Lutz F. Gruber, Erica F. Stuber, Lyndsie S. Wszola, Joseph J. Fontaine.

Source: Bayesian Analysis, Volume 14, Number 4, 1173--1199.

Abstract:
We present an integrated open population model where the population dynamics are defined by a differential equation, and the related statistical model utilizes a Poisson binomial convolution likelihood. Key advantages of the proposed approach over existing open population models include the flexibility to predict related, but unobserved quantities such as total immigration or emigration over a specified time period, and more computationally efficient posterior simulation by elimination of the need to explicitly simulate latent immigration and emigration. The viability of the proposed method is shown in an in-depth analysis of outdoor recreation participation on public lands, where the surveyed populations changed rapidly and demographic population closure cannot be assumed even within a single day.

Lloyd T. Elliott, Maria De Iorio, Stefano Favaro, Kaustubh Adhikari, Yee Whye Teh.

Source: Bayesian Analysis, Volume 14, Number 2, 313--339.

Abstract:
We propose a Bayesian nonparametric model to infer population admixture, extending the hierarchical Dirichlet process to allow for correlation between loci due to linkage disequilibrium. Given multilocus genotype data from a sample of individuals, the proposed model allows inferring and classifying individuals as unadmixed or admixed, inferring the number of subpopulations ancestral to an admixed population and the population of origin of chromosomal regions. Our model does not assume any specific mutation process, and can be applied to most of the commonly used genetic markers. We present a Markov chain Monte Carlo (MCMC) algorithm to perform posterior inference from the model and we discuss some methods to summarize the MCMC output for the analysis of population admixture. Finally, we demonstrate the performance of the proposed model in a real application, using genetic data from the ectodysplasin-A receptor (EDAR) gene, which is considered to be ancestry-informative due to well-known variations in allele frequency as well as phenotypic effects across ancestry. The structure analysis of this dataset leads to the identification of a rare haplotype in Europeans. We also conduct a simulated experiment and show that our algorithm outperforms parametric methods.

Chang-Jin Jeon
Nov 1, 1998; 18:8936-8946
Articles

The detection and segmentation of meaningful figures from their background is one of the primary functions of vision. While work in nonhuman primates has implicated early visual mechanisms in this figure–ground modulation, neuroimaging in humans has instead largely ascribed the processing of figures and objects to higher stages of the visual hierarchy. Here, we used high-field fMRI at 7 Tesla to measure BOLD responses to task-irrelevant orientation-defined figures in human early visual cortex (N = 6, four females). We used a novel population receptive field mapping-based approach to resolve the spatial profiles of two constituent mechanisms of figure–ground modulation: a local boundary response, and a further enhancement spanning the full extent of the figure region that is driven by global differences in features. Reconstructing the distinct spatial profiles of these effects reveals that figure enhancement modulates responses in human early visual cortex in a manner consistent with a mechanism of automatic, contextually driven feedback from higher visual areas.

SIGNIFICANCE STATEMENT A core function of the visual system is to parse complex 2D input into meaningful figures. We do so constantly and seamlessly, both by processing information about visible edges and by analyzing large-scale differences between figure and background. While influential neurophysiology work has characterized an intriguing mechanism that enhances V1 responses to perceptual figures, we have a poor understanding of how the early visual system contributes to figure–ground processing in humans. Here, we use advanced computational analysis methods and high-field human fMRI data to resolve the distinct spatial profiles of local edge and global figure enhancement in the early visual system (V1 and LGN); the latter is distinct and consistent with a mechanism of automatic, stimulus-driven feedback from higher-level visual areas.

No SARS-CoV-2 infections have yet been detected in our closest living relatives. But there is precedent for viruses jumping from people to other great apes

Laurie Baker says the rural population should be considered a special population when considering education reforms.

The number of English-learner students in U.S. schools has increased 28 percent since 2000; 43 of 50 states have experienced an uptick in enrollment, federal data indicate.

In five northern U.S. states, black students comprise more than a fifth of ELL enrollment.

Little is known about the pharmacokinetics and required dosage of metronidazole in preterm neonates.

