Brief Pain Inventory Items Research Articles

Effects of Combining Music Therapy, Light Therapy, and Chromotherapy in the Treatment of Chronic Pain Patients: A Pilot Study.

It is currently considered that around 30% of chronic pain patients are totally refractory to medical treatment. Among patients who remain responsive to medical treatment, it is estimated that between 20% and 50% are likely to discontinue treatment due to severe side effects. Given these therapeutic difficulties, a significant number of patients turn to complementary therapies. The LineQuartz® is a medical device that combines 3 complementary therapies, namely, music therapy, light therapy, and chromotherapy. We propose to evaluate its effectiveness in chronic pain patients. Between October 2021 and October 2022, 44 patients aged between 23 and 85 years (mean: 55.4 years) were included in a prospective study. All patients had background pain intensity greater than 4/10 on the Numerical Pain Scale (NS). Treatment consisted of 4 half-hour sessions, divided into one session per week for 3 weeks (21 days). Patients were assessed by the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression scale (HAD) the day before starting treatment (Day 0) and the day after the end of treatment (Day 22). Apart from the BPI item, "relationship with others," all items improved significantly (p < 0.050). Background pain intensity (NS) and frequency of painful attacks improved very significantly (p < 0.001). The HAD anxiety subscore was also significantly improved (p < 0.001). Discussion. This open pilot study supports the idea that LineQuartz® has a place among complementary therapies dedicated to the treatment of chronic pain. However, these results need to be confirmed by a controlled study.

Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain.

TPS12146 Background: Management of neuropathic cancer pain (NCP) refractory to regular opioids remains an important challenge. The efficacy of pregabalin for NCP except chemotherapy-induced peripheral neuropathy has already been confirmed in two randomised controlled trials (RCTs) compared with placebo. Duloxetine offers the potential of analgesia in opioid refractory NCP. However, there are no RCT of duloxetine for the management of opioid-refractory NCP as a first line treatment. Both classes of drugs have the potential to reduce NCP, but there has been no head-to-head comparison for the efficacy and safety, especially given differing side effect profiles. Methods: An international, multicentre, double-blind, dose increment, parallel-arm, RCT. Eligibility criteria include: adult cancer patients experiencing NCP refractory to opioids; Brief Pain Inventory (BPI)-item 3 (worst pain) ≥4; Neuropathic Pain on the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale ≥12 despite of an adequate trial of regular opioid medication (≥60mg/day oral morphine equivalent dose). The study will recruit inpatients and outpatients in Japan and Australia. Participants will be randomised (1:1 allocation ratio) to duloxetine or pregabalin. Dose escalation is to day 14 and from day 14 to 21 is a dose de-escalation period to avoid withdrawal effects. Dose escalation schedule in each-arm is shown in Table 1. The primary endpoint is the mean difference in BPI item 3 over the previous 24 hours on day 14 between groups. Null hypothesis is there is no difference in BPI item 3 in the previous 24 hours on day 14 between both groups for patients with opioid refractory NCP. Comparison of the BPI item 3 on day 14 between duloxetine groups and pregabalin groups will be conducted using a two-sided Student’s t-test at a significance level of 5% according to the intention-to-treat principle. Point estimates and 95% CIs for the difference between two groups will be calculated. A sample size of 160 participants is required with 67 subjects enrolled to date. The DSMC last reviewed the trial in December 2022 and case accumulation expected to be completed by the end of 2024. Table 1：Dose escalation schedule in each-arm. Duloxetine Arm Stage 1 (Day 1-3): Duloxetine (30 mg) 1 capsule (morning) and Placebo 1 capsule (bedtime) Stage 2 (Day 4-7): Same as Stage 1 Stage 3 (Day 8-14): Duloxetine (30 mg) 1 capsule twice a day (morning and bedtime). Pregabalin Arm Stage 1 (Day 1-3): Pregabalin (25 mg) 1 capsule twice a day (morning and bedtime). Stage 2 (Day 4-7): Pregabalin (75 mg) 1 capsule twice a day (morning and bedtime). Stage 3 (Day 8-14): Pregabalin (75 mg) 2 capsules (150 mg) twice a day (morning and bedtime). Clinical trial information: ACTRN12620000656932 , jRCTs051190087.

Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee

IntroductionIn patients with chronic pain, oral analgesics are essential treatment options to manage pain appropriately, improve activities of daily living abilities and achieve a higher quality of life (QOL). It...

Responder Analysis of Pain Relief After Surgery for the Treatment of Spinal Metastatic Tumors.

Central tendency analysis studies demonstrate that surgery provides pain relief in spinal metastatic tumors. However, they preclude patient-specific probability of treatment outcome. To use responder analysis to study the variability of pain improvement. In this single-center, retrospective analysis, 174 patients were studied. Logistic regression modeling was used to associate preoperative characteristics with rating the Brief Pain Inventory (BPI) worst pain item 0 to 4. Linear regression modeling was used to associate preoperative characteristics with minimal clinically important improvement (MCI) in physical functioning defined by a 1-point decrease in the BPI Interference Construct score from preoperative baseline to 6 months postoperatively. Patient-level analysis revealed that 60% of patients experienced an improvement in pain. At least half experienced a decrease in pain resulting in MCI in physical functioning. Cutpoint analysis revealed that 48% were responders. Increasing scores on the preoperative pain intensity BPI items, the MD Anderson Symptom Inventory (MDASI) Core Symptom Severity Construct, the MDASI Spine Tumor-Specific Construct, the presence of preoperative neurologic deficits, and postoperative complications were associated with lower probability of treatment success while increasing severity in all BPI pain items, and MDASI constructs were associated with increased probability of MCI in physical function. Significant mortality and loss to follow-up intrinsic to this patient population limit the strength of these data. Although patients with milder preoperative symptoms are likely to achieve better pain relief after surgery, patients with worse preoperative symptom also benefit from surgery with adequate pain relief with an improvement in physical function.

Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain: a JORTC-PAL16 trial protocol

IntroductionManagement of neuropathic cancer pain (NCP) refractory to regular opioids remains an important challenge. The efficacy of pregabalin for NCP except chemotherapy-induced peripheral neuropathy (CIPN) has already been confirmed in...

Pain Related Functional Limitations of Persons Injured in Car Accidents

Background: In medical psychology, the Brief Pain Inventory (BPI) allows for a separate assessment of pain intensity (scales of worst, least, and average pain) and of daily functional limitations due to pain (impairments of mood, ability to walk, work, interpersonal relations, sleep, and enjoyment of life). The present study evaluates the convergent validity of BPI’s measure of such functional limitations by calculating its correlations to other relevant clinical measures of psychological impairments caused by motor vehicle accidents (MVAs). &#x0D; Method: De-identified archival data were available on 50 persons injured in MVAs (age 20 to 86 years, mean=42.1 years, SD=16.4; 23 males, 27 females). Their MVA occurred 11 to 280 weeks prior to psychological testing with the BPI (average time lapse 73.3 weeks, SD=53.8). All patients were still experiencing active post-MVA symptoms requiring medical attention and therapy. With respect to convergent validity, we examined Pearson correlations of the BPI to the Insomnia Severity Index (ISI), Rivermead Post-Concussion Symptoms Scale, Subjective Neuropsychological Symptoms Scale (SNPSS), and to measures of depression, anger, and anxiety (Items 10 to 12 of the Whiplash Disability Questionnaire).&#x0D; Results: Functional interference of pain with daily activities (sum of BPI Items 9B to 9G) correlated significantly at p&lt;0.05, 2-tailed with Rivermead post-concussion scores (r=0.39), post-MVA subjective neuropsychological symptoms (r=0.45), insomnia scores (r=0.41), and ratings of depression (r=0.52), anger (r=0.46), and anxiety (r=0.44). When the sum of BPI ratings of worst, least, and average pain was added to the functional interference/limitations score, then this sum of 9 BPI items correlated significantly at p&lt;0.05, 2-tailed with Rivermead post-concussion scores (r=0.36), post-MVA subjective neuropsychological symptoms (r=0.46), insomnia scores (r=0.37), and ratings of depression (r=0.53), anger (r=0.50), and anxiety (r=0.40). &#x0D; Discussion and Conclusion: The results lend support to convergent validity of the BPI when applied to persons injured in vehicular accidents.

