Donor site pain associated with skin graft procedures is frequently intense and difficult to treat. Liposomal bupivacaine, a prolonged‐release local anesthetic indicated for single‐dose administration to produce postsurgical analgesia, may be a viable option in managing donor site pain. Postsurgical pain management following skin graft procedures in patients with burn injuries is often difficult and requires multimodal therapy for proper wound healing and recovery Opioids are a mainstay in the treatment of wound and procedural pain in patients with burn injuries because of their analgesic efficacy ®; bupivacaine liposome injectable suspension, Pacira Pharmaceuticals, Inc., Parsippany, NJ) can extend the duration of postsurgical analgesia while reducing opioid requirements. Liposomal bupivacaine, a multivesicular formulation of bupivacaine, is indicated for single‐dose administration into the surgical site to produce postsurgical analgesia in adults Although traditional local anesthetic formulations can provide effective and safe analgesia at the surgical site when administered as recommended, their duration of action is short, often lasting only 12 h or less All patients underwent skin graft procedures at the Timothy J. Harnar Burn Center at University Medical Center affiliated with the Texas Tech University Health Sciences Center in Lubbock, Texas (Cohort 1) 2. Standard silver‐based dressing was applied to the donor site following harvesting Patients in Cohort 1 underwent split‐thickness skin grafting at the Harnar Burn Center from March 2015 to August 2015. Patients whose donor site(s) were ≤10% of the total body surface area (TBSA) were included in the study. In accordance with the product label, liposomal bupivacaine 266 mg/20 mL was diluted with saline 0.9% to total volumes ranging from 45 to 120 mL to provide sufficient coverage of the surgical area Amounts of intravenous and oral opioids consumed were converted to oral morphine equivalents 2–400 cm2. Each patient was prepared for surgery according to standard protocol. Liposomal bupivacaine 266 mg/20 mL was diluted to a total volume of up to 250 mL with normal saline to ensure adequate coverage of the donor site, admixed with Pitkin's solution , and infiltrated into the skin donor site prior to harvesting. Skin grafts were collected from the anterolateral thigh, and standard Xeroform™ dressings  were applied to donor sites Patients in Cohort 2 underwent skin graft surgery at USAISR between February 2015 and March 2015. Donor sites were 20 cmt‐test using the T.TEST function in the Microsoft Excel software package  Baseline information on patient and injury characteristics, pain scores, and dosages of pain medications were recorded. Pain intensity was typically recorded every 4 h and was scored using a validated 11‐point numeric rating scale (NRS) in which the patient selected an integer from 0 (“no pain”) to 10 (“worst imaginable pain”) Demographic data and injury characteristics were recorded for each patient, and patients reported postsurgical pain at the donor site using the Defense and Veterans Pain Rating Scale (DVPRS) at 1, 4, 8, 12, 24, 36, 48, and 72 h after surgery 2, the average dose of liposomal bupivacaine administered was 0.52 mg/cm2.Cohort 1 included 20 patients ranging in age from 18 to 68 years (mean age: 41 years); 13 patients (65%) in the cohort were male. The dose of liposomal bupivacaine administered to each patient ranged between 89 and 266 mg (mean dose: 231 mg). The mean size of the burn area was 12% TBSA (range: 1–50% TBSA). Because the mean area of the patients’ donor sites was 441 cmThe mean patient‐reported pain scores declined steadily over POD 1 through POD 3 but were not significantly different from the pain scores recorded the day before surgery, as shown in Table 2, as shown in Table Cohort 2 consisted of five patients, four males, and one female, with a mean age of 32 years (range: 20–54 years). The mean size of the donor site area was 184 cmDuring the first 72 h after surgery, three patients reported no postsurgical pain  at time points when a pain score was recorded. In the other two patients, the pain score was 0 at most time points. DVPRS scores >0 were observed at 8 h after surgery in one patient and at 4 and 36 h after surgery in another patient, but those scores returned to 0 during subsequent time points , which make it difficult to generalize these findings to a larger population of burn‐injured patients with a greater variation in baseline comorbidities, opioid history, and burn size and severity. Variability in the dilution and dose of liposomal bupivacaine administered may have contributed to interpatient differences in analgesic efficacy. Clinicians have the flexibility to admix liposomal bupivacaine with bupivacaine HCl  prior to administration Although the data presented here are preliminary in nature, they support further investigation into the use of liposomal bupivacaine in burn patients undergoing skin graft surgery. Because of the limited duration of pain assessments, it would be desirable to include later time points in future studies to determine whether this agent can control pain beyond 3 days. Future research that is controlled for concomitant pain medication, comorbid conditions, and risk factors could help better define patients that may benefit most from this treatment.Liposomal bupivacaine may be a viable therapeutic option for providing donor site postsurgical analgesia for burn‐injured patients undergoing skin graft procedures. This treatment was able, in some cases, to completely relieve pain during the first 3 days following surgery. The absence of adverse events or other complications indicates that liposomal bupivacaine may be well tolerated in this surgical population. Larger randomized, controlled, studies are required to further investigate the use of liposomal bupivacaine in this setting.SD: involved in study concept and design; involved in the critical revision and review of the manuscript text and figures, as well as approval of the final draft for submission. JM: collected data; involved in the critical revision and review of the manuscript text and figures, as well as approval of the final draft for submission. CA: involved in study concept and collected data; involved in the critical revision and review of the manuscript text and figures, as well as approval of the final draft for submission.Sharmila Dissanaike, Jayne McCauley, and Carlo Alphonso have no financial or other conflicts of interest to report.


Epidural steroid injections (ESI) are the most common pain management procedure performed in the US, however evidence of efficacy is limited. In addition, there is early evidence that the high dose of corticosteroids used can have systemic side effects. We describe the results of a case series evaluating the use of platelet lysate (PL) epidural injections for the treatment of lumbar radicular pain as an alternative to corticosteroids.N = 470) treated with PL epidural injections presenting with symptoms of lumbar radicular pain and MRI findings that were consistent with symptoms. Collected outcomes included numeric pain score (NPS), functional rating index (FRI), and a modified single assessment numeric evaluation (SANE) rating.Registry data was obtained for patients (p < .0001) NPS and FRI change scores at all time points compared to baseline. Post-treatment FRI change score means exceeded the minimal clinically important difference beyond 1 month. Average modified SANE ratings showed 49.7% improvement at 24 months post-treatment. Twenty-nine (6.3%) patients reported mild adverse events related to treatment.Patients treated with PL epidurals reported significantly lower  for FRI, and reported subjective improvement through 2-year follow-up. PL may be a promising substitute for corticosteroid. Lumbar epidural steroid injection (ESI) is a non-surgical treatment for radicular pain and low back pain (LBP). The procedure typically consists of an injection combining a corticosteroid anti-inflammatory with a local anesthetic into the epidural space below the level of the conus medullaris. ESIs are the most commonly performed pain management procedures for LBP and radiculopathy or radicular pain in the United States Cohen . From 19Despite the popularity of the procedure with pain management specialists and other clinicians, there is no clear evidence demonstrating the efficacy of ESI as a means of improving function, decreasing disability, or reducing spine surgery rates  is potentially associated with a multitude of adverse effects that can disrupt function of the endocrine, cardiovascular, musculoskeletal, gastrointestinal, dermatologic, metabolic, and nervous systems . PRP is the concentration of platelets obtained after isolation from the peripheral whole blood sample. PRP is used to promote healing and believed to act via the release of growth factors (GF) found inside platelets (Mautner and Kneer Platelet lysate (PL) is created by lysing platelets and removing the cell debris, resulting in a GF-rich injectate, devoid of other platelet material  approved the registry data protocol. All patients (or their guardians if they were under 18 years of age) enrolled in the registry underwent an informed consent process before entering the registry. Enrolled patients were prospectively followed using an electronic system, ClinCapture software  that generates automated pre- and post-treatment questionnaires for evaluation at 1, 3, 6, 12, 18, 24 months, and annually thereafter.The registry protocol was as follows: patients were sent outcome and complications questionnaires. Up to five attempts were made at each time point to contact patients. If the patient failed to respond, that time point was lost to follow-up. Patients were exited from the registry at their request or if they elected for definitive surgery. For adverse events (AEs), broad tickler questions were asked to elicit a complaint. To enhance surveillance, all treating physicians were asked to report any complications related to the procedure. Any reported AEs were adjudicated by the treating physician and classified by relatedness and severity. For more details, please see the AE adjudication methodology already reported in prior publications  and foraminal and/or central canal stenosis. The only inclusion criteria was that the patient have lumbar radicular pain in need of treatment, while exclusion criteria was based on medical conditions that would preclude an epidural injection route . Injection timing and frequency was based on clinical indication and was not controlled. Outcome measures obtained at each time point were a Numeric Pain Score (NPS), a modified Single Assessment Numeric Evaluation rating (SANE), and the Functional Rating Index (FRI).NPS is a recognized way to quantify pain similar to a segmented version of the visual analogue scale, in which a whole number is selected to reflect the intensity of pain where 0 = no pain and 10 = worst possible pain  to remove all remaining lysed platelet membrane debris. The nanogram amount of hydrocortisone used with PL is one million times less than what is commonly used for ESI injections and is used for its anti-inflammatory properties at levels similar to endogenous glucocorticoids  and gender), and self-reported scores . Changes in the FRI and NPS scores were assessed using dependent two-group t-tests between the baseline and each post-treatment score. Subjects with missing scores were excluded from respective analyses. Differences between post-treatment time points were examined using a one-way analysis of variance (ANOVA) followed by post-hoc Tukey if warranted. All analyses were performed retrospectively utilizing R, a software environment for statistical computing and graphics, version 3.2.2.The selection process for the patient population is shown in Fig. N = 18), inflammation (N = 1), soreness (N = 2), muscle tightening (N = 1), stiffness (N = 2) and/or numbness (N = 1). Other AEs were categorized as dural puncture related  or skin reactions , which accounted for 20.7% of the total AEs. See Fig. Of the 470 patients, 44 (9.4%) reported a complaint. Of those patients, 29  were adjudicated by the attending physician as an adverse event (AE) related to the procedure. Of those 29 patients, 4 reported AEs at multiple time points, with the majority being pain related. For example, 23 patients (79.3% of the AEs) reported pain related events, with a 2 patients reporting more than 1 event (pain (N = 303) provided baseline NPS data, and those without baseline data were excluded from the respective analysis to limit missing data bias. Average baseline NPS was 5.1 (SD = 2.4). The change in scores from pre- to post-treatment was calculated for each patient at each time point. Change score averages ranged from 1.6–2.4, with each time point being statistically lower (p < .0001) than baseline . Post-hoc Tukey confirmed 18 month and 24 month NPS were significantly lower