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Drugs that are commercially available but have novel mechanisms of action should be explored as analgesics. This review will discuss haloperidol, miragabalin, palmitoylethanolamide (PEA), and clonidine as adjuvant analgesics or analgesics. Haloperidol is a sigma-1 receptor antagonist. Under stress and neuropathic injury, sigma-1 receptors act as a chaperone protein, which downmodulates opioid receptor activities and opens several ion channels. Clinically, there is only low-grade evidence that haloperidol improves pain when combined with morphine, methadone, or tramadol in patients who have cancer, pain from fibrosis, radiation necrosis, or neuropathic pain. Miragabalin is a gabapentinoid approved for the treatment of neuropathic pain in Japan since 2019. In randomized trials, patients with diabetic neuropathy have responded to miragabalin. Its long binding half-life on the calcium channel subunit may provide an advantage over other gabapentinoids. PEA belongs to a group of endogenous bioactive lipids called ALIAmides (autocoid local injury antagonist amides), which have a sense role in modulating numerous biological processes in particular non-neuronal neuroinflammatory responses to neuropathic injury and systemic inflammation. Multiple randomized trials and meta-analyses have demonstrated PEA's effectiveness in reducing pain severity arising from diverse pain phenotypes. Clonidine is an alpha2 adrenoceptor agonist and an imidazoline2 receptor agonist, which is U.S. Federal Drug Administration approved for attention deficit hyperactivity disorder in children, Tourette's syndrome, adjunctive therapy for cancer-related pain, and hypertension. Clonidine activation at alpha2 adrenoceptors causes downstream activation of inhibitory G-proteins (Gi/Go), which inhibits cyclic Adenosine monophosphate (AMP) production and hyperpolarizes neuron membranes, thus reducing allodynia. Intravenous clonidine has been used in terminally ill patients with poorly controlled symptoms, in particular pain and agitation.

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BACKGROUND: Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries. Therefore, we performed a scoping systematic review of opioid conversion studies to inform an international eDelphi guideline. METHODS: To ensure a comprehensive review, we conducted a systematic search across multiple databases (OVID Medline, PsycINFO, Embase, EBM-Cochrane Database of Systematic Reviews and Registered Trials, LILACS, IMEMR, AIM, WPRIM) using studies published up to June 2022. Additionally, we performed hand and Google Scholar searches to verify the completeness of our findings. Our inclusion criteria encompassed randomized and non-randomized studies with no age limit, with only a few pediatric studies identified. We included studies on cancer, non-cancer, acute, and chronic pain. The level and grade of evidence were determined based on the Multinational Supportive Care in Cancer (MASCC) criteria. RESULTS: Our search yielded 21,118 abstracts, including 140 randomized (RCT) and 68 non-randomized (NRCT) clinical trials. We compared these results with recently published conversion ratios. Modest correlations were noted between published reviews and the present scoping systematic review. CONCLUSION: The present scoping systematic review found low-quality evidence to support an opioid conversion guideline. We will use these data, including conversion ratios and type and route of administration, to inform an eDelphi guideline.

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The number needed to treat (NNT) is the inverse of the absolute risk difference, which is used as a secondary outcome to clinical trials as a measure relevant to a positive trial, supplementing statistical significance. The NNT requires dichotomous outcomes and is influenced by the baseline disease or symptom severity, the particular population, the type and intensity of the interventional, the duration of treatment, the time period to assessment of response, and the comparator response. Confidence intervals should always accompany NNT for the precision of its estimate. In this review, three meta-analyses are reviewed, which included the NNT in the analysis of response.

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Nausea and vomiting are common experiences and are often dreaded more than pain. This review discusses blonanserin, mirtazapine, and isopropyl alcohol as antiemetics. Blonanserin, an atypical antipsychotic with a high affinity for dopamine D2 and D3 receptors and serotonin receptor 5-HT2A, has less of a risk of extrapyramidal adverse effects. Transdermal blonanserin, available in Korea, Japan, and China in a small number of trials, has improved nausea in patients not responding to standard antiemetics. Mirtazapine is a noradrenergic and specific serotonergic antidepressant that has been used for multiple symptoms besides depression. There is little evidence that mirtazapine improves anorexia or nausea in advanced cancer but is as effective as olanzapine in reducing chemotherapy-induced nausea and vomiting. Isopropyl alcohol aromatherapy has been successfully used in the emergency department for nausea and vomiting with an onset to benefit more rapidly than standard antiemetics. Isopropyl alcohol prep pads can be used for home-going antiemetic therapy and as a bridge to treating acute nausea until standard antiemetics take effect.

