Pain Palliation Research Articles

Acceptability of bispectral Index monitoring in end-of-life care for dementia.

Assessing consciousness might benefit the care for people with Alzheimer's disease and other types of dementia at the end of life by indicating distressing symptoms and moments of awareness. This could guide symptom control and increase interaction with the person with dementia. This study aims to investigate the acceptability of a biosignal measurement of consciousness, the Bispectral Index monitoring (BIS), for persons with dementia at the end of life. Qualitative study using focus groups and interviews with demonstrations of BIS monitoring, with 17 individuals with dementia and 24 family caregivers. Qualitative content analysis was based on the theoretical framework of acceptability. People with dementia did not find BIS monitoring bothersome, yet acceptability varied across participants and situations. Family caregivers considered BIS acceptable for medical situations such as palliative sedation and pain assessment. Perceived effectiveness, ethicality, and usefulness considerations underpinned reasons and concerns around acceptability. Potential end-users expressed diverse attitudes towards BIS monitoring in dementia end-of-life care. If BIS or similar technologies are to be implemented in the future, care must be taken to ensure that the device has sufficient added value, that the person with dementia and family are well informed, and that the technology does not replace human care. Future research should investigate its efficacy and feasibility in the situations that were deemed acceptable.

Barriers to opioid use in the Arab world.

The Arab world consists of 22 countries, representing 5.5% of the world's population. Morphine consumption accounts for less than 1% of the world's consumption. This is the first study to identify barriers to opioid use in the Arab world. This study aimed to investigate the barriers to opioid use in pain management in the Arab world. Online survey was developed to investigate barriers to governance, prescribing, distributing, dispensing and administering, as well as educational barriers in the Arab world. The questionnaire was sent via email and a mobile app to one expert physician in pain management and one licensed pharmacist from each Arab country. With the exception of Tunisia, Djibouti and Comoros, 34(77%) participants from 19 Arab countries answered the survey. Most countries lack local opioid production, necessitate special licenses for physicians, and restrict opioid prescribing to medical specialists. Special prescription forms are mandated, and pharmacists lack the authority to correct prescription errors or accept refill or verbal orders on opioids. Storage requirements for empty ampoules and prescriptions are enforced. Nurses are not allowed to carry opioids during home visits, and only first degree relatives can collect opioids for patients. Furthermore, the integration of palliative care and pain management curricula into pharmacies and medical schools is lacking. There is a wide range of regulatory and other barriers to opioid use in the Arab world. There is a substantial need for regulatory review and reform, as well as for educational initiatives, in most Arab countries.

Effect of endoscopic ultrasound guided celiac plexus block on the palliation of pain in chronic pancreatitis (EPOCH Trial): study protocol for a randomized multicenter sham-controlled trial {1}

BackgroundCeliac plexus block has been commonly utilized for the treatment of chronic pancreatitis-associated abdominal pain. Prospective studies suggest efficacy in 30 to 50% of patients, although no randomized sham-controlled trials have been performed. The objective of this study is to assess the effect of endoscopic ultrasound (EUS)-guided celiac plexus block on abdominal pain in patients with documented chronic pancreatitis. MethodsThis is a two-arm randomized sham-controlled trial with blinded evaluators. The study will be conducted at multiple academic sites in the United States who are members of the United States Pancreatic Disease Study Group (USPG). Patients referred for EUS to exclude chronic pancreatitis as a cause of abdominal pain as well as those with established painful chronic pancreatitis undergoing EUS for another indication will be eligible. At the time of EUS with confirmation of chronic pancreatitis by standard EUS diagnostic criteria, patients will be randomized to either celiac plexus block or sham whereby an anesthetic and steroid combination will be injected into the celiac plexus or saline will be injected into the gastric lumen with the same type of needle as used for celiac plexus block, respectively. The main outcome measure will be a 50% reduction in abdominal pain using the Brief Pain Inventory Short Form (BPI-SF) at 1 month post-intervention. A number of secondary outcomes will be measured including visual analog scale (VAS), Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) pain scores, and quality of life using a pancreas-specific validated measure (PANQOLI).DiscussionIn this study, the effect of celiac plexus block on abdominal pain in patients with chronic pancreatitis will be compared to a sham intervention. This randomized trial will offer a definitive assessment of the role of celiac plexus block for the treatment of abdominal pain in this setting.Trial registration {2}ClinicalTrials.gov NCT 06178315. Registered on December 21, 2023

