Pain assessment is associated with important outcomes in ICU patients but remains challenging, particularly in non-communicative patients. Use of a reliable tool is paramount to allow any implementation of sedation/analgesia protocols in a multidisciplinary team. This study compared psychometric properties  of three pain scales: Behavioural Pain Scale , Critical Care Pain Observation Tool (CPOT) and Non-verbal Pain Scale (NVPS), the pain tool routinely used in this 16-bed medical ICU.th to 75th).Pain was assessed by at least one of four investigators and one of the 20 bedside nurses before, during and 10 minutes after routine care procedures in non-comatose patients  who were unable to self-report their pain intensity. The Confusion Assessment Method for the ICU was used to assess delirium. Non-parametric tests were used for statistical analysis. Quantitative data are presented as median . Responsiveness was significantly higher for BPS compared to CPOT and for CPOT compared to NVPS. For feasibility, BPS was rated as the easiest scale to remember but there was no significant difference in regards to users’ preference.A total of 258 paired assessments of pain were performed in 30 patients . All three scales demonstrated good psychometric properties. However, BPS and CPOT exhibited the best inter-rater reliability (weighted-κ 0.81 for BPS and CPOT) and the best internal consistency , which were higher than for NVPS  contains supplementary material, which is available to authorized users. Pain is a frequent event in Intensive Care Unit (ICU) patients, with an incidence of up to 50% in medical as well as surgical patients–3. Pain The protocol was approved by the Institutional Review Board of University of Chicago Hospitals . Written consent was obtained from the legally authorized representative or a proxy/surrogate decision-maker (patient’s next of kin) who gave consent on the patient’s behalf.The study took place in the 16-bed medical ICU of the University of Chicago Hospitals, an academic tertiary care hospital, from January 2012 to June 2012 (six months). All consecutive patients ≥18 yrs old were eligible for enrolment if they had a Richmond Agitation Sedation Scale (RASS), 22 abovInvestigators screened patients daily for eligibility including RASS assessment, self-report pain ability by the patient and possibilities to plan any routine procedures of care with the bedside nurse. After having obtained consent from the surrogate decision-maker and having enrolled the patient into the study, investigators planned different procedures of care with the bedside nurse including: (1) a simple repositioning of the patient in the bed (moving the patient up or onto their side), (2) a complete turning of the patient onto both sides in order to wash their back and change the sheets, (3) a tracheal suctioning if possible (intubated patients), and (4) a mobilisation by physiotherapist/occupational therapist if possible.Pain evaluation using the three different behavioural pain tools  was independently performed at the same time by two or three paired evaluators  in three conditions for each patient: (1) at rest, before any procedure; (2) during the care procedure; and (3) 10 minutes after the procedure. Every patient was assessed during a simple repositioning and a complete turning on both sides. Patients were evaluated during tracheal suctioning or mobilisation if possible. Turning and suctioning were chosen because they are the most common and/or painful procedures in the ICU setting, 25. RepFor all these measurements, investigators and the bedside nurse were blinded to each other, each observer using a separate sheet , similarly to the CPOT that includes both types of descriptors, either for intubated or non-intubated patients.2) between weight (kg) and height squared (m2). Type and doses of sedatives and analgesic drugs were collected before any procedures. In addition to the RASS measurement by investigators, delirium was assessed upon enrolment by the Confusion Assessment Method for the ICU (CAM-ICU)[Age, gender, height and weight, co-morbidities, and reason for admission to the ICU were recorded. Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were calCAM-ICU), 31. PhyCAM-ICU).1.1Inter-rater reliabilityInter-rater reliability of the three tools (primary endpoint) was tested by the weighted kappa coefficient. A kappa coefficient above 0.80, 0.60 and 0.40 is considered as measuring respectively a ‘near perfect’, ‘important’ and ‘moderate’ agreement . CompariTo deal with repeated measurements, a sensitivity analysis was performed taking into account first assessments only, as previously described . Moreove1.2Internal consistencyInternal consistency was measured using the Cronbach-α method . A Cronb1.3Discriminant validationDiscriminant validation was determined by comparing total scores obtained during different situations and stimuli, that is at rest and during a procedure  as well as during procedures with different durations and intensities, that is during a simple repositioning and during a complete turning. The Mann-Whitney-Wilcoxon test was used to test the difference between two different situations. We tested the responsiveness of the three tools as another way to measure change, that is the ability to detect change regarding different situations even if those changes are small. The magnitude of this property was assessed by the effect size . The eff1.4FeasibilityFeasibility was assessed by administering a standardised questionnaire once to the bedside nurses during their initial participation in the study interventions. The nurses were asked to rate their preference of each particular pain scale, as well as the degree of accuracy when used for routine practice or research purposes, and the ease of learning.Psychometric properties related to the use of pain tools were assessed using the new terminology as recomThe primary endpoint was the inter-rater reliability because this psychometric property is paramount and, if deficient, precludes implementation of a pain tool and associated diagnostic and therapeutic pain strategies by the ICU team, 4, 16. th to 75th percentiles. A P value of ≤0.05 was considered statistically significant. Data were analysed using the SAS software version 9.1 .Quantitative data are shown as medians and 25During the study period, 258 paired observations of pain behaviour were done with each pain tool in 30 patients by 24 observers (20 registered nurses (RNs), 4 investigators) during 75 procedures: repositioning, n = 30; turning onto both sides for bathing, massage and changing the sheets, n = 30; suctioning, n = 14; mobilisation for physical therapy, n = 1. A consort flow chart of patient enrolment is shown in Figure P<0.05 compared to BPS and CPOT). Using only the first assessments for each patient, the weighted kappa coefficients for BPS, CPOT and NVPS were unchanged at 0.88, 0.80 and 0.67, respectively.Inter-rater reliability was evaluated by weighted kappa coefficients, which are summarised in Table P<0.05). Inter-rater reliability was not significantly different in intubated compared to non-intubated patients for NVPS (0.71 ± 0.04 vs. 0.74 ± 0.05) and CPOT (0.80 ± 0.03 vs. 0.82 ± 0.05). BPS had a significantly greater inter-rater reliability in non-intubated than intubated patients . Finally, within an error of one point, inter-rater agreement was significantly (P<0.01) greater for BPS (81%) and CPOT (77%) than for NVPS (65%) for all the observations (before and during the procedures), as well as for observations made during the procedures only .Table P<0.01) and CPOT (P<0.001) compared to NVPS. The difference between BPS and CPOT was not significantly different (P = 0.48).Measurement of Cronbach-α coefficients showed a satisfactory internal consistency for each of the three scales: 0.80 for BPS, 0.81 for CPOT and 0.76 for NVPS. Cronbach-α was significantly greater for BPS (P = 0.15) and CPOT  contrary to NVPS .There was no significant difference in Cronbach-α coefficients between intubated and non-intubated patients for BPS  and a significant decrease 10 minutes after the procedure (P<0.001). The median scores were not significantly different between observations made at baseline and observations made after the procedure . Discriminant validation was also tested comparing median scores observed during two similar situations differing by the intensity and the length of the procedures, that is repositioning and turning onto both sides. There was also a significant difference between these two procedures for each of the three tools (P<0.001). Finally, turning and suctioning were the most painful procedures .Figure  Figure . DiffereResponsiveness of the scales was tested by the effect size coefficient, which was large (>0.80) for each of the three scales when calculated between baseline and observations done during the procedures: BPS = 1.99; CPOT = 1.55; NVPS = 1.46. BPS and CPOT demonstrated a significantly higher responsiveness than NVPS, as well as BPS compared to CPOT. The effect size coefficients also remained large when calculated between the repositioning and turning procedures , without any significant differences between the three scales.P = 0.02), but the BPS was the same as the NVPS (P = 0.07): BPS, 8[P values >0.49) between the three tools either with regard to accuracy  rated the three tools at a median of 7 to 8  for accuracy, usefulness and ease of learning. The BPS was rated higher with regard to ease of learning than the CPOT  or us . ObseThe main findings of this study are that BPS, CPOT and NVPS have good psychometric properties but BPS and CPOT have significantly higher inter-rater reliability, internal consistency and responsiveness than NVPS. Discriminant validation was good for all three scales. There was no difference in regards to feasibility except for BPS, which is rated a little easier to remember than the other scales, with only three domains of observation rather than four and six for CPOT