Management of pain in cancer patients- lessons from practices during the COVID-19: a qualitative study of cancer care providers' perspectives.

BACKGROUND: The ongoing COVID-19 pandemic has impacted health systems globally and affected managing many chronic conditions, including cancer. This study aimed to explore the perceptions of multi-disciplinary cancer care providers on how cancer pain management was affected by the COVID-19 pandemic. METHODS: Participants were eligible if they were cancer care providers of any specialty and discipline from two tertiary hospitals in Australia. Data were collected using semi-structured interviews to explore cancer care providers' perspectives on cancer pain management within COVID-19. Thematic analysis of interview transcripts used an integrated approach that started with inductive coding before coding deductively against a behaviour framework called the COM-B Model, which proposes that 'capability', 'motivation' and 'opportunity' are requisites for any behaviour. RESULTS: Twenty-three providers participated. Five themes were developed and interpreted from the analysis of data, namely: "Telehealth enables remote access to cancer pain management but also created a digital divide", "Access to cancer pain management in the community is compromised due to the pandemic", "COVID-19 negatively impacts hospital resource allocation", "Patients were required to trade off cancer pain management against other health priorities" and "Hospital restrictions result in decreased social and psychological support for patients with cancer pain". CONCLUSIONS: The landscape of cancer pain management in the Australian health system underwent substantial shifts during the COVID-19 pandemic, with lasting impacts. Cancer care providers perceived the pandemic to have significant adverse effects on pain management across multiple levels, with repercussions for patients experiencing cancer-related pain. A more adaptive health system model needs to be established in the future to accommodate vulnerable cancer patients.

A home-based self-directed EEG neurofeedback intervention for people with chronic neuropathic pain following spinal cord injury (the StoPain Trial): description of the intervention.

STUDY DESIGN: Randomised controlled trial. OBJECTIVES: The objective is to describe an electroencephalography (EEG) neurofeedback intervention that will be provided in a randomised controlled trial for people with neuropathic pain following spinal cord injury (SCI): the StoPain Trial. In this trial, participants in the treatment group will implement an EEG neurofeedback system as an analgesic intervention at home, while participants in the control group will continue with the treatments available to them in the community. SETTING: University-based study in Sydney, Australia. METHODS/RESULTS: This manuscript describes the rationale and components of the EEG neurofeedback intervention designed for individuals with SCI neuropathic pain and intended for home-based implementation. Our report is based on the criteria of the Template for Intervention Description and Replication (TIDieR) checklist, and includes why the efficacy of EEG neurofeedback will be investigated, what will be provided, who will administer it, and how, where, when, and how much the EEG neurofeedback intervention will be administered. CONCLUSIONS: This manuscript provides a detailed description of a complex intervention used in a randomised controlled trial. This description will facilitate the subsequent interpretation of the trial results and allow for the replication of the intervention in clinical practice and future trials. SPONSORSHIP: Australian Government Medical Research Future Fund (2020 Rare Cancers Rare Diseases and Unmet Needs Scheme: 2006020).

Prevalence and management of chronic nonmalignant pain in palliative care populations: A systematic review.

OBJECTIVES: To investigate the prevalence and current approaches to clinical management of chronic nonmalignant pain in patients referred to palliative care services. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD42021205432). Six databases were searched on 25 August 2020 and again on 11 July 2022: PubMed and Ovid MEDLINE, Elsevier Scopus, PsychINFO, the Cochrane Library, and CINAHL. Search included prevalence or intervention studies with patients who had chronic nonmalignant pain and were referred to palliative care services. Screening was undertaken independently by 2 reviewers. RESULTS: The searches returned 417 titles; subsequent screening identified 5 eligible studies, 4 from the USA and 1 from Hong Kong, including 2 cohort and 3 cross-sectional studies. Sample sizes ranged from 137 to 323, with a total of 1,056 patients. The prevalence of chronic nonmalignant pain ranged from 14% to 34% across different palliative care settings. There was significant crossover of pain types; 54% of patients with chronic no-malignant pain had additional cancer-related pain or cancer treatment-related pain. Opioids were used to manage stand-alone chronic nonmalignant pain for 39% of patients compared to 58% with mixed chronic nonmalignant pain and other pain diagnoses. SIGNIFICANCE OF RESULTS: Five studies have documented the prevalence of chronic nonmalignant pain of 14-34% in palliative care. Further research including prevalence and treatment studies would provide clearer evidence for best practice management of chronic nonmalignant pain in the palliative care setting.

