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.

Rehabilitation of executive dysfunction: A controlled trial of an attention and problem solving treatment group

In this study, the effectiveness of a group-based attention and problem solving (APS) treatment approach to executive impairments in patients with frontal lobe lesions was investigated. Thirty participants with lesions in the frontal lobes, 16 with left frontal (LF) and 14 with right frontal (RF) lesions, were allocated into three groups, each with 10 participants. The APS treatment was initially compared to two other control conditions, an information/education (IE) approach and treatment-as-usual or traditional rehabilitation (TR), with each of the control groups subsequently receiving the APS intervention in a crossover design. This design allowed for an evaluation of the treatment through assessment before and after treatment and on follow up, six months later. There was an improvement on some executive and functional measures after the implementation of the APS programme in the three groups. Size, and to a lesser extent laterality, of lesion affected baseline performance on measures of executive function, but there was no apparent relationship between size, laterality or site of lesion and level of benefit from the treatment intervention. The results were discussed in terms of models of executive functioning and the effectiveness of domain specific interventions in the rehabilitation of executive dysfunction.

The efficacy of functional endoscopic sinus surgery in the evolution of fever of unknown origin in ICU patients

Conclusion: Functional endoscopic sinus surgery (FESS) was found to be effective in treating fever of unknown origin (FUO) in intensive care unit (ICU) patients with rhinosinusitis, with 62% of patients showing improvement within 5 days of the procedure. Objective: To correlate improvement in FUO with FESS drainage of the paranasal sinuses. Methods: Fifty patients that developed FUO during ICU stay, with CT findings suggestive of rhinosinusitis, and showed no improvement in fever after clinical treatment underwent FESS for drainage of the paranasal sinuses and were evaluated for postoperative improvement of fever. Results: The study sample consisted of 50 patients (74% of whom were male, mean age 48.1 years). The most frequent diagnoses at ICU admission were tetanus, pulmonary disease, and cardiovascular disease. In all, 68% of patients underwent nasogastric or enteral intubation. CT scanning most commonly showed involvement of the sphenoid sinus. In 54% of cases, sinusitis was bilateral and extended throughout the maxillary, ethmoidal, and sphenoidal sinuses. Sinusectomy was performed in all patients, and pathological secretion in the paranasal sinuses was seen in 52% of patients during surgery. Gram-negative bacteria were the most commonly isolated organisms, followed by Gram-positive bacteria and fungi. Improvement of fever was found in 82% of patients after FESS; 38% of these improved within the first 48 h post-procedure, and the remaining 62% within the first 5 postoperative days.

A Randomized Controlled Trial of Cognitive Behavioral Group Therapy for Bipolar Disorder

Background: This study evaluated the effectiveness of adjunctive cognitive behavioral group therapy (CBGT) to prevent recurrence of episodes in euthymic patients with bipolar disorder. Methods: A randomized controlled single-blind trial was conducted with 50 patients with bipolar disorder types I and II followed up for at least 12 months in an outpatient service and whose disease was in remission. An experimental CBGT manual was developed and added to treatment as usual (TAU), and results were compared with TAU alone. Results: Intention-to-treat analysis showed that there was no difference between groups in terms of time until any relapse (Wilcoxon = 0.667; p = 0.414). When considering type of relapse, there was still no difference in either depressive (Wilcoxon = 3.328; p = 0.068) or manic episodes (Wilcoxon = 1.498; p = 0.221). Although occurrence of episodes also did not differ between groups (chi(2) = 0.28; p = 0.59), median time to relapse was longer for patients treated with CBGT compared to TAU (Mann-Whitney = -2.554; p = 0.011). Conclusions:Time to recurrence and number of episodes were not different in the group of patients treated with CBGT. However, median time to relapse was shorter in the TAU group. Studies with larger samples may help to clarify whether our CBGT approach prevents new episodes of bipolar disorder. Our findings also indicated that CBGT is feasible in euthymic patients with bipolar disorder and should be investigated in future studies. To our knowledge, this is the first publication of a controlled trial of CBGT for euthymic patients with bipolar disorder. Copyright (C) 2011 S. Karger AG, Basel