and NVPS. Scales’ preference was variable among users, with no scale demonstrating any consensus. In all, either BPS or CPOT appear to be superior tools and should be chosen in the ICU where no behavioural pain scale has been implemented yet, consistent with the recent Practice Guidelines.These data are consistent with a recent study aimed at comparing CPOT and NVPS in mostly intubated patients, which found a better inter-rater reliability for CPOT. MoreovePain is one of the most stressful events experienced by patients during their ICU stay, 41. At Finally, if using tools demonstrating the best psychometric properties such as BPS or CPOT might be recommended, it is unknown whether a small but significant difference in psychometric measurement is clinically relevant or not in regard to patients’ outcome. Also, clinical studies are still needed to determine which threshold is the most effective in regard to ICU outcome  but also in regard to outcome after ICU discharge ). Then, further studies are needed to determine how it would be the most effective to educate, train and assess healthcare givers when using subjective behavioural pain tools to increase their reliability in research and routine use. Results of this study showed that repeated education and training is paramount to assure important inter-rater reliability of a tool as previously showed with the use of sedation and delirium tools in the ICU setting. A diffeBPS, CPOT and NVPS demonstrate good inter-rater reliability in both intubated and non-intubated ICU patients unable to self-report their pain intensity. BPS and CPOT have significantly higher inter-rater reliability, internal consistency and responsiveness than NVPS, which psychometric properties remain, however, acceptable in general but not for the physiological domains. Discriminative validation is important for all three scales. There is no difference in regard to feasibility except for BPS, which is rated a little easier to remember. However, no scale demonstrated any consensus among users. Either BPS or CPOT should be used in intubated and non-intubated patients unable to self-report, particularly when no behavioural pain scale is already available in an ICU setting.BPS and CPOT have significantly higher inter-rater reliability and internal consistency than NVPS in intubated and non-intubated ICU patients unable to self-report their pain intensity.BPS demonstrates significantly highest responsiveness.Psychometric properties are acceptable for NVPS in general but not for the physiological domains.No scale demonstrates a better feasibility among users.Because of significantly better psychometric properties, either BPS or CPOT should be used in intubated and non-intubated ICU patients unable to self-report.Data sheet for observers’ pain assessments. This additional file provides the sheet used by the observers during the study to independently assess pain with each of the three tools: BPS, CPOT and NVPS. Note that descriptors and instruction of use were written for each tool to avoid any learning issues. (PDF 177 KB)Additional file 1:


Cigarette smoking is common among adults with chronic pain. The primary objective of this study was to determine the period prevalence of smoking in patients with chronic pain. A secondary objective was to determine the prevalence of smoking among patients with commonly occurring pain diagnoses including fibromyalgia, low back pain, and headache.This population study included 5350 patients  admitted to the Mayo Comprehensive Pain Rehabilitation Center from January 1998 through December 2012. Smoking status was determined using a self-report questionnaire.During the 15 year study period, the overall prevalence of smoking was 23.5 % (95 % CI 22.4 – 24.6). The prevalence of smoking in 2000, 2005, and 2010 was 24.2, 25.7, and 28.3 % respectively. The overall prevalence of smoking in patients with fibromyalgia, low back pain, and headache was 25.2 % (95 % CI 22.8 – 28.3), 22.8 % (95 % CI 21.3 – 25.9), and 21.2 % (95 % CI 17.9 – 24.7), respectively. In a multiple variable logistic model adjusted for age and sex, opioid use was significantly associated with status as a current smoker.The prevalence of smoking in patients with chronic pain has not declined when compared to the general population. The higher prevalence of smoking was consistently observed in commonly occurring pain diagnoses including fibromyalgia, back pain, and headache. Further research is needed to identify the potential factors that contribute to the high prevalence of smoking in this patient population. The single greatest preventable cause of death in the United States is cigarette smoking . The heaThe prevalence of smoking in the general population has declined over the past decade, but is still estimated at 19.3 % . HoweverThis study was approved by the Mayo Foundation Institutional Review Board, and all patients provided prior written consent for use of their medical records for research purposes. Inclusion criteria included admission to the Mayo Comprehensive Pain Rehabilitation Center from January, 1998 through December, 2012, age ≥ 18, and pain duration ≥ 6-months. Exclusion criteria included use of other forms of tobacco besides cigarettes including oral tobacco, cigars, or pipe. Patients who did not indicate smoking status were excluded from study participation. During this time period, 5617 patients with chronic pain were admitted to the pain treatment center; 267 patients (4.9 %) were excluded from study participation due to use of other forms of tobacco and missing data. The population study was comprised of 5350 individuals .The study setting was a 3-week, outpatient pain rehabilitation program. Descriptions of this treatment setting have been previously reported , 17, 18.Smoking status was assessed upon admission to the pain treatment center using a self-report questionnaire as previously described , 17. IncUpon admission, the primary anatomical site of chronic pain or underlying pain condition  was identified and used as the primary pain diagnosis. This approach for identifying the primary pain diagnosis has been extensively used in our pain treatment program , 17, 18.P < 0.05. All analyses were completed using JMP version 9.0.1 .The summary statistics for continuous data were reported as an average , and categorical data were reported as a number (percent). The demographics and clinical characteristics  were summarized for smokers and nonsmokers. The comparison between smokers and nonsmokers was made using chi-squared test for categorical variables and univariate analysis of variance for continuous variables. The proportion of smokers and nonsmokers in the year 2000 was compared to the proportion of smokers and nonsmokers in 2005 and 2010 using chi-squared tests. Multiple variable logistic regression analysis was used to assess the potential associations between smoking status (dependent variable) and opioid use (independent variable) in a model adjusted for age and sex. Similarly, multiple variable logistic regression analysis was used to assess the potential associations between smoking status and ethnicity in a model adjusted for age and sex. For purposes of this particular analysis, the Hispanic and African American groups were combined and the “undisclosed” ethnic group was omitted. Two-sided tests were used in all analyses, and the level of significance for all statistical tests was set at n = 5350) was comprised of 1256 smokers and 4094 nonsmokers. The total number of women was 3812 and the total number of men was 1538 (Table The population study (P > .1). Similarly, no significant difference was observed in the proportion of patients who smoked in the year 2000 compared to 2010 (P > .1).During the 15 year study period, the overall prevalence of smoking was 23.5 % (95 % CI 22.4 – 24.6). The yearly trend for smoking prevalence ranged from 19.9 to 28.3 % (95 % CI 24.2 – 32.7) , 22.8 % (95 % CI 21.3 – 25.9), and 21.2 % (95 % CI 17.9 – 24.7), respectively.P = < .001 ). In a logistic regression model adjusted for age and sex, no significant association was found between ethnicity and smoking status .In a logistic regression model adjusted for age and sex, opioid use was significantly associated with status as a current smoker  and African American (n = 22) adults with chronic pain was 11.5 and 31.8 %, respectively [Although no significant association was found between ethnicity and smoking status in our study, the prevalence of smoking among Hispanic and African Americans was mixed when compared to the general population. For example, in the general population the prevalence of smoking among Hispanics in 2000, 2005 and 2010 was 18.6, 16.2, and 12.5 %, respectively . During ectively , 15, 16.The three most commonly occurring pain diagnoses in our study sample were fibromyalgia, low back pain, and chronic headache, and the observed prevalence of smoking among patients in these diagnostic groups extends and confirms the observations of previous studies. The prevalence of smoking among patients with fibromyalgia during the 15 year study period was 25.2 %. In previous studies, the prevalence of smoking among patients with fibromyalgia ranged from 9.8 to 25.5 % , 39, 40.This study has limitations. First, the majority of study participants were Caucasian women residing in the United States, and all study participants were specifically referred for pain rehabilitation at a tertiary medical center. This is consistent with the referral pattern of our pain treatment program , 15, butIn summary, the prevalence of smoking in patients with chronic pain has not declined when compared to the general population. The high prevalence of smoking was consistently observed in commonly occurring pain diagnoses including fibromyalgia, back pain, and headache. The high prevalence of smoking among patients with chronic pain could be related, in part, to unique factors that exist in this patient population including concurrent opioid use.