Use of Essential Medicines for Pain Relief and Palliative Care: A Global Consensus Process

ContextThe WHO Model List of Essential Medicines includes 24 medications under the section Medicines for Pain and Palliative Care (EML). The Lancet Commission on Pain and Palliative Care developed the Lancet Essential Package (LEP), including 35 medications designed to alleviate serious health-related suffering worldwide. ObjectivesThis study aims to provide recommendations on the appropriate use of essential of medicines in palliative care. MethodsThe global palliative care community was invited to submit guidelines, of which 19/22 were selected. Data was extracted on initial dose, frequency, and maximum daily dose for medications in the LEP and in the WHO EML. For medications where guidance was not available or information differed, a 2-round Delphi process was conducted with 70 experts across regions and income levels. Consensus was set to ≥70% agreement. ResultsConsensus in the guidelines was identified for 24 medications on three parameters. Open questions (mostly on maximum daily dose) were included in the Delphi. 63 experts from 49 countries responded (RR = 90%). No consensus was achieved for the maximum daily dose for nine medications. Significant disparities in medication availability were noted between high-income and low/middle-income countries. ConclusionWe were able to partly achieve our goal, with limited evidence and a wide range of clinical practice described by the experts. This highlights an important gap in critical information which affects mostly the provision of palliative care at the primary care. Both limited availability and lack of training on the adequate use of essential medications may affect how clinicians manage symptoms, possibly relying on personal experience or trial and error, rather than evidence-based information.

Distributed Opioids in Morphine Equivalent: A Global Measure of Availability for Palliative Care

ContextEstimates of serious health-related suffering (SHS) demonstrate immense unmet need for palliative care, predominately in low- and middle-income countries (LMICs). Because opioids are essential medicines in palliative care (PC), measuring their availability can be used to evaluate the capacity of health systems to meet need. ObjectivesPresent the methodology for calculating Distributed Opioids in Morphine Equivalents (DOME)— introduced in the Lancet Commission on Global Access to Palliative Care and Pain Relief report - and how it can be used as a simple indicator to quantify unmet pain relief and PC need. MethodsUsing International Narcotics Control Board (INCB) data, DOME applies relative potency estimates to convert the annualized quantities of clinically appropriate opioids procured by a country to oral morphine equivalent milligrams. To quantify unmet need, an expert group proposed health condition-specific estimates for opioid need and used available data on the burden of SHS to posit the annual opioid quantity required by country for symptomatic treatment of pain or breathlessness. Comparing this to DOME generates DOME%SHSNEED, the proportion of opioids needed for palliative care that can be fulfilled by the opioid procured by a country during a year. ResultsDOME and DOME%SHSNEED can be used to measure, over time, the capacity of countries to meet PC need, as a key component of universal health coverage. Identifying access gaps disproportionately impacting LMICs can promote better health system performance and guide countries and institutions in policy making. ConclusionDOME and DOME%SHSNEED can be used to monitor health system progress to redress disparities and promote access to medically indicated opioid therapy in palliative care.