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Standardizing opioid management is challenging due to the absence of a ceiling dose, the unknown ideal therapeutic plasma level, and the lack of an clear relationship between dose and therapeutic response. Opioid rotation or conversion, which is switching from one opioid, route of administration, or both, to another, to improve therapeutic response and reduce toxicities, occurs in 20-40 percent of patients treated with opioids. Opioid conversion is often needed when there are adverse effects, toxicities, or inability to tolerate a certain opioid formulation. A majority of patients benefit from opioid conversion, leading to improved analgesia and less adverse effects. There are different published ways of converting opioids in the literature. This review of 20 years of literature is centered on opioid conversions and aims to discuss the complexity of converting opioids. We discuss study designs, outcomes and measures, pain phenotypes, patient characteristics, comparisons of equivalent doses between opioids, reconciling conversion ratios between opioids, routes, directional differences, half-lives and metabolites, interindividual variability, and comparison to package insert information. Palliative care specialists have not yet come to a consensus on the ideal opioid equianalgesic table; however, we discuss a recently updated table, based on retrospective evidence, that may serve as a gold standard for practical use in the palliative care population. More robust, well-designed studies are needed to validate and guide future opioid conversion data.

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CONTEXT: Half of the patients with cancer who undergo radiation therapy do so with palliative intent. OBJECTIVES: To determine the proportion of undergoing radiation in the last month of life, patient characteristics, cancer course, the type and duration of radiation, whether palliative care was involved, and the of radiation with aggressive cancer care metrics. METHODS: One thousand seven hundred twenty-seven patients who died of cancer between January 1, 2018, and December 31, 2019, were included. Demographics, cancer stage, palliative care referral, advance directives, use of home health care, radiation timing, and survival were collected. Type of radiation, course, and intent were reviewed. Chi-square analysis was utilized for categorical variables, and Kruskal-Wallis tests for continuous variables. A stepwise selection was used to build a Cox proportional hazard model. RESULTS: Two hundred thirty-three patients underwent radiation in the last month of life. Younger patients underwent radiation 67.3 years (SD 11.52) versus 69.2 years (SD 11.96). 42.6% had radiation within two weeks of death. The average fraction number was 5.5. Individuals undergoing radiation were more likely to start chemotherapy within the last 30 days of life, continue chemotherapy within two weeks of death, be admitted to the ICU, and have two or more hospitalizations or emergency room visits. Survival measured from the date of diagnosis was shorter for those undergoing radiation, 122 days (IQR 58-462) versus 474 days (IQR 225-1150). Palliative care consultations occurred later in those undergoing radiation therapy. CONCLUSION: Radiation therapy in the last month of life occurs in younger patients with rapidly progressive cancer, who are subject to more aggressive cancer care, and have late palliative care consults.

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The use of telemedicine in healthcare settings has continued to increase over the last few years. This has led to new communication-based concerns in palliative care settings. To date, there are no specific guidelines on telemedicine etiqettes relating to conducting online family meetings. This case report discusses some etiquette-failures in a telemedicine family meeting, and offers suggestions to improve communication etiqettes or 'webside manners' in these settings.

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Cannabis is becoming more popular and more available in the United States. It has been approved for use by multiple states for various conditions and several states now allow recreational cannabis. We explore the structure of cannabis distribution, the process of acquisition, outcomes, and the safety of cannabis in the United States.

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Breaking bad news can be a difficult process. This can further be complicated when such news needs to be delivered around the holiday season. Here, we discuss such a case, and provide recommendations on breaking bad news around the holiday season.

