Search

Patients with advanced cancer who have pain that responds poorly to opioid therapy pose a clinical challenge. Nabiximols (Nabiximols is the US Adopted Name [USAN] for Sativex [GW Pharma Ltd, Wiltshire, UK], which does not yet have an INN), a novel cannabinoid formulation, is undergoing investigation as add-on therapy for this population. In a randomized, double-blind, placebo-controlled, graded-dose study, patients with advanced cancer and opioid-refractory pain received placebo or nabiximols at a low dose (1-4 sprays/day), medium dose (6-10 sprays/day), or high dose (11-16 sprays/day). Average pain, worst pain and sleep disruption were measured daily during 5 weeks of treatment; other questionnaires measured quality of life and mood. A total of 360 patients were randomized; 263 completed. There were no baseline differences across groups. The 30% responder rate primary analysis was not significant for nabiximols versus placebo (overall P = .59). A secondary continuous responder analysis of average daily pain from baseline to end of study demonstrated that the proportion of patients reporting analgesia was greater for nabiximols than placebo overall (P = .035), and specifically in the low-dose (P = .008) and medium-dose (P = .039) groups. In the low-dose group, results were similar for mean average pain (P = .006), mean worst pain (P = .011), and mean sleep disruption (P = .003). Other questionnaires showed no significant group differences. Adverse events were dose-related and only the high-dose group compared unfavorably with placebo. This study supports the efficacy and safety of nabiximols at the 2 lower-dose levels and provides important dose information for future trials. PERSPECTIVE: Nabiximols, a novel cannabinoid formulation, may be a useful add-on analgesic for patients with opioid-refractory cancer pain. A randomized, double-blind, placebo-controlled, graded-dose study demonstrated efficacy and safety at low and medium doses. [ABSTRACT FROM AUTHOR]

Opioid rotation is a strategy applied during opioid therapy for pain that refers to a switch from one opioid to another in an effort to improve clinical outcomes (benefits or harms). It begins with the selection of a new drug at a starting dose that minimizes potential risks while ideally maintaining analgesic efficacy. The selection of a starting dose must be informed by an estimate of the relative potency between the existing opioid and the new one. Clinically relevant estimates of relative analgesic potency have been codified in the "equianalgesic dose table," which has been used with little modification for more than 40 years. New information about relative potency and the growing implementation of long-term opioid therapy for chronic pain provided a strong rationale for the convening of an expert panel to discuss the scientific foundation to opioid rotation and the elements that now should inform a clinical guideline for this practice. The panel affirmed both the value and the limitations of the current equianalgesic dose table and proposed a guideline intended to promote safety during opioid rotation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Short-acting opioids are commonly used to treat breakthrough pain (BTP) and rapid-onset formulations are being developed to improve the effectiveness of this approach. Fentanyl buccal tablet (FBT) is a new formulation of fentanyl that enhances transbuccal drug delivery via an effervescent reaction and may provide relatively rapid-onset analgesia. FBT was evaluated for BTP in opioid-treated patients with chronic low back pain--the first such study in a population with chronic non-cancer pain. DESIGN: Randomized, double-blind, placebo-controlled. Patients and setting: Patients with chronic low back pain receiving long-term opioid therapy at 16 pain treatment centers in the United States. PROCEDURES: Following open-label titration to identify an effective FBT dose, patients were randomly assigned to one of three double-blind dose sequences (six doses of FBT, three placebo) to treat nine BTP episodes. Pain intensity (PI), measured on an 11-point scale (0 = no pain; 10 = worst pain), and other outcomes were assessed for 2 h after dosing. DATA ANALYSIS: The primary efficacy measure was the sum of pain intensity differences (PIDs) for the first 60 min (SPID60); secondary efficacy measures included PIDs at other time points, pain relief (PR), meaningful PR, time to meaningful PR, use of supplementary BTP medication, and self/investigator-reported adverse events. RESULTS: Of the 124 patients screened, 105 patients were enrolled, 84 identified an effective FBT dose, and 77 entered the double-blind phase. SPID60 significantly favored FBT (p < 0.0001). All secondary measures also favored FBT, with PIDs and PR showing significant differences versus placebo as early as 10 and 15 min, respectively. An improvement in PI score of > or = 33% occurred in a significantly larger proportion of FBT-treated episodes versus placebo from 15 min (20% vs. 11%, p < 0.01) through 2 h (65% vs. 28%, p < 0.0001). Patients were approximately four times more likely to require supplemental opioids for BTP episodes following administration of placebo compared with episodes treated with FBT. AEs were typical for opioids, and were mostly reported during dose titration. Limitations of this study may be related to its open-label dose-titration phase (which has the potential to compromise blinding) and the recruitment of patients from pain clinics, which could potentially yield a study population that is not representative of the general population with BTP. CONCLUSIONS: FBT was efficacious and well tolerated in the treatment of BTP in opioid-treated patients with chronic low back pain. [ABSTRACT FROM AUTHOR]

