Implementation and Effectiveness of Integrating Palliative Care Into Ambulatory Care of Noncancer Serious Chronic Illness: Mixed Methods Review and Meta-Analysis.

PURPOSE: To perform a mixed methods review to evaluate the effectiveness and implementation of models for integrating palliative care into ambulatory care for US adults with noncancer serious chronic illness. METHODS: We searched 3 electronic databases from January 2000 to May 2020 and included qualitative, mixed methods studies and randomized and nonrandomized controlled trials. For each study, 2 reviewers abstracted data and independently assessed for quality. We conducted meta-analyses as appropriate and graded strength of evidence (SOE) for quantitative outcomes. RESULTS: Quantitative analysis included 14 studies of 2,934 patients. Compared to usual care, models evaluated were not more effective for improving patient health-related quality of life (HRQOL) (standardized mean difference [SMD] of 4 of 8 studies, 0.19; 95% CI, ‒0.03 to 0.41) (SOE: moderate) or for patient depressive symptom scores (SMD of 3 of 9 studies, ‒0.09; 95% CI, ‒0.35 to 0.16) (SOE: moderate). Models might have little to no effect on patient satisfaction (SOE: low) but were more effective for increasing advance directive (AD) documentation (relative risk, 1.62; 95% CI, 1.35 to 1.94) (SOE: moderate). Qualitative analysis included 5 studies of 146 patients. Patient preferences for appropriate timing of palliative care varied; costs, additional visits, and travel were considered barriers to implementation. CONCLUSION: Models might have little to no effect on decreasing overall symptom burden and were not more effective than usual care for improving HRQOL or depressive symptom scores but were more effective for increasing AD documentation. Additional research should focus on identifying and addressing characteristics and implementation factors critical to integrating models to improve ambulatory, patient-centered outcomes.

Pain Experiences of Adults With Sickle Cell Disease and Hematopoietic Stem Cell Transplantation: A Qualitative Study.

OBJECTIVE: Despite increasing use of hematopoietic stem cell transplantation (HSCT) for adults with sickle cell disease (SCD), little is known about pain management experiences throughout this process. The objective of this study was to explore patients' experiences with pain and pain management during and after HSCT for SCD. METHODS: We conducted a qualitative interview study with 10 patients who underwent HSCT for SCD. We transcribed interviews verbatim and inductively identified codes. We used thematic analysis alongside a constant comparative method to develop and refine a codebook that aided in the identification of themes. RESULTS: Four key themes emerged. (1) The pain trajectory: patients described a fluctuating course of pain during HSCT, which often extended long afterwards and impacted all aspects of life, particularly affected by pre-HSCT experiences; (2) The role of opioids-a double-edged sword: patients described opioids as reducing pain but insufficiently to balance significant adverse effects and burden; (3) Patient-centered decision making in pain management: patients described insufficient agency in decisions about opioid use and weaning; and (4) Consequences of health-related stigma: patients described experiences with stigma, mainly related to opioid use and weaning, as similar to pre-HSCT. CONCLUSIONS: From the perspective of patients who have undergone HSCT for SCD, clinicians should use a patient-centered approach, integrating non-opioid approaches into pain management, particularly psychosocial support. As transplant for SCD becomes increasingly available, incorporating patient perspectives may improve health care delivery and overall patient experiences.

Evaluation of the head and neck cancer patient population and the incidence of hospitalization at an academic medical center.

PURPOSE: Patients with head and neck cancer are at risk for disease- and treatment-related toxicities that may be severe enough to require hospitalization. The risk factors associated with hospitalization in these patients are not well defined. METHODS: We conducted a single-center, retrospective observational study of patients with head and neck cancer receiving chemotherapy at an academic medical center infusion clinic in a one-year period. The primary objective was to characterize the head and neck cancer population at an academic medical center. Secondary objectives included describing the clinical and social factors associated with hospitalization. RESULTS: There were 109 patients with head and neck cancer included in the analysis. Of these patients, 38 (35%) were hospitalized. The factors that were significantly associated with hospitalization on univariable logistic regression were former alcohol abuse, being on a nonstandard of care chemotherapy regimen, and having a chemotherapy agent discontinued. On multivariable logistic regression, the factor that was significantly associated with hospitalization was having a chemotherapy agent discontinued. The most common reasons for hospitalization included shortness of breath/respiratory failure, fever/neutropenic fever, and infection. The most common new supportive care medications prescribed at discharge were stool softeners or laxatives and opioids. CONCLUSION: This study identified several factors which may be useful to identify patients as high risk for hospitalization and the next steps will be to determine and study the role of the pharmacist in preventing hospitalization of these patients. Further studies are needed to assess the impact of adding a pharmacist to the head and neck cancer multidisciplinary team.

