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Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

A review of the literature on blood stream infections caused by contaminated intravenous infusates which are prepared in clinical care settings found that this common nursing procedure poses at times a significant and life-threatening risk to patients. The guidance and regulations surrounding the preparation of intravenous drugs in clinical care settings suggests that this procedure is extremely complex and poses many different potential hazards to patients. This thesis set out to determine how the infection risks are being addressed in practice by asking the questions: ‘What is the system of intravenous drug preparation in clinical care settings in NHS Scotland?’ and, ‘How does it work in practice?’ Several data sources were utilised: six locations, in specialities where the literature identified significant outbreaks had occurred, were examined for potential contamination risk. Observations (78) of infusate preparations were undertaken and, where available, written procedures were compared with observed practices. Finally, analyses were made of 71 questionnaires, completed by the nurses who prepare intravenous drugs, regarding their opinions of the procedures’ safety and when they perform redundancy checks. The conclusion of this study is that the system of preparing intravenous drugs in clinical care settings by nurses is, as a consequence of potential infusate contamination, error-prone and unreliable. The reasons for this conclusion are now detailed. o Due to a lack of mandatory environmental standards, and the provision of poor environments, there is a risk of infusate contamination from environmental sources and consequently, a risk to patients of infusate-related blood stream infections (IR-BSI). o Some in use equipment poses contamination risks to patients’ infusates. Equipment that could reduce the contamination risk is not always available and in some instances such safety-enhancing equipment has been removed. o There are no complete written procedures which mirror what is done in practice. At present, from a human-factors perspective, it is not easy for the nurse to do the right thing, or to be sure exactly what is the right thing to do. o The procedure, in practice, has the required elements of an aseptic procedure, but the execution of the procedure is more often not performed aseptically. o The procedure of intravenous drug preparation as observed is mainly an interrupted aseptic procedure and as such the recommencement of the aseptic procedure requires repeated hand hygiene. o The nurses’ opinions of safety vary, as did their assessment of the infection risk to their patients, but it is clear that intravenous drug preparation is not a much-loved nursing procedure and some nurses find it very stressful. o There is no asepsis quality control built into the system. Aseptic steps are the least likely to be performed as a redundancy check compared to the mandatory checks of ‘right patient, right drug and right dose’. o The information available to the nurses, from the drug companies, from the makers of equipment and from national agencies does not identify with sufficient clarity the infection risks, or detail how to negate them. Suggestions for improvement to the six procedures and environments are clear once the procedure steps are colour-coded as either aseptic or non-aseptic; validity testing of these improvements is however, still needed. The systems’ vulnerabilities observed in this research appear to stem from a chain of external influences including an underestimation of the problem size and the actions needed to prevent it in evidence-based guidelines and mandatory guidance. This leads to poor recognition of the risk of IR-BSI in clinical practice. The problem of infusate contamination causing IR-BSIs is further compounded by the fact that it is not caused by a single organism and does not always present as a disease in real time, that is, over the lifetime of the infusion. As a consequence, this presents surveillance difficulties in terms of definitions, data collection and analysis. Finally, although the diagnosis of a blood stream infection for an individual patient remains relatively easy, it is not easy to recognise a contaminated infusate as the origin of the problem. All these challenges make both the recognition of the problem and agreement on prevention strategies, extremely challenging. In summary, the main conclusion of this thesis is that the preparation of infusates in clinical care settings, which occurs approximately 3,000,000 times a year in NHSScotland, is from an aseptic perspective, error-prone and unreliable. Recommendations to optimise patient safety include, changing the procedure locally and, with the utmost urgency, the production of minimum environmental standards. The results of this study are relevant to all hospitals in Scotland and throughout the United Kingdom where the current regulations apply and similar procedures are performed.

