Venous thromboembolism in critically ill adult patients with hematologic malignancy: a population-based cohort study.

PURPOSE: The aim of this study was to describe the incidence of venous thromboembolism (VTE) and major bleeding among hospitalized patients with hematologic malignancy, assessing its association with critical illness and other baseline characteristics. METHODS: We conducted a population-based cohort study of hospitalized adults with a new diagnosis of hematologic malignancy in Ontario, Canada, between 2006 and 2017. The primary outcome was VTE (pulmonary embolism or deep venous thrombosis). Secondary outcomes were major bleeding and in-hospital mortality. We compared the incidence of VTE between intensive care unit (ICU) and non-ICU patients and described the association of other baseline characteristics and VTE. RESULTS: Among 76,803 eligible patients (mean age 67 years [standard deviation, SD, 15]), 20,524 had at least one ICU admission. The incidence of VTE was 3.7% in ICU patients compared to 1.2% in non-ICU patients (odds ratio [OR] 3.08; 95% confidence interval [CI] 2.77-3.42). The incidence of major bleeding was 7.6% and 2.4% (OR 3.33; 95% CI 3.09-3.58), respectively. The association of critical illness and VTE remained significant after adjusting for potential confounders (OR 2.92; 95% CI 2.62-3.25). We observed a higher incidence of VTE among specific subtypes of hematologic malignancy and patients with prior VTE (OR 6.64; 95% CI 5.42-8.14). Admission more than 1 year after diagnosis of hematologic malignancy (OR 0.64; 95% CI 0.56-0.74) and platelet count ≤ 50 × 109/L at the time of hospitalization (OR 0.63; 95% CI 0.48-0.84) were associated with a lower incidence of VTE. CONCLUSION: Among patients with hematologic malignancy, critical illness and certain baseline characteristics were associated with a higher incidence of VTE.

Impacts of antipsychotic medication prescribing practices in critically ill adult patients on health resource utilization and new psychoactive medication prescriptions.

BACKGROUND: Antipsychotic medications are commonly prescribed to critically ill adult patients and initiation of new antipsychotic prescriptions in the intensive care unit (ICU) increases the proportion of patients discharged home on antipsychotics. Critically ill adult patients are also frequently exposed to multiple psychoactive medications during ICU admission and hospitalization including benzodiazepines and opioid medications which may increase the risk of psychoactive polypharmacy following hospital discharge. The associated impact on health resource utilization and risk of new benzodiazepine and opioid prescriptions is unknown. RESEARCH QUESTION: What is the burden of health resource utilization and odds of new prescriptions of benzodiazepines and opioids up to 1-year post-hospital discharge in critically ill patients with new antipsychotic prescriptions at hospital discharge? STUDY DESIGN & METHODS: We completed a multi-center, propensity-score matched retrospective cohort study of critically ill adult patients. The primary exposure was administration of ≥1 dose of an antipsychotic while the patient was admitted in the ICU and ward with continuation at hospital discharge and a filled outpatient prescription within 1-year following hospital discharge. The control group was defined as no doses of antipsychotics administered in the ICU and hospital ward and no filled outpatient prescriptions for antipsychotics within 1-year following hospital discharge. The primary outcome was health resource utilization (72-hour ICU readmission, 30-day hospital readmission, 30-day emergency room visitation, 30-day mortality). Secondary outcomes were administration of benzodiazepines and/or opioids in-hospital and following hospital discharge in patients receiving antipsychotics. RESULTS: 1,388 propensity-score matched patients were included who did and did not receive antipsychotics in ICU and survived to hospital discharge. New antipsychotic prescriptions were not associated with increased health resource utilization or 30-day mortality following hospital discharge. There was increased odds of new prescriptions of benzodiazepines (adjusted odds ratio [aOR] 1.61 [95%CI 1.19-2.19]) and opioids (aOR 1.82 [95%CI 1.38-2.40]) up to 1-year following hospital discharge in patients continuing antipsychotics at hospital discharge. INTERPRETATION: New antipsychotic prescriptions at hospital discharge are significantly associated with additional prescriptions of benzodiazepines and opioids in-hospital and up to 1-year following hospital discharge.

New and Persistent Sedative Prescriptions Among Older Adults Following a Critical Illness: A Population-Based Cohort Study.

