Comparative accuracy of ChatGPT-4, Microsoft Copilot and Google Gemini in the Italian entrance test for healthcare sciences degrees: a cross-sectional study.

BACKGROUND: Artificial intelligence (AI) chatbots are emerging educational tools for students in healthcare science. However, assessing their accuracy is essential prior to adoption in educational settings. This study aimed to assess the accuracy of predicting the correct answers from three AI chatbots (ChatGPT-4, Microsoft Copilot and Google Gemini) in the Italian entrance standardized examination test of healthcare science degrees (CINECA test). Secondarily, we assessed the narrative coherence of the AI chatbots' responses (i.e., text output) based on three qualitative metrics: the logical rationale behind the chosen answer, the presence of information internal to the question, and presence of information external to the question. METHODS: An observational cross-sectional design was performed in September of 2023. Accuracy of the three chatbots was evaluated for the CINECA test, where questions were formatted using a multiple-choice structure with a single best answer. The outcome is binary (correct or incorrect). Chi-squared test and a post hoc analysis with Bonferroni correction assessed differences among chatbots performance in accuracy. A p-value of < 0.05 was considered statistically significant. A sensitivity analysis was performed, excluding answers that were not applicable (e.g., images). Narrative coherence was analyzed by absolute and relative frequencies of correct answers and errors. RESULTS: Overall, of the 820 CINECA multiple-choice questions inputted into all chatbots, 20 questions were not imported in ChatGPT-4 (n = 808) and Google Gemini (n = 808) due to technical limitations. We found statistically significant differences in the ChatGPT-4 vs Google Gemini and Microsoft Copilot vs Google Gemini comparisons (p-value < 0.001). The narrative coherence of AI chatbots revealed "Logical reasoning" as the prevalent correct answer (n = 622, 81.5%) and "Logical error" as the prevalent incorrect answer (n = 40, 88.9%). CONCLUSIONS: Our main findings reveal that: (A) AI chatbots performed well; (B) ChatGPT-4 and Microsoft Copilot performed better than Google Gemini; and (C) their narrative coherence is primarily logical. Although AI chatbots showed promising accuracy in predicting the correct answer in the Italian entrance university standardized examination test, we encourage candidates to cautiously incorporate this new technology to supplement their learning rather than a primary resource. TRIAL REGISTRATION: Not required.

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.

Mechanical Complications of Proximal Femur Fractures Treated with Intramedullary Nailing: A Retrospective Study.

Background and Objectives: This retrospective cohort study analyzes mechanical complications in hip fracture surgery using the Trochanteric Fixation Nail-Advanced (TFNA) implant. It investigates the correlation of these complications with demographic, intraoperative, and radiological factors, aiming to identify associated risk factors and suggest improvements in clinical surveillance and treatment strategies. Materials and Methods: We enrolled 253 patients diagnosed with pertrochanteric hip fractures treated between 2017 and 2021, with 126 meeting the criteria for a minimum 6-month follow-up. Data on demographics, American Anesthesia Association Classification (ASA), comorbidities, AO/OTA [AO (Arbeitsgemeinschaft für Osteosynthesefragen)/OTA (Orthopedic Trauma Association)] fracture classification, procedural details, and time to failure were collected. Radiographs were evaluated for reduction quality, the tip-apex distance (TAD), progressive varus deviation, and identification of mechanical complications. Statistical analysis was performed using SPSS software. Results: The predominant AO/OTA fracture classification was 31A2 in 67 cases (52.7%). Reduction quality was deemed good or acceptable in 123 cases (97.6%). The mean time to failure was 4.5 months (range: 2.2-6). The average TAD was 18 mm (range: 1.2-36), with a mean progressive varus deviation of 2.44° (range: 1.30-4.14). A good or acceptable reduction quality was observed in 97.6% of cases. Mechanical complications occurred in 21.4% of patients, with significant associations found with the lateral cortex fracture, use of a TFNA implant with a 130° angle, open reduction, and absence of prior osteoporosis treatment. Conclusions: The study provides insights into mechanical complications in proximal femur fractures treated with the TFNA nail, emphasizing the need for enhanced clinical and radiographic surveillance, especially in patients without osteoporosis treatment. Our findings support the necessity for further clinical studies comparing these outcomes with other implant designs and underscore the importance of personalized treatment strategies to reduce complication rates.

Which Portion of Physiotherapy Treatments' Effect Is Not Attributable to the Specific Effects in People With Musculoskeletal Pain? A Meta-Analysis of Randomized Placebo-Controlled Trials.

