Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients.

Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

Overutilization in laboratory medicine: tackling the problem with quality improvement science.

Overutilization of tests and treatments is a widespread problem in contemporary heath care, and laboratory medicine is no exception. It is estimated that 10-70% of laboratory tests may be unnecessary, with estimates in the literature varying depending on the situation and the laboratory test. Inappropriate use of laboratory tests can lead to further unnecessary testing, adverse events, inaccurate diagnoses, and inappropriate treatments. Altogether, this increases the risk of harm to a patient, which can be physical, psychological, or financial in nature. Overutilization in healthcare is driven by complex factors including care delivery models, litigious practice environments, and medical and patient culture. Quality improvement (QI) methods can help to tackle overutilization. In this review, we outline the global healthcare problem of laboratory overutilization, particularly in the developed world, and describe how an understanding of and application of quality improvement principles can help to address this challenge.

The ASH-ASPHO Choosing Wisely Campaign: 5 hematologic tests and treatments to question.

Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count 10 × 103 /µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.

Antithrombotic therapy for ambulatory patients with multiple myeloma receiving immunomodulatory agents.

BACKGROUND: Multiple myeloma is a malignant plasma cell disorder characterised by clonal plasma cells that cause end-organ damage such as renal failure, lytic bone lesions, hypercalcaemia and/or anaemia. People with multiple myeloma are treated with immunomodulatory agents including lenalidomide, pomalidomide, and thalidomide. Multiple myeloma is associated with an increased risk of thromboembolism, which appears to be further increased in people receiving immunomodulatory agents. OBJECTIVES: (1) To systematically review the evidence for the relative efficacy and safety of aspirin, oral anticoagulants, or parenteral anticoagulants in ambulatory patients with multiple myeloma receiving immunomodulatory agents who otherwise have no standard therapeutic or prophylactic indication for anticoagulation. (2) To maintain this review as a living systematic review by continually running the searches and incorporating newly identified studies. SEARCH METHODS: We conducted a comprehensive literature search that included (1) a major electronic search (14 June 2021) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE via Ovid, and Embase via Ovid; (2) hand-searching of conference proceedings; (3) checking of reference lists of included studies; and (4) a search for ongoing studies in trial registries. As part of the living systematic review approach, we are running continual searches, and we will incorporate new evidence rapidly after it is identified. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing the benefits and harms of oral anticoagulants such as vitamin K antagonist (VKA) and direct oral anticoagulants (DOAC), anti-platelet agents such as aspirin (ASA), and parenteral anticoagulants such as low molecular weight heparin (LMWH)in ambulatory patients with multiple myeloma receiving immunomodulatory agents. DATA COLLECTION AND ANALYSIS: Using a standardised form, we extracted data in duplicate on study design, participants, interventions, outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and minor bleeding. For each outcome we calculated the risk ratio (RR) with its 95% confidence interval (CI) and the risk difference (RD) with its 95% CI. We then assessed the certainty of evidence at the outcome level following the GRADE approach (GRADE Handbook). MAIN RESULTS: We identified 1015 identified citations and included 11 articles reporting four RCTs that enrolled 1042 participants. The included studies made the following comparisons: ASA versus VKA (one study); ASA versus LMWH (two studies); VKA versus LMWH (one study); and ASA versus DOAC (two studies, one of which was an abstract). ASA versus VKA One RCT compared ASA to VKA at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to VKA on all-cause mortality (RR 3.00, 95% CI 0.12 to 73.24; RD 2 more per 1000, 95% CI 1 fewer to 72 more; very low-certainty evidence); symptomatic DVT (RR 0.57, 95% CI 0.24 to 1.33; RD 27 fewer per 