Modeling Disease Severity in Multiple Sclerosis Using Electronic Health Records

Objective: To optimally leverage the scalability and unique features of the electronic health records (EHR) for research that would ultimately improve patient care, we need to accurately identify patients and extract clinically meaningful measures. Using multiple sclerosis (MS) as a proof of principle, we showcased how to leverage routinely collected EHR data to identify patients with a complex neurological disorder and derive an important surrogate measure of disease severity heretofore only available in research settings. Methods: In a cross-sectional observational study, 5,495 MS patients were identified from the EHR systems of two major referral hospitals using an algorithm that includes codified and narrative information extracted using natural language processing. In the subset of patients who receive neurological care at a MS Center where disease measures have been collected, we used routinely collected EHR data to extract two aggregate indicators of MS severity of clinical relevance multiple sclerosis severity score (MSSS) and brain parenchymal fraction (BPF, a measure of whole brain volume). Results: The EHR algorithm that identifies MS patients has an area under the curve of 0.958, 83% sensitivity, 92% positive predictive value, and 89% negative predictive value when a 95% specificity threshold is used. The correlation between EHR-derived and true MSSS has a mean R[superscript 2] = 0.38±0.05, and that between EHR-derived and true BPF has a mean R[superscript 2] = 0.22±0.08. To illustrate its clinical relevance, derived MSSS captures the expected difference in disease severity between relapsing-remitting and progressive MS patients after adjusting for sex, age of symptom onset and disease duration (p = 1.56×10[superscript −12]). Conclusion: Incorporation of sophisticated codified and narrative EHR data accurately identifies MS patients and provides estimation of a well-accepted indicator of MS severity that is widely used in research settings but not part of the routine medical records. Similar approaches could be applied to other complex neurological disorders.National Institute of General Medical Sciences (U.S.) (NIH U54-LM008748

Automated versus manual post-processing of perfusion-CT data in patients with acute cerebral ischemia: influence on interobserver variability

The purpose of this study is to compare the variability of PCT results obtained by automatic selection of the arterial input function (AIF), venous output function (VOF) and symmetry axis versus manual selection. Imaging data from 30 PCT studies obtained as part of standard clinical stroke care at our institution in patients with suspected acute hemispheric ischemic stroke were retrospectively reviewed. Two observers performed the post-processing of 30 CTP datasets. Each observer processed the data twice, the first time employing manual selection of AIF, VOF and symmetry axis, and a second time using automated selection of these same parameters, with the user being allowed to adjust them whenever deemed appropriate. The volumes of infarct core and of total perfusion defect were recorded. The cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and blood-brain barrier permeability (BBBP) values in standardized regions of interest were recorded. Interobserver variability was quantified using the Bland and Altman's approach. Automated post-processing yielded lower coefficients of variation for the volume of the infarct core and the volume of the total perfusion defect (15.7% and 5.8%, respectively) compared to manual post-processing (31.0% and 12.2%, respectively). Automated post-processing yielded lower coefficients of variation for PCT values (11.3% for CBV, 9.7% for CBF, and 9.5% for MTT) compared to manual post-processing (23.7% for CBV, 32.8% for CBF, and 16.7% for MTT). Automated post-processing of PCT data improves interobserver agreement in measurements of CBV, CBF and MTT, as well as volume of infarct core and penumbra

Influenza Viral Vectors Expressing Two Kinds of HA Proteins as Bivalent Vaccine Against Highly Pathogenic Avian Influenza Viruses of Clade 2.3.4.4 H5 and H7N9

The H5 and H7N9 subtypes of highly pathogenic avian influenza viruses (HPAIVs) in China pose a serious challenge to public health and the poultry industry. In this study, a replication competent recombinant influenza A virus of the Í5N1 subtype expressing the H7 HA1 protein from a tri-cistronic NS segment was constructed. A heterologous dimerization domain was used to combine with the truncated NS1 protein of 73 amino acids to increase protein stability. H7 HA1, nuclear export protein coding region, and the truncated NS1 were fused in-frame into a single open reading frame via 2A self-cleaving peptides. The resulting PR8-H5-NS1(73)H7 stably expressed the H5 HA and H7 HA1 proteins, and exhibited similar growth kinetics as the parental PR8-H5 virus in vitro. PR8-H5-NS1(73)H7 induced specific hemagglutination inhibition (HI) antibody against H5, which was comparable to that of the combination vaccine of PR8-H5 and PR8-H7. The HI antibody titers against H7 virus were significantly lower than that by the combination vaccine. PR8-H5-NS1(73)H7 completely protected chickens from challenge with both H5 and H7 HPAIVs. These results suggest that PR8-H5-NS1(73)H7 is highly immunogenic and efficacious against both H5 and H7N9 HPAIVs in chickens.Highlights:- PR8-H5-NS1(73)H7 simultaneously expressed two HA proteins of different avian influenza virus subtypes.- PR8-H5-NS1(73)H7 was highly immunogenic in chickens.- PR8-H5-NS1(73)H7 provided complete protection against challenge with both H5 and H7N9 HPAIVs

Influenza viral vectors expressing two kinds of HA proteins for bivalent vaccines against clade 2.3.4.4 and clade 2.3.2.1 H5 HPAIVs

AbstractThe H5 highly pathogenic avian influenza viruses (HPAIVs) in China pose a serious challenge to public health and the poultry industry. In this study, we constructed a replication-competent recombinant influenza A virus of clade 2.3.4.4 Н5N1 expressing the clade 2.3.2.1 H5 HA1 protein from a tricistronic NS segment. We used a truncated NS1 protein of 73 amino acids combined with a heterologous dimerization domain to increase protein stability. H5 HA1 and nuclear export information were fused in frame with a truncated NS1 open reading frame, separated by 2A self-processing sites. The resulting PR8-H5-NS1(73)H5 stably expressed clade 2.3.4.4 H5 HA and clade 2.3.2.1 H5 HA1 proteins and exhibited similar in vitro growth kinetics as the parental PR8-2344H5 virus. PR8-H5-NS1(73)H5 induced specific hemagglutination-inhibition (HI) antibody against clade 2.3.4.4 H5 that was comparable to that of the combination vaccine of PR8-2344H5 and PR8-2321H5. HI antibody titers were significantly lower against clade 2.3.2.1 H5 virus than with the combination vaccine. PR8-H5-NS1(73)H5 completely protected chickens from both clade 2.3.4.4 and clade 2.3.2.1 H5 HPAIVs challenge. Our results suggested that PR8-H5-NS1(73)H5 was highly immunogenic and efficacious against both clade 2.3.4.4 and clade 2.3.2.1 H5 HPAIVs in chickens.</jats:p