Understanding the influences on successful quality improvement in emergency general surgery: learning from the RCS Chole-QuIC project

Abstract: Background: Acute gallstone disease is the highest volume Emergency General Surgical presentation in the UK. Recent data indicate wide variations in the quality of care provided across the country, with national guidance for care delivery not implemented in most UK hospitals. Against this backdrop, the Royal College of Surgeons of England set up a 13-hospital quality improvement collaborative (Chole-QuIC) to support clinical teams to reduce time to surgery for patients with acute gallstone disease requiring emergency cholecystectomy. Methods: Prospective, mixed-methods process evaluation to answer the following: (1) how was the collaborative delivered by the faculty and received, understood and enacted by the participants; (2) what influenced teams’ ability to improve care for patients requiring emergency cholecystectomy? We collected and analysed a range of data including field notes, ethnographic observations of meetings, and project documentation. Analysis was based on the framework approach, informed by Normalisation Process Theory, and involved the creation of comparative case studies based on hospital performance during the project. Results: Chole-QuIC was delivered as planned and was well received and understood by participants. Four hospitals were identified as highly successful, based upon a substantial increase in the number of patients having surgery in line with national guidance. Conversely, four hospitals were identified as challenged, achieving no significant improvement. The comparative analysis indicate that six inter-related influences appeared most associated with improvement: (1) achieving clarity of purpose amongst site leads and key stakeholders; (2) capacity to lead and effective project support; (3) ideas to action; (4) learning from own and others’ experience; (5) creating additional capacity to do emergency cholecystectomies; and (6) coordinating/managing the patient pathway. Conclusion: Collaborative-based quality improvement is a viable strategy for emergency surgery but success requires the deployment of effective clinical strategies in conjunction with improvement strategies. In particular, achieving clarity of purpose about proposed changes amongst key stakeholders was a vital precursor to improvement, enabling the creation of additional surgical capacity and new pathways to be implemented effectively. Protected time, testing ideas, and the ability to learn quickly from data and experience were associated with greater impact within this cohort

Inherited variation in immune genes and pathways and glioblastoma risk

To determine whether inherited variations in immune function single-nucleotide polymorphisms (SNPs), genes or pathways affect glioblastoma risk, we analyzed data from recent genome-wide association studies in conjunction with predefined immune function genes and pathways. Gene and pathway analyses were conducted on two independent data sets using 6629 SNPs in 911 genes on 17 immune pathways from 525 glioblastoma cases and 602 controls from the University of California, San Francisco (UCSF) and a subset of 6029 SNPs in 893 genes from 531 cases and 1782 controls from MD Anderson (MDA). To further assess consistency of SNP-level associations, we also compared data from the UK (266 cases and 2482 controls) and the Mayo Clinic (114 cases and 111 controls). Although three correlated epidermal growth factor receptor (EGFR) SNPs were consistently associated with glioblastoma in all four data sets (Mantel–Haenzel P values = 1 × 10−5 to 4 × 10−3), independent replication is required as genome-wide significance was not attained. In gene-level analyses, eight immune function genes were significantly (minP < 0.05) associated with glioblastoma; the IL-2RA (CD25) cytokine gene had the smallest minP values in both UCSF (minP = 0.01) and MDA (minP = 0.001) data sets. The IL-2RA receptor is found on the surface of regulatory T cells potentially contributing to immunosuppression characteristic of the glioblastoma microenvironment. In pathway correlation analyses, cytokine signaling and adhesion–extravasation–migration pathways showed similar associations with glioblastoma risk in both MDA and UCSF data sets. Our findings represent the first systematic description of immune genes and pathways that characterize glioblastoma risk

Microdissection of Shoot Meristem Functional Domains

The shoot apical meristem (SAM) maintains a pool of indeterminate cells within the SAM proper, while lateral organs are initiated from the SAM periphery. Laser microdissection–microarray technology was used to compare transcriptional profiles within these SAM domains to identify novel maize genes that function during leaf development. Nine hundred and sixty-two differentially expressed maize genes were detected; control genes known to be upregulated in the initiating leaf (P0/P1) or in the SAM proper verified the precision of the microdissections. Genes involved in cell division/growth, cell wall biosynthesis, chromatin remodeling, RNA binding, and translation are especially upregulated in initiating leaves, whereas genes functioning during protein fate and DNA repair are more abundant in the SAM proper. In situ hybridization analyses confirmed the expression patterns of six previously uncharacterized maize genes upregulated in the P0/P1. P0/P1-upregulated genes that were also shown to be downregulated in leaf-arrested shoots treated with an auxin transport inhibitor are especially implicated to function during early events in maize leaf initiation. Reverse genetic analyses of asceapen1 (asc1), a maize D4-cyclin gene upregulated in the P0/P1, revealed novel leaf phenotypes, less genetic redundancy, and expanded D4-CYCLIN function during maize shoot development as compared to Arabidopsis. These analyses generated a unique SAM domain-specific database that provides new insight into SAM function and a useful platform for reverse genetic analyses of shoot development in maize

