Routinely collected data for randomized trials: promises, barriers, and implications

This work was supported by Stiftung Institut für klinische Epidemiologie. The Meta-Research Innovation Center at Stanford University is funded by a grant from the Laura and John Arnold Foundation. The funders had no role in design and conduct of the study; the collection, management, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript or its submission for publication.Peer reviewedPublisher PD

Computational Prediction of Intronic microRNA Targets using Host Gene Expression Reveals Novel Regulatory Mechanisms

Approximately half of known human miRNAs are located in the introns of protein coding genes. Some of these intronic miRNAs are only expressed when their host gene is and, as such, their steady state expression levels are highly correlated with those of the host gene's mRNA. Recently host gene expression levels have been used to predict the targets of intronic miRNAs by identifying other mRNAs that they have consistent negative correlation with. This is a potentially powerful approach because it allows a large number of expression profiling studies to be used but needs refinement because mRNAs can be targeted by multiple miRNAs and not all intronic miRNAs are co-expressed with their host genes

Barriers to data quality resulting from the process of coding health information to administrative data: a qualitative study

Abstract Background Administrative health data are increasingly used for research and surveillance to inform decision-making because of its large sample sizes, geographic coverage, comprehensivity, and possibility for longitudinal follow-up. Within Canadian provinces, individuals are assigned unique personal health numbers that allow for linkage of administrative health records in that jurisdiction. It is therefore necessary to ensure that these data are of high quality, and that chart information is accurately coded to meet this end. Our objective is to explore the potential barriers that exist for high quality data coding through qualitative inquiry into the roles and responsibilities of medical chart coders. Methods We conducted semi-structured interviews with 28 medical chart coders from Alberta, Canada. We used thematic analysis and open-coded each transcript to understand the process of administrative health data generation and identify barriers to its quality. Results The process of generating administrative health data is highly complex and involves a diverse workforce. As such, there are multiple points in this process that introduce challenges for high quality data. For coders, the main barriers to data quality occurred around chart documentation, variability in the interpretation of chart information, and high quota expectations. Conclusions This study illustrates the complex nature of barriers to high quality coding, in the context of administrative data generation. The findings from this study may be of use to data users, researchers, and decision-makers who wish to better understand the limitations of their data or pursue interventions to improve data quality

Aggregate data and curve fits of ¹⁵N urine enrichment from infants with tetralogy of Fallot (ToF) or heart failure (HF).

Urine sample collection times shown in Figs 4 and 5 were normalized to time elapsed since the most recent 15N-thymidine administration, which was set to 0 hr. X-axes indicate time from 15N-thymidine administration to urine sampling. One patient (M014) was excluded from polynomial fitting due to insufficient urine data. Y-axes indicate 15N/14N (%) in urine. Each symbol represents one urine sample. The 15N/14N isotope ratio in percent was graphed over time elapsed since preceding 15N-thymidine dose administration. The normalization of urine collection times to each corresponding dose administration time allowed for overlapping the 15N/14N atomic ratios to achieve a higher data density for curve fitting. Urine samples corresponding to the same 15N-thymidine administration have the same color according to the legend. Centered third-degree polynomial functions, indicated in solid blue lines, were used as the best nonlinear regression model to fit the data. Dashed blue lines indicate 95% confidence intervals of the fits. The R2 values indicate the goodness of fit. The fits show that administered doses were sufficient to maintain the 15N/14N isotope ratios above baseline during the 5-day labeling period (a) Results from infants with ToF. (b) Results from infants with HF. The threshold, i.e., the physiological 15N/14N atomic ratio is indicated with a dotted red horizontal line.</p

¹⁵N-thymdine administration and quantification in urine in infants.

(a) Tetralogy of Fallot (ToF) infants were given 15N-thymidine at home with the exception of one patient and heart failure (HF) infants received 15N-thymidine at the hospital. Each infant received five oral doses of 50 mg/kg 15N-thymidine in individual single-dose syringes over the course of five consecutive days. Families filled out daily logs to record timing of doses, urine output, and any issues with dose administration. Cotton balls were placed in diapers and collected in specimen bags after infants voided. Cotton balls were collected up to 24 hours following the last dose. Cotton balls that dried during transportation and handling processes were discarded. Viable cotton balls were squeezed to express urine samples into separate 1.5 mL Eppendorf tubes and urine volumes were recorded. Samples were dried, crushed using forceps and weighed. Dried samples were analyzed by elemental analyzer isotope ratio mass spectrometry (IRMS). Atomic ratios of 15N/14N in each urine sample were expressed. (b) Enrollment and follow up of all study participants.</p

Comparing different fitting functions for aggregate data of ¹⁵N urine enrichment from infants with ToF or HF.

Comparing different fitting functions for aggregate data of 15N urine enrichment from infants with ToF or HF.</p

Primary data for negative control urine measurements.

Primary data for negative control urine measurements.</p

¹⁵N enrichment levels after ¹⁵N-thymidine administration show temporal patterns in infants with tetralogy of Fallot (ToF).

Analysis of urine samples from six infants with ToF/PS who had received oral 15N-thymidine (50 mg/kg/day) was performed. Each graph has the patient study identifier and age at 15N-thymidine labeling indicated. Urine samples were extracted from diapers collected at home, dried, and subjected to Isotope Ratio Mass Spectrometry (IRMS) to quantify 15N/14N atomic ratios. The x-axes indicate timings of 15N-thymidine doses beginning with 00:00 hour of the day, and the Y-axes indicate the 15N/14N atomic ratios. Timing of 15N-thymidine administration is indicated with vertical green arrows (↓) and dotted lines. Each symbol (●) indicates one urine sample. Results of single samples are connected by solid black lines, unless > 24 hr apart. The threshold, i.e., the physiological 15N/14N atomic ratio, is indicated with a dotted red horizontal line.</p

¹⁵N enrichment levels after ¹⁵N-thymidine administration show temporal patterns in infants with severe heart failure (HF).

Analysis of urine samples from five infants on the wait list for heart transplantation, who had received oral 15N-thymidine (50 mg/kg/day) in the hospital was performed. Each graph has the patient code and age at 15N-thymidine labeling indicated. Urine samples were extracted from diapers collected in the hospital, dried, and subjected to Isotope Ratio Mass Spectrometry (IRMS) to quantify 15N/14N atomic ratios. The x-axes indicate timings of 15N-thymidine doses beginning with 00:00 hour of the day, and the Y-axes indicate the 15N/14N atomic ratios. Timing of 15N-thymidine administration is indicated with vertical green arrows (↓) and dotted lines. Each symbol (▲) indicates one urine sample. Results of single samples are connected by solid black lines, unless > 24 hr apart. The threshold, i.e., the physiological 15N/14N atomic ratio is indicated with a dotted red horizontal line.</p