Pediatric palliative care is a field which focuses on caring for and treating the symptoms and distress typically associated with life-limiting illness. Integrative medicine is supported by evidence and aims to heal the whole person, including all aspects of one’s lifestyle. Therapies offered by integrative medicine often empower patients and families, allowing for a sense of control. This review addresses the merging of integrative medicine philosophy and modalities with the care given to children with life-limiting illness. We review an introduction to integrative medicine, trends in its incorporation in the healthcare setting, application to patients receiving palliative care and the management of specific symptoms. A case study is offered to illustrate these principles. Integrative medicine is not a new concept, though in recent decades the terminology has become solidified and more widely used. Dating back to early human history, there are writings describing how humans are composed of body, mind and spirit, with healers addressing these realms together when illness occurred . The curIntegrative medicine is distinct from complementary and alternative medicine (CAM), which refers to a practice or treatment that differs from the conventional approach, or therapies which complement the conventional model. Integrative medicine, as its name suggests, intentionally integrates too-often separate approaches to healing, with an additional emphasis on empowering the patient with skills for self-care, promotion of wellbeing and self-management  of disease. Modern western medicine is based on a reductionist approach to the body and disease, dating back to the 1600s, out of which grew the current system of medical specialization and compartmentalization of organs and body systems . IntegraThere is clear and rising interest among patients as well as providers in a whole-person care model. Fellowships in integrative medicine are providing evidence-informed knowledge and tools for practice ; additioIn the most recent survey from the National Institutes of Health’s Center for Complementary and Integrative Health on the use of complementary health approaches, several trends are evident. This 2012 survey collected information on the use of various approaches, including dietary supplements, chiropractic or osteopathic manipulation, yoga, massage, and mind-body practices such as meditation. Findings from this survey demonstrated about 33% of adults and 11.4% of children use some form of complementary health approaches. The survey also found that roughly 59 million Americans spend money out-of-pocket on complementary health approaches, with total spending around $30.2 billion/year. Pain was one of the main reasons people sought out complementary therapies, and the most utilized mind-body approaches were chiropractic manipulation, meditation, massage and yoga. Interestingly, yoga has become more popular among children as well in the last 15 years: 3.1% of US children practiced yoga in 2012, compared to 2.3% in 2007. These are samples of a large set of data illustrating the increase in interest, use and willingness to pay for integrative (here described as complementary) therapies .The growing demand and value recognition of such therapies and practices has led many healthcare systems to incorporate integrative medicine’s modalities, practitioners and practices in service to their patients and families. A 2010 survey by Samueli Institute and the American Hospital Association’s Health Forum was conducted to study these trends, entitled Complementary and Alternative Medicine Survey of Hospitals . Out of Despite growing interest and demand for an integrative approach in healthcare, acceptance and adoption of these modalities into mainstream healthcare systems remains limited, and thus inaccessible for many patients and families. Contributing factors to this lack of access include inadequate numbers of trained practitioners, lack of insurance reimbursement for interventions, billing or productivity structures which do not support the time needed to do significant patient counseling and education, and other financial or ideological limitations of healthcare institutions and individual providers alike ,14. MediOne common example of a complex, multi-faceted problem seen from primary care to palliative care is anxiety. Children and teens are experiencing anxiety at unprecedented rates, and according to Kessler et al. in a National Comorbidity Survey of adolescents, the lifetime prevalence of any anxiety disorder was 31.9% between the ages of 13–18 years ,20.Our understanding of anxiety grows by the week, with more studies detailing the connection between gut health and its role in anxiety , depressNumerous studies, as well as centuries of tradition in eastern medicine, support the efficacy of mind-body techniques for management of anxiety, chronic pain, illness and stress. Examples include various types of meditation ; hypnosiThis example illustrates how complex and multifaceted many of today’s medical issues are, and ways in which integrative medicine can address that complexity using a myriad of tools and modalities suited for a variety of settings and preferences. Many such techniques can be employed in the outpatient, inpatient or community health care setting, with little to no cost and are adaptable to a variety of cultures, backgrounds, ages, disease-states and patient preferences. Specific domains in which integrative medicine providers offer care, interventions and education for patients may include nutrition, mind-body techniques, regulation of stress physiology, sleep support, therapeutic movement, Reiki and other energy work techniques, use of herbs and supplements, aromatherapy, mental health support and identification/modification of environmental factors contributing to disease. Knowledge of other healing systems, such as traditional Chinese medicine, Ayurveda, naturopathy, chiropractic and homeopathy, allows integrative medicine providers from an allopathic background to appreciate the role these fields play in healing, and appropriately counsel patients seeking care. We will briefly describe the following common, well-tolerated integrative modalities that can be used to support patients receiving hospice and palliative care: acupuncture/acupressure, relaxation and stress-physiology regulation techniques, essential oils, botanicals and supplements and reiki.Acupuncture is an ancient tradition in which the practitioner inserts thin needles in the body to manipulate specific points. It is a key component of traditional Chinese medicine and is also used for the management of distressing symptoms such as pain and nausea. Acupuncture points can also be stimulated noninvasively with the use of low level lasers or microcurrent. Acupuncture is safe when performed by qualified professionals and is well tolerated by children ,36. AcupThe ancient practices of meditation, yoga, tai chi and qi gong are making their way into western culture, as well as being utilized to address a range of present day health problems. In each of these practices, the activation of the parasympathetic nervous system, through intentional, regulated breathing, has been shown to improve autonomic nervous system balance, heart-rate variability, chronic pain, fibromyalgia, anxiety, depression, post-traumatic stress disorder and promote overall well-being ,38,39,40Aromatherapy is the use of aerosolized or inhaled essential oils, the potent extracts of roots, plants or herbs, for therapeutic purposes. Topical application of essential oils diluted in a carrier oil, with or without massage, is also a route by which therapeutic effects may be obtained. The parts of the plant used, the species, and the quality of the extract all bear on the quality of the essential oil and thus its therapeutic effect .Essential oils have been used for centuries in many cultures and have also made their way into western healing practices and alongside allopathic medicine in many places. Examples of these uses will follow, related to specific symptoms commonly encountered in patients who are receiving palliative care services.For some patients, due to the burden of polypharmacy, additional supplements are not desired. In others, taking supplements may improve symptoms and allow them to feel a greater sense of self-management over their treatment. Supplements can be taken orally, sublingually or absorbed through the skin. It is critical that any health care provider ask patients about their use of supplements and botanicals, with consideration to any possible side effects as well as drug interactions. An extensive treatment of this topic is beyond the scope of this paper; several specific supplements are covered below in the section on symptom management. Reiki is an ancient healing art which involves the gentle laying on of hands with the intent to connect the universal life-force energy with the person’s own innate power to heal. This treatment is individualized, can be empowering to the patient, and generally has no adverse effects or harm. Below we discuss the integrative approach to several common distressing symptoms to those receiving palliative care: nausea and vomiting, pain and neuropathic pain, stress, and dyspnea.Nausea and/or vomiting are common symptoms that develop in serious illness related to a wide range of disorders and/or the treatments used to address them. Traditional pharmacologic treatments, such as ondansetron and metoclopramide, do not come without side effects and limitations. Integrative therapies have been shown to provide significant relief as both primary and adjunct therapies in the management of nausea/vomiting with few side effects or adverse reactions. Herbal supplements, such as oral ginger, have long been regarded as a natural antiemetic, but its demonstrated effectiveness in scientific studies remains inconclusive. Currently, ginger has been used to address nausea/vomiting related to motion sickness, pregnancy, post-surgical and chemotherapy ,44,45. IAcupuncture and acupressure have also been utilized to address nausea and vomiting. Specific