Pain management is a very important aspect in the intensive care unit (ICU), as adequate pain control has been shown to be associated with better clinical outcomes in critically ill patients. A Numerical Rating Scale (NRS) ranging from 0 to 10 , which is based on a patient’s self-report, is the gold standard for pain evaluation in patients who can communicate their pain intensity. On the other hand, it is very difficult to evaluate the degree of pain in critically ill patients owing to decreased consciousness level, delirium, and the effect of sedation for mechanical ventilation management. The Behavioral Pain Scale (BPS) and Critical Care Pain Observation Tool (CPOT) have been developed for pain assessment in patients who cannot self-report their pain intensity, and recent research has confirmed their efficacy in clinical trials. In the study by Paolo et al., published in this journal, they have demonstrated that discriminant and criterion validities of BPS and CPOT are good for the assessment of pain in mechanically ventilated critically ill patients. Besides, the authors have also shown that the combination use of these two tools is superior to the use of each tool individually. In this commentary, I would like to describe the importance and the difficulty of pain assessment in critically ill patients, discuss the validity and the reliability of the two major pain assessment tools, BPS and CPOT, and consider the future direction of pain assessment in the ICU. The majority of critically ill patients in the intensive care unit (ICU) often experience pain during usual care, such as turning position, endotracheal suctioning, surgical wound care, and insertion or removal of drain and catheters during their ICU stay , 2. PainFor patients who cannot communicate their pain intensity, the Behavioral Pain Scale (BPS) and Critical Care Pain Observation Tool (CPOT) are recommended for pain assessment in an international guideline ) . AlthougIn the study by Paolo et al., the authors compared BPS and CPOT with regard to the criterion validity and the discriminant validity and evaluated BPS and CPOT both individually and in combination, with regard to their sensitivity and specificity for detection of pain, in mechanically ventilated critically ill patients during usual nursing care including painful procedures. They have demonstrated that both tools have similar good criterion and discriminant validities, and the combination use of both tools might improve the efficiency for pain assessment, since the combination use resulted in better sensitivity and specificity, compared with the use of either tool alone. Furthermore, they have shown that facial expression has the strongest effect on pain assessment. Although this study might bring a new insight to pain assessment, I would like to present several issues that should be discussed in this study.First, it is questionable whether the combination use of two pain assessment tools has a synergistic effect on the improvement of pain assessment, even though the combined use of both tools resulted in higher sensitivity than the use of either tool individually and higher specificity than the use of CPOT alone. Considering that BPS and CPOT include three common parameters, that is, facial expression, body movement (upper limb movement in BPS), and ventilator compliance, I wonder if only summing both scores reflects better pain assessment, compared with each scale alone. Regarding the discriminant validity and the criterion validity of the combination use of two tools, which was not evaluated in this study, the results of these evaluations would be expected to be better considering that the discriminant and criterion validities for each scale, BPS and CPOT, were good. Furthermore, the authors evaluated BPS and CPOT and the combination use of these tools regarding sensitivity and specificity in only conscious patients who could self-report their pain intensity. Since BPS and CPOT have been developed to evaluate pain intensity in unconscious patients who cannot communicate their pain levels effectively, the combination use of two tools should be evaluated in unconscious patients or patients with delirium. It is very surprising that there were no patients who developed delirium, even though critically ill patients were included and midazolam was used for sedation in this study. Second, the discriminant validity should be examined during both painful and non-painful procedures in the same population. If the values evaluated by pain assessment tools are increased by both painful and non-painful procedures, the validity and reliability are questionable. Thus, evaluation of the discriminant validity should be performed during morning care, including painful procedures, and evening care without painful stimulation, in this study. Finally, it is very important to evaluate the degree of pain intensity rather than to detect the presence or absence of pain and prescribe analgesics according to each patient’s degree of pain without adverse events. This study did not examine if the combination use of two pain assessment tools can evaluate the degree of pain better than either scale alone. Further study is warranted to examine whether the combination use of two pain assessment tools can evaluate the degree of pain intensity accurately.Appropriate pain management is a very important aspect when caring for critically ill patients in ICUs. However, pain assessment in patients who cannot communicate their pain levels due to unconsciousness or delirium imposes challenges on attending physicians and nurses. Among many pain assessment tools, BPS and CPOT are recommended for the evaluation of pain intensity in critically ill patients. Although some review articles have reported certain limitations for both pain assessment tools , 10, the


Community-based musculoskeletal physiotherapy is used to improve function and health related quality of life (HRQoL). The purpose of this retrospective, multi-centre observational study was to determine the association between community-based physiotherapy management for musculoskeletal disorders and changes in HRQoL.Four thousand one hundred twelve patients’ data were included in the study. Patients were included if they received a single period of treatment for a musculoskeletal injury or disorder. Patients were only included if they were being treated for a single morbidity. Patients received standard physiotherapy appropriate to their specific disorder, which could include health education/advice, exercise therapy, manual therapy, taping, soft tissue techniques, electrotherapy and/or acupuncture. Health related quality of life was assessed using the EQ-5D index.EQ-5D improved by 0.203 across all patients (d = 1.10). When grouped by anatomical site of symptom, the largest increases in EQ-5D was in foot pain  and lumbar pain . Improvements in EQ-5D greater than the minimum clinically important difference (MCID) were seen in 68.4% of all patients. The highest proportion of patients with positive responses to treatment were in ankle pain (74.2%) and thoracic pain (73.4%). The hand (40.5%), elbow (34.7%), and hip (33.9%) showed the greatest proportion of patients that did not respond to treatment.Community-based musculoskeletal physiotherapy is associated with improved health related quality of life. A randomised controlled trial is needed to determine any causal relationship between community-based physiotherapy and health related quality of life improvements. Musculoskeletal injuries and disorders are one of the largest contributors to pain and disability worldwide . Low bacThe EuroQol 5 Dimensions (EQ-5D) instrument provides an indication of general health status across five dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression . It alsoIn physiotherapy, EQ-5D has been used to assess the effectiveness of interventions such as the PhysioDirect telephone service , interveAll patients that received National Health Service (NHS) community-based physiotherapy from one of five centres  between January 2012 and April 2016 were included in the sample and data collected before and after their episode of care were assessed retrospectively. The mean new to review ratio across these centres within this period was 1:2.38. Patients entered the service either via referral from their general practitioner (GP), or through self-referral via “Physioline”, a telephone assessment and advice service. Those aged less than 16 years of age, or those with hearing impairments were excluded from the telephone self-referral system and entered only through GP referral.The study was approved by the Northumbria University Ethics Committee as a retrospective service evaluation.On first entry into the service, patients’ anatomical site of pain was coded into one of 13 categories, including the foot, ankle, knee, hip, sacroiliac, lumbar, thoracic, neck, temporomandibular, shoulder, elbow, wrist, hand, as well as “generalised pain” and “other disorders not otherwise stated”. Patients subsequently received physiotherapy-based management in a community setting appropriate to their disorder or injury. These interventions typically included exercise therapy, manual therapy, taping, soft tissue techniques, electrotherapy and/or acupuncture, and were chosen according to patient need, using shared decision making. Episodes of care usually involved an initial telephone triage and treatment assessment followed by face-to-face appointments, if required.Patients entering the service completed a pre-intervention EQ-5D. As only the English language version of the instrument was used, those unable to understand the English language sufficiently to answer the questions without the need for an interpreter did not complete a pre- or post-intervention EQ-5D and were excluded from this study.The EQ-5D was administered upon first entry into the physiotherapy service and requested upon discharge from the service following the completion of treatment. Within each of the five dimensions, a patient will receive an integer score from 1 to 5, where a score of 1 indicates the best outcome  for that dimension. From the individual dimension scores, an index is calculated according to national tariffs. As this study evaluated EQ-5D data from a UK population, the UK tariff was used to calculate the EQ-5D index , which cPrevious studies have presented the minimum clinically important difference (MCID) in EQ-5D index in musculoskeletal patients, including a MCID of 0.03  and 0.08The investigators had full access to the data from all five centres, which were recorded in a single nationwide system. Data were only included for patients that were being treated for a single morbidity, where the length of time in the service was between 2 and 16 weeks. This was to ensure that only data for a single treatment intervention were included, being deemed the minimum and maximum duration that a patient would remain in the service for a single bout of treatment. Given a study period of 4 years, some patients re-entered the service at a later date for a further assessment and treatment, and these were included in the study as separate records. Any duplicate records were removed prior to analysis. Patients were only included if their records showed both pre- and post-treatment EQ-5D index. Patients were excluded if they were referred to advanced community services (CATS), as those patients had their post-treatment EQ-5D within CATS which, therefore, did not make this a valid representation of community-based physiotherapy management. Sacroiliac pain, temporomandibular pain and general pain groups were removed from the dataset due to having very low patient numbers, and the other disorders not otherwise stated group was also removed as it did not pertain to any specific anatomical location.Demographic and EQ-5D data were evaluated for all patients, and for individual sites of pain. The number of patients of each gender were determined overall, as were the number of patients that received treatment within each site of pain. Age, days in service and EQ-5D data were reported as means (±SD) for all patients, by gender, and by site of pain. Changes in EQ-5D index between the start and end of treatment within the physiotherapy service