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Interruptions and medication errors: a mixed methods feasibility study
Get PDFBackground: Medication errors have been found to have numerous contributing factors and interruptions and distractions have been identified as a key cause. A scoping review was conducted to identify and evaluate educational interventions that have been employed to reduce medication interruptions and improve medication safety. Eight studies were found to have employed educational interventions often using multifaceted interventions making it difficult to determine the effectiveness of education alone.
The aim of this study is to determine if an educational intervention can change the way nurses manage interruptions in a Paediatric Intensive Care (PICU) setting, with a focus on the number of interruptions handled appropriately by nurses.
Methods: The study was conducted in a 31-bed PICU in the United Kingdom. An educational intervention, informed by the scoping review, was designed and developed, consisting of a teaching session on appropriate behaviour management strategies, a simulation session to practice strategies, and an eLearning module. A randomised, un-blinded trial design was selected, where participants were randomised to either receive the educational intervention alongside the standard training provided by the unit (intervention group) or to just receive the standard training (control group). Band 5 nurses new to the unit were invited to participate. Observational data was collected at two months to identify the management strategies used by the nurses and then participants were invited to take part in interviews to explore their experiences of the learning and the perceived impact this had.
Ethical, governance and Health Research Authority approval was sought and gained for this study.
Results: A total of 27 nurses were recruited to the study, with 11 randomised to the intervention group and 16 to the control group. Due to sickness and unavailability when the intervention was implemented, two participants randomised to the intervention group had to be switched to the control group.
A high rate of interruptions was found in the observational data, with 89% of medication episodes interrupted at least once. The main source of interruptions were nursing staff communications, ranging from questions about breaks, social conversations to clinical communication. Observation of the medication episodes showed that the main strategy used by both groups was multitasking, which was never adopted appropriately. The blocking strategy was found to be used least. Upon analysis, no statistical difference was found between the intervention and control groups in the strategies they adopted to manage their interruption.
Six themes emerged during the interviews: 1) Situational awareness, 2) Empowerment, 3) Simulation sessions, 4) Team cohesion, 5) Embedded in the culture and 6) Shared learning. All the participants reported they would recommend the educational intervention to their colleagues. The interview data supported findings from the with the observational study, where the nurses reported they didn’t always utilise the appropriate strategy but had an increased awareness of the interruption. A fear of being perceived as rude and lack of embedded education in the culture, were identified as the main barriers to using the blocking strategy.
Discussion: A high rate of interruptions was found to occur in PICU, with nurses one of the main sources of these. A need for a consistent approach among all professionals emerged from the interviews, allowing behaviours such as choosing to block an intervention to be understood in the moment and accepted. The main management strategy utilised by all participants was multitasking.
The high interruption rates observed and the nurses’ desire for change needs to be further explored. Although there was no statistical difference between the intervention and control groups, the education increased awareness of the issue and highlighted the need for this to be made more widely available within the organisation to encourage wider cultural change. This would make strategies to block interruptions more acceptable
Technical debt decision-making under uncertainty
Get PDFThe key to effective technical debt management (TDM) decision-making is to select a feasible and conclusive decision on time. Decision-making, in general, can suffer from uncertainties, obscuring a problem domain and challenging one from producing a useful decision. However, the presence of uncertainties in TDM decision-making is inadequately explored in the Technical Debt (TD) community.
This thesis investigates the presence of Information Uncertainty (uncertainty due to information deficiency), Deep Uncertainty (uncertainty due to unresolvable disagreement) and Erratic Uncertainty (uncertainty due to unpredictability of a problem domain) and their consequences in TD identification, TD measurement, TD prioritisation and TD monitoring.
We leverage goal-obstacle and the expected value of information to strategically mitigate Information Uncertainty in TD identification and measurement. By leveraging these analyses, Information Uncertainty can be managed regardless of information availability.
We leverage Many Objective Robust Decision-Making to implement a framework to mitigate Deep Uncertainty during TD prioritisation. The framework’s premise is to frame TD rankings in disagreements into different objective functions and utilise a set of decisions that perform well in those disagreements.
