Contextual factors, placebo and nocebo effects in physical therapy: clinical relevance and impact on research

A brief overview on placebo and nocebo effects Placebo and nocebo effects represent one of the most fascinating topics in the healthcare field. They represent complex and distinct psychoneurobiological phenomena where behavioural and neurophysiological changes occur during an interaction between the patient and the healthcare context (1). Placebo effects (Latin \u201cI shall please\u201d) are produced by a psychosocial context that is capable of positively affecting the patient's brain and therapeutic outcomes (2-4). On the contrary, nocebo effects (Latin \u201cI shall harm\u201d) are consequences of the negative perception of the ritual and therapeutic act on the patient's mind and body, so much so that it generates unwanted effects and side effects (5-7). Throughout the history of medicine, placebo and nocebo have been traditionally viewed as bothersome variables to check for in a clinical trial. In the last four decades, in light of some significant clinical and laboratory findings, they have become a source of research interest. Indeed, placebo and nocebo have been adopted as a conceptual model to examine the body-mind interaction and the human body systems, exploring their connection with different systems, mechanisms, diseases and therapeutic interventions (8, 9). In particular, placebo and nocebo effects have been studied in mood (10), cardiovascular, respiratory (11), gastrointestinal (12, 13), motor (14), immune and endocrine (15), and pain systems (16-18). Clinically, not all improvement or aggravation of patients\u2019 symptoms is due to placebo and nocebo effects. It is necessary to rule out the patients\u2019 modifications created by placebo and nocebo effects from the changes of outcomes related to other confounding elements. The elements which could create misinterpretations of the patients\u2019 clinical picture are: the spontaneous remission of the disease and symptom fluctuation (also called the natural history), the regression to the mean (a statistical phenomenon caused by selection biases), the patient\u2019s and clinician\u2019s biases during the reports of clinical conditions, and unidentified effects of concomitant co-interventions (8, 9). Different psychoneurobiological findings allowed the scientific community to begin to understand the underlying mechanisms of placebo and nocebo effects. From a theoretical perspective, two main psychological subjective constructs have been suggested to explain how placebo or nocebo effects act: the expectation and the conditioning. The social learning, reward, anxiety reduction, desire, motivation, memory, somatic focus, genetic and personality traits also represent alternative theories (19-25). \u201cAlternative\u201d however does not mean that these psychological mechanisms are mutually exclusive: they can interact simultaneously (26). Regarding the actual findings, placebo and nocebo interact with the brain modulatory systems at a neurochemical level, through the release of specific neurotransmitters. For instance, considering pain outcome as a model, the endogenous opioids, dopamine, cannabinoids, oxytocin and vasopressin are involved in placebo analgesia, while cholecystokinin, dopamine, opioid deactivation and cyclooxygenaseprostaglandins activation are implicated in nocebo hyperalgesia (27-29). Furthermore, recent advances in neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), suggest an involvement of specific neural correlates during placebo and nocebo effects, mainly the pain one. In fact, placebo and nocebo are able to activate or deactivate the four key brain regions commonly associated with the descending pain processing pathway: the dorsolateral prefrontal cortex, the rostral anterior cingulate cortex, the periaqueductal gray and the dorsal horn of spine (16). Nevertheless, they represent only a part of brain areas showing a change in their activity during placebo or nocebo (30-32). Therefore, the previously described evidence suggests that placebo and nocebo effects are concrete and genuine phenomena, triggered by different contexts, and capable of impacting the patients\u2019 brain. It is necessary to define what the context is, and why its parts are important from a clinical perspective (33). The healthcare context as a trigger of placebo and nocebo effects In 1955 Balint described the context as the \u201cwhole atmosphere around the therapy\u201d (34). The context is not a vacuum, but it embodies a healing space composed by internal, external and relational elements capable of interacting with the patient\u2019s disease (35). The internal elements consist of memories, emotions, expectations and psychological characteristics of the patient. The external elements include the physical aspects of therapy, such as the kind of treatment (pharmacological or manual) and the place in which the treatment is delivered. Relational elements are represented by all the social cues that characterize the patient-clinician relationship, such as the verbal information that the clinicians give to the patient, the communication style or the body language (36). In 2001, Di Blasi et al. defined these elements as \u201ccontextual factors\u201d. These factors have been grouped, from a clinical practice point of view, in five categories: a) clinician features, b) patient features, c) patient-clinician