than 1 month (p < .05 and p < .01 respectively), as well as 24 month scores were significantly lower than 3 month scores (p < .05).Sixty-four percent of patients N = 03 provid5.1 SD = .4. The cp < .005). Post-hoc Tukey showed significantly higher modified SANE scores between 1 month and both the 18 and 24 month post-treatment time points (p < .05). Scores trended toward a significant difference between the 3 month and 24 month time point (p = .07). Figure Of the 470 patients, 438 (93%) provided modified SANE rating responses. The patients’ last recorded responses averaged 42.4% improvement at an average of 16.6 months post-treatment. Modified SANE score means increased incrementally from 35.9% (SD = 34.2) at 1 month to 49.7% (SD = 42.1) at 24 months. A one-way ANOVA showed modified SANE scores differed significantly across time points (p < .0001), with the average change score ranging from 8.4 to 19 . Post-hoc Tukey showed 12 month scores were mildly lower than 1 month scores (p = .052). Eighteen month scores were significantly lower than 1 month scores (p < .005) and 3 month scores (p < .05). Scores at 24 months were significantly lower than 1 month scores (p < .0005), 3 month scores (p < .005) and 6 month scores (p < .05).We obtained baseline functional rating index scores for 239 51%) patients included in this analysis. Average baseline FRI score was 52.6 (SD = 20.6). The change in scores from pre- to post-treatment was calculated for each patient at each time point. The average change score at each time point was significantly different from baseline  treated with PL at every time point, which was sustained through the 24 month follow-up period. Based on FRI change scores, function increased (indicated by scores decreasing) after treatment with PL, with average change scores exceeding the minimal clinically important difference for all time points beyond 1 month post-treatment. The significant difference in pain and function at later time points compared to scores at 1, 3, and even 6 months may suggest that a continued effect of the PL occurs over time.Of the 470 patients, none reported any serious adverse events  with the majority of AEs related to post-treatment pain that was self-limiting (79.3% of AEs). Other complications such as dural leaks were not more common than the expected rate for traditional ESIs Epstein . Rare adThe properties of the growth factors and cytokines in PL may explain these findings, including enhancing nerve repair, improving blood supply, or reducing inflammation. These include transforming growth factor-beta (TGF-β), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), platelet-derived growth factors (PDGF), and others. Any or all of these acting individually or in conjunction may have accounted for the observed effects. For example, several GFs present in platelets have been identified as critical for nerve repair. PDGF stimulate the release of neurotrophic factors, which promote the regeneration of peripheral nerves (Monje et al. The procedure used in this study is quite different from more commonly used platelet rich plasma therapy, which was not used due to potential safety concerns regarding platelet aggregation. During epidurals, inadvertent vascular injections have been estimated at 8–12% Epstein . CoalescWhile the clinical use of PL compared to traditional PRP for orthopedic conditions has not been previously described, the effect of PL on human cells in vitro is well known. PL use for cell culture is described extensively in the literature and may provide some insight into its potential ability to stimulate local progenitor cells (Burnouf et al. Limitations of the current study include lack of a control group and randomization, missing data, multiple components of the injectate, lack of strict post-treatment controls, and potential patient bias. This study did not include an untreated control group or randomization of subjects, hence placebo effects cannot be ruled out. The outcome data collected in the registry was missing various endpoints for patients, though multiple attempts were made to collect outcomes for each time point. Although this is an inherent problem with registry data, this platform allows us to prospectively monitor long-term outcomes in a large population of patients. In addition, the treatment injectate contained platelet lysate, local anesthetic, and a nanogram dose of corticosteroid, any of which may have produced the clinical effect seen, either alone or in combination. However, the volume of local anesthetic and corticosteroid is dramatically less than what has been compared for epidural therapeutic purposes, which leads us to believe that it is the PL producing the clinical outcomes in this sample of patients (Manchikanti et al. This is the first publication highlighting the clinical use of platelet lysate injected into the lumbar epidural space for the treatment of lumbar radicular pain. The analysis of the registry data shows promise for use of this therapy to reduce pain and improve function. We observed no additional risk beyond traditional steroid epidurals. While there is a need for randomized controlled trials to determine efficacy, these results highlight a potentially promising alternative to reduce the deleterious effects of high dose steroids on patients, as well as offer a possible non-surgical alternative for patients with lumbar radicular pain.


To compare the impact of a single fraction (8 Gy × 1 fraction) and multifraction (3 Gy × 10 fractions) radiotherapy regimens on pain relief, recalcification and the quality of life (QoL) in patients with bone destructions due to multiple myeloma (MM).In all, 101 patients were included in a randomised prospective clinical trial: 58 patients were included in the control arm (3 Gy × 10 fractions) and 43 patients into the experimental arm (8 Gy × 1 fraction). The response rate was defined according to the International Consensus on Palliative Radiotherapy criteria. Recalcification was evaluated with radiographs. QoL questionnaires were completed before and 4 weeks after treatment.Pain relief was obtained in 81/101 patients (80.2%): complete response in 56 (69%) and partial in 25 patients (30.9%). No significant differences were observed in analgesic response between the groups. Significant factors for pain relief were female gender, age under 65, IgG MM type, presence of recalcification at the irradiated site. Recalcification was found in 32/101 patients (33.7%): complete in 17 (53.2%) and partial in 15 (46.2%). No significant differences were observed in recalcification between the groups. Significant factors for recalcification were Karnofsky index ≥ 60%, haemoglobin level ≤ 80 g/dl, MM stage II and analgesic response at the irradiated site. The QoL after radiotherapy was improved in the control group.The same analgesic and recalcification response was observed using two different radiotherapy regimens. Higher doses should be used to achieve a better QoL. Skeletal related events is one of the signs of multiple myeloma (MM) , 2. OsteBone pain is the first sign of MM for 70% of patients and the patients receive radiation at least once during their MM therapy . Where rResults of previous clinical trials have shown the same effect of pain relief and recalcification when applying different radiotherapy regimens for treatment of patients with solid tumour metastases –16. ThisFrom 2010–2015 a randomized prospective clinical trial was performed at the Lithuanian University of Health Sciences. Multifraction radiotherapy regimen (3 Gy × 10 fractions) was applied to the control group of patients and single fraction regimen (8 Gy × 1 fraction) was applied to the experimental group. In all, 58 patients were included in the control arm and 43 patients were included in the experimental arm. A random sampling was performed by a computerised programme. Inclusion criteria were the following: age over 18 years, diagnosis of MM according to the International Myeloma Working Group’s Criteria , presencA total of 101 patients  were included in the study. Patients’ characteristics are detailed in Table Pain intensity was assessed according to the visual analogue scale (VAS) . A pain QoL was assessed by using EORTC QLQ-C30 version 3 and EORTC QLQ-MY20 QoL questionnaires , 22. TheThe analgesic response rate was defined according to the International Consensus on Palliative Radiotherapy criteria .Since there is no common criteria of recalcification, we used criteria from other studies , 25: comAcute toxicity was assessed in the first 4 weeks after radiotherapy by applying RTOG (Radiation Therapy Oncology Group)/EORTC (European Organisation for Research and Treatment of Cancer) toxicity criteria .2 test and Fisher’s exact test for small expected frequencies were used to compare proportions among groups created by sociodemographic and clinical characteristics. McNemar test was used to compare the proportions of pain type before and after treatment. Wilcoxon signed-rank test was used to compare values of quantitative features not distributed by Normal law between two related populations. The Mann–Whitney U test was used to compare values of quantitative features not distributed by Normal law between two independent groups and Kruskal–Wallis test was used to compare them among three or more independent groups. Results of the analysis are presented as median . Means of quantitative data distributed by Normal law between two independent populations were compared using Student’s t‑test for independent populations. Observed differences were accepted as statistically significant if p-value < 0.05. Influence of demographic, clinical and symptom variables to pain relief, recalcification and QoL was analysed using binary logistic regression method. Stepwise variable removal procedure  was used to determine a model with variables which influence is statistically significant: all analysed parameters were entered to the initial logistic model and at each step of the procedure the least significant parameter was removed from the model until all remaining parameters showed a statistically significant influence on pain relief, recalcification or QoL. Findings of the model with the biggest Nagelkerke pseudo coefficient of determination which indicates goodness of fit of the model, and with the biggest percent of correct classification of all cases are published in the article. Results of the analysis are presented as odds ratio (OR) and 95% confidence interval (95% CI) of odds ratio. The influence of demographic, clinical and symptom variables to pain relief, recalcification and QoL was considered as statistically significant if the confidence interval of odds ratio did not include the value 1.Statistical data analysis was performed by using the IBM SSPS Statistics 23 for Windows . The χp < 0.001). Patients in the control group before treatment reported a median VAS of 8 , 4 weeks after radiotherapy their median VAS was 4 , after 12 and 24 weeks the median VAS was 0. Patients in the experimental group before treatment reported a median VAS of 8 , 4 weeks after radiotherapy the median VAS was 3 , after 12 and 24 weeks the median VAS was 0. No significant differences were observed in the groups in the median of pain score before therapy nor in its decrease during the monitored period , moderate in 30 (29.7%) and severe in 56 (55.4%). Thirty-six patients (64.3%) who indicated severe pain before treatment felt significantly less pain during 4 weeks after radiotherapy (McNemar p = 0.001). The median of the MED used before the treatment in the control group was 60  and in the experimental group it was also 60 . Four weeks after radiotherapy, in the control group the median MED was 10  and in the experimental group MED was 25 . At 12 and 24 weeks after radiation treatment, the median MED was 0 in both groups. No significant differences were observed in the groups in the median MED before treatment nor in its decrease during the monitored period  were using non-opioid drugs prior to radiotherapy and all of them ceased analgesic intake during the first 4 weeks after treatment. Seventy-nine patients (78.2%) were taking opioid analgesics. Consumption of opioid analgesics was significantly reduced at 4 weeks after radiotherapy (Wilcoxon 5.8% wereDuring the follow-up period pain relief was obtained in 81 patients 80.2%): complete response in 56 (69%) and partial response in 25 (30.9%). Manifestation of analgesic response is demonstrated in Table %: complep = 0.016), disease stage II (p = 0.03) and recalcification in the irradiated site (p = 0.011) were significant parameters for analgesic response, whereas other parameters  were not statistically significant.Univariate statistical analysis revealed that the age under 65 years  were evaluated for recalcification, X‑ray images of 6 patients were excluded due to early death. Recalcification was found in 32 patients (33.7%): complete in 17 (53.2%) and partial in 15 (46.2%). Manifestation