Finally, correlation analysis in the group of stroke survivors with pain showed that higher levels of disability were significantly related to higher psychological distress. This study confirms the negative influence of chronic pain on disability and HrQoL in post-stroke patients and presents preliminary insights on the association between chronic pain, disability, HrQoL, psychosocial distress, and the patient’s approach in dealing with personal difficulties and emotions. These findings carry further implications for multidisciplinary management of post-stroke patients with chronic pain.This study aims at exploring disability, health-related quality of life (HrQoL), psychological distress, and psychological features in post-stroke patients with chronic pain. An observational cross-sectional study involving 50 post-stroke patients (25 with chronic pain and 25 without pain) was conducted. The primary outcome was the self-reported level of disability and HrQoL which were both assessed through the Stroke Impact Scale 3.0. Both psychological distress and specific psychological features  were examined. Post-stroke patients with chronic pain reported statistically significant higher levels of disability and worse HrQoL, higher psychological distress and inflexibility, as well as a lower level of self-efficacy and problem-oriented coping strategies than patients without pain ( Pain is a common and highly disabling complaint in stroke survivors , more frAccording to the International Association for the Study of Pain (IASP), pain has been defined as “[a]n unpleasant sensory and emotional experience associated with or resembling that associated with, actual or potential tissue damage” . In linePatients who experience pain after stroke seem to be more inclined to lower levels of health-related quality of life (HrQoL) , worse cPost-stroke HrQoL depends on a comprehensive view of subjective health, including measures of the perceived physical, mental, and social well-being and functioning. Demographic factors, comorbidities, stroke severity, disability, and psychosocial factors  are significant predictors of HRQoL in stroke survivors . The psyIn line with the statements above, this study aims (I) at determining the difference in self-reported disability and HrQoL scores, psychological distress, and psychological features between a cohort of post-stroke patients with chronic pain and a cohort of post-stroke patients without pain, and (II) at determining the association between disability and HrQoL, pain  and psychological distress and features in the two cohorts of post-stroke patients: with and without pain. Hence, this study will provide preliminary insights on a poorly understood field such as chronic pain experience in post-stroke patients to support the need for a multidisciplinary assessment and management of these patients in the neurorehabilitation setting.This cross-sectional study is part of the “EXPLORE”  project, which arose from the collaboration between the Neurorehabilitation Unit and the Clinical Psychology Unit of the Verona University Hospital . The EXPLORE project aims at investigating the psychological distress, the psychological features, and HrQoL of patients presenting different chronic pain conditions ,28.This study was performed according to the latest version of the Declaration of Helsinki and approved by the Ethics Committee of the Verona University Hospital, Verona . The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations for reporting observational studies were followed .This study included patients with chronic pain compared with a group of post-stroke patients without pain. Post-stroke outpatients were recruited according to the following selection criteria.Inclusion criteria were age ≥18 and ≤85 years; diagnosis of stroke confirmed by a specialist in neurology and by radiologic findings (TC or RM); time from stroke ≥ three months; signature of the informed consent. Exclusion criteria were the presence of severe cognitive or communication deficits interfering with patients’ capacity to provide the informed consent or proper answers to the questionnaires. Patients with language difficulties were known to the Neurorehabilitation Unit, since they had already undergone previous speech and language rehabilitation in which their language abilities were acknowledged. After discussion with the speech and language therapists, the patients’ eligibility was further verified. In case of any unexpected communication difficulties occurring during the face-to-face assessment, the patient was excluded from the study. Patients with other neurological, orthopaedics, or medical comorbidities that could cause pain  and substance abusers were excluded. The patients were considered in the sub-group of stroke survivors with chronic pain if they (a) presented pain for at least three months, (b) rated their pain intensity as at least four on a 11-point Numeric Rating Scale (NRS) . A score of 4 on the intensity scale identifies moderate pain, which is considered to interfere with daily living activities significantly . PatientMedical charts of patient attending the Neurorehabilitation Unit between December 2018 and August 2019 were retrospectively reviewed. A physician performed an initial telephone screening interview lasting approximately 10 min that consisted of ad hoc questions to assess the presence of inclusion and exclusion criteria. During the telephone interview, patients were informed about the EXPLORE project. Moreover, the presence of pain and duration of pain in the previous three months were ascertained. Patients who fulfilled selection criteria and accepted to participate in the study were referred to a face-to-face visit at the Neurorehabilitation Unit. During this visit, they filled out a battery of paper–pencil questionnaires that investigated their sociodemographic and clinical characteristics, level of HrQoL, level of disability, pain, and psychological features.All patients gave their written informed consent to participate in the study.For each patient, sex, age, educational level, civil status, and work condition were collected to describe the sample’s sociodemographic characteristics. An ad hoc clinical record was created aimed at acquiring diagnosis information, stroke onset, interest in starting a psychological intervention, as well as the duration of the multidisciplinary rehabilitative care. Moreover, a multimodal assessment was conducted aimed at analysing their HrQoL, pain perception, psychological distress, and psychological features. The assessments lasted approximately one hour. The patients were helped in the event of difficulties by the researcher. The time since stroke (in months) was collected for all patients, whereas the duration of pain (in months) was collected only in the group with pain.The self-reported level of disability and HrQoL were evaluated through the Stroke Impact Scale (SIS) 3.0 ,32. The The multidimensional level of pain was evaluated through the Brief Pain Inventory (BPI) scale . BPI proThe psychological assessment was performed in line with the EXPLORE protocol ,28. PsycThe level of self-efficacy was evaluated through the General Self-Efficacy (GSE) scale, which is a 10-item scale rating “people’s optimistic self-beliefs to cope with a variety of difficult demands in life” on a four-point Likert-type scale (higher scores = higher levels of perceived self-efficacy) . Coping Potential sources of bias were addressed. Firstly, during the medical chart revision, the presence of post-stroke pain was not always reported. Hence, patients attending the Neurorehabilitation Unit in the reference period were contacted by phone for further investigations. Secondly, to avoid any specific influences in reporting data of the patients who decided to participate in the study, the telephone interviews were performed by two physicians who had never been in contact with them before. Moreover, an ad hoc telephone questionnaire was set up to be consistent among patients on the information collection. We cannot exclude a selection and questionnaire administration bias. The patients who were recruited and accepted to participate in the study should be not representative of all stroke survivors’ patients since, for example, they reported a level of cognitive functioning adequate to fill out questionnaires. Moreover, we cannot exclude that they were already more willing toward a possible psychological intervention and to undertake the psychological assessment. The fixed order of providing the questionnaire might be acknowledged as a possible administration bias. All the questionnaires used were validated instruments for the Italian context and already used in the context of neurological diseases ,28,42,43t-test for independent samples (or the Mann–Whitney test) was used to test statistical differences in demographic and clinical outcomes between the two groups. The Fisher test was used to check differences in sex between the two groups. A Pearson’s correlation (or Spearman’s correlation) was run to determine the relationship between the severity of disability and HRQoL assessed by the SIS, the BPI, and psychological features. The correlation strength was defined as very high (ρ > 0.9), high (ρ = 0.7–0.89), moderate (ρ = 0.5–0.69), low (ρ = 0.3–0.49), or very low (ρ < 0.29) [p-value for significance was set at 0.05. Bonferroni correction was applied for multiple correlation analyses on the same dependent variable. When exploring the association between the SIS  and pain, the alpha level for significance was set at 0.00625. When exploring the association between the SIS  and psychological outcomes, the alpha level was set at 0.004545. Statistics analyses were carried out through SPSS 26.0 .Descriptive statistics included frequency tables, means, and standard deviation (SD). Parametric or non-parametric tests were used for inferential statistics according to the data distribution (Shapiro–Wilk test). Outliers, defined as values laying two standard deviations above the mean values of the group, were excluded. The  < 0.29) . The p-vA total of 247 in-hospital clinical records were reviewed. Fifty-four patients were excluded because they did not meet the inclusion criteria. In the remaining 193 medical charts, 77 patients reported the presence of pain, of which 36 reported a pain intensity ≥4 (NRS) for at least three months. Among this group, 11 patients refused to participate in the study, so 25 patients with chronic post-stroke pain were included. In line with that, patients without chronic post-stroke pain were randomly contacted until reaching a sample of 25 patients per group. The randomisation process was done by assigning to the 116 medical charts of patients without pain a serial number from 1 to 116, from which 25 patients were extracted randomly through the ‘Random’ Excel function.The final sample was composed by 50 post-stroke outpatients , of those 25 with chronic pain  and 25 without pain . Demographic and clinical characteristics are reported in All patients were assisted by family members and were living in their home. No patients were institutionalised or living in a nursing home. In this cohort, 32% were female, and 20% were employees. Most patients were married (76%) with high-school qualification (34%). As far as the site of lesion was concerned, 48% were left lesion, 48% were right lesion, and 2% were bilateral. Most patients suffered from Partial Anterior Circulation Syndrome (61%) due to ischemic lesion (75%). Aphasia and neglect were present in 24% and 14% of patients, respectively. Patients had been on a rehabilitation program for neurorehabilitation on average for 26.43 months. More than half of the sample (66%) was interested in receiving psychological support.p = 0.002) as well as a higher percentage of ischemic stroke (p = 0.023) and aphasia (p = 0.04) than patients without pain. No significant between-group differences were found regarding the employment condition, civil status, brain lesion side and site, duration of the rehabilitation program, and interest in receiving psychological support.Patients with chronic pain did not differ for age and sex from patients without pain. Despite this, they had a significantly lower education level  and a mean duration of 21.48 (SD: 29.71) months. The most frequent type of pain was musculoskeletal pain, affecting six patients (24%), followed by shoulder pain, central post-stroke pain, and headache syndromes in five patients (20%), spasticity-related pain in three patients (12%), and complex regional pain syndrome in one (4%) patient. The mean time with pain was 21.48 (SD: 29.7) months. Pain occurred on average 15.04 (SD: 23.89) months after stroke onset. The results of BPI are reported in The SIS scores gathered from the overall sample as well as in the two cohorts of analysed patients are reported in p < 0.001), memory and thinking (p < 0.001), emotion (p = 0.024), communication (p < 0.01), ADL/IADL (p = 0.008), hand function (p = 0.016), and participation/role function (p < 0.001) compared to patient without pain (Patients with chronic pain reported significantly lower score (higher disability) in the SIS total score (out pain .p = 0.001) compared to patients without pain, indicating a higher level of psychological distress. In particular, 10 (40%) stroke survivors with chronic pain and three (12%) without pain obtained a GSI score > 0.57, which is considered a cut-off for the presence of psychological distress [p = 0.015), lower COPE-Problem Oriented (p < 0.001), and higher AAQ-II (p = 0.005) scores than the patient without pain.Psychological distress and psychological features scores are reported in distress ,45,46. Tp < 0.001; r = 0.46, p = 0.019). Moreover, a low negative correlation between length of care and the strength domain  was reported. Correlations between SIS and BPI are reported in p = 0.001) and the single domain scores concerning participation/role function  and memory and thinking . Negative correlation was found between the SIS total score and the BPI for interference with mood .In patients with chronic pain, the pain intensity assessed by the BPI and pain