Pharmacokinetics of antiretroviral drugs in infancy

Dosing in infancy is complicated by inadequate characterisation of pharmacokinetics, unpredictable drug concentrations and a lack of suitable dosage forms. Additional challenges are presented by the concomitant administration of interacting drugs (e.g. rifampicin in antituberculosis treatment) and disease conditions that may alter drug disposition. The extent and implications of breastmilk transfer of drugs to the infant are poorly understood. New technologies facilitate pharmacokinetic studies in infants and will improve access to therapeutic drug monitoring

Pharmacokinetics and safety of rifabutin in young HIV-infected children receiving rifabutin and lopinavir/ritonavir

ObjectivesCo-treatment of HIV and TB in young children is complicated by limited treatment options and complex drug–drug interactions. Rifabutin is an alternative to rifampicin for adults receiving a ritonavir-boosted PI. We aimed to evaluate the short-term safety and pharmacokinetics of rifabutin when given with lopinavir/ritonavir in children.Patients and methodsWe conducted an open-label study of rifabutin dosed at 5 mg/kg three times a week in HIV-infected children ≤5 years of age receiving lopinavir/ritonavir. Intensive steady-state pharmacokinetic sampling was conducted after six doses. The Division of AIDS 2004, clarification 2009, table for grading severity of adverse events was used to classify drug toxicities. The study was registered with ClinicalTrials.gov, number NCT01259219.ResultsSix children completed the study prior to closure by institutional review boards. The median (range) AUC0–48 of rifabutin was 6.91 (3.52–8.67) μg · h/mL, the median (range) Cmax of rifabutin was 0.39 (0.19–0.46) μg/mL, the median (range) AUC0–48 of 25-O-desacetyl rifabutin was 5.73 (2.85–9.13) μg · h/mL and the median (range) Cmax of 25-O-desacetyl rifabutin was 0.17 (0.08–0.32) μg/mL. The neutrophil count declined in all children; two children experienced grade 4 neutropenia, which resolved rapidly without complications. There was strong correlation between AUC0–48 measures and neutrophil counts.ConclusionsRifabutin dosed at 5 mg/kg three times per week resulted in lower AUC0–48, AUC0–24 and Cmax values for rifabutin and 25-O-desacetyl rifabutin compared with adults receiving 150 mg of rifabutin daily, the current recommended dose. We observed high rates of severe transient neutropenia, possibly due to immaturity of CYP3A4 in young children. It remains unclear whether a safe and effective rifabutin dose exists for treatment of TB in children receiving lopinavir/ritonavir

Defining International Critical Care Pharmacist Contributions to Sepsis and Exploring Variability

Purpose of Review To define international clinical pharmacist contributions to managing sepsis in critically unwell patients and explore variation. Recent Findings Clinical pharmacists improve clinical outcomes and cost efficiencies. They provide pharmaceutical advice on selection, administration, plus monitoring of antimicrobials and supportive therapies. Logistical activities reduce drug administration times. Guideline production, patient/clinician education, prescribing error identification, plus therapeutic optimisation activities are also reported. Summary A survey incorporating semi-structured interviews identified further antimicrobial stewardship, prescribing and digital contributions to optimise sepsis management. However, disparities associated with multidisciplinary team integration and intensive care unit service provision were found. Variability was attributed to multifaceted physical, social, financial, training and education themes. Findings empower collaborations between pharmacists and stakeholders to identify and overcome contribution barriers. Strategies to mitigate barriers and enhance sepsis contributions were envisaged by reported aspirations. These emphasised the importance of professional advocacy, interprofessional education and impactful implementation research

Ash agglomeration and deposition during combustion of poultry litter in a bubbling fluidized-bed combustor

peer-reviewedn this study, we have characterized the ash resulting from fluidized bed combustion of poultry litter as being dominated by a coarse fraction of crystalline ash composed of alkali-Ca-phosphates and a fine fraction of particulate K2SO4 and KCl. Bed agglomeration was found to be coating-induced with two distinct layers present. The inner layer (0.05–0.09 mm thick) was formed due to the reaction of gaseous potassium with the sand (SiO2) surface forming K-silicates with low melting points. Further chemical reaction on the surface of the bed material strengthened the coating forming a molten glassy phase. The outer layer was composed of loosely bound, fine particulate ash originating from the char. Thermodynamic equilibrium calculations showed slag formation in the combustion zone is highly temperature-dependent, with slag formation predicted to increase from 1.8 kg at 600 °C to 7.35 kg at 1000 °C per hour of operation (5.21 kg of ash). Of this slag phase, SiO2 and K2O were the dominant phases, accounting for almost 95%, highlighting the role of K-silicates in initiating bed agglomeration. The remaining 5% was predicted to consist mainly of Al2O3, K2SO4, and Na2O. Deposition downstream in the low-temperature regions was found to occur mostly through the vaporization–condensation mechanism, with equilibrium decreasing significantly with decreasing temperatures. The dominant alkali chloride-containing gas predicted to form in the combustion zone was KCl, which corresponds with the high KCl content in the fine baghouse ash

Intelligent mining of large-scale bio-data: bioinformatics applications

Today, there is a collection of a tremendous amount of bio-data because of the computerized applications worldwide. Therefore, scholars have been encouraged to develop effective methods to extract the hidden knowledge in these data. Consequently, a challenging and valuable area for research in artificial intelligence has been created. Bioinformatics creates heuristic approaches and complex algorithms using artificial intelligence and information technology in order to solve biological problems. Intelligent implication of the data can accelerate biological knowledge discovery. Data mining, as biology intelligence, attempts to find reliable, new, useful and meaningful patterns in huge amounts of data. Hence, there is a high potential to raise the interaction between artificial intelligence and bio-data mining. The present paper argues how artificial intelligence can assist bio-data analysis and gives an up-to-date review of different applications of bio-data mining. It also highlights some future perspectives of data mining in bioinformatics that can inspire further developments of data mining instruments. Important and new techniques are critically discussed for intelligent knowledge discovery of different types of row datasets with applicable examples in human, plant and animal sciences. Finally, a broad perception of this hot topic in data science is given