Access to medical care is a major national issue, and several surveys suggest that racial and ethnic differences influence access to care for chronic pain problems. To evaluate the influence of race and ethnicity on access to treatment for chronic pain, a cross-sectional telephone survey was performed in a nationally representative sample of 454 white, 447 African-American, and 434 Hispanic subjects with pain for > or =3 months. Questions explored demographics, pain and its treatment, and perceived access to care. A composite 'access' variable combined actual consultation with perceived access. Hispanics were younger, least likely to be insured, and had the least education and lowest income; 61% spoke Spanish at home. Hispanics were significantly less likely to have consulted a primary care practitioner for pain (70%) than whites (84%) or African-Americans (85%). A lower likelihood of consultation also was associated with speaking Spanish, being male, being relatively young (18-34 years old) or single, having limited education, and not being employed. Low 'access' to care was associated with being Hispanic and speaking Spanish, being younger or male, having low income or limited education, being employed, and agreeing that financial concerns prevented pain treatment. High 'access' was associated with being white or African-American; being older or female or living in a suburban area; having insurance, higher income, or college education; and being unemployed. In multivariate models, low 'access' was associated with Hispanic ethnicity and agreement that financial concerns prevented pain treatment. High 'access' was associated with more severe pain, having insurance or an income of US 25,000 dollars to US 74,000 dollars, and agreeing that 'A doctor or other health care provider is the first person I would go to to discuss my pain.' These data suggest that race/ethnicity, other demographic characteristics, and socioeconomic factors influence access to pain care. Hispanic ethnicity predicts limited access. PERSPECTIVE: The influence of race and ethnicity on access to health care is a major issue in the United States. A national telephone survey suggests that race and ethnicity, along with other demographic and socioeconomic factors, influence access to care for chronic pain. [ABSTRACT FROM AUTHOR]

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed. [ABSTRACT FROM AUTHOR]

Extended-release morphine formulations are widely used in the management of chronic pain. Avinza (morphine sulfate extended-release [MSER, Morphelan]) is a new, once-a-day, extended-release morphine formulation designed to reach target concentrations rapidly and maintain concentrations throughout a 24-hour period. The primary objective of this study was to compare the 24-hour steady-state pharmacokinetic (PK) profiles of morphine and its metabolites (morphine-6-glucuronide [M6G] and morphine-3-glucuronide [M3G]) following ingestion of MSER once-a-day and MS Contin (controlled-release morphine sulfate [CRM]) twice-a-day in patients with chronic moderate-to-severe pain. Ten patients with chronic moderate-to-severe pain were recruited into an open-label, multiple-dose, nonrandomized, two-period, single-center study. All patients were stabilized for a minimum of 7 days on a twice-daily dose of CRM associated with an optimal balance between pain control and side effects. Patients were then switched to the closest equivalent once-daily dose of MSER for a minimum of 10 days. Twenty-four hour steady-state PK profiles were obtained on the last day of each treatment period and additional clinical and safety assessments were performed. PK data were normalized to a 100-mg total daily dose prior to statistical analysis. Nine of the 10 patients completed the entire study. MSER and CRM demonstrated similar bioavailability (AUC) of morphine and its metabolites. Compared to CRM, MSER demonstrated a 19% lower maximum concentration (C(max)), a 66% higher minimum concentration (C(min)), and a 44% lower peak-to-trough fluctuation (%FI) over the 24-hour period. In addition, MSER maintained concentrations above 50% and 75% of the C(max) longer than CRM. Clinical efficacy and safety were comparable for MSER and CRM. Once-daily MSER approaches maximum morphine concentration more quickly, approximates maximum concentration longer, and demonstrates less fluctuation in morphine concentration during a 24-hour period than CRM dosed twice daily. The pharmacodynamic implications of this profile deserve further study. [ABSTRACT FROM AUTHOR]