duration were moderate and strongly correlated with the length of care respectively . Specifically, the SIS sub-scores referring to emotions  and participation  showed a negative correlation with the GSI. Regarding coping strategies, the SIS sub-scores referring to memory and thinking were significantly correlated with the COPE-PO . In the framework of psychological inflexibility, in the group with pain, there was a significant negative correlation between the SIS sub-scores in the emotion domains , and participation  and the AAQ-II.In this explorative study, we found evidence to support the negative influence of chronic pain on the self-reported levels of disability and HrQoL in post-stroke patients with and without pain. Our findings provide preliminary evidence to support an association between psychosocial features, the level of disability, the level of HrQoL, and chronic pain in post-stroke patients.By analysing the differences between the cohort with pain and the cohort without pain, the former reported higher levels of disability in the SIS total score and in the different domains. The differences in ADL/IADL, mobility, and hand function reached the MCID , indicating that disability severity in patients with chronic pain was significantly higher, also from a clinical point of view . A higheThe fact that patients with chronic pain did not differ from patients without pain in muscle strength and mobility performance suggests that the self-reported perception of general motor aspects were apparently not affected by chronic pain. In contrast, a self-reported higher disability was reported on hand function in chronic pain patients, confirming that upper limb pain syndromes mostly affect post-stroke patients with a negative impact on disability . HoweverAs regards psychological distress, a previous study by Zhang et al. showed that the mean level obtained at the SCL-90 was higher in post-stroke patients compared to the control group . In our Considering the other psychological features, chronic pain in post-stroke patients was associated with lower levels of self-efficacy, psychological flexibility, and problem-oriented coping strategies, therefore suggesting a more dysfunctional approach in dealing with personal difficulties, stress, and emotions. Self-efficacy beliefs for people experiencing chronic pain can negatively modify their expectation about their ability to perform a particular activity and their confidence to accomplish that task despite the pain. According to literature, lower self-efficacy levels are consistently related to greater clinical pain ratings in various chronic pain conditions . HoweverDue to the small sample of patients, we cannot identify demographic or clinical factors associated with the presence of post-stroke pain. However, in our small sample, patients with chronic pain presented lower levels of education, a higher percentage of ischemic stroke, and a higher percentage of aphasia. A low formal education level is commonly associated with a higher prevalence of several chronic pain conditions  and low The higher level of post-stroke pain in patients suffering from aphasia is in line with the one reported in the literature . People Patients with chronic pain had a longer duration of multidisciplinary rehabilitation care (in our sample twice as long as patients without pain) and therefore, more significant care effort also from an economic perspective . Longer The implication of these findings is relevant for a multidisciplinary assessment and management of chronic post-stroke patients. The fact that with the same perceived motor disability (mobility and strength), patients with chronic pain reported a greater disability in the domains related to emotional aspects emphasises the need for psychological interventions to promote a better emotional adjustment to the stroke experience and its consequences. This suggestion is confirmed also by the positive attitude of patients regarding psychological help, with the majority of the sample reporting interest for psychological interventions. Considering the psychological characteristics investigated in the current study, the psychological intervention might be targeted to promote problem-oriented coping strategies, psychological flexibility, and self-efficacy. However, further studies with a larger sample are needed to confirm our results.One of the strengths of this study is that it explored disability, HrQoL, and psychological distress and features in a cohort of patients generally overlooked in the literature and often under-recognised in clinical practice. Another strength of the study is the comprehensive protocol to explore diverse psychological aspects that can be impaired in patients with chronic pain and then addressed by multidisciplinary management. Moreover, the use of patient-reported outcome measures to evaluate the self-reported level of disability and HRQoL (SIS) should also be considered as a strength of the study. This instrument reports high validity, since an excellent correlation has been reported in post-stroke patients between the SIS cognitive factors and the MMSE, between the SIS physical factors and the Barthel Index and instrumental ADL, and between SIS emotional factor and anxiety and depression .The limitations of this study are the small sample of patients, the lack of pre-registration of the study, the cross-sectional nature of the study, which did not allow for an evaluation of the causative relationship between pain, HrQoL, and psychological distress, and the lack of information about the pharmacological treatment of the patients. Moreover, the patients who were recruited and accepted to participate in the study are not representative of all stroke survivors’ patients, since, for example, they reported a level of cognitive functioning adequate to fill out questionnaires. Moreover, we cannot exclude that they were already more willing to take part in a possible psychological intervention and to undergo psychological assessment. Finally, we cannot exclude a selection and questionnaire administration bias.Chronic pain is a common symptom in post-stroke patients increasing patients’ disability and affecting rehabilitation outcomes. To date, the management of these patients is a challenge in the neurorehabilitation setting . As a ma


The experimental group was instructed to listen to their favorite music using headphones during their operations at the center. The control group underwent the operations without listening to any music. The pain measurement during vascular access operation was measured by subjective pain and objective pain behavior; anxiety was measured by subjective anxiety and anxiety states. Results: The experimental group reported significantly lower subjective pain levels than the control group . Regarding objective pain behaviors, the experimental group had a significantly lower score than the control group . The experimental group had significantly lowered subjective anxiety compared to the control group . Regarding anxiety states, the experimental group had significantly lower scores than the control group . Conclusion: The results suggest that patient-selected music listening reduced hemodialysis patients’ pain and anxiety levels during vascular access operations. Therefore, music medicine can be included as a new clinical intervention.This study aimed to analyze the influence of patient-selected music listening on the pain and anxiety levels of hemodialysis patients after undergoing a vascular access operation. Methods: Sixty five patients were randomly assigned to the experimental group ( According to the analyses, there are approximately 3.2 million patients with end-stage renal disease worldwide. Of these, 78% have received either hemodialysis or peritoneal dialysis and 22% have undergone kidney transplants . With anReportedly, half the patients receiving dialysis treatment lived in North America, Europe, and Japan; terminal-stage kidney disease patients were most prevalent in Taiwan. Japan had 2525 patients per one million persons, and the United States (US) had 2138 . HemodiaEver since the radiocephalic arteriovenous fistula (RC-AVF), as developed by Brescia, Cimino, and Appell, was released, vascular access operation techniques and vascular prostheses have improved through ceaseless research efforts. Vascular access creation has become a common surgical operation in the US, with more than 500,000 procedures performed during the past decade . In addiMusic can affect the brain’s lymbic and autonomic nervous systems, causing emotional and physiological changes. Consequently, music can be used in the treatment of patients suffering from mental, emotional and physical pain . How theWhen patients listen to their preferred music for pain reduction helps to reduce the perception of pain . RegardiListening to music was shown to alleviate the pain, anxiety, and depression of gynecologic cancer patients who had received chemotherapy . When muPrevious studies suggested that when participants listened to music they enjoyed, music medicine proved to be an effective tool in reducing their physical and mental stress, as well as increasing their safety and pain thresholds . Howeverhttp://www.randomization.com accessed on 15 June 2018) was used to randomize the experimental group (32 people) and the control group (33 people).From June to October 2018, 142 patients undergoing vascular access surgery at S General Hospital in Seoul were given handouts and explanations regarding the recruitment of study subjects, and then those who agreed to participate in this study were selected. To calculate the sample size, we used the analysis method of ANCOVA, with effect size of 0.4, significance level of 0.05, and power of 0.8. The result was that at least 52 participants were needed. We selected a total of 65 participants, as we anticipated a 20% drop out rate. There were no drop outs, therefore 65 participants were analyzed. After giving temporary numbers to 65 participants, the randomization site program , this study measured a value that signified the degree of pain along a straight line of 10 cm. The higher the score, the more severe the pain experienced.To measure patients’ pain levels, an objective pain behavior checklist, as developed by Park , was utiSubjective anxietyAnxiety statesSubjective anxiety was measured using the VAS scale and rated on a scale from 0 to 10, with 0 indicating no anxiety and 10 indicating severe anxiety.Mood Status Profile Tool (POMS), modified by Lee  and baseThe collected data were analyzed using the SPSS Ver.25 program. The study results were analyzed using an independent t-test. In addition, to increase the accuracy of the analysis results, ANCOVA, in which the previous score was controlled as a covariate, was used. The reliability of the tool was verified by Cronbach’s α coefficient.A homogeneity test was conducted before participants underwent their operations to ensure that the control and experimental groups were homogeneous in terms of age, sex, number of vascular access operation, vascular types, periods of vascular use, music preferences, subjective anxiety levels, and anxiety states .p = 0.003). Therefore, music medicine reduced the patient’s subjective pain level during the vascular access surgery procedure  showed a significantly lower score than the control group (5.55 ± 3.55) . Therefore, the application of music medicine to patients undergoing vascular access surgery decreased the objective pain behavior  had a significantly lower score than the control group (4.67 ± 3.49 points) . The analysis of subjective anxiety indicated that the experimental and control groups had an average score of 2.59 ± 1.80 and 3.42 ± 3.37, respectively. This showed that the experimental group, which experienced the music therapy, had a significantly lowered subjective anxiety than the control group   were significantly lower than that of the control group (11.55 ± 12.17)  .This study analyzed the effects of music medicine on the pain experienced by hemodialysis patients who underwent vascular access operations. Our findings indicated that the experimental group, which experienced music therapy, demonstrated significantly lower subjective pain levels than the control group. This study was similar to the findings in Hosseini’s study  that musIn the present study, the effect of music medicine on patients’ anxiety levels was analyzed. The results indicated that the experimental group had significantly lower subjective and objective anxiety compared to the control group. In previous studies, music medicine was found to be effective at reducing the anxiety of patients who had undergone a surgical operation under localized anesthesia ,28. In tAccording to a study by Son et al. , the expOn the other hand, according to Kwon’s study  in whichOverall, music medicine was found to be effective in reducing pain and anxiety during vascular access in hemodialysis patients with vascular channel dysfunction. Pain is produced by the output of a widely distributed neural network in the brain. The neuromatrix, which is genetically determined and modified by sensory experience, is the primary mechanism that generates the neural pattern that produces pain .Music medicine is an effective nursing intervention that is economical and has no side effects in restoring the patient’s mental and physical health when performing simple procedures in the hospital. Based on this, the continuously repeated research on music therapy, which is a positive and new intervention for reducing pain and anxiety in patients, is necessary. According to the findings of this study, music medicine positively influenced the subjective and objective pain behaviors, subjective anxiety levels, and anxiety states of hemodialysis patients with vascular access dysfunctions during their vascular access surgery procedures. The research results can inform new clinical interventions to reduce pain and anxiety in patients. In light of this, it is necessary to conduct continuous and repeated research studies on music medicine within clinical settings when hemodialysis patients undergo vascular access surgery.