We propose a method to mitigate the consequence of Erratic Uncertainty in TDM monitoring: ineffective responsibility sharing. The method leverages Behavioural Cloning to filter the situation when developers/maintainers are necessary and utilises Replicator Dynamics to automatically resolve the TD monitoring situation when they are unnecessary, resulting in a more balanced workload between TD analysts and developers/maintainers.
The thesis individually evaluates the above contributions through various experiments with industrial cases, aiming for the effectiveness of the contributions compared to traditional approaches without the acknowledgement of uncertainties
The relationship between senescence and autophagy in human inflamed joint cell populations
Get PDFRheumatoid arthritis (RA) and osteoarthritis (OA) are both diseases of the articular joint affecting the synovium. The synovium is critical to maintain joint homeostasis by protecting the articular cartilage and secreting synovial fluid. In OA and RA, the synovial lining layer (LL) and sub-lining (SL) are challenged by many stressors such as inflammation. Although RA and OA have different origins, age is a relevant factor for both. However, the role of aging in the degenerative processes occurring in the synovium remain poorly understood. By using multiplex immunofluorescence and spectral flow cytometry, we investigated aging through the perspective of cellular senescence, DNA damage and autophagy regulation via TFEB in the fibroblasts, tissue resident macrophages (TRMs), lymphocytes and endothelial cells (ECs) in OA and RA. We found that the lining layer is highly affected by DNA damage, up regulated p53 and accumulation of p16+ cells in both diseases. Notably, the LL fibroblasts have a higher DNA damage response o activation and senescence compared to the SL populations. Other cell types such as ECs also up regulated the DNA damage response through p21 and p53 expression. This pro damage context promotes the master regulator of autophagy TFEB. We found that TFEB activity and expression is decreased in OA compared to RA specifically in the LL fibroblasts. Together, these data provide the first map of the cellular stressors involved in inflamed synovium, paving the way to promising new regulation involving autophagy, metabolism, inflammation and cellular senescence in arthritis
Optimisation of clozapine use during early years of schizophrenia – can clozapine be considered a disease modifying drug?
Get PDFIntroduction
It is increasingly recognised that schizophrenia may be an immunological disease. Although there has been some progress in the management of schizophrenia by way of innovative service development over the last two decades, drug treatment has remained essentially static, with no major breakthroughs since the arrival of clozapine in the 1980s. Contrast this with the progress that has been made in the treatment of established immunological conditions such as rheumatoid arthritis, where the use of disease modifying drugs has transformed the therapeutic landscape. New insights into the immunology of schizophrenia provide potential for better understanding of how current treatments work and also a road map for developing novel compounds. Clozapine remains the treatment of choice for treatment resistant schizophrenia (TRS). It is possible that clozapine’s superiority over traditional antipsychotics in TRS is down to its immunological effects. This raises the prospect that clozapine may be a disease modifying drug, capable of changing the course of disease, in which case earlier prescription of clozapine would be likely to produce better outcomes for patients. Clozapine is known to have effects on peripheral blood immune cells including neutrophils. Neutrophils have been shown to be elevated in schizophrenia, and there is much interest currently in the role of neutrophils in the pathogenesis of a number of immune conditions. A spike in neutrophils shortly after starting clozapine is commonly seen in clinical practice and has been reported in the literature. It is possible that these early changes in neutrophil counts following clozapine commencement may be linked with response to clozapine. In addition, clozapine has been found to be associated with secondary immunoglobulin deficiency which may also have value as a clinical biomarker in the treatment of TRS. In this thesis I have explored whether there is evidence in the literature that earlier clozapine is beneficial in TRS and have conducted my own study into the timing of clozapine and its effectiveness. I have also examined neutrophil and immunoglobulin trajectories with clozapine use and looked for evidence of an association with clinical outcome.
Hypothesis and methods
I have set out to test the following three hypotheses.
Hypothesis 1. Clozapine will be more effective if used earlier in the course of course of TRS. I have investigated this by conducting a meta-regression of the effect of age (as a proxy for duration of illness) on clozapine response from randomised controlled trial data of clozapine in comparison to other antipsychotic drugs. I have then conducted an observational study of anonymised patient records, using ordinal logistic regression, to look for an association between duration of prior psychotic illness and clozapine response.
