Pain Flare Research Articles

Local control and toxicity outcomes of stereotactic radiosurgery for spinal metastases of gastrointestinal origin.

Colorectal cancer (CRC) and other gastrointestinal (GI) cancers are believed to have greater radioresistance than other histologies. The authors report local control and toxicity outcomes of stereotactic radiosurgery (SRS) to spinal metastases from GI primary cancers. A retrospective single-center review was conducted of patients with spinal metastases from GI primary cancers treated with SRS from 2004 to 2017. Patient demographics and lesion characteristics were summarized using medians, interquartile ranges (IQRs), and proportions. Local failure (LF) was estimated using the cumulative incidence function adjusted for the competing risk of death and compared using Gray's test for equality. Multivariable analyses were conducted using Cox proportional hazard models, adjusting for death as a competing risk, on a per-lesion basis. Patients were stratified in the Cox model to account for repeated measures for clustered outcomes. Median survival was calculated using the Kaplan-Meier method. A total of 74 patients with 114 spine lesions were included in our analysis. The median age of the cohort was 62 years (IQR 53-70 years). Histologies included CRC (46%), hepatocellular carcinoma (19%), neuroendocrine carcinoma (13%), pancreatic carcinoma (12%), and other (10%). The 1- and 2-year cumulative incidence rates of LF were 24% (95% confidence interval [CI] 16%-33%) and 32% (95% CI 23%-42%), respectively. Univariable analysis revealed that older age (p = 0.015), right-sided primary CRCs (p = 0.038), and single fraction equivalent dose (SFED; α/β = 10) < 20 Gy (p = 0.004) were associated with higher rates of LF. The 1-year cumulative incidence rates of LF for SFED < 20 Gy10 versus SFED ≥ 20 Gy10 were 35% and 7%, respectively. After controlling for gross tumor volume and prior radiation therapy to the lesion, SFED < 20 Gy10 remained independently associated with worse LF (hazard ratio 2.92, 95% CI 1.24-6.89, p = 0.014). Toxicities were minimal, with pain flare observed in 6 patients (8%) and 15 vertebral compression fractures (13%). Spinal metastases from GI primary cancers have high rates of LF with SRS at a lower dose. This study found that SRS dose is a significant predictor of failure and that prescribed SFED ≥ 20 Gy10 (biological equivalent dose ≥ 60 Gy10) is associated with superior local control.

Patient-reported outcomes (PRO) from a phase I/II dose-escalation study of fractionated dose 177Lu-PSMA-617 for progressive metastatic castration-resistant prostate cancer (mCRPC).

45 Background: We performed the 1st dose-escalation study of PSMA-targeted radionuclide therapy with 177Lu-PSMA-617. Using dose-fractionation, we intended to deliver a dose-intense regimen designed to minimize radioresistance due to repopulation. Radionuclide therapy may be able to treat symptoms due to tumor and therefore may be associated with improvement in PRO. Methods: Inclusion: progressive mCRPC following potent AR-pathway inhibitor (ARPI, e.g. abi/enza) and taxane (or unfit/refuse chemo) without limit of # prior therapies, adequate organ function, ECOG performance status 0-2, without preselection for PSMA expression. Treatment was a single cycle of fractionated dose 177Lu-PSMA-617 on D1 and D15 (7.4 to 22 GBq in phase 1; 22.2 GBq in phase 2). PRO tools included FACT-P and BPI-SF at baseline and follow up. Results: 44 men with median age 69 (range 55-91), median PSA 182.97 (range 0.89-5541) were treated. 93% with bone, 45% nodal, 18% lung, 9% liver, 9% other visceral metastases. 55% with at least 1 prior chemo regimen, 52% &gt;2 prior ARPI, 27% with Ra223, 30% sip-T, 5% 177Lu-J591. 59.1% with &gt;50% PSA decline (66.7% at 22.2 GBq, n=21), median overall survival 16 months (95% CI 11-NR). High grade (Gr) toxicity was rare with 6.8% Gr 3 anemia and 2.3% Gr 3 platelets. Gr 1/2 treatment-emergent AE’s include 81.8% with pain flare, 61.4% xerostomia, 29.5% fatigue, 25% platelets, 25% anemia, 25% pain, 15.5% nausea. FACT-P scores tended to improve in all categories by D22 (1 week later), with overall FACT-P scores improving by mean of 8.9 points (p=0.07) at D22 and remaining improved at 12 wks. All BPI scores also improved, with BPI overall severity score improving by mean of 3.0 at D22 (p=0.008) and remained better than baseline at 12 wks. There was no clear association with any AE and PRO changes, but those with PSA decline tended to have improved pain scores (p=0.1). Conclusions: A single cycle of up to 22.2 GBq of 177Lu-PSMA-617 is safe with fractionated (D1 &amp; D15) dosing, with encouraging early efficacy signals in a population unselected for PSMA expression and improved quality of life and pain scores by validated PRO instruments. Clinical trial information: NCT03042468.