of recalcification is demonstrated in Table .1% were p = 0.004) and pain relief in the irradiated site (p = 0.011) were significant parameters for recalcification, whereas other parameters were not statistically significant.Univariate statistical analysis revealed that KI ≥ 60% , radiotherapy to pelvic bones (p = 0.038) and mild pain at admission (p = 0.004) were significant parameters for better evaluation of QLQ-C30 global health status scale before radiotherapy.Univariate statistical analysis revealed that KI ≥ 60% . Interestingly, the QoL after radiotherapy was only significantly improved in the control group (Table In the control group comparison of QLQ-C30 global health status, symptom, functional scales and QLQ-MY20 symptom scales revealed significant improvement of QoL after radiotherapy (up Table .Table 6EAcute toxicity was evaluated in the first 4 weeks after radiotherapy. The side effects were uncommon, low grade and reversible. No significant difference was found between the groups.Radiotherapy produces an analgesic effect by inhibiting chemical pain mediators and causing tumour shrinkage. The effect of radiation dose on pain relief is a matter of debate. The results of randomized clinical studies of palliative radiotherapy of bone metastases from solid tumours do not show superiority of any particular radiotherapy regimen , 27, 28.Some studies did not find a significant difference between the dose of radiation and pain reduction , 9, 11; In studies reported by Adamietz et al.  and MoseMose et al.  reportedAccording to the literature recalcification occurs in 40–50% of the irradiated bone destructions , 11, 12.Koswig and Budach  found thStolting et al.  reportedMose et al.  reportedNovel therapies have led to an improvement in survival, which has resulted in an increase in symptom burden due to the disease itself and the effects of treatments , 31. TheCaissie et al.  did not Two studies showed that higher KI correlate with better QLQ-C30 scales , 38. ThiThis study has potential limitations. The treatment arms were imbalance by age and the irradiated sites which could be a reason that QoL was improved in the control group. Additionally the logistic regression showed that age under 65 years has significant impact on pain relief. In the control group there were more young patients; thus this age discrepancy should be taken into consideration when comparing pain relief between groups.Our study revealed no significant differences in the analgesic and recalcification response between two different radiotherapy regimens; however, only multiple fraction radiotherapy achieved a significant improvement in QoL. Our study also suggests multiple fractionation regimens if a better QoL is important.


Current research suggests that nurses can influence the outcome for patients with acute coronary syndrome (ACS). The aim of this study has been to evaluate whether a course in cardiovascular nursing (CVN) can improve ambulance nurses’ (ANs’) prehospital care of patients experiencing suspected ACS, related to pain intensity.This is a cluster randomised controlled trial that was conducted in the ambulance services. Patients were allocated to one of two groups: in the first group, patients were treated by ANs who had attended the CVN course and in the second group patients were treated by ANs without this qualification. Inclusion criteria were: 1/pain raising suspicion of ACS, and 2/pain score ≥4 on a visual analogue scale (VAS). The primary outcome was the estimated intensity of pain or discomfort according to VAS 15 min after randomisation. Secondary outcomes were estimated intensity of pain or discomfort on admission to hospital and further requirement of pain treatment, as well as symptoms such as paleness and/or cold sweat; nausea and/or vomiting; anxiety, dyspnea, degree of alertness, respiratory depression and aggressiveness. A further secondary outcome measured was survival to 30 days. Lastly, a final diagnosis was made. A total of 38 ANs attended the CVN course. There were 1,747 patients who fulfilled the inclusion criteria.n = 332) compared with those treated by an AN who had not attended the course  . The ANs who had attended the course used higher doses of morphine.The pain score did not differ significantly between the two groups fifteen minutes after randomisation . On admission to hospital the pain score was significantly lower for patients treated by an AN who had attended the CVN course .The ClinicalTrials.gov Protocol Registration System (registration number  Acute coronary syndrome (ACS) is a common term used to describe a group of conditions resulting from acute myocardial ischemia (i.e. insufficient blood flow to heart muscle) and ranging from unstable angina pectoris to myocardial infarction .Acute myocardial infarction may present less typical symptoms . NeverthThe influence of nursing care on chest pain intensity in patients experiencing suspected ACS is an unexplored area in the ambulance services, especially research focusing on the ambulance nurses’ (ANs’) assessment and treatment of pain. There is a gap in knowledge regarding the assessment of pain, as well as of anxiety. These are aspects of the illness that are as important as the myocardial damage. The intensity of pain in ACS is a major healthcare interest since coronary heart disease is one of the most common causes of death worldwide . There iNurses strive to provide direct contact with and care for the patient, and to relieve patients’ stress and anxiety through assessment, diagnosis and counselling. The ANs describe their care as focusing on the patient’s physical disorder while simultaneously taking her/his lifeworld into account . This caIn the emergency department, the role of the registered nurse (RN) is assumed to be central to the provision of nursing care for patients with myocardial infarction . RNs’ coHowever, knowledge is insufficient concerning ANs’ importance in the prehospital setting for optimal pain treatment in cases of ACS. The ambulance services should be considered not only as a mode of transport but also as a place for initial diagnosis, triage and treatment .This study aims to evaluate whether a course in CVN improves ANs’ prehospital care of patients experiencing suspected ACS, related to pain intensity. According to this aim, the following hypothesis was formulated: “ANs who had attended a CVN course treated patients differently from those who had not attended a CVN course, regarding pain relief for patients experiencing suspected ACS.”A cluster randomised, controlled trial (RCT) was used involving an educational intervention for ANs. The patients included in the study were divided into two groups: A/those treated by an AN who had attended the CVN course  and B/those who were treated by an AN without this qualification (=standard education), i.e. a control group.In the EMS and the prehospital setting the procedure worked out in the following way: when the ambulance came to the patient with suspected ACS the ambulance staff included an AN with or without the CVN qualification. This meant in practice that if the AN had the CVN qualification, the patients belonged to the intervention group, while if the AN did not have the CVN qualification, they belonged to the control group. Thus the ANs’ qualification determined to which cluster the patient was allocated. Regardless of group allocation, and with the patients’ written informed consent, they were then randomised by an envelope method to treatment with midazolam or not. The primary results regarding midazolam were reported together with a consort flow diagram in Wireklint Sundström et al. .The study setting was the EMS system in Western Sweden and in the city of Halmstad (six ambulance services and 1.5 million inhabitants).Patients were included in the study if they complained of pain or discomfort that aroused suspicion of ACS and if they reported pain ≥4 on a visual analogue scale (VAS) . That thThe exclusion criteria were: 1/Systolic blood pressure <100 mmHg, 2/age <18 years, 3/under the influence of alcohol, 4/under the influence of drugs, 5/benzodiazepine abuse, 6/dementia, disorientation, 7/communication problems, 8/symptoms judged as being caused by trauma and 9/secondary transports .This study used patients’ outcomes to measure the effect of the CVN course for ANs. The entrance criteria for ANs were an RN qualification and a Bachelor of Science Degree. In Sweden there are two levels of AN working in the EMS: 1) RNs (Bachelor of Science Degree) and 2) RNs in Specialist Nursing, Prehospital Emergency Care  . Both grThe study involved about 500 ANs, 60 ambulances and one ambulance boat. All the ambulances were staffed with at least one AN. The CVN courses ran from August 2007 to December 2009 Table . Three cThe CVN course for ANs, amounting to 7.5 credits, II level (i.e. one-year Master’s Degree) Table  was deveVarious didactic methods were applied: lectures, seminars, workshops, drama, simulation training, and clinical practice at a Coronary Care Unit. Two theoretical examinations were included as well, culminating in the seminar “Prehospital care for patients experiencing ACS” Table . The stuVASs are used to measure subjectives, such as pain . The VASThe overall Cronbach’s coefficient alpha for the test-retest reliability on the three separate measures of pain intensity was 0.77 .All the measurements took place at three points in time: prior to randomisation, 15 min thereafter and on admission to a hospital. Evaluation of signs of heart failure and heart rhythm was carried out once, prior to randomisation. There was no written information apart from the regular guidelines for the personnel in ambulance services on how to assess outcomes.The primary outcome was the estimated intensity of pain or discomfort according to VAS as perceived and assessed by the patients 15 min after randomisation. The nurses assisted the patients in handling VAS and wrote down the measurements.A number of secondary outcome measurements were also implemented. These included estimated intensity of pain or discomfort according to VAS as perceived and assessed by the patients on admission to hospital, as well as any further requirements for pain treatment. Symptoms were also recorded, such as paleness, and/or cold sweat, nausea and/or vomiting, anxiety, dyspnea, degree of alertness, respiratory depression, and aggressiveness. Furthermore, survival to 30 days and a final diagnosis of acute myocardial infarction and ACS were also recorded.Acute myocardial infarction was defined in accordance with the diagnosis given in the hospital records. ACS was defined as a final hospital diagnosis of either myocardial infarction or unstable angina pectoris.U test was used for ordered/continuous variables. For survival analysis, Kaplan-Meier estimates were used and groups were compared using the log rank test. All tests are two-sided and a p-value of <0.05 for the primary outcome and <0.01 for other comparisons were considered statistically significant. To limit the risk of type I error due to multiple testing, we decided to use a nominal p-value of below 0.05 as significance level only for the primary outcome. All analyses were performed using SAS for Windows version 9.2. The power calculation for the trial was based on the estimated pain intensity as assessed by the patients and has been described in Wireklint Sundström (16).Fisher’s exact test was used to test for differences in dichotomous variables and the Mann-Whitney Patients were divided into two groups: those who were treated by ANs with the CVN course  and those who were treated by ANs without the CVN course. All in all, 1,747 patients took part in the study. Among them 332 (18 %) were treated by an AN who had taken part in the educational intervention. There were no statistically significant differences between the patients in the two groups regarding age, sex and previous history . Otherwise no statistically significant difference was found Table .Table 6TApart from pathological Q-waves being more frequent in patients treated by an AN who had attended the CVN course, no significant difference in terms of ECG recorded, ECG sent or ECG findings between the two groups was observed.No statistically significant differences were observed at randomisation or 15 min thereafter. However, a significantly lower proportion of patients treated by an AN who had attended the CVN course had back pain on arrival in hospital Table .Table 7Sp = 0.24). However, on admission to hospital the pain score was lower among patients treated by an AN who had attended the CVN course (p = 0.001). The proportion of patients free from pain (i.e. a pain score of 0) was significantly higher among patients treated by an AN who had attended the CVN course, both 15 min after randomisation and on admission to hospital.The primary outcome of intensity of pain 15 min after randomisation did not differ significantly between the two groups  compared to ANs without