Postoperative pain is common in the intensive care unit despite the administration of analgesia. Some trials suggest that massage can be effective at reducing postoperative pain in acute care units; however, its effects on pain relief in the intensive care unit and when pain severity is highest remain unknown.The objective is to evaluate the effectiveness of hand massage on the pain intensity (primary outcome), unpleasantness and interference, muscle tension, anxiety, and vital signs of critically ill patients after cardiac surgery.A 3-arm randomized controlled trial will be conducted. A total of 79 patients who are 18 years or older, able to speak French or English and self-report symptoms, have undergone elective cardiac surgery, and do not have a high risk of postoperative complications and contraindications to hand massage will be recruited. They will be randomly allocated (1:1:1) to standard care plus either 3 20-minute hand massages , 3 20-minute hand holdings (active control), or 3 20-minute rest periods (passive control). Pain intensity, unpleasantness, anxiety, muscle tension, and vital signs will be evaluated before, immediately after, and 30 minutes later for each intervention administered within 24 hours postoperatively. Peer-reviewed competitive funding was received from the Quebec Nursing Intervention Research Network and McGill University in December 2015, and research ethics approval was obtained February 2016.Recruitment started in April 2016, and data collection is expected to be complete by January 2017. To date, 24 patients were randomized and had data collection done.This study will be one of the first randomized controlled trials to examine the effect of hand massage on the pain levels of critically ill patients after cardiac surgery and to provide empirical evidence for the use of massage among this population.ClinicalTrials.gov NCT02679534; https://clinicaltrials.gov/ct2/show/NCT02679534 (Archived by WebCite at http://www.webcitation.org/6l8Ly5eHS) Undergoing cardiac surgery constitutes a major event for patients that is accompanied by physical and psychological symptoms such as postoperative pain -5 and anIn the ICU, postoperative pain can be compounded by routine ICU procedures such as turning, coughing, breathing, and chest tube removal, activities which are perceived to be the most painful in the immediate postoperative period ,5. GivenCardiac surgeries, such as coronary artery bypass grafting and valve replacement, rank among the most frequently performed surgical interventions worldwide  and neceUnrelieved postoperative pain can interfere with patients’ ability to cough and mobilize effectively, which predisposes them to postoperative complications such as atelectasis, pneumonia, and deep vein thrombosis ,5,14, thAmong the pharmacological approaches to pain control, opioids constitute the mainstay of treatment in the ICU ,20, yet A recent systematic review exploring the effectiveness of massage on postoperative outcomes among patients undergoing cardiac surgery  indicateOne pilot randomized controlled trial (RCT) conducted with 40 ICU patients post–cardiac surgery  showed pOverall, there is a paucity of high-level evidence on which to base massage therapy decisions in the management of pain in post–cardiac surgery ICU patients. Extrapolations of evidence from other patient populations and clinical settings are flawed by the differing health status and symptom severity of this specific subgroup of ICU patients. Future rigorous RCTs conducted in the context of the ICU and with cardiac surgery adults in their immediate postoperative period are essential to make recommendations for the use of massage in clinical practice including the minimal effective dose, body area massaged, and techniques employed.Inclusion criteria:18 years of age and olderAble to speak French or EnglishElective cardiac surgeryAble to answer questions and self-report symptomsExclusion criteria:Previous cardiac surgeryDiagnosis of cognitive or psychiatric disorderPulmonary artery pressure >50 mm HgRight ventricular failureSystolic left ventricular dysfunction (ejection fraction 35% or less)2Body mass index >30 kg/mProlonged bleeding from the chest drainage tubes (>200 mL/h)Having mechanical blood pressure support Receiving cardiac pacing with complete control of heart ratePeripheral intravenous line in the handsSuppurating/infective/inflammatory skin condition of the handsHypersensitivity to touchThe protocol is based on the neuromatrix theory of pain  where thThe primary aim of this research study is to compare the effect of 3 20-minute hand massage administrations by a trained nurse within 24 hours after cardiac surgery versus hand-holding  and standard care on the postoperative pain intensity of adult ICU patients.This research study is designed as a randomized, controlled, patient-blinded, single-center superiority trial with 3 parallel groups and a 1:1:1 allocation ratio. A modified Consolidated Standards of Reporting Trials flow diagram for individual RCTs of nonpharmacologic treatments will be used to document recruitment and retention of participants see  43]..43].This RCT targets adults admitted to the ICU after undergoing cardiac surgery in a university-affiliated hospital in Canada. A single setting was selected for this study because of standardized pain management practices and surgical techniques and single patient rooms. Patients will be screened for inclusion using the eligibility criteria seen in A power analysis was conducted using the G*Power 3 program  to estimGiven the low attrition rates observed with this patient population  and block sizes of 3, an allocation ratio of 1:1:1, and one strata to minimize the imbalance in the number allocated to each group. Then, the randomization schedule will be transcribed in sequentially numbered and opaque sealed envelopes by a research coordinator not involved in assignment allocation to ensure allocation concealment. The allocation list will be stored in a locked filing cabinet of the principal investigator and will not made accessible to the interventionist involved in enrollment and treatment allocation.Patient recruitment will begin preoperatively when eligibility criteria such as age and language spoken will be verified .The remaining eligibility criteria  will be evaluated post–cardiac surgery and ICU admission. After the collection of baseline data, patients meeting all the inclusion criteria will be randomly assigned to either hand massage, hand-holding, or standard care. As each participant enters the study, he or she receives the next envelope in the sequence, thereby concealing the interventionist’s and trial participants’ knowledge of the upcoming group assignment.The interventionist will then administer the assigned intervention  without informing participants of their group assignment until the end of data collection. Nurses and other ICU clinicians will also be masked to patients’ group assignment. The similarity of the hand massage and hand-holding therapy characteristics serves to mask study participants and clinicians with regard to the specific intervention received as observed in a feasibility and acceptability study where patients receiving hand-holding referred to the intervention as massage . ConversA modified Consolidated Standards of Reporting Trials flow diagram for individual RCTs of nonpharmacologic treatments will be used to document recruitment and retention of participants .The majority of massage studies include standard care control groups to examine the absolute efficacy of massage in improving outcome variables. While this is important in attributing benefits to the massage therapy itself, studies that involve the administration of massage by a trained therapist, as recommended in Cochrane Systematic Reviews , should Eligible patients will be randomized in equal proportions between hand massage, hand-holding, and standard care. One interventionist will deliver the hand massage and hand-holding interventions, which will be standardized across participants. The interventionist is a registered nurse with no previous experience in massage therapy who will be trained by a professional massage therapist through an accredited workshop of 6 hours including practical exercises and verification of competency, as was done in the pilot RCT .The first intervention (hand massage or hand-holding) will be delivered in the evening of the day of surgery and the remaining two interventions the day after when patients are still in the ICU. Overall, three interventions will be administered within 24 hours postoperatively over the course of two days.Patients assigned to the experimental group will receive a 20-minute hand massage by the interventionist in addition to the standard ICU care. Before administering the massage, a favorable environment will be created that promotes calmness such as dampening the light, reducing the alarm intensity, closing the curtains and door, and posting a “do not disturb” notice, and a comfortable positioning of the patient will be ensured ,30,46. AThe active control group will receive hand-holding by the same interventionist in addition to standard ICU care. The same hand hygiene and environmental adjustments will be made as for those receiving massage. Patients will have their hands held for 5-10 seconds and unscented hypoallergenic cream applied to both hands. Then, the interventionist will hold each of the patients’ hand in her hand for ten minutes with occasional stroking for a total of 20 minutes.The passive control group will receive the standard care administered in the ICU including a 20-minute rest period including the environmental adjustments of the experimental and active control groups. The interventionist will be outside of the patient room and have no contact with the patient throughout the 20 minutes. The standard care includes the pharmacological and nonpharmacological treatments  used to promote recovery and pain relief. In the study ICU, cardiac surgery patients are automatically prescribed a pain management protocol that includes the regular administration of morphine and breakthrough doses of analgesia as needed.The allocated interventions will be discontinued upon the participant’s withdrawal of consent or if skin irritation is suspected or patient comfort is disrupted due to the intervention itself, both of which will be reported as adverse events. Consenting participants will be retained in the trial whenever possible in spite of the discontinuation of the assigned intervention to allow remaining data collection and limit missing data.Concomitant interventions may be received by patients while participating in this trial. Consenting patients will be permitted to receive any of the pharmacological treatments prescribed by their treating physician and any of the nonpharmacological interventions offered in the ICU , and such data will be recorded. It is not prohibited that patients participate concomitantly in other research studies unless it involves any form of complementary therapy.Pain intensity is the primary outcome and will be captured using the 0 to 10 NRS score. The analysis metric will be the change in pain intensity from baseline (preintervention) to immediately after each intervention and 30 minutes later.1. Hygiene: Wash hands with warm water.2. Hold/connect/breathe: Make initial contact with patient, embrace hand, take a deep breath, and place feet on floor.3. Apply cream to entire hand, dorsal and palmer aspects, including phalanges.4. Spread (5 times) dorsal aspect of hand, using thumbs like opening a book. Repeat 5 times on palmer aspect, using the other 4 fingers to grip and glide. Spread again 5 times dorsal aspect of hand and 5 times palmer aspect.5. Gently shake bottom hand; vibration will help the patient relax and let go of any tension.6. Rotate wrists 3 times in each direction. Hold wrist with one hand while the other holds the patient’s hand and facilitates the passive rotation.7. Stretch the carpal ridge 3 times along wrist crease.8. Caterpillar walk on the dorsal aspect of the hand, between the bones .9. Pinch  aspect of the hand in between the metacarpals.10. Gently pull the webs of fingers.11. Knead (rock and roll) by making a fist on the palmer aspect of patient’s hand, gently rotate using the knuckles to apply pressure 5 times.12. Caterpillar walk on all areas of the palm, working proximally (towards the body) .13. Make small circles along the 5 zones of the palmer surface of the hand .14. Targeting key reflex areas, PRESS AND RELEASE 2 times in each area:  a. Shoulder-neck ridge (base of fingers)  b. Solar plexus , PRESS and SPREAD (diaphragm line—moving outwards in both directions) 5 times  c. Lateral aspect of palm  d. Medial aspect of palm  e. Pad of thumb14. Pinch lateral aspect of hand 3 times.15. Caterpillar walk on the medial border of thumb 3 times.16. Caterpillar walk on the fingers:  a. Caterpillar walk proximal making sure to cover all surface areas.  b. Rotate knuckles gently 3 times in each direction .  c. Gently pull fingers.17. Finishing touches: SWEEP entire hand, HOLD, and switch to other side.18. Hygiene: Once both hands have been massaged, wash hands with cold water.Pain unpleasantness, pain interference, muscle tension, anxiety, and vital signs will also be assessed in relation to each intervention, and means and standard deviations will be reported and used for data analysis.The NRS will be used to assess pain intensity. The NRS is an 11-point unidimensional self-report scale recommended for the assessment of pain intensity where 0 is no pain and 10 the worst possible pain. Details about the NRS and other assessment tools are summarized in The NRS will be used to assess the pain unpleasantness of patients. The unpleasantness dimension of symptom experience refers to the degree to which the person is bothered by the unpleasant symptom . The paiAn adapted version of the Brief Pain Inventory (BPI) will be used. The BPI is a short pain assessment scale developed to measure the intensity of pain during the last 24 hours (sensory dimension) and the interference of the pain in the patient’s life (cognitive dimension) ,60. The The assessment of muscle tension will be based on an ordinal scale derived from the behavioral pain scale Critical-Care Pain Observation Tool (CPOT), which was developed and tested for the assessment of pain in critically ill patients after cardiac surgery . EvaluatFor consistency and because intensity of anxiety is of interest in this study, the NRS will also be used to assess patients’ anxiety levels.Means of blood pressure  and heart and respiratory rates will be collected from the ICU bedside monitors for 1 minute at each assessment point.Sociodemographic  and medical-surgical data  will be collected using standardized data collection sheets. Prior to the delivery of each intervention (hand massage or hand-holding) and before the first data collection for the standard care group, patients will complete a self-administered data collection sheet with 5 short questions using the NRS for the self-report of pain intensity, pain unpleasantness, and anxiety, a body map for identifying the site of pain, and an open-ended question for a description of the quality of pain. The interventionist will be masked to patients’ self-reports, which will be accessed only at the end of data collection to verify for missing data. The form will be completed before, immediately after the intervention (hand massage or hand-holding), and 30 minutes later, for a total of 3 data collection points per intervention. Those assigned to standard care will complete the form at similar times. This bundle of assessments will be repeated for each of the 3 interventions. Muscle tension and vital signs will also be evaluated at the same assessment points.Finally, pain interference will be evaluated using a structured interview using the BPI on the second postoperative day to examine any carry-over effects.The data will be entered in the SPSS software version 22.0 (IBM Corp), and a random subset of data will be used to identify missing or erroneous values. This study aims to use intention-to-treat analysis by including every participant who has been randomized, regardless of group assignment, study withdrawal, or protocol deviations.Descriptive statistics will be calculated for sociodemographic and medical-surgical data and the baseline scores on all the outcome variables. Group differentiation in sociodemographic and medical-surgical characteristics for participant patients will be investigated using chi-square tests of independence for nominal level variables and one-way analyses of variance (ANOVA) for interval and ratio level variables. If group differences exist, the respective variable will be included as a covariate in the subsequent analyses. Frequencies and percentages of the location and descriptors of pain  will be calculated for each group and assessment point and used to describe the pain characteristics of participants. Data on pain location and quality will be compared over time.Repeated measures between ANOVA factors will be used to test for treatment , time , and interaction effect for pain intensity, pain unpleasantness, muscle tension, anxiety, and means of vital signs. This will be run for each intervention and each of these outcome variables. One ANOVA test will be performed for pain interference with the independent variable being group assignment . The main comparison of interest is between the hand massage and standard care group and the difference in means pre- and immediately posttreatment.Ethical approval has been granted by the Research Ethics Committee of the study setting in February 2016. This protocol has been independently peer reviewed by McGill University and the Quebec Nursing Intervention Research Network, who funded the study (F242710).Informed and written consent will be obtained from participants. The study’s aim and procedure, risks and benefits, right to refuse participation and withdraw at any time without any repercussions on the care provided, confidentiality of data, randomization process, and lack of financial incentives for participation in the study will be explained to patients. They will be equally informed that there is no guarantee that they will benefit from this study. While there are no known risks associated with hand massage and hand-holding, any harmful effects during these interventions will be noted and reported to the Research Ethics Committee.This study follows the most recent Consolidated Standards of Reporting Trials guidelines for nonpharmacological treatments and randomized controlled trials  and the The tools to be used for the assessment of the study outcomes have established validity and reliability in the population of interest in this study . Data coRecruitment started the end of April 2016, and to date 34 patients have already been recruited. Of these, 24 patients were randomized and had data collection done as several were medically unstable postoperatively or had their surgery cancelled/postponed. Data collection is expected to be complete by January 2017.Pain is one of the most common and severe symptoms cardiac surgery patients experience during their ICU stay. The adverse effects of unrelieved acute postoperative pain are numerous and can be taxing to cardiac surgery patients during their recovery but worryingly also on the long term. There is a general agreement in practice guidelines that multimodal approaches to pain management should be implemented in the ICU . MassageIn the proposed RCT, eligible and consenting patients will be randomly assigned to either the massage , hand-holding  or standard care group . While the administration of pleasant and potentially beneficial interventions  can helpA strength of this RCT is the administration of massage in the actual ICU environment and the clinical context of the first 24 hours post–cardiac surgery when monitoring is accrued, thus enabling an evaluation of the effectiveness of this intervention on the patient’s pain and related signs and symptoms. However, the same ICU environment could interfere with the delivery of some of the planned hand massages and hand-holding in the selected mode  and dose . In order to monitor these interferences and consider them in the interpretation of study findings, a camera will be used to videorecord the interventions. Nonetheless, even if these interventions can no longer be administered , attempts to continue collecting patients’ self-reports of symptoms will be prioritized over imputation for missing data.One of the anticipated limitations of this RCT is the lack of blinding of patients in the standard care group and the respective clinical personnel responsible for their care. Although environmental adjustments will be made, these patients will have already been informed of the 3 trial arms and their implications and could easily recognize their group assignment. Equally, it is expected that the ICU personnel will notice the absence of an active intervention and assume patient assignment to standard care. Given the unlikelihood of blinding related to the standard care group, patients could modify their self-report while the personnel could practice differently compared to when they see hand massage/hand-holding administrations, thereby increasing the risk of performance bias.Only the cardiac surgery ICU patient population will be included in this RCT, which will limit the generalizability of the findings to other ICU patients. Even so, this study will reveal the effectiveness of massage in this group of ICU patients suffering from intense pain and should be a trigger for further research internationally on the use of this intervention in the ICU in addition to the locally established standard care.This funded RCT will unravel the potential benefits to reduce ICU postsurgery pain by the use of massage therapy in cardiac surgery ICU patients compared to hand-holding and standard care. The results of this study will serve to inform clinical practice guidelines with regard to the dose, timing, and technique of massage administration for the relief of acute postoperative pain in the ICU in addition to analgesia. If effective, massage could be easily implemented in ICU practice with little resources to maximize pain relief in the acute postoperative period and prevent the serious adverse consequences of unrelieved pain.