Low back pain is a major cause of disability and can result in substantial morbidityand high healthcare costs. Botulinum toxin has been used successfully to alleviate painfor a number of conditions caused by muscle contractions or spasms.The aim of this study was to investigate the efficacy of botulinum toxin type A for treating chronic low back pain (CLBP).This was a single-blind, randomized clinical trial study. Fifty patients with CLBPreceived either BoNT-A (40 Ipsen units per injection) or saline in 5 sites in theparaspinal muscles (n = 25 per group). A visual analogue system (VAS) was used tomeasure pain levels at baseline and at 4 and 8 weeks post-injection. Disability wasassessed using the Oswestry low back pain disability questionnaire at baseline and at 8weeks post-injection.After 4 weeks, 76% of patients in the BoNT-A group reported pain relief compared to 20%in the saline group (P < 0. 005). Additionally, greater pain relief was experiencedby patients in the BoNT-A group at 8 weeks . By week 8,significant functional improvement (a minimum two-grade improvement between baseline andpost-treatment assessments) was demonstrated in a higher number of patients receivingBoNT-A than in the saline group . Patientsexperienced only minor side effects.BoNT-A improves CLBP with a low incidence of side effects and can be used as atherapeutic tool in the management of these patients. Back pain is a widespread cause of pain and disability and results in substantialhealthcare costs worldwide . AccordiChemical denervation using botulinum toxin has revolutionized treatment formany disorders involving excessive muscle activity , includiNey et al. reported a significant improvement in back and radicular painafter botulinum type A toxin injection ; ina stThe aim of this study was to assess pain and disability reduction following localClostridium BoNT-A hemagglutinin complex injections in paravertebral muscles at sites ofmaximum discomfort in CLBP patients. We investigated the minimal effective dose of toxin forsafe outpatient treatment.A total of 50 patients with CLBP who were referred to our clinic over the course of 18months were enrolled in this single-blind, randomized clinical trial. Patients who met thefollowing inclusion criteria were randomized to receive either BoNT-A  (n = 25) or saline (n = 25):CLBP for a period of at least 6 months;Ages 18–55 years old;Consent to participate.Exclusion criteria included the following: congenital or severe spine deformity; chronicsystemic disorder; history of allergic reaction to BoNT-A; current or planned pregnancy;breast feeding; history of neuromuscular junction disorder; presence of motor neurondisease; primary muscle weakness; malignancy; bleeding tendency, as well as the presenceof acute pathology; any previous injection in paravertebral muscles in a 6-month period;and suspected secondary gain. At each session, patients were evaluated for current andpast medical history and given a physical examination.BoNT-A was prepared by re-constituting frozen-dried toxin with sodium chloride injectionBP to a concentration of 100 Ipsen units/mL. The solution was drawn into a 1-mL syringeand injected through a 25-gauge needle. The needle size was adjusted according to thepatient’s level of body fat to ensure that the study treatment was delivered to thetarget injection site. Patients were given 5 injections of 40 Ipsen units each at 5equidistant lumbosacral sites (L1 to S1) in the paraspinal muscles. Tender or triggerpoints were chosen as starting points for injections in both groups. All patients wereinjected by the same person once unilaterally on the side of maximum discomfort. Duringthe study, patients were recommended to continue previously prescribed medication at theirnormal dosages.The level of pain was evaluated in each patient using the VAS . The degThe VAS consisted of a 10-cm horizontal line, labeled with “no low backpain” at one end and “worst low back pain” at the other end. Patientswere asked to mark the line at a point on the line corresponding to the level of pain theytypically experienced. The distance between the point of “no low back pain”and the patient’s mark was measured in centimeters and used as a numeric index ofpain severity and change in pain. A significant clinical improvement in pain relief wasdefined as a 50% or greater difference in pre- and post-treatment VAS scores. VASassessments were recorded at baseline and at 4 and 8 weeks post-treatment.Results were analyzed by an independent data management group. SPSS software version 15was used for statistical analysis . Patients were included in analysis onthe basis of intention-to-treat. The VAS score at baseline, 4 weeks, and 8 weeks wastested using repeated measures analysis of variance (ANOVA). The normality of variableswas evaluated using Kolmogorov–Smirnov tests. According to the normality of thevariable, the 2-sided paired and t-test (Wilcoxon signed-rank test) were used for between-and within-group comparisons, respectively. Demographic variables were compared usingFisher’s exact test and t-test. Adverse event frequencies were compared using thechi-square and Fisher’s exact tests.All 50 patients consented and completed the study. The mean age of patients was 42 years. Of the 25 patients in each group, 13 women were assigned tothe BoNT-A group and 14 women received saline. The mean duration of pain was 4 years (8months to 9 years) and the mean pain score on the VAS was 6. 5. At baseline, functionalimpairment was recorded in 4 to 10 subsets on the OLBPQ. On the basis of ANOVA results, we concluded that there was no significant differencesbetween the treatment and control groups. A comparison of both groups showed no baselinedifferences in VAS score and OLBPQ subsets .At week 4, 19 of 25 patients (76%) who received BoNT-A showed a clinical response on theVAS compared with 5 of 25 patients (20%) in the group receiving saline . At week 8, 16 of 25 patients (64%) in the BoNT-A group experiencedsignificant pain relief compared with 3 of 25 patients (12%) in placebo group .Functional improvement was also demonstrated in patients who received BoNT-A . By weekThere was no evidence of significant complications or pain exacerbation in eithergroup.The aim of this study was to assess pain and disability reduction following localClostridium botulinum type A toxin injections and placebo treatment in patients with CLBP.In this single-blind, placebo-controlled study, significant inter-group differences forindividual pain scores were demonstrated. Patients who received BoNT-A as a therapeuticintervention showed a lower pain score compared to the placebo group. Furthermore, our studyshowed a statistically significant difference in functional improvement in theBoNT-A-receiving group. Treatment was safe, and no side effects were observed. Our resultsare similar to those of a small, double-blind trial involving BoNT-A administration fortreating CLBP . SimilarBoNT-A is a potent inhibitor of acetylcholine release as wellas a number of other neurotransmitters and neuropeptides. Botulinum toxin exerts its effectsthrough inhibiting excessive acetylcholine release; it also has muscle relaxant properties,preventing stimulation of muscle nociceptors. It has also been postulated that botulinumtoxin may have an analgesic effect, although the precise mechanism of action is unknown, 31. Add


We developed a user-friendly Internet-based tool for patients undergoing total hip replacement (THR) due to osteoarthritis to predict their pain and function after surgery. In the first step, the key questions were identified by statistical modelling in a data set of 375 patients undergoing THR. Based on multiple regression, we identified the two most predictive WOMAC questions for pain and the three most predictive WOMAC questions for functional outcome, while controlling for comorbidity, body mass index, age, gender and specific comorbidities relevant to the outcome. In the second step, a pilot study was performed to validate the resulting tool against the full WOMAC questionnaire among 108 patients undergoing THR. The mean difference between observed (WOMAC) and model-predicted value was −1.1 points  for pain and −2.5 points  for function. The model-predicted value was within 20% of the observed value in 48% of cases for pain and in 57% of cases for function. The tool demonstrated moderate validity, but performed weakly for patients with extreme levels of pain and extreme functional limitations at 3 months post surgery. This may have been partly due to early complications after surgery. However, the outcome-prediction tool may be useful in helping patients to become better informed about the realistic outcome of their THR. Pain associated with OA can be relieved with analgesics, and, later, with total joint replacement. However, like any surgical procedure, THR is associated with some morbidity and mortality2, and does not fully alleviate pain or restore function in most individuals3. This may be partly explained by psychosocial and comorbid conditions that affect the outcome independent of the procedure.4Osteoarthritis (OA) is the leading cause of disability in old age.7 Its length of 24 items, however, restricts its use in elderly people.8 A further limitation of the WOMAC is that key demographic variables and co-morbid conditions, described as independent predictors of outcome in the literature, are not considered. For example, body mass index, mental health, comorbidities and age are important independent predictors of the outcome after THR.11Pain and functional limitation of the joint are the two factors that bother patients the most and cause them to undergo THR. The WOMAC (Western Ontario and McMaster Universities) osteoarthritis index is the most widely used tool that measures these outcomes. The WOMAC questionnaire has been thoroughly validated in clinical trials in