In the severe-CCI group, patients aged ≥ 80 years had 1.91-fold risk of TB compared with mild-CCI group (p = 0.0481). Severe-CCI group had significantly higher mortality than the mild-CCI group (p = 0.0366). Patients with TBI and more comorbidities had higher risk of TB infection with higher mortality rate.After traumatic brain injury (TBI), an inflammatory response in the brain might affect the immune system. The risk of pulmonary infection reportedly increases in patients with TBI. We aimed to evaluate the risk of tuberculosis (TB) in patients with TBI in Taiwan. All participants were selected from the intensive care unit (ICU). Patients with TBI were defined as patients in ICU with intracranial injury, and comparison cohort were patients in ICU without TBI diagnosis. There was a significant difference in TB risk between the patients with TBI and the comparison cohort according to age and the Charlson’s comorbidity index (CCI) score. Thus, we divided patients based on CCI into three groups for further analysis: mild (CCI = 0), moderate (CCI = 1/2), severe (CCI > 2). Mild-CCI group had a lower TB incidence rate (0.74%) and longer time to TB development (median: 2.43) than the other two groups. Moderate-CCI group had 1.52-fold increased risk of TB infection ( Host factors are important for pulmonary TB infection, and the risk factors include age2, use of oral glucocorticoids3 or inhalation corticosteroids4, diabetes mellitus6, administration of tumor necrosis factor (TNF-α) inhibitors7, organ transplantation8, substance abuse9, smoking10, silicosis11, malignancy12, chronic renal disease13, gastric surgery14, liver cirrhosis15 and chronic obstructive pulmonary disease16. According to WHO's Global Tuberculosis Report, the estimated deaths due to TB were approximately 1.4 million people in 201917. From 2011 to 2014, Taiwan was a country moderately burdened by TB, and the incidence of the disease was about 48–55 per 100,000 people18.Tuberculosis (TB) is one of the top ten causes of death in the world and remains the leading cause of death among infectious diseases; a total of 1.4 million people died from TB in 201919. Following TBI, the mechanisms of bacterial lung infections include cytokine release, HMGB1 release, and activation of the lymphatic system. The microglia and astrocytes in the brain initiate inflammatory activity and activate the neutrophils to adhere to blood–brain barrier, resulting in cell breakdown and increased permeability. Furthermore, TBI also increases neutrophil and inflammatory cytokines, including TNF-α, interleukin (IL)-1, and IL-6, within the pulmonary tissue19.Traumatic brain injury (TBI) is a global major cause of mortality and morbidity. After patients could survive from TBI, they may develop systemic immunosuppression and a high risk of bacterial lung infections21. Immunosuppression in brain injury is rapid and profound22. In the animal model, lymphocyte function was suppressed after brain injury, and the rate of pulmonary infections was significantly higher in the brain injury group compared with the control group23. In this study, we hypothesized that the changing immune status after TBI not only increases the risk of lung infections, but also increases the susceptibility of TB infection. Considering the association between level of consciousness and the inflammatory response, patients with TBI and intracranial injury may have a higher inflammatory response than patients without. Therefore, the aim of our study was to assess the risk of TB and the subsequent mortality among patients with TBI and intracranial injury, compared with patients without.Following TBI, the inflammatory response might affect the health status. The brain cells secrete cytokines and chemokines, activate the endothelial cells and microglial cells, and result in the migration of systemic neutrophils, lymphocytes, and monocytes into the injured brainhttp://nhird.nhri.org.tw/en/Data_Subsets.html). The database comprises detailed information regarding clinical visits for each insured person, including date of diagnosis; diagnostic codes according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM); payments for consultations; and prescription details. This study was conducted in compliance with the Declaration of Helsinki and has been approved by the Research Ethics Committee of Chi Mei Hospital (IRB permit number: 10803-E01). The requirement for informed consent was also waived by the approval of the Research Ethics Committee of Chi Mei Hospital.According to the claims of Taiwan’s national health insurance program, Taiwan established a medical claims database, National Health Insurance Research Database (NHIRD), for research propose. Almost 99% of inpatient and outpatient medical benefit claims for Taiwan’s 23 million residents were covered by NHIRD  between 2002 and 2012. Patients with TBI were defined as inpatients with a diagnosis code of TBI . The patients with TBI were either classified as patients without intracranial injury  or patients with intracranial injury , only those with intracranial injury were selected in this study. To understand the potential for TB development in patients with TBI with a more severe inflammatory response, those with intracranial injury were selected in this study. To ensure inclusion of new onset TBI, patients with a history of TBI diagnosis before 2002 were excluded. The comparison cohort were identified as patients without a TBI diagnosis but with ICU admission records in NHIRD. Considering the potential confounding bias that affects TB incidence, patients with a history of diabetes mellitus (DM), end-stage renal disease (ESRD), chronic obstructive pulmonary disease (COPD), cancer, or liver diseases were excluded from the study. To estimate the risk for new-onset TB, all patients with a history of TB before the date of hospital admission or diagnosis of TBI were excluded from both the case cohort and the comparison cohort. Additionally, patients who died on the day of admission were also excluded. For reducing potential selection bias, the comparison cohort was assembled by matching a patient with TBI and one without on index year, age, sex, and length of ICU stay. Finally, a total of 168,032 study participants  were included in our study. Furthermore, to estimate the association between risk of TB and potential severity among patients with TBI, the Charlson’s comorbidity index (CCI) score was used to further classify the participants into three groups: mild (CCI score = 0), moderate (CCI score = 1 or 2), and severe (CCI score > 2). The CCI score is commonly used as a surrogate to patients’ disease severityThe main event in this study was TB, which was identified using the ICD-9-CM codes, 010-012 and 010-018, with at least a two-time diagnosis (within 6 months) in an outpatient clinic or during hospital admission, according to the records of the NHI reimbursement datasets. Additionally, to reduce potential misclassification bias, patients with prescriptions of anti-TB drugs, including isoniazid, rifampin, pyrazinamide, ethambutol, were used to confirm the TB diagnosis. All study participants were followed-up until new-onset TB infection, death, or the end date of the study, December 31 2013. Demographic variables (age and sex) and clinical characteristics, including the length of hospital stay (LOS) and the length of ICU stay, were used as potential confounders to estimate the TB and mortality risk. The secondary outcome was the mortality in patients with TB. Mortality was defined as having a death record in the inpatient claim dataset; or outpatient claim dataset; or withdrawal from the insurance program and without reenrollment within 180 days of the last health care visit.Frequency with percentage and median with interquartile range (IQR) are used to present categorical variables and continuous variables, respectively. The distribution differences in age, sex, mortality, and TB between the study cohorts were examined using the Pearson’s chi-squared test. For continuous variables, including LOS, length of ICU stay, time to TB development, and time to death, Wilcoxon rank-sum test was used to compare the distribution difference between the study groups. Additionally, the cumulative incidence rate of TB was presented using the Kaplan–Meier failure plot, with the log-rank test to compare the trend difference.p value < 0.05.Cox proportional-hazards regression model was used to estimate the relative risk of TB between patients with TBI and those without after adjusting for age, sex, LOS, the length of ICU stay, and level of CCI for overall model and the stratified model which excluding the stratified variable Table . Subgroup < 0.05). Additionally, the incidence risk of TB was not significantly different between the TBI and non-TBI groups (Table p = 0.0003). Additionally, patients with TBI and mild-CCI had a lower risk of TB than patients without TBI . However, patients with TBI and moderate-CCI had 1.25-fold risk of TB incidence , compared with patients without TBI. The mortality risk between patients with TBI and non-TBI group did not show the statistical significant for overall and the subgroup of genders. Patients with TBI for patients aged ≥ 50 years, moderate-CCI, and severe-CCI had significant higher mortality risk than patients without TBI. However, compared with non-TBI patients, TBI patients show lower risk of mortality in patients aged < 50 years