Evidence is emerging that pain in rheumatoid arthritis (RA) exists without underlying inflammation. Our objective was to evaluate the prognostic value of pain classification at treatment initiation using the painDETECT questionnaire (PDQ). Outcomes were change in DAS28-CRP and RAMRIS synovitis score.RA patients initiating a disease-modifying anti-rheumatic drug (DMARD) or initiating/ switching a biological agent were included. Follow-up time was 4 months. Clinical examination, imaging ), and patient-reported outcomes were undertaken. The PDQ was used to differentiate pain mechanisms. Mean change (95% CI) was calculated using ANCOVA. Multivariable regression models were used to determine a prognostic value.A total of 102 patients were included; 75 were enrolled for MRI. Mean changes in baseline variables were greatest in the high PDQ classification group (> 18), while limited in the intermediate group (13–18). The 12 patients with high baseline PDQ score all changed pain classification group. No prognostic value of PDQ pain classification was found in relation to change of DAS28-CRP, RAMRIS score, or VAS pain. In the unadjusted model, RAMRIS score at baseline was associated with change in DAS28-CRP. The exploratory variables of DCE-MRI did not differ from other inflammatory variables.In RA patients a high PDQ score (non-nociceptive pain) at baseline was not associated with worse outcomes, in fact these patients had numerically greater improvement in DAS28-CRP. However, pain classification by PDQ was not independently associated with change in DAS28-CRP, RAMRIS score, or VAS pain in the prognostic models.Furthermore, patients classified with a high baseline PDQ score changed pain classification group. Patients with unclear pain mechanism had reduced numerically treatment response.H-3-2013-049.The study was approved by the Regional Ethics Committee of the Capital of Denmark April 18 2013; identification number The online version of this article (10.1186/s13075-018-1581-4) contains supplementary material, which is available to authorized users. Pain in rheumatoid arthritis (RA) has typically been regarded as nociceptive, that is, related to ongoing peripheral inflammation . HoweverThe painDETECT questionnaire (PDQ) is a self-administered pain classification instrument originally developed to differentiate neuropathic (non-nociceptive) from non-neuropathic (nociceptive) pain . It has Magnetic resonance imaging (MRI) is an objective and sensitive method to assess joint inflammation. The most common scoring system in the wrist and metacarpophalangeal (MCP) joints is the OMERACT  RA MRI scoring (RAMRIS) system . DynamicIn this study, we hypothesized that a high PDQ score would serve as an indicator of central sensitization and thus a prognostic factor for a poorer treatment outcome (DAS28-CRP change) in patients with RA initiating or intensifying anti-inflammatory treatment. A possible statistical interaction between central sensitization (high PDQ score) and inflammatory load (baseline synovitis defined by hand MRI RAMRIS score) was considered as part of the hypotheses. In the exploratory part of the study, we hypothesized that DCE-MRI would capture change in inflammation and thus a possible relation to inflammatory pain mechanisms (low PDQ score) better than conventional MRI.The Frederiksberg Hospital’s Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME)-cohort study was conducted according to a published protocol, which contained a detailed description of the methods and prespecified analysis , 20. It RA patients were recruited from departments and private clinics of rheumatology in the Copenhagen area and prospectively enrolled from March 2013 to September 2014. MRI was included in the examination program from May 2013. The examination program was conducted at Frederiksberg Hospital. Patients were assessed at treatment initiation (baseline) and after 4 months of treatment. Patients received routine care at the discretion of their rheumatologist during the trial period. Add-on of painkillers was allowed.To be eligible, patients had to fulfil either the 1987  or 2010 Major exclusion criteria were intra-articular or intra-muscular glucocorticoids administered less than 3 weeks prior to baseline; treatment with oral corticosteroids at doses equivalent to more than 10 mg prednisolone/day within the 3 weeks prior to baseline; inability to pause antidepressants, anticonvulsants or other centrally acting analgesics; initiation of csDMARD therapy more than 3 weeks prior to the baseline visit (only patients initiating csDMARDs); treatment with bDMARD initiated more than 1 week prior to the baseline visit (only patients initiating a bDMARD). Patients who had contraindications for MRI were excluded from the MRI arm of the study. Furthermore, patients with increased risk of neuropathic pain conditions (e.g. diabetes) were excluded due to the potential to confound the pain assessment.The patients underwent an examination program at baseline and follow-up, collecting information on demographics and medication and from patient-reported outcomes (PROs). Clinical examination including joint count and tender point examination conducted by the same assessor at both time points, imaging (MRI and DCE- MRI), and standard blood samples  were also performed.The following PROs were collected from each patient; the PDQ, the Stanford health assessment questionnaire disability index (HAQ-DI), the 36-item short form health survey (SF-36), generalized anxiety disorder assessment (GAD-10) and major depression inventory (MDI).The PDQ is a patient-administered pain classification tool that was developed in a population of patients with various pain conditions. It has been further validated for describing pain phenotypical features in patients with inflammatory arthritis by our group  and is vHAQ-DI is a measure of limitation of activities of daily living used for patients with RA. It assesses the patient’s ability to carry out everyday tasks. It includes a visual analogue scale (VAS) evaluation of pain, fatigue and global health (GH) .The SF-3® MR scanner according to a published scanning procedure ) or medians (with interquartile ranges [IQRs]) were reported and compared by r = 0.3 for a paired t test with a significance level of 0.05, a sample of a 100 pairs has a power of 80% (0.797) to detect a mean change of 0.5 DAS28-CRP units. A patient population, who can expect a change of this magnitude in their disease activity, is a reasonable cohort in which to study prognostic factors of treatment response. However, this number was not reached for the MRI subsample.Prior to executing the FRAME-cohort study, a power calculation was performed based on the assumption that it was feasible to include 100 RA patients during a study period of 1½ years , as no dThe prognostic value of the PDQ score, RAMRIS score, and their interaction at baseline in relation to change of DAS28-CRP was examined by multivariable regression models using the SAS PROC GLM. As the interpretation of PDQ by nature is trichotomous, the results were expressed as least squares means per category. According to the protocol, the model was adjusted for the following prespecified confounders: age (years), sex , disease duration (month), disease activity (DAS28-CRP at baseline), group (csDMARD/bDMARD), antiCCP-positive (yes/no) and concomitant prednisolone (yes/no). Subsequently, in the fully adjusted model covariates (i.e. possible confounders) that did not contribute to the model were removed; age, antiCCP-positive (yes/no) and concomitant prednisolone (yes/no).Secondary outcomes were change in RAMRIS synovitis score and VAS pain. Post hoc, to ensure robustness of results, a sensitivity analysis including baseline VAS pain as a confounder in the adjusted analysis of change in VAS pain was performed.On an exploratory basis the DCE-MRI variables IRExNvoxel (in ml) or MExNvoxel (in ml) for wrist were applied in the primary model examining DAS28-CRP and VAS pain change, replacing the RAMRIS synovitis score. For SRM, inter- and intra-reader agreements, intraclass correlation coefficients (ICC) (absolute agreement) for the four predefined DCE-MRI variables were tested beforehand on data from ten patients using SPSS software. Wrist and MCP joints were tested separately.Figure n = 66, n = 23, n = 12 for PDQ score < 13, 13–18, > 18, respectively. Statistically significant differences across the three PDQ classification groups were observed for tender joint count (TJC), tender point (TP) count, DAS28-CRP, physical function (HAQ-DI), VAS-fatigue, VAS-pain, VAS-GH, anxiety (GAD-10), depression (MDI), SF-36 PCS, and SF-36 MCS. A TP count ≥11 was found for higher proportions of patients with higher PDQ classification groups; however, this was not statistically significant. No differences were found across the groups for the biochemical and imaging variables.Baseline characteristics are described in Table Changes from baseline stratified by PDQ group are presented in Table p = 0.44) , sensitivity analysis excluded. In this analysis, baseline VAS pain was found to be significantly associated with change in VAS pain (p < 0.001). Baseline RAMRIS synovitis score was found to be statistically significantly positively associated with DAS28-CRP change in the unadjusted model (p = 0.01) and of RAMRIS change in both the unadjusted and the adjusted model (p ≤ 0.02).Baseline DAS28 was found to be statistically significantly associated with change in all outcomes in both adjusted models; DAS28, RAMRIS, and VAS pain  experienced the greatest numerical change in DAS28-CRP, self-reported disease severity measures, and objective inflammatory parameters, including MRI  would display constant high TJC and VAS GH as features of persistent pain hypersensitivity  and thus gain little or no change of DAS28-CRP following treatment initiation. In contrast however, this was not confirmed in the multiple regression analysis, we found that these patients , total hand RAMRIS synovitis score excluded. Thus, patients with an unclear pain mechanistic background had the poorest response to medical treatment also reflected in the U-shaped DAS28 remission pattern across the PDQ classification groups, indicating that the uncoupling of pain mechanism from present inflammation could be found in this group.In the multivariable regression analyses, the PDQ did not have prognostic value in relation to change of DAS28-CRP, RAMRIS score, or VAS pain. No interaction between PDQ score and baseline RAMRIS synovitis score was found in any of the regression analyses including the exploratory DCE-MRI analyses indicating no relation between ongoing inflammation and pain phenotype (pain classification group). However, in the light of the relatively small sub-sample of patients with a high PDQ score at baseline, it does not seem reasonable to reject any prognostic value of the PDQ at this point.p < 0.01) of change in the dependent variable  in all adjusted models. Furthermore, RAMRIS synovitis predicted DAS28-CRP change in the unadjusted model (p = 0.01), and RAMRIS synovitis change both in the unadjusted and the adjusted model (p ≤ 0.02). The impact of RAMRIS synovitis score on clinical change is not well documented [In contrast, DAS28-CRP at baseline was a significant predictor .The main strength of this study was the prospective design with a rigorous protocol and a prespecified analysis plan. Furthermore, the sample of RA patients was heterogeneous including patients from outpatient clinics and private rheumatologists in the Copenhagen area with a broad spectrum of disease severity. Thus, on one hand this heterogeneity gave the results potential for generalizable interpretation, on the other hand, it was the main limitation in relation to pain profiling, i.e. the constitution of the sample with notably the subgroup of patients with a high baseline PDQ score was small  for the DCE-MRI variables. (DOCX 16 kb)Additional file 2:Table of multivariable regression models including DCE-MRI variables examining change across PDQ categories expressed as least squares means (95% CI). (DOCX 16 kb)


Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is related to the plasma level of morphine and the required dose of morphine in an exploratory prospective study. The findings showed that a group of patients with a GG single nucleotide polymorphism (SNP) rs4680 in COMT required a significantly higher dose of morphine than a non-GG group. A biomarker for selection of opioids for cancer pain relief would be particularly useful clinically, and therefore we have planned a randomized comparative study of morphine and oxycodone, using the COMT rs4680 SNP as a biomarker. This study is aimed at verifying the assumption that patients in the GG group require an increased morphine dose for pain relief.The RELIEF study is a randomized, multi-institutional, open-label trial with a primary endpoint of the proportion of subjects requiring high-dose opioids, as calculated from the dose of a rescue preparation administered on day 0. Secondary endpoints include the Hospital Anxiety and Depression Scale, Short form McGill Pain Questionnaire-2, European Organization for Research and Treatment of Cancer QLQ-C15-PAL, Pain Catastrophizing Scale, and adverse events, Eligibility criteria are patients with advanced carcinoma with non-daily use of opioids in initial screening for registration; and cancer pain targeted for daily opioid treatment, NSAIDs or acetaminophen, NRS ≥3(average over 24 h), opioid-treatment naive within 30 h, no chemotherapy, radiotherapy, or bisphosphonate administration newly started within 2 weeks, and written informed consent at the time of second registration. Between November 2014 and June 2017, an estimated 110 patients from two sites in Japan were randomized (1:1) to morphine or oxycodone in GG and non-GG groups.A method for selection of appropriate opioids in cancer patients is a high unmet medical need. This study was designed to evaluate the efficacy of different opioids in patients with cancer based on gene polymorphism, as the first potential multi-institutional registration trial to be conducted in cancer patients with pain.UMIN000015579 Date of registration: 4 November 2014. It is updated once every six months, the latest update is 30 June 2017.Trial status.The enrollment started in November 2014. At the time of manuscript submission (July 2017), Three-quarters of patients have participated. We thus expect to complete the recruitment by March 2018. Opioids are important drugs for cancer pain relief, and definition of an appropriate required dose is needed to provide quick and potent pain relief. The required opioid dose is well known to vary widely among patients, but there have been few studies of biomarkers for the required dose and therapeutic efficacy, or for monitoring of pharmacodynamic effects of opioids. We have previously shown a relationship between cytokines and therapeutic efficacy of morphine  and a reA previous report indicated no relationship between genetic polymorphism and opioid requirement , but thiThe rationale for the planned study is that morphine and oxycodone are common drugs used for cancer pain, but biomarkers for selection of these drugs, definition of the required dose, and therapeutic efficacy are not available. Based on the above background, there is clearly a practical clinical need for a biomarker in opioid therapy. To identify a biomarker for selection of opioids for cancer pain relief, we planned a randomized comparative study of morphine and oxycodone using the COMT rs4680 SNP as a biomarker. In accordance with criteria described in a previous study of pain [Study objectives: A randomized controlled trial (RCT) will be performed with the design shown in Fig. Inclusion criteria are 1) patients with advanced malignant tumors, and 2) non-daily use of opioids. At the second registration, the criteria are 1) cancer pain targeted for daily treatment with opioids, NSAIDs or acetaminophen, 2) NRS ≥3 (average over 24 h), 3) opioid treatment-naive within 30 h, 4) no chemotherapy, radiotherapy, or bisphosphonate administration newly started within 2 weeks, and 5) written informed consent.The exclusion criteria are 1) patients with chronic renal failure , 2) patients with severe hepatic or respiratory failure, and 3) patients deemed ineligible for the study by the study coordinator or a collaborative investigator .The primary endpoint is the proportion of subjects requiring high-dose opioids calculated from use of the immediate-release preparation on day 0 in a parallel group comparison.The secondary endpoints are the Hospital Anxiety and Depression Scale (HADS) score for anxiety and depression; the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL for score for QOL; the Short-Form McGill Pain Questionnaire 2 (SF-MPQ2) score for pain characterization; and the Pain Catastrophizing Scale (PCS) for estimation of impact on pain prognosis. Adverse events  will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) ver. 4.0.The European Cooperative Oncology Group (ECOG) PS system will be used for evaluation of PS by primary physicians .The NRS will be used to evaluate pain for its better validity, sensitivity, and convenience compared to other scales  and its The HADS will be used for measurement of psychiatric symptoms (anxiety and depression) of patients with a physical disease. HADS is a screening tool that allows assessment based on a small number of items. Its reliability and validity have been verified internationally , 12.EORTC QLQ-C15-PAL will be used for evaluation of patient QOL. The reliability and validity of the Japanese version have been confirmed .The SF-MPQ-2 will be used to examine differences in effects due to pain mechanisms. The reliability and validity of the Japanese version have been verified .The severity of cancer-related pain is influenced by engagement of patients in catastrophic thinking, such as "my pain will undoubtedly never improve" . This efThe worst grade of an adverse event during the preceding period will be assessed using the CTCAE v.4.0, Japanese Clinical Oncology Group (JCOG) version.max about 1 h) and immediate-release oxycodone (Tmax about 2 h), respectively, with doses subjected to titration. Dose titration will be performed to decrease pain by ≥33% on the NRS pain scale, as well as reducing NRS to ≤3. The patients were tested with opioid according to the guideline for titration and following regular dosing  by specialized palliative care doctors. On this step, they explained potential benefits and adverse effects to their patients. Subsequently, the controlled-release opioid will be administered . In the first application of opioid treatment after occurrence of cancer pain, the patients will be divided into a GG group and a non-GG group based on the COMT rs4680 SNP and then undergo second registration, after which the protocol treatment will be started. Each group will be randomized into subgroups that will receive immediate-release morphine  serum chemokine levels, (2) polymorphisms in opioid function-related genes, (3) serum glycan analysis, and (4) psychological tests, QOL scale and others. Treatment will be performed in accordance with normal guidelines and will not be changed for this study.Sample handling: Blood will be collected at initial registration, before starting opioid treatment after second registration, and on days 1 and 8 after starting treatment. Samples will be collected and stored in the laboratory of the Department of Medical Oncology, Kindai University Faculty of Medicine. Samples will be encoded with identification numbers by a manager of personal information at the time of registration.Ethical issues: All patients are required to provide written informed consent. The study will be performed in accordance with the Declaration of Helsinki and the International Conference on Harmonization and Good Clinical Practice. The protocol has been approved by the Institutional Review Board at each study site.The null hypothesis is that the proportion of subjects requiring high-dose opioids is equal between the morphine and oxycodone groups for subjects with the GG genotype. This null hypothesis will be evaluated using Fisher’s exact test at the one-tailed significance level of 2.5%. The 95% confidence interval (CI) of the difference in the proportion of subjects requiring high-dose opioids will be calculated as an estimate of the therapeutic efficacy. The proportion of subjects requiring high-dose opioids and the 95% CI will also be calculated in each group.Sample size calculation: Our preliminary study [ry study  indicateThis study is the first multicenter RCT of the efficacy of opioids for cancer pain, other than psychogenic pain. We faced three major issues: (i) the heterogeneity of causes of pain, (ii) the absence of a standard of care in this setting, and (iii) the choice of the primary endpoint. Heterogeneity of causes of pains was handled by defining the subjects as patients with any cancer pain except for psychogenic pain. Next, we defined morphine and oxycodone as the standard of care, since these are opioids that are currently used as initial treatment in opioid-naïve patients. We planned to standardize selection for each opioid, because no standard technique has been established for this purpose. Finally, the primary endpoint was defined as the intergroup difference in the number of subjects requiring high-dose opioids based on the COMT rs4680 SNP, with the goal of examining this biomarker for selection of opioids, on the basis of results from previous studies.The GG COMT rs4680 polymorphism may emerge as a factor predicting therapeutic efficacy, a need for lower doses of oxycodone compared to morphine to exhibit efficacy, and fewer adverse events. Exploratory research may show that this biomarker can also predict side effects. Such findings will contribute to basic understanding of the pharmacological profile and therapeutic efficacy of opioids, as well as establish a practical clinical method for rapid pain relief.The study protocol was approved by the institutional review board in September 2014. Recruitment started in November 2014 and is currently ongoing.


