Orientador: Luis Guillermo Bahamondes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-15T23:50:03Z (GMT). No. of bitstreams: 1 Doria_RaquelFerreiraFerrazdoLago_D.pdf: 2578074 bytes, checksum: 341c6ac9f1772c408e5a1ea2a499da58 (MD5) Previous issue date: 2010 / Resumo: Avaliar a prevalência de sinais e sintomas no local de inserção no braço e a opinião das mulheres com relação à satisfação com o método e com o novo padrão de sangramento em usuárias de implantes subdérmicos liberadores de levonorgestrel (LNG; Jadelle®) e etonogestrel (ENG; Implanon®). Métodos: Os totais de 233 e 226 mulheres foram aceitas nos grupos de implantes liberadores de ENG e LNG, respectivamente. Os sinais locais foram avaliados pela inspeção e as mulheres foram questionadas sobre queixas relacionadas ao local do implante aos 14 dias e 3, 6, 12, 24 e 36 meses após a inserção no Brasil e na República Dominicana. O mesmo grupo, somente de mulheres brasileiras, sendo 120 no grupo das usuárias de implantes liberadores de ENG e 127 no grupo liberador de LNG, deu sua opinião com relação à satisfação com o método contraceptivo e com o novo padrão menstrual, através de um questionário desenvolvido para o estudo. Os questionários foram aplicados pessoalmente aos 3 e 6 meses, e em seguida a cada 6 meses, até 36 meses após a inserção. Resultados: Dor e outros sintomas (principalmente prurido) foram as queixas mais frequentemente relatadas (~20%) e foram observadas em uma proporção semelhante entre as usuárias de Implanon® e Jadelle®, e parestesia foi relatada com menos frequência Hiperpigmentação foi três vezes maior entre as usuárias de Jadelle® do que em usuárias de Implanon® (p< 0,0001) e foi mais prevalente entre as usuárias nãobrancas. Todos os sintomas e sinais foram relatados muito mais frequentemente por mulheres dominicanas. Embora todos os sinais locais apresentassem uma tendência a diminuir com o tempo de uso, não houve diferenças significativas quando comparadas as ocorrências aos 12, 24 e 36 meses de uso de ambos os tipos de implantes. No entanto, as usuárias do Jadelle® não apresentaram declínio na ocorrência de hiperpigmentação. O modelo de regressão logística ajustada pela cor e índice de massa corporal (IMC; kg/m2) mostrou que as mulheres brancas usuárias de Implanon® apresentaram risco (OR) menor de hiperpigmentação quando comparadas às usuárias de Jadelle® (OR 0,26; IC 95% 0,14-0,48; OR 0,34; IC 95% 0,14-0,81), respectivamente. Não houve correlação entre dor, parestesia e hiperpigmentação e a utilização dos dois tipos de implantes. Hiperpigmentação foi mais prevalente entre usuárias de Jadelle® de pele escura. Em relação à satisfação foram analisados 1200 questionários. A maioria das usuárias dos dois tipos de implantes estava satisfeita com o método, e a insatisfação foi de aproximadamente 15% ao longo dos 3 anos de observação. Além disso, cerca de 70% das mulheres declararam que a utilização dos implantes trouxe benefícios e só aproximadamente 5% referiram que o uso provocou danos. Com relação ao novo padrão menstrual, as usuárias estavam muito satisfeitas ou satisfeitas em aproximadamente 70%, independente do tipo de implante. A vida sexual das usuárias não apresentou alteração em mais de 70% das usuárias, independentemente do tipo de implante. As usuárias indicariam o método para outra mulher e em sua grande maioria o método foi aprovado pelo marido. Conclusões: Informar as usuárias de implantes sobre sinais e sintomas no local de inserção do implante indica uma boa qualidade de atendimento; no entanto não é necessário avaliar o local de inserção a cada visita em usuárias assintomáticas. Os resultados sobre a opinião das usuárias quanto à satisfação com o método foram similares aos de trabalhos anteriores. No entanto, os resultados devem ser interpretados com cautela porque as mulheres que participaram deste estudo não eram usuárias comuns de uma clínica de planejamento familiar, o que levou a maior orientação durante todo o estudo. Não se pode ignorar a possibilidade de que a alta satisfação seja uma consequência da insatisfação com outros métodos contraceptivos / Abstract: Objectives: The study was conducted to assess the prevalence of local signs and symptoms at the insertion site in the arm, and the evaluation of the women's satisfaction with the method and with the new bleeding patterns among users of subdermal releasing-implants, levonorgestrel (LNG, Jadelle®) and etonogestrel (ENG, Implanon®) systems. Methods: A total of 226 and 233 women were enrolled in the ENG and the LNG group, respectively. Local signs were