Role of Oxycodone Hydrochloride in Treating Radiotherapy-Related Pain.

Radiotherapy is commonly used to treat cancer patients. Besides the curable effect, radiotherapy also could relieve the pain of cancer patients. However, cancer pain is gradually alleviated about two weeks after radiotherapy. In addition, cancer patients who receive radiotherapy may also suffer from pain flare or radiotherapy-induced side effects such as radiation esophagitis, enteritis, and mucositis. Pain control is reported to be inadequate during the whole course of radiotherapy (before, during, and after radiotherapy), and quality of life is seriously affected. Hence, radiotherapy is suggested to be combined with analgesic drugs in clinical guidelines. Previous studies have shown that radiotherapy combined with oxycodone hydrochloride can effectively alleviate cancer pain. In this review, we firstly presented the necessity of analgesia during the whole course of radiotherapy. We also sketched the role of oxycodone hydrochloride in radiotherapy of bone metastases and radiotherapy-induced oral mucositis. Finally, we concluded that oxycodone hydrochloride shows good efficacy and tolerance and could be used for pain management before, during, and after radiotherapy.

Effect of an electronic quality checklist on prescription patterns of prophylactic antiemetic and pain flare medications in the context of palliative radiotherapy for bone metastases.

International guidelines are available to guide prescription of antiemetic and pain flare medications in patients receiving palliative radiotherapy for bone metastases, but prescription rates are quite variable. We hypothesized that a simple electronic quality checklist could increase the evidence-based use of these medications. We implemented an electronic quality checklist item in our center for all patients treated with palliative radiotherapy for lumbar spine bone metastases. We retrospectively reviewed patients in the 6-month pre- and post-intervention. Patients were stratified according to if they were treated within a dedicated rapid palliative (RPAL) radiotherapy program or not. Chi-square tests were used to compare rates of antiemetic and pain flare medications pre- and post-intervention and RPAL vs not. A total of 375 patients were identified with 42 (11.2%) treated in dedicated RPAL program. The proportion of patients treated with prophylactic antiemetic and pain flare medications pre-intervention (n = 226) and post-intervention (n = 149) was respectively 34.1% vs 59.1% (p < 0.001) and 26.1% vs 43.0% (p = 0.01). Observed differences for antiemetic prescription rates were greater for patients who were not treated within a dedicated palliative radiotherapy program, but this was not the case for pain flare medications. Our data shows that a simple quality checklist item can have a significant effect on the evidence-based use of prophylactic antiemetic and pain flare medications in patients treated with palliative radiotherapy for bone metastases. We believe such strategies should be routinely included in other clinical pathways to improve the use of symptom control medications.

Trunk Muscle Activation Patterns Differ Between Those With Low and High Back Extensor Strength During a Controlled Dynamic Task.