Hypothesis 2. Patients can be classified by neutrophil trajectory following clozapine commencement, and neutrophil trajectory can predict response to clozapine. I have taken the database that I created for paper 2, and linked this with ZTAS full blood count data, in order to conduct a latent class growth analysis (LCGA) of baseline and early neutrophil counts with clozapine and a logistic regression of neutrophil trajectory class against clinical outcome.
Hypothesis 3. Immunoglobulin levels fall with clozapine treatment and reduction in globulin level can predict response to clozapine. Combining my database from paper 2 with calculated globulin (CG) results obtained by a fellow CRIS researcher, I have compared CG counts pre and post clozapine prescription and have carried out a logistic regression of change in globulin score against clinical outcome.
Results
Paper 1 – Chapter 3
From a meta-analysis of 34 papers, meta-regression results failed to demonstrate an effect of age on clozapine response (p = 0.79, [95% CI -0.03 – 0.03]), however a linear regression of age against response using individual patient data from one study did show a significant effect of age, with younger age associated with greater response to clozapine (p=0.00, [95% CI -110.71 - -27.20]). Individual patient data from a second smaller study did not show a significant effect.
Paper 2 – Chapter 4
From a sample of 425 patients obtained using routine electronic clinical data, ordinal logistic regression results showed a significant association between duration of illness prior to commencing clozapine, and clozapine response (adjusted OR = 1.04 [95% CI 1.01 – 1.06]), indicating a 4% increase in the odds of a higher (worse) outcome CGI-S score per additional year of illness.
Paper 3 – Chapter 5
Using the same sample from paper 2, LCGA suggested 3 distinct classes of neutrophil trajectories, differing from outset with high, high-normal and low normal counts. Logistic regression showed that high-normal neutrophils were associated with higher odds of clozapine response (adjusted OR = 2.10 [95% CI 1.31 – 3.36]).
Paper 4 – Chapter 6
From a sample of 343 patients, 149 had pre and post calculated globulin (CG) levels available whilst 341 had only post CG levels. Mean CG level fell significantly following clozapine treatment (t = 2.74 p = 0.007). Logistic regression showed no association between change in CG level and clozapine response (adjusted OR 1.02 95% CI [0.89-1.16]). There was a significant association between CG level 1 year post clozapine and clozapine response (adjusted OR 1.06 95% CI [1.00-1.12]), but the data was of poor quality. Sex and ethnicity differences were found in CG levels pre and post clozapine.
Conclusions
The results from papers 1 and 2 provide support for the hypothesis that earlier clozapine is associated with better response to clozapine. Whilst the meta-regression results were not significant, there was evidence from limited individual patient data of an association between younger age, and shorter duration of illness, and better response to clozapine. In the paper I provide a critique of the meta-regression, both in terms of the methodology and the data quality. Paper 2 in comparison provided clearer evidence of an association between shorter duration of prior illness and clozapine response, and whilst it was an observational rather than experimental study, it had the advantage of being a sample of real-world clinical data.
Paper 3 provided evidence in support of differing neutrophil trajectories following clozapine initiation. However, rather than variation between classes in terms of a spike in neutrophil count with clozapine, neutrophil counts varied from the outset, with high normal neutrophil counts associated with a greater response to clozapine. These results are in keeping with a hypothesis that patients with high normal neutrophil counts, reflecting an ongoing inflammatory process, are more likely to respond to clozapine, and indicate that neutrophils may have utility as a biomarker to predict clozapine response in TRS.
Results from paper 4 support the hypothesis that immunoglobulin levels fall with clozapine treatment but failed to show an association between fall in CG level and response to clozapine. There were sex and ethnicity differences in CG levels both pre and post clozapine, with most patients who developed low CG levels on clozapine being white males. However, the data quality for this paper was poor and results need to be interpreted with caution.
In summary, the key findings from this thesis i.e. firstly, that earlier clozapine may be associated with better outcome in TRS and secondly, that neutrophil count can help predict response to clozapine, support the concept of clozapine acting as a disease modifier by reducing the burden of inflammation in TRS
Development of a tracking detector and kinematic reconstruction methods for the electron-ion collider
Get PDFThe Electron-Ion Collider (EIC) is a future facility that will be constructed at Brookhaven National Laboratory (BNL) over the next decade, to begin data-taking in the early 2030s.
