Canadian clinical experience on switching from standard half-life recombinant factor VIII (rFVIII), octocog alfa, to extended half-life rFVIII, damoctocog alfa pegol, in persons with haemophilia A ≥ 12 years followed in a Comprehensive Hemophilia Care Program in Canada.

INTRODUCTION: Damoctocog alfa pegol (BAY 94-9027, Jivi®) is an extended half-life recombinant factor (F)VIII replacement, indicated for the treatment of haemophilia A in patients aged ≥12 years. Following introduction of damoctocog alfa pegol in Canada in 2020, there have been no reports on routine clinical effectiveness and satisfaction, when switching from a previous FVIII product in Canada. AIM: To report changes in pharmacokinetics, effectiveness, utilization and patient satisfaction when switching to damoctocog alfa pegol prophylaxis from previous standard half-life octocog alfa (BAY 81-8973, Kovaltry®) treatment. METHODS: A single-centre, intra-patient comparison of pharmacokinetics and clinical outcomes was performed. Blood samples drawn once pre-dose and ≥2 times post-dose were measured by a one-stage assay to assess pharmacokinetic parameters including area under the curve (AUC, primary endpoint). Patient-reported outcomes data were collected using the Patient-Reported Outcomes, Burdens and Experiences questionnaire (PROBE). Clinical outcomes included annualized bleeding rate (ABR) and factor utilization. RESULTS: Dose-normalized AUC was significantly increased after switch to damoctocog alfa pegol from octocog alfa. Median (quartile [Q]1; Q3) annualized bleeding rates were 0.67 (0.00; 1.33) with damoctocog alfa pegol and 1.33 (0.00; 2.67) with octocog alfa. Half of the patients receiving damoctocog alfa pegol prophylaxis experienced zero bleeds (n = 9, 50.0%) versus 38.9% (n = 7) of patients treated with octocog alfa. Patients' good quality of life was maintained. CONCLUSION: This study provides routine clinical evidence supporting the benefits of switching from octocog alfa to damoctocog alfa pegol for patients with severe haemophilia A.

Test-retest reliability of a mobile application of the patient reported outcomes burdens and experiences (PROBE) study.

INTRODUCTION: The Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaire is a patient-reported outcome tool that assesses quality of life and disease burden in people with haemophilia (PWH). AIM: To assesses the test-retest reliability of PROBE when completed using the mobile phone application. METHODS: We recruited PWH, including carriers, and individuals with no bleeding disorders who attended haemophilia-related workshops or via social media. Participants completed PROBE three times (twice on the app: T1 and T2, and once on the web, T3). Test-retest reliability was analysed for T1 versus T2 (app to app, time period one) and T2 versus T3 (app to web, time period two). RESULTS: We enrolled 48 participants (median age = 56 [range 27-78] years). Eighteen participants (37.5%) were PWH and seven (14.6%) were carriers. On general health domain questions, we found almost perfect agreement, except for a question on the frequency of use of pain medication in the last 12 months [Kappa coefficient (κ) .72 and .37 for time period one and two, respectively] and any use of pain medications (κ .75) for time period two. For haemophilia-related questions, we found substantial to perfect agreement, except for the questions on the number of joint bleeds in the previous 6 months for time period one (κ .49) and the number of bleeds in the previous two weeks for time period two (κ .34). CONCLUSIONS: The results demonstrate the reliability of the PROBE app. The app can be used interchangeably with the paper and web platforms for PROBE administration.

Implementation, Clinical Benefit and Safety of a D-Dimer-Focused Pulmonary Embolism Testing Pathway in the Emergency Department.