1000, 95% CI 48 fewer to 21 more; very low-certainty evidence); PE (RR 1.00, 95% CI 0.25 to 3.95; RD 0 fewer per 1000, 95% CI 14 fewer to 54 more; very low-certainty evidence); major bleeding (RR 7.00, 95% CI 0.36 to 134.72; RD 6 more per 1000, 95% CI 1 fewer to 134 more; very low-certainty evidence); and minor bleeding (RR 6.00, 95% CI 0.73 to 49.43; RD 23 more per 1000, 95% CI 1 fewer to 220 more; very low-certainty evidence). One RCT compared ASA to VKA at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to VKA on all-cause mortality (RR 0.50, 95% CI 0.05 to 5.47; RD 5 fewer per 1000, 95% CI 9 fewer to 41 more; very low-certainty evidence); symptomatic DVT (RR 0.71, 95% CI 0.35 to 1.44; RD 22 fewer per 1000, 95% CI 50 fewer to 34 more; very low-certainty evidence); and PE (RR 1.00, 95% CI 0.25 to 3.95; RD 0 fewer per 1000, 95% CI 14 fewer to 54 more; very low-certainty evidence). ASA versus LMWH Two RCTs compared ASA to LMWH at six months follow-up. The pooled data did not confirm or exclude a beneficial or detrimental effect of ASA relative to LMWH on all-cause mortality (RR 1.00, 95% CI 0.06 to 15.81; RD 0 fewer per 1000, 95% CI 2 fewer to 38 more; very low-certainty evidence); symptomatic DVT (RR 1.23, 95% CI 0.49 to 3.08; RD 5 more per 1000, 95% CI 11 fewer to 43 more; very low-certainty evidence); PE (RR 7.71, 95% CI 0.97 to 61.44; RD 7 more per 1000, 95% CI 0 fewer to 60 more; very low-certainty evidence); major bleeding (RR 6.97, 95% CI 0.36 to 134.11; RD 6 more per 1000, 95% CI 1 fewer to 133 more; very low-certainty evidence); and minor bleeding (RR 1.42, 95% CI 0.35 to 5.78; RD 4 more per 1000, 95% CI 7 fewer to 50 more; very low-certainty evidence). One RCT compared ASA to LMWH at two years follow-up. The pooled data did not confirm or exclude a beneficial or detrimental effect of ASA relative to LMWH on all-cause mortality (RR 1.00, 95% CI 0.06 to 15.89; RD 0 fewer per 1000, 95% CI 4 fewer to 68 more; very low-certainty evidence); symptomatic DVT (RR 1.20, 95% CI 0.53 to 2.72; RD 9 more per 1000, 95% CI 21 fewer to 78 more; very low-certainty evidence); and PE (RR 9.00, 95% CI 0.49 to 166.17; RD 8 more per 1000, 95% CI 1 fewer to 165 more; very low-certainty evidence). VKA versus LMWH One RCT compared VKA to LMWH at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of VKA relative to LMWH on all-cause mortality (RR 0.33, 95% CI 0.01 to 8.10; RD 3 fewer per 1000, 95% CI 5 fewer to 32 more; very low-certainty evidence); symptomatic DVT (RR 2.32, 95% CI 0.91 to 5.93; RD 36 more per 1000, 95% CI 2 fewer to 135 more; very low-certainty evidence); PE (RR 8.96, 95% CI 0.49 to 165.42; RD 8 more per 1000, 95% CI 1 fewer to 164 more; very low-certainty evidence); and minor bleeding (RR 0.33, 95% CI 0.03 to 3.17; RD 9 fewer per 1000, 95% CI 13 fewer to 30 more; very low-certainty evidence). The study reported that no major bleeding occurred in either arm. One RCT compared VKA to LMWH at two years follow-up. The data did not confirm or exclude a beneficial or detrimental effect of VKA relative to LMWH on all-cause mortality (RR 2.00, 95% CI 0.18 to 21.90; RD 5 more per 1000, 95% CI 4 fewer to 95 more; very low-certainty evidence); symptomatic DVT (RR 1.70, 95% CI 0.80 to 3.63; RD 32 more per 1000, 95% CI 9 fewer to 120 more; very low-certainty evidence); and PE (RR 9.00, 95% CI 0.49 to 166.17; RD 8 more per 1000, 95% CI 1 fewer to 165 more; very low-certainty evidence). ASA versus DOAC One RCT compared ASA to DOAC at six months follow-up. The data did not confirm or exclude a beneficial or detrimental effect of ASA relative to DOAC on DVT, PE, and major bleeding and minor bleeding (minor bleeding: RR 5.00, 95% CI 0.31 to 79.94; RD 4 more per 1000, 95% CI 1 fewer to 79 more; very low-certainty evidence). The study reported that no DVT, PE, or major bleeding events occurred in either arm. These results did not change in a meta-analysis including the study published as an abstract. AUTHORS' CONCLUSIONS: The certainty of the available evidence for the comparative effects of ASA, VKA, LMWH, and DOAC on all-cause mortality, DVT, PE, or bleeding was either low or very low. People with multiple myeloma considering antithrombotic agents should balance the possible benefits of reduced thromboembolic complications with the possible harms and burden of anticoagulants. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Morbidity in an adenosine deaminase-deficient patient during 27 years of enzyme replacement therapy.