Physicians are often stuck between-a rock--the need to prescribe controlled substances--and a hard place--the fear of punishment by regulatory authorities. With the guidance our experts provide, you can put the two opposing forces in perspective. [ABSTRACT FROM AUTHOR]

The objective of this open-label, repeated-dose, single-treatment, multicenter study was to evaluate the outcomes associated with a standardized conversion from prior opioid therapy to a novel, once-daily, OROS osmotic technology, extended-release (ER) hydromorphone formulation in an outpatient population with chronic malignant or nonmalignant pain. The study period was divided into 3 phases: the prior opioid stabilization phase (> or =3 days), the conversion and titration phase (3-21 days), and the maintenance phase (14 days). Patients were evaluated at 5 visits during the study period. Analgesic efficacy was measured using the Brief Pain Inventory (BPI). At baseline, patients were required to have daily oral morphine equivalent requirements of > or =45 mg. Prior oral or transdermal opioid therapy was converted to single daily doses of ER hydromorphone (8, 16, 32, and 64 mg tablets) at a 5:1 (morphine equivalent to hydromorphone) ratio. Immediate-release (IR) hydromorphone was given as rescue medication for breakthrough pain. Among the 445 patients who enrolled, 404 received the study medication. Of these, 73 (18.1%) had chronic malignant pain and 331 (81.9%) had chronic nonmalignant pain. Dose stabilization (defined as a 3-day period during which the total daily dose of ER hydromorphone remained unchanged and < or =3 doses of IR hydromorphone per day were required) was attained by 73.8% of patients (298/404), of whom 70.1% (209/298) were stabilized with < or =2 titration steps. The mean +/- standard deviation (SD) time to dose stabilization was 12.1 +/- 5.7 days (range of 3 to 33 days). The mean +/- SD final daily dose of ER hydromorphone was 63.4 +/- 129.2 mg. The mean +/- SD final daily dose of IR hydromorphone was 11.5 +/- 36.4 mg, and the mean +/- SD final number of daily doses of IR hydromorphone was 1.7 +/- 1.3. Intent-to-treat and completer analysis demonstrated significant improvements in BPI ratings from prior opioid therapy to the end of ER hydromorphone therapy (P < 0.01 for all pairwise comparisons). Adverse events were consistent with those expected of an opioid agonist in such a patient group, affecting primarily the gastrointestinal and central nervous systems. This uncontrolled study delineates a regimen by which patients with chronic malignant or nonmalignant pain can be readily converted from prior opioid therapy and titrated to an appropriate maintenance dose of ER hydromorphone. Controlled longitudinal studies are required to further evaluate the use of ER hydromorphone in patients with discrete chronic malignant or nonmalignant pain conditions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Opioid analgesics are the cornerstone of management for malignant pain. Their use in managing chronic, nonmalignant pain, albeit controversial, has increased in recent years. The decisions about whether to initiate opioid therapy or continue it over time should be guided by a comprehensive patient assessment. During long-term treatment, this assessment should focus on a broad range of outcomes, each of which should be documented in the medical record. OBJECTIVE: The goal of this study was to develop an instrument, the Pain Assessment and Documentation Tool (PADT), to focus on key outcomes and provide a consistent way to document progress in pain management therapy over time. METHODS: Items that assess 4 domains (pain relief, patient functioning, adverse events, and drug-related behaviors) were generated with input from a MEDLINE literature search and experts in pain and addiction management. The original tool was field tested by clinicians who applied it to the assessment of patients receiving long-term opioid therapy for the management of chronic, nonmalignant pain. Data analysis and debriefing telephone interviews with a formalized set of questions were then used to rephrase, delete, and refine items to create the final tool. RESULTS: A 6-member expert panel contributed to the initial development of the PADT. Twenty-seven clinicians completed the preliminary version of PADT for 388 patients. The original 59-item tool was modified to create a 41-item tool. The revised PADT was formatted for use as a chart note designed to assist clinicians in assessing and documenting 4 main outcome domains during long-term opioid use. CONCLUSIONS: In this study, the PADT appeared to be a useful tool for clinicians to guide the evaluation of several important outcomes during opioid therapy and provide a simple means of documenting patient care. [ABSTRACT FROM AUTHOR]