In this study the pharmacokinetics of metronidazole in preterm neonates was investigated by measurement of the drug in dried blood-spot samples. A dosage regimen is proposed that should result in more appropriate, less frequent dosing in the most preterm neonates. (Read the full article)

There are a number of effective interventions designed to prevent childhood/adolescent depression. Such interventions tend to comprise screening and the subsequent provision of psychological therapy. However, the cost-effectiveness of routinely providing such interventions at a population level is not known.

By using economic modeling techniques, this study shows that the population cost-effectiveness of such preventive interventions for childhood/adolescent depression is very favorable, although implementation issues, particularly around the acceptability to providers, need to be addressed before widespread adoption. (Read the full article)

Parent-infant bed-sharing is a common behavior of breastfeeding mothers and various ethnic groups. Under certain circumstances, it is associated with an increased risk of sudden infant death. Blanket prohibitions against bed-sharing conflict with breastfeeding promotion and inhibit safe bed-sharing discussion.

Bed-sharing and sofa-sharing were almost mutually exclusive. Pakistani families avoided sofa-sharing and hazardous bed-sharing, and have a very low rate of sudden infant death syndrome. White British families were more likely to smoke, drink alcohol, and sofa-share with their infants. (Read the full article)

Sleep-disordered breathing is associated with neurobehavioral morbidity in children. Prior related research has generally been cross-sectional or short (ie, 1–2 years) follow-up studies of a single symptom (ie, snoring, obstructive sleep apnea, mouth breathing), with limited control for confounders.

Sleep-disordered breathing was assessed as a trajectory of combined symptoms from 6 months to 69 months, in more than 11 000 children. Sleep-disordered breathing was associated with 40% and 60% more behavioral difficulties at 4 and 7 years, respectively. (Read the full article)

Estimates of youth participation in strangulation activity, commonly referred to as the "choking game," range from 5% to 11%. Previous studies have documented correlations between youth choking game participation and health risks such as substance use and mental health issues.

Among Oregon eighth-graders surveyed, >6% had ever participated in the choking game. Participation was linked to poor nutrition and gambling among females, exposure to violence among males, and sexual activity and substance use among both genders. (Read the full article)

Recent systematic reviews revealed that educational dietary interventions were effective in improving nutritional status and food consumption in the first year after birth. We are not aware, however, of studies in developing countries that have evaluated their long-term effectiveness.

This randomized trial revealed that, in a low-income population, the delivery of home-based maternal counseling focusing on breastfeeding and complementary feeding during the first year of children’s lives significantly improved the lipid profile at 7 to 8 years old. (Read the full article)

Conflicting results exist concerning long-term outcome in healthy infants with metabolic acidosis at birth.

Neonates who appear well after perinatal metabolic acidosis do not have an increased risk of neurologic or behavioral problems in need of referral actions or pedagogic arrangements at the age of 6.5 years. (Read the full article)

Neonatal hyperbilirubinemia may progress to bilirubin encephalopathy. Findings from previous studies on long-term development of neonatal hyperbilirubinemia are conflicting.

Using Ages and Stages Questionnaire, we observed no association between bilirubin exposure and overall development in 1- to 5-year-old children who in the neonatal period had total serum bilirubin level ≥25 mg/dL and no or only minor neurologic symptoms. (Read the full article)

Many children are vaccinated against measles with a delay. This may influence effective measles vaccine coverage even in countries with high overall immunization levels. Official vaccine coverage statistics do not usually report on the impact of timeliness of measles vaccination.

Delayed measles vaccination results in 48.6% effective coverage in children aged 6 months to 2 years when 84.5% of 25-month-olds are up-to-date for 1 measles vaccination. Analyzing patterns of measles vaccination could help to address low coverage in infants and toddlers. (Read the full article)

Sleep disordered breathing (SDB) and behavioral sleep problems (BSPs) affect cognitive, behavioral, and language development. No studies have examined associations between SDB and BSPs across early childhood, and later special education need (SEN), on a population basis.

A history of SDB through 5 years of age was associated with ~40% increased odds of SEN at 8 years, among >11 000 children. BSPs were associated with 7% increased odds of SEN, for each additional ~12 months of reported BSPs. (Read the full article)

Risk of preterm birth (PTB) has been noted to be higher for newborns with congenital heart defects (CHDs). The role of associated anomalies, whether PTB is spontaneous or medically induced, or specific categories of CHDs have not been elucidated.

