Chronic Venous Insufficiency (CVI) is a condition in present in almost 27% of adults in which an insufficient amount of blood is pumped back to the heart due to damaged or poorly apposed one-way valves in the leg veins. During forward flow, vein valves allow blood to return to the heart while posing very little resistance to the flow. During gravity-driven reverse flow, normal valves close and prevent blood from flowing backward through the valve. Incompetent, or damaged, vein valves cannot prevent this reverse flow and lead to a pooling of blood at the feet. CVI is a painful disease presents itself in various ways, including varicose veins, ulcerations of the lower extremities, and severe swelling. Current therapies and treatments include compressive stockings, destruction or removal of affected veins, valve repair, and valve transplants. The implantation of prosthetic vein valves is a future treatment option that does not require an invasive surgery, human donor, or lengthy hospital stay. While no prosthetic vein valves are currently commercially available, this thesis describes the design, verification, and validation of a novel prosthetic vein valve. Verification tests include CFD simulations, functional tests, mechanical tests, and in vitro thromogenicity tests. The validation of the device was done through an animal study in sheep external jugular veins. CFD analysis verified that shear rates within the valve support its lower thrombogenicity as compared to a previous vein valve. Benchtop tests demonstrate superiority in short-term patency over a previous polymer valve. In a sheep study, patency was shown at 6 weeks, surpassing many autograft valves and showing great potential to meet the goal of 3 month patency in sheep.

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Class of 2012 Abstract / Specific Aims: The purpose of this study was to evaluate the effectiveness of various post-operative prophylaxis methods in lung transplant patients by comparing the incidence of venous thromboembolism (VTE) before and after the implementation of a standardized hospital order set at the University of Arizona Medical Center (UAMC) in April 2007. Methods: Paper and electronic medical charts were retrospectively reviewed if patients had a lung transplant date between October 31, 2003 – October 31, 2010. A computerized database was used to collect demographic data, length of stay (LOS), comorbid conditions, prophylaxis type (including dose/frequency), and date/type of thromboembolic events in the post-operative period prior to discharge and up to 1-year post- discharge. Main Results: Ninety-two patient charts were included in the study with 35 charts in the pre-order set (“Before”) group and 57 charts in the post- order set (“After”) group. All baseline characteristics were similar between groups except age (mean age difference 8.1 yrs, p=0.003), use of mycophenolate (Before n=24, After n=54; p=0.002), and use of medications that increase risk of VTE (Before n=6, After n=2; p=0.05). The April 2007 protocol significantly increased the number of patients receiving any method of prophylaxis (p<0.0001). However, receiving prophlyaxis did not significantly reduce event rates or readmissions due to VTE. Conclusions: Although implementation of the April 2007 protocol did not significantly reduce VTE event rates and readmissions, VTE prophylaxis should continue to remain a priority. Adherence to the implemented protocol may reduce the number of patients left without effective methods of prophylaxis.

Introduction and Background: Central venous catheters (CVCs) are extensively used worldwide. Mechanical, infectious and thrombotic complications are well described with their use and may be associated with prolonged hospitalisation, increased medical costs and mortality. CVCs account for an estimated 90% of all catheter-related bloodstream infections (CRBSI) and a host of risk factors for CVC-related infections have been documented. These include, most importantly, the duration of catheterisation. The duration of use of CVCs remains controversial and the length of time such devices can safely be left in place has not been fully and objectively addressed in the critically ill patient. Over the past few years, antimicrobial impregnated catheters have been introduced in an attempt to limit catheter-related infection (CRI) and increase the time that CVCs can safely be left in situ. Recent meta-analyses concluded that antimicrobial-impregnated CVCs appear to be effective in reducing CRI. Materials and Methods: This was a prospective randomised double-blind study performed in the adult multidisciplinary Intensive Care Unit (ICU) at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) over a four year period. The study entailed a comparison of standard triple-lumen versus antimicrobial impregnated CVCs on the rate of CRI. The aim was to determine whether the duration of catheter insertion time could safely be increased from the standard practice of seven days at the CMJAH adult multidisciplinary ICU to 14 days, to assess the influence of the antimicrobial impregnated catheter on the incidence of CRI, and to elucidate the epidemiology and risks of CRI. Results: One hundred and eighteen critically ill patients were included in the study which spanned 34 951.5 catheter hours (3.99 catheter years). Sixty-two patients received a standard triple-lumen catheter and 56, a chlorhexidine-silver sulfadiazine (CSS) impregnated triple-lumen catheter. The mean duration of placement for the full sample of 118 CVCs was 12.3 days (range, 1-14). No statistically significant difference in CRI rates between the two types of catheters could be demonstrated. The most common source of primary CRBSI was skin, followed by hub and infusate. The site of CVC insertion (internal jugular versus subclavian vein) and the use of parenteral nutrition were not noted to be risk factors for catheter infection. There was no clinical evidence of catheter-related thrombosis in either of the study groups. Conclusion: This study was unable to demonstrate that antimicrobial catheters provided any significant benefit over standard catheters, which it is felt, can safely be left in place for up to 14 days with appropriate infection control measures. The most common source of CRI was the skin. The administration of parenteral nutrition and the site of catheter insertion (internal jugular vein versus subclavian vein) were not noted to be risk factors for CRI. There was no clinical evidence of thrombotic complications in either of the study groups. This study offers direction for the use of CVCs in critically ill patients and addresses many of the controversies that exist.

