Comparison of Outcomes Following a Switch From a Brand to an Authorized Versus Independent Generic Drug.

Authorized generics are identical in formulation to brand drugs, manufactured by the brand company but marketed as a generic. Generics, marketed by generic manufacturers, are required to demonstrate pharmaceutical and bioequivalence to the brand drug, but repetition of clinical trials is not required. This retrospective cohort study compared outcomes for generics and authorized generics, which serves as a generic vs. brand proxy that minimizes bias against generics. For the seven drugs studied between 1999 and 2014, 5,234 unique patients were on brand drugs prior to generic entry and 4,900 (93.6%) switched to a generic. During the 12 months following the brand-to-generic switch, patients using generics vs. authorized generics were similar in terms of outpatient visits, urgent care visits, hospitalizations, and medication discontinuation. The likelihood of emergency department (ED) visits was slightly higher for authorized generics compared with generics. These data suggest that generics were clinically no worse than their proxy brand comparators.

Brand vs generic adverse event reporting patterns: An authorized generic-controlled evaluation of cardiovascular medications.

WHAT IS KNOWN AND OBJECTIVE: Some public scepticism exists about generics in terms of whether brand and generic drugs produce identical outcomes. This study explores whether adverse event (AE) reporting patterns are similar between brand and generic drugs, using authorized generics (AGs) as a control for possible generic drug perception biases. METHODS: Events reported to the FDA Adverse Event Reporting System from the years 2004-2015 were analysed. Drugs were classified as brand, AG or generic based on drug and manufacturer names. Reports were included if amlodipine, losartan, metoprolol extended release (ER) or simvastatin were listed as primary or secondary suspect drugs. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting labelled AEs compared to reporting these AEs with all other drugs. The Breslow-Day test compared RORs across brand, AG and generic. Interrupted time series analysis evaluated the impact of generic entry on reporting trends. RESULTS AND DISCUSSION: Generics accounted for significant percentages of total U.S. reports, but AGs accounted for smaller percentages of reports, including for amlodipine (14.26%), losartan (1.48%), metoprolol ER (0.35%) and simvastatin (0.70%). Whereas the RORs were significantly different for multiple brand vs generic comparisons, the AG vs generic comparisons yielded fewer statistically significant findings. Namely, only the ROR for AG differed from generic for amlodipine with peripheral oedema (P < .01). WHAT IS NEW AND CONCLUSION: Inconsistent reporting patterns were observed more between brand and generic compared with AG and generic. Use of AGs as a control for perception biases against generics is useful, but this approach can be limited by small AG report numbers. Requiring the manufacturer name to be printed on the prescription bottle or packaging could improve the accuracy of assignment for products being reported.

Random Forests approach for identifying additive and epistatic single nucleotide polymorphisms associated with residual feed intake in dairy cattle.

Feed efficiency is an economically important trait in the beef and dairy cattle industries. Residual feed intake (RFI) is a measure of partial efficiency that is independent of production level per unit of body weight. The objective of this study was to identify significant associations between single nucleotide polymorphism (SNP) markers and RFI in dairy cattle using the Random Forests (RF) algorithm. Genomic data included 42,275 SNP genotypes for 395 Holstein cows, whereas phenotypic measurements were daily RFI from 50 to 150 d postpartum. Residual feed intake was defined as the difference between an animal's feed intake and the average intake of its cohort, after adjustment for year and season of calving, year and season of measurement, age at calving nested within parity, days in milk, milk yield, body weight, and body weight change. Random Forests is a widely used machine-learning algorithm that has been applied to classification and regression problems. By analyzing the tree structures produced within RF, the 25 most frequent pairwise SNP interactions were reported as possible epistatic interactions. The importance scores that are generated by RF take into account both main effects of variables and interactions between variables, and the most negative value of all importance scores can be used as the cutoff level for declaring SNP effects as significant. Ranking by importance scores, 188 SNP surpassed the threshold, among which 38 SNP were mapped to RFI quantitative trait loci (QTL) regions reported in a previous study in beef cattle, and 2 SNP were also detected by a genome-wide association study in beef cattle. The ratio of number of SNP located in RFI QTL to the total number of SNP in the top 188 SNP chosen by RF was significantly higher than in all 42,275 whole-genome markers. Pathway analysis indicated that many of the top 188 SNP are in genomic regions that contain annotated genes with biological functions that may influence RFI. Frequently occurring ancestor-descendant SNP pairs can be explored as possible epistatic effects for further study. The importance scores generated by RF can be used effectively to identify large additive or epistatic SNP and informative QTL. The consistency in results of our study and previous studies in beef cattle indicates that the genetic architecture of RFI in dairy cattle might be similar to that of beef cattle.

