Introduktion: Intensivvårdsavdelningen är en högteknologisk miljö, vilket ställer höga krav på intensivvårdssjuksköterskan som vårdar kritiskt sjuka patienter. Intensivvårdspatienter är i behov av att transporteras inom sjukhuset. Dessa transporter är riskfyllda och ställer krav på intensivvårdssjuksköterskan. Syfte: Att beskriva intensivvårdssjuksköterskors upplevelser av patientsäkerheten vid intrahospitala transporter. Metod: Studien genomfördes som en integrativ litteraturstudie enligt Whittemore & Knafl (2005) med induktiv ansats. Totalt inkluderades tre kvalitativa studier, tre mixade metoder och tre kvantitativa studier samt en observationsstudie. Resultat: Baserades på 10 artiklar som berör intensivvårdssjuksköterskans upplevelser av patientsäkerheten vid intrahospitala transporter. Utifrån studiernas resultat identifierades faktorer som hotar och främjar patientsäkerheten under intrahospitala transporter som presenteras i de tre teman: Att samarbeta i teamet, Att arbeta förebyggande och Ökad arbetsbelastning. Konklusion: Forskningsområdet inom intensivvårdssjuksköterskors upplevelser av patientsäkerhet under intrahospitala transporter var begränsat. Intensivvårdssjuksköterskor upplevde att intrahospitala transporter var riskfyllda och krävande, där patientsäkerheten var hotad. Intrahospitala transporter kräver kompetens och förberedelser för att kunna utföra intrahospitala transporterna på ett patientsäkert sätt. Där fungerande utrustning, samarbete inom teamet, patientens kliniska status och vårdmiljö hade en betydande roll för att kunna utföra säkra intrahospitala transporter. / Introduction: The intensive care unit is a high-tech environment, which places high demands on the intensive care nurse who cares for critically ill patients. Intensive care patients need to be transported within the hospital. These transports are fraught with risk and place demands on the intensive care nurse. Aim: To describe intensive care nurses' experiences of patient safety during intrahospital transport. Method: The study was conducted as an integrative literature study according to Whittemore & Knafl (2005) with an inductive approach. In total, three qualitative studies, three mixed methods and three quantitative studies and one observational study were included. Results: Was based on 10 articles concerning the intensive care nurse's experiences of patient safety during intrahospital transport. Based on the results of the studies, factors that threaten and promote patient safety during intrahospital transport were identified, which are presented in the three themes: Working together in the team, Working preventively and Increased workload. Conclusion: The research area within intensive care nurses' experiences of patient safety during intrahospital transport was limited. Intensive care nurses felt that intrahospital transport was risky and demanding, where patient safety was threatened. Intrahospital transports require competence and preparation to be able to carry out the transports in a patient-safe way. Functioning equipment, collaboration within the team, the patient's clinical status and care environment played a significant role in being able to carry out safe transports.

Endozytose erfordert hohe Membrankrümmung und führt zu Flächenänderungen der Membranhälften. Dies kann durch eine Oberflächendifferenz zwischen den Schichten initiiert werden, die durch geänderte Lipidzusammensetzungen hervorgerufen werden kann. Daher wurde die Hypothese aufgestellt, dass Lipid-Transporter zu Beginn der Endozytose für veränderte Flächenverhältnisse verantwortlich sind. Um den Einfluss veränderter Flächen auf Endozytose zu untersuchen, wurden die Oberflächenverhältnisse der Membran durch Zugabe von Phospholipiden verändert und anschließend Endozytose gemessen. Abhängig von der Sorte wurden die Lipide nur in die äußere Schicht eingebaut oder auch auf die innere Seite transportiert, wodurch die entsprechende Seite vergrößert wurde. Die Zugabe verschiedener Aminophospholipide, die auf die innere Membranseite transportiert werden, führte zu gesteigerter „bulk flow“ Endocytose in K562-Zellen. Darüber hinaus deuten die Ergebnisse darauf hin, dass Clathrin-vermittelte Endozytose von Hep2-Zellen ebenfalls stimuliert wurde. Umgekehrt hatte die Zugabe von Lipiden, die auf der äußeren Hälfte bleiben, reduzierte „bulk flow“- oder Clathrin-vermittelte Endozytose in verschiedenen Zelllinien zur Folge. Bemerkenswert ist, dass auch Clathrin-vermittelte Endozytose durch die Lipidzugabe beeinflusst wurde, obwohl gerade in