this qualification. This is important, especially since there were no significant differences in demographics, previous history or cardiopulmonary findings between the two groups. Despite this, the ANs who had attended the CVN course showed the courage to use their knowledge in pain treatment with morphine in line with earlier recommendations . Thus, tIn compliance with earlier studies we highlight the fact that healthcare providers can influence the outcome for patients with ACS by providing skilled, efficient, and coordinated prehospital care , and we We found that ANs who had completed the CVN course reported patients’ anxiety at the time of randomisation with significantly greater frequency. One reasonable connection to education and training in cardiovascular nursing might be that improved knowledge of nursing care for patients with suspected ACS has increased the RNs’ awareness of and ability to recognise symptoms and signs of ACS. Therefore these results are in line with earlier studies that have noticed the need for management of anxiety after acute myocardial infarction  and thatHowever, the present results are not sufficiently satisfactory on all points. Only 23 % and 14 % respectively of the patients were free from pain on admission to hospital (shown in Table Our findings suggest that more education and training in cardiovascular nursing are utterly essential in order to meet patients’ need for and right to pain treatment and pain relief when ACS is suspected by the ambulance services, and also in order to meet new demands on professional development for ANs. It is likely that this type of education needs to be reinforced and intensified even further.The present study is to our knowledge unique with regard to the lifeworld and interdisciplinary approach towards ACS with its endeavour to develop an understanding of the possible connections between ANs having attended the CVN course and patients’ estimated intensity of pain in the prehospital setting. We argue that this approach is a strength.One limitation might be that both groups of nurses consisted of both RNs with only a Bachelor of Science Degree and RNs with this degree and also with a specialist Master’s Degree. This means that theoretically, knowledge in Caring Science/Nursing varied in both groups. Another possibly more realistic limitation might be that before the course we did not measure the attitudes and opinions of the ANs involved concerning pain treatment with morphine, nor their overall interest in caring for these patients and patients experiencing from ACS. Perhaps there was a selection bias because the nurses who applied to the CVN course already had a positive attitude to pain treatment and caring for this patient group.Finally, achieving a high rate of reliability must be regarded as problematical when there are many persons involved in the collection of data. Thus, involving several hundred RNs opens up the situation for deficiencies in implementation. The ambulance services are moreover a field that is inexperienced with regard to research. Taken all together, there are a number of circumstances that might lead to lack of reliability. We must take note of the fact that there is a risk of low reliability in this and other equivalent studies. The data in this study is also too limited to be able to function as a basis for a discussion about generalisability. These results should therefore solely be regarded as hypothesis-generating.An educational intervention was not shown to relate significantly to the primary outcome of patients scoring lower on the VAS pain scale after 15 min. Thus, patients with estimated intensity of pain ≥4 raising suspicion of ACS and treated by an AN who had recently completed the CVN course did not have less pain during the first 15 min after the ambulance’s arrival on scene. However, our data suggests that such an intervention was connected to more effective pain relief later on but still in the prehospital setting.This study underlines the ANs’ potential for assisting patients to experience less pain and achieve relief of symptoms despite illness deriving from ACS. Therefore, the results should encourage increased investments in the education of ANs whose work brings them into close contact with these patients. Further studies should be carried out for additional confirmation of the results found in the present trial and to identify factors associated with the prehospital care provided.


Premedication with benzodiazepines has been thought to reduce patient anxiety, pain perception, and non-catheter-induced coronary spasms and may increase procedure-related complications. We used to routinely provide premedication with diazepam and chlorpheniramine before cardiac catheterization procedures. However the benefits of such a treatment are not well established here. Therefore, we designed this study to test whether the routine use of premedication during coronary angiography is needed.A total of 200 consecutive patients scheduled to undergo either diagnostic or therapeutic coronary angiographic procedures were randomized to receive either premedication with diazepam (5 mg) and chlorpheniramine (4 mg) 60 minutes prior to their procedures (n = 100) or no premedication (n = 100). The administration of intravenous midazolam during the procedures was permitted at the operator’s discretion. The primary endpoints were anxiety and pain perception during the procedure.A total of 200 patients with similar baseline characteristics were randomized into two groups. The first group received oral premedication with diazepam (5 mg) and chlorphenamine (4 mg) 60 minutes prior to their procedures, and the other group did not receive premedication. We observed no differences in periprocedural pain perception  or anxiety . Interestingly, local pain was more pronounced in the premedicated patients than in the non-premedicated patients . There were no contrast-related reactions reported in either group.Treatment with oral diazepam and chlorphenamine prior to cardiac catheterization and percutaneous coronary intervention does not alter rates of anxiety, periprocedural pain. We used to routinely administer premedication with diazepam and chlorpheniramine to our patients undergoing cardiac catheterization procedures. We searched the literature for support for this approach, but the few relevant papers found only a neutral result when studying the effect of premedication on procedural outcomes . WhetherThis randomized, single-center, controlled trial compared premedication with diazepam and chlorphenamine to no premedication in stable patients undergoing diagnostic or interventional procedures. A total of 200 patients were equally divided to receive or not receive open-label oral diazepam (5 mg) and chlorphenamine (4 mg) before cardiac catheterization.This was a randomized, single-center, controlled clinical trial in which the patients were randomly divided equally into two groups (at a 1:1 ratio) and received either open-label oral diazepam (5 mg) and chlorphenamine (4 mg) or no premedication beforehand. The patients underwent either routine coronary angiography or PCI. This study only included adult patients who were referred for cardiac catheterization procedures. Any patients with acute myocardial infarction, decompensated heart failure or hemodynamic instability and any patients who were inappropriate due to high anxiety levels were excluded. The patients who were eligible for this clinical trial were given a detailed explanation of the study, and informed consent was obtained for the catheterization procedure. They were then randomized into one group that received premedication with diazepam (5 mg) 30 to 60 minutes prior to the procedures or a second group that did not receive the premedication.Randomization was achieved using an “alternating weekdays” procedure. All of the patients who arrived for their procedures on Saturday, Monday and Wednesday were given the premedication, and the patients undergoing their procedures on Sunday and Tuesday received no premedication prior to the procedures.It is also important to note that midazolam administration was permitted during the procedures and was performed at the operator’s discretion.A data collection form was developed to collect the required information during recovery (while the patients were entering and exiting the catheterization laboratory). In addition, it took the current hospital practice and policy into account. This form included the patient’s demographic and background variables, including height and weight, comorbid conditions, and previous ischemic heart disease, which consisted of any previous history of ST-elevated myocardial infarction, non-ST-elevated myocardial infarction, or coronary artery bypass grafting. In addition, it documented which procedure they underwent  and whether the procedure was elective or acute. The primary endpoint was patient pain and anxiety. One of the aims of this study was to measure the number of adverse events that the patients experienced while undergoing the procedure. Therefore, this aspect of the research sought to assess adverse effects, such as the composite of contrast-related allergies. Secondary endpoints included the number of non-catheter-induced spasms. The patient’s anxiety and pain assessment involved a patient questionnaire, which sought to measure the patient’s self-assessment of their perception of pain and anxiety in the periprocedural period.Diazepam  administration. Diazepam (5 mg) was administered within one hour of the procedure.Chlorphenamine (Allerfin) administration. Chlorphenamine (4 mg) was administered within one hour of the procedure.The primary endpoints included the effect of premedication on the patient’s anxiety and pain. The secondary endpoints included non-catheter-induced spasms and contrast-related allergies.The study protocol was reviewed and approved by the institutional ethics and research committee at Prince Sultan Cardiac Center, Riyadh.Statistical analyses were performed using SPSS for Windows 16.0 . The data are presented as the means ± standard deviations for the continuous variables and as absolute numbers (percentages) for the categorical variables. Comparisons between the two groups were performed using t-tests for the continuous variables and chi-squared tests for the categorical variables. A P-value of < 0.05 was considered to be statistically significant. An intention-to-treat analysis of all of the participants who were randomized into the treatment groups was used to determine the efficacy of the premedication therapy.This study is single-center study and may be subject to bias.A total of 200 consecutive patients with similar demographic characteristics  were ranCoronary spasms were observed in 0.03% of the patients, predominantly in the premedication group (0.05% versus 0.01%), and catheter-induced coronary spasms were more commonly observed than non-catheter-induced spasms . There was no gender deference in coronary spasm .None of our patients experienced clinically significant adverse reactions or contrast allergies.Premedication with diazepam and chlorphenamine is frequently used in the cardiac catheterization laboratory during coronary angiography and interventions. Nevertheless, data regarding their usefulness and efficacy are scarce. There is no standard premedication, and sedatives may be required in some patients to relieve their anxiety.Conscious sedation is practiced at some institutions where the sedation protocol varies according to the institution’s guidelines . RoutineAll of the patients received appropriate pain relief medication following the procedure.As in other studies, premedication with oral diazepam had little impact on the patients’ anxiety and pain perception . FurtherWe found that the patients who received premedication reported a higher rate of experiencing local pain.The findings of this study do not support the routine use of oral diazepam and chlorphenamine as premedications for patients undergoing coronary angiography and interventions.The main finding of this study was that premedication does not reduce patient anxiety or pain perception, in contrast to Woodhead et al., who observed significant pain relief in diazepam-premedicated patients .We examined the occurrence of non-catheter-induced coronary spasms with the use of premedications and compared our results to the observations by Bennett, who reported a higher incidence of spasms with sedation. Our study did not identify an increase in the number of non-catheter-related coronary spasms. In contrast, the number of catheter-induced spasms was significantly higher with premedication 4% versus 0% .Treatment with oral diazepam and chlorphenamine prior to cardiac catheterization and percutaneous coronary intervention did not alter the rates of anxiety, periprocedural pain, or contrast reactions. Premedication was associated with a higher incidence of catheter-induced coronary spasms.


