Anticoagulant use and associated outcomes in older patients receiving home palliative care: a retrospective cohort study.

BACKGROUND: The benefits and harms of anticoagulants for people near the end of life are not well understood, nor is it known what proportion of patients discontinue these medications. We aimed to characterize anticoagulant use in older recipients of home palliative care and describe patient and provider characteristics, as well as outcomes associated with anticoagulant discontinuation in this group. METHODS: Using linked administrative health databases, we conducted a population-based cohort study of patients aged 66 years and older who initiated home palliative care in Ontario from 2010 to 2018. We calculated the prevalence of anticoagulant use. We used multilevel logistic regression models to assess patient (e.g., sociodemographic, comorbidities) and physician (e.g., demographic, training, practice) factors associated with anticoagulant discontinuation after initiation of home palliative care. We defined discontinuation as either primary (no anticoagulant claim within 1.5 times the days' supply of the previous prescription) or secondary (no subsequent anticoagulant claim at any time after the index date). In secondary analyses, we used cause-specific hazards regression to explore subsequent thrombotic and bleeding events associated with anticoagulant discontinuation, and multivariable logistic regression for location of death. RESULTS: We identified 98 089 recipients of home palliative care, of whom 15.5% were taking anticoagulants at the time of the first palliative care visit. Depending on the definition of discontinuation, 18.0% to 24.4% of patients discontinued anticoagulants after the first home palliative care visit. Compared with warfarin, use of a direct oral anticoagulant (adjusted odds ratio [OR] 0.49, 95% confidence interval [CI] 0.43-0.56) and low-molecular-weight heparin (adjusted OR 0.56, 95% CI 0.47-0.66) were associated with a lower likelihood of discontinuation. Few patient or physician characteristics - and no comorbidities or indications for therapeutic anticoagulation - were associated with discontinuation. Anticoagulant discontinuation after beginning home palliative care was associated with similar rates of thrombosis (adjusted hazard ratio [HR] 1.06, 95% CI 0.81-1.39), lower rates of bleeding (adjusted HR 0.75, 95% CI 0.62-0.90) and a higher likelihood of a home death (adjusted OR 1.22, 95% CI 1.09-1.36) compared with continuing anticoagulation. INTERPRETATION: Among recipients of home palliative care in Ontario, anticoagulant use is common, and discontinuation is not influenced by comorbidities or indication for anticoagulation. Physician preference may play an important role; patients should be made aware of their options toward the end of life and supported in shared decision-making.

Practice review: Evidence-based and effective management of anaemia in palliative care patients.

BACKGROUND: Anaemia is a common sequela of advanced disease and is associated with significant symptom burden. No specific guidance exists for the investigation and management of anaemia in palliative care patients. AIM: We aim to offer a pragmatic overview of the approaches to investigate and manage anaemia in advanced disease, based on guidelines and evidence in disease specific patient groups, including cancer, heart failure and chronic kidney disease. DESIGN: Scoping review methodology was used to determine the strength of evidence supporting the investigation and management of anaemia in patients with advanced disease. DATA SOURCES: A search for guidelines was performed in 2020. National or international guidelines were examined if they described the investigation or management of anaemia in adult patients with health conditions seen by palliative care services written within the last 5 years in the English language. Searches of MEDLINE, the Cochrane library and WHO guidance were made in 2019 to identify key publications that provided additional primary data. RESULTS: Evidence supports patient-centred investigation of anaemia, results of which should guide targeted intervention. Blanket use of blood transfusion should be avoided, with evidence supporting a more restrictive approach to transfusion. Routine use of oral iron and erythropoetin stimulating agents (ESAs) are not recommended. Insufficient evidence exists to determine the effectiveness of IV iron in this patient group. CONCLUSION: We advocate early consideration and investigation of anaemia, guided by symptom burden and patient preferences. Correction of reversible causes should be the mainstay of treatment, with a restrictive approach to blood transfusion. Research is required to evaluate the efficacy of IV iron in these patients.

Red blood cell transfusion in myelodysplastic syndromes: A systematic review.