STUDY OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is overused during pulmonary embolism (PE) testing in the emergency department (ED), whereas prediction rules and D-dimer are underused. We report the adherence, clinical benefit, and safety of a D-dimer-only strategy to guide need for PE imaging in the ED. METHODS: This was a prospective multicenter implementation study in 2 EDs with historical and external controls. Patients with suspected PE underwent D-dimer testing and imaging (CTPA or ventilation-perfusion scan) when D-dimer levels were 500 ng/mL or more. PE was ruled out if D-dimer was less than 500 ng/mL or with negative imaging. The primary implementation outcome was the proportion of patients tested for PE in adherence with the pathway. The primary clinical benefit outcome was the proportion of patients tested for PE who received pulmonary imaging. The primary safety outcome was diagnosis of PE in the 30 days following negative PE testing postimplementation. RESULTS: Between January 2018 and June 2021, 16,155 patients were tested for PE, including 33.4% postimplementation, 30.7% preimplementation, and 35.9% in an external control site. Adherence with the D-dimer-only pathway was 97.6% (adjusted odds ratio (aOR) post- versus preimplementation 5.26 (95% confidence interval 1.70 to 16.26). There was no effect on the proportion undergoing PE imaging. Imaging yield increased aOR 4.89 (1.17 to 20.53). Two cases of PE (0.04%; 0.01% to 0.16%) were diagnosed within 30 days. CONCLUSION: In this Canadian ED study, the uptake of a D-dimer-only PE testing strategy was high. Implementation was associated with higher imaging yield and a D-dimer level of less than 500 ng/mL safely excluded PE.

Bleeding events in people with congenital haemophilia A without factor VIII inhibitors receiving prophylactic factor VIII treatment: A systematic literature review.

BACKGROUND: Evidence on bleeding rates in people with congenital haemophilia A (PwcHA) without inhibitors on factor VIII (FVIII) replacement products is inconsistent. AIM: This systematic literature review assessed bleeding outcomes in PwcHA using FVIII-containing products as prophylactic treatment. METHODS: A search was conducted using the bibliographic databases Medline, Embase and Cochrane Central Register of Controlled Trials on the Ovid platform. The search involved a bibliographic review of clinical trial studies, routine clinical care studies and registries and a search of ClinicalTrials.gov, EU Clinical Trials Register and conference abstracts. RESULTS: The search yielded 5548 citations. A total of 58 publications were included for analysis. In 48 interventional studies, the pooled estimated mean (95% confidence interval [CI]) annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR) and proportion of participants with zero bleeding events were 3.4 (3.0-3.7), 2.0 (1.6-2.5), and 38.5% (33.1-43.9), respectively. In 10 observational studies, the pooled estimated mean (95% CI) ABR, AJBR and proportion of participants with zero bleeding events were 4.8 (4.0-5.5), 2.6 (2.1-3.2), and 21.8% (19.9-47.5), respectively. A large variation in mean effect size for ABR, AJBR and zero bleeding event data across cohorts and cohort types was observed. Funnel plots indicated potential reporting bias for publications incorporating ABR and AJBR data across both interventional and observational studies. CONCLUSION: This meta-analysis shows that PwcHA without inhibitors still have bleeds despite FVIII prophylaxis. Improved standardization on capturing and reporting bleeding outcomes is needed so that effective comparisons between treatments can be made.

Comparison of YEARS and Adjust-Unlikely D-dimer Testing for Pulmonary Embolism in the Emergency Department.

STUDY OBJECTIVE: We prospectively assessed the diagnostic accuracy of YEARS and a modified age-adjusted clinical decision rule ("Adjust-Unlikely") for pulmonary embolism (PE) testing in the emergency department. METHODS: This study was conducted in tertiary care Canadian emergency departments. When the D-dimer was <500 ng/ml, PE was excluded. Pulmonary imaging for PE was performed when the D-dimer was ≥500 ng/ml. Patients were followed for 30 days, and PE outcomes were independently adjudicated. Physicians systematically recorded the presence or absence of YEARS items (PE most likely, hemoptysis, signs of deep venous thrombosis) prior to D-dimer testing and imaging. We analyzed the diagnostic accuracy of YEARS and the "Adjust-Unlikely" rule. Age adjustment (age x 10 in those >50 years old) was applied in patients where PE was not the most likely diagnosis and 500 ng/ml threshold when PE was most likely. RESULTS: One thousand seven hundred three patients were included, median age 62 (50, 74), 58% female, PE prevalence 8.0%. YEARS sensitivity for PE diagnosis was 92.6% (87.0, 96.0%) and specificity 45.0% (42.5, 47.5%). Adjust-Unlikely sensitivity was 100.0% (97.2, 100.0%) and specificity 32.4% (30.1, 34.8%). Posttest probability of PE in the group of patients with PE excluded by D-dimer between 500 ng/ml and the adjusted limit was 2.8% (1.6, 5.1%) for YEARS and 0.0% (0.0, 2.6%) for the "Adjust-Unlikely" rule. CONCLUSION: The "Adjust-Unlikely" rule would modestly reduce imaging and identify all cases of PE. YEARS would substantially reduce imaging but miss 1 in 14 cases of PE.