Few studies have attempted to describe the experience of symptoms in young children with cancer. This is due, in part, to the lack of validated symptom assessment scales for this patient population. The objective of this study was to evaluate the reliability and validity of a revised Memorial Symptom Assessment Scale (MSAS) in patients aged 7-12 as an instrument for the assessment of symptoms in young children with cancer. The MSAS (7-12) was administered to 149 children (inpatients and outpatients) who were undergoing treatment at either the Royal Marsden NHS Trust, London, United Kingdom or The Children's Hospital at Westmead, Sydney, Australia. Validity was evaluated by comparison with the medical record, parental report, and concurrent assessment on visual analogue scales for selected symptoms. The data provide evidence of the reliability and validity of MSAS (7-12) and demonstrate that children with cancer as young as 7 years can report clinically relevant and consistent information about their symptom experience. Young children with cancer experience multiple symptoms. Approximately one-third had experienced lethargy and/or pain and/or insomnia during the 48 hours prior to the completion of MSAS (7-12). The completion rate for MSAS (7-12) was high and the majority of children completed the instrument in a short period of time and with little difficulty. The instrument appears to be age appropriate and may be helpful to older children unable to independently complete MSAS (10-18). Systematic symptom assessment may be useful in future epidemiological studies of symptoms and in cancer chemotherapy drug trials. [ABSTRACT FROM AUTHOR]

Context: Estimates 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., Objectives: Present 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., Methods: Using 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., Results: DOME 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., Conclusion: DOME 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., Competing Interests: Disclosure/Conflict The authors report no conflicts of interest, (Copyright © 2024. Published by Elsevier Inc.)

Background: Educating Social Workers in Palliative and End-of-Life Care (ESPEC) is a nationally scalable continuing education program designed to improve the knowledge and skills of frontline health social workers caring for patients with serious illness. Objectives: This article describes ESPEC's rationale, development, and initial implementation. Design: Following the creation of consensus-derived core primary palliative care competencies for health primary care social workers based on the eight domains of palliative care outlined in the National Consensus Project Guidelines for Quality Palliative Care, an evidence-based curriculum was developed. This was used to develop a hybrid training model with a self-study component, synchronous instructor-led skills-based training, leadership training, and mentorship. The interactive curriculum incorporates patient scenarios highlighting the health social work role. Training targets high-impact skills-the biopsychosocial-spiritual assessment, advance care planning, family meetings, and interprofessional communication-and professional development. Settings/Subjects: ESPEC was launched in the United States in collaboration with the National Association of Social Workers (NASW) and the Social Work Hospice and Palliative Care Network (SWHPN). Results: The preliminary launch demonstrated high user acceptability, positive ratings for content and format, and gains in knowledge and competence. Conclusions: Data suggest that ESPEC can increase health social workers' knowledge and confidence as providers of palliative care interventions. National dissemination is ongoing.

