Medication safety incidents in paediatric oncology after electronic medication management system implementation

Objective: To explore medication safety issues related to use of an electronic medication management system (EMM) in paediatric oncology practice, through the analysis of patient safety incident reports. Methods: We analysed 827 voluntarily reported incidents relating to oncology patients that occurred over an 18‐month period immediately following implementation of an EMM in a paediatric hospital in Australia. We identified medication‐related and EMM‐related incidents and carried out a content analysis to identify patterns. Results: We found ~79% (n = 651) of incidents were medication‐related and, of these, ~45% (n = 294) were EMM‐related. Medication‐related incidents included issues with: prescribing; dispensing; administration; patient transfers; missing chemotherapy protocols and information on current stage of patient treatment; coordination of chemotherapy administration; handling or storing medications; children or families handling medications. EMM‐related incidents were classified into four groups: technical issues, issues with the user experience, unanticipated problems in EMM workflow, and missing safety features. Conclusions: Incidents reflected difficulties with managing therapies rich in interdependencies. EMM, and especially its ‘automaticity’, contributed to these incidents. As EMM impacts on safety in such high‐risk settings, it is essential that users are aware of and attend to EMM automatic behaviours and are equipped to troubleshoot them

Transition, height and well-being

Using newly available data, we re-evaluate the impact of transition from plan to market on objective and subjective well-being. We find clear evidence of the high social cost of early transition reforms: cohorts born around the start of transition are shorter than their older or younger peers. The difference in height suggests that the first years of reform were accompanied by major deprivation. We provide suggestive evidence on the importance of three mechanisms which partially explain these results: the decline of GDP per capita, the deterioration of healthcare systems, and food scarcity. On the bright side, we find that cohorts that experienced transition in their infancy are now better educated and more satisfied with their lives than their counterparts. Taken together, our results imply that the transition process has been a traumatic experience, but that its negative impact has largely been overcome

Electronic ordering and the management of treatment interdependencies: a qualitative study of paediatric chemotherapy

Background: There are serious safety risks associated with chemotherapy, often associated with interdependencies in regimens administered over months or years. Various strategies are used to manage these risks. Computerized provider order entry (CPOE) systems are also implemented to improve medication safety. Little is known regarding the effect of CPOE on how clinicians manage chemotherapy interdependencies and their associated safety strategies. Methods: We conducted a multi-method qualitative study in a paediatric hospital. We analysed 827 oncology incidents reported following CPOE implementation and carried out semi-structured interviews with doctors (n = 10), nurses (n = 6), a pharmacist, and oncology CPOE team members (n = 2). Results were interpreted according to safety models (ultra-safe, high-reliability organisations [HROs], or ultra-adaptive). Results: Incident reports highlighted two interrelated types of interdependencies: those within organisation of clinical activities and those inherent in chemotherapy regimens. Clinicians reported strategies to address chemotherapy risks and interdependencies. These included rigid rules and ‘no go’ contexts for treatment to proceed, typical of the ultra-safe model; use of time (e.g. planning only so far ahead) and sensitivity to operations, typical of HROs. We identified three different time horizons in CPOE use in relation to patients’ treatments: life-long, the whole regimen, and the ‘here and now’. CPOE supported ultra-safe strategies through automation and access to rules/standardisation, but also created difficulties and contributed to incidents. It supported the ‘here and now’ better than a life-long or whole regimen view of a patient treatment. Sensitivity to operations was essential to anticipate and resolve uncertainties, hazards, CPOE limitations, and mismatches between CPOE processes and workflow in practice. Conclusions: Within oncology, CPOE appears to move the ‘mix’ of risk strategies towards ultra-safe models of safety and protocol-mandated care. However, in order to operate ultra-safe strategies embedded in CPOE and stay on protocol it is essential for clinicians to be thoughtful and show sensitivity to operations in CPOE use. CPOE design can be advanced by better consideration of mechanisms to support interdependencies

Promising 3D in vitro models for studying tumour heterogeneity and testing novel therapeutic approaches in pancreatic cancer

In this study we produced 3D organotypic cultures and spheroids to mimic the complex microenvironment of pancreatic cancer and to test alternative therapeutic strategies

Associations between double-checking and medication administration errors: A direct observational study of paediatric inpatients