Deep learning to refine the identification of high-quality clinical research articles from the biomedical literature: Performance evaluation.

BACKGROUND: Identifying practice-ready evidence-based journal articles in medicine is a challenge due to the sheer volume of biomedical research publications. Newer approaches to support evidence discovery apply deep learning techniques to improve the efficiency and accuracy of classifying sound evidence. OBJECTIVE: To determine how well deep learning models using variants of Bidirectional Encoder Representations from Transformers (BERT) identify high-quality evidence with high clinical relevance from the biomedical literature for consideration in clinical practice. METHODS: We fine-tuned variations of BERT models (BERTBASE, BioBERT, BlueBERT, and PubMedBERT) and compared their performance in classifying articles based on methodological quality criteria. The dataset used for fine-tuning models included titles and abstracts of >160,000 PubMed records from 2012 to 2020 that were of interest to human health which had been manually labeled based on meeting established critical appraisal criteria for methodological rigor. The data was randomly divided into 80:10:10 sets for training, validating, and testing. In addition to using the full unbalanced set, the training data was randomly undersampled into four balanced datasets to assess performance and select the best performing model. For each of the four sets, one model that maintained sensitivity (recall) at ≥99% was selected and were ensembled. The best performing model was evaluated in a prospective, blinded test and applied to an established reference standard, the Clinical Hedges dataset. RESULTS: In training, three of the four selected best performing models were trained using BioBERTBASE. The ensembled model did not boost performance compared with the best individual model. Hence a solo BioBERT-based model (named DL-PLUS) was selected for further testing as it was computationally more efficient. The model had high recall (>99%) and 60% to 77% specificity in a prospective evaluation conducted with blinded research associates and saved >60% of the work required to identify high quality articles. CONCLUSIONS: Deep learning using pretrained language models and a large dataset of classified articles produced models with improved specificity while maintaining >99% recall. The resulting DL-PLUS model identifies high-quality, clinically relevant articles from PubMed at the time of publication. The model improves the efficiency of a literature surveillance program, which allows for faster dissemination of appraised research.

Prognostic factors for VTE and bleeding in hospitalized medical patients: a systematic review and meta-analysis.

There may be many predictors of venous thromboembolism (VTE) and bleeding in hospitalized medical patients, but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify prognostic factors for VTE and bleeding in hospitalized medical patients and searched Medline and EMBASE from inception through May 2018. We considered studies that identified potential prognostic factors for VTE and bleeding in hospitalized adult medical patients. Reviewers extracted data in duplicate and independently and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Of 69 410 citations, we included 17 studies in our analysis: 14 that reported on VTE, and 3 that reported on bleeding. For VTE, moderate-certainty evidence showed a probable association with older age; elevated C-reactive protein (CRP), D-dimer, and fibrinogen levels; tachycardia; thrombocytosis; leukocytosis; fever; leg edema; lower Barthel Index (BI) score; immobility; paresis; previous history of VTE; thrombophilia; malignancy; critical illness; and infections. For bleeding, moderate-certainty evidence showed a probable association with older age, sex, anemia, obesity, low hemoglobin, gastroduodenal ulcers, rehospitalization, critical illness, thrombocytopenia, blood dyscrasias, hepatic disease, renal failure, antithrombotic medication, and presence of a central venous catheter. Elevated CRP, a lower BI, a history of malignancy, and elevated heart rate are not included in most VTE risk assessment models. This study informs risk prediction in the management of hospitalized medical patients for VTE and bleeding; it also informs guidelines for VTE prevention and future research.

Accuracy and Acceptability of Wrist-Wearable Activity-Tracking Devices: Systematic Review of the Literature.

