Primary prevention of venous thromboembolism for cancer patients in randomized controlled trials: a bibliographical analysis of funding and trial characteristics.

Background: The majority of randomized controlled trials (RCTs) investigating venous thromboembolism (VTE) prophylaxis in patients with cancer involve commercial sponsorship. Commercial sponsorship overcomes feasibility limitations inherent in RCTs, such as recruitment and funding, but has attracted scrutiny for its potential for bias. Objectives: In RCTs of VTE prophylaxis in patients with cancer, how do trial characteristics compare between commercially sponsored RCTs and noncommercially sponsored RCTs? Methods: Medline, Embase, and Cochrane Central Register of Controlled Trials were searched for RCTs that investigated at least 1 pharmacologic intervention for VTE prophylaxis in adult patients with cancer. Screening and data extraction were conducted by independent reviewers. Outcomes included trial characteristics, reporting of favorable outcomes, protocol-manuscript discrepancies, and appraisal of spin. Outcomes were compared using the independent t-test, Mann-Whitney U-test, Pearson chi-squared test, and Fisher's exact test. Logistic regression was performed to identify factors associated with possible bias. Results: Of the 54 trials analyzed, 34 (63%) reported commercial sponsorship. Commercial sponsorship was not associated with the reporting of favorable outcomes, presence of spin, retrospective registration, or protocol-manuscript discrepancy. Spin was most prevalent in the abstract conclusions (9 out of 17 [53.3%]) and manuscript conclusions (8 out of 17 [46.7%]).Commercially sponsored trials had a higher rate of intention-to-treat analysis. Noncommercially sponsored trials were more likely to report retrospective registration of trial protocol and the use of composite primary outcomes. Conclusion: There were few significant differences between trial characteristics, suggesting that the evidence from commercially sponsored trials investigating VTE prophylaxis in patients with cancer is unlikely to be subject to bias attributable to commercial sponsorship.

Efficacy and safety of pre-operative insertion of inferior vena cava filter in patients undergoing bariatric surgery: a systematic review.

Prophylactic placement of inferior vena cava (IVC) filters prior to performing bariatric surgery is an intervention of unclear safety and efficacy with disagreement between current practice guidelines. To better characterize the risk and benefit of IVC filter insertion prior to bariatric surgery based on the current evidence. A systematic review of the literature of patients with prophylactic IVC filter insertion prior to bariatric surgery was performed and 32 studies were identified for inclusion into the review, of which none were randomized controlled trials. Meta-analysis was performed including the high-quality included studies. Seven high quality studies reported thrombotic events in patients undergoing bariatric surgery who had an IVCF and a control group which allowed for meta-analysis. The pooled odds ratio of venous thrombotic events in the IVC filter population versus the group without IVC filters was 1.57 (95%CI 0.89, 2.76). Among high quality studies 5 reported major bleeding with a rate of 0.76% and 6 reported on IVC filter complications with a rate of 0.67%. Overall no significant reduction in the rate of venous thrombosis was found with prophylactic IVC filter insertion. Use of IVC filters for prophylaxis remains a concern given the lack of clear efficacy in this setting and a small but present complication risk.

Direct oral anticoagulants after bariatric surgery-What is the evidence?

