Management Of Tendinopathy Research Articles

Nutraceutical supplement in the management of tendinopathies: a systematic review

Nutraceutical supplement in the management of tendinopathies: a systematic review

High-volume peritendinous injections in the management of Achilles tendinopathy

Introduction Achilles tendinopathy can be a significant problem, especially in the sporting population. When conservative treatment fails, injection therapy is often offered. There are various injectable therapies currently being employed for the treatment of recalcitrant Achilles tendinopathy, yet only sparse scientific evidence exists to support any specific injection treatment. High-volume peritendinous glucocorticoid injections are one such injection method growing in popularity, with early studies showing promising results. The aim of this study is to describe the methodology of this technique for the Achilles tendon along with assessing the effectiveness of this treatment, both sonographic and patient derived, at 24-week follow-up. Methods 43 participants with sonographically confirmed chronic Achilles tendinopathy elected to undergo a single high-volume peritendinous glucocorticoid injection in combination with a supervised rehabilitation program. Patients were injected with 1 mL celesone chronodose combined with 2mL xylocaine and 20 mL of cold normal saline. Blinded assessors evaluated participants pre-intervention and at 24-week follow-up sonographically using the Achilles Ultrasound Assessment Tool (AUAT) and clinically with the Victorian Institute of Sport Assessment - Achilles (VISA-A) score. Results At baseline (n=43) the mean AUAT score was 9.79 +/- 3.16 and VISA-A 45.21 +/- 19.75. At follow-up (n=37), this improved with a mean AUAT of 7 +/- 4.17 and VISA-A of 68.35 +/- 24.44. At 24-weeks after intervention, there was a statistically significant reduction in patient reported symptoms as assessed by the VISA-A (p > 0.001) along with a sonographic improvement in tendon morphology as assessed by the AUAT (p > 0.001). Conclusion In chronic Achilles tendinopathy, a single high-volume ultrasound guided peritendinous glucocorticoid injection leads to a significant reduction in pain and improvement in function when combined with exercise therapy. This clinical improvement is associated with a sonographic improvement in tendon morphology at 24-week follow-up. High-volume injections are a clinically applicable technique to improve patient outcomes when exercise therapy alone fails to progress the recalcitrant tendon.

Efficacy of heel lifts versus calf muscle eccentric exercise for mid-portion Achilles tendinopathy (the HEALTHY trial): study protocol for a randomised trial

BackgroundMid-portion Achilles tendinopathy is a common musculoskeletal condition characterised by degeneration of the Achilles tendon, which causes pain and disability. Multiple non-surgical treatments have been advocated for this condition including calf muscle eccentric exercise and in-shoe heel lifts. Although adherence is challenging, there is evidence to suggest that calf muscle eccentric exercise is effective in decreasing pain and improving function in people with Achilles tendinopathy. Heel lifts reduce ankle joint dorsiflexion and Achilles tendon strain, however their efficacy in the management of Achilles tendinopathy is unclear. This article describes the design of a parallel-group randomised trial comparing the efficacy of heel lifts to calf muscle eccentric exercise for Achilles tendinopathy.MethodsNinety-two participants with Achilles tendinopathy will be randomised to one of two groups: (i) a heel lift group that will receive pre-fabricated 12 mm in-shoe heel lifts (Clearly Adjustable®), or (ii) an exercise group that will be advised to carry out a calf muscle eccentric exercise program (twice a day, 7 days a week, for 12 weeks). Outcome measures will be obtained at baseline, 2, 6 and 12 weeks; the primary endpoint for assessing efficacy being 12 weeks. The primary outcome measure will be the total score of the Victorian Institute of Sport Assessment – Achilles (VISA–A) questionnaire. Secondary outcome measures will include thickness and integrity of the Achilles tendon (using ultrasound tissue characterisation [UTC]), participant perception of treatment effect on pain and function (using the 7-point Patient Global Impression of Change scale), severity of pain at the Achilles tendon (using a 100 mm visual analogue scale) in the previous week, health status (using the EuroQol-5D-5L™ questionnaire), physical activity levels (using the 7-day Recall Physical Activity Questionnaire) and calf muscle function (using the standing heel rise test). Data will be analysed using the intention to treat principle.DiscussionThe HEALTHY trial (Heel lifts versus calf muscle eccentric Exercise for AchiLles TendinopatHY) is the first randomised trial to compare the efficacy of heel lifts to calf muscle eccentric exercise in reducing pain and improving function in people with Achilles tendinopathy. A pragmatically designed trial was developed to ensure that if the interventions are found to be effective, the findings can be readily implemented in clinical practice.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12617001225303. Registered on August 22nd, 2017.