To evaluate the extent of remission of hyperalgesia, we recorded the visual analogue scale (VAS) scores during cotton swab reaction before and after treatment and in the resting and active pain states. In addition, blood samples were collected and plasma cytokine and neuropeptides such as interleukin-6 (IL-6), substance P (SP), and β-endorphin (β-EP) were measured by enzyme-linked immunosorbent assay (ELISA) at the admission (basic state), before the operation, and at 12 h postoperatively. The number of adverse events  within 12 h of the treatment were also documented. Our results showed that VAS scores during cotton swab reaction decreased after treatment in all patients (p < 0.05). Compared to group CP, plasma IL-6 and SP levels decreased (p < 0.05) and β-EP levels increased (p < 0.05) in groups NB, PRF, and CT. There were no significant differences in adverse events among groups (p > 0.05). We found that PRF in combination with NBT increased β-EP levels and decreased plasma IL-6 and SP, thereby alleviating pain and hyperalgesia in PHN patients. Taken together, our data suggest combined therapy of PRF and NBT is effective and safe for PHN patients.Caused by viral infection, postherpetic neuralgia (PHN) is the most common chronic neuropathic pain. Various treatment modalities such as early use of nerve block therapy (NBT) and pulsed radiofrequency (PRF) have been studied in reducing pain, however, no consistent success was achieved in all the patients treated with single regimen. The combined therapy of PRF and NBT with different targeting mechanism are of interest and remains to be determined. Here we investigated the combined effects of pulsed radiofrequency (PRF) with nerve block therapy (NBT) in PHN patients in a prospective randomized clinical trial. Sixty PHN patients were divided into four groups ( Postherpetic neuralgia (PHN) is the most common chronic nerve pain caused by chickenpox (herpes zoster) viral infection. PHN leads to burning pain that lasts long after the skin rash disappear in some patients. There are limited pain management options because the underlying mechanisms remains unclear. Recent studies showed that traditional oral drugs, nerve block therapy (NBT) and pulsed radiofrequency (PRF) can shorten pain duration in some patients . PHN canSensory abnormalities expressed in PHN patients includes dysesthesia , allodynia  or hyperalgesia (heightened pain response) . SeveralNerve inflammation caused by virus infection triggers the ongoing neuralgia pain. Local and systemic inflammation is one of the causes and biomarkers underlining PHN pain. Interleukin-6 (IL-6) is an inflammatory mediator secreted by T cells and macrophages and is associated with central sensitization in PHN patients . β-endorThe current trail aimed to systematically evaluate the efficacy and safety of a combined therapy of PRF and NBT compared to traditional single-modality treatment such as oral drugs, nerve blocker administration, and PRF for PHN patients by recording VAS score in cotton-swab test. We also explored the underlying analgesic mechanisms by measuring the plasma IL-6, SP, and β-EP.n = 15 in each group): the conventional puncture group (group CP), the nerve block therapy group (group NB), the PRF group (group PRF), and the combined treatment group .This study was a prospective, randomized clinical trial, performed in an urban hospital in China. The study protocol was approved by the Medical Ethics Committee of Wuxi People’s Hospital . This study was registered at the Chinese Ethics Committee of Registering Clinical Trials (ChiCTR-INR-17011094). A total of 90 patients who had PHN for more than 1 month were approached and 60 of them were enrolled and completed the study . All parAfter admission, routine examinations, including blood test for coagulation and hepatorenal function, were performed. All patients were given traditional oral drugs  and all treatment procedures were performed in the operating room. Patients were placed in an appropriate position with electrocardiographic monitoring and oxygen inhalation (2 l/min). Patients in group CP received a simultaneous conventional puncture in the affected nerve. Patients in group NB received a 5-ml local drug injection in the affected nerve . Vertebral nerve roots or nerves corresponding to the area of herpes zoster infection were identified if abnormal sensation occurred in the corresponding affected area . Patients in group PRF were treated with three courses of PRF . Patients in group CT received PRF treatment followed immediately by NBT. Patients in groups PRF and CT were punctured with Baliys PMF18-100-5 casing puncture needle, which was then connected to the PRF treatment instrument (Baylis PM230) probe. The test mode was 50 Hz, 0.3 V and the treatment mode was 42 °C, 120 s for three courses and the treatment interval was 1 min. After PRF treatment, 5 ml of the drug was injected for group CT patients. The puncture point was compressed to stop bleeding after the needle was removed. All patients returned to the ward after treatments followed by a 5–10 min observation period for stable vital signs and no complaints of discomfort.A 4-ml blood sample was collected at admission (baseline), before the operation, and at 12 h after the operation. The plasma cytokine and neuropeptides were detected by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions: IL-6 , β-EP , and SP .To access pain relief effect of various treatments, a clean cotton swab was used to brush the skin in the areas controlled by the affected nerves at a speed of 1–2 cm/s to induce pain and the VAS score was assessed at the admission (basic state), before the operation, and at 12 h after operation. VAS scores in the resting and active states were recorded as control. The VAS scores were interpreted as follows: 0, analgesia; 1–3, mild pain, which was bearable; 4–6, moderate pain, which could affect sleep; 7–10, severe, unbearable pain. The number of adverse events  within 12 h after operations was also recorded.χ2 test. Rank data were compared by the rank sum test. The sample size was calculated based on the primary outcome analysis of comparisons of VAS scores by one-way ANOVA. With a moderate effect size of 0.25, alpha error of 0.05, and four groups of patients, a sample size of 280 patients was required to achieve a statistical power of 0.95 . P < 0.05 was defined as statistically significant. The data were analyzed using SPSS 18.0 statistical software package .Data with normal distributions were presented as mean ± standard deviation. One-way ANOVA was used for comparisons among groups. Data with skewed distributions were presented as median with confidence intervals. The enumeration data were measured using the p >0.05). VAS scores in the resting and active states, and during cotton swab reactions decreased after each treatment. After enrollment, treatments including cervical and thoracolumbar paravertebral PRF therapy and NBT were performed accordingly. The most significant VAS score decrease was observed in group CT (P < 0.001), as shown in Here we enrolled and completed studies of total 60 PHN patients, of which 20 had chest and back pain, 35 had waist and back pain, and five had neck-shoulder-back pain . There wp < 0.05). The plasma IL-6 and SP decreased (p < 0.001) and plasma β-EP increased (p < 0.001) in each group after treatment. After treatment, the plasma IL-6 and SP were significantly lower (p < 0.001), while those of β-EP were significantly higher (p < 0.001) in groups NB, PRF, and CT, compared to those of group CP. The most significant increase of β-EP levels was observed in group CT  and no incidence of swelling, redness, and bleeding in puncture sites within 12 h after the operation (There were no significant differences in the number of adverse events among the four groups (peration .Postherpetic neuralgia is a common neuropathic pain that can seriously affect sleep and life quality of the patients. The main characteristics of PHN include spontaneous pain, paroxysmal electrical shock-like pain or acupuncture-like pain, hyperalgesia, and sensory loss. Once diagnosed, treatment regimen should be aimed at pain controlling and reducing adverse events related to treatments. To measure the extent of remission of the pain, the dynamic mechanical cotton swab reaction was used in this study . At presOur study showed that VAS scores significantly decreased after treatment, in the resting and active states and during cotton swab reaction in all 4 group patients, with the most significant decrease observed in group CT, suggesting that oral drugs, NBT, and PRF relieve pain and hyperalgesia in PHN patients. PRF was more effective in pain relief than NBT, and a combination of PRF and NBT was more effective than either PRF or NBT alone. In addition, there were no significant differences in nausea, vomiting, and constipation among the four groups of PHN patients. There was no incidence of swelling, redness, bleeding, or infection in the puncture points too. Taken together, our data suggest that the combined treatment of PRF with NBT is safe and effective for PHN patients.To understand the mechanism of our treatments, plasma cytokine and neuropeptides in PHN patients were measured. Increased inflammatory cytokine IL-6 in PHN patient plasma sensitizes central sensory and highly correlates with hyperalgesia . HoweverIn this study, we performed a randomized, parallel-group study in 60 outpatients to evaluate the efficacy and safety of four different treatment regimens. Limitations of the current study include its design as a single-center study and its small sample size. We did not assess the effects of liver or renal dysfunction on the treatment effects either. Sample size is an important factor to detect a statistically significant difference . Our stuIn conclusion, PRF combined with NBT could safely and effectively relieve pain and hyperalgesia in PHN patients by up-regulating the expression of β-EP and reducing the levels of IL-6 and SP in plasma.10.7717/peerj.4852/supp-1Supplemental Information 1Click here for additional data file.10.7717/peerj.4852/supp-2Supplemental Information 2Click here for additional data file.10.7717/peerj.4852/supp-3Supplemental Information 3Click here for additional data file.