Strategies for Addressing Cancer Patients' Complaints of Fatigue.

Cancer-related fatigue is a complex and common symptom for cancer patients. This article reviews important topics that oncology practitioners should know to better manage fatigue in this patient population. Our discussion includes identification and assessment of fatigue severity, as well as screening for comorbid conditions that may be contributing to an individual patient's fatigue. Finally, we review nonpharmacologic and pharmacologic interventions for the treatment of cancer-related fatigue and the associated literature supporting their effectiveness.

Association of goals of care meetings for hospitalized cancer patients at risk for critical care with patient outcomes.

BACKGROUND: Caring for cancer patients with advanced and refractory disease requires communication about care preferences, particularly when patients become ill enough to be at risk for critical care interventions potentially inconsistent with their preferences. AIM: To describe the use of goals of care discussions in patients with advanced/refractory cancer at risk for critical care interventions and evaluate associations between these discussions and outcomes. DESIGN: Cohort study describing patients/families' perceptions of goals of care meetings and comparing health care utilization outcomes of patients who did and did not have discussions. SETTING/PARTICIPANTS: Inpatient units of an academic cancer center. Included patients had metastatic solid tumors or relapsed/refractory lymphoma or leukemia and were at risk for critical care, defined as requiring supplemental oxygen and/or cardiac monitor. RESULTS: Of 86 patients enrolled, 34 (39%) had a reported goals of care discussion (study group). Patients/families reported their needs and goals were addressed moderately to quite a bit during the meetings. Patients in the study group were less likely to receive critical care (0% vs 22%, p = 0.003) and more likely to be discharged to hospice (48% vs 30%, p = 0.04) than the control group. Only one patient in the study group died during the index hospitalization (on comfort care) (3%) compared with 9(17%) in the control group (p = 0.08). CONCLUSION: Goals of care meetings for advanced/refractory cancer inpatients at risk for critical care interventions can address patient and family goals and needs and improve health care utilization. These meetings should be part of routine care for these patients.

Characterization of Outpatient Gabapentinoid Prescribing for Pain.

Two statements from national organizations outline recommended minimum effective doses of gabapentin and pregabalin for the treatment of diabetic peripheral neuropathy (DPN). However, studies of real-world gabapentinoid dosing demonstrate that the recommended dose targets are frequently not met and do not consider renal insufficiency. This study aimed to characterize gabapentinoid prescribing patterns in patients receiving primary care at two internal medicine clinics within an academic medical center. This retrospective chart review included adult outpatients who were newly initiated on gabapentin or pregabalin between October 1, 2017 and October 1, 2020 and reviewed for 12 months. A total of 1,221 patients were included in the study with 1,079 (88.4%) prescribed gabapentin and 142 (11.6%) prescribed pregabalin. Only 22.4% of patients prescribed gabapentin and 33.3% of patients prescribed pregabalin with adequate renal function met the minimum effective dosing of gabapentin 1800 mg per day and pregabalin 300 mg per day provided by the American Diabetes Association (ADA) and American Academy of Neurology (AAN). This study supports the need for optimization of gabapentinoid dosing to ensure an adequate trial at the minimum effective dose is completed.

The Application of Minimal Clinically Important Differences in Palliative Research: Interpretation of Results of a Systematic Review.

