Activity and toxicity of intramuscular 1000 iu/m2 polyethylene glycol-E. coli L-asparaginase in the UKALL 2003 and UKALL 2011 clinical trials.

In successive UK clinical trials (UKALL 2003, UKALL 2011) for paediatric acute lymphoblastic leukaemia (ALL), polyethylene glycol-conjugated E. coli L-asparaginase (PEG-EcASNase) 1000 iu/m2 was administered intramuscularly with risk-stratified treatment. In induction, patients received two PEG-EcASNase doses, 14 days apart. Post-induction, non-high-risk patients (Regimens A, B) received 1-2 doses in delayed intensification (DI) while high-risk Regimen C patients received 6-10 PEG-EcASNase doses, including two in DI. Trial substudies monitored asparaginase (ASNase) activity, ASNase-related toxicity and ASNase-associated antibodies (total, 1112 patients). Median (interquartile range) trough plasma ASNase activity (14 ± 2 days post dose) following first and second induction doses and first DI dose was respectively 217 iu/l (144-307 iu/l), 265 iu/l (165-401 iu/l) and 292 iu/l (194-386 iu/l); 15% (138/910) samples showed subthreshold ASNase activity (<100 iu/l) at any trough time point. Older age was associated with lower (regression coefficient -9.5; p < 0.0001) and DI time point with higher ASNase activity (regression coefficient 29.9; p < 0.0001). Clinical hypersensitivity was observed in 3.8% (UKALL 2003) and 6% (UKALL 2011) of patients, and in 90% or more in Regimen C. A 7% (10/149) silent inactivation rate was observed in UKALL 2003. PEG-EcASNase schedule in UKALL paediatric trials is associated with low toxicity but wide interpatient variability. Therapeutic drug monitoring potentially permits optimisation through individualised asparaginase dosing.

Participatory approaches to reaching the Sustainable Development Goals: Cyprus: leaving no one behind: Cyprus puts universal health coverage in place

Until recently, there was no universal health system in Cyprus. Health care was provided by two uncoordinated subsystems, which led to inefficiencies. While around 75% of the population was entitled to health care in public facilities, financed by general taxation, many still opted for private health care and paid out of pocket. As a result, the rate of out-of-pocket expenditure in Cyprus is among the highest in the European Union (EU), exceeding 45% of total health spending, compared to an EU28 average of 22% in 2016. Furthermore, the dual system had no links between public and private providers to ensure the continuity of care. This briefing addresses SDG 3 (good health and well-being), target 3.8 (achieve universal health coverage, including financial risk protection, access to quality essential health-care services and access to safe, effective, quality and affordable essential medicines and vaccines for all) and SDG 10 (reduced inequalities). It also addresses strategic direction 5 of the WHO “Roadmap to implement the 2030 Agenda for Sustainable Development, building on Health 2020” due to its focus on strengthening health systems for universal health coverage.