High prevalence of iron deficiency and socioeconomic disparities in laboratory screening of non-pregnant females of reproductive age: A retrospective cohort study.

Iron deficiency anemia (IDA) and non-anemic iron deficiency (NAID) are highly prevalent among non-pregnant females of reproductive age. Canada has no national screening guidelines for this population. Screening, when performed, is often with a complete blood count alone without ferritin or iron indices. The primary objective was to determine the prevalence of screening for NAID and IDA over a 3-year period in non-pregnant females of reproductive age who had tests performed at outpatient laboratories in Ontario, Canada. Retrospective cohort study of non-pregnant females ages 15-54 in Ontario, from 2017 to 2019. NAID was defined as ferritin <30 µg/L, anemia as hemoglobin <120 g/L, and IDA as ferritin <30 µg/L and hemoglobin <120 g/L. Annual household income was estimated using patient postal codes. A total of 784 132 non-pregnant females were included. The 82.1% were screened for iron deficiency, 38.3% had NAID and 13.1% had IDA; 55.6% with IDA had normal mean corpuscular volumes. The median household income was $89454.80 compared with a provincial median of $65285.00. Patients in the lowest income quintile had the highest odds of being anemic, and the lowest odds of having a ferritin checked. A large proportion of non-pregnant females of reproductive age in this cohort were screened for iron deficiency. In this relatively privileged cohort, NAID affected nearly 40%, and IDA 13%. Most patients with IDA did not have microcytosis. Low household income was associated with the greatest odds of anemia and the lowest odds of being screened, highlighting inequitable access to screening for IDA in Ontario, Canada.

Including the patient in patient blood management: Development and assessment of an educational animation tool.

BACKGROUND: Patient blood management (PBM) programs are effective at reducing transfusion-associated mortality and morbidity; however, patient engagement within the realm of PBM remains relatively unstudied. Our objectives were to develop a novel educational tool utilizing animation to educate preoperative patients about anemia and to evaluate the effectiveness of this intervention. STUDY DESIGN AND METHODS: We created a patient-facing animation for preoperative surgical patients. The animation addressed characters' health journeys from diagnosis to treatment, addressing the role of PBM. We utilized the concept of patient activation as a means to empower patients, and developed the animation to be as accessible as possible. Post-viewing, patients provided feedback utilizing an electronic survey. RESULTS: A final version of the animation can be found here: https://vimeo.com/495857315. A total of 51 participants viewed our animation, the majority of whom were planned to undergo joint replacement or cardiac surgery. Almost all (94%, N = 4) agreed that taking an active role in their health was the most important factor in determining their ability to function. The video was felt to be easy to understand (96%, N = 49), and 92% (N = 47) agreed that they had a better understanding of anemia and its treatment. After watching the animation, patients felt more certain that they could follow through with their PBM plan (98%, N = 50). DISCUSSION: To the best of our knowledge, there are no other PBM-specific patient education animations. Patients enjoyed learning about PBM though animation, and patient education may lead to better uptake of PBM interventions. We hope that other hospitals will be inspired to pursue this approach.

A population-based analysis of spirometry use and the prevalence of chronic obstructive pulmonary disease in lung cancer.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and lung cancer are associated diseases. COPD is underdiagnosed and thus undertreated, but there is limited data on COPD diagnosis in the setting of lung cancer. We assessed the diagnosis of COPD with lung cancer in a large public healthcare system. METHODS: Anonymous administrative data was acquired from ICES, which links demographics, hospital records, physician billing, and cancer registry data in Ontario, Canada. Individuals age 35 or older with COPD were identified through a validated, ICES-derived cohort and spirometry use was derived from physician billings. Statistical comparisons were made using Wilcoxon rank sum, Cochran-Armitage, and chi-square tests. RESULTS: From 2002 to 2014, 756,786 individuals were diagnosed with COPD, with a 2014 prevalence of 9.3%. Of these, 51.9% never underwent spirometry. During the same period, 105,304 individuals were diagnosed with lung cancer, among whom COPD was previously diagnosed in 34.9%. Having COPD prior to lung cancer was associated with lower income, a rural dwelling, a lower Charlson morbidity score, and less frequent stage IV disease (48 vs 54%, p < 0.001). Spirometry was more commonly undertaken in early stage disease (90.6% in stage I-II vs. 54.4% in stage III-IV). CONCLUSION: Over a third of individuals with lung cancer had a prior diagnosis of COPD. Among individuals with advanced lung cancer, greater use of spirometry and diagnosis of COPD may help to mitigate respiratory symptoms.

