Expert consensus-based guidance on approaches to opioid management in individuals with advanced cancer-related pain and nonmedical stimulant use.

BACKGROUND: Clinicians treating cancer-related pain with opioids regularly encounter nonmedical stimulant use (i.e., methamphetamine, cocaine), yet there is little evidence-based management guidance. The aim of the study is to identify expert consensus on opioid management strategies for an individual with advanced cancer and cancer-related pain with nonmedical stimulant use according to prognosis. METHODS: The authors conducted two modified Delphi panels with palliative care and addiction experts. In Panel A, the patient's prognosis was weeks to months and in Panel B the prognosis was months to years. Experts reviewed, rated, and commented on the case using a 9-point Likert scale from 1 (very inappropriate) to 9 (very appropriate) and explained their responses. The authors applied the three-step analytical approach outlined in the RAND/UCLA to determine consensus and level of clinical appropriateness of management strategies. To better conceptualize the quantitative results, they thematically analyzed and coded participant comments. RESULTS: Consensus was achieved for all management strategies. The 120 Experts were mostly women (47 [62%]), White (94 [78%]), and physicians (115 [96%]). For a patient with cancer-related and nonmedical stimulant use, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering. Buprenorphine/naloxone transition was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis. CONCLUSION: Study findings provide urgently needed consensus-based guidance for clinicians managing cancer-related pain in the context of stimulant use and highlight a critical need to develop management strategies to address stimulant use disorder in people with cancer. PLAIN LANGUAGE SUMMARY: Among palliative care and addiction experts, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering in the context of cancer-related pain and nonmedical stimulant use. Buprenorphine/naloxone transition as a harm reduction measure was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis.

Consensus-Based Guidance on Opioid Management in Individuals With Advanced Cancer-Related Pain and Opioid Misuse or Use Disorder.

Importance: Opioid misuse and opioid use disorder (OUD) are important comorbidities in people with advanced cancer and cancer-related pain, but there is a lack of consensus on treatment. Objective: To develop consensus among palliative care and addiction specialists on the appropriateness of various opioid management strategies in individuals with advanced cancer-related pain and opioid misuse or OUD. Design, Setting, and Participants: For this qualitative study, using ExpertLens, an online platform and methodology for conducting modified Delphi panels, between August and October 2020, we conducted 2 modified Delphi panels to understand the perspectives of palliative and addiction clinicians on 3 common clinical scenarios varying by prognosis (weeks to months vs months to years). Of the 129 invited palliative or addiction medicine specialists, 120 participated in at least 1 round. A total of 84 participated in all 3 rounds. Main Outcomes and Measures: Consensus was investigated for 3 clinical scenarios: (1) a patient with a history of an untreated opioid use disorder, (2) a patient taking more opioid than prescribed, and (3) a patient using nonprescribed benzodiazepines. Results: Participants were mostly women (47 [62%]), White (94 (78 [65%]), and held MD/DO degrees (115 [96%]). For a patient with untreated OUD, regardless of prognosis, it was deemed appropriate to begin treatment with buprenorphine/naloxone and inappropriate to refer to a methadone clinic. Beginning split-dose methadone was deemed appropriate for patients with shorter prognoses and of uncertain appropriateness for those with longer prognoses. Beginning a full opioid agonist was deemed of uncertain appropriateness for those with a short prognosis and inappropriate for those with a longer prognosis. Regardless of prognosis, for a patient with no medical history of OUD taking more opioids than prescribed, it was deemed appropriate to increase monitoring, inappropriate to taper opioids, and of uncertain appropriateness to increase the patient's opioids or transition to buprenorphine/naloxone. For a patient with a urine drug test positive for non-prescribed benzodiazepines, regardless of prognosis, it was deemed appropriate to increase monitoring, inappropriate to taper opioids and prescribe buprenorphine/naloxone. Conclusions and Relevance: The findings of this qualitative study provide urgently needed consensus-based guidance for clinicians and highlight critical research and policy gaps.

Consensus-based approach to managing opioids, including opioid misuse and opioid use disorder, in patients with serious illness: protocol for a modified Delphi process.

