The de novo FAIRification process of a registry for vascular anomalies

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Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses.

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

Effectiveness and usage of a decision support system to improve stroke prevention in general practice: A cluster randomized controlled trial

Adherence to guidelines pertaining to stroke prevention in patients with atrial fibrillation is poor. Decision support systems have shown promise in increasing guideline adherence. To improve guideline adherence with a non-obtrusive clinical decision support system integrated in the workflow. Secondly, we seek to capture reasons for guideline non-adherence. A cluster randomized controlled trial in Dutch general practices. A decision support system was developed that implemented properties positively associated with effectiveness: real-time, non-interruptive and based on data from electronic health records. Recommendations were based on the Dutch general practitioners guideline for atrial fibrillation that uses the CHA2DS2-VAsc for stroke risk stratification. Usage data and responses to the recommendations were logged. Effectiveness was measured as adherence to the guideline. We used a chi square to test for group differences and a mixed effects model to correct for clustering and baseline adherence. Our analyses included 781 patients. Usage of the system was low (5%) and declined over time. In total, 76 notifications received a response: 58% dismissal and 42% acceptance. At the end of the study, both groups had improved, by 8% and 5% respectively. There was no statistically significant difference between groups (Control: 50%, Intervention: 55% P = 0.23). Clustered analysis revealed similar results. Only one usable reasons for non-adherence was captured. Our study could not demonstrate the effectiveness of a decision support system in general practice, which was likely due to lack of use. Our findings should be used to develop next generation decision support systems that are effective in the challenging setting of general practic

Natural language processing algorithms for mapping clinical text fragments onto ontology concepts: a systematic review and recommendations for future studies

Background: Free-text descriptions in electronic health records (EHRs) can be of interest for clinical research and care optimization. However, free text cannot be readily interpreted by a computer and, therefore, has limited value. Natural Language Processing (NLP) algorithms can make free text machine-interpretable by attaching ontology concepts to it. However, implementations of NLP algorithms are not evaluated consistently. Therefore, the objective of this study was to review the current methods used for developing and evaluating NLP algorithms that map clinical text fragments onto ontology concepts. To standardize the evaluation of algorithms and reduce heterogeneity between studies, we propose a list of recommendations. Methods: Two reviewers examined publications indexed by Scopus, IEEE, MEDLINE, EMBASE, the ACM Digital Library, and the ACL Anthology. Publications reporting on NLP for mapping clinical text from EHRs to ontology concepts were included. Year, country, setting, objective, evaluation and validation methods, NLP algorithms, terminology systems, dataset size and language, performance measures, reference standard, generalizability, operational use, and source code availability were extracted. The studies’ objectives were categorized by way of induction. These results were used to define recommendations. Results: Two thousand three hundred fifty five unique studies were identified. Two hundred fifty six studies reported on the development of NLP algorithms for mapping free text to ontology concepts. Seventy-seven described development and evaluation. Twenty-two studies did not perform a validation on unseen data and 68 studies did not perform external validation. Of 23 studies that claimed that their algorithm was generalizable, 5 tested this by external validation. A list of sixteen recommendations regarding the usage of NLP systems and algorithms, usage of data, evaluation and validation, presentation of results, and generalizability of results was developed. Conclusion: We found many heterogeneous approaches to the reporting on the development and evaluation of NLP algorithms that map clinical text to ontology concepts. Over one-fourth of the identified publications did not perform an evaluation. In addition, over one-fourth of the included studies did not perform a validation, and 88% did not perform external validation. We believe that our recommendations, alongside an existing reporting standard, will increase the reproducibility and reusability of future studies and NLP algorithms in medicine

Acceptance and barriers pertaining to a general practice decision support system for multiple clinical conditions: a mixed methods evaluation

