A realist analysis of hospital patient safety in Wales:Applied learning for alternative contexts from a multisite case study

Background: Hospital patient safety is a major social problem. In the UK, policy responses focus on the introduction of improvement programmes that seek to implement evidence-based clinical practices using the Model for Improvement, Plan-Do-Study-Act cycle. Empirical evidence that the outcomes of such programmes vary across hospitals demonstrates that the context of their implementation matters. However, the relationships between features of context and the implementation of safety programmes are both undertheorised and poorly understood in empirical terms. Objectives: This study is designed to address gaps in conceptual, methodological and empirical knowledge about the influence of context on the local implementation of patient safety programmes. Design: We used concepts from critical realism and institutional analysis to conduct a qualitative comparative-intensive case study involving 21 hospitals across all seven Welsh health boards. We focused on the local implementation of three focal interventions from the 1000 Lives+ patient safety programme: Improving Leadership for Quality Improvement, Reducing Surgical Complications and Reducing Health-care Associated Infection. Our main sources of data were 160 semistructured interviews, observation and 1700 health policy and organisational documents. These data were analysed using the realist approaches of abstraction, abduction and retroduction. Setting: Welsh Government and NHS Wales. Participants: Interviews were conducted with 160 participants including government policy leads, health managers and professionals, partner agencies with strategic oversight of patient safety, advocacy groups and academics with expertise in patient safety. Main outcome measures: Identification of the contextual factors pertinent to the local implementation of the 1000 Lives+ patient safety programme in Welsh NHS hospitals. Results: An innovative conceptual framework harnessing realist social theory and institutional theory was produced to address challenges identified within previous applications of realist inquiry in patient safety research. This involved the development and use of an explanatory intervention–context–mechanism–agency–outcome (I-CMAO) configuration to illustrate the processes behind implementation of a change programme. Our findings, illustrated by multiple nested I-CMAO configurations, show how local implementation of patient safety interventions are impacted and modified by particular aspects of context: specifically, isomorphism, by which an intervention becomes adapted to the environment in which it is implemented; institutional logics, the beliefs and values underpinning the intervention and its source, and their perceived legitimacy among different groups of health-care professionals; and the relational structure and power dynamics of the functional group, that is, those tasked with implementing the initiative. This dynamic interplay shapes and guides actions leading to the normalisation or the rejection of the patient safety programme. Conclusions: Heightened awareness of the influence of context on the local implementation of patient safety programmes is required to inform the design of such interventions and to ensure their effective implementation and operationalisation in the day-to-day practice of health-care teams. Future work is required to elaborate our conceptual model and findings in similar settings where different interventions are introduced, and in different settings where similar innovations are implemented. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Risk factors for nosocomial bloodstream infections.

A retrospective study of 205 patients was performed to identify the risk factors associated with nosocomial bloodstream infection (BSI). The study occurred during a 5-month period in four medical-surgical intensive care units (ICUs) in Athens, Greece. Risk factors were determined using single and multivariate analyses. Thirty-five patients developed nosocomial BSI (17.1%). The incidence density (defined as the number of new cases of BSI divided by the total of patient-days in the population studied; Jarvis, 1997) of BSI was 14.3 per 1000 patient-days (total number of days that patients are in the ICU during the selected time period). A multivariate model showed that only three factors were significantly and independently responsible for nosocomial BSI: the length of ICU stay (adjusted odds ratios (AOR) 1.052, 95% confidence interval (CI) 1.018-1.087, P = 0.002); the presence of trauma at admission (AOR 2.622, 95% CI 1.074-6.404, P = 0.034); and nosocomial ventilator-associated pneumonia (AOR 6.153, 95% CI 2.305-16.422, P = 0.000). These results show that the factors that had most influence on the development of nosocomial BSI were those factors associated with the treatment received by patients during ICU stay

BET Proteins Are Required for Transcriptional Activation of the Senescent Islet Cell Secretome in Type 1 Diabetes