patients with hip and knee OA.The aim of the present study was to develop and validate a simple and comprehensive Internet-based assessment tool to help middle-aged and elderly patients undergoing THR predict their pain and functional level after the surgery.In the first step, the key questions were identified by statistical modelling in a data set of 375 patients undergoing THR. In the second step, a pilot study was performed to validate the resulting tool against the full WOMAC questionnaire among 108 patients undergoing THR. The study was approved by the appropriate ethics committee.12 we used data that were originally collected for a Swiss THR study.13 There were 375 participants, of mean age 70 years (SD 11), 261 (70%) of the participants were age 65 years or older, and 187 (50%) were men.In developing the hip QUALITOUCH outcome calculator (QOC),14 A standard package was used A predictive model was developed to estimate the change in WOMAC scores for pain as a result of THR surgery. A second predictive model was developed to estimate the change in WOMAC function scores. We identified the WOMAC questions that were the strongest predictors of change in WOMAC pain and function scores from pre- to postoperative value. To keep the tool short, we limited it to the two most predictive WOMAC questions that assessed pain and the three most predictive questions that evaluated function by regression analyses. The appropriate questions were identified by regression: the change in pain was regressed on WOMAC questions 1–5, and the change in function was regressed on WOMAC questions 8–24. Potential explanatory variables were removed by backwards elimination.P-value (as long as P > 0.05) was eliminated from the model; then the model was re-run and the procedure repeated until two questions with the smallest P-values remained in the model. These questions were: “How intense is your joint pain walking on a flat surface?” and “How intense is your joint pain sitting or lying in bed?”.The initial pain model contained scores for all pain-related WOMAC questions. The question with the highest Using the same procedure, the following three questions were selected for the post-surgery function model: “How difficult is it to go shopping?”, “How difficult is it to put on your socks?” and “How difficult is it sitting on a toilet and standing up again?”.15 showing that hip OA patients with musculoskeletal comorbidities, such as low back pain and OA of the non-operated hip, have less long term functional improvement after THR. The procedure was carried out separately for the pain and the function predictive models, and all variables maintained in the models were required to achieve a P-value of 0.15 or less. The following conditions were significant for prediction of pain: kidney disease, liver disease, back surgery, obesity, high blood pressure, total hip replacement, use of alcohol or drugs and total number of medicines taken by the patient. The following conditions were significant for prediction of function: back surgery, back pain, obesity, high blood pressure, total hip replacement, lung disease, height, use of alcohol or drugs and total number of medicines taken by the patient.At the second stage of model development, 17 comorbidity indicators: 13 from the Sangha comorbidity index  plus four additional yes/no questions assessing musculoskeletal pain , age, gender and body mass index, were included in the predictive models and exposed to a forward stepwise selection procedure. We included the four additional questions on musculoskeletal pain based on the work by Nilsdotter and colleaguesThe final models predicted change between pre- and post-surgery levels of pain and function. The 95% confidence intervals (95% CI) calculated by the models were very wide: on average 80 WOMAC points for pain and 72 points for function. Since the entire WOMAC scale is 100 points, such wide confidence intervals are of limited value. As a reasonable compromise between precision and usability, we used 70% confidence intervals which were on average 42 and 38 points for pain and function respectively.All participants answered the hip outcome calculator questions before surgery and an electronic version of the WOMAC questionnaire (version 3.1) before and at 3 months after THR surgery. We chose the 3 month follow-up as the time where most improvement after surgery is usually achieved. The range of the WOMAC subscale score was transformed to 0 to100 points, where a score of 0 indicated no pain or best function and 100 indicated maximum pain or absolute loss of function.Patients’ responses to the WOMAC questionnaire at 3 month follow-up and the outcome calculator before surgery were evaluated and compared to test the validity of the latter. The outcome calculator gave three estimates for change in pain and function: an average predicted change, and lower and upper limits for the 70% confidence interval as worst case and best case scenario estimates (see above on the reason why 70% rather than 95% CI were applied).The predictive model calculates probable change in pain and function. The change is calculated as a negative value in WOMAC score units, say -20. Then this calculated change is subtracted from the pre-surgery WOMAC score reported by a patient. The resulting difference is the predicted post-surgery score.Post-surgical WOMAC pain and WOMAC function scores reported by the participants were used as comparisons to evaluate validity of the model predictions.The final model-predicted point estimates and calculated 70% confidence intervals for change in pain and function used the standard procedure for the least-squares linear model.For the validity test of the outcome calculator, we calculated the differences between predicted post-surgical pain and function levels and the actual observed WOMAC pain and function levels reported by the study participants at 3 months after surgery. Average differences between observed and predicted values were calculated to evaluate size and direction of bias. Model performance was further assessed by estimating the probability that the predictive model under- or overestimated the true value and the probability that model-predicted results would not deviate from the true value by more than 20% on either side.To assess the intra-rater reliability of the outcome calculator, we evaluated agreement between two assessments in 11 participants by calculating the intraclass correlation coefficient (ICC) for the results for pain and function.The characteristics of the participants enrolled in the validation study are summarised in On average, the predictive models tended to be conservative and to overestimate postoperative pain levels by 1.12 WOMAC points (95% CI −3.76 to +1.52) and function levels by 2.49 points (95% CI −5.27 to + 0.29), see The distribution of differences between observed WOMAC scores at 3 months after surgery and model-predicted values for pain and function models (before surgery) are shown in Overall, the models for pain and function demonstrated similar predictive performance  and 2B. The model-predicted estimates were within 20% of the observed value 48% of the time for the pain model and 57% of the time for the function model . The 70%More than 50% of the study participants had various post-operative complications, the most frequent of which was post-operative haematoma. Participants whose level of pain was predicted with no more than 20% error were 13% less likely to have post-surgical complications after THR. Among patients whose level of functional impairment was predicted with an accuracy of within 20%, the likelihood of post-surgical complications was 9% less than for participants whose functional impairment levels was predicted less accurately. These differences, however, were not significant. Patients whose observed levels of pain and function were not covered by the model-predicted confidence intervals also tended to have higher probability of post-surgical complications by 14% and 17% respectively. These differences were not significant.Intra-rater reliability between two pain and function measurements repeated by 11 patients seven days apart was high. The ICC was identical for both pain and function measurements: ICC = 0.84 (95% CI 0.55–0.95).16 Our tool may help by providing patients with realistic expectations about the outcomes of their THR surgery. However, the hip outcome calculator will need further study and validation. Its overall performance was weak at high levels of pain and functional impairment. This may have been due to the models being designed with a limited number of questions so that the tool remained simple and user friendly. It may also have been due to the datasets that were used to develop and validate the models containing few data on extremely severe levels of pain and functional impairment after THR.The hip outcome calculator was designed to be a user-friendly, self-applied and Internet-based tool for patients undergoing THR to predict their pain and functional levels after surgery. In a pilot study, we found that it performed moderately well at predicting pain and function 3 months after THR. The models predicted post-surgical levels of pain and function with moderate accuracy. The models tended to provide conservative predictions which slightly overestimated observed pain and functional impairment. In a recent study, Mahomed and colleagues reported that patient expectation is an important predictor of outcome after THR.In summary, the hip outcome calculator demonstrated moderate validity, but performed weakly for patients with extreme levels of pain and extreme functional limitations at 3 months post surgery. This may in part be explained by early complications after surgery. However, the outcome calculator may be useful in helping patients to become better informed about the realistic outcome of their THR.