were analysed using paired samples t tests for each site of pain. A 95% confidence level was used for all statistical tests. All statistical comparisons were performed in IBM SPSS version 24. As observed in our data, as well as in previous studies, EQ-5D indices are often skewed towards a score of 1.0 , suggestn = 4832), 28,285 patients had a first EQ-5D recorded, of whom 5547 patients also had an end of episode EQ-5D recorded, who were included in the analysis. Those without a follow-up score  were either discharged after their telephone assessment only as a “one-stop shop”, or failed to return the EQ-5D score after discharge if seen face to face. There were 465 patients that had returned more than 2 EQ-5D scores, who were excluded from the analysis due to the data management system only retaining the first and last score. Of the 5547 patients with both a pre- and post-treatment EQ-5D, a further 1275 were excluded as they did not meet the remaining inclusion criteria. Due to very small patient numbers, those in the sacroiliac pain (n = 24), temporomandibular pain (n = 4), and generalised pain (n = 4) were excluded, as were patients classified as other disorder not otherwise stated (n = 128), leaving a final sample for analysis of 4112 patient records.Overall, 33,117 patient records were obtained. After removal of duplicates  years, and the mean time to complete treatment was 50 (±25) days (Table 7.4 yearsThe most common sites of pain reported included lumbar (24.2%), knee (19.3%), shoulder (17.2%) and neck (13.7%) pain. The least common sites of pain included hand (2.0%), wrist (2.1%), and foot (2.6%) pain.p < 0.001; CI = 0.197–0.203), with a large effect size (d = 1.10) , ankle (t(189) = 14.871, p < 0.001; CI = 0.183–0.211; d = 1.36), knee (t(790) = 28.882, p < 0.001; CI = 0.187–0.200; d = 1.14), hip (t(300) = 15.587, p < 0.001; CI = 0.159–0.182; d = 1.08), lumbar (t(990) = 30.004, p < 0.001; CI = 0.216–0.231; d = 1.13), thoracic (t(127) = 14.496, p < 0.001; CI = 0.147–0.170; d = 1.28), neck (t(562) = 22.968, p < 0.001; CI = 0.179–0.196; d = 1.09), shoulder (t(705) = 25.904, p < 0.001; CI = 0.185–0.200; d = 1.08), elbow (t(149) = 12.201, p < 0.001; CI = 0.144–0.172; d = 1.08), wrist (t(87) = 10.419, p < 0.001; CI = 0.141–0.174; d = 1.25) and hand (t(83) = 8.389, p < 0.001; CI = 0.122–0.160; d = 0.88) pain.. The largest proportion of positive responders was found in patients being treated for ankle (74.2%) and thoracic (73.4%) pain. The highest proportion of patients not showing a clinically meaningful increase in EQ-5D was found in patients being treated for hand (40.5%), elbow (34.7%), and hip (33.9%) pain.Overall, the EQ-5D index improved significantly by 0.203 (t(4111) = 62.453, The main findings of this study were that attending community-based physiotherapy for musculoskeletal injury was associated with a significant increase in EQ-5D, both overall, and in all sites of pain. Two thirds of patients overall and by gender reported a clinically meaningful increase in EQ-5D following physiotherapy management. Between 56.0–81.3% of patients showed clinically meaningful increases (>0.1) in EQ-5D index across all sites of pain, and less than 5% of patients showed reductions in EQ-5D overall, by gender, and across all sites of pain.Overall, EQ-5D improved significantly by 0.203 across all sites of pain over the intervention period, with a large magnitude of effect. We believe this finding may provide new evidence that face -to-face community-based physiotherapy interventions are efficacious across a range of musculoskeletal presentations in improving health-related quality of life. Given that 68.4% of patients reported a clinically meaningful increase in EQ-5D, this should provide confidence for investment in physiotherapy as a modality in any musculoskeletal healthcare pathway. However, this suggestion must be confirmed in a prospective randomised controlled trial, as changes in EQ-5D reported in the retrospective cohort used in the present study could also have been the result of improvement due to the natural course of the condition over time.Only a limited number of studies have previously explored the associations between musculoskeletal-specific interventions and EQ-5D, reporting improvements ranging from 0.04 to 0.31 across physiotherapy, advanced physiotherapy, and inpatient musculoskeletal care , 23, 30.The most commonly treated sites of pain were the lumbar spine 24.2%), knee 19.3%), shoulder (17.2%) and neck (13.7%). In a large sample of patients with chronic pain, Parsons et al. [4.2%, kne%, shouldAt baseline, EQ-5D was 0.648 across all patients, and was higher in male patients (0.661) than female patients (0.640). The lowest pre-treatment EQ-5D was found in patients with lumbar pain (0.603) and was highest in patients with thoracic pain (0.728). When grouped by site of pain, the largest improvement was seen in patients treated for foot (0.233) and lumbar (0.231) pain, and the smallest change was seen in patients receiving treatment for hand (0.160), although this still showed a large effect magnitude.Compared with a range of orthopaedic surgical interventions where EQ-5D was reported to increase by a mean of 0.18 , our cohThe EQ-5D provides an overall indication of health status which is independent of the disorder for which patients are receiving treatment. Some studies have suggested that it could be more relevant to develop disease specific outcome measures, rather than using generic HRQoL outcomes. For example, the STarT Back screening tool was developed to subgroup low back pain patients for targeted treatment . Whilst A limitation of this study was that it was a retrospective analysis of data collected as part of routine clinical practice. As such, it was only possible to determine whether there was an associated change in HRQoL over the time course of physiotherapy management, as discussed above. The time period between EQ-5D scores also differed between patients as the outcome was administered on first entry into the service and on successful discharge. As the service took a patient-centred approach to determining the most appropriate course of treatment, and due to patients presenting at varying stages of injury/dysfunction, such variance in treatment length was to be expected. A prospective randomised controlled trial is needed to determine whether there is a causal relationship between community-based physiotherapy for musculoskeletal disorder and improvements in HRQoL or whether these changes were due to the natural healing process.This was however, the largest reported sample of musculoskeletal patients with EQ-5D index both pre- and post-treatment to date, and used data from a typical population of patients receiving community-based physiotherapy management for musculoskeletal injury. For those patients that self-referred through the Physioline service, the pre-treatment EQ-5D was administered over the telephone rather than in a face-to-face consultation for GP referred patients. McPhail et al.  showed hAnother potential limitation of this study is that a large number of patients failed to complete a second EQ-5D, and so had to be excluded, which could lead to selection bias. Completing second scores involves patient (e.g. patient did not attend treatment) and clinician factors (e.g. clinician did not administer post-treatment EQ-5D) and is a common challenge in clinical practice. The outcomes of those not completing are unknown and open to speculation. However, given the size of the sample, we believe this study gives the best indication of the association between physiotherapy interventions and improvements in HRQoL. Baseline data for the excluded patients Tables  and 2 shIn conclusion, there was an association between community-based physiotherapy and improvements in HRQoL in all joint areas. Community-based physiotherapy management was associated with the highest proportion of patients reporting a clinically meaningful increased in EQ-5D in ankle pain and thoracic pain, and with the smallest proportion reporting clinically meaningful increases in EQ-5D in hand, elbow and hip pain. A randomized controlled trial is needed in order to determine any causal relationship of the associations observed between community-based physiotherapy for musculoskeletal disorder and improvements in HRQoL.


At 12 weeks, the BoNT-A injections resulted in greater improvements in TWSTRS total scores than the saline injections without statistical significance (p = 0.0783 for ANCOVA). Dysphagia occurred in three out of 16 patients: two after BoNT-A and one after saline. The dysphagia was transient and improved naturally within two weeks without any special treatment. BoNT-A injection for CD in adults with dyskinetic CP is relatively safe and improves pain and disability.We aimed to evaluate the efficacy and safety of injecting botulinum toxin A (BoNT-A) into the neck muscles to treat cervical dystonia (CD) in patients with dyskinetic cerebral palsy (CP). This was a randomized, double-blinded, placebo-controlled trial with cross-over design. We prospectively enrolled adults with dyskinetic CP who were over 20 years old and had been clinically diagnosed with CD for more than one year. The primary outcome measure was the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) at four weeks from the baseline TWSTRS. Seventeen patients were initially enrolled, but one patient was excluded after the final evaluation because of a violation of the study protocol. At four weeks, the BoNT-A injections showed significant improvement in TWSTRS total scores compared to the saline injections ( In adults with dyskinetic cerebral palsy (CP), cervical dystonia (CD) may result in neurologic sequelae such as pain, dysfunction, and cervical myelopathy ,2,3. SurBoNT has also been successfully used in patients with CP for treatment of the upper and lower extremities . HoweverThe main purpose of this study was to evaluate the efficacy and safety of injecting BoNT-A into the neck muscles of CD in patients with dyskinetic CP. In addition, we investigated whether clinical factors, such as cervical spondylosis, affect the therapeutic effect of BoNT-A injections in these patients.p-value of 0.05 (p = 0.6740 for period effect and p = 0.2097 for carry-over effect).Seventeen patients were initially enrolled, but one patient was excluded after the final evaluation because of a violation of the study protocol, which was four times of shoulder and neck injection within the follow-up period after the injection. Demographic and clinical data for the sixteen participants included in the study are presented in p = 0.0286 for ANCOVA). At 12 weeks, the BoNT-A injections had a tendency to show greater improvement than the saline injections, but this difference was not statistically significant (p = 0.0783).TWSTRS total scores at baseline, four weeks, and 12 weeks are presented in p = 0.0152), but there was no significant difference after 12 weeks (p = 0.6444). On the TWSTRS pain score .There was no significant difference between the two injections on the TWSTRS severity score B. At fouin score D, the Bop = 0.0603 and 0.1796, respectively). On the disability NRS (p = 0.1466). On the satisfaction NRS (p = 0.0176). lity NRS B, the Botion NRS C, which The Japanese Orthopedic Association (JOA) score was constant in most patients. In the BoNT-A group, the average JOA score increased by 0.06 points after four weeks of injection, and the score in the saline group decreased by 0.06 points after four weeks of injection. There was no statistically significant change detected by the ANCOVA between the two groups.When the clinical features of CD included retrocollis rather than anterocollis, the TWSTRS scores showed greater improvement four weeks after injection A, althouDysphagia occurred in three of 16 patients, two after the BoNT-A injection and one after the saline injection that may have been caused by altered neck muscle activity and balance of the head and neck posture . Two patOur study revealed that BoNT-A injections used to treat CD in patients with dyskinetic CP result in greater improvement of TWSTRS scores at four weeks compared with saline injections, especially on the pain and disability subscales.Previous work concerning BoNT-A injections