Contextual Factors-Enriched Standard Care on mechanical neck pain (ContextualizAR trial): Protocol for a randomised controlled trial.

BACKGROUND: Understanding the influence of contextual factors (CFs) on interventions for mechanical neck pain (MNP) is essential for evidence-based practice in physical therapy. However, the specific effects and synergies of combining different CFs remain unclear. OBJECTIVE: The primary purpose of this study will be to determine if a CFs-Enriched Standard Care (SC) approach is an effective treatment for MNP in terms of reducing pain and improving function. METHODS: This will be an assessor-blinded, 2-group (1:1) randomised clinical trial (RCT) aiming to enrol 94 participants with neck pain persisting for more than 4 weeks. Both groups will undergo 4 weeks of SC twice weekly, following established clinical practice guidelines. In the intervention group, CFs will be enhanced, encompassing the physical, psychological, and social elements inherent in the clinical encounter, based on existing evidence. The primary outcomes will encompass changes in pain and disability after 4 weeks of treatment, with a follow-up reassessment at week 12 post-treatment. Secondary outcomes will include changes in Active Range of Motion, Global Rating of Change, and Satisfaction with treatment. The change between groups after treatment and at the 12-week follow-up will be reported for all outcomes, considering the difference from scores recorded at baseline. RESULTS: We hypothesise that a 4-week CFs-Enriched SC approach will be superior to SC alone in terms of patient-reported disability and pain, with measurements conducted using the Northwick Park Neck Pain Questionnaire and the Numeric Pain Rating Scale, respectively. CONCLUSION: This RCT rigorously assesses the effect of purposeful manipulation of CFs during MNP treatment. By elucidating the role of these factors, our findings have the potential to significantly refine clinical practice in managing MNP, thereby enhancing patient care, and advancing the fields of physical therapy and rehabilitation.

Efficacy of 660 nm Photobiomodulation in Burning Mouth Syndrome Management: A Single-Blind Quasi-Experimental Controlled Clinical Trial.

Background: Burning mouth syndrome (BMS) is characterized by a burning sensation of the oral mucosa without any evidence of clinical signs or underlining condition. Several treatment modalities have been utilized with various results and levels of evidence. Lately, photobiomodulation (PBM) has emerged as a noninvasive effective therapy due to its anti-inflammatory and biostimulatory effects, especially the low-power laser setting of red wavelength. Objective: This single-blind quasi-experimental controlled clinical trial aimed to evaluate the PBM effectiveness at a low level of red laser light in patients with BMS compared with sham control. Materials and methods: Thirty patients diagnosed with BMS were consecutively assigned to intervention (PBM therapy) and control (sham) groups. The protocol for PBM dosimetry was as follows: laser 660 nm; spot size: 0.04 cm2; power output: 100 mW; emission mode: continuous wave; power density: 6 J/cm2; irradiation time: 10 sec per point within 1 cm2 surface area of the symptomatic area. The treatment protocol was based on once a week for a total of 10 sessions. Results: Our results showed no statistically significant difference in reduction of pain intensity between the two groups at all the evaluated timepoints during the course of treatment. However, in both groups, we observed a statistically significant reduction of maximum pain intensity of 50% compared with patient-self reporting before the treatment. Conclusions: Further randomized clinical trials to validate our positive results with a large sample size with a long-term follow-up and understanding further the sham placebo effect are warranted.

Caffeine, lactic acid, or nothing: What effect does expectation have on men's performance and perceived exertion during an upper body muscular endurance task?

Objective: We tested the impact of subjects' belief in an ingested substance's ergogenic or ergolytic properties on muscular endurance performance and perceived exertion. Methods: Trained men (n = 15, age = 41 ± 4 y; body mass = 82.1 ± 15.8 kg; height = 173 ± 8 cm; experience = 7.4 ± 2.3 y) completed one set to failure at 80% repetition maximum of the bench press under three conditions. In all conditions, subjects ingested capsules of an identical, inert substance (300 mg cellulose), but, in a randomized order, subjects were told that they were either ingesting caffeine (Placebo), lactic acid (Nocebo), or cellulose (Control) and received information on the respective alleged ergogenic/ergolytic/neutral effects of each. Repetitions completed and rating of perceived exertion (RPE) were recorded. The data were analyzed among conditions using a Friedman test with post hoc analyses accomplished through Durbin-Conover tests. Spearman correlations were used to compare repetitions performed and RPE between Nocebo and Placebo conditions. Statistical significance was set at P ≤ 0.05. Results: Subjects lifted more (P < 0.001) repetitions in the Placebo condition (14.1 ± 3.0) versus Control (10.3 ± 2.9) or Nocebo (7.5 ± 2.6), while Control and Nocebo performances were similar (P = 0.192). Lower RPE was noted in Placebo versus Control (P = 0.003) and Nocebo (P < 0.001) and lower in Control versus Nocebo (P = 0.025). Subjects who performed more repetitions with Placebo tended to perform fewer repetitions under the Nocebo condition (Spearman's Rho =-0.578). Conclusion: This study believes that the ergogenic or ergolytic properties of a substance can measurably impact upper-body muscular endurance performance and RPE in trained men.

