Chronic pain is a disabling symptom frequently reported in patients with breast cancer with a prevalence ranging from 25% to 60%, representing a major health issue. It has negative consequences on health status, causing psychological distress and affecting quality of life. Furthermore, the clinical management of chronic pain is often inadequate, and many patients do not benefit from the administration of pharmacological treatments. Alternative therapeutic options have been implemented to improve the psychophysical well-being of patients, including neuromodulation and complementary interventions.We aimed to investigate the effectiveness of a home care strategy combining computerized rehabilitation, transcranial direct current stimulation (tDCS), and remote telemonitoring via a web-based platform in patients with breast cancer suffering for chronic pain.A web-based structured survey aimed at monitoring chronic pain and its effect on psychological functions will be delivered to patients with breast cancer through social media and email. In total, 42 patients with breast cancer affected by chronic pain will be recruited during the medical screening visit. The patients will be randomly divided into 3 treatment groups that will carry out either tDCS only, exercise therapy only, or a combination of both over a 3-week period. All the treatments will be delivered at the patients’ home through the use of a system including a tablet, wearable inertial sensors, and a tDCS programmable medical device. Using web-based questionnaires, the perception of pain  and psychological variables  will be assessed at the beginning of treatment, 1 week after the start of treatment, at the end of treatment, 1 month after the start of treatment, and 3 months after the start of treatment. The system’s usability  and its involvement in the decision-making process (based on the 9-item shared decision-making questionnaire) will be also evaluated. Finally, at the end of the treatment, a digital focus group will be conducted with the 42 patients to explore their unexpressed needs and preferences concerning treatment.The study project is scheduled to start in June 2023, and it is expected to be completed by August 2025.We expect that the combination of tDCS and telemedicine programs will reduce pain perceived by patients with breast cancer and improve their mental well-being more effectively than single interventions. Furthermore, we assume that this home-based approach will also improve patients’ participation in routine clinical care, reducing disparities in accessing health care processes. This integrated home care strategy could be useful for patients with breast cancer who cannot find relief from chronic pain with pharmacological treatments or for those who have limited access to care due to poor mobility or geographical barriers, thus increasing the patients’ empowerment and reducing health care costs.PRR1-10.2196/49508 Chronic pain is related to a multitude of pathological conditions, with a prevalence of 20% to 30% in Europe, and it is considered one of the major health and social problems that our society is facing ,2. This In particular, chronic pain has been specifically investigated in patients with breast cancer, with a prevalence that varies from 25% to 60% of patients . ChronicMoreover, chronic pain has a detrimental impact on daily activities by negatively affecting patients’ quality of life and can cause high degrees of disability as well as the possible onset of psychiatric problems . It can The clinical management of chronic pain is often inadequate since it is still frequently hidden by patients with breast cancer and often neglected by health care professionals . In addiThe term “neuromodulation” refers to stimulation techniques that modify the activity of brain circuits . NeuromoThe restrictions imposed by the COVID-19 pandemic and the mobility limitations that patients face due to chronic pain conditions have brought about awareness of the need to develop new health services based on digital technologies . To address these needs, the use of “telemedicine” has been implemented. Telemedicine is a subset of telehealth that uses communications networks for the delivery of health care services and medical education from one geographical location to another, primarily to address challenges like uneven distribution and shortage of infrastructural and human resources . Among oThe development of computerized rehabilitation protocols at home in combination with noninvasive neuromodulation and monitoring by the clinical team could represent an innovative tool for improving the quality of life and life expectancy of patients at a relatively low cost . It has The growing use of protocols combining neuromodulation techniques and cognitive behavioral interventions through telemedicine, and the possibility of using them in diversified clinical populations, has led to the search for technological ecosystems capable of guaranteeing more personalized treatment approaches ,35. AccoThis protocol is part of the Technopain project aimed at evaluating a new home care strategy combining computerized training rehabilitation, noninvasive neuromodulation, and remote telemonitoring via a web platform. In this study, the use of telemedicine will allow the assessment of psychosocial and physical symptoms related to chronic pain in patients with breast cancer and the identification of its impact on patients’ quality of life and on decision-making related to their own clinical care. In addition, this study aims to investigate the acceptance of the technological approach and the related ethical challenges in order to define a framework of reliability and trust for future therapeutic application.In a first stage, patients will be invited to participate in a mixed method study through social media and email. The delivery and self-administration of questionnaires will take place through a structured survey that can be filled in on a smartphone, tablet, or computer via a web-based platform . After completing a web-based consent to data processing, participants will receive a link, which will allow them to access a web-based questionnaire aimed at monitoring the repercussions of chronic pain on psychological functions and on the performance of daily life activities. All data will be collected, anonymized, and stored in a password-protected electronic format.Subsequently, patients who have previously completed the questionnaires will be identified at a screening visit by the doctor and selected according to the eligibility criteria shown in Inclusion criteria:Diagnosed with breast cancer Aged ≥18 yearsUndergoing oncological treatments (postconservative or nonconservative surgery)Visual analogue scale score >4Completed and signed the informed consent form after a detailed explanation of the task and the tools used in the studyPossess sufficient cognitive skills to support a rehabilitation process mediated by an electronic deviceMontreal cognitive assessment score >15.5 (adjusted for age and years of education) Exclusion criteria:Started new pharmacological treatments or changed current therapies that act on pain within the last monthHave a bone marrow stimulator or intrathecal drug delivery pumpHave respiratory, cardiac, metabolic, or other conditions incompatible with at least 30 minutes of light or moderate intensity exercise as assessed by a specialistHave severe cognitive impairmentHave aphasia, dementia, or a psychiatric comorbidity interfering with communication or rehabilitation program complianceHave blindness or severe vision problems that may interfere with the use of the tabletPossess insufficient knowledge of the Italian language or inability to understand verbal and written instructionsConcomitant participation in another study or clinical trial involving rehabilitation therapy or administration of an investigational drugEach patient enrolled in the study will be provided with a tablet on loan for use, which will allow the collection of some symptomatologic manifestations and behavioral characteristics relating to the presence of chronic pain. All patients who have signed the informed consent form will be assigned an alphanumeric identification code through which they will be registered in a management software. Randomization is an integral part of the patient registration process and will take place automatically through an integrated randomization block with a 1:1 ratio, and each participant will be randomly assigned by the use of “RAND” formula in Excel (Microsoft Corp) to 1 of the 3 treatment groups described in 2 integrated inside sponges soaked in physiological solution to facilitate the flow of current.The delivery of tDCS will be administered through a programmable medical device called “HDCkit” (Newronica). This kit has been specifically designed for both research and clinical use and allows the administration of tDCS for use at home. The HDCkit comprises an “HCDstim” that delivers the tDCS treatment, a touch screen liquid crystal display “HDCprog” that is connected to the HDCStim and controls stimulation settings, and a “Mindcap” that guarantees the correct placement of the electrodes and the reproduction of the appropriate setup when the tDCS treatment is dispensed at home . In the Patients who plan to undergo exercise therapy will be provided with the kari system , a CE class 1/m medical device , on loanA member of the clinical team will educate each patient individually on the use of the kari system upon delivery of the same so that everyone acquires familiarity and independence in its safe use.The tablets will also be used for the periodic compilation of questionnaires and rating scales by patients. The data will be saved locally on the device at the end of each training session and then transmitted to the web management system. Once transferred to the web management system, the data are immediately available for consultation by clinical staff.The results of the clinical and functional evaluations will be collected anonymously on the patient data collection form.Patients in groups B and C will carry out exercise therapy sessions involving the use of the kari system at home for about 30 minutes a day under the remote supervision of the clinical staff via the web management system. This device allows researchers to remotely configure, customize, and quantitatively monitor an exercise therapy path for patients. A dedicated app guides the rehabilitation patient through the exercise therapy program configured by the professional. Monitoring is guaranteed by the integrated chat and video call functions, as well as by a web application accessible remotely by the therapist in which various quantitative factors related to the therapy can be monitored, such as adherence and program effectiveness.Patients assigned to groups A and C will receive tDCS treatment, where stimulation parameters will be personalized on the basis of the patients’ clinical characteristics, according to 1 of the methods described in To explore psychological variables and the individual impact of perceived pain, patients will be evaluated and receive a link with the questionnaires described in Finally, a focus group will be conducted with all the patients who took part in the study. The patients will be divided into groups of 14 participants based on the treatment group to which they were assigned. The aim of this investigation is to analyze the unexpressed needs, expectations, and preferences related to the home-based treatment. The focus groups will be conducted starting from a list of questions concerning the experience of the disease by the study participants, the relationship between the painful symptoms and the psychological significance, the expectations with respect to the treatment, and any difficulties encountered during the use of the technologies adopted during the rehabilitation program.A telematic platform will be used to carry out the focus group meetings at the end of the treatment. The duration of the focus group meetings will be between 60 and 90 minutes, and breaks will be provided every 45 minutes to avoid tiring the patients. Audio and video will be recorded from every meeting and subsequently analyzed using T-Lab software, which comprises several linguistic and statistical tools .At least 42 patients with breast cancer will be recruited for the study. The patients will be divided into 3 experimental groups, each consisting of 14 patients, based on the type of treatment performed . In case of dropouts, the recruitment of patients will continue until 42 participants complete the treatment.Since the present study is the first to evaluate the effects of tDCS in patients with different types of chronic pain over a 3-week period, to estimate the expected difference between the effect of tDCS and combined therapy (tDCS and exercise therapy), for the calculation of the sample size we relied on a recently published study  of 45 paThe sample number for each individual clinical center was calculated to demonstrate the difference between the change in the visual analogue scale (VAS) value at the beginning of treatment and after 1 week of treatment between the group of patients receiving tDCS and that receiving combined therapy. A Wilcoxon-Mann-Whitney test was performed using G*Power V3 software  with an t tests and ANOVA for repeated measures. In case the assumption of a normal distribution is not supported, a nonparametric Wilcoxon-Mann-Whitney test will be used. Statistical analysis will be performed on all participants who complete