Patients with myelodysplastic syndrome (MDS) frequently receive red blood cell (RBC) transfusions for anaemia resulting from ineffective erythropoiesis. While RBC transfusions may rapidly increase haemoglobin values, their impact on clinical and health services outcomes in MDS patients has not previously been summarized. We conducted a systematic review of the literature to evaluate risks and benefits of RBC transfusions in MDS patients. We searched electronic databases (MEDLINE, Embase, CENTRAL, CINAHL) from inception through June 4, 2021 to identify studies reporting data on RBC transfusions in MDS patients. Full text publications that assessed RBC transfusions as an intervention and reported at least one clinical, laboratory, or healthcare outcome associated with transfusion were included. Study characteristics, transfusion information and transfusion-related outcomes were extracted and reported. We identified 1243 original studies, of which 38 met eligibility requirements and were included. Fourteen reported on survival following diagnosis of MDS, with the majority reporting poorer survival among patients receiving or requiring more frequent transfusions. Nine reported on transfusion-related iron overload and its complications. Other outcomes included rates of allo/autoimmunization and adverse transfusion reactions, and healthcare costs incurred by patients with a greater transfusion burden. Only two studies reported on symptom relief following transfusion. This review underscores transfusion dependence as a negative prognostic factor for MDS patients and highlights the paucity of evidence surrounding quality of life and symptom-related outcomes following RBC transfusions in this population. Further study of patient-important outcomes associated with transfusion in MDS patients is warranted to improve therapeutic recommendations and inform resource allocation.

Red blood cell transfusion and associated outcomes in patients referred for palliative care: A retrospective cohort study.

BACKGROUND: We aim to describe the occurrence of red blood cell transfusion and associated predictive factors and outcomes among patients referred for palliative care. STUDY DESIGN AND METHODS: This retrospective cohort study used linked health administrative data of adults referred for palliative care at an academic hospital from 2014 to 2018. Multivariable regression models were employed to evaluate patient characteristics associated with transfusion and the relationship between transfusion status and location of death. Survival analyses were performed using log-rank tests and Cox proportional hazards modeling. RESULTS: Of 6980 evaluated patients, 885 (12.7%) were transfused following palliative care consultation. Covariate factors associated with transfusion included younger age, higher performance status, lower baseline hemoglobin, and a diagnosis of hematologic malignancy (OR = 2.97, 95% CI 2.20-4.01) or solid organ tumor (OR = 1.37, 95% CI 1.10-1.71) vs. noncancer diagnosis. Median survival from palliative care consultation was 19 (IQR 5-75) days; 83 (32-305) days in those transfused and 15 (4-57) days in the nontransfused group (p < .0001). Median survival following transfusion was 56 (19-200) days. Solid organ tumor diagnosis was independently associated with poor survival (HR = 1.7, 95% CI 1.39-2.09 vs. non-cancer diagnosis). Among individuals who survived ≥30 days, transfusion was associated with a higher likelihood of death in hospital (OR = 2.15, 95% CI 1.71-2.70 vs. home/subacute setting). DISCUSSION: Transfusions commonly occurred in patients receiving palliative care, associated with cancer diagnoses and favorable baseline prognostic factors. Poor survival following transfusion, particularly in solid organ tumor patients, and the twofold likelihood of death in hospital associated with this intervention have important implications in prescribing transfusion for this population.

Dying of amyotrophic lateral sclerosis: Health care use and cost in the last year of life.

OBJECTIVE: To describe health care service utilization and cost for decedents with and without amyotrophic lateral sclerosis (ALS) in the last year of life. METHODS: Using linked health administrative data, we conducted a retrospective, population-based cohort study of Ontario, Canada, decedents from 2013 to 2015. We examined demographic data, rate of utilization, and cost of health care services in the last year of life. RESULTS: We identified 283,096 decedents in Ontario, of whom 1,212 (0.42%) had ALS. Decedents with ALS spent 3 times as many days in an intensive care unit (ICU) (mean 6.3 vs 2.1, p < 0.001), and twice as many days using complex continuing care (mean 12.7 vs 6.0, p < 0.001) and home care (mean 99.1 vs 41.3, p < 0.001). A greater percentage of decedents with ALS received palliative home care (44% vs 20%, p < 0.001) and palliative physician home visits (40% vs 18%, p < 0.001) than decedents without ALS. Among decedents with ALS, a palliative physician home visit in the last year of life was associated with reduced adjusted odds of dying in hospital (odds ratio 0.65, 95% confidence interval 0.48-0.89) and fewer days spent in the ICU. Mean cost of care in the last year of life was greater for those with ALS ($68,311.98 vs $55,773.48, p < 0.001). CONCLUSIONS: In this large population-based cohort of decedents, individuals with ALS spent more days in the ICU, received more community-based services, and incurred higher costs of care in the last year of life. A palliative care physician home visit was associated with improved end of life outcomes; however, the majority of patients with ALS did not access such services.