Seeing Through the Blind: Belief about Treatment Randomization and Smoking Cessation Outcome among People with Current or Past Major Depressive Disorder who Smoke in a Placebo-Controlled Trial of Varenicline.

INTRODUCTION: Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial. METHODS: 175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed. RESULTS: Treatment arm belief was significantly associated with actual arm assignment (χ2(2)=13.0, p=0.002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, vs. "not sure" (RR=3.05 [1.41-6.60], p=0.005). Participants in the placebo arm were just as likely to believe they were taking placebo vs. "not sure" (χ2[2]=0.75, p=0.69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR=5.91 [2.06-16.92], p=0.001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline B=0.077 [0.002-0.192], p <0.05). CONCLUSIONS: Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline.

Sodium bicarbonate induces alkalosis, but improves high-intensity cycling performance only when participants expect a beneficial effect: a placebo and nocebo study.

The study aimed to investigate the effects of sodium bicarbonate (NaHCO3) intake with divergent verbal and visual information on constant load cycling time-to-task failure, conducted within the severe intensity domain. Fifteen recreational cyclists participated in a randomized double-blind, crossover study, ingesting NaHCO3 or placebo (i.e., dextrose), but with divergent information about its likely influence (i.e., likely to induce ergogenic, inert, or harmful effects). Performance was evaluated using constant load cycling time to task failure trial at 115% of peak power output estimated during a ramp incremental exercise test. Data on blood lactate, blood acid-base balance, muscle electrical activity (EMG) through electromyography signal, and the twitch interpolation technique to assess neuromuscular indices were collected. Despite reduced peak force in the isometric maximal voluntary contraction and post-effort peripheral fatigue in all conditions (P < 0.001), neither time to task failure, EMG nor, blood acid-base balance differed between conditions (P > 0.05). Evaluation of effect sizes of all conditions suggested that informing participants that the supplement would be likely to have a positive effect (NaHCO3/Ergogenic: 0.46; 0.15-0.74; Dextrose/Ergogenic: 0.45; 0.04-0.88) resulted in improved performance compared to control. Thus, NaHCO3 ingestion consistently induced alkalosis, indicating that the physiological conditions to improve performance were present. Despite this, NaHCO3 ingestion did not influence performance or indicators of neuromuscular fatigue. In contrast, effect size estimates indicate that participants performed better when informed that they were ingesting an ergogenic supplement. These findings suggest that the apparently ergogenic effect of NaHCO3 may be due, at least in part, to a placebo effect.

Da imaginação à neuroimagem: uma análise antropológica sobre a racionalidade do efeito placebo em ensaios clínicos / From imagination to neuroimage: An anthropological analysis on the rationality of the placebo effect in clinical trials

Resumo O efeito placebo é um ponto de passagem obrigatório para a compreensão da racionalidade envolvida nos ensaios clínicos randomizados. A partir da antropologia da ciência e da tecnologia, este artigo analisa como a noção de efeito placebo tem sido utilizada pela ciência na produção de fronteiras biossociais. Assim, enfoca fenômenos que inicialmente eram atribuídos à imaginação e analisa as consequências de novas metodologias científicas que têm reconhecido outras potencialidades desse efeito, mas tendem a privilegiar marcadores biológicos. O argumento central é que a disputa epistemológica oculta a existência múltipla do efeito placebo que pode ser reconhecida em função das diferentes práticas às quais ele confere racionalidade.

Abstract The placebo effect is an obligatory passage point to understand rationality in randomized clinical trials. From the perspective of science and technology studies, this paper analyzes how the notion of the placebo effect has been used by science in the production of biosocial borders. Thus, it will pay attention to the phenomena considered caused by imagination, and we will analyze the consequences of new methodologies that have recognized other potentialities of this effect but tend to favor biological markers. The central argument is that the epistemological dispute hides the multiple existences of the placebo effect to be recognized due to the different scientific practices to which it confers rationality.

Espiritualidade aplicada à medicina / Spirituality applied to medicine / Espiritualidad aplicada a la medicina

Resumo Espiritualidade é a força que une os diferentes aspectos componentes do ser e, quando trabalhada, proporciona uma vivência harmônica e promove equilíbrio entre bem-estar físico, social e mental. Nesse sentido, objetivou-se abordar, secularmente, como a espiritualidade é vista na medicina, sua influência na saúde e a percepção de profissionais e pacientes acerca desse assunto. Para tanto, realizou-se revisão narrativa que priorizou buscas na plataforma PubMed por meio dos seguintes descritores: "medicine and spirituality and secularismo" e "placebo effect and spirituality and medicine". Em seguida foram analisadas fontes referenciadas pela leitura dos artigos primordiais. Percebeu-se que há confusão quanto ao uso do termo espiritualidade e que a capacidade e efetividade do cuidado espiritual prestado por profissionais da saúde são débeis, contrastando com inúmeros benefícios oferecidos por essa atenção, que é uma ferramenta para um trabalho mais ético e humano.

Abstract Spirituality is a uniting force between different constituents of the human being and, when exercised, provides a harmonious experience and promotes balance between physical, social, and mental well-being. As such, this narrative review proposes a secular approach to how spirituality is understood by medicine, its influence on health, and how it is perceived by professionals and patients. Bibliographic search was conducted on the PubMed database, using the following descriptors: "medicine and spirituality and secularism" and "placebo effect and spirituality and medicine." After reading the primary articles, the referenced sources were analyzed. Results show a confusion on how the term spirituality is used and a weak capacity and effectiveness with respect to the spiritual care provided by health personnel, thus ignoring the several benefits offered by such care, which is a tool for a more ethical and humane work.

Resumen La espiritualidad es la fuerza que une los diferentes componentes del ser y al estimularse proporciona una experiencia armoniosa, además de promover el equilibrio de bienestar físico, social y mental. Ante lo anterior, este texto tuvo por objetivo abordar cómo se ve secularmente la espiritualidad en la medicina, su influencia en la salud y la percepción de profesionales y pacientes sobre este tema. Para ello, se realizó una revisión narrativa en la base de datos PubMed utilizando los siguientes descriptores: "medicine and spirituality and secularismo" y "placebo effect and spirituality and medicine". Después, se analizaron las fuentes mediante la lectura de los artículos principales. Se encontró una confusión con relación al uso del término espiritualidad, y es deficiente la habilidad y eficacia del cuidado espiritual que brindan los profesionales de la salud, contrastando con los numerosos beneficios de este cuidado, una herramienta para un trabajo más ético y humanizado.

Effects of pulsed electromagnetic field therapy on fatigue, walking performance, depression, and quality of life in adults with multiple sclerosis: a randomized placebo-controlled trial.

BACKGROUND: Multiple sclerosis has a great disability burden. Management of the disease is complex, and patients often seek new conservative approaches. OBJECTIVE: To investigate the effect of low-frequency pulsed electromagnetic field (PEMF) therapy, compared to placebo, on the level of fatigue, walking performance, symptoms of depression, and quality of life (QOL) in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: Forty-four adults with RRMS and minimal to significant disability were randomly assigned to a 4-week protocol using a PEMF or a placebo whole-body mat. The PEMF group were initially treated with 15Hz frequency, gradually increased to 30Hz (intensity between 25-35µT). The primary outcome was fatigue, assessed with the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Secondary measures included walking function (GAITRite system and Timed 25-Foot Walk test), the Beck Depression Inventory-II, and the Multiple Sclerosis International Quality of Life Questionnaire. Data were collected at baseline, after intervention, and at 3-months post-intervention (follow-up). RESULTS: There were no differences between groups for changes in fatigue symptoms from baseline to end of intervention (mean and 95% confidence interval FSS: -0.6, 95%CI: -1.3, 0.1; MFIS: -5.4, 95% CI: -15.1, 4.4) or at follow-up (FSS: -0.6, 95% CI: -1.4, 0.2; MFIS: -2.1, 95% CI: -10.9, 6.8). Similarly, both groups did not differ for any of the secondary outcomes at post-intervention or follow-up. CONCLUSIONS: Low-frequency PEMF therapy is no more effective than placebo to produce changes in fatigue, gait performance, severity of depression, and QOL in people with RRMS and minimal to significant disability.

Efficacy of the cognitive functional therapy (CFT) in patients with chronic nonspecific low back pain: a study protocol for a randomized sham-controlled trial.