INTRODUCTION: Adenosine deaminase (ADA) deficiency causes severe immunodeficiency that is lethal in infancy. Enzyme replacement therapy (ERT) can improve the metabolic, immune and non-immune abnormalities in patients prior to transplantation, however, its benefits over extended periods are not well characterized. We describe a 28-year-old female who received ERT for 27 years. She suffered from EBV negative B cell lymphoma of the hip at 14 years of age and Guillian-Barre Syndrome 2 years later. At 22 years of age, she experienced a gastrointestinal infection with Mycobacterium genavense. At 26 years of age, lymphoma reoccurred with multiple liver lesions followed by Mycobacterium genavense infection with dissemination to the brain. Throughout this period, ADA activity in the plasma was within the therapeutic range. Repeated evaluations demonstrated very low lymphocyte counts and impaired T cell function. CONCLUSIONS: ERT might be insufficient to maintain normal immunity over extended periods in some ADA-deficient patients.

Development and implementation of a quality improvement toolkit, iron deficiency in pregnancy with maternal iron optimization (IRON MOM): A before-and-after study.

BACKGROUND: Iron deficiency (ID) in pregnancy is a common problem that can compromise both maternal and fetal health. Although daily iron supplementation is a simple and effective means of treating ID in pregnancy, ID and ID anemia (IDA) often go unrecognized and untreated due to lack of knowledge of their implications and competing clinical priorities. METHODS AND FINDINGS: In order to enhance screening and management of ID and IDA in pregnancy, we developed a novel quality-improvement toolkit: ID in pregnancy with maternal iron optimization (IRON MOM), implemented at St. Michael's Hospital in Toronto, Canada. It included clinical pathways for diagnosis and management, educational resources for clinicians and patients, templated laboratory requisitions, and standardized oral iron prescriptions. To assess the impact of IRON MOM, we retrospectively extracted laboratory data of all women seen in both the obstetrics clinic and the inpatient delivery ward settings from the electronic patient record (EPR) to compare measures pre- and post-implementation of the toolkit: a process measure of the rates of ferritin testing, and outcome measures of the proportion of women with an antenatal (predelivery) hemoglobin value below 100 g/L (anemia), the proportion of women who received a red blood cell (RBC) transfusion during pregnancy, and the proportion of women who received an RBC transfusion immediately following delivery or in the 8-week postpartum period. The pre-intervention period was from January 2012 to December 2016, and the post-intervention period was from January 2017 to December 2017. From the EPR, 1,292 and 2,400 ferritin tests and 16,603 and 3,282 antenatal hemoglobin results were extracted pre- and post-intervention, respectively. One year after implementation of IRON MOM, we found a 10-fold increase in the rate of ferritin testing in the obstetric clinics at our hospital and a lower risk of antenatal hemoglobin values below 100 g/L (pre-intervention 13.5% [95% confidence interval (CI) 13.0%-14.11%]; post-intervention 10.6% [95% CI 9.6%-11.7%], p < 0.0001). In addition, a significantly lower proportion of women received an RBC transfusion during their pregnancy (1.2% pre-intervention versus 0.8% post-intervention, p = 0.0499) or immediately following delivery and in the 8 weeks following (2.3% pre-intervention versus 1.6% post-intervention, p = 0.0214). Limitations of this study include the use of aggregate data extracted from the EPR, and lack of a control group. CONCLUSIONS: The introduction of a standardized toolkit including diagnostic and management pathways as well as other aids increased ferritin testing and decreased the incidence of anemia among women presenting for delivery at our site. This strategy also resulted in reduced proportions of women receiving RBC transfusion during pregnancy and in the first 8 weeks postpartum. The IRON MOM toolkit is a low-tech strategy that could be easily scaled to other settings.

Treatment preferences of patients with relapsed and refractory multiple myeloma: a qualitative study.

BACKGROUND: Multiple myeloma is a haematological malignancy characterized by significant morbidity and mortality. This study sought to develop an in-depth understanding of patients' lived experiences of relapsed or refractory multiple myeloma (RRMM) and its treatment, and to identify which features of treatment were most important to them. METHODS: Qualitative interviews and focus groups (FGs) were conducted with 32 people living with RRMM across Canada. In Phase 1, interviews focused on participants' accounts of their experiences with the disease and its treatment and laid the groundwork for the FGs (Phase 2). The FGs developed a deeper understanding of patients' treatment priorities. Interview and FG transcripts were coded for emergent themes and patterns. RESULTS: The interviews identified important side effects that had significant impacts on patients' lives, including physical, cognitive, and psychological/emotional side effects. Participants also identified specific treatment features (attributes) that were important to them. These were compiled into a list and used in the FGs to understand patients' priorities. Higher prioritized attributes were: life expectancy, physical and cognitive side effects, and financial impact. Mode of administration, treatment intervals, psychological side effects, and sleep/mood effects were identified as lower priorities. CONCLUSIONS: RRMM and its treatments impact importantly on patients' quality-of-life across a range of domains. Patients prioritized treatment features that could enhance life expectancy, minimize side effects and offset financial burdens. IMPLICATIONS FOR CANCER SURVIVORS: A clear articulation of patient priorities can contribute to efforts to design treatment with patients' concerns in mind, thereby promoting a more patient-centered approach to care.

Tackling overutilization of hospital tests and treatments: Lessons learned from a grassroots approach.

Recent data suggest unnecessary medical testing and treatment is relatively common in Canada. A number of harms to patients can arise as a result of unnecessary tests and treatments. In addition to patient harm, unnecessary tests and treatments add to the cost of medical care. Inspired by the Choosing Wisely campaign, St. Michael's Hospital in Toronto, Ontario, developed a hospital-wide program to address many different forms of overutilization at our hospital. The program prioritizes harm reduction over cost-containment and aims to create sustainable change through grassroots clinician engagement. This article will review important lessons learned from the St. Michael's experience.

Five hematologic tests and treatments to question.

Choosing Wisely(®) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. The American Society of Hematology (ASH) released its first Choosing Wisely(®) list in 2013. Using the same evidence-based methodology as in 2013, ASH has identified 5 additional tests and treatments that should be questioned by clinicians and patients under specific, indicated circumstances. The ASH 2014 Choosing Wisely(®) recommendations include: (1) do not anticoagulate for more than 3 months in patients experiencing a first venous thromboembolic event in the setting of major, transient risk factors for venous thromboembolism; (2) do not routinely transfuse for chronic anemia or uncomplicated pain crises in patients with sickle cell disease; (3) do not perform baseline or surveillance computed tomography scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia; (4) do not test or treat for heparin-induced thrombocytopenia if the clinical pretest probability of heparin-induced thrombocytopenia is low; and (5) do not treat patients with immune thrombocytopenia unless they are bleeding or have very low platelet counts.

Identifying existing Choosing Wisely recommendations of high relevance and importance to hematology.

Choosing Wisely (CW) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. In an effort to learn from and leverage the work of others, the American Society of Hematology CW Task Force developed a method to identify and prioritize CW recommendations from other medical societies of high relevance and importance to patients with blood disorders and their physicians. All 380 CW recommendations were reviewed and assessed for relevance and importance. Relevance was assessed using the MORE(TM) relevance scale. Importance was assessed with regard to six guiding principles: harm avoidance, evidence, aggregate cost, relevance, frequency and impact. Harm avoidance was considered the most important principle. Ten highly relevant and important recommendations were identified from a variety of professional societies. Recommendations focused on decreasing unnecessary imaging, blood work, treatments and transfusions, as well as on increasing collaboration across disciplines and considering value when recommending treatments. Many CW recommendations have relevance beyond the society of origin. The methods developed by the ASH CW Task Force could be easily adapted by other Societies to identify additional CW recommendations of relevance and importance to their fields. Am. J. Hematol. 91:787-792, 2016. © 2016 Wiley Periodicals, Inc.

Hepatitis B virus screening before adjuvant chemotherapy in patients with early-stage breast cancer: a cost-effectiveness analysis.

Most patients with hepatitis B virus (HBV) have no symptoms, and many are unaware of the infection. However, HBV can reactivate with immunosuppression; chemotherapy causes reactivation in 22 % of hepatitis B surface antigen-positive patients. HBV reactivation can be fatal. HBV reactivation can be prevented, provided that HBV is recognized prior to chemotherapy. The objective of this study is to estimate the health and economic effects of HBV screening strategies in patients receiving adjuvant chemotherapy for breast cancer. We developed a state-transition microsimulation model to examine the cost-effectiveness of three HBV screening strategies: (1) "No screening"; (2) "Screen-and-Treat to prevent reactivation" (screen-all) with either lamivudine/tenofovir (LAM/TDF) or entecavir (ETV); and (3) "Screen-and-Treat high-risk only" (screen-HR) and treat with either LAM/TDF or ETV. Model data were obtained from the published literature. We used a payer's perspective, a lifetime horizon, and a 5 % discount rate for the analysis. "Screen-all" would prevent at least 38 severe reactivations per 100,000 persons screened over the lifetime of the cohort. "Screen-all" was associated with an increase of 0.0034-0.0035 QALYs and an additional cost of C$164-C$266 per person, which translated into an incremental cost-effectiveness ratio of C$47,808/QALY-C$76,527/QALY gained compared with "No screening" depending on the antiviral therapy received. "Screen-all" was the most cost-effective strategy, while "Screen-HR" was inferior in all scenarios tested. HBV screening before adjuvant chemotherapy for breast cancer patients would prevent a significant number of reactivations, would likely be moderately cost-effective, and may extend the lives of breast cancer patients.

The ASH Choosing Wisely® campaign: five hematologic tests and treatments to question.

Choosing Wisely® is a medical stewardship and quality improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The ASH is an active participant in the Choosing Wisely® project. Using an iterative process and an evidence-based method, ASH has identified 5 tests and treatments that in some circumstances are not well supported by evidence and which in certain cases involve a risk of adverse events and financial costs with low likelihood of benefit. The ASH Choosing Wisely® recommendations focus on avoiding liberal RBC transfusion, avoiding thrombophilia testing in adults in the setting of transient major thrombosis risk factors, avoiding inferior vena cava filter usage except in specified circumstances, avoiding the use of plasma or prothrombin complex concentrate in the nonemergent reversal of vitamin K antagonists, and limiting routine computed tomography surveillance after curative-intent treatment of non-Hodgkin lymphoma. We recommend that clinicians carefully consider anticipated benefits of the identified tests and treatments before performing them.

