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Background: Despite numerous published prospective studies, evidence to support use of prophylactic incisional negative pressure wound therapy, for obstetric and gynaecologic surgery, is conflicting. Aim: To evaluate if wound-related presentations to hospital were reduced following introduction of a guideline promoting selective use of prophylactic incisional negative pressure wound therapy. Methods: This was an observational cohort study. Electronic medical records were reviewed for all hospital presentations, within 30 days of primary surgery performed by laparotomy, where the responsible clinician was an obstetrician or gynaecologist. Rates of wound complications and costs associated with admission were compared pre- and post-guideline. Results: Among all those who underwent caesarean birth (n = 2788) or gynaecologic laparotomy (n= 263), 5% presented to hospital with SSI, and 1% with non-infected wound problems. No significant reductions in SSI hospital presentations, length of stay, or readmission costs were observed post-implementation. Likewise, no improvements were observed for non-infected wound problems or a composite of SSI and non-infected wound problems. Conclusions: This study does not support the selective approach used to direct prophylactic incisional negative pressure wound therapy. Further studies are required to better individualise risk assessment, and to determine if negative pressure wound therapy can reduce serious morbidity of SSI. When robust evidence is lacking, local outcomes should be evaluated systematically and reviewed before new treatments become standard care.

In February 2019, the Population Approach Group of Australia and New Zealand (PAGANZ) celebrated 20 years of providing education, mentoring, and support to the Australasian pharmacometrics community. This article provides insight into the history of this group and its operations to the present date. Refereed/Peer-reviewed

BACKGROUND AND OBJECTIVES: We aimed to study the impact of size, maturation and cytochrome P450 2D6 (CYP2D6) genotype activity score as predictors of intravenous tramadol disposition.METHODS: Tramadol and O-desmethyl tramadol (M1) observations in 295 human subjects (postmenstrual age 25 weeks to 84.8 years, weight 0.5-186 kg) were pooled. A population pharmacokinetic analysis was performed using a two-compartment model for tramadol and two additional M1 compartments. Covariate analysis included weight, age, sex, disease characteristics (healthy subject or patient) and CYP2D6 genotype activity. A sigmoid maturation model was used to describe age-related changes in tramadol clearance (CLPO), M1 formation clearance (CLPM) and M1 elimination clearance (CLMO). A phenotype-based mixture model was used to identify CLPM polymorphism.RESULTS: Differences in clearances were largely accounted for by maturation and size. The time to reach 50 % of adult clearance (TM50) values was used to describe maturation. CLPM (TM50 39.8 weeks) and CLPO (TM50 39.1 weeks) displayed fast maturation, while CLMO matured slower, similar to glomerular filtration rate (TM50 47 weeks). The phenotype-based mixture model identified a slow and a faster metabolizer group. Slow metabolizers comprised 9.8 % of subjects with 19.4 % of faster metabolizer CLPM. Low CYP2D6 genotype activity was associated with lower (25 %) than faster metabolizer CLPM, but only 32 % of those with low genotype activity were in the slow metabolizer group.CONCLUSIONS: Maturation and size are key predictors of variability. A two-group polymorphism was identified based on phenotypic M1 formation clearance. Maturation of tramadol elimination occurs early (50 % of adult value at term gestation).

To study the use of size, maturation and CYP2D6 genotype score as predictors of i.v. tramadol (M) disposition throughout human life, published observations were pooled [1-6].