CONTEXT: Interpreting clinical meaningfulness of patient reported outcomes (PROs) in palliative care research is key in evidence-based practice. Minimal clinically important differences (MCIDs) can help interpret whether changes in PROs are meaningful to patients. OBJECTIVE: To examine use of MCIDs in a recent systematic review on integrating palliative care into ambulatory care for U.S. adults with noncancer serious chronic illness and their effect on interpretation of key PROs. METHODS: Paired investigators abstracted MCIDs for each PRO in the systematic review from PubMed, tool specific websites, and Google Scholar. Investigators compared findings and resolved differences through consensus. MCIDs were interpreted alongside results from meta-analyses or individual studies to draw conclusions on effectiveness of interventions. RESULTS: MCIDs could be identified for 10 of 23 instruments affecting seven of nine outcomes. The most notable effect was for depressive symptoms, where three trials reported statistically significant differences that were not clinically meaningful based on available MCIDs. Although differences in statistical significance and MCIDs were noted for other outcomes, they were accounted for in meta-analyses or affected a minimal number of studies within the outcome category. CONCLUSIONS: Incorporating MCIDs affected the interpretation of almost all PROs in the systematic review. MCIDs are important measures of clinical meaningfulness for the interpretation of palliative care research involving PROs. Researchers should consider using instruments with well-established MCIDs and incorporate MCIDs, when available, in study design and interpretation.

Pharmacologic Interventions for Breathlessness in Patients With Advanced Cancer: A Systematic Review and Meta-analysis.

Importance: Improved survival in patients with advanced cancer has increased the need for better understanding of how to manage common symptoms that they may experience, such as breathlessness. Objective: To assess the benefits and harms associated with pharmacologic interventions for breathlessness in adults with advanced cancer. Data Sources: PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies published from database inception through May 31, 2020, using predefined eligibility criteria within a PICOTS (population, intervention, comparator, outcome, timing, setting) format. Study Selection: Randomized clinical trials (RCTs), non-RCTs, and observational studies with a comparison group that evaluated benefits and/or harms and cohort studies that reported harms were selected. Data Extraction and Synthesis: Two reviewers independently screened studies for eligibility, serially abstracted data, independently assessed risk of bias, and graded strength of evidence (SOE). Main Outcomes and Measures: Benefits and harms of pharmacologic interventions were compared, focusing on breathlessness, anxiety, exercise capacity, and health-related quality of life. When possible, meta-analyses were conducted and standardized mean differences (SMDs) calculated. Results: In this systematic review and meta-analysis, a total of 7729 unique citations were identified, of which 19 studies (17 RCTs and 2 retrospective studies) that included a total of 1424 patients assessed the benefits of medications for management of breathlessness in advanced cancer or reported harms. The most commonly reported type of cancer was lung cancer. Opioids were not associated with more effectiveness than placebo for improving breathlessness (SMD, -0.14; 95% CI, -0.47 to 0.18) or exercise capacity ( SMD, 0.06; 95% CI, -0.43 to 0.55) (SOE, moderate); most studies examined exertional breathlessness. Specific dose and/or route of administration of opioids did not differ in effectiveness for breathlessness (SMD, 0.15; 95% CI, -0.22 to 0.52) (SOE, low). Anxiolytics were not associated with more effectiveness than placebo for breathlessness or anxiety (reported mean between-group difference, -0.52; 95% CI, -1.045 to 0.005) (SOE, low). Evidence for other pharmacologic interventions was limited. Pharmacologic interventions demonstrated some harms compared with usual care, but dropout attributable to adverse events was minimal in these short-term studies (range 3.2%-16%). Conclusions and Relevance: Evidence did not support the association of opioids or other pharmacologic interventions with improved breathlessness. Given that studies had many limitations, pharmacologic interventions should be considered in selected patients but need to be considered in the context of potential harms and evidence of an association of nonpharmacologic interventions with improved breathlessness.

Nonpharmacological Interventions for Managing Breathlessness in Patients With Advanced Cancer: A Systematic Review.

