Fibromyalgia (FM) is a chronic pain syndrome with an unclear etiology. In addition to pain, FM patients suffer from a diverse array of symptoms and comorbidities, encompassing fatigue, cognitive dysfunction, mood disorders, sleep deprivation, and dizziness. Due to the complexity of FM, the diagnosis and treatment of it are highly challenging. The aim of the present work was to investigate some clinical and psychological characteristics of FM patients, and to uncover possible correlations with pharmacological and non-pharmacological therapies. We conducted a cross-sectional, questionnaire-based study aimed at evaluating pain, psychological traits, and the self-perceived effectiveness of pharmacological and non-pharmacological treatments in an Italian population of FM patients. Descriptive statistics, correlation, and inference analyses were performed. We found a prevalence of a neuropathic/nociplastic type of pain, which correlated with psychological traits such as anxiety, low mood, psychophysical discomfort, and the inability to relax. The pain type and psychological traits proved to play a role in determining the self-perceived effectiveness of therapeutic interventions. Patients revealed a better response to non-pharmacological therapies, particularly dietary interventions, relaxation techniques, and psychotherapy rather than pharmacological interventions. The sum of our data indicates that for better outcomes, the type of pain and psychological traits should be considered for tailor-made treatments considering non-pharmacological protocols as a complement to the use of drugs. Fibromyalgia (FM) is a complex syndrome mainly characterized by multisite pain and moderate-to-severe sleep problems or fatigue ,2. The sThe lack of clear pathophysiology is correlated with the lack of biomarkers, making the diagnosis of FM often challenging. The latest updated diagnostic criteria formulated by the American College of Rheumatology have set threshold values for a series of parameters, including symptom duration, widespread pain index, and a symptom severity scale . HoweverConsidering the drawbacks in FM diagnosis and patient management, there is a clear need to formulate a tenable pathophysiological model able to explain the insurgence of the disease. In this regard, the epidemiological traits and comorbidities associated with FM can provide useful insights into its etiology. The marked female-biased sex ratio and perimenopausal prevalence suggest a gonadal involvement , while sFM correlations with immunoendocrine and psychological factors come together with the recognized importance of body-mind aspects in the management of the disease . Psycho-®, https://www.office.com (accessed on 22 February 2021), Microsoft, Redmond WA, USA). Participants were recruited thanks to the collaboration of an Italian association of FM patients ), who shared with 520 addresses from its mailing list an information letter and the link to the survey. Participants joined the survey individually, freely, and anonymously. The acceptance of a full informed consent was mandatory to be able to start the survey. Patients aged between 18 and 65 years with an established FM diagnosis were included in the study . A more detailed analysis of pain was realized through a survey of a series of pain types, including pressure pain, numbness, tingling, sudden pain, burning, light contact, and occasional pain, on a scale from 1 to 5. Finally, participants answered the Italian translation of the painDETECT questionnaire (PD-Q), developed to detect neuropathic pain components, especially in chronic patients . A PD-Q A study-specific form was designed to investigate the self-perceived effectiveness  of pharmacological treatments  and non-pharmacological ones .In the third section of the survey, participants answered well-validated Italian versions of two questionnaires: the Cognitive Behavioural Assessment-Hospital (CBA-H) , and thehttps://www.r-project.org/ (accessed on 5 July 2021)) and MatLab .Data of sociodemographic and clinical characterizations were used for descriptive statistics. Correlation and inference analyses were applied to the following variables: intensities of seven types of pain , PD-Q scores, perceived effectiveness of treatments, and CBA-H and SREIS scores. Where appropriate, the goodness of fit for categorical variables was assessed by means of the chi-square test, while the difference in distribution for semi-quantitative scores was assessed by means of the Mann–Whitney test. For a multivariate analysis, the clustering of the variables was performed with the average linkage agglomerative algorithm based on pairwise correlations. The questionnaire scale reliability was evaluated for internal consistency according to Cronbach’s alpha (0–1.0). Data analyses were carried out using the software R , about 88% were females. Respondents were on average 47.9 years old (median = 50). A large proportion of the enrolled patients had a high level of education , while most of them were married or cohabitant with a partner (about 60%). Half of the patients had children, and jobs as white-collar or grey-collar workers (about 50%) .The biometric data reported by participants allowed for the derivation of body mass index (BMI) values , showingParticipants were also asked to report symptoms other than pain. Typically, FM-associated symptoms or comorbidities, such as fatigue, sleep disturbance, brain fog, dizziness, headache, anxiety, photophobia, depression, gastro-intestinal disorders, and diplopia, have been reported with different relative frequencies, as shown in Regarding psychological characteristics, according to the clinical cutoffs of the CBA-H  resulted in a prevalence of high scores, and consequently, a significantly unequal distribution of patients among the three pain categories defined by the test score cutoffs, with a marked prevalence of “high” subjects with respect to “low” and “intermediate” ones . “High” A correlation between the PD-Q test scores and the CBA-H clinical cutoffs has been investigated, and the significant results are reported in The perceived effectiveness of therapies reported by patients revealed in almost all cases a better response to non-pharmacological treatments with respect to pharmacological ones, as also highlighted by the clustering together of most non-pharmacological therapies in a dendrogram analysis . The catIf the different types of pain are considered, each subdivided into intensity levels, the higher effectiveness of non-pharmacological treatments with respect to pharmacological ones is almost totally confirmed across all pain types, though in some of them the prevalence of non-pharmacological treatments tends to diminish with the increasing severity of pain .A correlation between the CBA-H clinical cutoffs and the perceived effectiveness of non-pharmacological and pharmacological therapies has also been investigated, and significant results are reported in The sociodemographic and clinical characterizations of our sample of participants confirmed the typical FM patient profile: a high number of female patients, the onset of symptoms occurring at adult age prior to menopause (average age 42.3 ± 10.1 years), and a marked diagnostic delay ,35. DataSymptoms reported in addition to pain are related to current diagnostic guidelines . Sleep pThe pattern of perceived pain revealed the typical FM traits, with pressure pain being dominant and uncorrelated from other types of pain. The marked prevalence of this pain component is compatible with a central disorder of pain processing, according to the recent view of nociplastic pain . MoreoveAlthough pain is generally perceived as the most annoying symptom of FM, many other symptoms or co-morbidities are present and often reported as debilitating and impairing by patients. Despite a variable spectrum and different frequencies among patients, symptoms such as chronic fatigue, sleep disturbance, brain fog, depression, anxiety, headaches, and an irritable colon often occur . Our datFM subjects are frequently treated by combined therapies consisting of standard medications and non-pharmacological therapies or alternative medicines . In our Given the clear benefits of non-pharmaceutical interventions and the psychosomatic component reported by our cohort, our results confirm the relevance of alternative treatments in FM patients and the importance of considering the psychological component of the disease ,46,47. ODiet might be important in FM management, since macro- and micro-nutrients are known to affect oxidative stress, inflammation, and neuromodulation. Several food supplements  have been studied in relation to FM symptoms, but the results are inconclusive, except for a beneficial effect of vitamin D supplementation, given that FM patients generally present low Vitamin D levels ,50. HoweRelaxation techniques, including among others deep breathing, progressive muscle relaxation, autogenic training, guided imagery , biofeedback, mindfulness meditation, yoga, and tai chi , are aimThanks to the advances in the neurophysiology of pain, the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) no longer includes pain as a specific mental disorder . HoweverPsychological alterations in FM patients might worsen into full-blown psychiatric disorders, of which the most prevalent are anxiety disorders and depression . ParticuWe are aware of some limitations to this study, which are linked to the intrinsic nature of online anonymous surveys, where the self-selection of participants (more prone to/capable of/interested in responding) cannot be avoided. FM patients received an invitation letter to participate in the study, but the sharing of the link through social networks could not be controlled, possibly involving some non-probability snowball sampling effects. We had to trust the patients on their self-reported conditions, but the findings that main FM features, such as gender bias, the prevalence of symptoms, comorbidities, and diagnostic delay, are significantly represented in our study population makes us confident in the validity of our data.− a prevalence of neuropathic/nociplastic pain in FM patients, correlated with anxiety, low mood, psychophysical discomfort, and an inability to relax;− a perceived higher effectiveness of mind-body non-pharmacological treatments with respect to pharmacological ones;− the role of pain types and psychological traits in determining the self-perceived effectiveness of therapies;− a high self-perceived effectiveness of dietary interventions, relaxation techniques, and psychotherapy.Our study showed:The data agree with the hypothesis of a central origin and development of FM, with a direct involvement of psychic functions controlling mood, emotions, and anxiety, suggesting the need for patient-tailored, integrated interventions for better therapeutic outcomes.