By using population-based data, we found that PTB associated with CHDs was due to spontaneous PTB. Associated anomalies accounted for a small part of this increase, and there were specific associations between categories of CHDs and PTB. (Read the full article)

Inflammatory bowel disease pathogenesis is incompletely understood. Previous pediatric studies suggested associations between antibiotic use and inflammatory bowel disease development but were limited by recall bias, lack of controls, incomplete antibiotic capture, or included exposures between symptom onset and diagnosis.

Our population-based cohort study suggests that certain childhood antibiotic exposures are associated with an increased risk of developing inflammatory bowel disease. Our findings have implications for understanding the condition’s pathogenesis and provide additional stimulus for reducing unnecessary childhood antibiotic use. (Read the full article)

Understanding human disease genomics requires large population-based studies. There is lack of standardization, as well as social and ethical concerns surrounding the consent process for pediatric participation in a biorepository.

The study identifies specific barriers to pediatric participation in biorepositories relative to adults, and proposes strategies to improve ethical and responsible participation of pediatric-aged patients in large-scale genomics and biorepository-driven research without significantly increasing research burden for affected families. (Read the full article)

Among middle-aged adults, genotype scores predict incident type 2 diabetes but do not improve prediction models based on clinical risk factors including family history and BMI. These clinical factors are more dynamic in adolescence, however.

A genotype score also predicts type 2 diabetes from adolescence over a mean 27 years of follow-up into adulthood but does not improve prediction models based on clinical risk factors assessed in adolescence. (Read the full article)

Survival estimates for preterm infants are vital for counseling parents, informing care, and planning services. Widely use estimates of in-unit survival derived from a large UK population for infants born at <33 weeks’ gestational age have been available since 1999.

These survival charts have been updated and will be of use to clinicians, parents, and managers. An alternative method for graphical representation of survival probabilities is offered: contour survival plots. (Read the full article)

Despite numerous studies, evidence of the association between food-related parenting practices and child weight remains equivocal. Examination of this association within a sample of diverse adolescents is needed to inform anticipatory guidance provided by physicians working with parents of adolescents.

The current study explores associations between food-related parenting practices and weight status in a population-based sample of parent-adolescent pairs. This diverse sample allows for an in-depth examination of the role of gender, race/ethnicity, socioeconomic status, and grade level in this association. (Read the full article)

Botulinum spores are ubiquitous, found in the soil of most countries worldwide, and also in honey. It is well established that ingestion of honey by children aged <1 year can lead to infant botulism.

This study examines the prevalence of honey pacifier use among a pediatric population aged <1 year. We also assessed parental knowledge of the dangers of giving honey to children in this age group. (Read the full article)

Previous studies have reported that former late preterm infants are at increased risk for future learning and behavioral problems; thus it has been suggested that their development be closely monitored.

This population-based study indicates that the risk for attention deficit/hyperactivity disorder and learning disabilities may not be higher in former late preterm infants, and therefore intensive neurodevelopmental follow-up may not be required for all late preterm infants. (Read the full article)

Preschool language delay is associated with poorer academic performance, more limited employment opportunities, and relationship difficulties. Despite its importance within public health, there has been little progress toward effective population-based prevention and intervention approaches to improve outcomes.

It is feasible to identify low language in 4-year-olds on a population basis and deliver a 1-on-1 intervention. By age 5 years, this resulted in better phonological awareness and letter knowledge. There was weak evidence of better expressive, but not receptive, language. (Read the full article)

The etiology of childhood cancers is largely unknown. However, excessive fetal growth has been associated with some childhood cancers. One of the most consistent findings is that high birth weight is associated with an increased risk of childhood leukemia.

Examining large, population-based birth and cancer registry data from 4 Nordic countries, high birth weight was the most strongly associated with risk of many childhood cancers among several measures of fetal growth that have not previously been extensively assessed. (Read the full article)

Although fertility rates among adolescents have declined in recent years, certain groups of adolescent girls remain at risk. Whereas adolescents with major mental illness have many risk factors for teenage pregnancy, their fertility rates have not been yet to be examined.