IMPORTANCE: Breathlessness is a frequent and debilitating symptom in patients with advanced cancer. Often, in the context of breathlessness, aggressive cancer treatment is not beneficial, feasible, or aligned with goals of care. Targeted symptom-focused interventions may be helpful in this scenario. OBJECTIVE: To evaluate the advantages and harms of nonpharmacological interventions for managing breathlessness in adults with advanced cancer. EVIDENCE REVIEW: PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception through May 2020 for published randomized clinical trials (RCTs), nonrandomized controlled trials, and observational studies of the advantages and/or harms of nonpharmacological interventions on alleviating breathlessness in adults with advanced cancer. Only English-language studies were screened for eligibility, titles, abstracts, and full text. Risk of bias and strength of evidence (SOE) were independently assessed. The key outcomes reported in studies were breathlessness, anxiety, exercise capacity, health-related quality of life, and harms. Data were analyzed from October 1, 2019, to June 30, 2020. FINDINGS: A total of 29 RCTs (2423 participants) were included. These RCTs evaluated various types of interventions, such as respiratory (9 RCTs), activity and rehabilitation (7 RCTs), behavioral and psychoeducational (3 RCTs), integrative medicine (4 RCTs), and multicomponent (6 RCTs). Several nonpharmacological interventions were associated with improved breathlessness, including fan therapy (standardized mean difference [SMD], -2.09; 95% CI, -3.81 to -0.37; I2 = 94.3%; P for heterogeneity = .02; moderate SOE) and bilevel ventilation (estimated slope difference, -0.58; 95% CI, -0.92 to -0.23; low SOE), lasting for a few minutes to hours, in the inpatient setting. In the outpatient setting, nonpharmacological interventions associated with improved breathlessness were acupressure and reflexology (integrative medicine) (low SOE) and multicomponent interventions (combined activity and rehabilitation, behavioral and psychoeducational, and integrative medicine) (low SOE) lasting for a few weeks to months. Five of the 29 RCTs (17%) reported adverse events, although adverse events and study dropouts were uncommon. CONCLUSIONS AND RELEVANCE: Findings of this review include the safety and association with improved breathlessness of several nonpharmacological interventions for adults with advanced cancer. Guidelines and clinical practice should evolve to incorporate nonpharmacological interventions as first-line treatment for adults with advanced cancer and breathlessness.

Current state of opioid stewardship.

PURPOSE: The opioid epidemic continues to result in significant morbidity and mortality even within hospitals where opioids are the second most common cause of adverse events. Opioid stewardship represents one model for hospitals to promote safe and rational prescribing of opioids to mitigate preventable adverse events in alliance with new Joint Commission standards. The purpose of this study was to identify the prevalence of current hospital practices to improve opioid use. METHODS: A cross-sectional survey of hospital best practices for opioid use was electronically distributed via electronic listservs in March 2018 to examine the presence of an opioid stewardship program and related practices, including formulary restrictions, specialist involvement for high-risk patients, types of risk factors screened, and educational activities. RESULTS: Among 133 included hospitals, 23% reported a stewardship program and 14% reported a prospective screening process to identify patients at high risk of opioid-related adverse events (ORAEs). Among those with a prospective screening process, there was variability in ORAE risk factor screening. Formulary restrictions were dependent on specific opioids and formulations. Patient-controlled analgesia was restricted at 45% of hospitals. Most hospitals reported having a pain management service (90%) and a palliative care service providing pain management (67%). CONCLUSION: The absence of opioid stewardship and prospectively screening ORAEs represents a gap in current practice at surveyed hospitals. Hospitals have an opportunity to implement and refine best practices such as access to pain management specialists, use of formulary restrictions, and retrospective and prospective monitoring of adverse events to improve opioid use.

Non-pharmacologic treatments for symptoms of diabetic peripheral neuropathy: a systematic review.

Objective: To systematically assess benefits and harm of non-pharmacologic interventions for diabetic peripheral neuropathy (DPN) symptoms.Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from 1966 to May 24, 2016 for randomized controlled trials. Two reviewers evaluated studies for eligibility, serially abstracted data, evaluated risk of bias, and graded strength of evidence (SOE) for critical outcomes (pain and quality-of-life).Results: Twenty-three trials were included. For pain, alpha-lipoic acid was more effective than placebo (moderate SOE) and frequency-modulated electromagnetic stimulation was more effective than sham (low SOE) in the short-term but not the long-term. Electrical stimulation (including transcutaneous) was not effective for pain (low SOE). Spinal cord stimulation was more effective than usual care for pain (low SOE), but had serious complications, and studies had no sham arm. Evidence for cognitive behavioral therapy and acupuncture was insufficient; no exercise or physical therapy trials met inclusion criteria. No interventions reported sufficient evidence on quality-of-life. Most studies were short-term with unclear risk of bias.Conclusions: Alpha-lipoic acid and spinal cord stimulation were effective for pain; studies were short-term with quality deficits. Spinal cord stimulation had serious adverse events. Further research should address long-term outcomes and other non-pharmacologic treatments.