the treatment required by the protocol. Participants who do not complete all phases of the study  will be excluded from the data analysis. Furthermore, as suggested by recent scientific literature, Bayesian statistics will also be applied using JASP open-source software in order to better estimate the possible absence of an effect of therapeutic strategy [To evaluate the efficacy of the treatments, a statistical analysis will be conducted on the clinical scales, functional tests, and questionnaires using a dedicated software. Data distribution will be evaluated using Shapiro-Wilk tests. In the case of a normal distribution, statistical significance will be evaluated by applying parametric strategy . In partThis protocol was approved by the ethical committee of the Istituti di Ricovero e Cura a Carattere Scientifico European Institute of Oncology (April 2023). Written and verbal information will be provided and informed consent will be obtained from all participants. Participation in the study is voluntary and free. No additional fees will be charged to the participants, and no payments will be made.All the methodologies mentioned in the study protocol will be carried out according to the relevant guidelines and regulations.Patient data will be treated as strictly confidential and subject to anonymity so that it cannot be associated in any way with the individual. For this purpose, at the beginning of the study, the study doctor will assign to the participants a code with which they will be identified during all subsequent phases of the study. The data relevant to the study, with the exception of patients’ names, will be recorded, processed, and stored together with this code and all clinical data relating to the state of health. Only the physician and authorized parties will be able to link this code to the patients’ names.This information will be treated as strictly confidential in accordance with EU Regulation 679/2016, Legislative Decree 196/2003 as amended  and will only be used for research purposes in connection with this study.The project, Technopain, is scheduled to start in June 2023, and it is expected to be completed by August 2025. Results will be available following data analysis in the subsequent months.This innovative approach will contribute to furthering our understanding of the neurophysiological mechanisms of chronic pain and the related psychosocial and physical symptoms. Additionally, the suitability of the telemedicine approach for patients and clinicians will favor the application of new technologies able to improve patients’ well-being and access to care.The present study protocol represents an innovative approach to the management of chronic pain in patients with breast cancer without the adoption of pharmacological treatments. Consistent with previous studies ,59-62, wConsidering the beneficial effects of tDCS in increasing emotional well-being in psychiatric and neurological patients -65, we aAnother key objective of this integrated home care strategy will focus on limiting the impact of physical and psychosocial symptoms associated with chronic pain on patients’ daily lives ,7. They Finally, the project aims to support patients affected by chronic pain through decision aids during critical moments of the therapeutic journey . TelemonIt is possible to hypothesize several advantages following the application of this treatment. First, we expect a reduction in pain perceived by patients, since noninvasive brain stimulation methods and exercise therapy have been shown to have beneficial effects on the management and treatment of chronic pain in previous studies ,17,18. FAdditionally, we expect that the implementation of a home-based care system can facilitate patient adherence by reducing travel costs and establish a more direct and continuous exchange of information between patients and health care professionals.A main limitation of the present study could be the personal use of the home care strategy. Despite the many advantages of this technological approach, some patients may find it difficult to use the equipment without direct assistance from a health care professional. The self-management of the home care strategy could also have a negative influence on treatment adherence, causing possible dropouts during the study phases. For these reasons, it will be necessary to monitor patients’ motivation during treatment to prevent patients from neglecting rehabilitation.Patients should also be adequately informed of the possible risks linked to the administration of the treatments to reduce concerns about the occurrence of possible adverse effects of tDCS. In particular, adverse events could involve the appearance of local effects of the stimulation consisting of a slight burning sensation or skin redness. Nevertheless, it should be noted that participation in a trial involves strict control by the experimenter to limit any problems that may arise.Furthermore, the initial recruitment via social media and email could orient the sample toward younger and technologically experienced patients. However, we adopted this instrument to promote the recruitment of patients throughout the country to overcome geographical barriers related to the access to health care. Additionally, due to the use of digital devices during the rehabilitation program proposed in this study protocol, the enrollment of technologically savvy patients with breast cancer could facilitate the use of the home-based treatment.Finally, given the importance of subjective perception on the classification of pain, we chose to adopt several self-report tools to assess the personal experience of the patients with breast cancer. However, these instruments have limitations, as it is not possible to obtain objective information. When drawing conclusions, it will therefore be necessary to consider that the data may be influenced by various personal factors.The Technopain protocol is a new home care strategy that combines computerized training rehabilitation, noninvasive neuromodulation, and remote telemonitoring via a web platform for the treatment of psychosocial and physical symptoms related to chronic pain in patients with breast cancer. In particular, this approach will evaluate the impact of chronic pain on patients’ quality of life and will offer a rehabilitation program that can favor the treatment of the greatest number of patients through home delivery. This trial will primarily evaluate the fluctuation of perceived pain by patients during and after treatments, evaluating which of the different types of treatments is the most effective between the single treatments or their combination. In particular, we expect that this study will provide a useful treatment for all patients who cannot find relief from chronic pain with pharmacological treatments. Our ultimate aim is to encourage the development of personalized telemedicine, which can provide daily clinical assistance to patients, eliminating the economic and geographical barriers related to the use of health services.


The etiology of this epidemic is undeniably complicated and multifactorial. However, we must acknowledge that isolation, along with suffering seen from the COVID-19 pandemic has played a critical role in the exacerbation of this problem. Furthermore, we know that the lethality of drugs used has greatly increased because many drug cocktails are now laced with fentanyl, a potent and often deadly drug.Despite significant efforts from federal and state authorities, the opioid epidemic continues to devastate public health in the United States. On November 17, 2021, the Centers for Disease Control and Prevention National Center for Health Statistics released provisional data reporting >100,000 drug overdose deaths in the United States within the 12-month span ending April 2021,2 In this article, we touch on the concept of pain as the fifth vital sign, examine some studies comparing opioid prescribing habits in the United States versus some European countries, and conclude by recommending a call to action for surgical programs around the country.Despite the admitted complexity of the opioid epidemic, 1 causative factor that rarely gets acknowledged and discussed is the role we, as healthcare providers, play in this problem when we over prescribe narcotics to surgical patients. Seventy-one percent of people inappropriately using opioids have received the drugs through diversion of an appropriately obtained prescription, and in 55% of these cases, the drug is obtained from a family member or friend who has excess pills.New England Journal of Medicine titled “Addiction rare in patients treated with narcotics.”3 This thinking at the time equated pain control with opiate prescription, largely ignoring nonopiate drugs and nonpharmacologic therapies. These teachings have perhaps contributed to significant differences in narcotic prescribing practices in the United States.Those of us who were medical students in the 1990s and early 2000s in the United States will likely vividly remember being taught that pain was the “5th vital sign.” We were encouraged to treat pain with narcotic therapy to decrease any unnecessary suffering of our patients. In 1980, a short letter to the editor was published in 4 retrospectively compared patients who underwent fracture repair in a level I trauma center in the United States versus the Netherlands to determine opioid prescribing practices. After discharge for hip repair, 77% of American and 0 Dutch patients received opioids, and for ankle repair, 82% of American and 6% of Dutch patients received opioids. Given the proclivity to prescribe narcotics after discharge from surgery, the overall proportion of adult patients with excess narcotics ranges from 67% to 92% with the proportion of unused pills ranging from 42% to 71%.5Narcotic prescribing is dramatically higher in the United States than in some European countries. Lindenhovius et al6 studied 223,834 opioid-naive patients undergoing 4 common surgical procedures in the United States, Canada, and Sweden; the results were quite profound. The authors found that for every procedure examined, the United States and Canada filled narcotic prescriptions at a sevenfold higher rate than Sweden. Furthermore, the mean quantity of narcotics dispensed was significantly higher in the United States.6 There is no evidence that patients in any of these studies suffered more pain.Similarly, Ladha et alThese data tell a compelling story. Unwittingly and perhaps unknowingly, surgeons in the United States largely give too many patients narcotics, give too many pills in a prescription, and likely significantly underuse nonopiate pharmacologic therapies and nondrug therapies. Moreover, overprescribing is largely invisible as opiate prescribing is rarely routinely monitored as a quality metric to be used in quality improvement efforts.We propose a call to action to address this crisis. There needs to be ongoing quality assessments at the hospital level by continuous analysis of narcotic utilization in patients being discharged in the postoperative setting. This can be done with routine measurement of the percent of hospitalized patients discharged home with narcotics and the percent not on maximal nonopiate therapy and done by measuring the quantity of narcotics prescribed in morphine milligram equivalents (****MME). The Centers for Medicare & Medicaid Services National Surgical Quality Improvement Program can work on definitions for these measures, ensure standardized measurement, and transparently report the results. Health systems should monitor these metrics and share data with their board and community.8Utilization metrics are just part of the solution. We also need to provide guidelines and education for providers and patients. Develop hospital standards and guidelines for the use of narcotics and then provide education and training to all clinicians with prescribing authority on good narcotic stewardship. These guidelines should encourage the use of non-narcotic analgesic options, such as acetaminophen and ibuprofen. Although these medications have been available for a long time, their use in the United States during the perioperative period has waned over the decades. Ample data has shown the efficacy of non-narcotic analgesics for pain control and a reduction in the quantity of opioid-based narcotics needed for pain management.9 Health systems should complete their call to action by implementing known programs that have been shown to reduce narcotic use by patients. Programs such as enhanced recovery pathways, which use an evidence-based approach to the care of surgical patients by implementing multiple preoperative, intraoperative, and postoperative interventions, have reduced narcotic consumption by patients.10 Finally, the Federal government and foundations should fund research on alternatives to narcotics. As we look to the future, we must begin to address how we can be part of the solution, this call to action provides a start.Patients must also be educated in the perioperative period to prepare them and set appropriate expectations, as surgery and the resultant postoperative pain can be very distressing for many patients. Providing them with adequate knowledge and counseling for how the health care team will use a multimodal approach to manage their pain will likely lead to less stressful and anxiety-laden experience, and thus, lead to better compliance with narcotic consumption.The authors thank Christine G. Holzmueller, MS, for reviewing and editing the manuscript.