BACKGROUND: ICU survivors often have complex care needs and can experience insufficient medication reconciliation and polypharmacy. It is unknown which ICU survivors are at risk of new sedative use posthospitalization. RESEARCH QUESTION: For sedative-naive, older adult ICU survivors, how common is receipt of new and persistent sedative prescriptions, and what factors are associated with receipt? STUDY DESIGN AND METHODS: This population-based cohort study included ICU survivors aged ≥ 66 years who had not filled sedative prescriptions within ≤ 6 months before hospitalization (sedative-naive) in Ontario, Canada (2003-2019). Using multilevel logistic regression, demographic, clinical, and hospital characteristics and their association with new sedative prescription within ≤ 7 days of discharge are described. Variation between hospitals was quantified by using the adjusted median OR. Factors associated with persistent prescriptions (≤ 6 months) were examined with a multivariable proportional hazards model. RESULTS: A total of 250,428 patients were included (mean age, 76 years; 61% male). A total of 15,277 (6.1%) filled a new sedative prescription, with variation noted across hospitals (2% [95% CI, 1-3] to 44% [95% CI, 3-57]); 8,458 (3.4%) filled persistent sedative prescriptions. Adjusted factors associated with a new sedative included: discharge to long-term care facility (adjusted OR [aOR], 4.00; 95% CI, 3.72-4.31), receipt of inpatient geriatric (aOR, 1.95; 95% CI, 1.80-2.10) or psychiatry (aOR, 2.76; 95% CI, 2.62-2.91) consultation, invasive ventilation (aOR, 1.59; 95% CI, 1.53-1.66), and ICU length of stay ≥ 7 days (aOR, 1.50; 95% CI, 1.42-1.58). The residual heterogeneity between hospitals (adjusted median OR, 1.43; 95% CI, 1.35-1.49) had a stronger association with new sedative prescriptions than the Charlson Comorbidity Index score or sepsis. Factors associated with persistent sedative use were similar with the addition of female subjects (subdistribution hazard ratio, 1.07; 95% CI, 1.02-1.13) and pre-existing polypharmacy (subdistribution hazard ratio, 0.88; 95% CI, 0.80-0.93). INTERPRETATION: One in 15 sedative-naive, older adult ICU survivors filled a new sedative within ≤ 7 days of discharge; more than one-half of these survivors filled persistent prescriptions. New prescriptions at discharge varied widely across hospitals and represent the potential value of modifying prescription practices, including medication review and reconciliation.

Proton Pump Inhibitors in the Elderly Hospitalized Patient: Evaluating Appropriate Use and Deprescribing.

Background: Proton pump inhibitors (PPIs) are often prescribed for elderly patients without appropriate indication, or for longer durations than recommended. Objective: To review appropriateness of PPI use prior to and in hospital, and deprescribing rates across different hospital units. Methods: Retrospective analysis of patients ≥65 years admitted to 5 acute care units: intensive care unit, acute care for elderly, orthopedics, surgery, and medicine. Patients who were "non-naive" (prehospital PPI use) or "naive" (new PPI initiated in hospital) users were included. For both groups, demographics, reason for admission, length of stay, comorbidities, name and number of home medications, PPI name, dose and indication, and PPI discharge instructions were collected. For naive patients, duration of in-hospital use and prescriber specialty was recorded. Results: Among non-naive patients (n = 377), for 37 patients (10%), the indication for a PPI was not appropriate, and for 92 patients (24%), the indication was unclear. Most patients had their home PPI continued while in hospital (87%) and at discharge (90%). Among naive (n = 93) patients, for 8 patients (9%), the indication for a PPI was not appropriate, and for 25 (27%) patients, the indication was unclear. PPI was prescribed to only 16 (18%) by the gastrointestinal consult service. Most patients had their new PPI continued at discharge (74%); only 7 (9%) were discharged with a plan to reassess PPI indication. Conclusion: PPIs are infrequently deprescribed during hospital admission, despite inappropriate or unclear indications for use. Thorough medication reconciliation, documentation of PPI indication and duration, and institutional focus on deprescribing are encouraged.

Development of core outcome sets for effectiveness trials of interventions to prevent and/or treat delirium (Del-COrS): study protocol.

INTRODUCTION: Delirium is a common, serious and potentially preventable condition with devastating impact on the quality of life prompting a proliferation of interventional trials. Core outcome sets aim to standardise outcome reporting by identifying outcomes perceived fundamental for measurement in trials of a specific interest area. Our aim is to develop international consensus on two core outcome sets for trials of interventions to prevent and/or treat delirium, irrespective of study population. We aim to identify additional core outcomes specific to the critically ill, acutely hospitalised patients, palliative care and older adults. METHODS AND ANALYSIS: We will conduct a systematic review of published and ongoing delirium trials (1980 onwards) and one-on-one interviews of patients who have experienced delirium and family members. These data will inform Delphi round 1 of a two-stage consensus process. In round 2, we will provide participants their own response, summarised group responses and those of patient/family participants for rescoring. We will randomise participants to receive feedback as proportion scoring the outcome as critical or as group mean responses. We will hold a consensus meeting using nominal group technique to finalise outcomes for inclusion. We will repeat the Delphi process and consensus meeting to select measures for each core outcome. We will recruit 240 Delphi participants giving us 80% power to detect a 1.0-1.5 point (9-point scale) difference by feedback method between rounds. We will analyse differences for subsequent scores, magnitude of opinion change, items retained and level of agreement. ETHICS AND DISSEMINATION: We are obtaining research ethics approvals according to local governance. Participation will be voluntary and data deidentified. Support from three international delirium organisations will be instrumental in dissemination and core outcome set uptake. We will disseminate through peer-reviewed open access publications and present at conferences selected to reach a wide range of knowledge users.