Type 1 diabetes (T1D) results from the progressive loss of pancreatic beta cells as a result of autoimmune destruction. We recently reported that during the natural history of T1D in humans and the female nonobese diabetic (NOD) mouse model, beta cells acquire a senescence-associated secretory phenotype (SASP) that is a major driver of disease onset and progression, but the mechanisms that activate SASP in beta cells were not explored. Here, we show that the SASP in islet cells is transcriptionally controlled by Bromodomain ExtraTerminal (BET) proteins, including Bromodomain containing protein 4 (BRD4). A chromatin analysis of key beta cell SASP genes in NOD islets revealed binding of BRD4 at active regulatory regions. BET protein inhibition in NOD islets diminished not only the transcriptional activation and secretion of SASP factors, but also the non-cell autonomous activity. BET protein inhibition also decreased the extent of SASP induction in human islets exposed to DNA damage. The BET protein inhibitor iBET-762 prevented diabetes in NOD mice and also attenuated SASP in islet cells in vivo. Taken together, our findings support a crucial role for BET proteins in the activation of the SASP transcriptional program in islet cells. These studies suggest avenues for preventing T1D by transcriptional inhibition of SASP.AlumniNon UBCReviewedFacult

Infection probability score, apache II and karnofsky scoring systems as predictors of infection onset in haematology-oncology patients

Aim: To assess the predictive power of three systems: Infection Probability Score, APACHE II and KARNOFSKY score to the onset of healthcare-associated infections in haematology-oncology patients. Background: The high incidence of healthcare-associated infections is a frequent problem in haematology-oncology patients that affects morbidity and mortality of these patients. Design: A retrospective surveillance survey. Method: The survey was conducted for seven months in the haematology unit of a general hospital in Greece to assess the predictive power of Infection Probability Score, APACHE II and KARNOFSKY score to the onset of healthcare-associated infections. The sample consisted of 102 hospitalised patients. The diagnosis of healthcare-associated infections was based on the definitions proposed by CDC. Results: Among the participants, 53 (52%) were males and 49 (48%) were females with a mean age of 53·30 (SD 18·59) years old (range, 17-85 years). The incidence density of healthcare-associated infections (the number of new cases of healthcare-associated infections per 1000 patient-days) was 21·8 infections per 1000 patient-days. Among the 102 patients, healthcare-associated infections occurred in 32 (31·4%) patients who had a total of 48 healthcare-associated infections (47·5%). Among the 38 patients with neutropenia, 26 (68·4%) had more than one healthcare-associated infection. Of the 48 detected healthcare-associated infections, the most frequent type was blood-stream infection (n = 17, 35·4%), followed by Clostridium difficile infection (n = 11, 22·9%) and respiratory tract infection (n = 8, 3·4%). The best cut-off value of Infection Probability Score (IPS) for the prediction of a healthcare-associated infection was 10 with sensitivity of 59·4% and specificity of 74·3%. Conclusions: Between the three different prognostic scoring systems, IPS had the best sensitivity in predicting healthcare-associated infections. Relevance to clinical practice: IPS is an effective tool and should be used from nurses for the early detection of haematology-oncology patients who are susceptible to the onset of a healthcare-associated infection

Infection probability score, APACHE II and KARNOFSKY scoring systems as predictors of infection onset in haematology-oncology patients