BACKGROUND: Chronic low back pain is a public health problem, and there is strong evidence that it is associated with a complex interaction of biopsychosocial factors. Cognitive functional therapy (CFT) is a promising new intervention that deals with potentially modifiable multidimensional aspects of pain (e.g., provocative cognitive, movement, and lifestyle behaviors). METHODS: To investigate the efficacy of CFT compared with a sham intervention for pain intensity and disability post-intervention (immediately after the last session) in patients with non-specific chronic low back pain (CLBP). This study is a randomized controlled trial in which 152 (18-60 years old) patients with CLBP will be enrolled. The patients will be randomly allocated to receive (1) CFT intervention or (2) sham intervention. The experimental group will receive individualized CFT in a pragmatic manner (5 to 7 sessions) based on the clinical progression of the participants. The sham group will attend six sessions: consisting of 30 min of photobiomodulation using a detuned device and more than 15 min of talking about neutral topics. Patients from both groups also will receive an educational booklet (for ethical reasons). Participants will be assessed pre and post-intervention, 3 months, and 6 months after randomization. The primary outcomes will be pain intensity and disability post-intervention. The secondary outcomes will be: pain intensity and disability at 3- and 6-month follow-up, as well as self-efficacy, global perceived effect of improvement, and functioning post-intervention, 3-, and 6-month follow-up. The patients and the assessor will be blinded to the treatment administered (active vs. sham). STATISTICAL ANALYSIS: The between-group differences (effects of treatment), as well as the treatment effect for the primary and secondary outcomes, and their respective 95% confidence intervals will be calculated by constructing linear mixed models. DISCUSSION: To the best of our knowledge, the current study will be the first to compare CFT vs. sham intervention. Sham-controlled RCTs may help to understand the influence of non-specific factors on treatment outcomes. Considering complex interventions as CFT, it is imperative to understand the impact of contextual factors on outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04518891 . First Posted: August 19, 2020.

Efecto placebo en otorrinolaringología: revisión de la literatura / Placebo effect in otorhinolaryngology: a narrative review

Resumen La palabra placebo ha sido usada, indistintamente, para referir a una sustancia o procedimiento que es "inerte" ("placebo") y al efecto que ocurre como consecuencia de la administración de un placebo ("efecto placebo"). El efecto placebo es un fenómeno psicobiológico que ha sido explicado desde el conductismo (condicionamiento clásico), desde fenómenos preconscientes (expectativas o "efecto placebo clásico"), desde el cognitivismo (disonancia cognitiva) y también a nivel neurobiológico. No obstante, los ensayos clínicos abiertos que verifican la respuesta a placebo desafían el mecanismo de la expectativa, dando lugar al análisis bayesiano, que integra sensaciones, experiencias, predicciones y claves del contexto; biológicamente, el efecto placebo no es inerte. Por tanto, el placebo ocupa un lugar relevante en la práctica clínica y en la investigación biomédica. Se realizó una búsqueda sistemática sobre placebo y otorrinolaringología en las bases de datos PubMed/Medline, SciELO y Cochrane Library. Se incluyeron estudios primarios y revisiones sistemáticas de la literatura. En cuanto a intervenciones placebo, la literatura publicada indica mejorías significativas en síntomas nasales y calidad de vida en rinitis alérgica (estacional y perenne) y disminución del dolor posoperatorio en amigdalectomía. En la enfermedad de Méniere, las intervenciones placebo son comparables a las de uso habitual, incluyendo las quirúrgicas. No se encontraron ensayos clínicos abiertos en otorrinolaringología ni evidencia sobre otras patologías del área. Las intervenciones y el efecto placebo abren un campo de investigación y desarrollo en otorrinolaringología que desafía la comprensión actual de las patologías, su funcionamiento, su tratamiento y la relación terapéutica.

Abstract The word placebo has been used interchangeably to refer to a substance or procedure that is "inert" ("placebo") and the effect that occurs as a consequence of its administration ("placebo effect"). The placebo effect corresponds to a psychobiological phenomenon that has been explained from behaviorism (classical conditioning), from preconscious phenomena (expectations or "classical placebo effect"), from cognitivism (cognitive dissonance) and at the neurobiological level as well. Nevertheless, some open-label trials that verify the response to placebo challenge the expectation mechanism, giving rise to Bayesian analysis, which integrates sensations, experiences, predictions and context clues; therefore, biologically, the placebo effect is not inert. The placebo has a relevant place both in clinical practice and in biomedical research. We conducted a systematic search on placebo and otolaryngology in PubMed/Medline, SciELO and Cochrane Library databases. We included primary studies and systematic reviews. Regarding placebo interventions, the available literature points out significant improvements in nasal symptoms and quality of life in allergic rhinitis (seasonal and perennial) and a decrease in post-tonsillectomy pain. In Méniére's disease, placebo interventions have demonstrated to be comparable to treatment-as-usual, including surgical interventions. No open-label clinical trials were found in otolaryngology, as well as no evidence on other diseases in the area. Placebo interventions and their effects open a field of research and development in otolaryngology, challenging the current understanding of pathologies, their functioning, their treatment and the therapeutic relationship.

Psycho-Neuro-Endocrine-Immunological Basis of the Placebo Effect: Potential Applications beyond Pain Therapy.