A comfortable postoperative return to daily activities has increased the need to control inflammation after third molar surgery. Anti-inflammatory drugs and analgesics are not exempt from adverse effects such as allergies and chronic gastritis, and they are not without cost. The association between low-level laser and auricular acupuncture can be an alternative when conventional drugs are contraindicated. Among its advantages, we can mention the low risk of side effects, low cost and simplicity of application. The objective of this study is to evaluate the efficiency of low-level laser at auriculotherapy points in reducing postoperative pain in lower third molar surgery.Ninety bilateral, symmetrical lower third molar surgeries will be performed in 45 healthy patients. Each patient will be their own control, through a split-mouth crossover study. One side of the mouth will be randomly chosen and, immediately after surgery, will be treated with low-level laser. After 21 days, the contralateral side will be operated on with low-level laser simulation used postoperatively. This regimen (laser application or not) will be repeated at 24 and 48 h after surgery. All patients will be requested to take analgesics (acetaminophen) if they have pain, i.e. in case of pain. Neither the surgeon nor the patients will know the assigned treatment. The primary variable will be postoperative pain assessed using a Visual Analog Scale, and the secondary variables will be trismus, edema, local temperature, dysphagia, presence of infection and painkiller ingestion. These variables will be assessed at baseline, 24 h, 48 h and 7 days after surgery. Blood samples for systemic inflammatory cytokine  analysis will be assessed at baseline and 24 h after surgery.Some authors believe that using a wavelength of 633 to 670 nm is a good option for laser therapy in the field of acupuncture. This wavelength can penetrate biological tissue to a depth of about 3 mm. However, for auriculotherapy points, the stimulus  does not penetrate so deeply. For this reason, we chose a laser wavelength of 660 nm (red wavelength).NCT02657174, registered on 11 January 2016.ClinicalTrials.gov Identifier: The online version of this article (doi:10.1186/s13063-016-1540-9) contains supplementary material, which is available to authorized users. Third molar surgery is the most common surgical procedure in dentistry. The postoperative period of third molar surgery is usually accompanied by pain, trismus and swelling, and controlling these symptoms is essential for patient comfort. An inflammatory reaction followed by phlogistic symptoms are common and compromise the quality of life of patients during the first 3 days after surgery –3, and aAcupuncture is an integral part of a system called Traditional Chinese Medicine. According to the World Health Organization (WHO) it stimulates certain points that are distributed throughout the body’s surface using needles, moxibustion, electricity, laser or acupressure , 16. It There is only one clinical study to date that evaluates the effect of laser therapy to auricular points for pain reduction in dentistry , and theThe protocol was approved by the Research Ethics Committee of Nove de Julho University (UNINOVE), number #1100869. This study had all necessary consent approved by Nove de Julho University Ethical Committee for any patients who will be involved in the study, including an Informed Consent Form that patients will need to sign to participate. The study is in accordance with the Declaration of Helsinki. Patients who accept participation will sign the Informed Consent Form after verbal (by HSF) and written explanation of the study. The sample will comprise 45 healthy patients of both genders aged from 18 to 28 years who require surgical removal of bilateral symmetrical lower third molars. Patients will undergo two surgeries with a 21-day interval between them in a split-mouth crossover design. The surgeries will be performed by the same surgeon in the Dental Clinic at Nove de Julho University, São Paulo, Brazil, from June 2016 until February 2017.t test for paired groups, since we have two groups (right side and left side) on the same patient. The effect size was determined using the formula:The sample size was calculated (G* Power software version 3.1.9.2) by a We select the worst scenario, that is, the largest standard deviation (SD) between means. The mean values of control and treated groups, as well as the SD were taken from one particular study . The errThe study will include healthy patients  with their teeth in position IIB according to Pell and Gregory , with anAn external researcher, who will not participate in this research (IPT), will perform randomization using Microsoft Excel, 2013 version. As the letters are drawn (A or B), they will be placed into opaque envelopes labeled with sequential numbers. The envelopes will be sealed and remain in numerical order in a safe place until the completion of surgery. The same researcher (IPT) (not involved in the study) will prepare the envelopes. To decide the side of intervention, we will randomize into 45 blocks (1:1) of 90 surgeries designed as A or B. This corresponds to 45 blocks, either AB or BA. As the study will be performed in a double-blind manner, neither the patient nor the operator will know which treatment will be applied in each of the two surgeries. The only person who will know the treatment performed (JSR) will be the researcher who is responsible for the application of the laser to the auriculotherapy points. This data will only be revealed after statistical analysis.G1 –  45 third molar surgeries will be performed in a conventional manner . At the G2 – (control) 45 surgeries will be performed in the conventional manner, identical to G1. The patient will receive low-level laser, albeit turned off in order to block the passage of light, to the same auricular points used in G1.This is a controlled, randomized, double-blind, split-mouth, crossover clinical trial. In a split-mouth study, a patient functions as their own control:The surgeries will be performed with two cartridges (1.8 mL) of the local anesthetic (LA) mepivacaine 2 % with epinephrine 1:1,000,000. The time delay between the surgery on each side will be 21 days.Acetaminophen (750 mg) 8/8 h will be provided for all patients. They will be instructed to use this only in case of pain, and only for 3 days.A medical prescription for acetaminophen with codeine phosphate 30 mg (Tylex® Janssen-Cilag) will be provided only in case of severe pain. Patients who need to use this will be excluded from the study. Data from these patients will only be described, but not included in the analysis of results. This exclusion will not jeopardize their treatment for ethical reasons. Any adverse event will be reported in the study. Any important protocol modifications will be communicated.The researcher who will apply the laser will mark the points that will be irradiated on the outer atrium of the patient’s ear with a red gel pen to avoid interference with red laser light (λ = 660 nm). The low-level laser points will be irradiated on the same operated side, based on Oleson ; see FigThe World Federation of Acupuncture and Moxibustion Societies (WFAS), F7, B Dongjiu Mansion, Xizhaosi street, Dong Cheng District, Beijing. 100061, China. TEL: 86-10-64011210, 10.1186/s13063-016-1540-9 FAX: 86-10-64018354 E-mail: wfas1987@foxmail.com, owing to the fact that there are numerous classifications and auriculotherapy maps used in several countries, has established some norms for the standardization of auricular acupuncture points by bringing together experts who promoted the so-called ISAAPs  . The namShen Men – relieves pain, anxiety and inflammatory diseases, (2) Sympathetic – SNV – activation by the sympathetic nervous system of parasympathetic sedation, reducing neurovegetative imbalance, (3) Stomach – its related function is to relieve toothache, (4) Toothache 3 – pain relief of the lower teeth, (5) Jaw – relieves pain in the lower teeth, tension and anxiety, and (6) Adrenal  – stimulation of adrenal hormones relieving stress. It is indicated for inflammation and hypersensitivity.The points to be used in this study are listed below along with their main function: (1) 2. The energy delivered per point will be 1 J in 10 s. The radiant exposure will be 354 J/cm2 and irradiance will be 35.4 W/cm2. In the control side, the device will remain turned off, so neither the patient nor the surgeon will know to which side it is really being applied. We asked DMC  to silence the device.The red laser diode  (ANVISA 80030810157) with a wavelength of 660 nm (±10 nm) will be used. The power of the appliance is 100 mW. The diameter of the fiber optic device is 600 μm and, thus, a spot (area) of 0.002826 cmAll the variables described below will be evaluated by the same operator at baseline, and 24 h, 48 h and 7 days after each surgery. The primary outcome will be postoperative pain assessed by a Visual Analog Scale (VAS). Secondary outcomes will be trismus, edema, local temperature, dysphagia, and presence of infection .The pain will be assessed by applying a VAS, consisting of a 100-mm line numbered in centimeters, with two closed ends. One end is labeled “0” and the other “100,” meaning “no pain” and “worst pain already felt,” respectively. Each patient will be instructed to mark a vertical line with the point that best matches the intensity of pain during the evaluation. Instructions on marking will always be given to the patient by the same operator . These aThe criteria for the determination of edema will follow preestablished measurements: (1) the corner of the eye to the angle of the jaw, 2) the tragus to the labial commissure, and (3) the tragus to the pogonion ; see Fig the tragFor the evaluation of the presence of trismus the inter-incisor measurement  will be used with a digital caliper . During clinical examination (7 days before the surgery), the patient will be asked to perform their maximum mouth opening, which will be measured in millimeters .The local temperature will be measured in the mandibular angle region 2 cm above the lower jaw board .Fever (systemic) is usually an indicator of infection. Since, in case of infection pain is usually worse, this may become a bias. The temperature will be measured using a digital thermometer .The assessment of dysphagia will be conducted through a numerical scale: 0 – indicates total absence of dysphagia; 1 – dysphagia for solid food; 2 – dysphagia for any food, liquid or solid.Rescue medication intake – the quantity of medicine ingested will be counted and statistically analyzed. All patients will be advised to take only acetaminophen in case of pain. We will ask for tablet return in order to monitor adherence to intervention protocols. A flowchart is presented for an overview of the study Fig. Fig. 3FloBlood samples will be collected in dry tubes and sent to the laboratory of Biophotonics Applied to Health Sciences (Nove de Julho University). After centrifugation, serum will be stored in 1.5-mL tubes at −80 °C. Plasma levels of inflammatory markers of TNF-α, IL-1, IL-6 and IL-8 will be quantified using commercial