and mild-CCI group . Patients with moderate-CCI and severe-CCI were significantly older than those with mild-CCI. The severe-CCI group had a longer LOS and length of ICU stay, compared with the other two groups. Furthermore, the mild-CCI group had a lower TB incidence rate (0.74%) and longer time to TB  than the other two groups. The moderate-CCI and severe-CCI groups had a higher percentage of TB incidence rate  and higher mortality rate  than the mild-CCI group. Figure To understand the baseline difference among patients with TBI with different levels of CCI, the baseline information of the patients with TBI and mild-CCI, moderate-CCI, and severe-CCI is shown in Table p < 0.0001), compared with those with mild-CCI. For patients with TBI and severe-CCI, the adjusted HR was 1.24-fold  than those in the mild-CCI group. For different age groups, patients with TBI in the moderate-CCI group had a higher TB incidence; however, patients in the severe-CCI group aged ≥ 80 years had the highest TB incidence rate . Compared with the mild-CCI group, patients in the moderate-CCI group aged 50–64 years and 65–79 years had a significant relative risk of 1.94  and 1.65 , respectively. In the severe-CCI group, patients with TBI aged ≥ 80 years showed significant TB risk compared with those in the mild-CCI group .Table p = 0.0102), compared with those in the mild-CCI group. Males also showed a significant relative risk for TB between the moderate-CCI and mild-CCI groups .Additionally, males presented a higher TB incidence rate than females among the three groups. However, females had a significant relative risk for TB in the moderate-CCI group  than those in the mild-CCI group. Patients aged < 50 years were merged due to less events; however, among those aged 50–64 years, patients in the moderate-CCI group presented a 2.6-fold higher mortality risk than those in the mild-CCI group. Further, patients aged 65–79 years in the severe-CCI group had a significant mortality risk , compared with those in the mild-CCI group.Furthermore, the relative mortality risk among patients with TBI and TB is shown in Table In our study, we observed that the risk of TB was not significantly different between the patients with TBI and patients without TBI admitted in the ICU. This implies that patients with TBI had similar TB risk compared with the high-risk patients in the ICU. However, we observed that the level of CCI scores might majorly affect the risk of TB development in patients with TBI and those with mild- and moderate-CCI. Furthermore, patients with TBI and moderate- and severe-CCI had a higher TB incidence rate and higher mortality than those with mild-CCI.The risk of TB increased with age and was higher among males. We observed that patients with TBI aged 50–64 years in the moderate-CCI group had the highest risk of developing TB, compared with those in the mild-CCI group; the risk of mortality was also the highest in the moderate-CCI group. There were no statistically significant differences in mortality among the patients aged ≥ 80 years in the moderate-CCI versus mild-CCI groups, and severe-CCI versus mild-CCI groups. To our knowledge, this is the first study to delineate the relationship between TB and TBI. The possible mechanism for increased risk of TB in patients with TBI was alterations in immune system function after TBI, along with presence of comorbidities.28.TBI leads to brain damage via direct or indirect injury. These indirect (secondary or delayed) mechanisms begin with an acute inflammatory response encompassing destruction of the blood–brain barrier and brain cells, tissue swelling, and edema. Subsequently, cell recruitment, and restoration and stimulation of peripheral blood cells and tissue-resident immune cells ensues. The immune mediators, such as chemotactic factors and interleukins, augment the inflammatory response and result in possibly harmful or helpful sequelae of TBI22 observed the occurrence of infections in nine (75%) of 12 patients after TBI. These patients with TBI had immune system impairment, which included deficiencies such has neutrophil superoxide release, immunoglobulins, complement system components, properdin, alternate C pathway, T cells, T helper cells, T suppressor cells, and natural killer cells. These immune deficiencies probably contributed to the high rate of infections. Munno et al.29 studied the relationship between persistent vegetative status after TBI and immune system. They observed that patients had profound impairment of phagocytosis and killing of monocytes, and low serum levels of interferon gamma. Wolach et al.30 also observed impaired humoral immunity in patients with post-comatose unawareness. Patients also had decreased levels of complement system components, hemolytic activity of the classical complement pathway, immunoglobulins, and neutrophil killing activity; however, neutrophil function of chemotaxis, random migration, and superoxide anion release was normal. All of these factors contribute to increased susceptibility of TB infection in immunosuppressed patients with TBI.Cytokines such as TNF-α and IL-6 are important mediators that initiate and maintain inflammation after TBI. Brain injuries result in immune system suppression and subsequent infection. Immunosuppression in brain injury is profound and may be associated with infection after TBI. Wolach et al.After further analysis of the comorbidities via CCI in the patients with TBI, we observed that compared with mild-CCI, the moderate-CCI group had a higher risk of TB between the ages of 35 and 79, and the severe-CCI group had higher risk of TB in patients aged ≥ 80 years. There were no statistically significant differences in TB incidence among patients ≤ 35 years in the moderate- and severe-CCI group, compared with the mild-CCI group. This might have been due to the small number of patients in that group, which provided inadequate statistical power to demonstrate a difference. After stratification by age, each group (moderate-CCI and severe-CCI) had a limited number of patients, and the sample size was too small to have enough statistical power to detect.31. CCI is a standardized method to evaluate comorbidities, which was originally used in 1987 to predict 1-year all-cause mortality due to the 17 underlying conditions24; it has been validated and widely used clinically.Comorbidities play an important role in the severity and mortality in patients with TB. Factors such as advancing age and co-infection with HIV have been linked to mortality in patients with TB infectionsIn our study, we demonstrated that CCI was associated with mortality in the patients who developed TB after TBI, and we observed that patients with TBI aged ≤ 80 years in the moderate-CCI group had higher risk of mortality of developing TB. CCI has been shown to be an independent predictor of mortality and long-term survival. The patients with moderate-CCI had a higher risk of mortality compared with patients with mild-CCI. The same result was observed in the severe-CCI group compared with the mild-CCI group, though only in those aged 65–79 years, due to the small sample size in other age groups. Whether different comorbidities or age have an impact on TB incidence after TBI needs further investigation, and more studies are required to confirm the impact of comorbidities on mortality.32. A study has shown that TBI activates the sympathetic nervous system, and further upregulates the expression of programmed cell death-1 on CD4+ and CD8+ T cells, which, in turn, impairs their function and contributes to immunosuppression33.Beside the brain injury itself, it is increasingly evident that a brain injury also changes the systemic immune response in a way that makes patients with TBI more susceptible to infections in the post-injury period; these infections are associated with morbidity and mortality and can be an added challenge to treat patients. Further research to better understand immunosuppression rather than TBI-induced immunosuppression is more important for the development of effective therapeutic strategies for helping these patientsThere are some limitations to our study. Based on the database, we were unable to analyze the type of TBI during hospitalization; the mortality risk may have been related to the type of TBI. We also lacked data regarding functional outcomes and consciousness level after patient discharge. Besides, we could not rule out any long-term mortality that might have been caused by the sequelae associated with TBI, or indirectly, by other diseases. We also did not have the laboratory and imaging data, including brain computed tomography scan.Despite these limitations, our study enrolled a large number of patients with TBI with different comorbidities, divided them according CCI scores, and underwent long-term follow-up at various hospitals. Therefore, our findings may have broad generalizability to this population and provide valid estimates of the population characteristics.Patients with TBI with more comorbidities increased the risk of TB infection. A careful survey and diagnosis are important for determination of a subsequent treatment strategy. The long-term mortality risk in patients with TB after TBI was significantly higher than the corresponding risk in patients with mild-CCI. Our findings might provide some information for clinicians to improve long-term care strategies in elderly patients with TBI.