Purpose: Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer., Patients and Methods: One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival., Results: Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated., Conclusion: This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

Background: Poorly controlled pain remains a problem for many patients with end-stage kidney disease requiring hemodialysis (ESKD/HD) and customary approaches to pain management (e.g., opioids, non-steroidals) confer substantial risk. Accordingly, non-pharmacologic therapies are needed for use in this population. Non-invasive transcranial Direct Current Simulation (tDCS) constitutes a promising nonpharmacologic method for pain management in affected individuals., Aims: This study seeks to: 1) determine the effects of an 8-week course of at-home tDCS vs. sham tDCS on pain intensity, pain interference, medication usage, quality of life, and mood; 2) determine if tDCS effects vary by race/ethnicity; and 3) ascertain patient satisfaction with device use., Methods: This double-blind, randomized, sham-controlled clinical trial will enroll 100 ESKD/HD patients with moderate-to-severe (≥4 on 0-10 scale) chronic pain. The active study intervention consists of 20 min of tDCS delivered over the primary motor cortex 5 days/week for 8 weeks. The comparator is a sham procedure that provides no effective stimulation. The primary outcome analysis will evaluate efficacy of tDCS for pain reduction after two months of stimulation. We will also assess the effects of treatment on analgesic consumption, pain interference, depressed mood, and quality of life. The statistical plan will include fixed classification factors for treatment (vs. sham), clinic sites, and assessment time, and the interaction of these factors adjusting for covariates (e.g., race/ethnicity, pain level)., Conclusion: At-home tDCS constitutes a promising nonpharmacologic treatment for pain mitigation in persons with ESKD/HD. This unique RCT could transform the way pain is managed in this vulnerable population., Trial Registration: NCT05311956., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Van Zyl, Knotkova, Kim, Henderson Jr., Portenoy, Berman, Frederic and Reid.)

Opinion Statement: Specialists in palliative care view the family meeting as a means to engage patients and their families in a serious illness discussion that may clarify the values of patients and caregivers, provide information, determine care preferences, and identify sources of illness-related distress and burden. The family meeting is considered the best practice for achieving patient- and family-centered care in palliative care. Although studies of the family meeting are limited, those extant suggest that these interventions may reduce caregiver distress, mitigate the perception of unmet needs, prepare family members for caregiving, and improve bereavement outcomes. The experience of palliative care specialists further suggests that the family meeting may reinforce the therapeutic alliance with families, promote consensus, and reduce the need for ad hoc meetings. Physician satisfaction may be enhanced when the treatment plan includes the opportunity to show empathy and see the family's perspective-core elements of the clinical approach to the family meeting. In the oncology setting, the potential to achieve these positive outcomes supports the integration of the family meeting into practice. Clinical skills for the planning and running of family meetings should be promoted with consideration of a standardized protocol for routine family meetings at critical points during the illness and its treatment using an interdisciplinary team. Further research is needed to refine understanding of the indications for the family meeting and determine the optimal timing, structure, and staffing models. Outcome studies employing validated measures are needed to better characterize the impact of family meetings on patient and family distress and on treatment outcomes. Although better evidence is needed to guide the future integration of the family meeting into oncology practice, current best practices can be recommended based on available data and the extensive observations of palliative care specialists., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Pharmacogenomic analysis may improve the efficacy or safety of the drugs used in palliative care. Decision support systems may promote clinical integration of this information. Objectives: To determine the feasibility and acceptability of a pharmacist-directed pharmacogenomic decision support system in the care of patients with advanced illness and explore the drug-gene and drug-drug interactions that occur in this population. Methods: Physicians or nurse practitioners from two U.S. hospice agencies identified opioid-treated patients receiving multiple other drugs. Buccal samples and clinical data were obtained from consenting patients. A pharmacist used the proprietary MedWise™ platform to evaluate the current medications in terms of genotype and phenotype, created a standardized report describing potential interactions and recommended actions that may reduce the associated risk. Clinicians could access the report online and completed Likert-type scales to assess use and satisfaction with the system. Results: Twenty clinicians and 100 patients participated. The reports revealed that 74 drugs were subject to 462 drug-gene interactions and 77 were involved in 691 drug-drug interactions; only 4 and 16 patients, respectively, had no drug-gene or drug-drug interactions. Clinicians routinely checked the reports and used the information to change ≥1 treatments in 55 (55%) patients. Almost all clinicians rated the system likely to improve the quality of care and all "agreed" or "strongly agreed" to recommend the system to colleagues. Conclusion: This pharmacist-directed pharmacogenomic decision support system was perceived positively and was integrated into practice. Further studies are warranted to its clinical integration and its outcomes.