Report from the Third Conference in Zielona Góra: palliative medicine, supportive care, and pain management

Report from the Third Conference in Zielona Góra: palliative medicine, supportive care, and pain management

Epidural Analgesia for Palliative Pain Management for A Patient with An Advanced Stage Prostate Cancer: A Case Report

Introduction: Patients with advanced-stage cancer should be able to stay at home with their families without suffering from pain. This case report aims to discuss challenges in pain management of a patient with bone metastasis of prostate cancer who received epidural analgesia at home. Challenges were related to the patients, health professionals, and system. Understanding each factor will bring insights to develop a workable pain management program in the palliative setting. Case Presentation: A 66-year-old male was diagnosed with left sacroiliac joint pain due to metastatic prostate cancer. After a three-year history of prostate cancer and ineffective chemotherapy, the patient complained of pain in the left hip that did not improve with conventional medications (paracetamol, tramadol, and Morphine Sustained Release/MST). In response, the consideration of an epidural implant emerged as a potential solution, offering the prospect of home-based care and autonomous medication administration through an epidural continuous block with intermittent drug injection. Conclusions: This case highlights home-based interventional pain management for cancer, addressing challenges at the patient, health professional, and system level. Overcoming these challenges requires a multidisciplinary approach and robust institutional policies. The insights gained offer valuable lessons for hospitals aiming to enhance the competence of pain and palliative care teams and establish comprehensive support systems in hospital and home settings.

Pharmacopeial parametric release strategy in microbiological quality control of radiopharmaceuticals

Nuclear medicine is used to assess body functionality at various levels of biological organization and is increasingly employed for both diagnostic and therapeutic purposes. Nearly 5% of radiopharmaceuticals are used therapeutically, whereas approximately 95% are used for diagnosis. Diagnostic radiopharmaceuticals are generally considered safe because they are administered in subpharmacological doses, and the radiotracer components are employed in minimal doses. Consequently, the radiation exposure to the body during nuclear medicine investigations is typically low. However, when radiopharmaceuticals are used for therapeutic applications such as tumor ablation and bone pain palliation, the emitted radiation is highly localized and potent. Radiotracers and radiation doses are more carefully selected for young patients, as the radiation-induced risk of adverse health effects is greater in children than in adults. Radiopharmaceutical preparations should adhere to the established standards of pharmacopoeia worldwide to ensure safety and efficacy. Adherence to current good manufacturing practices, sterility, and good radiation practices are prerequisites for ensuring effective quality assurance and quality control systems during radiopharmaceutical preparation. The quality control test parameter for radiopharmaceuticals primarily involves physicochemical and biological tests. However, significant concerns exist regarding the biological testing of radiopharmaceuticals, necessitating their parametric release. The time-intensive traditional sterility test, bacterial endotoxin test, and rabbit pyrogen tests have been critical quality control issues due to the short half-lives of most radiopharmaceuticals, as they should be dispensed at the earliest to ensure optimal diagnostic/therapeutic benefit. Therefore, manufacturers of radiopharmaceuticals, dispensers, and nuclear medicine specialists should be cognizant of the issues posed by biological quality control as a primary obstacle to ensuring consistent quality through parametric release from a compendial test method standpoint.

Targeted Radionuclide Therapy for the Treatment of Metastatic Bone Disease: A Retrospective Analysis in Moscow, Russia

Introduction: Metastatic bone disease (MBD) is a common complication of advanced cancer, causing significant morbidity and negatively impacting patients' quality of life. Targeted radionuclide therapy (TRT) has emerged as a promising treatment modality for MBD, offering targeted delivery of therapeutic radiation to bone metastases while minimizing damage to healthy tissues. Methods: A retrospective cohort study was conducted at leading oncology centers in Moscow, Russia, between 2018 and 2023. Patients with MBD who received TRT with either Strontium-89 or Samarium-153 were included. Data on patient demographics, primary tumor type, number of bone metastases, pre-treatment pain scores, performance status, and survival outcomes were collected. Results: A total of 150 patients were included in the study (mean age 62 years, 55% female). The most common primary tumor types were prostate (35%), breast (25%), and lung (15%). The median number of bone metastases was 5 (range 1-20). Pre-treatment pain scores were high (median 7 on a 0-10 scale). A significant reduction in pain scores was observed post-TRT (median 3, p<0.001). Overall survival at 1 year was 75%, with a median survival of 18 months. Favorable prognostic factors included a lower number of bone metastases, good performance status, and absence of visceral metastases. Conclusion: TRT is a safe and effective treatment option for patients with MBD in Moscow, Russia, offering significant pain palliation and improved quality of life.