The Italian Questionnaire for Cancer Breakthrough Pain Diagnosis, a Multicenter Validation Study.

IntroductionThe literature lacks formally validated and reliable tools for the diagnosis of breakthrough cancer pain (BTcP). The Italian Questionnaire for BTcP diagnosis (IQ-BTP) is an 11-item questionnaire aimed at detecting potential-BTP and classifying it into three likelihood classes: high, intermediate, and low.MethodsA multicenter, prospective, and observational study was designed to validate the IQ-BTP. In three consecutive visits with each cancer patient, the demographic and clinical details of the patient, the Brief Pain Inventory (BPI) scores, IQ-BTP outcomes, and clinicians' autonomous BTcP diagnosis (gold standard) and the agreement of this diagnosis with IQ-BTP outcomes were recorded. The assessed domains for IQ-BTP validation were: Validity, including content and face validity, construct validity (hypothesis testing, and cross‐cultural validity\\measurement invariance), and criterion validity; Reliability (internal consistency, reliability, and measurement error); Interpretability, and Responsiveness.ResultsSeven palliative and pain management facilities in Italy recruited 280 patients, yielding 753 evaluations. Using the IQ-BTP, the rate of potential-BTcP was 27.2%, of which its likely presence was high in 52.7% of patients, intermediate in 38.5, and low in 8.8%. The BPI item scores differed significantly between the two IQ-BTP classes (no-BTcP and potential-BTcP classes). The correlation of the latter class with BPI items was significant but low. The IQ-BTcP showed two principal components, accounting for 66.6% of the variance. Cronbach’s α was 0.71. The agreement rate between the gold standard and IQ-BTP outcomes was 82%. Cohen's kappa was 0.535. The IQ-BTP showed sensitivity and specificity of 69 and 86%, respectively.ConclusionsThe IQ-BTP extensive formal validation showed satisfactory psychometric and validity properties. Its content, face, construct, and criterion validities and its reliability, interpretability, and responsiveness were shown. Its use enabled potential-BTcP to be identified and differentiated into three likelihood classes with direct therapeutic and epidemiological implications. The latter may be confirmed in future studies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-021-00274-9.

Evidence for the BUAS-test ability to diagnose lumbar radicular pain.

Differential diagnosis of low back pain (LBP) is complex and a prominent issue at all health-care levels; guidance may come from patients' history cues and clinical examination signs. Human and animal studies report that diagnosis of lumbar radicular pain (LRP) may come from evaluating subjective responses of injured lumbar nerves to a strain applied at the buttock. The Buttock Applied Strain (BUAS-test) test may guide the differential diagnosis of LBP. Following an ex-adiuvantibus criterion, clinical improvement of LRP, diagnosed with the BUAS-test and congruently treated, may support this test diagnostic ability. Among 258 LRP patients, who, upon first visit (V1), tested positive on the BUAS-test (with/without positive Straight Leg Raising Test, SLRT), the effect of gabapentin prescription on painDETECT (PD) questionnaire and Brief Pain Inventory (BPI) outcomes was quantified in the follow-up visit (V2). To support BUAS-test diagnostic ability, we hypothesized that, at V2, >50% of the sample would present negative PD outcome, significant (t-test) and ⩾2 points V2-V1 differences for each of the BPI-item's score. We used multinomial logistic regression (MLR) and χ2 analyses to evaluate the PD-V2 outcomes' dependence upon independent variables. Of the sample, 77% reported a negative PD-V2 outcome. V2-V1 differences of all BPI items were significant and >2 points. PD-V2 outcomes showed significant associations with SLRT-V1 and PD-V1, respectively, but not with gender, age group or pain site. MLR showed a significant relationship between SLRT-V1 and PD-V2 outcomes. Among LRP patients, diagnosed by the BUAS-test and treated with gabapentin, all prespecified endpoints were reached. These results may be considered a piece of ex-adiuvantibus evidence for the BUAS-test ability to diagnose LRP. While positive BUAS-test implies potential LRP, the co-presence with positive SLRT may imply a severer LRP condition. Further prospective research, in different settings and direct clinical measures, is needed.