OBJECTIVE: We aimed to quantify the proportion not attributable to the specific effects (PCE) of physical therapy interventions for musculoskeletal pain. DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched Ovid, MEDLINE, EMBASE, CINAHL, Scopus, PEDro, Cochrane Controlled Trials Registry, and SPORTDiscus databases from inception to April 2023. STUDY SELECTION CRITERIA: Randomized placebo-controlled trials evaluating the effect of physical therapy interventions on musculoskeletal pain. DATA SYNTHESIS: Risk of bias was evaluated using the Cochrane risk-of-bias tool for randomized trials (RoB 2). The proportion of physical therapy interventions effect that was not explained by the specific effect of the intervention was calculated, using the proportion not attributable to the specific effects (PCE) metric, and a quantitative summary of the data from the studies was conducted using the random-effects inverse-variance model (Hartung-Knapp-Sidik-Jonkman method). RESULTS: Sixty-eight studies were included in the systematic review (participants: n = 5238), and 54 placebo-controlled trials informed our meta-analysis (participants: n = 3793). Physical therapy interventions included soft tissue techniques, mobilization, manipulation, taping, exercise therapy, and dry needling. Placebo interventions included manual, nonmanual interventions, or both. The proportion not attributable to the specific effects of mobilization accounted for 88% of the immediate overall treatment effect for pain intensity (PCE = 0.88, 95% confidence interval [CI]: 0.57, 1.20). In exercise therapy, this proportion accounted for 46% of the overall treatment effect for pain intensity (PCE = 0.46, 95% CI: 0.41, 0.52). The PCE in manipulation excelled in short-term pain relief (PCE = 0.81, 95% CI: 0.62, 1.01) and in mobilization in long-term effects (PCE = 0.86, 95% CI: 0.76, 0.96). In taping, the PCE accounted for 64% of disability improvement (PCE = 0.64, 95% CI: 0.48, 0.80). CONCLUSION: The outcomes of physical therapy interventions for musculoskeletal pain were significantly influenced by factors not attributable to the specific effects of the interventions. Boosting these factors consciously to enhance therapeutic outcomes represents an ethical opportunity that could benefit patients. J Orthop Sports Phys Ther 2024;54(6):391-399. Epub 11 April 2024. doi:10.2519/jospt.2024.12126.

Evidence-informed and consensus-based statements about SAFEty of Physical Agent Modalities Practice in physiotherapy and rehabilitation medicine (SAFE PAMP): a national Delphi of healthcare scientific societies.

OBJECTIVE: A shared consensus on the safety about physical agent modalities (PAMs) practice in physiotherapy and rehabilitation is lacking. We aimed to develop evidence-informed and consensus-based statements about the safety of PAMs. STUDY DESIGN AND SETTING: A RAND-modified Delphi Rounds' survey was used to reach a consensus. We established a steering committee of the Italian Association of Physiotherapy (Associazione Italiana di Fisioterapia) to identify areas and questions for developing statements about the safety of the most commonly used PAMs in physiotherapy and rehabilitation. We invited 28 National Scientific and Technical Societies, including forensics and lay members, as a multidisciplinary and multiprofessional panel of experts to evaluate the nine proposed statements and formulate additional inputs. The level of agreement was measured using a 9-point Likert scale, with consensus in the Delphi Rounds assessed using the rating proportion with a threshold of 75%. RESULTS: Overall, 17 (61%) out of 28 scientific and technical societies participated, involving their most representative members. The panel of experts mainly consisted of clinicians (88%) with expertise in musculoskeletal (47%), pelvic floor (24%), neurological (18%) and lymphatic (6%) disorders with a median experience of 30 years (IQR=17-36). Two Delphi rounds were necessary to reach a consensus. The final approved criteria list comprised nine statements about the safety of nine PAMs (ie, electrical stimulation neuromodulation, extracorporeal shock wave therapy, laser therapy, electromagnetic therapy, diathermy, hot thermal agents, cryotherapy and therapeutic ultrasound) in adult patients with a general note about populations subgroups. CONCLUSIONS: The resulting consensus-based statements inform patients, healthcare professionals and policy-makers regarding the safe application of PAMs in physiotherapy and rehabilitation practice. Future research is needed to extend this consensus on paediatric and frail populations, such as immunocompromised patients.

Performance of ChatGPT Compared to Clinical Practice Guidelines in Making Informed Decisions for Lumbosacral Radicular Pain: A Cross-sectional Study.