COVID-19 vaccine immunogenicity and safety surrounding fourth and subsequent vaccine doses in patients with hematologic malignancies.

BACKGROUND: Immune response to COVID-19 vaccine is diminished in patients with hematologic malignancy. There is limited data regarding response to vaccine doses in these patients. PURPOSE: To quantify the humoral immune response engendered by 4th and subsequent doses of SARS-CoV-2 vaccination as measured by anti-Spike (anti-S) antibody levels, based on dried blood spot (DBS) testing, in patients with hematologic malignancies. Anti-S binds to the spike protein of the SARS-CoV-2 virus and is indicative of vaccine immunogenicity. METHODS: We conducted a prospective study of hematologic malignancies between August 2021 and January 2023 at 12 sites across Canada. Participants were followed longitudinally and submitted finger-prick DBS cards at set intervals associated with vaccination. Samples were processed via high throughput ELISA assay to detect serum antibodies against nucleocapsid (N) and spike (S) proteins. RESULTS: We obtained 3071 samples on 790 unique patients. Of these, 372 unique participants with 1840 samples had anti-S results available post-4th, 5th or 6th COVID-19 vaccine dose and were included for analysis. Three hundred thirty-three patients of the 372 participants submitted a DBS sample post 4th dose. Of these, 257 patients (77.2%) had a positive anti-S antibody. A total of 198 patients had paired samples pre- and post-dose 4, of which 59 (29.7%) had a negative anti-S antibody pre-dose 4. Of these, 20 (33.4%) developed positive anti-S antibody post-dose 4. One hundred forty-nine patients submitted a DBS sample post-dose 5. Of these, 135 patients (90.6%) had positive anti-S antibody. A total of 52 had paired samples pre- and post-dose 5. Six (8.7%) had a negative anti-S antibody pre-dose 5, of which two (33.3%) developed positive anti-S antibody post-dose 5. Of these 372 patients, 123 (34%) reported COVID-19 infection and 4 (1%) had a COVID-19 related hospitalization. There were no reported deaths from COVID-19. CONCLUSIONS: This prospective cohort study showed that humoral immune response improved with subsequent doses of COVID-19 vaccines.

Reducing unnecessary diagnostic phlebotomy in intensive care: a prospective quality improvement intervention.

BACKGROUND: Critically ill patients receive frequent routine and recurring blood tests, some of which are unnecessary. AIM: To reduce unnecessary routine phlebotomy in a 30-bed tertiary medical-surgical intensive care unit (ICU) in Toronto, Ontario. METHODS: This prospective quality improvement study included a 7-month preintervention baseline, 5-month intervention and 11-month postintervention period. Change strategies included education, ICU rounds checklists, electronic order set modifications, an electronic test add-on tool and audit and feedback. The primary outcome was mean volume of blood collected per patient-day. Secondary outcomes included the number blood tubes used and red cell transfusions. Balancing measures included the timing and types of blood tests, ICU length of stay and mortality. Outcomes were evaluated using process control charts and segmented regression. RESULTS: Patient demographics did not differ between time periods; total number of patients: 2096, median age: 61 years, 60% male. Mean phlebotomy volume±SD decreased from 41.1±4.0 to 34.1±4.7 mL/patient-day. Special cause variation was met at 13 weeks. Segmental regression demonstrated an immediate postintervention decrease of 6.6 mL/patient-day (95% CI 1.8 to 11.4 p=0.009), which was sustained. Blood tube consumption decreased by 1.4 tubes/patient-day (95% CI 0.4 to 2.4, p=0.005) amounting to 13 276 tubes (95% CI 4602 to 22 127 tubes) saved over 11 months. Red blood cell transfusions decreased from 10.5±5.2 to 8.3±4.4 transfusions/100 patient-days (incident rate ratio 0.56, 95% CI 0.35 to 0.88, p=0.01). There was no impact on length of stay (2 days, IQR 1-5) and mortality (18.1%±2.0%). CONCLUSION: Iterative improvement interventions targeting clinician test ordering behaviour can reduce ICU phlebotomy and may impact red cell transfusions. Frequent stakeholder consultation, incorporating stewardship into daily workflow, and audit and feedback are effective strategies.