in CD reported that TWSTRS scores improved in 29 of 37 (78%) patients and were more effective than placebo . One stuIn patients with dyskinetic CP, failure to receive appropriate early treatment for the dyskinetic hyperactivity may result in the herniation of an intervertebral disc, spondylosis, malalignment, instability of the cervical spine, or a combination of these ,19. PainIn the patients with dyskinetic CP who participated in the study, the TWSTRS total score decreased by 7.14 points (17%) at four weeks and 5.16 points (12%) at 12 weeks after BoNT-A injection compared with the baseline score. The TWSTRS severity score decreased by 2.5 points (13%), disability by 0.81 (6%), and pain by 3.83 (35%) at four weeks after the injection. The pain subscale showed the most significant decline with a statistically significant difference. Therefore, BoNT-A injection is helpful in reducing the TWSTRS pain subscale score in dyskinetic CP, contributing to the reduction in the TWSTRS total score (17%), which is slightly less than the 20% reported by Zoons et al.  to be clAnother study  of idiopThere have been many studies of idiopathic CD ,14,15, bWhen clinical manifestations of CD included retrocollis rather than anterocollis, the TWSTRS score showed a greater improvement at four weeks after injection A. AnteroThere are some limitations to our study. We used a cross-over design due to the small number of dyskinetic CP patients in our research hospital. We failed to recruit 28 patients as initially intended due to the low incidence of this condition. Since there is not a large population of patients with dyskinetic CP, the number of participants we were able to recruit was insufficient for a randomized controlled trial. As patients with dyskinetic CP do not visit tertiary hospitals frequently in South Korea, it was very difficult to recruit patients. Also, there was an absence of long-term follow-up data and we did not observe the effect of regularly applied BoNT injections on pain, disability, spondylosis, and myelopathy in the CD of patients with dyskinetic CP. Lastly, TWSTRS pain and disability scores improved at four weeks after the BoNT-A injection, but not the NRS disability and pain scores. As NRS disability and pain scores are assessed by the patient and the TWSTRS score is determined by the clinician, the TWSTRS score should be more sensitive.Botulinum toxin injection for CD in adults with dyskinetic CP is relatively safe and can improve the pain and disability related to CD. This was a prospective, randomized, double-blind, placebo-controlled, cross-over study. Participants were randomly assigned to two groups, and depending on group assignment they were injected either first with BoNT-A and then saline or first saline and then BoNT-A . A thirdThis study was registered as a clinical trial (registration number: NCT01860196). All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All participants provided written informed consent and the Seoul National University Hospital Institutional Review Board (IRB) approved the study design before participation (IRB No. 1207-028-416).We included patients with dyskinetic CP who were over 20 years old and had been clinically diagnosed with CD for more than one year. We excluded the following participants: (1) those who had an allergic reaction to BoNT-A; (2) those with a fixed cervical range of motion limitation; (3) those with uncontrolled symptoms due to fever, infection, malignancy, or uncontrolled epilepsy; (4) women who were pregnant or lactating; (5) those who, at screening, were participating in other clinical trials or were taking muscle relaxants, benzodiazepine, or anticholinergic drugs within four weeks of screening; (6) those who had received a botulinum toxin injection within the previous six months; and (7) those who had been treated with intrathecal baclofen, selective peripheral denervation, or deep brain stimulation. ®, also known in Korea as Meditoxin® . Neuronox® and Meditoxin® are equivalent to BOTOX [One vial of BoNT-A (100 U) was diluted in 2 mL of normal saline to a concentration of 5 U per 0.1 mL. The maximum dose given per visit was 200 units. The BoNT-A used in this study was Neuronoxto BOTOX  and haveto BOTOX  and in sto BOTOX . Electroto BOTOX ,36, who A flowchart of the overall study design is presented in The Toronto Western Spasmodic Torticollis Rating Scale  consists of three subscales that grade the severity (range 0–35), disability (range 0–30), and pain (range 0–20) of the CD.Patients rated their pain, disability, and satisfaction using the Numerical Rating Scale (NRS). The NRS pain score was a scale designed such that the far left (0) indicated “no pain” and the far right (10) indicated the “worst pain imaginable”. Similarly, on the NRS disability score, the far left (0) indicated “no disability” and the far right (10) indicated the “worst disability”. On the NRS satisfaction score, which was not applicable to the baseline evaluation, the far left (0) indicated “no satisfaction” and the far right (10) indicated the patient was “very satisfied.”The Japanese Orthopedic Association (JOA) score  is composed of seven categories  and is a scoring system that evaluates severity of myelopathy . To evaluate the clinical factors affecting the effect of BoNT-A injection, clinical variables such as the dystonia pattern (anterocollis or retrocollis), the Kellgren grade for cervical spondylosis, and the injection doses for each muscle were also recorded ,39. ThesAll post-injection adverse events were recorded. Discomfort, reduced general condition, headache, dry mouth, injection site pain, neck/shoulder pain, blurred vision, voice alteration, viral infection, dizziness, back pain, tiredness, and inability to lift the head due to weakness were also investigated and recorded. A Video Fluoroscopy Swallowing Study (VFSS) was performed three times  for each patient, and additional VFSS was performed when dysphagia occurred after the injection to confirm and identify the abnormal findings.p-value of 0.05 was used as the threshold for statistical significance. A carry-over effect was defined as a significant difference in the TWSTRS score at four weeks between the two treatment sequences [Statistical analyses were performed using IBM SPSS 20 software  and SAS. A equences . AnalysiThe ANCOVA model was used to compare the changes on the TWSTRS at four weeks and 12 weeks after injections. In this model, the factor was the medication used  and the covariate was the baseline value of the TWSTRS. The NRS pain score and NRS disability score were also analyzed using the ANCOVA model. The NRS satisfaction score was analyzed using the Wilcoxon signed-rank test for the comparison of the BoNT-A and saline groups at four weeks and 12 weeks after the injections since baseline satisfaction scores were not applicable for this item. The ANCOVA model was used to determine whether clinical factors affected the degree of improvement after BoNT-A injection. The degree of improvement was defined as the change in the TWSTRS total score at four weeks.


Central pain mechanisms may be prominent in subsets of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritis (SpA). The painDETECT questionnaire (PDQ) identifies neuropathic pain features, which may act as a proxy for centrally mediated pain.The objectives were to quantify and characterize pain phenotypes (non-neuropathic vs. neuropathic features) among Danish arthritis patients using the PDQ, and to assess the association with on-going inflammation.The PDQ was included onto the DANBIO touch screens at 22 departments of Rheumatology in Denmark for six months. Clinical data and patient reported outcomes were obtained from DANBIO. A PDQ-score >18 indicated neuropathic pain features, 13–18 unclear pain mechanism and <13 non-neuropathic pain.Pain data  was available for 15,978 patients. 7,054 patients completed the PDQ . 52% of all patients and 63% of PDQ-completers had VAS pain score ≥ 30 mm. The distribution of the PDQ classification-groups (<13/ 13-18/ >18) were; RA: 56%/24%/20%. PsA: 45%/ 27%/ 28%. SpA: 55% / 24%/ 21%. More patients with PsA had PDQ score >18 compared to RA and SpA (p<0.001). For PDQ > 18 significantly higher scores were found for all patient reported outcomes and disease activity scores. No clinical difference in CRP or swollen joint count was found. Logistic regression showed increased odds for having VAS pain ≥39 mm (the median) for a PDQ-score >18 compared to <13 .More than 50% of the Danish arthritis patients reported clinically significant pain. More than 20% of the PDQ-completers had indication of neuropathic pain features, which was related to a high pain-level. PDQ-score was associated with DAS28-CRP and VAS pain but not with indicators of peripheral inflammation (CRP and SJC). Thus, pain classification by PDQ may assist in mechanism-based pain treatment. Pain in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondyloarthritis (SpA) is traditionally considered to be of peripheral nociceptive origin, i.e. pain elicited by activation of afferent sensory nerve fibers (C-fibers) in the inflamed synovium . IncreasChronic pain has been most thoroughly investigated in RA where pain is reported to persist despite regression of inflammatory signs  and emerTreatment of inflammatory arthritis is based on disease activity measures that are fully or partially composed of subjective indicators related to pain perception. Pain hypersensitivity may lead to continuous high reports of for example tender joints, pain and poor global health and thus an overestimation of inflammatory activity. Identification of possible underlying pain mechanisms may, therefore, be of great importance and assist clinical decision making. The painDETECT questionnaire (PDQ) is a patient administered screening questionnaire originally developed to identify neuropathic pain . Based oThe purpose of this study was to report the prevalence of pain phenotypes (non-neuropathic vs. neuropathic pain features) as assessed by the PDQ in the Danish arthritis population  and to investigate the association between pain phenotype and inflammation. Furthermore, the study aimed to describe differences in patient characteristics across PDQ-classification groups.http://parkerinst.dk/research). The DANBIO-registry is a clinical quality assurance registry which was initiated in year 2000. It is based on Danish rheumatologists registering and continuously reporting data on their patients diagnosed with inflammatory arthritis when seen in daily care. It covers >90% of adults treated with biologics due to rheumatic disease and data on patients treated with disease-modifying antirheumatic drugs, DMARDs, are also collected [The study was designed as a descriptive, cross sectional survey including patients registered in DANBIO, the Danish nationwide rheumatologic registry . All patients registered as having any form of RA, PsA, other SpA, unspecific arthritis (UA) or ‘no diagnosis’ were eligible and invited to participate in the survey. Patients were asked to accept participation, decline or indicate ‘no pain 4 weeks prior to the survey’ on the touch screens. Patients choosing the two latter categories were excluded from filling in the PDQ, while clinical data from DANBIO were obtainable from all patients visiting the touch screens in the study period.The primary focus was on the diagnostic groups: RA, PsA and other SpA. All patients were included in the overall pain analysis, while only patients with a complete PDQ response were included in the PDQ subanalyses. The first complete questionnaire and corresponding clinical data from the same date were extracted for analyses (CRP +/- 14 days).Patient consent was obtained on the touch screen prior to the redirection to the PDQ. According to Danish legislation, surveys do not require approval by Ethics Committees and registrations and publications of data from clinical registries do not require patient consent or approval by Ethics Committees. Approval was obtained from the Danish Data Protection Agency.The PDQ is a symptom-based assessment tool originally developed to assist identification of neuropathic pain in patient with low back pain . It is cInformation on demographics and treatment were registered