Patients sought the same number of pieces of advice, were equally confident, and used advice in similar ways to revise their estimates. Thus, patients with BPD did trust advice. However, patients gave higher hostility ratings to the portrayed persons. In conclusion, patients with BPD showed no cognitive biases in seeking, evaluating, and integrating socially provided information. While the study implies emotional rather than cognitive biases in the disorder, cognitive biases may still prove to be useful treatment targets in order to encourage delaying and reflecting on extreme emotional responses in social interactions.Research suggests that patients with borderline personality disorder (BPD) share a range of cognitive biases with patients with psychosis. As the disorder often manifests in dysfunctional social interactions, we assumed associated reasoning styles would be exaggerated in a social setting. For the present study, we applied the Judge-Advisor System by asking participants to provide initial estimates of a person’s age and presumed hostility based on a portrait photo. Afterwards, we presented additional cues/advice in the form of responses by anonymous previous respondents. Participants could revise their estimate, seek additional advice, or make a decision. Contrary to our preregistered hypothesis, patients with BPD (The online version contains supplementary material available at 10.1007/s00406-022-01539-w. Borderline personality disorder (BPD) is a mental disorder that, according to the DSM-5 , has sevBPD patients show a range of reasoning biases , such asThe Judge-Advisor System  has mosThe JAS paradigm consists of a judgment and an advice phase. In the judgment phase, participants make an initial judgment, e.g., estimating the age of a person based on a photograph. In the advice phase, participants receive advice, e.g., in the form of responses by previous respondents. Participants are free to adjust or not to adjust their initial judgment. The main outcome is the degree to which each participant changes their initial judgment in response to advice. Studies with clinical populations found that patients with schizophrenia  and deprThe JAS has been demonstrated to be a valuable tool for investigating reasoning and decision making in the social context, specifically how advice is sought and used. For the present study, we are the first to apply the JAS to BPD. Participants made judgments about persons based on portrait photographs of the persons. One such judgment was neutral (estimating the person’s age), and the other judgment was related to BPD symptomology (rating the person’s hostility). BPD patients tend to rate others as, for example, less trustworthy –41. AfteApplying the JAS may inform us about how patients with BPD seek and use advice. This has high practical relevance  and advThe JAS paradigm provides measures on information sampling (number of pieces of advice before making a decision), confidence in the decision, and information integration/belief flexibility (adjustment of estimate in response to advice). For each of the three outcomes, we formulated a specific hypothesis (see below).Preliminary evidence suggests that patients with BPD seek less information before coming to a conclusion. First, patients “jump to conclusions” according to self-report , 22. SecH1: Patients with BPD seek less advice than controls.The JAS can also investigate confidence in judgments. Two studies suggest an overconfidence bias for patients with BPD; that is, patients with BPD are more often highly confident in judging emotions when such confidence is not justified  or show H2: Patients with BPD rate their confidence higher than controls.Advice weighting is the degree the estimates are adjusted in line with advice, which is a measure of belief flexibility. Patients with schizophrenia and participants with elevated levels of psychotic-like-experiences use advice more , 38. As H3: Patients with BPD weight advice more than controls.This study is the first to test the JAS paradigm in patients with BPD. The (adapted) JAS task allows to investigate how patients with BPD evaluate and use socially provided information. As outlined above, we assumed patients with BPD  to seek less advice, to be more confident and to weight advice more.https://aspredicted.org/xv9fn.pdf). At that point, data from four patients (10.5%) and six healthy controls (20%) had already been collected but not analyzed. Prior to data collection, the local medical board’s ethics committee approved the trial .On 20 June 2018 (time-stamped), we non-publicly uploaded our study protocol on AsPredicted  via leaflets and word of mouth. Inclusion criteria for patients and healthy controls were (a) age 18–65 years, (b) fluency in German, (c) IQ ≥ 70 as estimated by a vocabulary test, and (d) no neurological disorder. An additional criterion for the clinical sample was a BPD diagnosis according to the DSM-IV, verified with the German version of the Structured Clinical Interview for DSM-IV , HC: M = 27.8 (SD = 7.4), t (65.23) = 0.95, p = 0.344) or gender  = 0.205, p = 0.651).We recruited SCID-II, ). The exSCID-II, ). We verAge task) for all four portraits in random order, followed by the question “How hostile is this person?” (Hostility task) with the photos in the same order. Participants entered their estimates on a visual analogue scale (using a slider) with a range from 0 (labeled “not hostile”) to 100 (labeled “hostile”). After participants gave their initial estimates, we showed them the same photos, this time along with advice. In all instructions, we avoided the term “advice.” Instead, the instructions said that they would see randomly selected answers from participants in a pilot study . However, this advice was not real; we computed it, based on each participant’s initial estimates, in the same way for all participants .The procedure followed the standard sequence of a Judge-Advisor System , illustNumber of Requests for Advice (NoRfA) was the number of times a participant requested advice before giving the final estimate (range 0–3), and Confidence was the participant’s confidence rating for the final estimate (range 1–4). As the standard measure for advice integration ). Patients rated the persons as more hostile than healthy controls with medium effect size , HC: M = 23.3 (SD = 17.6); t(64.36) = 3.25, p = 0.002; d = 0.79, 95% CI ).All initial age estimates were in the range 24–62 years. Patients and healthy controls estimated with similar accuracy the age of the depicted persons  did not significantly differ from healthy controls on any pooled outcome , objecting to a previous finding in which participants with depression had higher advice-taking scores than healthy controls in a JAS task [As outlined in the supplementary materials S1, we ran a series of post hoc analysis. However, there was no indication for an effect of certain trial types (different distances of advice) and no indication that outliers contributed to the incorrect conclusion of the null-effects. Furthermore, currently depressed patients with BPD in our sample . Additionally, symptom severity was neither correlated with NoRfA  nor with Confidence .We preregistered an expected relationship between symptom severity (BSL-23) and advice weighting in the patient group. However, there was no indication of a correlation between these two variables (n = 38): Rosenberg Self-Esteem Scale , Beck Depression Inventory-II , HDRS , Beck Suicidal Scale , or estimated IQ . Consequently, and further elaborated in the Supplementary Materials S1, there was no indication of a mediation by self-esteem on the relationship between symptom severity and JAS outcome measures. See Supplementary Materials S1 for correlations between outcomes.Moreover, no pooled score  correlated significantly with any other investigated variable in the patient sample  to inveOur study and hypotheses were prompted by prior research that has linked BPD with cognitive biases initially found in patients with schizophrenia , 22, whiThe findings were robust across different experimental manipulations. Results were similar for both the neutral task type (estimating a person’s age) and the borderline-specific task (estimating a person’s hostility). Different distances of advice  did not evoke any group differences. Also, post hoc analysis did not suggest that results were driven by outliers. Moreover, there were no correlations with psychopathological measures on borderline symptomology, depression, or suicidality. Finally, the subgroup of patients with BPD currently fulfilling criteria for depression did not differ from healthy controls (contradicting a previous study by Hofheinz ).In conclusion, our hypotheses were not confirmed. In the context of advice, patients with BPD thus seemed able to use other participants’ advice to improve their answers in an estimation task. In the light of the vast research on the trust bias in BPD , it is wFirst, patients did not show a jumping to conclusions bias  despiteSecond, regarding confidence, patients with BPD were slightly—but non-significantly—less confident than healthy controls, which again counters one of our hypotheses. Findings thus speak against an overconfidence bias in BPD, which we assumed based on previous findings , 52. On Third, although we had assumed that patients with BPD would weight advice more than healthy controls, no group differences emerged; patients adjusted their advice marginally more than controls. Hence, in term of belief updating, the data suggest neither a belief inflexibility  nor an In sum, patients with BPD sought and used anonymous advice the same as healthy controls. This highlights that patients with BPD do not seem to have cognitive biases in evaluating information coming from others. Patients with BPD were not overly hasty and did not naively use information from others , nor were they overly skeptical . Instead, patients evaluated their own and others’ skills in the estimation tasks in a healthy manner. In other words, patients with BPD trusted the previous participants’ judgements. Thus, this study also contributes to the vast research on trust in BPD : IntereTo integrate the findings with other research on trust in BPD, we have to note one important aspect of the JAS paradigm used here: participants were given no reason to expect hostile advice as it was given in the form of “randomly selected answers by previous participants.” This means that patients trusted the anonymous advice of a stranger, who had no knowledge about the existence of the patient and who could be expected to answer the estimation question to the best of their knowledge. In that sense, the paradigm resembles studies with little interaction with the trustee. For example, Preuss et al.  did not We would like to draw several cautious inferences from the data. Patients with BPD attribute more hostility to others, but this emotional bias is not general; for example, they are not less open to advice than healthy individuals, suggesting that patients can trust others, such as therapists, in some situations. Also, patients did not require additional information or interaction with or about the advisors, suggesting that in anonymous therapeutic settings like online interventions, patients might be open to advice. To disentangle this, future studies should manipulate information about the advisor  and see whether the finding translates to therapeutic content.This study also adds to the field of cognitive bias research on BPD. For schizophrenia, basic research has identified specific cognitive biases that are successfully targeted in interventions, such as metacognitive training . TentatiThe study has some strengths, in our opinion. The analyses were preregistered, which by some experts is regarded as an important criterion for good scientific practice , and theApplying the JAS paradigm from social psychology, we investigated how patients with BPD seek and use  information. In two estimation tasks, patients with BPD did not behave differently compared to healthy controls. Patients sought the same number of pieces of advice before submitting their final estimate, were similarly confident in their final estimate, and adjusted their initial estimate equally in response to the advice. This contradicted our preregistered hypotheses. These results suggest that the lack of trust in others observed in patients with BPD may not be driven by cognitive biases but rather by other factors such as emotional biases . This raises the hope that patients with BPD may be able to deal with advice the same way healthy individuals do, for example, when receiving advice within a therapeutic setting or in systemic therapy approaches like family therapy.Supplementary file1 (DOCX 21 KB)Supplementary file2 (DOCX 13 KB) Below is the link to the electronic supplementary material.