Effects of an Indomethacin Oral Spray on Pain Due to Oral Mucositis in Cancer Patients Treated With Radiotherapy and Chemotherapy: A Double-Blind, Randomized, Placebo-Controlled Trial (JORTC-PAL04)

ContextOral mucositis (OM) pain due to anticancer chemo- and radiotherapy has a very negative impact on patient quality of life. However, no high-quality studies have been performed regarding the analgesic efficacy of indomethacin (IM) oral spray for OM pain. ObjectivesThis randomized, placebo-controlled, double-blind trial aimed to evaluate the analgesic efficacy of IM oral spray for OM pain due to anticancer chemo- and radiotherapy. MethodsFrom July 2015 to December 2016, we enrolled adult cancer patients with OM pain that was due to anticancer chemo- or radiotherapy and was rated 4 or higher on Brief Pain Inventory (BPI) Item 5. Patients were randomly assigned in a 1:1 ratio to receive either IM oral spray or placebo.The primary endpoint was the change in the BPI Item 6 (“current pain”) score from before to 30 minutes after treatment. Secondary endpoints were the areas under the curves of BPI Item 6 at 15, 60, 120, 180, and 240 minutes after treatment; five items related to meals and conversation from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, Head and Neck Module 35; the Clinical Global Impressions-Improvement (CGI-I) scale; and adverse events. ResultsA total of 60 patients were assigned to receive IM oral spray (n = 33) or placebo spray (n = 27). The average change in the BPI item 6 score from before to 30 minutes after treatment was −1.85 (95% confidence interval: −2.37 to −1.32) in the IM spray group and −0.59 (−1.02 to −0.16) in the placebo group, indicating a significant difference (−1.26, −1.94 to −0.57, P < 0.01). The pain improvement persisted for 180 minutes. The intergroup differences in ability to drink liquids, ease in conversing, and CGI-I were all significant (P = 0.03, P = 0.02, and P < 0.01, respectively). No serious adverse events were reported. ConclusionIM oral spray alleviated short-term OM pain due to anticancer chemo- and radiotherapy, and may reduce the difficulty in eating meals.

Maintenance of effect of duloxetine in Chinese patients with pain due to osteoarthritis: 13-week open-label extension data

BackgroundThe objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data.MethodsThis was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed.ResultsOf 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was − 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was − 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p < 0.01). No deaths or suicide-related events occurred. Seven (4.0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event.ConclusionThe analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase.Trial registrationClinicalTrials.gov identification number NCT01931475. Registered 29 August 2013.

The contribution of pain in determining the health status of cancer patients with bone metastases: A secondary analysis of data from three Phase III registration trials

We aimed to provide a simple, descriptive health-status profile for cancer patients with bone metastases, based on the EuroQol EQ-5D, a tool commonly used to measure health utility scores, and to evaluate its association with the Brief Pain Inventory (BPI), a legacy pain-assessment tool. Although pain is one of five health-status dimensions measured by the EQ-5D, our understanding of how pain relates to the other EQ-5D dimensions is limited. We derived data from 5500 patients with bone metastases who completed the EQ-5D and BPI. Regression analyses examined how BPI severity and interference scores correlated with EQ-5D utility scores and how BPI items associated with EQ-5D items, for the entire sample and by disease-type subgroup. Regardless of cancer site, the percentage of patients reporting moderate/severe problems in each of the five EQ-5D dimensions were pain/discomfort, 78%; usual activities, 58%; mobility, 55%; anxiety/depression, 57%; and self-care, 26%. BPI pain interference explained more of the variability in the EQ-5D utility scores than did pain severity (R2 =41% vs. 34%). BPI worst pain, average pain, pain now, interference with general activity, and interference with work significantly predicted EQ-5D pain/discomfort, with odds ratio estimates <1. Pain/discomfort was the worst-rated dimension of the EQ-5D in this population, but the relationship of this item to BPI pain severity was modest, suggesting that the single pain item of the EQ-5D may be of limited utility in studies for which pain is an endpoint. Health-status dimensions include more than pain. We examine the contribution of pain severity and pain-related functional interference in determining the health status of cancer patients with bone metastases. The pain dimension from a health-status measure may be an inadequate metric in clinical trials/clinical practice when pain is an important outcome.