Biomedical informatics training at the University of Wisconsin-Madison.

OBJECTIVES: The purpose of this paper is to describe biomedical informatics training at the University of Wisconsin-Madison (UW-Madison). METHODS: We reviewed biomedical informatics training, research, and faculty/trainee participation at UW-Madison. RESULTS: There are three primary approaches to training 1) The Computation & Informatics in Biology & Medicine Training Program, 2) formal biomedical informatics offered by various campus departments, and 3) individualized programs. Training at UW-Madison embodies the features of effective biomedical informatics training recommended by the American College of Medical Informatics that were delineated as: 1) curricula that integrate experiences among computational sciences and application domains, 2) individualized and interdisciplinary cross-training among a diverse cadre of trainees to develop key competencies that he or she does not initially possess, 3) participation in research and development activities, and 4) exposure to a range of basic informational and computational sciences. CONCLUSIONS: The three biomedical informatics training approaches immerse students in multidisciplinary training and education that is supported by faculty trainers who participate in collaborative research across departments. Training is provided across a range of disciplines and available at different training stages. Biomedical informatics training at UW-Madison illustrates how a large research University, with multiple departments across biological, computational and health fields, can provide effective and productive biomedical informatics training via multiple bioinformatics training approaches.

Biology and medicine of turtles and tortoises.

Turtles and tortoises are unique reptiles that are gaining popularity as pets. Their anatomy and defense posture hinder, but do not preclude, clinical assessment and performance of routine diagnostic and therapeutic procedures by the clinician. A basic working knowledge of chelonian taxonomy, anatomy, physiology, husbandry, common diseases, and therapeutics will enable the veterinarian to provide health care to this order of reptiles.

Sloth bear immobilization with a ketamine-xylazine combination: reversal with yohimbine.

Five captive sloth bears (Melursus ursinus) were immobilized with a combination of ketamine (5.80 to 9.75 mg/kg of body weight) and xylazine (1.40 to 2.44 mg/kg), given IM. The youngest bear was immobilized twice, 62 days apart; all other bears were immobilized only once. Induction times were 4 to 25 minutes. After completion of various intended procedures, yohimbine (0.125 mg/kg) was administered IV. Arousal times were 2 to 20 minutes and bears were standing in 17 to 51 minutes. Compared with reported recovery times of 2 to 3 hours for bears immobilized with ketamine-xylazine combinations but not given an antagonist, results of the present study indicated that yohimbine reduces anesthesia recovery times in sloth bears immobilized with ketamine-xylazine combination.

Sarcocystis encephalitis in a cockatiel.

A sporozoan organism was considered to be the causative agent of central nervous system disease in a cockatiel. The ultrastructural characteristics were typical of the coccidian group Apicomplexa, and the fact that organisms were free within the cytoplasm of infected cells and not within a vacuole, indicated they were Sarcocystis. Light and electron microscopic evaluation of brain tissue demonstrated protozoal organisms associated with areas of necrosis. Differential diagnosis of central nervous system disease in pet birds should include protozoal encephalitis.

Monoclonal antibodies to gel-excised glial filament protein and their reactivities with other intermediate filament proteins.

A series of 14 monoclonal antibodies (MAs) has been obtained from a single rat-mouse fusion using gel-excised bovine glial filament (GF) proteins as immunogens. These MAs were characterized by two separate immunochemical assays and by two different immunohistochemical methods. Nine MAs demonstrated specificity for GF proteins. One MA also recognized an epitope shared by intermediate filaments (IF) of the vimentin class (VF). Using the enzyme-linked immunosorbent assay, four of the MAs recognized 200,000, 150,000, and 51,000 dalton proteins, suggesting that these MAs were specific for GF proteins (the 51,000 dalton protein) and neurofilament (NF) proteins (the two high-molecular-weight proteins). However, in both of the immunohistochemical assay systems, these MAs stained neurons and their processes but not astroglial cells. These observations strongly suggest that the 51,000-dalton protein recognized by these four MAs was not derived from GF proteins but instead represents derivatives of NF protein subunits comigrating in gels with GF proteins. These data provide additional information concerning the unique and shared antigenic determinants of the three classes of IF (NF, GF, and VF) of the CNS. In addition, they draw attention to the fact that proteins of certain IF may undergo degradation and comigrate in gels with the proteins of unrelated IF. This emphasizes the need for the use of independent immunochemical and immunohistochemical assays in the characterization of the specificity of MAs.