Idiopathic adhesive capsulitis is a condition of uncertain etiology characterized by pain and decreased shoulder range of motion (ROM) that occurs without a known intrinsic disorder. Many treatments have been advocated, yet the best option remains unclear. The purpose of this study was to determine if arthrographic injection of the shoulder joint with steroid and local anesthetic results in decreased pain and increased shoulder function in a cohort of patients with idiopathic adhesive capsulitis.This is a retrospective case series of patients who were treated with an arthrographic steroid and local anesthetic injection for adhesive capsulitis. The injections were all given by the same musculoskeletal radiologist using image guidance, and the patients were all from the same surgeon's practice. Patients were evaluated with the Shoulder Pain and Disability Questionnaire (SPADI) and Constant Shoulder Score and their shoulder ROM was tested. Descriptive statistics in the form of counts, percentages, means and standard deviations were used, as well as parametric and non-parametric tests.Thirty-three shoulders in 25 patients were examined. The average length of follow-up was 17 months. Sixty-nine percent of the cohort continued to complain of some shoulder pain in the post-injection follow-up clinic, however, their pain had improved from 8.8/10 pre-injection to 2.2/10 post-injection (p=0.01). The average score of the SPADI Pain, SPADI Disability and Constant Score were 36, 31 and 64, respectively.All patients who received an arthrographic injection using steroid and local anesthetic reported improved pain and mobility. In addition, those who had tried other treatment modalities felt that the injection had been the most beneficial. The cet al. showed that 50% of patients treated non-operatively had continued mild pain or stiffness or both [Initially, frozen shoulder was felt by some to be a self-limiting condition with a favorable natural history , 7. Howe or both , 11.Many forms of treatment have been advocated for frozen shoulder including physiotherapy, injection with steroid, distension arthrogram, manipulation under anesthetic and arthoscopic releases , 12, 13.et al. randomly assigned patients diagnosed with adhesive capsulitis to receive either arthrographic joint distension with steroid and saline or a placebo consisting of simply the arthrogram. They found that patients receiving the distension arthrogram with steroid and saline had significant improvements at 3 weeks in their SPADI, PET, overall pain, active abduction and internal rotation with their hand behind their back [One randomized control trial evaluated the use of an intra-articular corticosteroid injection in a diabetic population with adhesive capsulitis. The researchers found that those patients treated with the injection had less pain at 6 weeks, better function at 12 weeks, but no lasting differences when compared with the control group who did not receive an injection . Buchbineir back . A receneir back . As the The objective of this retrospective study was to determine if arthrographic injection of the shoulder joint with steroid in the mid tern resulted in decreased pain and increased shoulder function in a cohort of patients who presented with adhesive capsulitis.2This is a retrospective case series study of patients who had been treated with an image-guided arthrographic injection using steroid for adhesive capsulitis in one surgeon’s practice. The inclusion criteria comprised patients between 18-70 years of age with a diagnosis of primary adhesive capsulitis that was treated with an image-guided arthrographic injection using 40 mg of Triamcinilone and 5cc of 1% Lidocaine by the same musculoskeletal radiologist. The minimum follow-up was 3 months. The exclusion criteria included patients who developed adhesive capsulitis secondary to trauma or who had had a previous surgery on the affected shoulder.Patients were evaluated with questionnaires and their range of shoulder motion tested with a goniometer. Questionnaires included the SPADI (Shoulder Pain and Disability Index) and the Constant Score Shoulder questionnaire. The SPADI is a validated, self-report measure developed to evaluate patients with shoulder pathology. It contains two domains; one is a 5-item subscale that measures pain and the other an 8-item subscale that measures disability. The pain dimension has five questions regarding the severity of an individual’s pain and the functional activities dimension has eight questions designed to measure the degree of difficulty a patient has while carrying out the activities of daily living. The scores from both dimensions are averaged to derive a total score with 0 being the best outcome (less disability) and 100 the worst (greater disability) .The Constant Score is also a validated instrument used to assess pain and function of a diseased shoulder. It has a maximum score of 100: 15 points are allocated for a subjective assessment of pain, 20 points for shoulder function, 40 points for an objective measure of ROM and 25 points for shoulder strength. A higher score illustrates better function . SubjectStatistical analysis included descriptive statistics in the form of counts, percentages, means and standard deviations to summarize demographic and other study variables. Parametric and non-parametric tests were used to compare variables between sexes, as well as pre and post injection differences when possible. An alpha value <.05 was considered statistically significant.31) for a summary of patient characteristics.A total of 33 shoulders in 25 patients were enrolled in the study. Eighteen of the participants were female and 7 were male with an average age of 57 years and a range of 47-70 years. Twenty-six of the shoulders examined were right with 7 left and 83% of the cohort were right hand dominant. The average follow-up was 17 months post-injection with a range of 4-41 months. Multiple co-morbidities were identified in the cohort. The most common were diabetes, pulmonary disease and heart disease at 44%, 21% and 18% respectively. Please refer to , physiotherapy (67%), massage therapy (47%) and acupuncture (17%). For those who tried physiotherapy and massage, the average number of sessions were 27 and 5 respectively. The patients taking medications mostly took Tylenol or aspirin daily.Of the 6 patients that received 2 injections, 3 were men and 3 were women. All were right hand dominant expect 1. Half of these patients were diabetic and all were taking insulin; one was a smoker. They all reported taking weekly medication for the pain with minimal improvement. The one patient that had 3 injections was also diabetic and on insulin; was right hand dominant and was taking Tylenol for the pain with no relief. The average pain severity score of these 7 patients was 9.5Sixty-nine percent of the cohort continued to complain of some shoulder pain in the post-injection follow-up clinic, however, their pain had improved from a mean of 8.8/10 pre-injection to 2.2/10 post-injection (p=0.01). The average score of the SPADI Pain was 36/100 and the SPADI Disability was 31/100 for a total of 67/100. This is within the normative average of 61/100. The Constant Score total was 64/100 which is below the normal average of approximately 84 for this age group. Range of motion measures included forward flexion which was 130.5° (opposite=139.8), abduction was 120.2° (opposite=142.5), and based on the Constant scoring system of 0-10, external rotation was 8 and internal rotation was 4.3 for the index side (opposite= 9 on average for both). No patients reported any increased pain with the injection or within 24 hours post-injection and there were no other reported complications. Furthermore, there were no statistically significant differences on any measures between the men and women in our cohort.We found injections with steroid increased shoulder motion and function, and significantly decreased pain in our cohort, although not entirely. This same finding was reported in a recently published systematic review examining intra-articular steroid injection for frozen shoulder . The optet al. produced similar results finding that patients treated with intra-articular steroid injection had improved pain and function scores than those treated with a saline injection alone or in combination with supervised physiotherapy. They did however identify that those patients who received a combination of an intra-articular steroid injection and supervised physiotherapy program had the fastest improvement in their range of motion [et al. identified the short-term benefit of intra-articular steroid injection when compared with mobilization, ice and rest back in 1984 [et al. studied intra-articular steroid injection versus a course of oral steroid in the treatment of adhesive capsulitis [Carette f motion . These ff motion . These f in 1984 . Lookingpsulitis . They foThe strengths of this study include that all patients were recruited from the same surgeon’s practice and thus had the same evaluation, received the same recommendations and were offered the same treatment options. In addition, all of the arthrographic steroid injections were performed by the same experienced musculoskeletal radiologist who used a standard technique with each patient receiving 40 mg of Triamcinilone and 5cc of 1% Lidocaine. There were no complications in our cohort such as infection, facial flushing or increased pain post-injection. This is consistent with the literature as arthrographic injection using steroid is considered a relatively benign and inexpensive procedure with few inherent risks to the patient .This study had several limitations inherent to a retrospective study. The response rate was quite low; however, all patients were recruited from the same surgeon’s practice, which although limited our numbers, added to the consistency. The follow-up interval had a wide range from 4-41 months. Consequently, it would have been preferable to stratify the results but unfortunately, the small number of participants did not allow for this to be accomplished. In addition, the number of injections varied from 1-3 in the index shoulder of our participants, which could have influenced their response to the treatment. Finally, we did not have any pre-injection data for our subjects such as their range of motion, SPADI or Constant score. Subjectively, they all reported significant improvements in their level of pain, motion and functional abilities.Arthrographic injection with steroid is a safe treatment option for patients with adhesive capsulitis that appears beneficial in improving both pain and range of motion. Despite the limitations in our study, we feel arthrographic injection with steroid is a viable treatment option with very little downside. Thus, we continue to recommend it as a treatment option for patients with frozen shoulder.Future directions include a randomized control trial in which we will compare arthrographic injection with steroid, local anesthetic and saline to injection with local anesthetic and saline alone to determine whether steroid is actually of benefit to this patient population.