Background Double-checking the administration of medications has been standard practice in paediatric hospitals around the world for decades. While the practice is widespread, evidence of its effectiveness in reducing errors or harm is scarce. Objectives To measure the association between double-checking, and the occurrence and potential severity of medication administration errors (MAEs); check duration; and factors associated with double-checking adherence. Methods Direct observational study of 298 nurses, administering 5140 medication doses to 1523 patients, across nine wards, in a paediatric hospital. Independent observers recorded details of administrations and double-checking (independent; primed-one nurse shares information which may influence the checking nurse; incomplete; or none) in real time during weekdays and weekends between 07:00 and 22:00. Observational medication data were compared with patients' medical records by a reviewer (blinded to checking-status), to identify MAEs. MAEs were rated for potential severity. Observations included administrations where double-checking was mandated, or optional. Multivariable regression examined the association between double-checking, MAEs and potential severity; and factors associated with policy adherence. Results For 3563 administrations double-checking was mandated. Of these, 36 (1·0%) received independent double-checks, 3296 (92·5%) primed and 231 (6·5%) no/incomplete double-checks. For 1577 administrations double-checking was not mandatory, but in 26·3% (n=416) nurses chose to double-check. Where double-checking was mandated there was no significant association between double-checking and MAEs (OR 0·89 (0·65-1·21); p=0·44), or potential MAE severity (OR 0·86 (0·65-1·15); p=0·31). Where double-checking was not mandated, but performed, MAEs were less likely to occur (OR 0·71 (0·54-0·95); p=0·02) and had lower potential severity (OR 0·75 (0·57-0·99); p=0·04). Each double-check took an average of 6·4 min (107 hours/1000 administrations). Conclusions Compliance with mandated double-checking was very high, but rarely independent. Primed double-checking was highly prevalent but compared with single-checking conferred no benefit in terms of reduced errors or severity. Our findings raise questions about if, when and how double-checking policies deliver safety benefits and warrant the considerable resource investments required in modern clinical settings

First report in italy of the exotic mosquito species Aedes (Finlaya) koreicus, a potential vector of arboviruses and filariae

BACKGROUND: In the Veneto region (north-eastern Italy) an entomological surveillance system has been implemented since the introduction of the Asian tiger mosquito (Aedes albopictus) in 1991. During the routine monitoring activity in a tiger mosquito-free area, an unexpected mosquito was noticed, which clearly did not belong to the recorded Italian fauna. FINDINGS: At the end of May 2011, twelve larvae and pupae were collected in a small village in Belluno province (Veneto region) from a single manhole. Ten adults reared in the laboratory were morphologically and genetically identified as Aedes (Finlaya) koreicus (Edwards, 1917), a species native to Southeast Asia. The subsequent investigations carried out in the following months in the same village provided evidence that this species had become established locally. Entomological and epidemiological investigations are currently ongoing in the surrounding area, to verify the eventual extension of the species outside the village and to trace back the route of entry into Italy. CONCLUSIONS: This is the first report in Italy of the introduction of the exotic mosquito Ae. koreicus. This species has been shown experimentally to be competent in the transmission of the Japanese encephalitis virus and of the dog heartworm Dirofilaria immitis and is considered a potential vector of other arboviruses. Thus, the establishment of this species may increase the current risk or pose new potential threats, for human and animal health. This finding considerably complicates the entomological monitoring of the Asian tiger mosquito Ae. albopictus in Italy and stresses the importance of implementing the entomological surveillance for the early detection of and the rapid response against invasive mosquito species

Providing psychological support to parents of childhood cancer survivors: ‘cascade’ intervention trial results and lessons for the future

We conducted a three‐armed trial to assess Cascade, a four‐module group videoconferencing cognitive behavior therapy (CBT) intervention for parents of childhood cancer survivors currently aged <18 years. We allocated parents to Cascade, an attention control (peer‐ support group), or a waitlist. The primary outcome was parents’ health‐related quality of life (PedsQL‐Family Impact/EQ‐5D‐5L) six months post‐intervention. Parents also reported their anxiety/depression, parenting self‐agency, fear of recurrence, health service and psychotropic medication use, engagement in productive activities, confidence to use, and actual use of, CBT skills, and their child’s quality of life. Seventy‐six parents opted in; 56 commenced the trial. Cascade achieved good parent engagement and most Cascade parents were satisfied and reported benefits. Some parents expressed concerns about the time burden and the group format. Most outcomes did not differ across trial arms. Cascade parents felt more confident to use more CBT skills than peer-support and waitlisted parents, but this did not lead to more use of CBT. Cascade parents reported lower psychosocial health scores for their child than waitlisted parents. Cascade parents’ health service use, psychotropic medication use, and days engaged in productive activities did not improve, despite some improvements in waitlisted parents. Our trial was difficult to implement, but participants were largely satisfied. Cascade did not improve most outcomes, possibly because many parents were functioning well pre‐enrolment. We used these findings to improve Cascade and will trial the new version in future