evaluated and women were questioned regarding complaints related to the insertion site at 14 days and 3, 6, 12, 24, and 36 months after insertion in Brazil and Dominican Republic. The same Brazilian women were randomly enrolled in the satisfaction study of ENG group (120) and the LNG group (127), respectively. The opinion of satisfaction with the bleeding pattern and with the method was evaluated through a questionnaire developed for the study. The questionnaires were applied face- toface at the 3, 6, and every 6 months thereafter up to 36 months after insertion. Results: Pain and other symptoms (mostly pruritus) were the most frequently reported complaints (~20%), and were observed in a similar proportion among both Implanon® and Jadelle® users; paresthesia was less frequently reported. Hyperpigmentation was three fold higher among users of Jadelle® than Implanon® users (p< 0.0001) and was more prevalent among non-white users. All symptoms and signs were reported much more frequently by Dominican women. The logistic regression model adjusted by race and body mass index (BMI; kg/m2) showed that users of Implanon® and white women presented lower risk of hyperpigmentation when compared to Jadelle's users (OR 0.26, 95% CI 0.14-0.48; OR 0.34, 95% CI 0.14-0.81, respectively). There was no relation between pain, paresthesia and hiperpigmentation and the use of the implants. Hiperpigmentation was more prevalent between users of Jadelle® in non-white women. The total number of questionnaires for the satisfaction study was 1,200. The results showed that most of these users of contraceptive implants were satisfied with both implants at the different visits and the regret with the method did not reach ~15% at any time through the 3 years of observation. In addition, almost 70% of the women declared that the use of the implants offered benefits for her and only ~5% referred that the use provoke harm for her. Regarding the women's response to changes in their bleeding patterns following insertion of the implant, the percentage who stated that they were very satisfied or satisfied was 70% in both methods. There was no change in the reported frequency of sexual interc urse during use of the implants and no change in their libido. Moreover, all the women in both groups stated that they would recommend the method to a friend or relative and most of them declared that their partner approved of this contraceptive method. Conclusions: Although information relating to local symptoms and signs at the implant site should be provided to current and potential users as a component of good quality of care, we do not recommend evaluation of the insertion site at every visit in women with no complaints. The results about satisfaction with the method are in agreement with previous findings. However, the results must be interpreted with caution because the women are participating in a research study and were not common clients of a family planning clinic. We cannot ignore the possibility that the high satisfaction was a consequence of dissatisfaction with alternative methods / Doutorado / Tocoginecologia / Doutor em Tocoginecologia

Objective: A systematic review and meta-analysis was performed to evaluate the safety and efficacy of drug-eluting stents (DES) vs bare-metal stents (BMS) in atrial fibrillation (AF) patients. Methods: We systematically searched 5 engines until May 2019 for cohort studies and randomized controlled trials (RCTs). Primary outcomes were major bleeding and major adverse cardiac events (MACE) including cardiac death, myocardial infarction, target vessel revascularization (TVR) or stent thrombosis. Effects of inverse variance random meta-analyses were described with relative risks (RR) and their 95% confidence intervals (CI). We also stratified analyses by type (triple [TAT] vs dual [DAT]) and duration (short-vs long-term) of antithrombotic therapy. Results: Ten studies (3 RCTs; 7 cohorts) including 10,353 patients (DES: 59.6%) were identified. DES did not show higher risk of major bleeding than BMS (5.6% vs 6.9%, RR 1.07; 95%CI, 0.89–1.28, p = 0.47; I2 = 0%) or MACE (12% vs 13.6%; RR 0.96; 95%CI 0.81–1.13, p = 0.60; I2 = 44%). Although, DES almost decreased TVR risk (6.4% vs 8.4%, RR 0.78; 95%CI, 0.61–1.01, p = 0.06; I2 = 15%). Stratified analyses by type and duration of antithrombotic therapy showed no differences in major bleeding or MACE between both types of stents. In DES, long-term TAT showed higher major bleeding risk than long-term DAT (7.7% vs 4.7%, RR 1.48, 95%CI 1.08–2.03, p = 0.01; I2 = 12%). For both types of stents, MACE risk was similar between TAT and DAT. Conclusions: In patients with AF undergoing PCI, DES had similar rate of major bleeding and MACE than BMS. DAT seems to be a safer antithrombotic therapy compared with TAT. / Janssen Pharmaceuticals / Revisión por pares