The Oxford Hip Score is used to evaluate the outcome after total hip arthroplasty. The Oxford Hip Score was developed more than 20 years ago with only some degree of patient involvement. We question if the Oxford Hip Score is still relevant for the present-day total hip artrhoplasty patients. We aimed to determine whether the Oxford Hip Score contains items that are relevant for present-day patients with osteoarthritis undergoing total hip arthroplasty, thus investigating the content validity.Patients aged 60–75 years, undergoing total hip arthroplasty for primary osteoarthritis were recruited to participate in focus group interviews preoperatively and at 3 and 12 months after primary total hip arthroplasty. We conducted 6 focus group interviews in which 30 patients participated. The interviews were audio-recorded and transcribed verbatim. Using Interpretative Phenomenological Analysis, we inductively organised the interview transcripts into particular items/themes which we then compared to items in the Oxford Hip Score.We identified 6 general items with 41 sub-items. The 6 general items were pain, walking, physical activities, functional abilities, quality of life and psychological health. We found that items in the Oxford Hip Score were all in some way relevant to the patients but that the Oxford Hip Score lacks several important items relevant for present-day total hip artrhoplasty patients, including several physical activities, functional abilities and certain aspects of quality of life and psychological health.We found that the Oxford Hip Score lacks important items for present-day patients in our population. Due to findings regarding several additional items that are not present in the Oxford Hip Score, particularly concerning physical activities and quality of life, we question the content validity of the Oxford Hip Score for a present-day population. Our findings indicate a need for a revision of the Oxford Hip Score. Patient-reported outcome measures (PROMs) are important in the evaluation of patient outcome and quality of life following total hip arthroplasty (THA) , 2. Hip-In this study, we opted to focus on the Oxford Hips Score (OHS) as it is used in research worldwide , 9, is iThe content of the OHS was developed by a research team that interviewed 20 patients and reviewed established questionnaires resulting in a list of 20 items. Through modification and retesting, this list ultimately morphed into a 12-item questionnaire assessing pain and function of the hip  . IPA is The total sample of interview patients consisted of 13 (46%) women and 15 (54%) men with a mean age of 70 years and there was no significant difference in the distribution of gender or age between the periods or hospitals Table .Table 2CFrom the analysis of the transcripts, we identified 6 general and 41 sub-items. The 6 general items were pain, walking, physical activities, functional abilities, quality of life and psychological health Table . By comp‘The most important thing was to achieve pain relief… And after surgery, when you discover that you are completely pain free, it is fantastic’ .Patients also described uncomfortable episodes of sudden shooting pain and how pain affected their sleep. The patients described how being awakened by their pain at night was both disturbing and disruptive to their daily lives due to resulting exhaustion.‘For me, the biggest challenge has been being able to sleep well at night. Because getting your sleep at night, for my part, has meant that I get 1–2 h extra per day’ .The patients also focused on other sub-items related to pain not covered by the OHS, including the use of pain medication and repayment of pain following activity. The patients wished to underline the weak correlation between the intake of pain medication and the extent to which they experienced pain. They attributed great importance to the pain medication item.‘The physician could see that the hip was severely damaged, he just couldn’t understand that I was still able to run, or at least I did despite the pain and I didn’t take any pain medication even though I was in pain’ .Pain is covered by the OHS as the description of pain, the experience of sudden pain and nightly pain. Many of the patients indicated pain as one of the greatest challenges and described pain relief as a spectacular feeling.‘The fact is that I really want to go for a walk but when I am done walking… then I am completely worn out when I get home’ .This aspect of walking is covered by the OHS. However, we also found aspects of walking such as walking pace and walking on uneven terrain that the OHS does not cover. These aspects also affect the patients’ quality of life as they feel unable to keep pace with their relatives or walk on the beach when on holiday.The patients discussed many aspects of walking ability and there was a consensus that this was a significant factor of THA where they experienced problems, for example, no longer being able to walk the desired distance and limping due to pain.Sub-items that demanded more physical exertion than that required to complete everyday functions were categorised as physical activities. Physical activities are not covered by the OHS, which focuses more on everyday activities. We found that patients have fairly high demands regarding their level of physical activities. For example, they place great importance on their ability to participate in cycling, running, sport and lifting heavy objects; the most predominantly important activities were cycling and sports.‘When I ride a bike, I feel that there isn’t the same mobility in the hip that there used to be. I used to cycle a lot’ .The patients also emphasised the importance of the ability to participate in their preferred sports and several described sports as activities that are part of a healthy social life, thereby enhancing their quality of life.‘But it is just because there is so much social connected to it. You get around and play with and are together with the same people’ .The ability to ride a bike was described as important both as a method of transportation and a form of gentle exercise.‘I have a daughter who lives on the 4th floor, and I keep myself from visiting her because the stairs are a nuisance for me. Alternatively, I must take pain medication before I go, and then it sort of works when I get there, and then I can climb the stairs’ .However, we found that the patients’ demands for functional abilities went beyond those covered by the OHS. They included sitting down, standing up, lying on the operated site and, most predominantly, the ability to lower one-self onto and get up from the floor.Several everyday functions are covered by the OHS: bathing, putting on socks, shopping, using the car, climbing stairs, completing household tasks and getting up from a chair. These were all mentioned during the interviews, with some being more predominant, such as climbing stairs and putting on socks.‘For many years I haven’t been able to get on the floor and up again without many strange movements and maybe a helping hand, but I can do that now, so that is huge progress for me. I think it matters greatly, particularly when you have small children that you want to play with…’ .Patients’ ability to lower themselves to the floor to retrieve fallen objects was found to represent an important everyday activity. For several patients, this function was linked to the ability to play with their grandchildren.‘Quality of life, for me, is being able to walk on the beach and climbing stairs effortlessly and being able to walk … So that it is kind of the parameter for … Well cleaning and vacuuming is something I could buy myself out of, if it had to come to that, but the other things are quality of life to me’ .The patients also described how the pain was affecting social life and holidays:‘And then again, as you say, the social stuff. The fact that you are forced to be the one that sets the limitations all the time or staying home instead… Also, in relation to the pain, it makes me mad and less happy than I used to be’ .Quality of life was very important for the patients we interviewed, yet, this is a category not covered by the OHS. The ability to engage in activities that enhance the individuals’ quality of life was emphasised as very important and the description of such activities illustrated that quality of life concerns more than the ability to accomplish typical daily activities.Psychological health, which could be considered an extension of quality of life, is also not covered by the OHS. Though many of the sub-items related to psychological health were not predominant, they were mentioned during the interviews and included fear of falling and/or dislocating the hip and awareness of the hip.‘It's so tiring to be the one to put a stop to things’ .A more predominant theme regarding psychological health was the feeling of being a burden to others.This study investigated the content validity of the OHS using a qualitative approach.We found that there are several additional items that present-day patients deem relevant which are not included in the OHS. This indicates that the OHS fails to cover all the important items regarding living with an artificial hip, which questions the content validity of the OHS.There are limited studies investigating the patients’ perspectives on the OHS. Wylde et al.  allowed A Dutch translation and validation of the OHS from Gosens et al.  attempteThe group of researchers who developed the OHS published a review of the OHS in 2007 . In contThe findings of additional items in this study may be attributable to the decrease in physical limitations and increase in self-reported health , 30, as The development in lifestyle are illustrated in our findings as we found that quality of life ventures beyond the ability to accomplish typical daily activities and that patients expressed a need for a full and functioning social life. A study from Garbuz et al.  also higThe strengths of this study include the method of focus group interviews, which are conducive for studying the validity of a structured instrument and can provide insight regarding patients’ perspectives , 20. By One author conducted all the interviews and performed reading and coding of the transcripts before discussing the results with the other authors. Due to the nature of this form of qualitative analysis, the interpretation of findings is likely affected in some way by this one author. We did, however, base the interviews on open-ended questions and transcribed verbatim all patient statements which were extracted without filter, limiting the subjectivity of the analysis.The patients in our study did not mention sensitive topics such as sexual function, which could be a limitation of this study, due to its focus-group-interview structure. Further, it should be acknowledged that this study was conducted within the context of Danish culture, with items such as cycling being particularly popular among Danish communities. Our findings may not be generalisable to other cultures.This study showed that the OHS lacks important items for present-day patients in our population. Due to the findings of several additional important items, we question the content validity of the OHS in a present-day population.The additional items identified in this study as relevant to patients suggest that present-day patients have high expectations of life with THA.Considering the results obtained by previous studies , 27, 28 Thus, patient involvement is of the utmost importance throughout all the steps involved in the development and validation of a PROM to ensure content validity. As shown in this study, patient preferences may change over time and this calls into question the use of PROMs that have not undergone validation within recent years.