BACKGROUND: Numerous wrist-wearable devices to measure physical activity are currently available, but there is a need to unify the evidence on how they compare in terms of acceptability and accuracy. OBJECTIVE: The aim of this study is to perform a systematic review of the literature to assess the accuracy and acceptability (willingness to use the device for the task it is designed to support) of wrist-wearable activity trackers. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and SPORTDiscus for studies measuring physical activity in the general population using wrist-wearable activity trackers. We screened articles for inclusion and, for the included studies, reported data on the studies' setting and population, outcome measured, and risk of bias. RESULTS: A total of 65 articles were included in our review. Accuracy was assessed for 14 different outcomes, which can be classified in the following categories: count of specific activities (including step counts), time spent being active, intensity of physical activity (including energy expenditure), heart rate, distance, and speed. Substantial clinical heterogeneity did not allow us to perform a meta-analysis of the results. The outcomes assessed most frequently were step counts, heart rate, and energy expenditure. For step counts, the Fitbit Charge (or the Fitbit Charge HR) had a mean absolute percentage error (MAPE) <25% across 20 studies. For heart rate, the Apple Watch had a MAPE <10% in 2 studies. For energy expenditure, the MAPE was >30% for all the brands, showing poor accuracy across devices. Acceptability was most frequently measured through data availability and wearing time. Data availability was ≥75% for the Fitbit Charge HR, Fitbit Flex 2, and Garmin Vivofit. The wearing time was 89% for both the GENEActiv and Nike FuelBand. CONCLUSIONS: The Fitbit Charge and Fitbit Charge HR were consistently shown to have a good accuracy for step counts and the Apple Watch for measuring heart rate. None of the tested devices proved to be accurate in measuring energy expenditure. Efforts should be made to reduce the heterogeneity among studies.

Non-severe haemophilia: Is it benign? - Insights from the PROBE study.

INTRODUCTION: There are limited data on the impact of haemophilia on health status and health-related quality of life (HRQL) in people with non-severe (mild and moderate) haemophilia. AIM: To evaluate the health status of people living with mild or moderate haemophilia. METHODS: Data on respondents with no bleeding disorder (NoBD), mild and moderate haemophilia patients were drawn from the PROBE study. Respondents were enrolled using network patient organizations. This analysis was performed as a cross-sectional study. Primary outcomes were reported bleeding, acute and chronic pain, activities of daily living and HRQL. RESULTS: A total of 862 respondents with NoBD (n = 173), mild (n = 102) and moderate (n = 134) haemophilia were eligible, with a median age of 33, 42 and 43, respectively. In relation to haemophilia-related sequalae, 53% of male and 29% of female patients with mild and 83% of males with moderate haemophilia had more than 2-3 bleeds in the last 12 months. Reporting of acute and chronic pain is less in those with NoBD compared to the mild and moderate cohorts for both genders. Multivariate analysis demonstrates significant reductions in quality of life using VAS, EQ-5D-5L and PROBE for males with mild and moderate haemophilia (P ≤ .001) with only PROBE indicating a significant reduction for females with mild (P = .002). CONCLUSION: People affected by mild or moderate haemophilia report a significant HRQL impact due to haemophilia-related bleeding. Future research is needed to identify the optimal care management of patients with mild and moderate haemophilia.

Outcomes for studies assessing the efficacy of hemostatic therapies in persons with congenital bleeding disorders.

INTRODUCTION: Management strategies and hemostatic treatments to achieve control of bleeding are relevant across many disease areas. Identification of primary outcomes for studies assessing hemostatic intervention was the objective of a National Heart, Lung and Blood Institute (NHLBI) sponsored multidisciplinary initiative. The aim of this report is to summarize the evidence reviewed, and the outcomes identified by the subgroup tasked to assess outcomes for inherited bleeding disorders. METHODS: The subgroup decided to focus on haemophilia, the prototypal congenital bleeding disorder and the one with the largest available body of evidence. MEDLINE, EMBASE and PsycINFO, The Cochrane Review, CINAHL, and Web of Science were searched for systematic and narrative reviews on outcomes used in haemophilia clinical trials. Three different clinical goals were identified as typical objectives of future research. RESULTS: Out of 1322 unique citations, 24 reviews published in the period 2002-2019 were included. We identified 113 outcome measures, categorized in 6 domains: health-related quality of life (HRQoL), comorbidities and mortality, overall physical functioning and participation, bleeding and hemostasis, joint health, and costs and resource use. Three different clinical goals were identified as typical objectives of future research: Episodic 'on demand' replacement therapy, prevention of bleeding (Prophylaxis), and long-term and overall impact of bleeding. For each of these scenarios, specific outcomes were recommended. CONCLUSIONS: Primary outcomes for clinical trials assessing the efficacy of hemostatic treatment in achieving control, prevention and limiting long-term consequences of bleeding in inherited bleeding disorders are suggested, and their strength and limitations discussed.

Evaluation of the sexual health in people living with hemophilia.

