Christine L. Watt

Opioids are first-line therapy for cancer pain, yet up to 30% of patients fail to achieve adequate control at standard doses. Opioid response is partly genetically mediated, and understanding these factors may improve symptom management. This project aimed to assess the feasibility of using tumor bank DNA for pharmacogenetic analyses and to validate previously identified genetic variants associated with opioid response using existing genetic and clinical data. In this retrospective cohort study, clinical data (morphine equivalent daily dose, demographics) and genetic data (single-nucleotide polymorphisms) were analyzed across 31 candidate loci. Adult deceased patients with melanoma, colorectal, or lung cancer treated with opioids between 2016 and 2021 and with available tumor bank DNA were included. Patients without sufficient DNA or not deceased were excluded. Of 3503 potential samples, 502 met the inclusion criteria. The median morphine equivalent daily dose was 40 mg (range 1–2140 mg). Eleven loci across six genes may be associated with higher (OPRM1, TAOK3, NFKBIA, COMT, and RHBDF2) and lower (COMT and GCH1) opioid dose requirements (p < 0.05, not significant after Bonferroni correction). Ultimately, tumor bank DNA is a feasible resource for pharmacogenetic research. Identified loci may contribute to variability in opioid response and support future personalized pain management strategies.

Patients with multiple sclerosis (MS) require increasing health care support, particularly in the last year of life. Despite the benefits of palliative care in addressing symptom burden and improving quality of life, its integration into MS care remains inconsistent. This study aimed to characterize health care utilization and palliative care access among people with MS in the last years of life and to identify key factors associated with hospital death and receipt of palliative care. A retrospective cohort study was conducted using linked health administrative databases in Ontario, Canada. The cohort consisted of all decedents aged 18 years or older who died in Ontario between April 2016 and March 2020, and we compared health care utilization in decedents with MS to the rest of the cohort. The identification of MS cases was based on a validated algorithm. Demographics, health care utilization, palliative care involvement, and medical interventions were analyzed. Predictors of palliative care receipt and hospital deaths were evaluated using multivariable logistic regression models. MS decedents (n = 1,975; mean age 68 years; 66.4% female) were younger and had fewer comorbidities than non-MS decedents (n = 500,904; mean age 77). High percentage of MS decedents had outpatient neurology visits in the last 5 years of life (49.4%) but a steep decline closer to death (2.7% in the last month). Palliative care use was similar (58.0% vs 56.9%) but occurred earlier in MS (61.9% vs 59.6% in the last 5 years). Multivariable regression showed that rural residence was associated with increased odds of hospital death (odds ratio [OR] 1.81, 95% CI 1.21-2.70) and lower odds of receiving palliative care (OR 0.74, 95% CI 0.55-0.99), while receiving palliative care within the last 5 years of life reduced the odds of hospital death (OR 0.47, 95% CI 0.37-0.60). Higher comorbidity and increased outpatient visits to urology were associated with a greater odd of receiving palliative care (OR 3.64, 95% CI 2.50-5.29 and OR 1.47, 95% CI 1.20-1.80). Although palliative care receipt was comparable between MS and non-MS decedents, rural disparities and high hospital deaths persist. Earlier palliative integration, particularly through neuropalliative care, could improve quality of life and reduce hospitalizations.

Background: Psychological and existential suffering affects many people with advanced illness, and current therapeutic options have limited effectiveness. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective therapy for refractory depression, but no previous study has used rTMS to treat psychological or existential distress in the palliative setting. Aim: To determine whether a 5-day course of “accelerated” rTMS is feasible and can improve psychological and/or existential distress in a palliative care setting. Design: Open-label, single arm, feasibility, and preliminary efficacy study of intermittent theta-burst stimulation to the left dorsolateral prefrontal cortex, 600 pulses/session, 8 sessions/day (once per hour) for 5 days. The outcomes were the rates of recruitment, completion of intervention, and follow-up (Feasibility); and the proportion of participants achieving 50% improvement on the Hamilton Depression Rating Scale (HDRS) or Hospital Anxiety and Depression Scale (HADS) 2 weeks post-treatment (Preliminary Efficacy). Setting/participants: Adults admitted to our academic Palliative Care Unit with advanced illness, life expectancy >1 month and psychological distress. Results: Due to COVID-19 pandemic-related interruptions, a total of nine participants were enrolled between August 2021 and April 2023. Two withdrew before starting rTMS, one stopped due to clinical deterioration unrelated to rTMS, and six completed the rTMS treatment. Five of six participants had a >50% improvement in HDRS, HADS-Anxiety, or both between baseline and the 2 week follow up; the sixth died prior to the 2-week follow-up. In this small sample, mean depression scores decreased from baseline to 2 weeks post-treatment (HDRS 18 vs 7, p = 0.03). Side effects of rTMS included transient mild scalp discomfort. Conclusions: Accelerated rTMS improved symptoms of depression, anxiety, or both in this small feasibility and preliminary efficacy study. A larger, sham-controlled study is warranted to determine whether rTMS could be an effective, acceptable, and scalable treatment in the palliative setting. Trial registration: NCT04257227