IntroductionA common dental problem is the fear of pain during needle prick for giving local anesthesia (LA). The needle prick pain during dental procedures often varies with sex and age. Perception of pain depends on various factors, which can be psychological and biological. This perception of pain may change the behavior of patients toward dental treatments. Traditionally, lidocaine gel formulation was utilized before the parenteral dosage form. The lidocaine gel formulation is considered the drug of choice for LA in dental surgery. Currently, amitriptyline has been utilized in dental practice because of its beneficial pharmacology. Hence, the present study has been undertaken to compare the anesthetic ability of amitriptyline as an intraoral topical anesthetic agent with lidocaine gel.MethodsThis study was a comparative clinical study between two medications' anesthetic properties. This study included 120 patients indicated for bilateral orthodontics  procedures. All the subjects were divided into amitriptyline and lidocaine groups. Both anesthetic gels were applied at separate sites before the injection of LA. The time of the onset of anesthesia was noted and analyzed. Patients were selected on the basis of inclusion and exclusion criteria. Individuals aged 18 to 30 years who were systemically healthy and orthodontically indicated for bilateral premolar extraction were included in this study. Again, patients with a history of neurological disorders and allergies to amitriptyline and lidocaine were excluded from the current study.ResultsSignificant differences emerged between groups at five and 10 minutes, with amitriptyline-induced partial numbness (36.7% and 6.7%). At 40 and 45 minutes, both groups showed varied partial and complete numbness, with amitriptyline leading to partial recovery  and lidocaine resulting in partial recovery (81.7%). When comparing the visual analog scale (VAS) scores, both groups exhibited a similar simultaneous effect at 15 minutes. Nonetheless, amitriptyline displayed significantly lower scores at 25 and 35 minutes (p < 0.001) in comparison to lidocaine. Similar observations were made when controlling for pain intensity.ConclusionIt was concluded that amitriptyline holds both anesthetic and analgesic properties. Nevertheless, this study was unable to generalize the study findings because of the small sample size and being a single-center study. However, the VAS scores of anesthetic and analgesic pharmacodynamics properties of amitriptyline were statistically significantly lower than lidocaine, particularly at 25 and 35 minutes. Additionally, amitriptyline-induced anesthetic and analgesic pharmacology, especially pharmacokinetics properties, depends on the location and pattern of pain. It is well observed that individuals differ from each other in a variety of ways. Plato, in 360 BC, stated, "No two persons are born exactly alike, but each differs from the other in natural endowments" . Such inPain experiences in dental treatment, especially in dental anesthesia, can generate different responses among patients that change their behavior toward the dentist. Patients decided to avoid dental procedures at some point due to anxiety and pain-related concerns ,11. HighLidocaine is a common local anesthetic and antiarrhythmic drug in the amide-type local anesthetics class . It is wGenerally, lidocaine gel has been extensively used in dental surgery to minimize pain because of needle pricks while administrating LA, especially for children -24. AlthAmitriptyline is considered the first-generation antidepressant as an alternative agent to induce topical anesthesia in various dental procedures ,30. AmitThe present study has been undertaken to compare the anesthetic and analgesic ability of amitriptyline as an intraoral topical anesthetic agent with lidocaine gel.Patient populationThis study was a comparative study to identify the anesthetic and analgesic properties of lidocaine and amitriptyline. A total of 120 patients who were orthodontically indicated for bilateral premolar extraction were selected for this study. The subjects were enrolled at Narsinhbhai Patel Dental College and Hospital, Gujarat, India , and they obtained all the necessary permissions. Amitriptyline, in the form of powder, was obtained from a pharmaceutical company . A single dose of the 0.2-gram drug was dissolved in 10 ml of water. Two percent of hydroxypropyl methylcellulose (HPMC) was further added to it. The solution was stirred for 12 hours using the magnetic stirrer at 37°C.Clinical evaluationPatients were blinded as they never knew which drug was used. There were two sets of operators (dentists): the first set applied topical anesthesia, and the other set recorded the clinical data. Hence, all were blinded. Before medication was applied, patients were asked to rinse the oral cavity with 0.2% chlorhexidine mouthwash, and then the injection sites were cleaned with sterile cotton. Proper suction was deployed at the test and control sites so that the salivary secretions did not dilute the drugs. Amitriptyline 2% in gel form was applied at group A areas, and 2% lidocaine was used at group B sites. Patients were asked to wait for 15 minutes ; therebyStatistical analysisTo check the difference in numbness score between the amitriptyline and lidocaine treatment groups, the chi-square test was used when the observation had 2 x 2 contingency observations. The multivariate regression model assessed the treatment group difference in VAS score and pain control score at various time intervals, and the regression model was adjusted by age and sex. To examine the overall treatment effects on numbness score, VAS score, and pain control score at various time intervals, repeated measure ANOVA was used, and the model was adjusted by age and sex. For statistical analysis, STATA-15  was used, and for graphical presentation, GraphPad Prism 8.3.2  was used. A p-value of 0.05 and below was considered significant and a p-value above 0.05 was considered statistically insignificant.This was a comparative study regarding analgesic and anesthetic properties between amitriptyline and lidocaine for dental procedures. The analysis involves a comparison of numbness scores between two treatment groups, namely, amitriptyline and lidocaine, at different time intervals. Noteworthy differences were detected between the groups at the five and 10-minute marks. In these instances, the amitriptyline group reported a partial feeling of numbness , while the lidocaine group exhibited complete numbness  compared to amitriptyline. While comparing the VAS score between the two treatment groups, it was observed that lidocaine had a significantly (p < 0.001) higher score at 25 minutes and 35 minutes compared to amitriptyline , lidocaine binds to the receptor. These receptors in the ion channel gate have more affinity toward the lidocaine molecules in the activated state  who were orthodontically indicated for bilateral extraction. Cámara et al., in their research work, concluded that there was a negligible difference in the intensity of pain between men and women . In contThis study found that amitriptyline-induced numbness scores were statistically significantly p < 0.001) higher initially at five and 10 minutes than those for lidocaine  used the ANOVA repeated measure test to reveal a statistically significant difference between study groups' mean pain scores. Salimi et al. (2019) further concluded that amitriptyline possesses adequate efficacy to induce local dermal anesthesia and is more efficient than available existing medications .The current study observed that lidocaine had a significantly higher score at 25 minutes regarding the VAS score and pain control score  . This stIn this study, the measurement of control of dental pain and the intensity was assessed; both the VAS score and pain rating score were statistically higher at 25 minutes with the amitriptyline group than that of the lidocaine group. One Cochrane review reported no confirmation from good quality randomized controlled research to brace topical lidocaine for the management of neuropathic pain. However, this review acknowledges that some individual research denoted that lidocaine efficiently minimized pain . One morLimitations of the studyThis study possesses a small sample size and was carried out in a single center. This study obtained no financial support. Additionally, other limitations include the willingness to participate in the study, time period, and limited access to information. Therefore, we can extend our sample size and make it multi-center research. Thereby, we could generalize this study data. We expect in our next study we could overcome financial constraints and will be able to increase the sample size. Additionally, we will conduct multi-center research. Thenceforth, we will be able to generalize the data.This research concluded that the anesthetic properties and analgesic effects of amitriptyline depend on the location and pattern of pain. It is advisable to compare amitriptyline with several other medications available possessing LA effects. Also, the efficacy should be checked at different sites in the oral cavity. As different regions of the oral mucosa, such as the palatal mucosa and buccal mucosa, have different thicknesses and keratinization. The prospect of amitriptyline lies in surgeons' ability to modify the delivery system so that the pharmacokinetics of amitriptyline is altered and released slowly at the specific site and acts for a longer duration.