BACKGROUND: Obesity is a global epidemic and bariatric surgery is used with increasing frequency to treat its complications. The extent to which bariatric surgery alters the efficacy, safety, and pharmacokinetics of direct oral anticoagulants (DOACs) is unknown. AIMS: In this review, we summarize the evidence supporting the use of DOACs after bariatric surgery and apply our findings to resolve several clinical cases. MATERIALS & METHODS: We systematically searched MEDLINE, EMBASE, Cochrane Library, CINAHL and ClinicalTrials.gov from January 1, 2000, to June 15, 2021 for randomized and non-randomized studies evaluating the use of DOACs for any indication after bariatric surgery. Two reviewers independently screened titles, abstracts, and full-text articles. Clinical and pharmacokinetic outcomes were pooled by random-effects meta-analysis with inverse variance weighting. We used the Newcastle-Ottawa scale to assess risk of bias in non-randomized studies and assessed the certainty of evidence with GRADE. RESULTS: From 2519 records, we included 28 studies (n = 3229 patients): no randomized trials, 7 cohort studies, 6 case series, and 15 case reports. Incidence rates for arterial thromboembolism, venous thromboembolism and major bleeding were: 0.73 (95% confidence interval [CI]: 0.01-5.10), 2.45 (95% CI: 0.40-7.94), and 3.40 (95% CI: 0.80-9.36) events per 100 patient-years, respectively. The pooled proportion of peak direct oral anticoagulant drug levels within the expected range was 58% (95% CI: 39%-74%). CONCLUSION: There appears be substantial risk of DOAC malabsorption after bariatric surgery that could affect clinical outcomes, however the certainty of evidence was very low. PROSPERO: CRD42020202636.

Tyrosine kinase inhibitors and tumor lysis syndrome in hematologic malignancies: A systemic review.

BACKGROUND: Effective treatments for hematologic malignancies include therapies that target tyrosine kinase (TK) signaling pathways. Tumor lysis syndrome (TLS) is an oncologic emergency that can occur due to rapid turnover following the initiation of treatments for hematologic malignancy. The incidence of TLS is under-reported and it is unclear as to whether TK inhibitors (TKIs) are associated with TLS. OBJECTIVE: To conduct a systematic review to determine the incidence of TLS with TKIs. METHODS: A search was performed using EMBASE, MEDLINE, and Web of Science electronic databases, as well as a manual search of the American Society of Hematology and American Society of Clinical Oncology abstract databases. Keywords included: "tumor lysis syndrome," "tyrosine kinase inhibitors," "lymphoma," and "leukemia." RESULTS: We identified a total of 57 publications that commented on the incidence of TLS with TKIs for hematologic malignancy. Thirty-nine of those publications reported TLS as an adverse event. TLS was described as an adverse event among essentially all the subclasses of TKIs that are used to manage hematologic malignancies. CONCLUSION: The overall number of articles commenting on TLS as an adverse event is sparse and there needs to be more transparency regarding the incidence of TLS when employing newer targeted therapies. Physicians should consider the risk of TLS on an individual basis and the added risk of TLS when using TKIs to treat hematologic malignancy.

Prognostic Factors Associated With Development of Venous Thromboembolism in Critically Ill Patients-A Systematic Review and Meta-Analysis.

OBJECTIVE: To identify prognostic factors for the development of venous thromboembolism in the ICU. DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to March 1, 2021. STUDY SELECTION: We included English-language studies describing prognostic factors associated with the development of venous thromboembolism among critically ill patients. DATA EXTRACTION: Two authors performed data extraction and risk-of-bias assessment. We pooled adjusted odds ratios and adjusted hazard ratios for prognostic factors using random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. DATA SYNTHESIS: We included 39 observational cohort studies involving 729,477 patients. Patient factors with high or moderate certainty of association with increased odds of venous thromboembolism include older age (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29 per 10 yr), obesity (adjusted odds ratio, 1.25; 95% CI, 1.18-1.32), active malignancy (adjusted odds ratio, 1.70; 95% CI, 1.18-2.44), history of venous thromboembolism (adjusted odds ratio, 4.77; 95% CI, 3.42-6.65), and history of recent surgery (adjusted odds ratio, 1.77; 95% CI, 1.26-2.47). ICU-specific factors with high or moderate certainty of association with increased risk of venous thromboembolism include sepsis (adjusted odds ratio, 1.41; 95% CI, 1.12-1.78), lack of pharmacologic venous thromboembolism prophylaxis (adjusted odds ratio, 1.80; 95% CI, 1.14-2.84), central venous catheter (adjusted odds ratio, 2.93; 95% CI, 1.98-4.34), invasive mechanical ventilation (adjusted odds ratio, 1.74; 95% CI, 1.36-2.24), and use of vasoactive medication (adjusted odds ratio, 1.86; 95% CI, 1.23-2.81). CONCLUSIONS: This meta-analysis provides quantitative summaries of the association between patient-specific and ICU-related prognostic factors and the risk of venous thromboembolism in the ICU. These findings provide the foundation for the development of a venous thromboembolism risk stratification tool for critically ill patients.

