Antibiotic Prescribing during Infancy and Risk of Treated Obstructive Airway Diseases during Early Childhood: A Registry-Based Nationwide Cohort Study in Denmark

Widespread antibiotic use leads to bacterial resistance, and antibiotic use in early life may be associated with asthma in childhood. To date, studies of this association have led to inconsistent findings. Additionally, data are limited regarding cohort effects on antibiotic use in children, which may impact underlying susceptibility to adverse effects. Using nationwide registry data on all children born in Denmark during 2004-2012, our objectives were to (1) examine birth-season and birth-year cohort effects on antibiotic prescribing during the first year of life (henceforth, ‘infancy’), and (2) to estimate 1-, 2-, and 3-year risk differences (RD) for the association between antibiotic prescribing during infancy and treated airway diseases from 2-5 years of age, using propensity scores (PS) and instrumental variables. The 1-year risk of redeeming at least one antibiotic prescription during infancy was 39.5 per 100 children. The hazard of first redeemed antibiotic prescription increased with age throughout infancy, and peaked in February; as a result, season of birth impacted overall 1-year risk of redeeming an antibiotic prescription during infancy and age at first redeemed antibiotic prescription. Amoxicillin prescribing was dynamic over the study period, but decreased after distribution of a bulletin on rational antibiotic use in general practice and rollout of two nationwide pneumococcal vaccination programs. In PS analyses, antibiotic exposure was associated with increased risk of treated airway diseases by age 5, compared with no exposure (3-year RD = 4.5 per 100 children, 99% confidence interval (CI): 4.2, 4.8). PS-based dose-response analysis suggested that each additional redeemed antibiotic prescription was associated with increased risk of 2.4 per 100 children (99% CI: 2.3, 2.5). RDs were negligible in a PS-based head-to-head comparison between two antibiotics with similar indications but differing spectrum of antibacterial activity – amoxicillin and penicillin V (3-year RD = -0.1 per 100 children, 99% CI: -0.6, 0.3). Results from instrumental variable analyses also cast some doubt on the presence of a causal effect, but were imprecise. These results suggest that antibiotic exposure during infancy may increase the risk of treated airway diseases, but further exploration is needed using data and methods capable of addressing potential residual confounding.Doctor of Philosoph

High Repetition Rate, LINAC-based Nuclear Resonance Fluorescence FY 2009 Final Report

Nuclear Resonance Fluorescence (NRF), which is possible for nuclei with atomic numbers greater than helium (Z=2), occurs when a nuclear level is excited by resonant absorption of a photon and subsequently decays by reemission of a photon. The excited nuclear states can become readily populated, provided the incident photon’s energy is within the Doppler-broadened width of the energy level being excited. Utilizing continuous energy photon spectra, as is characteristic of a bremsstrahlung photon beam, as the inspection source, ensures that at least some fraction of the impinging beam will contribute to the population of the excited energy levels in the material of interest. Upon de-excitation, either to the ground state or to a lower-energy excited state, the emitted fluorescence photon’s energy will correspond to the energy difference between the excited state and the state to which it decays. As each isotope inherently contains unique nuclear energy levels, the NRF states for each isotope are also unique. By exploiting this phenomenon, NRF photon detection provides a well-defined signature for identifying the presence of individual nuclear species. This report summarizes the second year (Fiscal Year [FY] 2009) of a collaborative research effort between Idaho National Laboratory, Idaho State University’s Idaho Accelerator Center, and Pacific Northwest National Laboratory. This effort focused on continuing to assess and optimize NRF-based detection techniques utilizing a slightly modified, commercially available, pulsed medical electron accelerator

Trends and Patterns of Urodynamic Studies in U.S. Women, 2000–2012

To estimate utilization rates for cystometrograms and describe trends in urodynamic procedures among U.S. women from 2000 to 2012

Inches, Centimeters, and Yards: Overlooked Definition Choices Inhibit Interpretation of Morphine Equivalence