Past trends and future projections of palliative care needs in Chile: analysis of routinely available death registry and population data

BackgroundThe number of people with palliative care needs is projected to increase globally. Chile has recently introduced legislation for universal access to palliative care services for patients with severe and terminal illnesses, including non-cancer conditions. We aimed to estimate the number of people affected by serious health-related suffering and need for palliative care in Chile to 2050.MethodsWe used data on all deaths registered in Chile between 1997-2019 and population estimates for 1997–2050. We used Poisson regression to model past trends in causes of death adjusted by age, sex and population estimates, to project the number of deaths for each cause from 2021 to 2050. We applied the Lancet Commission on Palliative Care and Pain Relief weights to these projections to identify decedents and non-decedents with palliative care needs.ResultsPopulation palliative care needs in Chile are projected to increase from 117 (95% CI 114 to 120) thousand people in 2021 to 209 (95% CI 198 to 223) thousand people in 2050, a 79% increase (IRR 1.79; 95% CI 1.78–1.80). This increase will be driven by non-cancer conditions, particularly dementia (IRR 2.9, 95% CI 2.85–2.95) and cardiovascular conditions (IRR 1.86, 95% CI 1.83–1.89). By 2050, 50% of those estimated to need palliative care will be non-decedents (not expected to die within a year).ConclusionsChile will experience a large increase in palliative care needs, particularly for people with dementia and other non-cancer conditions. Improved availability of high-quality services, expanded clinician training and new sustainable models of care are urgently required to ensure universal access to palliative care.

Interdisciplinary Pain Board for Managing Patients with Palliative Care Needs and Substance Use Disorder: A Pilot Study.

Context: Patients with cancer-related pain and concurrent substance use disorder (SUD) present a unique set of challenges for palliative care clinicians. A structured forum for interdisciplinary collaboration is needed to effectively manage this complex population. Objectives: Describe the feasibility and acceptability of a palliative care Complex Pain Board (CPB), an interdisciplinary team meeting to provide concrete care recommendations for patients with cancer-related pain and concurrent SUD and/or psychosocial complexity. Methods: We conducted a retrospective analysis of cases presented at CPB between May 2021 and June 2022 and a cross-sectional analysis of CBP participant surveys. Results: Among 28 cases included for analysis, gastrointestinal cancers (n = 7, 25.9%) and multiple myeloma (n = 5, 18.5%) were the most frequent cancer diagnoses. Primary reasons for referral were SUD (n = 22, 78.6%) and provider/team distress (n = 13, 46.4%). The most frequent recommendations made at CBP were encouraging interdisciplinary collaboration (n = 18, 64.3%), maintaining healthy boundaries (n = 15, 53.6%), and SUD management (n = 13, 46.4%). Of 14 scheduled meetings, most meetings involved the presentation of ≥1 cases (n = 12, 86%). Among 40 CBP participant surveys, most attendees (n = 38, 95%) were likely or highly likely to continue to attend. Conclusion: CPB is a feasible and acceptable intervention that allows for palliative care clinicians to collaborate and receive interdisciplinary team feedback and peer support on the management of patients with cancer-related pain and concurrent SUD and/or psychosocial complexity in the ambulatory care setting. Key Message: A regular, interdisciplinary team meeting (CPB) is a feasible and acceptable intervention to help palliative care clinicians manage challenging cases involving patients with cancer and concurrent SUD and/or psychosocial complexity.

