Impact of prior hospital mortality versus surgical volume on mortality following surgery for congenital heart disease

ObjectiveOur objective was to assess the relationships of a hospital’s past adjusted in-hospital mortality and surgical volume with future in-hospital mortality after surgery for congenital heart disease.MethodsUsing the Pediatric Health Information Systems database, we (1) calculated hospital surgical volume and standardized mortality ratio (= observed number of deaths/expected number of deaths adjusted for surgery type) for January 2004 through June 2006 for children (0-18 years) after surgery for congenital heart disease at 38 hospitals and (2) assessed the relationship between these values and subsequent mortality during July 2006 through December 2008. We constructed Poisson regression models to estimate risk of mortality, adjusting for age, race, sex, genetic syndrome, insurance type, and surgery type (using the Risk Adjustment in Congenital Heart Surgery method).ResultsThere were 49,792 hospital encounters during 2004 through 2008 for pediatric patients having surgery for congenital heart disease, with an overall in-hospital mortality of 3.45%. For the 24,112 eligible encounters during July 2006 through December 2008, a hospital’s prior standardized mortality ratio was significantly associated with postoperative in-hospital mortality (P < .0001), and a hospital’s prior surgical volume had only borderline significance (P = .0792). On stratified analysis, past standardized mortality ratio was associated with mortality for both lower- and higher-risk surgical risk categories (P = .0105 and .0015, respectively). Hospital surgical volume was not significantly associated with mortality for lower-risk categories (P = .4122), but it was borderline significant for higher-risk categories (P = .0678).ConclusionsIn this data set, prior hospital surgical volume tended to be associated with improved mortality after higher-risk operations in pediatric patients with congenital heart disease, whereas prior hospital postoperative mortality was significantly associated with mortality across all risk strata of congenital heart surgery

Association of Digoxin With Interstage Mortality: Results From the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use Dataset

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139107/1/jah31279.pd

Statistical competencies for medical research learners: What is fundamental?

IntroductionIt is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from 'fundamental' (necessary for all) to 'specialized' (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.MethodsWe surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by 'fundamental' and 'specialized.'ResultsThere were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one's own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).ConclusionWe have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature

Databases for Congenital Heart Defect Public Health Studies Across the Lifespan

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139106/1/jah31841_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139106/2/jah31841.pd

Discovery of Diverse Small Molecule Chemotypes with Cell-Based PKD1 Inhibitory Activity

Protein kinase D (PKD) is a novel family of serine/threonine kinases regulated by diacylglycerol, which is involved in multiple cellular processes and various pathological conditions. The limited number of cell-active, selective inhibitors has historically restricted biochemical and pharmacological studies of PKD. We now markedly expand the PKD1 inhibitory chemotype inventory with eleven additional novel small molecule PKD1 inhibitors derived from our high throughput screening campaigns. The in vitro IC50s for these eleven compounds ranged in potency from 0.4 to 6.1 µM with all of the evaluated compounds being competitive with ATP. Three of the inhibitors (CID 1893668, (1Z)-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one; CID 2011756, 5-(3-chlorophenyl)-N-[4-(morpholin-4-ylmethyl)phenyl]furan-2-carboxamide; CID 5389142, (6Z)-6-[4-(3-aminopropylamino)-6-methyl-1H-pyrimidin-2-ylidene]cyclohexa-2,4-dien-1-one) inhibited phorbol ester-induced endogenous PKD1 activation in LNCaP prostate cancer cells in a concentration-dependent manner. The specificity of these compounds for PKD1 inhibitory activity was supported by kinase assay counter screens as well as by bioinformatics searches. Moreover, computational analyses of these novel cell-active PKD1 inhibitors indicated that they were structurally distinct from the previously described cell-active PKD1 inhibitors while computational docking of the new cell-active compounds in a highly conserved ATP-binding cleft suggests opportunities for structural modification. In summary, we have discovered novel PKD1 inhibitors with in vitro and cell-based inhibitory activity, thus successfully expanding the structural diversity of small molecule inhibitors available for this important pharmacological target

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Cost and Cost-Effectiveness Assessments of Newborn Screening for Critical Congenital Heart Disease Using Pulse Oximetry: A Review

Screening newborns for critical congenital heart disease (CCHD) using pulse oximetry is recommended to allow for the prompt diagnosis and prevention of life-threatening crises. The present review summarizes and critiques six previously published estimates of the costs or cost-effectiveness of CCHD screening from the United Kingdom, United States, and China. Several elements that affect CCHD screening costs were assessed in varying numbers of studies, including screening staff time, instrumentation, and consumables, as well as costs of diagnosis and treatment. A previous US study that used conservative assumptions suggested that CCHD screening is likely to be considered cost-effective from the healthcare sector perspective. Newly available estimates of avoided infant CCHD deaths in several US states that implemented mandatory CCHD screening policies during 2011–2013 suggest a substantially larger reduction in deaths than was projected in the previous US cost-effectiveness analysis. Taking into account these new estimates, we estimate that cost per life-year gained could be as low as USD 12,000. However, that estimate does not take into account future costs of health care and education for surviving children with CCHD nor the costs incurred by health departments to support and monitor CCHD screening policies and programs