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.

The safety and efficacy of ferumoxytol in the treatment of iron deficiency: a systematic review and meta-analysis.

INTRODUCTION: Ferumoxytol is an intravenous (IV) iron formulation for treatment of iron deficiency (ID) that faced post-marketing reports of serious adverse events (SAEs). OBJECTIVES: To determine the safety and efficacy of ferumoxytol compared to other iron formulations and placebo. METHODS: We searched the Cochrane Library, Medline, and EMBASE from inception until February 2018 as well as trial registries and reference lists of relevant articles for randomized or quasi-randomized controlled trials. RESULTS: The review included nine studies with 5691 participants. Studies were at low risk of bias. When comparing ferumoxytol to other IV iron formulations, there is moderate quality evidence (QE) of little to no difference in treatment emergent adverse events (TEAEs) (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.80-0.97), treatment related adverse events (TRAEs) (RR 0.73, 95% CI 0.61-0.88), SAEs (RR 1.13, 95% CI 0.77-1.67), hypotension or hypersensitivity reactions (RR 0.58, 95% CI 0.31-1.09), or composite cardiovascular outcomes (RR 0.56, 95% CI 0.24-1.29), low QE of little to no difference in related SAEs (RR 0.55, 95% CI 0.05-6.16), and high QE of little to no difference in the number of patients with an increase in hemoglobin by at least 1 g/dL (RR 1.04, 95% CI 0.96-1.12). Ferumoxytol had less TEAEs compared to oral iron (RR 0.78, 95% CI 0.61-0.98), but more compared to placebo (RR 1.62, 95% CI 1.01-2.61). DISCUSSION: Ferumoxytol is as efficacious and safe as alternative IV iron formulations with no clear safety concerns.

Iron deficiency anemia among women: An issue of health equity.

Iron deficiency is the most common and widespread nutritional deficiency in the world. For women, the risk of iron deficiency and iron deficiency anemia increases due to iron demands during pregnancy and regular iron losses due to menstruation during reproductive years. These interrelated conditions are of public health concern as they are highly prevalent, and the negative consequences such as chronic fatigue, cognitive impairment and poor quality of life are broad and multifaceted. People of low socioeconomic status are at higher risk of iron deficiency due to low intake of expensive iron-rich foods, and decreased access to healthcare. In this review, we applied a health equity lens to describe the current state of care for women with iron deficiency with or without anemia. We have highlighted several structural challenges that span from the laboratory diagnosis, inconsistent screening guidelines, and stigma associated with heavy menstrual bleeding, to treatment barriers.

Tranexamic acid for management of heavy vaginal bleeding: barriers to access and myths surrounding its use.

Tranexamic acid is safe and effective for the treatment of heavy vaginal bleeding during menstruation and childbirth. It improves the quality of life, facilitates participation in school and work, and reduces the risk of death from postpartum hemorrhage. Despite its well-established benefits, individual- and structural-level barriers preclude its widespread utilization, hindering effective patient care and perpetuating health inequities in women's health. We first describe the evidence for the use of tranexamic acid in treating heavy menstrual bleeding and postpartum hemorrhage. Barriers to tranexamic acid use, including structural sexism, period poverty, misinformation in product monograph labeling, stigmatization of vaginal blood loss, and drug access, are then discussed. Finally, we summarize relevant data presented during the 2023 International Society on Thrombosis and Haemostasis Congress.

Patient-centered care in von Willebrand disease: are we there yet?