Studies performed for the optimisation of the tracking system of ePIC, the EIC project detector, are presented. The EIC physics programme places stringent requirements on the tracking system, which must be high precision, low mass and well integrated. Simulations are performed for various tracking geometries, which are implemented in Geant4-based frameworks with varying levels of realism for the geometry and reconstruction, and the performance is evaluated. The design of the tracking system has been iteratively updated in line with such performance studies and projections of the technology, which inform the current ePIC tracking design. It is found that in order to achieve the EIC physics goals with the 1.7 T solenoidal magnetic field to be used in ePIC, large area tracking layers built using high precision and low mass monolithic silicon sensors are required. The performance targets are challenging to meet in the endcap trackers for a 1.7 T field, and so a combination of measurements from the tracking and calorimetry systems will be required.
An accurate reconstruction of the kinematic variables x, y, and Q^2 is essential for the EIC inclusive physics programme. The ability of the ePIC detector to reconstruct the kinematic variables is studied, and the resolutions of the methods optimised throughout the phase space. Conventional reconstruction methods usually rely on two of the four measured quantities (energy and polar angle of the scattered electron and hadronic final state). A novel reconstruction method is presented whereby the kinematic variables, and the energy of possible initial state photon radiation, are reconstructed through a kinematic fit of all measured quantities in a Bayesian framework using informative priors. The method is validated for smeared generated DIS events, fully simulated ePIC events, and is also applied to simulations and data from the H1 experiment at the HERA collider
An exploration of the role of the detective figure in 20th century African American crime fiction
Get PDFThis thesis examines the role of the detective figure in African American crime fiction, and how this changed throughout the 20th Century. The role of this character changed as the genre became politicized and used by African American writers as a space for social critique. The detective took on a new responsibility, as a representation of the African American community, and mouthpiece for real-world concerns and issues. Crime writers achieved this using a range of methods - from the subversive anti-detective novel tradition, to the discussion of W.E.B DuBois’ theory of ‘double consciousness’, to utilizing elements of the popular pulp fiction trend, to choosing historically black settings such as Harlem as backdrops for their stories. This thesis ends with the assertion that the detective figure within African American crime fiction was assigned a new role as they became inspiring symbols for a frustrated community of people
The celebrity wellness and lifestyle sector: maintaining dominant gender norms and structures in a postfeminist online culture
Get PDFPostfeminism, which is evolving and increasingly intertwining with neoliberalism, is a topic that needs to be (re)explored to establish a better understanding of it and its effects on women’s lives. How postfeminism operates within the online sphere is an important area to research due to social media platforms, which play a significant role in identity construction, constantly undergoing transformations. This thesis aims to explore how postfeminism is evolving by looking at Poosh, a celebrity-run wellness lifestyle site promoted through Instagram. The wellness industry is a pertinent area to look at due to its emergence being linked to postfeminism and social media. Furthermore, my research explored the normative portrayal of motherhood within Poosh, as the concept of postfeminist motherhood has so far only received sparse attention in the literature. The thesis found that while some postfeminist sensibilities seem to have evolved superficially, at the core they remain the same, and still contribute towards maintaining dominant norms and structures. Moreover, while ‘correct’ parenting techniques are being reframed within postfeminism, in particular due to neoliberalism’s influence, to help produce future happy productive and resistant neoliberal subjects; childrearing is still portrayed as the woman’s main responsibility
On the relation between asymptotic behaviour of Neumann eigenvalue counting functions and the inner Minkowski content of fractal drums
Get PDFWe define a class of well-foliated domains for which explicit lower bounds for the first non-trivial eigenvalue of the Neumann Laplacian are obtained. We show that -Rohde snowflakes for fall into this class. We establish conditions on snowflake-like domains and quasidisks that ensure well-foliatedness via bi-Lipschitz invariance. We prove that domains for which any sufficiently small inner -parallel neighbourhood can be covered (with uniformly bounded multiplicity of the cover) by at most well-foliated domains allow an upper bound of the remainder term of the spectral counting function of the Neumann Laplacian at asymptotic to . It is discussed how the cardinality of this cover relates to the upper inner Minkowski content and in particular we show that -Rohde snowflakes satisfy this property whenever their upper inner Minkowski content is positive and finite. Applying the above results we obtain explicit bounds in the cases of homogeneous -Rohde snowflakes for and of the classical Koch snowflake. Finally we construct a family of fractal sprays whose gaps have fractal boundary and find non-trivial terms in the asymptotic expansion of the spectral counting function and the volume of the inner -parallel neighbourhood with comparable scaling behaviour