relationship, d) intervention features, and e) healthcare setting features (37). As a whole, contextual factors constitute the therapeutic ritual and healing symbols surrounding the patient-clinician encounter, capable of producing changes in the patient at perceptual, neurophysiological and cognitive levels (38). Indeed, contextual factors convey a hidden meaning, actively detected and analysed by the patient, which is essential for the perception of care and the interpretation of the therapeutic intervention (39, 40). When these contextual stimuli and cues are filtered by the patient\u2019s perspective and mind-set (41), they are translated into a complex cascade of psycho-neuroimmunoendocrine events, thus triggering placebo and nocebo effects and influencing the course of illness (42, 43). From a clinical perspective, the contextual factors pervade every healthcare action (history taking, physical examination, therapy and prognosis) and directly affect the quality of the health-related outcome (44-46). A positive context, that is characterized by the presence of positive contextual factors, can improve therapeutic outcome by producing placebo effects, while a negative context, characterized by the presence of negative contextual factors, can aggravate therapeutic outcome by creating nocebo effects(47, 48). For example, during the same treatment delivery (e.g. painkillers), the use of positive verbal suggestion (e.g. \u201cThis therapy will help you and it will decrease pain\u201d) can improve musculoskeletal pain, while the adoption of verbal suggestion of uncertainty (e.g. \u201cThis therapy could help you and sometimes it decrease pain\u201d) can aggravate patient\u2019s pain (49). The presented studies offer a starting point for reflection about the role of the contextual factors surrounding the administration of a healthcare treatment: they can be a source of improvement of the efficacy of the therapy or implicated in the manifestation of adverse effects. The logical consequence is to wonder whether context, placebo and nocebo effects have been taken into consideration in a specific healthcare field, such as physical therapy. The link between placebo, nocebo effects and physical therapy Throughout the history of physical therapy and rehabilitation, placebo and nocebo effects have been considered as problematic phenomena for two main reasons. From a research point of view, they have represented confounding factors capable of limiting the internal validity of the study design and reducing the external validity of the findings (50). From a clinical point of view, they have embodied troublesome and nonspecific variables able to attenuate the therapeutic role of specific therapies such as massage, joint mobilization and therapeutic exercise (51, 52). As a consequence, for many years the role of placebo and nocebo effects was debated worldwide by clinicians and researchers (53-55). At the end of the first decade of the twenty-first century the scientific community began to investigate the mechanisms of action of joint, soft tissue and neural therapeutic intervention, consequently revaluing the role of placebo and nocebo effects in physiotherapy (56). Recent studies have suggested a mechanical and neurophysiological mechanism (peripheral, spinal and supraspinal) linked to the therapeutic strategies adopted by physical therapists (57). Among the supraspinal mechanisms, the placebo and nocebo effects have assumed an important top-down role in inducing changes in patient\u2019s symptoms (58), thus becoming elements that clinicians should adopt in clinical practice (59). Recently, also the context in which interventions are delivered has been suggested as a moderator of clinical effects (60). A new line of research has indicated the context as responsible for a larger non-specific component of treatment efficacy in physical therapy (61). Despite these promising advances, the following issues remain unexplored: 1) What are the contextual factors? 2) How can the contextual factors trigger placebo and nocebo effects? 3) Which therapeutic outcomes can be influenced by the contextual factors? 4) Are the physical therapists aware of the use of contextual factors in clinical practice? 5) What is the role of contextual factors in research? General organization of the research project The main goal of this PhD research project is to investigate the relevance of the contextual factors as triggers of placebo/nocebo effects and their impact on therapeutic outcomes in physiotherapy. Different studies were conducted during the 3-year period of PhD training (2015-2018). The results, relative discussions and implications are reported in the chapters of the present dissertation as follows: \u2022 Chapter I: a conceptual model regarding the role of the contextual factors as triggers of placebo, nocebo responses and influencers of physical therapy outcomes; \u2022 Chapter II: the model of contextual factors regarding musculoskeletal pain, which is a common outcome encountered by physical therapists; \u2022 Chapter III: the link between the determinants of patient satisfaction in outpatient musculoskeletal physiotherapy clinics and the contextual factors; \u2022 Chapter IV: the knowledge, attitude and behaviour of Italian physiotherapists specialized in manual therapy towards contextual factors; \u2022 Chapter V: the translational value of contextual factors and their relevance for physical therapy research