Background Many studies have investigated the use of clinical decision support systems as a means to improve care, but have thus far failed to show significant effects on patient-related outcomes. We developed a clinical decision support system that attempted to address issues that were identified in these studies. The system was implemented in Dutch general practice and was designed to be both unobtrusive and to respond in real time. Despite our efforts, usage of the system was low. In the current study we perform a mixed methods evaluation to identify remediable barriers which led to disappointing usage rates for our system. Methods A mixed methods evaluation employing an online questionnaire and focus group. The focus group was organized to clarify free text comments and receive more detailed feedback from general practitioners. Topics consisted of items based on results from the survey and additional open questions. Results The response rate for the questionnaire was 94%. Results from the questionnaire and focus group can be summarized as follows: The system was perceived as interruptive, despite its design. Participants felt that there were too many recommendations and that the relevance of the recommendations varied. Demographic based recommendations (e.g. age) were often irrelevant, while specific risk-based recommendations (e.g. diagnosis) were more relevant. The other main barrier to use was lack of time during the patient visit. Conclusion These results are likely to be useful to other researchers who are attempting to address the problems of interruption and alert fatigue in decision support.</p

Reasons for intentional guideline non-adherence: A systematic review

Reasons for intentional non-adherence to guidelines are largely unknown. The objective of this systematic review was to gain insight into and categorize reasons for intentional non-adherence and their validity. Non-adherence might be a conscious choice by either the clinician or the patient, and is not influenced by external factors (e.g. lack of knowledge or resources). We use the term intentional non-adherence to describe this class of reasons for not following guideline recommendations. Two independent reviewers examined MEDLINE citations for studies that investigated reasons for guideline non-adherence. The obtained articles were assessed for relevance and quality. Our search yielded 2912 articles, of which 16 matched our inclusion criteria and quality requirements. We planned to determine an overall ranking of categories of non-adherence. Seven studies investigated clinical reasons and performed adjudication, while nine studies did not perform adjudication. Non-adherence varied between 8.2% and 65.3%. Meta-analysis proved unfeasible due to heterogeneity of study methodologies. The percentage of reasons deemed valid by adjudication ranged from 6.6% to 93.6%. Guideline non-adherence was predominantly valid; contra-indications and patient preference were most often reported as reasons for intentional non-adherence. We found a wide range of rates of non-adherence to clinical guidelines. This non-adherence is often supported by valid reasons, mainly related to contra-indications and patient preference. Therefore, we submit that many guideline deviations are intentional and these deviations do not necessarily impact quality of car

Frequency and risk factors for under- and over-treatment in stroke prevention for patients with non-valvular atrial fibrillation in general practice.

OBJECTIVE: To determine adequacy of antithrombotic treatment in patients with non-valvular atrial fibrillation. To determine risk factors for under- and over-treatment. DESIGN: Retrospective, cross-sectional study of electronic health records from 36 general practitioners in 2008. SETTING: General practice in the Netherlands. SUBJECTS: Primary care physicians (n = 36) and patients (n = 981) aged 65 years and over. MAIN OUTCOME MEASURES: Rates of adequate, under and over-treatment, risk factors for under and over-treatment. RESULTS: Of the 981 included patients with a mean of age 78, 18% received no antithrombotic treatment (under-treatment), 13% received antiplatelet drugs and 69% received oral anticoagulation (OAC). Further, 43% of the included patients were treated adequately, 26% were under-treated, and 31% were over-treated. Patients with a previous ischaemic stroke were at high risk for under-treatment (OR 2.4, CI 1.6-3.5), whereas those with contraindications for OAC were at high risk for over-treatment (OR 37.0, CI 18.1-79.9). Age over 75 (OR 0.2, CI: 0.1-0.3]), diabetes (OR 0.1, CI: 0.1-0.3), heart failure (OR 0.2, CI: 0.1-0.3), hypertension (OR 0.1, CI: 0.1-0.2) and previous ischaemic stroke (OR 0.04, CI: 0.02-0.11) protected against over-treatment. CONCLUSIONS: In general practice, CHADS2-criteria are being used, but the antithrombotic treatment of patients with atrial fibrillation frequently deviates from guidelines on this topic. Patients with previous stroke are at high risk of not being prescribed OAC. Contraindications for OAC, however, seem to be frequently overlooked