Development, validation and psychometric properties of a diagnostic/prognostic tool for breakthrough pain in mixed chronic-pain patients

Background/ObjectiveBreakthrough pain (BTP) shows variable prevalence in different clinical contexts of cancer and non-cancer patients. BTP diagnostic tools with demonstrated reliability, validation and prognostic capability are lacking. We report the development, psychometric and validation properties of a diagnostic/prognostic tool, the IQ-BTP, for BTP recognition, its likelihood and clinical features among chronic-pain (CP) patients. Methods. Patientsn=120 consecutive mixed cancer/non-cancer CP in/outpatients. Development, psychometric analyses and formal validation included: Face/Content validity (by ‘experts’ opinion and assessing the relationship between the IQ-BTP classes and criteria derived from BTP operational-case-definition); Construct validity, by Principle Component Analysis (PCA); and the strength of Spearman correlation between IQ-BTP classes and the Brief Pain Inventory (BPI) items; Reliability, by Cronbach's alpha statistics. Associations with clinical/demographic moderators were assessed applying χ2 analysis. ResultsPotential-BTP was found in 36.7% of patients (38.4% of non-cancer and 32.4% of cancer patients). Among these the likelihood for BTP diagnosis was ‘high’ in 25%, ‘intermediate’ in 41% and, ‘low’ 34% of patients. Analyses showed significant differences between IQ-BTP classes and between the latter BPI pain-item scores. Correlation between IQ-BTP classes and BPI items was moderate. PCA and scree test identified 3 components accounting for 62.3% of the variance. Cronbach's alpha was 0.71. ConclusionsThe IQ-BTP showed satisfactory psychometric and validation properties. With adequate feasibility it enabled the allocating of cancer/non-cancer CP patients in three prognostic classes. Results are sufficient to warrant a subsequent impact study of the IQ-BTP as prognostic model and screening tool for BTP in both CP populations.

The Significant Contribution of Pain in Determining the Health Status of Patients with Multiple Myeloma (MM)

BACKGROUND: Most cancer patients with bone metastases report significant pain and substantial impairment in their ability to function. In particular, patients with MM are susceptible to bone pain because of bone damage. Patient-reported outcomes such as a general health outcome measure and a legacy pain instrument may provide valuable information in determining the impact of this condition. The goal of this study was to provide a descriptive profile of health status for cancer patients using the EQ-5D-3L (EQ-5D), a commonly used tool to measure health utility scores. Another goal is to evaluate the predictive information provided by the Brief Pain Inventory (BPI), a self-report pain assessment tool designed to capture pain severity and interference in patients. These information may be useful in estimating the health status of patients where the EQ-5D was not administered.METHODS: Data was pooled across three denosumab registrational trials '20050136', '20050103', and '20050244'. Patients completed the EQ-5D and the BPI at baseline. Eligible patients had histologically confirmed advanced cancers, radiographic evidence of at least one bone metastasis (or lytic bone lesion from multiple myeloma), ECOG of 2 or better and adequate organ function. Using data from patients with MM (N=168), descriptive statistics were used to present summary information on health-related quality of life states and utility scores. Linear regressions were used to examine how BPI severity and interference subscale scores relate with EQ-5D utility scores. Ordinal regressions were used to evaluate how well BPI items predict EQ-5D individual items. Bonferroni adjustments were made when evaluating the relationships of BPI items to individual EQ-5D items. These analyses were repeated using data across several groups of cancer patients to determine if similar results can be obtained (breast cancer, N=2,044, prostate cancer, N=1,819 and others, N=1,509).RESULTS: About 9% of MM patients reported perfect health compared with 11% of all cancer patients. Of the 5 dimensions measured by the EQ-5D, the MM cohort rated pain (80%) the highest with moderate to extreme problems. This was followed by usual activities (68%), mobility (63%), anxiety/depression (49%), and self-care (36%). Similar order was observed across all cancer groups, but with slightly lower percentages for most items: pain (78%), usual activities (58%), mobility (55%), anxiety/depression (57%), and self-care (26%). Although pain interference subscale score explained more of the variability in the EQ-5D utility scores compared with pain severity items in the MM cohort (39% vs 31%) and for all patients (41% vs 34%), model fit was less than ideal (mean squared error=0.23 - 0.25). Hence, BPI items were fitted into individual EQ-5D items. Ordinal regression models fitting BPI items into individual EQ-5D items for the MM cohort showed good predictive power as measured by the concordance index c for mobility (86%), self-care (80%), usual activities (83%), pain (90%) and anxiety/depression (78%). For all patients, similar model fit were obtained for mobility (83%), self-care (78%), usual activities (81%), pain (90%) and anxiety/depression (72%). Further examination of the ordinal regression models across all groups showed that three BPI pain severity items, 'pain at its worst', 'average pain' and 'pain now' in addition to interference with activity and interference with work significantly predicted the EQ-5D pain item. Five interference items, activity, walking ability, work, sleep and enjoyment of life significantly predicted the EQ-5D usual activities item. Finally, 'pain now' and four interference items, relationship with others, enjoyment of life, mood, and activity significantly predicted the EQ-5D anxiety/depression item.CONCLUSIONS: Patients with MM reported several functional limitations on the EQ-5D. Majority of the patients reported moderate to extreme problems in all EQ-5D dimensions except self-care. Model fit of ordinal regression models relating BPI items with EQ-5D items are reasonable underscoring the benefit of using the BPI for planning patient care and health status evaluation. This consistency was also found across cancer groups that primarily include breast and prostate. The resultant model demonstrates the significant contribution of pain severity and interference in determining health status in this patient population. DisclosuresMendoza:Amgen Inc.: Consultancy. Shi:Amgen Inc.: Consultancy. Ma:Amgen Inc.: Employment. Zhang:Amgen Inc.: Employment. Qian:Amgen Inc.: Employment. Cleeland:Amgen Inc.: Consultancy.