Two common ways of assessing the clinical relevance of treatment outcomes are the minimal important difference (MID) and the patient acceptable symptom state (PASS). The former represents the smallest change in the given outcome that makes people feel better, while the latter is the symptom level at which patients feel well.We recruited 124 patients with a humeral shaft fracture to a randomised controlled trial comparing surgery to nonsurgical care. Outcome instruments included the Disabilities of Arm, Shoulder, and Hand (DASH) score, the Constant-Murley score, and two numerical rating scales (NRS) for pain (at rest and on activities). A reduction in DASH and pain scores, and increase in the Constant-Murley score represents improvement. We used four methods  to determine the MID, and two methods (the ROC and 75th percentile) for the PASS. As an anchor for the analyses, we assessed patients’ satisfaction regarding the injured arm using a 7-item Likert-scale.The change in the anchor question was strongly correlated with the change in DASH, moderately correlated with the change of the Constant-Murley score and pain on activities, and poorly correlated with the change in pain at rest .Depending on the method, the MID estimates for DASH ranged from -6.7 to -11.2, pain on activities from -0.5 to -1.3, and the Constant-Murley score from 6.3 to 13.5.The ROC method provided reliable estimates for DASH , the Constant-Murley Score , and pain on activities .The PASS estimates were 14 and 10 for DASH, 2.5 and 2 for pain on activities, and 68 and 74 for the Constant-Murley score with the ROC and 75th percentile methods, respectively.Our study provides credible estimates for the MID and PASS values of DASH, pain on activities and the Constant-Murley score, but not for pain at rest. The suggested cut-offs can be used in future studies and for assessing treatment success in patients with humeral shaft fracture.ClinicalTrials.gov NCT01719887, first registration 01/11/2012.The online version contains supplementary material available at 10.1186/s12874-022-01776-6. Medical interventions should be aimed at improving patients’ health and well-being. Accordingly, patients’ symptoms and function lie at the heart of evaluating the effects of treatments. Due to their subjective nature, symptoms and function need to be assessed using patient-reported outcome measures (PROMs). Two of the most common PROMs for evaluating treatment outcome in patients with humeral shaft fractures are the Disabilities of the Arm, Shoulder, and Hand (DASH) score and Constant-Murley score –3. PatieBut what is the minimal benefit that justifies use of a medical intervention? Over the past decades, we have witnessed increasing calls to replace statistical significance with ‘clinical relevance’ – our treatments should generate benefits that patients consider meaningful. To inform the magnitude of such effects on different outcome instruments, two important concepts have been developed: the minimal important difference (MID)  and the The MID is “the smallest difference in score in the domain of interest which patients perceive as beneficial and which would mandate, in the absence of troublesome side effects and excessive cost, a change in the patient’s management” . PASS isTo our knowledge, there are no previous studies reporting PASS, and only one study reporting MID estimates for two outcome measures (DASH and Constant-Murley score) in patients with humeral shaft fractures . TherefoThe FISH trial was a randomised clinical trial comparing the effectiveness of surgical treatment with open reduction and plate fixation and non-surgical treatment with functional bracing for closed humeral shaft fractures. The execution of the FISH trial has been described in detail previously , 6, 7. TWe included adult patients (18 years and older) with a closed, unilateral, and displaced humeral shaft fracture. Patients were excluded if they had a previous injury or a condition affecting the function of the injured upper limb, pathological fracture, other concomitant injury affecting the same upper limb, other fracture, cognitive disabilities affecting the patient compliance, or polytrauma. Characteristics of participants 6 weeks after the fracture are presented in Table For the MID and PASS analyses, we included data from all 82 randomised participants and 42 participants who declined to be randomised (opted to choose their preferred treatment) but gave consent for prospective follow-up using the same outcomes as for the FISH trial. Accordingly, the study sample for the analyses consisted of data from 124 participants.The four outcomes analysed were the DASH score, the Constant-Murley score, and the numerical rating scale (NRS) for pain of the upper extremity, both at rest and on activities. DASH is a validated and responsive questionnaire of self-rated upper extremity disability and symptoms with a score ranging from 0 to 100 (higher is worse) . The ConAs the anchor for determining both the MID and the PASS, we used the following subjective global rating question: “How satisfied are you with the overall condition of your injured upper limb and its effect on your daily life?” . The answer options for this anchor question were from 1 to 7 in this order: “Very satisfied”, “Satisfied”, “Somewhat satisfied”, “Not satisfied nor dissatisfied”, “Somewhat dissatisfied”, “Dissatisfied”, and “Very dissatisfied”. All outcomes were collected at 6 weeks, 3, 6, 12, and 24 months after the injury.MIDs for improvement by of each of the four outcome measures were determined using four methods.For the three anchor-based methods, we calculated change in each outcome for each previous follow-up point by deducting the earlier score from the later score, thus a negative change in DASH and pain NRS represents improvement and conversely, a negative change in the Constant-Murley score indicates worsening.receiver operating characteristic (ROC) method, we dichotomised the anchor question between better than the previous follow-up point  and not better than the previous follow-up point. The change in the outcome score was calculated always from the previous follow-up time point to the next follow-up point . The optimal discrimination values for the outcome scores  were determined by ROC analysis using the closest point to top left corner method to maximise specificity and sensitivity [For the sitivity . Nonparasitivity . To meassitivity .mean difference of the change method, we calculated the difference in outcomes between participants who had improved one point in the subjective global rating from those who had not improved from the previous follow-up.For the mean change method, we calculated the mean change with 95% confidence intervals (CIs) for the population whose response to the anchor question  was one point higher than in the previous follow-up point.For the predictive modelling method, we used logistic regression analysis to calculate MIDs as described by Terluin et al. [For the n et al.  In this To assess the correlation of anchor and target outcome measures, we calculated Spearman’s rho for the change of the anchor and 1) the change in each of the outcomes, 2) prescores, and 3) postscores . The 95%ROC method and the 75th percentile method. For the ROC method, we dichotomised the participants based on their responses to the subjective global rating anchor question: those responding “Very satisfied” and “Satisfied” on a 7-item Likert scale were deemed to have reached to a patient acceptable symptom state (PASS) while those responding anything between “Somewhat satisfied” to “Very dissatisfied” were deemed not to have reached the PASS. Determination of the optimal cut off and 95% CIs was carried out in the same way as for the MID.For PASS estimates, we used the 75th percentile method, we calculated the PASS as the 25th percentile score for the Constant-Murley score, and the 75th percentile score for the DASH score and for the pain-NRS (at rest and on activities) in participants who responded either “Very satisfied” or “Satisfied” on the subjective global rating question.For the For the primary analysis, we performed the MID and PASS analyses by combining all the different time points into one analysis to obtain a sufficient number of anchor–outcome pairs. We also determined the MID values separately for every follow-up point as a secondary analysis (Tables Sn = 38) or functional bracing (n = 44) groups. Of 58 who declined randomisation, 42 consented to follow-up (declined cohort), providing us with data from 124 participants . The change in the Constant-Murley score  was moderately correlated to the anchor. The correlation to pain NRS on activities  was moderate, and poor for pain NRS at rest . Correlations between the postscore of the outcomes and the change of the anchor ranged between -0.01 and 0.06. Correlation between the prescore of the outcomes and the change in the anchor was negative for the DASH score, pain NRS at rest, and pain NRS on activities. The correlation was positive for the Constant-Murley score  and Constant-Murley (7.6 points) scores had an acceptable discrimination. Pain on activities (-0.5 points) discriminated poorly with the ROC method.The PASS values with the ROC method for DASH (14 points) and Constant-Murley score (68 points) had excellent discrimination. The discrimination was good with the pain on activities (2.5 points). The 75th percentile method yielded more stringent limits for PASS in all the outcomes .We suggest that differences smaller than the smallest point estimates of the MIDs from this study are unlikely to be clinically meaningful. Conversely, differences above the upper limits are very likely to be clinically important to patients. Depending on the potential benefits and inherent risks of treatment methods, researchers may choose either the lower or upper limit of the suggested MID when interpreting the clinical relevance of treatment effects. For PASS, the upper point estimate depicts the cut-off above which the patients are very likely to be satisfied with the treatment outcome and conversely, the lower point estimate reflects the level below which the patients are unlikely to be satisfied.We identified one previous prospective comparative study on the MID of two different outcomes in patients with humeral shaft fractures reporting the MID of 6.7 points for DASH and 6.1 points for the Constant-Murley score , 17. HowWe decided to use a prospective anchor question for our analyses , which is the method used often in the MID analyses for degenerative conditions. In a trauma setting, it is not possible to obtain reliable baseline data prior the injury. Our approach may be less susceptible to recall bias as the participants did not have to remember their symptoms state several months ago—a task that people tend to fail in , 19.A strength of our study is high internal validity as we used prospective homogenous data from a randomised clinical trial performed by experienced research personnel with little missing data. We also used the most common outcome instruments to assess the outcome of treatment in patients with upper extremity injuries and the methods for obtaining several MID and PASS estimates. In addition, our determination to analyse the MID and PASS was published in the protocol article, prior to any access to trial data .An obvious limitation of our study is that the results are obtained from a randomised clinical trial with stringent inclusion and exclusion criteria . Thus, our results may not be directly applicable to all patients with this injury. Second, the ROC analyses can be biased if the proportion of improved participants is markedly different from 50% . HoweverBoth the MID and PASS are valuable tools both in medical research and clinical practice. The MID provides a tool for future trial sample size calculations. However, when contemplating different treatment methods during shared decision-making in clinical settings, the concept of PASS may be more understandable for patients . The cliWe provide credible estimates for the MID and PASS for adult patients with humeral shaft fractures including several of the most used methods and outcomes. Depending on the application, the upper or lower limit of the established MIDs and PASS values should be chosen. The MID might be more useful especially for scientific purposes , whereas the PASS concept is—in addition to scientific applications—more understandable to patients, and accordingly, we advocate its use as a more appropriate measure for gauging treatment success in patients with a humeral shaft fracture.Additional file 1.