OBJECTIVE: To compare the accuracy of an artificial intelligence chatbot to clinical practice guidelines (CPGs) recommendations for providing answers to complex clinical questions on lumbosacral radicular pain. DESIGN: Cross-sectional study. METHODS: We extracted recommendations from recent CPGs for diagnosing and treating lumbosacral radicular pain. Relative clinical questions were developed and queried to OpenAI's ChatGPT (GPT-3.5). We compared ChatGPT answers to CPGs recommendations by assessing the (1) internal consistency of ChatGPT answers by measuring the percentage of text wording similarity when a clinical question was posed 3 times, (2) reliability between 2 independent reviewers in grading ChatGPT answers, and (3) accuracy of ChatGPT answers compared to CPGs recommendations. Reliability was estimated using Fleiss' kappa (κ) coefficients, and accuracy by interobserver agreement as the frequency of the agreements among all judgments. RESULTS: We tested 9 clinical questions. The internal consistency of text ChatGPT answers was unacceptable across all 3 trials in all clinical questions (mean percentage of 49%, standard deviation of 15). Intrareliability (reviewer 1: κ = 0.90, standard error [SE] = 0.09; reviewer 2: κ = 0.90, SE = 0.10) and interreliability (κ = 0.85, SE = 0.15) between the 2 reviewers was "almost perfect." Accuracy between ChatGPT answers and CPGs recommendations was slight, demonstrating agreement in 33% of recommendations. CONCLUSION: ChatGPT performed poorly in internal consistency and accuracy of the indications generated compared to clinical practice guideline recommendations for lumbosacral radicular pain. J Orthop Sports Phys Ther 2024;54(3):1-7. Epub 29 January 2024. doi:10.2519/jospt.2024.12151.

Wearable Devices to Improve Physical Activity and Reduce Sedentary Behaviour: An Umbrella Review.

BACKGROUND: Several systematic reviews (SRs), with and without meta-analyses, have investigated the use of wearable devices to improve physical activity, and there is a need for frequent and updated syntheses on the topic. OBJECTIVE: We aimed to evaluate whether using wearable devices increased physical activity and reduced sedentary behaviour in adults. METHODS: We conducted an umbrella review searching PubMed, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, MedRxiv, Rxiv and bioRxiv databases up to February 5th, 2023. We included all SRs that evaluated the efficacy of interventions when wearable devices were used to measure physical activity in adults aged over 18 years. The primary outcomes were physical activity and sedentary behaviour measured as the number of steps per day, minutes of moderate to vigorous physical activity (MVPA) per week, and minutes of sedentary behaviour (SB) per day. We assessed the methodological quality of each SR using the Assessment of Multiple Systematic Reviews, version 2 (AMSTAR 2) and the certainty of evidence of each outcome measure using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations). We interpreted the results using a decision-making framework examining the clinical relevance and the concordances or discordances of the SR effect size. RESULTS: Fifty-one SRs were included, of which 38 included meta-analyses (302 unique primary studies). Of the included SRs, 72.5% were rated as 'critically low methodological quality'. Overall, with a slight overlap of primary studies (corrected cover area: 3.87% for steps per day, 3.12% for MVPA, 4.06% for SB) and low-to-moderate certainty of the evidence, the use of WDs may increase PA by a median of 1,312.23 (IQR 627-1854) steps per day and 57.8 (IQR 37.7 to 107.3) minutes per week of MVPA. Uncertainty is present for PA in pathologies and older adults subgroups and for SB in mixed and older adults subgroups (large confidence intervals). CONCLUSIONS: Our findings suggest that the use of WDs may increase physical activity in middle-aged adults. Further studies are needed to investigate the effects of using WDs on specific subgroups (such as pathologies and older adults) in different follow-up lengths, and the role of other intervention components.

Is Adding Education to Trunk and Hip Exercises Beneficial for Patellofemoral Pain? A Randomized Controlled Trial.

OBJECTIVE: To investigate the effect of adding education to trunk and hip exercises in patients with patellofemoral pain (PFP). DESIGN: A randomized controlled trial. SETTING: Research laboratory. PARTICIPANTS: Sixty patients with PFP (N=60) were randomly assigned to either an experimental group (education followed by trunk and hip exercises, n=30) or a control group (trunk and hip exercises, n=30). INTERVENTIONS: Both groups received 8 weeks of trunk and hip exercises, while patients in the experimental group participated in 3 prior education sessions. MAIN OUTCOME MEASURES: The primary outcome was pain; secondary outcomes were pain catastrophizing, kinesiophobia, function, and muscle strength. Outcomes were assessed at baseline, after 8 weeks (post-intervention), and 3 months post-intervention (follow-up). RESULTS: No significant between-group differences were observed for pain outcome post-intervention. The experimental group showed superiority over the control group in the improvement of pain catastrophizing (mean difference: -2.32; 95% confidence interval [CI] -1.059 to 0.028) and kinesiophobia (mean difference: -3.56; 95% CI -1.067 to -0.035) at post-intervention. In the experimental group, improvements were maintained at follow-up assessment for all outcomes, except muscle strength. CONCLUSION: Adding education to trunk and hip exercises was associated with greater improvements in psychological outcomes than trunk and hip exercises alone after the intervention. Education can be incorporated when designing trunk and hip exercises for patients with PFP.