Motor vehicle collisions (MVCs) are the second most common injury mechanism resulting in emergency department (ED) visits by older adults. MVCs result in substantial pain and psychological distress among younger individuals, but little is known about the occurrence of these symptoms in older individuals. We describe the frequency of and characteristics associated with pain, distress, and anticipated time for physical and emotional recovery for older adults presenting to the ED after MVC in comparison to younger adults.In-person interviews were conducted for adults presenting to one of eight EDs after MVC without an obvious fracture or injury requiring admission as part of two prospective studies. Pain severity was assessed using a 0–10 verbal scale. Distress was assessed using the Peritraumatic Distress Inventory (range 0–52). Patients were asked to estimate their expected time for physical and emotional recovery; these responses were dichotomized to <30 or ≥30 days. ED pain and distress and associations between patient and collision characteristics and ED pain and distress were examined for patients age 65 years and older and patients age 18 to 64.Older (n = 96) and younger (n = 943) adults had the same mean pain scores . Distress scores were lower in older than in younger adults . A higher percentage of older adults than younger adults had an anticipated time to physical recovery ≥30 days . Similarly, older adults were more likely to have an anticipated time for emotional recovery ≥30 days . Older adults were less likely than younger adults to have moderate or severe neck pain (score ≥4)  or back pain  but more likely to have moderate or severe chest pain . Pre-MVC depressive symptoms and pain catastrophizing were positively associated with pain and distress in both older and younger adults.In our cohort, older adults who presented to the ED after MVC experienced similar pain severity as younger patients and less distress but were more likely to estimate their times for physical and emotional recovery to be 30 days or more. Increased emergency provider awareness of acute pain and distress symptoms among older patients experiencing MVC may improve outcomes for these patients. Adults age 65 years and older make an estimated 250,000 US emergency department (ED) visits each year for evaluation after motor vehicle collision (MVC), making this the second most common cause of injury resulting in ED visits for this age group ,2. The nAmong younger adult MVC patients who are discharged to home after ED evaluation, acute pain and distress symptoms are common . These sThe objective of this study is to compare pain, distress symptoms, and recovery expectations between older and younger adults who present to the ED after MVC and are discharged to home, and to examine associations between patient and collision characteristics and pain and distress symptoms for these two age groups.We analyzed cross-sectional data obtained as part of two prospective cohort studies of patients evaluated in the ED following MVC. The two studies, European American CRASH (EA CRASH) and Older Adult CRASH (OA CRASH), each enrolled patients from the same eight EDs in four no-fault insurance states , where litigation associated with MVC is relatively uncommon. Details of the methods for EA CRASH have been reported . A summaPatients who presented to the ED within 24 hours of an MVC with injuries unlikely to require admission were screened for eligibility. EA CRASH enrollment was limited to non-Hispanic European American adults age 18 to 65 years. Exclusions based on self-reported race and ethnicity were made in EA CRASH in order to prevent population stratification bias associated with genetic analyses performed as part of the study . OA CRASth percentile of scores for the entire cohort.Study participants were interviewed by trained research assistants in the ED using a standardized questionnaire with explicit definitions of study variables. These interviews assessed sociodemographic and crash characteristics, pain, and psychological symptoms  and traits . The severity of motor vehicle damage was rated by study participants as minor, moderate, or severe, with severe damage defined as the vehicle not being drivable. Agreement between ED patient descriptions of the severity of vehicle damage and police reports have previously been described . Pain seIn the study of younger adults, depressive symptoms were measured using the 20-item Center for Epidemiologic Studies Depression Scale-Revised (CES-D-20) ) or a twSociodemographic characteristics of participants age 65 years and older (older adults) and those age 18 to 64 years (younger adults) were summarized using proportions for categorical variables and means and standard deviations for continuous variables. Anticipated times to physical and emotional recovery were non-normally distributed. Most patients anticipated that they would recover in the first 14 days; a second cluster of patients anticipated physical and emotional recovery ≥30 days. Based on this distribution, anticipated times to physical and emotional recovery were dichotomized into less than 30 days vs. 30 days or more. Pain scores and distress symptom scores among subgroups of patients defined by sociodemographic, psychological, and collision characteristics are reported as means and associated 95% confidence intervals separately for older and younger adults. The extent to which associations between patient characteristics and outcomes differed between younger and older adults was tested using linear regression models including variables for 1) age group, 2) the patient or collision characteristic, and 3) a term for the interaction between the age group and the patient or collision characteristic. A p-value <0.05 for the interaction term was defined as indicating a statistically significant interaction, indicating that the relationship between the characteristic and the outcome was different for younger vs. older adults. All available data were used for analyses, and no sample size calculation was performed. Analyses were conducted using Stata IC 11.0 .The EA CRASH study screened 10,634 adults between February 2009 and October 2011; OA CRASH screened 561 adults between June 2011 and March 2013. From these two studies, 948 adults from EA CRASH and 91 adults from OA CRASH met eligibility criteria, consented to participation, and met subsequent criteria for these analyses . However, the prevalence of substantial distress (distress score ≥ 13 ) was nevAmong younger adults, females and those with less formal education had higher rates of pain and distress Tables , 5. TrenSensitivity analyses were conducted in which the sample of older adults was further restricted in order to make them more similar to the younger cohort. Among the subset of older adults who were not taking daily opioids prior to the collision, did not have a fracture, and were discharged home (n = 68), the mean pain score  and mean distress score  were similar to scores for the overall sample of older adults. Comparisons between these scores and scores for younger patients did not change the overall findings that older patients had similar pain scores, lower distress scores, and were more likely to have an anticipated time for physical recovery or emotional recovery of 30 days or more when compared to younger adults.We compare results from two studies with minor differences in inclusion and exclusion criteria and assessment measures. In the study of younger adults, 5% of patients were excluded because they were unwilling to provide a blood sample; this was not an exclusion criterion for the older sample. The OA CRASH study used different instruments for assessing depressive symptoms than EA CRASH. Although the accuracies of each of these three instruments for identifying depressive symptoms when compared to a criterion standard diagnosis of depression is good or excellent (area under ROC >0.8 for each of the three measures vs. criteria standard ), it is Only 67% and 46% of eligible patients participated in the EA CRASH and OA CRASH studies, respectively. Among eligible patients, reasons for non-participation were similar for younger and older adults. For both studies, some patients declined to participate because they were either in too much pain, were too overwhelmed or stressed, or were too weak, ill, or tired. The total number of patients who decline participation for any of these reasons was 15% of eligible patients in the EA CRASH study and 19% of eligible patients in the OA CRASH. Non-enrollment of these and other patients likely creates some selection bias, but whether selection bias due to eligible patients declining to participate results in over- or under-estimates of pain and distress symptoms is unknown. Also, only non-Hispanic Caucasian patients were enrolled in EA CRASH, and the analysis of participants in OA CRASH was restricted to non-Hispanic Caucasians. The experiences of pain and distress and the effect of age on these experiences may be different in other racial and ethnic groups .Adults age 65 and older are a growing injury population -28, but Persistent pain after MVC is a major public health problem and acute pain is the strongest single risk factor for persistent pain . Our finPosttraumatic stress disorder (PTSD) is another common and morbid health problem resulting from MVC , and theOlder adults were more likely than younger adults to have an anticipated time to physical recovery or emotional recovery of 30 days or more. Patient’s expectations for health outcomes are correlated with and likely influence actual health outcomes , and eviIn our sample, pain catastrophizing was strongly associated with both pain severity and distress symptoms among both younger and older adults. Pain catastrophizing has previously been associated with pain severity among adults with spinal cord injury  and assoAmong younger adults, those with less formal education had more pain and distress; this relationship was previously described for a subset of this cohort . IncreasA greater proportion of older adults than younger adults experienced moderate or severe chest pain and fewer experienced moderate or severe back or neck pain. Persistent neck, shoulder, and back pain after MVC (i.e. whiplash syndrome) is a well described phenomenon . It is uMore older adults came to the ED via ambulance than younger adults. Contrary to our expectations, recent work by our group does not support the presence of a lower threshold for ambulance transport for older adults experiencing MVC . AmbulanPrior studies have characterized outcomes after minor blunt trauma in older adults, but have included a large proportion of patients who presented to the ED after a fall ,55. MVCs