Master of Science / Department of Clinical Sciences / Elizabeth Davis / Differences in pharmacokinetics and drug disposition exist between young and adult animals which become especially important for drugs with a narrow therapeutic index. While the pharmacokinetics and plasma concentrations of intravenous lidocaine have been studied in adult horses, determination of the disposition in foals is necessary before appropriate clinical use can be determined. This study examined the disposition of intravenous lidocaine in healthy (phase I) and hospitalized (phase II) foals. Phase I consisted of 6 healthy 4-10 week old foals administered a 6-hour intravenous lidocaine infusion. Phase II consisted of 8 hospitalized foals (2-136 days old) administered intravenous lidocaine. A bolus (1.3 mg/kg) of lidocaine was administered intravenously to all foals followed by a 50 µg/kg/min infusion. Plasma lidocaine and monoethylglycinexylidide (MEGX) concentrations were determined. In phase I, plasma lidocaine concentrations remained below the suggested adult target range of 1-2 µg/mL with MEGX concentrations approximately half that of the parent drug. Total body clearance of lidocaine was 72.2 ± 7.8 mL/min/kg, elimination half-life (t₁/₂) was 26.3 ± 3.7 min, peak concentration (C[subscript]m[subscript]a[subscript]x) was 0.79 ± 0.07 µg/mL, and the volume of distribution (V[subscript]d) was 1.8 ± 0.4 L/kg. The C[subscript]m[subscript]a[subscript]x for MEGX was 0.36 ± 0.11 µg/mL, t₁/₂ was 60 ± 6 min and time to peak concentration (T[subscript]m[subscript]a[subscript]x) was 279.6 ± 90.3 min. In phase II, the severely compromised foals that were eventually euthanized had the largest fluctuations in plasma lidocaine and MEGX concentrations; foals that were discharged from the hospital had plasma concentrations below the target adult range similar to foals in phase I. In conclusion, despite low plasma lidocaine concentrations, the clinical benefits observed in foals may be due to the presence of metabolites. Further research in a larger population of unhealthy foals is required before comprehensive dosing recommendations can be made.

L’administration intraveineuse d’ADN thérapeutique rencontre de nombreux obstacles liés à sa dégradabilité, ainsi qu’à sa difficulté à pénétrer les cellules en raison de sa taille importante et de son hydrophilie. Des lipoplexes conjugués à de l’acide hyaluronique (HA) de haut poids moléculaire ont été développés afin de délivrer de l’ADN plasmidique à l’intérieur de cellules cancéreuses exprimant le récepteur membranaire CD44, récepteur clé du développement tumoral. L’emploi d’HA conjugué au phospholipide DOPE (HA-DOPE) et d’un plasmide modèle GFP a permis d’obtenir des lipoplexes d’environ 250 nm, chargés négativement, protégeant efficacement l’ADN contre les nucléases et activant peu la fraction C3 du système du complément. Dans un modèle cellulaire exprimant CD44, la transfection optimale a été obtenue par l’utilisation de lipides avec 10% d’HA-DOPE complexés à de l’ADN selon un rapport 2:1. Ces lipoplexes sont internalisés par la voie des cavéoles et de façon dépendante du récepteur CD44. Cette formulation a été appliquée à la vectorisation d’un gène thérapeutique, codant pour le récepteur des estrogènes β (ERβ), qui est un potentiel suppresseur de tumeur. Sur un modèle in vivo de xénogreffes de cellules humaines de cancer du sein estrogéno-dépendant et exprimant CD44, la diminution du volume tumoral, ainsi que de l’indice de prolifération Ki67 ont permis de montrer l’effet anticancéreux par voie intraveineuse des lipoplexes conjugués à l’HA. / Intravenous administration of therapeutic DNA faces many obstacles related to its degradability and its difficulty to penetrate into the cells due to its large size and its hydrophilicity. Lipoplexes conjugated with high molecular weight hyaluronic acid (HA) have been designed in order to deliver plasmid DNA inside cancer cells expressing the membrane receptor CD44, a key receptor in the development of tumors. The use of HA conjugated to the phospholipid DOPE (HA-DOPE) and of the GFP model plasmid lead to obtain lipoplexes around 250 nm, negatively charged, which efficiently protect the DNA against nucleases and slightly stimulate the C3 fraction of the complement system. In a cellular model expressing CD44, the optimal transfection was obtained by using lipids containing 10% of HA-DOPE complexed to DNA at a 2:1 ratio. Internalization of these lipoplexes is mediated by the caveolae pathway and involves the CD44 receptor. This formulation was applied to the delivery of a therapeutic gene encoding the estrogen receptor β (ERβ), which is a potential tumor suppressor. On an in vivo xenograft model of estrogen-dependent breast cancer cells expressing CD44, decrease of the tumor volume, as well as decrease of the Ki67 proliferation index, have shown the anticancer activity of the lipoplexes conjugated to HA following intravenous administration.