Digital Health Competencies Among Health Care Professionals: Systematic Review

Digitalization is not fully implemented in clinical practice, and several factors have been identified as possible barriers, including the competencies of health care professionals. However, no summary of the available evidence has been provided to date to depict digital health competencies that have been investigated among health care professionals, the tools used in assessing such competencies, and the effective interventions to improve them

“Do Not Mix Apples with Oranges” to Avoid Misinterpretation of Placebo Effects in Manual Therapy: The Risk Is Resulting in a Fruit Basket. Comment on Molina-Àlvarez et al. Manual Therapy Effect in Placebo-Controlled Trials: A Systematic Review and Meta-Analysis. Int. J. Environ. Res. Public Health 2022, 19, 14021

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Clinical and functional results of Optetrack Total Knee Arthroplasty after 6 to 13 years: findings from a retrospective study

Introduction: Total Knee Arthroplasty (TKA) is considered the gold standard in the treatment of knee osteoarthritis and post-traumatic knee deformities. The aim of the study was to report the functional results of a group of OptetrackTM TKA patients over a period between 6 and 13 years after surgery. Material and methods: A group of 47 TKA prostheses applied to 39 patients (32 women) were analysed retrospecti- vely. All patients received the same type of TKA and the same rehabilitation program. Patients were assessed before sur- gery and 3, 6 and 12 months after surgery; follow-ups were performed annually. Assessment was based on Knee Range of Motion (ROM) and a Knee Rating Score (IKS) composed of two partial scores: Knee Score (KS) and Functional Score (FS). The variables in uencing the IKS score were identi ed using a Generalized Linear Model. Results: The mean follow-up was 9.95 years (range 6–13). Mean age was 81.2 years (range 62–95). At the last fol- low-up, the mean IKS score increased from 78.6 (range 15–155) to 145.2 (range 58–200). Mean KS increased from 40.5 (range 0–96) to 85.7 (range 50–100); mean FS increased from 38.9 (range 0–75) to 60.9 (range 0–100). Mean knee ROM increased from 87.6° to 108.4° (range 50°–130°). Preoperative IKS score, male sex and age at surgery were positively correlated to the IKS score at follow-up. Conclusions: TKA improved pain score, while the functional score decreased over time. Good preoperative IKS score and male sex were considered good outcome predictors; old preoperative age was considered as unfavourabl

The Knowledge of Contextual Factors as Triggers of Placebo and Nocebo Effects in Patients With Musculoskeletal Pain: Findings From a National Survey