New therapies for symptoms in Alzheimer's disease (AD) are urgently needed. Prior studies suggest that transcranial direct current stimulation (tDCS), a noninvasive neuromodulatory method, may be a safe and potentially effective treatment, but conclusions have been limited by small-sample sizes and brief stimulation protocols. This double-blind randomized trial involving 100 older adults with mild-to-moderate AD examines effects of 6 months of at-home active tDCS or sham delivered over the dorsolateral prefrontal cortex. The primary outcome is global cognitive performance. Secondary outcomes include executive-control/spatial selective attention, functional neuroplasticity, depressive symptoms, quality of life and the durability of effects 3 months after the stimulation period. The results will provide evidence on the efficacy of multimonth at-home tDCS in the AD treatment. =Clinical trial identifier NCT04404153 (Clinicaltrials.gov).

Context: Patients with left ventricular assist devices (LVADs) need expert palliative care at the end of life. In the U.S., hospice may provide this care, but few patients enroll, and information about hospice experience with LVAD-implanted patients is limited., Objective: To describe hospice experience with LVAD-implanted patients., Methods: This is a retrospective descriptive study of all LVAD-implanted patients admitted to a hospice agency. Data were extracted from the electronic health record., Results: The 13 patients had a mean age of 63 years (range 20-89) and a mean LVAD duration of 32.5 months (range 8.2-70.0). Hospice diagnosis was heart failure in 10 patients and cancer in three patients; all patients were multimorbid. Eight patients enrolled in hospice on one occasion, four had two enrollments, and one had five. All patients received services for <180 days, three for <7 days, and four patients for >90 days. Just-in-time inservicing was used to prepare hospice teams for challenging care needs, including bleeding, delirium, infections, and mechanical failure. Of the nine patients who died while receiving hospice services, one enrolled with a plan to deactivate the LVAD immediately after hospice enrollment, and six died after discontinuation of the LVAD or other life-sustaining therapy during the course of hospice care. Five deaths occurred in a hospice inpatient unit., Conclusion: To provide specialist palliative care to LVAD-implanted patients, hospices must be prepared to manage complex and highly varied needs. To do this, hospices must have adequate staff support and access to acute care., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Breakthrough cancer pain (BTcP) is a variegated phenomenon, that often presents in different ways in each individual, and may change its presentation in the same individual during the course of disease. An appropriate assessment is fundamental for depicting the pattern of BTcP in individuals. This information is determinant for a personalised management of BTcP. The use of opioids as needed, is recommended for the management of BTcP. There are several options which should be chosen according to the individual pattern of BTcP. In general, a drug with a short onset and offset should be preferred. Although oral opioids may still have specific indications, fentanyl products have been found to be more rapid and effective, providing analgesia in 5-15 min. The most controversial point regards the opioid dose to be used. The presence of tolerance suggests using a dose that is proportional to the dose used for background analgesia. In contrast, regulatory studies have suggested using the minimal available dose to be titrated until the effective dose. Further large studies should definitely settle this never-ending question.

