Learning curves, taking instructions, and patient safety:using a theoretical domains framework in an interview study to investigate prescribing errors among trainee doctors

ABSTRACT:

Who makes prescribing decisions in hospital inpatients?:An observational study

Errors involving drug prescriptions are a key target for patient safety initiatives. Recent studies have focused on error rates across different grades of doctors in order to target interventions. However, many prescriptions are not instigated by the doctor who writes them. It is important to clarify how often this occurs in order to interpret these studies and create interventions. This study aimed to provisionally quantify and describe prescriptions where the identity of the decision maker and prescription writer differed.

Maternal Religiosity, Family Resources and Stressors, and Parent-Child Attachment Security in Northern Ireland

This study explores the associations between mothers' religiosity, and families' and children's functioning in a stratified random sample of 695 Catholic and Protestant motherchild dyads in socially deprived areas in Belfast, Northern Ireland, a region which has experienced centuries of sectarian conflict between Protestant Unionists and Catholics Nationalists. Findings based on mother and child surveys indicated that even in this context of historical political violence associated with religious affiliation, mothers' religiosity played a consistently positive role, including associations with multiple indicators of better family functioning (i.e., more cohesion and behavioral control and less conflict, psychological distress, and adjustment problems) and greater parentchild attachment security. Mothers' religiosity also moderated the association between parentchild attachment security and family resources and family stressors, enhancing positive effects of cohesion and mother behavioral control on motherchild attachment security, and providing protection against risks associated with mothers' psychological distress. Findings are discussed in terms of implications for understanding the role of religiosity in serving as a protective or risk factor for children and families.

Clinical outcomes and inflammatory biomarkers in current smokers and exsmokers with severe asthma

Clinical outcomes are worse in current smokers and exsmokers with mild-to-moderate asthma compared with never smokers, but little is known about the influence of smoking status in patients with severe asthma.

Improving attainment across a whole district: school reform through peer tutoring in a randomized controlled trial

Districts are an important unit for administrative purposes, but they vary little in their impact on students’ attainment, at least in the UK. Further, government attempts to raise attainment are often disappointing. The project described in this article aimed to engage schools in reform to change students’ attainment and attitudes in schools across a whole district. The intervention, peer tutoring, has a good research pedigree in small-scale studies, but scaling it up to district-level implementation has not been rigorously evaluated. Over 2 years, 129 elementary schools in 1 Scottish district were randomly assigned to different interventions. The implementation was not perfect, but the results were positive with respect to cross-age tutoring, which had effect sizes of about 0.2. Despite limitations, the study demonstrates that it is possible to carry out a clustered randomized controlled trial (RCT) on a large scale working with districts and suggests that peer tutoring has promise when scaled up.

The Interlaboratory Robustness Of Next-Generation Sequencing (IRON) Study Phase II: Deep-Sequencing Analyses Of Hematological Malignancies Performed In 8,867 Cases By An International Network Involving 27 Laboratories

Introduction: Amplicon deep-sequencing using second-generation sequencing technology is an innovative molecular diagnostic technique and enables a highly-sensitive detection of mutations. As an international consortium we had investigated previously the robustness, precision, and reproducibility of 454 amplicon next-generation sequencing (NGS) across 10 laboratories from 8 countries (Leukemia, 2011;25:1840-8).

Aims: In Phase II of the study, we established distinct working groups for various hematological malignancies, i.e. acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and multiple myeloma. Currently, 27 laboratories from 13 countries are part of this research consortium. In total, 74 gene targets were selected by the working groups and amplicons were developed for a NGS deep-sequencing assay (454 Life Sciences, Branford, CT). A data analysis pipeline was developed to standardize mutation interpretation both for accessing raw data (Roche Amplicon Variant Analyzer, 454 Life Sciences) and variant interpretation (Sequence Pilot, JSI Medical Systems, Kippenheim, Germany).