BackgroundCholecystectomy is one of the most commonly performed surgical procedures, and it is indicated for symptomatic gallstone disease. Symptoms of gallstone disease vary; many patients complain of the persistence of symptoms post-operatively. Hence, it is imperative to know the characteristics of symptoms that predict post-operative resolution.MethodologyA prospective cross-sectional study was performed at a tertiary care centre. Patient demography and pre-operative symptoms were noted. Post-operative persistence or relief of symptoms was also documented. The occurrence of any new symptoms was noted. Data were collected at three and six months after surgery.ResultsPain was the most common (85%) symptom. The mean frequency of pain was 2.45 per year (range 0-10). The mean duration of pain was 39.7 minutes (range 15-90 minutes). The right hypochondrium (39%) and the epigastric region (42%), along with 8% of patients who experienced pain in both places, were the most frequent locations of pain. The radiation of pain to the right-side scapula is present in 48% of patients.The pain persisted after one-week follow-up in 28 (34%) of patients, 26 (22%) at the end of one month, and 18 (21%) at the end of six months. Dyspepsia was unresolved in 25%, 20%, and 13% of individuals after one week, one month, and six months, respectively. Upper abdominal discomfort was still persistent in 29%, 26%, and 24% of study subjects at the time of follow-up periods, respectively. Similar persistence is found in symptoms of post-prandial fullness and nausea, where unresolved complaints of post-prandial fullness were present in 18%, 13%, and 10% of patients, respectively, and 26%, 14%, and 10% of patients complained of nausea.ConclusionThe persistence of symptoms such as upper abdominal discomfort, dyspepsia, post-prandial fullness, and nausea is present, which gradually decreases in severity and presentation over the course of time after the surgical procedure. Some symptoms present after surgery, such as flatulence. Such persistent symptoms might lead to a decreased outcome in terms of patient satisfaction. Patients with atypical pain or dyspepsia need to be counselled pre-operatively regarding the poor resolution of such symptoms. Gallstone disease is a common condition affecting about 10-15% of the population ,3. GallsSymptomatic cholelithiasis is defined as the presence of gallstones with typical biliary colic pain. However, ‘typical biliary colic’ has been poorly characterized. Upper gastrointestinal motility disorders, gastroesophageal reflux disease, peptic ulcers, and irritable bowel syndrome can have symptoms like gallstones. Non-specific symptoms like nausea, post-prandial upper abdominal discomfort, and dyspepsia may persist after cholecystectomy. Pain and dyspepsia are often the presenting symptoms of post-cholecystectomy syndrome . The comCholecystectomy carries a significant complication rate and may be deemed unnecessary if symptoms are not attributed to cholelithiasis. The current study was designed to find out the demography and factors predicting the relief of symptoms after laparoscopic cholecystectomy to enable us to better counsel the patients pre-operatively.PatientsThe study was performed at a tertiary care centre in central India. The study was a prospective cross-sectional survey. The objectives of the study were to characterize the symptoms associated with relief after surgery and to find out the nature and incidence of new symptoms following cholecystectomy. Consecutive patients (>18 years of age) undergoing laparoscopic cholecystectomy for uncomplicated symptomatic gallstones between December 2019 and October 2021 were included in the study. Exclusion criteria were open cholecystectomy, complicated gallstone disease, previous upper abdominal surgery, and cholecystectomy done with other procedures. Patient demography and pre-operative symptoms were noted. Complicated gallstone disease was defined as gallstones present either with recurrent biliary pain or with some complications like acute cholecystitis, acute pancreatitis, cholangitis, or jaundice. Open cholecystectomy was excluded as wound complications may be a confounding factor. The institutional ethical committee approved the study. Symptomatic gallstone disease is defined by the presence of gallstones, upper abdominal pain, and/or atypical upper abdominal symptoms like dyspepsia, nausea, vomiting, flatulence, bloating, and heartburn. The diagnosis was confirmed by ultrasonography.ProcedurePatients were consulted pre-operatively and explained about the research protocol. Laparoscopic cholecystectomy was performed using the standard four ports. The gallbladder was extracted through the epigastric port. After obtaining informed consent, patients’ demography and pre-operative symptoms were noted. A biliary symptom questionnaire was used. A visual analogue score (VAS) was used for pain scoring. Co-morbidities were also recorded. Post-operative persistence or relief of symptoms was also documented. Occurrences of any new symptoms were noted. Data were collected at one week, one month, and six months after surgery. Data were collected through face-to-face and telephone interviews. The minimum follow-up period was six months. Patients with persistent pain post-operatively were evaluated for other possible diagnoses using upper gastrointestinal endoscopy and magnetic resonance cholangiopancreatography (MRCP). The persistence of symptoms was defined by symptoms like those in the pre-operative period with varied severity.Statistical analysisQuantitative data were expressed as median and range, while qualitative variables were expressed as numbers . The Chi-Square test or Fisher's exact test evaluated the differences in qualitative variables between various groups. Changes in symptoms over time were analyzed by the Wilcoxon signed rank test. Data were fed into a Microsoft Excel worksheet  and analyzed using the Statistical Package for Social Science  statistical software for Windows. The normalcy of the data was tested using the one-sample Kolmogorov-Smirnov test. Paired data comparisons were performed using the paired T-test (parametric) and the Wilcoxon signed rank test (non-parametric). A p-value of <0.05 was considered significant.DemographyA total of 100 patients were included during the study period (December 2019 to October 2021). All patients were diagnosed with gallstone disease based on symptoms and ultrasound findings. All patients underwent laparoscopic cholecystectomy, and none required conversion to open. The post-operative period was uncomplicated, with a post-operative stay of three to five days. There were 62 (62%) females and 38 (38%) males . The mean duration of pain was 39.7 minutes (range 15-90 minutes). The most common location of pain was the epigastric region (42%), followed by the right hypochondrium (39%), while 8% of patients had pain at both locations. Radiation of pain to the right-side scapula was reported in 48% of patients. The nature of pain was colicky in 54%, pricking in 23%, and stabbing in 15%. In 56% of cases, the pain was precipitated or aggravated by food. Medications for pain were needed in 85% of patients. Twenty-seven percent of patients required hospitalization for pain. The pain was localized in 61% of patients and diffused over the entire abdomen in 39%. Analgesics were required in 85% of pain episodes.USG characteristicsMultiple gallstones were present in 69%, and 31% had a single stone. The echogenicity of the liver was diffusely raised in 54% of individuals, mildly enhanced in 18% of subjects, and grossly normal in 25% of the studied USG patients. The gall bladder was over-distended in 17% of cases, while it was normal size in the remaining 83% of cases on USG findings. The gall bladder wall was thickened in 15% of patients, while the rest (85%) had normal wall thickness. Pericholecystic fluid was seen in 15% of cases. The common bile duct (CBD) diameter on USG was found to be within the normal range (diameter is 3.9 mm), and a dilated CBD (of diameter 6.6mm) was found in one patient. Intrahepatic biliary radical (IHBR) was grossly normal for 99% of the study population; it was found to be dilated for 1%, though. Dilated IHBR, however, was not associated with jaundice or CBD.Post-op symptomsA total of 100 patients took part in a questionnaire regarding demography, symptoms, and follow-up, among whom 82 (82%) patients complained of pre-operative pain. Patients were followed at one week, one month, and six months , upper abdominal discomfort (52%), post-prandial fullness (28%), nausea (46%), and vomiting (35%); 26% of patients presented after two to four episodes of pain. The commonest location of pain was the epigastric area (42%). Radiation of pain to the right scapula was noted in 48% of patients. A similar study found that relief from biliary pain was around 92%, but relief from other symptoms present pre-operatively was low [Post-cholecystectomy syndrome is often caused by choledocholithiasis, gastroesophageal reflux disease, dysfunction of the sphincter of Oddi, remnants of cystic duct stumps, and dropped stones that cause abscesses. Post-cholecystectomy duodenogastric reflux may lead to gastritis . In a prNew symptoms like pain, diarrhoea, and flatulence can arise post-operatively. Persistence of pain in up to 33% of the patients and de novo pain in up to 14% were reported in a systematic review. Diarrhoea (85%) and constipation (76%) were the persistent symptoms most often reported, whereas upper abdominal pain and vomiting were the least often reported. Flatulence (62%) was the most often reported new symptom . In our Pain is reported to be the most common symptom to resolve after cholecystectomy. The severity of persistent symptoms decreases over time. Flatulence is the most often reported new symptom post-operatively. Atypical symptoms should be investigated pre-operatively with further work-up like upper gastrointestinal endoscopy. Such patients should be assured of the benign nature of the problem and treated symptomatically. In the presence of atypical symptoms, pre-operative counselling regarding the possible persistence of symptoms should be done. Patients presenting with atypical symptoms showing stones in imaging studies should also have GERD and IBS ruled out and treated if present to improve the outcome of cholecystectomy when offered.