Orientador: Elenice Deffune / Banca: Sonia Regina Pérez Evangelista Dantas / Banca: Hélio Amante Miot / Resumo: As úlceras venosas são impactantes e representam um grande desafio médico devido ao entrelaçamento de comorbidades e causas multifatoriais, sendo de suma importância o surgimento de inovações tecnológicas na abordagem terapêutica que sejam acessíveis aos seus portadores. Diante dessa realidade, este trabalho se propôs a abordar as úlceras venosas comparando um produto existente no mercado, Hidrocolóide (HC), com uma proposta in house, o Gel de Plaquetas (GP), através da diminuição da área, avaliação descritiva da vascularização e queixas referidas. Participaram do estudo 17 pacientes, perfazendo um total de 22 úlceras venosas que foram acompanhados durante 90 dias, utilizando um dos produtos citados, de acordo com o randomização, em associação com o uso de faixas elásticas. A distribuição do grupo, segundo a randomização foi de 13 lesões no grupo de hidrocolóide e 9 no grupo de gel de plaquetas. A média percentual de redução das áreas das feridas foi de 57,78% para hidrocolóide e de 53,45% para gel de plaquetas, não apresentando diferenças estatisticamente significativas. O desempenho dos produtos estudados apresentaram grande similaridade no percentual de redução de área, o que indica que é preciso um estudo amostral maior para evidenciar superioridade de um produto sobre o outro. Porém quando comparados, quanto ao menor tempo de acompanhamento (D15), o gel de plaquetas apresentou melhor desempenho, com redução maior do que o hidrocolóide em tempo reduzido semelhante. A análise histológica no momento pré e pós tratamento sugere que o GP atua de forma a estimular a regeneração dos tecidos (estroma coeso) e de forma mais definitiva (distribuição dos vasos difusa na derme reticular). O aspecto do fechamento da lesão é mais consistente quando comparado com os pacientes que usaram HC onde se observou a formação de uma fina epiderme frágil... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Venous ulcers are striking and represent a major challenge due to the commingling of medical comorbidities and multifactorial causes, with the emergence of great importance to technological innovations in therapeutic approaches that are accessible to their patients. Given this reality, this study proposes to address venous ulcers comparing a product on the market, hydrocolloid (HC) with a proposed in-house, the Platelet Gel (GP), by decreasing the area and descriptive evaluation of vascularization complaints referred. The study included 17 patients, a total of 22 venous ulcers who were followed for 90 days, using one of the products listed, according to the randomization, in association with the use of compression elastic. The distribution of the group, according to randomization was 13 injuries in the hydrocolloid group and 9 in the group of platelet gel. The average percentage reduction of wound areas was 57.78% for hydrocolloid and 53.45% for platelet gel, showing no statistically significant differences. The performance of the products studied showed great similarity in the percentage of area reduction, which indicates that it is necessary to study a larger sample to demonstrate the superiority of one product over another. But when compared, for the shortest time of follow-up (D15), the platelet gel performed better, with greater reductions than the hydrocolloid in a short time like that. Histological analysis in the D0 and D90 of the treatment suggests that the GP acts to stimulate the regeneration of tissues (stroma together) and more definite form (diffuse distribution of vessels in the reticular dermis). The appearance of the closure of the injury is more consistent when compared with patients who used HC we observed the formation of a thin skin, fragile, observed in histological sections showed that a distribution of vessels in the papillary dermis. Histological sections confirmed... (Complete abstract click electronic access below) / Mestre