diesem Weg viele Proteine involviert sind, die Krümmung induzieren können. Dies passt zu einem neuen Modell wie Lipidtransporter in Endozytose involviert sind. Durch den Transport von Lipiden und die zusätzliche Interaktion mit Endozytoseproteinen, könnten diese Transporter zwei Mechanismen zur Erzeugung von Krümmung miteinander verbinden: Membrankrümmung induziert durch eine Flächenasymmetrie zwischen den Membranhälften und durch Wechselwirkung mit Proteinen. Die Ergebnisse dieser Arbeit deuten darauf hin, dass die für Endozytose notwendige Krümmung durch die durch Lipidtransport induzierte Flächenasymmetrie der Membranschichten unterstützt wird. / Endocytic engulfment requires high local membrane curvature and causes significant area changes of the membrane leaflets. This can be initiated by differences between the surface areas of the two monolayers related to leaflet specific modulation of lipid composition. Thus, it was proposed that lipid translocators, pumping phospholipids from the outer to the inner leaflet, account for monolayer area asymmetry as an early step in endocytosis. To elucidate the influence of this asymmetry on endocytosis, surface area relation was altered by adding exogenous phospholipids to living cells and changes in endocytic activity were quantified. Depending on the lipid species, exogenous lipids were only incorporated into the outer layer or subsequently translocated across the plasma membrane thereby increasing either the outer or inner surface area. Addition of different analogues of aminophospholipids, which are translocated to the inner leaflet, led to an enhancement of bulk flow endocytosis in K562 cells. Moreover, our data indicate that clathrin-mediated endocytosis of Hep2 cells was stimulated as well. Inversely, addition of phospholipids, which remain on the outer layer, reduced bulk flow or clathrin-mediated endocytosis in various cell lines. Notably, also clathrin-mediated endocytosis was influenced by the addition of lipids, although many proteins noted for their ability to induce membrane curvature are known to be implicated in this pathway. This corroborates a recent model how aminophospholipid translocases are implicated in endocytosis. Upon translocating lipids and additionally interacting with endocytic accessory proteins, lipid translocators could integrate two processes to generate curvature: membrane bending based on monolayer area asymmetry and protein-related mechanisms. Collectively, findings in the present study suggest that curvature generation in endocytosis is supported by the induction of monolayer area asymmetry mediated by the translocation of lipids.

Mitglieder der CCC1 like Proteinfamilie sind Metalltransportproteine und Homologe zum vakuolären Eisen- und Mangantransporter CCC1 aus S. cerevisiae. VIT1-Homologe als CCC1-like Proteine pflanzlicher Herkunft können eine Anwendung in der Eisen-Biofortifikation finden. Bei der Überexprimierung von TaVIT2 in Weizen wurde von der 4 fachen Erhöhung des Eisen- und Mangangehalts im Mehl berichtet (Connorton et al., 2017). Die Überexprimierung von OsVIT1 oder OsVIT2 in Reis hat zur Erhöhung sowohl vom Eisengehalt als auch von Zink- und Mangangehältern geführt (Zhang et al., 2012). In dieser Arbeit wurden 6 CCC1-like Proteine aus A. thaliana bezüglich ihrer Substratspezifität untersucht. VIT1 und fünf VIT-Like Proteine (VTLs) wurden an ihren N- und C Termini modifiziert und im Hefekomplementationsverfahren auf ihre Fähigkeit Eisen, Mangan oder Zink zu transportieren untersucht. Ein einfacher Algorithmus zur Modifizierung von Membranproteinen durch Entfernung mehrerer AS-Reste vom N- bzw. vom C-Terminus ist beschrieben. Es sollte untersucht werden, ob diese Modifizierung einen Einfluss auf die Hefekomplementation hat. Native und modifizierte VTLs wurden mittels GFP-Fusion in den Zelllokalisierungsstudien untersucht. Es sollte festgestellt werden, ob Modifikationen die Zelllokalisierung beeinflussen. Eine Lokalisierung an der Vakuolenmembran wurde für VIT1, VTL1-4 und für einige modifizierte VTL4-Konstrukte nachgewiesen. Dagegen zeigte das VTL5-Konstrukt vorwiegend eine Plasmamembranlokalisierung. Die Entfernung von 21 AS vom N Terminus von VTL4 bzw. von 23 AS vom N-Terminus von VIT1 hatten keinen Effekt auf die Komplementation der Δccc1 Mutante. Dagegen zeigten die entsprechenden Konstrukte keine Komplementation der Δpmr1 Mutante. Es wurden modifizierte Konstrukte von AtVIT1 und AtVTL4 gefunden, die nicht in der Lage waren Mangan und Zink zu transportieren und dadurch für Eisen spezifisch gewesen