ELISA kits  according to the manufacturer’s instructions.The data will be tabulated on an Excel table developed for research.t test will be applied. For nonparametric data and scores the Mann-Whitney test will be applied. Data will be presented as means ± SD and the p value set at 0.05.By the end of the study, randomized groups will be revealed and statistical analysis will be performed as group A or group B. The meaning of A or B will be known after statistical analysis. The data will be evaluated by comparing the two groups: experimental and control groups (“gold standard”). Data will be submitted to the Shapiro-Wilk test to test for data normality. If the data is normal a homogeneous This study aims to evaluate the effectiveness of auriculotherapy stimulation with laser on postoperative pain in patients undergoing third molar surgery. The main rationale for conducting this study is for the reduction of postoperative anti-inflammatory drug and analgesic use because of the frequency of adverse effects associated with their use , 9. ExtrSome specific techniques are proposed to evaluate tooth position. The Winter and the Pell and Gregory techniques are the most common. Despite the Winter technique being simpler and more easily reproducible , it doesA red diode laser with a wavelength of 660 nm (±10 nm) will be used. It has been proved that a wavelength of 650 to 950 nm can penetrate biological tissue to a depth of 3 mm . However2 [2 to 10 J/cm2 or more [It has been shown that the irradiance required to achieve the same effect as an acupuncture needle must be greater than 1.3 W/cm2 . Other a or more . One of  or more ).The auricular points were chosen based on the Chinese School , as suggPostoperative pain will be our primary variable, so it is very important to measure it properly. Patients will always take the same medication regardless of which side has been operated on. Acetaminophen will be given to patients because it is a safe and potent analgesic for acute soft tissue pain, showing no inferiority when compared with NSAIDs . AlthougFor pain measurement, a VAS will be included as the main instrument for assessing the patients’ experience of pain. This scale is graduated in centimeters, which allows the use of parametric tests, which in turn improves accuracy of data analysis. Infection parameters (systemic disease) will also be evaluated. Such patients will be excluded from the study, but accounted for and described according to the CONSORT statement. The anti-inflammatory drugs and analgesics have been classically used for treating pain after third molar surgeries, but they are not exempt from adverse effects, such as allergies and chronic gastritis. The association between low-level laser and auricular acupuncture may be a low-risk alternative to abolish the need for, or reduce the quantity of, these postoperative medications.This trial has not initiated patient recruitment at the time of submission.


The purpose of this article is to evaluate the improved safety and efficacy of transscleral cyclophotocoagulation (TSCPC) by performing it in the operating room.This is a retrospective review of 17 eyes of 16 patients who received TSCPC for uncontrolled glaucoma on maximum tolerated medication.P < .001). Visual acuity was measured at the final follow-up visit and was stable in 13 eyes (76.47%), improved in 2 eyes (11.75%), and decreased in 2 eyes (11.75%). Nine of the eyes (52.94%) saw a reduction in the number of medications taken, whereas 8 had no change. Two eyes had resolved complications of cystoid macular edema (CME) and subconjunctival hemorrhages. The overall success rate is determined to be 88%.Mean intraocular pressure (IOP) prior to surgery was 30.85 ± 6.24 mm Hg and was reduced to 14.48 ± 3.53 mm Hg after treatment for an average reduction in IOP of 48.56% at the final visit (TSCPC performed in the operating room may have greater safety and efficacy for patients with uncontrolled glaucoma. Both contact and noncontact methods have been explored; however, direct contact allows for conjunctival and scleral compression, which leads to a more direct transfer of energy. The transmitted energy from the laser causes destruction of both the ciliary epithelium and blood vessels, which leads to coagulative necrosis of the ciliary body. TSCPC has proved to be a successful surgical method to lower IOP–5 while not increasing visual field loss. However, many ophthalmologists hesitate to perform this procedure due to its painful nature and high risk of complications such as hypotony and phthisis bulbi.,8 Trabeculectomy has often been considered the most effective method in controlling glaucoma, but the number of trabeculectomies performed worldwide is steadily decreasing. This trend is mainly due to the long-term morbidity associated with the procedure.,10 Thus, glaucoma research is looking for alternatives with equal efficacy and far less complications. TSCPC presents to be a viable alternative if pain and complications are minimized.The use of cyclophotocoagulation procedures for the treatment of glaucoma have increased significantly in the past decade.; however, many physicians are noticing that the IOP-lowering ability may be compromised. Since the inception of this MicroPulse technology, many physicians have avoided performing the traditional continuous-wave TSCPC because of the perceived equal efficacy and decreased morbidity rate associated with the MicroPulse method. In our practice, we have continued to perform the continuous-wave TSCPC, but have opted to administer this procedure in the operating room (OR) rather than in the clinic. When performed in the OR, this procedure can be administered with heavy sedation, which has allowed for better tolerability for the patient enabling the surgeon to more accurately apply laser pulses.In order to combat these issues, Iridex recently developed a new method of laser delivery known as MicroPulse Laser Therapy. This delivery mode uses repetitive, short pulses of laser administration separated by rest periods. It has been shown that this method allows for a more selective targeting of the ciliary bodyIn this case series, we evaluate the efficacy and safety of TSCPC in treating glaucoma when moved to the OR as opposed to being performed in the clinic. We also explore the possible advantages of using the continuous-wave method over the MicroPulse delivery system.2A retrospective chart review was done on 17 eyes of 16 patients who received TSCPC for treatment of the following forms of glaucoma: pseudoexfoliation, primary open angle, angle recession, congenital, neovascular, traumatic, and other secondary forms of glaucoma Table . All opet test in which a P value of <.05 was considered statistically significant. A Kaplan-Meier analysis was generated to determine survival rates using the previously described success definition to compensate for the varying follow-up times. All statistical analyses were performed on Microsoft Excel. This observational study was done with the approval of the Institutional Review Board.The procedure was performed under monitored anesthesia care with topical lidocaine. An OcuLight SLx semiconductor diode 810 nm laser was used with the contact G-probe and applied by a single operator. Laser treatment consisted of 18 to 21 applications over 270° using an average of 2000 mW of power for 1 to 2 seconds. Prednisolone acetate 1% was given postoperatively for 1 week. The mean follow-up time was 156.3 ± 10.2 days (range: 3–50 months) with an average of 6.8 ± 2.2 visits. At each follow-up visit an examination was done that included IOP and BCVA measurements, an account of the number of glaucoma medications, a pain determination using a verbal analog scale in which the patient was asked to gauge their pain as no pain, mild pain, moderate pain, or severe pain and an examination for possible complications caused by the procedure. Pain was considered prolonged if the patient reported any discomfort for at least 2 consecutive visits. Statistical analysis of the difference in IOP and number of glaucoma medications before and after surgery was carried out using a Student 3t test was used to compare average preoperative IOP to each follow-up time and each interval gave a statistically significant reduction of IOP (P < .001). Visual acuity was measured at the final follow-up visit and was stable in 13 eyes (76.47%), improved in 2 eyes (11.75%), and decreased in 2 eyes (11.75%). However, 1 patient who had a decreased acuity suffered a visual cortex stroke during the follow-up period so the true number of eyes that experienced decreased vision attributable to the TSCPC procedure was considered to be 1 (5.88%)  were suffered; minor complications were seen in 2 (11.11%) of the eyes . The average reduction in IOP was 48.56% at the final visit. Figure 4–5; however, there is conflicting data on the complication rates of this procedure. Ramli et al and Murphy et al both reported that there was a significant risk of developing serious complications such as hypotony, while Osman et al and Ansari and Gandhewar reported no significant risk for development of these complications. This conflicting data, along with many reports of operative and postoperative pain associated with this procedure,17 merit consideration on how to maintain good outcomes while lowering complications and pain. Our series saw a significant decrease in IOP (P < .0001) in all 17 eyes at their final visits, and all patients had a final IOP in the successful range (5–22 mm Hg) at the final follow-up. In all cases, the number of glaucoma medications was either maintained or reduced. Another important variable considered in this study was intraoperative or prolonged pain, which was reported in 0 of the 17 eyes. The 2 patients who were considered failures both underwent a second TSCPC procedure due to uncontrollable IOP and progressing vision loss. Of these 2 patients, one of them received a successful outcome after only 1 additional application, whereas the other could not maintain a stable IOP and experienced substantial visual field loss after multiple applications of the G-probe. It is useful to point out that this case was rather complex and the patient received TSCPC after multiple failed procedures. Given this, a success rate of 88.24% is rather conservative and is probably higher. To our knowledge, no previous study on TSCPC reports a success rate this high with a complication and pain percentage this low after only 1 treatment. Prior to this study, our clinic performed all TSCPC procedures in the clinic and saw a success rate of 33%. After moving TSCPC to the OR, we saw an increase in success rates which points to the possibility of a correlation between improved outcomes and OR surgical practices. Osman et al reported a similar reduction in IOP in a similar cohort of patients when performed in the clinic. However, they also saw a significantly higher rate of pain and complications.In recent years TSCPC using the G-probe has become a more viable tool to treat refractory glaucoma; however, many surgeons still hesitate to use this procedure due to the potential for serious complications and its painful nature. Many studies