It is proposed that reduced function in one of the spinal systems (active, passive, and neural) outlined by Panjabi could increase the risk of experiencing a low back injury (LBI). Also proposed is that reduced function in any one system can be compensated for by adjusting the time-varying recruitment of trunk muscles. This study addressed whether those with reduced active system function (WEAK), measured as back extensor strength, would have different trunk muscle activation patterns than those with higher function (STRONG), and secondly whether this relationship would be modified following recovery from a LBI. Sixty men participated, 30 recently recovered from LBI (rLBI, 4–12 weeks post injury) and 30 who had not had a LBI in the last year (ASYM). ASYM and rLBI participants were separated into STRONG and WEAK sub-groups if their isometric back extensor strength was above or below their group median, respectively. Trunk electromyograms from 24 muscle sites were recorded during a highly controlled horizontal transfer task. Principal component analysis captured key muscle activation patterns (amplitude and temporal); then analysis of variance models tested for strength or group*strength effects on these patterns consistent with the two main objectives. Significant strength, or group by strength effects were found for 3/4 electromyographic comparisons. In general, the WEAK group required higher activation amplitudes of abdominal and back extensor muscles, and greater temporal responsiveness of back extensor muscles only to the changing external moments than those who were STRONG. Group by strength interactions found that participants in the rLBI group had greater differences between WEAK and STRONG participants for overall muscle activation amplitudes in both abdominal and back extensor muscles. This increase in muscle activation was interpreted as compensation for lower maximum force properties whereas the increased temporal responsiveness captured a greater need to modify the agonist back extensors muscle activation patterns only in response to changes in the dynamic moments. Interactions captured that the recent experience of pain (rLBI) modified the magnitude of adjustment in muscle activation patterns potentially adapting to an increased risk of instability (painful flare) events associated with a deficit (lower strength) of the active system.

Strukturert pasientforløp ved urinsyregikt

Pharmacological treatment and follow-up of gout is often inadequate.The patients risk repeated, painful arthritis flares and some develop chronic tophaceous gout and joint damage. Since 1 March 2017, a structured care pathway has been established for patients with gout at the Department of Rheumatology, Haukeland University Hospital. Patients were placed on preventive medication, the majority on allopurinol, and were regularly monitored. Patient education is key to the care pathway. The treatment goal is to lower the concentration of serum urate to a level below a defined threshold value (360 µmol/l for non-tophaceous gout or 300 µmol/l for tophaceous gout). Patient data were collected on a continuous basis and recorded in a research database. The care pathway is assessed after 18months. A total of 103patients have been included, of whom 93 (90%) are men, with an average age of 63 years and large variations in duration of the disease (min.-max. 0-36 years). Eight patients left the care pathway during the project. The average level of serum urate at inclusion was 446 µmol/l (min.-max. 144-751 µmol/l). The average maximum dose of allopurinol was 333mg (min.-max. 100-700mg). Survival analysis showed that three months after the start of urate-lowering therapy, 49% of the patients had achieved their analytical treatment goal. Altogether 83% achieved the goal within six months. The majority (70%) were free of flares after achieving the treatment goal. A standardised care pathway for gout enables adaptation of preventive treatment through regular monitoring. The care pathway helps the vast majority of patients to achieve treatment goals, which is crucial to avoid arthritis flares.

Strategies to Mitigate Toxicities From Stereotactic Body Radiation Therapy for Spine Metastases.

Improvements in systemic therapy are translating into more patients living longer with metastatic disease. Bone is the most common site of metastasis, where spinal lesions can result in significant pain impacting quality of life and possible neurological dysfunction resulting in a decline in performance status. Stereotactic body radiation therapy (SBRT) of the spine has emerged as a promising technique to provide durable local control, palliation of symptoms, control of oligoprogressive sites of disease, and possibly augment the immune response. SBRT achieves this by delivering highly conformal radiation therapy to allow for dose escalation due to a steep dose gradient from the planning target volume to nearby critical organs at risk. In our review, we provide an in-depth review and expert commentary regarding seminal literature that defined clinically meaningful toxicity endpoints with actionable dosimetric limits and/or clinical management strategies to mitigate toxicity potentially attributable to SBRT of the spine. We placed a spotlight on radiation myelopathy (de novo, reirradiation after conventional external beam radiation therapy or salvage after an initial course of spinal SBRT), plexopathy, vertebral compression fracture, pain flare, esophageal toxicity, myositis, and safety regarding combination with concurrent targeted or immune therapies.

Spine radiosurgery in adolescents and young adults: early outcomes and toxicity in patients with metastatic Ewing sarcoma and osteosarcoma.