Development and implementation of procedures for outpatient naloxone prescribing at a large academic medical center.

PURPOSE: An interprofessional initiative to operationalize outpatient naloxone prescribing at a large academic medical center is described. SUMMARY: The initiative was carried out by a work group of clinical pharmacists and pharmacy administrators in collaboration with physicians and nursing staff leaders from multiple practice settings. An opioid overdose risk-assessment guide was developed on the basis of literature review and expert opinion. An institutional policy to guide identification of high-risk patient populations and facilitate naloxone prescribing and dispensing was developed and vetted by multiple expert committees. Patient education materials were created, and patients at high risk for opioid overdose were educated about overdose risk factors and naloxone use by a pharmacist and/or nurse before discharge or, in some cases, by outpatient pharmacists; when feasible, patients' friends, family members, and/or caregivers were included in education sessions. Interventions included distribution of a pamphlet emphasizing the importance of contacting emergency medical services personnel immediately in the event of an overdose, depicting the process for administration of injectable and nasal spray formulations of naloxone, and providing information on other first-response steps. Collaboration with outpatient pharmacies allowed for successful dispensing of naloxone prescriptions. CONCLUSION: The implementation of an outpatient naloxone prescribing policy at a large academic medical center created a streamlined approach for the interprofessional healthcare team to use in providing naloxone education and improved naloxone access to patients at high risk for opioid overdose.

Searching ClinicalTrials.gov did not change the conclusions of a systematic review.

OBJECTIVES: We assessed the effect of searching ClinicalTrials.gov on the conclusions of a systematic review. STUDY DESIGN AND SETTING: We conducted this case study concurrently with a systematic review. We searched ClinicalTrials.gov on March 9, 2016, to identify trial records eligible for inclusion in the review. Two independent reviewers screened ClinicalTrials.gov records. We compared conclusions and strength of evidence grade with and without ClinicalTrials.gov records for 31 comparisons and 2 outcomes. RESULTS: We identified 106 trials (53 in the peer-reviewed literature only, 23 in ClinicalTrials.gov only, and 30 in both sources). For one comparison, the addition of results identified through ClinicalTrials.gov reduced the pooled effect size. We found evidence of selective outcome reporting for two comparisons and suspected publication bias for another two comparisons. For all other comparisons, searching ClinicalTrials.gov did not change conclusions or the strength of evidence grading for the two outcomes. CONCLUSION: Our search of ClinicalTrials.gov bolstered suspicions of reporting biases but did not change either the conclusions or the strength of evidence grading. Further research is needed to determine the effect of searching ClinicalTrials.gov on the conclusions of systematic reviews in different topic areas and as the new rules for registration of trial results take effect.

Gabapentin for Cough in Cancer.

Cough is a common problem among cancer patients, especially lung cancer patients. Gabapentin has been shown to be effective in reducing cough number and severity in patients with idiopathic refractory cough. The authors report here the successful use of gabapentin at usual doses to treat cough in cancer patients, including two with lung cancer, with minimal side effects. Gabapentin may be a useful addition to the symptom management toolbox for palliation of cancer symptoms.

Pharmacotherapy for diabetic peripheral neuropathy pain and quality of life: A systematic review.