Red Blood Cell Transfusion in Palliative Care: A Survey of Palliative Care Physicians.

Background: Red blood cell transfusion is one therapeutic option for the treatment of anemia. Current transfusion practices and factors influencing the decision to prescribe this therapy are not well understood. Objective: To explore current transfusion practices, attitudes, and factors that influence the decision to transfuse among palliative care physicians. Design: Self-administered questionnaire addressing clinical experiences and decision making pertaining to blood transfusion. Setting/Subjects: Specialist palliative care physicians at two Canadian academic centers. Measurements: Descriptive, presented as the number/proportion of respondents indicating a specific answer. Results: Of 62 physicians surveyed, 29 (47%) responded to the study questionnaire. For patients with solid tumors and hematologic malignancies, respectively, 79% and 82% of respondents reported prescribing blood transfusion; 59% and 46% reported that they would seldom recommend its discontinuation. Factors influential in the decision to transfuse included symptoms of anemia (97%), bleeding (62%), low hemoglobin (52%, of whom 87% indicated a hemoglobin threshold <70 g/L), and pressure from patients/families (48%). Physicians routinely reassessed patients for symptomatic improvement following transfusion, but 72% did not use an objective symptom scale. Twenty-six (90%) respondents believed that transfusion provided symptomatic benefit; the majority had observed adverse reactions to transfusion. Most perceived a lack of evidence to guide transfusion therapy in palliative care, and 79% indicated willingness to enroll their patients in a trial aiming to address this question. Conclusions: Most palliative care specialists consider red blood cell transfusion to have a role in symptom management, but many clinical and nonclinical factors influence their decisions to provide or discontinue transfusions. Prospective clinical trials will likely be needed to inform transfusion practices in this population.

Thromboembolic disease in palliative and end-of-life care: A narrative review.

Venous thromboembolism (VTE) is both common and a potential contributor to symptom burden in patients receiving palliative and end-of-life care. Many of the VTE treatment and prophylaxis recommendations are drawn from data of clinical trials assessing conventional VTE and cancer-associated thrombosis that excluded patients receiving specialist palliative or hospice care. In this group, the epidemiology of VTE and associated outcomes, as well as the risks and benefits of treatment in keeping with a palliative approach are of growing clinical and research interest. This narrative review summarizes current knowledge and challenges in the management of thromboembolic disease in palliative care, highlighting the complexity of decisions surrounding VTE treatment and prophylaxis.

Red blood cell transfusion in adult palliative care: a systematic review.

BACKGROUND: The risks and benefits of red blood cell (RBC) transfusion in palliative care patients remain poorly understood. We reviewed the literature to summarize available information on RBC transfusion in this population. STUDY DESIGN AND METHODS: We searched electronic databases (MEDLINE, Embase, PsycINFO, CINAHL) from inception through September 2016 to identify studies reporting data on palliative patients receiving RBC transfusion. Original studies that assessed RBC transfusion as an intervention and reported at least one clinical outcome were included. Study characteristics, results on transfusion-related outcomes, and authors' conclusions on the value of transfusion in palliative patients were abstracted and reported. RESULTS: We identified 1839 studies, of which 137 were selected for data extraction and 13 were included (11 case series, one prospective cohort, and one retrospective cohort). Nine studies addressed symptom relief following transfusion using subjective symptom scales, of which eight (89%) indicated some degree of short-term benefit and one study (11%) showed no benefit. Posttransfusion survival was reported in four studies-one demonstrated prolonged survival in patients receiving RBC transfusion; three had no comparison group. Other outcomes reported included hemoglobin values posttransfusion in four studies and adverse events following transfusion in three studies. CONCLUSIONS: In palliative care, RBC transfusion may provide symptom relief and improve subjective well-being, though the duration and magnitude of this effect, and transfusion-associated risks specific to this population remain unclear. Currently, no high quality evidence exists to support or guide the use of RBC transfusion in this population. Moreover, the clinical heterogeneity within the palliative population limits the interpretation of most studies.