Reducing unnecessary fixation of midshaft clavicle fractures.

PURPOSE: Displaced midshaft clavicle fractures have a non-union rate of 10-20%. Those who unite with conservative treatment have similar outcomes to those who undergo operative treatment; therefore, protocols to identify potential non-unions are important to avoid unnecessary surgery. The aim of this study is to report one such protocol. METHODS: A protocol was introduced, where all isolated closed displaced midshaft clavicle fractures were initially managed non-operatively in a sling. At 2 weeks patients were assessed clinically and those who were struggling with their symptoms were offered surgery, with the remainder mobilised as comfortable. All cases treated at one centre over a three-year period, with a minimum follow-up of one-year underwent case note review. RESULTS: Between 2015 and 2017 613 clavicle fractures were managed through clinic. 347 were middle third (56%), 75% were male, mean age 41(range16-97). Forty-one middle third clavicle fracture patients underwent early fixation. Eleven patients required late fixation for symptomatic delayed, non- or malunion, 6 for symptomatic non-unions and 1 was a symptomatic malunion. For displaced fractures the early operative rate was 17.8%, and symptomatic non/malunion rate was 3.2%. This led to a total operative rate of 21%. CONCLUSION: A protocol for managing clavicle fractures has demonstrated an effective management of these injuries. It is cost-effective reducing the number of patients with displaced fractures requiring fixation with a fixation rate of 21% whilst reducing the rate of symptomatic non- and malunion (3.2%). The management pathway is simple and could be introduced into any orthopaedic outpatient department with ease.

Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus.

Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications. Risks vary significantly between individuals based on cancer status, treatment, and other characteristics. To facilitate the evidence-based management of anticoagulant therapy in this patient population, a committee of 11 Canadian clinical experts updated a consensus-based algorithm for the acute and extended treatment of symptomatic and incidental CAT that was developed in 2018. Following a systematic review of the literature, updates to the algorithm were discussed during an online teleconference, and the algorithm was subsequently refined based on feedback from committee members. Clinicians using this treatment algorithm should consider bleeding risk, type of cancer, and drug-drug interactions, as well as patient and clinician preferences, in tailoring anticoagulation for patients with CAT. Anticoagulant therapy should be adapted as the patient's cancer status and management change over time.

Iron supplementation following bariatric surgery: A systematic review of current strategies.

Iron deficiency (ID) and iron deficiency anemia (IDA) are common following bariatric surgery; however, there are limited standardized treatment recommendations for their management. The purpose of this study was to review the current strategies for iron supplementation following bariatric surgery and assess their relative efficacy in managing ID and IDA. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched to January 2021. Primary outcomes of interest were prevention or improvement in ID or IDA with iron supplementation. Forty-nine studies with 12,880 patients were included. Most patients underwent Roux-en-Y gastric bypass (61.9%). Iron supplementation was most commonly administered orally for prevention of ID/IDA and was effective in 52% of studies. Both IV and oral iron were given for treatment of ID/IDA. Fifty percent (3/6) of the oral and 100% (3/3) of the IV supplementation strategies were effective at treating ID. Iron supplementation strategies employed following bariatric surgery are highly variable, and many do not provide sufficient iron to prevent the development of ID and IDA, potentially due to poor patient adherence. Further high-quality prospective trials, particularly comparing intravenous and oral iron, are warranted in order to determine the ideal dosage, route, and duration of iron supplementation.

Long-term risk of recurrent venous thromboembolism after a first contraceptive-related event: Data from REVERSE cohort study.