to pediatrics, there is a rising popularity of acupuncture, with now over one-third of pediatric pain treatment programs offering services . StudiesAromatherapy, via direct application or inhalation, may also provide benefit in the management of nausea and vomiting. For example, the use of peppermint oil has been recognized as an effective treatment for controlling nausea . Other pIn chronic disease, throughout the continuum of care and at the end-of-life, many patients struggle with uncontrolled pain. The balance between comfort and over sedation can be difficult for caretakers and families. The most common pharmacologic approach to pain management currently relies heavily on opioid medications, which may have unintended side effects. The Support study, which included more than 4000 hospitalized patients at the end-of-life, demonstrated that over 50% of patients suffered from moderate to severe pain in the days before their death . IntegraIn recent years, various relaxation techniques in the management of pain have been studied. These include progressive muscle relaxation, guided imagery, and autogenic training, with the goal of inducing one’s own natural relaxation response, described above. For example, a meta-analysis of randomized clinical trials utilizing guided imagery for pain control demonstrated a significant reduction in non-musculoskeletal pain in 11 out of 15 trials reviewed . StudiesAcupuncture has become increasingly recognized in western medicine for the management of both acute and chronic pain, making it a viable adjunct for patients suffering with pain at the end-of-life. One Cochrane review concluded that acupuncture demonstrated effectiveness as a treatment for pain associated with migraines, headaches, neck pain, arthritis, and low back pain, all of which often plague those in the end-of-life . A majorAs one of its many benefits, aromatherapy has been used for pain relief, especially when combined with therapeutic massage, and is another modality to be considered in the management of pain, as well as anxiety and stress. A meta-analysis of literature examining the effectiveness of aromatherapy in treating multiple types of pain found a significant positive effect in reducing pain, typically reported on a visual analog scale . SpecifiNeuropathic pain can be a significant cause of discomfort and distress to those receiving palliative care and at the end-of-life. Neuropathy can result from multiple etiologies, but the mechanism of pain remains the same, with nerve damage and resultant hyperexcitability of peripheral nerves. Traditional therapy modalities for neuropathic pain, such as neuroleptic drugs, antidepressants, and opioids, have variable success and frequent unwanted side effects. Topical capsaicin is a treatment modality that may be considered for neuropathic pain. Produced from chili peppers, capsaicin binds nociceptors in the skin, leading to initial stimulation and release of substance P. Research has shown that repeat applications of capsaicin can deplete substance P, ultimately resulting in nerve desensitization . SeveralAny clinician caring for a patient who is receiving palliative care must be prepared to address the psychological symptoms common at the end-of-life in addition to the physical ones. Furthermore, the psychological and the physical are physiologically interconnected. Depression and anxiety may plague patients and non-pharmacologic treatments have long been utilized in the management of depression and anxiety. Mind-body and relaxation techniques, previously detailed for pain relief, have been shown to provide significant relief of depression, anxiety, and stress. A Cochrane meta-analysis of 15 randomized controlled studies of relaxation techniques with patients diagnosed with depression showed improvement compared to no or minimal traditional treatment. It is important to note, the most significant positive outcome was demonstrated when combined with psychological therapies, such as cognitive behavioral therapy . FurtherAs noted, aromatherapy and/or massage have also demonstrated benefit in overall well-being, mood, and sleep patterns. A randomized control trial of aromatherapy massage in the hospice setting found statistically significant improvements in sleep scores and depression reduction . Reiki has been shown to have benefits of relaxation, decreased pain perception, anxiety reduction, overall sense of well-being, and quality-of-life in the palliative patient population . SimilarPatients often experience shortness of breath, or dyspnea, related to their underlying disease process and this can worsen during the last six months of life and at the end-of-life. Beyond the physical discomfort, dyspnea can also be anxiety-provoking for many patients and caregivers who have to watch their loved ones suffer. Although the most effective management is to modify the underlying etiology, often in the terminally ill this is not possible. Traditional therapies such as opioids, steroids, nebulizers, and supplemental oxygen can be effective, but not always sufficient . ComplemBelow we provide a case illustration to demonstrate how integrative medicine can be used in practice to improve quality of life.Janey was a 16-year-old who presented to her general practitioner with complaints of abdominal pain and was found to have angiosarcoma of the spleen with metastasis to the liver, spine and portal venous system. She was being raised by her grandparents due to parental substance abuse. Following the diagnosis, she underwent first line therapy with chemotherapy and radiation. Unfortunately, the social disconnection from her peers created by her medical therapies and the psychological distress of her diagnoses led to a mental health crisis that resulted in a suicide attempt by overdose. While Janey recovered medically in the hospital, the Integrative Medicine team was consulted in the hopes that they might offer a more holistic approach to the impacts of cancer on Janey’s life. The integrative medicine practitioner worked intensively with Janey around the use of guided imagery to relieve anxiety and fears related to her diagnosis and uncertain future. Specifically, they chose to focus on scenes in which Janey traveled to Bora Bora, which she had seen in a travel magazine and viewed as the most relaxing location she could imagine. This technique combined with diaphragmatic breathing and aromatherapy was particularly helpful during times of heightened anxiety when waiting for results of imaging studies to evaluate the effectiveness of her ongoing treatment. Computed tomography (CT) scans early in the second year of her treatment showed progression of the hepatic portion of her cancer. Discussions about the possibility that she may not be cured became more frequent with her medical team. While she proceeded with a new chemotherapy regimen, she also began planning a Make-A-Wish trip to Bora Bora. Planning her trip motivated her to intensify her practice of integrative strategies and she began a daily meditation practice and engaged in biofeedback. With minimal medications, she had excellent symptom management and was able to enjoy the trip and add more depth to her subsequent imagery work.By the third year of her cancer journey, her tumor was again growing more quickly, and Janey struggled with progressive abdominal pain. She was very reluctant to use opioid pain medications due to fears about addiction raised by her parents’ substance abuse histories. She was motivated to maintain as normal a life as possible despite her medical condition and prioritized having a job babysitting for the neighbors’ children each afternoon. Her palliative care physician and integrative medicine practitioner worked with her to design a plan involving long- and short-acting pain medications, as well as mind-body practices, to enable her to maintain function, acceptable pain control and still attend to her responsibilities and relationships. This plan was quite effective for many months before the cancer progressed. At that time, she had processed many of her fears about addiction with psychology support and was able to accept increased medication for pain control when integrative techniques alone could not manage her symptoms. Janey was aware that she was approaching the end of her life and worked with a child life specialist to participate in legacy activities. Janey spent many weeks planning for a wedding to her longtime boyfriend and utilized her arsenal of imagery, breathing, aromatherapy and techniques learned in biofeedback to minimize medications used during the ceremony and reception. As her liver failure progressed, nausea became a prominent symptom and she sought new strategies for treatment. She found a combination of lorazepam and acupressure wrist bands with peppermint aromatherapy and imagery to be most effective. Near the end of her life, she became minimally wakeful and less able to utilize strategies herself. However, her husband and grandparents were able to perform massage with her lavender essential oil and use home music therapy provided through hospice to keep her relaxed as she died. Family participation in integrative strategies made loved ones feel empowered to help Janey through the last stage of her life and has provided crucial legacy memories to help them through their grief.This case illustrates the numerous ways that integrative medicine modalities were employed alongside, and at times in place of, pharmaceutical and conventional treatments, equipping Janey and her family to manage her disease and symptoms. The shared locus of control  concept is also demonstrated in the combination of integrative therapies as well as medication management, which provided Janey with the ability to live out her life in meaningful ways. Integrative medicine is the multimodal approach to improved quality of life and patient care that respects and builds upon the strengths of the patient in combination with appropriate medical management. In the setting of palliative and end-of-life care an integrative approach can serve to reduce symptom burden and empower patients and their families.


Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM.Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL.Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0–1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups . Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity.BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients.clinicaltrials.gov (February the 20th 2019).NCT03847220. Retrospectively registered on  Breast cancer represents 25% of all cancer cases worldwide . BetweenBone metastasis (BM), the most common site of disease in MBC patients , greatlyBetter understanding of the disease’s overall impact on HRQoL requires questionnaires designed to assess patients’ perception of their pain and other potentially life-limiting symptoms. The questionnaire designed by the European Organization for Research and Treatment of Cancer (EORTC), QLQ-C30, and the functional assessment of cancer therapy (FACT-G) assess general cancer-related HRQoL issues. The corresponding breast cancer modules focus on image and sexual life issues, lymphedema of the arm, and surgery incision pain, i.e., challenges found in both metastatic and non-metastatic patients. However, 50–70% of patients with BM present with bone pain and related threats to HRQoL . The QuaBOMET-QoL was later reduced to 10 items (BOMET-QoL-10) and validated using a similar population of patients with BM. In that validation study, factorial analyses identified a single dimension which accounted for 45.8% of explained variance. The disease’s impact on HRQoL did not vary significantly across clinical variables such as number and location of bone metastases and time since diagnosis. However, it did vary significantly by presence, number, and duration of irruptive pain crises, pain management index (PMI), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) . ReporteIn most cases, BOMET-QoL-10 questionnaire scores correlated statistically significantly, and at least moderately, with EORTC QLQ-30 and BOMET-QoL dimensions, confirming convergent validity. Also, BOMET-QoL-10 scores experienced a statistically significant increase  throughout the study . The effMBC patients with BM have disease-specific complications with particular impacts on HRQoL. Thus, the main objective of the present study was to evaluate the aplicability of BOMET-QoL-10 in this patient population, regardless of treatment received. Secondary objectives included: 1) Evaluating the differences on BOMET-QoL-10 scoring when patients have skeletal-related events (SREs) and BM symptoms; 2) Exploring the association between BOMET-QoL-10 scores and other measures of self-perceived health status and pain such as ECOG PS and Visual Analog Scale (VAS); and 3) Assessing whether the magnitude of the effect of BM treatment on patients´ HRQoL reaches clinical significance.This was a prospective, observational, multicenter study of MBC patients who received systemic therapy according to local guidelines. MBC patients were eligible for inclusion with age above 18 and diagnosed with BM, ability to understand and complete the questionnaires, estimated life expectancy of at least 8 months, and absence of co-morbidities.Study visits were pre-specifed in the protocol as a first baseline visit and 6 follow up visits at 4, 8, 12, 16, 20 and 24 months after baseline visit.Figure changes in perceived health status (compared to that at baseline) were collected at follow-up visits. General health status was based on both patient’s and health professional’s responses ranging from “very good” to “very bad” on a 7-point Likert scale.To assess HRQoL and perceived health data participants completed the BOMET-QoL-10 questionnaire  of 23 points for BOMET-QoL-10 scores (same as BOMET-QoL), a 20% patient drop-out rate, an estimation of HRQoL with a precision of ±3.25, and having at least 80% power to detect a difference ≥ 0.20 SD between BOMET-QoL-10 scores at baseline and at last follow-up (visit 7) with a 0.05 level of significance. However, due to recruitment limitations, we recalculated the target recruitment to 174 by slightly lowering our precision in estimating QoL to a ± 3.75 instead, while keeping the other parameters the same.χ2) or Fisher exact tests. Associations between ordinal variables were described using Kendall’s Tau. We used means, standard deviations, medians, and ranges (minimum and maximum) to describe continuous variables. Depending on variables’ distributions either Student t-tests or Mann–Whitney U-tests were used for comparisons. Likewise, we used Pearson r coefficients or Spearman’s rank correlation coefficients (ρ) to assess associations between variables of interest. Relationships between BOMET-QoL-10 scores and ECOG PS scores, perceived health status, and presence of SREs and AEs were analyzed.Categorical variables were described using frequencies and their differences were tested using Chi-square . The higher the BOMET-QoL-10, the higher quality of life (HRQoL).To assess the clinical usefulness of our results we calculated the effect size of the questionnaire’s scores for patients receiving any specific medical intervention for BM, at any visit(s) during the study, versus patients who did not. The minimum effect size (d) for the difference between groups to be considered a clinically significant improvement in HRQoL was set at d ≥ 0.20. The effect size was calculated using the standardized mean difference, defined in this case as the ratio of the difference in mean scores between baseline and last follow-up and the standard deviation of scores at baseline.To evaluate the correlation between the reduction in pain (according to pain VAS) and the HRQoL on the BOMET-QoL questionnaire, we compared the difference of mean values of those parameters between baseline and last follow-up visit.. We categorized this as: “Gets worse” if the difference was negative, “Stays the same” if the difference was zero and “Improves” if the difference was positive.Finally, to evaluate the evolution of BOMET-QoL-10 scores, when explicitly mentioned, certain analyses only included those questionnaires with no missing data. All tests were two-tailed with an α = 0.05. Analyses were conducted using SPSS version 17.0 .From October 2007 to May 2010, 174 patients were recruited at 15 GEICAM hospitals distributed throughout Spain. One hundred seventy-two were eligible and enrolled in the study. Only 83 of them completed the last follow-up visit at 24 months. Missing data for specific questions or instruments varied across assessments, as reflected in in Tables Patients’ median age was 59 years (range: 30–89) and only 14% lived alone. The median time between breast cancer diagnosis and study enrollment was 4.4 years (Range: 0–36.8). Over half of the patients (52.7%) were stage IV at diagnosis. The most common BM sites were the spine (76.2%), pelvis (53.5%), and ribs (45.3%). In addition, visceral metastases were present in 40.7% of patients. SREs were reported in 18.6% of patients, the most common one being pathologic fractures (25.0%). Almost 70% of patients presented symptoms, mostly lower back pain (37.0%) and weakness (32.8%). Further, 23.3% of patients presented irruptive pain, of whom, 72.5% reported the pain to be incidental and clearly linked to oncological and neuropathic pain. Over 50% of patients presented chronic conditions, 19.2% were osteoarticular and 34.3% were non-osteoarticular comorbidities.  to the 24-month follow-up (n = 83). There was no significant trend in BOMET-QoL-10 scores over the 7 visits. In fact, baseline and last follow-up global average scores  were were not statistically significant different  completed the BOMET-QoL-10 in less than 10 min in all visits, with a high completion rate. The small proportion of unanswered items throughout the entire follow-up ranged between 0% and 1.2%. Based on fully-completed questionnaires, we calculated the global average score for each visit from baseline (p < 0.001) . These patterns of correlations held true for the scores reported in every visit (Table p = 0.003).Further, as expected, BOMET-QoL-10 lower scores were negatively correlated with the number of BM-related symptoms  reported ECOG PS scores between 0 and 1. We compared BOMET-QoL-10 scores for each visit between two groups formed by patients with ECOG PS scores 0–1 versus those with ECOG PS scores > 1, to assess the differences in QoL within these groups. The former reported significantly higher BOMET-QoL-10 scores (range: 26.5 to 28.0) than the latter (range: 17.3 to 22.9). Differences between patients with ECOG PS 0–1 and > 1 were statistically significant overall and for every visit, except in visit 3 (Table p = 0.956). Thus, BOMET-QoL-10 scores for highly stable patients were consistently stable throughout the study.We also evaluated the values of BOMET-QoL-10 scores for those patients (up to 42 patients between visits 4 and 5) reporting their perceived health status between visits remaining “more or less the same.” As expected, their corresponding BOMET-QoL-10 scores did not vary between consecutive visits either. There were 26 highly stable patients who reported the same perceived health status from baseline all throughout the last follow-up. As expected, BOMET-QoL-10 global mean for these highly stable patients was unchanged between baseline and visit 7   and that for patients reporting neither SREs nor AEs at any of the visits during the same period . The average score for the first group was significantly lower than that of the second group (p ≤ 0.007) (data not shown).In addition we compare the BOMET-QoL-10 scores between patients with SREs sit Fig. . Resultsspecific treatment for BM reported a clinically significant improvement in HRQoL throughout the study compared to those patients who did not. The magnitude of the treatment’s effect for BM was calculated as the difference between the BOMET-QoL-10 mean values at visit 7 in these two groups divided by a combined standard deviation. The relative overall study variability yielded an effect size of 0.203 in BOMET-QoL-10 scores, which is greater than our pre-set value for clinical significance (0.200)  Table ).Table With increasing rates of survival after a breast cancer diagnosis a growing number of patients are at risk for MBC , 19. ForAside from BOMET-QoL, QLQ-BM22, a widely used tool, is the only other HRQoL instrument designed specifically for BM patients. QLQ-BM22 is a useful and reliable instrument especially when administered in combination with the QLQ-C30 . SeveralBOMET-QoL-10 has been shown to closely reflect variations in relevant pain and wellness measures, having good internal consistency, and being highly reliable among cancer patients with BM , 22. Ourany of the visits vs. not). Further, the instrument’s scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. Perceived pain was directly proportional to HRQoL and VAS scores and BOMET-QoL-10 scores also varied accordingly as patient’s pain improved or worsened. As expected, the BOMET-QoL-10 and ECOG PS scores were inversely proportional throughout the study. This supports previously reported results based onQLQ-C30 and QLQ-BM22 [BOMET-QoL-10 scores for overall HRQoL remained stable over time for the sample as a whole. This lack of variability may reflect the influence of aspects other than the socio-demographic and clinical factors assessed here. However, when patients were grouped by disease status  BOMET-QoL-10 scores reflected the differences in group wellness one would expect at each visit and throughout the study  were recruited by 5 of the 15 participant research centers. As palliative care populations tend to be highly heterogeneous, a limited number of recruiting centers may have resulted in a less diverse sample of participants than expected. This may have introduced an unknown bias  and reduA third limitation is the small number of patients completing the entire 24-month study. This is the result of an initial small sample size compounded by a much higher lost-to-follow-up rate (51.7%) than anticipated (20%). However, recent adaptation and validation studies of HRQoL instruments as well as HRQoL assessments of palliative care