Backgrounds: Contextual factors (CFs) have been recently proposed as triggers of placebo and nocebo effects in musculoskeletal pain. CFs encompass the features of the clinician (e.g. uniform), patient (e.g. expectations), patient-clinician relationship (e.g. verbal communication), treatment (e.g. overt therapy), and healthcare setting (e.g. design). To date, the researchers' understanding of Italian patients' knowledge about the role of CFs in musculoskeletal pain is lacking.Objectives: The aim of this study was to investigate attitudes and beliefs of Italian patients with musculoskeletal pain about the use of CFs in clinical practice.Methods: A national sample of Italian patients with musculoskeletal pain was recruited from 12 outpatient private clinics in Italy. An invitation to participate in an online survey was sent to patients: a) exhibiting musculoskeletal pain; b) aged 18-75; c) with a valid e-mail account; and d) understanding Italian language. Survey Monkey software was used to deliver the survey. The questionnaire was self-reported and included 17 questions and 2 clinical vignettes on the patients' behavior, beliefs, and attitudes towards the adoption of CFs in clinical practice. Descriptive statistics and frequencies described the actual number of respondents to each question.Results: One thousand one hundred twelve patients participated in the survey. Five hundred seventy-four participants were female (52%). The average age of patients was 41.7 +/- 15.2 years. Patients defined CFs as an intervention with an unspecific effect (64.3%), but they believed in their clinical effectiveness. They identified several therapeutic effects of CFs for different health problems. Their use was considered ethically acceptable when it exerts beneficial psychological effects (60.4%), but it was banned if considered deceptive (51.1%). During clinical practice, patients wanted to be informed about the use of CFs (46.0%) that are accepted as an addition to other interventions to optimize clinical responses (39.3%). Moreover, patients explained the power of CFs through body-mind connections (37.1%).Conclusion: Patients with musculoskeletal pain had positive attitudes towards the use and effectiveness of CFs when associated with evidence-based therapy. They mostly perceived the adoption of CFs in clinical practice as ethical

Italian nurses’ experiences of the COVID-19 pandemic through social media: A longitudinal mixed methods study of Internet posts

Objective: To examine the experience of Italian nurses posted on social media and discover changes, if any, over the waves. Methods: A mixed methods study reported according to the Good Reporting of a Mixed Methods Study criteria. All narratives (texts, letters and interviews) posted by Italian nurses from February 2020 to May 2020 (first wave) and from October 2020 to May 2021 (second/third wave) on the five most famous Italian professional social media platforms. The data were analysed qualitatively (first wave) and then quantitatively (second/third wave). Results: A total of 380 narratives (202,626 words, 2510 quotes) were posted in the first wave, and 161 (68,388 words, 835 quotes) in the second/third wave. In the first wave, the following five themes emerged: (a) ‘sharing what is happening within myself’ (891; 35.5%); (b) ‘experiencing unprecedented working conditions’ (749; 29.8%); (c) ‘failing to rehabilitate the image of nurses in society’ (376; 15%); (d) ‘experiencing a deep change’ (253; 10.1%) and (e) ‘do not abandon us’ (241; 9.6%). The same themes and subthemes also emerged in the second/third wave with some significant differences, indicating changes in the lived experience of nurses. Moreover, in the second/third wave, a new theme emerged: ‘experiencing the mixed emotions towards jabs’. Conclusions: By analysing their posts, Italian nurses continue to face challenges during the COVID-19 pandemic, with changes in their lived experiences across the waves. Governments, nursing associations and health care organizations should consider these changes to design policies to prevent the further loss of nurses

Intrarater and Inter-rater Reliability of Active Cervical Range of Motion in Patients With Nonspecific Neck Pain Measured With Technological and Common Use Devices: A Systematic Review With Meta-regression

Objectives The purpose of this systematic review was to compare intrarater and inter-rater reliability of active cervical range of motion (ACROM) measures obtained with technological devices to those assessed with low-cost devices in patients with nonspecific neck pain. As a secondary outcome, we investigated if ACROM reliability is influenced by the plane of the assessed movement. Methods Medline, Scopus, Embase, the Cochrane Library, CINHAL, PEDro, and gray literature were searched until August 2016. Inclusion criteria were reliability design, population of adults with nonspecific neck pain, examiners of any level of experience, measures repeated at least twice, and statistical indexes on reliability. A device was considered inexpensive if it cost less than \ue2\u82\uac500. The risk of bias of included studies was assessed by Quality Appraisal of Reliability Studies. Results The search yielded 35 151 records. Nine studies met all eligibility criteria. Their Quality Appraisal of Reliability Studies mean score was 3.7 of 11. No significant effect of the type of device (inexpensive vs expensive) on intraclass correlation coefficient (ICC) was identified for intrarater (ICC = 0.93 vs 0.91; P >.99) and inter-rater reliability (ICC = 0.80 vs 0.87; P >.99). The plane of movement did not affect inter-rater reliability (P =.11). Significant influences were identified with intrarater reliability (P =.0001) of inexpensive devices, where intrarater reliability decreased (P =.01) in side bending, compared with flexion-extension. Conclusions The use of expensive devices to measure ACROM in adults with nonspecific neck pain does not seem to improve the reliability of the assessment. Side bending had a lower level of intrarater reliability