Incidence of pain flare following palliative radiotherapy for symptomatic bone metastases: multicenter prospective observational study.

BackgroundPalliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. Pain flare, a transient worsening of the bone pain after RT, has been described in previous reports with different incidence rates. The aim of the study was to prospectively evaluate the incidence of pain flare following RT for painful bone metastases and evaluate its effects on pain control and functionality of the patients.MethodsBetween June 2010 and June 2014, 204 patients were enrolled in this study and 135 patients with complete data were evaluable. Pain flare was defined as a 2- point increase in worst pain score as compared with baseline with no decrease in analgesic intake or a 25 % increase in analgesic intake as compared with baseline with no decrease in worst pain score. All pain medications and worst pain scores were collected before, daily during, and for 10 days after RT. The Brief Pain Inventory (BPI) was filled out on the pretreatment and at the 4 weeks follow-up visit.ResultsThere were 90 men (66.7 %) and 45 women (33.3 %). Mean age was 66 years (SD 9.8). The most common primary cancer site was lung in 42 patients (31.1 %), followed by prostate in 27 patients (20.0 %). Forty-two patients (31.1 %) patients received a single fraction of 8 Gy and 83 (61.5 %) received 20 Gy in five fractions.The overall pain flare incidence across all centers was 51/135 (37.7 %). The majority of pain flares occurred on days 1–5 (88.2 %). The mean duration of the pain flare was 3 days (SD: 3). There were no significant relationships between the occurrence of pain flare and collected variables.All BPI items measured four weeks after end of RT showed significant improvement as compared with pretreatment scores (p < 0.001). No significant differences in BPI time trends were found between patients with and without flare pain.ConclusionPain flare is a common event, occurring in nearly 40 % of the patients that receive palliative RT for symptomatic bone metastases. This phenomenon is not a predictor for pain response.

Final analysis of COMET-2: Cabozantinib (Cabo) versus mitoxantrone/prednisone (MP) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) with moderate to severe pain who were previously treated with docetaxel (D) and abiraterone (A) and/or enzalutamide (E).

