Studies of antihypertensive drug persistence and adherence in the Glasgow Blood Pressure Clinic

Hypertension (HTN) is a major risk factor for cardiovascular diseases including stroke, coronary heart disease (CHD), chronic renal failure, peripheral vascular disease, myocardial infarction, congestive heart failure and premature death. The prevalence of HTN in Scotland is very high and although a high proportion of the patients receive antihypertensive medications, blood pressure (BP) control is very low. Recommendations for starting a specific antihypertensive class have been debated between various guidelines over the years. Some guidelines and HTN studies have preferred to start with a combination of an antihypertensive class instead of using a single therapy, and they have found greater BP reductions with combination therapies than with monotherapy. However, it has been shown in several clinical trials that 20% to 35% of hypertensive patients could not achieve the target BP, even though they received more than three antihypertensive medications. Several factors were found to affect BP control. Adherence and persistence were considered as the factors contributing the most to uncontrolled hypertension. Other factors such as age, sex, body mass index (BMI), alcohol intake, baseline systolic BP (SBP), and the communication between physicians and patients have been shown to be associated with uncontrolled BP and resistant hypertension. Persistence, adherence and compliance are interchangeable terms and have been used in the literature to describe a patient’s behaviour with their antihypertensive drugs and prescriptions. The methods used to determine persistence and adherence, as well as the inclusion and exclusion criteria, vary between persistence and adherence studies. The prevalence of persistence and adherence have varied between these studies, and were determined to be high in some studies and low in others. The initiation of a specific antihypertensive class has frequently been associated with an increase or decrease in adherence and persistence. The tolerability and efficacy of the initial antihypertensive class have been the most common methods of explaining this association. There are also many factors that suggest a relationship with adherence and persistence. Some factors in previous studies, such as age, were frequently associated with adherence and persistence. On the other hand, relationships with certain factors have varied between the studies. The associations of age, sex, alcohol use, smoking, baseline systolic blood pressure (SBP) and diastolic BP (DBP), the presence of comorbidities, an increase in the number of pills and the relationship between patients and physicians with adherence and persistence have been the most commonly investigated factors. Most studies have defined persistence in terms of a patient still taking medication after a period of time. A medication possession ratio (MPR) ≥ 80 has been used to define compliance. Either of these terminologies, or both, have been used to estimate adherence. In this study, I used the same definition for persistence to identify patients who have continued with their initial treatment, and used persistence and MPR to define patients who adhered to their initial treatment. The aim of this study was to estimate the prevalence of persistence and adherence in Scotland. Also, factors that could have had an effect on persistence and adherence were studied. The number of antihypertensive drugs taken by patients during the study and factors that led to an increase in patients being on a combination therapy were also evaluated. The prevalence of resistance and BP control were determined by taking the BP after the last drug had been taken by persistent patients during five follow-up studies. The relationship of factors such as age, sex, BMI, alcohol use, smoking, estimated glomerular filtration rate (eGFR), and albumin levels with BP reductions for each antihypertensive class were determined. Information Services Division (ISD) data, which includes all antihypertensive drugs, were collected from pharmacies in Scotland and linked to the Glasgow Blood Pressure Clinic (GBPC) database. This database also includes demographic characteristics, BP readings and clinical results for all patients attending the GBPC. The case notes for patients who attended the GBPC were reviewed and all new antihypertensive drugs that were prescribed between visits, BP before and after taking drugs, and any changes in the hypertensive drugs were recorded. A total of 4,232 hypertensive patients were included in the first study. The first study showed that angiotensin converting enzyme inhibitor (ACEI) and beta-blockers (BB) were the most prescribed antihypertensive classes between 2004 and 2013. Calcium channel blockers (CCB), thiazide diuretics and angiotensin receptor blockers (ARB) followed ACEI and BB as the most prescribed drugs during the same period. The prescription trend of the antihypertensive class has changed over the years with an increase in prescriptions for ACEI and ARB and a decrease in prescriptions for BB and diuretics. I observed a difference in antihypertensive class prescriptions by age, sex, SBP and BMI. For example, CCB, thiazide diuretics and alpha-blockers were more likely to be prescribed to older patients, while ACEI, ARB or BB were more commonly prescribed for younger patients. In a second study, 4,232 and 3,149 hypertensive patients were included to investigate the prevalence of persistence in the Scottish population in 1- and 5-year studies, respectively. The prevalence of persistence in the 1-year study was 