Fertility rates among adolescent girls with major mental illness are almost 3 times higher than among unaffected adolescents and are not decreasing to the same extent. Mental health considerations are highly important for pregnancy prevention and for perinatal interventions targeting adolescents. (Read the full article)

There are misconceptions regarding childhood phimosis. Textbooks still teach that male children should have retractable foreskin by age 3. Young children are referred for evaluation for phimosis, which is a commonly used diagnosis for postneonatal circumcision.

We found a high prevalence of physiologic phimosis in kindergarten children, up to 44% at age 6. We also reviewed the incidence of other congenital abnormalities in this coastal Chinese city. The management and complications of these conditions were analyzed. (Read the full article)

Asthma is a clinical condition treated mostly at primary care community clinics. Epidemics of asthma exacerbation occur annually with return to school after summer vacation and have been reported in many countries, including Israel.

In 82 234 asthmatic children, unscheduled primary care physician visits and drug prescriptions for asthma exacerbations peaked in September after a summer trough, with a lesser peak in late autumn and fluctuations through the winter months. (Read the full article)

In addition to seizures, school-aged children with epilepsy can have coexisting cognitive and behavioral difficulties, but the spectrum and prevalence of such difficulties are uncertain.

This study provides population-based data on the prevalence of common comorbid cognitive impairments and factors associated with such diagnoses in school-aged children with "active" epilepsy. (Read the full article)

Autism prevalence is reported to be highest among non-Hispanic white children, lower in Hispanic and African American/black children, and highly variable in Asian/Pacific Islanders. More comorbid intellectual disability and delays in expressive language have been observed among Hispanic and African American children.

Maternal nativity is a risk factor for childhood autism in US populations. We observed higher risk of severe autism phenotypes in children of foreign-born black, Central/South American, Filipino, and Vietnamese mothers and US-born African Americans and Hispanics compared with US-born whites. (Read the full article)

Indoor tanning has gained widespread popularity among adolescents and young adults. Incidence rates of early-onset basal cell carcinoma also appear to be rising. Scant evidence exists on the impacts of early exposure and whether it leads to early occurrence of this malignancy.

In a US population-based study, indoor tanning was associated with an elevated risk of basal cell carcinomas occurring at or before the age of 50 years, with an increasing trend in risk with younger age at exposure among adolescents and young adults. (Read the full article)

For newborn infants, extreme hyperbilirubinemia (≥24.5 mg/dL) is associated with risk for severe bilirubin encephalopathy. The causal factor of extreme hyperbilirubinemia is often not established. The genotype of Gilbert syndrome, the UGT1A1*28 allele, is considered a potential risk factor.

The UGT1A1*28 allele was not associated with risk for developing extreme hyperbilirubinemia. (Read the full article)

Using large nationwide registers, we were unable to detect any association between augmentation of labor and ADHD in offspring. Our findings do not support a causal role of perinatal exposure to oxytocin during delivery on the development of ADHD. (Read the full article)

This is the first population-based study regarding the epidemiologic characteristics of pediatric zoster among only those who had contracted varicella.

The herpes zoster (HZ) incidence among only children with varicella infection is higher than previously reported. The HZ incidence increased for children contracting varicella aged <2 years. After a vaccination program, the HZ risk increased for those contracting varicella aged ≥2 years. (Read the full article)

Burns are a leading cause of pediatric emergency department visits and hospitalizations and are often associated with significant long-term physical and psychological consequences and long-term medical and nursing treatments. Little is known of the long-term impacts of burns on mortality.

Children with burns had a 1.6 times greater rate of long-term mortality than a matched population-based cohort of children with no injury. Total mortality burden based on in-hospital deaths alone underestimates the true burden from both minor and severe burns. (Read the full article)

Disparities in asthma morbidity are exacerbated by underutilization of preventive controller medications. Community pharmacies are well positioned for an increased role in population health. The Asthma Medication Ratio, currently used at the patient-level, could be adapted for use at the pharmacy-level.

A newly developed Pharmacy-level Asthma Medication Ratio was associated with population-level childhood asthma morbidity. Collaborative relationships between physicians, community pharmacists, and patients (and families) have the potential to promote testable interventions aimed at reducing asthma morbidity and cross-community disparities. (Read the full article)

Preschool language delay predicts poorer academic performance, employment opportunities, and social relationships. Language for Learning, a systematic, population-based intervention for 4-year-olds with low language, is feasible, acceptable and has short-term benefits, but long-term benefits are unknown.