A administração de catecolaminas por via intravenosa é uma prática comum no ambiente hospitalar, principalmente em Unidade de Terapia Intensiva (UTI), Hemodiálise e Pronto Socorro (PS). Apesar de se tratar de um procedimento que demanda cuidados de enfermagem bastante específicos, este pode ser realizado por qualquer membro da equipe de enfermagem, até mesmo sem supervisão direta de um enfermeiro. Para prestar cuidados de enfermagem adequados aos pacientes que recebem catecolaminas por via intravenosa é necessário que o profissional que realiza o procedimento disponha de conhecimento específico acerca da prática realizada. Em unidades como UTI, PS e Hemodiálise, espera-se que o enfermeiro exerça supervisão direta desses cuidados, já que são unidades em que os pacientes apresentam condições mais críticas e geralmente instáveis. Desta forma, é esperado que o enfermeiro detenha todo o conhecimento necessário para administrar as catecolaminas com segurança, minimizando assim os riscos para o paciente. Estes conhecimentos devem ser aprofundados englobando desde ciências básicas como anatomia e fisiologia, até aspectos mais específicos como a escolha do cateter, recomendações de uso dos materiais disponíveis, conhecimentos farmacológicos direcionados e recomendações e cuidados durante a infusão desse tipo de medicamento. Este estudo avaliou o grau de conhecimento dos enfermeiros do Hospital Universitário (HU) da Universidade de São Paulo (USP) quanto à administração de catecolaminas de infusão contínua por via intravenosa. Foram sujeitos deste estudo somente os enfermeiros que atuam em unidades onde a administração de catecolaminas é prática comum. A pesquisa limitou-se aos enfermeiros que atuam em unidades de cuidados de adultos por considerar que há peculiaridades existentes no cuidado do paciente adulto e pediátrico no que diz respeito à administração de drogas vasoativas e à necessidade de atualização e vivência prática da situação. Assim, através de questionário estruturado, procedeu-se a avaliação do conhecimento dos enfermeiros atuantes nas unidades de Hemodiálise, PS de adultos e UTI de adultos com relação à administração de catecolaminas por via intravenosa. Os dados obtidos com a aplicação dos questionários foram submetidos a análises estatísticas para definir se o conhecimento apresentado pelos enfermeiros avaliados é condizente com o preconizado pela literatura para realização segura de tal procedimento / Catecholamine management through intravenous route is a common practice in the hospital setting, mainly at the Intensive Care Unit (ICU), Hemodialysis and Emergency Room (ER). Although it\'s a procedure that demands very specific nursing care, this can be made by any member of the nursing staff, even without direct supervision of a nurse. For delivering optimal nursing care to patients who receive catecholamine through intravenous route, it\'s necessary the provider who makes the procedure to have specific knowledge on this practice. In settings like ICU, ER and Hemodialysis, the nurse is expected to have direct supervision in these procedures, once they are units where patients present more critical and generally unstable conditions. This way, the nurse is supposed to have all the knowledge necessary to manage catecholamine safely, thus minimizing the risks for the patient. This knowledge must be deepen involving from basic sciences such as anatomy and physiology, to more specific aspects, such as the catheter chosen, recommendations for use of available material, specified pharmacological knowledge and recommendations and care during infusion of this type of medication. This study evaluated the knowledge level of nurses from University Hospital (HU) of University of Sao Paulo (USP) regarding to catecholamine management of continuous infusion through intravenous route. Subjects of the study were only the nurses who work in setting where catecholamine management is a common practice. The research limited to nurses who work in adult care, considering that there are peculiarities in adult and pediatric care related to vasoactive medication management and the need of upgrade and practical experience of the situation. Thus, through a structured questionnaire, it was made an evaluation of knowledge of nurses who work in Hemodialysis units, adult ER and adult ICU regarding to catecholamine management through intravenous route. The data obtained through the questionnaires were submitted to statistic analyses to define if the knowledge presented by the evaluated nurses is according to what is advised by literature to make safely such procedure