The adjuvant analgesics are a large and diverse group of drugs that were developed for primary indications other than pain and are potentially useful analgesics for one or more painful conditions. The "adjuvant" designation reflects their early use as opioid co-analgesics for cancer pain. During the past 3 decades, their role in pain management has changed with the advent of many new entities, emerging data from numerous analgesic trials, and growing clinical experience. Many of these drugs are now used as primary analgesics for specific types of chronic pain. With proper patient selection and cautious administration, they can potentially contribute meaningfully to the management of chronic pain in older adults. A practical approach categorizes the many adjuvant analgesics by broad indications: multipurpose drugs and drugs that target neuropathic pain, musculoskeletal pain, and cancer pain, respectively. This article reviews the status of the evidence supporting the analgesic potential of the adjuvant analgesics and discusses best practices in terms of drug selection and dosing. J Am Geriatr Soc 68:691-698, 2020., (© 2020 The American Geriatrics Society.)

Background: Novel models that improve generalist-level palliative care for cystic fibrosis (CF) are needed to address the burden of this illness. A screening-and-triage model has the potential to identify clinical problems requiring immediate follow-up by CF professionals. This study describes such a model and its immediate impact on care delivery for CF patients during a two-year period., Methods: Eligible adults completed monthly online screening for sources of distress. If results revealed one or more "indicators of concern" on two consecutive screenings, this triggered an attempted triage by a social worker. Completed triages led to prompt follow-up by CF professionals for clinical problems, if indicated. Process data were summarized and generalized linear mixed models were used to evaluate baseline patient characteristics (symptom distress, quality of life, and sociodemographics) associated with the need for prompt follow-up., Results: A total of 1,015 monthly surveys were completed by 74 patients; 634 (66 patients) had >1 indicators of concern; and 164 surveys (46 patients) had >1 indicators for two consecutive surveys (e.g., global distress, pain, dyspnea, and psychological symptoms). The 164 attempted triages yielded 84 completed triages (51.2%), of which 39 (46.4%) required prompt follow-up. In multivariable analyses, older patients and those with higher symptom distress at baseline were more likely to require prompt follow-up (p < .05)., Conclusions: Web-based screening that assesses varied domains of distress or burden can identify a subset of CF patients whose clinical problems may benefit from immediate medical or psychological attention. Additional investigations should improve screening efficiency., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest associated with this research., (Copyright © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Context: Minimizing bias in randomized controlled trials (RCTs) includes intention-to-treat analyses. Hospice/palliative care RCTs are constrained by high attrition unpredictable when consenting, including withdrawals between randomization and first exposure to the intervention. Such withdrawals may systematically bias findings away from the new intervention being evaluated if they are considered nonresponders., Objectives: This study aimed to quantify the impact within intention-to-treat principles., Methods: A theoretical model was developed to assess the impact of withdrawals between randomization and first exposure on study power and effect sizes. Ten reported hospice/palliative care studies had power recalculated accounting for such withdrawal., Results: In the theoretical model, when 5% of withdrawals occurred between randomization and first exposure to the intervention, change in power was demonstrated in binary outcomes (2.0%-2.2%), continuous outcomes (0.8%-2.0%), and time-to-event outcomes (1.6%-2.0%), and odds ratios were changed by 0.06-0.17. Greater power loss was observed with larger effect sizes. Withdrawal rates were 0.9%-10% in the 10 reported RCTs, corresponding to power losses of 0.1%-2.2%. For studies with binary outcomes, withdrawal rates were 0.3%-1.2% changing odds ratios by 0.01-0.22., Conclusion: If blinding is maintained and all interventions are available simultaneously, our model suggests that excluding data from withdrawals between randomization and first exposure to the intervention minimizes one bias. This is the safety population as defined by the International Committee on Harmonization. When planning for future trials, minimizing the time between randomization and first exposure to the intervention will minimize the problem. Power should be calculated on people who receive the intervention., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Numerous studies have characterized the pain reported by patients with advanced illness in terms of descriptors such as severity, but few have measured pain-related distress. Distress may be important in the clinical approach to pain. To evaluate pain-related distress among adult patients with advanced illness and pain following enrollment in an urban, specialist-level, community-based palliative care program., Method: In a retrospective cross-sectional analysis, data were extracted from the electronic health records of all patients who were able to complete the pain item from the Condensed Memorial Symptom Assessment Scale at the start of care. Bivariate and multivariate analyses evaluated the associations between distress and both sociodemographics and disease-related information., Results: The 506 patients completing the pain item had a mean (SD) age of 70.7 years (13.8); 64.2% were women, 32.1% were Hispanic, 32.6% were white, and 27.7% were black. Of the 503 patients who indicated some level of distress on a 0-4 scale, 221 (43.7%) had high distress, defined as a score ≥3 ("quite a bit" or "very much"). Cancer diagnosis and poor performance status (unable to care for self) were predictors of high pain-related distress (both p &lt; 0.05).Significance of resultsAmong patients with advanced illness who reported pain at the start of care by a specialist palliative care program, high pain-related distress was common, particularly among those with cancer or poor physical function. Further studies are needed to explore the extent to which pain-related distress should inform the assessment and management of pain.