BACKGROUND: Knowledge about sexual health, difficulty with sexual activity and intimacy (sexual difficulty), in people with hemophilia is little understood. OBJECTIVES: The objectives were to determine the prevalence of sexual difficulty in people living with hemophilia (PWH) compared to people with no bleeding disorders (PWNoBD), and to determine factors associated with it. METHODS: This was an analysis of the PROBE study. We recruited individuals who had hemophilia A or B (PWH) and PWNoBD who were 18 years old or older. We calculated proportions of participants with sexual difficulty and odds ratios (ORs) adjusted for sex and age with 95% confidence intervals. RESULTS: There were 2007 PWH and 1972 PWNoBD. Mean (standard deviation) age was 41 (15) years in PWH and 42 (13) years in PWNoBD. Sexual difficulty was reported in 302 (15.1%) PWH and 79 (4.0%) PWNoBD. The odds of sexual difficulty were significantly higher in PWH (OR 3.82, 95% CI 2.85, 5.11). Among PWH, older age, experiencing acute or chronic pain in the past 12 months, bleeds within the past two weeks, ≥3 spontaneous joint bleeds (past six months), limitation of range of motion of any joints, and any life- or limb-threatening bleeds in the past 12 months were associated with sexual difficulty. CONCLUSIONS: Sexual difficulty is more prevalent in people living with hemophilia and associated with markers of disease severity. Sexual health issues should be incorporated in comprehensive hemophilia care, future research, and hemophilia related health policy.

Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries.

Background: The large observed variability in hemophilia prevalence prevents robust estimation of burden of disease. Objective: To estimate the prevalence and prevalence at birth of hemophilia and the associated life expectancy disadvantage. Design: Random-effects meta-analysis of registry data. Setting: Australia, Canada, France, Italy, New Zealand, and the United Kingdom. Participants: Male patients with hemophilia A or B. Measurements: Prevalence of hemophilia as a proportion of cases to the male population, prevalence of hemophilia at birth as a proportion of cases to live male births by year of birth, life expectancy disadvantage as a 1 - ratio of prevalence to prevalence at birth, and expected number of patients worldwide based on prevalence in high-income countries and prevalence at birth. Results: Prevalence (per 100 000 males) is 17.1 cases for all severities of hemophilia A, 6.0 cases for severe hemophilia A, 3.8 cases for all severities of hemophilia B, and 1.1 cases for severe hemophilia B. Prevalence at birth (per 100 000 males) is 24.6 cases for all severities of hemophilia A, 9.5 cases for severe hemophilia A, 5.0 cases for all severities of hemophilia B, and 1.5 cases for severe hemophilia B. The life expectancy disadvantage for high-income countries is 30% for hemophilia A, 37% for severe hemophilia A, 24% for hemophilia B, and 27% for severe hemophilia B. The expected number of patients with hemophilia worldwide is 1 125 000, of whom 418 000 should have severe hemophilia. Limitation: Details were insufficient to adjust for comorbid conditions and ethnicity. Conclusion: The prevalence of hemophilia is higher than previously estimated. Patients with hemophilia still have a life expectancy disadvantage. Establishing prevalence at birth is a milestone toward assessing years of life lost, years of life with disability, and burden of disease. Primary Funding Source: None.

Interventions to prevent, delay or reverse frailty in older people: a journey towards clinical guidelines.

BACKGROUND: Age-related frailty is a multidimensional dynamic condition associated with adverse patient outcomes and high costs for health systems. Several interventions have been proposed to tackle frailty. This correspondence article describes the journey through the development of evidence- and consensus-based guidelines on interventions aimed at preventing, delaying or reversing frailty in the context of the FOCUS (Frailty Management Optimisation through EIP-AHA Commitments and Utilisation of Stakeholders Input) project (664367-FOCUS-HP-PJ-2014). The rationale, framework, processes and content of the guidelines are described. MAIN TEXT: The guidelines were framed into four questions - one general and three on specific groups of interventions - all including frailty as the primary outcome of interest. Quantitative and qualitative studies and reviews conducted in the context of the FOCUS project represented the evidence base. We followed the GRADE Evidence-to-Decision frameworks based on assessment of whether the problem is a priority, the magnitude of the desirable and undesirable effects, the certainty of the evidence, stakeholders' values, the balance between desirable and undesirable effects, the resource use, and other factors like acceptability and feasibility. Experts in the FOCUS consortium acted as panellists in the consensus process. Overall, we eventually recommended interventions intended to affect frailty as well as its course and related outcomes. Specifically, we recommended (1) physical activity programmes or nutritional interventions or a combination of both; (2) interventions based on tailored care and/or geriatric evaluation and management; and (3) interventions based on cognitive training (alone or in combination with exercise and nutritional supplementation). The panel did not support interventions based on hormone treatments or problem-solving therapy. However, all our recommendations were weak (provisional) due to the limited available evidence and based on heterogeneous studies of limited quality. Furthermore, they are conditional to the consideration of participant-, organisational- and contextual/cultural-related facilitators or barriers. There is insufficient evidence in favour of or against other types of interventions. CONCLUSIONS: We provided guidelines based on quantitative and qualitative evidence, adopting methodological standards, and integrating relevant stakeholders' inputs and perspectives. We identified the need for further studies of a higher methodological quality to explore interventions with the potential to affect frailty.