141 Background: Cabo inhibits tyrosine kinases including MET and VEGFRs. In a phase 2 study in mCRPC pts, Cabo was associated with improvements in pain, bone scans, measurable disease, and circulating tumor cells. COMET-2 compared the effects of Cabo versus MP on pain palliation in men with progressive mCRPC. Methods: In this double-blind, controlled phase 3 study (NCT01522443), pts with moderate to severe pain and disease progression following D, and A and/or E were randomized 1:1 to receive Cabo (60 mg qd) or MP (12 mg/m2 q3wk and 5 mg bid, resp). All pts were required to have a 7-day average of 4+ pain per Brief Pain Inventory (BPI) item 3 while on an optimized narcotics regimen at baseline. Randomization was stratified by prior cabazitaxel and ECOG performance status. The primary endpoint was pain response (≥30% reduction in BPI item 3) at week 6, confirmed at week 12, without increase in narcotics. The original sample size (N = 246) was selected to achieve at least 90% power to detect an increase in pain response with Cabo (25%) vs. MP (8%) using a two-sided α = 0.05 chi-squared test. The secondary efficacy endpoints were bone scan response (BSR) and overall survival (OS). Results: 119 pts were randomized between March 2012 and July 2014. Randomization was concluded prior to reaching the planned sample size because the companion study COMET-1 did not show a significant OS benefit compared to P in a similar population. Pain response rates were 15% for Cabo vs 17% for MP (P = 0.773). BSR rates were 31% for Cabo vs 5.2% for MP. Median OS was 9 months for Cabo vs 7.9 months for MP. Most frequent G3/4 AEs in the Cabo arm were anemia (22% vs 26% MP), hypertension (22% vs 0% MP), fatigue (18% vs 8.8% MP), and AST increased (10% vs 1.8% MP), with fewer pts discontinuing study treatment for AEs in the Cabo arm (16% vs 26% MP). Conclusions: The primary endpoint of improving pain response was not achieved in this heavily pretreated population. The key secondary endpoints of BSR and OS showed trends favoring the Cabo arm, and no new safety signals were observed at the dose of 60 mg. Clinical trial information: NCT01522443.

Psychometric properties and validation of the Italian version of the Mainz pain staging system as a tool for pain-patients referral selection

Indications are lacking on which patient to refer to pain facilities. Pain-chronicity stage and outcome prognosis may be used for such aims. The Mainz pain-staging system (MPSS) classifies pain patients in three chronicity stages that respectively require more extensive management. We explored the psychometric and validation properties of its Italian version towards its application as screening/referral tool. I-MPSS was administered to n=120 mixed non-cancer-pain outpatients. Psychometric analyses and formal validation included: content validity, by assessing the hypothesis of an existing relationship between the I-MPSS classes and criteria derived from an operational case definition of chronic pain; construct validity, by principle component analysis (PCA); the autonomous construct of the I-MPSS was assessed by the strength of the Spearman correlation between its classes and the brief pain inventory (BPI) items; and reliability, by applying Cronbach's alpha statistics. Associations between psychosocial moderators and the I-MPSS were assessed applying χ(2) analyses. Quantitative and qualitative analyses showed significant differences between I-MPSS classes for health care and drug utilization; BPI item scores significantly differed between the classes; Spearman correlation between I-MPSS classes and BPI items was mostly moderate or mild. PCA and scree test identified four components accounting for 63.7% of the variance. Cronbach's alpha was 0.842. The I-MPSS showed satisfactory psychometric and validation properties. With adequate feasibility, it enabled the screening of mixed non-cancer-pain outpatients in three chronicity/prognostic stages. Results are sufficient to warrant its use for a subsequent impact study as a prognostic model and screening tool for referring pain patients.

Acute and Long-term Treatment of Late-Life Major Depressive Disorder: Duloxetine Versus Placebo

To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder. Multicenter, 24-week (12-week short-term and 12-week continuation), randomized, placebo-controlled, double-blind trial. United States, France, Mexico, Puerto Rico. Age 65 years or more with major depressive disorder diagnosis (one or more previous episode); Mini-Mental State Examination score≥20; Montgomery-Asberg Depression Rating Scale total score≥20. Duloxetine 60 or 120 mg/day or placebo; placebo rescue possible. Primary-Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary-Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression-Severity scale, Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment. Compared with placebo, duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and 20. Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged, with significance also seen at week 24. There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase, most BPI items and half of the NRS measures in the continuation phase. More duloxetine-treated patients completed the study (63% versus 55%). A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event (15.3% versus 5.8%). Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome, several secondary measures at multiple time points suggested efficacy. Duloxetine had significant and meaningful beneficial effects on pain.