Ewing's sarcoma in a young man mimicking lateral elbow pain: A case report with 2 years follow-up.

BACKGROUND AND PURPOSE: Lateral elbow pain represents a common musculoskeletal disorder, mostly non-specific and benign. In rare cases, it can be the first symptom of a severe disease such as Ewing's sarcoma (ES). ES is the second most common primary malignant bone tumor in the young population, with a high probability of an unfavourable prognosis. CASE PRESENTATION: This case report presents the history of a young man presenting to the physical therapist with a diagnosis of "epicondylitis" in the right elbow, which was later revealed to be an aggressive ES of the ulna. Findings raising clinical doubts were (a) constant pain even at night and not dependent on load, (b) significant loss of function, (c) patient's young age, and (d) a palpable mass in the elbow. RESULTS: After diagnosis, the patient received medical (chemotherapy, radiotherapy and surgery) and a rehabilitation program. After treatment, the patient improved elbow function, decreased disability and returned to social participation, maintaining positive outcomes at the 2-year follow-up. DISCUSSION: In summary, this case report emphasizes the importance of differential diagnosis and screening for referral of red flags in physical therapy. Moreover, it describes the rehabilitation of a patient with ES, enriching the scientific literature in the field.

Identifying priority gaps in contextual factors research and force-based manipulation. An international and interdisciplinary Delphi study.

OBJECTIVE: To establish priority gaps related to contextual factors (CFs) research and force-based manipulation (FBM). METHODS: A three-round Delphi following recommended guidelines for conducting and reporting Delphi studies (CREDES) involving international and interdisciplinary panelists with expertise in CFs and FBM. Round 1 was structured around two prompting questions created by the workgroup. Ranking of each priority gap was done by calculating composite scores for each theme generated. Consensus threshold was set with an agreement ≥75% among panelists. Median and interquartile range were calculated for each priority gap to provide the central tendency of responses. Wilcoxon rank-sum test was used to evaluate the consistency and stability of responses between rounds 2 and 3. RESULTS: Forty-six panelists participated in all three rounds of the Delphi. Consensus was reached for 16 of 19 generated themes for priority gaps in CFs research and FBM. The ranking of each identified gap was computed and presented. Wilcoxon rank-sum test was non-significant (P > .05), demonstrating consistency and stability of results between rounds. CONCLUSION: The result of this Delphi provides international and interdisciplinary consensus-based priority gaps in CFs research and FBM. The gaps identified can be used to generate future research inquiries involving CFs research and FBM.

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.

Pros and Cons of Using Artificial Intelligence Chatbots for Musculoskeletal Rehabilitation Management.

SYNOPSIS: Artificial intelligence (AI), specifically large language models (LLMs), which focus on the interaction between computers and human language, can influence musculoskeletal rehabilitation management. AI chatbots (eg, ChatGPT, Microsoft Bing, and Google Bard) are a form of large language models designed to understand, interpret, and generate text similar to what is produced by humans. Since their release, chatbots have triggered controversy in the international scientific community, including when they have passed university exams, generated credible scientific abstracts, and shown potential for replacing humans in scientific roles. The controversies extend to the field of musculoskeletal rehabilitation. In this Viewpoint, we describe the potential applications and limitations, and recommended actions for education, clinical practice, and research when using AI chatbots for musculoskeletal rehabilitation management, aspects that may have similar implications for the broader health care community. J Orthop Sports Phys Ther 2023;53(12):1-7. Epub 14 September 2023. doi:10.2519/jospt.2023.12000.

"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.

We read with interest the systematic review with the meta-analysis by Miguel Molina-Álvarez et al. [...].

Comparing kinematic asymmetry and lateral step-down test scores in healthy, chronic ankle instability, and patellofemoral pain syndrome female basketball players: a cross-sectional study.