OBJECTIVE: To systematically assess the effect of pharmacologic treatments of diabetic peripheral neuropathy (DPN) on pain and quality of life. METHODS: We searched PubMed and Cochrane Database of Systematic Reviews for systematic reviews from 2011 to October 12, 2015, and PubMed, Embase, and the Cochrane Central Register of Controlled Trials for primary studies from January 1, 2013, to May 24, 2016. We searched Clinicaltrials.gov on March 9, 2016. Two reviewers independently evaluated studies for eligibility, serially abstracted data, and independently evaluated risk of bias and graded strength of evidence (SOE). RESULTS: We updated a recently completed systematic review of 57 eligible studies with 24 additional published studies and 25 unpublished studies. For reducing neuropathy-related pain, the serotonin-norepinephrine reuptake inhibitors duloxetine and venlafaxine (moderate SOE), the anticonvulsants pregabalin and oxcarbazepine (low SOE), the drug classes tricyclic antidepressants (low SOE) and atypical opioids (low SOE), and botulinum toxin (low SOE) were more effective than placebo. We could not draw conclusions about quality of life due to incomplete reporting. All studies were short-term (less than 6 months), and all effective drugs had more than 9% dropouts from adverse effects. CONCLUSIONS: For reducing pain, duloxetine and venlafaxine, pregabalin and oxcarbazepine, tricyclic antidepressants, atypical opioids, and botulinum toxin were more effective than placebo. However, quality of life was poorly reported, studies were short-term, drugs had substantial dropout rates, and opioids have significant risks. Future studies should evaluate longer-term outcomes, use methods and measures recommended by pain organizations, and assess patients' quality of life.

Successful Treatment of Opioid-Refractory Cancer Pain with Short-Course, Low-Dose Ketamine.

Opioids remain the mainstay of treatment for severe cancer pain, but up to 20% of patients have persistent or refractory pain despite rapid and aggressive opioid titration, or develop refractory pain after long-term opioid use. In these scenarios, alternative agents and mechanisms for analgesia should be considered. This case report describes a 28-year-old man with metastatic pancreatic neuroendocrine cancer with severe, intractable pain despite high-dose opioids including methadone and a hydromorphone patient-controlled analgesia (PCA). After treatment with short-course, low-dose ketamine, his opioid requirements decreased by 99% and pain ratings by 50%, with the majority of this decrease occurring in the first 48 hours. As this patient's pain and opioid regimen escalated, he likely experienced some component of central sensitization and hyperalgesia. Administration of ketamine reduced opioid consumption by 99% and potentially "reset" neuronal hyperexcitability and reduced pain signaling, allowing for improved pain control.

Team Leadership and Cancer End-of-Life Decision Making.

End-of-life decision making in cancer can be a complicated process. Patients and families encounter multiple providers throughout their cancer care. When the efforts of these providers are not well coordinated in teams, opportunities for high-quality, longitudinal goals of care discussions can be missed. This article reviews the case of a 55-year-old man with lung cancer, illustrating the barriers and missed opportunities for end-of-life decision making in his care through the lens of team leadership, a key principle in the science of teams. The challenges demonstrated in this case reflect the importance of the four functions of team leadership: information search and structuring, information use in problem solving, managing personnel resources, and managing material resources. Engaging in shared leadership of these four functions can help care providers improve their interactions with patients and families concerning end-of-life care decision making. This shared leadership can also produce a cohesive care plan that benefits from the expertise of the range of available providers while reflecting patient needs and preferences. Clinicians and researchers should consider the roles of team leadership functions and shared leadership in improving patient care when developing and studying models of cancer care delivery.

Ziconotide-induced psychosis: a case report.

Ziconotide is used intrathecally in the management of severe chronic pain that contains a warning against neuropsychiatric adverse events. The definition of psychiatric events is broad and management strategies are vague. This case report describes a 49-year-old female who was admitted to the acute psychiatric unit to address auditory hallucinations and paranoid ideation persisting for 3 weeks. Approximately 3 months ago, an intrathecal pump with ziconotide was implanted to treat pain. Upon hospital admission, the pump was infusing at a rate of 4.9 mcg/24 hours. Because the drug could not be immediately discontinued, risperidone 0.5 mg nightly was initiated and subsequently, the pump was drained of ziconotide, rinsed, and refilled with normal saline. The patient reported no hallucinations or apparent delusions several hours later and was eventually discharged with resolution of psychotic symptoms and continuation of risperidone for 10 days. Despite the identification of neuropsychiatric effects, limited information is available to characterize the presentation and guide specific management aside from recommendations to discontinue the infusion and possible use of psychotropic medications or necessity for hospitalization. This case report characterizes one presentation of hallucinations and paranoia associated with ziconotide intrathecal infusion. Clinicians should be aware of the management strategies to mediate these adverse effects, including expected time to adverse effect resolution, removal of ziconotide from the pump, and role for short-term use of antipsychotics.