Context: Care provided to seriously ill patients by frontline social workers is a component of generalist-level palliative care. The core competencies for high-quality generalist-level palliative social work are necessary to promote training curricula and best practices but have not yet been defined in the U.S., Objective: The objective of this study was to develop consensus-derived core competencies for generalist-level palliative social work., Methods: Fifty-five proposed social work competencies were categorized by the eight domains of palliative care identified by the National Consensus Project for Quality Palliative Care. The competencies were rated by 41 regionally dispersed, Master's level social workers selected through purposive and snowball sampling using a Delphi method. Each was rated as essential for generalist-level palliative social work, acceptable with modifications, or rejected based on the judgment that it was not essential for generalist-level palliative social work or was outside the scope of practice. Consensus was defined as >70% agreement to accept or reject a competency. Three review rounds were needed to achieve consensus on all competencies., Results: Two competencies were added to the original list. Of the 57 proposed competencies, 41 were accepted (19 after modification) and 16 were rejected. Competencies in the social, spiritual, cultural, and ethical/legal aspects of care domains were relatively more likely to be accepted compared with those in structure and processes of care, physical care, psychological care, and care of patient at the end of life., Conclusion: The 41 consensus-derived competencies for generalist-level palliative social work may inform the development of training curricula and standards for high-quality care., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

ABSTRACTObjectives:Little is known about the experience of family caregivers of adults with cystic fibrosis (CF). This information is important for the identification of caregivers at risk for burden., Methods: This was a longitudinal analysis of survey data obtained from caregivers of adult CF patients participating in an early intervention palliative care trial. Caregivers completed the validated Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period. Mixed-effects modeling evaluated multivariate associations with positive and negative caregiver perceptions over time., Results: Of the 54 caregivers, 47.9% were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9% were married; and 63.0% were employed. At baseline, the BASC revealed large variations in positive and negative perceptions of caregiving. Although average scores over time were unchanging, variation was greater across caregivers than within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact of caregiving in the sample was higher than the negative impact. Multivariate analysis revealed that patients' baseline pulmonary function and their full-time employment status predicted caregiver burden over time., Significance of Results: Caregivers of CF patients varied in their positive and negative caregiving experiences, although burden levels in individual caregivers were stable over time. When the disease was advanced, caregivers of CF patients experienced more overall burden but also more positive impact. This suggests that the role of caregivers may become more meaningful as disease severity worsens. In addition, full-time patient employment was associated with lower caregiver burden regardless of disease severity. This suggests that burden in CF caregivers may be predicted by financial strain or benefits conferred by patient employment. These associations require further investigation to determine whether highly burdened caregivers can be identified and assisted using tailored interventions.