INTRODUCTION: The risk of recurrent venous thromboembolism (VTE) after combined oral contraceptive (COC) use is variably reported. We assessed the long-term risk of recurrent VTE in women on COC at the time of a first VTE, in comparison to women without COC use. Our secondary aim assessed the impact of COC use on the recurrent VTE risk in high-risk and low-risk hyperpigmentation, edema, or redness in either leg; D-dimer level ≥250 µg/L; obesity with body mass index ≥30; or older age, ≥65 years (HERDOO2) subgroups. METHODS: The REVERSE cohort study derived the HERDOO2 clinical decision rule to predict recurrent VTE in patients who discontinued anticoagulation after 5-7 months for a first unprovoked VTE. Incidence rates of recurrent VTE among women with and without COC exposure were calculated as the number of recurrent VTE over the number of person-years of follow-up, and Cox proportional hazards model was used to compare risks between groups. RESULTS: The risk of recurrent VTE among COC users was 1.1% (95% confidence interval [CI] 0.3-2.9) per patient-year as compared with 3.2% per patient-year (95% CI 2.4-4.3) among nonusers (hazard ratio 0.37; 95% CI 0.1-1.0). Women who were COC users and high risk by HERDOO2 score had a recurrence rate of 3.5% (95% CI 0.4-12.5) compared with 6.1% (95% CI 4.3-8.5) among women who were non-COC users and at high risk by HERDOO2 score (HR 0.6, 95% CI 0.1-2.5). CONCLUSIONS: Women who were COC users at the time of an otherwise unprovoked VTE event had a lower VTE recurrence rate during long-term follow-up, compared with nonusers. The use of HERDOO2 rule may help identify higher risk women with COC use.

Double Blind Pilot Randomized Trial Comparing Extended Anticoagulation to Placebo Following Major Lung Resection for Cancer.

Venous thromboembolism (VTE), which comprises pulmonary embolus (PE) and deep vein thrombosis (DVT), is a significant cause of postoperative morbidity and mortality. This pilot randomized control trial (RCT) evaluated the feasibility of a full-scale RCT investigating extended thromboprophylaxis in patients undergoing oncological lung resections. Patients undergoing oncological lung resections in 2 tertiary centers received in-hospital, thromboprophylaxis and were randomized to receive post-discharge low-molecular-weight heparin (LMWH) or placebo injections once-daily for 30 days. At 30 days postoperatively, all patients underwent chest computed tomography with PE protocol and bilateral leg venous ultrasound. Primary outcomes included feasibility and safety; VTE incidence and 90-day survival were secondary outcomes. Between December 2015 and June 2018, 619 patients were screened, of whom 62.7% (165/263) of eligible patients consented to participate, and 133 (81%) were randomized. One-hundred and 3 patients, (77.4%), completed the 90-day study follow-up. Reasons for non-participation pre-randomization included patient discomfort and LMWH/placebo administration challenges. Post-randomization withdrawals were due to patient preference, surgeon preference and minor adverse events. Six asymptomatic VTE events (5 PE and 1 DVT) were detected within 30 days (3 in each group), for an overall incidence of 7%. There were 3 minor and no major adverse events. This study is the first to demonstrate the feasibility and safety of a full-scale extended thromboprophylaxis RCT in thoracic surgical oncology. Our results demonstrate that, while recruitment and retention rates were modest, the study design is feasible and with minimal adverse events and no intervention-related mortality.

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

BACKGROUND: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. METHODS: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. RESULTS: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. CONCLUSION: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.

Olecranon fractures in the elderly during the COVID-19 pandemic: Is non-operative treatment reasonable? Review of the current evidence.

The current COVID-19 global pandemic presents a major challenge and unprecedented pressures on health systems. The national guidelines in the UK advise non-operative treatment of fractures whenever possible to reduce the risk of surgical intervention to both patient and healthcare staff. The elderly population over 70 years are highlighted as a high-risk group in this pandemic as well as being often high risk for surgery in general due to co-morbidities. This article reviews the current literature regarding treatment of displaced olecranon fractures in the elderly. Literature search of the available databases. One randomised controlled trial has been published, comparing operative versus non-operative treatments of olecranon fractures in this age group. The study was terminated prematurely due to the high complication rate in the operative group. No difference in functional scores was recorded. Other published retrospective case series report good functional outcome scores and high satisfaction rates in the majority of patients in whom olecranon fractures were treated non-operatively. Non-operative treatment of olecranon fractures in elderly patients seems to be safe and an acceptable management option in these unprecedented times.