Quality of reporting in abstracts of RCTs published in emergency medicine journals: a systematic survey of the literature suggests we can do better.

OBJECTIVE: We investigated the association between the publication of the Consolidated Standards of Reporting Trials extension for abstracts (CONSORT-EA) and other variables of interest on the quality of reporting of abstracts of randomised controlled trials (RCTs) published in emergency medicine (EM) journals. METHODS: We performed a survey of the literature, comparing the quality of reporting before (2005-2007) with after (2014-2015) the publication of the dedicated CONSORT-EA in 2008. The quality of reporting was measured as the sum of items of the CONSORT-EA checklist reported in each abstract, ranging from 0 to 15. The main explanatory variable was the period of publication: pre-CONSORT-EA versus post-CONSORT-EA public. Other explanatory variables were journal's endorsement of the CONSORT statement, number of centres participating in the study, study's sample size, type of intervention, significance of results, source of funding and study setting. We analysed the data using generalised estimation equations, performing a univariate and a multivariable analysis. RESULTS: We retrieved 844 articles, and randomly selected 60 per period for review, after stratifying for journal. The mean (SD) number of items reported was 6.4 (1.9) in the period before and 6.9 (1.8) in the period after the publication of the CONSORT-EA, with an adjusted mean difference (aMD) of 0.47 (95% CI -0.13 to 1.06). Abstracts of trials of pharmacological interventions had a significantly larger mean number of reported items than those of trials of non-pharmacological interventions (aMD 1.59; 95% CI 0.94 to 2.24). CONCLUSIONS: The quality of reporting in abstracts of RCTs published in EM journals is low and was not significantly impacted by the publication of a dedicated CONSORT-EA.

Padua prediction score or clinical judgment for decision making on antithrombotic prophylaxis: a quasi-randomized controlled trial.

The Padua prediction score (PPS) has been suggested as the best available model for the assessment of the risk of venous thromboembolism (VTE) in hospitalized medical patients. The impact of its use in clinical practice has never been prospectively evaluated. According to a quasi-randomized study design, consecutive patients admitted to Internal Medicine Section 1 were allocated to a PPS-based decisional strategy suggesting thromboprophylaxis in patients with PPS score ≥4, and those admitted to Section 2 to a clinical judgment-based strategy. Study patients underwent complete compression ultrasonography of the lower limbs at discharge. The primary outcome was symptomatic or asymptomatic VTE during hospital stay. Secondary outcomes were VTE excluding isolated distal deep vein thrombosis, bleedings, and appropriate thromboprophylaxis. 628 patients were included in the analysis, 235 in the PPS group, and 393 in the clinical judgment group. The two groups differed for length of hospital stay, prevalence of recent trauma or surgery, and stroke. Compared with control, the PPS group had a significantly lower incidence of VTE (8.5 vs. 15.5 %, OR 0.51, 95 % CI 0.30-0.86), also after adjusting for thromboprophylaxis use and patient PPS-risk category (OR 0.54, 95 % CI 0.31-0.94). In conclusion, the use of PPS was associated with a higher rate of appropriate thromboprophylaxis prescription; no significant differences were found in the other secondary outcomes. The use of PPS for the assessment of risk for VTE is associated with a reduced incidence of VTE compared with the clinical judgment. These result needs to be confirmed in future studies.

Computed tomography to assess risk of death in acute pulmonary embolism: a meta-analysis.

