The effect of Computerised Physician Order Entry on prescribing errors: An interrupted time-series study at a secondary referral hospital in Australia.

BACKGROUND: Computerised Physician Order Entry (CPOE) software is increasingly used across the world to improve medication safety. However, few high-quality studies have reviewed the impact of CPOE on prescribing errors and patient harm. OBJECTIVE: To investigate the effect of a hybrid CPOE-paper prescribing system on prescribing errors at a secondary hospital site. DESIGN: An interrupted time-series study was conducted by identifying prescribing errors via prospective medical chart review before and after the implementation of CPOE across three medical wards. PARTICIPANTS: The medication orders of all patients admitted to the medical wards during the study period were reviewed. INTERVENTION: Implementation of a CPOE across three medical wards. MEASURES: A blinded expert panel risk stratified the errors according to level of severity, preventability and potential for harm. Pearson's chi square and segmented regressions were used to determine if there were differences in prescribing errors pre- and post-CPOE implementation. KEY RESULTS: A total of 10,535 medication orders were reviewed pre-CPOE and 13,841 medication orders reviewed post-CPOE. Analysis demonstrated that after implementation of CPOE there were reductions in the proportion of orders with one or more of any error (-30.1%, 95 %CI: -36.5%, -23.7%, p < 0.001). Reductions in the proportion of orders with one or more errors were seen across the error categories of dosing errors (-20.1%, 95 %CI: -25.1%, -15%, p < 0.001), procedural/administrative errors (-18.9%, 95 %CI: -22.8%, -15%, p < 0.001), and therapeutic errors (-2.6%, 95 %CI: -4.1%, -1%, p = 0.002). Post-CPOE there were reductions in the proportion of orders with at least one non-intercepted serious error (-12.6%, 95 %CI: -16.4%, -8.8%, p < 0.001). CONCLUSION: The introduction of CPOE was associated with reductions in prescribing errors. There is also evidence that this translated into a reduced risk of harm to patients post-CPOE implementation through the reduction in actual adverse drug events.

Family-based cardiac screening in relatives of victims of sudden arrhythmic death syndrome.

AIMS: Sudden arrhythmic death syndrome (SADS) occurs when a person suffers a sudden, unexpected death, with no cause found at postmortem examination. We aimed to describe the cardiac screening outcomes in a population of relatives of SADS victims METHODS AND RESULTS: Prospective and retrospective cohort study of consecutive families attending the Family Heart Screening clinic at the Mater Misericordiae Hospital in Dublin, Ireland, from January 2007 to September 2011. Family members of SADS victims underwent a standard screening protocol. Adjunct clinical and postmortem information was sought on the proband. Families who had an existing diagnosis, or where the proband had epilepsy, were excluded. Of 115 families identified, 73 were found to fit inclusion criteria and were retained for analysis, with data available on 262 relatives. Over half of the screened family members were female, and the mean age was 38.6 years (standard deviation 15.6). In 22 of 73 families (30%), and 36 of 262 family members (13.7%), a potentially inheritable cause of SADS was detected. Of the population screened, 32 patients (12.2%) were treated with medication, and 5 (1.9%) have received implantable cardiac defibrillators. Of the five families with long QT syndrome (LQTS) who had a pathogenic gene mutation identified, three carried two such mutations. CONCLUSION: In keeping with international estimates, 30% of families of SADS victims were found to have a potentially inherited cardiac disease. The most common positive finding was LQTS. Advances in postmortem standards and genetic studies may assist in achieving more diagnoses in these families.

Pairing centers recruit a Polo-like kinase to orchestrate meiotic chromosome dynamics in C. elegans.

Faithful segregation of homologous chromosomes during meiosis requires pairing, synapsis, and crossing-over. In C. elegans, homolog pairing and synapsis depend on pairing centers (PCs), special regions near one end of each chromosome that interact with the nuclear envelope (NE) and cytoplasmic microtubules. Here, we report that PCs are required for nuclear reorganization at the onset of meiosis. We demonstrate that PCs recruit the Polo-like kinase PLK-2 to induce NE remodeling, chromosome pairing, and synapsis. Recruitment of PLK-2 is also required to mediate a cell cycle delay and selective apoptosis of nuclei containing unsynapsed chromosomes, establishing a molecular link between these two quality control mechanisms. This work reveals unexpected functions for the conserved family of Polo-like kinases, and advances our understanding of how meiotic processes are properly coordinated to ensure transmission of genetic information from parents to progeny.

Mutations affecting spindle pole body and mitotic exit network function are synthetically lethal with a deletion of the nucleoporin NUP1 in S. cerevisiae.

Nuclear pore complexes (NPCs) are embedded in the nuclear envelope of eukaryotic cells and function to regulate passage of macromolecules in and out of the nucleus. Nup1 is one of 30 nucleoporins comprising the NPC of the yeast Saccharomyces cerevisiae and is located on the nucleoplasmic face of the NPC where it plays a role in mRNA export and protein transport. In order to further characterize the function of Nup1 we used a genetic approach to identify mutations that are synthetically lethal in combination with a deletion of NUP1 (nup1Delta). We have identified one such nup1 lethal mutant (nle6) as a temperature sensitive allele of nud1. NUD1 encodes a component of the yeast spindle pole body (SPB) and acts as scaffolding for the mitotic exit network (MEN). We observe that nle6/nud1 mutant cells have a normal distribution of NPCs within the nuclear envelope and exhibit normal rates of nuclear protein import at both the permissive and restrictive temperatures. nup1Delta also exhibits synthetic lethality with bub2Delta and bfa1Delta, both of which encode proteins that colocalize with Nud1 at spindle pole bodies and function in the mitotic exit network. However, we do not observe genetic interactions among nle6/nud1, bub2Delta, or bfa1Delta and mutations in the nucleoporin encoding genes NUP60 or NUP170, nor is nup1Delta synthetically lethal with the absence of components downstream in the mitotic exit network, including Lte1, Swi5, and Dbf2. Our results suggest a novel functional connection between Nup1 and proteins comprising both the spindle pole body and early mitotic exit network.