Thesis (Master of Emergency Medical Care)--Cape Peninsula University of Technology, 2018. / Physical injury is a major cause of premature death and disability worldwide (WHO, 2015). Mortality statistics for South Africa indicate that approximately half of all injury-related deaths were intentionally inflicted, often as a result of sharp-force injuries (Donson 2009). Cape Town is reputed to be a violent city (Nicol et al., 2014). Pre-hospital emergency care providers are often the first medical contact for injured patients. Previously, it was understood that high volume crystalloid administration would improve survival and was standardised in the management of shock (Santry & Alam 2010). However, over-administration of crystalloid fluid can cause patient harm by potentially worsening injuries and can be detrimental to a patients survival. Current evidence supports the practice of lower volume crystalloid intravenous fluid administration- permissive hypotension. Little is known about pre-hospital emergency care providers intravenous fluid management practices for penetrating injury. Injury surveillance data for victims of penetrating injury is also scarce with the majority of current data taken from mortality sources. Surveilling pre-hospital cases may yield opportunities for prevention from premature mortality and morbidity. The aim of this study is to undertake surveillance of penetrating injury and related intravenous fluid resuscitation in the pre-hospital emergency care environment. A prospective observational descriptive survey was conducted in the Cape Metropole1. Over three consecutive months, emergency care providers documented parameters related to mechanism of injury, scene vital signs, hospital vital signs, intravenous fluid resuscitation and basic patient demographic information for patients with penetrating injury. A predetermined inclusion and exclusion criteria was used to sample patients.

PhD / The aims of this study were to test the efficacy of immunoglobulin and its Fab and Fc fragment in the treatment of experimental autoimmune neuritis (EAN) in Lewis rats, to investigate which portion of immunoglobulin is operative in the effect of IVIg, and to clarify the possible mechanisms by which immunoglobulin exerts its action in the treatment of rats EAN. EAN was induced by immunization with whole bovine peripheral nerve myelin. The immunized rats were randomized into groups, assessed clinically, electrophysiologically, and histologically, and intravenously injected with normal saline, albumin, human IVIg preparation, purified Fab or Fc fragments. The treatment efficacy was compared between normal saline and albumin groups, albumin and IVIg groups, albumin and Fab groups, albumin and Fc groups, Fab and Fc groups, Fab and IVIg groups, and Fc and IVIg groups. Methods of myelin isolation, antibody purification, and Western blot techniques were also applied. The results revealed that treatment with Fc fragment and IVIg at the onset of signs of disease effectively prevented further progression of disease, shortened disease duration, and facilitating recovery from illness as shown in clinical, electrophysiological and histological parameters. In the study which the efficacy of albumin and IVIg was compared, 5 out of 17 rats (29%) in the albumin group and 12 out of 17 (71%) in the IVIg group completely recovered from the clinical disease by day 30. The animals receiving IVIg treatment exhibited lower clinical scores, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades. In the study which the efficacy of albumin, Fab fragment, Fc fragment, and IVIg was compared, 0 out of 8 (0%) in the albumin group, 1 out of 8 (13%) in the Fab group, 4 out of 8 (50%) in the Fc group, and 6 out of 9 (67%) rats in the IgG group completely recovered from the clinical disease by day 30. The animals receiving Fc fragment and IVIg treatment exhibited lower clinical scores, less prominent weight loss, less prolongation of S wave latencies, better maintained S wave amplitudes, less reduction of distal motor NCVs, better maintained distal and proximal CMAP amplitudes, and lower histological grades.