Population ascertainment at age 4 followed by a yearlong, one-on-one home program benefited phonological skills (an important literacy determinant) at age 6, but not the primary language outcomes. To be cost-effective, future follow-up would need to demonstrate lasting academic benefits. (Read the full article)

De novo mutations of the sodium channel gene SCN1A are the major cause of Dravet syndrome, an infantile-onset epileptic encephalopathy. The incidence of this genetic disorder in the United States is unclear.

Dravet syndrome due to SCN1A mutation is twice as common in the United States as previously thought. Genetic testing should be considered in children with ≥2 prolonged febrile seizures by 1 year of age. (Read the full article)

Linezolid is the first synthetic oxazolidone agent to treat infections caused by Gram-positive pathogens. Infected patients with liver dysfunction (LD) are more likely to suffer from adverse reactions such as thrombocytopenia when standard-dose linezolid is used than patients with LD who didn't use linezolid. Currently, pharmacokinetics data of linezolid in patients with LD are limited. The study aimed to characterize pharmacokinetics parameters of linezolid in patients with LD, identify the factors influencing the pharmacokinetics, and propose an optimal dosage regimen. We conducted a prospective study and established population pharmacokinetics model with the Phoenix NLME. The final model was evaluated by goodness-of-fit plots, bootstrap analysis, and prediction corrected-visual predictive check. A total of 163 concentration samples from 45 patients with LD were adequately described by a one-compartment model with first-order elimination along with prothrombin activity (PTA) and creatinine clearance as significant covariates. Linezolid clearance (CL) was 2.68 L/h (95% confidence interval [CI]: 2.34-3.03 L/h); the volume of distribution (Vd) was 58.34 L (95% CI: 48.00-68.68 L). Model-based simulation indicated that the conventional dose was at risk for overexposure in patients with LD or severe renal dysfunction; reduced dosage (300 mg/12 h) would be appropriate to achieve safe (C_min, ss at 2-8 ug/mL) and effective targets (the ratio of AUC_0-24 at steady state to MIC, 80-100). In addition, for patients with severe LD (PTA <= 20%), the dosage (400 mg/24 h) was sufficient at an MIC <= 2 ug/mL. This study recommended therapeutic drug monitoring for patients with LD.

Carbapenem pharmacokinetic profiles are significantly changed in critically ill patients because of the drastic variability of the patients' physiological parameters. Published population PK studies have mainly focused on specific diseases and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of Extracorporeal Membrane Oxygenation (ECMO) and Continuous Renal Replacement Therapy (CRRT). A two-compartment population PK model with Creatinine clearance (CrCL), body weight (WT), and ECMO as fixed effects was developed using the non-linear mixed effect model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates based on the pharmacokinetic/pharmacodynamic index (f%T>MIC) for the range of clinically relevant minimum inhibitory concentrations(MICs). The results showed that there may be insufficient drug use in the clinical routine drug dose regimen, and 750mg Q6h could achieve a higher treatment success rate. The blood concentrations of imipenem in ECMO patients were lower than that of non-ECMO patients, therefore dosage may need to be increased. The dosage may need adjustment for patients with CrCL ≤ 70ml/min, but dose should be lowered carefully to avoid the insufficient drug exposure. Dose adjustment is not necessary for patients within the WT ranging from 50-80 kg. Due to the large variation in PK profile of imipenem in critically ill patients, TDM should be carried out to optimize drug regimens.

Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations (n=196) were assessed in 78 critically ill patients following continuous infusion of piperacillin/tazobactam (ratio 8:1). The initial dose of 8, 12 or 16 g (piperacillin component) was determined by individual creatinine clearance (CRCL). Piperacillin concentrations were compared to the EUCAST clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L), and the following PK/PD targets were evaluated: 100% fT>1xMIC and 100% fT>4xMIC. A population pharmacokinetic model was developed using NONMEM 7.4.3 consisting of a one-compartment disposition model with linear elimination separated into non-renal and renal (linearly increasing with patient CRCL) clearances. Target attainment was predicted and visualized for all individuals based on the utilized CRCL dosing algorithm. The target of 100% fT>1xMIC was achieved for all patients based on the administered dose, but few patients achieved the target of 100% fT>4xMIC. Probability of target attainment for a simulated cohort of patients showed, that increasing the daily dose by 4 g increments (piperacillin component) did not result in substantially improved target attainment for the 100% fT>4xMIC target. To conclude, in patients with high CRCL combined with high-MIC bacterial infections, even a CI regimen with a daily dose of 24 g may be insufficient to achieve therapeutic concentrations.