Impact of PCA strategies on pain intensity and functional assessment measures in adults with sickle cell disease during hospitalized vaso‐occlusive episodes

Clinical trials of sickle cell disease (SCD) pain treatment usually observe only small decrements in pain intensity during the course of hospitalization. Sub-optimal analgesic management and inadequate pain assessment methods are possible explanations for these findings. In a search for better methods for assessing inpatient SCD pain in adults, we examined several pain intensity and interference measures in both arms of a randomized controlled trial comparing two different opioid PCA therapies. Based upon longitudinal analysis of pain episodes, we found that scores from daily average Visual Analogue Scales (VAS) and several other measures, especially the Brief Pain Inventory (BPI), were sensitive to change in daily improvements in pain intensity associated with resolution of vaso-occlusive pain. In this preliminary trial, the low demand, high basal infusion (LDHI) strategy demonstrated faster, larger improvements in various measures of pain than the high demand, low basal infusion (HDLI) strategy for opioid PCA dosing, however, verification in larger studies is required. The measures and statistical approaches used in this analysis may facilitate design, reduce sample size, and improve analyses of treatment response in future SCD clinical trials of vaso-occlusive episodes.

Efficacy of the Sustained-Release Hydromorphone in Neuropathic Pain Management: Pooled Analysis of Three Open-Label Studies

ABSTRACTThis pooled analysis was designed to determine whether the analgesic response to treatment with OROS® hydromorphone, as measured by the “pain on average” scale of the Brief Pain Inventory (BPI), was different in patients with neuropathic pain compared to those with nociceptive pain, after adjusting for differences in baseline characteristics. Three open-label studies on patients with neuropathic and nociceptive malignant and nonmalignant chronic pain were analyzed. A mixed model for repeated measures linear regression analysis was used to compare the effect of OROS® hydromorphone on patients with neuropathic and nociceptive pain, adjusting for potentially confounding factors. Data from patients with pure neuropathic pain and mixed pain were also compared. Safety and tolerability was assessed by recording the number of adverse events. The primary outcome was “pain on average” (BPI item 5) over time. Secondary outcomes were the effect of OROS® hydromorphone on other BPI items including “pain relief” and “interference with sleep.” Patients with neuropathic pain showed a similar response to treatment with OROS® hydromorphone to those patients with nociceptive pain. There was no statistically significant difference between the pain groups (difference between groups −0.552 at visit 7; P = .060 for overall difference between groups). For some outcome variables, treatment was more effective for patients with neuropathic pain. The treatment was generally well tolerated. This pooled analysis shows that treatment with OROS® hydromorphone had similar efficacy for neuropathic and nociceptive pain.

Development and introduction of a pain score documentation chart in the acute oncology setting

AbstractBackground: Recommendations to improve cancer pain management include the introduction of routine and clearly visible documentation of pain scores. Whilst this practise has been adopted in many cancer and palliative care units, longitudinal evidence to support the view that the practise has provided improved analgesic outcomes for patients is limited. The aims of this study were threefold; (i) to collaboratively develop a locally acceptable pain documentation chart; (ii) to test this chart by comparing patient‐reported and nurse‐documented scores with pain scores collected by researchers using validated measures; and (iii) to examine whether or not pain scores and analgesia scores longitudinally improved over the study period.Methods: Using a multidisciplinary approach, a pain score documentation chart was developed for use on an acute hospital's oncology ward. Prior to the chart's introduction, the brief pain inventory (BPI) was administered to 45 in‐patients. The patients were then asked to report on a regular basis their numeric pain scores, which were documented on the chart. At the time of discharge or after 7 days, the BPI was repeated. The pain chart scores and the BPI item, ‘average pain experienced in the preceding 24 h’ were correlated.Results: The initial chart scores significantly correlated with the first BPI score (P = 0.001), and a similar relationship was found between scores collected at the end of the study period (P = 0.020). Analgesic scores improved, patients were satisfied with the approach taken to their analgesic management and the pain scores were charted with a similar frequency to vital signs (pulse, temperature, blood pressure).Conclusions: Pain score charting is feasible and acceptable to patients and nursing staff in an acute hospital. Most importantly, this process has the potential to improve the analgesic outcomes of cancer patients.