Psychosocial characteristics of chronic pain in cancer survivors referred to an Australian multidisciplinary pain clinic.

OBJECTIVE: To describe the clinical and psychosocial characteristics of chronic pain in cancer survivors referred to one Australian hospital's ambulatory pain clinic over a 7-year period (2013-19), and to compare cancer treatment-related pain with comorbid non-malignant pain. METHOD: Retrospective chart review including responses to standardized self-report questionnaires (Brief Pain Inventory, Depression Anxiety Stress Scale, Pain Self-Efficacy Questionnaire, Pain Catastrophizing Scale), routinely collected in all patients referred to pain clinics at Australian and New Zealand hospitals. RESULTS: Of 3510 new referrals during the study period, 267 (7.5%) had a history of cancer and 176 (5.0%) met the study's eligibility criteria. Their average age was 63 ± 13 years, with 55% female. Breast cancer survivors were commonest, followed by hematological, prostate, melanoma, and colorectal, a median of 3 years post-diagnosis. Pain was attributed to cancer treatment in 87 (49%), surgery being the commonest modality. Multimodal treatment (n = 89, 58%) was significantly commoner in the treatment-related pain group (p < 0.001). Average pain severity was moderate, as was pain-related disability and distress. Pain cognitions were often maladaptive (low pain self-efficacy, high pain catastrophizing), predicted by pre-existing anxiety and depression. Associations between pain cognitions and outcomes were medium-to-large. Differences between treatment pain and comorbid pain were small-to-medium. Their scores were similar to Australian pain clinic norms. CONCLUSION: Cancer treatment causes tissue damage, but pain-related distress and disability in survivors is associated with maladaptive pain cognitions. Survivors with poor pain outcomes should be evaluated for unhelpful thoughts and beliefs especially when they have pre-existing depression or anxiety.

Prognostic value of the Memorial Sloan Kettering Prognostic Score in metastatic pancreatic adenocarcinoma.

BACKGROUND: The Memorial Sloan Kettering Prognostic Score (MPS), a composite of the neutrophil-lymphocyte ratio (NLR) and albumin, is an objective prognostic tool created as a more readily available alternative to the Glasgow Prognostic Score. A prior analysis of patients with metastatic pancreatic adenocarcinoma (mPDAC) suggested that the MPS may predict survival, although it did not control for clinically relevant factors. METHODS: MPS scores were calculated for patients with mPDAC treated at Memorial Sloan Kettering Cancer Center from January 1, 2011, to December 31, 2014. An MPS scale of 0 to 2 was used: 0 for an albumin level ≥ 4 g/dL and an NLR ≤ 4 g/dL, 1 for either an albumin level < 4 g/dL or an NLR > 4 g/dL, and 2 for an albumin level < 4 g/dL and an NLR > 4 g/dL. Performance status, antineoplastic therapy, presence of thromboembolism (TE), radiation therapy, and metastatic sites were also analyzed. The associations with overall survival were examined with time-dependent Cox proportional hazards regression analyses. RESULTS: A multivariate model revealed that higher MPS scores at diagnosis (hazard ratio for MPS of 2 vs MPS of 0, 1.41; 95% confidence interval, 1.13-1.76), liver metastases, radiation therapy, hospital admissions, TE, and performance status were associated with worse overall survival. The median overall survival for patients with MPS scores of 0, 1, and 2 were 12.9, 9.0, and 5.4 months, respectively. CONCLUSIONS: The MPS, an easily calculated composite of the NLR and albumin, is an objective tool that may predict survival in mPDAC independently of performance status, disease characteristics, and cancer therapy. LAY SUMMARY: The Memorial Sloan Kettering Prognostic Score (MPS) is a new scoring system that incorporates markers of inflammation found in individuals' blood at the diagnosis of metastatic pancreatic cancer. Data suggest that the MPS may help to determine prognosis.