Objective: Morphine-standardized doses are used in clinical practice and research to account for molecular potency. Ninety milligrams of morphine equivalents (MME) per day are considered a "high dose" risk threshold in guidelines, laws, and by payers. Although ubiquitously cited, the "CDC definition" of daily MME lacks a clearly defined denominator. Our objective was to assess denominator-dependency on "high dose" classification across competing definitions. Methods: To identify definitional variants, we reviewed literature and electronic prescribing tools, yielding 4 unique definitions. Using Prescription Drug Monitoring Programs data (July to September 2018), we conducted a population-based cohort study of 3,916,461 patients receiving outpatient opioid analgesics in California (CA) and Florida (FL). The binary outcome was whether patients were deemed "high dose" (>90 MME/d) compared across 4 definitions. We calculated I2 for heterogeneity attributable to the definition. Results: Among 9,436,640 prescriptions, 42% overlapped, which led denominator definitions to impact daily MME values. Across definitions, average daily MME varied 3-fold (range: 17 to 52 [CA] and 23 to 65 mg [FL]). Across definitions, prevalence of "high dose" individuals ranged 5.9% to 14.2% (FL) and 3.5% to 10.3% (CA). Definitional variation alone would impact a hypothetical surveillance study trying to establish how much more "high dose" prescribing was present in FL than CA: from 39% to 84% more. Meta-analyses revealed strong heterogeneity (I2 range: 86% to 99%). In sensitivity analysis, including unit interval 90.0 to 90.9 increased "high dose" population fraction by 15%. Discussion: While 90 MME may have cautionary mnemonic benefits, without harmonization of calculation, its utility is limited. Comparison between studies using daily MME requires explicit attention to definitional variation

Trends in Antibiotic Use by Birth Season and Birth Year

OBJECTIVES: We examined 2 birth cohort effects on antibiotic prescribing during the first year of life (henceforth, infancy) in Denmark: (1) the birth season effect on timing and overall occurrence of antibiotic prescribing, and (2) the birth year effect amid emerging nationwide pneumococcal vaccination programs and changing prescribing guidelines. METHODS: We linked data for all live births in Denmark from 2004 to 2012 (N = 561 729) across the National Health Service Prescription Database, Medical Birth Registry, and Civil Registration System. Across birth season and birth year cohorts, we estimated 1-year risk, rate, and burden of redeemed antibiotic prescriptions during infancy. We used interrupted time series methods to assess prescribing trends across birth year cohorts. Graphical displays of all birth cohort effect data are included. RESULTS: The 1-year risk of having at least 1 redeemed antibiotic prescription during infancy was 39.5% (99% confidence interval [CI]: 39.3% to 39.6%). The hazard of a first prescription increased with age throughout infancy and varied by season; subsequently, Kaplan-Meier-derived risk functions varied by birth season cohort. After rollout of a first vaccination program and new antibiotic prescribing guidelines, 1-year risk decreased by 4.4% over 14 months (99% CI: 3.4% to 5.5%); it decreased again after rollout of a second vaccination program by 6.9% over 3 years (99% CI: 4.4% to 9.3%). CONCLUSIONS: In Denmark, birth season and birth year cohort effects influenced timing and risk of antibiotic prescribing during infancy. Future studies of antibiotic stewardship, effectiveness, and safety in children should consider these cohort effects, which may render some children inherently more susceptible than others to downstream antibiotic effects

High Repetition Rate, LINAC-Based Nuclear Resonance Fluorescence FY 2008 Final Report

This summarizes the first year of a multi-laboratory/university, multi-year effort focusing on high repetition rate, pulsed LINAC-based nuclear resonance fluorescence (NRF) measurements. Specifically, this FY2008 effort centered on experimentally assessing NRF measurements using pulsed linear electron accelerators, operated at various repetition rates, and identifying specific detection requirements to optimize such measurements. Traditionally, interest in NRF as a detection technology, which continues to receive funding from DHS and DOE/NA-22, has been driven by continuous-wave (CW), Van de Graff-based bremsstrahlung sources. However, in addition to the relatively sparse present-day use of Van de Graff sources, only limited NRF data from special nuclear materials has been presented; there is even less data available regarding shielding effects and photon source optimization for NRF measurements on selected nuclear materials