Early life patterns of common infection: a latent class analysis

Early life infection has been implicated in the aetiology of many chronic diseases, most often through proxy measures. Data on ten infectious symptoms were collected by parental questionnaire when children were 6 months old as part of the Avon Longitudinal Study of Parents and Children, United Kingdom. A latent class analysis was used to identify patterns of infection and their relationship to five factors commonly used as proxies: sex, other children in the home, maternal smoking, breastfeeding and maternal education. A total of 10,032 singleton children were included in the analysis. Five classes were identified with differing infectious disease patterns and children were assigned to the class for which they had a highest probability of membership based on their infectious symptom profile: ‘general infection’ (n = 1,252, 12.5%), ‘gastrointestinal’ (n = 1,902, 19.0%), ‘mild respiratory’ (n = 3,560, 35.5%), ‘colds/ear ache’ (n = 462, 4.6%) and ‘healthy’ (n = 2,856, 28.5%). Females had a reduced risk of being in all infectious classes, other children in the home were associated with an increased risk of being in the ‘general infection’, ‘mild respiratory’ or ‘colds/ear ache’ class. Breastfeeding reduced the risk of being in the ‘general infection’ and ‘gastrointestinal’ classes whereas maternal smoking increased the risk of membership. Higher maternal education was associated with an increased risk of being in the ‘mild respiratory’ group. Other children in the home had the greatest association with infectious class membership. Latent class analysis provided a flexible method of investigating the relationship between multiple symptoms and demographic and lifestyle factors

Mobile phone use and risk of glioma in adults: case-control study

Objective To investigate the risk of glioma in adults in relation to mobile phone use. Design Population based case-control study with collection of personal interview data. Setting Five areas of the United Kingdom. Participants 966 people aged 18 to 69 years diagnosed with a glioma from 1 December 2000 to 29 February 2004 and 1716 controls randomly selected from general practitioner lists. Main outcome measures Odds ratios for risk of glioma in relation to mobile phone use. Results The overall odds ratio for regular phone use was 0.94 (95% confidence interval 0.78 to 1.13). There was no relation for risk of glioma and time since first use, lifetime years of use, and cumulative number of calls and hours of use. A significant excess risk for reported phone use ipsilateral to the tumour (1.24, 1.02 to 1.52) was paralleled by a significant reduction in risk (0.75, 0.61 to 0.93) for contralateral use. Conclusions Use of a mobile phone, either in the short or medium term, is not associated with an increased risk of glioma. This is consistent with most but not all published studies. The complementary positive and negative risks associated with ipsilateral and contralateral use of the phone in relation to the side of the tumour might be due to recall bias

Antagonistic Interaction of BLADE-ON-PETIOLE1 and 2 with BREVIPEDICELLUS and PENNYWISE Regulates Arabidopsis Inflorescence Architecture1[C][W][OA]

The transition to flowering in many plant species, including Arabidopsis (Arabidopsis thaliana), is marked by the elongation of internodes to make an inflorescence upon which lateral branches and flowers are arranged in a characteristic pattern. Inflorescence patterning relies in part on the activities of two three-amino-acid loop-extension homeodomain transcription factors: BREVIPEDICELLUS (BP) and PENNYWISE (PNY) whose interacting products also promote meristem function. We examine here the genetic interactions between BP-PNY whose expression is up-regulated in stems at the floral transition, and the lateral organ boundary genes BLADE-ON-PETIOLE1 (BOP1) and BOP2, whose expression is restricted to pedicel axils. Our data show that bp and pny inflorescence defects are caused by BOP1/2 gain of function in stems and pedicels. Compatible with this, inactivation of BOP1/2 rescues these defects. BOP expression domains are differentially enlarged in bp and pny mutants, corresponding to the distinctive patterns of growth restriction in these mutants leading to compacted internodes and clustered or downward-oriented fruits. Our data indicate that BOP1/2 are positive regulators of KNOTTED1-LIKE FROM ARABIDOPSIS THALIANA6 expression and that growth restriction in BOP1/2 gain-of-function plants requires KNOTTED1-LIKE FROM ARABIDOPSIS THALIANA6. Antagonism between BOP1/2 and BP is explained in part by their reciprocal regulation of gene expression, as evidenced by the identification of lignin biosynthetic genes that are repressed by BP and activated by BOP1/2 in stems. These data reveal BOP1/2 gain of function as the basis of bp and pny inflorescence defects and reveal how antagonism between BOP1/2 and BP-PNY contributes to inflorescence patterning in a model plant species

Allergy and glioma risk: Test of association by genotype

Although epidemiological studies have suggested an association between atopy and glioma risk, these observations have been based on self-reporting of allergic conditions raising the possibility that associations may be noncausal and arise as a consequence of bias, reverse causation or other artifacts. Genetic information provides an alternative approach to investigate the relationship avoiding such biases. We analyzed 1,878 glioma cases and 3,670 controls for variants at 2q12, 5q12.1, 11q13 and 17q21 that are associated with asthma or eczema risk at p < 5.0 × 10−7. The SNP rs7216389, which tags the 3′ flanking region of ORMDL3 at 17q21 and has been associated with childhood asthma, was correlated with increased glioma risk (OR = 1.10; 95% CI: 1.01–1.19). These data provide evidence for a correlation between asthma susceptibility and glioma risk and illustrate the value of using genetics as an investigative tool for developing etiological hypotheses