Regional citrate anticoagulation for PrismaFlex continuous renal replacement therapy.

BACKGROUND: Since Mehta et al. reported the first successful use of regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) in 1990, RCA is increasingly used for CRRT because it provides filter patency with minimal risk of bleeding. However, RCA has been associated with significant metabolic complications including hypocalcemia, hypernatremia, metabolic alkalosis, and citrate toxicity. OBJECTIVE: To describe our experience with a newly implemented RCA protocol with acid citrate dextrose formula A (ACD-A) and intravenous calcium gluconate, for use with PrismaFlex CRRT in critically ill patients with acute kidney injury. METHODS: A retrospective chart review was conducted from May 1, 2006, until May 1, 2007, in a 16-bed medical-surgical university-affiliated intensive care unit. Data collected included dialysis filter life, patient and circuit metabolic parameters, and units of packed red blood cells transfused. RESULTS: Forty-eight patients received dialysis with citrate (n = 178 filters). Circuit clotting occurred in 24% of all filters. Mean +/- SD filter life was 38.4 +/- 25.9 hours, and filter survival at 48 hours was 38.2%. Persistent metabolic alkalosis while on CRRT was identified in 6 of 45 (13.3%) patients. Mild hypocalcemia (ionized calcium <3.6 mg/dL) occurred in 11 (23%) patients, but no patient had an ionized calcium level less than 2.8 mg/dL. Six patients, 3 with acute leukemia, required transfusion of 2 or more units of packed red blood cells in 24 hours. CONCLUSIONS: We found that anticoagulation of PrismaFlex CRRT with ACD-A and intravenous calcium gluconate provided reasonable filter patency, but with minor metabolic complications. Close monitoring of electrolyte and acid-base balance is required to minimize metabolic derangements.

Clarifying the role of rasburicase in tumor lysis syndrome.

Tumor lysis syndrome (TLS) is a complication of malignancies with high tumor cell proliferation, tumor burden, and chemosensitivity. It manifests with the release of intracellular components and results in hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. These biochemical abnormalities may lead to serious complications such as renal failure, cardiac dysrhythmias, and death. Rasburicase, a recombinant urate oxidase enzyme, is a new agent indicated in the treatment or prophylaxis of hyperuricemia in pediatric patients with cancer who are at high risk for TLS. We reviewed the evidence for treatment with this agent compared with standard therapy with allopurinol. Rasburicase may be considered for use in patients with hyperuricemia at presentation and in patients at high risk for TLS that would otherwise result in a delay in chemotherapy. However, randomized controlled trials are required to establish the comparative efficacy of rasburicase in the adult population. Preliminary evidence suggests that single-dose or reduced-dose rasburicase may be effective in the prophylaxis and the treatment of hyperuricemia and TLS. However, to our knowledge, there is no evidence comparing clinically relevant outcomes such as acute renal failure or dialysis.

CNS relapses of acute promyelocytic leukemia after all-trans retinoic acid.

OBJECTIVE: To review the role of all-trans retinoic acid (ATRA) and arsenic trioxide in central nervous system (CNS) relapses of acute promyelocytic leukemia (APL). CASE SUMMARY: A 69-year-old white man diagnosed with APL presented with bleeding diathesis. His molecular and cytogenetic studies were positive for promyelocytic leukemia-retinoic acid receptoralpha (PML-RARalpha) and t(15;17) transformation. Complete molecular and cytogenetic remission was achieved with ATRA, daunorubicin, and cytarabine. Within 6 months, the patient was readmitted for investigation of severe global headaches and an ataxic gait. His peripheral blood and cerebral spinal fluid were positive for PML-RARalpha fusion protein. Intrathecal chemotherapy and radiation, as well as ATRA, were the main treatment modalities provided. Molecular and cytogenetic remission was again obtained. Three months later, a second relapse occurred in the CNS and the peripheral blood. DISCUSSION: APL is typically treated with anthacycline-based chemotherapy and ATRA. Approximately 85-95% of patients achieve complete remission (CR); however, the relapse rate has been reported to be about 30-40%. A thorough literature search (MEDLINE, EMBASE, CANCERLIT, 1966-January 2002) revealed only 54 cases of extramedullary disease, of which 35 involved the CNS. CONCLUSIONS: The introduction of ATRA has improved patient survival dramatically. APL relapse, in general, has been in part attributable to repetitive or prolonged exposure to ATRA and the possibility of additional chromosomal changes, making the disease more refractory to treat. Given the evidence, one could argue that, with repeated ATRA treatment, CR duration may be shortened. However, limited data are available to guide the appropriate management of APL relapsed to the CNS with either ATRA, chemotherapy, or arsenic trioxide. In our opinion, treatment using arsenic trioxide is an unconventional option worthy of exploring.