Transition from acute to chronic pain after surgery.

Over the past decade there has been an increasing reliance on strong opioids to treat acute and chronic pain, which has been associated with a rising epidemic of prescription opioid misuse, abuse, and overdose-related deaths. Deaths from prescription opioids have more than quadrupled in the USA since 1999, and this pattern is now occurring globally. Inappropriate opioid prescribing after surgery, particularly after discharge, is a major cause of this problem. Chronic postsurgical pain, occurring in approximately 10% of patients who have surgery, typically begins as acute postoperative pain that is difficult to control, but soon transitions into a persistent pain condition with neuropathic features that are unresponsive to opioids. Research into how and why this transition occurs has led to a stronger appreciation of opioid-induced hyperalgesia, use of more effective and safer opioid-sparing analgesic regimens, and non-pharmacological interventions for pain management. This Series provides an overview of the epidemiology and societal effect, basic science, and current recommendations for managing persistent postsurgical pain. We discuss the advances in the prevention of this transitional pain state, with the aim to promote safer analgesic regimens to better manage patients with acute and chronic pain.

Deprescribing long-term opioid therapy in patients with chronic pain.

Proposed regulatory changes will limit the access to opioids by Australian patients with chronic pain, many of whom are under the care of consultant physicians. This review summarises points of consensus on opioid deprescribing that emerged from the interaction of an expert panel and the audience at a symposium on the topic held in Sydney in 2019. Each of these consensus points speaks to the need for an individualised, patient-centred approach. In other words, 'treat the patient, not the pill count'.

A randomized open-label study of guideline-driven antiemetic therapy versus single agent antiemetic therapy in patients with advanced cancer and nausea not related to anticancer treatment.

BACKGROUND: Nausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared. METHODS: This randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score < 3/10 at 72 h. RESULTS: Nausea scores and distress from nausea improved over time in the majority of the 185 patients randomized. For those who completed each treatment day, a greater response rate was seen in the guideline arm than the single agent arm at 24 h (49% vs 32%; p = 0.02), but not at 48 or 72 h. Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59). Over 80% of all participants reported an improved global impression of change. There were few adverse events worse than baseline in either arm. CONCLUSION: An etiology-based, guideline-directed approach to antiemetic therapy may offer more rapid benefit, but is no better than single agent treatment with haloperidol at 72 h. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ANZCTRN12610000481077 .

Automatic referral to standardize palliative care access: an international Delphi survey.

PURPOSE: Palliative care referral is primarily based on clinician judgment, contributing to highly variable access. Standardized criteria to trigger automatic referral have been proposed, but it remains unclear how best to apply them in practice. We conducted a Delphi study of international experts to identify a consensus for the use of standardized criteria to trigger automatic referral. METHODS: Sixty international experts stated their level of agreement for 14 statements regarding the use of clinician-based referral and automatic referral over two Delphi rounds. A consensus was defined as an agreement of ≥70% a priori. RESULTS: The response rate was 59/60 (98%) for the first round and 56/60 (93%) for the second round. Twenty-six (43%), 19 (32%), and 11 (18%) respondents were from North America, Asia/Australia, and Europe, respectively. The panel reached consensus that outpatient palliative care referral should be based on both automatic referral and clinician-based referral (agreement = 86%). Only 18% felt that referral should be clinician-based alone, and only 7% agreed that referral should be based on automatic referral only. There was consensus that automatic referral criteria may increase the number of referrals (agreement = 98%), facilitate earlier palliative care access, and help administrators to set benchmarks for quality improvement (agreement = 86%). CONCLUSIONS: Our panelists favored the combination of automatic referral to augment clinician-based referral. This integrated referral framework may inform policy and program development.

The Tri-Institutional Pain Registry-Analysis of Outpatient Pain Management at a Specialized Cancer Center.