Results: We will report on the design, standardization, quality control aspects, landscape of mutations, as well as the prognostic and predictive utility of this assay in a cohort of 8,867 cases. Overall, 1,146 primer sequences were designed and tested. In detail, for example in AML, 924 cases had been screened for CEBPA mutations. RUNX1 mutations were analyzed in 1,888 cases applying the deep-sequencing read counts to study the stability of such mutations at relapse and their utility as a biomarker to detect residual disease. Analyses of DNMT3A (n=1,041) were focused to perform landscape investigations and to address the prognostic relevance. Additionally, this working group is focusing on TET2, ASXL1, and TP53 analyses. A novel prognostic model is being developed allowing stratification of AML into prognostic subgroups based on molecular markers only. In ALL, 1,124 pediatric and adult cases have been screened, including 763 assays for TP53 mutations both at diagnosis and relapse of ALL. Pediatric and adult leukemia expert labs developed additional content to study the mutation incidence of other B and T lineage markers such as IKZF1, JAK2, IL7R, PAX5, EP300, LEF1, CRLF2, PHF6, WT1, JAK1, PTEN, AKT1, IL7R, NOTCH1, CREBBP, or FBXW7. Further, the molecular landscape of CLL is changing rapidly. As such, a separate working group focused on analyses including NOTCH1, SF3B1, MYD88, XPO1, FBXW7 and BIRC3. Currently, 922 cases were screened to investigate the range of mutational burden of NOTCH1 mutations for their prognostic relevance. In MDS, RUNX1 mutation analyses were performed in 977 cases. The prognostic relevance of TP53 mutations in MDS was assessed in additional 327 cases, including isolated deletions of chromosome 5q. Next, content was developed targeting genes of the cellular splicing component, e.g. SF3B1, SRSF2, U2AF1, and ZRSR2. In BCR-ABL1-negative MPN, nine genes of interest (JAK2, MPL, TET2, CBL, KRAS, EZH2, IDH1, IDH2, ASXL1) have been analyzed in a cohort of 155 primary myelofibrosis cases searching for novel somatic mutations and addressing their relevance for disease progression and leukemia transformation. Moreover, an assay was developed and applied to CMML cases allowing the simultaneous analysis of 25 leukemia-associated target genes in a single sequencing run using just 20 ng of starting DNA. Finally, nine laboratories are studying CML, applying ultra-deep sequencing of the BCR-ABL1 tyrosine kinase domain. Analyses were performed on 615 cases investigating the dynamics of expansion of mutated clones under various tyrosine kinase inhibitor therapies.

Conclusion: Molecular characterization of hematological malignancies today requires high diagnostic sensitivity and specificity. As part of the IRON-II study, a network of laboratories analyzed a variety of disease entities applying amplicon-based NGS assays. Importantly, the consortium not only standardized assay design for disease-specific panels, but also achieved consensus on a common data analysis pipeline for mutation interpretation. Distinct working groups have been forged to address scientific tasks and in total 8,867 cases had been analyzed thus far.

Would people with Parkinson's disease benefit from palliative care?

Parkinson's disease (PD) is a chronic, progressive, degenerative disorder of the nervous system, causing substantial morbidity and has the capacity to shorten life. People with PD and their families can find the disease devastating. Nevertheless, this population of patients is not usually considered a group to be supported by palliative care specialists. But the nature of the illness and the challenges of managing its many physical and psychological effects raises questions about the potential benefits of a palliative care approach. The purpose of this project was to describe the experience of PD and consider the relevance of palliative care for this population. Semi-structured interviews were conducted with eight people with PD, 21 family caregivers and six health professionals. Five themes were developed from the data analysis: (1) emotional impact of diagnosis; (2) staying connected; (3) enduring financial hardship; (4) managing physical challenges; and (5) finding help for advanced stages. These data revealed that people with PD and family caregivers are confronted with similar issues to people with typical palliative care diagnoses, such as advanced cancer, and that a palliative approach may be helpful in the care of people with PD and their families.

Current treatments in diabetic macular oedema:systematic review and meta-analysis

The aim of this systematic review is to appraise the evidence for the use of anti-VEGF drugs and steroids in diabetic macular oedema (DMO) as assessed by change in best corrected visual acuity (BCVA), central macular thickness and adverse events

Relations Between Political Violence and Child Adjustment: a four-wave test of the role of emotional insecurity about community

This study further explored the impact of sectarian violence and children's emotional insecurity about community on child maladjustment using a 4-wave longitudinal design. The study included 999 mother-child dyads in Belfast, Northern Ireland (482 boys, 517 girls). Across the 4 waves, child mean age was 12.19 (SD = 1.82), 13.24 (SD = 1.83), 13.61 (SD = 1.99), and 14.66 years (SD = 1.96), respectively. Building on previous studies of the role of emotional insecurity in child adjustment, the current study examines within-person change in emotional insecurity using latent growth curve analyses. The results showed that children's trajectories of emotional insecurity about community were related to risk for developing conduct and emotion problems. These findings controlled for earlier adjustment problems, age, and gender, and took into account the time-varying nature of experience with sectarian violence. Discussion considers the implications for children's emotional insecurity about community for relations between political violence and children's adjustment, including the significance of trajectories of emotional insecurity over time.

Social Identity and Youth Aggressive and Delinquent Behaviors in a Context of Political Violence

The goal of the current study was to examine the moderating role of in-group social identity on relations between youth exposure to sectarian antisocial behavior in the community and aggressive behaviors. Participants included 770 mother-child dyads living in interfaced neighborhoods of Belfast. Youth answered questions about aggressive and delinquent behaviors as well as the extent to which they targeted their behaviors toward members of the other group. Structural equation modeling results show that youth exposure to sectarian antisocial behavior is linked with increases in both general and sectarian aggression and delinquency over one year. Reflecting the positive and negative effects of social identity, in-group social identity moderated this link, strengthening the relationship between exposure to sectarian antisocial behavior in the community and aggression and delinquency towards the out-group. However, social identity weakened the effect for exposure to sectarian antisocial behavior in the community on general aggressive behaviors. Gender differences also emerged; the relation between exposure to sectarian antisocial behavior and sectarian aggression was stronger for boys. The results have implications for understanding the complex role of social identity in intergroup relations for youth in post-accord societies.