The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations regarding its effects. During recent years, it has been discovered that the placebo response not only has neurobiological functions on analgesia, but that it is also capable of generating effects on the immune and endocrine systems. The possible integration of changes in different systems of the organism could favor the well-being of the individuals and go hand in hand with conventional treatment for multiple diseases. In this sense, classic conditioning and setting expectations stand out as psychological mechanisms implicated in the placebo effect. Recent advances in neuroimaging studies suggest a relationship between the placebo response and the opioid, cannabinoid, and monoaminergic systems. Likewise, a possible immune response conditioned by the placebo effect has been reported. There is evidence of immune suppression conditioned through the insular cortex and the amygdala, with noradrenalin as the responsible neurotransmitter. Finally, a conditioned response in the secretion of different hormones has been determined in different studies; however, the molecular mechanisms involved are not entirely known. Beyond studies about its mechanism of action, the placebo effect has proved to be useful in the clinical setting with promising results in the management of neurological, psychiatric, and immunologic disorders. However, more research is needed to better characterize its potential use. This review integrates current knowledge about the psycho-neuro-endocrine-immune basis of the placebo effect and its possible clinical applications.

Suplementação com açaí (Euterpe Oleracea Martius) para o tratamento do zumbido crônico: efeitos na percepção, níveis de ansiedade e biomarcadores de metabolismo oxidativo / Supplementation with açaí (Euterpe Oleracea Martius) for the treatment of chronic tinnitus: effects on perception, anxiety levels and oxidative metabolism biomarkers

RESUMO Objetivo Investigar os efeitos da suplementação antioxidante com extrato de açaí no incômodo com o zumbido crônico e a relação com os níveis de ansiedade e metabolismo oxidativo, não excluindo a sobreposição de enfermidades. Método Ensaio clínico, randomizado, controlado por placebo. Participaram 30 indivíduos, com média de 50,5 anos, 14 do sexo masculino e 16 do feminino, com limiares auditivos normais ou perda auditiva sensorioneural até grau leve bilateralmente, divididos em dois grupos: Grupo Placebo (sem ativo) e Grupo Açaí (100mg de extrato de açaí). Aplicaram-se os seguintes procedimentos antes e após três meses dos tratamentos: Tinnitus Handicap Inventory (THI), Inventário de Ansiedade de Beck (BAI) e amostras de sangue para avaliação de biomarcadores de estresse oxidativo (Peroxidação Lipídica e Carbonilação de proteínas). Resultados Houve redução do incômodo do zumbido para o grupo açaí, verificado por meio do THI (p=0,006). Diferenças significativas foram constatadas na pontuação dos sintomas comuns para os quadros de ansiedade no grupo placebo (p=0,016) porém, o mesmo não foi observado para os biomarcadores de metabolismo oxidativo, apesar de haver uma diminuição dos valores pós-tratamento para os grupos. Conclusão A suplementação antioxidante oral, com extrato de açaí, manifestou efeitos favoráveis no zumbido, reduzindo o desconforto com o sintoma, independente da etiologia de base, podendo ser considerada uma modalidade de tratamento. Entretanto, o efeito dessa suplementação nos sintomas de ansiedade e em biomarcadores de estresse oxidativo precisa de maior investigação.

ABSTRACT Purpose To investigate the effects of antioxidant supplementation with açaí extract on the discomfort with chronic tinnitus and the relationship with the levels of anxiety and oxidative metabolism, not excluding the overlap of diseases. Methods Randomized, placebo-controlled clinical trial. 30 individuals participated, with an average of 50.5 years, 14 males and 16 females, with normal hearing thresholds or sensorineural hearing loss up to mild degree, divided into two groups: Placebo Group (without active) and, Açaí Group (100mg of açaí extract). The following procedures were applied before and after three months of treatments: Tinnitus Handicap Inventory (THI), Beck's Anxiety Inventory (BAI) and blood samples for evaluation of oxidative stress biomarkers (Lipid Peroxidation and Protein Carbonylation). Results There was a reduction in the discomfort of tinnitus for the açaí group verified through THI (p = 0.006). Significant differences were found in the score of common symptoms for anxiety disorders in the placebo group (p = 0.016), however, the same was not observed for oxidative metabolism biomarkers, although there was a decrease in post-treatment values for all groups. Conclusion Oral antioxidant supplementation, with açaí extract, showed favorable effects on tinnitus, reducing discomfort with the symptom, regardless of the underlying etiology, and can be considered a treatment modality. However, the effect of this supplementation on anxiety symptoms and oxidative stress biomarkers needs further investigation.

El rol del placebo frente a los antidepresivos y aportes a la relación médico-paciente / Role of placebo versus antidepressants and contribution to the doctor-patient relationship

Resumen La literatura actual ofrece la posibilidad de aportar argumentos tanto a favor como en contra a la discusión sobre la eficacia de los medicamentos antidepresivos. Tanto la metodología, modelos de estudio y herramientas utilizadas para comparar la eficacia de los medicamentos plantean controversia. Este debate se agudiza al considerar la existencia del efecto placebo en resultados que promueven o cuestionan el uso de estos medicamentos. Entender los mecanismos de acción del placebo no solo permite una mejor comprensión de los resultados de la investigación con relación al uso de antidepresivos, sino que además respecto a la efectividad de los distintos tratamientos que hoy en día se utilizan en salud mental.