The number of prehospital deaths caused by large bleedings could be decreased if civilian people would act in time to help the injured patient. One way to help is to stop the bleeding with a tourniquet application. However, the tourniquet needs to be placed correctly in order to stop the bleeding. Therefore laypersons need to be educated in bleeding control to increase the rate of successful tourniquet application. This study used human error identification techniques such as Hierarchical Task Analysis and Systematic Human Error Reduction and Prediction Approach to identify possible errors of four commonly used tourniquet models: the CAT-7, Delfi-EMT, SAM-X and SWAT-T. The results show that many predicted errors are time-oriented and critical. Video analysis of tourniquet application was performed to map occurred use errors from the videos with the predicted ones. The goal was to identify problems that could be solved by training or redesigns of the tourniquets. The results show that the most common errors for all participants during tourniquet application were of six error types. The errors were to not check time or write down time of application, to take too much time to place the tourniquet around the limb, to place the tourniquet upside down, to place the tourniquet band over the securing mechanism instead of between and lastly to not secure the tourniquet correctly before transporting the patient. The untrained laypersons made more errors than the trained laypersons and professional emergency personnel group. The trained laypersons also made fewer errors in a calm setting than in a stressed setting, comparing to the professional group who did the same error types in both settings. The results indicate that untrained laypersons not only make more errors but also more critical errors than trained laypersons and professional emergency personnel. Future research should empirically test other tourniquet models than the CAT in the goal of finding use errors to be reduced. Overall the results are in line with previous studies that show the need for education of bleeding control techniques in the civilian population.

The last decade has seen an emergence of various types of cloud services and development frameworks offered by leading companies in the software industry. While each of these services has been used to solve specific tasks, their specifications have changed over time as they have matured. Therefore, integrating these components to solve a whole new task tends to get tricky due to their incompatible and experimental nature. While some technology components might continue to be developed, others might deprecate. In this thesis, using a user-centered design and agile development approach, we have attempted to develop a cloud solution using microservice software architecture by integrating state-of-the-art technology components to solve a totally new task of providing a non-intrusive technology experience during walking meetings. We present our results based on interaction with the research group, user studies as a part of the research study “Movement of the mind”, and expectations of the working prototype within the context of walking meetings. We also present the features of the prototype and our motivation for choosing the tools to develop them. Finally, we discuss the development challenges faced during our attempt and conclude whether it is plausible to integrate various components of bleeding-edge technology to solve complex real-life problems or rather wait for these technologies to mature. / Under det senaste decenniet har marknaden erbjudits en mängd olika typer av molntjänster och utvecklings-ramverk framtagna av ledande företag inom mjukvaruindustrin. Dessa tjänster har ofta använts för att lösa specifika uppgifter. Olika komponenterna som ingår i dessa specifika lösningar har med tiden utvecklats ändrats allteftersom de har mognat. Att integrera dessa komponenter för att lösa en helt ny uppgift tenderar därför att bli svårt på grund av deras instabila, inkompatibla och experimentella karaktär. Medan vissa teknikkomponenter kan fortsätta att utvecklas kan andra avstanna och utgå. Vi har närmat oss detta problemområde genom agil och iterativ utveckling samt användar-centrerad design-metod. En moln-baserad lösning