Pharmacovigilance of biosimilars and other biologicals within the hospital : current practices and future challenges

In the coming decade, many patents for biological pharmaceuticals will expire. Consequently, the market for biosimilars has the potential to grow rapidly. For safety reasons, the more extensive use of a greater variety of biologicals increases the importance of adequate traceability of each administered product and batch. In essence, accurate pharmacovigilance and post-marketing surveillance are needed. This paper summarizes the associated challenges faced by hospitals, and their role in the current and future pharmacovigilance of biosimilars and other biologicals. Recent experience at the Ghent University Hospital in Belgium is described to provide an example of the contribution hospitals can make to the improved pharmacovigilance of biologicals

Evaluation of human albumin use in a university hospital in Belgium

In 1996 - 1997, a drug use evaluation (DUE) of human albumin was conducted in the Ghent University Hospital (Belgium) to determine the pattern and appropriateness of the albumin use. The DUE was followed by permanent review of the albumin consumption. This paper describes how the DUE was carried out and how the albumin use in our hospital changed over time. Method: The study was based on criteria for indications and end of treatment, accepted by consensus of the physicians prescribing albumin. Albumin treatment episodes were classified as appropriate or inappropriate according to these criteria. Results: For 115 treatment episodes in 90 patients, the researchers found 21 (18.3%) deviations from the developed criteria. After analysis, half out of them were considered as minor. Most deviations involved starting treatment too early (n = 17). Follow-up results indicated that the overall consumption of albumin dropped by 50.1% from 1994 to 1999, while the consumption of colloid solutions during the same period remained stable. Conclusion: A good compliance with internally developed criteria for indications and end of treatment with human albumin was observed. Discussion with the clinicians involved led to the development of stricter criteria and a continuous decrease in albumin consumption

Elastin fragmentation inatheroscleroticmice leads to intraplaque neovascularization, plaque rupture, myocardial infarction, stroke, and sudden death

AIMS: There is a need for animal models of plaque rupture. We previously reported that elastin fragmentation, due to a mutation (C1039G(+/−)) in the fibrillin-1 (Fbn1) gene, promotes atherogenesis and a highly unstable plaque phenotype in apolipoprotein E deficient (ApoE(−/−)) mice on a Western-type diet (WD). Here, we investigated whether plaque rupture occurred in ApoE(−/−)Fbn1(C1039G+/−) mice and was associated with myocardial infarction, stroke, and sudden death. METHODS AND RESULTS: Female ApoE(−/−)Fbn1(C1039G+/−) and ApoE(−/−) mice were fed a WD for up to 35 weeks. Compared to ApoE(−/−) mice, plaques of ApoE(−/−)Fbn1(C1039G+/−) mice showed a threefold increase in necrotic core size, augmented T-cell infiltration, a decreased collagen I content (70 ± 10%), extensive neovascularization, intraplaque haemorrhage, and a significant increase in matrix metalloproteinase-2, -9, -12, and -13 expression or activity. Plaque rupture was observed in 70% of ascending aortas and in 50% of brachiocephalic arteries of ApoE(−/−)Fbn1(C1039G+/−) mice. In ApoE(−/−) mice, plaque rupture was not seen in ascending aortas and only in 10% of brachiocephalic arteries. Seventy percent of ApoE(−/−)Fbn1(C1039G+/−) mice died suddenly, whereas all ApoE(−/−) mice survived. ApoE(−/−)Fbn1(C1039G+/−) mice showed coronary plaques and myocardial infarction (75% of mice). Furthermore, they displayed head tilt, disorientation, and motor disturbances (66% of cases), disturbed cerebral blood flow (73% of cases; MR angiograms) and brain hypoxia (64% of cases), indicative of stroke. CONCLUSIONS: Elastin fragmentation plays a key role in plaque destabilization and rupture. ApoE(−/−)Fbn1(C1039G+/−) mice represent a unique model of acute plaque rupture with human-like complications

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04-1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15-1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7-3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64-7.71) and mortality (RR=19.80; 95% CI, 5.87-66.7). Conclusions: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants