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Background: Information exists as unstructured medical text in healthcare databases. Such information is not routinely considered in safety surveillance but typically relies solely on structured (coded) data. Natural language processing (NLP) may allow the capture of concepts from unstructured data and thus enhance safety surveillance capability.Objectives: We sought to assess the added contribution of unstructured data extracted from medical text by NLP for detecting acute liver dysfunction (ALD) in patients with inflammatory bowel disease (IBD).Methods: Using a previously developed rule, we evaluated structured and unstructured NLP-extracted terms from a commercially available electronic medical record (EMR) system. The rule was intended to identify ALD diagnosis and timing of onset and was the result of three iterations of rule development using 150 ALD candidate cases. We evaluated the performance of the rule with or without NLP among all candidate cases and among 50 new cases with clinical adjudication.Results: NLP terms were necessary for the diagnosis of 9% of cases and for ruling out 3% of false-positive cases. Inclusion of NLP terms led to an identification of an additional  9% of ALD-onset dates, with consequent earlier recognition in 5%.Conclusions: NLP-derived terms in one large commercially available EMR system modestly improved the sensitivity and specificity in the identification of ALD and identified earlier onset. [ABSTRACT FROM AUTHOR]

Cinnamyl alcohol dehydrogenase (CAD) catalyzes the final step in monolignol biosynthesis, reducing sinapaldehyde, coniferaldehyde, and p-coumaraldehyde to their corresponding alcohols in an NADPH-dependent manner. Because of its terminal location in monolignol biosynthesis, the variation in substrate specificity and activity of CAD can result in significant changes in overall composition and amount of lignin. Our in-depth characterization of two major CAD isoforms, SbCAD2 (Brown midrib 6 [bmr6]) and SbCAD4, in lignifying tissues of sorghum (Sorghum bicolor), a strategic plant for generating renewable chemicals and fuels, indicates their similarity in both structure and activity to Arabidopsis (Arabidopsis thaliana) CAD5 and Populus tremuloides sinapyl alcohol dehydrogenase, respectively. This first crystal structure of a monocot CAD combined with enzyme kinetic data and a catalytic model supported by site-directed mutagenesis allows full comparison with dicot CADs and elucidates the potential signature sequence for their substrate specificity and activity. The L119W/G301F-SbCAD4 double mutant displayed its substrate preference in the order coniferaldehyde > p-coumaraldehyde > sinapaldehyde, with higher catalytic efficiency than that of both wild-type SbCAD4 and SbCAD2. As SbCAD4 is the only major CAD isoform in bmr6 mutants, replacing SbCAD4 with L119W/G301F-SbCAD4 in bmr6 plants could produce a phenotype that is more amenable to biomass processing. [ABSTRACT FROM AUTHOR]

Background: When an exclusionary criterion is an imperfect screen, some ineligible patients will remain in a study. Medical record review for outcome adjudication can reveal such individuals. Objective: To ascertain the circumstances under which it is advisable to remove outcome cases first found to be ineligible on chart review. Methods: The impact on the relative risk caused by removal of ineligible outcome cases was examined under different circumstances of confounding, prevalence, and efficacy of the screening criterion for exclusions. The result is illustrated by a hospital-based cohort study in which electronic medical record diagnosis served to exclude ineligible cases, and review of text notes for putative outcome cases revealed that the codes were only 95% sensitive. Other hypothetical scenarios provide further evidence. Results: If a condition to be excluded is a confounder of the exposure–outcome relation, residual confounding will continue to bias a study after application of an imperfect screening criterion. Removal of ineligible outcome cases after chart review creates a new bias, distinct from residual confounding. The new bias does not depend on the magnitude of the confounder–outcome association, and will be small if the exclusion criterion has resulted in a low prevalence of the exclusionary condition. The new bias caused by removal of ineligible outcome cases is almost certain to be smaller than the confounding bias that can result if they are retained. Conclusions: Outcome cases first discovered at chart review to be study-ineligible should be removed from the study, even when similar scrutiny is infeasible for non-cases.

Introduction Nonarteritic anterior ischemic optic neuropathy ( NAION), a rare visual disorder, has been reported in men using phosphodiesterase type 5 inhibitors ( PDE5i) for erectile dysfunction. Aim We examined whether intermittent use of PDE5i is associated with acute NAION onset within approximately five half-lives following drug ingestion. Methods One hundred two ophthalmology centers in the United States and Europe identified potential cases of NAION. An expert adjudication committee conducted a blind review of the records of those with recent PDE5i use to classify cases as Definite, Possible, or not NAION. Subjects provided information on PDEi use via telephone interview. Each NAION case's PDE5i exposure immediately prior to onset was compared against his recent patterns of use in an observational case-crossover design. A sample size of 40 cases with intermittent PDE5i exposure in the 30 days prior to NAION onset was needed to detect an odds ratio ( OR) of 3.0 with 80% power. Main Outcome Measures The daily relative risk for acute NAION on days within five half-lives of PDE5i use vs. other days was estimated via an OR obtained from conditional logistic regression. Results Among 43 Definite NAION cases with PDE5i exposure in the prior 30 days, the OR was 2.15 (95% confidence interval [ CI]: 1.06, 4.34). When 21 Possible NAION cases were included (n = 64), the OR was 2.36 (95% CI: 1.33, 4.19). Conclusions We found an approximately twofold increased risk of acute NAION within five half-lives of PDE5i use compared with use in a more prior time period. Bias from inaccurate recall of exposure was unlikely to have substantially affected the results. Based on our results, we estimate that weekly use of PDE5i adds three NAION cases per 100,000 men 50 years and older annually. Campbell UB, Walker AM, Gaffney M, Petronis KR, Creanga D, Quinn S, Klein BEK, Laties AM, Lewis M, Sharlip ID, Kolitsopoulos F, Klee BJ, Mo J, and Reynolds RF. Acute nonarteritic anterior ischemic optic neuropathy and exposure to phosphodiesterase type 5 inhibitors. J Sex Med 2015;12:139-151. [ABSTRACT FROM AUTHOR]