Pain related to burn injuries is one of the most troublesome pain intensity. This study aimed to investigate the effect of massage on anticipatory anxiety, procedural pain intensity, vital signs and relaxation level of patients with burn injury.In this quasi-experimental study, through convenience sampling, 60 hospitalized adult burn patients were selected from a specialized burn and reconstructive hospital. Subjects were assigned to massage and control groups through simple randomization. Massage was offered by using non aromatic oil about 10-15 minutes before wound care on intact part of the body once a day for 20 minutes on patients’ bedside for 3 consecutive days. In the 3 days, the control group did not received any massage and were asked to stay at bed. Demographic and clinical characteristics and vital signs, Visual Analogue Scale and the Persian version of Burn Specific Pain Anxiety Scale were used to determine baseline and procedural pain, anxiety and relaxation levels and anticipatory anxiety. No significant difference was noted between mean score of pain intensity, anxiety and relaxation level, and vital signs in massage and control groups after intervention following wound care. In massage and control groups, there was no significant differences between mean scores of anticipatory anxiety before and after intervention. There was no significant difference between the mean scores of anticipatory anxiety in massage and control groups after intervention prior wound care.Massage was shown not to have any effect on anticipatory anxiety and procedural pain.  After burn injuries, patients encounter variety of painful procedures in the treatment course.5 and sleep problems.6 Also it can interfere with their compliance and result in less trust to health care providers and not cooperating with them.1 Finally, it would cause delay in wound healing and recovery process. As a result, effective strategies should be considered for reducing anxiety, distress and pain related to burn wound care for improving the overall well-being of patients.Also the anticipation of painful procedures can lead to anxiety and fear. Pain related to procedures and its anticipatory anxiety result in detrimental impact on patients including fears, post-traumatic stress, metabolic and immunologic disturbances,7 Low doses of opioids are not effective and with higher doses, side effects become progressively troublesome. Complementary therapies may use in addition to analgesics to decrease procedural pain and its related anxiety.8The primary choice of relieving pain and anxiety in burn patients are opioids. Repeated administration of opioids can result in tolerance and increasing doses of opioids should be done to achieve effective relief. Also it can result in physical dependence.9 It is a simple technique for managing pain through different ways, including induction of physical and psychological relaxation responses, increased blood flow and parasympathetic activity,10 releasing endorphins, decreasing inflammation, secretion of catecholamine, oxygen consumption, muscle spasm,11 closing the gate of pain,12 and promoting a feeling of well-being and receiving good care.13 Massage may improve the function of immune system too.14 Nurses should investigate the effects of different non-pharmacological interventions on pain.15 Further researches are necessary prior to massage become mainstream intervention for pain and anxiety relief. Massage is a common complementary therapy that often has been applied with inadequate evidence for its efficacy.16 Investigating this issue could provide evidence regarding the possible utilization of non-pharmacological interventions during wound care of burn patients.17 Field et al.18 reported that massage can reduce pursuits, pain and psychological symptoms after burn injury. Hernandez-Reif et al.19 noted that massage in burn patients can increase pain threshold and patients tolerance for procedural pain. Although some studies of massage indicated that it may have useful effects in patients with various conditions, but methodological issues in these studies limit their internal validity and generalizability.9,20,21 The other reason for these compromises is that research regarding complementary therapies and symptom management often have less financial supports,22,23 even though symptom management is critical for the patient’s quality of life.24Limited studies have evaluated the benefits of massage prior to burn wound care in reducing procedural pain and anticipatory anxiety. However, the effect of jaw relaxation before wound care on pain-related anxiety in burn patients was investigated and significantly reported less pain-related anxiety after intervention and before wound care.This study aimed to investigate the effect of massage that implemented before wound care on anticipatory anxiety, procedural pain intensity, vital signs and relaxation level. It was hypothesized that compared to control group, burn patients who received massage would have a greater decrease in anticipatory anxiety; reduction in procedural pain intensity; decrease in blood pressure and pulse rate; reduction in anxiety level and increase in relaxation level. This study was a quasi-experimental, pretest-posttest comparison group design. Ethical approval was granted from Research Ethical Committee of Tehran University of Medical Sciences. Confidentiality and anonymity were guaranteed throughout the study. Informed consent form was signed by all participants and they also gave verbal agreement to receive massage before each session.This study was carried out in Motahari Burn and Reconstructive Center affiliated to Iran University of Medical Sciences in Tehran, Iran. The sample size was estimated 30 subjects for each massage and control groups with medium effect size (ES) of 0.65, power 85%, an alpha of .05, and 10% drop-out rate. The homogeneity of groups was assessed regarding demographic and clinical variables. Burn patients were asked to participate in this study between November 2013 and March 2014. Inclusion criteria of participants were 1) age older than 18 years; 2) having no cognitive disorder; 3) at least 72 hrs. passed from burn, 4) patients with severe burn injury  more than 20%) and 5) to be able to communicate verbally. The exclusion criteria were deterioration of patient’s condition and not receiving intervention in all 3 sessions of the study.Through convenience sampling, 60 patients were recruited. After obtaining informed consent, participants were allocated to massage and control groups based on simple randomization method. Blinding participants, massage therapists, or researcher was not possible because of the nature of intervention; however, a co-researcher who conducted data gathering and entry was blind about the groups. st day before intervention, demographic and clinical characteristics of patients in both massage and control groups were determined by a brief interview and use of medical records. Demographic characteristics included age, gender, marital status, educational level, adequacy of income, ethnicity and occupation status. Clinical characteristics included history of hospitalization due to burn injury, cause of burn, TBSA, burn degree, and burn parts of the body. The 3 researcher-designed forms were considered to document demographic and clinical characteristics, and vital signs . In 1In 3 consecutive days after intervention and wound care, vital signs  of patients in two groups were measured and documented by co-researcher. The brachial pulse and respiration rates were counted for a minute in a comfortable position for patient. Blood pressure was monitored by portable analog sphygmomanometer through auscultation. 