Determining prescriptions in electronic healthcare record data: methods for development of standardized, reproducible drug codelists

OBJECTIVE: To develop a standardizable, reproducible method for creating drug codelists that incorporates clinical expertise and is adaptable to other studies and databases. MATERIALS AND METHODS: We developed methods to generate drug codelists and tested this using the Clinical Practice Research Datalink (CPRD) Aurum database, accounting for missing data in the database. We generated codelists for: (1) cardiovascular disease and (2) inhaled Chronic Obstructive Pulmonary Disease (COPD) therapies, applying them to a sample cohort of 335 931 COPD patients. We compared searching all drug dictionary variables (A) against searching only (B) chemical or (C) ontological variables. RESULTS: In Search A, we identified 165 150 patients prescribed cardiovascular drugs (49.2% of cohort), and 317 963 prescribed COPD inhalers (94.7% of cohort). Evaluating output per search strategy, Search C missed numerous prescriptions, including vasodilator anti-hypertensives (A and B:19 696 prescriptions; C:1145) and SAMA inhalers (A and B:35 310; C:564). DISCUSSION: We recommend the full search (A) for comprehensiveness. There are special considerations when generating adaptable and generalizable drug codelists, including fluctuating status, cohort-specific drug indications, underlying hierarchical ontology, and statistical analyses. CONCLUSIONS: Methods must have end-to-end clinical input, and be standardizable, reproducible, and understandable to all researchers across data contexts

Examining Associations between Body Mass Index in 18⁻25 Year-Olds and Energy Intake from Alcohol:Findings from the Health Survey for England and the Scottish Health Survey

Evidence on the relationship between alcohol consumption and body mass index (BMI) is mixed, particularly for young adults. This study explored the relationship between energy obtained from alcoholic beverages and BMI using data for 18-25 year-olds (n = 7691) from pooled cross-sections of the 2008⁻2014 Health Survey for England and the Scottish Health Survey. Energy obtained from alcoholic beverages (excluding mixers) on the heaviest drinking day in the past week was expressed as percentage of total recommended dietary allowance (RDA) of energy (% RDA Energy). Linear regressions were estimated of BMI on alcohol intake categories controlling for intake frequency, physical activity, longstanding illness and other covariates, with separate analyses for men and women, and by beverage type. Significant associations with BMI were observed with the 'Very High' category of alcohol intake (>75% RDA Energy) for men (p 50% to 75% RDA Energy) (p 0⁻25% RDA Energy) category. Young adults drinking the highest levels of alcohol on a single occasion were more likely to be obese than those with the lowest intake. Interventions to address internationally rising youth obesity rates should also consider reducing alcohol consumption by increasing alcohol prices, and reducing availability and marketing exposure

O/IR Polarimetry for the 2010 Decade (GAN): Science at the Edge, Sharp Tools for All

Science opportunities and recommendations concerning optical/infrared polarimetry for the upcoming decade in the field of Galactic science. Community-based White Paper to Astro2010 in response to the call for such papers.Comment: White Paper to the Galactic Neighborhood (GAN) Science Frontiers Panel of the Astro2010 Decadal Surve

O/IR Polarimetry for the 2010 Decade (PSF): Science at the Edge, Sharp Tools for All

Science opportunities and recommendations concerning optical/infrared polarimetry for the upcoming decade in the fields of planetary systems and star formation. Community-based White Paper to Astro2010 in response to the call for such papers.Comment: White Paper to the Planetary Systems and Star Formation (PSF) Science Frontiers Panel of the Astro2010 Decadal Surve

Understanding Polarized Foreground from Dust: Towards Reliable Measurements of CMB Polarization

Science opportunities and recommendations concerning optical/infrared polarimetry for the upcoming decade in the field of cosmology. Community-based White Paper to Astro2010 in response to the call for such papers.Comment: White Paper to the Cosmology and Fundamental Physics (GCT) Science Frontiers Panel of the Astro2010 Decadal Surve

Validity and reliability of an online self-report 24-h dietary recall method (Intake24): a doubly labelled water study and repeated-measures analysis.