Conservative management of tendinopathies around hip

Conservative management of tendinopathies around hip

Considering Genetics in Tendinopathy Management

Considering Genetics in Tendinopathy Management

Fibromodulin: Structure, Physiological Functions, and an Emphasis on its Potential Clinical Applications in Various Diseases.

Fibromodulin (FMOD) is one of the small leucine-rich proteoglycans. A search of the literature did not reveal any paper that specifically reviews the potential clinical applications of FMOD in the management of human diseases. First, the structure and physiological functions of FMOD were reviewed. Then its potential clinical applications in various diseases including diseases of the skin, tendons, joints, intervertebral discs, blood vessels, teeth, uterus, bone and kidney were reviewed. FMOD is able to switch the adult response to skin wounding to the desired fetal response of scarless healing. Lowered levels of FMOD would be desirable in the management of tendinopathy, uterine fibroids, tumors resistant to radiotherapy, glioblastomas, small-cell lung cancer, and primary liver/lung fibrosis. In contrast, increased levels of FMOD would be desirable in the management of acute tendon injuries, osteoarthritis, rheumatoid arthritis, temporo-mandibular disease, joint laxity, intervertebral disc disease, neo-intimal hyperplasia of vein grafts, teeth caries, periodontal disease, endometrial atrophy, osteoporosis and diabetic nephropathy. Furthermore, FMOD may be used as a prognostic marker of cerebrovascular events in patients undergoing carotid endarterectomy and a marker for prostatic cancer. Finally, the use of FMOD in the treatment of symptomatic endometrial atrophy should be explored in women who are unable to use the standard estrogen management for endometrial atrophy. The review concluded that clinical trials in humans should be initiated to investigate the potential therapeutic effects of FMOD.

Does reporting of imaging findings affect patient's perception of treatment efficacy in Achilles tendinopathy? A randomised clinical trial

Introduction: Imaging has been increasingly used in Achilles tendinopathy to aid in the diagnosis and management of Achilles tendinopathy. However, there is a limited relationship between findings observed on imaging and the clinical presentation. Further, evidence in lower back pain has suggested that imaging may have an iatrogenic effect on patients that results in increased medicalization and poorer clinical outcomes. The aim of this study was to investigate whether the reporting of imaging findings after treatment alter patient outcomes and perception of treatment efficacy.

The Use of Ultrasound-Guided Injections for Tendinopathies

The purpose of the study was to review the efficacy and safety of common ultrasound-guided injections for tendinopathy conditions. Corticosteroid injections have historically been the most common injection used for tendinopathy; however, there are an increasing number of injections including platelet-rich plasma, hyaluronan, polidocanol, botulinum toxin, and high volume saline injections. There is growing evidence that while corticosteroid injections for tendinopathies usually have short-term efficacy, they may result in medium-term harm, particularly for tennis elbow (lateral epicondylitis). Corticosteroid injections appear to have more clinical utility for tenosynovitis conditions. There is insufficient evidence regarding other injection options to make a broad recommendation in favour, although individual trials for certain tendons illustrate benefits for some of the non-corticosteroid options. When considering the use of ultrasound-guided corticosteroid injections for tendinopathies, the risk of possible medium-term harm must be weighed up against any short-term efficacy. Other injection-based therapies may be appropriate in certain clinical situations; however, the evidence and clinical circumstances must be considered for the particular tendon and patient. Load-based rehabilitation remains the cornerstone of tendinopathy management.

Association of the efficacy of Cyriax therapy in patients with epicondylitis: meta-analysis

Introduction: Epicondylitis or tennis elbow is a common disease of the elbow that has a clear occupational profile, like other upper extremity chronic tendinopathies, and can appear associated with them simultaneously. Deep transverse friction (or Cyriax) has been one of the physiotherapy interventions suggested for the management of tendinopathy. However, the conclusions of the investigations have been inconsistent. Therefore, this study aimed to clarify the association between Cyriax treatment and tennis elbow through a meta-analysis. Material and methods: The PubMed and EBSCO databases were retrieved to collect all publications on the association between Cyriax treatment and epicondylitis. Results: The literature search consisted of 10 articles (that included 240 cases and 227 controls) for a qualitative analysis and six more (that included 121 cases and 122 controls) for the quantitative one. Conclusion: This meta-analysis could not support a signifi cant association between Cyriax therapy and epicondylitis. Therefore, it is suggested to implement this physical therapy only as a complementary treatment.