patients have been based on small samples followed for short periods of time ranging from 1 to 6 months , 23, 26.n = 111) to those who did not report either during the study (n = 61) their overall average scores were significantly different (p < 0.007).Unfortunately, the lower numbers limited the evaluation of the study’s secondary objectives and actual differences may have gone undetected given the low statistical power of some of our comparisons. For instance, even though BM-associated pain is quite common and often undertreated in MBC patients , BOMET-QThe study also has some important strengths. First, the longitudinal administration of the same tool to patients with BM in seven occasions over a 2-year period represents a solid assessment of the user-acceptance, respondent burden of the tool, and stability of the measurement. As aforementioned, this contrasts with other studies which include just one or two follow-ups over periods of time under 1 year , 23, 26,The regular surveillance of HRQoL issues in patients with advanced disease and receiving palliative care can be used to guide pain management therapy  and otheThis instrument exhibits longitudinal and cross-validation, construct validity, as well as feasibility and it is sensible to detect some changes related with the disease evolution and their treatment. BOMET-QoL-10 is sensitive to the number of symptoms, pain level, ECOG PS, presence of SREs and/or AEs, and the effects of BM-specific treatment.Further research is needed to test this tool in larger samples of breast cancer patients with BM as well as in other homogenous cancer populations with BM, e.g., prostate or lung cancer patients with BM. Further steps would involve translation and cross-cultural adaptation of the tool to other languages and countries.Additional file 1. BOMET-QoL 10 points itemsAdditional file 2. Breast Cancer Treatments at baselineAdditional file 3. Treatments for bone metastasis per visitAdditional file 4. BOMETQoL items evolution through study visits and mean standardized global scoreAdditional file 5. Correlation between the number of symptoms at visit 7 and the BOMET-QoL global score


In well-controlled rheumatoid arthritis (RA) without significant joint damage, a substantial proportion of patients complain of persistent pain. Previous studies have identified different pain phenotypes in RA, in which non-nociceptive pain phenotypes are associated with higher concurrent disease activity scores. In this longitudinal study, we explored associations between pain phenotypes and long-term disease activity outcome in RA patients. Secondly, we explored whether pain phenotype is associated with comorbid conditions.One hundred eighty established RA patients were classified with a nociceptive (61%) or a non-nociceptive (39%) pain phenotype, based on their responses to the painDETECT-questionnaire. Two years of clinical follow-up data on disease activity outcomes were collected. Information on comorbid diseases was derived from electronic patient files.p < 0.001) and a twofold lower chance of achieving sustained DAS28 remission . Only the tender joint count and patient global health significantly differed between the pain phenotype groups. Patients with a non-nociceptive pain phenotype had more often been diagnosed with concurrent fibromyalgia  and other pain-associated comorbid diseases  compared with patients with a nociceptive pain phenotype.Patients with a non-nociceptive pain phenotype showed higher mean disease activity scores (DAS28, 2.57; 95% CI, 2.37–2.77 vs. 2.11; 95% CI, 1.94–2.27; This longitudinal study showed consistently worse long-term disease activity outcomes in RA patients with a non-nociceptive pain phenotype which appeared to be mainly due to differences in the subjective components of the disease activity score.NTR578.The DREAM cohort study is registered in the Netherlands Trial Register:  In recent years, there have been many improvements in the treatment of rheumatoid arthritis (RA), and in most patients, joint inflammation can now generally be well controlled . HoweverOn average, RA patients demonstrate lower pain thresholds and also more signs of hyperalgesia, an increased response to a stimulus which is normally painful, compared with healthy controls . The widThe painDETECT questionnaire (PD-Q) was developed in 2006 to identify neuropathic pain components in patients with chronic low back pain . It inclBesides the different pain mechanisms, several studies suggest that different comorbid conditions may also independently alter commonly used RA-specific outcome measures, including composite disease activity measures such as the DAS28, categorical states of remission, and functional disability assessments . A recenThe first aim of this longitudinal study was to explore the course of disease activity in RA patients with different pain phenotypes. Secondly, we explored the associations between comorbid diseases and different pain phenotypes. While previous studies examining associations between pain and disease activity in RA have mostly been cross-sectional, we now examined longitudinal differences in DAS28 scores and remission rates between patients with predominantly nociceptive or non-nociceptive pain phenotypes, as determined by the PD-Q screener.mijnreumacentrum.nl. The current study is a 2-year longitudinal follow-up study of the cross-sectional study by Koop et al.  (p < 0.001). Perceived pain intensity was also substantially higher in the non-nociceptive pain phenotype group, with a median VAS score of 45.5 out of 100 compared with 14 out of 100 in the nociceptive pain phenotype group.The non-nociceptive pain group additionally reported significantly lower mental and physical quality of life and more disability (p = 0.004). Additionally, they had almost a twofold increased risk to have a pain-associated comorbid disease .Patients in the non-nociceptive pain phenotype group had slightly more comorbidities compared with the nociceptive pain phenotype group, but this difference was not significant Table . Only fip for time = 0.128). The time*group interaction was not significant, indicating that the trajectories of the DAS28 did not significantly change over time between groups.Figure Like the baseline scores, only the tender joint count scores and the VAS general health scores were significantly different between the pain phenotype groups over time Table . No signSustained remission was further categorized into periods of short (between 6 and 9 months), medium (between 9 and 12 months), and long (12 months or longer) sustained remission.p = 0.02) and an even smaller chance of achieving remission for at least 12 months . A medium and long sustained remission of 9 and 12 months, respectively, was achieved by 26/71 (36.6%) and 32/71 (45.1%) of the non-nociceptive pain patients, compared with 67/109 (61.5%) and 63/109 (57.8%) of the nociceptive pain patients.There was a large discrepancy in achieving sustained remission across the two pain phenotype groups. A total of 79/109 (72.5%) of the patients in the nociceptive pain phenotype group achieved a sustained remission of 6 months at least once during follow-up Table . In the Rheumatoid arthritis has always been considered an inflammatory joint disease, causing inflammatory or nociceptive pain. In this study, however, only 61% of the RA patients fulfilled the criteria for a nociceptive pain phenotype, as categorized by the PD-Q. A previous study also using the PD-Q in RA by Christensen et al. in 2016 showed comparable proportions of nociceptive and non-nociceptive pain phenotypes: 65% of the RA patients experienced nociceptive pain and the remaining 35% non-nociceptive pain . These rThe lack of a golden standard to measure the relatively new concept of central sensitization is a common problem in pain research. Furthermore, features that may be indicative of central sensitization tend to overlap with features indicative of neuropathic pain, making it difficult to distinguish between the two . TherefoIn the current study, RA patients with a non-nociceptive pain phenotype were found to have a nearly 12-fold increased risk to have a concurrent clinical diagnosis of fibromyalgia. This is however not unexpected. One of the theories on the pathophysiology of fibromyalgia (FM) is based around the concept of central sensitization; therefore, the American College of Rheumatology (ACR) fibromyalgia diagnostic criteria are commonly used to define central sensitization . AssuminPatients in the current non-nociceptive pain phenotype group had more severe rheumatic disease and worse treatment outcomes, i.e., higher mean disease activity scores and lower remission rates. This has also commonly been reported in RA patients with concurrent FM . MoreoveInterestingly, patients with non-nociceptive pain tended to have a slightly higher BMI and were more often anti-CCP negative. The higher BMI in the non-nociceptive pain phenotype may be related to previous findings showing higher pain severity scores in  RA patients who are overweight or obese , 38. ThePain sensitization is often measured with the PD-Q. However, in the previously mentioned study by Lee et al., sensitization was determined with quantitative sensory testing (QST), including testing for pressure pain thresholds, conditioned pain modulation, and temporal summation, and disease activity was measured with the Clinical Disease Activity Index (CDAI), a composite measure that includes a TJC, SJC, patient global assessment, and assessor global assessment on disease activity. The study by Lee et al. corroborates our current results on disease activity in RA and especially on the more subjective components of the disease activity scores: the TJC and patient global assessment of disease activity were also significantly higher in patients with indications of pain sensitization, while the SJC did not differ between the groups . The SJCAlthough there was a significant difference in mean DAS28 scores between the two pain phenotype groups, on average both were below the remission cutoff value of 2.6 during the follow-up period. However, to achieve “sustained” remission, the disease activity score must be below 2.6 at every assessment over a period of at least 6 months. In the nociceptive pain group, 72% of the patients reached sustained remission compared with 55% of the non-nociceptive pain patients. Similar findings were found for achieving 9 or 12 months of sustained remission. These results are congruent with previous research, because known predictive factors for reaching sustained remission are earlier time to remission, lower baseline disease activity, mild disability, lower TJC, and less pain , 41. TheA remarkable finding in the current study was the comparable use of anti-rheumatic drugs in both groups. Although the nociceptive pain group used slightly more biological DMARDs than the non-nociceptive pain group, this difference was not significant. The lack of difference may be explained by the mean disease activity scores. In both groups, the mean DAS28 was below 3.2, which indicates low disease activity . AlthougTo our knowledge, this is the first longitudinal study examining associations between different pain phenotypes and long-term disease activity outcomes in RA patients. A previous cross-sectional study by Koop et al. demonstrated the presence of different pain phenotypes in RA patients . Our curThis longitudinal study of 2-year follow-up showed that RA patients with a non-nociceptive pain phenotype reported higher pain scores, more severe disability, and a lower physical and mental quality of life compared with RA patients with a nociceptive pain phenotype. Concomitant fibromyalgia was more common in patients with a non-nociceptive pain phenotype. Furthermore, patients with a non-nociceptive pain phenotype showed consistently worse disease activity outcomes, with higher mean DAS28 scores and lower rates of sustained remission. Both at baseline and during follow-up, these higher disease activity scores were mostly caused by the more subjective components of the DAS28: a higher TJC and a worse patient assessment of global health.