Preoperative prediction of Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study.

BACKGROUND: Diagnostic criteria for Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS) have been defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, leads to blood transfusion, or is judged to be the direct cause of death. Preoperative prediction guides for BIMS can facilitate informed consent and planning of perioperative care. METHODS: In a prospective cohort study of 16 079 participants aged ≥45 yr having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011, 17.3% (2782) experienced BIMS. An electronic risk calculator for BIMS was developed and internally validated by logistic regression with bootstrapping, and further simplified to a risk index. Decision curve analysis assessed the potential utility of each prediction guide compared with a strategy of identifying risk of BIMS based on preoperative haemoglobin <120 g L-1. RESULTS: With information about the type of surgery, preoperative haemoglobin, age, sex, functional status, kidney function, history of high-risk coronary artery disease, and active cancer, the risk calculator accurately predicted BIMS (bias-corrected C-statistic, 0.84; 95% confidence interval, 0.837-0.852). A simplified index based on preoperative haemoglobin <120 g L-1, open surgery, and high-risk surgery also predicted BIMS, but less accurately (C-statistic, 0.787; 95% confidence interval, 0.779-0.796). Both prediction guides could improve decision making compared with knowledge of haemoglobin <120 g L-1 alone. CONCLUSIONS: BIMS, defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, leads to blood transfusion, or that is judged to be the direct cause of death, can be predicted by a simple risk index before surgery. CLINICAL TRIAL REGISTRATION: NCT00512109.

Treatment of cancer-associated thrombosis: The evolution of anticoagulant choice and clinical insights into practical management.

Low-molecular-weight heparin (LMWH) therapy is recommended over vitamin K antagonists (VKAs) for the treatment of cancer-associated thrombosis (CAT) and extended therapy is recommended in those with active cancer to prevent recurrent thrombosis. However, the inconvenience of daily subcutaneous injections and the cost of LMWH therapy hinder long-term use. Observational data demonstrate that persistence with LMWH therapy is low in clinical practice and that many patients are switched to oral alternatives - namely VKAs and direct oral anticoagulants (DOACs). Recently, the efficacy and safety of apixaban, edoxaban, and rivaroxaban versus LMWH therapy for the treatment of CAT have been demonstrated in randomized trials. This review provides a critical evaluation of studies with DOACs in this setting and an update on the guidance regarding anticoagulant use for the treatment of CAT. In recognition of the heterogeneity of patients with cancer and the challenges of CAT, patient cases with expert clinical perspectives are presented.

Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study establishing diagnostic criteria and prognostic importance.

BACKGROUND: We aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS. METHODS: This was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery. RESULTS: Of 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin <70 g L-1, transfusion of ≥1 unit of red blood cells, or that was judged to be the cause of death. Bleeding independently associated with mortality after noncardiac surgery occurred in 17.3% of patients (2782). Death occurred in 5.8% of patients with BIMS (161/2782), 1.3% (39/3028) who met bleeding screening criteria but not BIMS criteria, and 1.1% (115/10 269) without bleeding. BIMS was associated with mortality (adjusted hazard ratio: 1.87; 95% confidence interval: 1.42-2.47). We estimated the proportion of 30-day postoperative deaths potentially attributable to BIMS to be 20.1-31.9%. CONCLUSIONS: Bleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, blood transfusion, or that is judged to be the cause of death, is common and may account for a quarter of deaths after noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT00512109.

Evaluating prophylactic heparin in ambulatory patients with solid tumours: a systematic review and individual participant data meta-analysis.