This systematic review aims to review clinical studies on the use of ketamine infusion for patients with treatment-resistant complex regional pain syndrome (CRPS).The following systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021228470). Studies for the systematic review were identified through three databases: PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Reviews. Inclusion criteria for studies consisted of randomized clinical trials or cohort studies that conducted trials on the use of ketamine infusion for pain relief in patients with CRPS. Exclusion criteria for studies included any studies that were systematic reviews, meta-analyses, case reports, literature reviews, or animal studies. In the included studies, the primary outcome of interest was the post-drug administration pain score.In this systematic review, 14 studies met the inclusion criteria and were reviewed. In these studies, the dosage of ketamine infusion used ranged from 0.15 mg/kg to 7 mg/kg with the primary indication being the treatment of CRPS. In 13 of the studies, ketamine infusion resulted in a decrease in pain scores and relief of symptoms.Patients who received ketamine infusion for treatment-resistant CRPS self-reported adequate pain relief with treatment. This suggests that ketamine infusion may be a useful form of treatment for patients with no significant pain relief with other conservative measures. Future large-scale studies, including randomized double-blind placebo-controlled trials on the use of ketamine infusion for CRPS, must be conducted in a large-scale population to further assess the effectiveness of ketamine infusion in these populations. Complex regional pain syndrome (CRPS) presents with pain in an extremity or extremities following trauma. The typical patient is a middle-aged female with an upper limb insult, causing lasting pain and/or concurrent dysfunction in the sensory, motor, autonomic, and trophic domains . CRPS isAmong the diverse therapies available for CRPS, including immunomodulation, hyperbaric oxygen therapy, and psychological therapy, medicinal approaches are typically the first-line therapy . In partPharmacology and mechanism of action of ketamineKetamine is composed of a chiral center at the C-2 carbon of the cyclohexanone ring so that two enantiomers exist: S(+)-ketamine and R(-)-ketamine. The S-enantiomer has greater pharmacological potency due to a greater affinity for the PCP-binding site on the NMDA. Accordingly, preparations containing only the S-enantiomer are desirable.Traditionally, ketamine is administered via IV or intramuscular routes. Alternative routes of administration include insufflation/intranasal, inhalational, oral, topical, epidural, and rectal modes. It is both water and lipid-soluble. These qualities allow for its rapid distribution throughout the body and ability to cross the blood-brain barrier. The predominant route of metabolism is via hepatic cytochrome P450 enzymes, with 12% remaining protein-bound in plasma. Ketamine's half-life in plasma is approximately 2.5 to 3 hours, rapidly metabolizing to norketamine, hydroxynorketamine, and dehydronorketamine. Approximately 4% of the unmetabolized drug is excreted via the urine .The therapeutic range of ketamine makes it one of the safest sedative agents for most emergency clinical and preclinical situations . In low Ketamine exerts its effects through a variety of pathways. Its primary mechanism is as a non-competitive antagonist at the PCP-binding site of the NMDA receptors in the central nervous system (CNS) . At thisKetamine also acts on other non-NMDA pathways that affect pain and mood regulation. It acts as an antagonist of nicotinic and muscarinic cholinergic receptors, as well as blocking sodium and potassium channels. Ketamine activates high-affinity D2 dopamine receptors and l-type voltage-gated calcium channels, promotes γ-aminobutyric acid A (GABA-A) signaling, and enhances descending modulatory pathways -15.Given the high co-prevalence rate of chronic pain and depression, the antidepressant and post-traumatic stress disorder (PTSD) relieving effects of ketamine have generated interest in the psychiatric community. The mood-enhancing effects of ketamine have been shown to emerge about four hours after intravenous administration, well after the drug has been cleared from the bloodstream. This suggests a neuromodulatory effect that persists for one to two weeks .This article was previously posted to the medRxiv preprint server on April 27, 2021.MethodsThe following systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) website (CRD42021228470) and the systematic review follows the guidelines listed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. In the review, studies describing the use of ketamine infusion for CRPS were researched to validate the use of the treatment.Search StrategyAn electronic literature search using three databases was conducted by the team. The databases PubMed, Cochrane Reviews, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) were searched using the terms “Ketamine” or “Ketamine infusion” and “CRPS” or “Complex Regional Pain Syndrome” to find peer-reviewed clinical studies. No date limiters were used. The initial search resulted in 101 non-duplicate entries from the three databases. After the application of inclusion/exclusion criteria, 87 articles were excluded from the search and 14 studies were included in the study.Inclusion and Exclusion CriteriaInclusion criteria consisted of all studies that were randomized controlled trials or studies that observed the effect of the use of ketamine infusion for pain relief in patients with CRPS. Exclusion criteria consisted of nonpeer-reviewed studies, systematic or meta-analysis reviews, case reports, and animal studies. All articles were reviewed by both reviewer AP and reviewer AC separately and any disagreements were resolved by tiebreaker reviewer SD. After the review process, both reviewer AP and AC had a 95% agreement rate for the studies to be included.Data ExtractionOf the studies to be included in the paper, the following data were extracted for discussion: 1) length of ketamine infusion, 2) follow-up period, 3) dose of ketamine used, 4) outcomes of interest, and 5) post-procedural pain scores.ResultsStudy CharacteristicsA total of 101 articles were identified as meeting the keyword search between the databases. After removing duplicates, 84 articles were screened, and 56 did not meet inclusion criteria based on their respective titles and abstracts. The remaining 28 articles were reviewed in full text and an additional 14 articles were excluded due to meeting exclusion criteria. Fourteen total articles were selected to be included in this review  or verbal numeric rating scale (NRS), which range from 0 (no pain) to 10 (worst possible pain). Instead of a pain score, Kirkpatrick et al. measured pain threshold, which is defined as the amount of stimulation before the pain is experienced . In 13 oOther measured outcomes included morphine-equivalent intake, plasma levels of ketamine, quality of life, functional improvement, cognitive effects, and side effects of ketamine infusion. Sheehy et al. measured oral morphine-equivalent opioid intake and found that while ketamine reduced pain intensity, it did not reduce overall opioid intake . GoldberFunctional improvement, including the ability to work, activity level, active range of motion, and effect on movement disorder, was measured in four studies. Kiefer et al. showed that ability to work was significantly improved three months post-treatment, with an even greater improvement by six months . SchwartCognitive effects were assessed by Koffler et al. who found that there were significant improvements in brief auditory attention and processing speed, no changes in learning, memory, nor motor speed, and a slight decline in motor strength . Side efThe findings from all 14 included studies are summarized in Table DiscussionA double-blind placebo-controlled study observing the effects of outpatient IV ketamine for the treatment of CRPS was conducted by Schwartzman et al. . In thisAnother study by Sigtermans et al. explored the use of ketamine on pain relief for patients with CRPS type 1 (CRPS-1). In the study, 60 CRPS-1 patients were included in a double-blind randomized placebo-controlled trial . NotablyA longitudinal study by Sheehy et al. observing the effects of subanesthetic ketamine infusions for the treatment of children and adolescents with chronic pain was also reviewed . In thisThe prolonged painful stimulus causes an increased release of glutamate from nociceptive afferents onto the dorsal horn neurons. This glutamate stimulates NMDA receptors on second-order neurons which leads to an increase in pain intensity (windup) and causes central sensitization. Correl et al. posit that blocking these NMDA receptors is what propagates ketamine’s ability to treat CRPS . TemporaAt the pharmacological level, Sigtermans et al. studied the S(+) variant of the compound due to its greater availability and two-fold greater analgesic potency than S(-) or racemic mixtures . They foEscalating doses of ketamine infusion, starting at 60 mg/hr to 200 mg/hr, based on quantitative sensory testing to direct treatment, demonstrate that ketamine has its most potent effect on regions of pain. A distinction is made when treating extremity pain in patients with CRPS, with pain threshold plateaus being realized between three and four days, and greater than four days of ketamine treatment for patients with CRPS of the lower and upper extremities, respectively . SimilarA five-year retrospective analysis by Patil and Anitescu studying the efficacy of outpatient ketamine infusions revealed that 50% of patients with severe refractory pain of multiple etiologies realized pain relief for up to three weeks with minimal side effects after receiving mean ketamine doses per infusion of 0.9 (± 0.4) mg/kg with a median duration between infusions of 233 days . All patKetamine infusions can provide significant analgesia to patients with CRPS that is refractory to conservative methods of pain management. One observational study by Goebel et al. evaluated the short- and long-term analgesic effects of 4.5-day, low-dose (0.9 mg/kg/hr) racemic ketamine (RK) infusions in five patients with refractory CRPS . The stuKetamine, norketamine, and the downstream metabolites likely play an important role in the analgesic properties and efficacy of ketamine infusions. Goldberg et al. conducted an observational study to determine the effects of a five-day moderate dose, continuous racemic ketamine infusion while evaluating for S-ketamine, R-ketamine, S-norketamine, and R-norketamine plasma levels . SixteenWhile several studies have shown ketamine infusions to be an effective analgesic for pain management in patients with refractory CRPS, a pilot open-label study by Kiefer et al. analyzing the efficacy of subanesthetic ketamine infusion in refractory CRPS patients found that treatment did not offer pain relief . Four stFuture StudiesOverall, the included studies generally reported adequate pain relief with varying protocols of ketamine infusion for treatment-resistant CRPS. Heterogeneity was significant in these studies due to variations in dosage, protocols, a number of subjects, combinations of pharmacological agents administered, and rescue analgesics. Despite these differences, some valuable trends can be observed and may provide direction in future studies for the utility of ketamine infusion. Of interest would be identifying the ideal time course in the treatment regimen to use ketamine for maximal efficacy. Also, dosage stratification should be explored based on age, the severity of pain as per numerical scale ratings, and time of living with the disease. With new innovations in pain management, such as neurostimulation and implantable pumps, a comparative study with ketamine should also be undertaken to understand the safest way to address pain control. Ketamine’s concurrent influence on psychology should be further understood as pain is a complex entity that affects numerous functionalities. In addition, the biopsychosocial model of pain and the interdisciplinary approach that can be taken to alleviate pain secondary to CRPS must be studied. In many cases, the use of ketamine has been shown to relieve symptoms of depression and PTSD so the effect of ketamine on pain relief, mental health benefits, and the social effects, such as improvement of quality of life, are all potential areas of study. Strengths and LimitationsThe strengths of this review included select studies that were published in peer-reviewed journals with thorough methodology and low dropout rates. However, this systematic review also had several notable limitations, including significant heterogeneity of the included studies in regard to study design, sample size, dosing strategies, and tools used to measure variables and outcomes. Among the 14 studies reviewed , several confounding factors were identified, including variable ketamine dosing strategies and durations of treatment, observational design in studies, and the use of other nonopioid multimodal analgesia. Study subjects were assessed for pain scores and other outcomes at varying intervals, which may influence outcomes of recall, in turn, increasing the risk of recall bias. Moreover, pain is subjective and challenging to measure despite the utilization of validated scales.Patients who received ketamine infusion for treatment-resistant CRPS reported adequate pain relief with treatment. Given the results, this suggests that ketamine infusion may be a useful form of treatment for patients with no significant pain relief with other conservative measures. Although pain scores were reduced with ketamine use in all but one study reviewed, parameters, such as functional improvement and quality of life, were not as well studied. In addition, one of the included studies observed the effects of ketamine in pediatric patients with chronic pain syndromes signaling a scope for use in younger patients. Future large-scale studies, such as randomized double-blind, placebo-controlled trials, must be conducted to better correlate the use of ketamine infusion in CRPS patients with improved pain scores, changes in parameters , and effectiveness by age cohorts.