som bland annat integrerat bleeding-edge teknikkomponenter har utvecklats och utvärderats med syfte att ge en icke-påträngande tekniskt support för gå-möten. De resultat som här presenteras och diskuteras baseras på interaktion med forskargruppen inom projektet "Med rörelse i tankarna", användarstudier och användartesteter i fält på olika arbetsplatser där den prototyp som utvecklats sökt motsvara användarnas utryckta förväntningar på tekniskt support för gångmöten. Vi diskuterar också prototypens egenskaper och vår motivation för val av metoder för att utveckla den. Slutligen diskuterar vi de utvecklingsutmaningar vi ställdes inför under vårt försök och om det är rimligt att integrera olika bleeding-edge komponenter för att lösa komplexa verkliga problem eller huruvida man hellre bör vänta på att dessa teknologier nått en stabilare mognadsgrad.

This study investigated possible solutions to the current wartime problem of junctional hemorrhaging, or massive traumatic hemorrhaging in non-tourinquetable areas such as the neck, groin, or armpit. Junctional hemorrhaging has been identified as a major contributor to potentially survivable deaths seen on the battlefield today and therefore is a priority for the U.S. armed and coalition forces (Kragh et al., 2011a; Bozeman, 2011). Common tourniquets today are standard issue and carried by soldiers in the military, but are limited to distal extremity trauma. As the battlefield has changes however, trauma has transformed from commonly seen gunshot wounds to more extreme trauma such as dismounted complex blast injuries which typically includes loss of one or more appendages. These newly found situations render the traditional tourniquet ineffective. Thus, the development of a new tourniquet to control hemorrhaging from regions such as the neck, armpit, and groin has been deemed necessary. The development of a new tourniquet for hemorrhage control included market research, preliminary testing to determine design restraints, design ideation, finite element analysis, manufacturing a prototype, and prototype testing. Research and comparisons were done of the strengths and weaknesses of tourniquets already approved by the Food and Drug Administration (FDA). Next, design limitations were found using preliminary testing on a blood-flow replicate model developed by Tracey Cheung. The results from this testing provided a framework for designing a new tourniquet. A new approach to control junction hemorrhaging was then designed, built, and tested on the Cheung model. To verify the design, simplified models were analyzed using finite element analysis. The prototype was then tested and compared against the FDA approved tourniquets, listing the advantages and possible shortcomings.

Oral health may serve as an indicator of overall systemic health, with each disease or condition manifesting differently in the oral cavity. Sickle cell disease (SCD) is a genetic disorder in which sickled red blood cells cause blood vessel occlusion and potentially bleeding in specific sites (e.g., gastrointestinal and intracranial bleeding). With SCD being one of the most common hereditary diseases in the world, it is essential to understand the disease and improve awareness to better treat this population. While studies have been done to evaluate the oral health of persons with SCD, few have explored the occurrence of gingival bleeding and their experience with dental care. Due to this gap in the literature, the present study investigates the potential relationship between SCD, gingival bleeding, and certain other oral manifestations. Adults with and without SCD responded to an online questionnaire regarding oral health and dental care. The data was collected and analyzed during the 2022 spring semester. The data collected from Qualtrics was downloaded into JASP for statistical analysis. While there was a greater prevalence of gingival bleeding and caries in those with SCD, analysis of the sample showed no significant association between the oral manifestations and SCD. A deeper subgroup analysis suggested that those with SCD and no employment may be at higher risk for dental caries, orofacial pain, and gingival bleeding. Further investigation is necessary to determine the direct effect of the disease. The findings may justify further studies to include clinical evaluations by oral health care providers and larger quantity of participants. A better understanding of the relationship between SCD and oral health may lead to oral hygiene improvement strategies geared explicitly toward persons with SCD.