There are limited data on spine stereotactic radiosurgery (SRS) in treating adolescent and young adult (AYA) patients. SRS has the advantages of highly conformal radiation dose delivery in the upfront and retreatment settings, means for dose intensification, and administration over a limited number of sessions leading to a decreased treatment burden. In this study, the authors report the oncological and toxicity outcomes for AYA patients with metastatic sarcoma treated with spine radiosurgery and provide clinicians a guide for considerations in dose, volume, and fractionation. An institutional review board-approved database of patients treated with SRS in the period from October 2014 through December 2018 was queried. AYA patients, defined by ages 15-29 years, who had been treated with SRS for spine metastases from Ewing sarcoma or osteosarcoma were included in this analysis. Patients with follow-ups shorter than 6 months after SRS were excluded. Local control, overall survival, and toxicity were reported. Seven patients with a total of 11 treated lesions were included in this study. Median patient age was 20.3 years (range 15.1-26.1 years). Three patients had Ewing sarcoma (6 lesions) and 4 patients had osteosarcoma (5 lesions). The median dose delivered was 35 Gy in 5 fractions (range 16-40 Gy, 1-5 fractions). The median follow-up was 11.1 months (range 6.8-26.0 months). Three local failures were observed within the follow-up period. No acute grade 3 or greater toxicity was observed. One patient developed late grade 3 toxicity consisting of radiation enteritis. This patient had previously received radiation to an overlapping volume with conventional fractionation. SRS re-irradiation for this patient was also performed concurrently with chemotherapy administration. No late grade 4 or higher toxicities were observed. No pain flare or vertebral compression fracture was observed. Three patients died within the follow-up period. SRS for spine metastases from Ewing sarcoma and osteosarcoma can be considered as a treatment option in AYA patients and is associated with acceptable toxicity rates. Further studies must be conducted to determine long-term local control and toxicity for this treatment modality.

Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae

BackgroundRA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities.MethodsPeople from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n = 719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥ 0.6 points if inactive RA). A ≥ 4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups.ResultsDAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode.ConclusionFlares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.

Palindromic rheumatism as part of the rheumatoid arthritis continuum.

Palindromic rheumatism is a distinctive syndrome that has a long-recognized association with rheumatoid arthritis (RA). Palindromic rheumatism is characterized by intermittent flares of pain, erythema and swelling in and around the joints, which are typically severe and unpredictable. The observation that most patients with palindromic rheumatism haveRA-related autoantibodies and that many eventually develop RA has led to palindromic rheumatism often being viewed as a relapsing-remitting variant of RA. However, the clinical andimaging phenotypes of palindromic rheumatism suggest important distinctions from RA and imply underlying mechanistic differences between the two conditions. Furthermore, the pattern of inflammation seen in palindromic rheumatism has interesting parallels with that seen in other groups of symptomatic individuals at risk of developing RA. In this Review, we explore the concept of palindromic rheumatism as part of the RA continuum and propose an updated disease paradigm for this unique syndrome.

1293 Non-Steroidal Anti-Inflammatory Drug-Induced Acute Pancreatitis: A Case Report

INTRODUCTION: Ibuprofen-induced acute pancreatitis, a diagnosis secondary to the use of non-steroidal anti-inflammatory drugs (NSAID) is an extremely rare occurrence. Common culprits such as obstruction, alcohol consumption, infection, direct trauma, and medication (sans NSAID) adverse effect can be attributable to the majority of cases reported. The following case report describes a patient with acute pancreatitis secondary to a 3-week use of Ibuprofen for chronic shoulder pain. Alternative causes of acute pancreatitis were excluded through the patient's clinical history, laboratory findings, and diagnostic imaging. Although a rare risk factor, our aim is to further demonstrate that patients with chronic NSAID use can develop these complications and should be considered among the differential diagnoses. CASE DESCRIPTION/METHODS: Our patient was a 44 yo F with significant past medical history of hyperlipidemia, cholelithiasis status post cholecystectomy (2003), and acute pancreatitis (2010) secondary to choledocholithiasis who presented with a 2-week history of abdominal pain. The pain was described as an intermittent burning pain, rated 8/10 that radiated to the back. It was associated with nausea, vomiting and diarrhea but not associated with eating. She reported that she did not use any palliative measures for the pain, but indicated that she had been taking 800 mg Ibuprofen every 8 hours for the past 3 weeks for an acute flare of chronic right shoulder pain. She denied recent travel, sick contacts at home, or any change in eating habits. She also denied Ibuprofen use during the last episode of acute pancreatitis in 2010. She was a non-tobacco smoker, non-alcohol drinker, and did not use any illicit drugs. DISCUSSION: The incidence of drug-induced pancreatitis is low and generally includes HMG-CoA Reductase Inhibitors, ACE Inhibitors, Oral Contraceptives/Hormone Replacement Therapy, diuretics, HAART therapy, and Valproic acid as some of the more common offending agents. The mechanisms of these drugs are not well known but one case report of ibuprofen – induced pancreatitis suggests a possible mechanism related to a reduction in systemic glutathione, which therefore prevents an appropriate response against oxidative stresses. In this case of suspected diagnosis of Ibuprofen-induced acute pancreatitis, we did not perform a re-challenge test on the patient to confirm the suspected diagnosis; however, the patient demonstrated no other contributing factors that could be linked to the condition.