The response of the circulatory system to gravity and hydrostatic forces has been well studied, for example the hydrostatic indifferent point (the location at which pressure does not change with posture) of the venous system has been established to be an important determinant of orthostatic responses and it has been found to be located near the diaphragm. However, the role of the abdomen has been less researched; for example, it appears that the concept that the abdominal compartment may have its own hydrostatic indifferent point has been overlooked. The goal of the present study was to establish the location of the abdominal hydrostatic indifferent point (HIPab) and to test the hypothesis that binding of the lower abdomen would shift the location of the HIPab cranially. Intra-abdominal pressure was measured using a modified wick needle technique in the supine and upright posture before and after binding of the lower abdomen in 7 anesthetized rats. In the unbound condition, the HIPab was located 5.2 ± 0.3 cm caudal to the xyphoid, meaning the hepatic veins were exposed to relatively large negative interstitial pressures during head-up tilt. Binding of the lower abdomen significantly (p <0.05) shifted the HIPab cranially by 1.7 cm. Thus, the relatively caudal location of the HIPab causes a relatively large hepatic transmural pressure owing to the fall in interstitial pressure during upright posture. The cranial shift of the HIPab by binding of the lower abdomen lessens the fall in hepatic extramural pressure and thereby protects the hepatic veins from distension.

Secondary lymphoedema and venous oedema of the limb are the consequence of an imbalance between tissue fluid infiltrate and drainage, which leads to interstitial fluid accumulation, tissue changes, limb discomfort and morbidity. Numerous conservative therapies have been developed to address some of these negative outcomes, with a proportion of these being labour and cost intensive. This makes the investigation of cost effective and easy to implement home based regimes very important. One such therapy is limb exercise, which can be beneficial for limb oedemas through changes in both interstitial pressure and calf muscle activation. Therefore, this thesis explored the benefits of different exercise regimes for limb oedema of both lymphatic and vascular origin. This was achieved through a systematic review of existing conservative therapies for limb oedemas and four clinical trials investigating the benefits of home based exercise regimes. Results demonstrated that various positive and significant outcomes could be gained from the implementation of such regimes, including improvements in both subjective and objective parameters. These results reveal how these chronic and disabling conditions can be maintained by the patient in the home environment in between health care visits. It also demonstrates how self maintenance may alleviate the burden on the health care system.

Records of all neurosurgical inpatients admitted to Royal North Shore Hospital since 1976 have been prospectively kept in a relational database. Demographic details, diagnoses, operations and complications have been entered continuously since 1982 by the author of this study. Complications are monitored at monthly review meetings attended by medical staff. The recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE) at these meetings, despite continual improvements in patient care, prompted this study. It aims to use the database to study changes in the incidence of DVT and PE over the previous twenty years; to find what database variables predict these complications; and whether use of mechanical and pharmacological agents has had an impact on DVT and PE rate. Univariate analysis of the incidence of DVT and PE by age, sex, length of stay (LOS), admission month, diagnosis, operation and surgeon over time was run. Any significant variables were then analysed by multivariate logistic regression. The DVT rate was low by world standards, but rose from 0.6% in 1979-83 to 1.2% in 1984-88, then rose exponentially to 3.60% in 1994-98 with a significantly increasing trend over the twenty years (c2 MH =114.20, with IDF, P<0.001). PE rate doubled significantly over the twenty years from 0.6% to 1.2% (c2 MH =17.94 with 1DF, P<0.001). Age, LOS, diagnosis, operation and surgeon were significant predictors of DVT and PE. After adjustment for LOS, time period and age, vascular surgery was found to be the strongest predictor of DVT (OR=2.82, 95% CI: 2.08-3.82, c2 =43.91, P<0.01). Vascular diagnosis was the strongest diagnosis predictor. No effect of sex or month of admission was shown. After adjustment for LOS, time period and age, spinal fusion was the strongest predictor of PE (OR=4.04, 95% CI: 1.81-9.03). Anterior communicating artery aneurysm was the diagnosis most highly associated with PE. The rise in DVT rate may be due to increased complexity of surgical and nursing management, and some screening of patients with the introduction of duplex scanning. The doubling of PE rate is unexplained. The risk of brain or spinal cord haemorrhage makes prophylactic anticoagulation a difficult choice. This study reveals groupings which can be used to determine appropriate prophylaxis. Use of mechanical and pharmaceutical agents is not recorded consistently in the database, but it is known approximately when they were introduced. No impact on the rate of DVT and PE can be demonstrated by these agents. More vigilant and widespread use of mechanical prophylaxis might be just as effective in controlling DVT and PE.