INTRODUCTION: Von Willebrand Disease is the most common inherited bleeding disorder. Paradoxically, affected individuals are often misdiagnosed and experience substantial diagnostic delay. There are sex-specific health disparities in VWD rooted in the stigmatization of vaginal bleeding, which leads to symptom dismissal, lack of timely access to care and lower health-related quality of life. AREAS COVERED: Following the core elements of patient-centered care - respect for patient preferences, values, and needs, we describe the current state of VWD care. Challenges of diagnostic delay, serial misrecognition of abnormal bleeding, and symptom dismissal are barriers that disproportionately affect women with VWD. These negative effects are further amplified in individuals living in low- and middle-income countries. We describe the importance of coordinated multidisciplinary care, as well as the need for patient education and empowered self-advocacy. EXPERT OPINION: While tremendous work has been done to improve the diagnosis and management of VWD, timely and high-quality research is urgently needed to address care gaps. Systemic changes such as resource investment, dedicated research funding for novel treatment modalities, and effective knowledge translation strategies to address structural barriers are needed to facilitate effective patient-centered care for VWD.

Management and outcomes of patients with chronic obstructive lung disease and lung cancer in a public healthcare system.

HYPOTHESIS: There is limited data on the care and outcomes of individuals with both chronic obstructive pulmonary disease (COPD) and lung cancer, particularly in advanced disease. We hypothesized such patients would receive less cancer treatment and have worse outcomes. METHODS: We analyzed administrative data from the province of Ontario including demographics, hospitalization records, physician billings, cancer diagnosis, and treatments. COPD was defined using the ICES-derived COPD cohort (1996-2014) with data from 2002 to 2014. Descriptive statistics and multivariable analyses were undertaken. RESULTS: Of 105 304 individuals with lung cancer, 43 375 (41%) had stage data and 36 738 (34.9%) had COPD. Those with COPD were likely to be younger, have a Charlson score ≤ 1, have lower income, to live rurally, and to have stage I/II lung cancer (29.8 vs 26.5%; all p<0.001). For the COPD population with stage I/II cancer, surgery and adjuvant chemotherapy were less likely (56.8 vs. 65.9% and 15.4 vs. 17.1%, respectively), while radiation was more likely (26.0 vs. 21.8%) (p all < 0.001). In the stage III/IV population, individuals with COPD received less chemotherapy (55.9 vs 64.4%) or radiation (42.5 vs 47.5%; all p<0.001). Inhaler and oxygen use was higher those with COPD, as were hospitalizations for respiratory infections and COPD exacerbations. On multivariable analysis, overall survival was worse among those with COPD (HR 1.20, 95% CI 1.19-1.22). CONCLUSIONS: A co-diagnosis of COPD and lung cancer is associated with less curative treatment in early stage disease, less palliative treatment in late stage disease, and poorer outcomes.

Randomized trials of therapeutic heparin for COVID-19: A meta-analysis.

BACKGROUND: Pulmonary endothelial injury and microcirculatory thromboses likely contribute to hypoxemic respiratory failure, the most common cause of death, in patients with COVID-19. Randomized controlled trials (RCTs) suggest differences in the effect of therapeutic heparin between moderately and severely ill patients with COVID-19. We did a systematic review and meta-analysis of RCTs to determine the effects of therapeutic heparin in hospitalized patients with COVID-19. METHODS: We searched PubMed, Embase, Web of Science, medRxiv, and medical conference proceedings for RCTs comparing therapeutic heparin with usual care, excluding trials that used oral anticoagulation or intermediate doses of heparin in the experimental arm. Mantel-Haenszel fixed-effect meta-analysis was used to combine odds ratios (ORs). RESULTS AND CONCLUSIONS: There were 3 RCTs that compared therapeutic heparin to lower doses of heparin in 2854 moderately ill ward patients, and 3 RCTs in 1191 severely ill patients receiving critical care. In moderately ill patients, there was a nonsignificant reduction in all-cause death (OR, 0.76; 95% CI, 0.57-1.02), but significant reductions in the composite of death or invasive mechanical ventilation (OR, 0.77; 95% CI, 0.60 0.98), and death or any thrombotic event (OR, 0.58; 95% CI, 0.45-0.77). Organ support-free days alive (OR, 1.29; 95% CI, 1.07-1.57) were significantly increased with therapeutic heparin. There was a nonsignificant increase in major bleeding. In severely ill patients, there was no evidence for benefit of therapeutic heparin, with significant treatment-by-subgroup interactions with illness severity for all-cause death (P = .034). In conclusion, therapeutic heparin is beneficial in moderately ill patients but not in severely ill patients hospitalized with COVID-19.