wären. Diese wären gute Kandidaten für eine eisenselektive Biofortifikation. / CCC1 like protein family are metal transport proteins with high homology to the S. cerevisiae vacuolar iron and manganese transporter CCC1. The plant members of this family such as VIT1-homologue might find an application in iron biofortification of crops. An almost 4-fold increase in the iron content in flour of TaVIT2 overexpressing wheat was demonstrated (Connorton et al., 2017), but the overexpressing plants showed a significant increase in manganese content as well. OsVIT1 or OsVIT2 overexpressing in rice (Zhang et al., 2012) lead to increased iron, zinc and manganese. In this thesis six member of A. thaliana CCC1-like proteins were investigated for their substrate specificity. VIT1 itself and five other VIT1-like proteins (called VTLs) were modified at their N- and C-termini and investigated for iron, manganese and zinc transport capacity via a yeast complementation assay. A simple algorithm to modify membrane proteins by removing AA rests from their N- and / or C-terminal regions is presented, and the effects of these modifications on the functionality of the modified protein by the yeast complementation test are reported. The cell localization of native and modified VTLs was studied using fusion to GFP to determine if modifications would alter the subcellular localization in yeast. VTL1-4 as well as VIT1 were localized to the vacuolar membrane of yeast cell. VTL5 was predominantly localized to the plasma membrane of the yeast cell. Some modified VTL4 constructs could still be localised to the vacuolar membrane. Removal of 21 AA from the N-terminus of AtVTL4 as well as removal of 23 AA from the N-terminus of AtVIT1 didn't affect the complementation of the Δccc1 mutant. In contrast no complementation of Δpmr1 mutant was seen with the same constructs. Certain modified forms of AtVIT1 and AtVTL4 were unable to transport either manganese or zinc. We propose that they might be iron-specific, and thus would be candidates for a selective iron biofortification.

ABC-Transmembrantransporter sind an der Aufnahme, Verteilung und Ausscheidung vieler Arznei- und Fremdstoffe beteiligt. Sie spielen eine Schlüsselrolle in der Pharmakokinetik und in der Ausscheidung toxischer endogener oder exogener Substanzen. Das Ziel der hier präsentierten Untersuchungen war deshalb, den Einfluss genetischer Polymorphismen des bekanntesten Vertreters dieser Proteinfamilie, MDR1 (ABCB1) zu untersuchen. Darüberhinaus sollte der ebenfalls zur ABC-Transporterfamilie gehörende hepatozelluläre Exporter für monoanionische Gallensäuren identifiziert und charakterisiert werden. MDR1 erwies sich als ein hochpolymorphes Gen mit zahlreichen Einzelbasenaustauschen (SNPs). Die meisten SNPs waren intronisch oder stumm. Für den nichtkodierenden SNP im Exon 26 3435C>T ergab sich bei homozygoten Trägern des T-Allels eine im Vergleich zum Wildtyp geringere intestinale P-Glykoprotein Expression mit einer entsprechend höheren und schnelleren Absorption von Digoxin. Die Auswertung pharmakokinetischer Profile von Digoxin in Individuen mit MDR1-Haplotypen der miteinander verbundenen SNPs in Exon 21 2677 und Exon 26 3435 untermauerte die beobachteten pharmakogenetischen Effekte. Nach oraler Einzelgabe von 1 mg Digoxin konnten wahrscheinlich aufgrund der Überschreitung der P-Glykoprotein Transportkapazität keine genotypischen Unterschiede beobachtet werden. Der biliäre Exporter für monoanionische Gallensäuren (Bsep) konnte als ein 160 kDa Glykoprotein aus einer Rattenleber cDNA-Bibliothek identifiziert werden und gehört ebenfalls zur ABC Transporter-Familie. Die transkriptionelle Regulation und Möglichkeiten der Modulation der Expression des Bsep-Gens wurden in vitro und in Tiermodellen der Cholestase untersucht. Dabei zeigte sich, dass Gallensäuren über ein proximales FXRE-Motiv die Bsep Promotoraktivität stimulierten. Arzneistoffe hatten ebenfalls einen Einfluss auf die Transkription des Bsep-Gens. Die adaptive Regulation hepatozellulärer Transporter während der Cholestase ergab eine verminderte Expression der meisten basolateralen Aufnahmetransporter und eine unveränderte oder heraufregulierte Proteinmasse kanalikulärer (apikaler) Efflux-Transporter. Dieses Regulationsmuster dient dem Schutz der Leberzelle, indem eine intrazelluläre Anreicherung toxischer Gallensäuren vermindert und der Gallefluss für eine intakte biliäre Clearance aufrechterhalten wird. / ABC transmembrane transporters are involved in absorption, distribution and excretion of diverse drugs and