Hormonal regulation of skeletal muscle metabolism
Get PDFNicotinamide Adenine Dinucleotide (NAD+) is a cofactor for enzymes serving cellular metabolic reactions and a consumed substrate for sirtuins and poly (adenosine diphosphate-ribose) polymerases (PARPs), enzymes that regulate protein deacetylation and DNA repair, and translate changes in energy and cell status into metabolic adaptations. Deranged NAD+ homeostasis and concurrent mitochondrial dysfunction are key features of ageing and age-related metabolic disease. Contemporary NAD+ precursors (vitamin B3 derivatives) showed promise as therapeutic nutraceuticals to restore target tissue NAD+ in at risk groups and have demonstrated improvements in mitochondrial function and sirtuin-dependent signalling in pre-clinical studies. We conducted the NADMet (Nicotinamide Adenine Dinucleotide and Skeletal Muscle Metabolic Phenotype) clinical study to examine whether NAD+ can be increased in human tissues using oral nutraceutical approaches and assess for a potential role in combating metabolic disease and the unwanted effects of ageing. The results showed that the oral supplementation of the NAD+ precursor, nicotinamide riboside, in aged men was safe and well-tolerated leading to an increase in the skeletal muscle NAD+ metabolome and induced a specific transcriptomic signature without altering muscle specific or systemic metabolism.
NAD+ is also a parent molecule for NADPH which is a cofactor for the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme that regenerates glucocorticoids in the sarcoplasmic reticulum (SR) of skeletal muscle. The maintenance of the SR NADPH/NADP+ ratio is poorly understood. This work suggests a novel level of regulated glucocorticoid metabolism in skeletal muscle whereby 11β-HSD1 activity can be influenced by cellular redox status and NAD+ levels beyond the SR
The South’s connection and political response to European fascism during the interwar period (1919-1939)
Get PDFThis dissertation argues that the U.S. South’s connections — commonalities, networks, and exchanges — and political response to European fascism were distinct from the rest of the United States during the interwar period. While the allegations of fascism levelled against the South by its critics were exaggerated, it was the U.S. region that most closely mirrored the racial, labour, and political practices of fascist Europe during the 1930s. These similarities underpinned the region’s relatively affirmative political response to fascism as demonstrated by the discourse of southern politicians. Case studies illuminate how individual southern politicians engaged in the discourse of fascism both to undermine the more progressive elements of the New Deal and to protect the traditional racial, political, and economic social structures of the South. The South’s distinct response to European fascism shifted U.S. domestic policy rightward and offered encouragement to European fascists via transnational exchanges.
The methodology for this thesis was informed by the nature of the questions being studied and the depth of the available historiography. A hermeneutical approach was utilized to interpret the interwar discourse to uncover insights on topics ranging from the nature of fascism to the South’s political response. Comparative and transnational methods were deployed to understand the similarities and entanglements between the South and fascist Europe. The Congressional Record and the personal and professional papers of southern congressmen were foundational primary sources. Secondary sources utilized generally fell within one of three categories. First, those few texts that explicitly explore the connections between fascist Europe and the U.S. South; second, a much larger body of work comprised of monographs that discuss the South and fascist Europe separately; and third, the new and emerging body of research on transnational fascism. The monographs provided background and context while the handful of sources on direct comparison and the exchange of ideas offered starting points from which to extend the historiography.
The South’s connection to the interwar transnational fascist movement provides meaningful context to better understand the contemporary rise of right-wing populism. Southern symbols and ideas have metastasized and are now used globally by the right. The South may have been militarily conquered and its Jim Crow laws may have been banished, but the ideas and practices that underpinned the conception of the South as America’s fascist region continue to manifest within the rising tide of global right-wing populist movements. In such ways the memories of the interwar South continue to shape understanding of current events and inspire actions in the present as well
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