tests. Results. Results presented an accuracy of 94.6% for Elements Diagnostic, 91.9% for Root ZX, 73.0% for Just II, and 64.9% for direct digital radiography when considering the margin of +/- 1 mm in relation to the control measurement. Comparisons with the actual control measurements resulted in accuracy results of 13.51%, 13.51%, 10.10%, and 2.70%, respectively. Conclusions. Root ZX and Elements Diagnostic are more accurate in determining working length when compared with Just II and Schick direct digital radiography. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111:e44-e49)

Influence of dentin on pH of 2% chlorhexidine gel and calcium hydroxide alone or in combination

The aims of endodontic treatment in cases of apical periodontitis are to reduce as much as possible the number of microorganisms inside the root canal system and to inactivate toxins produced by them. Most of the times, these objectives are not achieved solely by chemomechanical preparation, and intracanal dressing may be necessary. In these cases, calcium hydroxide is used as a root canal dressing due to its well-known and recognized antimicrobial activity. Chlorhexidine has a wide spectrum of antimicrobial activity and its association with calcium hydroxide has been recommended in an attempt to amplify antimicrobial effects of calcium hydroxide. It is also known that dentin exerts a buffering effect under wide pH variations, and may be responsible for decreasing the antimicrobial activity of drugs inside the root canal. The objectives of this study were to assess the pH of 2% chlorhexidine gel and calcium hydroxide alone or in combination, as well as the influence of dentin on the pH of these compounds. Dentin powder was obtained from bovine teeth and added as 1.8% to the volume of the medications. All substances were individually stored in plastic flasks, in triplicate. A pH meter was used at five different moments to assess pH in viscous medium: immediately after preparation and after 24 h, and 7, 14, and 21 days. Results were analyzed by paired Student`s t-test. Statistically significant differences were observed in the 2% chlorhexidine gel group alone or associated with calcium hydroxide and added of dentin powder (P < 0.05). Mean pH values indicated the influence of dentin powder because of a significant increase in pH. Calcium hydroxide with propylene glycol as the vehicle always showed high pH, demonstrating that this compound was not affected by the presence of dentin.

Electronic working length determination in primary teeth by Propex and Digital Signal Processing

The purpose of this study was to evaluate the accuracy of electronic apex locators Digital Signal Processing (DSP) and ProPex, for root canal length determination in primary teeth. Fifteen primary molars (a total of 34 root canals) were divided into two groups: Group I - without physiological resorption (n = 16); and Group II - with physiological resorption (n = 18). The length of each canal was measured by introducing a file until its tip was visible and then it was retracted 1 mm. For electronic measurement, the devices were set to 1 mm short of the apical resorption. The data were analysed statistically using the intraclass correlation coefficient (ICC). Results showed that the ICC was high for both electronic apex locators in all situations - with (ICC: DSP = 0.82 and Propex = 0.89) or without resorption (ICC: DSP = 0.92 and Propex = 0.90). Both apex locators were extremely accurate in determining the working length in primary teeth, both with or without physiological resorption.

Explaining sleep duration in adolescents: The impact of socio-demographic and lifestyle factors and working status

Previous studies found students who both work and attend school undergo a partial sleep deprivation that accumulates across the week. The aim of the present study was to obtain information using a questionnaire on a number of variables (e.g., socio-demographics, lifestyle, work timing, and sleep-wake habits) considered to impact on sleep duration of working (n = 51) and non-working (n = 41) high-school students aged 14-21 yrs old attending evening classes (19:00-22:30h) at a public school in the city of Sao Paulo, Brazil. Data were collected for working days and days off. Multiple linear regression analyses were performed to assess the factors associated with sleep duration on weekdays and weekends. Work, sex, age, smoking, consumption of alcohol and caffeine, and physical activity were considered control variables. Significant predictors of sleep duration were: work (p < 0.01), daily work duration (8-10h/day; p < 0.01), sex (p = 0.04), age 18-21 yrs (0.01), smoking (p = 0.02) and drinking habits (p = 0.03), irregular physical exercise (p < 0.01), ease of falling asleep (p = 0.04), and the sleep-wake cycle variables of napping (p < 0.01), nocturnal awakenings (p < 0.01), and mid-sleep regularity (p < 0.01). The results confirm the hypotheses that young students who work and attend school showed a reduction in night-time sleep duration. Sleep deprivation across the week, particularly in students working 8-10h/day, is manifested through a sleep rebound (i.e., extended sleep duration) on Saturdays. However, the different roles played by socio-demographic and lifestyle variables have proven to be factors that intervene with nocturnal sleep duration. The variables related to the sleep-wake cyclenaps and night awakeningsproved to be associated with a slight reduction in night-time sleep, while regularity in sleep and wake-up schedules was shown to be associated with more extended sleep duration, with a distinct expression along the week and the weekend. Having to attend school and work, coupled with other socio-demographic and lifestyle factors, creates an unfavorable scenario for satisfactory sleep duration.

Working at night and work ability among nursing personnel: when precarious employment makes the difference

To test the association between night work and work ability, and verify whether the type of contractual employment has any influence over this association. Permanent workers (N = 642) and workers with precarious jobs (temporary contract or outsourced; N = 552) were interviewed and filled out questionnaires concerning work hours and work ability index. They were classified into: never worked at night, ex-night workers, currently working up to five nights, and currently working at least six nights/2-week span. After adjusting for socio-demography and work variables, current night work was significantly associated with inadequate WAI (vs. day work with no experience in night work) only for precarious workers (OR 2.00, CI 1.01-3.95 and OR 1.85, CI 1.09-3.13 for those working up to five nights and those working at least six nights in 2 weeks, respectively). Unequal opportunities at work and little experience in night work among precarious workers may explain their higher susceptibility to night work.

Compatibility and decomposition kinetics studies of prednicarbate alone and associated with glyceryl stearate

In this work, TG/DTG and DSC techniques were used to the determination of thermal behavior of prednicarbate alone and associated with glyceryl stearate excipient ( 1: 1 physical mixture). TG/DTG curves obtained for the binary mixture showed a reduction of approximately 37 degrees C to the thermal stability of drug (T(dm/dt-0) (Max)(DTG)). The disappearance of stretching band at 1280 cm(-1) (nu(as) C-O, carbonate group) and the presence of streching band with less intensity at 1750 cm(-1) (nu(s) C-O, ester group) in IR spectrum obtained to the binary mixture submitted at 220 degrees C, when compared with IR spectrum of drug submitted to the same temperature, confirmed the chemical interaction between these substances due to heating. Kinetics parameters of decomposition reaction of prednicarbate were obtained using isothermal (Arrhenius equation) and non-isothermal (Ozawa) methods. The reduction of approximately 45% of activation energy value (E(a)) to the first step of thermal decomposition reaction of drug in the 1:1 (mass/mass) physical mixture was observed by both kinetics methods.