Baloxavir marboxil, a prodrug of cap-dependent endonuclease inhibitor, baloxavir acid, reduces the time to improvement of influenza symptoms in patients infected with type A or B influenza virus. To characterize its pharmacokinetics, a population pharmacokinetic model for baloxavir acid was developed using 11846 plasma concentration data items from 1827 subjects including 2341 plasma concentration data items from 664 patients at high risk of influenza complications. A three-compartment model with first-order elimination and first-order absorption with lag time well described the plasma concentration data. Body weight and race were found to be the most important factors influencing clearance and volume of distribution. The exposures in high-risk patients were similar to those in otherwise healthy patients, and no pharmacokinetic difference was identified regarding any risk factors for influenza complications.

Exposure-response analyses were performed regarding the time to improvement of symptoms and the reduction in the influenza virus titer in high-risk patients. The analyses suggested that body weight-based dosage, 40 mg for patients weighing < 80 kg and 80 mg for patients weighing ≥ 80 kg, can shorten the time to improvement of influenza symptoms and reduce virus titer for both type A and B influenza virus regardless of the exposure levels of the high-risk patients as well as for the otherwise healthy influenza patients.

The results of our population pharmacokinetic and exposure-response analyses in patients with risk factors of influenza complications should provide useful information on the pharmacokinetic and pharmacodynamic characteristics of baloxavir marboxil and also for the optimization of dose regimens.

Dihydroartemisinin-piperaquine has shown excellent efficacy and tolerability in malaria treatment. However, concerns have been raised of potentially harmful cardiotoxic effects associated with piperaquine. The population pharmacokinetics and cardiac effects of piperaquine were evaluated in 1,000 patients, mostly children enrolled in a multicentre trial from 10 sites in Africa. A linear relationship described the QTc-prolonging effect of piperaquine, estimating a 5.90ms mean QTc-prolongation per 100ng/mL increase in piperaquine concentration. The effect of piperaquine on absolute QTc-interval estimated a mean maximum QTc-interval of 456ms (EC₅₀=209ng/mL). Simulations from the pharmacokinetic-pharmacodynamic models predicted 1.98-2.46% risk of having QTc-prolongation > 60ms in all treatment settings. Although piperaquine administration resulted in QTc-prolongation, no cardiovascular adverse events were found in these patients. Thus, the use of dihydroartemisinin-piperaquine should not be limited by this concern.

Omadacycline, a novel aminomethylcycline antibiotic with activity against Gram-positive and -negative organisms, including tetracycline-resistant pathogens, received FDA approval in October, 2018 for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). A previously-developed population pharmacokinetic (PK) model based on Phase 1 intravenous and oral PK data was refined using data from infected patients. Data from 10 Phase 1 studies used to develop the previous model were pooled with data from three additional Phase 1 studies, a Phase 1b uncomplicated urinary tract infection study, one Phase 3 CABP study, and two Phase 3 ABSSSI studies. The final population PK model was a three-compartment model with first-order absorption using transit compartments to account for absorption delay following oral dosing and first-order elimination. Epithelial lining fluid (ELF) concentrations were modeled as a sub-compartment of the first peripheral compartment. A food effect on oral bioavailability was included in the model. Sex was the only significant covariate identified, with 15.6% lower clearance for females relative to males. Goodness-of-fit diagnostics indicated a precise and unbiased fit to the data. The final model, which was robust in its ability to predict plasma and ELF exposures following omadacycline administration, was also able to predict the central tendency and variability in concentration-time profiles using an external Phase 3 ABSSSI dataset. A population PK model, which described omadacycline PK in healthy subjects and infected patients, was developed and subsequently used to support pharmacokinetic-pharmacodynamic (PK-PD) and PK-PD target attainment assessments.

Robert Guthrie
Sep 1, 1963; 32:338-343
ARTICLES