Osteoarthritis negatively impacts the patient’s quality of life. Qualitative research is an effective tool in detecting the various emotions experienced by patients with osteoarthritis. Such studies play a crucial role in promoting comprehension of the patient’s experiences of health and illness among healthcare professionals, including nurses. The purpose of this study is to examine patients’ perceptions during the pre-admission process for total hip replacement (THR). The study utilized a qualitative descriptive methodology with a phenomenological approach. A sample of patients awaiting THR consented to participate in the study and were interviewed until data saturation was achieved. The results of the phenomenological analysis resulted in the identification of three themes: 1—Surgery generates mixed feelings; 2—Pain negatively impacts daily life activities; 3—Pain requires personal strategies to be alleviated. Patients awaiting THR demonstrate frustration and anxiety. They experience intense pain during daily activities, which persists even during night rest.  Osteoarthritis is widely recognized as the most prevalent joint disease globally. Specifically, hip osteoarthritis (HO) is particularly linked to significant societal limitations and associated impairments ,2. Pain Surgical intervention should be considered for patients who have not experienced improvement through less invasive treatments, including physiotherapy, injections, or pain management with analgesics ,5,6. THRIn addiction to pain, disability and participation restriction are important aspects to assess in the care plan . These pAt present, there are limited studies that have assessed the qualitative aspects of patient experience following THR. Some studies suggest that patients report improved quality of life, reduced pain, and improved mobility after THR. However, other studies report dissatisfaction with prosthesis function, aesthetic appearance, and limited range of motion. Research is needed to fully understand the patient’s perspective on THR and to develop a standardized approach to evaluating patient satisfaction .Qualitative research is probably the best way to understand patients’ needs and contexts and could improve therapeutic strategies and their assessment . KnowingThis study aims to explore patients’ experiences during pre-admission for THR.Qualitative research examines, characterizes, and interprets the human experience, and interviews are predominantly utilized to generate qualitative data .This study employed a qualitative research design. By utilizing qualitative research, the researcher gained an understanding of the patients’ beliefs and values and the way these beliefs and values are shaped by the context in which they are studied . InterviThe descriptions are exhaustive and expressed in a language that is accessible to those who experience the phenomenon.Collection of verbal data;Reading of the data;Breaking of the data into parts;Organization and expression of the data from a disciplinary perspective;Synthesis or consolidation of the data for the expression of the pattern of the phenomenon .Giorgi’s analytical method endeavors to uncover the essence of the phenomenon as perceived by a human, through the detection of crucial themes . This meData were obtained through unstructured interviews. The interview scheduling was based on the pre-admission list for surgical procedures. The inclusion criteria were as follows: adult patients undergoing pre-admission for THR due to HO and having given informed consent to participate in the study. The exclusion criteria were as follows: patients who did not give consent to participate in the study and to use the data; age under 18; no knowledge of the Italian language; and cognitive deficits that do not allow them to describe their experience. All participants received clear explanations regarding the research objectives and interview methods. The participants consented to take part and were interviewed until sufficient information was obtained. The conclusion of the interviews was determined by the absence of significant information from subsequent participants.From July 2022 to August 2022, data were gathered through qualitative interviews at the Orthopaedic and Traumatological Surgery Department of a university hospital in Rome, Italy. Participants were selected based on the pre-admission list for surgery and interviewed. The interviews, which lasted between 5 and 15 min, were digitally recorded and transcribed verbatim.Prior to conducting the interviews, the research team discussed the central themes of the study with the participants and encouraged them to provide narrative responses to the questions. The participants then provided informed consent.The questions were designed to allow respondents the flexibility to direct the flow of the conversation and structure it to ensure that critical topics were addressed.The following questions were asked: Can you tell me about your health problem? What changes  did it bring about in your life? What are your fears (emotions/thoughts) about the future of your illness? How do you sleep? How is the quality of sleep? Would you like to add more?The data analysis was performed using Giorgi’s descriptive phenomenological method. During the first step, the researcher collected verbal data through audio recording the interviews. Each day, the interviews were transcribed verbatim to ensure the accuracy of the collected data. This transcription preserved the exact wording of the participants. During the second step of the data analysis, the researcher thoroughly reviewed the transcriptions with an open mind to gain a general understanding of the information gathered. In the third step, the transcriptions were divided into smaller segments, and each segment was re-examined line by line to identify the “units of meaning,” which are distinct and meaningful units within the descriptions. In the fourth step, each identified unit of meaning was analyzed and reorganized to enhance its disciplinary significance and express it in terms relevant to the clinical context. Finally, in the last step, similar units of meaning were grouped and combined into larger subcategories to synthesize the meaning of the data. In the abstraction phase, subcategories with conceptual and semantic similarities were grouped into generic categories. These categories were intended to represent the underlying essence of the data, and the relationships among them were made explicit through the identification of themes and sub-themes.A senior researcher experienced in qualitative research oversaw all phases of the analysis. The research team engaged in discussions to resolve any discrepancies until a consensus was achieved.To ensure the validity and reliability of the results, the Lincoln and Guba criteria were adopted, which evaluate the trustworthiness of qualitative research in terms of credibility, reliability, confirmability, and transferability. To further enhance credibility, the research continued sampling and data collection until saturation was reached. Reliability was ensured using the triangulation technique, which requires the involvement of multiple researchers in the analysis process. This provides multiple perspectives and confirms the results, adding depth and breadth to the study phenomenon and leading to multiple conclusions. Confirmability was established with audit trails, in which two independent researchers reviewed the survey process to ensure that the results were supported by the data. Transferability was demonstrated through a description of the socio-demographic characteristics of the participants and a thorough and accurate description of the methodology, research process, and results.The study was conducted according to the Declaration of Helsinki and was approved by the Institutional Review Board of Campus Bio-Medico University of Rome .Eligible patients were contacted by telephone on their pre-admission day and were provided with verbal information about the purpose of the study, the mode of the interview, and the requirement for digital audio recording. Prior to the start of the interview, all participants signed an informed consent form to indicate their agreement to participate in the study. Anonymity was protected by identification codes during the transcription of the interviews and throughout the data analysis process, ensuring that no individual participant could be traced in the study report. Participants were informed that they had the option to withdraw from the study at any time.The study included a sample of 12 patients who were awaiting THR. The sample consisted of 7 females and 5 males with a mean age of 69 years .Three main themes are deduced from this phenomenological analysis. The first theme is “Surgery generates mixed feelings”; the second theme is “Pain negatively impacts daily life activities”; the third theme is “Pain requires personal strategies to be alleviated”.The results of the qualitative study indicated that patients undergoing THR experience a range of emotions. Firstly, there is a general fear associated with their condition. This fear is mainly due to the patient’s personal medical history and the uncertainty generated by the waiting period for the surgery. Many patients reported that they do not know when the surgery will take place or how the postoperative period and recovery process will unfold, leading to frustration and numerous thoughts:“[B]ecause I have a job, I’m worried about the post operation: it’s long and so I’ll have to figure out how to handle it because it’s actually quite challenging, we talk about an abundant month, so this gives me a bit of tension…”“Now I’m like this: I’m waiting, then I hope I’m okay, I think Oh, God, if it’s not okay I can’t walk anymore. I get three thousand troubles in my head…”The results of the qualitative study indicate that patients undergoing THR exhibit a range of emotions. A general sense of fear and uncertainty prevails due to their personal medical history and the wait for the surgery. Participants expressed frustration and various thoughts about the unknown timing of the surgery and the postoperative and recovery process. Despite this, many patients also expressed optimism, confidence, and hope that the intervention will alleviate their pain and physical limitations caused by osteoarthritis, allowing them to return to their daily life activities. The surgery is perceived as the only solution for many participants who have had to abandon hobbies because of osteoarthritis:“I hope to improve. I’m optimistic; I’ve forgotten how to walk without feeling pain, without limping, it’s something I see far. I want to be what I was…”The feelings of discouragement and frustration are seen in many patients, mainly because of the fear of not being able to return to the workplace or to their usual activities. Many patients report that osteoarthritis and the consequent decrease in mobility have led to the abandonment of various activities they perform daily, such as work, spending time on the house, playing with grandchildren, or walking:“I’m a bit depressed, because I volunteer, I was with my niece, I went around, Fiumicino-Rome, I took buses, I was a person who walked a lot. Then I stopped and I’m depressed…”“I feel this fact very heavy; it depresses me, I have a little depression because I can’t do things, I can’t walk…”Waiting for surgery also generates a feeling of nervousness and fatigue in these patients:“I’ve been fighting with this hip for years, now I’ve really reached the limit…”HO can result in decreased mobility and significant physical disability that affects an individual’s independence in performing daily activities such as walking, ascending stairs, bathing, and rising from a seated position:“It changes your life, you don’t live anymore… making a move in the bed is a sacrifice, taking a shower is a sacrifice, putting on pants is a sacrifice…”“You can’t make certain movements: my leg doesn’t allow me, even to put a sock, I need to put myself in suitable positions to do it…”This reduced mobility is reported not only during normal daily activities but also during night rest when patients experience severe pain leading to a worsening of the quality and quantity of sleep. Night pain is, in fact, a complex problem, affecting both the beginning of sleep and the maintenance of the same.