The use of intravenous inotropic medications in advanced heart failure (HF) has been shown to improve symptoms and decrease hospitalizations, prompting support for their use as a palliative measure for symptom management. Recommendations regarding inotrope management and method of discontinuation at the end of life are not specifically detailed in the literature and current guidelines. This case report describes the use of milrinone in a patient with advanced HF during the terminal phase of illness in a non-monitored palliative care unit setting, including dose reduction and discontinuation of milrinone. Increased patient anxiety during the weaning process was managed with midazolam. The provision of individualized milrinone therapy in non-monitored palliative care settings is feasible and well-tolerated using the presented detailed recommendations for its use and administration, monitoring, dose reduction and discontinuation and proactive symptom management at the end of life. Further research is needed for the optimal management of terminally ill patients with advanced HF. Supplemental data for this article is available online at here. show

Delirium is a distressing neuropsychiatric disorder affecting patients in palliative care. Although many delirium screening tools exist, their utility, and validation within palliative care settings has not undergone systematic review. To systematically review studies that validate delirium screening tools conducted in palliative care settings. Systematic review with narrative synthesis (PROSPERO ID: CRD42019125481). A risk of bias assessment via Quality Assessment Tool for Diagnostic Accuracy Studies-2 was performed. Five electronic databases were systematically searched (January 1, 1982–May 3, 2020). Quantitative studies validating a screening tool in adult palliative care patient populations were included. Studies involving alcohol withdrawal, critical or perioperative care were excluded. Dual-reviewer screening of 3749 unique titles and abstracts identified 95 studies for full-text review and of these, 17 studies of 14 screening tools were included (n = 3496 patients). Data analyses revealed substantial heterogeneity in patient demographics and variability in screening and diagnostic practices that limited generalizability between study populations and care settings. A risk of bias assessment revealed methodological and reporting deficits, with only 3/17 studies at low risk of bias. The processes of selecting a delirium screening tool and determining optimal screening practices in palliative care are complex. One tool is unlikely to fit the needs of the entire palliative care population across all palliative care settings. Further research should be directed at evaluating and/or adapting screening tools and practices to fit the needs of specific palliative care settings and populations.

Background: Delirium is a distressing neurocognitive disorder that is common among terminally ill individuals, although few studies have described its occurrence in the acute care setting among this population. Aim: To describe the prevalence of delirium in patients admitted to acute care hospitals in Ontario, Canada, in their last year of life and identify factors associated with delirium. Design: Population-based retrospective cohort study using linked health administrative data. Delirium was identified through diagnosis codes on hospitalization records. Setting/participants: Ontario decedents (1 January 2014 to 31 December 2016) admitted to an acute care hospital in their last year of life, excluding individuals age of 105 years at admission, those not eligible for the provincial health insurance plan between their hospitalization and death dates, and non-Ontario residents. Results: Delirium was recorded as a diagnosis in 8.2% of hospitalizations. The frequency of delirium-related hospitalizations increased as death approached. Delirium prevalence was higher in patients with dementia (prevalence ratio: 1.43; 95% confidence interval: 1.36–1.50), frailty (prevalence ratio: 1.67; 95% confidence interval: 1.56–1.80), or organ failure–related cause of death (prevalence ratio: 1.23; 95% confidence interval: 1.16–1.31) and an opioid prescription (prevalence ratio: 1.17; 95% confidence interval: 1.12–1.21). Prevalence also varied by age, sex, chronic conditions, antipsychotic use, receipt of long-term care or home care, and hospitalization characteristics. Conclusion: This study described the occurrence and timing of delirium in acute care hospitals in the last year of life and identified factors associated with delirium. These findings can be used to support delirium prevention and early detection in the hospital setting.