Physiotherapy Management in Common Tendon Injuries: Review of Reviews

Background: Numerous systematic reviews have been published on tendinopathies that deals with specific therapies on a specific location. Clinical therapists find it difficult to synthesize these results into their practice as evidence is conflicting between the sites of tendinopathy. The objective of this systematic review is to see the effectiveness of physiotherapy interventions (both active- exercise and passive- physical agents) in the management of tendinopathies. Methods: Articles were selected from Web of Science (WoS) by entering keywords in mid-December 2017. Articles published in the English language, between 2000 and 2017 were selected. The author selected 14 reviews from 31 possible reviews for this article and all, but one was indexed in PubMed too. Seven, 1, 3 and 3 were the number of articles that were carried treatment, physiotherapy, exercise and physical agents in their titles. Shoulder, hip or knee, ankle locations were dealt in 6, 4 and four articles respectively. Results: Current evidence-based literature shows that exercise especially eccentric one is the definite physiotherapy treatment option for treating lower limb and some upper limb tendinopathies. However, reviews show that other forms of exercises particularly stabilization as a promising option in upper limb conditions. Physical agents (Ultra Sound [US], Transcutaneous electrical nerve stimulation [TENS] are showing conflicting results hence not recommended at this point. The LASER can be used in Shoulder tendinopathies. Conclusion: The traditional concept of eccentric training in tendinopathies is challenged by recent reviews which show stabilization and other types of exercises also improving pain and function in tendinopathies. Well-designed large RCT trials are required to see the effectiveness of physical agents, different types of exercise training on tendinopathies.

EVALUATING THE PROGRESS OF MID-PORTION ACHILLES TENDINOPATHY DURING REHABILITATION: A REVIEW OF OUTCOME MEASURES FOR SELF- REPORTED PAIN AND FUNCTION

Management of mid-portion Achilles tendinopathy is a challenge for both clinicians and researchers. Alteration in tendon structure, muscle performance and pain processing mechanisms have been suggested as mechanisms driving improvement in pain and function. However, few trials have used consistent outcome measures to track changes in pain and function. 1) To identify all outcomes measures used in trials utilizing exercise-based interventions for mid-portion Achilles tendinopathy (AT) that assess self-reported pain and function and to report on the reliability and validity of the identified measures, and 2) Propose measures to optimally assess self-reported pain and function in patients with AT. Literature Review. Three major electronic databases were searched from inception until May 2016 for studies using isometric, eccentric or isotonic loading protocols for mid-portion AT. Randomized and non-randomized trials of isometric, eccentric or isotonic loading in people with mid-portion AT. Forty-six studies were included and all outcome measures assessing self-reported pain and function were extracted. While a variety of outcome measures have been used, few have provided reliability data. There is evidence to suggest that the Victorian Institute of Sports Assessment- Achilles (VISA-A) is the only valid and reliable measure of self-reported pain and function for people with mid-portion AT. No other outcome measures have been validated in mid-portion AT. The VISA-A remains the gold standard for assessing pain and function in mid-portion AT. However, while the validity or reliability of the Numerical Rating Scale (NRS) of pain during a functional task has not been established it may be a better measure of immediate treatment effect. 5.

Synergistic activity of platelet rich plasma and high volume image guided injection for patellar tendinopathy.