Keeping it "straight": how to do spinal tumor ablation with vertebral augmentation

This technical review provides a comprehensive overview of spinal tumor ablation and vertebral augmentation. These percutaneous minimally invasive procedures offer significant survival and palliative pain relief benefits for patients with pathological vertebral fractures. Vertebral augmentation, which includes vertebroplasty and kyphoplasty, involves injecting cement into fractured vertebral bodies to restore height. While vertebroplasty involves the direct injection of cement into a fractured vertebral body, kyphoplasty involves using a balloon to create a low-pressure cavity to allow for cement injection to restore the vertebral body height. Over the years, this technique has evolved into a straightforward process, though it presents certain technical challenges discussed in this article.

Immersive Virtual Reality for Pain and Anxiety Management Associated with Medical Procedures in Children and Adolescents: A Systematic Review.

(1) Objectives: The purpose of this study was to investigate the studies that evaluate the effectiveness of immersive virtual reality (VR) as a distraction technique for pain and anxiety associated with medical procedures in children and adolescents. (2) The methods involved a systematic review of randomized controlled trials retrieved from databases in health sciences (Pubmed, CINHAL, Scopus, WOS, ProQuest, Cuiden Plus, InDICEs-CSIC). PRISMA guidelines were followed. (3) Results: Twelve trials were included. Four involved venipuncture, four involved surgical procedures, one involved vaccination, one involved burn care, one involved secondary wound closure, and the last one involved subcutaneous port access. (4) Discussion: Children who undergo medical procedures often experience pain and anxiety, which affects their physical condition and their relationships with caregivers and health professionals. Immersive VR is an effective alternative to medications to help in these cases. No author found statistically significant differences against the use of VR for distraction and palliation of pain and anxiety, which seems to be more effective at a younger age. It is important to personalize the immersive VR experience and equipment. (5) Conclusions: VR, when used with analgesics and anesthetics, appears effective in managing pain and distress caused by medical procedures.

A nationwide neurosurgical inter-disciplinary service for cancer-related refractory pain

PurposeNeurosurgical ablative procedures, such as cordotomy and cingulotomy, are often considered irreversible and destructive but can provide an effective and individualized solution for cancer-related refractory pain, when all other approaches have been unsuccessful. This paper provides an in-depth exploration of a novel approach to managing refractory cancer pain. It involves an interdisciplinary team led by a neurosurgeon at a renowned national referral center.Methodsa retrospective analysis of the medical records of all sequential patients who underwent their initial evaluation at our interdisciplinary refractory cancer pain clinic from February 2017 to January 2023.ResultsA total of 207 patients were examined in the clinic for a first visit during the study period. All patients were referred to the clinic due to severe pain that was deemed refractory by the referring physician. The mean age was 61 ± 12.3 years, with no significant sex difference (P = 0.58). The mean ECOG Performance Status score was 2.35. Conservative measures had not yet been exhausted in 28 patients (14%) and 9 patients were well controlled (4%). Neurosurgical ablative procedures were recommended for 151 (73%) of the patients. Sixty-six patients (32%) eventually underwent the procedure. 91 patients (44%) received a negative recommendation for surgery. Thirty-five patients (17%) were referred for further invasive procedures at the pain clinic.ConclusionAn Interdisciplinary cooperation between palliative care specialists, pain specialists, and neurosurgeons ensures optimal patient selection and provides safe and effective neurosurgery for the treatment of refractory cancer-related pain.