Current literature offers the possibility to contribute to the discussion about the effectiveness of antidepressants, with arguments both in favor and opposing it. Methodology, study models, and tools used to compare drug effectiveness, all raise controversy. This debate is intensified when involving the existence of placebo effect in results either promoting or questioning the use of these drugs. Understanding the mechanism of action of placebo not only allows for a better grasp of study results around antidepressant use but could also contribute to the effectiveness of distinct treatments used nowadays in mental health.

Effects of Individualized Ischemic Preconditioning on Protection Against Eccentric Exercise-Induced Muscle Damage: A Randomized Controlled Trial.

BACKGROUND: The effects of ischemic preconditioning (IPC) versus a deceptive sham protocol on indirect markers of exercise-induced muscle damage (EIMD) after the application of individualized occlusion pressure were examined. The goal of using a sham protocol is to control for the potential effect of placebo. HYPOTHESIS: IPC would surpass the sham protocol in protecting against EIMD. STUDY DESIGN: A randomized, double-blinded, clinical trial. LEVEL OF EVIDENCE: Level 1. METHODS: Thirty healthy young men were randomly assigned to an eccentric exercise for the knee extensor muscles preceded by IPC (4 × 5 minutes of individualized total occlusion pressure) or sham protocol (4 × 5 minutes using 20 mm Hg). Maximal voluntary isometric torque (MVIT), rate of torque development, muscle soreness, pressure pain threshold, knee range of motion, thigh girth, and creatine kinase (CK) activity were assessed before IPC or sham protocol and up to 72 hours after the eccentric EIMD. Affective valence and perceived exertion were also evaluated. RESULTS: MVIT decreased 17.1% in the IPC and 18.1% in the sham groups, with no differences between groups. Differences from baseline were observed in the sham group for muscle soreness at 48 hours (P < 0.001) and 72 hours (P = 0.02), and for CK activity at 72 hours (P = 0.04). Muscle soreness was reduced in the IPC group at 48 hours compared with the sham group (∆ = 15.8 mm; P = 0.008) but without achieving the minimal clinically important difference. IPC induced a smaller perceived exertion than the sham protocol (∆ = 1.1 a.u.; P = 0.02). The remaining outcomes were not statistically different in both groups. CONCLUSION: IPC does not surpass the sham protocol to protect against mild EIMD of the knee extensors muscles. CLINICAL RELEVANCE: Although IPC is a noninvasive, low-cost, and easy-to-administer intervention, the IPC effects can, in part, be explained by the placebo effect. In addition, individualized IPC promotes attenuation in perceived exertion during eccentric exercise.

The efficacy of placebo for the treatment of cancer-related fatigue: a systematic review and meta-analysis.

PURPOSE: Cancer-related fatigue (CRF) is a common symptom among patients with cancer. The efficacy of placebo, however, was never the main objective of any meta-analysis. Predicting the efficacy of placebo may facilitate researchers in designing future clinical trials for the treatment of CRF. METHODS: We performed a systematic review searching for prospective clinical trials comparing any treatment versus placebo for the treatment of CRF. We included studies that enrolled patients with any primary site of neoplasia and any stage of cancer. We excluded all studies that assessed fatigue related to any treatment. The primary endpoint of this study is the mean effect of placebo on fatigue according to the Functional Assessment of Chronic Illness (FACIT-F) and Brief Fatigue Inventory (BFI) scales. The secondary endpoint was the proportion of patients who reported improvement in fatigue (response rate). RESULTS: We found 520 studies, and 29 studies with 3758 participants were included in the meta-analysis. Placebo had a mean effect of + 4.88 (95%CI + 2.45 to + 7.29) using the FACIT-F scale, although it was statistically worse than the interventions studied (p = 0.005). Using the BFI scale, placebo had an average effect of + 0.64 (95%CI + 0.02 to + 1.30), although it was also worse than the other interventions studied (p = 0.002). In terms of the response rate, 29% (95%CI 25-32%) of patients taking a placebo reported a significant improvement in CRF compared with 36% of patients treated with other interventions (p = 0.030). CONCLUSIONS: Placebo treatments had a significant effect on CRF, and predicting these effects may help design future studies for CRF.

Actitudes de los médicos familiares mexicanos sobre el uso de placebos en la práctica clínica.