Using contextual factors to elicit placebo and nocebo effects: An online survey of healthcare providers' practice

Contextual factor use by healthcare professionals has been studied mainly among nurses and physiotherapists. Preliminary results show that healthcare professionals use contextual factors without specifically labelling them as such. The main objective of this study was to evaluate knowledge and explore voluntary contextual factor use among various healthcare professions. The results aim to facilitate hypothesis-generation, to better position further research to explain and characterise contextual factor use. We conducted a web-based questionnaire cross-sectional observational study on a non-probabilistic convenience sample. Face and content validity were tested through cognitive interviews. Data were analysed descriptively. The target population was the main healthcare profession, or final year students, defined by the French public health law. The countries of distribution of the questionnaire were the French-speaking European countries. Among our 1236 participants, use of contextual factors was widespread. Those relating to the therapeutic relationship (e.g., communication) and patient characteristics (e.g., past experiences) were reportedly the most used. Meanwhile, contextual factors related to the healthcare providers' characteristics and their own beliefs were reported as less used. Despite high variability, respondents suggested contextual effects contribute to approximately half of the overall effect in healthcare and were perceived as more effective on children and elderly adults. Conceptual variations that exist in the literature are also present in the way healthcare providers consider contextual effects. Interestingly, there seems to be common ground between how physiotherapists, nurses and physicians use different contextual factors. Finally, in the present study we also observed that while there are similarities across usage, there is lack of both an epistemological and ethical consensus among healthcare providers with respect to contextual factors

Comparing the effects of differential and visuo-motor training on functional performance, biomechanical, and psychological factors in athletes after ACL reconstruction: a randomized controlled trial

Variation during practice is widely accepted to be advantageous for motor learning and is, therefore, a valuable strategy to effectively reduce high-risk landing mechanics and prevent primary anterior cruciate ligament (ACL) injury. Few attempts have examined the specific effects of variable training in athletes who have undergone ACL reconstruction. Thereby, it is still unclear to what extent the variations in different sensor areas lead to different effects. Accordingly, we compared the effects of versatile movement variations (DL) with variations of movements with emphasis on disrupting visual information (VMT) in athletes who had undergone ACL reconstruction. Forty-five interceptive sports athletes after ACL reconstruction were randomly allocated to a DL group (n = 15), VT group (n = 15), or control group (n = 15). The primary outcome was functional performance (Triple Hop Test). The secondary outcomes included dynamic balance (Star Excursion Balance Test (SEBT)), biomechanics during single-leg drop-landing task hip flexion (HF), knee flexion (KF), ankle dorsiflexion (AD), knee valgus (KV), and vertical ground reaction force (VGRF), and kinesiophobia (Tampa Scale of Kinesiophobia (TSK)) assessed before and after the 8 weeks of interventions. Data were analyzed by means of 3 × 2 repeated measures ANOVA followed by post hoc comparison (Bonferroni) at the significance level of p ≤ 0.05. Significant group × time interaction effects, main effect of time, and main effect of group were found for the triple hop test and all eight directions, SEBT, HF, KF, AD, KV, VGRF, and TSK. There was no significant main effect of group in the HF and triple hop test. Additionally, significant differences in the triple hop test and the seven directions of SEBT, HF, KF, KV, VGRF, and TSK were found between the control group and the DL and VMT groups. Between group differences in AD and the medial direction of SEBT were not significant. Additionally, there were no significant differences between VMT and the control group in the triple hop test and HF variables. Both motor learning (DL and VMT) programs improved outcomes in patients after ACL reconstruction. The findings suggest that DL and VMT training programs lead to comparable improvements in rehabilitation