Platelet rich plasma and high volume image guided injections of saline have been used in the treatment of patellar tendinopathy with positive results. As the different mechanisms of action do not interfere each other, it can be hypothesized that they can be used in combination. Aim of this study was twofold: first, to evaluate the efficacy of these two treatments in the management of patellar tendinopathy; second, to verify whether the combination of these therapies could provide further advantages. Fifty-four patients suffering from patellar tendinopathy were enrolled. After clinical (VAS and VISA-P) and sonographic evaluation, two ultrasound guided injections (2weeks apart) of platelet rich plasma, high-volume image-guided injections of saline, or both in association were performed. The VAS and VISA-P scores obtained from the three treatments groups (18 patients in each group) were compared across the different follow-up times (3 and 6months). In the short term both treatments showed comparable efficacy, whereas in the medium term the positive effects of high-volume image-guided injections gradually diminished and platelet rich plasma showed greater efficacy. Better results (reduced pain, improved function and increased number of subjects who exhibited optimal recovery [> 20 points in VISA-P score]) were observed when both procedures were associated. The contemporaneous administration of platelet rich plasma and high volume image guided injections of saline treatments, which influence tendon repair by means of different mechanisms, grants a greater improvement for patellar tendinopathy. This finding has clinical relevance, given that this condition has a substantial impact on sports and work performance. III.

Achilles Tendinopathy.

Achilles tendinopathy is a common cause of disability. Despite the economic and social relevance of the problem, the causes and mechanisms of Achilles tendinopathy remain unclear. Tendon vascularity, gastrocnemius-soleus dysfunction, age, sex, body weight and height, pes cavus, and lateral ankle instability are considered common intrinsic factors. The essence of Achilles tendinopathy is a failed healing response, with haphazard proliferation of tenocytes, some evidence of degeneration in tendon cells and disruption of collagen fibers, and subsequent increase in noncollagenous matrix. Tendinopathic tendons have an increased rate of matrix remodeling, leading to a mechanically less stable tendon which is more susceptible to damage. The diagnosis of Achilles tendinopathy is mainly based on a careful history and detailed clinical examination. The latter remains the best diagnostic tool. Over the past few years, various new therapeutic options have been proposed for the management of Achilles tendinopathy. Despite the morbidity associated with Achilles tendinopathy, many of the therapeutic options described and in common use are far from scientifically based. New minimally invasive techniques of stripping of neovessels from the Kager's triangle of the tendo Achillis have been described, and seem to allow faster recovery and accelerated return to sports, rather than open surgery. A genetic component has been implicated in tendinopathies of the Achilles tendon, but these studies are still at their infancy.

The Role of the Vascular and Structural Response to Activity in the Development of Achilles Tendinopathy: A Prospective Study

Background: Several risk factors have been suggested in the development of Achilles tendinopathy, but large-scale prospective studies are limited. Purpose: To investigate the role of the vascular response to activity of the Achilles tendon, tendon thickness, ultrasound tissue characterization (UTC) of tendon structure, and foot posture as possible risk factors in the development of Achilles tendinopathy. Study Design: Cohort study; Level of evidence, 2. Methods: The study began with 351 first-year students at Ghent University. After 51 students were excluded, 300 were tested in the academic years 2013-2014 and 2014-2015 and were followed prospectively for 2 consecutive years by use of a multilevel registration method. Of those, 250 students were included in the statistical analysis. At baseline, foot posture index and UTC were investigated bilaterally. Blood flow and tendon thickness were measured before and after a running activity. Cox regression analyses were performed to identify significant contributors to the development of Achilles tendinopathy. Results: During the 2-year follow-up, 27 of the included 250 participants developed Achilles tendinopathy (11%). Significant predictive effects were found for female sex and blood flow response after running (P = .022 and P = .019, respectively). The risk of developing Achilles tendinopathy increased if the blood flow increase after running was reduced, regardless of sex, foot pronation, and timing of flow measurements. The model had a predictive accuracy of 81.5% regarding the development of Achilles tendinopathy, with a specificity of 85.0% and a sensitivity of 50.0%. Conclusion: This prospective study identified both female sex and the diminished blood flow response after running as significant risk factors for the development of Achilles tendinopathy. UTC of tendon structure, Achilles tendon thickness, and foot posture did not significantly contribute to the prediction of Achilles tendinopathy. A general evaluation of tendon structure by UTC, measurement of tendon thickness, or determination of the foot posture index will not allow clinicians to identify patients at risk for developing Achilles tendinopathy. Furthermore, it may be possible to improve blood flow after activity by using noninvasive techniques (such as prostaglandins, compression stockings, heat, massage, and vibration techniques). These techniques may be useful in the prevention and management of Achilles tendinopathy, but further research is needed.

Pathogenesis and Management of Tendinopathies in Sports Medicine.