xenobiotics. They are key factors in pharmacokinetics and in the elimination of toxic endogenous or exogenous compounds. Therefore, the aim of the present study was to investigate the influence of genetic polymorphisms of the best known member of this protein family, MDR1 (ABCB1). In addition, the identity of another ABC transporter assumed to be the major hepatocellular export pump for monoanionic bile acids should be revealed and characterized. MDR1 turned out as a highly polymorphic gene with many single nucleotide polymorphisms (SNPs). Most of the SNPs were intronic or silent. Homozygous carriers of the non-coding SNP in exon 26 3435C>T had lower intestinal P-glycoprotein expression rates and thus enhanced absorption of the model compound digoxin as compared to wildtype controls. The analysis of pharmacokinetic profiles in different MDR1-haplotypes of the linked SNPs in exon 21 2677 and exon 26 3435 supported the above data. An oral single dose of 1 mg digoxin did not result in genotypic differences of tested genotypes, probably because this dose was above the maximal transport capacity of P-glycoprotein. The biliary export pump for monoanionic bile acids (Bsep) was identified as an 160 kDa glycoprotein of the ABC transporter family by screening a rat liver cDNA library. The transcriptional regulation and modulatory factors of Bsep (Abcb11) gene expression were analyzed in vitro and in animal models of cholestasis. The promoter activity of Bsep was stimulated by bile acids via a proximal FXRE motif. Drugs were also able to modify Bsep gene transcription. Adaptive regulation of hepatocellular transporters during cholestasis followed a pattern of diminished expression of most basolateral uptake carrier systems and maintained or even upregulated protein mass of canalicular (apical) exporters. This pattern serves as a protective mechanism of the liver cells preventing intracellular accumulation of toxic bile acids and providing unimpaired biliary flow and clearance.

BACKGROUND: The neurotransmitter noradrenaline (NA) mediates arousal, attention and mood and exerts anti-inflammatory and neuroprotective effects. Its projections reach hypothalamic nuclei which regulate the neuroendocrine stress response. Changes in noradrenergic signalling were reported in multiple sclerosis (MS) and psychiatric illness and may account for the high prevalence of comorbid depression and fatigue in MS patients. Associated studies of our study group—investigating stress response in obese and non-obese subjects—have shown increased activity of the stress axes including an association between hypothalamic-pituitary-adrenal (HPA) axis responsiveness and central noradrenaline transporter. OBJECTIVES: (i) To evaluate central NA transporter (NAT) availability in vivo in immunotherapy-naïve relapsing-remitting multiple sclerosis (RRMS) patients compared to healthy controls (HC), (ii) to measure hypothalamic-pituitary-adrenal (HPA) axis responsiveness and the arginine-vasopressin surrogate (AVP) copeptin in patients with RRMS and clinically isolated syndrome (CIS) compared to HC, (iii) to test whether HPA axis responsiveness is differentially associated to NAT availability in RRMS patients and HC. METHODS: 22 patients (11 RRMS, 11 CIS) were enrolled and compared to 22 sex- and age-matched HC. (i) Positron emission tomography (PET) was performed in 11 RRMS and 12 HC applying the NAT-selective radiotracer S,S-[11C]O-methylreboxetine ([11C]MRB) for intergroup comparison. (ii) All patients underwent the combined dexamethasone/corticotropin releasing hormone (dex/CRH) test. Plasma ACTH and cortisol curve parameters, and copeptin after dexamethasone intake were derived. (iii) MRB-PET imaging data were correlated to curve indicators and copeptin obtained from the dex/CRH test in RRMS patients. RESULTS: (i) RRMS patients show increased NAT availability in almost all subcortical regions, reaching statistical significance in the thalamus, amygdala, putamen and pons/midbrain. No association with clinical or psychometric variables was found. (ii) Immunotherapy-naïve RRMS patients show no significant changes in cortisol, ACTH or copeptin indices. (iii) There is no correlation between HPA axis indicators and NAT availability in RRMS patients. In HC, NAT availability correlated positively with cortisol curve indicators. CONCLUSION: This study supports the evidence for increased NAT availability in immunotherapy-naïve RRMS patients compared to HC. The increased NAT availability was shown in the subcortical brain regions (relevant to attention and emotional regulation) of the RRMS patients. In this cohort, no correlation with physical or psychometric scores was found. It will be further of interest, if these NAT changes longitudinally predispose to the psychiatric comorbidities which are frequently seen in MS patients or if they do in larger, more heterogenous sample sizes. Our cohort of early RRMS and CIS did not display a statistically significant alteration in the HPA axis responsiveness compared to HC. No association between NAT availability and HPA axis responsiveness could be detected in RRMS patients.:TABLE OF CONTENTS LIST OF ABBREVIATIONS…………………….