Coagulopathy of hospitalised COVID-19: A Pragmatic Randomised Controlled Trial of Therapeutic Anticoagulation versus Standard Care as a Rapid Response to the COVID-19 Pandemic (RAPID COVID COAG - RAPID Trial): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days. TRIAL DESIGN: Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial PARTICIPANTS: The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Participants are recruited from hospital sites in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and the United States of America. The inclusion criteria are: 1) Laboratory confirmed COVID-19 (diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification) prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission; 2) Admitted to hospital for COVID-19; 3) One D-dimer value above the upper limit of normal (ULN) (within 5 days (i.e. 120 hours) of hospital admission) AND EITHER: a. D-Dimer ≥2 times ULN OR b. D-Dimer above ULN and Oxygen saturation ≤ 93% on room air; 4) > 18 years of age; 5) Informed consent from the patient (or legally authorized substitute decision maker). The exclusion criteria are: 1) pregnancy; 2) hemoglobin <80 g/L in the last 72 hours; 3) platelet count <50 x 109/L in the last 72 hours; 4) known fibrinogen <1.5 g/L (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 5) known INR >1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 6) patient already prescribed intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration); 7) patient already prescribed therapeutic anticoagulation at the time of screening [low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban)]; 8) patient prescribed dual antiplatelet therapy, when one of the agents cannot be stopped safely; 9) known bleeding within the last 30 days requiring emergency room presentation or hospitalization; 10) known history of a bleeding disorder of an inherited or active acquired bleeding disorder; 11) known history of heparin-induced thrombocytopenia; 12) known allergy to UFH or LMWH; 13) admitted to the intensive care unit at the time of screening; 14) treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening; 15) Imminent death according to the judgement of the most responsible physician; 16) enrollment in another clinical trial of antithrombotic therapy involving hospitalized patients. INTERVENTION AND COMPARATOR: Intervention: Therapeutic dose of LMWH (dalteparin, enoxaparin, tinzaparin) or high dose nomogram of UFH. The choice of LMWH versus UFH will be at the clinician's discretion and dependent on local institutional supply. Comparator: Standard care [thromboprophylactic doses of LMWH (dalteparin, enoxaparin, tinzaparin, fondaparinux)] or UFH. Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is generally considered standard care. MAIN OUTCOMES: The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Secondary outcomes include (evaluated up to day 28): 1. All-cause death 2. Composite of ICU admission or all-cause death 3. Composite of mechanical ventilation or all-cause death 4. Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation; 5. Red blood cell transfusion (>1 unit); 6. Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; 7. Renal replacement therapy; 8. Hospital-free days alive; 9. ICU-free days alive; 10. Ventilator-free days alive; 11. Organ support-free days alive; 12. Venous thromboembolism (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 13. Arterial thromboembolism (defined as suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 14. Heparin induced thrombocytopenia; 15. Trajectories of COVID-19 disease-related coagulation and inflammatory biomarkers. RANDOMISATION: Randomisation will be stratified by site and age (>65 versus ≤65 years) using a 1:1 computer-generated random allocation sequence with variable block sizes. Randomization will occur within the first 5 days (i.e. 120 hours) of participant hospital admission. However, it is recommended that randomization occurs as early as possible after hospital admission. Central randomization using an interactive web response system will ensure allocation concealment. BLINDING (MASKING): No blinding involved. This is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 462 patients (231 per group) are needed to detect a 15% risk difference, from 50% in the control group to 35% in the experimental group, with power of 90% at a two-sided alpha of 0.05. TRIAL STATUS: Protocol Version Number 1.4. Recruitment began on May 11th, 2020. Recruitment is expected to be completed March 2022. Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04362085 Date of Trial Registration: April 24, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Heparin for Moderately Ill Patients with Covid-19.

