AIMSSaliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates.
METHODSDatabases were searched up to and including September 2016. Studies were included based on PICO as follows: P: infants and neonates being treated with any medication, I: salivary TDM vs. C: traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data.
RESULTSTwenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent/very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Any compound with an acid dissociation constant (pKa) within physiological range (pH 6-8) gave a more varied response.
CONCLUSIONThere is significant potential for infantile saliva testing and in particular for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude, any compound with a pKa within physiological range (pH 6-8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.
Although genome sequencing is increasingly available in clinical and research settings, many questions remain about the interpretation of sequencing data. In the MedSeq Project, we explored how much effort is required to evaluate and report on more than 4,500 genes reportedly associated with monogenic conditions, as well as pharmacogenomic (PGx) markers, blood antigen serotyping, and polygenic risk scores in 100 individuals (50 with cardiomyopathy and 50 healthy) randomized to the sequencing arm. We defined the quality thresholds for determining the need for Sanger confirmation. Finally, we examined the effort needed and new findings revealed by reanalyzing each genome (6-23 months after initial analysis; mean 13 months). Monogenic disease risk and carrier status were reported in 21% and 94% of participants, respectively. Only two participants had no monogenic disease risk or carrier status identified. For the PGx results (18 genotypes in six genes for five drugs), the identified diplotypes prompted recommendation for non-standard dosing of at least one of the analyzed drugs in 95% of participants. For blood antigen studies, we found that 31% of participants had a rare blood antigen genotype. In the cardiomyopathy cohort, an explanation for disease was identified in 48% of individuals. Over the course of the study, 14 variants were reclassified and, upon reanalysis, 18 new variants met criteria for reporting. These findings highlight the quantity of medically relevant findings from a broad analysis of genomic sequencing data as well as the need for periodic reinterpretation and reanalysis of data for both diagnostic indications and secondary findings.
The development of a pronounced iliotibial band (ITB) is an anatomically distinct evolution of humans. The mechanical behaviour of this “new” structure is still poorly understood and hotly debated in current literature. Iliotibial band syndrome (ITBS) is one of the leading causes of lateral knee pain injuries in runners. We currently lack a comprehensive understanding of the healthy behaviour of the ITB, and this is necessary prior to further investigating the aetiology of pathologies like ITBS. Therefore, the purpose of this narrative review was to collate the anatomical, biomechanical and clinical literature to understand how the mechanical function of the ITB is influenced by anatomical variation, posture and muscle activation. The complexity of understanding the mechanical function of the ITB is due, in part, to the presence of its two in-series muscles: gluteus maximus (GMAX) and tensor fascia latae (TFL). At present, we lack a fundamental understanding of how GMAX and TFL transmit force through the ITB and what mechanical role the ITB plays for movements like walking or running. While there is a range of proposed ITBS treatment strategies, robust evidence for effective treatments is still lacking. Interventions that directly target the running biomechanics suspected to increase either ITB strain or compression of lateral knee structures may have promise, but clinical randomised controlled trials are still required.
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