Functional pain assessments are critical in total hip arthroplasty. This pilotstudy investigated a novel functional pain scale—the Activity-BasedChecks of Pain (ABCs)—and its correlations with the 0 to 10 numericrating scale (NRS) and outpatient milligram of morphine equivalents (MMEs)prescribed and needed in the first 2 weeks after total hip arthroplasty.U testsABCs and NRS were collected at the baseline, inpatient, and 2-week follow-up.Primary outcome metrics were needed for pain medication at the time of painscale completion, MMEs prescribed at discharge, and MMEs taken. IndividualABC functions and composite score were analyzed using Spearman rho andMann-Whitney P< 0.01; ρ = 0.402, P < 0.05; andρ = 0.563, P < 0.01). ABC or NRS scores didnot correlate with MMEs prescribed. Last in-house NRS correlated with MMEstaken postoperatively .Specific ABCs functions—“sitting up” , “walking in room”, and “walkingoutside room” —on the day of discharge correlated with MMEs taken.ABC and NRS scores were greatest preoperatively (n = 39). At each stage,the ABCs correlated with the NRS (ρ = 0.450, ABCs scale correlates with NRS. Neither scale correlated with MMEs prescribedat discharge, suggesting pain is undervalued in analgesic planning.Clinicians should assess pain with functions found to correlate with MMEstaken—“sitting up,” “walking in room,”and “walking outside room.” Pain managementdifficulties are compounded by the current methods of pain assessment. Noteworthy isthat pain is inherently subjective and influenced by an individual's experiences,expectations, and culture.3 Yet thecomplex nature of pain is often reduced to a unidimensional articulation of itsintensity, as indicated by the prevalence of the NRS in clinical practice. Althoughthese rating scales are simple and easy to complete, they cannot assess metrics ofcritical clinical importance and importance to patients, such as the effect of pain onthe ability to perform activities of daily life. Furthermore, in 2018, the JHACOreleased expanded guidelines on pain management to include an emphasis on assessing andmanaging functional pain.4 However, theNRS remains the predominant pain assessment in clinical settings.6In the years since, issues associated with analgesic overuse have come to dominate thepain dialog.Although often considered pathologic, pain can also be part of the normal healingprocess, particularly postoperatively. It is important for pain to be adequatelycontrolled to prevent both unnecessary suffering and complications. In 2000, the JointCommission on Accreditation of Healthcare Organizations made recommendations thatclaimed pain was a patients' rights issue and emphasized the need to quantify painby placing it on a 10-point numeric rating scale (NRS).In response to the recognized need for a functional pain scale, the Activity-Based Checksof Pain—Functional Pain Scale (ABCs) was developed. Briefly, the ABCs is a novelpain assessment tool that is intended to efficiently, visually, and meaningfully reflectboth pain and its functional implications. The purpose of this prospective cohort studywas to investigate the correlation of the composite ABCs and the NRS with (1) eachother, (2) reported need for pain medication at the time the pain scale was completed,(3) milligrams of morphine equivalents (MMEs) prescribed on postoperative discharge, and(4) patient-reported use of MMEs during the first 2 postoperative weeks in patientsundergoing total hip arthroplasty (THA). Secondary outcomes include determining whetherthere are specific functions within the ABCs are driving the overall pain score and aremost predictive of analgesic needs. The main intention of this pilot study was to gainknowledge that could justify a larger, more expansive study to confirm the validity andusability of the functional pain assessment tool developed.78910 Its facevalidity was established through discussions and informal focus groups withsurgeons from multiple subspecialties and key stakeholders in nursing,psychology/psychiatry, and physical therapy. Functions increase in difficultybecause the scale progresses from the top to the bottom, asking patients firstabout pain associated with “sleeping” and progressing to assessingpain with a more involved function such as “walking up astep.”This study underwent Institutional Review Board review and received approvalbefore commencement of any study activities. The ABCs' simple and visualformat Figure  is intenThis study was done at an urban, academic hospital. The subjects considered forinclusion were English-speaking, older than 18 years, and scheduled to undergounilateral primary THA. Exclusion criteria included the following: known paindisorders, history of pain medication abuse, revision arthroplasty, traumatichip fracture, and patients with cognitive disabilities.Subjects undergoing unilateral THA were prospectively enrolled the morning oftheir surgery in the preoperative clinical area. At this time, a study teammember oriented the patient to the ABCs and how to correctly complete it.Subject demographics and SF-12 health scores were recorded. The SF-12 wascollected because baseline emotional and physical well-being affect pain.Baseline pain data were collected using the ABCs and NRS. Both scales werecompleted at the same time. During each subject's inpatient stay, the ABCsand NRS data were collected twice daily as was patient-reported need for painmedication at the time of pain scale completion. For data analysis, each of theseven functions on the ABC scale was assigned a different weight depending onphysician perceived difficulty. These values were summed to represent thecomposite 10-point ABC score. Both the function-specific score and composite ABCscore were used in data analysis. Quantity of opioid analgesics prescribed atdischarge, in MMEs, was collected. Two weeks after the participants’surgery date, subjects were contacted through telephone and were asked to reportthe number of opioids taken and to rate their current pain on both the ABCs andthe NRS. If a participant was unable to be reached on the date exactly 2 weekspostoperation, then they were called for up to 3 days after this to gather ABCsand NRS scores and MMEs taken to be included in analysis. Patients withincomplete follow-up data after this 14 to 17 day postoperative period wereexcluded from analysis.U test.Significance was set a priori at P < 0.05.Data were analyzed using SPSS version 26. Descriptive statistics for scalevariables were reported using the median and interquartile range (IQR). TheSpearman rho test was used to assess correlation between scale variables. Groupcomparisons were done using the Mann-Whitney 11SF-12 was collected at baseline, and the median score was 27 ± 7.1. SF-12scores and correlation with composite ABC, NRS, MMEs prescribed, and MMEs taken aregiven in Table P < 0.01) and baseline NRS (ρ =−0.388 P < 0.05). It did not correlate with MMEsprescribed or taken. The physical SF-12 did not significantly correlate with thebaseline composite ABCs, baseline NRS, or MMEs prescribed and MMEs taken. Worsescores on the SF-12 indicate worse mental health. Although higher scores wereassociated with higher scores on the pain scales, they did not correlate withincreased MMEs taken postoperatively.Fifty-one patients were enrolled in this study. Nine patients were lost to follow-upafter 5 unsuccessful attempts to contact them through telephone postoperatively.Three patients were lost to follow-up after suffering another injury that causednotable pain and a decrease in function that disqualified them from continued studyparticipation. No patients withdrew. Thirty-nine participants completed the studythrough the 2-week follow-up. The median age of the participants was 59 years IQR:51 to 70). Of the 39 participants who completed their 2-week follow-up, 21 werewomen (53.8%). Five patients were identified as Black (12.8%) and 33 as White(84.6%). State demographics are reflected in our study population with 50.2% woman,86.3% White, and 6.1% Black. to 70. OP < 0.01; ρ = 0.402 P< 0.05; and ρ = 0.563 P < 0.01,respectively).Pain on both the NRS and the composite ABCs was greatest preoperatively. The medianvalues throughout the study are given in Table P < 0.05) with the exception of the NRS at the follow-up,where no significant difference was observed (P = 0.429). Atbaseline, no individual function significantly correlated with “yes”or “no” self-reported need for pain medication. At the last inpatientpain recording, “sitting up” (P = 0.046),“walking in room” (P = 0.003), and“walking outside the room” (P = 0.019)significantly correlated with answering “yes” in need of painmedication. At the 2-week follow-up, “walking up stairs” significantlycorrelated with “yes” in need of pain medication (P= 0.009). A summary of “yes” or “no” self-reportedneed for pain medication with respect to ABCs, NRS, and the individual functionspain scores is given in Table The median NRS and composite ABCs at each stage of this study were then stratified bythe patient's self-reported need for pain medication Figure . Pain wa P = 0.00, and“waP = 0.245) compared with women. Although there wasno statistically significant difference between sexes in MMEs prescribed, womenconsumed a smaller proportion of prescribed MMEs than men .No notable correlation was observed between composite ABC scores collected atbaseline, or before discharge, or at the 2-week postoperative follow-up and MMEsprescribed at discharge. No notable correlation was observed between NRS scorescollected at baseline, or before discharge, or at the 2-week postoperative follow-upand MMEs prescribed at discharge. The median MMEs prescribed were 625 (IQR: 450 to938), with the median MMEs taken being 270 (IQR: 113 to 483). Sex differences inMMEs prescribing and consumption patterns were noted. Men were prescribed less MMEs during the 2-week postoperative period. Althoughthe composite ABCs scores did not correlate with MMEs taken in the 2-weekpostoperative period, pain with 3 functions before discharge were significantlycorrelated. At the last inpatient scale completion, the followingfunctions—“sitting up” (ρ = 0.418 P< 0.01), “walking in room” (ρ = 0.353P < 0.05), and “walking outside room”(ρ = 0.362 P < 0.05)—correlated with MMEstaken during the 2-week postoperative period. Finally, although the 2-week NRS didnot correlate with the ABCs function, “out of bed to chair”significantly correlated with MMEs taken (ρ = 0.406 P< 0.05) during the 2-week postoperative period  ABCs and NRS to each other, (2) reported need for painmedication at the time the pain scale was completed, (3) milligrams of morphineequivalents (MMEs) prescribed on postoperative discharge, and (4) patient-reporteduse of MMEs during the first 2 postoperative weeks in patients undergoing THA. Thisis a pilot study that was done to gain knowledge to justify a larger, more expansivestudy to confirm the validity and usability of the functional pain assessment tooldeveloped. We found that pain levels with three ABCs functions—sitting up,walking in room, and walking outside of the room—on the day of dischargemarkedly correlated with self-reported MME needs in the first 2 weeks after surgery.The composite ABCs score did not correlate, indicating that pain with certainfunctions may be more important than global ratings of pain for analgesia needs.Interestingly, neither the NRS nor the composite ABCs score correlated with MMEsprescribed at discharge, indicating that prescribing is standard for a givenprocedure, rather than taking into account the patients’ reported pain andfunction. Although some individual functions did correlate with MME needs, thecomposite ABCs did not. This illustrates that although the functional recovery inthe perioperative period from THA is dynamic and potentially difficult to adequatelyassess, there are functional markers than can guide management postoperatively. TheABCs composite score of all functions correlated with the NRS at baseline,throughout the hospital stay, and at the follow-up. The NRS at discharge