Chest pain is one of the most frequent causes of emergency department (ED) visits in high-income countries. Little is known about chest pain patients presenting to EDs of low- and middle-income countries (LMICs). The objective of this study was to describe the characteristics of chest pain patients presenting to emergency departments (EDs) of Pakistan and to determine the utilization of ED resources in the management of chest pain patients and their outcomes.This study used pilot active surveillance data from seven major EDs in Pakistan. Data were collected on all patients presenting to the EDs of the participating sites to seek emergency care for chest pain.A total of 20,435 patients were admitted to the EDs with chest pain. The majority were males  and the mean age was 42 years (SD+/- 14). The great majority  of patients were admitted to the EDs of public hospitals compared to private hospitals and only 3% arrived by ambulance. Electrocardiograms (ECGs) were used in more than half of all chest pain patients  while cardiac enzymes were performed in less than 5% of cases. Chest X-rays were the most frequently performed radiological procedure ; more than half of the admitted chest pain patients were discharged from the EDs and less than 1% died in the ED.Chest pain is a common presenting complaint in EDs in Pakistan. The majority received an ECG and the use of diagnostic testing, such as cardiac enzymes, is quite uncommon. Chest pain is a frequently occurring symptom affecting 20-40% of the general population worldwide -3. It isChest pain can be cardiac (angina) as well as non-cardiac in origin -15. PatiStudies identifying characteristics of chest pain are mostly from developed countries, hence the data on global prevalence of chest pain in developing countries is scant . ExaminiThe objective of this paper is to look at characteristics of chest pain patients presenting to EDs of Pakistan and to determine the utilization of ED resources in the management of chest pain patients and their outcomes.The Pakistan National Emergency Departments surveillance (Pak-NEDS) was an active pilot surveillance conducted from November 2010 - March 2011 in seven major emergency departments in Pakistan: Aga Khan University (AKU) and Jinnah Post-graduate Medical Center in Karachi; Benazir Bhutto Hospital in Rawalpindi; Lady Reading Hospital in Peshawar; Mayo Hospital in Lahore; Sandeman Provincial Hospital in Quetta; and Shifa International Hospital in Islamabad. All the sites were tertiary care urban centers. The AKU and the Shifa International Hospital are private hospitals while the rest are public hospitals. AKU was the main coordinating center for the study. Ethical approval for the study was taken from all participating sites. Data was collected on males and females of all age groups presenting to the emergency departments of the participating sites to seek emergency care for various medical and surgical conditions including chest pain. The total number of patients enrolled during the study period was 274,436. Chest pain as the major complaint and as the second and third presenting symptom was widely distributed among admitted patients. In this paper, we analysed only those who were admitted to the emergency departments with chest pain as a chief complaint.A one-page standardized tool was developed based on an ambulatory care survey tool from the Centers for Disease Control and Prevention, USA and previous surveillance work done in Pakistan . The tooData was entered at AKU using Epi Info™ version 3.3.2. All data were tabulated using Stata, version 12  and SPSS version 20  and used simple descriptive analytic methods. Available data on admitted chest pain patients was classified using simple, one-way, two-way, and complex tabulation statistical methods; frequency distribution and percentage calculations were reported for categorical variables. During the Pak-NEDS study period, 20,435 patients were admitted to the EDs with chest pain as a major complaint. Only up to 1%  of all patients were admitted to the ED with other major complaints where chest pain was noted as the second  or third  additional presenting complaint, respectively. This number was considered negligible and thus the analysis only focused on patients who were admitted to the ED with chest pain as the chief complaint.Considering differences in the presentation and the clinical course of chest pain between the adult and pediatric populations, we focused only on adult patients, between the ages of 18 and 90 years old ; correspondingly, patients younger than 18 years  and older than 90 years  were excluded from further analysis. This decreased the total sample size to 19,752 patients. Age distribution was studied in the following main groups (in years): 18-30, 31-45, 46-60, 61-75, 75-90, and 81-90. For the multiple-response variables such as physical examination, diagnostic and screening services, conducted procedures, and visit disposition, only single, all available response options were considered in the analysis. For the variables with missing data, the percentage of missing data is presented.Of the 19,752 patients, 58%  were males and 39%  were females. Almost 35%  of all patients admitted with chest pain symptoms were in the 30-45 age group and less than 2% (n = 360) were in the 75-90 age group. The mean age of all admitted patients was 42 years (SD ±14). Age distribution as well as the mean age was similar among men and female   of all chest pain patients were admitted to the ED of public hospitals and since the number of patients admitted to private hospitals was low , the analysis did not stratify results by hospital type. Less than 3% (n = 585) were delivered to the hospital by ambulance and 92% used other modes of transportation. Almost 18%  of all admitted chest pain patients had been treated for chest pain in the last 72 hours before their current visit to the emergency department. For the majority of patients , this was the first episode of care for chest pain, and for 31% , this was the first visit to the ED within the last 12 months  were performed for more than half  of patients. Chest X-rays were the most frequently performed diagnostic test and were used in up to 21%  of patients; cardiac enzymes were measured in only 5% , with as low as 1% (n = 224) measured among females  of patients with chest pain were admitted to the hospitals, slightly higher for males compared to females (17% vs. 15%). A total of 157 (0.8%) of patients with chest pain died in the emergency department. The mortality rate was 25% higher for males compared to females .This study looked at the characteristics of chest pain patients presenting at selected EDs in Pakistan. The analysis showed that more than 7% of all admitted patients had a complaint of chest pain. This finding is consistent with the numbers cited in published sources, which show that the prevalence of chest pain patients in EDs ranges between 2.4% and 20% in the United States, UK, and Europe ,4,7,19. Patients presenting with chest pain were found to be young, with a mean age of 42 years and more likely to be males. This trend is comparable with other reports showing that patients with an MI from LMICs were younger than patients from high-income countries (HICs) -2627]. . 27]. AnPakistan has variable ambulance service quality with uneven coverage . The finType and duration of chest pain, findings on the ECG and chest x-ray, and in some cases biomarkers are primary modalities used for triaging patients with chest pain in the emergency department. ECG is considered critical for decision-making; in many high-income settings, ECG done within 10-15 minutes of presentation to emergency department is considered one of the indicators for quality of care in chest pain management in the emergency department. In this study, only 55% of patients with chest pain had an ECG in the emergency department, with a higher rate shown in older patients. Additionally, biomarkers were rarely used in the emergency department, perhaps due to non-availability of the tests in the emergency department.Less than 20% of all patients with chest pain were admitted to the hospital. This is a relatively low number of admission compared to findings in the US (35%) , but comThe Pak-NEDS study has several limitations, some of which were mentioned above. Due to a lack of a large amount of clinical information, analyses did not explore in detail: the characteristics of chest pain ; risk factors and patient history ; the results of conducted screening and diagnostic tests; provisional diagnoses; or conducted treatment. Furthermore, we could not determine whether any chest pain management algorithms, diagnostic protocols, and guidelines were used and followed for the management of chest pain patients in the EDs.The issue of missing information could partially be explained by poor documentation of symptoms, conducted diagnostic tests, provided treatment, and discharge diagnosis by medical staff. Thus, it is difficult to pass judgment on the use of ED resources in the management of chest pain patients. Clinical documentation should be inherent to every patient encounter . CompletThe participating sites were general EDs, but there are some centers in Pakistan specialized to handle chest pain patients; therefore, the results may underestimate the true picture of chest pain burden in Pakistan. Finally, the pilot surveillance study does not include information on the follow-up of chest pain patients, which makes it difficult to learn about the long-term effects of chest pain management in the EDs in Pakistan.In conclusion, the findings of this study showed a high burden of chest pain in Pakistan, with higher numbers in younger adults. There is a gap between international evidence on the management of chest pain patients and practice in Pakistan. Globally, closing the gap between evidence and practice has focused on individual clinician and institutional approaches, including the use of clinical practice guidelines and protocols -39. ThisThe authors declare that they have no competing interests.NP led the development of initial and revised manuscript; BA and RM reviewed and provided extensive feedback on various versions of the manuscript. NP performed data management and analysis and NZ helped with the process of analysis. NZ, MMK and JR critically reviewed the draft and all authors approved the final version of the manuscript.