The effect of extension assist orthosis with pneumatic bladders on pain and function for patients with early knee osteoarthritis.

There are few non-invasive treatment options to slow the progression of osteoarthritis (OA). Recently, a novel knee unloader brace with knee extension assist has become commercially available. Therefore, the purpose of this study was to evaluate the preliminary effectiveness of using a novel unloader brace with extension assist to improve pain and functional outcomes for patients with knee OA. Thirty subjects (17 control group, 13 brace group) completed baseline and 6-week follow up testing with no brace. Patients were randomized into a Brace or No Brace group after baseline testing. Functional tests [timed up and go (TUG), stair climbing test (SCT) and six-minute walk (6MW)], self-reported measures [Knee Outcome Survey (KOS), pain, Patient Specific Functional Scale (PSFS)] and isometric knee extension strength were assessed. Repeated measure ANOVAs were used to identify differences in group and time. Pearson correlation coefficients were calculated for both average number of steps in the brace and exercises compliance compared to change in clinical scores for each group. There was a significant interaction effect for "worst pain" (P=0.002), the brace group improved from a 7.3/10 to 4.7/10 at follow-up (P=0.006) while the control group had no change. There was an effect of time for the SCT (P=0.02), "best knee pain" (P=0.050), and knee extension range of motion (ROM) (P=0.041). There were no significant correlations between exercise compliance and change in outcomes, but when the groups were collapsed there was a significant correlation between compliance and change in knee extension ROM (r=0.526; P=0.025). The extension assist pneumatic unloader brace group demonstrated a significant and important reduction in the "worst knee pain". This may indicate that wearing the brace was able to reduce painful flares. Both groups improved over time for the SCT, "best knee pain", and knee extension ROM, which can be attributed to the stretching protocol. This unloader brace is a promising non-invasive treatment option for patients with knee OA when combined with a stretching program.

P37 Exploring the experience of pain flares in adolescent inflammatory and non-inflammatory musculoskeletal disorders: a phenomenological study

Abstract Background Adolescents with inflammatory and non-inflammatory rheumatic musculoskeletal disorders (RMD) experience acute exacerbations in pain, referred to as pain flares in the adult literature. But little remains known about what pain flares are, why they occur, how they are managed and what lasting effects they have during adolescence. This study explored the lived experience of pain flares in adolescents with RMD. Methods Adolescents with juvenile idiopathic arthritis (JIA) or chronic idiopathic pain syndromes (CIPS) were recruited from a UK tertiary paediatric and adolescent rheumatology centre. Data were collected using semi-structured interviews and visual aids, and analysed using interpretative phenomenological analysis. Results Participants were eight females and two males aged between 13 and 17 years (M = 14.7, SD = 1.25). Four participants had JIA and six had CIPS. All participants experienced periods when pain deviates from their usual variation in pain, but none reported using the term pain flare to describe these experiences. These experiences were conceptualised as a journey of change from their 1) daily life with pain, 2) pre-flare period, 3) flare period, to their 4) post-flare period. 1) In daily life, adolescents report a level of pain that is usual for them which they manage and continue their daily routines around. 2) Pain, at times, increased beyond usual levels and adolescents reported noticing when a pain flare was coming on (e.g. due to physical exertion). They employed strategies for managing the pre-flare period, however, if they did not succeed in preventing a flare, or when flares occurred without a trigger or controllable cause, pain began to intrude on their lives. 3) All pain flares were described as an increase in the intensity of their usual pain, and were also associated with an increase in the location, duration and/or quality of pain; an increase in other unpleasant symptoms such as fatigue, psychological symptoms, headaches and/or sickness; and a reduction in physical, emotional, cognitive and/or social functioning. The frequency of flares was variable, ranging from weekly flare events to less than two a year. Flares were generally short lived, lasting a few hours to a few days. The majority of flares were managed with parental input, with adolescents seeking medical support when a flare was perceived to be associated with infection in JIA. 4) As flares were brought under control, the pain returned to usual levels but the psychological symptoms outstayed the pain. Participants took actions to regain the level of normality experienced in daily life. Conclusion Participants had varying interpretations of what constitutes a flare, but the key finding was that flares are not only an increase in pain intensity, but other features are also required to change. These findings help to differentiate flares from normal variation in pain. Conflicts of Interest The authors declare no conflicts of interest.