The aim of this study was to compare effects of an individualized with a standardized risk assessment for adverse drug reactions to improve drug treatment with antithrombotic drugs in older adults. A randomized controlled trial was conducted in general practitioner (GP) offices. Patients aged 60 years and older, multi-morbid, taking antithrombotic drugs and at least one additional drug continuously were randomized to individualized and standardized risk assessment groups. Patients were followed up for nine months. A composite endpoint defined as at least one bleeding, thromboembolic event or death reported via a trigger list was used. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. In total, N = 340 patients were enrolled from 43 GP offices. Patients in the individualized risk assessment group met the composite endpoint more often than in the standardized group (OR 1.63 [95%CI 1.02–2.63]) with multiple adjustments. The OR was higher in patients on phenprocoumon treatment (OR 1.99 [95%CI 1.05–3.76]), and not significant on DOAC treatment (OR 1.52 [95%CI 0.63–3.69]). Pharmacogenenetic variants of CYP2C9, 2C19 and VKORC1 were not observed to be associated with the composite endpoint. The results of this study may indicate that the time point for implementing individualized risk assessments is of importance.

Determining the prognosis or risk of an individual experiencing a specific health outcome within a certain time period is essential to improve health. An important aspect of prognostic research is the development of risk assessment models (RAMs). In support of the movement towards personalized medicine, health care professionals have employed RAMs to stratify an individual patient’s absolute risk of developing a health condition and select the optimal management strategy for that patient. The development of RAMs is generally conducted using data driven methods or through expert consensus. However, these methods present limitations. Accordingly, we recognized the need to select factors for RAM development or update that are evidence-based and clinically relevant using a structured and transparent approach. In this sandwich thesis, I highlight the methods used to select prognostic factors for VTE and bleeding RAMs for hospitalized medical patients. However, the same methods can be applied to any clinical outcome of interest. This work presents a conceptualized and tested novel mixed methods approach to select prognostic factors for VTE and bleeding in hospitalized medical patients that are evidence-based, clinically meaningful and relevant. Our findings may inform the development of new RAMs, the update of widely used RAMs, and external validation and prospective impact assessment studies. Also, these findings may assist decision makers in evaluating the risk of an individual having an outcome to optimize patient care. / Thesis / Doctor of Philosophy (PhD) / Measuring the probability of an individual experiencing a specific health outcome in a certain period of time based on that individual’s risk factors is important to improve health. Prediction tools are often used to calculate the probability of an outcome. Health care practitioners use prediction tools to assess an individual’s risk of a certain health outcome and in turn provide individualized management. Prediction tools include a number of agreed upon risk factors that should be assessed in order to best estimate the risk of an outcome. These risk factors are usually selected through exploring sets of data or by consulting a group of experts in the field. However, these methods have limitations. Therefore, we recognized that it is important, when developing prediction tools, to select risk factors that are evidence-based and clinically relevant by adopting a systematic, comprehensive, structured and transparent approach. These sets of risk factors can then aid health researchers when developing new prediction tools or updating existing ones and help clinicians predicting risk. In this thesis, I highlight the methods used to select factors for prediction tools that evaluate the risk of having a venous clot or a bleeding event in patients that are hospitalized for a medical condition. However, the same methods can be applied to any clinical condition and outcome of interest. This work presents a new approach that we conceptualized and tested to select risk factors for venous clots and bleeding events in hospitalized medical patients that are evidence-based, clinically meaningful and relevant. Our findings may inform the development of new prediction tools, the update of widely used tools, and the design of studies to validate these tools. Also, these findings may assist decision makers in evaluating the risk of an individual having an outcome to optimize patient care.