Objectives: The Outpatient Pain Clinics at Memorial Sloan Kettering Cancer Center participated in developing a pain registry to gain insight on the referral and management of cancer pain as related to demographic information, cancer history, prescription records, and interventional pain procedures stored in the institutional database. Methods: Five cohorts (subsets of one another) were defined and compared to describe demographics and differences in management and outcomes by age, race, sex, and cancer type. Clinic patients were compared with the entire institution to determine factors associated with better pain relief and reduced side effects. Results: A small percentage were referred to a pain specialist. A total of 1,043 patients completed 3,544 surveys. Compared with the institution, there were higher proportions of patients age 51 to 60 years, nonwhites, and patients with thoracic, abdominal, and head and neck cancers. Medical management controlled pain with three drug categories in 40% of visits. Short-acting opioids were the only category that statistically provided good pain relief with fewer side effects. Pain scores were improved with increasing opioid dose. Management differed by sex, age, and race; women consistently had lower doses of opioids, poorer pain control, more side effects, and were prescribed a greater variety of medications. Conclusions: A limited set of medications was required to manage most patients in the clinic, supporting the continued place of opioids and the World Health Organization analgesic ladder in managing cancer pain. Women may need a more nuanced approach for obtaining the best balance of pain relief and side effects.

Referral criteria for outpatient specialty palliative cancer care: an international consensus.

Although outpatient specialty palliative-care clinics improve outcomes, there is no consensus on who should be referred or the optimal timing for referral. In response to this issue, we did a Delphi study to develop consensus on a list of criteria for referral of patients with advanced cancer at secondary or tertiary care hospitals to outpatient palliative care. 60 international experts (26 from North America, 19 from Asia and Australia, and 11 from Europe) on palliative cancer care rated 39 needs-based criteria and 22 time-based criteria in three iterative rounds. Nearly all experts responded in each round. Consensus was defined by an a-priori agreement of 70% or more. Panellists reached consensus on 11 major criteria for referral: severe physical symptoms, severe emotional symptoms, request for hastened death, spiritual or existential crisis, assistance with decision making or care planning, patient request for referral, delirium, spinal cord compression, brain or leptomeningeal metastases, within 3 months of advanced cancer diagnosis for patients with median survival of 1 year or less, and progressive disease despite second-line therapy. Consensus was also reached on 36 minor criteria for specialist palliative-care referral. These criteria, if validated, could provide guidance for identification of patients suitable for outpatient specialty palliative care.

Effects of denosumab on pain and analgesic use in giant cell tumor of bone: interim results from a phase II study.

BACKGROUND: Giant cell tumor of bone (GCTB) is an aggressive primary osteolytic tumor. GCTB often involves the epiphysis, usually causing substantial pain and functional disability. Denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κΒ ligand (RANKL), is an effective treatment option for patients with advanced GCTB. This analysis of data from an ongoing, open-label study describes denosumab's effects on pain and analgesic use in patients with GCTB. MATERIAL AND METHODS: Patients with unresectable disease (e.g. sacral or spinal GCTB, or multiple lesions including pulmonary metastases) were enrolled into Cohort 1 (N = 170), and patients with resectable disease whose planned surgery was associated with severe morbidity (e.g. joint resection, limb amputation, or hemipelvectomy) were enrolled into Cohort 2 (N = 101). Patients received denosumab (120 mg) subcutaneously every four weeks, with additional doses on study days 8 and 15. Patients assessed worst pain severity with the Brief Pain Inventory - Short Form (BPI-SF) at baseline, at each visit for the first six months, and every three months thereafter. RESULTS: Clinically relevant pain improvement was reported by 29% of patients in Cohort 1 and 35% in Cohort 2 during week 1 and by ≥ 50% of patients in each cohort at each study visit from months 2-30. Median time to clinically relevant improvement was 30 (95% CI 16, 57) days in Cohort 1 and 15 (95% CI 15, 29) days in Cohort 2. Results in patients with moderate/severe pain at baseline were similar. Fewer than 30% of patients in Cohort 1 and 10% in Cohort 2 experienced clinically relevant pain worsening at any visit through 27 months. Most patients had no/low analgesic use during the study. CONCLUSION: Most patients treated with denosumab experienced clinically relevant decreases in pain within two months.