Entanglement-enhanced testing of multiple quantum hypotheses

Quantum hypothesis testing has been greatly advanced for the binary discrimination of two states, or two channels. In this setting, we already know that quantum entanglement can be used to enhance the discrimination of two bosonic channels. Here, we remove the restriction of binary hypotheses and show that entangled photons can remarkably boost the discrimination of multiple bosonic channels. More precisely, we formulate a general problem of channel-position finding where the goal is to determine the position of a target channel among many background channels. We prove that, using entangled photons at the input and a generalized form of conditional nulling receiver at the output, we may outperform any classical strategy. Our results can be applied to enhance a range of technological tasks, including the optical readout of sparse classical data, the spectroscopic analysis of a frequency spectrum, and the determination of the direction of a target at fixed range

An MRD-stratified pediatric protocol is as deliverable in adolescents and young adults as in children with ALL

Pediatric regimens have improved outcomes in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL). However, results remain inferior to children with ALL. The Australasian Leukaemia and Lymphoma Group (ALLG) ALL06 study (anzctr.org.au/ ACTRN12611000814976) was designed to assess whether a pediatric ALL regimen (Australian and New Zealand Children’s Haematology and Oncology Group [ANZCHOG] Study 8) could be administered to patients aged 15 to 39 years in a comparable time frame to children as assessed by the proportion of patients completing induction/ consolidation and commencing the next phase of therapy (protocol M or high-risk [HR] treatment) by day 94. Minimal residual disease (MRD) response stratified patients to HR treatment and transplantation. From 2012 to 2018, a total of 86 patients were enrolled; 82 were eligible. Median age was 22 years (range, 16-38 years). Induction/consolidation was equally deliverable in ALL06 as in Study 8. In ALL06, 41.5% (95% confidence interval [CI], 30.7-52.9) commenced protocol M or HR therapy by day 94 vs 39.3% in Study 8 (P = .77). Median time to protocol M/HR treatment was 96 days (interquartile range, 87.5-103 days) in ALL06 vs 98 days in Study 8 (P = .80). Induction mortality was 3.6%. With a median follow-up of 44 months (1-96 months), estimated 3-year disease-free survival was 72.8% (95% CI, 62.8-82.7), and estimated 3-year overall survival was 74.9% (95% CI, 65.3-84.5). End induction/consolidation MRD negativity rate was 58.6%. Body mass index ≥30 kg/m2 and day 79 MRD positivity were associated with poorer disease-free survival and overall survival. Pediatric therapy was safe and as deliverable in AYA patients as in children with ALL. Intolerance of pediatric ALL induction/consolidation is not a major contributor to inferior outcomes in AYA ALL

Measurable residual disease analysis in paediatric acute lymphoblastic leukaemia patients with ABL-class fusions

Background: ABL-class fusions including NUP214-ABL1 and EBF1-PDGFRB occur in high risk acute lymphoblastic leukaemia (ALL) with gene expression patterns similar to BCR-ABL-positive ALL. Our aim was to evaluate new DNA-based measurable residual disease (MRD) tests detecting these fusions and IKZF1-deletions in comparison with conventional immunoglobulin/T-cell receptor (Ig/TCR) markers. Methods: Precise genomic breakpoints were defined from targeted or whole genome next generation sequencing for ABL-fusions and BCR-ABL1. Quantitative PCR assays were designed and used to re-measure MRD in remission bone marrow samples previously tested using Ig/TCR markers. All MRD testing complied with EuroMRD guidelines. Results: ABL-class patients had 46% 5year event-free survival and 79% 5year overall survival. All had sensitive fusion tests giving high concordance between Ig/TCR and ABL-class fusion results (21 patients, n = 257 samples, r2 = 0.9786, P < 0.0001) and Ig/TCR and IKZF1-deletion results (9 patients, n = 143 samples, r2 = 0.9661, P < 0.0001). In contrast, in BCR-ABL1 patients, Ig/TCR and BCR-ABL1 tests were discordant in 32% (40 patients, n = 346 samples, r2 = 0.4703, P < 0.0001) and IKZF1-deletion results were closer to Ig/TCR (25 patients, n = 176, r2 = 0.8631, P < 0.0001). Conclusions: MRD monitoring based on patient-specific assays detecting gene fusions or recurrent assays for IKZF1-deletions is feasible and provides good alternatives to Ig/TCR tests to monitor MRD in ABL-class ALL