wascorrelated with MMEs used. However, patient reported the need for medication at thetime of pain scale completion was even more strongly correlated. This suggests thatunidimensional measurements of pain intensity may not be useful for guidinganalgesia prescribing decisions, highlighting one of the benefits of linking painwith function during assessments. This may indicate that patients believe pain ispathologic and requires treatment, rather than basing decisions about analgesia onhow pain is affecting their functionality. Although not a primary outcome, we alsonoted significant differences in pain prescribing and usage patterns between men andwomen patients.12Common hospital discharge criteria include the ability to independently transfer inand out of bed, a chair, and a toilet seat; independently ambulate approximately 150feet; and independently negotiate stairs.13 Previously developed pain assessment studies have attemptedto include functional metrics. For example, the Osteoarthritis-Function-ComputerAdaptive Test (OA-FUNCTION-CAT) was designed for clinical research purposes to trackoutcomes in patients with osteoarthritis. The test consists of 125 written promptsregarding functional activities. The patient assesses a range offunctions—“turning in bed” to “sitting down on a soft,low couch” to “jumping and landing on your rightleg.”14 Such largenumbers of functions to assess, however, can lead to survey fatigue and overalldifficulty completing assessments. The Defense and Veterans Pain Rating Scale, whichis similar to a NRS, also attempts to assess function, containing a question onsleep and activity.15 The Defenseand Veterans Pain Rating Scale reportedly included these functions to urge thepatient to consider how pain affects their life and provide the opportunity to gaugelongitudinal progress.16 Althoughthese potentially represent improvements over unidimensional scales, they have notbeen implemented to guide real-time decision-making.Pain associated with performance of functional tasks is important to assess,especially in the postoperative setting when patients must meet various functionalmilestones to be discharged.17 Languagebarriers, time constraints, and disparities of the education level may be mitigatedby tools that bridge communication gaps, such as infographics.18 In addition, the ABCs assessesfunctions that can be done both in a hospital and at home. Patients complete thesame checklist hours after their surgery as they do 2 weeks after the surgery. Thisallows for consistent longitudinal pain and function monitoring. Although notinvestigated in this study, the ABCs was designed to be customizable to reflect thesurgery done and anticipated pain associated with that specific surgery that maylimit function. This would allow surgeons and other providers to add additionalfunctional outcomes specific to their patient population.The ABCs scale is unique in multiple ways. First, it uses infographics illustratingthe activity in question, whereas most other pain assessment tools only containtext. Infographics are an emerging tool used in health care to enhance theunderstanding of health conditions and give patients the ability to make decisionsfor themselves.19However, many patients still feel as if their pain is not understood andundertreated even when receiving opioid prescriptions.20The scale used in this study contained important functions to assess, in increasingorder of difficulty, as determined by several key informant interviews withorthopaedic surgeons. Interestingly, we found that “walking upstairs,” which was deemed by the surgeons to be the most difficultpostoperative task and therefore placed at the bottom of the scale, was typicallynot the most painful for our participants at different parts of their recovery.However, this study showed that sitting up, walking in room, and walking outsideroom were the most important functions before discharge, and out of bed to chair wasthe most important function at the 2-week postoperative follow-up. Functionalimportance was determined because these are the actions that markedly correlatedwith MMEs taken. More studies of pain related to function may help determine whichfunctions are the most important and predictive of analgesic needs from the patientperspective, rather than the provider perspective. This insight is important tofacilitate meaningful communication between patients and their care teams. Forexample, previous studies have shown that patients report higher self-efficacy,lower pain intensity, and less pain interference within their lives if they perceivepatient-centered communication.21 For example,the Michigan OPEN recommendations for the quantity of 5 mg hydrocodone-acetaminophentablets to prescribe after THA are 0 to 30 tablets (0 to 150 MMEs).22 In our study, subjectsconsistently received opioid prescriptions that ranged from 3 to 6 times thisamount. High-risk prescribing is determined to be greater than 90 MMEs per day andtherefore suggests a higher risk of adverse events.23 According to this designation, all of theparticipants in our study were receiving high-risk prescriptions and were thus moresusceptible to adverse events.At discharge, patients were not consistently prescribed the same pain control regimenwithin our cohort. The range of MMEs prescribed was 450 to 939 for men and 488 to938 for women. The reasons for these variations are unclear, given that thecomposite ABCs, individual functions included on the ABCs, or NRS correlated withMMEs prescribed at discharge. Furthermore, all patients in our study underwentanalogous procedures. Complex, bilateral, and traumatic cases were intentionallyexcluded. Noteworthy is that procedure-specific opioid prescription guidelines areavailable, but they are often based on expert opinion rather than evidence and tendto be quite broad.24-26 Our findings similarly support the importance ofmultimodal and functional pain assessment. For example, we found 3 functions on theday of discharge—“sitting up,” “walking in room,”and “walking outside room”—to correlate with MMEs needed in thefirst 2 weeks after postoperative discharge home. These individual functions weremore important than the composite ABCs score. At discharge, the NRS did correlatewith MMEs taken at r = 0.571. However, at the 2-week follow-up, only“out of bed to chair” correlated with MMEs taken, indicating thatassessing this function at the 2-week follow-up is important for understanding apatient's analgesic needs at that point of dynamic functional improvement. Inaddition, pain ratings are interpreted differently among clinicians and patientsbased on their previous experiences with pain, culture, and comorbidities , further demonstrating the need for tools to facilitatephysician-patient communication regarding pain management plans.27 Pain assessment linking pain withfunction provides a better contextual understanding of pain and may facilitatephysician-patient communication regarding pain management plans and expectations.This is particularly important in the setting of procedures, such as THA, which aimto improve function.Procedure-specific, restrictive opioid protocols are gaining popularity, likely toensure similar treatment for similar pathologies. However, previous studies havecautioned against using unidimensional patient-reported rating of pain to decideopioid prescription choices because these pain scores fail to account for thesubjective, complex nature of pain and because their use has been implicated infostering the prescription opioid epidemic.29 One explanationfor this is that female patients with cancer have been found to be more hesitant totake pain medication and adhere to prescribed pain regimens despite reportinggreater pain intensity than their male counterparts.30 Interestingly, we found no differences in painreporting between male and female patients, yet the male patients took higherproportions of their prescribed pain medication. Further research is needed todelineate the biological and social underpinning for this phenomenon.In our study, we found that female patients took a smaller proportion of theirprescribed MMEs than male patients did at our 2-week follow-up time point. Theproportion of MMEs taken as prescribed, 42.0% for women and 59.2% for men, indicatesthat providers are overprescribing to both sexes, leaving opioids unused, andpotentially available for misuse. Although there is evidence that opioid use inwomen has increased in the past decade, the women in our study still took fewer oftheir prescribed opioid analgesics than the men.The study was not without limitations. The sample size was relatively small for 39patients. However, subject demographics closely reflect that of the state in whichthe study was done, enhancing external validity. Twelve patients were lost tofollow-up between discharge and first postoperative visit. Administering the visualsurvey over the phone could have led to researcher bias because we were the onesinterpreting the responses and recording the results. The 2-week follow-up call wasdone over the phone, and therefore, patients self-reported the number of MMEs taken.We did not collect data on when these pain medications were consumed but rathercollected a total number over the 2-week postoperative period. We attempted tominimize the variability in the telephone 2-week postoperative survey delivery byhaving the same two research team members call the patients and following apredetermined script. The process of self-report is subject to recall bias andsocial desirability bias. The latter is particularly true for behaviors that may beperceived as high-risk such as taking large amounts of opioid analgesics. However,we do not think that these factors markedly biased results because patients wereasked to count remaining opioid medications to determine how many had been taken.Finally, study team members were not involved in the clinical care of subjects, andstudy results were not shared with their surgical teams. The scale does leave roomfor interpretation on certain function such as “sleeping” or“lying down.” Anecdotally, some patients did not count“napping” as sleeping, and there was ambiguity about what constitutes“lying down” versus “sitting up.” Study participantswere enrolled the day of surgery, and information relayed on the day of surgery maybe difficult for patients to retain, given that they typically have to manage alarge amount of information from a variety of different providers on the day oftheir surgery. Surgery under general anesthesia also has the potential to causeretrograde amnesia. However, we do not think that this markedly affected resultsbecause research persons were present and available to answer any questions eachtime the patient completed the ABCs pain scale. Finally, it is important to rememberthat patient experience of pain is inherently variable and subjective, influenced byprecounseling by the surgical team, previous experiences with pain, or culturalnorms surrounding expressing pain. Future work will include qualitative componentsof the patient pain experience to inform future iterations of the ABCs and ensurethat it is of maximum benefit to both patients and their care teams for assessmentof, and communications about, pain.This study demonstrated that pain with specific functions on the ABCs after THAbefore discharge is correlated with MMEs taken in the first 2 postoperative weeks.Pain levels did not influence the amount of MMEs prescribed at discharge. Assessmenttools, such as the ABCs, that include functional metrics may better communicate painand analgesia needs. Clinicians should incorporate function, especially those foundto correlate with MMEs taken—“sitting up,” “walking inroom,” and “walking outside room”—and functionalimprovement postoperatively to guide prescribing patterns. Pain assessment tools,and subsequently patient-provider communication, require functional measures toadequately capture pain management needs. Additional studies are needed to validatethis pilot study among a larger, more diverse cohort.