25 High internal consistency and good validity of Persian version of BSPAS has been reported.26 BSPAS has 9 items; each including a visual analogue scale (VAS), with digits ranging from 0  to 10 (the worst imaginable way). The patients were asked to rate VAS for each item, then the total score was calculated by summing the scores for all items. The range of the scores was 0–90. The higher the value rated, the anticipatory anxiety level was greater. Anticipatory anxiety should be measured before painful procedures including wound care.8 In current study, in 3 consecutive days before wound care and intervention, and about 10-15 minutes after intervention, the patients were asked to fill the scale to measure anticipatory anxiety.Behavioral Pain Scale to assess pain (BSPAS) is a self-reporting scale and measures anticipatory anxiety in burn patients experiencing painful procedures.8 The VAS was a reliable and valid scale to measure subjective information including pain intensity and anxiety level.27,28 After intervention and wound care, patients in both groups were asked to rate their pain intensity on a VAS, ranging from 0 (no pain/discomfort) to 100 (the worst pain). The higher the value rated, the greater the pain intensity was. Also patients were asked to rate their relaxation levels at that point of time on a VAS, ranging from 0 (quiet relax) to 100 (no relaxation). The higher the value rated, the relaxation level was lower. A separate VAS, ranging from 0 (no anxiety) to 100 (highest anxiety level), were used for assessing anxiety among patients in both groups. The higher the value rated, the greater the anxiety level was.Wound care procedures were long lasting with fluctuations in pain. Its related pain intensity and distress was measured following wound care to have accurate measurement.Massage was offered on intact part of the body once a day for 20 minutes on patients’ bedside for 3 consecutive days. Burned part of the body had dressing and 2 co-researchers who were certified massage therapists performed massage for the patients. By coordinating with staff, using paravan and closing the door, co-researchers facilitated patients’ relaxing during intervention. Participants were draped with a sheet over the body and only the needed portions of the body for massage were exposed. Swedish massage  was performed by using non-aromatic oil about 10-15 minutes before wound care. The therapists performed massage in a comfortable position for patient from shoulders to toes and vice versa on only intact portions of the body and within one inch of dressing. They applied massage in the direction of the patients’ heart. During massage intervention, the speed, depth and pressure of the hands on body were tried to be stable. In 3 days, the control group did not receive massage and were asked to stay at bed. Data was analyzed using SPSS software . A P≤0.05 was considered statistically significant. The average score of outcome measures in three days was considered for data analysis. All Data was normally distributed. Patients’ baseline demographic and clinical characteristics were summarized using descriptive statistics. Between-group differences at baseline were investigated using Chi-square and Fisher’s Exact test for categorical data and independent t-test for continuous data. Paired t-test was used to compare pain, anxiety and relaxation levels, and vital sign levels within groups. Mean scores of changes in these variables before and after intervention was considered for comparing groups. Sixty burn patients participated in the study (30 patients in each groups), with dropout rates of 0% and response rate of 100%. Patients’ demographic and clinical characteristics were presented in nd to 3rd degree burns. In all patients, more than two body areas had burn injuries. The mean TBSA was 33.00% (8.96) and 32.03% (8.17) in massage and control groups, respectively. Also patients’ baseline characteristics before intervention were similar in massage and control groups  years. All in both groups were pre-medicated for pain related to wound care. In massage and control groups, the majority of participants experienced flame 2l groups .The mean procedural pain intensity, and level of anxiety, relaxation and vital signs in massage and control groups were demonstrated in The mean anticipatory anxiety in both massage and control groups awere summarized in In this study, we assessed the effect of massage on anticipatory anxiety, procedural burn pain intensity and anxiety and relaxation level showing that massage did not decrease anticipatory anxiety and procedural pain anxiety level and vital signs among burned patients. The study hypotheses were rejected and indicated that compared to control group, burn patients who received massage did not have any decrease in anticipatory anxiety; procedural burn pain intensity; anxiety level; blood pressure; respiratory rate and pulse rate. The data suggest that massage did not increase in relaxation level in experimental group compared with control group. 29 reported that massage before or during treatment reduced anxiety and pruritus and increased relaxation level in children with burns and eczema. Hernandez-Reif et al.19 reported that burn children in a massage group indicated less distress behaviors and movement during wound care as compared with control group. Also nurses reported that wound care for children in experimental group was easier than control group. The study findings indicated that massage did not decrease anticipatory anxiety due to wound care in burn patients. Inconsistent with current results, Fieldet al.30 indicated that 30 minutes massage for 5 days before debridement reduced anxiety and cortisol levels in burn patients. The difference may be related to the fact that in this study patients experienced severe burn injuries (TBSA more than 20%). As Hanafiah et al.31 mentioned that burn size, depth and location, anxiety and depression, inflammation, healing progression and grafting can influence pain intensity. The differences between the results of current study with previous research can be related to different research population. The literature mostly focused on burn children and in current study on burn patients who were adults. They may differ in experience and perception of and response to distress related to wound care. Also Field et al.32 found significant relationship between TBSA and pain scores and illustrated that TBSA is a significant predictor of burn pain. Also they found that higher levels of anxiety and depression were related to higher pain scores. Because of bidirectional relation between pain and anxiety, there was no significant reduction in procedural pain intensity and anxiety level after wound care. Also massage did not continue in dressing room which can be another reason for not effecting on procedural pain, anxiety and relaxation and physiologic measure. Byers et al.33 indicated that during treatment anxiety and procedural pain, level of burn patients was higher than the baseline and background anxiety. However, it might be difficult to relax and stay stable for massage simultaneous with conducting wound care.Loncar According to our findings, massage was not effective in managing anticipatory anxiety and procedural pain intensity in burn patients with severe injury. The data suggest that massage did not improve procedural anxiety and relaxation levels and physiologic measures among patients with burn. Any invasive procedure can produce pain and anticipatory anxiety. Not preventing and treating pain and anxiety may cause detrimental effects in burn patients. Therefore, more research is needed to investigate different complementary therapies for controlling procedural pain and anticipatory anxiety. Also nurses play important and paradoxical roles in managing pain in burn patients and it is essential to consider most effective approaches to manage it. In our study, random allocation was not conducted; however, homogeneity of the groups was tested. Therefore, it is recommended to replicate this study by considering random allocation too. In this study, the sample size was small, so it is recommended to conduct further investigation with larger sample sizes. In current study, Swedish massage was used and the results indicated no efficay. It is recommended to investigate and compare other techniques of massage to indicate the most effective one for improving anticipatory anxiety and procedural pain in burn patients. Also, in current research; 20 minute massage was performed 10 to 15 minutes before procedure. Since there is not standard time length for conducting massage, it is recommended to investigate different time intervals for massage to determine the effective time for improving patients’ symptoms. Also, there is not information about wash out period time of massage and perhaps conducting massage immediately before wound care and continuing it in dressing room can affect on anticipatory anxiety and procedural pain intensity. Therefore, further researches are recommended too. Because of the nature of the intervention, Hawthorne effect should also be considered in the study.