Image-guided elastoplasty is an innovative method for percutaneous vertebral augmentation with a silicone elastomeric material. Our aim was to evaluate its technical success, safety and efficacy as well as the rate of secondary fractures.Nineteen patients  underwent elastoplasty between 2010 and 2016. A total of 33 vertebrae were treated. A total of 2–6 mL of silicone-based elastomeric polymer material (VK100) was used. Visual analogue scale (VAS) and Oswestry disability index (ODI) pain scores were used.p < 0.001 for both comparisons). After vertebroplasty, 14 of 15 patients (93%) removed the brace and 16/19 (84%) completely stopped using any drugs for pain relief (p < 0.001 for both pre-procedure versus post-procedure comparisons). At a mean follow-up time of 26.5 ± 28.1 months , no secondary fracture occurred.In all cases, it was possible to complete the procedure . No major complications occurred. In 6/19 (31.5%) patients, asymptomatic leakage of the material was observed during the procedure. Full pain recovery was obtained in 18/19 (94%) patients. One patient with a painful angioma did not experience any change in symptoms. VAS and ODI were significantly reduced after the procedure, from 7.9 ± 1.1 to 0.7 ± 1.4 and from 79.6 ± 12% to 9.9 ± 14% respectively (Taking into consideration the relatively small sample size, image-guided elastoplasty seems to be a safe procedure providing effective pain control over time. Elastoplasty is an innovative method for vertebral augmentation with a silicone elastomeric material.In a series of 19 patients, elastoplasty was a safe and effective procedure.No symptomatic leakage of elastomeric material or cases of pulmonary embolism were observed.Percutaneous vertebral augmentation is increasingly used to achieve vertebral stabilisation and pain relief from symptomatic vertebral lesions. With this technique, the stiffness of the vertebral body is rapidly restored, reporting significant pain relief and improvement in quality of life –4. The mTherefore, the use of a silicone elastomeric material (VK100) has been proposed to achieve vertebral stabilisation with a pliable material that has a modulus closer to that of bone, thus theoretically reducing the risk of adjacent fractures . HoweverThus, the primary aim of our work was to investigate the technical feasibility and safety of VK100 elastoplasty. The secondary aim was to assess pain management and the rate of secondary fractures following VK100 elastoplasty.Institutional review board approval was obtained and patient informed consent was waived for this retrospective study. From 2003 to 2016, 4580 patients with back pain and different kinds of vertebral lesions were presented to the same interventional radiologist with more than 13 years of experience; they were treated by percutaneous vertebral augmentation at different institutions. Out of those patients, 19  underwent elastoplasty in a single institution. The indication for the treatment was the same as for standard vertebral augmentation, which has been previously reported .Patients with no more than two vertebral fractures were selected for elastoplasty and prepared for treatment at one of the institutions where the material was available. Fourteen patients had osteoporotic fractures, two patients had traumatic fractures, one patient had a painful myeloma localisation and one patient had a painful vertebral non-aggressive angioma. Fifteen patients used a brace and all were using drugs for pain relief. A total of 33 vertebrae were treated (range T6–L5). Data of all treated patients were prospectively collected in a dedicated database and retrospectively extracted and analysed.Elastoplasty was always performed using a sterile technique in conjunction with prophylactic intravenous antibiotics (2 g of Ceftriaxone) in a dedicated angiosuite equipped with flat-panel digital fluoroscopy . The procedure was always performed with the anaesthesiologist in the room. Based on the patient’s condition, it was decided whether to perform the procedure under sedation  or general anaesthesia. Vital signs  were monitored throughout the whole procedure. Under fluoroscopic guidance, a 22-gauge Quincke needle was placed over the pedicle periosteum and local anaesthesia with ≤ 2 mL of 2% lidocaine hydrochloride was administered. Bevelled access cannulas  were inserted using the oblique projection and subsequently advanced in the anteroposterior projection. Once the desired position of the needles was achieved and confirmed, 2–6 mL of silicone-based elastomeric polymer material  were gently manually injected under continuous fluoroscopic monitoring.VK100 is composed of two paste components mixed during application. Component A is composed of dimethyl methylvinyl siloxanes (86%), barium sulfate powder (14%) and a platinum catalyst . Component B is composed of dimethyl methylvinyl siloxanes (78%), barium sulphate powder (15%) and a methylhydrogensiloxane cross-linker (7%).VK100 injection was stopped when satisfactory intervertebral material distribution was observed. When leakage outside the vertebral body was detected, the procedure was immediately interrupted and symptoms or modifications of the vital signs were checked. After some minutes, injection was cautiously restarted. If leakage was still present, the injecting needle was slightly moved or rotated and injection restarted. When VK100 injection was complete, the cannulas were withdrawn. Patients were discharged after 4–6 h of observation. A case is shown in Figs. Primary endpoints of the study were the technical success and safety of the procedure. Technical success was defined according to previously reported criteria for interventional procedures  as the aSecondary endpoints were the technical efficacy in achieving pain relief and the rate of secondary fractures during follow-up Fig. . Visual All patients underwent a thoracic and lumbosacral spine x-ray examination and a clinical visit one month after the procedure. The number of patients who stopped to use a brace and number of patients who stopped using any medication for pain management were recorded. After the examination and discharge, patients were asked to immediately contact the interventional radiologist who performed the procedure if they experience any increase or restart of the back pain. In such cases, magnetic resonance imaging (MRI) or computed tomography (CT) of the spine were performed to asses for the presence of secondary fractures. Where no pain was reported by the patients, clinically relevant secondary fractures were excluded.U test. The number of patients who needed a brace and pain medications before and after the treatment was compared using Fisher’s exact test. Analysis was performed using GraphPad Prism 5 software . A p value < 0.05 was considered significant.VAS and ODI scores before and after the procedure were compared using the Mann-Whitney In all cases it was possible to complete the procedure and to reach a satisfactory filling of the vertebral body . No major complications occurred. In 6/19 patients (31.5%), a minimal leakage of the material was seen during the procedure. No change in the vital signs or symptoms were recorded in these cases. After a few minutes it was always possible to restart the procedure and conclude it as planned. None of these patients had modifications of the saturation parameters or symptoms after the procedure.p < 0.001) and from 79.6 ± 12% to 9.9 ± 14% (p < 0.001), respectively. Of 15 patients, 14 (93%) no longer required a brace after the procedure (p < 0.001) and 16/19 (84%) completely stopped using any drugs for pain relief after treatment (p < 0.001).The procedure was effective in achieving an improvement in clinical symptoms in 18/19 patients . One patient with painful angioma did not experience any change in symptoms. VAS and ODI scores were significantly reduced after the procedure, from 7.9 ± 1.1 to 0.7 ± 1.4 . According to the subjective experience of the interventional radiologist, it was not more technically difficult than standard vertebroplasty with PMMA.Practitioners have suggested that VK100 may cause an increased rate of leakage due to viscosity. However, viscosity is a moving target. During the curing of PMMA or the cross-linking of VK100, the viscosity is changing. Viscosity test data demonstrate that VK100 is equivalent to PMMA as used in vertebral augmentation. At an ambient temperature of 68–69 °F, it was shown that the average viscosity of VK100 at the time of injection into the vertebral body is 167,900 centipoise (cP) and the average viscosity of PMMA cements commonly used for vertebroplasty is 136,300 cP [The experience of the operator may play a relevant role in reducing the complication rate. Appropriate training should be used to achieve optimal results. In our series, all the procedures were performed by the same operator with more than 13 years of experience in vertebral augmentation procedures and no major complications occurred.Minor leakage of VK100 outside the vertebral body was seen in about 30% of cases during the procedure. Material leakage has been reported to occur in vertebroplasty in a highly variable rate. In a systematic review of 15 studies, leakage of cement outside the vertebral body was reported in a range of 3.3–75.6% . Rate ofOne of the most critical complications related to extravertebral leakage of injected material is pulmonary embolism. This occurrence has been reported in a variable range for PMMA procedures –22. Kim , mean pain scores, measured using a 0 to 10 VAS score, improved significantly from 7.8 to 3.1 (a 60.3% reduction) immediately after percutaneous vertebroplasty [Regarding the efficacy in pain relief, in a systematic review on patients with osteoporotic vertebral compression fracturesroplasty . In our During the follow-up, no new vertebral fractures occurred in our series. In the literature, several studies reported on the development of new vertebral compression fractures in patients treated with vertebroplasty –26. In aSome limitations of the present study need to be taken into consideration. First, this is a retrospective analysis on a limited number of patients treated over a long time period for different pathologies by a single operator with much experience in vertebral augmentation. These results might therefore not apply to the everyday clinical practice of any centre. Second, the presence of pulmonary embolism was evaluated only based on patient symptoms. This was due to the fact that we considered unjustified the radiation exposure associated with a chest CT in asymptomatic patients. Third, the occurrence of new vertebral fractures during follow-up has been only evaluated at one month with x-ray examinations and afterward only on the basis of clinical symptoms reported by the patients. Even if this might have determined an underestimation of new vertebral fractures, it should be underlined that the aim of the treatment is to solve the patient’s symptoms and that repeated radiological examinations in asymptomatic patients could be not justified.In conclusion, elastoplasty with VK100 provided results in terms of pain relief similar to those reported for the most widely used vertebral augmentation techniques. The rate of minor complications was low and similar to that reported for other vertebral augmentation techniques. Finally, the absence of new vertebral fractures at one month after the procedure supports the rationale for applying elastic material for vertebral augmentation. However, even if the results from our preliminary experience are encouraging, further large prospective studies should be conducted to better define the role of elastoplasty among vertebral augmentation techniques.