Pain is one of the most significant symptoms of rheumatoid arthritis that reduce the quality of life. The purpose of the study was to determine the effect of eucalyptus on pain and the quality of life in patients with rheumatoid arthritis.t-test, chi-square, Fisher's exact test, and analysis of covariance.In this randomized clinical trial, 70 patients with rheumatoid arthritis were selected by random sampling. In the eucalyptus group, 1 mL of eucalyptus oil was inhaled for 5 min, 3 times a day, for one month. The control group received placebo inhalation. Both groups used routine treatments. Data were collected using a questionnaire of demographics, the numerical pain rating scale (NRS), and Quality of Life (SF-12). Statistical analysis was done using 19th edition SPSS software and applied on paired The mean score of pain severity in the eucalyptus group significantly decreased in comparison with the control group (P < 0.001). The severity of pain there was no statistical difference in both groups before, the first, and the second weeks after the intervention, (p > 0.05); however, in the third and fourth weeks after the intervention, the mean severity of pain in the eucalyptus group was lower than in the control group, and these differences were statistically significant between the two groups (p < 0.05). Also, the patients' quality of life in the eucalyptus group was increased significantly (P < 0.001).The eucalyptus leads to pain reduction, and consequently, improves the quality of life of patients with rheumatoid arthritis.2018-10-07; https://en.irct.ir/trial/33573.IRCT20160110025929N15 Registration date:  RARheumatoid ArthritisDMARDsDisease-Modifying Anti Rheumatic Drugs1Rheumatoid arthritis is a chronic and inflammatory joint disease ,2, the m2The study was a randomized clinical trial. The project was conducted on patients with RA, referred to the clinic . In thisBased on the following formula, the number of patients in each group was estimated at 29 patients, however, considering of 15% of the sample attrition, 35 patients were invited in each group.The inclusion criteria were age 18–60 years, no use of aromatherapy in the past month, absence of a history of allergy, allergic rhinitis, asthma, and chronic pulmonary disease, having at least one year of the definitive diagnosis of articular rheumatism. Exclusion criteria included allergy to eucalyptus, changing the disease process, death, and the patient migrates to another place. The primary and secondary outcomes were pain and quality of life.1Demographic and clinical questionnaires include age, gender, job, education, marital status , duratio2The numerical pain rating scale (NRS), the numerical pain scale with the values of 0 (no pain) to 10 (severe pain) was also used to record the pain severity. The patients recorded the pain before and after the intervention ,22.3The Quality of Life (SF-12), the SF-12 questionnaire consisting of 8 subscales, the general perception of personal health, physical performance, physical health, emotional disorders, physical pain, social performance, joy, having energy for life, and mental health was used to measure. The reliability of this scale has been previously calculated based on the “test-retest”. Cronbach's alphas were respectively 0.86 and 0.76, for physical and mental dimensions, respectively ,23. In tThe research tools were:In this study, the validity of the tools was confirmed by 10 nursing faculty members.Interventions:1Eucalyptus oil was prepared by a reputable pharmaceutical company in 2019. The essential oil used in the present study is from the species of Myrtassa which was prepared from the leaves of the plant. In the eucalyptus group, eucalyptus essential oil was placed on a 2 * 4- inch gas pad that attached to the patient's clothing with pins and was incubated for 5 min, 3 times a day. Pain score was measured 2 min later.2In the control group was used distilled water instead of eucalyptus. Both groups received medication as prednisolone (once a day), indomethacin (twice a day), celecoxib (twice a day), methotrexate (three numbers a week), and acetaminophen (once a day). Also, the eucalyptus group used eucalyptus as complementary medicine.After obtaining informed consent for data collection, patients were randomly divided into control and eucalyptus groups.t-test, chi-square, Fisher's exact test, and analysis of covariance. The study protocol was approved by the Ethics Committee with the number of IR-UMSHA.REC.1397.408. The IRCT code was IRCT20160110025929N15.Data were analyzed using 19th edition SPSS software and paired 3The findings of this research showed that most of patients were women, married, illiterate, urban, non-smoking, having more than 4 years RA, having 3–4 joints involved based on criterion DSA28, and movement limitation. The two groups were similar in terms of the time of diagnosis, family history of rheumatoid arthritis, and movement limitation .Table 1DThe result showed that there was no statistical difference between the mean scores of the severity of pain in both groups before the study, (P = 0.580); also the first (P = 0.530), and the second weeks after the intervention (P = 0.458); however, at the third weeks (P = 0.003) and the fourth weeks after the intervention (P = 0.001) there was a statistical difference in both groups .Table 2CAlso, the results showed that there was no statistical difference between the quality of life in both groups before the study (P = 0.5); however, after the intervention, there was a statistical difference between the quality of life in both groups (p < 0.001), so that total quality of life to increase from 28.26 ± 3.23 to 37.51 ± 4.57 in eucalyptus group .Table 3C4According to the results of the current study, it can be argued that the pain of patients who used eucalyptus oil inhalation was significantly reduced. The study of Kim showed that the anxiety reduced significantly after eucalyptus inhalation (p < 0.001) in comparison to the control group . MassageSince one of the limitations of this study was the small number of samples due to time constraints, it is recommended that future studies be performed with more samples. Another limitation of this study was the low follow-up time to assess the quality of life. It is also suggested that studies be carried out with longer periods. Also despite instructing the patient not to use other complementary medicine methods, it was possible that some patients had used other non-pharmacological interventions.5The results of this study showed that eucalyptus oil reduced pain and increased quality of life. Therefore, along with other treatments, eucalyptus oil can also be used as a complementary treatment.Kord-Varkaneh, Karampourian, Oshvandi made substantial contributions to the conception and design of the study. Sampling was carried out under the supervision of Basiri. Data analysis was performed by Mohammadi. Kord-Varkaneh and Karampourian were involved in the writing-up of the manuscript. All read and approved the final manuscript.The study protocol was approved by the Ethics Committee with the number 9708224883 - IR-UMSHA.REC.1397.408. The IRCT code was IRCT20160110025929N15.Authors are given permission to publish the manuscript.Hamadan University of Medical Sciences, Hamadan, Iran.The authors have no conflicts of interest to declare.


We retrospectively analyzed the data from patients admitted to the intensive care unit (ICU) of the Hospital of L’Aquila during the first and second waves of pandemic to identify pain related to COVID-19. Pain was evaluated by using the Numerical Rating Scale, and the assessment for neuropathic disturbances of pain was performed with von Frey’s hair and Lindblom tests. Pain increased significantly during hospitalization . Female patients were affected by somatic pain in 32.8% of the cases and by somatic pain and pain with neuropathic features (NFs) in 23.5% of the cases, during the ICU stay. Somatic pain and pain with NFs affected more frequently patients with cardiological and respiratory comorbidities. Patients treated with continuous positive airway pressure via helmet had a higher frequency of somatic pain and pain with neuropathic disturbances . The frequency of somatic pain and pain with neuropathic disturbances was lower in patients sedated with propofol combined with ketamine. Females have been associated with a higher risk of somatic pain and pain with NFs. Patients with cardiological and respiratory comorbidities undergoing noninvasive ventilation had higher levels of pain. As conclusion, ketamine may reduce the promotion or the worsening of pain in COVID-19 patients. Persistent post-intensive care (PPIC) somatic pain with neuropathic features (NFs) is often part of this syndrome. There is a potential risk of post-COVID syndrome following ICU in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,2,3,4,5.Actually, the question whether the clinical history and pharmacological treatments, including SAs and NMBAs, can influence the development or the increase in somatic pain with NFs in patients requiring respiratory support is poorly understood .Considering the lack of studies assessing persistent symptoms, including pain following ICU discharge, this study aimed to investigate somatic pain associated with NFs in PICS of SARS-CoV-2 patients admitted in ICU for respiratory support.To accomplish this, we retrospectively reported the clinical features and treatments and their possible influence on the development or the increase in pain in SARS-Cov-2 patients requiring ICU admission for respiratory support .2We retrospectively analyzed the data from SARS-Cov-2 patients admitted to the ICU of the COVID Hospital of L’Aquila  in accordance with the STROBE Statement.2.1Data were collected from electronic medical records. The information was collected from emergency department records and discharge reports. COVID-19 infection was confirmed by nasopharyngeal swabs and by real-time polymerase chain reaction assay performed by the hospital-based clinical laboratory . We inclThe objective was to investigate the clinical characteristics associated with pain development in ICU admitted respiratory support SARS-Cov-2 patients.2.2Baseline variables included the following: demographic data, presence of comorbidities, and treatments administered during the permanence in ICU.−2), time spent in ICU (days), development of acute respiratory distress syndrome , ventilation strategy , SA and NMBA consumption, and history of somatic pain and NFs at the moment of hospital admission (yes/no) and at ICU discharge (yes/no).Data collected included the following: sex, age, body mass index  arising from the skin, soft and musculoskeletal tissue, due to actual or threatened damage to non-neural tissue with activation of nociceptors. Pain was defined according to the International Association for the Study of Pain (IASP) .Pain levels were evaluated according to Numerical Rating Scale . Patients with an NRS score ≥4 were considered with somatic pain.We considered as NFs of pain the combination of sensory loss and pain either with or without sensory hypersensitivity phenomena in the somatic painful area .The assessment for NFs of pain was performed by testing the skin of arms, legs, abdomen, and back using von Frey’s hair test and the Lindblom test ,15,16.The positivity of the tests for one of the evaluated features  was considered a sign of neuropathic disturbance, due to a somatosensory nervous system abnormal function .At the time of this analysis, our institution experienced shortages of fentanyl, sufentanil, midazolam, and dexmedetomidine. The decision about the use of SAs was led by the drug’s availability during the emergency. For this reason, our strategy for patient sedation was the continuous intravenously (IV) adjunctive infusion of ketamine (PK) or remifentanil to propofol (PR). SAs were administered at the moment of ICU admission and during the hospitalization, based on the need of respiratory support.−1 h−1 of IV propofol combined with 0.05–0.10 μg kg−1 min−1 of IV remifentanil or combined with 0.12 mg kg−1 h−1 of IV ketamine [Patients received 3–5 mg kgketamine ,19.