Tendinopathy is a major clinical problem in sports medicine and is often difficult to treat. Traditional therapeutic approaches have focused on reducing inflammation, yet research suggests that little to no inflammation is present in the tendons that fail to heal. The purpose of this review was to evaluate the effectiveness of the available treatment options for tendinopathy and to inform best clinical practices. A narrative review. A comprehensive search of electronic databases (PubMed, Google Scholar and Web of Science) was conducted to identify relevant studies through June 2016. Studies were deemed relevant if they were published in English and contained original research on the management of tendinopathy in humans. Studies varied in methodological quality and were often limited by small sample size and lack of sufficient control groups. Critical evaluation of the literature suggests that physical therapy with or without eccentric exercise should be considered a first-line treatment. Corticosteroids and nonsteroidal anti-inflammatory drugs provide short-term symptomatic relief, but long-term efficacy has not been demonstrated. Inconsistent results do not support the routine use of prolotherapy, platelet-rich plasma injections and topical nitric oxide patches. Operative intervention should be reserved until conservative measures fail or an obvious operative lesion is present. While numerous therapeutic modalities exist for tendinopathy in the athlete, the ideal treatment protocol has not been clearly defined. The development of new targeted therapies for tendinopathy is likely to follow a greater understanding of the cellular and molecular mechanisms that underlie its pathogenesis.

Evidence to Practice Review: Best Practices in Patellar Tendinopathy Management

Patellar tendinopathy (PT) is a degenerative condition that is common in sporting populations due to the loads placed on the tendon during dynamic activity. PT often occurs in overtraining situations; however, it may also occur in conjunction with and/or worsen through poor biomechanics, persistent inflammation, and altered movement patterns. Although we have evidence to support the prevalence of this injury, we do not have a clear understanding of the contributing factors and pathophysiology that lead the pain and disability reported in athletes with PT. The purpose of this evidence to review manuscript was to review and summarize a systematic review on interventions to treat PT. The authors aimed to include any randomized controlled trial that treated patients with PT and used the VISA-P as an outcome measure. Seven different PT interventions were described and summarized by the authors in this review. On the conservative end of the treatment spectrum, eccentric loading programs and extracorporeal shockwave therapy were found to be effective at reducing pain. More invasive approaches often utilized after failed conservative treatment such as platelet-rich plasma injections and arthroscopic tenotomy were also deemed effective. Therapeutic ultrasound and sclerosing treatments were found to be ineffective treatments, and corticosteroid injections were labeled as contraindicated against in patients with PT. This review has shown that both conservative and invasive treatment approaches can reduce pain in patients with PT. However, there is still no consensus on the optimal treatment protocols for patients with PT due to the variability in treatments and lack of consistency in protocols. Thus, we recommend utilizing an individualized approach and appropriate clinical judgement to guide treatments derived from a thorough patient history and physical/biomechanical examination to identify interventions with the highest likelihood of resolving symptoms.

The effect of load on Achilles tendon structure in novice runners

ObjectivesTo observe the changes in Achilles tendon structure in novice runners, with loading prescriptions of 100% body weight compared to 20% body weight. DesignRandomised crossover. MethodsTwenty novice runners participated in two separate running bouts spaced 14days apart, one of high load at 100% body weight, and one of low load at 20% body weight. Tendon structure was measured by ultrasonographic tissue characterisation on 6 occasions; immediately prior to each run, 2 and 7days after each run. ResultsThe interaction effect of time and condition was not found to be significant for echotypes I–IV [Wald chi-square=2.8, d.f.=2, P=0.247; Wald chi-square=2.888, d.f.=2, P=0.236; Wald chi-square=1.385, d.f.=2, P=0.5; Wald chi-square=4.19, d.f.=2, P=0.123], respectively. A significant effect of time was found for echotypes III [Wald chi-square=6.785, d.f.=2, P=0.0.034] and IV [Wald chi-square=7.491, d.f.=2, P=0.0.024]. ConclusionsThe decrease in echotypes III and IV suggest that moderate loads can be applied to the Achilles tendon without compromising tendon structure. Low to moderate loads may be beneficial in the management of Achilles tendinopathy. Further studies should focus on protocols with higher loading and/or repetitive loading in athletic populations with and without Achilles tendinopathy to assess any differences in tendon structure.