A digital health intervention to support patients with chronic pain during prescription opioid tapering: a pilot randomised controlled trial.

Introduction: Recent changes in opioid prescribing guidelines have led to an increasing number of patients with chronic pain being recommended to taper. However, opioid tapering can be challenging, and many patients require support. Objectives: We evaluated the feasibility, acceptability, and potential efficacy of a codesigned digital health intervention to support patients with chronic pain during voluntary prescription opioid tapering. Methods: In a pilot randomised controlled trial, participants received a psychoeducational video and 28 days of text messages (2 SMS/day) in addition to their usual care (intervention) or usual care alone (control). The feasibility, acceptability, and potential efficacy of the intervention were evaluated. The primary outcome was opioid tapering self-efficacy. Secondary outcomes were pain intensity and interference, anxiety and depression symptom severity, pain catastrophising, and pain self-efficacy. Results: Of 28 randomised participants, 26 completed the study (13 per group). Text message delivery was high (99.2%), but fidelity of video delivery was low (57.1%). Most participants rated the messages as useful, supportive, encouraging, and engaging; 78.5% would recommend the intervention to others; and 64.2% desired a longer intervention period. Tapering self-efficacy (Cohen d = 0.74) and pain self-efficacy (d = 0.41) were higher, and pain intensity (d = 0.65) and affective interference (d = 0.45) were lower in the intervention group at week 4. Conclusion: First evidence supports the feasibility, acceptability, and potentially efficacy of a psychoeducational video and SMS text messaging intervention to support patients with chronic pain during voluntary prescription opioid tapering. Definitive trials with longer intervention duration are warranted.

How is postoperative pain after hip and knee replacement managed? An analysis of two large hospitals in Australia.

BACKGROUND: Multimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for analgesic use in the immediate postoperative period after hip and knee replacements in Australia. OBJECTIVES: To describe analgesic prescribing patterns in the inpatient postoperative phase for patients undergoing hip and knee replacement. METHODS: Retrospective study of electronic medical record data from two major hospitals in Sydney, Australia. We identified analgesic medication prescriptions for all patients aged 18 years and older who underwent hip or knee replacement surgery in 2019. We extracted data on pain medications prescribed while in the ward up until discharge. These were grouped into distinct categories based on the Anatomical Therapeutic Chemical classification. We described the frequency (%) of pain medications used by category and computed the average oral morphine equivalent daily dose (OMEDD) during hospitalisation. RESULTS: We identified 1282 surgeries in 1225 patients. Patients had a mean (SD) age of 69 (11.8) years; most (57.1%) were female. Over 99% of patients were prescribed opioid analgesics and paracetamol during their hospital stay. Most patients (61.4%) were managed with paracetamol and opioids only. The most common prescribed opioid was oxycodone (87.3% of patients). Only 19% of patients were prescribed nonsteroidal anti-inflammatories (NSAIDs). The median (IQR) average daily OMEDD was 50.2 mg (30.3-77.9). CONCLUSION: We identified high use of opioids analgesics as the main strategies for pain control after hip and knee replacement in hospital. Other analgesics were much less frequently used, such as NSAIDs, and always in combination with opioids and paracetamol.

Early implementation of palliative care can improve patient outcomes.

Patients with cancer experience many complex issues throughout the trajectory of the disease. These range from the physical consequences of cancer and treatment to the psychological, social, and spiritual issues associated with living with the disease. An individualized, comprehensive, and interdisciplinary approach is needed to reduce patient suffering and ensure appropriate symptom management and support from the time of first diagnosis to end of life. Data from randomized clinical trials prove that patients provided with early palliative care can experience relief of symptoms and improvements in quality of life, mood, satisfaction, resource use, and advanced care planning. Professional organizations such as ASCO have begun to develop recommendations that integrate palliative care into standard oncologic care from the time a person is diagnosed with metastatic or advanced cancer. NCCN has a palliative care guideline that recommends early and ongoing assessment of palliative care needs and referral to specialist palliative care services in more complex cases. In turn, oncologists need to consider how best to screen patients and integrate early palliative care with routine oncologic care, within the context of their busy clinics, to ensure that patients, families, and caregivers receive timely support.