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Palliative care has several tools and questionnaires which are commonly used for patient-related outcomes and prognosis. As an example, the Surprise Question (I would or would not be surprised that this person would have died in a year) has been used as a screen for palliative care referral but also used as a prognostic tool. Diagnostic tests, prognostic tools, and tools for gauging outcomes have certain sensitivity and specificity in predicting a diagnosis or outcome. Clinicians often use positive and negative predictive values in judging the merits of a diagnostic tool or questionnaire. However positive and negative predictive values are highly dependent on the prevalence of disease or outcome in a population and thus are not portable across studies. Likelihood ratios are both portable across populations but also provide the strength of the diagnostic or predictive measure of a test or questionnaire. In this article, we review the value and limitations of likelihood ratios and illustrate the value of using likelihood ratios using 3 studies centered on the Surprise Question published in 2022.

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Pain management in palliative care (PC) is becoming more complex as patients survive longer with life-limiting illnesses and population-wide trends involving opioid misuse become more common in serious illness. Buprenorphine, a generally safe partial mu-opioid receptor agonist, has been shown to be effective for both pain management and opioid use disorder. It is critical that PC clinicians become comfortable with indications for its use, strategies for initiation while understanding risks and benefits. This article, written by a team of PC and addiction-trained specialists, including physicians, nurse practitioners, social workers, and a pharmacist, offers 10 tips to demystify buprenorphine use in serious illness.

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BACKGROUND: Medicare cancer expenditures in the last month of life have increased. Aggressive cancer care at the end-of-life (ACEOL) is considered poor quality care. We used Geisinger Health Plan (GHP) last month's costs for cancer patients who died in 2018 and 2019 to determine the costs of and influence of Palliative Care (PC) on ACEOL. METHOD: Patients with GHP ages 18-99 who died in 2018 and 2019 were included. Demographic, clinical characteristics, and Charlson Comorbid Index were compared across care groups defined as no ACEOL indicator, 1 or more than 1 indicator. Differences between groups were compared with Kruskal-Wallis tests and one-way ANOVA for 3 groups. Median two-sample tests and independent t-tests compared groups of 2. A P-value 1. There were incremental cost increases with each additional ACEOL indicator (p = < .0001). Palliative Care <90 days before death was associated with increased costs while consultations >90 days before death lowered cost (P < .0001) due to reduced chemotherapy in the last month. Completed ADs reduced cost by $4000. DISCUSSION: ACEOL indicators multiply costs during the last month of life. Palliative care instituted >90 days before death reduces chemotherapy in the last month of life and AD reduces health care costs. CONCLUSION: Cancer health care costs increase with indicators of ACEOL. Palliative care consultations >90 days before death; ADs reduce cancer health care costs.

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OBJECTIVE(S): For patients with cancer, the emergence of acute palliative care units (APCU) may hold promise in curtailing hospital readmissions. The study aims to describe the characteristics of patients readmitted to an APCU. METHODS: This retrospective study examined patients with cancer readmitted within 30 days to an APCU. Readmissions were further classified as either potentially preventable or non-preventable. RESULTS: Out of 734 discharges from July 1, 2014 to July 1, 2015, 69 (9%) readmissions were identified and analyzed. For index admissions, median length of stay was five days, and one (1%) was discharged home with hospice care. For readmissions, median time from index admission to readmission was nine days, median length of stay was six days, three (4%) patients died, and 20 (30%) went home with hospice. Ten (14.5%) readmissions were deemed potentially preventable (95% CI 7.2-25.0%). Race/ethnicity-White/Black/Hispanic/Others-was 60%, 10%, 20% and 10%, respectively, among potentially preventable readmissions and 76%, 22%, 2% and 0%, respectively, among potentially non-preventable readmissions (P = .012). Potentially preventable readmissions were more likely to have venous thromboembolism (40% vs. 12%, P = .046) and more reasons for readmission (median 2 vs. 1, P = .019). CONCLUSIONS: Among patients with cancer readmitted to an APCU, one out of seven was potentially preventable and a far larger proportion was discharged with hospice care compared to the index admission. Recognition of disease course, meaningful goals of care discussions and timely transition to hospice care may reduce rehospitalization in this population.

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