“When I’m in the bed I can’t turn around with this leg…”“[A]lso sleeping is a problem… making a movement in the bed is a sacrifice…”“I sleep badly, with pain I cannot turn in bed…”“I don’t have a good quality of sleep, I find it hard to turn around in bed…”Most of the study participants reported that they had utilized various methods to alleviate their pain prior to seeking care at the orthopedic department and undergoing surgery. The initial management of coxarthrosis typically includes FANS, educational programs, exercise, weight loss (for eligible patients), corticosteroid injections, or hyaluronic acid injections, as well as other medications:“I also did injections of hyaluronic acid, but they didn’t help so I raised my hands and thought it was time for the surgery…”“Now I’m applying ice pack[s], because I did punctures, dicloreum, contramal, they work on me and then I took Oki but now even that so I’m trying the ice…”We recommend an exercise program that does not involve high-impact activities. Water exercises also improve function:“I used to ski, I couldn’t do it anymore. I couldn’t do many sports. Same issue with [t]ennis was the same, I avoided it. The only sport I could do was the pool…”Most of the patients reported pain during the night rest, and a majority of them implement the same strategy to improve the quality of sleep:“I must sleep with the pillow between my legs… otherwise I have to put my hand on the buttock when I lie down, so I feel better…”“I sleep badly, with a pillow between my legs and always in the same position, I cannot turn around because I have continuous pain even at night…”Literature has shown that the pre-operative experiences of patients undergoing THR are commonly reported. With regard to the first theme, “Surgery generates mixed feelings,” from the literature emerges the conclusion that patients feel that a sense of uncertainty prevails about the surgery and, specifically, what treatments should have been undertaken before. The most prevalent belief among patients is that undergoing surgery was an inevitable turning point from which there was no return . AnotherPatients who do not achieve adequate pain relief and functional improvement from conservative treatments may be eligible for surgical intervention. However, treatment may not always align with guidelines, recommendations, or patients’ preferences, leading to dissatisfaction and decreased treatment adherence ,21.With regard to the second theme, “Pain negatively impacts daily life activities,” the literature confirms that the positive effect of THR on health-related quality of life is well established. Patients with advanced arthrosis commonly experience depressive symptoms due to their inability to carry out routine activities, resulting in a lack of physical strength, stability, and agility. They report difficulties in performing household chores and are often compelled to give up their cherished hobbies, such as walking, playing sports, or spending time with their grandchildren. This forced sedentary lifestyle contributes to depression, by definition. Significant improvement after THR was observed in the dimensions of motion, discomfort, and symptoms, as well as in the dimensions of distress, daily activities, and vitality .The importance of effectively managing pain and receiving proper information and support to increase confidence in early discharge programs and postoperative management has been established . PersistIn orthopaedic patients, pain assessment is often conducted using Visual Analog Scales (VAS). However, these scales have several limitations, as they fail to take into account the intricacy of an individual’s pain experience .Patients with osteoarthritis (OA) often experience exacerbated night pain, resulting in a decrease in sleep quality. This decrease in sleep quality has been shown to correlate with the radiographic severity of the disease. Pain has been established as a contributing factor to reduced sleep quality, and decreased sleep quality has been linked to heightened pain sensitivity . Night pNight pain is a multifaceted issue that impedes both sleep onset and sleep continuation. In terms of decreased sleep quality, patients often face difficulties finding and maintaining a comfortable sleep position, leading to reductions in both sleep quality and quantity. THR has been observed to alleviate osteoarthritic hip pain in a significant number of patients . The quaWith regard to the third theme, “Pain requires personal strategies to be alleviated,” from the literature emerges the conclusion that a lot of patients try to alleviate pain through a conservative method such as the use of FANS, hyaluronic acid or corticosteroid infiltrations, or physiotherapy. As reported in the literature, patients tend to exercise caution in utilizing pharmacological interventions, such as drugs or injections, to alleviate their symptoms due to the potential for adverse effects, including infections, gastrointestinal issues, hypertension, and headaches. In addition, patients express concern about the possibility of developing tolerance to the medications or having to escalate their dosage over time to maintain symptom relief. This fear of drug dependence or resistance further contributes to their reluctance to utilize pharmacological interventions .Consequently, many patients do not comply with their prescribed pain medication regimen, leading to difficulties in effectively managing pain in their daily lives. This often includes a reduction in physical activity, which can result in exacerbated pain and decreased physical function .However, if the pain persists for more than six months, the orthopedic surgeon recommends surgical treatment for them to reduce the symptomatology.Individuals’ beliefs regarding chronic pain influence their attitudes and behaviors towards pain management. There is often confusion regarding the origin and variability of chronic pain, and without sufficient information and guidance from healthcare providers, individuals may lack knowledge about appropriate actions to take and instead adopt a strategy of avoiding physical activity to mitigate the risk of further harm .This study shows how patients feel waiting for a THR surgery. They are frustrated and discouraged and experience great fear. The major problem related to these sensations is the pain that is present at any time of the day, even during night rest, and this implies a worsening of the quality of life. To manage this pain, many patients use a conservative method, which, in the long run, leads to fear of not being able to recover completely. These results help professionals better understand the patients’ experiences and to anticipate some needs: this is important for making the patient feel involved in the treatment, as well as adding content to the pre-operative educational process, which also improves post-operative outcomes.


The pathogenesis of pain in fibromyalgia is still not completely understood. A disrupted emotional modulation could affect the physiology of nociception and contributes to an altered perception of pain. The aim of this study was to test the role of emotional arousal and valence in pain susceptibility in fibromyalgia using the International Affective Picture System (IAPS) paradigm and the Fibromyalgia Severity Scale (FSS). The study focused on comparing emotional arousal and valence between patients with fibromyalgia and the control group. The secondary objective was to examine the correlation between emotional indices and scores on the FSS and the duration of the disease. The 20 patients with fibromyalgia enrolled showed a higher mean arousal score for all the stimuli, including a higher score for unpleasant and socially unpleasant stimuli. The valence scores for social-relevant stimuli were also higher. Increased arousal to unpleasant and socially unpleasant images and increased valence of them correlated with the duration of the disease and the severity of symptoms and could reflect impairment in social cognition and marked sensitivity to pain in interaction with central nociceptive dysregulation. Relevant advances have been made to better understand the pathophysiology of fibromyalgia (FM)  and to pA complex interaction between environmental, psychological, and sensory factors can modulate individual vulnerability to chronic pain. The relationship between an impaired pain regulatory system, sensory inputs, environment, psychological vulnerability, and comorbid psychological conditions can result in individual or multiple functional pain syndromes . Data seNeurophysiological studies have demonstrated the lack of habituation of the cortical responses and an imbalance of the cortical excitability due to repetitive pain stimuli compatible with the central sensitization mechanism having a possible role . SensitiSome researchers have correlated hypersensitivity to pain with impaired central pain modulation . Others Symptoms such as fatigue, sleep disturbances, cognitive impairment, depression, anxiety, and eating disorders reinforce the hypothesis of psychological involvement in the syndrome, both in cognitive and emotional processes . FurtherDuschek et al.  found thA disruption of the emotional modulation of nociception can contribute to FM . TherefoFM also appears to be associated with a disruption of supra-spinal processes related to positive affect and emotional modulation of pain, but not with circuits from the brain to the spinal cord that modulate spinal nociceptive processes .Studies with event-related evoked potentials have also been reported in the literature showing abnormalities  in patients with FM compared to controls with respect to representative images of angry, painful, happy, and neutral stimuli, suggesting an altered emotional influence on image processing .The emotional dimension deals with the unpleasantness related to the noxious stimuli and with the consequent behavior.The distinction between the sensory discriminant and the affective component of pain is well-known. The localization of a noxious stimulus requires the activation of the primary somatosensory cortex while the attribution of unpleasantness involves the medial pain system . CentralBoth impaired regulation of one's own affective emotions and the recognition of those of others have been reported in FM and linked to social cognition impairment.The role of stress in emotional recognition has been debated . CorbettEmotional reactivity as an expression of the limbic network system can strongly influence autonomic balance, such that patients have shown increased sympathetic activity and reduced autonomic response to stress .The relationship between pain and negative emotions needs experimental studies to clarify the impact of these variables on the patient's behavior functions , 35. We The rationale of this study is to evaluate the role of EA and EV for emotional patterns in FM to better characterize the alteration of emotional processing mechanisms both in qualitative and quantitative terms and to relate the alterations to the clinical pattern of the syndrome.We hypothesized that one's emotional state in response to external stimuli, interacting with central sensitization, is related to FM severity and duration.Even if other measures of emotional processing have been used , the IntThe objectives were to compare EA and EV between FM patients and a control group and to investigate the correlation between IAPS indexes  and the This was an observational study carried out on outpatients of the S. Salvatore Hospital of L'Aquila, in central Italy.The Ethical Committee of L'Aquila  approved the study, and it has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. We obtained written informed consent from all participants.In total, 20 patients  with FM syndrome (FM group) were recruited for the study among the outpatients