according to the DANBIO registry standard. Before consulting their rheumatologist patients regularly complete commonly used standardized patients reported outcomes  on the DDAS28-crp (disease activity score 28 joints–CRP)  used forASDAS (ankylosing spondylitis disease activity score)  used forBASMI-365 (Bath ankylosing spondylitis metrology index undertaken within the last year) : a standSAS software  was used for the statistical analyses. The PROC UNIVARIATE statement was used for visual inspection of the distribution of variables. Potential group differences were tested using the non-parametric Kruskal-Wallis test for continuous variables and Chi-square test for categorical variables. Correcting for multiple testing (65 repeated tests) two-sided p-values < 0.001 (0.05/65) were regarded as statistically significant when comparing potential PDQ classification-group differences. Due to the ‘real life’ character of DANBIO complete data for all variables were not available. Only available data were used for calculations.To address the possible presence of sensitization in more ways also the swollen to tender joint count ratio (STR) was calculated according to previously published procedures  and compTo quantify a potential increased risk for rating higher than or equal to the median VAS-pain associated with the PDQ classification-groups  logistic regression analysis was performed. For pragmatic reasons the median VAS for PDQ-completers was chosen as cut off (39 mm). Prior to conducting the logistic regression, an analysis of possible interaction between the PDQ classification-group and diagnosis was performed, which proved insignificant (y = ‘diagnosis’ ‘PDQ classification-group’ ‘diagnosis*PDQ classification-group’ (interaction); p-value for interaction = 0.76, p-value for PDQ ‘classification-group’ <0.001, p-value for ‘diagnosis’ < 0.001). Hence, the ‘PDQ classification-group’ and ‘diagnosis’ were applied as main effects in the unadjusted Model 1. Separate models were run for each pain classification and disease comparison. Based on clinical significance and plausibility the following a priori selected confounders were included in the adjusted Model 1: sex, age, disease duration, CRP, and status of treatment with biologics (yes/no). Accepted level of covariance between independent variables was Spearman’s Rho < 0.3. Backward deletion of variables with a p-value > 0.1 was performed to make a more parsimonious adjusted model (Model 2). Results from the logistic regression analyses are reported as odds ratios with confidence intervals (95%CI).The main results of this study, the distribution of the PDQ classification-groups (<13/ 13-18/ >18), are illustrated in Patient characteristics stratified by PDQ-score are shown in A higher number of women was observed in the higher PDQ classification-groups along with higher absolute values of all patient reported outcomes e.g. patient’s scores for pain, fatigue, global health and disability , doctor’s global score and disease activity scores for the three diseases . There were no differences across PDQ classification-groups in CRP, serology and current treatment with a biological agent. Furthermore, the median swollen joint count (SJC) was 0 for all categories; however the interquartile range varied slightly (p<0.001).Some differences across PDQ classification-groups only related to one of the diagnoses:In patients with RA, higher tender joint count (TJC) and number of patients currently treated with DMARD and previously treated with Biologics were observed in the higher PDQ classification-group, while age was higher in the low PDQ classification-group.In PsA patients higher absolute values in the higher PDQ-classification-groups for TJC and higher fraction of patients treated with more than one biological drug were seen.In patients with other SpA a lower proportion of HLA-B27 positive patients was observed in the higher PDQ classification-groups, though not (borderline) statistical significant.Finally, a stratified analysis of the number of biologic agents received by the patients  did not reveal any differences.BMI only differed across PDQ-classification-groups for RA-patients (p<0.001), where a higher value was observed in the higher classification-groups, while no difference in smoking habits was observed for any diagnosis (data not shown).The proportions of STR groups within PDQ classification-group are shown in The results of the logistic regression analysis quantifying the risk of high pain rating are shown in The patients with PsA and SpA were more likely to have a VAS pain score at or above the median compared to patients with RA.This registry-based, nationwide cross-sectional study of Danish patients with inflammatory arthritis showed that despite intensive treatment and generally low disease activity scores, 63 percent reported clinical significant residual pain (VAS pain ≥ 30 mm). This number was 52 percent in the overall study population (n = 14339). Clinically acceptable levels of pain in patients with inflammatory diseases are, however, a matter of debate. Wolfe et al., including 12,090 patients with RA, reported the best cut-point for an acceptable level of pain to be 2.0 on a 10 cm VAS , whereasOf the subsample evaluated with the PDQ (n = 7054), more than 20% had a PDQ-score > 18, indicating the presence of primarily neuropathic pain features, while 45–56% depending on diagnosis had a score < 13 indicating the absence of such pain characteristics. In comparison to patients with RA and SpA, patients with PsA more frequently had a PDQ score > 18 (28%) and less frequent a PDQ score < 13 (45%). This observation was further substantiated by higher proportions of a low STR in the high PDQ classification-groups for RA and PsA. Furthermore significantly higher proportions of PsA patients had a low STR, whereas lower proportions had a high STR in comparison to RA.This also indicated that pain phenotype in PsA patients is harder to distinguish based only on more conventional clinical indices and that other instruments such as the PDQ may be needed.Overall these findings suggest that contributions from central pain mechanisms may be more prominent in patients with PsA. The existence of a preclinical phase in patients with PsA prior to the diagnosis of the disease has recently been reported . This phAmong PDQ-completers significantly and clinically relevant higher levels of pain, fatigue, and negative impact on global health were observed across PDQ classification-groups for all diagnoses with the poorest levels of PROs in the high PDQ classification-group (>18). This tendency was also observed for the TJC and composite disease activity scores (DAS28 and ASDAS), which were found to be low in the low PDQ classification-group and moderate in the intermediate and high PDQ classification-groups. However, no clinically relevant group differences were observed in objective inflammatory indices  indicating a larger contribution from non-inflammatory factors to the observed disease activity scores in the high PDQ-group (>18) across all diagnoses.Doctor’s perception of overall disease activity was strikingly lower than patients self-report and the difference found across pain phenotypes was only borderline clinically relevant reflecting that doctors primarily evaluate the overall disease activity based on more objective indices.The logistic regression analysis for the presence of pain at or above the median VAS pain supported that a high PDQ score better explained the presence of high levels of pain than a low score. Thus, patients presenting with neuropathic pain features had a 10-fold higher risk of having high levels of pain.In the absence of any diagnostic gold standards, mechanism-based pain classification is based on the assumption that this can be done clinically, based on identifiable and discriminatory patterns of symptoms and signs assumed to reflect the underlying pathophysiology. Current scientific evidence, however, suggests that both neuropathic pain and pain conditions characterised primarily by augmented central pain processing may share similar neurobiological underpinnings . Given tStill, since pain is frequently used as a proxy for inflammation in the evaluation of rheumatic diseases, it is important to recognize that not all pain is inflammatory. Interestingly, the study indicated a more intensive level of treatment across PDQ classification-groups. Although there were no differences in the numbers of patients receiving biological treatment across PDQ classification-groups, patients in the high PDQ classification-group were more likely to have received more than one biological agent (PsA) and to have been changed back to DMARDs after having been treated with biological agents (RA). These findings further indicate that treatment failure is more prevailing in patients with signs of augmented central pain processing . PreviouIt has been proposed that disease duration is related to the development of pain hypersensitivity in RA . The resThe study had some limitations: the data sampled from the DANBIO registry were not complete; however, considering the large sample size we find that the descriptive statistics were representative. The more than 7,000 patients accepting to participate in the PDQ-survey had higher ratings on VAS pain and other PRO’s than those declining, which might have skewed the distribution of PDQ-scores. Detailed general demographic and clinical information, including information about possible comorbidities associated with neuropathic pain, were not obtainable in this registry-based study and may also have influenced the study findings. The study design being cross-sectional did not allow for advanced multivariable modelling, which could have added more unique information on association between certain variables or characteristics and pain phenotype. More prospective studies involving prognostic factor research are desirable.Furthermore, although the PDQ has been used to assess neuropathic pain features as a proxy of central sensitization, the cut off values were established and validated in a sample of neuropathic pain patients with a clearly defined peripheral factor, e.g. polyneuropathy and post herpetic neuralgia. The traditional PDQ cut off values may therefore not be valid for the concept of central sensitization in patients with inflammatory disorders. However, aside from construct validity, our group has shown that the PDQ has acceptable psychometric properties, including unidimensionality, scaling properties and test-retest reliability when applied in patients with inflammatory arthritis (in review). Lastly, this registry-based study did not examine if patients also fulfilled the criteria for a diagnosis of FM; a pain condition that by many is considered to represent the upper end of a pain hypersensitivity continuum. However, the existence of a gradual transition from acute physiological pain to more chronic pain states driven by changes in neural processing in the central nervous system is increasingly being recognized . NocicepIn conclusion, more than 50% of this large Danish population of patients with inflammatory arthritis reported significant pain and among those who completed the PDQ, approximately 20% were classified as having primarily neuropathic pain features; a possible proxy for central sensitization. The PDQ-score was associated with composite disease activity scores and PROs, but not with “objective markers” of peripheral inflammation (CRP and swollen joint count). Patients with indication of a central pain mechanism were found to have a 10-fold higher risk of having a high pain level than those with an indication of non-neuropathic pain. Pain classification by PDQ in patients with inflammatory arthritis may assist the advancement of pain mechanism-based treatment approaches and alignment of the expected outcome of anti-inflammatory treatment.Patient consent was obtained on the touch screen prior to the redirection to the PDQ. According to Danish legislation, surveys do not require approval by Ethics Committees and registrations and publications of data from clinical registries do not require patient consent or approval by Ethics Committees. Approval was obtained from the Danish Data Protection Agency.