−1 h−1 of rocuronium bromide was administered to patients who required OTT or underwent resupination procedure, during IMV.A continuous IV infusion of 0.4 mg kgThe sedation strategy was titrated to achieve a moderate to deep sedation (−3 to −4) using the Richmond Agitation and Sedation Scale .2O, while for the NIV strategy PEEP values were 8–10 cm H2O with pressure support (PS) of 8–12 cm H2O. Patients treated with IMV received a tidal volume of 4–6 mL kg−1, PEEP values from 13 to 24 cm H2O, and respiration rates were titrated in order to maintain pulse oximetry >90% and a pH >7.2 [The respiratory support consisted of NIV procedures (CPAP with helmet or NIV via FFM or helmet) or IMV procedures via OTT followed or not by Ts. The respiratory support in patients treated with CPAP consisted of positive-end respiratory pressure (PEEP) values of 8–10 cm H pH >7.2 . Arteria pH >7.2 .Specific pharmacological treatment with antiviral therapy, including hydroxychloroquine, lopinavir/ritonavir, remdesivir, and plasma taken from convalescent donors of COVID-19, was administered ,24 in al2.3We describe qualitative and ordinal variables as frequencies and percentages, respectively, and quantitative continuous variables as mean values and standard deviations (SD). The proportion within groups was compared using Cochran’s test. The Chi-square test or the Fisher exact test was used for categorical variables, while the Kruskal–Wallis test was used to compare continuous variables among independent groups.The level of significance was set to 0.05. Statistical analysis was performed with Stata 14.Informed consent: Written informed consent was obtained from all subjects or their proxies or legal surrogates.Ethical approval: This study was approved by L’Aquila and Teramo Ethics Committee .3During the study period, 123 patients fulfilled the inclusion criteria. As reported in During admission, 59 out of 123 patients reported pain , and they were classified as patients with somatic pain (36), pain with NFs (11), and patients with somatic pain and pain with NFs (12), as reported in p < 0.001). p < 0.05). This indicates a decrease in the proportion of patients with pain with NFs (9% vs 6%) during the permanence in ICU. Just 6% of the admitted patients were pain-free.At ICU discharge, 116 patients reported pain , indicating a significant difference over time  was noted between the somatic pain and somatic pain with NFs, indicating that during the permanence in ICU, there was an increase in the proportion of patients with these symptoms. At the moment of ICU discharge, only 6% of the patients were pain free, and we observed a decrease in the number of patients with NFs of pain (9% vs 6%). These data seem to be aligned with the extensive body of literature, which clearly suggests that during ICU treatment up to 40% to 70% of the patients experience pain [We found that the distribution of the patients with pain increased significantly over time . A significant difference  who are also affected with cardiological disease has been demonstrated, but it is still not possible to clearly qualify the strength of this association . Recent Our data underline that ventilation strategy may influence pain development or attribute to an increasing level of pain in critically ill SARS-Cov-2 patients. Pain in ICU patients is a complex multifactorial condition. Intubated and mechanically ventilated patients cannot fit the IASP definition of pain, as they cannot self-report pain sensations or assess their intensity . RespectKetamine also has anti-inflammatory properties. Significant decrease in plasma levels of interleukin-6 (IL-6) and C-reactive protein was observed after administration of ketamine in general surgical and cardiac surgical patients, as reported by Dale et al., compared with an opioid-based sedation . After kOn the contrary, remifentanil is an ultra-short-acting µ-opioid receptor agonist, which often generates and strengthens postoperative pain sensitization, known as remifentanil-induced postoperative hyperalgesia. Evidence suggests that the transient receptor potential vanilloid 1 (TRPV1) is involved in the development of neuropathic pain and hyperalgesia . ContinuDifferently from remifentanil, the immune modulation effect and the NMDA receptor signaling pathway inhibition provide prolonged continuous IV infusion of ketamine (>10 days), which may attenuate the COVID-19-induced or increased neuropathic pain, avoiding central sensitization and pain hypersensitivity . FurtherSeveral limitations affect this research. First, this was a retrospective observational study with all related limitations of this design. An important drawback was that the correlation between weaning time from respiratory support and SAs results from ABGA and LUSS test, NMBA consumption and specific pharmacological treatment with antiviral therapy were not studied. Furthermore, we were not able to investigate other determinant conditions , which may in turn promote the development of PPIC somatic pain with NF after the ICU discharge. In addition, we were not able to evaluate the time spent in prone position by each patient and the rehabilitation time. There was also a lack of data regarding specific pharmacological pain treatments among survivors.In conclusion, our findings confirm the presence of somatic pain with NFs as a part of PICS in SARS-CoV-2 patients admitted in ICU for respiratory support. Sex, comorbidities, ventilatory strategy, and SAs might influence the development or the increase in somatic pain and neuropathies, presumably mitigating the long-term nociceptive hypersensitivity COVID19- and opioid-related effects. We believe that findings add significant evidence to the growing literature on pain prevention and treatment as a part of PICS, after acute phase of COVID 19 infection in critically ill patients. Further studies will be needed to confirm our findings.


Unrecognized pain in the Intensive Care Unit (ICU), due to inadequate assessment and therapeutic management, is associated with increased morbidity and mortality. Despite the availability of validated pain monitoring tools, such as the Critical-Care Pain Observational Tool (CPOT), these scales are not commonly used in clinical practice, with healthcare professionals often relying on their clinical impression. Our study aims to determine the agreement between the pain examination performed by ICU professionals and the CPOT.Prospective cohort study that included critically ill patients and physicians, nurses and physiotherapists from an ICU in Bahia, Brazil. During bedside clinical rounds, the CPOT score was applied to assess the pain of hospitalized patients, and health professionals were interviewed to ascertain their perception of the patient's pain for a maximum of five consecutive days. Correlations were assessed using the Spearman rank tests. Hierarchical cluster analysis was employed to show the results of CPOT score and pain assessment by healthcare professionals at each study time. And the Kappa statistic was calculated to assess the agreement between the CPOT score vs. the pain assessment by healthcare providers.p = 0.005). Physician assessments were significant only in day 1. On the presence of pain, the professionals' assessments and CPOT revealed mild to a moderate agreement.One hundred one patients were included in the study with median age of 74 years (IQR 61.5–83.5), a predominance of women (55.4%) and a median SAPS 3 score of 45 (IQR 39.5–53.0). The correlation between the professional's pain assessment and the CPOT were mostly statistically significant, ranged from negligible to weak, being the highest index obtained in the evaluation of nurses on day 5 (Kappa index = 0.43, Healthcare professional's pain assessment displayed a weak positive correlation with a validated pain scale and poor agreement amongst members of the ICU team, particularly when the pain was felt to be absent. Thus, this study highlights the importance of routine tools for pain assessment in the ICU for all members of multidisciplinary teams. Pain is perhaps the most stressful event that patients experience during their stay in the intensive care unit (ICU). It is associated with an acute response to stress, characterized by changes in heart and respiratory rate, blood pressure and neuroendocrine secretion , 2. ApprWhile prior studies have highlighted the importance of pain in the ICU, many factors hinder caregiver's ability to communicate effectively with patients, including the use of sedative agents, mechanical ventilation, and changes in sensorium . In the Given the severity of life-threatening conditions in the critically ill, prompt recognition and management of pain may be overlooked. While there are validated and recommended pain assessment scales such as the Critical-Care Pain Observational Tool (CPOT) for critically ill patients, prior work demonstrates that these are rarely used routinely in the ICU . Recent This study aims to assess the concordance between pain assessment performed by ICU professionals and a validated pain assessment scale in critically ill patients.This research was approved by the Research Ethics Committee of the Federal University of Bahia under the number 2.249.687 and CAAE 73835317.5.0000.5577. And was conducted in compliance with the Helsinki declaration.Prospective observational and analytical cohort study conducted from September to October 2017 in a tertiary ICU in Salvador, Bahia, Brazil. All patients ≥18 years old, consecutively admitted to the ICU, who provided informed consent, were included in the study. The multidisciplinary team included 13 physicians, 18 nurses, and 16 physiotherapists who also provided informed consent. Patients with a stay of fewer than 24 h, conditions that compromised the expression of pain behaviors, such as decortication or decerebration, and use of neuromuscular blockers, were excluded.The demographic characteristics, clinical and laboratory data were obtained from the electronic medical records of the patients. These included: age, primary ICU admission diagnosis, comorbidities, vital signs, level of consciousness through the Glasgow Coma Scale (GCS) and the Richmond Agitation Sedation Scale (RASS) score, arterial blood gas test, hemogram, serum creatinine, total serum bilirubin, use of vasoactive drugs, analgesics, sedatives, or drugs with the potential to interfere in the patient's perception of pain, such as anxiolytics and anti-depressants. The total number and type of painful procedures performed were recorded every 24 h, including orotracheal suctioning, arterial puncture, wound care, thoracocentesis, and chest tube removal.All researchers received the same rigorous training to properly apply the CPOT, in which each one applied the score to hospitalized patients and compared the responses to ensure that there was inter-observer agreement in order to reduce measurement bias. The behavioral parameters of CPOT included facial expression, body movements, body tension and ventilator compliance in intubated patients or vocalization in patients with spontaneous breathing. Each behavior was rated from 0 to 2, resulting in a possible total score ranging from 0 to 8, where >2 points represents the presence of pain . A CPOT In the studied ICU, daily clinical rounds are performed at the patient's bedside with the physician, physiotherapist and nurse responsible for the patient. Immediately before the visit, the researchers applied the CPOT to the patient. The study team also noted the presence or absence of tracheostomy, mechanical ventilation and ventilatory support. Then, after each patient visit, healthcare professionals were interviewed individually, being asked whether the patient was in pain and, if so, to rate the pain intensity from 0 to 10. There was no communication among the professionals regarding their pain evaluation. Patients and healthcare providers underwent daily evaluations by for up to 5 days.p < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS 24.0 (IBM statistics), Graphpad Prism 7.0  and JMP 12.0 . Finally, the Kappa (K) statistic was calculated to assess the agreement between the presence of an unacceptable amount pain according to CPOT score vs. the pain assessment by nurses, physicians, and physiotherapists at each study time. The Kappa statistic was interpreted by Landis and Koch criteria. Bland-Altman analyses were conducted to provide a visual representation of the concordance between the methods.Categorical data were presented as proportions and continuous data as medians and interquartile ranges (IQR). Correlations were assessed using the Spearman rank tests. Hierarchical cluster analysis (Ward's method) was employed to show the results of CPOT score and pain assessment by nurses, physicians and physiotherapists at each study time. A There were 111 admissions over the study period and 10 exclusions . Patients were followed up for a maximum of five consecutive days, with 336 pain assessments being performed  . The medDuring the 5 days of evaluation, 