72.9%, while it was only 62.8% in the 5-year study. Those patients taking ARB and ACEI showed high rates of persistence and those taking diuretics and alpha blockers had low rates of persistence. The association of persistence with clinical characteristics was also investigated. Younger patients were more likely to totally stop their treatment before restarting their treatment with other antihypertensive drugs. Furthermore, patients who had high SBP tended to be non-persistent. In a third study, 3,085 and 1,979 patients who persisted with their treatment were included. In the first part of the study, MPR was calculated, and patients with an MPR ≥ 80 were considered as adherent. Adherence rates were 29.9% and 23.4% in the 1- and 5-year studies, respectively. Patients who initiated the study with ACEI were more likely to adhere to their treatments. However, patients who initiated the study with thiazide diuretics were less likely to adhere to their treatments. Sex, age and BMI were different between the adherence and non-adherence groups. Age was an independent factor affecting adherence rates during both the 1- and 5-year studies with older patients being more likely to be adherent. In the second part of the study, pharmacy databases were checked with patients' case notes to compare antihypertensive drugs that were collected from the pharmacy with the antihypertensive prescription given during the patient’s clinical visit. While 78.6% of the antihypertensive drugs were collected between clinical visits, 21.4% were not collected. Patients who had more days to see the doctor in the subsequent visit were more likely to not collect their prescriptions. In a fourth study, 3,085 and 1,979 persistent patients were included to calculate the number of antihypertensive classes that were added to the initial drug during the 1-year and 5-year studies, respectively. Patients who continued with treatment as a monotherapy and who needed a combination therapy were investigated during the 1- and 5-year studies. In all, 55.8% used antihypertensive drugs as a monotherapy and 44.2% used them as a combination therapy during the 1-year study. While 28.2% of patients continued with treatment without the required additional therapy, 71.8% of the patients needed additional therapy. In all, 20.8% and 46.5% of patients required three different antihypertensive classes or more during the 1-year and 5-year studies, respectively. Patients who started with ACEI, ARB and BB were more likely to continue as monotherapy and less likely to need two more antihypertensive drugs compared with those who started with alpha-blockers, non-thiazide diuretics and CCB. Older ages, high BMI levels, high SBP and high alcohol intake were independent factors that led to an increase in the probability of patients taking combination therapies. In the first part of the final study, BPs were recorded after the last drug had been taken during the 5 year study. There were 815 persistent patients who were assigned for this purpose. Of these, 39% had taken one, two or three antihypertensive classes and had controlled BP (controlled hypertension [HTN]), 29% of them took one or two antihypertensive classes and had uncontrolled BP (uncontrolled HTN), and 32% of the patients took three antihypertensive classes or more and had uncontrolled BP (resistant HTN). The initiation of an antihypertensive drug and the factors affecting BP pressure were compared between the resistant and controlled HTN groups. Patients who initiated the study with ACEI were less likely to be resistant compared with those who started with alpha blockers and non-thiazide diuretics. Older patients, and high BMI tended to result in resistant HTN. In the second part of study, BP responses for patients who initiated the study with ACEI, ARB, BB, CCB and thiazide diuretics were compared. After adjusting for risk factors, patients who initiated the study with ACEI and ARB were more respondent than those who took CCB and thiazide diuretics. In the last part of this study, the association between BP reductions and factors affecting BP were tested for each antihypertensive drug. Older patients responded better to alpha blockers. Younger patients responded better to ACEI and ARB. An increase in BMI led to a decreased reduction in patients on ACEI and diuretics (thiazide and non-thiazide). An increase in albumin levels and a decrease in eGFR led to decreases in BP reductions in patients on thiazide diuretics. An increase in eGFR decreased the BP response with ACEI. In conclusion, although a high percentage of hypertensive patients in Scotland persisted with their initial drug prescription, low adherence rates were found with these patients. Approximately half of these patients required three different antihypertensive classes during the 5 years, and 32% of them had resistant HTN. Although this study was observational in nature, the large sample size in this study represented a real HTN population, and the large pharmacy data represented a real antihypertensive population, which were collected through the support of prescription data from the GBPC database. My findings suggest that ACEI, ARB and BB are less likely to require additional therapy. However, ACEI and ARB were better tolerated than BB in that they were more likely to be persistent than BB. In addition, users of ACEI, and ARB have good BP response and low resistant HTN. Linkage patients who participated in these studies with their morbidity and mortality will provide valuable information concerning the effect of adherence on morbidity and mortality and the potential benefits of using ACEI or ARB over other drugs.