Panic disorder (PD) is highly prevalent in patients with non-cardiac chest pain (NCCP). This study aims to explore the role of psychological factors  common to NCCP and PD in predicting chest pain levels in patients with both conditions.This association was investigated in emergency department patients with NCCP and PD receiving either evidence-based treatment of PD or treatment as usual. Patients were assessed at baseline and 14 weeks later for post-treatment.n = 66). At 3 months follow-up (n = 53), changes in heart-related fear was the only factor independently associated with changes in chest pain intensity. Even in patients with PD, fear specific to cardiac sensations seems to play a central role in determining NCCP intensity.Only heart-focused fear and attention for cardiac sensations independently explained a significant portion of the variance in baseline pain (These results suggest that the efficacy of intervention for patients with PD and comorbid NCCP could be improved by targeting heart-related fear and attention.NCT00736346 Non-cardiac chest pain (NCCP) is a very common motive for medical consultations , 2. AlthA significant portion of negative outcomes related to NCCP stems from its comorbidity with PD, which is up to 11 times more prevalent in patients with NCCP than in the general population –10. The There are several possible explanations for the strong relationship between PD and NCCP. First, NCCP may occur during a panic attack , 13. HowIn fact, AS—the belief that anxiety symptoms have negative consequences—seems to be involved in the development and maintenance of NCCP and PD , 17. It Heart-focused fear represents catastrophic interpretations of cardiac symptoms , which aThus, heart-focused attention is also likely involved in the development and maintenance of NCCP , 23–25. Finally, avoidance is a key factor in the maintenance of PD and NCCP through its impact on fear of symptoms , 22, 26.To our knowledge, no study to date has specifically explored the relationships between AS, as well as fear, attention, and avoidance of cardiac sensations in patients with comorbid PD and NCCP. A clearer understanding of these relationships is essential to increase the efficacy of interventions for patients with both conditions.The first objective of this study is to investigate the relationships between AS, heart-focused fear, attention and avoidance, as well as panic symptoms, and chest pain level in patients with comorbid PD and NCCP. The second objective is to document the relationships between changes in AS, heart-focused fear, attention and avoidance, as well as panic symptoms, and reduction in perceived chest pain intensity following evidence-based intervention for PD or usual care.Patients were recruited from three academic emergency departments (EDs) between November 2005 and December 2009 in the course of a larger trial . PatientDemographic and medical interview: A structured interview was used to collect sociodemographic data and medical history.The Anxiety Disorders Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (ADIS-IV) . This inThe Panic and Agoraphobia Scale (PAS) , 30: ThiThe Anxiety Sensitivity Index (ASI) , 32: ThiThe Short-form McGill Pain Questionnaire, chest pain version (SF-MPQ-CP) : This 15The Cardiac Anxiety Questionnaire (CAQ) : This 18Graduate students in clinical psychology assessed NCCP patients in each of the three sites. PD and other disorders were evaluated using the ADIS-IV . Eligibl2 test or Fisher’s exact test.Two groups of patients were created. The first group included the entire sample ; the second included only patients with post-intervention data (prospective sample). This approach was chosen as 18.5 % of patients presented missing data. Analyses of variance were conducted to compare patients with post-intervention data with patients without post-intervention data on continuous variables. Comparisons on categorical variables were conducted with χFor the first objective, a Pearson’s correlation matrix was generated to identify factors significantly related to chest pain in the cross-sectional sample among AS, components of heart-focused anxiety, PD intensity and age. All variables significantly associated with SF-MPQ-CP scores were entered in the first step of a hierarchical linear regression analysis to determine their independent contribution to pain level. As a second step, sex was added to the model, as it has been shown to influence how AS relates to NCCP .For the second objective, change scores were created to establish relationships between changes on the ASI, PAS, CAQ subscales, and SF-MPQ-CP in the prospective sample. These scores were obtained by subtracting post- from pre-intervention results. A correlation matrix was used to identify relationships between change scores on the ASI, PAS, and CAQ subscales, and those on the SF-MPQ-CP as well as age of participants. Variables significantly correlated with change in chest pain intensity were included in the first step of a hierarchical linear regression analysis with change in SF-MPQ-CP scores as the dependant variable. Sex was added as a potential confounding variable in the second step.n = 53) of participants provided post-intervention data and were included in the prospective group  and heart-focused fear subscale  scores were significantly correlated with SF-MPQ-CP score  = 8.857; p < 0.001). Sex did not significantly contribute to the model (results not shown). See Table Only the CAQ heart-focused attention subscale  = 4.315; p < 0.01. However, only change in the CAQ heart-focused fear subscale contributed significantly to the model (p = 0.038)  were associated with NCCP intensity; together, they explained 19.5 % of the variance in pain scores. However, only the effect of attention was statistically significant.The prospective analysis revealed that change in AS, as well as in fear, attention, and avoidance of cardiac sensations were correlated with changes in NCCP over a period of 14 weeks of evidence-based intervention for PD or usual care. However, only change in fear contributed significantly to change in chest pain intensity, independently of other factors, explaining 20.3 % of its variance.At first glance, the absence of significant results for avoidance, PD severity, and AS seems to contradict theoretical models of NCCP, as well as the literature in this area , 10, 16.r = 0.4 to 0.5) between change in avoidance and change in AS, heart-focused attention, and fear of cardiac symptoms than between change in avoidance and change in reported pain (r = 0.3). Another possibility is that avoidance contributes to pain-related disability, rather than to pain itself. Furthermore, the absence of an effect of fear independent of the effect of heart-focused attention on perceived pain may be explained by the central role of attention in pain perception [Furthermore, avoidance does not seem to contribute to chest pain independently of its relationship with other dimensions of heart-focused anxiety. There are two main explanations for this finding. First, avoidance is generally conceptualized as a response designed to manage fear of symptoms , 15, 38.rception , 15, 23.In the prospective component of the study, only change in heart-focused fear was related to change in pain, independently of change in AS, heart-focused avoidance, and heart-focused attention. This result suggests a central role of fear in the experience of NCCP. Furthermore, the observed inter-correlations indicate that change in fear is the variable most strongly correlated with change in all other variables. This result is also consistent with the literature, and with models of PD, NCCP and common vulnerability factors for pain and anxiety , 39, 40.The apparently contradictory results between the cross-sectional and prospective components of the study can be reconciled by highlighting the importance of heart-focused attention and heart-focused fear in perceived chest pain. Attention plays a central role in pain perception. In fact, leading theoretical models for pain suggest that change in pain is essentially attributable to change in attention to pain , 15, 26.The negative findings concerning the role of AS and PD severity in determining pain severity in this sample could be due to specific characteristics of patients with PD and comorbid NCCP. Studies have shown that PD severity and the level of AS are lower in PD patients with comorbid NCCP than in patients with PD alone , 42. TheOverall, the results of this study suggest that NCCP is a condition independent of PD instead of a symptom of this anxiety disorder. The results of this study also provide a possible explanation for the relatively weak effect of intervention for PD on NCCP severity. Although PD intervention generally reduces AS and fear of symptoms, it appears that directly targeting fear of cardiac symptoms is essential for reducing NCCP intensity. This is not surprising since chest pain is the defining symptom of NCCP. However, none of the exposure exercises used in cognitive-behavioural therapy reliably provoke chest pain. Furthermore, modification of interpretation of symptoms mostly addresses the link between symptoms and anxiety, which may be insufficient to impact fear of cardiac symptoms. In this case, the addition of a module that more specifically targets heart-focused fear and heart-focused attention could increase the efficacy of PD intervention to reduce comorbid NCCP.The present study has some limitations that must be taken into consideration in interpreting the results. First, some of our negative results may be attributable to the limited sample size, particularly for the prospective component of the study. Second, the present study addressed AS, heart-focused attention, heart-focused fear, cardio-protective avoidance, and PD in the context of NCCP. However, NCCP and PD are also associated with other psychological factors such as alexithymia and neuroticism , which mThe primary strengths of this study are the inclusion of both cross-sectional and prospective components, and the use of well validated measures. Finally, to our knowledge, this is the first study to document variables related to NCCP intensity and change in variables related to NCCP levels in a sample of PD patients.Heart-focused fear and heart-focused attention explain a significant portion of level of chest pain in PD patients with NCCP. Decrease in fear of sensations seems to be a central factor implicated in NCCP reduction. The efficacy of intervention for patients with PD and NCCP could be improved by more specifically targeting this construct.


Symptomatic severe AS has poor outcomes unless treated. Transcatheter aortic valve replacement (TAVR) numbers are growing fast. Amyloidosis is caused by the deposition of abnormally folded protein resulting in progressive organ dysfunction. Wild-type transthyretin amyloid (wtATTR) affects the heart, causing a restrictive cardiomyopathy—deposits can be found in up to 25% of individuals >85 years of age at autopsy NCT03029026), which seeks the prevalence and impact of occult cardiac amyloid in the elderly (aged 75 years and over) with severe AS. The bone tracer was DPD. Scans were graded using planar and single-photon emission tomography/computed tomography images  0.40 ± 011 cm2/m2; left ventricle: mean ejection fraction 54 ± 11%, mean stroke volume indexed to BSA 38 ± 10 ml/m2, mean septal thickness 13 ± 2 mm (range 7 to 21 mm).We recruited 101 patients  who underwent DPD scintigraphy between October 2016 and August 2017, representing a quarter of patients on the Barts Heart Centre TAVR pathway. Echocardiographic baseline findings were: 2 vs. 38 ± 11 ml/m2); however, this did not reach statistical significance (p = 0.11 for both).Cardiac ATTR was diagnosed in 14 patients . Perugini grade was 1 (n = 4) and 2 (n = 10). In this subgroup, 50% were male, with a mean age of 88 ± 6 years. The mean aortic valve gradient and stroke volume indexed to BSA were slightly lower in the DPD-positive cohort . There was 1 periprocedural permanent pacemaker, 1 implantable cardiac defibrillator, and 1 spinal cord infarction in the DPD-positive cohort. There were also 2 deaths pre-TAVR in the DPD-positive cohort (14%).These findings support the work of Castaño et al. The confirmation of such a high prevalence of occult amyloid in TAVR patients has implications. Cardiac amyloid profoundly alters the myocardium and is likely to affect clinical presentation and outcomes . The importance of ongoing studies is high.