131I-mIBG Therapy in the Management of High-Risk Neuroblastoma: A Retrospective Study from a Tertiary Level Hospital in South India

Abstract Introduction Neuroblastoma is the most common extracranial solid tumor in childhood. The data on the treatment experience with 131iodine-meta-iodo-benzyl-guanidine (131I-mIBG) and clinical outcome data are meager from India. Objectives This article studies the efficacy and treatment outcomes in patients treated with 131I-mIBG in high-risk neuroblastoma. Materials and Methods The study group consisted of 201 consecutive patients (aged between 1 and 15 years) with biopsy-proven neuroblastoma who underwent 131I-mIBG scans from 2012 to 2022. The majority of these children had a disease that was inoperable or had poor response to chemotherapy. Patients with positive scintigraphy were considered for therapy with 131I-mIBG. The findings were analyzed and correlated with the final diagnosis and outcomes obtained from survival during follow-up and reviewing patient records. Results Thirty-nine children, 22 males and 17 females, with a median age of 4 years had positive 131I-mIBG scintigraphy. Intra-abdominal primary lesions and osseous lesions were the most common sites of uptake on 131I-mIBG scan. Of these, 13 had upfront chemotherapy and 26 had surgery followed by chemotherapy. All the patients underwent therapy with 131I-mIBG. Fourteen patients had multiple therapies while the remaining 25 had only one therapy. Eight patients had no follow-up, and 13 had disease relapse. The remaining 18 had regression of disease which was confirmed by follow-up 131I-mIBG scintigraphy and with bone scintigraphy in patients with osseous metastases. Conclusion 131I-mIBG scintigraphy should be preferred in intermediate and high-risk neuroblastoma to know the extent of the disease and also for patient selection for early therapy with 131I-mIBG. It holds significant utility in the management of metastatic neuroblastoma, facilitating palliative pain relief and tumor size reduction in inoperable or metastatic disease.

Re-re-irradiation for palliation: knowns, unknowns, and next steps.

With improving rates of survival among patients with metastatic malignancies, the request for palliative re-irradiation and re-re-irradiation continues to grow despite an absence of standardized guidelines. With only limited data regarding extra-cranial third-course palliative radiation, many radiation oncologists may feel uncomfortable proceeding with third-course irradiation of the same site. The review explores the available modern data regarding re-re-irradiation. A literature review identified four modern peer-reviewed studies investigating palliative, extra-cranial third-course irradiation with external beam radiation. These studies were retrospective, small, and heterogenous. While they reported comparable rates of pain palliation to first course irradiation and low rates of acute toxicity, interpretation is complicated by heterogeneous treatment parameters and insufficient reporting of cumulative dose equivalents and time intervals. With limited data available, it is critical to prioritize patient safety and quality of life in palliative radiotherapy. Patient selection should be meticulous, considering factors such as initial treatment response and predicted life expectancy. Conformal radiation techniques, strict immobilization, and daily image guidance should be employed to minimize toxicity to organs at risk (OARs). Long-term follow-up is essential for identifying and managing late toxicities effectively. Despite the scarcity of data, retrospective series suggest that extra-cranial third course irradiation can provide effective pain palliation comparable to first-course irradiation with tolerable rates of toxicity. However, careful consideration of patient prognosis and adherence to established principles of palliative radiotherapy are essential in decision-making. Further research and long-term follow-up are needed to refine treatment strategies and ensure safe and efficacious care delivery in this complex clinical scenario.

Emergency physicians' and nurses' perception on the adequacy of emergency calls for nursing home residents: a non-interventional prospective study.