Social effects of collaborative learning in primary schools

There is conflicting evidence on whether collaborative group work leads to improved classroom relations, and if so how. A before and after design was used to measure the impact on work and play relations of a collaborative learning programme involving 575 students 9e12 years old in single- and mixed-age classes across urban and rural schools. Data were also collected on student interactions and teacher ratings of their group-work skills. Analysis of variance revealed significant gains for both types of relation. Multilevel modelling indicated that better work relations were the product of improving group skills, which offset tensions produced by transactive dialogue, and this effect fed through in turn to play relations. Although before intervention rural children were familiar with each other neither this nor age mix affected outcomes. The results suggest the social benefits of collaborative learning are a separate outcome of group work, rather than being either a pre-condition for, or a direct consequence of successful activity, but that initial training in group skills may serve to enhance these benefits.

The Protective Role of Group Identity: Sectarian Antisocial Behavior and Adolescent Emotion Problems

The protective role of strength of group identity was examined for youth in a context of protracted political conflict. Participants included 814 adolescents (M_age = 13.61, SD = 1.99 at Time 1) participating in a longitudinal study in Belfast, Northern Ireland. Utilizing hierarchical linear modeling, the results show that the effect of exposure to sectarian antisocial behaviors has a stronger effect on youth emotion problems for older adolescents. The results also show that youth with higher strength of group identity reported fewer emotion problems in the face of sectarian antisocial behavior but that this buffering effect is stronger for Protestants compared to Catholics. Implications are discussed for understanding the role of social identity in postaccord societies.

Adolescents' educational outcomes in a social ecology of parenting, family, and community risks in Northern Ireland

This study examines the influence of social ecological risks within the domains of parenting, family environment, and community in the prediction of educational outcomes for 770 adolescents (49% boys, 51% girls, M = 13.6 years, SD = 2.0) living in a setting of protracted political conflict, specifically working class areas of Belfast, Northern Ireland. Controlling for religious community, age, and gender, youths' lower academic achievement was associated with family environments characterized by high conflict and low cohesion. School behaviour problems were related to greater exposure to community violence, or sectarian and nonsectarian antisocial behaviour. Youths' expectations about educational attainment were undermined by conflict in the family environment and antisocial behaviour in the community, as well as parenting low in warmth and behavioural control. Findings underscore the importance of considering family and community contributions to youths' educational outcomes. Suggestions regarding targeted interventions toward promoting resilience are discussed, such as assessing both child and family functioning, developing multidimensional interventions for parents, and building community partnerships, among others.

Pre-storage of gelified reagents in a lab-on-a-foil system for rapid nucleic acid analysis

Reagent pre-storage in a microfluidic chip can enhance operator convenience, simplify the system design, reduce the cost of storage and shipment, and avoid the risk of cross-contamination. Although dry reagents have long been used in lateral flow immunoassays, they have rarely been used for nucleic acid-based point-of-care (POC) assays due to the lack of reliable techniques to dehydrate and store fragile molecules involved in the reaction. In this study, we describe a simple and efficient method for prolonged on-chip storage of PCR reagents. The method is based on gelification of all reagents required for PCR as a ready-to-use product. The approach was successfully implemented in a lab-on-a-foil system, and the gelification process was automated for mass production. Integration of reagents on-chip by gelification greatly facilitated the development of easy-to-use lab-on-a-chip (LOC) devices for fast and cost-effective POC analysis.

A Superfamily of Actin-Binding Proteins at the Actin-Membrane Nexus of Higher Plants

Complex animals use a wide variety of adaptor proteins to produce specialized sites of interaction between actin and membranes. Plants do not have these protein families, yet actin-membrane interactions within plant cells are critical for the positioning of subcellular compartments, for coordinating intercellular communication, and for membrane deformation [1]. Novel factors are therefore likely to provide interfaces at actin-membrane contacts in plants, but their identity has remained obscure. Here we identify the plantspecific Networked (NET) superfamily of actin-binding proteins, members of which localize to the actin cytoskeleton and specify different membrane compartments. The founding member of the NET superfamily, NET1A, is anchored at the plasma membrane and predominates at cell junctions, the plasmodesmata. NET1A binds directly to actin filaments via a novel actin-binding domain that defines a superfamily of thirteen Arabidopsis proteins divided into four distinct phylogenetic clades. Members of other clades identify interactions at the tonoplast, nuclear membrane, and pollen tube plasma membrane, emphasizing the role of this superfamily in mediating actin-membrane interactions.