………………………………………......4 LIST OF FIGURES…..….………………………….….……..…………………………..…5 I BIBLIOGRAPHIC DESCRIPTION…………………………..……………………………6 II INTRODUCTION…..…..………………………………………………………….............7 2.1 Multiple sclerosis — Background and scope……………....…………………..........7 2.1.1 Diagnostic criteria, subtypes and clinical features……….............….…………....7 2.1.2 Multiple sclerosis and its impact on daily life: fatigue.…...…...….............………9 2.2. Noradrenaline — neurotransmitter and immunomodulator…...…………….........10 2.2.1 Noradrenaline in the context of multiple sclerosis…………………….................11 2.2.2 Noradrenaline in the context of neuroinflammation and neurogenesis.............12 2.3 Noradrenaline transporter as regulator of noradrenergic transmission….…........13 2.3.1 Noradrenaline transporter imaging……………………………............................14 2.4 Neuroendocrine stress response……...…..……………………..……..……….......14 2.4.1 Noradrenaline in the context of stress response regulation…...........................15 2.4.2 Stress axis regulation in multiple sclerosis……….............……….....................16 III METHODS……………......……………………………………………………..……....19 3.1 Objectives and hypotheses.....……..…………………………………………….......19 3.2 Study design………………..….....………………………………….…..…………….20 3.3 Hypothalamic-pituitary-adrenal axis assessment using the combined dexamethasone/CRH test…….……...........……….....................................................21 3.4 Questionnaires……...…………………….....…………………………………………22 3.4.1 Beck-Depression-Inventory……………….............……….………………………22 3.4.2 Würzburger Erschöpfungsinventar bei MS….…………..….............……………22 3.5 PET imaging, imaging data processing and analysis………………….....………..23 3.6 Statistical analysis………………….………………………………………….....……23 IV RESULTS………….......……………………………………………….........................24 4.1 Changes of central noradrenaline transporter availability in immunotherapy-naïve multiple sclerosis patients – Publication….....……...…………24 4.2 HPA axis responsiveness does not differ between HC and RRMS or CIS patients…...………………………………...……………………………………….25 4.3 In RRMS patients, noradrenaline transporter availability of selected brain regions does not correlate with neuroendocrine indicators of stress responsiveness, but do positively correlate in healthy controls………………..….…..25 V SUMMARY………………….…………………………………………………………….31 5.1 Significantly changed noradrenaline transporter availability in RRMS patients in brain regions relevant to attention, vigilance and mood………….............31 5.2 Noradrenaline transporter availability is not significantly associated with psychometric and physical scores……..…………………...........................................32 5.3 HPA responsiveness does not significantly differ between early-stage RRMS patients, CIS patients and healthy controls………..…………………..............32 5.4 NAT DVR of selected brain regions do not reveal a significant association to HPA response in RRMS patients, but in healthy controls………...……..................33 5.5 Limitations..………………………………………………………………………….....35 5.6 Future directions…………………………………………………………………….....35 VI PUBLICATION BIBLIOGRAPHY…….……………………....…………….................36 VII ANHANG…….………..…...…..………..………………………………………………49 7.1 Publikationen…………..……….....…..……………………………………................49 7.1.1 Publikationen als Ko-Autorin…...…………..………..............…………………….50 7.1.1.1 Central noradrenaline transporter availability is linked with HPA axis responsiveness and copeptin in human obesity and non-obese controls……..50 7.1.1.2 Post-dexamethasone serum copeptin corresponds to HPA axis responsiveness in human obesity...............................................................................51 7.2 Erklärung zum wissenschaftlichen Beitrag der Promovendin zur Publikationspromotion…………...........………………………………………………52 7.3 Erklärung über die eigenständige Abfassung der Arbeit...…....…………...…......53

No description available.