Online self-reported 24-h dietary recall systems promise increased feasibility of dietary assessment. Comparison against interviewer-led recalls established their convergent validity; however, reliability and criterion-validity information is lacking. The validity of energy intakes (EI) reported using Intake24, an online 24-h recall system, was assessed against concurrent measurement of total energy expenditure (TEE) using doubly labelled water in ninety-eight UK adults (40-65 years). Accuracy and precision of EI were assessed using correlation and Bland-Altman analysis. Test-retest reliability of energy and nutrient intakes was assessed using data from three further UK studies where participants (11-88 years) completed Intake24 at least four times; reliability was assessed using intra-class correlations (ICC). Compared with TEE, participants under-reported EI by 25 % (95 % limits of agreement -73 % to +68 %) in the first recall, 22 % (-61 % to +41 %) for average of first two, and 25 % (-60 % to +28 %) for first three recalls. Correlations between EI and TEE were 0·31 (first), 0·47 (first two) and 0·39 (first three recalls), respectively. ICC for a single recall was 0·35 for EI and ranged from 0·31 for Fe to 0·43 for non-milk extrinsic sugars (NMES). Considering pairs of recalls (first two v. third and fourth recalls), ICC was 0·52 for EI and ranged from 0·37 for fat to 0·63 for NMES. EI reported with Intake24 was moderately correlated with objectively measured TEE and underestimated on average to the same extent as seen with interviewer-led 24-h recalls and estimated weight food diaries. Online 24-h recall systems may offer low-cost, low-burden alternatives for collecting dietary information.UK Medical Research Council support is acknowledged by S. B., S. E. H. and K. L. W. (MC UU 12015/3), by F. I. and N. G. F. (MC UU 12015/5), N. W. (MC UU 12015/1) and M. C. V. (MC U105960384). S. B., K. L. W., N. G. F. and N. W. also acknowledge National Institute for Health Research (NIHR) Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). A. J. A. is funded by NIHR as an NIHR Research Professor and is a member of FUSE. Cost of isotope work was part funded by a grant from MedImmune Ltd to S. B., part funded by Newcastle University. Food Standards Scotland (previously Food Standards Agency Scotland) funded study 1 and study 3 which are included in the reliability analysis

Potent Activity of the HIV-1 Maturation Inhibitor Bevirimat in SCID-hu Thy/Liv Mice

The HIV-1 maturation inhibitor, 3-O-(3',3'-dimethylsuccinyl) betulinic acid (bevirimat, PA-457) is a promising drug candidate with 10 nM in vitro antiviral activity against multiple wild-type (WT) and drug-resistant HIV-1 isolates. Bevirimat has a novel mechanism of action, specifically inhibiting cleavage of spacer peptide 1 (SP1) from the C-terminus of capsid which results in defective core condensation.Oral administration of bevirimat to HIV-1-infected SCID-hu Thy/Liv mice reduced viral RNA by >2 log(10) and protected immature and mature T cells from virus-mediated depletion. This activity was observed at plasma concentrations that are achievable in humans after oral dosing, and bevirimat was active up to 3 days after inoculation with both WT HIV-1 and an AZT-resistant HIV-1 clinical isolate. Consistent with its mechanism of action, bevirimat caused a dose-dependent inhibition of capsid-SP1 cleavage in HIV-1-infected human thymocytes obtained from these mice. HIV-1 NL4-3 with an alanine-to-valine substitution at the N-terminus of SP1 (SP1/A1V), which is resistant to bevirimat in vitro, was also resistant to bevirimat treatment in the mice, and SP1/AIV had replication and thymocyte kinetics similar to that of WT NL4-3 with no evidence of fitness impairment in in vivo competition assays. Interestingly, protease inhibitor-resistant HIV-1 with impaired capsid-SP1 cleavage was hypersensitive to bevirimat in vitro with a 50% inhibitory concentration 140 times lower than for WT HIV-1.These results support further clinical development of this first-in-class maturation inhibitor and confirm the usefulness of the SCID-hu Thy/Liv model for evaluation of in vivo antiretroviral efficacy, drug resistance, and viral fitness