Patients with stroke admitted at the neurology/neurosurgery ward of the Academic Medical Centre in Amsterdam, The Netherlands, may experience problems in communication, such as aphasia, severe confusion/delirium or severe language barriers. This may prevent self-reported pain assessment; therefore, pain behaviour observation scales are needed. In this project, we therefore aimed to implement the Rotterdam Elderly Pain Observation Scale (REPOS) by video training.We used a stepped-wedge cluster design with clusters of four to five nurses with intervals of 2 weeks, for a total study duration of 34 weeks. Primary endpoint was the proportion of shifts in which nurses used the REPOS when caring for an eligible patient. A questionnaire was send biweekly to assess self-perceived competence and attitude on pain measurement in patients able or unable to self-report pain intensity. No other strategies were used to promote the use of the REPOS.Though the proportion of shifts in which trained nurses cared for eligible patients increased from 0% at baseline to 83% at the end of the study, the proportion of cumulative shifts where the REPOS was used decreased from 14% to 6%, respectively. Process evaluation suggests that this decrease can (in part) be attributed to low and varying prevalence of eligible patients and opportunities for practice. In total, 24 (45.3%) nurses had used the REPOS at least once after 34 weeks, with a median of two times (1–33). Nurses perceived themselves 'competent' to 'very competent' in pain behaviour observation. There was no negative attitude towards pain measurement.This study shows that education alone may not be effective when implementing a pain behaviour observation scale for non-communicative patients with Acquired Brain Injury. Individual motivation of health professionals and individual patient factors may be of influence for the use of the REPOS. Even in modern medicine, stroke has a severe impact on patients all over the world. While mortality rate is dropping and both primary prevention and acute treatment have improved, it is estimated that from 2025, Europe will count 1.5 million new patients with stroke per year due to the ageing population.Aphasia is present in about one-third of all patients with acute stroke in varying forms and severity.Besides these effects originated by the stroke itself, the Academic Medical Centre (AMC) in Amsterdam, The Netherlands, often comes across patients unable to speak Dutch. Amsterdam hosts many multi-lingual people of different backgrounds. There are about 180 different ethnicities in the city and at least 35% of the population has a non-Western migration background.At the neurology/neurosurgery nursing ward of the AMC, the ‘AMC Neurocentre’, patients are often admitted with one or more of the above-mentioned communication disorders. This may interfere with common nursing practices or communication, in particular the measurement of pain intensity. Addressing pain is considered as being fundamental or basic nursing care and essential for delivering high care quality.According to international guidelines, self-reported pain instruments are considered the best possible method. Commonly used instruments are the Numerical Rating Scale (NRS), Visual Analogue Scale, Wong-Baker Faces Pain Scale-Revised and the Verbal Rating Scale.The Rotterdam Elderly Pain Observation Scale (REPOS) has been developed in 2009 for older patients incapable of reporting pain themselves. It is a Dutch scale with 10 behaviours that may indicate the presence of pain.Though single-component  implementation strategies are generally considered less effective, there is also no compelling evidence that multifaceted strategies are more effective in changing healthcare professionals’ behaviour.Training the entire ‘AMC Neurocentre’ nursing team at once is costly, logistically complicated and may not provide a sustainable solution that withstands regular changes within the team. We therefore chose a more gradual educational strategy by using a stepped-wedge cluster design with parts of the nursing team as clusters. We hypothesise that the risk of contamination from this design will cause the number of nurses using the REPOS to increase faster than the number of nurses receiving training and may be used as a potential method of implementation itself.In this evidence-based quality improvement study, we aim to evaluate (a) whether an educational strategy can increase the use of the REPOS in patients with severe aphasia, confusion or language barriers and (b) whether the risk of contamination from a stepped-wedge cluster design within a nursing team has an effect on the speed of implementation.We consider the implementation successful whether at the end of the study…….the REPOS is used in ≥85% of the shifts in which nurses care for eligible patients…pain assessment is compliant (≥1 REPOS measurement per 12 hours) in ≥85% of patient days.The ‘AMC Neurocentre’ is part of a tertiary care setting with regional responsibilities. It provides specialised care in cerebrovascular diseases such as intra-arterial thrombectomy and coiling of intracranial aneurysms. It operates 20 regular nursing beds and nine beds on the Brain Care Unit, a Stroke Unit for acute cerebrovascular care. A multidisciplinary team is available, consisting of neurologists, neurosurgeons, nurses, nursing aids, physiotherapists, occupational therapists and speech therapists. In 2017 the unit had 129 admissions per month on average, of which 108 (83%) had a length of stay longer than 24 hours. The average length of stay was 7.2 days.The participants of this study were registered nurses working at the ‘AMC Neurocentre’, with either an Associate (or similar) or Bachelor degree in nursing. Nurses who were not involved in nursing care activities, for example due to illness, or who had a temporary contract (<two months) were not included in the study.The instrument to be implemented is the REPOS, a pain behaviour observation tool developed for elderly patients unable to use self-reported pain instruments.The REPOS consists of 10 behavioural items that are associated with the presence of pain, each worth one point. The nurse observes the patient for a minimum of 2 min, at least twice a day, once during ambulation or nursing care activities and once during rest. If the REPOS shows a score of 2 or higher, the nurse will assess possible causes for the observed behaviour and provide a second pain score that reflects their clinical judgement. This is a NRS score where zero indicates that the nurse assumes there is no pain present that causes the behaviour and 10 indicates that the nurse assumes the worst imaginable pain is present. A list of other possible causes of the observed behaviour  aids the nurse in choosing an appropriate NRS. The REPOS is documented in the electronic patient file and evaluated daily during rounds with the physicians.The aim of pain behaviour observation with the REPOS is to provide insight in pain intensity for non-communicative patients and eventually more adequate pain treatment. As the treatment of pain is dependent on adequate pain assessment, this study focuses on the implementation of the REPOS and not the treatment of pain itself.The initiative for video training was based on desires of the nursing team to be classically trained and approved by the staff advisor on education prior to the start of the study. Every 2 weeks clusters of four to five nurses received a standardised training for 45 min at two consecutive days, with a total of 14 clusters. Nurses were allocated to a cluster based on the planned working schedule for each time period. Clusters were therefore random at first, but as the study progressed the untrained nurses would deliberately be scheduled to work on days of the video training.The video training started with a short introductory presentation, explaining the aim of pain behaviour observation, the content of the local hospital protocol and how to use and document the REPOS. An online training module with 12 practice videos of real patients, developed by the designers of the REPOS, was then used to familiarise the nurses with the scale.No motivational strategy was used to promote the use of the REPOS. Every 2 weeks however, alternating the training periods, a questionnaire was send as part of the study. This may be considered as a repeated reminder.Data were obtained from patient data files by the first author as part of a regular quality evaluation (PV). Besides the indication for pain behaviour observation, no patient characteristics were collected.The primary outcomes reflect behaviour of nurses, as this best reflects actual implementation.Proportion of shifts in which nurses used the REPOS when caring for an eligible patient.Proportion of patient days at which pain assessment was compliant to local hospital protocol (≥1 REPOS measurement per 12 hours)Secondary outcomes were as follows: (a) the self-perceived competence in pain behaviour observation of patients able and unable to self-report pain and (b) the attitude towards pain measurement. The self-perceived competence was measured with a 4-point Likert scale, where a higher score meant the nurse felt more competent .Recognising pain in patients that can communicate well.Measuring pain intensity in patients that can communicate well.Recognising pain in patients that cannot communicate well or are (severely) confused.Measuring pain intensity in patients that cannot communicate well or are (severely) confused.etal (2010), consisting of four questions with a 5-point Likert scale.Attitude was measured with an adaption of the Negative Pain Belief Scale (NPBS) by Shugarman 10.1136/bmjoq-2018-000447.supp1Supplementary dataData for secondary outcomes were collected with a questionnaire that was send every 2 weeks by email. To promote completion of the survey a reward, in form of a gift card worth 5–25 euro, was allotted among every 10 completed questionnaires and reminders were send out daily for 1 week.To assess mechanism(s) through which the implementation strategy  may or may not work, the following data were collected for process evaluation:Percentage of trained nurses .Proportion of shifts during which trained nurses cared for eligible patients.Number of trainings completed, including video's shown and repeated.Experienced workload as a barrier in pain assessment.Nursing views on their influence on pain treatment.Process data are used for a side-by-side analysis of the primary outcome.Verbal responses of the participants were gathered by the trainer (PV) both during and after training to provide qualitative insights to above-mentioned data. At the end of the second day of training, nurses were asked an open-ended question how they experienced the video training.For analyses, we used descriptive statistics and inferential statistics. All data were first tested for normality by a Kolmogorov-Smirnov test, a Q–Q plot and Levene’s test.2 test or Fisher’s exact test, when appropriate. Normally distributed continuous data were tested with the independent samples Students’ t-test and in case of skewed data, with the independent samples Mann-Whitney U test. Data were analysed with R Statistics (V.1.0.153) and SPSS .Categorical variables were expressed as n (%). Continuous normally distributed variables were expressed by their mean and SD, not normally distributed data by their median and minimum and maximum range for skewed distributions. To test groups, categorical variables were tested using the Pearson’s χMethods of Hussey and Hughes (2007) were used for power