Although pain management is a fundamental aspect of care in emergency departments (EDs), inadequate treatment of pain is unfortunately common. There are multiple local protocols for pain assessment in the ED. This study evaluated whether the initial assessment and treatment of pain in the ED are in accordance with the in-hospital protocol of the ED at a Norwegian University Hospital.Prospective data on pain assessment and initial treatment in the ED were collected from nursing and physician documentation. The patients’ perceptions of subjective pain were recorded using a numerical rating scale (NRS) that ranged from 0 to 10.Seventy-seven percent of the 764 enrolled patients were evaluated for pain at arrival. Female patients had a higher probability of not being asked about pain, but there was no difference in the percentage of patients asked about pain with respect to age. Additionally, patients with low oxygen saturation and systolic blood pressure were less likely to be asked about pain. Of those with moderate and severe pain (58 %), only 14 % received pain relief.Assessment and treatment of pain in the ED are inadequate and not in line with the local protocols. A focus on strategies to improve pain treatment in the ED is a necessary aspect of developing optimal acute patient care in Norway in the future. Pain is often referred to as the fifth vital sign  and is ohttp://www.predicare.se) [In November 2012, a 20-day prospective study was conducted at St. Olav’s Hospital in Trondheim, Norway, where ED patient data were collected daily during the period of highest patient influx (noon-10 p.m.) . Relevancare.se) .Patient perception of subjective pain should be evaluated at arrival according to local procedures at St. Olav’s Hospital. The pain is evaluated using a numeric rating scale (NRS), which measures the degree of pain on an 11-point scale from 0 to 10 , 21, whep < 0.05. The chi-square test was used to assess significant differences between the different patient groups. When more than 20 % of the squares in the chi-square calculation had an expected value less than 5, Fisher’s exact test was used. Unless otherwise specified, the percentage was calculated for the patients for whom the relevant variable was obtained.The statistics software SPSS version 22.0  was used to analyze the data. The paired t-test was used for normally distributed data, and statistical significance was set at The Regional Committee for Medical and Health Research Ethics (REK) in Norway and the Data Protection Officer at St. Olav’s Hospital, Trondheim, approved the study.n = 764). The average age was 58.5 years (SD 26.7 years), and the proportion of women was 52.1 %. The patient distribution was characteristic of the general patient population distribution at our ED for all of 2012 with respect to age, gender, chief complaints (Emergency Symptoms and Signs (ESS) in RETTS), and acuity level. The proportion of patients who were asked about pain upon arrival at the ED was 77 % (n = 586), and the group was not significantly different from the group that was not asked about pain with respect to age, gender, and acuity level. In the group that was not asked about pain , 10.5 % of the patients had a systolic blood pressure below 100 mmHg , whereas in the group that was asked about pain, 2.6 %  had a lower blood pressure (p = 0.000). There was also a significant difference in the average blood pressure between the two groups (p = 0.022). At the same time, significantly more patients with oxygen saturation below 95 % were not asked about pain . The difference in the mean oxygen saturation was relatively small but significant, with values of 97.5 % and 95.8 %, respectively, among the patients asked about pain and those not asked about pain (p = 0.011). The most common chief complaints in both groups were abdominal pain, chest pain, breathing difficulties, and neurological and infectious conditions. The differences between the patients who were and were not asked about pain are shown in Table In the study, 764 patients were included (n = 586), 58 % (n = 340) stated that they were in pain  indicated that they had pain that was more severe than mild (NRS > 3). There was no significant age difference between the patients who were asked about pain and those who were not asked about pain; however, there were significantly more women than men who were not asked about pain .Of the patients who were asked about pain  were treated with pain medications. There was no difference in age (p = 0.544) or gender (p = 0.188) between the patients who did or did not receive analgesia. The study was not designed to identify the drugs or interventions that were used for pain management.According to the local ED procedures, the goal is to treat all patients with moderate and severe pain. The average pain scores in patients who reported pain on arrival to the ED was 4.9 (median 5.0). There was no significant difference in the pain scores between those who were and were not treated for their pain (4.59 versus 4.91). Of the group of patients with moderate and severe pain , 14.2 % (This study reveals a known phenomenon; specifically, patients do not receive optimal assessment and treatment of pain in the ED. Twenty-three percent of patients were not asked about their pain, and only 14.3 % of the patients who reported moderate to severe pain received treatment for their pain. A study by Barletta and colleagues showed a significant difference in the pain scores between patients who received pain treatment and those who did not , but theOther hospitals that also have guidelines for pain management additionally struggle with low compliance with pain level documentation. Only 49.2 % of the patients were asked about their pain in triage , and, ofPain in the elderly is a common problem in the ED , and paiOf the patients with moderate to severe pain, few received pain management in the ED. There was no difference in age or gender between the patients who did or did not receive analgesics. In one study , approxiAdequate pain management should be a primary goal of health care professionals in the ED, but the pain assessment and treatment performed by nurses have been shown to be suboptimal . The docPain is one of the most common reasons for seeking emergency medical care; thus, it is important for healthcare professionals to focus on effectively assessing and treating pain. Despite guidelines and in-service educational programs, the assessment and treatment of pain in our ED are inadequate. This prospective study reveals that the management of pain is not in accordance with internal procedures. Pain management is accepted as a quality indicator of care, and additional focus on strategies to improve pain management in the ED is necessary to ensure that all patients receive optimal pain assessment and treatment.


Conventional, intravenous, patient-controlled analgesia, which is only administered by demand bolus without basal continuous infusion, is closely associated with inappropriate analgesia. Pharmacokinetic model-based dosing schemes can quantitatively describe the time course of drug effects and achieve optimal drug therapy. We compared the efficacy and safety of a conventional dosing regimen for intravenous patient-controlled analgesia that was administered by demand bolus without basal continuous infusion (group A) versus a pharmacokinetic model-based dosing scheme performed by decreasing the dosage of basal continuous infusion according to the model-based simulation used to achieve a targeted concentration (group B) following robot-assisted laparoscopic prostatectomy.In total, 70 patients were analyzed: 34 patients in group A and 36 patients in group B. The postoperative opioid requirements, pain scores assessed by the visual analog scale, and adverse events  were compared on admission to the postanesthesia care unit and at 0.5, 1, 4, 24, and 48 h after surgery between the 2 groups. All patients were kept for close observation in the postanesthesia care unit for 1 h, and then transferred to the general ward.P < 0.05). There were no differences in the adverse events between the 2 groups.The fentanyl requirements in the postanesthesia care unit for groups A and B were 110.0 ± 46.4 μg and 77.5 ± 35.3 μg, respectively. The pain scores assessed by visual analog scale at 0.5, 1, 4, and 24 h after surgery in group B were significantly lower than in group A (all We found that the pharmacokinetic model-based dosing scheme resulted in lower opioid requirements, lower pain scores, and no significant adverse events in the postanesthesia care unit following robot-assisted laparoscopic prostatectomy in comparison with conventional dosing regimen. Therefore, conventional dosing regimens for intravenous PCA,2 which are performed by intermittent bolus administration without the basal continuous infusion of opioids, may exhibit inadequate analgesic effects during the immediate postoperative period in patients in the postanesthesia care unit who have undergone robot-assisted laparoscopic prostatectomy (RALP).Laparoscopic surgery may induce more severe pain in comparison with open laparotomy due to inappropriate pain management during the immediate postoperative period.3 Together with these properties, its tolerability and wide therapeutic range make fentanyl a suitable opioid for PCA.2 In terms of the respiratory effects of fentanyl, the basal continuous infusion of 0.12 to 0.67 μg/kg/h fentanyl does not result in significant respiratory depression.5 However, the basal continuous infusion of intravenous PCA is not usually recommended for postoperative pain management due to the risk of opioid accumulation and concerns about respiratory depression.6 As respiratory depression is closely related to high plasma concentrations of fentanyl, which may be caused by not only continuous infusion but also by high bolus doses,8 target-concentration strategies may be safer and more effective than conventional dosing regimens. However, little is known about the efficacy and safety of pharmacokinetic model-based fentanyl dosing schemes, which can quantitatively describe the time course of drug effects and achieve optimal drug therapy,9 for adequate pain management following RALP.The pharmacokinetic characteristics of fentanyl include its short duration of action, high lipid solubility, rapid distribution to fat and skeletal muscle, and a high extraction ratio drug.In our present study, we compared the opioid requirements in the postanesthesia care unit, visual analog scale (VAS) scores for pain, and adverse events during the postoperative period between a conventional dosing regimen and pharmacokinetic model-based dosing scheme in patients who underwent RALP.2. Patients who had taken opioids or analgesics before surgery were also excluded. Before surgery, all patients were instructed