Repeated cannulation of children during the course of treatment is distressing for the child, their family and to their nurses. Some paediatric units endeavour to minimise recannulation by employing strategies to reduce complications such as phlebitis and thrombosis formation. One strategy is to infuse low dose heparin and hydrocortisone (HEPHC). However, its effectiveness in prolonging cannula survival is inconclusive. There is also concern about the potential risks of administering these preparations to children. A randomised, controlled, blinded trial was conducted that examined the effectiveness of continuous infusion of low dose HEPHC in a group of children requiring long term intravenous antibiotics in a general paediatric unit. Comparisons of cannula complications and cannulae survival times were made in children receiving either continuous infusions of clear fluids or low dose HEPHC. The results demonstrated that there was no statistically significant difference (Logrank statistic=l.l, p=0.3) in cannula survival times between the two groups. It was also found that the bacterial and fungal colonisation of cannula for these children was extremely low. Based on these findings it is recommended that routine administration of low dose HEPHC to extend cannula survival time be discontinued. The findings also support current practice of removing cannula in children only when a complication occurs on completion of treatment.

The aim of this thesis was to determine the relevant dose of arbepoetin-alfa (DA) in patients with lymphoproliferative diseases (LPD) and chemotherapy induced anemia (CIA), to study the clinical impact of intravenous (IV) iron supplementation combined with epoetin beta treatment, to identify factors that might predict hemoglobin (Hb) response to treatment with epoetins and to investigate safety of DA. A dose-finding phase II study was able to assess a reasonable DA dose of 2.25 μg/kg once weekly for the treatment of CIA in patients with LPD. Dose-response trends were observed for the different dose cohorts although not statistically significant for any of the endpoints. However a significantly higher proportion of patients achieved Hb response (increase ≥2 g/dL) in the combined DA groups than in placebo (P<0.001). A larger pivotal phase II trial was performed in a similar setting o confirm that the dose 2.25μg/kg once weekly was appropriate and safe. The proportion of patients achieving Hb response was significantly higher in the DA group (60%) than in the placebo group (18%) (P<0,001) and resulted in higher mean changes in Hb than placebo from baseline, 2.66 g/dl versus 0.69 /dl. Also a significantly lower proportion of patients in the DA group (31%) received RBC tranfusions than in the placebo group (48%). The short-term safety of DA with the tested dose was confirmed. The efficacy of DA was consistent for all end points independent of malignancy type or baseline endogenous erythropoietin serum levels. The correction of moderate anemia in truly iron repleted patients with clinically stable LPD not receiving hemotherapy or RBC transfusions with epoetin beta treatment, with or without IV iron treatment was studied in an open label randomized trial. Also the impact on iron kinetics was assessed. The mean change in Hb concentration from baseline to end of treatment (EOT ) was 2.91 versus 1.50 g/dL respectively (P<0.0001). There was a significant (P<0.0001) difference in mean Hb at EOT between the iron and no-iron groups (13.0 g/dL versus 11.8 g/dL). Hb response was achieved by significantly more patients in the iron group (P=0.0012)than in the no-iron group (93% versus 53%) and the median time to achieve a Hb response was 6 weeks in the iron group compared with 12 weeks in the no-iron group. The mean weekly epoetin dose per patient was statistically significant lower in the iron group at week 13 (P =0.029) and at least 25% lower at EOT. To investigate the long-term safety of DA in cancer patients with CIA four previously published double blind, randomized placebo-controlled phase II -III studies were analysed (n = 1.129). Median durations of progression-free survival and overall survival was comparable between DA and placebo for lung cancer (median follow up 15.8 months), for LPD (median follow up 32.6 months) and in the pooled population (follow up 4 months).