calculation for the main outcomes, with 16 time periods and 13 clusters with at least one observation per time period. With an alpha of 0.05, a power of ≥0.8 can be obtained for increase in proportions from 0% to ≥15% or 15% to ≥42%.The research protocol was approved by the medical ethical committee of the AMC Hospital on January 6, 2017. Data were collected for routine quality control by PV in the role of staff advisor on quality and patient safety. Other than the indication for pain behaviour observation and the duration of communication disorders, no individual patient data were collected.The study was conducted in 2017 from February 27th to September 29th. A total of 835 individual patient files were evaluated for patients eligible for pain measurement with the REPOS. This resulted in the inclusion of 88 patient files (639 patient days) for analysis of our primary endpoint. The frequencies of indications for the use of the REPOS are shown in During the study period, 68 nurses were employed at the Neurocentre, of which 62 were included in the study. Most nurses (51.4%) had an Associate degree (or similar) and 52.9% had less than 5 years of experience in neuroscience nursing. Further characteristics are shown in The proportion of shifts in which trained nurses cared for eligible patients increased significantly from 0% at start of the study to 83% at the end of the study .All trainings were held at the end of the day shift and were held on two consecutive days, except for cluster 10 in which training days were 1 day apart. Nurses were interested in the training and eager to learn about the REPOS, often asking the trainer when they would be scheduled for training. Some clearly stated they were waiting for the training before they would use the REPOS. Reactions to the training were generally positive. Frequently mentioned quotes during the debriefing of the video training were as follows:‘The REPOS is not complicated, but it requires some practice’‘I am able to use the REPOS right away’‘The videos are good for practice, because we can rewind and pause the behaviour’‘It is difficult to rely on something  that is so subjective’‘I find it hard to determine when I should use the REPOS’Participants found the nuances in word choice  the most difficult and much of the discussions during training were on the interpretation of the pain behaviours as described by the original designers of the scale. This was an important aspect of the training though, as it contributed to good inter-rater agreement.Planning of biweekly training based on existing working schedules proved logistically complex. As more nurses were trained, it became more difficult to find 2 days were enough untrained nurses would be present. It also proved difficult to start the training on time, as it was planned at the end of the day shift. The training had a median duration of 85 min (85–90) per training, during which a median of 14 videos (10–15) were observed. Videos were played one to three times (median 1) before a substantial inter-*rater agreement (kappa ≥0.67) was achieved.The REPOS was documented 138 times for 36 (41%) eligible patients, of which 48 (35%) were measured by trained nurses. The proportion of nurses that at some point during the study period used the REPOS at least once for eligible patients increased gradually from 4  to 24 (45.3%) at the end of the study , with a median of two times (1–33). Four nurses were responsible for 62% of all REPOS measurements and 51% of all REPOS measurements were performed in 8% (n=7) of all eligible patients.In total, there were 96 nursing shifts  with at least one REPOS measurement. Overall, the proportion of cumulative shifts in which the REPOS was used (when required) decreased from 14% at baseline to 6% at the end of the study . The OR of cumulative shifts with versus without a REPOS measurement compared with baseline increased during time period 1 through 6, but declined again after that . These cIn 16  patient days, the REPOS measurement was compliant to local hospital protocol (≥1 REPOS measurement per 12 hours). The proportion of compliant patient days did not change significantly over the course of the study, ranging from 0% to 16% (in T6).During the study, all nurses cared at least one shift for eligible patients, with a median of 27 shifts (1–57). The chance of exposure to an eligible patient fluctuated due to varying prevalence and started to decrease drastically after T7. In the first three time periods, an average of 166 REPOS measurements was required, whereas in the last three time periods an average of 33 REPOS measurements were required. In time period 14 (18–22 weeks), only eight REPOS measurements were required. This decrease in chance for practical application of acquired skills and knowledge may (in part) have attributed to decline of the use of the REPOS. The number of required and performed REPOS measurements, both cumulative and per time period, are shown in On average, the questionnaire was completed by 55% of the employed nurses per time period of 2 weeks. The completion rate decreased over the duration of the study from 76% to 39% .At the start of the study, 97% of the nurses that completed the questionnaire considered themselves 'competent' to 'very competent' in recognising and measuring pain in patients who are able to communicate adequately. This increased to 100% at the end of our study. For patients that require pain behaviour observation, 86% of the nurses considered themselves 'competent' to 'very competent' at the start of the study, which increased to 93%.During the study, there was one measurement of one nurse (0.3%) with a negative attitude towards pain measurement (NPBS >12). All other time periods there was no negative attitude among nurses. The NPBS did not change significantly during the study.From the 361 responses to the questionnaire, the participants agreed or strongly agreed 300 (83.1%) times with the statement ‘my colleagues find pain assessment an important part of the nursing profession’. In 94 responses (17.7%), the participants agreed or strongly agreed with the statement ‘I am unable to measure pain in patients who can’t communicate well or are severely confused due to lack of time or increased workload’. In 87 (24.1%) of the responses, they were neutral on this statement and in 180 (49.9%) they disagreed or strongly disagreed. For the statement ‘nurses have no influence on the treatment of pain’, nurses disagreed in 349 (96.7%) of their responses.In this evidence-based quality improvement study, we aimed to evaluate an educational implementation strategy to implement a pain behaviour observation scale. For this purpose, we used a stepped-wedge cluster design within one nursing team, expecting the risk of contamination to be of positive influence on the speed of implementation. Despite a consistently executed video training, where inter-rater agreement was obtained within clusters, our aims for implementation were not achieved. Though there was a significant increase in the proportion of trained nurses that cared for patients that required pain behaviour observation with the REPOS, the actual use, which is equivalent to behaviour in our view, decreased during the study period.We chose this single-component implementation strategy because our nurses explicitly asked for education, which is quite common among healthcare professionals when there is a need to change practice or implement scientific innovations. Though we are aware of the positive impact of motivational strategies, we deliberately wanted to evaluate the effect of education alone and to determine whether we should acknowledge healthcare professionals’ wishes for educational strategies in future implementation projects.The process data in this study provides insight in mechanisms that may have prevented nurses from using the REPOS more frequently. The results of the NPBS show, for example, that there was no negative attitude towards pain measurement in general and pain behaviour observation in particular. The questionnaire results show that lack of time or increased workload was not a barrier for pain measurement or behavioural pain observation. This is in accordance with studies on ‘care left undone’ during nursing shifts, which show that pain management and treatment are least likely to be reported as missed.Data on the provided training show that limited repetition of videos (maximum three times) were needed to acquire a substantial agreement among the nurses. This indicates that the videos were suited for acquiring basic skills to use the REPOS for pain behaviour observation. In order to maintain and improve these skills, it seems that practicing with actual patients is important. In at least six time periods, both the number of individual patients and the number of required REPOS measurements were very low, down to 4 required REPOS measurements per week in time period 14. During the study, the chance for nurses to be exposed to eligible patients decreased and as such the chance of nurses practicing their acquired skills decreased as well. After video training, the nurses were eager to practice, but for some nurses several weeks passed before they got the first opportunity to use the REPOS.It is noticeable that most REPOS measurements were performed by the same group of nurses. These nurses used the REPOS before training and continued to do so after training. This may indicate that individual motivation is more important than mere training.The qualitative insights gathered during and after training also indicate that nurses find it hard to indicate when a patient requires a REPOS measurement instead of other instruments. This is also reflected by the fact that more than half of the REPOS measurements were performed in only 8% of the eligible patients. This suggests that once a nurse starts using the REPOS others may follow, but if nobody starts using it the patient receives no form of pain assessment.The choice for a stepped-wedge cluster design within a single nursing team, whereby multiple measurements were done by the same nurses, has shown some limitations in this study. Due to the decrease in the actual use of the REPOS, formal analysis using a generalised mixed model or generalised estimation equation was not possible. Therefore, we analysed between and within baseline and every time point towards an allowable statistical procedure. Another limitation of this study was that actual knowledge and skills, obtained at the end of training, was not consistently measured. We are therefore unable to prove that the training itself guaranteed the skills and knowledge needed in daily nursing care. In future studies, a standardised test reflecting learning points of the training should be incorporated in the measurements. The feedback at the end of the training was generally positive, but this may have been due to interviewer bias as the evaluation was done by the trainer himself. In future, similar quality improvement studies we suggest to perform a barrier and facilitator analysis to determine both required training forms and skills measurement.This study shows that education alone may not be effective when implementing an evidence-based quality improvement. Pain behaviour observation for non-communicative patients with acquired brain injury may be more complicated than merely providing knowledge and (simulated) practice. Future implementation projects or research should include an extensive assessment of potential barriers  and facilitators in order to adequately select a motivational strategy alongside education.