Aim: To assess the predictive power of three systems: Infection Probability Score, APACHE II and KARNOFSKY score to the onset of healthcare-associated infections in haematology-oncology patients. Background: The high incidence of healthcare-associated infections is a frequent problem in haematology-oncology patients that affects morbidity and mortality of these patients. Design: A retrospective surveillance survey. Method: The survey was conducted for seven months in the haematology unit of a general hospital in Greece to assess the predictive power of Infection Probability Score, APACHE II and KARNOFSKY score to the onset of healthcare-associated infections. The sample consisted of 102 hospitalised patients. The diagnosis of healthcare-associated infections was based on the definitions proposed by CDC. Results: Among the participants, 53 (52%) were males and 49 (48%) were females with a mean age of 53·30 (SD 18·59) years old (range, 17-85 years). The incidence density of healthcare-associated infections (the number of new cases of healthcare-associated infections per 1000 patient-days) was 21·8 infections per 1000 patient-days. Among the 102 patients, healthcare-associated infections occurred in 32 (31·4%) patients who had a total of 48 healthcare-associated infections (47·5%). Among the 38 patients with neutropenia, 26 (68·4%) had more than one healthcare-associated infection. Of the 48 detected healthcare-associated infections, the most frequent type was blood-stream infection (n = 17, 35·4%), followed by Clostridium difficile infection (n = 11, 22·9%) and respiratory tract infection (n = 8, 3·4%). The best cut-off value of Infection Probability Score (IPS) for the prediction of a healthcare-associated infection was 10 with sensitivity of 59·4% and specificity of 74·3%. Conclusions: Between the three different prognostic scoring systems, IPS had the best sensitivity in predicting healthcare-associated infections. Relevance to clinical practice: IPS is an effective tool and should be used from nurses for the early detection of haematology-oncology patients who are susceptible to the onset of a healthcare-associated infection. © 2010 Blackwell Publishing Ltd

The Transcription Factor YY1 Is Essential for Normal DNA Repair and Cell Cycle in Human and Mouse β-Cells.

Identifying the mechanisms behind the β-cell adaptation to failure is important to develop strategies to manage type 2 diabetes (T2D). Using db/db mice at early stages of the disease process, we took advantage of unbiased RNA sequencing to identify genes/pathways regulated by insulin resistance in β-cells. We demonstrate herein that islets from 4-week-old nonobese and nondiabetic leptin receptor-deficient db/db mice exhibited downregulation of several genes involved in cell cycle regulation and DNA repair. We identified the transcription factor Yin Yang 1 (YY1) as a common gene between both pathways. The expression of YY1 and its targeted genes was decreased in the db/db islets. We confirmed the reduction in YY1 expression in β-cells from diabetic db/db mice, mice fed a high-fat diet (HFD), and individuals with T2D. Chromatin immunoprecipitation sequencing profiling in EndoC-βH1 cells, a human pancreatic β-cell line, indicated that YY1 binding regions regulate cell cycle control and DNA damage recognition and repair. We then generated mouse models with constitutive and inducible YY1 deficiency in β-cells. YY1-deficient mice developed diabetes early in life due to β-cell loss. β-Cells from these mice exhibited higher DNA damage, cell cycle arrest, and cell death as well as decreased maturation markers. Tamoxifen-induced YY1 deficiency in mature β-cells impaired β-cell function and induced DNA damage. In summary, we identified YY1 as a critical factor for β-cell DNA repair and cell cycle progression

The Transcription Factor YY1 is Essential for Normal DNA Repair and Cell Cycle in Human and Mouse β-cells

Identifying the mechanisms behind the β-cell adaptation-to-failure is important to develop strategies to manage type 2 diabetes (T2D). Using db/db mice at early stages of the disease process, we took advantage of unbiased RNAseq to identify genes/pathways regulated by insulin resistance in β-cells. We demonstrate herein that islets from 4-week-old non-obese and non-diabetic leptin-receptor deficient db/db mice exhibited downregulation of several genes involved in cell-cycle regulation and DNA repair. We identified the transcription factor Yin Yang 1 (YY1) as a common gene between both pathways. The expression of YY1 and its targeted genes was decreased in the db/db islets. We confirmed the reduction in YY1 expression in β-cells from diabetic db/db mice, mice fed high fat diet (HFD) and individuals with T2D. ChIP-seq profiling in EndocBH1 cells, a human pancreatic β-cell line, indicated that YY1 binding regions regulate cell-cycle control, DNA damage recognition and repair. We then generated mouse models with constitutive and inducible YY1 deficiency in β-cells. YY1 deficient mice developed diabetes early in life due to β-cell loss. β-cells from these mice exhibited higher DNA damage, cell cycle arrest and cell death as well as decreased maturation markers. Tamoxifen-induced YY1 deficiency in mature β-cells impaired β-cell function and induced DNA damage. In summary, we identified YY1 as a critical factor for β-cell DNA repair and cell-cycle progression