BACKGROUND: Study-level meta-analyses provide high-certainty evidence that heparin reduces the risk of symptomatic venous thromboembolism for patients with cancer; however, whether the benefits and harms associated with heparin differ by cancer type is unclear. This individual participant data meta-analysis of randomised controlled trials examines the effect of heparin on survival, venous thromboembolism, and bleeding in patients with cancer in general and by type. METHODS: In this systematic review and meta-analysis we searched MEDLINE, Embase, and The Cochrane Library for randomised controlled trials comparing parenteral anticoagulants with placebo or standard care in ambulatory patients with solid tumours and no indication for anticoagulation published from the inception of each database to January 14, 2017, and updated it on May 14, 2020, without language restrictions. We calculated the effect of parenteral anticoagulant administration on all-cause mortality, venous thromboembolism occurrence, and bleeding related outcomes through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect, adjusting for age, cancer type, and metastatic status. Interaction terms were tested to investigate effects in predefined subgroups. This study is registered with PROSPERO, CRD42013003526. FINDINGS: We obtained individual participant data from 14 of 20 eligible randomised controlled trials (8278 [79%] of 10 431 participants; 4139 included in the low-molecular-weight heparin group and 4139 in the control group). Meta-analysis showed an adjusted relative risk (RR) of mortality at 1 year of 0·99 (95% CI 0·93-1·06) and a hazard ratio of 1·01 (95% CI 0·96-1·07). The number of patients with venous thromboembolic events was 158 (4·0%) of 3958 with available data in the low-molecular-weight heparin group compared with 279 (7·1%) of 3957 in the control group. Major bleeding events occurred in 71 (1·7%) of 4139 patients in the control population and 88 (2·1%) in the low-molecular-weight heparin group, and minor bleeding events in 478 (12·1%) of 3945 patients with available data in the control group and 652 (16·6%) of 3937 patients in the low-molecular-weight heparin group. The adjusted RR was 0·58 (95% CI 0·47-0·71) for venous thromboembolism, 1·27 (0·92-1·74) for major bleeding, and 1·34 (1·19-1·51) for minor bleeding. Prespecified subgroup analysis of venous thromboembolism occurrence by cancer type identified the most certain benefit from heparin treatment in patients with lung cancer (RR 0·59 [95% CI 0·42-0·81]), which dominated the overall reduction in venous thromboembolism. Certainty of the evidence for the outcomes ranged from moderate to high. INTERPRETATION: Low-molecular-weight heparin reduces risk of venous thromboembolism without increasing risk of major bleeding compared with placebo or standard care in patients with solid tumours, but it does not improve survival. FUNDING: Canadian Institutes of Health Research.

Iron deficiency following bariatric surgery: a retrospective cohort study.

Iron deficiency is a common consequence of bariatric surgery and frequently leads to anemia. Our study reports the incidence and predictors of iron deficiency, iron deficiency anemia (IDA), and IV iron use after bariatric surgery. We conducted a retrospective study of all adult patients who underwent bariatric surgery from January to December 2012 at the regional bariatric surgery center in Hamilton, Ontario, Canada, and were followed for at least 6 months. Time-to-event data were presented as Kaplan-Meier curves. Cox regression analysis was used to identify outcome predictors. A total of 388 patients met the inclusion criteria. Iron deficiency, IDA, and the use of IV iron were reported in 43%, 16%, and 6% of patients, respectively, with a mean follow-up of 31 months. The cumulative incidence of iron deficiency and IDA increased with longer follow-up, and there was a significant increase in IV iron use starting 3 years after surgery. Malabsorptive procedures (hazard ratio [HR], 1.92; 95% confidence interval [CI], 1.20-3.06; P = .006) and low baseline ferritin (HR, 0.96; 95% CI, 0.95-0.97; P < .001) were associated with an increased risk of iron deficiency. Young age (HR, 0.90; 95% CI, 0.82-0.99; P = .028), baseline anemia (HR, 19.6; 95% CI, 7.85-48.9; P < .001), and low baseline ferritin (HR, 0.96; 95% CI, 0.95-0.98; P < .001) were associated with an increased risk of IDA. Our results suggest that IDA is a delayed consequence of bariatric surgery and that preoperative assessment of patient risk may be possible.