7 patients (6.9%) required mechanical ventilation on day 1, 5 (6.1%) on day 2, 5 (7.8%) on day 3, 4 (8.5%) on day 4, and 4 (10.3%) on day 5. Analgesic use varied throughout hospitalization with 37 (36.6%) on the first day of evaluation, which increased until the third day of hospitalization. Opiate use on day 1 included 19 (18.8%) patients, though this similarly increased until the third day of evaluation. Sedatives were used in a minority of patients, the greatest use being on day 2 with 6 (7.3%) patients. The median RASS ranged from −1 to 0 on most study days. Arterial puncture was the most frequent procedure in patients . In contrast, wound debridement was the least performed procedure . These findings are detailed in r = 0.34, p < 0.001). Physiotherapists' evaluations suffered less daily variation of correlation with CPOT compared with nurses and physicians, though similarly did not reach statistical significance (Multidisciplinary team members included 13 (27.7%) physicians, 18 (38.3%) nurses, and 16 (34%) respiratory therapists. Professionals' pain assessments correlated insignificantly with CPOT, ranging from negligible  to weak . Physician evaluations demonstrated poor correlation with CPOT, only achieving significant correlation on day 1 (ificance . There iificance .p < 0.001). The proportion of agreement in the presence or absence of pain varied daily between 67.1 and 76.9%, with the lowest kappa index of agreement observed in the evaluation of physicians on day 3  and the highest index obtained in the evaluation of nurses on day 5 .In the presence of pain, the overall agreement between professionals' assessments and CPOT was greater on the first day  of the CPOT scale in pain detection. The poor correlation and agreement between CPOT pain assessments and the multidisciplinary team found in our study suggest that subjective pain assessment performed by health professionals is inadequate to identify the existence of pain in ICU patients, especially in those unable to report their pain. The results of our study reinforce recommendations that a validated behavioral scale should be used as an alternative to detect pain and evaluate its intensity –18.Our study found that physicians, nurses, and physiotherapists pain assessments demonstrated slightly positive agreement on days 1 and 2. In addition, subjective pain assessments by health professionals were in most agreement when no pain was noted, whereas pain assessments >0 demonstrated wide variability for the same patient at the same time. The lack of at least a moderate agreement in subjective pain evaluation by physicians, nurses, and respiratory therapists suggests the absence of a common standard in the assessment of pain performed by these professionals. Therefore, the establishment of a systematic pain assessment protocol throughout the stay in the ICU may have a beneficial effect, reducing the consequences of inadequate pain management.Our study has several limitations including a small sample in a single center and the non-individualization of pain assessments by professionals. This is balanced with the ability to evaluate multiple members of a multidisciplinary team during the study period in a more granular way with the results that complement previous studies. A few patients in our study underwent mechanical ventilation combined with rare use of sedatives, leading to limited comparisons between subjective assessments and CPOT in sedated and intubated critically ill patients. While this patient population differs from prior studies, it nonetheless demonstrated similar limitations of subjective pain assessments when compared to CPOT, even in non-intubated and minimally sedated patient populations. The gold standard for assessing the presence of unacceptable levels of pain is still self-reported pain by the patient. The CPOT was developed from retrospective chart reviews and physiological parameters were excluded in the initial assessment. In addition, the application of the tool in specific situations, such as patients with delirium, requires further evidence .This study identified no significant positive agreement between CPOT and bedside pain assessments by physicians, nurses and physiotherapists. The lack of agreement between interprofessional assessments in the presence of pain highlights the urgent need to properly address pain systematically in critically ill patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Research Ethics Committee of the Federal University of Bahia under the number 2.249.687 and CAAE 73835317.5.0000.5577. The patients/participants provided their written informed consent to participate in this study.KA, NF, and BA were responsible for study design, implementation, manuscript preparation, and had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. RS, RM, IF, TC, VS, MO, AG, and SA contributed substantially to the study design, data analysis and interpretation, and writing and review of the manuscript. KA and MA were responsible for advanced statistical analysis, figure generation, and manuscript review and preparation. All authors contributed to the article and approved the submitted version.This study was supported in part by the intramural research program of FIOCRUZ. The work of BA was supported by a grant from NIH. IF was supported by UNEB: PICIN/UNEB. KF received a fellowship from the Programa Nacional de Pós-Doutorado, The work of BA was supported by grants from NIH (U01AI115940 and U01AI069923). BA was a senior scientist from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. TC received a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Finance code: 001). Fogarty International Center and National Institute of Child Health & Human Development of the National Institutes of Health under (Award Number D43 TW009763 through a research scholarship awarded to MA) and by the NIH (U01AI069923). MA received a research fellowship from the Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB), Brazil.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The opioid crisis in the United States remains a major issue that is directly linked to the prescribing practices of physicians. There is a lack of consistency in post-operative prescribing of narcotic medications. We have designed a retrospective study to evaluate factors that contribute to the prescription of opioids following common laparoscopic procedures. In this study, we analyzed peri-operative medications and pain requirements and how they relate to the frequency in which narcotics are prescribed at Saint Joseph’s University Medical Center (SJUMC), a level two trauma center and teaching hospital. We also studied how the frequency of narcotic prescriptions is related to patient demographics and surgeon practices. We propose that standardizing pain medication protocols will be an effective way to decrease overall narcotic use as well as prescriptions for common laparoscopic procedures. Opioids are a very common medication used to control acute and chronic pain; however, the epidemic of opioid addiction, abuse, and overuse has become a salient topic in the contemporary medical literature. This heightened focus comes in response to an astoundingly morbid series of epidemiologic studies exposing trends. One hundred and thirty Americans die every day from opioid overdose , and oneIt is imperative to identify current peri-operative pain management strategies to develop more effective post-operative pain control and lower narcotic prescriptions. We reviewed all patients from May 1, 2017, to April 30, 2018, who underwent uncomplicated laparoscopic appendectomies and laparoscopic cholecystectomies in an effort to identify surgeons’ opioid prescribing practices at Saint Joseph’s University Medical Center (SJUMC). It was our goal to identify factors positively contributing to opioid prescribing to decrease the overall prescriptions of narcotics in an effort to positively impact the opioid epidemic.Seven hundred seventy-four patients who underwent uncomplicated minimally invasive appendectomy and cholecystectomy procedures during a one-year period from May 1, 2017, to April 30, 2018, at SJUMC were evaluated retrospectively after obtaining approval from the institutional review board (IRB). Patients who had complications were removed from the data set as to not skew the information. Demographic variables including sex, surgeon type , administration of local anesthetic, surgery type, hospital length of stay, and narcotic use in the post-operative anesthesia care unit (PACU) were evaluated. Opioid medications were equilibrated using morphine equivalents (MEQ) .Logistical regression models were created using R version 3.2.4© software  to establish which individual variables were most associated with narcotic prescriptions upon discharge. Then, a multivariate logistical regression was performed to find which variables jointly contributed to narcotic prescription. By performing data analysis along with these calculations, we were able to isolate individual variables and determine which factors played a role in patients being discharged with prescriptions for narcotics.Our retrospective analysis of 774 patients showed that sex, surgeon type, administration of local anesthetic, surgery type, hospital length of stay, and narcotic use in the PACU were the most statistically significant multivariate factors that correlated discharge with prescription for narcotics Table . Table 1Table The epidemic of opioid abuse and opioid overdosing has prompted a rethinking of pain management in surgical patients. In 2019, over 70,500 people died from drug overdose. Additionally, another 10.1 million people misused prescription opioids that same year. A significant of those people were first-time users. It is estimated that approximately 1.6 million people misused prescription pain relievers for the first time . In thisAs mentioned, approximately 63% of females in this study received opioid scripts as opposed to 52% of males. According to Bartley and Fillingim, sex differences in pain showed that women have an increased risk of severe clinical pain as well as chronic pain . HoweverAll of these variables may be due to the surgeon’s perception of the patient’s future pain requirement and preference of individual surgeons. The lack of standardized pain control regimen post-operative allows for individual surgeon preferences to have a significant impact on opioids over prescription which in turn can have a negative impact on the opioid epidemic.Robotic cholecystectomies are also more likely to get a narcotic script than laparoscopic appendectomies and laparoscopic cholecystectomies  Table . Since mWhen evaluating which patients get narcotics earlier in the PACU, there are a few notable variables. Our study showed statistically that 64% of patients receiving narcotics in the PACU were discharged with opioid scripts. Decreasing narcotic use in the PACU would help reduce the number of patients that are discharged with opioid scripts. In a retrospective study conducted by Chavez et al., using an opioid sparing protocol pre-intervention and post-intervention was effective in managing acute pain in the PACU. It also reduced PACU length of stay and improved patient outcomes . ImplemeA longer post-operative stay was shown less likely result in narcotic prescription on discharge Table . This maThis study is limited by retrospective analysis and therefore we can only draw conclusions from a non-controlled data set. At the time of creation of this study, there was no set protocol for pain control medications or dosing. Currently, in a study by Chou et al., it is recommended that operative pain management should begin in the pre-operative period. This should be carried out through the post-operative period and should be tailored individually to each patient . Our datThe link between the prescription of opioids and eventual opioid addiction has been clearly demonstrated. The lack of protocolized peri-operative pain management strategies has resulted in a wide variation in prescribing practices. Hospital systems and teaching institutions should use their influence over surgeons and residents to shape evidence-based prescribing practices to limit opioid prescriptions. This can be achieved by standardizing the use of NSAIDS and local anesthetics to limit post-operative pain. Patients should also be monitored to accurately assess their pain medication requirements. These protocols and best practices may be best implemented in a multidisciplinary effort to create order sets and quality metrics to ensure enforcement.