Few prospective studies have examined the relationship between a patient’s expectation of pain improvement and the pain prognosis. The aim of this prospective study was to investigate whether patients’ expectation to pain reduction was associated with pain intensity after morphine treatment in opioid treatment-naïve patients with various types of cancerThe subjects were patients scheduled for cancer pain treatment with morphine who were taking nonsteroidal anti-inflammatory drugs daily. Morphine treatment was performed according to the standard method, including titration . Simple regression analysis was performed between pain intensity numerical rating scale (NRS) (day 8) as the dependent variable, expectation of pain decrease NRS (day 1), tumor types, and the following covariates as independent variables: patients’ characteristics such as age, gender, PS (day 1), genotype of catechol-O-methyltransferase, total scores of Hospital Anxiety and Depression Scale (day 1), and pain intensity NRS (day 1). Multiple regression analysis was performed using forced entry methods with pain intensity NRS (day 8) as the dependent variable, and expectation of pain decrease NRS (day 1) and the covariates as independent variables that had a p value <0.05 in the simple regression models.A total of 100 patients with baseline data were included, and 97 patients  met the inclusion criteria. Patients with a high expectation of pain decrease NRS had a significantly lower pain intensity NRS (day 8) (p = 0.001).Non-pharmacological factors such as expectations for pain treatment could also be important factors to treat cancer pain, which might be associated with communication skills in physicians. Pain is a common symptom in cancer patients , 2 that There is a need for a multifaceted approach to non-cancer chronic pain that includes the effects of catastrophizing (exaggeration of pain)  and expeFurthermore, almost all guidelines have mentioned the importance not only the use of pharmacological therapy  but also the non-pharmacological therapy including reduction of pain catastrophizing and rise of expectation of patients in chronic non-cancer pain because safe and effective chronic opioid therapy for chronic non-cancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion , 19.On the other hand, in treating cancer patients, the main approaches to cancer pain  are drug therapies, such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since the report is less about the importance of non-drug therapies , which are often frequently used in chronic pain models of non-cancer, results and guidelines of non-cancer patients study , 19 mighHowever, there are few studies on expectation of symptom improvement before treatment in cancer patients , and theIn this prospective study, we investigated whether patients’ expectation to pain reduction was associated with pain intensity after morphine treatment in a cohort of opioid treatment-naïve patients with various types of cancer.This prospective study was conducted from 2009 to 2012 at the Kindai University Faculty of Medicine and Sakai Hospital. A total of 100 patients with opioid treatment-naïve and histologically confirmed malignant neoplasms who were scheduled to undergo opioid treatment were evaluated in the study. They were recruited and selected by non-probabilistic convenience sampling by their physician’s selections from the outpatient and inpatient service of Department of Medical Oncology. Of these patients, 97 met inclusion criteria of ≥18 years of age, a verified cancer diagnosis, cancer pain suitable for morphine treatment , daily use of non-steroidal anti-inflammatory drugs, and ability to give signed informed consent. Three patients were ineligible, 1 patient did not meet inclusion criteria, 1 patient was due to medical event, and 1 patient withdrew consent. All 97 patients underwent gene expression analysis, but only 91 patients were evaluated in genotype analysis because the DNA samples were insufficient in 6 cases. The required dose of morphine (day 8) was evaluated in 85 patients, excluding 12 who could not continuously receive morphine due to adverse effects or death  performance status (PS), and types of primary malignant neoplasm were recorded. Morphine treatment was performed according to the standard method, including titration  by specialized palliative care doctors. On this step, they explained standardized information about potential benefits and adverse effects to their patients. Assessments were conducted pre-treatment (day 1) and 1 week after treatment (day 8).This study was approved by the Regional Committee for Medical Research Ethics, Kindai University Faculty of Medicine and informed consent was obtained from all individual participants included in the study.Pain score was assessed with 0–10 Numerical Rating Scale  (pain intensity NRS) on day 1 (pre-treatment) and on day 8 (1 week after treatment) by asking patients by the following question; “How intense was your average pain for the past 24 hours?”Patients’ expectation of a decrease in pain determined via a questionnaire with a 0–10 NRS (0 = no improvement to 10 = full improvement) on day 1 (pre-treatment) (expectation of pain decrease NRS (day 1)) and on day 8 (1 week after treatment). Nurses who were not related to this study handed questionnaires to patients. The questionnaire had the following question; “How much do you think your pain will get better?” The questionnaire was self-administered.To assess correlations with pain intensity NRS (day 1 and day 8), anxiety/depression before treatment (day 1) and on day 8 was evaluated using the Hospital Anxiety and Depression Scale (HADS). In accordance with a systematic review by Cosco et al. , we use O-methyltransferase (COMT) 472G→A  also modulate the genetic response to opioid medications [OPRM1 118A→G  and COMT 472G→A . The treatment outcome of morphine was examined based on the plasma concentration of morphine and the required dose according to genotype on days 1, 2, and 8 [The single nucleotide polymorphisms (SNPs) of catechol-ications . We perf2, and 8 . On day COMT forward, 5′-GAT TCA GGA GCA CCA GCC CTC C-3′ and reverse (intronic), 5′-CAC TGA GGG GCC TGG TGA TAG TG-3′. PCR was performed in a 20-μl volume containing 20 ng of template, 0.5 μM of each primer, Ampdirect Plus , and 0.5 units of NovaTaq™ DNA Polymerase . Amplification was performed for 35 cycles . The resulting PCR fragments consisting of 210 bp (COMT) were directly sequenced with the corresponding forward and reverse primers, respectively [Genomic DNA isolated from blood samples using a QIAamp® DNA Blood Mini Kit (Qiagen) was amplified with the following primers: ectively .p value <0.05 in simple linear regression analysis, which means that the required level for p values was <0.00625 with Bonferroni correction for multiple tests in eight simple regression models. A two-sided significance level of 0.05 was used for multiple regression analysis. All statistical analyses were performed using SPSS software .All data are expressed as mean ± standard deviation. We first undertook a bivariate relationship using linear regression analysis between pain intensity NRS (day 8) as the dependent variable and expectation of pain decrease NRS (day 1) and the following covariates as an independent variable: patients’ characteristics such as age, gender, PS (day 1), genotype of COMT, pain intensity NRS (day 1), and total scores of HADS (day 1). We also tested the association between pain intensity NRS (day 8) and cancer types (pancreatic cancer or not) because pancreatic cancer patients had significantly lower expectation of pain decrease NRS (day1) than the other cancer patients. Then, multiple linear regression analysis was performed using forced entry methods with pain intensity NRS (day 8) as the dependent variable and expectation of pain decrease NRS (day 1) and the covariates as independent variables that had a The characteristics of the 97 patients  are shown in Table p value  and leverage (0.11).With regard to simple regression analysis with pain intensity NRS (day 8) as the dependent variable, only expectation of pain decrease (day 1) and PS (day 1) reached the set ue Table . Then, mp = 0.001, partial correlation coefficient = 0.36). Those with a low PS also had a significantly lower pain intensity NRS (day 8) (p = 0.001) (Table Patients with a high expectation of pain decrease NRS on day 1 had a significantly lower pain intensity NRS (day 8) (1) Table . The norr = 0.199).Pain intensity NRS (day 8) showed almost no correlation with HADS total score on day 8 (The results of this study show that patients with an expectation for pain decrease NRS (day 1) had a significantly lower pain intensity NRS (day 8). To our knowledge, this is the first prospective study to examine the effect of an expectation of a change in pain before morphine treatment on pain score 1 week later in opioid-naïve patients with various cancers and PS. The results are consistent with findings in non-cancer patients  that pain score is decreased in patients who expect pain improvement , 13.To explain how a health expectation influences the outcome, research on the mechanisms of placebo effects, of which expectancy is generally considered to be the core mechanism, provides more well-grounded suggestions for the causal influence of expectations on pain and other outcomes and for suggestions to improve pain management by modulating expectations .According to the response expectancy theory of Kirsch et al., response expectancy is defined as the anticipation of automatic, subjective, and behavioral responses to particular situational cues, and studies of the effects of placebos reveal that response expectancies can produce lasting changes in pain .g = 0.15) in clinical analgesic trials (studies used only placebo as a control condition) as compared to studies of placebo analgesia mechanisms (Hedges’ g = 0.95). Further comparison between acute and chronic pain indicated that magnitudes of placebo analgesic effects have been smaller (Hedges’ g = 0.33) in chronic pain than acute procedural pain (Hedges’ g = 0.67) in the recent meta-analyses by Peerdeman et al. [An investigation of the effects of the expectation of pain decrease NRS (day 1) indicated some effects on pain intensity NRS (day 8)  in the present study. According to the meta-analyses on placebo and expectancy effects by Vase et al. , it was n et al. . Althougn et al. .Our results suggest that pain relief in cancer patients can be improved by increasing the patient’s expectation of pain improvement. However, these findings are from a prospective observational study, and an interventional study is required for further evaluation.p = 0.001), which may be because most of low PS patients were inpatients who received improved pain control due to more frequent contact with medical staff.Patients with low PS also had lower pain intensity NRS (day 8) (This study has several limitations. First, 20–40% of cancer patients have mental disorders that require therapy . Scores Within these limitations, we conclude that cancer patients with pain who expect to have relief from pain before pain control treatment are more likely to have an actual improvement of pain. For control of cancer pain, it may be helpful for oncologists and palliative care doctors to develop their communication skills. By improving the communication skills to improve the doctor-patient relationship, the amount of required dose of analgesics can be reduced by the rise of “expectations” of a patient and the reduction of pain. It may be possible to treat cancer patients of chemical coping –22, whic