We aimed to understand whether ankle dorsiflexion range of motion (ROM) and dynamic knee valgus (DKV) kinematic inter-limb asymmetries would be associated with the Lateral Step-Down Test (LSD) in basketball players with chronic ankle instability (CAI), patellofemoral pain (PFP) and healthy controls (HC). An observational cross-sectional study with a between-subject design was employed. Female basketball athletes with CAI (n = 20), PFP (n = 20) and HC (n = 20) were recruited. Ankle dorsiflexion-ROM, DKV angle during a single-limb squat, and LSD quality were measured bilaterally. The Asymmetry index (ASI) was calculated to identify between-limb percentage imbalances. The correlation matrix between the tasks was calculated. Ankle dorsiflexion-ROM was less in the CAI and PFP than in the HC group regardless of limb (p < 0.001). DKV angle was greater in the CAI and PFP than in the HC group bilaterally (p < 0.001). LSDs were similar between the PFP and CAI groups (p = 0.698) but worse than the HC group (p = 0.001). The ASI showed asymmetry across all tasks (p < 0.001), with the greatest asymmetry for the DKV angle. The correlation matrix between tasks on both limbs was significant (p < 0.05). Our findings suggest significant asymmetries in ankle dorsiflexion-ROM and frontal plane knee control are present in female basketball athletes with CAI and PFP, and thus, highlights need to evaluate and reduce limb asymmetries in these populations.

An international consensus definition for contextual factors: findings from a nominal group technique.

Objective: Emerging literature suggests contextual factors are important components of therapeutic encounters and may substantially influence clinical outcomes of a treatment intervention. At present, a single consensus definition of contextual factors, which is universal across all health-related conditions is lacking. The objective of this study was to create a consensus definition of contextual factors to better refine this concept for clinicians and researchers. Design: The study used a multi-stage virtual Nominal Group Technique (vNGT) to create and rank contextual factor definitions. Nominal group techniques are a form of consensus-based research, and are beneficial for identifying problems, exploring solutions and establishing priorities. Setting: International. Main outcome measures: The initial stages of the vNGT resulted in the creation of 14 independent contextual factor definitions. After a prolonged discussion period, the initial definitions were heavily modified, and 12 final definitions were rank ordered by the vNGT participants from first to last. Participants: The 10 international vNGT participants had a variety of clinical backgrounds and research specializations and were all specialists in contextual factors research. Results: A sixth round was used to identify a final consensus, which reflected the complexity of contextual factors and included three primary domains: (1) an overall definition; (2) qualifiers that serve as examples of the key areas of the definition; and (3) how contextual factors may influence clinical outcomes. Conclusion: Our consensus definition of contextual factors seeks to improve the understanding and communication between clinicians and researchers. These are especially important in recognizing their potential role in moderating and/or mediating clinical outcomes.

Physiotherapy Screening for Referral of a Patient with Peripheral Arterial Disease Masquerading as Sciatica: A Case Report.

Many causes potentially underline pain in the lower extremities, presenting a real challenge for primary care clinicians in the recognition of the source of the patient's complaints. Peripheral arterial disease (PAD) is defined as a total or partial blockage of the vessels that supply blood from the heart to the periphery. PAD of the lower extremities may masquerade as lumbosacral radiculopathy (LSR)-a common source of leg pain. Physiotherapists should be able to screen for PAD in people presenting with pain in the lower extremities. Failure to correctly screen for PAD could put the patient at risk of severe disability and possible permanent sequelae. This case report outlines the relevant concepts relating to the pathophysiology, screening, and differential diagnosis of PAD, and then further describes the relevant findings from the history and physical examination from the physiotherapist's perspective in a patient with an unusual symptom presentation. Although the patient was referred by a physician with a diagnosis of LSR, our case highlights the pivotal role of skilled physiotherapists in triaging a severe lower-limb PAD in need of referral. Therefore, this case report aims to increase clinicians' awareness of the clinical features of a complex case of PAD.

The Biology of Placebo and Nocebo Effects on Experimental and Chronic Pain: State of the Art.

(1) Background: In recent years, placebo and nocebo effects have been extensively documented in different medical conditions, including pain. The scientific literature has provided strong evidence of how the psychosocial context accompanying the treatment administration can influence the therapeutic outcome positively (placebo effects) or negatively (nocebo effects). (2) Methods: This state-of-the-art paper aims to provide an updated overview of placebo and nocebo effects on pain. (3) Results: The most common study designs, the psychological mechanisms, and neurobiological/genetic determinants of these phenomena are discussed, focusing on the differences between positive and negative context effects on pain in experimental settings on healthy volunteers and in clinical settings on chronic pain patients. Finally, the last section describes the implications for clinical and research practice to maximize the medical and scientific routine and correctly interpret the results of research studies on placebo and nocebo effects. (4) Conclusions: While studies on healthy participants seem consistent and provide a clear picture of how the brain reacts to the context, there are no unique results of the occurrence and magnitude of placebo and nocebo effects in chronic pain patients, mainly due to the heterogeneity of pain. This opens up the need for future studies on the topic.