P36 Adolescents’ experiences of fluctuating pain in musculoskeletal disorders: a qualitative systematic review and thematic synthesis

Abstract Background Adolescents with chronic musculoskeletal pain experience pain that fluctuates within and across days. The aim of this review was to (i) synthesise the qualitative literature on adolescents’ experiences of fluctuating pain in musculoskeletal disorders, (ii) identify the concept of pain flare and how this may differ from daily fluctuation of pain, and (ii) identify knowledge gaps to inform the design of future research. Methods Six electronic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, OpenGrey and Scopus) and reference lists of relevant articles were searched from inception to June 2018. Articles were eligible for inclusion if they were qualitative studies exploring the experiences of pain in adolescents, aged between 10–19 years, diagnosed with juvenile idiopathic arthritis (JIA) and chronic idiopathic pain syndromes (CIPS). Comprehensiveness of reporting was assessed using the Consolidated Criteria for Reporting Qualitative Health Research (COREQ) framework, and studies were analysed using thematic synthesis. Results Of the 3,787 records identified, 32 studies were included from 11 countries. 536 young people with JIA or CIPS participated in the studies, of which 509 had a diagnosis of JIA, and 27 with CIPS. Interviews were conducted in 29 studies, with 9 studies also combining interviews with focus groups, observations, questionnaires, researcher journaling, visual depictions and diaries. Although all included studies reported adolescent’s experience of pain, only 19 studies provide insight into the impact of fluctuating pain on an individual’s life and lived experience. 21 studies included data from parents, siblings, health professionals and/or individuals with other chronic illnesses, but efforts were made to only extract data referring to or expressed by adolescents with JIA or CIPS. Ages of patients ranged from 3 to 23 years, but all studies averaged within the adolescent range. Principal findings were synthesised under three themes: 1) symptom experience, 2) disruption and loss, and 3) regaining control. These themes can be seen to describe a journey through which the adolescent experiences fluctuating pain and associated symptoms, encounters the challenges to lifestyle that fluctuating pain presents, followed by employing coping strategies to regain a sense of control of their lives and pain. Each stage is experienced differently depending on individual factors such as adolescents’ developmental status, pain condition, and duration of the pain experience. Conclusion Adolescents with chronic musculoskeletal pain live with a daily background level of symptoms which frequently fluctuate and are associated with functional and emotional difficulties. It is not clear whether these symptoms and challenges are experienced as part of normal fluctuations in pain, or whether they reflect symptom exacerbations classified as flares. Further research is needed to explore the frequency and characteristics of pain flares, and how they differ from their normal fluctuations in pain. Conflicts of Interest The authors declare no conflicts of interest.

Is cholecalciferol a potential disease-modifying anti-rheumatic drug for the management of rheumatoid arthritis?

Vitamin D is a pleiotropic molecule with a well-characterised immunomodulatory activity in vitro; however, its potential clinical application in autoimmune conditions has yet to be clarified. Several authors have investigated the use of vitamin D as a disease-modifying anti-rheumatic drug (DMARD) in rheumatoid arthritis (RA), obtaining divergent conclusions. This systematic review summarises and critically analyses the findings of papers assessing the impact of vitamin D supplementation on pain relief, disease activity, functional status and flare rate. We conclude that the correction of hypovitaminosis D may have a beneficial effect on pain perception; moreover, the achievement of an adequate plasma vitamin D concentration obtained with high-dose regimens might evoke immunomodulatory activities of vitamin D and favourably impact on disease control. Nevertheless, the current evidence is still not strong enough to support the use of cholecalciferol as a DMARD in RA, and further studies are required to clarify this issue.