Cost analysis of the very elderly admitted to intensive care units.

BACKGROUND: Very elderly patients are often admitted to intensive care units (ICUs) despite poor outcomes and frequent preference to avoid unnecessary prolongation of life. We sought to determine the cost of ICU admission for the very elderly and the factors influencing this cost. METHODS: This prospective, observational cohort study included patients ≥80 years old admitted to 22 Canadian ICUs from 2009 to 2013. A subset of consenting individuals comprised a longitudinal cohort followed over 12 months. Costs were calculated from ICU length of stay and unit costs for ICU admission from a Canadian academic hospital. A generalized linear model was employed to identify cost-predictive variables. RESULTS: In total, 1671 patients were included; 610 were enrolled in the longitudinal cohort. The average age was 85 years; median ICU length of stay was 4 days. Mortality was 35% (585/1671) in hospital and 41% (253/610) at 12 months. The average cost of ICU admission per patient was $31,679 ± 65,867. Estimated ICU costs were $48,744 per survivor to discharge and $61,783 per survivor at 1 year. For both decedents and survivors, preference for comfort measures over life support was an independent predictor for lower cost (P < 0.01). CONCLUSIONS: Considering the poor clinical outcomes, and that many ICU admissions may be undesired by very elderly patients, ICU costs in this population are substantial. Our finding that a preference for comfort care predicted a lower cost independent of mortality reinforces the importance of early goals of care discussions to avoid both undesired and potentially non-beneficial interventions, consequently reducing costs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01293708 . Registered on 10 February 2011.

Association of hospital and physician case volumes with cardiac monitoring and cardiotoxicity during adjuvant trastuzumab treatment for breast cancer: a retrospective cohort study.

BACKGROUND: Adjuvant trastuzumab is the standard of care for patients with HER2 overexpressing breast cancer, but use of trastuzumab may lead to cardiotoxicity. Our goal was to evaluate the relationship between hospital and physician case volume and cardiac outcomes in this population. METHODS: In this retrospective cohort study, we identified all female patients in Ontario with a breast cancer diagnosis in 2003-2009 who underwent treatment with trastuzumab through a provincial drug-funding program and linked these patients to administrative databases to ascertain patient demographics, treating hospital and physician characteristics, admissions to hospital, cardiac risk factors, cardiac imaging and comorbidities. Insufficient cardiac monitoring was defined as per the Canadian Trastuzumab Working Group guideline. Cardiotoxicity was defined as receiving fewer than 16 of 18 doses of trastuzumab because of heart failure admission, heart failure diagnosis or discontinuation of the drug after cardiac imaging. We constructed hierarchical multivariable logistic regression models to evaluate the effect of annual hospital volume, cumulative physician volume and treatment period on cardiac monitoring and cardiotoxicity. RESULTS: Of 3777 women treated by 214 oncologists at 68 hospitals, 918 (24.3%) had insufficient cardiac monitoring and cardiotoxicity developed in 640 (16.9%). Cardiotoxicity occurred in 389 (42.4%) and 251 (8.8%) patients in the insufficient- and sufficient-monitoring groups, respectively. Higher annual hospital and cumulative physician volumes, and more recent calendar period, were all independent predictors for decreased cardiotoxicity. Adjustment for rates of cardiac monitoring annulled the relationships between case volume and cardiotoxicity. INTERPRETATION: Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres.

Reproductive fitness and genetic transmission of tetralogy of Fallot in the molecular age.

BACKGROUND: Individuals with tetralogy of Fallot (TOF) now routinely survive to reproductive age and beyond. Reproductive fitness of adults with TOF and recurrence risks to offspring are of increasing interest in the modern era, especially given recent molecular genetic discoveries. METHODS AND RESULTS: After excluding individuals with known genetic syndromes, 543 unrelated adults with TOF underwent a detailed family history assessment and molecular characterization for rare copy number variations using high-resolution genome-wide microarrays. Men and women with TOF had significantly fewer offspring compared with an age-matched comparison group without congenital heart disease (CHD; P=0.0004). No aspect of rare copy number variation burden was a predictor of decreased reproductive fitness. Corresponding with the advent of modern surgical repairs, reproductive fitness of women began to exceed that of men (P=0.0490). Recurrence risk for CHD in offspring was 4.8%, with no significant differences between men and women with TOF. The risk of severe CHD in offspring (2.3%) far exceeded population expectations (relative risk, 15.6; 95% confidence interval, 7.9-31.0). Most cases of vertical transmission of CHD were not explained by the transmission of a large rare copy number variation. Although conotruncal lesions (31.5%) were the most commonly reported CHD in relatives, the familial spectrum of disease included many anatomically discordant lesions. CONCLUSIONS: Men and women with TOF have reduced reproductive fitness. Their offspring are at significantly elevated risk for severe CHD. These results support the importance of genetic counseling for both men and women with complex CHD. Many inherited genetic variants remain to be discovered.

