Impact of haemoglobin variants on the use of haemoglobin A1c for the diagnosis and monitoring of diabetes: a contextualised review.

HbA1c is the established test for monitoring glycaemic control in diabetes, and intervention trials studying the impact of treatment on glycaemic control and risk of complications focus predominantly on this parameter in terms of evaluating the glycaemic outcomes. It is also the main parameter used when targets for control are being individualised, and more recently, it has been used for the diagnosis of type 2 diabetes. For laboratories performing this test and clinicians utilising it in their decision-making process, a thorough understanding of factors that can impact on the accuracy, and appropriate interpretation of the test is essential. The changing demographic in the Irish population over the last two decades has brought this issue sharply into focus. It is therefore timely to review the utility, performance and interpretation of the HbA1c test to highlight factors impacting on the results, specifically the impact of haemoglobin variants, and the impact of these factors on its utilisation in clinical practice.

The pharmacokinetic interaction between ivacaftor and ritonavir in healthy volunteers.

AIMS: The aim of this study was to determine the pharmacokinetic interaction between ivacaftor and ritonavir. METHODS: A liquid chromatography mass spectrometry (LC-MS) method was developed for the measurement of ivacaftor in plasma. An open-label, sequential, cross-over study was conducted with 12 healthy volunteers. Three pharmacokinetic profiles were assessed for each volunteer: ivacaftor 150 mg alone (study A), ivacaftor 150 mg plus ritonavir 50 mg daily (study B), and ivacaftor 150 mg plus ritonavir 50 mg daily after two weeks of ritonavir 50 mg daily (study C). RESULTS: Addition of ritonavir 50 mg daily to ivacaftor 150 mg resulted in significant inhibition of the metabolism of ivacaftor. Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf obv ) increased significantly in both studies B and C compared to study A (GMR [95% CI] 19.71 [13.18-31.33] and 19.77 [14.0-27.93] respectively). Elimination half-life (t1/2 ) was significantly longer in both studies B and C compared to study A (GMR [95% CI] 11.14 [8.72-13.62] and 9.72 [6.68-12.85] respectively). There was no significant difference in any of the pharmacokinetic parameters between study B and study C. CONCLUSION: Ritonavir resulted in significant inhibition of the metabolism of ivacaftor. These data suggest that ritonavir may be used to inhibit the metabolism of ivacaftor in patients with cystic fibrosis (CF). Such an approach may increase the effectiveness of ivacaftor in 'poor responders' by maintaining higher plasma concentrations. It also has the potential to significantly reduce the cost of ivacaftor therapy.

Hormonal contraceptive use in Ireland: trends and co-prescribing practices.

Hormonal contraceptives are highly prevalent. Currently, little is known about Irish hormonal contraceptive trends to date since the 1995 British media contraceptive controversy. The aim of this study was to examine recent trends in contraceptive use in Ireland and to determine the frequency of co-prescriptions with important interacting medications. Approximately 40% of the Irish population are prescribed 70% of total medicines under the Irish GMS scheme. Medicines were identified using the WHO Anatomical Therapeutic Chemical (ATC) classification system. Regression analysis was used to examine trends over time. Of all contraceptives dispensed in 2013, oral contraceptives were used the most (74%) and long acting reversible contraceptives (LARCs) the least (7.5%). Fourth generation combined oral contraceptives (COCs) predominated, although a slight significant decline was shown (P < 0.0001). Second and third generation COCs were significantly increasing and decreasing, respectively (P < 0.0001). Progestin-only pills were significantly increasing (P < 0.0001 across age groups). Low rates of contraceptive co-prescribing with important interacting drugs are shown. However, 93.6% of those on enzyme-inducing anti-epileptic medications were co-prescribed ineffective contraception containing <50 µg oestrogen.Irish prescribing trends of second and third generation COCs have remained consistent since 1995. The slow decline in fourth generation COC uptake follows new evidence of an increased risk of venous thromboembolism (VTE) reported in 2011. The low, but increasing, uptake of LARCs is consistent with other countries. Co-prescribing practices involving hormonal contraceptives requires continued vigilance. This study emphasizes the need to optimize co-prescribing practices involving hormonal contraceptives and anti-epileptic medications and highlights the need to address the barriers to the currently low uptake of LARC methods in Ireland.