Spanish Consensus Statement: Clinical Management and Treatment of Tendinopathies in Sport.

On October 15, 2016, experts met at Clínica CEMTRO in Madrid, Spain, under the patronage of the Spanish Society for Sports Traumatology (SETRADE), the Spanish Society of Sports Medicine (SEMED), the Spanish Association of Medical Services for Football Clubs (AEMEF), the Spanish Association of Medical Services for Basketball Clubs (AEMB), F.C. Barcelona, and Clínica CEMTRO. The purpose was to consider the most appropriate clinical management and treatment of tendinopathies in sports, based on proven scientific data described in the medical literature as well as on each expert’s experience. Prior to the meeting, each expert received a questionnaire regarding clinical management and treatment of tendinopathies in sports. The present consensus document summarizes the answers to the questionnaire and the resulting discussion and consensus regarding current concepts on tendinopathies in sports.

Cyriax's deep friction massage application parameters: Evidence from a cross-sectional study with physiotherapists

BackgroundDeep friction massage is one of several physiotherapy interventions suggested for the management of tendinopathy. ObjectivesTo determine the prevalence of deep friction massage use in clinical practice, to characterize the application parameters used by physiotherapists, and to identify empirical model-based patterns of deep friction massage application in degenerative tendinopathy. Designobservational, analytical, cross-sectional and national web-based survey. Methods478 physiotherapists were selected through snow-ball sampling method. The participants completed an online questionnaire about personal and professional characteristics as well as specific questions regarding the use of deep friction massage. Characterization of deep friction massage parameters used by physiotherapists were presented as counts and proportions. Latent class analysis was used to identify the empirical model-based patterns. Crude and adjusted odds ratios and 95% confidence intervals were computed. ResultsThe use of deep friction massage was reported by 88.1% of the participants; tendinopathy was the clinical condition where it was most frequently used (84.9%) and, from these, 55.9% reported its use in degenerative tendinopathy. The “duration of application” parameters in chronic phase and “frequency of application” in acute and chronic phases are those that diverge most from those recommended by the author of deep friction massage. ConclusionWe found a high prevalence of deep friction massage use, namely in degenerative tendinopathy. Our results have shown that the application parameters are heterogeneous and diverse. This is reflected by the identification of two application patterns, although none is in complete agreement with Cyriax's description.

FORTALECIMENTO MUSCULAR EXCÊNTRICO NO TRATAMENTO DA TENDINOPATIA DE AQUILES: UMA REVISÃO SISTEMÁTICA

INTRODUÇÃO: A Fisioterapia, no manejo da tendinopatia de Aquiles, utiliza-se de recursos físicos moduladores da inflamação e analgésicos. Como parte do tratamento fisioterapêutico a literatura tem sugerido o exercício de fortalecimento excêntrico com eficaz na resolução de tendinopatias. OBJETIVO: O presente estudo teve como objetivo a busca de evidências científicas sobre o uso do exercício de fortalecimento excêntrico no manejo da Tendinopatia de Aquiles. MÉTODOS: Para a composição da revisão foi realizada busca por estudos nas base de dados virtuais Pubmed e PEDro. Os descritores utilizados foram as seguintes: Eccentric, tendinopathy, Achilles Tendonitis. Para compor o estudo os artigos deveriam obedecer os seguintes critérios de elegibilidade: artigos publicados na língua inglesa, intervalo de publicação entre 2013 a 2017, ensaios clínicos randomizados, com pontuação superior a 6 na escala de qualidade PEDro. RESULTADOS: Foram localizados um total de 87 artigos, dos quais apenas 21 referiam-se a temática em questão. Dos 21 artigos 14 foram excluídos pelos seguintes motivos: 3 por consistirem em relatos de caso, 1 classificado como revisão de literatura, 1 caracterizava-se como comentário clinico, 1 envolvia um estudo com modelo animal, 1 era um projeto de pesquisa, 5 não classificavam-se com ensaios clínicos randomizados, 1 obteve nota inferior a 6 na escala de qualidade PEDro e 1 deles proporcionava descrição incompleta dos resultados. CONCLUSÃO: O fortalecimento muscular excêntrico caracteriza-se como uma modelo terapêutico de escolha para o manejo da tendinopatia de aquiles, a combinação com outras modalidades potencializa seus efeitos fisiológicos.