Pain Flare-Effect Prophylaxis With Corticosteroids on Bone Radiotherapy Treatment: A Systematic Review.

Radiotherapy for metastatic bone pain can induce a transitory increase in pain known as pain flare. Several studies have described the use of prophylactic corticosteroids to prevent pain flare. However, the role and efficacy of corticosteroids to prevent pain flare remain unclear. To summarize the available evidence with regard to the efficacy and toxicity of prophylactic corticosteroids for the prevention of pain flare. This was a systematic review (PROSPERO protocol CRD42018090351) of peer-reviewed studies published in the Cochrane, Medline, and Scopus databases through September 2018. Studies carried out in adult patients treated with radiotherapy for bone metastases who received prophylactic corticosteroids to prevent pain flare were eligible for inclusion. The Cochrane Collaboration tool was used to assess risk of bias. The evidence grade was determined according to the GRADEpro tool. A total of 4,407 studies were identified. Of these, 4 clinical trials (CT) and 1 prospective cohort study met the inclusion criteria. The overall incidence of pain flare was 28%, and 21% vs. 37% in the prophylaxis vs. non-prophylaxis groups; the relative risk reduction was 43%. In the 3 studies that compared corticosteroids to placebo, the relative risk reductions were 25%, 67%, and 72%. The most common treatment regimen was oral dexamethasone at 8 mg once daily from the first day of radiotherapy for 5days. One study administered methylprednisolone. No severe toxicity was reported in any of the studies. Overall, the findings of this systematic review indicate that glucocorticoids appear to be an effective prophylactic treatment to prevent pain flare in patients undergoing radiotherapy for bone metastases. New CT are needed to confirm these results and to determine the optimal dose of dexamethasone.

Prevalence, Severity, and Correlates of Pain Flares in Response to a Repeated Sit-to-Stand Activity: A Cross-sectional Study of 14 902 Patients With Knee and Hip Osteoarthritis in Primary Care.

To determine prevalence, severity, and clinical correlates of pain flares in response to a repeated sit-to-stand activity. Cross-sectional. The analyses included 11 013 patients with knee osteoarthritis (OA) and 3889 patients with hip OA who completed a 30-second chair-stand test before starting the Good Life with osteoArthritis in Denmark treatment program. Prevalence and severity of pain flares were evaluated by change in self-reported joint pain intensity on an 11-point numeric rating scale after the test. Correlates with pain flares (an increase on the numeric rating scale of 2 points or greater) were assessed using regression analyses. One out of 3 patients with knee OA and 1 out of 5 patients with hip OA experienced pain flares (numeric rating scale of 2 or greater). Low knee/hip confidence, 3 or more painful body sites, fewer than 12 chair stands in 30 seconds, and body mass index of 30 kg/m2 or greater were associated with pain flares in response to the 30-second chair-stand test in patients with knee and hip OA. Low self-efficacy and joint stiffness were associated with pain flares in patients with knee OA. Using pain medication was associated with pain flares in patients with hip OA. Pain flares in response to a repeated sit-to-stand activity were common in patients with knee and hip OA. The clinical correlates associated with pain flares included joint confidence, functional performance, and body mass index, and are potentially modifiable with patient education, exercise therapy, and weight loss, respectively. J Orthop Sports Phys Ther 2020;50(6):309-318. Epub 6 Sep 2019. doi:10.2519/jospt.2019.9125.

A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET)

BackgroundBone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic.MethodsThis is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24–48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode.DiscussionIf a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures.Trial registrationThe Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials.gov (NCT03831243) on February 5th 2019.

Changes in whole body pain intensity and widespreadness during urologic chronic pelvic pain syndrome flares-Findings from one site of the MAPP study.