The purpose of this study was to determine whether oxybuprocaine hydrochloride gel could alleviate pain during male catheterization.  Between September 2021 and March 2022, a randomized controlled trial was conducted at the Urology Department of Harbin Medical University Cancer Hospital (China). A total of 192 adult male patients requiring catheterization were enrolled and randomly assigned to one of two groups: 96 in the test group and 96 in the control group. The test group included patients who received oxybuprocaine hydrochloride gel as urethral lubricant, while patients in the control group received liquid paraffin. The preoperative and postoperative pain scores were compared using nonparametric tests. p=0.694). Postoperative pain scores increased significantly in the test  and control groups  groups. Postoperative pain scores were significantly lower in the test group (mean ± SD = 31.98 ± 2.57 mm) than those in the control group (mean ± SD = 38.96 ± 2.02 mm (p < 0.001).  At the baseline, there was no significant difference between the two groups. There was no significant difference in preoperative pain scores between the test group (mean ± SD = 20.04 ± 2.68 mm) and the control group (mean ± SD = 20.21 ± 3.23 mm) ( The use of oxybuprocaine hydrochloride gel significantly reduced pain during male urethral catheterization. The study provides evidence for clinicians to use oxybuprocaine hydrochloride gel during male catheterization. Catheterization allows urine to drain from the bladder. Catheterization involves inserting a catheter made of latex, polyurethane, or silicone into the bladder via the urethra to drain urine . CatheteThe male urethra is a fibromuscular tube that drains urine from the bladder. It has a longer, more complicated curse than the female urethra, making it more susceptible to injury during catheterization. Urethral stricture, urinary incontinence, erectile dysfunction, and infertility have been reported as iatrogenic urethral catheterization injuries . DespiteOxybuprocaine hydrochloride is a highly permeable and rapidly absorbed anesthetic. It binds to sodium channels and reversibly stabilizes the neuronal membrane that decreases its permeability to sodium ions. When administered as gel, oxybuprocaine hydrochloride provides adequate anesthesia for diagnostic purposes and small operations. It is suitable for catheter insertion providing analgesia. Prior studies focused on the application of anesthetic gels during cystoscopy procedures , 10. OnlThis is a randomized controlled study conducted at the Urology Department of Harbin Medical University Cancer Hospital (China) between September 2021 and March 2022. The study protocol was approved by the local ethics committee. The trial was strictly designed in accordance with the CONSORT statement . PatientWe enrolled male patients over the age of 50 who required indwelling or intermittent catheterization. We collected information about patients' history of hypertension, diabetes, indwelling or intermittent catheterization, and urinary tract infection. The exclusion criteria were as follows: altered mental state, impaired vision, inability to report visual analogue scale (VAS) scores, refusal to use treatments, or suspected allergy to oxybuprocaine hydrochloride gel. A study nurse was responsible for enrolling patients after explaining the study's objectives to them. Patients who agreed to participate were randomly assigned to receive either oxybuprocaine hydrochloride gel or liquid paraffin by selecting an envelope from a box containing either the study gel or liquid paraffin. The practice nurse opened the envelope and dispensed 10 ml of the study gel or liquid paraffin onto a sterile catheter tray. Before catheterization, the study nurse scored the patients using the VAS scale (0–100 mm). The study nurse injected 5 ml of either oxybuprocaine hydrochloride gel or liquid paraffin into the urethra and applied the remaining 5 ml onto the catheter surface. Approximately 5 minutes after catheterization, subjects were scored again using the VAS scale. VAS scores of 33 mm or less were categorized as mild pain, VAS scores between 34 and 67 mm were categorized as moderate pain, and VAS scores between 68 and 100 mm were categorized as severe pain. All the procedures were performed by a single study nurse.t test and one-way ANOVA. Homogeneity of variance was tested by Levene's test. The paired sample t test was used for intragroup comparison. Categorical data were compared by Fisher's exact probability method. The level of significance was 0.05 .SPSS Statistics 20.0 was used for statistical analysis. Data were compared between groups by the independent sample p=0.869). Regarding baseline characteristics, there were no significant differences between the two groups  of patients in the oxybuprocaine hydrochloride gel group was 61.57 ± 4.95 years, while the mean age (± standard deviation) of patients in the control group was 61.45 ± 5.51 years (o groups .p=0.694). Postoperative pain scores increased significantly in the test  and control  groups. Postoperative pain scores in the test group were significantly lower than those in the control group (p < 0.001) (The preoperative pain scores were not significantly different between the test (mean ± SD = 20.04 ± 2.68 mm) and control (mean ± SD = 20.21 ± 3.23 mm) groups (< 0.001) . The adm< 0.001) .p > 0.05) (p > 0.05) (There was no significance difference in catheter size distribution between the two groups ( > 0.05) . No stat > 0.05) .All 96 patients of the test group were included in the safety analysis. During the study, the most common reported adverse events were itching (8.3%), erythema (7.3%), dermatitis (6.3%), and elevated blood pressure (4.2%). The adverse events disappeared in a few minutes, and no other interventions were used. No serious adverse events were observed .Catheterization is widely used in hospitals, particularly, during surgical procedures when the majority of patients are awake and require preoperative indwelling catheterization . HoweverRegional anesthetic gels are rarely used in conventional catheterization procedures . LidocaiThe catheter type and catheter size may aggravate the pain sensation during catheterization , 20. LarDespite the study being a randomized controlled trial, we faced a number of limitations that might influence the findings. The VAS scores could not accurately reflect patients' perception of pain during the catheterization process. The majority of participants experienced pain in specific areas of the urethra; thus, mapping pain to specific areas of the urethra may increase the validity of our study. In addition, we did not check whether patients have experienced pain during previous catheterizations. They might be more tense and nervous during our investigation, affecting the individual pain scores.Conventional procedures do not include regional anesthesia prior to catheterization. In this study, the application of oxybuprocaine hydrochloride gel was safe and effective in alleviating pain during male urethral catheterization.