Factors associated with timely COVID-19 vaccination in a population-based cohort of patients with cancer.

BACKGROUND: In many jurisdictions, cancer patients were prioritized for COVID-19 vaccination because of increased risk of infection and death. To understand sociodemographic disparities that affected timely receipt of COVID-19 vaccination among cancer patients, we undertook a population-based study in Ontario, Canada. METHODS: Patients older than 18 years and diagnosed with cancer January 2010 to September 2020 were identified using administrative data; vaccination administration was captured between approval (December 2020) up to February 2022. Factors associated with time to vaccination were evaluated using multivariable Cox proportional hazards regression. RESULTS: The cohort consisted of 356 535 patients, the majority of whom had solid tumor cancers (85.9%) and were not on active treatment (74.1%); 86.8% had received at least 2 doses. The rate of vaccination was 25% lower in recent (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.72 to 0.76) and nonrecent immigrants (HR = 0.80, 95% CI = 0.79 to 0.81). A greater proportion of unvaccinated patients were from neighborhoods with a high concentration of new immigrants or self-reported members of racialized groups (26.0% vs 21.3%, standardized difference = 0.111, P < .001), residential instability (27.1% vs 23.0%, standardized difference = 0.094, P < .001), or material deprivation (22.1% vs 16.8%, standardized difference = 0.134, P < .001) and low socioeconomic status (20.9% vs 16.0%, standardized difference = 0.041, P < .001). The rate of vaccination was 20% lower in patients from neighborhoods with the lowest socioeconomic status (HR = 0.82, 95% CI = 0.81 to 0.84) and highest material deprivation (HR = 0.80, 95% CI = 0.78 to 0.81) relative to those in more advantaged neighborhoods. CONCLUSIONS: Despite funding of vaccines and prioritization of high-risk populations, marginalized patients were less likely to be vaccinated. Differences are likely due to the interplay between systemic barriers to access and cultural or social influences affecting uptake.

COVID-19 and Other Viral Infections in Patients With Hematologic Malignancies.

COVID-19 and our armamentarium of strategies to combat it have evolved dramatically since the virus first emerged in late 2019. Vaccination remains the primary strategy to prevent severe illness, although the protective effect can vary in patients with hematologic malignancy. Strategies such as additional vaccine doses and now bivalent boosters can contribute to increased immune response, especially in the face of evolving viral variants. Because of these new variants, no approved monoclonal antibodies are available for pre-exposure or postexposure prophylaxis. Patients with symptomatic, mild-to-moderate COVID-19 and risk features for developing severe COVID-19, who present within 5-7 days of symptom onset, should be offered outpatient therapy with nirmatrelvir/ritonavir (NR) or in some cases with intravenous (IV) remdesivir. NR interacts with many blood cancer treatments, and reviewing drug interactions is essential. Patients with severe COVID-19 should be managed with IV remdesivir, tocilizumab (or an alternate interleukin-6 receptor blocker), or baricitinib, as indicated based on the severity of illness. Dexamethasone can be considered on an individual basis, weighing oxygen requirements and patients' underlying disease and their perceived ability to clear infection. Finally, as CD19-targeted and B-cell maturation (BCMA)-targeted chimeric antigen receptor (CAR) T-cell therapies become more heavily used for relapsed/refractory hematologic malignancies, viral infections including COVID-19 are increasingly recognized as common complications, but data on risk factors and prophylaxis in this patient population are scarce. We summarize the available evidence regarding viral infections after CAR T-cell therapy.