'Yes, the century is an ashen sun': poem and subject in the philosophy of Alain Badiou

This thesis examines the relation between philosophy, the poem and the subject in the mature philosophy of Alain Badiou. It investigates Badiou’s decisive contribution to these questions primarily by means of comparison, especially to Martin Heidegger, Philippe Lacoue-Labarthe and Theodor Adorno, as well as by analysing Badiou’s readings of poems and prose by Paul Celan and Samuel Beckett respectively as sites of potential dialogue with his immediate predecessors. The thesis stresses the importance of French philosophy’s German heritage, emphasising not only Badiou’s radical departure from Heidegger and his legacy, but also the former’s wholesale rejection of philosophies that would, in the wake of twentieth-century violence and beyond, proclaim their own end or completion. The thesis argues Badiou’s innovative readings of Celan and Beckett to be crucial to understanding this endeavour: for Badiou, both writers use the poem to affirm novel conceptions of subjectivity capable of transcending the historical conditions of their presentation. The title quotation from Badiou’s The Century, ‘Yes, the century is an ashen sun’, anticipates both the affirmative nature of these subjective figures, and their presience, beyond the bounds of a twentieth-century ‘ashen sun’ pervaded by melancholy, for the ‘new suns’ of the twenty-first. The thesis is in four chapters. The first chapter unfolds the central concepts of Badiou’s departure from Heidegger using Paul Celan’s poems to focus the enquiry. It is guided by two of Badiou’s most condensed declarations about the poem, that, firstly, ‘the modern poem harbours a central silence’, and secondly, that ‘Celan completes Heidegger’. The second chapter exposes the political implications of Heidegger’s writings on Friedrich Hölderlin and the role of the subject therein, offering at its close some thoughts about what Badiou calls, following Philippe Lacoue-Labarthe, the poem’s ‘becoming-prose’. It concludes by drawing the poem and politics into relation by way of the philosophical category of the subject. The third chapter reads Badiou’s concept of ‘anabasis’ against Heidegger’s ‘homecoming’ in order to think the possibility of a collective political subject’s formation in the wake of Auschwitz. The final chapter examines the imbrication of the Two of love and the ‘latent poem’ in Badiou’s reading of Samuel Beckett’s late prose, contrasting this ‘affirmative’ reading of Beckett to Theodor Adorno’s earlier emphases on negation. Following its investigations of subjectivity, poem and prose throughout, the thesis concludes by returning to the title quotation in order to unfold the particular relations between subject, affirmation and negation Badiou’s philosophy enacts, and to offer further routes forward for research regarding Badiou’s philosophy and aesthetic figuration.

Geometry and topography in James Joyce's Ulysses and Finnegans Wake

Following the development of non-Euclidean geometries from the mid-nineteenth century onwards, Euclid’s system had come to be re-conceived as a language for describing reality rather than a set of transcendental laws. As Henri Poincaré famously put it, ‘[i]f several geometries are possible, is it certain that our geometry [...] is true?’. By examining Joyce’s linguistic play and conceptual engagement with ground-breaking geometric constructs in Ulysses and Finnegans Wake, this thesis explores how his topographical writing of place encapsulates a common crisis between geometric and linguistic modes of representation within the context of modernity. More specifically, it investigates how Joyce presents Euclidean geometry and its topographical applications as languages, rather than ideally objective systems, for describing visual reality; and how, conversely, he employs language figuratively to emulate the systems by which the world is commonly visualised. With reference to his early readings of Giordano Bruno, Henri Poincaré and other critics of the Euclidean tradition, it investigates how Joyce’s obsession with measuring and mapping space throughout his works enters into his more developed reflections on the codification of visual signs in Finnegans Wake. In particular, this thesis sheds new light on Joyce’s developing fascination with the ‘geometry of language’ practised by Bruno, whose massive influence on Joyce is often assumed to exist in Joyce studies yet is rarely explored in any great detail.