how to use the PCA pump and VAS for pain scoring by our acute pain service team. No patients were premedicated before surgery.The protocol was approved by the institutional review board of Asan Medical Center, Seoul, Republic of Korea , and written informed consent was obtained from patients with prostate cancer who underwent RALP between April 2015 and September 2015. This study was registered with the ClinicalTrials. gov database (NCT02402621). Exclusion criteria included allergies to opioids, history of chronic pain, history of alcohol or drug abuse, history of sleep apnea or respiratory complications, American Society of Anesthesiologists physical status ≥ 3, age < 20 years or ≥ 70 years, and body mass index > 30 kg/mAfter applying a routine monitoring system , general anesthesia was induced using a bolus intravenous injection of 5 mg/kg thiopental sodium and 0.6 mg/kg rocuronium and maintained using 5 to 6 vol% desflurane plus an effect-site target-controlled infusion 2 to 5 ng/mL remifentanil with 50% oxygen in medical air. Patients were mechanically ventilated at a constant tidal volume of 6 to 8 mL/kg, and the respiratory rate was adjusted to maintain the end-tidal carbon dioxide partial pressure between 35 and 40 mm Hg during the operation.10Patients were randomly allocated to receive the conventional dosing regimen performed by intermittent bolus administration without basal continuous infusion (group A) or the pharmacokinetic model-based dosing scheme performed by decreasing the dose of basal continuous infusion according to the model-based simulation in order to achieve a targeted concentration (group B) Figure . Figure 12 which indicates severe pain, the physician intravenously administered a bolus of 25 μg fentanyl. The opioid requirements in the postanesthesia care unit were measured. All patients were kept for close observation in the postanesthesia care unit for 1 h and then transferred to the general ward. VAS scores and adverse events  were measured on admission to the postanesthesia care unit and at 0.5, 1, 4, 24, and 48 h after surgery by an investigator who was blind to the treatment groups. The definitions of respiratory depression, desaturation, and sedation were a respiratory rate < 12 breaths/min, oxygen saturation < 90%, and level of sedation so that the patient has a normal response to verbal stimuli, respectively. The total fentanyl dose administered during the postoperative period was calculated by combining the infused fentanyl doses and any other opioids or analgesics that were administered during the postoperative period. All opioids and analgesics were recorded and converted to fentanyl-equivalent doses using morphine sulfate equivalents.15 The total duration of surgery (from the start of surgery to the end of surgery in minutes) and time to extubation from the end of surgery (from the end of surgery to extubation in minutes) were also recorded.In the postanesthesia care unit, if the VAS score  of the patient was ≥ 6,16 and below the concentration that can result in unwanted side effects4—was determined according to the pharmacokinetic parameters of fentanyl as follows:10Vcentral (L): 26.6, k10 (min–1): 0.0332, k12 (min–1): 0.172, k13 (min–1): 0.131, k21 (min–1): 0.1, k31 (min–1): 0.0177, and Ke0 (min–1): 0.147. In this present study, we determined the targeted concentration, which is slightly higher than the minimal effective concentration throughout the postoperative period, and then simulated the cumulative drug amount in order to maintain these concentrations using NONMEM® VII level 2 . After simulating the time-concentration curve using various dosing schemes, we selected the optimal dosing regimen that could maintain the appropriate concentrations and entered the basal rate into the intravenous PCA infusion pump . Deterministic simulations using point estimates of the fixed-effect parameters were performed to provide an illustration of the predicted time courses of the plasma and effect-site concentrations after fentanyl administration. Variances in the random-effect parameters  were set to 0. Figure The optimal dosing scheme for model-based PCA infusion—that is, maintaining the target concentration above the minimal effective concentration of 0.23 ng/mL17 The total estimated number of patients was 73 after considering a 10% dropout rate. Data such as demographics, surgical duration, time to extubation from the end of surgery, opioid requirements, and VAS score were compared with using Student's t test or Mann–Whitney U test, as appropriate. The American Society of Anesthesiologists physical status and incidences of adverse events were measured by using the χ2 test or Fisher's exact test, as appropriate. Statistical analysis and randomization were conducted using R , SigmaStat 3.5 for Windows , and SPSS 22 for Windows . Data are expressed as the mean ± SD, or number (percentage) as appropriate. In this study, P < 0.05 was considered statistically significant.The sample size was estimated based on the power calculation, which showed that ≥33 patients per group were necessary to achieve 80% power and detect a 20% difference between computer-controlled alfentanil infusion and conventional PCA morphine infusion in order to reduce opioid requirements.This study included 73 patients who underwent RALP. After randomization, however, 3 patients were not included in the analysis due to the development of intraoperative paroxysmal atrial fibrillation with a rapid ventricular rate, refusal to participate in the trial just before induction, or an unanticipated change to laparotomy due to severe peritoneal adhesion, respectively Figure .The patient characteristics and outcomes for groups A and B are compared in Table Among our patients who underwent RALP, the pharmacokinetic model-based dosing scheme for fentanyl PCA demonstrated significant reductions in opioid requirements in the postanesthesia care unit and pain scores assessed by VAS during the postoperative period without developing any significant opioid-related complications in comparison with the conventional dosing regimen. Our data suggest that both the plasma and effect-site concentrations did not decrease below the minimal effective concentration of fentanyl in the model-based PCA group. However, in the conventional PCA group, we believe the fentanyl concentration decreased to below the minimal effective concentration around admission to postanesthesia care unit, which may have resulted in moderate to severe pain.20 Although fentanyl has a wide therapeutic window, large on-demand doses or high basal infusion rates are associated with the risk of respiratory depression.22 In addition, the long context-sensitive half-time of fentanyl after a long period of infusion results in a dramatic increase in its concentration, which may be associated with postoperative complications such as respiratory depression, nausea, and vomiting.24 For these reasons, basal continuous infusion is not routinely recommended as a postoperative analgesia.Fentanyl is a highly lipophilic drug, which facilitates its distribution into the brain, and is well suited for intravenous PCA. Furthermore, using fentanyl for intravenous PCA demonstrates considerable analgesic efficacy with good tolerability.1 Furthermore, in our present study, the administration of only the demand dose of fentanyl—without basal continuous infusion—demonstrated inadequate pain relief in the postanesthesia care unit in patients who underwent RALP. Similar to the previous simulation results, the fentanyl concentration progressively decreased to the minimal effective concentration at ∼30 min after the first fentanyl bolus injection. This time course of the concentration was inversely related to the trends of the pain scores, which increased abruptly after admission to the postanesthesia care unit and peaked at 30 min after admission. In addition, the simulated fentanyl concentration of the demand dose plus an additional fentanyl bolus in the postanesthesia care unit showed not only an abrupt increase in the fentanyl effect-site concentration to > 2 ng/mL—which may produce fentanyl-related complications—but also that the fentanyl concentration could have decreased to below the minimal effective concentration of 0.23 ng/mL and thereby resulted in inappropriate pain management. Considering the appropriate dosing scheme for managing postoperative analgesia, there are problematic concerns regarding the lack of basal continuous infusion with a demand bolus dose, which may have led to an insufficient fentanyl concentration below the minimal effective concentration.However, pain after laparoscopic surgery is known to be more intense during the immediate postoperative period in comparison with after open laparotomy.9 The model-based dosing scheme is very popular in drug development area, especially in first-in-human studies and trials on optimal dosing regimens.26 In addition, these approaches helped to achieve successful registration of the drug and were identified as a more efficient trial design that reduced the required number of subjects and thereby saved time. Therefore, model-based PCA, which can restrict concentrations within the therapeutic range, can provide tailored postoperative analgesic management approaches.Taken together, we adapted pharmacokinetic model-based PCA as an advanced method for reducing the period during which the fentanyl concentration is below the minimal effective concentration during the postoperative period. We found that the model-based dosing scheme reduced analgesic requirements in the postanesthesia care unit and pain scores during the postoperative period among patients who underwent RALP. Pharmacokinetic model-based dosing schemes, which can provide a quantitative description of the time course of drug effects and offer great potential for achieving optimal drug therapy, are increasingly used within most therapeutic areas.27 except children and overweight patients.29 Therefore, our results are promising for the postoperative pain management of patients who undergo RALP.In terms of study limitations, we did not examine the predictive performance of the simulated PCA regimen, which should take blood samples at predetermined time points. In addition, our simulation did not include interindividual variations in the pharmacokinetic parameters of fentanyl. However, the pharmacokinetic model of fentanyl is largely accepted to be valid for all patients,In conclusion, pharmacokinetic model-based PCA, which can provide optimal basal infusion in order to achieve a concentration above the minimal effective concentration, significantly decreases the opioid requirements and pain scores without inducing serious adverse events immediately following RALP. These results provide a better understanding of effective pain management following RALP.