To investigate changes in whole body pain during urologic chronic pelvic pain syndrome (UCPPS) flares. UCPPS participants at one site of the multidisciplinary approach to the study of chronic pelvic pain research network reported their daily flare status and pain levels in 7 pelvic/genital and 42 extrapelvic body areas (scale = 0-10) for 10 days at baseline and during their first flare. Linear mixed models and conditional logistic regression were used to investigate symptom changes during flares. Analyses were stratified by chronic overlapping pain condition (COPC) status. Fifty-five out of 60 participants completed the study, 27 of whom provided information on both nonflare (n = 281) and flare (n = 208) days. Pelvic/genital pain intensity (mean change = 3.20 of 10) and widespreadness (mean = 1.48) increased significantly during flares for all participants (all P interaction > .1), whereas extrapelvic pain intensity increased significantly only among participants with COPCs (mean = 2.09; P interaction < .0001). Pelvic/genital and extrapelvic pain also varied on nonflare days but symptom fluctuations were generally ≤1 point (80.0%-100% of participants). Increases of ≥2 points in pelvic/genital pain intensity (odds ratio (OR) = 22.0, 95% confidence interval (CI) = 4.0-118.6) and ≥1 point in urination-related pain (OR = 9.10, 95% CI = 1.74-47.7) were independently associated with flare onset for all participants. Our observations of extrapelvic pain increases during flares for patients with COPCs and our independent associations between pelvic/genital/urination-related pain intensity and flare onset may provide insight into mechanisms underlying flare development (eg, common biologic pathways between UCPPS phenotypes and flares), flare management (eg, local vs systemic therapies by COPC status), and patient flare definitions.

Fractionated Spine Stereotactic Body Radiotherapy for Treatment of Primary and Metastatic Sarcoma

Sarcomas are biologically characterized by aggressive local spread and a relative insensitivity to radiotherapy. Our group previously reported that single fraction spine stereotactic radiosurgery (sSRS) for sarcomas was associated with suboptimal local control. This study analyzes whether fractionated sSRS is associated with improved radiographic control and reduced risk for pain flare as compared to single fraction sSRS. We conducted a retrospective review of patients with metastatic or primary spine sarcoma treated with sSRS at a single tertiary care institution over a decade. Patient, treatment and dosimetric variables and clinical outcomes were retrospectively reviewed using an IRB-approved prospective database. Rates of radiographic failure and pain flare were compared with the chi squared test. A total of 76 patients underwent sSRS for primary or metastatic sarcoma between 2006 and 2016 with a mean follow up was 16 months. Of these, 18 patients were treated with fractionated sSRS. Patients treated with fractionated sSRS tended to be younger (42.4±22.9 vs. 53.9±14.3; p=0.01), have a lower KPS (71.8±12.4 vs. 80.2±11.5; p=0.01), and were more likely to have oligometastatic disease (77.8% vs. 44.8%; p=0.05). All other patient characteristics were similar. Patients treated with single fraction sSRS received an average dose of 15Gy (range 10-18Gy). Patients treated with fractionated sSRS received a mean dose of 30 Gy (range, 24-40 Gy) in 3-5 fractions. In single fraction patients 24/58 (41.4%) experienced radiographic progression as compared to 4/18 (22.2%) in fractionated sSRS patients (p=0.14). Univariable competing risk regression with death as a competing risk showed that fractionated sSRS was associated with a decreased risk of radiographic progression (HR=0.52, 0.17-1.59; p=0.25), although this finding was not significant. Additionally, in single fraction patients, 10/58 (17.2%) experienced pain flare as compared to 1/18 (5.6%) in fractionated sSRS patients (p=0.22). Similarly, univariable competing risks analysis showed that fractionated sSRS was associated with a decreased risk of pain flare (HR=0.30, 0.04-2.15; p=0.23), although this was not statistically significant. Treatment of primary and metastatic sarcoma with sSRS has demonstrated a trend towards superior radiographic control and decreased pain flares. In our experience from a small sample, we have seen a two-fold decrease in radiographic failure and three-fold decrease in pain flare among patients treated with fractionated sSRS. Although patients treated with fractionated sSRS tended to be younger, they had a lower functional status and were more likely to have oligometastatic disease. Further research with larger sample sizes is warranted to establish the role of fractionated sSRS in this population.