Self-administration of medicines by patients whilst in hospital is being increasingly promoted despite little evidence to show the risks and benefits. Pain control after total knee replacement (TKR) is known to be poor.The aim of the study was to determine if patients operated on with a TKR who self-medicate their oral analgesics in the immediate post-operative period have better pain control than those who receive their pain control by nurse-led drug rounds ).n = 71) were given medications by a nurse after their TKR. PaDSMaP patients (n = 73) took oral medications for analgesia and co-morbidities after two 20 min training sessions reinforced with four booklets. Primary outcome was pain ) at 3 days following TKR surgery or at discharge (whichever came soonest). Seven patients did not undergo surgery for reasons unrelated to the study and were excluded from the intention-to-treat (ITT) analysis.A prospective, parallel design, open-label, randomised controlled trial comparing pain control in patient-directed self-management of pain (PaDSMaP) with nurse control of oral analgesia (TAU) after a TKR. Between July 2011 and March 2013, 144 self-medicating adults were recruited at a secondary care teaching hospital in the UK. TAU patients  analysis of the 60% of patients able to self-medicate found reduced pain compared to the TAU group at day 3/discharge, . One patient in the self-medicating group over-medicated but suffered no harm.Self-medicating patients did not have better (lower) pain scores compared to the nurse-managed patients following TKR. This cohort of patients were elderly with multiple co-morbidities and may not be the ideal target group for self-medication.ISRCTN10868989. Registered 22 March 2012, retrospectively registered.The online version of this article (10.1186/s12913-018-3146-2) contains supplementary material, which is available to authorized users. The effectiveness of the self-administration of medication (SAM) in the hospital setting has recently been reviewed . It was This study investigated if a patient’s level of pain and satisfaction with care might be influenced by who is in control of the analgesic medications i.e. whether it is patient-directed self-management of pain (PaDSMaP) or under nurse control ). Self-medicating may allow the patient to have more control and take the analgesia “by the clock”  but alsoTraditionally patient controlled analgesia (PCA) has often involved patients being in control of intravenous programmable pumps delivering opioid medications . These hOverall pain levels and pain on mobilization.Patient satisfaction with the management of their pain.Satisfaction with pain management information provided.More global outcomes, such as quality of life (QOL) and activities of daily living (ADLs).Time to mobilization, and whether time to mobilization is associated with frequency of adverse events, and improvements in ADLs, QOL and pain at 6 weeks after the operation.Incidence of adverse events.Quantity and type of pain medications used whilst inpatients.Our study aimed to investigate whether patients who were in control of all of their oral analgesics experienced lower levels of pain compared to TAU. The primary objective was to investigate if PaDSMaP reduces pain at 3 days or on discharge, whichever is sooner, after primary TKR operation compared to TAU. Secondary objectives investigated whether the PaDSMaP and TAU groups differ in terms of;The trial was registered at the Clinical Trials Registry with the International Standard Randomised Controlled Trials Number ISRCTN10868989) in March 2012. Patient recruitment commenced in August 2011 before registration due to an oversight of the trial team. It had been assumed that it had been registered earlier. The purpose and method of the research were explained to the patients at the pre-admission clinic about 2 weeks prior to their operation when written consent was obtained. The study protocol was published in Trials [0868989 iWe conducted a prospective, parallel design, open label, randomised controlled, superiority trial of patient-directed self-management of pain (PaDSMaP) compared with nurse control of oral analgesia (TAU) after a total knee replacement . ParticiCompetent adults were recruited from patients waiting to undergo a unilateral total knee replacement. The key inclusion criterion was that these patients were able to manage their medications at home. They also had to be English-speaking and literate. We excluded patients that were; opiate-tolerant, opiate-dependent or using modified-release opiate preparations, or had a history of drug or alcohol abuse within the last 5 years. The reasoning for this was that patients who have an established opiate tolerance might be expected to need to continue on an equivalent opiate regimen to prevent opiate withdrawal, and may also require more opiate to ensure equivalent analgesia, and thus would not be comparable to the rest of the population. Other exclusion criteria included expecting post-operative intensive care, or were not competent by reason of dementia or other cause. Post-operatively patients had to be awake and breathing independently, and able to answer questions and follow commands (i.e. competent). Patients were expected to require standard step 1–3 oral analgesics, the 48 patients that received regional blocks or epidural analgesia, started PaDSMaP or TAU as soon as they began oral analgesia. These inclusion and exclusion criteria were in line with the hospital’s drug self-administration policy .The research nurses checked patient eligibility and consent against a checklist. Patients were allocated a personal 6-digit ‘PIN’ identifier that allowed them access to the independent telephone randomisation service at the Clinical Trials Unit (CTU) at the University of East Anglia (UEA). On entry of a valid PIN, the system generated a unique Study Code and randomly allocated the patients to either the PaDSMaP or TAU arm of the trial. The study code and allocation was sent in an email to the research team and stored in the trial database on the secure CTU server at UEA.A computer generated randomisation list allocated the patients in a 1:1 ratio to PaDSMaP or TAU groups. Randomisation was unstratified. Patients were allocated in randomly distributed blocks of four and six. The patients were randomised, assessed and trained in the pre-operative clinic or at their homes. Patients, their clinical team and the research team were all aware of their allocation. As the intervention was under the control of the patients and the primary outcome (pain VAS) was a patient-reported measure it was impossible to blind patients or clinical staff as to participant’s allocation. It was originally planned to blind the statistician to allocation but as we accidentally included information on duration of self-medication in the statistician’s database they were unblinded, however the analysis plan was pre-specified and approved in a blinded fashion and therefore any potential bias was minimised.All participants received the TKR information sheet that is provided as standard to everyone undergoing the operation  received the Modified Caledonian Technique (MCT) Norwich Enhanced Recovery Programme (NERP) . This prThe PaDSMaP package  was deveConsultation with lay representatives and healthcare professionals highlighted that it would be inconsistent to allow self-medicating patients to be in control of their oral analgesia but not their oral co-morbid medications. Therefore if patients were prescribed medications for their co-morbidities they were usually in control of these. In general no specific training was provided regarding these medications as patients were expected to have sufficient knowledge to take them appropriately. However patients on anti-hypertensive or anti-coagulant medications were specifically warned to check with nursing staff that it was appropriate for them to take these medications after the operation.Patients were assessed by a nurse for their competency to manage their own medications, by checking patients were orientated as to location and time, and that they could remember and follow simple instructions . PatientThe UK’s Misuse of Drugs Act (1971) aims to prevent high risk “controlled” medications from being misused, obtained illegally or causing harm. The legislation places legal requirements on the method of prescribing and dispensing of controlled medications. Due to these requirements, any patients prescribed controlled medications  received them direct from the nurses as they were not approved for self-medication protocols at the hospital . In pracWard staff  were trained by the research team about the purpose of the study, the information that the patients would receive and how to assess competency of participants to self-medicate after the operation.At baseline we measured a number of factors in order to provide a description of the characteristics of our sample. Some of these have been identified by other studies as factors that can affect post-operative pain and recovery, and so were possible confounders Tables , 3, 4 1–23. BaseThe primary outcome was pain levels at discharge or after 3 days post-operatively (whichever was the sooner), using a non-graded 100 mm VAS . The paiPain levels; static and after mobilisation (3 times a day for days 1–3) and static pain at 6 weeks. Pain VAS were recorded at mealtimes as these were relatively stable in the ward setting; Breakfast 08:00, Lunch 13:00, Supper 17:45. Pain after mobilisation scores related to pain at that moment.Satisfaction with pain levels (SWP), medication usage (Days 1–3 and 6 weeks).Satisfaction with Information About Medicines Scale (SIMS)   , 27, ActTime to mobilisation was measured from the time the patient returned to the ward after the operation to the time they managed their first transfer out of the bed.Adverse events up to 6 weeks were extracted from patient notes.Secondary outcome measures for the patients were:We planned to investigate medication usage but realised that the high level of variation in the individualised analgesic protocols after surgery  jobs away”. Every patient when asked if they had the option to self-medicate for a similar operation responded positively. Healthcare professionals expressed positive views about the empowering nature of self-medication but had realistic concerns about capacity, documentation and accountability. The paternalistic nature of healthcare was evident ; a qualitative investigation of the acceptability of self-medicating with oral analgesics in the context of a randomised controlled trial following total knee replacement, Unpublished qualitative data from this trial).p < 0.001) based on 133 observations, Adj R-squared = 0.7225). This leads to a mean cost per quality of life adjusted year (QALY) of > £390,000 [The cost effectiveness analysis  showed t£390,000 .Seventy-two patients in each arm was calculated to be sufficient to detect a between-group difference of 0.5 standard deviations in the VAS pain intensity with 80% power using an independent samples t-test. Dahlen , 32. HowP < 0.10 when examined individually as a predictor of the primary outcome, adjusting for variables in (i), were included in a multiple predictor model and then eliminated one by one until all potential predictors had P < 0.10); this resulted in further adjustment by gender and number of prescribed medications. The assumptions of the models were checked using residual analysis which found no outliers or heavily influential observations.Linear regression models were used to compare primary and secondary outcomes between the intervention and control. There is no single ‘right’ way of selecting covariates for adjustment. In particular Pocock  says thaThe main analysis was conducted on an ITT basis. For a per protocol analysis successful self-medication was defined as those who started self-medicating and were continuing at 72 h/discharge, even if they stopped for a period during the hospital stay.Linear regression models were used to investigate, for those randomised to the self-medication group, which baseline variables individually predicted successful self-medication. In order to account for repeated measures, mixed linear regression models were used to compare series of VAS scores measured at breakfast, lunch and supper over the 72 h follow up period, between groups.In the light of the results, unplanned analyses used the same methods to additionally adjust by day 1 breakfast static VAS scores. SPSS v18 was used for the analysis. The