INTRODUCTION: Management of opioid misuse and opioid use disorder (OUD) among individuals with serious illness is an important yet understudied issue. Palliative care clinicians caring for individuals with serious illness, many of whom may live for months or years, describe a complex tension between weighing the benefits of opioids, which are considered a cornerstone of pain management in serious illness, and serious opioid-related harms like opioid misuse and OUD. And yet, little literature exists to inform the management of opioid misuse and OUDs among individuals with serious illness. Our objective is to provide evidence-based management guidance to clinicians caring for individuals with serious illness who develop opioid misuse or OUD. METHODS AND ANALYSIS: We chose a modified Delphi approach, which is appropriate when empirical evidence is lacking and expert input must be used to shape clinical guidance. We sought to recruit 60 clinicians with expertise in palliative care, addiction or both to participate in this study. We created seven patient cases that capture important management challenges in individuals with serious illness prescribed opioid therapy. We used ExpertLens, an online platform for conducting modified Delphi panels. Participants completed three rounds of data collection. In round 1, they rated and commented on the appropriateness of management choices for cases. In round 2, participants reviewed and discussed their own and other participants' round 1 numerical responses and comments. In round 3 (currently ongoing), participants again reviewed rounds 1 and 2, and are allowed to change their final numerical responses. We used ExpertLens to automatically identify whether there is consensus, or disagreement, among responses in panels. Only round 3 responses will be used to assess final consensus and disagreement. ETHICS AND DISSEMINATION: This project received ethical approval from the University of Pittsburgh's Institutional Review Board (study 19110301) and the RAND Institutional Research Board (study 2020-0142). Guidance from this work will be disseminated through national stakeholder networks to gain buy-in and endorsement. This study will also form the basis of an implementation toolkit for clinicians caring for individuals with serious illness who are at risk of opioid misuse or OUD.

Expert Panel Consensus on Management of Advanced Cancer-Related Pain in Individuals With Opioid Use Disorder.

Importance: Opioid use disorder (OUD) is an important comorbidity in individuals with advanced cancer, in whom pain is common. Full-agonist opioid medications are the cornerstone of cancer pain management, but the existing literature does not address how to manage cancer pain in patients with OUD. Objective: To conduct an expert panel to develop consensus on the appropriateness of management of cancer pain in individuals with co-occurring advanced cancer and OUD. Evidence Review: A 3-round modified Delphi process was completed from August to October 2020 with 2 cases: patient with advanced cancer, pain, and OUD treated with buprenorphine-naloxone or methadone. Participants rated management strategies in round 1, discussed results in round 2, and provided final responses in round 3. ExpertLens, an online approach to conducting modified Delphi panels, was used. Participants were experts in palliative care, addiction, or both, recruited by email from palliative care and addiction-focused professional groups, lists from prior studies, and snowball sampling. Data analysis was performed from November 2020 to July 2021. Findings: Of 120 experts (median age, 40-49 years), most were White (78 participants [94%]), female (74 participants [62%]), and held MD or DO degrees (115 participants [96%]); 84 (70%) participated in all rounds. For a patient with OUD taking buprenorphine-naloxone, it was deemed appropriate to continue buprenorphine-naloxone with thrice-daily dosing. Continuing buprenorphine-naloxone and adding a full-agonist opioid was deemed to be appropriate for patients with a prognosis of weeks to months and of uncertain appropriateness for patients with a prognosis of months to years. For a patient with OUD taking methadone dispensed at a methadone clinic, it was deemed appropriate to take over prescribing and dose twice or thrice daily. Continuing methadone daily while adding another full-agonist opioid was deemed appropriate for patients with a prognosis of weeks to months and of uncertain appropriateness for those with a prognosis of months to years. Conclusions and Relevance: The findings of this qualitative study provide urgently needed, consensus-based guidance for clinicians and highlight critical research and policy gaps needed to facilitate implementation.

Protective effect of kava constituents in an in vitro model of oral mucositis.

PURPOSE: Oral mucositis is a debilitating inflammatory disorder observed in patients undergoing active cancer treatment, particularly cancer of the head and neck region. A key pathway believed to be involved in the pathogenesis of oral mucositis is the formation of reactive oxygen species (ROS). The identification of compounds that can inhibit this pathway may therefore be of benefit in treating this disorder. The kava plant (Piper methysticum) contains various constituents, including flavokawain A (FKA), flavokawain B (FKB), yangonin, methysticin and kavain. These constituents are known to be biologically active and possess anti-oxidative properties. This study therefore focused on examining these constituents for their effect on ROS formation in an in vitro oral mucositis model. METHODS: Cell proliferation was assessed in normal oral keratinocytes (OKF6) treated with and without kava constituents, namely FKA, FKB, yangonin, methysticin and kavain using an MTS in vitro assay. Oxidative stress was assessed by co-treating and pre-treating OKF6 cells with H2O2. The effects were quantified by analysis of ROS production, using a CM-H2DCFDA assay. RESULTS: Pre-treatment of cells for 24 h with 2.5 µg/ml kavain and 5 µg/ml FKA demonstrated a significant protective anti-oxidative effect. Similarly, FKB at a concentration of 2.5 µg/ml, demonstrated a trend of ROS reduction but was observed to be cytotoxic at concentrations greater than 5 µg/ml. Reduction in ROS production by methysticin and yangonin was compromised by their cell cytotoxicity. CONCLUSION: This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis.

Standardizing care to manage bleeding disorders in adolescents with heavy menses-A joint project from the ISTH pediatric/neonatal and women's health SSCs.

