Workflow to improve patient recruitment for clinical trials within hospital information systems – a case-study

<p>Abstract</p> <p>Background</p> <p>The identification of suitable patients is a common problem in clinical trials that is especially evident in tertiary care hospitals.</p> <p>Methods</p> <p>We developed and analysed a workflow, which uses routine data captured during patient care in a hospital information system (HIS), to identify potential trial subjects. Study nurses or physicians are notified automatically by email and verify eligibility.</p> <p>Results</p> <p>As a case study we implemented the system for acute myeloid leukemia (AML) trials in Münster. During a test period of 50 days 41 patients were identified by the system. 13 could be included as new trial patients, 7 were already included during earlier visits. According to review of paper records no AML trial patient was missed by the system. In addition, the hospital information system further allowed to preselect patients for specific trials based on their disease status and individual characteristics.</p> <p>Conclusion</p> <p>Routine HIS data can be used to support patient recruitment for clinical trials by means of an automated notification workflow.</p

Confab - Systematic generation of diverse low-energy conformers

<p>Abstract</p> <p>Background</p> <p>Many computational chemistry analyses require the generation of conformers, either on-the-fly, or in advance. We present Confab, an open source command-line application for the systematic generation of low-energy conformers according to a diversity criterion.</p> <p>Results</p> <p>Confab generates conformations using the 'torsion driving approach' which involves iterating systematically through a set of allowed torsion angles for each rotatable bond. Energy is assessed using the MMFF94 forcefield. Diversity is measured using the heavy-atom root-mean-square deviation (RMSD) relative to conformers already stored. We investigated the recovery of crystal structures for a dataset of 1000 ligands from the Protein Data Bank with fewer than 1 million conformations. Confab can recover 97% of the molecules to within 1.5 Å at a diversity level of 1.5 Å and an energy cutoff of 50 kcal/mol.</p> <p>Conclusions</p> <p>Confab is available from <url>http://confab.googlecode.com</url>.</p

Information Discovery on Electronic Health Records Using Authority Flow Techniques

<p>Abstract</p> <p>Background</p> <p>As the use of electronic health records (EHRs) becomes more widespread, so does the need to search and provide effective information discovery within them. Querying by keyword has emerged as one of the most effective paradigms for searching. Most work in this area is based on traditional Information Retrieval (IR) techniques, where each document is compared individually against the query. We compare the effectiveness of two fundamentally different techniques for keyword search of EHRs.</p> <p>Methods</p> <p>We built two ranking systems. The traditional BM25 system exploits the EHRs' content without regard to association among entities within. The Clinical ObjectRank (CO) system exploits the entities' associations in EHRs using an authority-flow algorithm to discover the most relevant entities. BM25 and CO were deployed on an EHR dataset of the cardiovascular division of Miami Children's Hospital. Using sequences of keywords as queries, sensitivity and specificity were measured by two physicians for a set of 11 queries related to congenital cardiac disease.</p> <p>Results</p> <p>Our pilot evaluation showed that CO outperforms BM25 in terms of sensitivity (65% vs. 38%) by 71% on average, while maintaining the specificity (64% vs. 61%). The evaluation was done by two physicians.</p> <p>Conclusions</p> <p>Authority-flow techniques can greatly improve the detection of relevant information in EHRs and hence deserve further study.</p

Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS

$\textbf{Objective:}$ To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS). $\textbf{Methods:}$ The impact of alemtuzumab 12 mg vs SC IFN-β-1a 44 μg on MRI measures was evaluated in patients with RRMS who were treatment-naive (CARE-MS I) or who had an inadequate response, defined as at least one relapse, to prior therapy (CARE-MS II). $\textbf{Results:}$ Both treatments prevented T2-hyperintense lesion volume increases from baseline. Alemtuzumab was more effective than SC IFN-β-1a on most lesion-based endpoints in both studies ($p$ < 0.05), including decreased risk of new/enlarging T2 lesions over 2 years and gadolinium-enhancing lesions at year 2. Reduced risk of new T1 lesions ($p$ < 0.0001) and gadolinium-enhancing lesion conversion to T1-hypointense black holes ($p$ = 0.0078) were observed with alemtuzumab vs SC IFN-β-1a in CARE-MS II. Alemtuzumab slowed brain volume loss over 2 years in CARE-MS I ($p$ < 0.0001) and II ($p$ = 0.012) vs SC IFN-β-1a. $\textbf{Conclusions:}$ Alemtuzumab demonstrated greater efficacy than SC IFN-β-1a on MRI endpoints in active RRMS. The superiority of alemtuzumab was more prominent during the second year of both studies. These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-β-1a in RRMS. $\textbf{ClinicalTrials.gov identifier:}$ NCT00530348 and NCT00548405. $\textbf{Classification of evidence:}$ The results reported here provide Class I evidence that, for patients with active RRMS, alemtuzumab is superior to SC IFN-β-1a on multiple MRI endpoints.Dr. Havrdova was supported by the Czech Ministry of Education, PRVOUK-P26/LF1/4. The CARE-MS studies were funded by Sanofi Genzyme and Bayer HealthCare Pharmaceuticals

Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics.

OBJECTIVE:To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia. STUDY DESIGN:Included were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS:Twenty-five serum biomarkers along with maternal age &lt;34 years and poverty status identified &gt;80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing). CONCLUSION:Together with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia

Adrenergic β2 receptor activation stimulates anti-inflammatory properties of dendritic cells in vitro

Vagal nerve efferent activation has been shown to ameliorate the course of many inflammatory disease states. This neuromodulatory effect has been suggested to rest on acetylcholine receptor (AChR) activation on tissue macrophages or dendritic cells (DCs). In more recent studies, vagal anti-inflammatory activity was shown involve adrenergic, splenic, pathways. Here we provide evidence that the adrenergic, rather than cholinergic, receptor activation on bone marrow derived DCs results in enhanced endocytosis uptake, enhanced IL-10 production but a decreased IL-6, IL-12p70 and IL-23 production. In antigen specific T cell stimulation assays, adrenergic β2 receptor activation on bone marrow DCs led to an enhanced potential to induce Foxp3 positive suppressive Treg cells. These effects were independent of IL10-R activation, TGFβ release, or retinoic acid (RA) secretion. Hence, adrenergic receptor β2 activation modulates DC function resulting in skewing towards anti-inflammatory T cell phenotypes

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research