Trends and Patterns of Urodynamic Studies in U.S. Males, 2000–2012

ObjectiveTo evaluate trends in urodynamic procedures in the U.S. males from 2000–2012 and determine if a 2010 decline in reimbursement was associated with decreased utilization.Subjects and methodsWe analyzed 2000–2012 administrative healthcare claims from Truven Health’s Marketscan Database and evaluated males ≥18 years of age. We identified cystometrograms and any concurrent procedures using procedure billing codes. Covariates included age, year of cystometrogram, region and associated diagnosis codes. We estimated standardized cystometrogram utilization rates per 10,000 person-years (PY). We used age, region, and calendar year adjusted Poisson regression models to estimate the independent effect of calendar year and region.ResultsDuring 127,558,186 PY of observation, we identified 153,168 cystometrograms for an overall utilization rate of 12.0 per 10,000 PY (95% CI 11.9–12.1). Cystometrogram utilization increased with age, peaking at age 85 with a rate of 77.7 per 10,000 PY (95% CI 74.7–80.7). Adjusted cystometrogram utilization rate ratios show that compared to a referent of 2000–2004, utilization was significantly higher in each year 2005 to 2011 among all patients and in 2012 among patients ≥ 65. Standardized utilization rates peaked in 2008 at 12.4 per 10,000 PY (95% CI 12.2–12.6), remained elevated until 2010, then decreased slightly in 2011 and substantially in 2012 to 8.5 per 10,000 PY (95% CI 8.4–8.7).ConclusionsUtilization of urodynamic procedures increased until 2010 and decreased thereafter. Utilization was greatest among men older than 65

Risk factors associated with the presence and severity of food insecurity in rural Honduras

OBJECTIVE: To identify factors associated with the presence and severity of food insecurity among a sample of Honduran caregivers of young children. DESIGN: Cross-sectional study in which the dependent variable, household food insecurity, was measured using a fourteen-item questionnaire developed and validated in a population of similar cultural context. A predictive modelling strategy used backwards elimination in logistic regression and multinomial logit regression models to compute odds ratios and 95% confidence intervals for food insecurity. SETTING: Rural Honduras in the department of Intibucá, between March and April 2009. SUBJECTS: Two-hundred and ninety-eight Honduran caregivers of children aged 6-18 months. RESULTS: Ninety-three per cent of households were classified as having some degree of food insecurity (mild, moderate or severe). After controlling for caregiver age and marital status, compared with caregivers with more than primary-school education, those with less than primary-school education had 3·47 (95% CI 1·34, 8·99) times the odds of severe food insecurity and 2·29 (95% CI 1·00, 5·25) times the odds of moderate food insecurity. Our results also found that child anthropometric status was not associated with the presence or severity of food insecurity. CONCLUSIONS: These results show that among the sociodemographic factors assessed, food insecurity in rural Honduras is associated with maternal education. Understanding key factors associated with food insecurity that are unique to Honduras can inform the design of interventions to effectively mitigate the negative impact of food insecurity on children

Four Competing Definitions of Morphine Equivalence Insidiously Inhibit Evidence Synthesis

Analysis of opioid milligrams of morphine equivalents (MME) per day definitions. Presented virtually at the 37th annual International Conference on Pharmacoepidemiology and Therapeutic Risk Management

Drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19: a disproportionality analysis of U.S. food and drug administration adverse event reporting system (FAERS) data

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59–3.46), 3.16 (2.68–3.73), and 5.39 (4.63–6.26) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (3.98; 3.15–5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09–6.94), and compared with remdesivir (3.85; 3.03–4.89). Conclusions In the FAERS, we observed a disproportional signal for drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19