BACKGROUND: Bleeding disorders (BD) are under-recognized in adolescents with heavy menstrual bleeding (HMB). OBJECTIVES: The lack of clinical guidelines and variable symptomatic management of HMB created the imperative to standardize HMB care to identify and manage BD in adolescents. METHODS: We convened an international working group (WG), utilized the results of a literature review to define knowledge gaps in HMB care, and used the collective clinical experience of the WG to develop care considerations for adolescents with BD and HMB. We then solicited input on the appropriateness of HMB care considerations from expert stakeholders representing hematology, adolescent medicine, and obstetrics-gynecology. We conducted an expert panel online, using the ExpertLens platform. During a three-round online modified-Delphi process, the expert panel rated the appropriateness of 21 care considerations using a 9-point scale to designate care as appropriate (7-9), uncertain (4-6), or inappropriate (1-3) covering screening for BD, the laboratory work-up, and management of adolescents with BD that present with HMB. We used the RAND/UCLA appropriateness method to determine the existence of consensus among the interdisciplinary panel of experts. RESULTS: Thirty-nine experts participated in the panel. The experts rated fifteen HMB care considerations as appropriate, six as uncertain, and none as inappropriate. CONCLUSIONS: The HMB care statements represent the first set of HMB care considerations in adolescents with BD, developed with broad expert input on appropriateness. Although likely to be of interest to a range of clinicians who routinely manage adolescents with HMB, additional research is required in many key areas.

Using an Online, Modified Delphi Approach to Engage Patients and Caregivers in Determining the Patient-Centeredness of Duchenne Muscular Dystrophy Care Considerations.

Purpose. To determine the patient-centeredness of endocrine and bone health Duchenne muscular dystrophy (DMD) care considerations using the RAND/PPMD Patient-Centeredness Method (RPM), which is a novel, online, modified-Delphi approach to engaging patients and caregivers in clinical guideline development. Methods. We solicited input on the patient-centeredness of care considerations from 28 individuals with DMD and 94 caregivers, randomly assigned to 1 of 2 mixed panels. During a 3-round online modified-Delphi process, participants rated the importance and acceptability of 19 DMD care considerations (round 1), reviewed and discussed the initial results (round 2), and revised their original ratings (round 3). Patient-centeredness was operationalized as importance and acceptability of recommendations. We considered a care consideration to be patient-centered if both panels deemed it important and acceptable. Results. Ninety-five panelists (78%) participated in this study. Of these, 88 (93%) participated in round 1, 74 (78%) in round 2, and 56 (59%) in round 3. Panelists deemed 12 care considerations to be patient-centered: 3 weight management, 3 bone health, 4 vertical growth, and 2 puberty recommendations. Seven care considerations did not meet patient-centeredness criteria. Common reasons were lack of evidence specific to DMD and concerns about insurance coverage, access to treatment, and patient safety. Conclusions. Using the RPM, Duchenne families considered most care considerations to be patient-centered. Besides being clinically appropriate, these considerations are likely to be consistent with the preferences, needs, and values of Duchenne families. While all relevant care considerations should be discussed during patient-provider encounters, those that did not meet patient-centeredness criteria in particular should be carefully considered as part of joint decision making between Duchenne families and their providers. Study Registration: HSRProj 20163126.

Development of a Canadian Core Clinical Dataset to Support High-quality Care for Canadian Patients with Rheumatoid Arthritis.

OBJECTIVE: To develop a Canadian Rheumatoid Arthritis Core Clinical Dataset (CAN-RACCD) to standardize documentation encouraging high-quality care. METHODS: A set of candidate elements was drafted through meetings with 27 rheumatologists, researchers, and patients, and supplemented with focused literature reviews. A 3-round online-modified Delphi consensus process was held with rheumatologists (n = 26), allied health professionals (n = 7), and patients (n = 4); for the remainder there was no demographic information. Participants rated both the importance and feasibility of documenting candidate elements on a Likert scale of 1-9, contributed to an online moderated discussion, and re-rated the elements for inclusion in the CAN-RACCD. Elements were included in the final set if importance and feasibility ratings had a median score of ≥ 6.5 and there was no disagreement among participants. RESULTS: Fifty-five individual elements in 10 subgroups were proposed to the Delphi participants: measures of RA disease activity; dates to calculate waiting times, disease duration, and disease-modifying antirheumatic drug start; comorbidities; smoking status; patient-reported pain and fatigue; physical function; laboratory and radiographic investigations; medications; clinical characteristics; and vaccines. All groups were included in the final set, with the exception of vaccination status. Additionally, 3 individual elements from the smoking subgroup were eliminated with a recommendation to record smoking status as never/ever/current, and 2 elements relating to coping and effect of fatigue were eliminated due to low feasibility and importance ratings. CONCLUSION: The CAN-RACCD stands as a national recommendation on which data elements should be routinely collected in clinical practice to monitor and support high-quality RA care.