Wondrous transformations: rereading and rewriting wonder in contemporary anglophone and francophone fairy tales

This thesis compares contemporary anglophone and francophone rewritings of traditional fairy tales for adults. Examining material dating from the 1990s to the present, including novels, novellas, short stories, comics, televisual and filmic adaptations, this thesis argues that while the revisions studied share similar themes and have comparable aims, the methods for inducing wonder (where wonder is defined as the effect produced by the text rather than simply its magical contents) are diametrically opposed, and it is this opposition that characterises the difference between the two types of rewriting. While they all engage with the hybridity of the fairy-tale genre, the anglophone works studied tend to question traditional narratives by keeping the fantasy setting, while francophone works debunk the tales not only in relation to questions of content, but also aesthetics. Through theoretical, historical, and cultural contextualisation, along with close readings of the texts, this thesis aims to demonstrate the existence of this francophone/anglophone divide and to explain how and why the authors in each tradition tend to adopt such different views while rewriting similar material. This division is the guiding thread of the thesis and also functions as a springboard to explore other concepts such as genre hybridity, reader-response, and feminism. The thesis is divided into two parts; the first three chapters work as an in-depth literature review: after examining, in chapters one and two, the historical and contemporary cultural field in which these works were created, chapter three examines theories of fantasy and genre hybridity. The second part of the thesis consists of textual studies and comparisons between francophone and anglophone material and is built on three different approaches. The first (chapter four) looks at selected texts in relation to questions of form, studying the process of world building and world creation enacted when authors combine and rewrite several fairy tales in a single narrative world. The second (chapter five) is a thematic approach which investigates the interactions between femininity, the monstrous, and the wondrous in contemporary tales of animal brides. Finally, chapter six compares rewritings of the tale of ‘Bluebeard’ with a comparison hinged on the representation of the forbidden room and its contents: Bluebeard’s cabinet of wonder is one that he holds sacred, one where he sublimates his wives’ corpses, and it is the catalyst of wonder, terror, and awe. The three contextual chapters and the three text-based studies work towards tracing the tangible existence of the division postulated between francophone and anglophone texts, but also the similarities that exist between the two cultural fields and their roles in the renewal of the fairy-tale genre.

State-narco networks and the ‘War on Drugs’ in post-transition Bolivia, with special reference to 1989-1993

This thesis examines the development of state-narco networks in post-transition Bolivia. Mainstream discourses of drugs tend to undertheorise such relationships, holding illicit economies, weak states and violence as synergistic phenomena. Such assumptions fail to capture the nuanced relations that emerge between the state and the drug trade in different contexts, their underlying logics and diverse effects. As an understudied case, Bolivia offers novel insights into these dynamics. Bolivian military authoritarian governments (1964-1982), for example, integrated drug rents into clientelistic systems of governance, helping to establish factional coalitions and reinforce regime authority. Following democratic transition in 1982 and the escalation of US counterdrug efforts, these stable modes of exchange between the state and the coca-cocaine economy fragmented. Bolivia, though, continued to experience lower levels of drug-related violence than its Andean neighbours, and sustained democratisation despite being a major drug producer. Focusing on the introduction of the Andean Initiative (1989-1993), I explore state-narco interactions during this period of flux: from authoritarianism to (formal) democracy, and from Cold War to Drug War. As such, the thesis transcends the conventional analyses of the drugs literature and orthodox readings of Latin American narco-violence, providing insights into the relationship between illicit economies and democratic transition, the regional role of the US, and the (unintended) consequences of drug policy interventions. I utilise a mixed methods approach to offer discrete perspectives on the object of study. Drawing on documentary and secondary sources, I argue that state-narco networks were interwoven with Bolivia’s post-transition political settlement. Uneven democratisation ensured pockets of informalism, as clientelistic and authoritarian practices continued. This included police and military autonomy, and tolerance of drug corruption within both institutions. Non-enforcement of democratic norms of accountability and transparency was linked to the maintenance of fragile political equilibrium. Interviews with key US and Bolivian elite actors also revealed differing interpretations of state-narco interactions. These exposed competing agendas, and were folded into alternative paradigms and narratives of the ‘war on drugs’. The extension of US Drug War goals and the targeting of ‘corrupt’ local power structures, clashed with local ambivalence towards the drug trade, opposition to destabilising, ‘Colombianised’ policies and the claimed ‘democratising mission’ of the Bolivian government. In contrasting these US and Bolivian accounts, the thesis shows how real and perceived state-narco webs were understood and navigated by different actors in distinct ways. ‘Drug corruption’ held significance beyond simple economic transaction or institutional failure. Contestation around state-narco interactions was enmeshed in US-Bolivian relations of power and control.