Medication administration errors and mortality: Incidents reported in England and Wales between 2007 ̶ 2016

BackgroundMedication administration errors may contribute to patient mortality, thus additional understanding of such incidents is required.ObjectivesTo analyse medication administration errors reported in acute care resulting in death, to identify the drugs concerned, and to describe medication administration error characteristics (location of error, error type, patient's age) by drug group.MethodsMedication administration errors reported in acute care in 2007 ? 2016 (n = 517,384) were obtained from the National Reporting and Learning System for England and Wales. Incidents reported as resulting in death (n = 229) were analysed. Drugs were classified by two researchers using the British National Formulary. Drug categories were described by medication administration errors' year, location, patient age, and error category based on the incidents’ original classification.ResultsErrors were most often reported on wards (66.4%, n = 152), and in patients aged over 75 years (41.5%, n = 95). The most common error category was omitted medicine or ingredient (31.4%, n = 72); most common drug groups were cardiovascular (20.1%, n = 46) and nervous system (10.0%, n = 23). Most errors in patients under 12 years concerned drugs to treat infection; cardiovascular drugs were most common among other age groups.ConclusionsIn order to prevent these most serious of medication administration errors, interventions should focus on avoiding dose omissions, and administration of drugs for patients over 75 years old, as well as safe administration of parenteral anticoagulants and antibacterial drugs.     

GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding,self-association and cellular degradation

GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C > T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (k_cat) and normal affinity for α-D-glucose, and resistance to limited proteolysis by trypsin comparable with wild-type. When stably expressed in HEK293 cells and MIN6 β-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY.     

Treatment with bortezomib‐based regimens improves overall response and predicts for survival in patients with primary or secondary plasma cell leukemia: Analysis of the Greek myeloma study group

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, with poor outcome. Bortezomib‐based regimens (BBR) are highly effective in myeloma, but there is limited information about their efficacy and safety in PCL. Thus, we retrospectively collected data from 42 consecutive PCL patients (25 with primary PCL‐pPCL and 17 with secondary PCL‐sPCL) to explore the role of BBR in this entity. BBR were administered in 29 of 42 patients, while 6 of 25 patients with pPCL underwent autologous transplantation. Objective response (≥partial response) was significantly higher in patients treated with BBR versus conventional therapies (69% vs. 30.8%, P = 0.04); 27.5% of patients treated with BBR achieved at least very good partial response (vgPR). The highest ORR was observed in pPCL patients treated with BBR (88.9%; ≥vgPR: 33.3%). In BBR‐group, grade 3 of 4 hematological, neurological and renal toxicity and neutropenic infections were observed in 41.4%, 7%, 3.4%, and 31%, respectively. With a median follow‐up of 51 months, median overall survival (OS) for patients treated with BBR versus conventional therapies was 13 versus 2 months (P < 0.007). Median OS of patients with pPCL and sPCL treated with BBR was 18 and 7 months, respectively (P < 0.001). In the multivariate analysis normal PLTs, treatment with BBR and high quality response were the only powerful predictors for survival. Our study carrying the longest reported median follow‐up, demonstrated that treatment of PCL with BBR induces high response rates and prolongs survival over conventional therapies, regardless of additional autologous transplantation rescue or established high risk features, with manageable toxicity. Am. J. Hematol. 89:145–150, 2014. © 2013 Wiley Periodicals, Inc.