Sickle Cell Disease (SCD) is a disease that affects many around the world and often accounts for frequent hospital admissions every year, secondary to uncontrolled pain. Marijuana is increasingly being used for its medicinal ability to treat pain in chronic medical conditions. Therefore, it is imperative to determine how effective it would be in providing pain relief to patients with SCD. We systematically screened five databases for relevant data: PubMed, Medline, PubMed Central (PMC), Cochrane Library, and Google Scholar. The inclusion and exclusion criteria were implemented. A quality appraisal was then done using the Cochrane Bias assessment for randomized controlled trials (RCTs), Newcastle-Ottawa tool for observational studies, and Scale for the Assessment of Narrative Review Articles (SANRA) checklist for traditional review articles. From seven articles, information was gathered; one systematic review, one RCT, two surveys, one cross-sectional study, one retrospective study, and one questionnaire-based study. Our review concluded that based on the literature assessed, marijuana use in SCD patients either worsened their painful crises or offered little to no help compared to opioids or hydroxyurea usage. There were limited RCTs published in addition to papers investigating the long-term effects of marijuana use in SCD. We hope that further data is gathered in these areas to sufficiently address whether cannabis use is efficacious for pain relief in patients with SCD. South America, Central America, Sub-Saharan Africa, the Caribbean, Saudi Arabia, Turkey, Italy, Greece, and India all share a common issue. While sickle cell disease (SCD) affects millions worldwide, if your ancestors came from one of these regions, the chances are that there is an increased probability of being affected by this disorder according to the Centers for Disease Control and Prevention .SCD results in more than 113,000 hospital admissions a year, most for uncontrolled pain, and currently affects more than 100,000 adults in the United States . SCD repSCD considerably reduces life expectancy by approximately 30 years . NumerouDespite the increasing popularity of the use of marijuana and its derivatives, not much has been studied on a large scale concerning its effect on the sickle cell population. In this systematic review, the goal is to ascertain whether marijuana use can help with managing pain in patients with SCD and can be considered as a viable adjunct in hopes of alleviating reliance on opioids and, by extension, reducing hospital admissions.Methods The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines were employed for conducting this systematic review .Search Sources and StrategyPubMed, Medline, PubMed Central (PMC), Cochrane Library, and Google Scholar were searched for literature published between 2011-2021.The databases were explored using three search keywords and then combining these results with the Boolean "AND." For the keyword "Marijuana," we used concept identification words: marijuana, weed, ganja, and cannabis. These concept words were joined using the Boolean "OR," and a medical subject heading (MeSH) search strategy was formulated. For the keyword, "Pain," only pain was utilized. For the keyword "Sickle Cell Disease," concept identification words used were sickle cell disease and sickle cell anemia; the Boolean "OR" was again used to combine these two concept identification words. Finally, all MeSH search strategies were compiled using the Boolean "AND," which was then entered into PubMed. The following is the MeSH strategy employed: Marijuana OR Weed OR Ganja OR Cannabis ("Marijuana Use/adverse effects" (Majr) OR "Marijuana Use/drug therapy"(Majr) OR "Marijuana Use/pharmacology" (Majr) OR "Marijuana Use/therapeutic use" (Majr) OR "Marijuana Use/therapy" (Majr) ) AND Pain  OR "Pain/drug effects" (Majr) OR "Pain/drug therapy" (Majr) OR "Pain/rehabilitation" (Majr) OR "Pain/therapy" (Majr)) AND Sickle cell disease OR sickle cell anemia  OR "Anemia, Sickle Cell/rehabilitation" (Majr) OR "Anemia, Sickle Cell/therapy" (Majr))Eligibility CriteriaDuplicates were screened and removed. Then the remaining papers were screened based on title and abstracts. The full text of the results was then evaluated based on the quality analysis of the paper. Only relevant papers that satisfied >60% of assessment criteria in the quality appraisal were included. Of the articles that were selected, only those published in English during the years 2011-2021 were included. They also had to focus on human subjects, specifically the adult population of >18 years. Papers that focused on animal studies and/or included the pediatric population were excluded. The pediatric population was excluded due to the lack of data on documented use of marijuana in the younger sickle cell population.Risk Bias Assessment:The quality of studies included was assessed using the following tools displayed and only articles satisfying >60% of the appraisal parameters were included as seen in Table ResultsSearch OutcomeA total of 10,633 papers were identified using the MeSH and keywords through five databases and produced 9,520 results after 1,113 duplicates were removed. Results were preliminarily screened based on the eligibility criteria (inclusion and exclusion) and then on the title and abstract, which produced a total number of 11 articles. After a quality appraisal check, only seven articles were employed. The seven articles included one systematic review, one randomized control trial (RCT), and five observational studies. These articles included the effects of marijuana on patients with sickle cell anemia in terms of pain management and other effects related to cannabis use. The frequency of hospitalizations secondary to painful crises was noted. The PRISMA flow diagram displays the article filtering process as seen in Figure Actual ResultsOur systematic review gathered information from the limited data available on patients with SCD on pain management. This included surveys, retrospective analysis, patient self-reports, and urine screening detection. While all selected articles shared the common objective to study the relationship between marijuana and pain in SCD patients, the number of participants, demographics, and criteria for the studies all differed. The relevant information from each of the seven published papers is summarized in Table DiscussionThe Effects of Cannabis on Pain Management in SCD PatientsA cross-sectional survey by Curtis et al. examined SCD adults using cannabis daily contrasted against those who used other therapeutics. Both parties were assessed based on parameters such as quality of life, health care usage, and patient self-reported outcomes . The desAbrams et al. conducted an RCT with 23 participants to determine the effectiveness of inhaled cannabis compared to an inhaled placebo for chronic pain relief in adults with SCD. Similar to the survey conducted by Curtis et al., a pain rating assessment was used to record this data ,17. WhilMiodownik et al. surveyed 78 patients from 2017 to 2018 to determine the reasons that may contribute to SCD patients using marijuana, the prevalence of this occurring in urban populations in the United States, as well as the clinical characteristics that may lead to this. The survey was conducted at outpatient centers focused on caring for adult patients with SCD . The datRoberts et al. sought data on reasons why SCD patients would use marijuana in the United States even though this usage may not have been legal in the state in which they resided. A survey study was carried out in an urban medical center, which catered specifically to SCD adults . A self-In 2017, Ballas was determined to discover whether SCD patients using marijuana had less acute VOCs that required hospitalization. A retrospective study involving 72 adult African American patients from a sickle cell center from 1994 through 2009 was employed . The goaKalu et al. formulated a self-administered anonymous questionnaire that was distributed amongst 103 SCD patients. The purpose of this study was to determine how often marijuana was used amongst SCD patients, with a focus on those who did and did not utilize hydroxyurea as part of their treatment plan . In contThe Effects of Cannabis on Mood in SCD PatientsWhile marijuana use was being observed for its effects on pain relief, some of the literature published noted additional adverse effects on the participants. In the RCT conducted by Abrams et al., there was no difference in pain rating between the placebo and marijuana participants . HoweverLimitationsThis systematic review, which consisted of seven published pieces of literature, has limitations. One such limitation was that only one RCT was sourced from our five databases. This could have been partly due to our eligibility criteria, which focused on literature published in English within the past 10 years with a focus on adults greater than 18 years of age. As a result, several papers may have been excluded simply because they did not meet the inclusion/exclusion criteria. There were also differences in the number of subjects between papers such as Kalu et al., which had a sample size of 103 participants, compared to Roberts et al., which had only 57 patients. The individual limitation of each study regarding study length, sample size, and drug effects made it difficult to facilitate adequate comparisons.We aimed to determine whether marijuana can be used to relieve pain in SCD patients and, therefore, by extension, can be successfully employed as an adjunct in the future to reduce the frequent and often dependent use of opioids. However, based on the results of the literature gathered, there seems to be a split decision. Not many clinical trials were found to substantially address whether cannabis use significantly impacted improving pain relief in SCD patients. While the information gathered from the different surveys and studies did provide some insight, they contradicted each other in terms of findings. Therefore, at this point, a definitive conclusion cannot be made. Ideally, new research is necessary to further address this topic with a focus on the long-term effects of cannabis use and objectively assessing pain relief utilizing records on hospital/ED visits for more than two years.


Metastatic spread of prostate cancer to the skeleton may result in debilitating bone pain. In this review, we address mechanisms underpinning the pathobiology of metastatic prostate cancer induced bone pain (PCIBP) that include sensitization and sprouting of primary afferent sensory nerve fibres in bone. We also review current treatments and pain responses evoked by various treatment modalities in clinical trials in this patient population.We reviewed the literature using PubMed to identify research on the pathobiology of PCIBP. Additionally, we reviewed clinical trials of various treatment modalities in patients with PCIBP with pain response outcomes published in the past 7 years.Recent clinical trials show that radionuclides, given either alone or in combination with chemotherapy, evoked favourable pain responses in many patients and a single fraction of local external beam radiation therapy was as effective as multiple fractions. However, treatment with chemotherapy, small molecule inhibitors and/or immunotherapy agents, produced variable pain responses but pain response was the primary endpoint in only one of these trials. Additionally, there were no published trials of potentially novel analgesic agents in patients with PCIBP.There is a knowledge gap for clinical trials of chemotherapy, small molecule inhibitors and/or immunotherapy in patients with PCIBP where pain response is the primary endpoint. Also, there are no novel analgesic agents on the horizon for the relief of PCIBP and this is an area of large unmet medical need that warrants concerted research attention. For patients with prostate cancer, bone is the most common organ of metastasis with a prevalence of ~ 90% for men with metastatic castrate-resistant disease , 80, 99 3, on the surface of metastatic prostate tumour cells promotes their adherence to endothelial cells in the bone marrow . Th. Thc.f. In a systematic review of 26 randomized trials in patients with painful uncomplicated bone metastases due to mCRPC Table , the anaA pilot trial  in men with mCRPC who were receiving androgen deprivation therapy (ADT), showed that aerobic and resistance exercise interventions prescribed by an exercise physiologist and remotely monitored, were well tolerated over a 12 week period  or docetaxel at 75 mg/m2 (D75), plus prednisone once-daily, for a median of 9 treatment cycles [c.f. the androgen-signalling-targeted inhibitor group (19%) , asymptomatic/minimally symptomatic, chemotherapy-naïve patients with mCRPC without visceral metastases, and whose disease had progressed during hormonal treatment, and ADT had been discontinued, were recruited and randomized to receive ipilimumab or placebo every 3 weeks for up to 4 doses (Table t cycles . Overallt cycles . In othet cycles . EncouraIn summary, from the foregoing, administration of a radionuclide either alone or in combination with chemotherapy, to patients with mCRPC improved pain responses in many patients Table . AdditioIn men with mCRPC, the prevalence of bone metastases is 90% and median survival time is 12–53 months. Bone metastases may result in SREs and debilitating bone pain that greatly impair the QoL of patients. Current treatments for alleviating PCIBP include radiotherapy, bone-targeting therapy, and analgesic/adjuvant agents that are mainly palliative in nature, aimed at improving pain relief and patient QoL. Recent clinical trials show that radionuclides, given either alone or in combination with chemotherapy, improved pain responses in many patients and a systematic review showed unequivocally that a single fraction of local EBRT was as effective as multiple fractions. However, treatment with chemotherapy, small molecule inhibitors and/or immunotherapy agents, did not improve pain responses in the majority of trials (Table


Dialysis-related myofascial pain in hemodialysis (HD) patients is an important issue that is associated with many other psychosomatic problems. Effective interventions are required to alleviate pain in this group. Chinese herbal medicine (CHM) may be a potential therapeutic treatment for reducing pain. The aim of this study is to evaluate the effects of a classic CHM formula intervention on pain intensity, daily function, quality of life (QOL), and safety in patients receiving HD in a dialysis center within the context of southern Taiwan.This will be a randomized, open label, cross-over trial with two parallel groups in a pre- and post-test study. Forty patients reporting myofascial pain related to the arteriovenous (AV) fistula in the arm during regular HD sessions will be recruited. Participants will receive 4 weeks of treatment with Juan Bi Tang (JBT) and 4 weeks of no treatment in a random order, separated by a washout period of 2 weeks. Treatment doses (3 g JBT) will be consumed thrice daily. The primary outcome measure will be the Kidney Disease Quality of Life 36-Item Short-Form Survey. Secondary outcomes will include the Fugl-Meyer Assessment-arm, Visual Analogue Scale (VAS) of pain, and grip strength. Outcomes will be collected before and after each intervention, for a total of four times per participant. The safety evaluation will focus on adverse events (AEs).This study will be the first to use CHM to treat patients receiving HD with dialysis-related myofascial pain in their fistula arm and to perform a complete assessment of the treatment, including records of QOL, arm function and muscle power, severity of pain, and safety. The results of the study will provide convincing evidence on the use of JBT as an adjuvant treatment for dialysis-related myofascial pain.Clinicaltrials.gov registry (NCT04417101) registered 30 May 2020. Myofascial pain syndrome (MPS) is characterized by localized pain , paresthMyofascial pain syndrome is often more serious in females than in males, and its prevalence apparently increases with age . CurrentOne major complication of chronic kidney disease (CKD) or end stage kidney disease (ESRD) is rheumatic disorders, and over half (60%) of patients receiving hemodialysis (HD) develop musculoskeletal disorders . TherefoFactors such as comorbidities, dialysis type, metabolic disorders, nutritional factors, biomechanical imbalance, and/or physio-psychological deconditioning may simultaneously contribute to the development of dialysis-related myofascial pain , 13. HowThere is no definitive treatment for dialysis-related myofascial pain, and the most common treatment modality is based on condition-specific and stepwise pain management for ESRD , 19. AspPrescriptions for Ji Sheng Fang (CE 1253). As joint pain is one of the most common symptoms of Bi syndrome, some scholars often translate it as “Arthralgia syndrome.” Clinically, Bi syndrome covers many musculoskeletal diseases, such as rheumatoid arthritis, osteoarthritis, rheumatism, fibromyalgia, or myofascial syndrome  and blood in the meridians due to the invasion of pathogenic wind, cold, and dampness. According to traditional Chinese medicine (TCM), open meridians and normal circulation of the qi and blood are associated with an absence of pain, while obstruction of the meridians and the flow of qi and blood are associated with the presence of pain. Juan Bi Tang is used for treating pain in the upper limbs by warming up meridians so as to dissipate cold, eliminate dampness, activate the qi and blood, and also resolve stasis  therapy for pain management. CHM therapy is safe and inexpensive, and it can alleviate the pain and anxiety associated with several diseases , 24. Morsyndrome . The base stasis . AlthougClinicalTrials.gov (NCT04417101). The Standard Protocol Items: Recommendation for Interventional Trials (SPIRIT) 2013 checklist is provided in This single-center, two-phase study will last 12 weeks. It will be a randomized, prospective, crossover, open-label study comprising two groups and two treatment sequences, each consisting of 4 weeks of daily treatments separated by a 2-week washout period . In totaParticipants will be recruited from Kaohsiung CGMH via posters and advertisements on the official hospital website. The recruitment period is planned to last 18 months. All participants will provide informed consent before randomization. The schedule of patient enrollment, intervention, and assessment is illustrated in Participants meeting the following criteria are eligible:Age of 20 years or older;Treatment with conventional HD three times a week via an arteriovenous (AV) fistula for at least 3 months;Myofascial trigger points in one or more muscles around the AV fistula, namely, the brachioradialis, the flexor carpi radialis, the palmaris longus, and/or the pronator teres , accompaOnset of symptoms within 1 month before enrollment;Exquisite tenderness on palpation in the taut band, with moderate intensity of pain at baseline ;No change of painkillers, muscle relaxants, or anti-inflammatory medications and no use of topical anesthetics in the past week.The exclusion criteria are as follows:Severe systemic disease  interfering with therapy attendance;Comorbid conditions such as rheumatoid arthritis, stroke, chronic liver disease, radiculopathies of the upper limb, recent history of cervical/shoulder/arm surgery, or trauma;Depression and/or presence of a psychiatric disorder;Treatment with CHM for dialysis-related myofascial pain in the past month;Allergic reactions  to CHM;Inability to comprehend or sign an informed consent form.Study participation will be terminated under the following conditions:Occurrence of severe complications and/or general health deterioration  level);Occurrence of a severe adverse event (AE) of any type during the intervention;Voluntary withdrawal from the trial, absence from two consecutive interviews, or loss to follow-up.Rx. Angelica Sinensis當歸, 4 g Rx. Paeoniae Rubra赤芍, 4 g Rx. Astragali黃耆, 4 g Rz. Curcuma Longae薑黃, 1 g Rx. et Rz. Notopterygii羌活, 4 g Rx. Saposhnikoviae防風, 3 g Rz. Zingiberis Recens生薑, 2 g Fr. Zizyphi Jujube大棗, and 1.5 g Rx. Glycyrrhizae Preparata炙甘草. These raw herb materials, together with starch excipient, are extracted and concentrated according to a standardized Chinese formula (see: http://www.koda.com.tw/tqm04_e.aspx). The participants will be instructed to take JBT orally in doses of 3 g (per bag) each time, thrice daily, for 4 weeks. Patients will return each week to the outpatient clinic for evaluation, medication, and counting of any unconsumed bags. Weekly compliance below 75% will be considered a deviation from the protocol and will lead to exclusion from further participation in the study. Participants in the non-treatment period will receive simple self-care measures for MPS based on the non-pharmacologic intervention in patients with CKD by Pham et al.  manufactured in accordance with Good Manufacturing Practices (GMP) and tested before factory release. Juan Bi Tang consists of 4 g m et al. . These wm et al. . The durRoutine medication for maintenance HD will be continued. The medication regimen will be recorded at every visit, and participants will need to inform the study assistant of any changes to their medication, supplements, and even exercise. Additional acupuncture, herbal prescriptions, or other interventions by other TCM practitioners will not be permitted during the treatment period.n = 20) or group B (n = 20) according to a randomized list generated in Microsoft Excel 2016. Participants will be coded with identification numbers to guarantee confidentiality during data analysis. The physicians will have no access to the sequence, and the investigators will distribute the drugs. All members of the research team will be explicitly instructed not to inform the participants of their allocations. The clinical outcomes assessor will be blinded to the allocations to decrease the risk of observer bias. Participants' files will be kept in a box in a locked cabinet only accessible by an assistant until the end of the study.The participants will be allocated into group A , at 6 weeks (at the beginning of period II), at 10 weeks (at the end of period II), and at follow-up . A research assistant will be trained to ensure the accuracy of outcome assessments and data collection.http://www.rand.org/health/surveys_tools/kdqol.html). The instrument is composed of 12 general health items and 24 kidney-specific items. The items on general health are summarized into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. The 24 kidney-specific items comprise three scales: symptoms and problems, burden of kidney disease, and effects of kidney disease . The raw scores are transformed into a linear range of 0–100, where higher scores indicate better QOL , a self-report measure developed for health-related concerns of individuals who visit dialysis facilities for treatment . The KDQtter QOL .Secondary outcome measures will include arm motor function evaluated with the Fugl-Meyer Assessment for upper extremity (FMA-UE); muscle power threshold, measured with a grip algometer; and self-reported degree of pain [Visual Analogue Scale (VAS) score].Upper limb function will be assessed with the FMA-UE, a stroke-specific test for measuring motor impairment and recovery . The FMAHandgrip strength will be measured with a digital handgrip dynamometer . Two consecutive measurements of the fistula-side hand will be performed at an interval of 30 s, and the maximal isometric reading will be used for data analysis . Hand stPain perception will be recorded immediately after cannulation on a VAS, a non-graduated horizontal line of 100 mm where 0 = no pain at all and 100 = as painful as possible. The VAS and grip strength measures will be assessed immediately before the first treatment; at 4, 6, and 10 weeks after the first treatment; and at follow-up.Juan Bi Tang is described in the ancient literature of TCM as relatively safe, and previous clinical studies have reported no major toxicity in therapeutic doses –39. Howe*Power version 3.1.9.2 for the differences in the outcome measure between both groups was conducted to determine the investigated sample size to achieve adequate power . For repeated measures ANOVA analysis, to achieve 80% power and a 25% effect size . A p-value <0.05 will be considered statistically significant.Both intention-to-treat (ITT) and per-protocol (PP) analyses will be applied in the present trial. Continuous data will be presented as mean ± SD, and categorical data will be presented as frequencies and proportions. The Student's qi and blood. In a previous study, compared to Western medicine, JBT was found to be safe and particularly beneficial to arthritis patients with the cold and deficiency pattern  The study of different safe and lower cost can be considered for scientific use of techniques related to TCM in dialytic patients. Nevertheless, a few study limitations should be noted. First, this study will be an open-label study because of the difficulty of preparing a suitable placebo; the pharmaceutical technology of CHM powder does not yet allow such a process because of the distinctive colors, tastes and smells of the preparations (Rx. et Rz. Notopterygii (T1/2 = 190–768 min); however, its washout period is only 64 h (The strengths of this study include: (1) This study is the first pilot randomized cross-over trial to evaluate the feasibility of JBT for the treatment of dialysis-related myofascial pain. (2) The design of the trial is based on TCM syndromes because dialysis-relayed myofascial pain can be inferred to inadequate arations . Moreovenly 64 h . To mininly 64 h . In the The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Institutional Review Board at Chang Gung Memorial Hospital . The patients/participants provided their written informed consent to participate in this study.M-YT and Y-YL devised the study question and design. M-YT developed the idea into the full protocol and wrote the article draft. Y-HC and H-YN reviewed the protocol. Y-CH calculated the sample size and specified the statistical strategy. M-YT and Y-TH will be in charge of enrolling participants and conducting all the procedures. All authors have read and approved the final manuscript.This study was funded by Chang Gung Memorial Hospital with grant number CORPG-8K0091. The funders have had no role in study design and will not have any role in the trial design, manuscript writing, or decision making for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.