BACKGROUND: Heparin, in addition to its anticoagulant properties, has anti-inflammatory and potential anti-viral effects, and may improve endothelial function in patients with Covid-19. Early initiation of therapeutic heparin could decrease the thrombo-inflammatory process, and reduce the risk of critical illness or death. METHODS: We randomly assigned moderately ill hospitalized ward patients admitted for Covid-19 with elevated D-dimer level to therapeutic or prophylactic heparin. The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation or ICU admission. Safety outcomes included major bleeding. Analysis was by intention-to-treat. RESULTS: At 28 days, the primary composite outcome occurred in 37 of 228 patients (16.2%) assigned to therapeutic heparin, and 52 of 237 patients (21.9%) assigned to prophylactic heparin (odds ratio, 0.69; 95% confidence interval [CI], 0.43 to 1.10; p=0.12). Four patients (1.8%) assigned to therapeutic heparin died compared with 18 patients (7.6%) assigned to prophylactic heparin (odds ratio, 0.22; 95%-CI, 0.07 to 0.65). The composite of all-cause mortality or any mechanical ventilation occurred in 23 (10.1%) in the therapeutic heparin group and 38 (16.0%) in the prophylactic heparin group (odds ratio, 0.59; 95%-CI, 0.34 to 1.02). Major bleeding occurred in 2 patients (0.9%) with therapeutic heparin and 4 patients (1.7%) with prophylactic heparin (odds ratio, 0.52; 95%-CI, 0.09 to 2.85). CONCLUSIONS: In moderately ill ward patients with Covid-19 and elevated D-dimer level, therapeutic heparin did not significantly reduce the primary outcome but decreased the odds of death at 28 days. Trial registration numbers: NCT04362085 ; NCT04444700.

Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial.

OBJECTIVE: To evaluate the effects of therapeutic heparin compared with prophylactic heparin among moderately ill patients with covid-19 admitted to hospital wards. DESIGN: Randomised controlled, adaptive, open label clinical trial. SETTING: 28 hospitals in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and US. PARTICIPANTS: 465 adults admitted to hospital wards with covid-19 and increased D-dimer levels were recruited between 29 May 2020 and 12 April 2021 and were randomly assigned to therapeutic dose heparin (n=228) or prophylactic dose heparin (n=237). INTERVENTIONS: Therapeutic dose or prophylactic dose heparin (low molecular weight or unfractionated heparin), to be continued until hospital discharge, day 28, or death. MAIN OUTCOME MEASURES: The primary outcome was a composite of death, invasive mechanical ventilation, non-invasive mechanical ventilation, or admission to an intensive care unit, assessed up to 28 days. The secondary outcomes included all cause death, the composite of all cause death or any mechanical ventilation, and venous thromboembolism. Safety outcomes included major bleeding. Outcomes were blindly adjudicated. RESULTS: The mean age of participants was 60 years; 264 (56.8%) were men and the mean body mass index was 30.3 kg/m2. At 28 days, the primary composite outcome had occurred in 37/228 patients (16.2%) assigned to therapeutic heparin and 52/237 (21.9%) assigned to prophylactic heparin (odds ratio 0.69, 95% confidence interval 0.43 to 1.10; P=0.12). Deaths occurred in four patients (1.8%) assigned to therapeutic heparin and 18 patients (7.6%) assigned to prophylactic heparin (0.22, 0.07 to 0.65; P=0.006). The composite of all cause death or any mechanical ventilation occurred in 23 patients (10.1%) assigned to therapeutic heparin and 38 (16.0%) assigned to prophylactic heparin (0.59, 0.34 to 1.02; P=0.06). Venous thromboembolism occurred in two patients (0.9%) assigned to therapeutic heparin and six (2.5%) assigned to prophylactic heparin (0.34, 0.07 to 1.71; P=0.19). Major bleeding occurred in two patients (0.9%) assigned to therapeutic heparin and four (1.7%) assigned to prophylactic heparin (0.52, 0.09 to 2.85; P=0.69). CONCLUSIONS: In moderately ill patients with covid-19 and increased D-dimer levels admitted to hospital wards, therapeutic heparin was not significantly associated with a reduction in the primary outcome but the odds of death at 28 days was decreased. The risk of major bleeding appeared low in this trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04362085.

Intravenous iron versus oral iron or observation for gastrointestinal malignancies: a systematic review.

BACKGROUND: Anemia is a common condition in patients with gastrointestinal cancer. Current evidence for the use of intravenous compared with oral iron in this clinical setting is inconclusive. A systematic review was performed to assess evidence on the efficacy of intravenous iron versus oral/observation in gastrointestinal cancer patients in the preoperative and postoperative setting. MATERIALS AND METHODS: We searched Medline and Embase from inception until December 2017 with no language restrictions. Outcomes included hemoglobin response, red blood cell transfusion, and adverse events. Screening, data abstraction, and risk of bias appraisal were performed by two independent reviewers. The risk of bias was assessed using the Cochrane tools for randomized and nonrandomized studies. RESULTS: A total of 10 studies (three randomized-controlled trials and seven nonrandomized studies) were included. Of the six preoperative studies, five reported that hemoglobin was significantly higher in the intravenous group compared with oral iron/observation. Among the four postoperative studies, three studies suggested that hemoglobin was significantly higher in the intravenous group compared with oral iron/observation. The overall risk of bias for all randomized-controlled trials was low. Quality assessments for nonrandomized studies found the risk of bias to be moderate for four studies and critical for three studies. CONCLUSION: Despite the limitations of the current body of evidence, there is a likely benefit to the use of intravenous iron in this patient population. Further confirmatory research is needed to draw empirical conclusions.

Bone health in symptomatic carriers of haemophilia A: a protocol for a multicentre prospective matched-cohort study.

INTRODUCTION: Haemophilia A is an X linked inherited bleeding disorder, caused by a decrease in coagulation factor VIII. Persons with haemophilia experience repeated musculoskeletal bleeding, which can lead to decreased range of motion, irreversible joint damage, low bone mineral density (BMD), and are at greater risk for osteoporosis. Women heterozygous for this mutation, also known as haemophilia A carriers, can have bleeding symptoms and even experience joint bleeding evidenced by radiological soft tissue and osteochondral changes. The prevalence of low BMD as a risk factor for osteoporosis has never been evaluated in carriers of haemophilia, and given the recent findings which suggest subclinical musculoskeletal bleeding in carrier women, we hypothesise that they too are at risk of impaired bone health. METHODS AND ANALYSIS: This is a national multicentre prospective matched-cohort study to compare BMD T-scores among symptomatic haemophilia A carriers, 50 years of age or older, with age-matched and body mass index-matched non-carriers (1:1). A total of 40 symptomatic carriers and 40 matched non-carriers will be recruited from St. Michael's Hospital, Kingston General Hospital in Ontario, Canada and Foothills Medical Centre in Alberta, Canada. Multivariable linear regression models will be used to estimate the effect of haemophilia carriership on BMD T-scores, adjusting for age, body mass index and other relevant covariates. ETHICS AND DISSEMINATION: The protocol was designed and will be conducted in compliance with applicable laws, rules and regulations. Research ethics approval was obtained from St. Michael's Hospital, Foothills Medical Centre, and Kingston General Hospital. Findings will be presented at international venues such as the American Society of Haematology and the World Federation of Haemophilia World Congress. The authors of this study will seek publication in journals such as Blood, Journal of Thrombosis and Haemostasis, American Journal ofHematology and British Journal ofHaematology.

Iron deficiency anemia in gastric cancer: a Canadian retrospective review.

BACKGROUND: Gastric cancer is highly prevalent amongst men and women. Previous studies have described the high prevalence of iron deficiency anemia (IDA) in gastrointestinal cancer patients, but few have focused on the gastric cancer population. We aimed to determine the point prevalence of patients with gastric cancer who developed IDA and chemotherapy-induced anemia, and to identify types and frequencies of IDA therapies. PATIENTS AND METHODS: A retrospective review was carried out for 126 gastric cancer patients from 2006 to 2016 at St Michael's Hospital, Toronto, Canada. Patient demographics, laboratory (ferritin, iron parameters) and clinical data regarding IDA were reviewed. IDA was defined as transferrin saturation less than 20%, ferritin less than 100 µg/l, and hemoglobin less than 130 g/l in men and less than 120 g/l in women. RESULTS: Of the 126 patients with gastric cancer identified (median age 70, interquartile range: 59-77), 64.3% were men. Only 18.3% of patients had a self-reported history of IDA, 40% had IDA at the time of gastric cancer diagnosis, and 58.7% were anemic. A total of 77 patients received chemotherapy, and of these, 54.2% developed chemotherapy-induced anemia. At the final follow-up, 21.4% of patients were diagnosed with IDA along their treatment course, and 79.4% were anemic. Red blood cell transfusions were most frequently prescribed (48.4%; median: 4 U; interquartile range: 2-6), compared with oral (31.8%) or intravenous iron (16.7%) therapy. CONCLUSION: The point prevalence of IDA was high in our gastric cancer patients despite inconsistent screening for IDA. Our findings indicate the need for a consistent diagnostic and therapeutic approach to IDA in this vulnerable patient population.

Association of Metformin with Breast Cancer Incidence and Mortality in Patients with Type II Diabetes: A GRADE-Assessed Systematic Review and Meta-analysis.

Background: Preclinical data suggest that metformin may reduce breast cancer incidence and improve cancer prognosis. However, the current evidence in observational studies is inconclusive. A systematic review and meta-analysis was conducted to assess the effect of metformin on the incidence of breast cancer and all-cause mortality in patients with type II diabetes (T2D).Methods: A literature search was performed on Medline, EMBASE, and the Cochrane library from inception to November 2016. Outcomes were incidence of breast cancer and all-cause mortality. Risk of bias and overall certainty of evidence was assessed using the Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development, and Evaluation (GRADE), respectively. Meta-analyses were performed using the most fully adjusted ORs or HRs and 95% confidence intervals (95% CI) as effect measures.Results: A total of 12 observational studies were included for breast cancer incidence and 11 studies for all-cause mortality. No significant association was found between metformin exposure and incidence of breast cancer (OR = 0.93; 95% CI, 0.85-1.03; I2 = 35%). A 45% risk reduction was observed for all-cause mortality (HR = 0.55; 95% CI, 0.44-0.70; I2 = 81%). Presence of publication bias is strongly suspected for both outcomes using Egger's funnel plots.Conclusions: The use of metformin may improve overall survival in patients with T2D and breast cancer. No effect of metformin on the incidence of breast cancer was observed. Interpretation of results is limited by the observational nature of the studies and resulting biases.Impact: Clinical trials are warranted to determine the role of metformin in breast cancer risk reduction and prognosis. Cancer Epidemiol Biomarkers Prev; 27(6); 627-35. ©2018 AACR.

Incidence and identification of risk factors for trastuzumab-induced cardiotoxicity in breast cancer patients: an audit of a single "real-world" setting.

Management of human epidermal growth factor receptor-2-positive (HER2+) breast cancer patients includes the combination of adjuvant chemotherapy and trastuzumab. A meta-analysis reported that <5% of HER2+ breast cancer patients will develop trastuzumab-induced cardiotoxicity (TIC). Observational data suggest that incidence is much higher. We aimed to determine the incidence, time to development, and risk factors associated with TIC among less selected patients. A retrospective cohort study was carried out in 160 HER2+ breast cancer patients who received adjuvant chemotherapy with trastuzumab from January 2006 to June 2014 at St. Michael's Hospital, Toronto, Canada. Patient demographics, cardiovascular history, and TIC were recorded. TIC was defined as symptomatic (heart failure) or asymptomatic [decline in left ventricular ejection fraction (LVEF) by ≥10% or LVEF ≤ 50%]. Of the 160 patients [median age 52 (IQR 45-60), 48.1% on anthracycline-based chemotherapy], 34 patients (21.3%) experienced TIC (median follow-up 55.4 months). The median time to development of TIC was 28.5 weeks during trastuzumab therapy. Those with TIC were more likely to have undergone a mastectomy (52.9 vs. 33.3%, p = 0.04). However, after adjusting for anthracycline-based chemotherapy, and radiotherapy, mastectomy was not independently associated with TIC (HR 2.02; 95% CI 0.88-4.63). The incidence of TIC is higher in our "real-world" population compared to clinical trial data. The median time to development of TIC was 28 weeks after trastuzumab initiation, approximately the 10th treatment of trastuzumab. Timely identification and management of patients is important to avoid irreversible cardiac toxicity and improve breast cancer survival.