The aim of this study was to compare the pain severity, health-related quality of life (HRQoL), and risk of continue having pain with prognostic risk scores (PRS), between patients referring greater trochanteric pain syndrome (GTPS) and chronic low back pain (CLBP). n = 51) and CLBP (n = 51) groups. The primary outcome was pain severity which was assessed with the Spanish version of the Graded Chronic Pain Scale (GCPS). The secondary outcome was the HRQoL which was measured using the Spanish version of EuroQoL Five Dimensions and Five Levels (EQ-5D-5L) as well as the PRS.  A descriptive, cross-sectional design using nonprobability convenience sampling was performed. A total sample of 102 patients were recruited from two primary health-care centers and divided into GTPS ( Significant differences (P<0.05) were found within both groups in the pain severity global score with a medium effect size showing greater values for the CLBP group with regards to the GTPS group. The PRS in both groups did not show statistical differences (P>0.05). Nevertheless, subjects referring CLBP showed greater levels in the PRS than patients with GTPS. Comparing both groups, the HRQoL showed statistical differences (P<0.05) in the “pain/discomfort” domain in the CLBP group with respect to the GTPS group, but not in the other domains.  Patients who suffered from CLBP showed greater pain severity and HRQoL discomfort with regard to patients with GTPS. Despite greater scores for CLBP, the PRS did not seem to be different between both conditions. Worldwide, chronic low back pain (CLBP) may be considered as one of the main musculoskeletal conditions, which causes disability for the life years . CLBP isRecently, the greater trochanteric pain syndrome (GTPS) appeared as a common nonosteoarthritic hip condition reported usually in the primary health-care services –11. ThisIndeed, GTPS comprised patients' substantial proportion referred from primary health care in order to evaluate CLBP. Primary care physicians should be able to stablish an early diagnosis and prognosis in order to reduce costly patient referrals and avoid unnecessary surgery , 14. GTPA descriptive, cross-sectional design using nonprobability convenience sampling was performed. All participants were recruited since September 2016 to February 2017 and diagnosed as GTPS or CLBP by the referenced general practitioner from two primary health-care centers in Madrid, Spain, and were derived to the physical therapy unit. All the subjects gave their written informed consents. This study was accepted by the Southeast Local Research Committee of the Primary Health Care Management Code 16/15). The reporting of the study followed the “STrengthening the Reporting of OBservational studies in Epidemiology” (STROBE) guidelines [. The repThe inclusion criteria for the present study were (1) patients referring low back pain , 6 or (2The exclusion criteria were (1) presence of other musculoskeletal injury, neurological, or systemic condition that could affect balance/gait , (2) cogA sociodemographic questionnaire containing gender, age, height, weight, civil state, level of education, and pain intensity was self-reported by the study participants.Pain Severity. The pain severity was assessed by means of the Spanish version of the Graded Chronic Pain Scale (GCPS). This scale is a self-reported instrument consisting of two subscales; the first scale evaluates the pain intensity, and the second scale assesses the perceived disability. The scale is formed by a total of 8 items, 7 of them are 11 points as Likert format, and the other item evaluates the perpetuation of pain, asking the number of pain days in the previous 6 months. The Spanish version of the GCPS has proven to be a valid and reliable instrument for assessing the severity of chronic pain. Concretely, high internal consistency (Cronbach's α = 0.87) and intraclass correlation coefficient (ICC = 0.81) have been described [escribed . The totescribed .Health-Related Quality of Life (HRQoL). It was measured by the Spanish version of EuroQoL Five Dimensions and Five Levels (EQ-5D-5L). This self-reported questionnaire has been widely used in the literature to report perceived health quality of life in many conditions and translated into 130 languages [Sum Score that it is a severity index obtained with the summation of the levels in each dimension of the instrument, subtracting 5 points and multiplying the result by 5. It results on a 0-to-100 range new scale where more points mean more severity. Another way to interpret the results on the EQ-5D-5L is by means of the Index (EQ-Index); this approach compares the values in the five dimensions with 3125 different hypothetic health states adjusted by country population, being the “0” value assigned to death and “1” to the perfect health status. Values less than 0 are considered in the index, being those statuses interpreted as “worse than being dead.”anguages –21. The EQ-VAS) in which subjects are asked to self-rate their health, from 0 “The worst health you can Imagine” to 100 “The best health you can imagine.” Finally, the Spanish EQ-5D-5L presented minimal floor and ceiling effects (<3%) and a Cronbach's α of 0.86 [The second part of the questionnaire is a vertical 20 cm Visual Analogue Scale ( of 0.86 .Prognostic Risk Score (PRS). The PRS is an instrument to determine the probability of having pain in the next years. This tool is based on the perspective of a chronic pain continuum health status, nor a unique state of the subjects who referred pain during 3 or 6 months . It was calculated for each subject with the rules proposed by Von Korff and Miglioretti [lioretti  and usedlioretti , 25 withlioretti . In addilioretti , 25.r of 0.74 [The average pain intensity in the last seven days was measured by means of a Visual Analogue Scale (VAS). This scale consists of a horizontal 100 mm line, in which the patients must indicate their pain intensity. At the left side of the line appears the text “no pain” and at the right side appears “worst possible pain.” This instrument had demonstrated its validity and reliability measuring the pain intensity, showing ICCs among pain scales from 0.65 to 0.88 with a median  of 0.74 , 27.∗Power 3.1.9.2 for Mac OS X  to determine a sufficient sample size considering a one-tailed t-test with two groups and a medium effect size to achieve clinically relevant differences (d = 0.50) in the primary variable (pain severity) to obtain a statistical power of 80% using an α error of 0.05. Based on the aforementioned assumptions, we estimated a sample size of at least 102 subjects [Sample size was calculated with the Gsubjects .P value < 0.05. Parametric tests were used because the sample size (greater than 30 subjects per group) was sufficient to be supported by the central limit theorem [t-test for independent samples was used to compare the quantitative outcomes between subjects with GTPS and CLBP, and the chi-square test was used for the categorical ones. Furthermore, the effect sizes of the primary outcomes were calculated based on the following formula d size effect may be interpreted as slight (d lower than 0.20), fair (d from 0.20 to 0.49), moderate (d from 0.50 a 0.79), or large  [Data analyses were performed on SPSS for Mac OS X, Version 22.0  with a 95% confidence interval (CI) and considering statistically significant differences if  theorem . The conn = 51) and another group of patients with CLBP (n = 51). Sociodemographic variables did not show any statistically significant difference (P > 0.05) between both groups. Descriptive variables of both groups are presented in Tables A total sample of one hundred and two subjects were analyzed in this study and divided into two groups, one group of patients diagnosed of GTPS n = 5 and anott-test, a statistical significant difference (P < 0.05) was found between both groups in the pain severity global score with a medium effect size  showing greater values of the CLBP group with regard to the GTPS group. The results of the comparison for the other quantitative variables are presented in Regarding Student's The chi-square test comparing the PRS in both groups did not show statistical differences, as presented in P < 0.05) in the “pain/discomfort” domain of the CLBP group with respect to the GTPS group, but not in the other domains, as presented in Moreover, the chi-square test comparing the HRQoL between groups showed statistical differences (To the authors' knowledge, this may be considered as the first study comparing both common conditions, CLBP and GTPS. CLBP seemed to show greater pain severity and HRQoL discomfort with respect to GTPS. The prognostic risk seemed to be similar between both musculoskeletal pathologies. Despite this, there is a tendency towards poorer quality of life, higher pain severity, and prognostic risk in the patients who suffer from CLBP with regard to patients who suffer from GTPS. These findings coincide with prior research about musculoskeletal conditions related to quality of life and pain severity , 12, 13.Here, we show a challenge in the differential diagnosis between both conditions which may commonly be considered as comorbidities in patients referred to primary health-care and physical therapy units , 12–14. Although both CLBP and GTPS conditions may be focused as main musculoskeletal disorders for treating in primary health-care environments , 14, patSeveral limitations and methodological aspects should be taken into account regarding the present research. First, physical factors, such as pressure pain thresholds , recurrePatients who suffered from CLBP showed greater pain severity and HRQoL discomfort with regard to patients with GTPS. Despite greater scores for CLBP, the PRS did not seem to be different between both conditions.