Study using the NCCN guidelines for palliative care to screen patients for palliative care needs and referral to palliative care specialists.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Palliative Care recommend screening all patients for palliative care (PC) needs and to call a PC consult when referral criteria are met. The goal of this pilot project was to evaluate the feasibility of implementing the screening and referral components of the NCCN Guidelines for Palliative Care in patients admitted to the Gastrointestinal Oncology Service (GIOS) at a comprehensive cancer center (CCC). Floor nurses performed the initial screening of all patients admitted to the 2 teams-Team A and Team B-of the GIOS on one floor of Memorial Hospital for 3 months. In addition, only the patients admitted to Team A were evaluated according to the referral criteria, triggering a PC consult if results were positive. Nurses were surveyed regarding satisfaction with and the acceptability of screening. During the study period, 229 (90%) total admissions were screened, with 169 (73%) having positive results. Of the Team A admissions, 72 (64%) met the referral criteria. More consults occurred for patients in Team A (47 vs 15; P=.001). In 30% of the referral criteria-triggered consults, the PC needs were manageable by the primary team. Nurses reported screening to be easy and quick (<5 minutes per patient) but only somewhat helpful. Being unfamiliar with many patients and families, floor nurses often felt unable to screen them accurately for some issues. In conclusion, screening was feasible, increasing access to PC, but accuracy and usefulness are concerns. With a consult indicated in 64% patients, yet with 30% being manageable by the primary team, the current criteria may be too sensitive for the inpatient environment of a CCC. More evaluation is needed before widespread implementation can be recommended.

Tolerability and Efficacy of a 10:25 Preparation of Δ9-Tetrahydrocannabinol and Cannabidiol for Treatment of Chronic Back or Neck Pain: A Multiple-Dose Escalation Study.

Introduction: The aim was to demonstrate the safety and tolerability of cannabidiol (CBD) with Δ9-THC in patients with moderate to severe chronic back or neck pain unresponsive to over-the-counter non-opioid analgesics. Methods: This was a non-randomized, single-arm, open-label study. Participants received escalating doses of an oromucosal-administered combination containing 10 mg/mL of Δ9-THC, 25 mg/mL of CBD. On day 1, patients received once-daily 0.5 mL Cybis® 10:25 (5 mg Δ9-THC plus 12.5 mg CBD daily), escalated at days 8, 15, and 22 to 0.5 mL twice-daily (bd) (10 mg Δ9-THC plus 25 mg CBD daily), 1.0 mL bd (20 mg Δ9-THC plus 50 mg CBD daily), and 1.5 mL bd (30 mg Δ9-THC plus 75 mg CBD daily), respectively. The primary outcome was safety and tolerability, with secondary objectives including pharmacokinetic and efficacy outcomes. Results: 28 patients were enrolled in the study. Their median age was 63.3 years, and half were female. The median history of neck/back pain was 10 years. The pharmacokinetics following single doses of 0.5 mL were variable; however, there were dose-dependent increases in trough levels of CBD and Δ9-THC. Cybis® 10:25 was well tolerated, with the majority of adverse events of mild severity. The most common adverse events were nausea, vomiting, fatigue, dizziness, headache, paresthesia, and anxiety. There were dose-dependent improvements in numerical pain rating scores (p < 0.001), with clinically significant reductions in pain at 1.0 mL bd and 1.5 mL bd doses (28.8% and 34.1% reductions, respectively, p < 0.001). Depressive symptoms and stress had dose-dependent reductions (p = 0.0182, p < 0.01, respectively). Conclusion: In patients with chronic neck/back pain, CBD and Δ9-THC are well tolerated and doses of 1.0 mL bd and 1.5 mL bd showed clinically significant reductions in pain compared to baseline pain scores.