INTRODUCTION: The use of placebo has spread in clinical practice despite being controversial. In Mexico, the practice of family medicine is predominantly institutional and works with an essential medications list. OBJECTIVE: To determine the frequency and family doctor attitude regarding the use of placebos in clinical practice. METHOD: Cross-sectional, observational, multicenter study of 307 family doctors with active practice in 27 states of the Mexican Republic. A questionnaire was used with sociodemographic data and consensus-developed questions about frequency of use and attitudes. For analysis, the square-chi test was used. RESULTS: 75% used placebos (95% CI=69.7-79.4%); 122 (39.7%) used pure placebos, mainly water (p < 0.05), and 220 (71.6%), impure placebos, mainly vitamins and laboratory tests. They were used more in patients with medically unexplained physical symptoms (178, 45.5%), including 122 (31.2%) "healthy worried" patients, or who had chronic conditions (40, 12.5%). Reasons for prescription: 249 (81%) for the psychological effect, when they showed benefit (176, 57%), even when it implied deceiving (78, 25%) or insufficient evidence of efficacy (57, 19%). The main reason was because of patient insistence. CONCLUSIONS: More impure placebos were used, mainly in healthy worried patients and in those with chronic conditions.

INTRODUCCIÓN: El uso de placebo se ha extendido en la práctica a pesar de ser polémico. En México, la práctica de medicina familiar es predominante institucional y trabaja con un cuadro básico de medicamentos. OBJETIVO: Determinar la frecuencia y actitud del médico familiar en la utilización de placebos en la práctica clínica. MÉTODO: Estudio transversal, observacional, multicéntrico, en 307 médicos familiares con práctica activa, en 27 estados de la República Mexicana. Se usó cuestionario con datos sociodemográficos, preguntas sobre frecuencia de uso y actitudes elaboradas por consenso. Se analizó con chi cuadrada. RESULTADOS: 75 % utilizó placebos (IC 95 % = 69.7-79.4 %); 122 (39.7 %) placebos puros, principalmente agua (p < 0.05), y 220 (71.6 %) placebos impuros, principalmente vitaminas y exámenes de laboratorio. Los usaron más en pacientes con síntomas físicos no explicados médicamente (178, 45.5 %), incluidos 122 (31.2 %) pacientes "sanos preocupados" o con padecimientos crónicos (40, 12.5 %). Motivos de prescripción: 249 (81 %) por el efecto psicológico, cuando demostraron beneficio (176, 57 %), aun cuando implicara engaño (78, 25 %) o evidencia de eficacia insuficiente (57, 19 %). El principal motivo fue por insistencia del paciente. CONCLUSIONES: Se utilizaron más placebos impuros, principalmente en pacientes sanos preocupados y en aquellos con padecimientos crónicos.

Actitudes de los médicos familiares mexicanos sobre el uso de placebos en la práctica clínica / Attitudes of Mexican family physicians on the use of placebos in clinical practice

Resumen Introducción: El uso de placebo se ha extendido en la práctica a pesar de ser polémico. En México, la práctica de medicina familiar es predominante institucional y trabaja con un cuadro básico de medicamentos. Objetivo: Determinar la frecuencia y actitud del médico familiar en la utilización de placebos en la práctica clínica. Método: Estudio transversal, observacional, multicéntrico, en 307 médicos familiares con práctica activa, en 27 estados de la República Mexicana. Se usó cuestionario con datos sociodemográficos, preguntas sobre frecuencia de uso y actitudes elaboradas por consenso. Se analizó con chi cuadrada. Resultados: 75 % utilizó placebos (IC 95 % = 69.7-79.4 %); 122 (39.7 %) placebos puros, principalmente agua (p < 0.05), y 220 (71.6 %) placebos impuros, principalmente vitaminas y exámenes de laboratorio. Los usaron más en pacientes con síntomas físicos no explicados médicamente (178, 45.5 %), incluidos 122 (31.2 %) pacientes “sanos preocupados” o con padecimientos crónicos (40, 12.5 %). Motivos de prescripción: 249 (81 %) por el efecto psicológico, cuando demostraron beneficio (176, 57 %), aun cuando implicara engaño (78, 25 %) o evidencia de eficacia insuficiente (57, 19 %). El principal motivo fue por insistencia del paciente. Conclusiones: Se utilizaron más placebos impuros, principalmente en pacientes sanos preocupados y en aquellos con padecimientos crónicos.

Abstract Introduction: The use of placebo has spread in clinical practice despite being controversial. In Mexico, the practice of family medicine is predominantly institutional and works with an essential medications list. Objective: To determine the frequency and family doctor attitude regarding the use of placebos in clinical practice. Method: Cross-sectional, observational, multicenter study of 307 family doctors with active practice in 27 states of the Mexican Republic. A questionnaire was used with sociodemographic data and consensus-developed questions about frequency of use and attitudes. For analysis, the square-chi test was used. Results: 75% used placebos (95% CI=69.7-79.4%); 122 (39.7%) used pure placebos, mainly water (p < 0.05), and 220 (71.6%), impure placebos, mainly vitamins and laboratory tests. They were used more in patients with medically unexplained physical symptoms (178, 45.5%), including 122 (31.2%) “healthy worried” patients, or who had chronic conditions (40, 12.5%). Reasons for prescription: 249 (81%) for the psychological effect, when they showed benefit (176, 57%), even when it implied deceiving (78, 25%) or insufficient evidence of efficacy (57, 19%). The main reason was because of patient insistence. Conclusions: More impure placebos were used, mainly in healthy worried patients and in those with chronic conditions.