Self-Esteem, Confidence, and Relationships in Brazilian Men with Erectile Dysfunction Receiving Sildenafil Citrate: A Randomized, Parallel-Group, Double-Blind, Placebo-Controlled Study in Brazil

Psychosocial manifestations of erectile dysfunction (ED) differ across cultures. Understanding the treatment response to ED medications within cultural groups can aid in resource allocation and in developing treatment strategies. Evaluate the effect of sildenafil treatment on self-esteem, confidence, and sexual relationship satisfaction in Brazilian men with ED. The Self-Esteem and Relationship (SEAR) questionnaire, a validated, 14-question instrument developed to specifically address self-esteem and relationship issues within the context of ED. Men aged 18 years or older with a clinical diagnosis of ED (<= 21 on the Sexual Health Inventory for Men) and in a stable relationship with a partner during the study were eligible. The primary end point was a change from baseline in the self-esteem subscale of the SEAR questionnaire. Thirteen Brazilian sites participated in a randomized, double-blind, placebo-controlled trial of sildenafil treatment for ED. Patients were randomized to receive either 50 mg of sildenafil (adjustable to 25 mg or 100 mg based on patient response) or matching placebo approximately 1 hour before anticipated sexual activity but not more than once a day. At the end of double-blind treatment, 63 and 66 patients in the placebo and sildenafil groups, respectively, from 13 Brazilian sites were assessed for efficacy. Brazilian patients receiving sildenafil had significantly greater improvements in their scores on the SEAR self-esteem subscale (42.9 [95% confidence interval 35.7-50.0]) compared with placebo (21.1 [95% confidence interval 13.7-28.6]; P < 0.0001). Effect sizes ranged from 0.91 to 1.25 for individual SEAR components. The psychosocial parameters in Brazilian men with ED assessed by the SEAR questionnaire showed significant improvements in self-esteem, confidence, and relationships after treatment with sildenafil. Glina S, Damiao R, Abdo C, Afif-Abdo J, Tseng L-J, and Stecher V. Self-esteem, confidence, and relationships in Brazilian men with erectile dysfunction receiving sildenafil citrate: A randomized, parallel-group, double-blind, placebo-controlled study in Brazil. J Sex Med 2009;6:268-275.

The risk of chikungunya fever in a dengue-endemic area

Background. Chikungunya, an alphavirus of the Togaviridae family, causes a febrile disease transmitted to humans by the bite of infected Aedes mosquitoes. This infection is reaching endemic levels in many Southeast Asian countries. Symptoms include sudden onset of fever, chills, headache, nausea, vomiting, joint pain with or without swelling, low back pain, and rash. According to the World Health Organization, there are 2 billion people living in Aedes-infested areas. In addition, traveling to these areas is popular, making the potential risk of infections transmitted by the bite of infected Aedes mosquitoes very high. Methods. We proposed a mathematical model to estimate the risk of acquiring chikungunya fever in an Aedes-infested area by taking the prevalence of dengue fever into account. The basic reproduction number for chikungunya fever R-0chik can be written as a function of the basic reproduction number of dengue R-0dengue by calculating the ratio R-0chik/R-0dengue. From R-0chik, we estimated the force of infection and the risk of acquiring the disease both for local residents of a dengue-endemic area and for travelers to this area. Results. We calculated that R-0chik is 64.4% that of R-0dengue. The model was applied to a hypothetical situation, namely, estimating the individual risk of acquiring chikungunya fever in a dengue-endemic area, both for local inhabitants (22% in steady state) and for visiting travelers (from 0.31% to 1.23% depending on the time spent in the area). Conclusions. The method proposed based on the output of a dynamical model is innovative and provided an estimation of the risk of infection, both for local inhabitants and for visiting travelers.