Transfusion of fresh but not old stored blood reduces infarct size and improves cardiac function after acute myocardial infarction in anemic rats*.

OBJECTIVES: We recently demonstrated that transfusion of fresh blood to 100 g/L hemoglobin in anemic animals offers cardioprotection after acute myocardial infarction. The objective of this study was to compare the cardioprotective effects of fresh vs. stored blood when transfused in anemic rats after acute myocardial infarction. STUDY DESIGN: Randomized animal study. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats weighing 200-300 g. INTERVENTION: Myocardial infarction was induced by coronary artery ligation in 49 male Sprague-Dawley rats weighing 200-300 g, 38 of which were anemic (80-90 g/L) and 11 with normal hemoglobin levels. Anemic animals were randomized to receive fresh blood (within 4 hrs), stored blood (7 days), or no transfusion immediately after myocardial infarction. MEASUREMENTS AND MAIN RESULTS: At 24 hrs after myocardial infarction, cardiac function, infarct size, and apoptosis were determined. Erythrocyte ATP, 2,3-DPG, hemoglobin, and free hemoglobin levels in the supernatant were determined. Transfusion with fresh but not stored blood significantly decreased infarct size and myocardial apoptosis in anemic rats when compared to anemic animals not undergoing transfusion. Cardiac function and survival were significantly improved in the anemic animals undergoing fresh blood transfusion compared to control anemic animals. Analysis of stored red blood cells showed reductions of intracellular ATP and 2,3-DPG levels and free hemoglobin was increased in the supernatant. CONCLUSIONS: The prolonged storage of blood negates the beneficial effects of fresh blood transfusion, which include reductions in infarct size and myocardial apoptosis, and improvements in cardiac function and short-term survival after acute myocardial infarction in this animal model.

Erythropoietin is equally effective as fresh-blood transfusion at reducing infarct size in anemic rats.

OBJECTIVE: We recently demonstrated that transfusion of anemic animals up to 100 g/L hemoglobin with fresh blood protects the heart from ischemic injuries following myocardial infarction. Erythropoietin has cardioprotective effects independent of its erythropoietic activity. The objective of this study was to compare the cardioprotective effects of erythropoietin treatment to fresh-blood transfusion in anemic rats after acute myocardial infarction. DESIGN: Randomized animal study. SETTING: University laboratory. SUBJECTS: Male Sprague-Dawley rats weighing 200-300 g. INTERVENTION: Myocardial infarction was induced by coronary artery ligation in 76 rats, 55 of which were anemic (80-90 g/L) and 21 of which had normal hemoglobin levels. Animals were randomized to erythropoietin (2000 units/kg), fresh-blood transfusion to 100 g/L hemoglobin, or saline-treatment groups immediately following myocardial infarction. MEASUREMENTS AND MAIN RESULTS: At 24 hrs after myocardial infarction, cardiac function and infarct size were determined. Myocardial apoptosis was determined by caspase-3 activity and terminal deoxynucleotidyl transferase d-UTP nick end labeling (TUNEL) assay. Infarct size was significantly decreased in anemic rats treated with erythropoietin or blood transfusion compared to those in the saline-treatment group. Cardiac function, as measured by maximal positive and minimal negative first derivatives of left ventricular pressure, was better preserved in the normal hemoglobin groups and the erythropoietin- or transfusion-treated anemic animals compared to saline-treated anemic animals. Myocardial caspase-3 activity and TUNEL-positive nuclei were significantly increased in anemic rats but were decreased by erythropoietin treatment or red blood cell transfusion. CONCLUSIONS: Erythropoietin treatment is equally effective as fresh-blood transfusion in anemic rats after acute myocardial infarction at reducing infarct size, myocardial apoptosis, and improving cardiac function.