Placebo and nocebo response magnitude on temporomandibular disorder-related pain: A systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review (SR) was to answer the following question: "In adult patients with temporomandibular disorder (TMD)-related pain, what is the placebo or nocebo effect of different therapies?" METHODS: A SR was performed with randomised clinical placebo-controlled trials on diagnosed painful TMD studies from five main databases and from three grey literature. Studies included must have sample older than 18 years, with painful TMD, which diagnosis was done by Research Diagnostic Criteria (RDC/TMD) or Diagnostic Criteria (DC/TMD). RESULTS: Out of 770 articles obtained, 42 met the inclusion criteria for qualitative and 26 for quantitative analysis. Meta-analysis indicated mean variation on pain intensity for placebo therapy was higher on laser acupuncture with 45.5 mm point reduction, followed by avocado soya bean extract with 36 mm and amitriptyline 25 mg with 25.2 mm. Laser showed a 29% of placebo effect, as well medicine with 19% and other therapies with 26%. Possible nocebo effect of 8% pain increase was found for intra-articular injection of Ultracain. CONCLUSIONS: Based on the available data, the placebo response could play a major effect on TMD pain management and may be responsible from 10% to 75% of pain relief. Laser acupuncture, avocado soya bean and amitriptyline promoted the higher placebo effect. Possible nocebo effect was found only for Ultracain injection with 8%. CLINICAL RELEVANCE: Clinicians could apply such evidence to optimise pain management and judgement about treatment efficacy, and researches may find it useful when designing their investigations.

La crítica y la educación médica: hacia un conocimiento liberador. Parte II / Critique and medical education: towards liberating knowledge. Part II

Resumen La crítica del quehacer médico como espacio educativo implicó caracterizar el entramado de lógicas, ideas y prácticas prevalentes: la disyunción y el reduccionismo; el binomio salud-enfermedad; la historia natural de la enfermedad; la medicalización de la vida social; la tecnologización deshumanizante de la práctica médica, y la medicina supresora reduccionista. La crítica continúa discutiendo la contribución de ese entramado al control social como agente de la dominación de los intereses de lucro sin límites y como expresión del poder de la industria de la salud, justificándose con la argumentación de alternativas tendientes a superar ese entramado: la lógica transdisciplinaria y el concepto de organismo como totalidad jerarquizada e interactuante con su entorno respecto de la disyunción y el reduccionismo; la historia cultural de la enfermedad como alternativa a la historia natural de la enfermedad y al binomio salud-enfermedad; el bien vivir, la búsqueda de la superación espiritual, intelectual, moral y convivencial que confiere sentido profundo a la vida humana, como alternativa a la medicalización y antídoto de la tecnologización deshumanizante y los rasgos degradantes; la medicina estimulante de fuerzas curativas endógenas para afecciones crónicas no trasmisibles, cuyo fundamento de factibilidad y credibilidad radica en la omnipresencia del efecto placebo con respecto a la medicina supresora, basada en fármacos con efectos secundarios indefectibles. Sin una educación basada en la crítica, difícilmente el conocimiento liberador podrá acompañar y orientar a médicos y otros profesionales a organizarse en la búsqueda, desde su ámbito, de un mundo inclusivo, igualitario, justo, solidario y cuidadoso del ecosistema planetario.

Abstract The critique of medicine begins at unveiling and specifying its network of predominant logics, ideas and practices: logics of disjunction and reductionism; the health-disease binomial; the natural history of the disease; the medicalization of social life; the dehumanizing technologization of medical practice and reductionist suppressive medicine. It goes on to argue about its role as agents of domination of limitless profit interests and as an expression of the power of the health industry, justifying itself with the proposal of alternatives tending to overcome that network: transdisciplinarity and the concept of organism as hierarchical totality and interacting with its environment, with respect to disjunction and reductionism; the cultural history of the disease in relation to the health-disease binomial and the dehumanizing technologization; good living, the search for spiritual, intellectual, moral and coexistence growth as meaning of human life, as an alternative to the medicalization and antidote of degrading traits and stimulating medicine of the endogenous healing forces of the organism whose foundation of possibility and credibility is the placebo effect as an alternative to suppressive therapy for non-communicable chronic conditions, based on the pharmacological effect with unfailing side effects. It concludes that without an education based on critique, liberating knowledge would hardly accompany and guide the various social groups in the search for an inclusive, pluralistic, egalitarian, fair, solidary and caring of the planetary ecosystem world.