The aim of this study was to evaluate whether right ventricle dilation at computed tomography (CT) angiography can be used to assess the risk of death in patients with acute pulmonary embolism. Medline and EMBASE were searched up to April 30, 2013. Studies reporting on the association between right ventricle dilation (right-to-left ventricle diameter) or dysfunction (inter-ventricular septal bowing) at CT angiography and death at 30 days, as well as at 3 months in patients with acute pulmonary embolism, were included in a systematic review and meta-analysis. CT-detected right ventricle dilation was associated with an increased 30 day-mortality in all-comers with pulmonary embolism (OR 2.08 (95% CI 1.63-2.66); p<0.00001) and in haemodynamically stable patients (OR 1.64 (95% CI 1.06-2.52); p=0.03), as well as with death due to pulmonary embolism (OR 7.35 (95% CI 3.59-15.09); p<0.00001). An association between right ventricle dilation and 3-month mortality was also observed (OR 4.65 (95% CI 1.79-12.07); p=0.002). Right-to-left ventricle dilation as assessed by CT angiography can be used to evaluate risk of death in all-comers with pulmonary embolism and in haemodynamically stable patients.

Treatment switch to nonacog beta pegol factor IX in hemophilia B: A Canadian cost-consequence analysis based on real-world factor IX consumption and clinical outcomes.

Background: The Canadian Bleeding Disorders Registry (CBDR) is a source of real-world data for Canadian patients with hemophilia B. Nonacog beta pegol (N9-GP), an extended half-life (EHL) recombinant factor IX (FIX) concentrate, was awarded a Canadian Blood Services contract in 2018 and subsequently made available across Canada (except Québec) to adult patients. For most patients already on another EHL FIX treatment, a switch to N9-GP occurred. Objectives: This study estimates the impact on treatment costs of a switch from a prior FIX to N9-GP based on annualized bleed rates and FIX consumption volumes before and after N9-GP switch from the CBDR. Methods: Real-world data from the CBDR for total FIX consumption and annualized bleed rates were used to inform a deterministic 1-year cost-consequence model. The model considered that the EHL to N9-GP switches were from eftrenonacog alfa and the standard half-life switches were from nonacog alfa. Because FIX prices are confidential in Canada, the model assumed cost parity for annual prophylaxis with each FIX based on the product monograph recommended dosing regimen to calculate an estimated price per international unit for each product. Results: The switch to N9-GP resulted in improvements in real-world annualized bleed rates and therefore reductions in annual breakthrough bleed treatment costs. Switching to N9-GP also resulted in reduced real-world annual FIX consumption for prophylaxis. Overall, annual treatment costs were 9.4% and 10.5% lower after the switch to N9-GP from nonacog alfa and eftrenonacog alfa, respectively. Conclusion: N9-GP improves clinical outcomes and may be cost-saving vs nonacog alfa and eftrenonacog alfa.

Introducing the Library of Guidance for Health Scientists (LIGHTS): A Living Database for Methods Guidance.

Importance: Improving methodological quality is a priority in the health research community. Finding appropriate methods guidance can be challenging due to heterogeneous terminology, poor indexing in medical databases, and variation in formats. The Library of Guidance for Health Scientists (LIGHTS) is a new searchable database for methods guidance articles. Observations: Journal articles that aim to provide guidance for performing (including planning, design, conduct, analysis, and interpretation), reporting, and assessing the quality of health-related research involving humans or human populations (ie, excluding basic and animal research) are eligible for LIGHTS. A team of health researchers, information specialists, and methodologists continuously identifies and manually indexes eligible guidance documents. The search strategy includes focused searches of specific journals, specialized databases, and suggestions from researchers. A current limitation is that a keyword-based search of MEDLINE (and other general databases) and manual screening of records were not feasible because of the large number of hits (n = 915 523). As of September 20, 2022, LIGHTS included 1246 articles (336 reporting guidelines, 80 quality assessment tools, and 830 other methods guidance articles). The LIGHTS website provides a user-oriented search interface including filters for study type, specific methodological topic, research context, guidance type, and development process of the guidance. Automated matching of alternative methodological expressions (eg, enter loss to follow-up and find articles indexed with missing data) enhances search queries. Conclusions and Relevance: LIGHTS is a peer-supported initiative that is intended to increase access to and use of methods guidance relevant to health researchers, statisticians, methods consultants, methods developers, ethics boards, peer reviewers, journal editors, and funding bodies.