confirm the IOP-lowering ability of TSCPC and a possibility of contamination. However, in our practice when TSCPC is performed in the OR, the cost of the G-probe is covered by the OR facility fee. This could reduce the financial burden for surgeons in a similar situation and make them more likely to use the G-probe as directed, which also may allow for greater efficacy and better safety.There are several reasons we believe why performing TSCPC in the OR could produce more successful outcomes. First, when performed in an OR the patient can receive much better pain control by being placed under monitored anesthesia which would allow for much better tolerability during the procedure and thus more accurate laser applications. The G-probe by Iridex is sold as a single use probe and is priced anywhere from 100 to 220 US dollars. Many surgeons reuse the probe up to 50 times to cut down on surgeon's fees. Repeat use of the G-probe leads to both a fluctuation in energy output reported an average reduction in IOP of 40%, a success rate of 73.3% after initial treatment in 19 eyes using a similar definition of success, and a complication rate of 5.3%. Comparing our outcomes to this study, we see that the continuous-wave method of TSCPC has a stronger IOP-lowering ability and even though we see a greater complication rate in our cohort, we believe that due to the small number of patients in each study and the mildness of our complications that the complication difference between the groups is not significant. We feel that a greater number of patients are required to draw any true conclusions about the difference in complication rates of the 2 delivery methods. However, MicroPulse TSCPC lowers pressure in a much more passive manner by using short bursts of energy to increase uveoscleral outflow while continuous-wave TSCPC is more destructive to the ciliary body. This, along with the fact that the MicroPulse technology allows for no scaring, provides obvious safety advantages over conventional TSCPC. We believe that electing to perform either MicroPulse or conventional TSCPC should be based on the target postoperative IOP and all factors, including possible safety advantages, should be taken into account.In comparing our outcomes to those of the MicroPulse delivery system, we found a similar cohort of patients who underwent MicroPulse TSCPC. Kuchar et al5Our study suggests that TSCPC, when performed under heavy sedation and proper G-probe use is employed, leads to better outcomes and a greater clinical efficacy. We conclude that TSCPC should still be considered earlier for treating refractory glaucoma and can be used in a variety of glaucoma types.


To compare the self-reported ratings of functional interference caused by pain between patients who did and did not respond to palliative radiotherapy for bone metastases during their last three months of life.A prospectively gathered Brief Pain Inventory (BPI) database compiled from patients receiving palliative radiotherapy for painful bone metastases was reviewed. Demographic and clinical data, pain response rates and self-reported ratings of functional interference caused by pain were analyzed for those patients who died within three months of beginning radiotherapy.From 400 patients in the database, 83 died within 3 months of beginning radiotherapy. There were 54 male and 29 female patients. Their median age was 69 years and their median KPS was 70. The three most common primary cancers were lung (40%), gastrointestinal (16%) and breast (14%). For patients with available follow-up information the 1-month overall pain response rate was 78% and the 2-month rate was 83%, which include both complete and partial responses as defined by the International Bone Metastases Consensus. At 1 month, patients responding to treatment reported significantly less interference by pain on their general activity, walking ability, normal work, sleeping, and enjoyment of life than did patients not responding to treatment.Patients that responded to treatment reported less functional interference due to pain than did patients who did not respond. Despite being very near the end of life, patients responding to palliative radiotherapy for painful bone metastases may benefit from more than pain relief alone. Bone metastases cause significant pain and functional disability as a result. They are effectively palliated with external beam radiotherapy , 2; howeThere is very limited data on the efficacy of radiotherapy for palliating pain from bone metastases among patients nearing the end of life , and no The Brief Pain Inventory (BPI) is a pain assessment questionnaire that was designed for use with patients with cancer -9. It meThe study population was selected from a cohort of patients that received palliative radiotherapy for bone metastases between May 2003 and November 2007 at the Rapid Response Radiotherapy Program (RRRP) at the Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada. All data was extracted from a prospectively gathered database that contained oncologic demographic data including dates of death, as well as BPI questionnaire responses. Data from patients dying within three months of the first day of radiotherapy was selected for analysis. All patients completed baseline BPI questionnaires in person on the day of initial assessment, and trained clinical research assistants attempted to have all patients complete follow-up BPI questionnaires over the telephone at 1 and 2 months following the end of radiotherapy. Data from 1 week prior to and 1 week following the 1 and 2 month follow-up time points respectively was permitted. Patients with data from both the baseline and the 1 and/or 2 month follow-up time points formed the ‘study population’ for all analyses, while those patients with baseline data only formed the ‘lost to follow-up population’. Other data analyzed included age, gender, Karnofsky Performance Status (KPS), the primary cancer site, the site of irradiated bone metastases, and the fractionation schedule employed (single or multiple). Analgesic consumption for the 24 hour period preceding the time of assessment was also recorded each time the BPI was administered, and opioid consumption was converted to a daily total oral morphine equivalent. Approval for this study was obtained from the research ethics board of the Sunnybrook Health Sciences Center.Response to radiotherapy was defined according to the endpoints of the International Bone Metastases Consensus . A complThe Statistical Analysis Software (SAS version 9.2 for Windows) was used for all analyses. Descriptive statistics summarized demographic data. The Fisher exact test compared categorical demographic variables between the study population and the lost to follow-up population, while the Wilcoxon rank-sum non-parametric test compared continuous variables between those groups. The Wilcoxon rank-sum non-parametric test also compared BPI functional interference scores between responders and non-responders. Two-sided P-values of < 0.05 were considered statistically significant for all analyses.The BPI database contained 400 patients in total, and 83 of them had died within 3 months of beginning radiotherapy. There were 54 males and 29 females. Their median age was 69 years and their median KPS was 70. The three most common primary cancers were lung (40%), gastrointestinal (16%) and breast (14%). Sixty-nine percent of these patients received single fraction therapy. Both baseline and follow-up data were available for 42% of the cohort (n = 35), and these patients constituted the study population. The remaining 48 patients constituted the lost to follow-up population. The baseline demographic and clinical characteristics of these cohorts are displayed in Comparisons between the study population and patients lost to follow-up with respect to baseline demographics, clinical information and BPI functional domain ratings are listed in Ninety-one percent of patients in the study population were available for the 1 month time point analysis (n = 32), while only 17% were available for the 2 month time point (n = 6). The 1 month overall response rate for available patients was 78%  while the 2 month overall response rate for available patients was 83% .The BPI functional interference scores at 1-month following radiotherapy for responders and non-responders respectively (mean ± SD) were: general activity (4.00 ± 4.07 for responders vs. 9.00 ± 1.91 for non-responders), mood (3.29 ± 3.87 vs. 5.50 ± 4.37), walking ability (3.71 ± 4.16 vs. 7.14 ± 3.08), normal work (3.95 ± 4.36 vs. 8.57 ± 3.78), relations with other people (2.57 ± 3.72 vs. 5.00 ± 4.38), sleeping (2.45 ± 3.28 vs. 6.67 ± 3.88), and enjoyment of life (4.62 ± 4.33 vs. 8.67 ± 2.16). P-values from comparisons between the responder and non-responder ratings at 1 and 2 months are listed in This is the first study that has investigated the effect of palliative radiotherapy for bone metastases on the functional abilities of patients within their last 3 months of life. Although it seems intuitive that the patients who responded to treatment also reported significantly less functional interference due to their pain at one month, this relationship had not been formally evaluated previously in a population of patients with such a limited lifespan. The distinction is important, as patients with painful bone metastases nearing the end of life commonly suffer from comorbidities and declining performance status that could mask any functional benefit that would otherwise be seen following pain relief from radiotherapy. Wu and colleagues noted a significant correlation between pain reduction and improvements in BPI functional interference scores among 109 patients who received palliative radiotherapy for bone metastases; however, the survival times of the cohort were not reported . Our groBetween 1996 and 1998, 1157 patients were enrolled into the Dutch Bone Metastases Study which demonstrated that a single 8 Gy fraction and six 4 Gy fractions are equally effective at providing pain relief from uncomplicated bone metastases . The outRecent discussions have emphasized the need to better integrate palliative radiotherapy into the treatments commonly offered to patients nearing the end of life , 16. TheSome limitations of the present study warrant comment. Having follow-up data missing from over half of the study population poses a risk of sampling bias; however, partly controlling for this was a comparison of baseline demographic and clinical characteristics between the study population and patients lost to follow-up that did not show many differences. Unfortunately, high attrition rates and missing data are common challenges encountered in palliative care research . The preIn summary, despite their short survival times, patients reported pain relief following radiotherapy, and responders reported superior functional abilities compared to non-responders. Patients with estimated survival times of three months who suffer from painful bone metastases should be considered for palliative radiotherapy, as they may derive not only pain relief from treatment, but also improved functional abilities prior to passing away.