The main aim of the thesis was to measure antidepressant (AD) non-compliance, to determine which factors are closely associated with AD non-compliance and the consequences of prolonged AD non-compliance in the private health sector of South Africa. The empirical study followed an observational, prospective, cohort study using longitudinal medicine claims data provided by a nationally representative Pharmaceutical Benefit Management company (PBM) from 1 January 2006 to 31 December 2011. Failure to respond to AD treatment and achieving remission has severe neurobiological and clinical consequences. The clinical consequences include increased social and functional impairment, higher risk for recurrence and relapse of a depressive episode, a weak treatment outcome, significant increase in treatment cost, over-utilization of health care systems, and ultimately an increased suicide risk. However, the neurobiological consequences are much more far reaching. One of the more serious yet under-recognized neurobiological complications of AD non-compliance is the development of antidepressant discontinuation syndrome (ADS), which is the result of non-compliance or the abrupt discontinuation of AD treatment. Altered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems. After the first four months only 34% (n=12 397) of patients were compliant. What’s more a statistically significant association was found between active ingredient consumed and compliance (p < 0.0001). Only 26.2% of patients who received amitriptyline-containing products were complaint compared to 38.8% and 38.7% in the cases of venlafaxine and duloxetine, respectively. The current study found that females have a significantly higher prevalence of MDD and HIV/AIDS when compared to males. The co-morbidity between HIV/AIDS and major depressive disorder (MDD) had a significant effect on AD treatment compliance as patients diagnosed with both HIV/AIDS and MDD (74.43. ± 32.03, 95%Cl: 71.51-77.34) displayed a lower compliance vs. MDD patients (80.94% ± 29.44, 95%Cl: 80.56-81.33). Noteworthy, observations were that 75% (p < 0.0217; Cramer’s V = 0.0388) of venlafaxine and 28.6% (p < 0.0197; Cramer’s V = -0.0705) of the paroxetine items were compliant in patients diagnosed with both HIV/AIDS and MDD. The overall compliance (35.19% acceptable compliance; n = 42 869) of patients taking both ADs and GDs was weak. In the group receiving both AD and GDs, an increased AD treatment period was associated with a significant increase (p < 0.0001) in AD compliance (406.60 days; 95%Cl: 403.20 – 409.90 vs. 252.70 days; 95%Cl: 250.20 – 255.20). In this cohort amitriptyline (29.57%), mirtazapine (31.36%) and fluoxetine (32.29%) were associated with the lowest levels of compliance, while duloxetine (40.67%) was found to have the highest compliance. Lastly, ADs with highest non-compliance were associated with an increase use in GDs. Alprazolam (n = 10 201) and zolpidem (n = 9 312) were the most frequently dispensed GDs in combination with AD treatment. In conclusion the current study confirms that AD non-compliance is as big an obstacle in developing countries as it is in developed countries. Antidepressant treatment non-compliance has far reaching consequences especially with the development of ADS which further complicates MDD and might be a precursor for the development of TRD. Several factors were found to be closely associated with AD treatment non-compliance which include; pharmacological class of AD, gender, chronic co-morbid illnesses and a short treatment period. / PhD (Pharmacy Practice), North-West University, Potchefstroom Campus, 2015

The main aim of the thesis was to measure antidepressant (AD) non-compliance, to determine which factors are closely associated with AD non-compliance and the consequences of prolonged AD non-compliance in the private health sector of South Africa. The empirical study followed an observational, prospective, cohort study using longitudinal medicine claims data provided by a nationally representative Pharmaceutical Benefit Management company (PBM) from 1 January 2006 to 31 December 2011. Failure to respond to AD treatment and achieving remission has severe neurobiological and clinical consequences. The clinical consequences include increased social and functional impairment, higher risk for recurrence and relapse of a depressive episode, a weak treatment outcome, significant increase in treatment cost, over-utilization of health care systems, and ultimately an increased suicide risk. However, the neurobiological