from the Clinical Neurophysiology Unit during a six-month period considering their completed eligibility. We excluded from the study all patients with a history of psychiatric symptoms previous or coexisting with the onset of FM syndrome and with an inability to provide informed consent.Furthermore, 20 healthy subjects  with no clinical evidence or family history of the FM syndrome matched for sex, age, and race-ethnicity were recruited for the control group .s were taking medications.The diagnosis of FM was made by a senior neurologist and defined according to the American College of Rheumatology (ACR)  includina priori defined as emotional involvement and reaction to the pathological condition.Clinical Global Impression-Severity (CGI-S)  was usedThis experience formed the basis of CGI-S of illness rating along a 7-point Likert scale where 1 is “normal, not ill” and 7 is “extremely ill”.EA and EV assessments were carried out using the IAPS paradigm which consists of a set of static images based on a dimensional model of emotion. In total, 90 color pictures were chosen from IAPS depicting events with different kinds of affective valence, i.e., unpleasant, pleasant, and neutral events. Unpleasant and pleasant events are also distinguished in these pictures as involving or not involving social human conditions. For example, pictures with social involvement included depictions of mother–child or familial interactions (pleasant) and outcomes of violence (unpleasant) while pictures without social involvement included landscape scenes or flowers (pleasant) and snakes, contamination, or pollution (unpleasant). Neutral images consisted of pictures of furniture or appliances. The five emotional categories of the IAPS are: (1) neutral, (2) pleasant, (3) unpleasant, (4) socially pleasant, and (5) socially unpleasant . For eacThe subjects were tested individually in a dimly lit room. They were seated in front of a 15-inch computer monitor at 50 cm. During the test session, subjects were instructed that a series of 90 trials would be presented and that for each trial they would be asked to rate the valence and arousal of that picture.Trials started with a 2-s full-screen presentation of one picture. The presentation order of the pictures depicting neutral, pleasant, and unpleasant scenes, with or without social involvement, was randomized for each subject. Then, after a 1-s black screen, a display containing a smaller version of the same picture (located in the upper part) and the valence scale (located in the lower part) was presented. This display remained visible for 3 s or until the participant responded. After the participants' valence rating, another display was presented in which the valence scale was substituted with the arousal scale. Similarly, the display remained visible for 3 s or until the participant responded. If the subjects did not respond within 3 s, an omission was recorded. Those who showed more than 5% of omitted responses were excluded from the two samples and were not considered in the analysis. No subjects in our study were excluded for this reason.To evaluate the clinical features of FM, the duration of the illness (months) was noted and the Fibromyalgia Severity Scale (FSS), consisting of both the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) , was admAll the patients underwent an anxiety and depression evaluation by means of the Zung Self-Rating Anxiety Scale (SAS) and Beck Depression Inventory-II (BDI-II).The SAS is a 20-item self-report rating scale built to measure anxiety levels, based on scoring in 4 groups of symptoms: cognitive, autonomic, motor, and central nervous system symptoms. Each question is scored on a Likert-type scale of 1-4 . The total scores range from 20 to 80. The standardized cutoffs are 21-40: low anxiety level; 41-60: moderate anxiety level; and 61-80: high anxiety level ] and anxiety [20.1 ± 3.0 vs. 19.2 ± 3.3 ] The interquartile range is specified in Student's p > 0,05) as reported in The investigated groups had similar social and demographic characteristics  for all the pictures. In particular, the FM group had a higher mean score in every type of picture shown . However, the valence rating was different between groups for socially pleasant pictures (p = 0.0044) and for socially unpleasant pictures (p = 0.0485) with the FM group showing a significantly higher score  had BDI-II scores between 10 and 13  and 8 patients (40%) between 14 and 16 (mild depression). Furthermore, 12 patients (60%) had SAS scores between 14 and 20 (very low anxiety level) and 8 patients (40%) between 22 and 25 (low anxiety level). The scores for depression and anxiety did not support a relevant clinical diagnosis. Due to the clinical features of FM, it is common to find some psychological symptoms, but, if these do not sustain a well-defined DSM-V disorder, we considered the patients with FM to be without psychiatric comorbidity. The even smaller sample of patients with some depressive and/or anxious responses to the test does not allow for a reliable statistical analysis.The main objective of this study was to compare emotional arousal and valence between patients with fibromyalgia and a control group, specifically examining the role of emotional arousal and valence in these patients' pain susceptibility, through the paradigm of the IAPS and the FSS. The secondary purpose of the study itself was to investigate the correlation between emotional indices, FSS scores, and disease duration.The intensity of negative emotions is positively associated with increased pain intensity, irritability, physical and mental tension, functional limitations, number of sensitive points, insomnia, cognitive deficits, fatigue, and the impact of the disease on quality of life. These patients often feel isolated, misunderstood, or rejected by relatives, friends, health professionals, and in general by their social context.Successful adaptation to chronic pain thus requires the ability to self-regulate or exercise control over one's bodily symptoms, thoughts, emotions, and behaviors . In partKoechlin et al.  suggest Specifically, the stress associated with the experience of chronic pain reduces glutamate, an excitatory neurotransmitter in the medial prefrontal cortex, resulting in emotional dysregulation.Collectively, these results demonstrate that neurobiological processes underlie emotion dysregulation in chronic pain.Chronic pain presents constant challenges to the person with FM and requires adequate coping strategies. Due to these constant challenges, it is likely that in some cases the flexible adaptation of coping strategies to the context will fail or that, after continuous challenges to deal with chronic pain and/or related problems, the individual will not be able to cope with these challenges, resulting in the variability of negative emotions .Many pain syndromes such as migraine , lower bNeuroimaging and neurophysiological approaches have brought experimental evidence to support the network disruption, but they do not show clinical usefulness to detect and quantify cognitive and behavioral disturbances in pain syndromes. A neuropsychiatric approach and a neuropsychological assessment represent important diagnostic tools , 54.Stimulation by images with different affective content affects subjective pain for a cognitive mechanism of attentive engagement .Godinho et al.  showed tAn abnormal sustained arousal or sustained “stress” response to environmental stimuli may facilitate the establishment of a low threshold for pain and a central sensitization state, contributing to the development and maintenance of pain syndromes . CognitiOur results seem to confirm the hypothesis that EA and EV can be considered involved in the clinical expression of FM. In our sampling, arousal was increased in response to the pictures of the IAPS and increased more significantly to unpleasant stimuli and pictures with social relevance. Valence seemed to be higher for the stimuli with social context. From a speculative point of view, this could underline the role of social cognition as a psycho-biological terrain of the increased susceptibility to pain perception in FM. Not only is the regulation of one's own emotions altered in FM but also, even less referred to, the detection of emotional signals from the environment  and reprThe anterior cingulate cortex and the insula are involved in the emotional aspect of pain and the link between pain threshold and emotional state could be established in the limbic system . AbnormaOtherwise, central sensitization itself can induce greater pain which acts as a stressor, driving abnormal emotional reactivity. The arousal scores of unpleasant and socially unpleasant pictures were highly positively related to the duration of illness and to the SSS score.The higher arousal elicited by neutral stimuli shows some kind of modality-unspecific dispositional baseline of emotional arousal . EmotionA reliable link between abnormal arousal and stress may reside in individual efficiency in terms of emotional intelligence. If the latter is high, it acts as a stress buffer. If it is low, exposure to stressful situations causes less adaptive responses, insufficient coping strategies, and stress . StressoThe patients with FM showed different patterns of arousal during the observation of the images. Due to the lesser adaptive capacity to all stimuli, they manifested abnormal arousal to all the images regardless of the content, including emotionally neutral ones . FurtherEV impairment seems to be related to the duration of the illness and to the severity but not to the distribution of pain . ChronicOn these bases, emotional pathology could represent both the prerequisite and the consequence of pain. The correlation with the duration of illness indicates the possibility of the establishment of a vicious circle between alteration of the ER and the syndrome that, over time, causes a further emotional dysfunction linked to the factors of chronic pain and amplification, regardless of the presence of anxiety and depression .An alternative interpretation could be that both pain sensitivity and emotional reactivity are related to dysfunction in the limbic system. Localization of the pain may depend more on peripheral factors. Patients with FM report high levels of disease burden in terms of pain and health status .Moreover, there is evidence that the decoding of emotions in patients with FM is impaired, regardless of psychological comorbidities and drugs..In our study, the effects of psychological symptoms such as anxiety and depression are relatively negligible since patients with SAS scores higher than 40 and/or BDI scores higher than 20 were excludedBased on these considerations, many studies using evidence-based psychological therapies have been made for FM . Group tFM can be considered a heterogenous condition. In its pathogenesis, peripheral and centrally driven painful conditions coexist. Patients fall along a continuum in which both impairments may be predominant . Brain fThe study has several limitations. The main one is that the clinical sample is small, due also to the situation determined by the COVID-19 pandemic. It is not easy to increase the sample size, but it is useful to continue the research as soon as possible depending on the course of the pandemic. Moreover, the tests must be administered in the presence of the patients because the images of the IAPS must be presented under the supervision of a psychologist.No causal inference is demonstrable based on the study design but some relationships among the different issues can be hypothesized. Moreover, there was no assessment using the IAPS preceding the onset of FM.Future studies are needed to better clarify the role of emotional testing in patients with FM, taking into account the differences between the various measuring instruments adopted. With adequate weighting, IAPS could be adopted as an additional tool to evaluate emotional arousal and valence. Moreover, the relationship between a general greater emotional excitability and reactivity to stimuli with social content must be focused on.