Chronic pain is a major economic and social health problem. Up to 79% of chronic pain patients are unsatisfied with their pain management. Meeting patients’ expectations is likely to produce greater satisfaction with care. The challenge is to explore patients’ genuine expectations and needs. However, the term expectation encompasses several concepts and may concern different aspects of health‐care provision.This review aimed to systematically collect information on types and subject of patients’ expectations for chronic pain management.We searched for quantitative and qualitative studies. Because of the multidimensional character of the term “expectations,” the search included subject headings and free text words related to the concept of expectations.A framework for understanding patients’ expectations was used to map types of expectations within structure, process or outcome of health care.Twenty‐three research papers met the inclusion criteria: 18 quantitative and five qualitative. This review found that assessment of patients’ expectations for treatment is mostly limited to outcome expectations . Patients generally have high expectations regarding pain reduction after treatment, but expectations were higher when expressed as an ideal expectation (81‐93% relief) than as a predicted expectation (44‐64%).For health‐care providers, for pain management and for pain research purposes, the awareness that patients express different types of expectations is important. For shared decision making in clinical practice, it is important that predicted expectations of the patient are known to the treating physician and discussed.Structure and process expectations are under‐represented in our findings. However, exploring and meeting patients’ expectations regarding structure, process and outcome aspects of pain management may increase patient satisfaction. The aim of this study was therefore to systematically explore the literature for information on patients’ expectations of CNCP management. As the term “expectations” comprises a broad range of concepts which can refer to several aspects of health‐care delivery, we start this review by defining and classifying expectations according to type of expectation and according to Donabedian's health‐care model of structure, process and outcome of care.1.1Expectations are generally explained as “a strong belief that something will happen or be the case.”1.1.1ThompsonIdeal expectations are visions, aspirations, needs, hopes and desires, related to the patient's views of the potential for a service.Normative expectations are expectations about what should or ought to happen, mostly derived from what users are told, or led to believe, or think that they ought (or to which one has a right) to receive from health services.Predicted expectations are beliefs about what will actually happen and are likely to result from personal experiences, reported experiences of others and other sources of knowledge such as in the media.KravitzIn this study, we consider “expectations as probabilities” and “predicted expectations” to reflect the same type of expectations. Throughout the study, we will refer to this as predicted expectations.1.1.2Patients may express their expectations regarding several aspects of health‐care delivery. The Donabedian's health‐care model provides a standard for examining health services and evaluating quality of health care and distinguishes between structure, process and outcome of care (SPO).1.1.3The term “expectations” is sometimes undefined, imprecise or multi‐interpretable; therefore, a conceptual framework is used to categorize the findings from the papers in this review Figure . Expecta22.1The main objective of this systematic review was to classify patients’ expectations regarding CNCP management according to the framework of understanding expectations Figure . Seconda2.2This systematic review explored expectations regarding CNCP management reported in quantitative, in qualitative, as well as in mixed methods research papers. The combination of quantitative, mixed methods and qualitative research was expected to generate a more complete and deeper insight than either method alone.2.3Expectations of patients undergoing pain management continually change when experiences accumulate.Studies were considered eligible for review if they met the following inclusion criteria: (i) patients were questioned about expectations before or during CNCP management; (ii) the study population consisted of adult patients with chronic (≥3 months) non‐cancer‐related pain; (iii) measuring expectations was (one of) the objective(s) of the study, and the method for obtaining information on patients’ expectations was described. Exclusion criteria were as follows: (i) cancer‐related pain, (ii) pain duration of less than 3 months or (iii) pain duration not specified.In case of inadequate or missing information about expectation(s) or definition of chronic pain, authors of the article were contacted for information. Studies were excluded from this review if multiple studies were identified, with overlap in study populations and findings. When this was the case, only the most appropriate (to our review objective) study was included to avoid potential duplication of data sets.2.4A literature search was performed for suitable articles published between 1990 and 2016, archived in Medline, PSYCHINFO, CINAHL and EMBASE. Owing to the broad range of concepts related to the term “expectations,” the search included subject headings and free text words connected to the construct expectations.2.5Quality assessment of the qualitative research papers was conducted by two independent reviewers(JG/CL) according to the Qualitative Assessment and Review Instrument (QARI).Assessment of the quantitative and mixed methods research papers was performed with the Mixed Method Appraisal Tool (MMAT).2.6Extraction of findings of the qualitative papers was performed using the Qualitative Assessment and Review Instrument (QARI). . An expectation finding was defined as a theme, metaphor or data by the author supported by quotes from the patient, fieldwork observations or other data. Only unequivocal and credible findings were considered for evaluation; these are findings that are matter of fact, directly reported/observed and not open to challenge.To categorize patients’ expectations, a metasynthesis of the papers is presented in a tabular summary, using the framework of Figure Mixed methods studies in this systematic review were evaluated as quantitative papers because the analyses were quantitative, although the assessment often was mostly qualitatively performed. Three authors JG/CD/PW independently categorized the types of expectations. Differences in categorization were discussed and solved in a consensus meeting.33.1Figure 3.2Table 3.3The quality of the studies was appraised using the MATTAs our interest only related to pain management expectations, and these were collected mostly at baseline, all the quantitative and mixed methods papers were appraised as descriptive studies. On item 4.3 (“Are measurements appropriate”), for 11 of the 18 quantitative papers, the scores were zero because these studies used self‐constructed questionnaires without validation. The quality of the quantitative papers was good to excellent with ten papers reaching 50‐54%, seven 75% and one paper scoring 100%.Most qualitative studies Table b scored 3.43.4.1Table Qualitative studies described more frequently (N=7) value expectations. Sixty per cent of qualitative papers described both value and predicted expectations.3.4.1.1Table Only value expectations were found regarding structure of care; these value expectations were expressed as ideals or necessities. Patients expressed the desirability of fellow patient involvement in a chronic pain management service, mostly to support the patients in their contact with the professionals and achieve validation of their pain problem3.4.1.2Research addressing expectations regarding process of care was found in one quantitative3.4.1.3Most studies, all 18 quantitative and three (of five) qualitative, reported outcome expectations, of which 15 papers showed outcome expectations only. Fifteen papers reported predicted outcome expectations and 13 studied value expectations.Almost all of the quantitative studies investigated predicted expectations in terms of pain management goals, like expected outcome. Four studies focused on value expectations, for example desired, disappointing, worthwhile or outcome needed to consider the pain management a success.Four papers studied expected pain relief before pain treatment and related this to the pain reduction acquired after treatment. All showed that patients expected a substantially larger reduction in pain from the treatment than they attained.The qualitative studies Table  also shoWithin each setting of care delivery, that is primary care, CAM, surgery, rehabilitation, pain centres, most CNCP patients expected pain relief; however, some patients did not expect pain relief but expressed the desire and need for physical improvement and being able to walk with the grandkids for instance, or do daily living chores without limitations. Some patients expressed the need to learn to cope with the CNCP, or to learn tools for better control of the complaints.4In this review, we systematically searched for quantitative and qualitative studies addressing expectations of chronic pain patients regarding CNCP management and categorized expectations according to the type of expectation and Donabedian's health‐care model of structure, process and outcome.This review found that assessment of CNCP patients’ expectations for pain management is mostly limited to outcome expectations. Furthermore, we found that patients answer differently to questions pertaining predicted expectations than to questions about ideal expectations. Patients’ ideal expectations are higher than their predicted expectations; some patients hope for, or desire, a full cure, but predict to gain little or nothing from pain management. This discrepancy between ideal and predicted expectations could be due to negative experiences in the past, or it could be that patients lower their expectations as a way to avoid disappointment.Results of the papers in our review showed that overall CNCP patients’ expectations of pain reduction after treatment are high. This is most certainly true for the ideal expectations. This alone can lead to dissatisfaction with pain management. Improvement of pain management could be the answer . However, it is known that often, even if the clinical outcome expectations are met, some patients are still dissatisfied.Our results show that the expectations as expressed by the patients depended on which way the questions were asked. For instance, when asking for desired  levels of pain after treatment, patients reported to wish for up to 98% pain relief versus when asked “what to expect the treatment to do” (predicted expectation), patients reported far more realistic pain reductions of 50%. Therefore, it is highly probable that the relationship between “value” expectations and outcome differs from the relation between “predicted” expectations and outcome. Six studies in this review demonstrated this by assessing the relation between outcome and expectations.We found that most quantitative papers did not use validated expectation scales. This could be due to the fact that applied research into patients’ expectations is still in its infancy. Developing and validating expectation scales that comprise structure, process and outcome expectations as well as the different types of expectations would be helpful for shared decision making and could provide a useful tool for expectation management during pain therapies.The incorporation of findings into a predefined expectation framework can be seen as a strength of this systematic review. Working with a framework to categorize types of expectations found in the papers leads to a better understanding of the broad concept and terms related to “expectations.” However, the original papers did not always provide a typology of expectations, leaving this open to our interpretation. Specifically, within value expectations, distinguishing between necessities and normative expectations was particularly challenging. The categorization was therefore performed by three authors independently , and differences were discussed until consensus was reached.Another strength of this systematic review is the combination of quantitative, mixed methods and qualitative studies. Qualitative findings added context or explanatory powers to the quantitative data, whereas quantitative data were useful to assess the size of the topic of interest. Furthermore, we found that qualitative findings provided more information about expectations regarding process and structure of care. However, some qualitative studies also restricted themselves to asking focused questions and explored or reported outcome expectations only.For health‐care providers, for pain management and for pain research purposes, the awareness that patients express different types of expectations is important. For health‐care providers, it points at the importance of asking the right question about expectations in shared decision making and in expectation management. A validated questionnaire that incorporates all types of expectations that are assessed before the first consultation would be a useful tool to ensure manageable answers from the patient and discover genuine needs that should be incorporated into the pain treatment plan. Furthermore, this asset could also help in shared decision making to discover and discuss unrealistic expectations for treatment so as to avoid disappointment and dissatisfaction with care.Health‐care providers and policymakers should grasp the opportunity to improve on structure, process and outcome of care and thereby attain higher patient satisfaction by better meeting patients’ expectations.4.1This systematic review showed that little information could be found about structure and process expectations of CNCP patients. We like to point out that this could be a lost opportunity to derive higher patient’ satisfaction for CNCP management. It is known that structure and process components of care can influence pain patient’ satisfaction.Understanding the expectations and needs of patients is essential in shared decision making.Differentiating between types of expectations could also be important if patients are in the process of accepting the pain better and consequently struggling less with the pain.