consequences are much more far reaching. One of the more serious yet under-recognized neurobiological complications of AD non-compliance is the development of antidepressant discontinuation syndrome (ADS), which is the result of non-compliance or the abrupt discontinuation of AD treatment. Altered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems. After the first four months only 34% (n=12 397) of patients were compliant. What’s more a statistically significant association was found between active ingredient consumed and compliance (p < 0.0001). Only 26.2% of patients who received amitriptyline-containing products were complaint compared to 38.8% and 38.7% in the cases of venlafaxine and duloxetine, respectively. The current study found that females have a significantly higher prevalence of MDD and HIV/AIDS when compared to males. The co-morbidity between HIV/AIDS and major depressive disorder (MDD) had a significant effect on AD treatment compliance as patients diagnosed with both HIV/AIDS and MDD (74.43. ± 32.03, 95%Cl: 71.51-77.34) displayed a lower compliance vs. MDD patients (80.94% ± 29.44, 95%Cl: 80.56-81.33). Noteworthy, observations were that 75% (p < 0.0217; Cramer’s V = 0.0388) of venlafaxine and 28.6% (p < 0.0197; Cramer’s V = -0.0705) of the paroxetine items were compliant in patients diagnosed with both HIV/AIDS and MDD. The overall compliance (35.19% acceptable compliance; n = 42 869) of patients taking both ADs and GDs was weak. In the group receiving both AD and GDs, an increased AD treatment period was associated with a significant increase (p < 0.0001) in AD compliance (406.60 days; 95%Cl: 403.20 – 409.90 vs. 252.70 days; 95%Cl: 250.20 – 255.20). In this cohort amitriptyline (29.57%), mirtazapine (31.36%) and fluoxetine (32.29%) were associated with the lowest levels of compliance, while duloxetine (40.67%) was found to have the highest compliance. Lastly, ADs with highest non-compliance were associated with an increase use in GDs. Alprazolam (n = 10 201) and zolpidem (n = 9 312) were the most frequently dispensed GDs in combination with AD treatment. In conclusion the current study confirms that AD non-compliance is as big an obstacle in developing countries as it is in developed countries. Antidepressant treatment non-compliance has far reaching consequences especially with the development of ADS which further complicates MDD and might be a precursor for the development of TRD. Several factors were found to be closely associated with AD treatment non-compliance which include; pharmacological class of AD, gender, chronic co-morbid illnesses and a short treatment period. / PhD (Pharmacy Practice), North-West University, Potchefstroom Campus, 2015

No description available.

Att arbeta som nyutbildad intensivvårdssjuksköterska kan upplevas som väldigt krävande. Det krävs både specificerad kunskap om olika komplexa sjukdomstillstånd och att intensivvårdssjuksköterskan ska kunna hantera den högteknologiska miljön som en intensivvårdsavdelning utgör. När patienter vårdas på intensivvårdsavdelning förekommer olika intrahospitala transporter under vårdtiden, vilket medför ökade risker för patienterna. Tidigare studier visar att det förekommer ett högre antal oväntade händelser och en större otrygghet bland intensivvårdssjuksköterskor med kort arbetserfarenhet av intensivvård i samband med intrahospitala transporter. Syftet med detta examensarbete var att beskriva behov hos intensivvårdssjuksköterskor med mindre än fem års arbetserfarenhet för att känna sig trygga i samband med intrahospitala transporter av kritiskt sjuka patienter. Nio intensivvårdssjuksköterskor med &lt;5 års arbetserfarenhet av intensivvård deltog i studien. Datainsamlingen genomfördes med semistrukturerade intervjuer, vilka sedan analyserades med en kvalitativ innehållsanalys. Analysen resulterade i tre kategorier: behov av att ha kompetent vårdpersonal med god samarbetsförmåga, behov av att ha en miljö som är anpassad för transporter och behov av att genomföra en omsorgsfull planering för att känna sig förberedd, vilka sedan resulterade i ett tema: behov av att känna kontroll över situationen med stöd från vårdteamet. Resultatet av denna studie visar vikten av att det implementeras en rutin vid intensivvårdsavdelningar för nyutbildade intensivvårdssjuksköterskor som tar anställning vid arbetsplatserna. Största vikten bör läggas på att intensivvårdssjuksköterskor ska omges av ett kompetent vårdteam med en tillåtande miljö, där det finns tid och möjlighet för god och individanpassad handledning.