Background: Dogs with acquired chronic liver disease often have hemostatic derangements. It is currently unknown whether dogs with acquired chronic liver disease have decreased platelet function and alterations in von Willebrand factor (vWF) that may contribute to hemostatic abnormalities. Hypothesis: Dogs with chronic liver disease have prolonged platelet closure time (CT), assessed with the PFA-100®, and buccal mucosal bleeding time (BMBT), and increased vWF concentration compared to healthy dogs. Animals: Eighteen dogs with chronic acquired liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy and eighteen healthy age-matched control dogs. Methods: Prospective study. BMBT, CT using the PFA-100®, and vWF antigen were measured in dogs with chronic liver enzyme elevation undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy. After undergoing ultrasound-guided needle biopsy, dogs were monitored for hemorrhage with serial packed cell volume measurements and focused assessment with sonography. An unpaired t-test was used for normally distributed data and the Mann-Whitney test was used when non-Gaussian distribution was present. The level of significance was set at P <0.05. Results: The CT was not different between the two groups (P = 0.27). The BMBT was significantly longer in the liver disease group compared to the control group (P = 0.019). There was no difference in the mean vWF antigen of the two groups (P = 0.077). Conclusions and clinical relevance: These results demonstrate mild impairment of primary hemostasis in dogs with chronic liver disease based on prolongation of BMBT. / Master of Science / Background: Dogs with chronic liver disease often have abnormal blood clotting activity. It is currently unknown whether dogs with chronic liver disease have decreased platelet function and alterations in von Willebrand factor (vWF) that may contribute to blood clotting abnormalities. Platelet function can be assessed using the PFA-100®, which measures platelet closure time (CT), and buccal mucosal bleeding time (BMBT). The PFA-100 simulates blood in circulation to assess platelet function. BMBT is a crude but readily available test to assess platelet function in practices without sophisticated methods of assessing platelet function. Hypothesis: Dogs with chronic liver disease have prolonged CT and BMBT, which both suggest platelet dysfunction. Additionally, dogs with chronic liver disease have increased vWF concentration compared to healthy dogs. Animals: Eighteen dogs with chronic acquired liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy and eighteen healthy age-matched control dogs. Methods: Prospective study. BMBT, CT, and vWF antigen were measured in dogs with chronic liver disease undergoing ultrasound-guided needle biopsy of the liver or laparoscopic liver biopsy. After undergoing ultrasound-guided needle biopsy, dogs were monitored for hemorrhage. Results: The CT was not different between the two groups but the BMBT was significantly longer in the liver disease group compared to healthy dogs. There was no difference in the mean vWF antigen between the two groups. Conclusions and clinical relevance: These results demonstrate mild impairment of blood clotting activity in dogs with chronic liver disease based on prolongation of BMBT compared to healthy dogs. Prolongation of BMBT compared to healthy dogs is suggestive of endothelial dysfunction and/or platelet dysfunction in dogs with chronic liver disease.

Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear. Thus, we compared the platelet receptor composition of patients with (bleeder group, n = 18) and without NSB (non-bleeder group, n = 18) prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and after bleeding complications in the post-implant period. Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Bleeders and non-bleeders were comparable regarding clinical characteristics, von Willebrand factor diagnostics and the aggregation capacity before and after LVAD implantation (p > 0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (33%; n = 6), epistaxis (22%; n = 4), hematuria or hematoma (17%; n = 3, respectively) and cerebral bleeding (11%; n = 2). Prior to LVAD implantation, a restricted surface expression of the platelet receptors P-selectin and GPIIb/IIIa was observed in the bleeder group (P-selectin: 7.2 ± 2.6%; GPIIb/IIIa: 26,900 ± 13,608 U) compared to non-bleeders (P-selectin: 12.4 ± 8.1%, p = 0.02; GPIIb/IIIa: 36,259 ± 9914 U; p = 0.02). We hypothesized that the reduced platelet receptor expression of P-selectin and GPIIb/IIIa prior to LVAD implantation may be linked to LVAD-related NSB.