Oestrogen treatment for tall stature in girls: estimating the effect on height and the error in height prediction

Objective  To determine the effect of oestrogen treatment on attenuating the growth of tall girls after adjusting for error in height prediction.
Design  Retrospective cohort study.
Patients  Tall girls assessed by Australian paediatric endocrinologists between 1959 and 1993. A total of 279 girls received oestrogen treatment (diethylstilboestrol or ethinyl oestradiol) and 367 girls were assessed but not treated.
Measurements  Estimated mature height (EMH) was calculated using radiographic assessment of bone age in adolescence. Final adult height was self-reported at follow-up. To control for error in the EMH predictions and their different distributions by treatment status, pairs of treated and untreated girls, matched on EMH within 1 cm, were selected for analysis. Covariate adjusted estimates of treatment effect (final height – EMH) were calculated.
Results  In the sample of 108 matched pairs, the mean difference between the final height and EMH was –1·4 cm (SE 0·29) in the treated group and 1·1 cm (SE 0·23) in the untreated group, giving an unadjusted treatment effect of –2·5 cm (95% CI –3·2 to 1·8). A regression model based on 107 pairs of treated and untreated girls contained a significant interaction between bone age at treatment initiation and treatment, which estimated an approximately 1 cm per year decrease in treatment effect. The treatment effect was greatest in those commencing treatment at an early bone age and was significant if initiated before a bone age of 15 years.
Conclusions  On average, oestrogen treatment resulted in an adult height that was less than predicted. Although treatment was more effective in the least mature girls, the mean height difference was relatively modest for most treated girls.     

Understanding rational non-adherence to medications. A discrete choice experiment in a community sample in Australia

ABSTRACT: BACKGROUND: In spite of the potential impact upon population health and expenditure, interventions promoting medication adherence have been found to be of moderate effectiveness and cost effectiveness. Understanding the relative influence of factors affecting patient medication adherence decisions and the characteristics of individuals associated with variation in adherence will lead to a better understanding of how future interventions should be designed and targeted. This study aims to explore medication-taking decisions that may underpin intentional medication non-adherence behaviour amongst a community sample and the relative importance of medication specific factors and patient background characteristics contributing to those decisions. METHODS: A discrete choice experiment conducted through a web-enabled online survey was used to estimate the relative importance of eight medication factors (immediate and long-term medication harms and benefits, cost, regimen, symptom severity, alcohol restrictions) on the preference to continue taking a medication. To reflect more closely what usually occurs in practice, non-disease specific medication and health terms were used to mimic decisions across multiple medications and conditions.161 general community participants, matching the national Australian census data (age, gender) were recruited through an online panel provider (participation rate: 10%) in 2010. RESULTS: Six of the eight factors (i.e. immediate and long-term medication harms and benefits, cost, and regimen) had a significant influence on medication choice. Patient background characteristics did not improve the model. Respondents with private health insurance appeared less sensitive to cost then those without private health insurance. In general, health outcomes, framed as a side-effect, were found to have a greater influence over adherence than outcomes framed as therapeutic benefits. CONCLUSIONS: Medication-taking decisions are the subject of rational choices, influenced by the attributes of treatments and potentially amenable to intervention through education, strategic pricing and the altering of dosing characteristics. Understanding individual treatment preferences is thus an important step to improving adherence support provision in practice. Re-framing future interventions and policies to support rational and informed individual patient choices, is the way forward to realising the full potential health and economic benefits from the efficacious use of medications.     

MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13

Many human aneuploidy syndromes have unique phenotypic consequences, but in most instances it is unclear whether these phenotypes are attributable to alterations in the dosage of specific genes. In human trisomy 13, there is delayed switching and persistence of fetal hemoglobin (HbF) and elevation of embryonic hemoglobin in newborns. Using partial trisomy cases, we mapped this trait to chromosomal band 13q14; by examining the genes in this region, two microRNAs, miR-15a and -16-1, appear as top candidates for the elevated HbF levels. Indeed, increased expression of these microRNAs in primary human erythroid progenitor cells results in elevated fetal and embryonic hemoglobin gene expression. Moreover, we show that a direct target of these microRNAs, MYB, plays an important role in silencing the fetal and embryonic hemoglobin genes. Thus we demonstrate how the developmental regulation of a clinically important human trait can be better understood through the genetic and functional study of aneuploidy syndromes and suggest that miR-15a, -16-1, and MYB may be important therapeutic targets to increase HbF levels in patients with sickle cell disease and β-thalassemia.     

Complications of CT-guided percutaneous needle biopsy of the chest: prevention and management

OBJECTIVE: The objective of this article is to describe potential complications of percutaneous needle biopsy of the chest, discuss the risk factors associated with the development of complications, and explain how to prevent complications and manage complications when they occur. CONCLUSION: Pneumothorax and pulmonary hemorrhage are the most common complications of percutaneous needle biopsy of the chest, whereas air embolism and tumor seeding are extremely rare. Attention to biopsy planning and technique and postprocedural care help to prevent or minimize most potential complications.