number of co-morbidities was compared between individual included and excluded from the per-protocol analysis using a Mann-Whitney test.n = 448). Of the 665 patients screened for eligibility for the RCT 23% were excluded because they were not managing their own medications at home . A further 28% refused to participate, often because they felt unsure of their ability or desire to self-medicate after a major operation.Between July 2011 and March 2013, 144 competent adults about to undergo a primary unilateral TKR were recruited  are characterised in Tables Seventy-one patients were randomly allocated to TAU, and 73 to the PaDSMaP group. However seven patients  did not undergo surgery for reasons unrelated to the study and were excluded them from the ITT analysis. The remaining patients  assesses commonly held beliefs about medicine . The basn = 7, or anxiety n = 1), and four who started, stopped and then restarted before the end of day 3 (due to losing competency n = 3 or anxiety n = 1)), 21 never started , and 41 were classed as having successfully completed the self-medicating protocol  prescriptions. Although at the initiation of the project we were assured that no patients self-medicated on the ward, we found that one diabetic patient allocated to the TAU group did self-medicate with their injectable insulin. All of their remaining medications were delivered by the nurses as usual.Little difference was observed between the two groups’ baseline characteristics Tables , 3, 4. MNo evidence was found for a between group difference in ITT mean pain score (static VAS for the previous 4 h) at 72 h/discharge Table . SimilarUsing the per protocol definition, patients who were able to self-medicate had significantly lower static VAS  and mobilised VAS  at 72 h/discharge compared to TAU patients.p = 0.007 Wilcoxon Mann Witney).Forty-one of 68 patients randomised to self-medicate were ‘successful’ as defined for the per protocol analysis. Only one of 30 baseline variables considered individually showed a significant bivariate association with successful self-medicating. The number of co-morbidities was significantly higher in the group that were unable to self-medicate In an unplanned analysis suggested by the research nurses, lower static pain scores at day 1 breakfast were a highly significant predictor of successful self-medication. , those in PaDSMaP able to self-medicate (n = 41), and those in PaDSMaP unable to self-medicate (nurse medicated) (n = 27), indicated a particularly large effect between those patients that were unable to self-medicate and TAU on day 1, which reduces by day 3, suggesting again that individual pain time points should be considered separately. The three groups pain scores were significantly different from each other at each of breakfast, lunch and supper of day 1, . This led to an exploratory analysis in which we compared the primary outcome, static VAS at 72 h/discharge, between groups, adjusting by day 1 breakfast VAS. This investigates whether group predicts the primary outcome for those with the same pain level at breakfast day 1. In the ITT analysis group this was not significant , but day 1 breakfast’s pain score was a strong predictor of the primary outcome .An unplanned ‘three group’, repeated measures analysis comparing TAU . The patient had started self-medicating at lunchtime on day 1 after surgery. On day 2 at 08:15 the pain team found the patient was a little confused and unsure what medications he had taken. The prescription chart had not been filled in accurately and 30 ml of Oramorph was unaccounted for. After the overdose, Trust policies  were folOne other patient in the self-medicating group had a medication error. She had brought in her prescribed pregabalin and co-codamol 30/500 from home, and on the morning of day 1 after surgery she started self-medication and took these medications from her home pack. However the patient had been prescribed paracetamol and oxycontin post-operatively. The error was noticed by 08:30 before the patient was given her inpatient pack of medications, and oxycontin was omitted from her morning medication dosage as it was contraindicated with the co-codamol. The patient was reassessed for competency to self-medicate and was assessed as not competent, the medications from home were removed from her locker and she was placed back under the care of the ward nurses for medication delivery which adhered to the hospital prescribed regimen.Eight patients stated to the nurses that they were anxious about managing to self-medicate after their operation. Five of these patients never started self-medicating, one returned to usual nursing care, one stopped but then re-started self-medicating, one continued self-medicating with support.There were no medication errors in the TAU group. However over the period of the trial 11 other medication errors occurred on the trial ward in the general patient population of 276, all of whom had nurse controlled medication delivery. These errors included missed medications, incorrect dosage, and incorrect medications. None resulted in any harm to the patients.Although we recorded a substantial number of other adverse events such as confusion, dizziness, nausea, or vomiting, none of these were determined to be trial-related by our Data Monitoring Committee, which had an independent chair. However these symptoms were the usual reasons given by participants for not self-medicating within the 3 days after surgery that were monitored for the study.This is the first ever RCT of patient controlled oral analgesia that allowed for patients to self-medicate with individualised poly-pharmacy analgesia protocols and additionally be in control of their co-morbid medications, as far as we are aware . PreviouThe ITT analysis showed that the pain levels of patients allocated to self-medicate were not superior to those whose medications were dispensed by ward nurses at 3 days/discharge (primary endpoint). Per protocol analysis of the 60% who managed to self-medicate showed that they had reduced levels of pain, however this analysis was underpowered so must be regarded with caution. The size of pain reduction was similar to that shown by meta-analyses of PCA trials . This suGreater pain on day 1 after the operation and more co-morbidities predicted those who were unable to self-medicate. This suggests that those with more pain do not start self-medicating or may stop self-medicating. Those patients with higher numbers of co-morbidities may be less well after their operations, thus preventing them from being able to self-medicate.Since 21% of patients who started self-medicating were unable to continue self-medicating (either temporarily or permanently) within the 3 days after the operation due to confusion, dizziness or vomiting, it highlights the importance of on-going assessment of the patient’s wellbeing and competency to self-medicate by the nurses on their usual drug rounds. Although there are some risks from over-medication, this appears to happen infrequently. As far as we are aware this is the first time an overdose has been reported in an oral self-medicating RCT, with a total of 127 self-medicating patients –39. It sConsidering the small pain score differences and the emphasis placed on early mobilisation in the NERP protocol , it was The highly specialist Pharmacists on the ward did prepare the drug packs and drug charts for each patient, and the research nurses conducted the two training sessions. Therefore if this protocol was adopted more generally, workload changes would have to be evaluated.The population selected were elderly, had co-morbidities, and the operation required a high level of opiates in order to control pain levels suitably. All of these factors led to a high incidence of adverse events such as confusion, dizziness or vomiting post-operatively, which were the usual reasons for patients not self-medicating. As 40% of patients were unable to complete the self-medicating protocol, the study was effectively under-powered.The high rate of co-morbidities in our population was due to ASA grade 1 patients  generalObviously only patients willing to participate in the trial were recruited. Many of those who refused stated that they were concerned about their ability to manage the perceived complexity of self-medication after an operation. Overall our participants had more positive beliefs regarding the benefits of taking medications when compared to other chronic conditions . TherefoThere was rarely more than one self-medicating patient on the ward at any one time. Sawhney  showed tThere were a few missing pain scores, mostly in the intermediate time points. We know that at least some of these scores were missing due to patients’ unwillingness to complete the research outcomes when they were in severe pain i.e. they were not missing at random. Therefore the intermediate time point’s pain scores may have been under-estimated.Due to the trial allowing patients to be prescribed individualised analgesia, it is impossible to compare the analgesic “dose” between the groups. Patients were prescribed a range of analgesics. Although the daily Equivalent Oral Morphine Dose (EOMD) could be estimated , it woulAs noted in our introduction the evidence base is limited and not consistent. Striebel’s two studies , 39 claiCurrently elective surgical patients have all their inpatient medications controlled by healthcare professionals, yet patients are expected to manage to self-medicate once they are discharged home. For patients capable of self-medication there are potential benefits in terms of improved pain control. However this study demonstrated that self-medication was not suitable for all and a patient’s ability to self-medicate needs to be assessed on an on-going basis. The factors which may limit the ability of adults to self-medicate include having high pain levels on day 1, having higher numbers of co-morbidities, and suffering from adverse events of the surgery and anaesthesia such as confusion and nausea.Our cost effectiveness analysis  showed tWe are aware that there are significant political pressures on hospitals to implement self-medicating policies in order to improve patients’ autonomy and dignity , 47–50. Further research is needed to identify how important this reduction in pain and improvement in autonomy is to patients; whether it is worth the additional training time needed for staff and patients; or if the implementation of self-medication should be for all eligible patients in inpatient settings, and finally, and the evaluation of the health economic implications. The risks of the protocol need to be quantified and management protocols developed that include the development of predictive tools to identify patients unlikely to manage self-medication. Finally the development of a method to calculate the overall analgesic dose for patients prescribed combinations of opioid and non-opioid medications would be helpful.This is the first randomised controlled trial of patient controlled oral analgesia that examined individualised multi-medication analgesia. It compared the usual delivery of pharmacological analgesia by nurse-led rounds with patients self-medicating with their drugs held in special locked bed-side cabinets. The self-medicating patients (PaDSMaP) had pain scores that were not superior to the nurse-managed patients (TAU). However 40% of those allocated to self-medication were not able to self-medicate. The 60% that were able to self-medicate had lower pain scores than those managed by nurse-managed care. This cohort of patients were elderly with multiple co-morbidities and may not be the ideal target group for self-medication.Additional file 1:CONSORT checklist for PaDSMaP Study. (DOC 218 kb)Additional file 2:Consent for Patients about to undergo Total Knee Replacement Surgery. (PDF 802 kb)Additional file 3:Information Sheet for Patients in the PaDSMaP Study. (PDF 800 kb)Additional file 4:Consent form for Patients in the PaDSMaP Study. (PDF 741 kb)Additional file 5:Training pamphlets for the PaDSMaP study. (PDF 1589 kb)