A considerable percentage of daily emergency calls are for nursing home residents. With the ageing of the overall European population, an increase in emergency calls and interventions in nursing homes (NH) is to be expected. A proportion of these interventions and hospital transfers may be preventable and could be considered as inappropriate by prehospital emergency medical personnel. The study aimed to understand Belgian emergency physicians' and emergency nurses' perspectives on emergency calls and interventions in NHs and investigate factors contributing to their perception of inappropriateness. An exploratory non-interventional prospective study was conducted in Belgium among emergency physicians and emergency nurses, currently working in prehospital emergency medicine. Electronic questionnaires were sent out in September, October and November 2023. Descriptive statistics were used to analyze the overall results, as well as to compare the answers between emergency physicians and emergency nurses about certain topics. A total of 114 emergency physicians and 78 nurses responded to the survey. The mean age was 38 years with a mean working experience of 10 years in prehospital healthcare. Nursing home staff were perceived as understaffed and lacking in competence, with an impact on patient care especially during nights and weekends. General practitioners were perceived as insufficiently involved in the patient's care, as well as often unavailable in times of need, leading to activation of Emergency Medical Services (EMS) and transfers of nursing home residents to the Emergency Department (ED). Advance directives were almost never available at EMS interventions and transfers were often not in accordance with the patient's wishes. Palliative care and pain treatment were perceived as insufficient. Emergency physicians and nurses felt mostly disappointed and frustrated. Additionally, differences in perception were noted between emergency physicians and nurses regarding certain topics. Emergency nurses were more convinced that the nursing home physician should be available 24/7 and that transfers could be avoided if nursing home staff had more authority regarding medical interventions. Emergency nurses were also more under the impression that pain management was inadequate, and emergency physicians were more afraid of the medical implications of doing too little during interventions than emergency nurses. Suggestions to reduce the number of EMS interventions were more general practitioner involvement (82%), better nursing home staff education/competences (77%), more nursing home staff (67%), mobile palliative care support teams (65%) and mobile geriatric nursing intervention teams (52%). EMS interventions in nursing homes were almost never seen as necessary or indicated by emergency physicians and nurses, with the appropriate EMS level almost never being activated. The following key issues were found: shortages in numbers and competence of nursing home staff, insufficient primary care due to the unavailability of the general practitioner as well as a lack of involvement in patient care, and an absence of readily available advance directives. General practitioners should be more involved in the decision to call the Emergency Medical Services (EMS) and to transfer nursing home residents to the Emergency Department. Healthcare workers should strive for vigilance regarding the patients' wishes. The emotional burden of deciding on an avoidable hospital admission of nursing home residents, perhaps out of fear for medico-legal consequences if doing too little, leaves the emergency physicians and nurses frustrated and disappointed. Improvements in nursing home staffing, more acute and chronic general practitioner consultations, and mobile geriatric and palliative care support teams are potential solutions. Further research should focus on the structural improvement of the above-mentioned shortcomings.

Optimal production and purification of n.c.a.143Pr as a promising palliative agent for the treatment of metastatic bone pain

This study proposes the beta-emitting radioisotope 143Pr as a promising candidate for palliative treatment of metastatic bone pain due to its desirable physical decay characteristics. An optimized process was developed for the production and purification of non-carrier-added 143Pr using a medium flux research reactor. Calculations were performed to determine the optimal irradiation time and cooling period for irradiating 1 mg of natural cerium oxide to indirectly produce 143Pr through the decay of 143Ce. Following irradiation and cooling, extraction chromatography was employed to efficiently isolate 143Pr from the irradiated target material. A column containing Ln-resin was used along with nitric acid as the mobile phase and an optional oxidation step with NaBrO3/ascorbic acid to separate 143Pr from impurities such as 143Ce and 141Ce. Radionuclidic purity of over 99.995% was achieved as confirmed through gamma spectroscopy, demonstrating effective separation of 143Pr. Additional quality control analyses established the chemical and radiochemical purity of the purified 143Pr nitrate product. With a half-life of 13.6 days and maximum beta energy of 0.937 MeV, 143Pr exhibits favorable properties for palliative bone pain therapy. This study therefore provides a viable method for producing high-purity 143Pr through the optimized irradiation and purification processes described. Further investigation is warranted to explore potential clinical applications of 143Pr for palliation of metastatic bone cancer pain.

Dangerous Variation or Patient-Centered Care? Palliative Care and Pain Providers' Comfort, Experiences, and Approaches when Treating Cancer Pain With Coexisting Aberrant Behaviors.

Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain. We conducted telephonic semi-structured interviews with palliative care and pain medicine providers. Participants discussed their own comfort and experience level with identifying and managing ADB in patients with life-limiting illness. They were subsequently presented with a series of standardized scenarios and asked to describe their concerns and management strategies. 95 interdisciplinary pain and palliative care specialists were contacted; 37 agreed to participate (38.9%). Analysis of interview contents revealed several central themes: (1) widespread discomfort and anxiety regarding safe and compassionate opioid prescribing for high-risk patients, (2) belief that widely used risk-mitigation tools such as opioid contracts and urine drug screens provided inadequate support for decision-making, and (3) lack of institutional and organizational support and guidance for safe prescribing strategies. Most clinicians reported self-education regarding addiction and alternative prescribing/pain management strategies. Providers varied widely in their willingness to discontinue opioid prescribing in a patient with aberrant behavior and pain associated with life-limiting illness. Providers caring for patients demonstrating ADB and cancer-related pain struggle to balance safe prescribing with symptom management. Increased guidance is needed regarding opioid prescribing, monitoring, and discontinuation in high-risk patients.

Pembrolizumab and low-dose, single-fraction radiotherapy for patients with relapsed or refractory multiple myeloma: a prospective, single-centre, single-group, open-label, phase 2 pilot trial in the USA

Currently, the use of radiotherapy alone for people with multiple myeloma is limited to palliation of pain, pending fracture, and control of spinal-cord compression. Single immune-checkpoint inhibitors, such as anti-programmed death-1 (anti-PD1), have not been successful. We aimed to evaluate the activity and safety of the combination of pembrolizumab and low-dose, single-fraction, hypofractionated radiotherapy to treat patients with relapsed or refractory multiple myeloma. For this prospective, single-centre, single-group, open-label, phase 2 trial, we recruited patients with relapsed or refractory multiple myeloma from the Winship Cancer Institute (Emory University, Atlanta, GA, USA). Key inclusion criteria were aged 18 years or older, Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1, relapsed or refractory multiple myeloma as indicated by progression under International Myeloma Working Group (IMWG) criteria, and adequate candidacy for both pembrolizumab and radiotherapy. Baseline and post-treatment assessments were serial bone-marrow biopsy, peripheral blood collections, staging, serial serum and urine paraprotein analysis, serial PET-CT imaging, and a physical examination. On day 1, patients received hypofractionated 8 gray in 1 fraction (8 Gy/1 fx) radiotherapy to either symptomatic or progressing extra-osseous or osseous myeloma sites. Patients also received pembrolizumab (200 mg/kg intravenously) on day 2 or 3, then once every 3 weeks (±7 days) for 2 years or until progressive disease, unacceptable toxicity, withdrawal of consent, loss to follow-up, or death. Dose reduction and interruptions were not allowed. The primary outcome was acute toxicity defined as grade 3 or worse toxicity at 3 months within the radiated site when used in combination with pembrolizumab. All patients were analysed per protocol and included in safety analyses. This trial is registered on ClinicalTrials.gov (NCT03267888); it is completed and closed to accrual. 32 patients were screened between June 1, 2018, and Sept 2, 2022, and 25 were enrolled in the trial and treated on protocol. Of the 25 treated patients, 11 (44%) were female and 14 (56%) were male. 19 (76%) patients were White and six (24%) were Black or African American. Toxicity, as the primary outcome, was deemed to be acceptable as no grade 4 or 5 adverse events were observed. At 3-month follow-up, eight (32%) of 25 patients had treatment benefit (one had stable disease, three had partial response, two had very good partial response, and two had complete response). There was no grade 3 or worse radiation-related toxicity within irradiated volumes. One (4%) patient of the 25 who received combination treatment had a grade 3 pembrolizumab-related adverse event. There were no treatment-related deaths. Combination treatment of low-dose, single-fraction radiotherapy with pembrolizumab was safe, with early promise of response activity. Our approach could be an option for patients with relapsed or refractory multiple myeloma who have not responded to previous treatment. Larger trials to substantiate our findings are needed. Merck Sharp & Dohme.